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Radiotherapy

Evidence Update

July 2018

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Contents

Current Journals: Tables of Contents 2

Training Sessions/ Outreach Librarian 3

Latest Evidence: NICE, The Cochrane Library, UpToDate®, Colleges 5

Recent Database Articles 8

Library Opening Times and Contact Details 40

Current Journals: Tables of Contents

Click on journal title (+ Ctrl) for hyperlink

Journal Month Volume Issue

Radiotherapy and Oncology

June 2018 127 3

International Journal of Radiation Oncology Biology and Physics

August 2018 101 5

Clinical Oncology

August 2018 30 8

If you require full articles please email: library@uhbristol.nhs.uk

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Your Outreach Librarian Sarah Barrett

Whatever your information needs, the library is here to help. Just email us at

library@uhbristol.nhs.uk

Outreach: Your Outreach Librarian can help facilitate evidence-based practice for all

in the team, as well as assisting with academic study and research. We also offer

one-to-one or small group training in literature searching, critical appraisal and

medical statistics. Get in touch: library@uhbristol.nhs.uk

Literature searching: We provide a literature searching service for any library

member. For those embarking on their own research it is advisable to book some time

with one of the librarians for a one-to-one session where we can guide you through the

process of creating a well-focused literature research. Please email requests to

library@uhbristol.nhs.uk

Lunchtime Drop-in Sessions All sessions last one hour

July (13.00-14.00)

19th (Thu) Literature Searching

23rd (Mon) Critical Appraisal

August (12.00-13.00)

1st (Wed) Statistics

6th (Mon) Literature Searching

16th (Thu) Critical Appraisal

22nd (Wed) Statistics

30th (Thu) Literature Searching

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Departmental News

News, Research, Conferences, Training etc

Please contact us with any departmental news you wish to share with your

colleagues in your Evidence Update bulletin.

library@uhbristol.nhs.uk

Library Clinic

August 8th: Foyer, Education Centre 12.00-14.00

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December 11th: Welcome Centre, BRI 10.00-16.00

Stop by and find out more about

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answer any questions you may

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Latest Evidence

Impact_of_travel_time_on_rates_of_treatment_with_radiotherapy

Source: Public Health England - PHE - 22 June 2018

Safer radiotherapy: error data analysis

Source: GOV UK - Source: Public Health England - PHE - 31 May 2018

Analysis of radiotherapy errors and near misses reported voluntarily by NHS radiotherapy departments.

Long-term side effects of radiotherapy , with or without chemotherapy, for glioma

Theresa A Lawrie , Jonathan Evans , David Gillespie , Sara Erridge , Luke Vale , Ashleigh Kernohan and Robin

Grant

Online Publication Date: June 2018

Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy for primary pelvic

cancers

Theresa A Lawrie , John T Green , Mark Beresford , Linda Wedlake , Sorrel Burden , Susan E Davidson , Simon

Lal , Caroline C Henson and H. Jervoise N Andreyev

Online Publication Date: January 2018

OpenAthens login required. Register here: https://openathens.nice.org.uk/

General principles of radiation therapy for head and neck cancer

Author: Shlomo A Koyfman, MD

Section Editors: Bruce E Brockstein, MD; David M Brizel, MD; Marshall R Posner, MD

Deputy Editor: Rebecca F Connor, MD

Literature review current through: Jun 2018. | This topic last updated: Jun 04, 2018.

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Overview of gastrointestinal toxicity of radiation therapy

Authors: Brian G Czito, MD; Jeffrey J Meyer, MD; Christopher G Willett, MD

Section Editor: Reed E Drews, MD

Deputy Editor: Shilpa Grover, MD, MPH, AGAF

Literature review current through: Jun 2018. | This topic last updated: Apr 11, 2018.

Radiation-induced lung injury

Authors: Kenneth R Olivier, MD; Tobias Peikert, MD

Section Editors: James R Jett, MD; Steven E Schild, MD

Deputy Editor: Helen Hollingsworth, MD

Literature review current through: Jun 2018. | This topic last updated: Jun 21, 2018.

Management of recurrent or persistent non-muscle invasive bladder cancer

Authors: Peter Black, MD, FACS, FRCSC; Wassim Kassouf, MD, CM, FRCS

Section Editor: Seth P Lerner, MD

Deputy Editor: Sadhna R Vora, MD

Literature review current through: Jun 2018. | This topic last updated: Jun 19, 2018.

Overview of the treatment of brain metastases

Authors: Jay S Loeffler, MD; Patrick Y Wen, MD

Section Editor: Lisa M DeAngelis, MD, FAAN, FANA

Deputy Editor: April F Eichler, MD, MPH

Literature review current through: Jun 2018. | This topic last updated: Jul 11, 2018.

Nonsurgical therapies for localized hepatocellular carcinoma: Transarterial embolization,

radiation therapy, and radioembolization

Authors: Steven A Curley, MD, FACS; Keith E Stuart, MD; Jonathan M Schwartz, MD; Robert L

Carithers, Jr, MD; Klaudia U Hunter, MD

Section Editors: Kenneth K Tanabe, MD; Christopher G Willett, MD

Deputy Editor: Diane MF Savarese, MD

Literature review current through: Jun 2018. | This topic last updated: May 29, 2018.

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Royal College of Radiologists Update on Radiotherapy for Gynaecological Cancer This programme provides an update for clinical oncologists, radiographers and specialist nurses involved in gynaecological cancer. Friday 5 October 2018

The Society of Radiographers

Therapeutic radiographers and students: Please complete urgent surveys to recruit next

generation

The Office for Students (OfS) is funding the development of a student recruitment and awareness campaign for therapeutic radiography. Annual Radiotherapy Conference 2019 Hilton Newcastle Gateshead 25-27 January 2019

e-Learning programme to prepare staff for proton beam therapy centres

The Proton Beam Therapy (eProton) programme is a web-based e-learning resource produced in

partnership with The Royal College of Radiologists (RCR), the Institute of Physics and Engineering in

Medicine (IPEM), College of Radiographers (CoR) and Health Education England e-Learning for

Healthcare (HEE e-LfH).

Institute of Physics and Engineering in Medicine Medical Physics and Engineering Conference & Biennial Radiotherapy Meeting 2018 Date: 18 Sep 2018 Location: York Racecourse Medical Physics and Engineering Conference & Biennial Radiotherapy Meeting 2018 Our annual event is being held over 3 days, the first day is our free to attend members day followed by two full days of scientific programme.

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Recent Database Articles

Below is a selection of articles recently added to the healthcare databases, grouped in the

categories:

CHHIP Trial outcomes

Late effects of radiotherapy – bowel toxicities

If you would like any of the articles in full text, or if you would like a more focused search on

your own topic, please contact us: library@bristol.nhs.uk

CHHIP Trial outcomes

1. How will the CHHiP trial affect the future of prostate radiotherapy?

Author(s): Dearnaley, David; Hall, Emma

Source: Expert review of anticancer therapy; Jul 2018; vol. 18 (no. 7); p. 607-609

Publication Date: Jul 2018

Publication Type(s): Journal Article

2. Ki67 Is an Independent Predictor of Recurrence in the Largest Randomized Trial of 3 Radiation Fractionation Schedules in Localized Prostate Cancer.

Author(s): Wilkins, Anna C; Gusterson, Barry; Szijgyarto, Zsolt; Haviland, Joanne; Griffin, Clare; Stuttle, Christine; Daley, Frances; Corbishley, Catherine M; Dearnaley, David P; Hall, Emma; Somaiah, Navita; CHHiP Trial Investigators

Source: International journal of radiation oncology, biology, physics; Jun 2018; vol. 101 (no. 2); p. 309-315

Publication Date: Jun 2018

Publication Type(s): Journal Article

Available at International Journal of Radiation Oncology*Biology*Physics - from PubMed Central

Abstract:PURPOSETo assess whether the cellular proliferation marker Ki67 provides prognostic information and predicts response to radiation therapy fractionation in patients with localized prostate tumors participating in a randomized trial of 3 radiation therapy fractionation schedules (74 Gy/37 fractions vs 60 Gy/20 fractions vs 57 Gy/19 fractions).METHODS AND MATERIALSA matched case-control study design was used; patients with biochemical/clinical failure >2 years after radiation therapy (BCR) were matched 1:1 to patients without recurrence using established prognostic factors (Gleason score, prostate-specific antigen, tumor stage) and fractionation schedule. Immunohistochemistry was used to stain diagnostic biopsy specimens for Ki67, which were scored using the unweighted global method. Conditional logistic regression models estimated the prognostic value of mean and maximum Ki67 scores on BCR risk. Biomarker-fractionation interaction terms determined whether Ki67 was predictive of BCR by fractionation.RESULTSUsing 173 matched pairs, the median for mean and maximum Ki67 scores were 6.6% (interquartile range, 3.9%-9.8%) and 11.0% (interquartile range, 7.0%-15.0%) respectively. Both scores were significant predictors of BCR in models adjusted for established prognostic factors. Conditioning on matching

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variables and age, the odds of BCR were estimated to increase by 9% per 1% increase in mean Ki67 score (odds ratio 1.09; 95% confidence interval 1.04-1.15, P = .001). Interaction terms between Ki67 and fractionation schedules were not statistically significant.CONCLUSIONSDiagnostic Ki67 did not predict BCR according to fractionation schedule in CHHiP; however, it was a strong independent prognostic factor for BCR.

3. The Efficacy and Safety of Conventional and Hypofractionated High-Dose Radiation Therapy for Prostate Cancer in an Elderly Population: A Subgroup Analysis of the CHHiP Trial.

Author(s): Wilson, James M; Dearnaley, David P; Syndikus, Isabel; Khoo, Vincent; Birtle, Alison; Bloomfield, David; Choudhury, Ananya; Graham, John; Ferguson, Catherine; Malik, Zafar; Money-Kyrle, Julian; O'Sullivan, Joe M; Panades, Miguel; Parker, Chris; Rimmer, Yvonne; Scrase, Christopher; Staffurth, John; Stockdale, Andrew; Cruickshank, Clare; Griffin, Clare; Hall, Emma; CHHiP Investigators

Source: International journal of radiation oncology, biology, physics; Apr 2018; vol. 100 (no. 5); p. 1179-1189

Publication Date: Apr 2018

Publication Type(s): Journal Article

Abstract:PURPOSEOutcome data on radiation therapy for prostate cancer in an elderly population are sparse. The CHHiP (Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer) trial provides a large, prospectively collected, contemporary dataset in which to explore outcomes by age.METHODS AND MATERIALSCHHiP participants received 3 to 6 months of androgen deprivation therapy and were randomly assigned (1:1:1) to receive 74 Gy in 37 fractions (conventional fractionation), 60 Gy in 20 fractions, or 57 Gy in 19 fractions. Toxicity was assessed using clinician-reported outcome (CRO) and patient-reported outcome questionnaires. Participants were categorized as aged < 75 years or ≥ 75 years. Outcomes were compared by age group.RESULTSOf 3216 patients, 491 (15%) were aged ≥ 75 years. There was no difference in biochemical or clinical failure rates between the groups aged < 75 years and ≥ 75 years for any of the fractionation schedules. In the group aged ≥ 75 years, biochemical or clinical failure-free rates favored hypofractionation, and at 5 years, they were 84.7% for 74 Gy, 91% for 60 Gy, and 87.7% for 57 Gy. The incidence of CRO (grade 3) acute bowel toxicity was 2% in both age groups. The incidence of grade 3 acute bladder toxicity was 8% in patients aged < 75 years and 7% in those aged ≥ 75 years. The 5-year cumulative incidence of CRO grade ≥ 2 late bowel side effects was similar in both age groups. However, in the group aged ≥ 75 years, there was a suggestion of a higher cumulative incidence of bowel bother (small or greater) with 60 Gy compared with 74 Gy and 57 Gy. Patient-reported bladder bother was slightly higher in the group aged ≥ 75 years than the group aged < 75 years, and there was a suggestion of a lower cumulative incidence of bladder bother with 57 Gy compared with 74 Gy and 60 Gy in patients aged ≥ 75 years, which was not evident in those aged < 75 years.CONCLUSIONSHypofractionated radiation therapy appears to be well tolerated and effective in men aged ≥ 75 years. The 57-Gy schedule has potential advantages in that it may moderate long-term side effects without compromising treatment efficacy in this group.

4. Methodology for tissue sample collection within a translational sub-study of the CHHiP trial (CRUK/06/016), a large randomised phase III trial in localised prostate cancer.

Author(s): Wilkins, Anna; Stuttle, Christine; Hassan, Shama; Blanchard, Claire; Cruickshank, Clare; Griffin, Clare; Probert, Jake; Corbishley, Catherine M; Parker, Chris; Dearnaley, David; Hall, Emma

Source: Clinical and translational radiation oncology; Mar 2018; vol. 10 ; p. 1-6

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Publication Date: Mar 2018

Publication Type(s): Journal Article

Abstract:BackgroundThis article presents the methodology for tissue sample collection in Trans-CHHiP, the main translational study within the CHHiP (Conventional or Hypofractionated High dose intensity modulated radiotherapy in Prostate cancer, ISRCTN 97182923) trial. The CHHiP trial randomised 3216 men with localised prostate cancer to 3 different radiotherapy fractionation schedules. Trans-CHHiP aims to identify biomarkers of fraction sensitivity.MethodsWe outline the process of tissue collection, including central review by a study-specific specialist uropathologist and comparison of the centrally-assigned Gleason grade group with that assigned by the recruiting-centre pathologist.Results2047 patients provided tissue from 107 pathology departments between August 2012 and April 2014. A highly motivated Clinical Trials Unit chasing samples and a central Trans-CHHiP group that regularly reviewed progress were important for successful sample collection. Agreement in Gleason grade group assigned by the recruiting centre pathologist and the central study-specific uropathologist occurred in 886 out of 1854 (47.8%) cases. Key lessons learned were the need for prospective consent for tissue collection when recruiting patients to the main trial, and the importance of Material Transfer Agreement (MTA) integration into the initial trial site agreement.ConclusionsThis methodology enabled collection of 2047 patient samples from a large randomised radiotherapy trial. Central pathological review is important to minimise subjectivity in Gleason grade grouping and the impact of grade shift.

Late effects of radiotherapy – bowel toxicities

1. Three year follow-up after rehabilitation-a randomised study among radiated prostate cancer patients

Author(s): Dieperink K.; Johansen C.; Hansen S.; Hansen O.; Wagner L.; Andersen K.K.; Minet L.R.

Source: Supportive Care in Cancer; 2018; vol. 26 (no. 2)

Publication Date: 2018

Publication Type(s): Conference Abstract

Abstract:Introduction: Rehabilitation may help PCa patients treated with androgen deprivation therapy and radiotherapy. Objectives The purpose was a) to study the long-term effects of a multidisciplinary rehabilitation intervention for prostate cancer (PCa) patients and b) to study status of treatment-related adverse effects and quality of life (QoL) at different time points. Methods PCa patients n=161 were in 2010-2012 randomized to either a 4 hour programof two nurse lead psychosocial support sessions followed by two instructive sessions by a physical therapist (n= 79), or usual care (n= 82). The primary outcome, irritative urinary sum-score (EPIC-26) was significantly improved after six month. In this follow-up study all participants reported disease-specific QoL (EPIC-26) and general QoL (SF-12) three years after radiotherapy. PSA and the pelvic floor strength were examined. Survival status, descriptive analysis and linear regression analysis adjusting for baseline scores were conducted. Results Six patients had deceased, one from the intervention group and five from the control group. 143/155 (92%) responded to the questionnaire. Three years after radiotherapy none of the EPIC domains were significantly different between groups. However, patients in the intervention group showed a trend for better irritative urinary sum score (0-100) with 86.1 SD 13.3 compared to 82.9 SD 15.0 in controls P=.069. Significantly more patients in the control group had moderate to severe bowel problems 10 (14.3%) compared to the intervention group 2 (2.9%) P=.016. Conclusions We did not find a long-term effect of multidisciplinary rehabilitation in irradiated PCa patients. However, the intervention may positively influence bowel QoL.

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2. Prospective analysis of hydrogel spacer for patients with prostate cancer undergoing radiotherapy

Author(s): Chao M.; Chan Y.; Bolton D.; Troy A.; Sengupta S.; Wasiak J.; Lim Joon D.; Lawrenstchuk N.; Ho H.; Ding W.; Subramanian B.; Spencer S.; Mcmillan K.; Liu M.; Tan A.; Cham C.W.; Pham T.; Temelcos C.

Source: BJU International; 2018

Publication Date: 2018

Publication Type(s): Article In Press

Available at BJU international - from Wiley Online Library Free Content - NHS

Abstract:Objective: To report on the dosimetric benefits and late toxicity outcomes after injection of hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy (RT). Patients and Methods: In all, 76 patients with a clinical stage of T1-T3a prostate cancer underwent general anaesthesia for fiducial marker insertion plus injection of the HS into the perirectal space before intensity-modulated RT (IMRT) or volumetric-modulated arc RT (VMAT). HS safety, dosimetric benefits, and the immediate- to long-term effects of gastrointestinal (GI) toxicity were assessed. Results: There were no postoperative complications reported. The mean (range) prostate size was 66.0 (25.0-187.0) mm. Rectal dose volume parameters were observed and the volume of rectum receiving 70 Gy (rV70), 75 Gy (rV75) and 78 Gy (rV78) was 7.8%, 3.6% and 0.4%, respectively. In all, 21% of patients (16/76) developed acute Grade 1 GI toxicities, but all were resolved completely by 3 months after treatment; whilst, 3% of patients (2/76) developed late Grade 1 GI toxicities. No patients had acute or late Grade >=2 GI toxicities. Conclusion: Injection of HS resulted in a reduction of irradiated rectal dose volumes along with minimal GI toxicities, irrespective of prostate size.

3. Comparative assessment of late toxicity in patients of carcinoma cervix treated by radiotherapy versus chemo-radiotherapy - Minimum 5 years follow up

Author(s): Misra S.; Lal P.; Kumar EP S.; Rastogi N.; Tiwari A.; Singh S.; Das K.J.M.; Kumar S.

Source: Cancer Treatment and Research Communications; 2018; vol. 14 ; p. 30-36

Publication Date: 2018

Publication Type(s): Article

Abstract:Background: A randomised trial was carried out comparing chemo-radiation (CTRT) vs. radiotherapy (RT) in patients of carcinoma cervix and showed similar rates of pelvic disease control, disease free survival and overall survival. Late toxicity is presented. Methods: Between December 2000 and July 2006, 180 patients of carcinoma cervix were randomly assigned to RT + weekly cisplatin (n = 94) or RT alone (n = 86). Late toxicity was prospectively scored using RTOG criteria in 156 evaluable patients, 79 and 77 respectively and is presented as crude incidence for rectum, bladder, small intestine, vagina, skin and bone and also as actuarial incidence for rectum and bladder. Results: The median follow up of surviving patients was 10.4 years (minimum - 6.5 years). Crude incidence, CTRT vs. RT, of late toxicities were: rectal (7.5% vs. 5%, p = 0.22), bladder (15% vs. 10.4%, p = 0.76), small bowel (3% vs. 1.2%, p = 0.51), vagina (25% vs. 35%, p = 0.35) while the actuarial risk of grades 3-5 rectal and bladder toxicities by 5 years were 13% vs. 10% (p = 0.698) and 16% vs. 14.8% (p = 0.783) respectively. Bladder toxicity appeared later then rectal toxicity (median 49.4 vs. 21.4 months). Severe bone toxicity (fractures) were higher in the CTRT arm, 5% vs. 0%, p = 0.018. On multivariate analysis vaginal involvement (p = 0.016) and bulky tumor (p = 0.020) were associated with severe vaginal morbidity while rectal point dose > 80% (p = 0.040) was associated with a higher incidence of rectal toxicity. Conclusion: Bone toxicity was significantly increased by

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addition of CT to RT and patients continued to experience toxicity at longer periods of follow up albeit disease free.

4. Early Results of Extreme Hypofractionation Using Stereotactic Body Radiation Therapy for High-risk, Very High-risk and Node-positive Prostate Cancer

Author(s): Murthy V.; Gupta M.; Mulye G.; Maulik S.; Munshi M.; Krishnatry R.; Phurailatpam R.; Mhatre R.; Prakash G.; Bakshi G.

Source: Clinical Oncology; Jul 2018; vol. 30 (no. 7); p. 442-447

Publication Date: Jul 2018

Publication Type(s): Article

Abstract:Aims: Stereotactic body radiotherapy (SBRT) in low- and intermediate-risk prostate cancer has shown encouraging results. However, its use in high-risk patients is limited due to lack of data regarding adequate radiotherapy dose, need for pelvic nodal treatment and androgen deprivation therapy. Herein we report our experience of SBRT in this subgroup. Materials and methods: Analysis of a prospectively maintained database of 68 consecutive patients of the National Comprehensive Cancer Network (NCCN) high-risk, very high-risk and node-positive adenocarcinoma prostate treated with SBRT was undertaken. All patients were treated with rotational intensity-modulated radiotherapy with daily image guidance. The dose delivered to the prostate and gross node was 35-37.5 Gy in 5 alternate day fractions. Node-positive patients received 25 Gy to pelvic nodal regions until the common iliac nodes. Treatment was delivered in 7-10 days. All patients received long-term androgen deprivation therapy (79% medical and 21% surgical). Results: Most patients (65%) had a Gleason score >= 8. The median prostate-specific antigen was 42. Twenty patients were high risk (30%), 11 (16%) very high risk and 37 (54%) node positive. No acute Radiation Therapy Oncology Group grade >= 3 genitourinary or gastrointestinal toxicity was noted. Acute grade 2 genitourinary and gastrointestinal toxicity were 12% and 3%, respectively. Late grade 3 genitourinary and gastrointestinal toxicity was 3% and 0%, respectively. There was no increase in acute or late gastrointestinal toxicity with prophylactic pelvic nodal radiotherapy. Prior transurethral resection of prostate (n = 11) did not increase toxicity. At a median follow-up of 18 months, 97% patients were alive and 94% were biochemically controlled. Conclusion: SBRT is safe in the treatment of high-risk, very high-risk and node-positive prostate cancer, even with prophylactic pelvic radiotherapy or prior transurethral resection of prostate. Longer follow-up is required to determine efficacy.

5. Patient reported outcomes in NRG Oncology RTOG 0938, evaluating two ultrahypofractionated regimens for prostate cancer.

Author(s): Lukka, Himanshu R; Pugh, Stephanie L; Bruner, Deborah W; Bahary, Jean-Paul; Lawton, Colleen A F; Efstathiou, Jason A; Kudchadker, Rajat J; Ponsky, Lee E; Seaward, Samantha A; Dayes, Ian S; Gopaul, Darindra D; Michalski, Jeff M; Delouya, Guila; Kaplan, Irving D; Horwitz, Eric M; Roach, Mack; Pinover, Wayne H; Beyer, David C; Amanie, John O; Sandler, Howard M; Kachnic, Lisa A

Source: International journal of radiation oncology, biology, physics; Jun 2018

Publication Date: Jun 2018

Publication Type(s): Journal Article

Abstract:BACKGROUNDThere is considerable interest in very short (ultrahypofractionated) radiotherapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience and resource allocation benefits.OBJECTIVETo demonstrate that detectable changes in health related quality of life measured by the bowel and urinary domains of the

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Expanded Prostate Cancer Index Composite (EPIC-50) were not substantially worse than baseline.DESIGN, SETTING, AND PARTICIPANTSXXXX is a non-blinded randomized phase II study of NCCN low risk prostate cancer where each arm is compared to a historical control.INTERVENTION(S)Patients were randomized to five fractions (7.25Gy in two weeks), or twelve fractions (4.3Gy in 2.5 weeks).OUTCOME MEASUREMENTS AND STATISTICAL ANALYSISThe co-primary endpoints were the proportion of patients with a change in EPIC bowel score at one year (baseline to one-year) >five points and in EPIC urinary score >two points tested with a one-sample binomial test.RESULTSand Limitations: 127 patients were enrolled to five fractions (121 analyzed) and 128 to twelve fractions (125 analyzed). Median follow-up for all patients at the time of analysis was 3.8 years. The one year frequency for >five point change in bowel score for five and twelve fractions were 29.8%(p<0.001) and 28.4%(ptwo point change in urinary score for five and twelve fractions were 45.7%(p<0.001) and 42.2%(p<0.001) respectively. For five and twelve fractions 32.9% of patients had a drop in 1 year EPIC sexual score ≥ 11 points (p=0.34) while 30.9% of patients had a drop in 1 year EPIC sexual score ≥11 points (p=0.20) in the twelve fraction arm respectively. DFS at two years is 93.3% (95% CI: 88.8, 97.8) and 88.3% (95% CI: 82.5, 94.0) in the five and twelve fraction arms, respectively. There was no late grade 4 or 5 treatment-related urinary or bowel toxicity.CONCLUSIONSThis study confirms that based on changes in bowel and urinary domains and toxicity (acute and late) the five and twelve fractions regimens are well tolerated. These ultrahypofractionated approaches need to be compared to current standard radiotherapy regimens.

6. 18F-FDG-PET/CT guided external beam radiotherapy volumes in inoperable uterine cervical cancer.

Author(s): Adam, Judit A; Arkies, Hester; Hinnen, Karel; Stalpers, Lukas J; van Waesberghe, Jan H; Stoker, Jaap; van Os, Rob; Laan, Janna J; Mom, Constantijne H; van Eck-Smit, Berthe L

Source: The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of...; Jun 2018

Publication Date: Jun 2018

Publication Type(s): Journal Article

Abstract:BACKGROUNDIn patients with advanced stage cancer of the uterine cervix who undergo irradiation with curative intent, there is the necessity to treat all suspicious nodes on imaging. Our hypothesis was that adding PET/CT to the imaging workup would alter the EBRT treatment plan, either resulting in an extended EBRT field to the para-aortal region or an additional boost to suspicious nodes. Since extended field radiotherapy or additional boost can cause toxicity, our secondary aim was to assess the incidence of severe late bowel toxicity in patients treated with extended para-aortal EBRT-field compared to elective pelvic EBRT.METHODSEighty-eight patients were enrolled. First, the optimal radiation treatment plan (EBRT and boost) was retrospectively determined based on MRI or PET/CT. Second, the severe bowel toxicity caused by the extended para-aortal field was assessed, based on the executed radiotherapy.RESULTSBased on MRI 8/88 patients would receive EBRT with para-aortic extension, this was 21/88 for PET/CT. Based on MRI 47/704 lymph node regions would receive additional boost, while based on PET/CT 91/704. Late severe bowel toxicity was seen in 12/84 patients, 6/65 in the group who received elective pelvic irradiation and 6/19 with para-aortal extension. Significant worse overall survival was seen of patients who needed para-aortal EBRT.CONCLUSIONSAddition of PET/CT would lead to an extension of the elective EBRT volume and more suspicious lymph nodes would receive a boost. However, when deciding to irradiate suspicious nodes on imaging, late severe bowel toxicity has to be taken into account.

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7. Adjuvant chemoradiotherapy versus radiotherapy alone in high-risk endometrial cancer: A systematic review and meta-analysis.

Author(s): Yi, Lilan; Zhang, Hongman; Zou, Jingwen; Luo, Peng; Zhang, Jian

Source: Gynecologic oncology; Jun 2018; vol. 149 (no. 3); p. 612-619

Publication Date: Jun 2018

Publication Type(s): Journal Article Review

Abstract:BACKGROUNDThe benefits of adjuvant chemoradiotherapy (CRT) for high-risk endometrial cancer (HREC) in International Federation of Gynecology and Obstetrics (FIGO) stages I-III remain controversial. A systematic review and meta-analysis was conducted to evaluate the clinical effectiveness and safety of postoperative CRT over radiotherapy (RT) alone, exclusively for patients with HREC for the following key endpoints: overall survival (OS), progression-free survival (PFS), the local recurrence rate, the distant metastasis rate, cancer-specific survival (CSS), grade III/IV acute and late toxicities, and the small bowel obstruction rate.METHODSFive databases, namely, PubMed, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov, were systematically explored and supplemented by manual searching to identify relevant studies published before Dec 9, 2017. Only prospective randomized controlled trials (RCTs) conducted for HREC comparing CRT and RT alone after surgery were included. All statistical analyses were performed using RevMan Version 5.3 software.RESULTSSix eligible trials involving 2105 patients were identified for the final meta-analysis (CRT: n = 1064; RT: n = 1041). No statistically significant differences were evident between the CRT and RT groups regarding OS (n = 2105, RR = 1.02, 95% CI 0.98-1.06, P = 0.40). Additionally, no differences were apparent in terms of the local recurrence rate (n = 690, RR = 0.48, 95% CI 0.19-1.18, P = 0.11) or distant metastasis rate (n = 1445, RR = 0.94, 95% CI 0.72-1.23, P = 0.67). However, CRT significantly prolonged overall five-year PFS (80.2% vs. 74.5%, +5.7%; RR = 1.08, P = 0.005) and five-year CSS (86.1% vs. 79.0%, +7.1%; RR = 1.09, P = 0.03). A higher incidence of grade III/IV toxicities (P < 0.00001) was evident with CRT, while grade III/IV late toxicities and the small bowel obstruction rate were not significantly different between the two groups.CONCLUSIONSFor patients with endometrial cancers with stage I-III risk factors, adjuvant CRT can significantly improve PFS and CSS compared with RT. With the exception of increased acute toxicities, CRT is well accepted and tolerated in HREC patients.

8. Hypofractionated simultaneous integrated boost (IMRT-SIB) with pelvic nodal irradiation and concurrent androgen deprivation therapy for high-risk prostate cancer: Results of a prospective phase II trial

Author(s): Magli A.; Urpis M.; Prisco A.; Polsinelli M.; Trovo M.; Moretti E.; Crespi M.; Foti C.; Scalchi P.; Tullio A.; Giannarini G.; De Giorgi G.; Tonetto F.; Bravo G.

Source: Prostate Cancer and Prostatic Diseases; Jun 2018; vol. 21 (no. 2); p. 269-276

Publication Date: Jun 2018

Publication Type(s): Article

Abstract:Objective: The approach for treating high-risk prostate cancer still presents different unresolved issues. We report the safety and efficacy of a radiation therapy strategy based on the combination of moderate hypofractioned simultaneous integrated boost (SIB) and Image Guidance. Materials and methods: In this phase II trial of patients with high-risk prostate cancer, Image Guided SIB-IMRT plans (Simultaneous Intensity Modulated-Intensity Modulated Radiotherapy) were delivered between 2009 and 2012. All patients enrolled (41) received in 25 fractions a total dose of 67.5 Gy (2.7 Gy/fraction) to the prostatic volume, 56.25 Gy (2.25 Gy/fraction) to the seminal vescicles, and 50 Gy (2.0 Gy/fraction) to the pelvic lymph nodes (LN) chains with concurrent

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androgen deprivation therapy (ADT). The image-guided radiotherapy (IGRT) procedure was performed using three gold seeds. RTOG late gastrointestinal and genitourinary toxicities and 6-year biochemical relapse-free survival (BRFS) were assessed in combination of their statistical correlation with clinical factors and dosimetric parameters. Results: Rate of late genitourinary toxicity grade 2 was 9.8%, while rates of late gastrointestinal toxicity were 14.6% and 2.4%, for grade 1 and 2, respectively. Diabetes and maximum doses to rectum appeared to be statistically relevant risk factors for late rectal toxicity. Five-year BRFS was 95.1%. Conclusions: In our study, we observed positive results in terms of toxicity and good efficacy in a cohort of high-risk prostate cancer patients treated with a multimodality therapy approach comprising hypofractionation, irradiation of pelvic nodes (common iliac nodes included), and concurrent ADT. These favorable results may merit further investigation in a phase III randomized trial to confirm that whole pelvic radiation therapy (WPRT) combined with moderate hypofractionation and ADT could be performed safely and effectively.

9. Clinical evaluation of intensity-modulated radiotherapy for locally advanced pancreatic cancer

Author(s): Goto Y.; Nakamura A.; Ashida R.; Sakanaka K.; Itasaka S.; Mizowaki T.; Shibuya K.; Matsumoto S.; Kanai M.; Isoda H.; Masui T.; Takaori K.; Kodama Y.; Hiraoka M.

Source: Radiation Oncology; Jun 2018; vol. 13 (no. 1)

Publication Date: Jun 2018

Publication Type(s): Article

Available at Radiation Oncology - from BioMed Central

Available at Radiation Oncology - from Europe PubMed Central - Open Access

Available at Radiation Oncology - from EBSCO (MEDLINE Complete)

Abstract:Background: The purpose was to retrospectively evaluate the effect of intensity-modulated radiotherapy (IMRT) on gastrointestinal (GI) toxicities and outcomes compared to three-dimensional conformal radiotherapy (3DCRT) for locally advanced pancreatic cancer (LAPC). Methods: We included 107 consecutive patients who underwent CRT for LAPC from September 2001 to March 2015; 80 patients underwent 3DCRT and 27 patients underwent IMRT. They were compared for GI toxicities, locoregional progression free survival (LRPFS), distant metastasis free survival (DMS), and overall survival (OS). Results: Median radiation dose and fractions for 3DCRT and IMRT were 54 Gy/30 fr. and 48 Gy/15 fr. The regimens of CRT consisted of weekly gemcitabine 250 mg/m2 (for 3DCRT) or 1000 mg/m2 (for IMRT). Acute GI toxicity >=grade 2 occurred in 32 patients (40%) treated with 3DCRT compared with five patients (19%) treated with IMRT. Late GI toxicity of grade 3 occurred in 10 patients (12%) treated with 3DCRT and one patient (4%) treated with IMRT. Patients who underwent IMRT had superior 1-year LRPFS (73.1% vs. 63.2%, p = 0.035) and 1-year OS (92.3% vs. 68.2%, p = 0.037) as compared with those treated with 3DCRT. Multivariate analysis showed that in IMRT patients, higher dose (>=45 Gy) was an independent factor for better LRPFS and OS. Conclusions: LAPC patients treated with hypofractionated full-dose gemcitabine IMRT had improved OS and LRPFS without increased GI toxicities when compared to those of patients treated with conventionally fractionated low dose gemcitabine 3DCRT. In IMRT patients, higher dose was an independent favorable prognostic factor for better LRPFS and OS, which suggests that dose escalation with IMRT for LAPC is a promising strategy.

10. Two courses of stereotactic body radiation therapy for pancreatic cancer: Dose accumulation and toxicity

Author(s): Cao Y.; Zhu X.; Yu C.; Sun Y.; Zhang H.; Liu Y.; Qing S.; Li J.

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Source: Medical Physics; Jun 2018; vol. 45 (no. 6)

Publication Date: Jun 2018

Publication Type(s): Conference Abstract

Abstract:Purpose: To assess the accumulated dose of two courses of stereotactic body radiation therapy (SBRT) for pancreatic cancer by deformed registration. Methods: Forty patients received two courses of SBRT for the same region. Due to different doses to target volumes and organs ta risk (OARs) and fractionation schemes, all treatment schedules were recalculated to an Equivalent Dose of 2 Gy per fraction (EQD2). An alpha/beta value of 10 Gy (Gy10) was employed for the tumor dose and acute effects, and the value determined as 3 Gy (Gy3) concerning late effects. The accumulated dose distribution and doses to OARs were calculated using deformed registration with MIM System (version: 6.6.8). A dose reduction of 25% and 50% was allowed for the interval of 6-12 months and more than 12 months, respectively. No dose reduction was permitted when re-irradiation was done within 6 months after the first radiotherapy. Results: The median radiation dose of PTV in the first and second SBRT was 49.58 Gy10 and 41.85 Gy10, respectively. The median accumulated Dmax, D1 and V10 of the stomach, duodenum and the bowel were 36.75 Gy3, 27.87 Gy3 and 66.41 cc; 30.36 Gy3, 22.13 Gy3 and 18.66 cc; 35.76 Gy3, 28.06 Gy3 and 119.48 cc, respectively. The median accumulated Dmaxof the spinal cord was 6.42 Gy3. The median cumulative Dmean and D2/3 of the left and right kidney were 4.62 Gy3 and 3.03 Gy3; 2.67 Gy3 and 2.10 Gy3, respectively. The median cumulative Dmean and D50% of the liver was 4.28 Gy3 and 3.03 Gy3, respectively. No grade 3-4 toxicity occurred. Conclusion: The cumulative doses with MIM software to OARs as dose constraints were acceptable and safe, which could be used as a reference in the treatment planning for re-irradiation with SBRT after prior SBRT for pancreatic cancer.

11. Salvage radiotherapy after radical prostatectomy: Long-term results of urinary incontinence, toxicity and treatment outcomes

Author(s): van Dessel L.F.; Reuvers S.H.M.; Bangma C.H.; Aluwini S.

Source: Clinical and Translational Radiation Oncology; Jun 2018; vol. 11 ; p. 26-32

Publication Date: Jun 2018

Publication Type(s): Article

Abstract:Purpose: For patients with local recurrent disease after radical prostatectomy (35-54%) salvage radiotherapy (SRT) is the treatment of choice. In the post prostatectomy setting, SRT may impose risk at increased toxicity. As data on long-term toxicity, especially on urinary incontinence, are scarce, we report on the long-term treatment outcomes, toxicity and urinary incontinence rates after SRT. Materials and methods: Patients with biochemically recurrent prostate cancer after radical prostatectomy, who were treated with SRT (3D-CRT) at our institution between 1998 and 2012, were included in this retrospective cohort analysis. Primary endpoint was urinary incontinence rate. Secondary endpoints were acute and late grade >=2 genitourinary (GU) and gastrointestinal (GI) toxicity rates, biochemical progression-free survival (bPFS), distant metastasis-free survival (DMFS), disease specific survival (DSS), and overall survival (OS). Results: 244 patients were included. Median follow-up after SRT was 50 months (range: 4-187 months). Before start of SRT 69.7% of patients were continent for urine. After SRT de novo urinary incontinence complaints (grade >= 1) occurred in the respective acute and late phase in 6.1% and 17.6% of patients. Respective acute grade >=2 GU and GI toxicity was 19.2% and 17.6%. Late grade >=2 toxicity for GU was 29.9% and for GI was 21.3%, respectively. The respective 5-year bPFS, OS, DSS and DMFS rates were 47.6%, 91.8%, 98.8% and 80.5%. Conclusions: Experience at our institution with SRT demonstrates that this results in good long-term biochemical control. However, toxicity and urinary incontinence rates were high.

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12. A treatment planning study of prone vs. supine positions for locally advanced rectal carcinoma : Comparison of 3-dimensional conformal radiotherapy, tomotherapy, volumetric modulated arc therapy, and intensity-modulated radiotherapy.

Author(s): Scobioala, Sergiu; Kittel, Christopher; Niermann, Philipp; Wolters, Heidi; Susek, Katharina Helene; Haverkamp, Uwe; Eich, Hans Theodor

Source: Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]; May 2018

Publication Date: May 2018

Publication Type(s): Journal Article

Abstract:PURPOSETo ascertain the optimal radiation technique and radiation position for the neoadjuvant radiotherapy of patients with rectal cancer.MATERIALS AND METHODSTreatment plans with similar dose objectives were generated for 20 selected patients. Dosimetric comparison was performed between prone and supine positions and between different radiation techniques. Dosimetric indices for the target volume and organs at risk (OAR) as well as normal tissue complication probability (NTCP) of late small bowel toxicity were analyzed.RESULTSThe helical tomotherapy (HT) in the prone position provided the optimal dose homogeneity in the target volume with the value of 0. Superior conformity values were obtained for Sliding Window (SW), Rapid Arc (RA) and HT compared to three-dimensional conformal radiotherapy (3D-CRT) techniques. All of the techniques showed dose reduction to OAR in the high-dose area in prone position versus supine position. Pairwise comparison revealed significantly higher small bowel protection by RA in the prone position in the high-dose area (V75, V45Gy). Similarly, superior bladder sparing was found for 3D-CRT in the prone position at higher doses (V50, V75). More healthy tissue in the radiation volume was involved by application of 3D-CRT with no relevant difference between positions. The mean values of NTCP for the small bowel did not show clinically meaningful variation between the techniques.CONCLUSIONAll techniques provided superior sparing of OAR in the prone position. At higher radiation doses, treatment in prone position resulted in significant OAR protection, especially concerning small bowel sparing by RA and bladder sparing by 3D CRT.

13. BioPro-RCMI-1505 trial: multicenter study evaluating the use of a biodegradable balloon for the treatment of intermediate risk prostate cancer by intensity modulated radiotherapy; study protocol.

Author(s): Pasquier, David; Bogart, Emilie; Bonodeau, François; Lacornerie, Thomas; Lartigau, Eric; Latorzeff, Igor

Source: BMC cancer; May 2018; vol. 18 (no. 1); p. 566

Publication Date: May 2018

Publication Type(s): Journal Article

Available at BMC Cancer - from BioMed Central

Available at BMC Cancer - from Europe PubMed Central - Open Access

Available at BMC Cancer - from ProQuest (Hospital Premium Collection) - NHS Version

Available at BMC Cancer - from EBSCO (MEDLINE Complete)

Available at BMC Cancer - from PubMed Central

Abstract:BACKGROUNDProspective trials have demonstrated the advantage of dose-escalated radiotherapy for the biochemical and clinical control of intermediate risk prostate cancer. Dose escalation improves outcomes but increases risks of urinary and bowel toxicity. Recently the contribution of "spacers" positioned in the septum between the rectum and the prostate could

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improve the functional results of intensity modulated radiation therapy (IMRT). To date most of the evaluated devices were polyethylen glycol (PEG) and hyaluronic acid (HA). Men on the Spacer arm had decreased bowel toxicity and less decline in both urinary and bowel quality of life as compared to Control men in a randomized trial.METHODSThis is an interventional, multi-center study to evaluate the use of biodegradable inflatable balloon for patients with intermediate risk prostate cancer treated by IMRT (74 to 80 Gy, 2 Gy/fraction) with daily image guided radiotherapy.DISCUSSIONThis multicenter prospective study will yield new data regarding dosimetric gain and implantation stages of Bioprotect balloon. Acute and late toxicities and quality of life will be registered too.TRIAL REGISTRATIONNCT02478112 , date of registration: 15/06/2015.

14. "Give me five" ultra-hypofractionated radiotherapy for localized prostate cancer: non-invasive ablative approach.

Author(s): Marvaso, Giulia; Riva, Giulia; Ciardo, Delia; Gandini, Sara; Fodor, Cristiana; Zerini, Dario; Colangione, Sarah Pia; Timon, Giorgia; Comi, Stefania; Cambria, Raffaella; Cattani, Federica; De Cobelli, Ottavio; Orecchia, Roberto; Jereczek-Fossa, Barbara A

Source: Medical oncology (Northwood, London, England); May 2018; vol. 35 (no. 6); p. 96

Publication Date: May 2018

Publication Type(s): Journal Article

Abstract:Ultra-hypofractionated radiotherapy (RT) is given over a shorter time with larger doses with respect to conventional fractionation in patients with localized prostate cancer (PCa). The use of hypofractionation is supported both from the radiobiological point of view (the low α/β-ratio in PCa and dose escalation) and from the rising number of clinical evidences. The aim of this study is to review our data regarding oncological outcomes, namely biochemical progression-free survival (b-PFS) and clinical progression-free survival (c-PFS), acute and long-term toxicities in patients treated with a ultra-hypofractionated RT. A series of 194 patients with clinically localized PCa treated primarily with ultra-hypofractionated RT using image-guided intensity modulated RT (IG-IMRT) at our Institute from 2012 to 2015 was included in this analysis. According to NCCN risk group classification, 65 (33.5%) patients were low risk, 101 (52.1%) intermediate risk, and 28 (14.4%) high risk. Androgen deprivation therapy (ADT) was given to 61 patients (31.4%). A 169 patients (87.1%) received 35 Gy in 5 fractions, while 25 patients (13%) received 32.5 Gy in 5 fractions (usually given in patients with comorbidity). The median duration of the treatment was 10 days (IQR 9-12). Biochemical relapse was defined as a rise of prostate specific antigen (PSA) > 2 ng/ml above nadir. b-PFS, c-PFS, and freedom from gastro-intestinal (GI) and genito-urinary (GU) toxicity curves were calculated by the Kaplan-Meier method. Log-rank test and multivariate Cox models were used to investigate the role RT dose and heterogeneity by NCCN risk groups adjusting for prognostic factors. Data on acute and late term toxicities were collected according to RTOG/EORTC grading system. With a median follow-up of 30 months, 17 patients experienced PSA failure (9%). The 3-year b-PFS was 87% for all patients and rates stratified for the NCCN risk were 94, 82, and 66% for low-, intermediate-, and high-risk groups, respectively. Log-rank tests indicate that biochemical progression was significantly greater for patients with initial PSA (iPSA) greater than 7 ng/ml (P = 0.04), high- and intermediate-risk groups (P = 0.002), low total dose (P = 0.02) and Gleason score (GS) equal or greater than 7 (P = 0.04). No statistically significant association was found with T stage nor ADT. In multivariate analyses, total dose (P = 0.03) and risk groups (P = 0.03) remained significantly associated with recurrence. Acute and late GI and GU toxicity were acceptable. The toxicity of ultra-hypofractionated IG-IMRT in a large clinical cohort of PCa patients was tolerable and confirmed that this treatment is safe and offers excellent tumor control. Moreover, the hypofractionated RT allows to deliver the whole RT over 10 days with a sensible impact in patients' quality of life and potential overall health system and social benefits.

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15. Absorbable Hydrogel Spacer Use in Prostate Radiotherapy: A Comprehensive Review of Phase 3 Clinical Trial Published Data.

Author(s): Karsh, Lawrence I; Gross, Eric T; Pieczonka, Christopher M; Aliotta, Philip J; Skomra, Christopher J; Ponsky, Lee E; Nieh, Peter T; Han, Misop; Hamstra, Daniel A; Shore, Neal D

Source: Urology; May 2018; vol. 115 ; p. 39-44

Publication Date: May 2018

Publication Type(s): Journal Article

Abstract:OBJECTIVETo provide an update on SpaceOAR System, a Food and Drug Administration-approved hydrogel indicated to create distance between the prostate and the rectum which has been studied in phase 2 and 3 clinical trials. Here, we review and summarize these clinical results including the safety of prostate-rectum spacer application technique, the implant quality and resulting rectal dose reduction, acute and long-term rectal, urinary, and sexual toxicity, as well as patient-reported outcomes.MATERIALS AND METHODSA prospective, randomized patient-blinded clinical study was performed comparing image-guided intensity modulated prostate radiotherapy (79.2 Gy in 44 fractions) in men with or without prostate-rectum hydrogel spacer. Patients were followed up for 3 years, allowing assessment of long-term safety and efficacy.RESULTSSpacer application was well tolerated with a 99% technical success rate. The mean additional space created between the prostate and the rectum was just over 1 cm, which allowed significant rectum and penile bulb radiation dose reduction, resulting in less acute pain, lower rates of late rectal toxicity, and improved bowel and urinary quality of life (QOL) scores from 6 months onward. Improvements in sexual QOL were also observed at 37 months in baseline-potent men, with 37.5% of control and 66.7% of spacer men capable of "erections sufficient for intercourse."CONCLUSIONProstate-rectum hydrogel spacer application is a relatively safe technical procedure that is well tolerated and has a high technical success rate. Spacer application significantly reduces rectal radiation dose and results in long-term reductions in rectal toxicity, as well as improvements in bowel, urinary, and sexual QOL.

16. Bowel radiation injury: Promises of cell and tissue engineering

Author(s): Mathieu N.; Moussa L.; Demarquay C.; Durand C.; Squiban C.; Linard C.; Semont A.; Chapel A.

Source: Cytotherapy; May 2018; vol. 20 (no. 5)

Publication Date: May 2018

Publication Type(s): Conference Abstract

Abstract:Bowel radiation injury is an insidious disease associated with substantial morbidity and mortality. Moreover, it's an increasing problem as more patients receive radiotherapy and survive longer after their tumor treatment. Bowel radiation injury results from the treatment of several cancers by radiotherapy in which normal colorectal tissues are present in the irradiation field. The clinical expression of bowel complications associated to radiotherapy resembles chronic bowel disease of other etiologies. However, recent studies have identified differences and specialists have proposed that complications following pelvic radiotherapy should be recognized as a 'new disease' by Andreyev et al. The growing number of cases declared every year highlights the importance of understanding the mechanisms involved and of finding effective therapies. There is no unified approach for the assessment and treatment of this disease partly due to insufficient knowledge about the mechanism involved in the development of bowel radiation injury. However, unresolved inflammation is hypothesized to have an important role in late side effects. We used an experimental model of radiation proctitis developed in rats that reproduces severe colonic mucosal damages and fibrosis similar to those observed in patients treated by radiotherapy (Semont, 2010).

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We evaluated the benefit of immunomodulatory mesenchymal stromal cells isolated from adipose tissue (Ad-MSC) to reduce late side effects (Bessout, 2013-15 and Durand, 2015). We demonstrated a therapeutic benefit on different crucial functions of the colon and determined pleiotropic action mechanisms of the cell therapy treatment. Since, MSC therapy has been proposed to 4 patients over-irradiated during their radiotherapy treatment leading to substantial improvement in the clinical response (Voswinkel, 2013). Our pre-clinical studies also identified targets to potentiate the therapeutic effect of Ad-MSC. We have thus highlighted a biomaterial-assisted MSC therapy to alleviate colonic radiation-induced damage (Moussa, 2017). Moreover, we also tested a new treatment procedure to optimize the paracrine effect of MSC. Our studies provide evidence for the potential of Ad-MSC to limit radiation effects on the colon and could open new perspectives in the optimization of the treatment using tissue engineering and its use in other colonic inflammatory diseases.

17. Postoperative hypofractionated radiotherapy for prostate cancer

Author(s): Tramacere F.; Pignatelli A.; Vinella M.; Portaluri M.; Arcangeli S.; Bracci S.

Source: Anticancer Research; May 2018; vol. 38 (no. 5); p. 2951-2956

Publication Date: May 2018

Publication Type(s): Article

Abstract:Aim: To retrospectively investigate outcomes, and acute and late complications following postoperative hypofractionated 3D conformal radiotherapy. Patients and Methods: Sixty-nine consecutive patients underwent radical prostatectomy. Radiotherapy was delivered to the prostatic fossa by means of a7-fieldLINACwith 6-15 MV to a total dose of 62.5 Gy in 25 fractions (2.5 Gy per fraction) in five consecutive weeks. Results: Median follow-up was 54.7 months (range=38-76 months). Five-year overall survival, metastasis-free survival and biochemical relapse-free survival were 91.1%, 84.6% and 66.7%, respectively. Grade 2 or more genitourinary and gastrointestinal acute toxicity was reported in 12% and 5% of patients, respectively. Urinary incontinence grade 2 or more was recorded in 19%. Conclusion: Postoperative radiotherapy either in the adjuvant or salvage setting resulted in acceptable rates of acute and late toxicity with good tumor control while reducing overall treatment time. Confirmatory results from an ongoing prospective trial are awaited.

18. Are endometrial cancer radiotherapy results age related?

Author(s): Rovirosa, Á; Cortés, K S; Ascaso, C; Glickman, A; Valdés, S; Herreros, A; Camacho, C; Sánchez, J; Zhang, Y; Li, Y; Sabater, S; Arenas, M; Torne, A

Source: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico; Apr 2018

Publication Date: Apr 2018

Publication Type(s): Journal Article

Abstract:OBJECTIVETo analyze the impact of age on radiotherapy results based on cancer-specific survival (CSS), vaginal-cuff relapses (VCR) and complications analysis in 438 patients with endometrial carcinoma (EC) receiving postoperative radiotherapy (PRT) divided into three age groups for analysis.MATERIALS AND METHODSFrom 2003 to 2015, 438 patients with EC were treated with PRT and divided into three age groups: Group-1: 202 patients < 65 years; Group-2: 210 patients ≥ 65 and < 80 years; Group-3: 26 patients ≥ 80 years. Vaginal toxicity was assessed using the objective LENT-SOMA criteria and RTOG scores were recorded for the rectum, bladder, and small bowel.STATISTICSChi square and Student's t tests, Kaplan-Meier survival study for analysis of CSS.RESULTSThe mean follow-up was 5.6 years in Group-1, 5.6 years in Group-2 and 6.3 years in

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Group-3 (p = 0.38). No differences were found among the groups in distribution of stage, grade, myometrial invasion, Type 1 vs. 2 EC and VLSI (p = 0.97, p = 0.52, p = 0.35, p = 0.48, p = 0.76, respectively). There were no differences in rectal, bladder and vagina late toxicity (p = 0.46, p = 0.17, p = 0.75, respectively). A better CSS at 5 years was found in Group-1 (p = 0.006), and significant differences were found in late severe small bowel toxicity in Group-3 (p = 0.005). VCR was increased in Group-3 (p = 0.017).CONCLUSIONSPatients ≥ 65 years had a worse outcome in comparison to younger patients. Late vaginal, rectal and bladder toxicities were similar in the three groups, although an increase of severe late small bowel toxicity led to IMRT in patients ≥ 80 years. Further larger studies are needed including quality of life analysis in patients ≥ 80 years.

19. Assessment of bowel and anal sphincter function after neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

Author(s): Rosa, Consuelo; Di Tommaso, Monica; Caravatta, Luciana; Vinciguerra, Annamaria; Augurio, Antonietta; Perrotti, Francesca; Allajbej, Albina; Regoli, Marco; Zecca, Isaia Al; Di Nicola, Marta; Genovesi, Domenico

Source: Tumori; Apr 2018 ; p. 300891618765580

Publication Date: Apr 2018

Publication Type(s): Journal Article

Abstract:PURPOSETo report long-term effects on anorectal function and bowel disorders and late toxicity rate of preoperative chemoradiotherapy in patients with locally advanced rectal cancer.METHODSBetween 2000 and 2016, 201 patients treated with different neoadjuvant schedules of chemotherapy and radiotherapy doses were retrospectively analyzed. The Memorial Sloan-Kettering Cancer Center score was used for the evaluation of anal sphincter function.RESULTSThe median follow-up time was 68 months (interquartile range 35-113 months). Radical resection was performed in 188 (93.5%) patients with a pathologic complete response rate of 26.4%. Overall sphincter function resulted excellent in 105 (52.2%) patients, good in 13 (6.5%), fair in 10 (5.0%), and poor (incontinence) in 40 (19.9%), with a persistent stoma rate of 16.4%. A further evaluation on 194 patients showed an improvement of sphincter function after 2 years in 11.9% of them. Seventy-three patients presenting stoma or poor sphincter function were re-evaluated for quality of life (QoL) indexes. Twenty-one (29%), 19 (26%), and 24 (33%) of them declared some variations concerning well-being, fatigue, and ability to perform daily activities. The 5-year overall survival, disease-free survival, and local recurrence rates were 88.0% ± 2.6%, 86.3% ± 2.5%, and 94.6% ± 1.9%, respectively.CONCLUSIONSIn our study, neoadjuvant chemoradiotherapy was associated with good results in terms of sphincter function, late toxicities, and QoL indexes. A routine use of assessment scales could contribute to a better selection of patients with increased risk of developing functional disorders who could benefit from neoadjuvant therapy.

20. The Efficacy and Safety of Conventional and Hypofractionated High-Dose Radiation Therapy for Prostate Cancer in an Elderly Population: A Subgroup Analysis of the CHHiP Trial.

Author(s): Wilson, James M; Dearnaley, David P; Syndikus, Isabel; Khoo, Vincent; Birtle, Alison; Bloomfield, David; Choudhury, Ananya; Graham, John; Ferguson, Catherine; Malik, Zafar; Money-Kyrle, Julian; O'Sullivan, Joe M; Panades, Miguel; Parker, Chris; Rimmer, Yvonne; Scrase, Christopher; Staffurth, John; Stockdale, Andrew; Cruickshank, Clare; Griffin, Clare; Hall, Emma; CHHiP Investigators

Source: International journal of radiation oncology, biology, physics; Apr 2018; vol. 100 (no. 5); p. 1179-1189

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Publication Date: Apr 2018

Publication Type(s): Journal Article

Abstract:PURPOSEOutcome data on radiation therapy for prostate cancer in an elderly population are sparse. The CHHiP (Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer) trial provides a large, prospectively collected, contemporary dataset in which to explore outcomes by age.METHODS AND MATERIALSCHHiP participants received 3 to 6 months of androgen deprivation therapy and were randomly assigned (1:1:1) to receive 74 Gy in 37 fractions (conventional fractionation), 60 Gy in 20 fractions, or 57 Gy in 19 fractions. Toxicity was assessed using clinician-reported outcome (CRO) and patient-reported outcome questionnaires. Participants were categorized as aged < 75 years or ≥ 75 years. Outcomes were compared by age group.RESULTSOf 3216 patients, 491 (15%) were aged ≥ 75 years. There was no difference in biochemical or clinical failure rates between the groups aged < 75 years and ≥ 75 years for any of the fractionation schedules. In the group aged ≥ 75 years, biochemical or clinical failure-free rates favored hypofractionation, and at 5 years, they were 84.7% for 74 Gy, 91% for 60 Gy, and 87.7% for 57 Gy. The incidence of CRO (grade 3) acute bowel toxicity was 2% in both age groups. The incidence of grade 3 acute bladder toxicity was 8% in patients aged < 75 years and 7% in those aged ≥ 75 years. The 5-year cumulative incidence of CRO grade ≥ 2 late bowel side effects was similar in both age groups. However, in the group aged ≥ 75 years, there was a suggestion of a higher cumulative incidence of bowel bother (small or greater) with 60 Gy compared with 74 Gy and 57 Gy. Patient-reported bladder bother was slightly higher in the group aged ≥ 75 years than the group aged < 75 years, and there was a suggestion of a lower cumulative incidence of bladder bother with 57 Gy compared with 74 Gy and 60 Gy in patients aged ≥ 75 years, which was not evident in those aged < 75 years.CONCLUSIONSHypofractionated radiation therapy appears to be well tolerated and effective in men aged ≥ 75 years. The 57-Gy schedule has potential advantages in that it may moderate long-term side effects without compromising treatment efficacy in this group.

21. Acute toxicity of the bowel after stereotactic robotic radiotherapy for abdominopelvic oligometastases.

Author(s): Frelinghuysen, Michael; Schillemans, Wilco; Hol, Lieke; Verhoef, Cornelis; Hoogeman, Mischa; Nuyttens, Joost Jan

Source: Acta oncologica (Stockholm, Sweden); Apr 2018; vol. 57 (no. 4); p. 480-484

Publication Date: Apr 2018

Publication Type(s): Journal Article

Abstract:AIMTo correlate dose-volume histogram (DVH) parameters with appearance of grade ≥2 acute and late gastrointestinal toxicity of stereotactic body radiotherapy (SBRT) in patients with abdominopelvic solitary or oligometastatic disease outside the liver.MATERIAL AND METHODSAcute and late bowel toxicity of 84 abdominopelvic oligometastatic patients was registered. A logistic regression was performed between different DVH parameters and presence of grade ≥2 acute and late toxicity. A Normal Tissue Complication Probability (NTCP) model was built with significant parameters to determine complication probabilities (CP).RESULTSThirteen (15%) of 84 patients experienced of grade ≥2 acute toxicity, while 8 (10%) reported late toxicity complications. A significant relationship was found for EQD2 (V30Gy, V40Gy, V50Gy and V65Gy) and grade ≥2 acute toxicity. Dmax and D2 were not significant. Late grade ≥2 toxicity was not significantly correlated with any DVH parameter. According to our NTCP model for V40Gy, an irradiated bowel volume of 10 cm3 of V40Gy resulted in CP of grade ≥2 acute toxicity of less than 10%. Local control was 87% at 2 years and 82% at 5 years. Overall survival was 61% at 2 years and 32% at 5 years.CONCLUSIONSAfter SBRT for abdominopelvic oligometastases, in general, the presence of

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acute and late toxicity was low. A significant relationship was found for V30Gy, V40Gy, V50Gy and V65Gy and grade ≥2 acute toxicity. We estimated acute complication probabilities per volume of irradiated bowel by V40Gy and V50Gy.

22. Low-risk prostate cancer patients treated with hypofractionated radiation therapy: Long term outcomes, toxicity and sexual function

Author(s): Marinelli L.; Reverberi C.; Osti M.F.; De Sanctis V.; Tronnolone L.; Giuliani M.; Valeriani M.

Source: Anticancer Research; Apr 2018; vol. 38 (no. 4); p. 2515

Publication Date: Apr 2018

Publication Type(s): Conference Abstract

Abstract:Aim: To assess efficacy and toxicity rates in low-risk prostate cancer patients scheduled for image-guided hypofractionated radiotherapy (HFRT). Patients and Methods: Ninety low-risk prostate cancer patients [Gleason score <=6, prostate-specific antigen (PSA)<=10 ng/ml, clinical stage T1/T2a-b N0 M0 assessed with multiparametric contrast-enhanced MRI] were treated with HFRT from March 2007 to February 2017. Clinical target volume (CTV) encompassed prostate with proximal seminal vescicles, and adding 5 mm margin in all directions from CTV to create planning target volume (PTV). Treatment schedule was delivered with imageguided RT 3D-conformal RT, for a total dose of 60 Gy in 20 fractions (5 fractions/week) to PTV, daily cone beam computed tomography was performed. Acute and late toxicities were evaluated according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring scale. Results: Ranging from 8 to 129, median follow up reached 66 months. The actuarial 8-year overall survival (OS) was 97.3% (median not reached). Eight-year biochemical relapse free survival (BRFS) was 98.9%, with no clinical local recurrence. Median PSA at diagnosis was 3.25 ng/ml (range=1.71- 9.98) and at the last follow-up was 0.39 ng/ml (range=0.02-2.11). Acute mild to moderate toxicities were: grade 1-2 gastrointestinal (GI) toxicity occurred in 14 patients (15.5%), grade 1-2 genitourinary (GU) toxicity in 35 cases (38.9%), meanwhile grade 3 GU toxicity occurred in only 2 patients (2.2%). Sexual function was scored as: absence (A), presence of erection but insufficient (I) or sufficient (S) for intercourse. Before RT, 4.4 % had A, 44.4% had I and 51.1% had S. After RT, 36.7% of patients presented A, 45.6% I, and 17.8% S (chi square p=0.011). Patients under 70 years presented A in 16.7% of cases, I in 60%, and S in 23.3%. In patients over 70 years, 46.7% presented A, 38.3% I and 15.0% S (chi square p=0.021). Conclusion: HFRT is a safe and well-tolerated treatment option in low-risk prostate cancer. Despite that overall sexual function significantly worsened, age might be a predictive factor to maintain any form of sexual function after therapy.

23. Evaluation of outcomes after stereotactic hypofractionated radiotherapy for prostate cancer

Author(s): Beltramo G.; Zanetti I.B.; Bergantin A.; Martinotti A.S.; Redaelli I.; Bonfanti P.; Bresolin A.; Bianchi L.C.; Longo G.; Maggioni M.; Dormia G.; Locatelli C.

Source: Anticancer Research; Apr 2018; vol. 38 (no. 4); p. 2492-2493

Publication Date: Apr 2018

Publication Type(s): Conference Abstract

Abstract:Background/Aim: In accordance with the new radiobiological knowledge concerning prostate cancer, several randomized trials support the use of high doses of radiation. Hypofractionated stereotactic radiotherapy schedules are now proposed as a suitable approach in patients with localized prostate cancer. We retrospectively report collected data from a cohort of localized prostate cancer patients treated with Cyberknife (CK) Stereotactic Body Radiotherapy

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Treatment (SBRT) in our Center. Patients and Methods: From July 2007 to 2016, a retrospective analysis was carried out on 217 consecutive patients with a median age of 75 years (range=52-86), median prostate volume of 75.6 cc (range=37.03-163.16), and clinically localized prostate cancer. Cyberknife was used to deliver fiducial-based imageguided hypofractionated SBRT. The majority of patients 116 (53%) were low-risk, 60 patients (28%) were intermediaterisk, and 41 patients (19%) were high-risk (according to the National Comprehensive Cancer Network criteria). Pretreatment prostate-specific antigen (PSA) ranged from 1.51 to 51 ng/ml (median=8.51 ng/ml). Seventeen (41%) of 41 high-risk patients received androgen deprivation therapy (ADT), that was not administered to any low-/intermediaterisk patient. Computed tomography and magnetic resonance imaging were used for treatment planning in all patients. The course of radiotherapy consisted of 38 Gy over 4 fractions (9.5 Gy/fraction) given daily to the planning target volume (PTV), which was defined as the clinical target volume (CTV) on prostate (plus at least 1 cm extension in seminal vesicles in intermediate- and high-risk patients) expanded 3 mm in all directions, except posteriorly (2 mm). Heterogeneous dose planning was used; dose was normalized to the 75% isodose line in order for the prescription dose to cover at least 95% of PTV. Real-time intrafractional motion tracking was used. Radiation therapy oncology group (RTOG) toxicity grades were assigned for genitourinary and gastrointestinal symptoms. Results: With a median follow-up of 61 months (range=12-120), the 6-year actuarial PSA relapse-free survival rate was 94.4% (confidence interval=90.8%-98.2%) with 98.2% for low-risk, 94.5% for intermediate-risk, and 85.6% for high-risk. In total 23 (10.5%) patients died during the follow-up for unrelated causes, only one (0.5%) died for prostate cancer with bone metastases. The patterns of PSA response showed a gradual decline with a PSA nadir below 1.0 ng/ml, 12 months after the radiation treatment. The majority of patients did not report any early genitourinary (53.5%) or gastrointestinal (79.3%) toxicities. Limited acute urinary symptoms (frequency, dysuria, urgency, hesitancy, and a nocturia) were common: 46.5% of patients reported grade I or II toxicity, no one experienced grade III or worse symptoms. Moreover, 20.3% of patients reported grade I or II acute gastrointestinal symptoms, such as diarrhea, constipation, and proctitis, while only one patient experienced a grade III acute proctitis. Grade IV rectal toxicity was not observed. Regarding late toxicity, 78.3% of patients experienced grade 0 genitourinary toxicity, 18% experienced grade I or II symptoms, while 3% reported grade III toxicity (most of them after repeated urologic instrumentation, in two patients, urethral dilatation was required for bulbar urethral stricture). In one patient (0.5%) a grade IV bladder fistula was observed. The median time from CK course of radiotherapy completion to the occurrence of late grade III-IV genitourinary toxicity was 29 months (range=18-45). The majority of patients (95%) did not experienced late gastrointestinal toxicity, only Grade I or II symptoms were observed in 10 patients (4.6%), while grade III or higher was not reported. Discussion and Conclusion: Our preliminary data confirm that Cyberknife SBRT represents a non invasive method for the definitive treatment of localized prostate cancer with results not inferior to standard fractionated radiotherapy in terms of biochemical control rates at up to 6 years and early and late toxicities. Long-term follow-up is needed in order to evaluate the maintenance of biochemical and clinical outcomes and late toxicity results.

24. Hypofractionated stereotactic radiotherapy with cyberknifer system in localized prostate cancer: A monoistitutional experience

Author(s): Borzillo V.; Di Franco R.; Totaro G.; Ametrano G.; Cammarota F.; Muto P.; Quarto G.; Sorrentino D.; Perdona S.

Source: Anticancer Research; Apr 2018; vol. 38 (no. 4); p. 2549-2551

Publication Date: Apr 2018

Publication Type(s): Conference Abstract

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Abstract:Background/Aim: Hypofractionated Stereotactic radiotherapy (HySRT), that delivers higher dose on the target tissue in small number (<=5) of fractions with low dose to adjacent organs- at-risk, is increasingly used in the treatment of localized prostate cancer (LPC), given the favorable radiobiological profile of prostate cancer (PCa) at high radiation doses (1, 2, 3). In this study we reported our initial experience with HySRT using CyberKnifeR System (CK) in the treatment of LPC. Patients and Methods: From February 2013 to October 2017, 123 patients with LPC, median age 72 years, were treated with CK-HySRT. Ten days before the HySRT, all patients were submitted to the eco-guided implants of 4 gold intraprostatic fiducial markers to allow CK to track, detect and correct target movements during the radiotherapy session. All patients underwent a simul-CT and MRI, and contouring was performed on image fusion. All patients were treated with CK HySRT in 5 fractions of 7-7.25 Gy/fraction for a total dose of 35-36,25 Gy. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated using RTOG scale, biochemical control using mean decrease of PSA level during follow-up. In this study, we have analyzed the results in the 102 patients with almost 3 months of follow-up. Results: Overall, 102/123 patients that had almost 3 months of follow-up and were analyzed. Patients and tumor characteristics are shown in Table I. Median follow-up was 17 months. Three patients died of nonrelated cancer causes. Gastrointestinal acute toxicity was 23% and 13% for G1 and G2 (perineal pain and rectal tenesmus), respectively (Figure 2). Genitourinary acute toxicity was 55% for G1 (dysuria) and 23% for G2 (urgency and nocturia) (Figure 2). G2 Genitourinary late toxicity was 4% (Figure 4) and G2 Gastrointestinal late toxicity (Figure 3) was 3%. All patients responded with decreased levels of PSA (Figure 1). The PSA drop between the start of the therapy and 21 months of follow-up, was significant with p<0.01 (p=0.00001). Conclusion: HySRT is an effective and safe treatment option for patients with LPC. The results of multiple prospective trials have shown biochemical control rates of 90%-100% for low-risk and 84%-100% for intermediate-risk PCa, and the average incidence of grade G3, GI or GU toxicity ranges between 0.17%-0.28% and 0.61%-1.61% for acute and late effects, respectively. In our experience CK-HySRT seems to be safe and reliable in the treatment of LPC. No severe toxicities were reported and the patients were very compliant. Careful patient selection is critical to achieve maximum effectiveness by CK HySRT. More patients and longer follow-up are necessary in order to evaluate the real advantage of HySRT with respect to standard fractionation in terms of overall survival, biochemical free survival and late toxicity (Table presented).

25. New technologies in radiotherapy for prostate cancer: Feasibility, dosimetric aspects and clinical results in patients with at least 5-year follow-up

Author(s): Sicilia A.; Trodella L.E.; D'Angelillo R.M.; Fiore M.; Lurato A.; Carnevale A.; Greco C.; Miele M.; Trecca P.; Trodella L.; Ramella S.

Source: Anticancer Research; Apr 2018; vol. 38 (no. 4); p. 2478

Publication Date: Apr 2018

Publication Type(s): Conference Abstract

Abstract:Background/Aim: Radiotherapy (RT) for prostate cancer has been constantly evolving over the last few decades, improving overall survival, cancer-specific and time progression of the disease. Different studies have shown a strong association between survival and RT doses (>=76 Gy). Advanced RT techniques such as modulated intensity (IMRT) and modulated intensity dynamic volumetric therapy (VMAT) facilitate and allow higher doses, minimizing the side effects on healthy surrounding tissues. Patients and Methods: A total of 261 prostate cancer patients referred to our institution for radical treatment, from January 2010 to December 2014, have been reviewed. Dosimetric comparison between IMRT and VMAT was made to evaluate the constraints (dose limits) for the organs at risk (OARs) in the district: the rectum, the bladder, the femoral heads, and the penile bulb. In addition, toxicity was assessed (according to CTCAE version 4.02 scale),

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progressionfree survival (PFS) and overall survival (OS). Progression disease has been evaluated from a clinical point of view, through laboratory and radiological examinations. Results: Patients (49 at low-risk, 101 at intermediate-risk, and 111 at high-risk) were treated with radical RT for a total dose of 80 Gy (the pelvis was included in the volume of treatment in 57 patients). Of those, 208 were treated with IMRT technique and 53 with VMAT technique. Average age of patients was 72 years (range=42-86 years). Median PSA was 7.47 ng/ml and the minimum follow-up was 30 months. Dosimetric data showed that VMAT technique achieved better compliance with constraints for OARs, reducing the percentage of patients that deviated from dose limits. No patient exhibited Grade 2 Gastrointestinal (GI) and Genitourinary (GU) toxicity. G2 GI and G2 GU toxicity was reported in 13.5% and 5.7% of patients, respectively, at 5 years. PFS at 5 years was 82% for low- and intermediate- risk patients and 81% for high-risk patients. At 5 years, OS of the entire cohort was 93.2%. OS of the population by risk class stratification, at 5 years, can be summarized as follows: at 100% low-risk; in the intermediaterisk of 90% and in the high-risk of 93%. Conclusion: Reviewing our patients with at least 5-year follow-up, low acute and late toxicity was observed. This evidence could support the adoption of further dose escalation mainly in high-risk patients.

26. "give me five" ultra hypofractionated radiotherapy (RT) for localized prostate cancer (PCA): Safety without losing efficacy

Author(s): Marvaso G.; Riva G.; Ciardo D.; Fodor C.; Zerini D.; Gandini S.; Comi S.; Cattani F.; De Cobelli O.; Orecchia R.; Jereczek-Fossa B.A.

Source: Anticancer Research; Apr 2018; vol. 38 (no. 4); p. 2527-2528

Publication Date: Apr 2018

Publication Type(s): Conference Abstract

Abstract:Background/Aim: Ultra-hypofractionated radiotherapy (RT) is given over a shorter time with larger doses per treatment in patients with localized prostate cancer (PCa). The use of hypofractionation is supported both from the radiobiological point of view (the low a/b-ratio in PCa and dose escalation) and from the rising number of clinical evidences. The aim of this study was to review our data regarding oncological outcomes (biochemical progression-free survival and progression-free survival), acute and long-term toxicities in patients treated with a short course of RT (ultrahypofractionation). Patients and Methods: A series of 194 patients with clinically localized PCa treated primarily with ultra-hypofractionated RT using image-guided intensitymodulated radiation therapy (IG-IMRT), in our Institute from 2012 to 2015, were included in this analysis. Patients according to NCCN risk group classification were low-risk 65 (33.5 %), intermediate-risk 101 (52.1%), and high-risk 25 (14.4%). Androgen deprivation therapy (ADT) was given to 81 patients (41.7 %). A total of 169 patients (87%) received a dose of 35 Gy in 5 fractions, while for 25 patients (13%) the dose level was 32.25 Gy. The median duration of the treatment was 10 days [interquartile range (IQR)=9-12]. Biochemical relapse free survival (b-PFS) was defined as a rise of prostatespecific antigen (PSA) >2 ng/ml above nadir. b-PFS as well as clinical progression free survival, freedom from gastrointestinal (GI) toxicity and from genitourinary (GU) toxicity curves were calculated by the Kaplan-Meier method. Log-rank test and multivariate Cox models were used to investigate the role of RT dose and heterogeneity in NCCN risk groups adjusting for prognostic factors. Data on acuteand late-term toxicities were collected according to RTOG/EORTC grading system. Results: With a median follow-up of 30 months (2.5 years), there were 17 patients who experienced PSA failure (9%). The 3-year biochemical free survival rate was 87% for all patients, rates stratified for the NCCN risk were: 94%, 82% and 66% for low-, median-, and high-risk groups, respectively. Log-rank tests indicated that biochemical progression was significantly greater for patients with initial PSA (iPSA) >7 ng/ml (p=0.04), high- and intermediate- risk groups (p=0.002), low total dose (p=0.02) and Gleason score (GS) >=7 (p=0.04). No significant association was found with T stage or ADT. In multivariate analyses

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total dose (p=0.03) and risk groups (p=0.03) remained significantly associated with recurrence. Acute and late GI and GU toxicity were acceptable. Conclusion: The toxicity of ultra-hypofractionated IG-IMRT in a large clinical cohort of PCa patients were tolerable and confirmed that this treatment is safe and offers excellent tumor control. Moreover, the hypofractionated RT allows to deliver the whole RT over 10 days with a sensible impact in patients' quality of life and potential overall health system and social benefits.

27. Moderate hypofractionated postprostatectomy volumetric arc therapy with image guidance (VMAT-IGRT): Feasibility and acute toxicity

Author(s): Villa E.; Motta M.; Ravasio A.; Gualano R.; Vavassori V.; Cirelli S.; Marai G.

Source: Anticancer Research; Apr 2018; vol. 38 (no. 4); p. 2544-2545

Publication Date: Apr 2018

Publication Type(s): Conference Abstract

Abstract:Background/Aim: Moderate hypofractionation may have a role in a post-prostatectomy setting, allowing reduction of treatment time and improving local control, but the risk of toxicity may be increased. The aim of this analysis was to evaluate acute toxicity in patients with prostate cancer (PC) who underwent radical prostatectomy and treated with hypofractionated regimen and volumetric modulated arc therapy (VMAT). Materials and Methods: From March 2011 to September 2017, 131 patients who underwent radical prostatectomy, received hypofractionated radiotherapy; 89 were treated in an adjuvant setting, because of the presence of at least one histopathological risk factor (Gleason score >7, positive surgical margins, seminal vesicle invasion, extracapsular invasion) and 39 with salvage intent at biochemical relapse (PSA>0.2 ng/ml), or in 3 cases for a clinical relapse. The median age was 67 years old, all the patients had an ECOG performance status of 0 to 2. Seventyfive patients were treated only on prostate bed whereas 56 were treated also on lymph node areas. Eighty-six patients underwent hormonal treatment. Patients were treated with VMAT (RapidArc) and Simultaneous Integrated Boost (SIB) in 30 fractions for a total dose of 66 or 67.5 Gy to the tumor bed (2.2-2.25 Gy/fraction), and 54 Gy to the lymph node volume (1.8 Gy/fraction), respectively. Genitourinary and gastrointestinal toxicities were scored according to CTCAE version 3.0. Urinary symptoms were evaluated also with IPSS questionnaire at baseline and at the end of radiotherapy in 113 patients. Results: All the patients completed the planned treatment. Acute gastrointestinal and rectal toxicity was mild with G2 as a maximum grade in 9 patients (6.9%), and none G3. The maximum acute genitourinary toxicity was G3 in 7 patients (5.3%), of whom 5 patients were treated in adjuvant and 2 in salvage setting. G2 acute genitourinary toxicity was observed in 40 patients (30.5%). Analyzing each G3 symptom, we recorded urinary frequency in 2 patients (1.5%), urinary incontinence in 1 patient (0.7%) and nocturia in 6 patients (4.6%) (Figure 1). Maximum grade of dysuria and spasm was G2 in 2 patients (1.5%). No hematuria or stenosis greater than G1 were observed. We also evaluated IPSS score pre- and post-RT in 113 patients and calculated DELTA (delta). Mean variation was DELTA=6 points (range=[-10]-[+18]). In 18 patients we didn't record any variation between baseline and the end of treatment; 36 patients had an improvement of IPSS score (7 with DELTA>5 points - 6.2%) while 59 had an IPSS deterioration (10 with DELTA>5 points- 8.8%). Conclusion: According to our results, moderate postoperative hypofractionated RT (2.2-2.25 Gy/fraction) seems to be feasible and safe, with a good acute toxicity profile, without unacceptable detrimental effects. Longer follow-up is needed to assess late toxicity and clinical outcomes (Table presented).

28. Functional and psychological comparative and prospective analysis of patients with prostate cancer submitted to radical prostatectomy, external radiotherapy or active surveillance

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Author(s): Maggi M.; Sciarra A.; Gentilucci A.; Salciccia S.; Gentile V.; Musio D.; Tombolini V.; Guandalini A.

Source: Journal of Urology; Apr 2018; vol. 199 (no. 4)

Publication Date: Apr 2018

Publication Type(s): Conference Abstract

Abstract:INTRODUCTION AND OBJECTIVES: To evaluate the functional and psychological impact of different primary treatments in patients with Prostate Cancer (PC) . We assessed different mental health measures over time using validated questionnaires in men who underwent Active Surveillance (AS), Radical Prostatectomy (RP) or External Radiotherapy (EBRT) (at 1-, 3-, 6-, 12-month interval after therapy). METHODS: We conducted a single-centre prospective non randomized study. In total 220 patients with a diagnosis of PC, suitable for primary treatments, were included in the analysis. Inclusion criteria were: localized or locally advanced PC (T1-T3,N0,M0); primary treatment such as RP, EBRT or AS; no evidence of disease progression during the follow-up. Our evaluation was mainly based on self-administered and validated questionnaires on functional and psychological parameters. Urinary symptoms and incontinence were evaluated using the ICS male SF and the IPSS questionnaires. Erectile function was assessed using the International Index of Erectile Function-5 (IIEF-5). Health related QoL was evaluated using the SF-12 standard questionnaire and the UCLA-PC Index (urinary, bowel and sexual function). Anxiety, depression and PD were evaluated using HADS, PHQ-9 and PDI. The repeated measure analysis of variance (ANOVA) univariates and multivariates analysis were performed. RESULTS: Some baseline socio-demographic characteristics of our population significantly (p <0,05) influenced results in terms of questionnaire scores in the post-treatment follow-up, whereas baseline clinical characteristics of the tumor were less associated. Functional aspects were differently influenced by the three treatments. In particular EBRT was associated with a significant (p <0,01) worsening in bowel function (UCLA-bowel at 1-month follow-up), whereas RP was associated with a significant (p <0,01) worsening in urinary (IPSS) and sexual (IIEF-5) functions. Regarding psychological function, EBRT was associated with a higher and significant (p< 0,01) worsesing in PD, anxiety and depression (HADS and PHQ-9), in particular at 1-month but also in the long-term follow-up. AS was associated with a significant (p< 0,01) increase of depression scores (HADS and PHQ-9) only at 12-month interval. RP was associated with the lowest variation in all PD questionnaires. At the multivariate analysis the choice of treatment was a significant factor influencing PD scores but it depended from functional results. CONCLUSIONS: The different primary treatments indicated for PC are able to significantly influence PD, anxiety and depression of our patients during the follow-up, in particular EBRT showed a short-term whereas AS a long-term effect. This impact is more realated to the funcional modification due to treatments than to the treatment choice itself.

29. Modern intensity-modulated radiotherapy with image guidance allows low toxicity rates and good local control in chemoradiotherapy for anal cancer patients

Author(s): De Bari B.; Jumeau R.; Bourhis J.; Ozsahin M.; Lestrade L.; Kountouri M.; Miralbell R.; Zilli T.; Franzetti-Pellanda A.; Biggiogero M.; Matzinger O.

Source: Journal of Cancer Research and Clinical Oncology; Apr 2018; vol. 144 (no. 4); p. 781-789

Publication Date: Apr 2018

Publication Type(s): Article

Abstract:Purpose: To report outcomes of a population of anal cancer patients treated with modern intensity-modulated radiotherapy and daily image-guided radiotherapy techniques. Methods: We analyzed data of 155 patients consecutively treated with intensity-modulated radiotherapy +/- chemotherapy in three radiotherapy departments. One hundred twenty-two patients presented a stage II-IIIA disease. Chemotherapy was administered in 138 patients, mainly using mitomycin C and

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5-fluorouracil (n = 81). All patients received 36 Gy (1.8 Gy/fraction) on the pelvic and inguinal nodes, on the rectum, on the mesorectum and on the anal canal, and a sequential boost up to a total dose of 59.4 Gy (1.8 Gy/fraction) on the anal canal and on the nodal gross tumor volumes. Results: Median follow-up was 38 months (interquartile range 12-51). Toxicity data were available for 143 patients: 22% of them presented a G3+ acute toxicity, mainly as moist desquamation (n = 25 patients) or diarrhea (n = 10). Three patients presented a late grade 3 gastrointestinal toxicity (anal incontinence). No grade 4 acute or late toxicity was recorded. Patients treated with fixed-gantry IMRT delivered with a sliding window technique presented a significantly higher risk of acute grade 3 (or more) toxicity compared to those treated with VMAT or helical tomotherapy (38.5 vs 15.3%, p = 0.049). Actuarial 4-year local control rate was 82% (95% CI 76-91%). Conclusions: Modern intensity-modulated radiotherapy with daily image-guided radiotherapy is effective and safe in treating anal cancer patients and should be considered the standard of care in this clinical setting.

30. Moderate Hypofractionation in Patients with Low-risk Prostate Cancer: Long-term Outcomes.

Author(s): Valeriani, Maurizio; Bonfili, Pierluigi; Reverberi, Chiara; Marinelli, Luca; Ferella, Letizia; Minniti, Giuseppe; DE Sanctis, Vitaliana; Osti, Mattia Falchetto; Bonome, Paolo; Tronnolone, Lidia; Varrassi, Emilia; Gravina, Giovanni Luca; Franzese, Pietro; Tombolini, Vincenzo; DI Staso, Mario

Source: Anticancer research; Mar 2018; vol. 38 (no. 3); p. 1671-1676

Publication Date: Mar 2018

Publication Type(s): Journal Article

Abstract:BACKGROUND/AIMTo evaluate outcomes in patients with low-risk prostate cancer treated with hypofractionated radiotherapy (HyRT).PATIENTS AND METHODSBetween April 2004 and December 2015, 175 patients with low-risk prostate cancer were treated with HyRT 60 Gy in 20 fractions with or without image guidance and reduction of margin from clinical target volume to planning target volume.RESULTSThe median follow-up was 66 months. The 8-year overall survival for the whole patient cohort was 88.9%. The 8-year biochemical no evidence of disease was higher in patients treated with image-guided HyRT (98.8% vs. 88%, p=0.023). During treatment, patients treated with image-guided HyRT presented a lower rate of grade 1-2 gastrointestinal toxicity (25.3% vs. 42.2%, p=0.001). At the last follow-up, the grade 1 Gastro-intestinal toxicity rate was 4.0% and the grade 1-2 genito-urinary toxicity rate was 25.1%.CONCLUSIONOur study demonstrated the efficacy of the schedule used with a low rate of acute and late toxicities. Therefore, reduction of margins with image-guided HyRT is safe.

31. Phase I and II trial on infusional 5-fluorouracil and gefitinib in combination with preoperative radiotherapy in rectal cancer: 10-years median follow-up

Author(s): Gambacorta M.A.; Chiloiro G.; Valentini V.; De Paoli A.; Navarria F.; Palazzari E.; Lupattelli M.; Frattegiani A.; Solazzo A.P.; Barbaro B.; Alfieri S.; Vecchio F.M.; Lenkowicz J.; Bertola G.; Minsky B.

Source: Clinical and Translational Radiation Oncology; Mar 2018; vol. 10 ; p. 23-28

Publication Date: Mar 2018

Publication Type(s): Article

Abstract:Purpose: The aim of this study is to evaluate the long term survival of the addition of gefitinib to chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and materials: This previously published multicentre, open-label, phase I-II study, enrolled patients (pts) with LARC to receive CRT with concurrent 5-fluorouracil continuous intravenous infusion and a dose

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escalation of orally administered gefitinib, followed 6-8 weeks later by surgery. An intra-operative radiotherapy boost of 10 Gy was planned. Adjuvant chemotherapy was administrated in ypN1-2 pts. After a median f/u of >10 years, we analyzed Local Control (LC), Metastasis Free Survival (MFS), Disease Free Survival (DFS), Disease Specific Survival (DSS) and Overall Survival (OS). Predictive endpoints of clinical outcomes were tested by univariate and multivariate analysis. Variables analyzed included: age, gefitinib dose and interruptions, adjuvant CT, surgery type, ypT, ypN, and TRG grade. We have also analyzed late toxicity according to CTCAEv4. Results: Of the 41 initially enrolled pts, 39 were evaluable (27M, 12F). With a median f/u of 133 months, LC, MFS, DFS, OS and DSS at 5 years were 84%; 71%; 64%; 87% and 92%, respectively. The OS and DSS at 10 years were 61,5% and 76%, respectively. Grade 3-4 late toxicity occurred in 38% of pts: sexual (28,2%) and gastrointestinal toxicities (10,2%). Conclusion: Long term outcomes and late toxicity were similar to previously reported series. The addition of gefitinib did not improve outcomes in LARC. Gefitinib is not recommended for rectal cancer patients who received 5-FU based preoperative CRT. Further studies may identify if gefitinib is beneficial in selected group of patients.

32. Moderate hypofractionated radiotherapy after prostatectomy for cancer patients: Toxicity and clinical outcome

Author(s): Barra S.; Belgioia L.; Marcenaro M.; Corvo R.; Callegari S.; Pastorino A.; Trapani L.; Cavagnetto F.; Garelli S.

Source: Cancer Management and Research; Mar 2018; vol. 10 ; p. 473-480

Publication Date: Mar 2018

Publication Type(s): Article

Available at Cancer management and research - from Europe PubMed Central - Open Access

Available at Cancer management and research - from PubMed Central

Abstract:Background: After radical prostatectomy (RP) radiotherapy (RT) plays a role, both as adjuvant or salvage treatment. If negative features are present such as extracapsular extension, seminal vesicle invasion, lymph invasion, and positive surgical margins, RT after RP reduces the risk of recurrence, although it is associated with an increased risk of acute and late toxicities. An intensified RT delivered in a shortened time could improve clinical outcome and be safely combined with hormonal therapy (HT). The aim of this study was to determine the acute and late toxicities associated with hypofractionated RT and to assess the impact of the addition of HT to RT in high-risk prostate cancer (PC) patients on overall response and toxicity. Materials and methods: Sixty-four PC patients undergoing RP were included in this retrospective study. All patients were recommended to receive adjuvant or salvage RT. Prescription doses were 62.5 Gy in 25 fractions to prostate bed, 56.25 Gy in 25 fractions to seminal vesicles bed, and 50 Gy in 25 fractions to pelvis if indicated. HT was administered to patients with additional adverse pathologic features including Gleason score >7, prostate-specific antigen >20 ng/mL before surgery, or prostate-specific antigen with rapid doubling time after relapse or nodal involvement. After completion of RT, patients were observed after 4 weeks, and then followed-up every 3-6 months. Acute and late toxicities were assessed using Common Terminology Criteria for Adverse Events v4 and Radiation Therapy Oncology Group scale, respectively. Results: For acute toxicity, only grade 1 gastrointestinal and genitourinary toxicities were detected in 17% and 11% of patients, respectively. As regards late toxicity, only 5% of the patients developed grade 1 gastrointestinal adverse event; grade 1, grade 2, and grade 3 genitourinary toxicity was recorded in 5%, 3.3%, and 3.3% of patients, respectively. Two and 5 years overall survival were 98% and 96%, respectively. The curves stratified for treatment show a slight difference between patients receiving RT or RT+HT, but the differences did not reach statistical significance (p=0.133). Conclusion: In patients with PC undergoing RP, hypofractionated RT may

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contribute to achieve a high overall survival with an acceptable toxicity profile. Combination of RT and HT is also well tolerated and efficacious.

33. Postoperative hypofractionated radiation therapy in prostate Carcinoma: A systematic review

Author(s): Siepe G.; Buwenge M.; Capocaccia I.; Cammelli S.; Guido A.; Arcelli A.; Ntreta M.; Morganti A.G.; Nguyen N.P.; Macchia G.; Deodato F.; Cilla S.; Mattiucci G.C.; Guerri S.

Source: Anticancer Research; Mar 2018; vol. 38 (no. 3); p. 1221-1230

Publication Date: Mar 2018

Publication Type(s): Review

Abstract:Background/Aim: A systematic review on toxicity, local control (LC), overall survival (OS), and biochemical relapse-free survival (bRFS) after postoperative hypofractionated radiotherapy (HFRT) on prostate cancer (PCa) was performed. Materials and Methods: Based on the PRISMA methodology, studies reporting clinical results after adjuvant or salvage HFRT were included. Results: A total of 1,208 patients from 17 eligible studies were included. Median follow-up was 30 months. No case of severe acute gastrointestinal (GI) toxicity was recorded. Grade >=3 acute genitourinary (GU) toxicity ranged between 0% and 3%. Different rates of grade >=2 late GI (range=0-8.7%) and GU (range=0-66%) toxicity were recorded. Encouraging results on LC, OS, and bRFS were reported. Conclusion: Acute toxicity does not seem to be increased in patients receiving postoperative HFRT, but the results of late-GU toxicity are conflicting. Further prospective studies are needed before including postoperative HFRT in clinical practice.

34. The 5-year outcomes of moderately hypofractionated radiotherapy (66 Gy in 22 fractions, 3 fractions per week) for localized prostate cancer: a retrospective study.

Author(s): Hashimoto, Yaichiro; Motegi, Atsushi; Akimoto, Tetsuo; Mitsuhashi, Norio; Iizuka, Junpei; Tanabe, Kazunari; Ishii, Yuka; Kono, Sawa; Izumi, Sachiko; Karasawa, Kumiko

Source: International journal of clinical oncology; Feb 2018; vol. 23 (no. 1); p. 165-172

Publication Date: Feb 2018

Publication Type(s): Journal Article

Abstract:BACKGROUNDHypofractionated radiotherapy using fewer and larger fractional doses may be more beneficial than conventional external-beam radiotherapy for localized prostate cancer. We evaluated the 5-year outcomes of moderately hypofractionated radiotherapy for localized prostate cancer.METHODSWe retrospectively evaluated 195 patients with localized prostate cancer (T1-3N0M0) who underwent intensity-modulated radiotherapy (IMRT) (66 Gy delivered in fractions of 3 Gy every other weekday) between May 2005 and December 2011. Patients received androgen deprivation therapy depending on the perceived intermediate or high risk of their disease. A prostate-specific antigen nadir +2.0 ng/ml indicated biochemical failure. We assessed toxicity using the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria, and patient-reported outcomes using the Expanded Prostate Cancer Index Composite (EPIC).RESULTSThe risk classifications (proportion) were low risk (13.8%), intermediate risk (35.9%), and high risk (50.3%). The median follow-up was 69 months. Thirteen (6.66%) patients experienced biochemical failure within a median of 40 months (interquartile range, 25-72 months). The 5-year overall survival rate and no biological evidence of disease rate were 97.7% and 92.4%, respectively. Based on the RTOG/EORTC criteria, no patient experienced acute or late toxicity of grade 3 or higher. The EPIC scores revealed significant differences in the average value of all domains (p < 0.01). At 1 month postradiotherapy completion, the general urinary and

32

bowel domain scores had decreased, but these scores returned to baseline level by 3 months post radiotherapy.CONCLUSIONSThe moderately hypofractionated radiotherapy protocol yielded short-term satisfactory clinical outcomes with acceptable toxicity.

35. Rectal balloon use limits vaginal displacement, rectal dose, and rectal toxicity in patients receiving IMRT for postoperative gynecological malignancies

Author(s): Wu C.-C.; Wuu Y.-R.; Yanagihara T.; Jani A.; Xanthopoulos E.P.; Tiwari A.; Deutsch I.; Wright J.D.; Burke W.M.; Hou J.Y.; Tergas A.I.

Source: Medical Dosimetry; Feb 2018; vol. 43 (no. 1); p. 23-29

Publication Date: Feb 2018

Publication Type(s): Article

Abstract:Pelvic radiotherapy for gynecologic malignancies traditionally used a 4-field box technique. Later trials have shown the feasibility of using intensity-modulated radiotherapy (IMRT) instead. But vaginal movement between fractions is concerning when using IMRT due to greater conformality of the isodose curves to the target and the resulting possibility of missing the target while the vagina is displaced. In this study, we showed that the use of a rectal balloon during treatment can decrease vaginal displacement, limit rectal dose, and limit acute and late toxicities. Little is known regarding the use of a rectal balloon (RB) in treating patients with IMRT in the posthysterectomy setting. We hypothesize that the use of an RB during treatment can limit rectal dose and acute and long-term toxicities, as well as decrease vaginal cuff displacement between fractions. We performed a retrospective review of patients with gynecological malignancies who received postoperative IMRT with the use of an RB from January 1, 2012 to January 1, 2015. Rectal dose constraint was examined as per Radiation Therapy Oncology Group (RTOG) 1203 and 0418. Daily cone beam computed tomography (CT) was performed, and the average (avg) displacement, avg magnitude, and avg magnitude of vector were calculated. Toxicity was reported according to RTOG acute radiation morbidity scoring criteria. Acute toxicity was defined as less than 90 days from the end of radiation treatment. Late toxicity was defined as at least 90 days after completing radiation. Twenty-eight patients with postoperative IMRT with the use of an RB were examined and 23 treatment plans were reviewed. The avg rectal V40 was 39.3% +/- 9.0%. V30 was65.1% +/- 10.0%. V50 was 0%. Separate cone beam computed tomography (CBCT) images (n = 663) were reviewed. The avg displacement was as follows: superior 0.4 + 2.99 mm, left 0.23 +/- 4.97 mm, and anterior 0.16 +/- 5.18 mm. The avg magnitude of displacement was superior/inferior 2.22 +/- 2.04 mm, laterally 3.41 +/- 3.62 mm, and anterior/posterior 3.86 +/- 3.45 mm. The avg vector magnitude was 6.60 +/- 4.14 mm. For acute gastrointestinal (GI) toxicities, 50% experienced grade 1 toxicities and 18% grade 2 GI toxicities. For acute genitourinary (GU) toxicities, 21% had grade 1 and 18% had grade 2 toxicities. For late GU toxicities, 7% had grade 1 and 4% had grade 2 toxicities. RB for gynecological patients receiving IMRT in the postoperative setting can limit V40 rectal dose and vaginal displacement. Although V30 constraints were not met, patients had limited acute and late toxicities. Further studies are needed to validate these findings.

36. Does the Use of Volumetric Modulated Arc Therapy Reduce Gastrointestinal Symptoms after Pelvic Radiotherapy?

Author(s): White, K L; Varrassi, E; Routledge, J A; Barraclough, L H; Livsey, J E; McLaughlin, J; Davidson, S E

Source: Clinical oncology (Royal College of Radiologists (Great Britain)); Jan 2018; vol. 30 (no. 1); p. e22

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Publication Date: Jan 2018

Publication Type(s): Journal Article

Abstract:AIMSGrowing numbers of patients with cancer are surviving after treatment with pelvic radiotherapy. We evaluated the technique of volumetric modulated arc therapy (VMAT), which delivers a decreased dose to the organs at risk. We aimed to determine outcomes of this technique in terms of patient-reported acute toxicity and late effects and correlate the frequency of gastrointestinal symptoms with the volume of bowel receiving radiation dose.MATERIALS AND METHODSPatients who were to receive VMAT for gynaecological malignancy completed patient-reported outcomes at baseline, the end of treatment, 8 weeks and 1 year. The rates of patient-reported toxicity were correlated with the volume of bowel irradiated.RESULTSThe frequencies of patient-reported gastrointestinal symptoms increased in the acute toxicity phase and tended to improve at 1 year, with the exception of faecal incontinence and rectal bleeding (P 0.05 at all dose levels) and reported toxicity, suggesting that other factors are involved in the development of toxicity.CONCLUSIONAlthough VMAT decreases the dose delivered to the small bowel, this does not translate into a reduction in patient-reported toxicity.

37. Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy for primary pelvic cancers

Author(s): Lawrie T.A.; Green J.T.; Beresford M.; Wedlake L.; Burden S.; Davidson S.E.; Lal S.; Henson C.C.; Andreyev H.J.N.

Source: Cochrane Database of Systematic Reviews; Jan 2018; vol. 2018 (no. 1)

Publication Date: Jan 2018

Publication Type(s): Review

PubMedID: 29360138

Available at Cochrane Database of Systematic Reviews - from Cochrane Collaboration (Wiley)

Abstract:Background: An increasing number of people survive cancer but a significant proportion have gastrointestinal side effects as a result of radiotherapy (RT), which impairs their quality of life (QoL). Objectives: To determine which prophylactic interventions reduce the incidence, severity or both of adverse gastrointestinal effects among adults receiving radiotherapy to treat primary pelvic cancers. Search methods: We conducted searches of CENTRAL, MEDLINE, and Embase in September 2016 and updated them on 2 November 2017. We also searched clinical trial registries. Selection criteria: We included randomised controlled trials (RCTs) of interventions to prevent adverse gastrointestinal effects of pelvic radiotherapy among adults receiving radiotherapy to treat primary pelvic cancers, including radiotherapy techniques, other aspects of radiotherapy delivery, pharmacological interventions and non-pharmacological interventions. Studies needed a sample size of 20 or more participants and needed to evaluate gastrointestinal toxicity outcomes. We excluded studies that evaluated dosimetric parameters only. We also excluded trials of interventions to treat acute gastrointestinal symptoms, trials of altered fractionation and dose escalation schedules, and trials of pre- versus postoperative radiotherapy regimens, to restrict the vast scope of the review. Data collection and analysis: We used standard Cochrane methodology. We used the random-effects statistical model for all meta-analyses, and the GRADE system to rate the certainty of the evidence. Main results: We included 92 RCTs involving more than 10,000 men and women undergoing pelvic radiotherapy. Trials involved 44 different interventions, including radiotherapy techniques (11 trials, 4 interventions/comparisons), other aspects of radiotherapy delivery (14 trials, 10 interventions), pharmacological interventions (38 trials, 16 interventions), and non-pharmacological interventions (29 trials, 13 interventions). Most studies (79/92) had design limitations. Thirteen studies had a low risk of bias, 50 studies had an unclear risk of bias and 29 studies had a high risk of bias. Main findings

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include the following: Radiotherapy techniques: Intensity-modulated radiotherapy (IMRT) versus 3D conformal RT (3DCRT) may reduce acute (risk ratio (RR) 0.48, 95% confidence interval (CI) 0.26 to 0.88; participants = 444; studies = 4; I2 = 77%; low-certainty evidence) and late gastrointestinal (GI) toxicity grade 2+ (RR 0.37, 95% CI 0.21 to 0.65; participants = 332; studies = 2; I2 = 0%; low-certainty evidence). Conformal RT (3DCRT or IMRT) versus conventional RT reduces acute GI toxicity grade 2+ (RR 0.57, 95% CI 0.40 to 0.82; participants = 307; studies = 2; I2 = 0%; high-certainty evidence) and probably leads to less late GI toxicity grade 2+ (RR 0.49, 95% CI 0.22 to 1.09; participants = 517; studies = 3; I2 = 44%; moderate-certainty evidence). When brachytherapy (BT) is used instead of external beam radiotherapy (EBRT) in early endometrial cancer, evidence indicates that it reduces acute GI toxicity (grade 2+) (RR 0.02, 95% CI 0.00 to 0.18; participants = 423; studies = 1; high-certainty evidence). Other aspects of radiotherapy delivery: There is probably little or no difference in acute GI toxicity grade 2+ with reduced radiation dose volume (RR 1.21, 95% CI 0.81 to 1.81; participants = 211; studies = 1; moderate-certainty evidence) and maybe no difference in late GI toxicity grade 2+ (RR 1.02, 95% CI 0.15 to 6.97; participants = 107; studies = 1; low-certainty evidence). Evening delivery of RT may reduce acute GI toxicity (diarrhoea) grade 2+ during RT compared with morning delivery of RT (RR 0.51, 95% CI 0.34 to 0.76; participants = 294; studies = 2; I2 = 0%; low-certainty evidence). There may be no difference in acute (RR 2.22, 95% CI 0.62 to 7.93, participants = 110; studies = 1) and late GI toxicity grade 2+ (RR 0.44, 95% CI 0.12 to 1.65; participants = 81; studies = 1) between a bladder volume preparation of 1080 mls and that of 540 mls (low-certainty evidence). Low-certainty evidence on balloon and hydrogel spacers suggests that these interventions for prostate cancer RT may make little or no difference to GI outcomes. Pharmacological interventions: Evidence for any beneficial effects of aminosalicylates, sucralfate, amifostine, corticosteroid enemas, bile acid sequestrants, famotidine and selenium is of a low or very low certainty. However, evidence on certain aminosalicylates (mesalazine, olsalazine), misoprostol suppositories, oral magnesium oxide and octreotide injections suggests that these agents may worsen GI symptoms, such as diarrhoea or rectal bleeding. Non-pharmacological interventions: Low-certainty evidence suggests that protein supplements (RR 0.23, 95% CI 0.07 to 0.74; participants = 74; studies = 1), dietary counselling (RR 0.04, 95% CI 0.00 to 0.60; participants = 74; studies = 1) and probiotics (RR 0.43, 95% CI 0.22 to 0.82; participants = 923; studies = 5; I2 = 91%) may reduce acute RT-related diarrhoea (grade 2+). Dietary counselling may also reduce diarrhoeal symptoms in the long term (at five years, RR 0.05, 95% CI 0.00 to 0.78; participants = 61; studies = 1). Low-certainty evidence from one study (108 participants) suggests that a high-fibre diet may have a beneficial effect on GI symptoms (mean difference (MD) 6.10, 95% CI 1.71 to 10.49) and quality of life (MD 20.50, 95% CI 9.97 to 31.03) at one year. High-certainty evidence indicates that glutamine supplements do not prevent RT-induced diarrhoea. Evidence on various other non-pharmacological interventions, such as green tea tablets, is lacking. Quality of life was rarely and inconsistently reported across included studies, and the available data were seldom adequate for meta-analysis. Authors' conclusions: Conformal radiotherapy techniques are an improvement on older radiotherapy techniques. IMRT may be better than 3DCRT in terms of GI toxicity, but the evidence to support this is uncertain. There is no high-quality evidence to support the use of any other prophylactic intervention evaluated. However, evidence on some potential interventions shows that they probably have no role to play in reducing RT-related GI toxicity. More RCTs are needed for interventions with limited evidence suggesting potential benefits.

38. Postoperative Strahlentherapie beim Prostatakarzinom: Morbiditat nach lokaler Radiatio vs. lokaler Radiatio und BeckenbestrahlungPostoperative radiotherapy for prostate cancer: Morbidity of local-only or local-plus-pelvic radiotherapy

Author(s): Waldstein C.; Dorr W.; Potter R.; Widder J.; Goldner G.

Source: Strahlentherapie und Onkologie; Jan 2018; vol. 194 (no. 1); p. 23-30

35

Publication Date: Jan 2018

Publication Type(s): Article

Available at Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] - from PubMed Central

Abstract:Purpose: The aim of this work was to characterise actuarial incidence and prevalence of early and late side effects of local versus pelvic three-dimensional conformal postoperative radiotherapy for prostate cancer. Materials and methods: Based on a risk-adapted protocol, 575 patients received either local (n = 447) or local-plus-pelvic (n = 128) radiotherapy. Gastrointestinal (GI) and genitourinary (GU) side effects (>=grade 2 RTOG/EORTC criteria) were prospectively assessed. Maximum morbidity, actuarial incidence rate, and prevalence rates were compared between the two groups. Results: For local radiotherapy, median follow-up was 68 months, and the mean dose was 66.7 Gy. In pelvic radiotherapy, the median follow-up was 49 months, and the mean local and pelvic doses were 66.9 and 48.3 Gy respectively. Early GI side effects >= G2 were detected in 26% and 42% of patients respectively (p < 0.001). Late GI adverse events were detected in 14% in both groups (p = 0.77). The 5-year actuarial incidence rates were 14% and 14%, while the prevalence rates were 2% and 0% respectively. Early GU >= G2 side effects were detected in 15% and 16% (p = 0.96), while late GU morbidity was detected in 18% and 24% (p = 0.001). The 5-year actuarial incidence rates were 16% and 35% (p = 0.001), while the respective prevalence rates were 6% and 8%. Conclusions: Despite the low prevalence of side effects, postoperative pelvic radiotherapy results in significant increases in the actuarial incidence of early GI and late GU morbidity using a conventional 4-field box radiotherapy technique. Advanced treatment techniques like intensity-modulated radiotherapy (IMRT) or volumetric modulated arc radiotherapy (VMAT) should therefore be considered in pelvic radiotherapy to potentially reduce these side effects.

39. Long-term outcomes of a dose-reduction trial to decrease late gastrointestinal toxicity in patients with prostate cancer receiving soft tissue-matched image-guided intensity-modulated radiotherapy

Author(s): Sasaki N.; Yamazaki H.; Shimizu D.; Suzuki G.; Masui K.; Nakamura S.; Okabe H.; Nishikawa T.; Yoshida K.

Source: Anticancer Research; Jan 2018; vol. 38 (no. 1); p. 385-391

Publication Date: Jan 2018

Publication Type(s): Article

Abstract:Background/Aim: We experienced an unexpected high incidence of gastrointestinal (GI) toxicity in patients undergoing image-guided intensity-modulated radiotherapy (IG-IMRT) using helical tomotherapy in our initial 2.2 Gy/fraction schedule for prostate cancer; hence, a dose-reduction trial from 2.2 Gy to 2 Gy/fraction was conducted using modified planning target volume (PTV) contouring. Patients and Methods: We compared 130 patients treated using 2.2 Gy/fraction (Group A) and 144 treated using the 2 Gy/fraction (Group B) with modified PTV (excluding rectal volume) with a median follow-up period of 62 months. Prescribed dose was 72.6-74.8 Gy in 33-34 fractions (Group A) and 72-74 Gy in 36-37 fractions (Group B). Results: Patients in Group B had a reduced rectal and bladder V10-V70 and were irradiated at the maximal dose. Their cumulative incidence of grade =2 GI toxicity at 5 years improved from 10.1% [95% confidence interval (CI), 4.9-15.3%] to 1.4% (0-3.3%). Grade 2= urinary toxicity also decreased from 5.5% (1.5-9.4%) in Group A to 1.4% (0-3.3%, p=0.0167) in Group B. The biochemical failure-free 5-year survival rate was 89.1% (95%CI=83.6-95.4%) and 87.5% (82.0-92.9%, p=0.75) in groups A and B, respectively. Conclusion: The reduced dose fraction schedule decreased the incidence of late GI toxicity without compromising

36

prostate-specific antigen control. Careful target volume definition and fraction size are important even for IG-IMRT.

40. Dose-escalated radiotherapy for unresectable or locally recurrent pancreatic cancer: Dose volume analysis, toxicity and outcome of 28 consecutive patients.

Author(s): Zschaeck, Sebastian; Blümke, Bibiana; Wust, Peter; Kaul, David; Bahra, Marcus; Riess, Hanno; Klein, Fritz; Sinn, Marianne; Pelzer, Uwe; Budach, Volker; Ghadjar, Pirus

Source: PloS one; 2017; vol. 12 (no. 10); p. e0186341

Publication Date: 2017

Publication Type(s): Journal Article

Available at PloS one - from Public Library of Science (PLoS)

Available at PloS one - from Europe PubMed Central - Open Access

Available at PloS one - from EBSCO (MEDLINE Complete)

Available at PloS one - from Europe PubMed Central

Abstract:PURPOSEThe role of radiotherapy for unresectable pancreatic cancer is controversial. A benefit of additional radiotherapy is supported by some observations. A dose-effect relationship was recently found by dose escalation employing image guided and intensity modulated radiotherapy.METHODSWe retrospectively evaluated 28 consecutive patients, all with history of extensive prior therapies for unresectable locally advanced/ recurrent pancreatic cancer (LAPC/LRPC). Treatment was delivered by helical tomotherapy after daily position verification with computed tomography. Dose to the planned target volume (PTV) was 51 Gy, while the dose to the macroscopic tumor was escalated by a simultaneous integrated boost to a median cumulative dose of 66 Gy (60-66 Gy). Concomitant chemotherapy consisted mainly of capecitabine (n = 23).RESULTS10 of 28 patients presented acute toxicities > grade 2, one patient succumbed to gastrointestinal bleeding after treatment. No correlations of toxicities and dose volume histograms (DVH) of retrospectively delineated small bowel loops were observed, although average small bowel volume receiving ≥ 20 Gy was 374 ml. DVH analyses revealed a correlation of splenic parameters and acute toxicity: Vomiting, anorexia, dehydration, hematologic toxicity, fatigue, combined gastro-intestinal toxicity wit R-values between 0.392 and 0.561 (all p-values > 0.05). Only one patient developed late toxicities > grade 2. With an average follow-up time in surviving patients of 14 months median overall survival time was 19 months and median time to local recurrence 13 months. In 8 patients with available imaging of local recurrence: 5 in field recurrences, 2 marginal recurrences and one lymph node recurrence outside the high dose radiation field were observed. In univariate analysis only ΔCA-19-9 during radiotherapy was associated with local control (p = 0.029) and overall survival (p = 0.049).CONCLUSIONDose escalated normo-fractionated radiotherapy for LAPC/LRPC seems feasible and suitable to prolong local control and in consequence long-term survival. However, in-field local progression is still frequently observed and possibilities to increase the local effectiveness should be evaluated. Exposure of the spleen was predictive for acute toxicity and should be further investigated.

41. Socioeconomic status as an independent risk factor for severe late bowel toxicity after primary radiotherapy for cervical cancer.

Author(s): Laan, J J; van Lonkhuijzen, L R C W; van Os, R M; Tytgat, K M; Dávila Fajardo, R; Pieters, B R; Stalpers, L J A; Westerveld, G H

Source: Gynecologic oncology; Dec 2017; vol. 147 (no. 3); p. 684-689

37

Publication Date: Dec 2017

Publication Type(s): Journal Article

Abstract:OBJECTIVETo evaluate the frequency of and risk factors for severe late bowel toxicity after curative radiotherapy in women treated for locally advanced cervical cancer.METHODSIncluded were 515 women treated for locally advanced cervical cancer with primary radiotherapy with curative intent from 1992 to 2013. Bowel toxicity was graded according to the Common Terminology Criteria for Adverse Events. Associations between risk factors and severe late bowel toxicity were assessed using Cox proportional hazards regression models.RESULTSMedian follow-up was 78months. Fifty-nine patients developed severe late bowel toxicity. The actuarial 3-year and 5-year severe late bowel toxicity rates were both 13%. In the multivariable analysis, factors significantly associated with severe late bowel toxicity were: smoking (HR 2.59 [1.48-4.55]), severe acute bowel toxicity (HR 2.46 [1.24-4.49]), previous major abdominal surgery (HR 2.35 [1.20-4.60]), hypertension (HR 2.33 [1.23-4.40]), parametrial boost (HR 2.18 [1.10-4.33]), low socioeconomic status (HR 2.05 [1.17-3.59]) and low BMI (HR 0.93 [0.88-0.99]). First symptoms of severe late bowel toxicity were reported after a median follow-up of 9months, but occurred up to 10years after end of treatment. Only one third of the patients with severe late bowel toxicity were referred to a gastroenterologist.CONCLUSIONSSevere late bowel toxicity is a frequent complication of definitive radiotherapy for cervical cancer. Several independent risk factors were found which warrant further research. A standardized and structured approach in the early diagnostics and management of bowel toxicity is needed.

42. Salvage re-irradiation for local failure of prostate cancer after curative radiotherapy: Dosimetric and radiobiological modelling of rectal toxicity

Author(s): Dipasquale G.; Zilli T.; Rouzaud M.; Miralbell R.; Fiorino C.

Source: Physica Medica; Dec 2017; vol. 44 ; p. 22

Publication Date: Dec 2017

Publication Type(s): Conference Abstract

Abstract:Introduction. To assess the impact of radiation dose and clinical parameters on rectal toxicity following salvage external beam radiation therapy (EBRT) with or without a brachytherapy (BT) boost for exclusive local failure after primary-EBRT for prostate cancer. Methods. Fourteen patients with no residual toxicity after primary EBRT (-BT) were re-irradiated after a median time interval of 6.1 years (4.7-10.2). The median NTD2Gy was 74 Gy (66-98.4) at primary-RT and 85.1 Gy (70-93.4) at re-irradiation. Rectal dose volume histograms of both treatments (converted to NTD2Gy) and the corresponding normal-tissue-complication-probability (NTCP) values for gastro-intestinal (GI) toxicity were calculated. Results. The 5-year Grade P3 GI toxicity-free survival rate was 57.1 +/- 13.1%. Five patients developed Grade 4 GI toxicity. Rectal V70Gy and the maximum dose to 1 cc of rectum at primary EBRT were both predictive for Grade P3 GI toxicity; 12.2% vs. 3.8%, p = .042 and 72.2 Gy vs. 66.8 Gy, p = .0027, respectively. When adding primary-RT and re-irradiation plans, the median maximum dose to 1 cc of rectum was 139.8 Gy (126.7-147.8) vs. 125.9 Gy (99.1-133.1) (p = .0063) for Grade P3 and Grade 62 GI toxicity groups. Higher NTCP values at primary-RT were predictive for GradeP3 toxicity (p < .05). Conclusions. A higher rectal NTCP value, even in the absence of high-grade late-toxicity after primary-RT, is correlated with an increased risk of severe rectal side-effects after salvage reirradiation. Rectum doses greater than 70 Gy at primary-RT, and NTCP values of more than 10%, might predict for grade P3 rectal toxicity at re-irradiation, with a possible threshold for total rectum dose of around 130 Gy.

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43. Tolerance of Orthotopic Ileal Neobladders to Radiotherapy: A Multi-institutional Retrospective Study

Author(s): Ballas L.; Bian S.X.; Sargos P.; Orre M.; Daneshmand S.; Eapen L.J.

Source: Clinical Genitourinary Cancer; Dec 2017; vol. 15 (no. 6); p. 711-716

Publication Date: Dec 2017

Publication Type(s): Article

Abstract:Micro-Abstract The present multi-institutional retrospective study describes the tolerance of orthotopic neobladders to moderate doses of pelvic radiotherapy in 25 patients. In the setting of high-risk muscle-invasive bladder cancer, adjuvant radiotherapy is currently under investigation in multiple international clinical trials. To the best of our knowledge, the present study is the first to report that orthotopic neobladders can tolerate moderate doses of pelvic radiotherapy without significant toxicity. Background The present retrospective study analyzed the tolerance of orthotopic ileal neobladders to radiotherapy by reviewing the acute and late toxicity in patients who underwent postoperative radiotherapy after radical cystectomy/cystoprostatectomy. Materials and Methods A multi-institutional database was created for patients who had undergone radical cystectomy/cystoprostatectomy and neobladder reconstruction, followed by adjuvant radiotherapy (RT). The patient and tumor characteristics were recorded. The RT data were reviewed to determine the treatment technique used, the radiation dose received by the neobladder, and acute and late toxicity evaluated using the Common Terminology Criteria for Adverse Events, version 4.0, scale. Results A total of 25 patients were included, with a median age of 64 years. Of the 25 patients, 18 received a dose of 45 to 50.4 Gy. The most common reasons for postoperative radiotherapy were close or positive surgical margins and pT3-pT4 or N+ disease. Ten patients underwent intensity modulated RT. All but 1 patient completed the RT course. Of the patients who completed their RT schedule, none had grade >= 3 acute gastrointestinal toxicity. One patient who received concurrent chemotherapy developed grade 3 acute genitourinary toxicity. Three patients reported late grade 1 genitourinary toxicity (frequency of urination, mild leakage at night), with no reports of chronic gastrointestinal toxicity. None of the patients experienced neobladder perforation, leak, or fistula. Conclusion The use of moderate doses of pelvic RT (range, 45-50.4 Gy) was well tolerated among the 25 patients who underwent RT after cystoprostatectomy with orthotopic neobladder creation. This finding supports the use of postoperative RT to moderate doses in this patient population when clinically indicated.

44. Toxicity after post-prostatectomy image-guided intensity-modulated radiotherapy using Australian guidelines

Author(s): Chin S.; Aherne N.J.; Shakespeare T.P.; Last A.; Assareh H.

Source: Journal of Medical Imaging and Radiation Oncology; Dec 2017; vol. 61 (no. 6); p. 804-811

Publication Date: Dec 2017

Publication Type(s): Article

Abstract:Introduction: We evaluated single institution toxicity outcomes after post-prostatectomy radiotherapy (PPRT) via image-guided intensity-modulated radiation therapy (IG-IMRT) with implanted fiducial markers following national eviQ guidelines, for which late toxicity outcomes have not been published. Methods: Prospectively collected toxicity data were retrospectively reviewed for 293 men who underwent 64-66 Gy IG-IMRT to the prostate bed between 2007 and 2015. Results: Median follow-up after PPRT was 39 months. Baseline grade >=2 genitourinary (GU), gastrointestinal (GI) and sexual toxicities were 20.5%, 2.7% and 43.7%, respectively, reflecting ongoing toxicity after radical prostatectomy. Incidence of new (compared to baseline) acute grade >=2 GU and GI toxicity was 5.8% and 10.6%, respectively. New late grade >=2 GU, GI and sexual toxicity occurred in 19.1%,

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4.7% and 20.2%, respectively. However, many patients also experienced improvements in toxicities. For this reason, prevalence of grade >=2 GU, GI and sexual toxicities 4 years after PPRT was similar to or lower than baseline (21.7%, 2.6% and 17.4%, respectively). There were no grade >=4 toxicities. Conclusions: Post-prostatectomy IG-IMRT using Australian contouring guidelines appears to have tolerable acute and late toxicity. The 4-year prevalence of grade >=2 GU and GI toxicity was virtually unchanged compared to baseline, and sexual toxicity improved over baseline. This should reassure radiation oncologists following these guidelines. Late toxicity rates of surgery and PPRT are higher than following definitive IG-IMRT, and this should be taken into account if patients are considering surgery and likely to require PPRT.

45. Outcomes of post-prostatectomy radiotherapy at a Regional Cancer Centre

Author(s): Nicholls L.; Winter A.; Harwood A.; Bagga P.; Wong W.; Khoo E.; Plank A.

Source: Journal of Medical Radiation Sciences; Dec 2017; vol. 64 (no. 4); p. 259-265

Publication Date: Dec 2017

Publication Type(s): Article

Available at Journal of medical radiation sciences - from Wiley Online Library Free Content - NHS

Available at Journal of medical radiation sciences - from Europe PubMed Central - Open Access

Abstract:Introduction: To investigate the efficacy and toxicity of radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer at Radiation Oncology Centres, Toowoomba. Methods: The electronic medical records of 130 consecutive patients with histologically proven prostate adenocarcinoma who underwent post-prostatectomy RT between January 2008 and December 2014 were analysed. Primary endpoint was Biochemical Recurrence (BCR) after RT. BCR was defined by PSA > 0.2 ng/mL and BCR endpoints were analysed using Kaplan-Meier methods. The impact of RT technique and the rates of acute and late toxicities are also reported. Toxicities were graded according to Radiation Therapy Oncology Group (RTOG) criteria. Results: Median follow-up time after RT (regardless of technique) was 28 months. BCR occurred in 32 of the 126 patients (25%) whose prostate specific antigen (PSA) levels have been monitored post-RT. At 24 and 36 months, 85% and 75% of patients were BCR-free, respectively. Patients with a pre-RT PSA above 0.2 ng/mL had a higher probability of recurrence than patients with values below 0.2 ng/mL (P = 0.03). RT technique, pelvic nodal irradiation, androgen deprivation therapy, T staging or surgical margin did not significantly impact BCR results. No patient experienced acute toxicities greater than grade 2. Grade 1 or 2 late gastrointestinal (GI) toxicity occurred in 11% and 1 patient experienced a grade 3 event. 12% of patients developed grade 1 or 2 late genitourinary (GU) toxicity, with evidence of grade 3 severity in only 1 patient. Evidence of a trend in reduction in late GI toxicity with the use of intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) was apparent but not with late GU toxicity. Conclusion: At our regional centre, early RT (PSA < 0.2 ng/mL) was associated with significant improvement in BCR-free survival. Rates of toxicity mirror those of landmark trials which suggest no detriment for our regional prostate cancer patients. The use of IMRT/VMAT techniques was associated with a trend towards reduced rates of GI toxicity.

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