esophageal cancer-role of rt
TRANSCRIPT
Management of carcinoma esophagus DR BHARTI DEVNANI
MODERATOR:- DR ANJALI K. PAHUJA
Localised disease Metastasis
Definitive therapy Palliative therapy
Diagnostic workupo
rk
up
. At the time of diagnosis, approximately 80% patients have locally advanced or distant disease
EVOLUTION OF TREATMENT
Non surgical treatment Radiation therapy alone Combined modality therapy(CT+RT) Intensification of the radiation dose
Surgical treatmentSx aloneSx+adjuvantPreop CT + Sx
RT ALONE
6
RADIATION ALONE
AUTHOR NO OF PTS DOSE 2 YRS SURVIVAL
5 YRS SURVIVAL
Pearson 208 50Gy/4Wks NA 17%
Beatty et al 344 >40Gy to > 50Gy
21% 0%
Schuchmann et al
127 <45Gy>45 Gy
0%0%
Newaishy et al
444 50-55Gy/4 Wks
19% 9%
Okawa et al 96 NR 9%(I-20%,II-10%,III-3%,IV-0%)
Lederman et al
263 11%(yrs) 7%
COMBINED MODALITY TREATMENT (CT+RT V/S RT ALONE)
RTOG 85-01 TRIAL(RT ALONE V/S CMT)
RANDOMISE
Wk 1
50Gy/25 fractions
Wk 5 Wk 11
CDDP 75mg/m2 Day 1 and 5-FU 1gm/m2 C.I. day 1- 4
CT+RT
RT
Wk 8
64Gy/32 fractions
RESULTS OF RTOG 85-01 TRIALComp-liance
Gr III toxicity
Gr IV Gr V Localfailure
Distfailure
Median and 5yr survival
CT+RT (n=61)
54% 44% 20% 3% 43% 22% 12.5 mo, 27%
RT (n=60)
83% 25% 3% 0 64% 38% 8.9 mo, 0%
P-value
Sig Sig Sig Sig Sig Sigp<0.0001
All patients who received RT alone were dead of disease by 3 years. Established chemoradiation as the conventional nonsurgical treatment for esophageal cancer
Herskovic A et al. NEJM 1992;326:1593-1598
10
CONCURRENT CT+RT- META ANALYSIS OF 11RCT
Cochrane Database of Systematic Reviews
RESULTS OF METANALYSIS
Concomitant RTCT provided significant reduction in mortality with a HR of 0.73.
The absolute survival benefit for RTCT at 1yr and 2 yr was 9%and 4% respectively.
There was an absolute reduction of local recurrence rate of 12%
INTENSIFICATION OF RADIATION DOSE (BY BRACHYTHERAPY BOOST)
The cumulative incidence of fistula was 18%/year and the crude incidence was 14%.
Esophageal fistulas were treatment-related rather than tumor-related of the six treatment-related fistulas, three were fatal .
Occurred in the region of the brachytherapy.
Five of the six patients developing fistulas received 15 Gy brachytherapy dose. (median-3.9 months)
The other patient received just one fraction of 5 Gy and developed a fistula within 0.5 months.
HIGH DOSE V/S STANDARD RADIATION DOSE
17
RANDOMISE
Wk 1
50.4Gy/28 fractions
Wk 5 Wk 13
CDDP 75mg/m2 Day 1 and 5-FU 1gm/m2 C.I. day 1- 4
StandardCT+RT
CT + High dose RT
Wk 9
64.8Gy/36 fractions
Wk 1 Wk 5 Wk 11 Wk 15
Minsky BD et al. JCO 2002;20:1167-1174
No significant difference in survival(p=NS)
MS-18 v/s 13 months2 yr survival—40% v/s 31%
No significant difference in time to first failure(52% v/s 56%)
(local /regional failure or locoregional persistance of
cancer)
This trial demonstrated that for patients who receive concurrent chemotherapy with radiation, higher doses of radiation therapy do not offer a local/regional control or survival advantage.
PREOPERATIVE CHEMORADIATION THERAPY
20
PRE OP.CT+RT+S VS S
AUTHOR MEDIAN FOLLOW UP
REGIMEN NO OF PTS
Ro resection/Dist Met
PATH CR LOCOREG FAILURE
3-Yr Survival
SURVIVAL DIFF
Urba et al
8.2 5fu+cddp+Vbl+RT+SS
50
50
90 60%90 65%
28-
19%42%P=0.02
30
16
p=0.15
Boset et al
4.6 Cddp+RT+SS
143138
81 69
26---
3436
NS
Walsh et al
1.5 5fu+cddp+RT+SS
58
58
NR NR
25 32
6
P+0.01
Burmeister et al
5.4 5fu+cddp+RT+SS
128
128
80 59
16
---
35
30
NS
Tepper et al
6.0 5fu+cddp+RT+SS
30
26
NRNR
33 13
15
39
16
P=0.008
9 RCT 1116 patients
Three-year survival (odds ratio 0.66, 95% confidence interval 0.47to 0.92; P 0.016).
Rate of complete resection (odds ratio 0.53, 95% confidence interval0.33 to 0.84; P 0.007).
Compared with surgery alone, neoadjuvant chemoradiation and surgery
Improved 3-year survival
Reduced local-regional cancer recurrence.
Higher rate of complete (R0) resection.
Pathological complete response in 21% patients
Survival benefit was most pronounced when CT+RT were given concurrently instead of sequentially
Lancet Oncol 2011; 12: 681–92
Provides strong evidence for a survival benefit of neoadjuvantchemoradiotherapy or chemotherapy over surgery alone in patients with oesophageal carcinoma. clear advantage ofneoadjuvant chemoradiotherapy over neoadjuvant chemotherapy has not been established.
CAN SURGERY BE AVOIDED
46 Gy20 Gy
In patients with locally advanced thoracic esophageal cancers, especially epidermoid, who respond to chemoradiation, there is no benefit for the addition of surgery after chemoradiation compared with the continuation of additional chemoradiation.
chemoradiation alone entailed fewer early deaths and a shorter hospital stay
More locoregional relapses. Because clinical prognostic factors donot help in
choosing between both strategies, further studies comparing surgery and chemoradiation should search for newpredictive factors and evaluate new tools to detect early responders.
PET scan was reported to discriminate responders from nonresponders as early as 14 days after starting chemoradiation and should be re-evaluated in future studies.
The study suggests that there is no difference in clinical toxicity profiles or survival outcomes with either definitive chemoradiotherapy or chemoradiation followed by surgery in management of locally advanced esophageal cancer.
Future studies are necessary to investigate dose escalation of chemoradiotherapy, thereby reducing the risk of treatment failures in patients treated without surgery.
RADIATION
The design and delivery of radiation therapy for esophageal cancer requires a knowledge of the –
Natural history of the disease Patterns of failure Anatomy, Radiobiologic principles. Use of proper equipment Implementation of methods to decrease
treatment-related toxicity Close collaboration with the physics and
technology staff are essential. As radiation oncology is both an art and a
science.
RADIOTHERAPY
CurativeDose-50.4 Gy/28# Conventional Conformal 3 D CRT IMRT IGRT Arc Respiratory gating Proton
Palliative
EBRTDose-30 Gy/10#
Brachytherapy12 Gy/#18 Gy/3#
TECHNIQUES OF RADIATION THERAPY
External beam radiotherapy Important considerations for RT
Nearby vital structures: spinal cord. lungs, heart Movement in target tissue and vital structures: lungs,
heart Variable density of tissues: lungs
TECHNIQUES OF RADIATION THERAPY
SIMULATION
Extent of the disease should be known based on imaging Barium swallow, CT, PET Endoscopy. During simulation, the patient is positioned, straightened,
and immobilized on the simulation table. Arms are generally placed overhead. Palpable neck disease should be marked with a radio-
opaque wire Administration of oral contrast to delineate the esophagus is
used. Some authors recommend placing the patient in the prone
position for treatment to displace the esophagus away from the spinal cord
Conventional technique
TREATMENT PORTALS
Parallel opposed AP-PA fields
EBRT TECHNIQUES
Initial phase (39.6-41.4 Gy)
- 5cm prox and distal margins
- 2 cm lateral margins
Off cord Boost: After 40-44Gy
3 field technique -- one direct anterior and two lateral/ posterior oblique
Advantages - Homogeneous dose distribution- Tumor better covered - Critical organs are out of the field
‘T’ shaped AP-PA field:
Upper cervical esophagus lesion - Treated from laryngopharynx to carina - Supraclavicular and upper mediastinal LN s irradiated electively
AP-PA fields with lung shielding
BORDERS:
Superior: Thyroid notchLateral : Junction of medial 2/3rd and lateral 1/3rd clavicleLower: Adequate margins from lesion (include upper mediastinal LNs)
Shielding: 5 HVL lead shield from 1cm below the Clavicles Lung correction factor
-Co 60 - dose decreased by 4%/cm- For 4 MV - 3% /cm - 10 MV -2 %/cm of lung
NORMAL TISSUE TOLERANCE
Organ TD5/5 Gy TD50/5 Gy Field size
Spinal cord 4750
-70
20cm5-10cm
Heart 4060
5070
Whole1/3rd
Lung 17.545
24.565
Whole1/3rd
APPROPRIATE TARGET VOLUME AND NEED OF ELECTIVE NODAL IRRADIATION IN CONFORMAL THERAPIES
•In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume.•Local failure and distant metastases remained the predominant problems.•A longitudinal margin of 3 cm from the GTV to the CTV1 is probably enough
BASIS OF OMITTING ENI
Recurrence was with in GTV
1. Recurrene pattern(in-field) Predominant failure pattern in with esophageal SCC was
local in-field or distant failures. Regional nodal recurrence (out-of-field) was infrequent (8%) in the absence of elective node irradiation.
2. Biological behavior of the disease Esophageal cancer is characterized by a high rate of
nodal involvement and its spread pattern is not always predictable. Also, skip node metastases are frequently observed. Thus the biological behavior of this disease makes it difficult to define in advance the extent of coverage of elective nodal irradiation.
3. Toxicities If distant lymph node areas were irradiated
prophylactically, patients would then experience more severe radiation complications and have a poorer treatment tolerance.
In CRT for esophageal SqCC, ENI was effective for preventing regional nodal failure. TheUPPER THORACIC esophageal carcinomas had significantly more local recurrences than the middle or lower thoracic sites.
No global consensus on whether or not ENI should be performed.
POST-OPERATIVE MANAGEMENT IN CASES OF UPFRONT SURGERY
WHEN NO PRE –OP RT+CCT RECIEVEED
RECEIVED PRE-OP RT+CCT
TARGATED THERAPIES
TRASTUZUMAB + CHEMOTHERAPY IN ADVANCED HER2+ GASTRIC CANCER: TOGA STUDY
Rationale: a subpopulation of gastric cancers overexpress HER2
*
(n = 584)
R
Patients with advanced
gastric adenocancer screened for HER2 status
(N = 3803)
Stratified by ECOG PS, advanced vs metastatic, gastric vs GEJ,
measurable disease, capecitabine vs 5-FU
Patients with HER2+
advanced gastric cancer(n = 810; 22% of successful screenings)
5-FU or Capecitabine* + Cisplatin 80 mg/m2 q3w x 6 +
Trastuzumab 6 mg/kg q3w until PD
(8 mg/kg loading dose)(n = 294)
5-FU or Capecitabine* + Cisplatin 80 mg/m2 q3w x 6
(n = 290)
Bang YJ, et al. Lancet. 2010;376:687-697.
Outcome Chemotherapy +
Trastuzumab(n = 294)
Chemotherapy Alone(n = 290)
HR (95% CI) P Value
Median OS, mos
13.8 11.1 0.74 (0.60-0.91)
.0046
Median PFS, mos
6.7 5.5 0.71 (0.59-0.85)
.0002
Established transtuzumab and chemotherapy is a new standard of care for Her-2 neu expressing advanced gastric
and EGJ adenocarcinoma.Significant OS benefit
Safety profile were similar
PALLIATIVE CARE
IMPORTANCE OF PALLIATIVE CARE IN CA ESOPHAGUS
Majority of the patients diagnosed with advanced disease(80%) therefore palliation is an important goal.
1.Dysphagia
2.ObstructionEBRTBTEBRT+CCTSurgeryEndoscopic lumen restorationStenting
3.Pain(WHO pain ladder)
4. Nausea and vomitting (Antiemetics)
5.BleedingAcute bleedingChronic bleeding
6.Tracheo-oesophageal fistula
Fractionated BT is the best modality of palliation in comparison to all other modalities.for advanced esophageal cancers. It offers best palliation both in terms of survival(6.2) as well as symptom
free duration40% pts were free of dysphagia for one yr.
16Gy/2# or 18 Gy/3#
Versus
Dysphagia improved more rapidly after stent placement than after brachytherapy, but longterm relief of dysphagia was better after brachytherapy.
Stent placement had more complications than brachytherapy which was mainly due to an increased incidence of late haemorrhage .
No difference for median survival (p=0·23).
Quality-of-life scores were in favour of brachytherapy compared with stent placement.
Total medical costs were also much the same for stent placement (€8215) and brachytherapy (€8135).
Due to better long-term relief of dysphagia with fewer complications brachytherapy is recommended as the primary treatment for palliation of dysphagia from oesophageal cancer.
BRACHYTHERAPY
Procedure• After placing the patient in left lateral position, a fibre-
optic endoscope is passed. • The esophagus will be evaluated for extent of residual
tumor, presence of ulcer and stricture. • If suitable for brachytherapy, a stainless steel guide wire
will be passed through the biopsy channel of the endoscope and passed beyond the tumor site
• Depending upon the site of lesion, the length of selectron boogie will be adjusted by altering position of the mouth piece, so that lower end of the boogie is 2cm beyond the lower limit of initial lesion.
• The boogie will be threaded over the guide wire, which is then withdrawn
BRACHYTHERAPY
Prescription
1 cm from the mid-source / mid-dwell position without optimization
BRACHYTHERAPY ON TREATMENT
SURGICAL APPROCHES FOR ESOPHAGOGASTRECTOMY
Transthoracic approach
Transhiatal approch
TRANSTHORACIC APPROACH
Right thoracotomy & laparotomy Ivor lewis Mckeown
(with cervical anastomosis)
APPROACHES TTE IVOR LEWIS
APPROACHES TTE MCKEOWN
•Transient myelosuppression (30%)
• Esophagitis
• Dysphagia
• Pneumonitis
• Perforation with fistula or
hemorrhage
• Skin changes: hair loss, redness
• Pericarditis
• Nausea/ vomiting
• LOW/LOA
• Stenosis/ strictureOccurs in 60 % of casesStricture requiring dilatation-15-20 %
• Pneumonitis/ pulmonary fibrosis
• Esophagotracheobronchial fistulae
• Aortic rupture and hemorrhage
• Pericarditis with pericardial
constriction
• Transverse myeiltis
• Myocardial damage
• Radionecrosis of bone
COMPLICATIONS OF CRT
PROBLEMS WITH TRIMODALITY
Haematological toxicity – 30 % Mucositis Gr 3,4 Oesophagitis Pulm complications (ARDS) 14 % Surgical complications - anastomotic leak 6 % Local recurrence 6 % Operative deaths 6 %
TOXICITY TUMOUR CONTROL
MANAGING COMPLICATIONS
Smoking cessation
Nutrition maintenance:
- Assess radiation tolerability before starting radiation
- Plenty of fluids, frequent sips of cool liquids
- Disprin and local anesthetic gargles
- Avoid hot spicy, dry food
- Ryles tube insertion: Grade 3-4 dysphagia/ <1500kcal/day
Respiratory physiotherapy: to improve pulmonary function
During radiation, check patient status at least once a week
Antiemetics, Antacids, soothening agents be prescribed when needed
Treatment interruptions or dose reductions for manageable acute
toxicities should be avoided.
THANK U
PHOTODYNAMIC THERAPY
PRINCIPLE:
- Uses photosensitiser (Hematoporphyrin) and red (WL=630nm) LASER
- Resultant free radicals destroy DNA of rapidly dividing cells.
INDICATIONS:
Barrets esophagus
Early esophageal cancer
Persistant or recurrent esophageal cancer post RT, CCT, Sx
ADVERSE EFFECTS:
Local swelling and inflammation
Photosensitivity: shield skin and eyes for 4 hours
SURGERY
Resection should include
Lower esophagus to a point above azygos vein
Celiac lymph nodes
Left gastric lymph nodes
Division of left gastric artery
Proximal part of stomach
Pyloroplasty