five years treatment outcomes of postoperative radiotherapy in
TRANSCRIPT
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Five Years Treatment Outcomes of Postoperative Radiotherapy in Saudi Women with Uterine Cancers
Asiri MA, Tunio MA, Mohamed R, Bayoumi Y, Alhadab A, Saleh RM, AlArifi MS, Alobaid A ,K Salama, B Obaidat
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Introduction: Uterine cancers are the tenth most common in KSA.
Second most common gynecologic malignancies in KSA
Surgery is the primary treatment (TAH+BSO & PND
Five year survival rates of 78%
(PORTEC) and (GOG-99) shown significant reduction of
the risk of pelvic and vaginal recurrence by adjuvant
radiotherapy,
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PORTEC-1 trial
426 patients
15-year actuarial locoregional recurrence (LRR) rates
6% for EBRT
15.5% for no adjuvant radiation therapy
(p < 0.0001).
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Uterine sarcomas :3%-7% of all uterine malignancies
Dismal prognosis.
Histologically divided into three parts :
Leiomyosarcoma,
Carcinosarcoma or MMM
Endometrial stromal sarcoma .
(a)TAH+ BSO followed by adjuvant radiotherapy and systemic
chemotherapy due to increased tendency to metastasize
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PURPOSE:
Evaluation of long term treatment outcomes and toxicity profile of postoperative radiotherapy (PORT) in Saudi women with uterine cancers treated in Radiation Oncology Department , CCC-KFMC
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METHODS AND MATERIALS:
Medical records review.2007 and 2012FIGO IB- IVATAH-BSO +/- PLND. All uterine cancers who received PORT post TAHBSO.45-50.4 Gy in 25-28 fractions+HDR .Data :
The safety profile, Pathology & RadiologyLocoregional control (LRC) Distant metastases control (DMC) Overall survival (OS)
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Postoperative Radiation therapy techniques:
(CT) simulator with Contrast , 5 mm slice .CTV : [vaginal cuff, parametrial soft tissue, external, internal iliac, presacral and common iliac lymph nodes](PTV) = CTV + 1 cm margin.OAR : (urinary bladder, rectum, small bowel).(RTOG) contouring guidelines (3DCRT)/IMRT treatment planning
Dose : 45-50.4 Gy in 25-28 fractions, 1.8 Gy per fraction,(HDR) vaginal brachytherapy (VBT) :15-20 Gy in 3-4 sessions .
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Adjuvant chemotherapy:Indications :
Papillary serous Clear cell types CarcinosarcomaFIGO III, IVA endometrial cancers.
Before starting radiation therapy. 4 cycles of Paclitaxal (175mg/m2) and Carboplatin (350 mg/m2) every 21 days.
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Toxicity and Response evaluation:
Weekly evaluation .weight, performance status, hematology/chemistry and side effects. The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0,(RTOG) Late Radiation Morbidity Scoring Criteria .3 monthly FU for first two years 6 monthly for 3rd to 5th year .Physical and per vaginal examination, Pap smear .CT chest, abdomen and pelvis annually.
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RESULTS: Median follow-up period was 60 months (range, 12-70)
89 patients.
histological type
Endometrial (59 patients), (66.3%)
Carcinosarcoma (17 patients) (19.0%)
Leiomyosarcoma (13 patients) (14.7%).
Median age at time of diagnosis was 57.6.
Median time between surgery and radiotherapy was 7.1 weeks
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Variables Endometrial carcinoma (n = 59)
Leiomyosarcoma (n = 13)
Carcinosarcoma (n = 17)
Age (years) 57.6 (44-80) 51.1 (40-65) 56.0 (40-75) Symptoms
PV bleeding PV discharge
Pelvic pain
51 (86.5%) 31 (52.4%) 6 (10.1%)
8 (61.5%) -
5 (38.5%)
12 (70.5%) 3 (17.7%) 2 (11.8%)
Co-morbids
HTN DM
HTN+DM
31 (52.4%) 31 (52.4%) 21 (35.7%)
5 (38.5%) 6 (46.0%)
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8 (47.1%) 9 (52.9%)
- Median BMI (kg/m2) 35.9 25.7 30.1
FIGO staging
I II III
IVA
38 (64.4%) 9 (15.3%) 10 (16.0%) 2 (3.3%)
3 (23.1%) 8 (61.5%) 2 (15.4%)
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6 (35.3%) 7 (41.2%) 4 (23.5%)
- Elevated baseline CA125
levels 5 (8.5%) - 7 (41.2%)
Presence of LVSI 40 (67.8%) - 1 (5.9%) Cell type
Papillary serous Clear cell
3 (5.1%) 1(1.7%)
- -
- -
Positive pelvic lymph nodes 6 (10.1%) - - Positive PALN 1 (1.7%) - -
Tumor size above 5 cm 12 (20.4%) 7 (54.0%) - Grade
GI GII GIII
12 (20.4%) 15 (25.4%) 32 (54.2%)
13(100%) - -
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17 (100%) ER/PR (+) 6 (10.1%) 3 (23.1%) 1 (5.9%)
Squamous metaplasia (+) 3 (5.1%) - - Adjuvant chemotherapy 22 (37.3%) - 13 (76.5%)
Median chemotherapy cycles 4 (3-6) - 6 (4-8) Adjuvant EBRT
45.0 Gy 50.4 Gy
37 (62.7%) 22 (37.3%)
6 (46.0%) 7 (54.0%)
5 (29.5%) 12 (70.5%)
Vaginal brachytherapy
Patients characteristics
Variables
Endometrial carcinoma
(n = 59)
Leiomyosarcoma
(n = 13)
Carcinosarcoma
(n = 17)
Age (years)
57.6 (44-80)
51.1 (40-65)
56.0 (40-75)
Symptoms
PV bleeding
PV discharge
Pelvic pain
51 (86.5%)
31 (52.4%)
6 (10.1%)
8 (61.5%)
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5 (38.5%)
12 (70.5%)
3 (17.7%)
2 (11.8%)
Co-morbids
HTN
DM
HTN+DM
31 (52.4%)
31 (52.4%)
21 (35.7%)
5 (38.5%)
6 (46.0%)
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8 (47.1%)
9 (52.9%)
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Median BMI (kg/m2)
35.9
25.7
30.1
FIGO staging
I
II
III
IVA
38 (64.4%)
9 (15.3%)
10 (16.0%)
2 (3.3%)
3 (23.1%)
8 (61.5%)
2 (15.4%)
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6 (35.3%)
7 (41.2%)
4 (23.5%)
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Elevated baseline CA125 levels
5 (8.5%)
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7 (41.2%)
Presence of LVSI
40 (67.8%)
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1 (5.9%)
Cell type
Papillary serous
Clear cell
3 (5.1%)
1(1.7%)
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Positive pelvic lymph nodes
6 (10.1%)
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Positive PALN
1 (1.7%)
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Tumor size above 5 cm
12 (20.4%)
7 (54.0%)
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Grade
GI
GII
GIII
12 (20.4%)
15 (25.4%)
32 (54.2%)
13(100%)
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-
-
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17 (100%)
ER/PR (+)
6 (10.1%)
3 (23.1%)
1 (5.9%)
Squamous metaplasia (+)
3 (5.1%)
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Adjuvant chemotherapy
22 (37.3%)
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13 (76.5%)
Median chemotherapy cycles
4 (3-6)
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6 (4-8)
Adjuvant EBRT
45.0 Gy
50.4 Gy
37 (62.7%)
22 (37.3%)
6 (46.0%)
7 (54.0%)
5 (29.5%)
12 (70.5%)
Vaginal brachytherapy
15 Gy 3
20 Gy 4
49 (84.0%)
10 (16.0%)
10 (76.9%)
3 (23.1%)
13 (76.5%)
4 (23.5%)
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RESULTS: LRC :
80.9%, for leiomyosarcoma87.1% for carcinosarcoma100%, for endometrial carcinoma
DMC :69.3% for endometrial45% for leiomyosarcoma16.3% for carcinosarcoma
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RESULTS: Five-year OS rates :
71.1%, for endometrial60% for leiomyosarcoma16.3%, for carcinosarcoma
Acute grade 3 and 4 proctitis/enteritisseen only in 4 patients (4.5%) and latetoxicities were minimal.
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Toxicity
Grade 1, 2 n (%) Acute Late
Grade 3, 4 n (%) Acute Late
Hematological Anemia Neutropenia Thrombocytopenia
- - - - - -
- - 2 (2.25%) - - -
skin 5 (5.6%) 2 (2.25%) - 1 (1.1%) Small bowel 4 (4.5%) 4 (4.5%) - 1 (1.1%) Nausea/vomiting 4 (4.5%) - - - Vaginitis
3 (3.4%) 1 (1.1%) - -
Cystitis 2 (2.25%) - - -
Incidence of grade 2 and 3 acute and late toxicities
Toxicity
Grade 1, 2 n (%)
Acute Late
Grade 3, 4 n (%)
Acute Late
Hematological
Anemia
Neutropenia
Thrombocytopenia
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2 (2.25%) -
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skin
5 (5.6%) 2 (2.25%)
1 (1.1%)
Small bowel
4 (4.5%) 4 (4.5%)
1 (1.1%)
Nausea/vomiting
4 (4.5%) -
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Vaginitis
3 (3.4%) 1 (1.1%)
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Cystitis
2 (2.25%) -
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Factors
Locoregional recurrence
OR (95% CI)
Distant metastasis
OR (95% CI)
Overall survival
OR (95% CI) Age (>50 vs. 30 vs. 30)* 3.4 (1.6-9.4) 1.1 (0.9-2.0) 3.6 (1.8-9.7)
FIGO (> IB vs. < IB) 1.7 (1.2-3.2) 3.9 (1.4-7.6) 3.6 (1.2-6.2) N (N1 vs. N0)* 1.1 (0.9-2.0) 1.1 (0.89-1.9) 1.8 (1.2-2.2)
ogy (endometrial vs. non-endometrial)* 1.2 (1.1-2.1) 2.3 (2.0-5.5) 4.2 (3.8-8.2) Grade ( > G2 vs. < G2)* 0.9 (0.8-1.1) 0.8 (0.6-1.1) 0.8 (0.7-1.1)
Tumor size ( > 5 cm vs. < 5 cm)* 0.9 (0.8-1.1) 4.2 (3.9-9.2) 3.8 (3.2-8.9) LVSI ( present vs. absent)* 3.3 (2.5-10.2) 1.1 (0.9-2.0) 1.1 (0.9-1.2) SCM (present vs. absent)* 0.9 (0.8-1.1) 1.0 (0.9-1.1) 1.1 ((0.9-1.2)
ER/PR (present vs. absent)* 0.9 (0.8-1.1) 1.1 (0.8-1.9) 1.1 (0.9-1.2) Elevated CA-125 (Yes vs. No)* 1.1 (0.9-1.2) 1.1 (0.9-2.0) 1.1 (0.9-1.2)
Adjuvant CT (No Vs. Yes)* 1.1 (0.9-1.1) 2.3 (1.8-7.2) 1.9 (1.4-3.2) juvant RT dose ( 50.4 Gy vs. 45 Gy)* 1.1 (0.9-1.2) 1.1 (1.0-1.2) 0.9 (0.9-1.1)
Cox Proportional Hazard analysis of prognostic factors on Locoregional, distant control and overall survival
Factors
Locoregional recurrence
OR (95% CI)
Distant metastasis
OR (95% CI)
Overall survival
OR (95% CI)
Age (>50 vs. 30 vs. 30)*
3.4 (1.6-9.4)
1.1 (0.9-2.0)
3.6 (1.8-9.7)
FIGO (> IB vs. < IB)
1.7 (1.2-3.2)
3.9 (1.4-7.6)
3.6 (1.2-6.2)
N (N1 vs. N0)*
1.1 (0.9-2.0)
1.1 (0.89-1.9)
1.8 (1.2-2.2)
Histology (endometrial vs. non-endometrial)*
1.2 (1.1-2.1)
2.3 (2.0-5.5)
4.2 (3.8-8.2)
Grade ( > G2 vs. < G2)*
0.9 (0.8-1.1)
0.8 (0.6-1.1)
0.8 (0.7-1.1)
Tumor size ( > 5 cm vs. < 5 cm)*
0.9 (0.8-1.1)
4.2 (3.9-9.2)
3.8 (3.2-8.9)
LVSI ( present vs. absent)*
3.3 (2.5-10.2)
1.1 (0.9-2.0)
1.1 (0.9-1.2)
SCM (present vs. absent)*
0.9 (0.8-1.1)
1.0 (0.9-1.1)
1.1 ((0.9-1.2)
ER/PR (present vs. absent)*
0.9 (0.8-1.1)
1.1 (0.8-1.9)
1.1 (0.9-1.2)
Elevated CA-125 (Yes vs. No)*
1.1 (0.9-1.2)
1.1 (0.9-2.0)
1.1 (0.9-1.2)
Adjuvant CT (No Vs. Yes)*
1.1 (0.9-1.1)
2.3 (1.8-7.2)
1.9 (1.4-3.2)
Adjuvant RT dose ( 50.4 Gy vs. 45 Gy)*
1.1 (0.9-1.2)
1.1 (1.0-1.2)
0.9 (0.9-1.1)
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Toxicity profile
Grade 1 and 2 acute side effects : 4 patients (3.42%) had grade 3 enteritis.
Systemic chemotherapy, Febrile neutropenia :
2 patients (5.7%) Late toxicity :
1 patient who presented with sub-acute intestinal obstruction which was managed conservatively.
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Locoregional control, distant control and overall survival ratesEndometrial carcinoma:
LRC, DMC, DFS and OS were 80.9%, 69.3%, 70.6% and 71.1% respectively.
5 patients developed locoregional recurrences (in-field).
1 patient had vaginal recurrences (1.7%)
3 patients had pelvic nodal recurrence (5.1%).
8 patients had Distant metastases (13.6%) 2 patients (3.4%) had simultaneous locoregional failures.
Lungs (4 patients),
liver (1 patient) and
para-aortic lymph nodes (3 patients)
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Carcinosarcoma:
LRC, DMC, DFS and OS were 87.1%, 16.3%, 17.9% and 16.3% respectively.
Despite excellent LRC rates, majority of patients (59%) developed metastases lungs (6 patients), bones (3 patients) brain (one patient).
carcinosarcoma and absence of chemotherapy are poor prognostic factors for DMC.
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Leiomyosarcoma:
LRC, DMC, DFS and OS were 100%, 45%, 64.3% and 60%
respectively.
4 patients developed distant metastasis;
lungs (3 patients and bones (1 patient).
Tumor size above 5 cm was found important prognostic
factor for DMC.
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Discussion: Postoperative pelvic radiation therapy (PORT) (IMRT) in
uterine malignancies were not studied in Saudi population previously.
endometrial carcinoma and carcinosarcoma were in obese with median BMI > 30 Kg/m2 and associated with poor LRC and OS
(leiomyosarcoma and carcinosarcoma) was significantly high in our study as compared to reported western literature
LRC, DMC, DFS and OS for endometrial carcinoma and sarcoma were equal to other studies .
Tumor size above 5 cm was found important prognostic factor for DMC and OS in leiomyosarcoma .
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Discussion:Incorporation of adjuvant chemotherapy prior to adjuvant radiotherapy was associated with reduced LRC (p value 0.003)
Minimal impact of additional adjuvant chemotherapy on distant control, dfs and os.
The possible explanation : delayed pelvic radiotherapy,
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Conclusion:
Saudi women with endometrial cancers were found
more obese with BMI > 30 k/m2 and are associated with
co-morbidities, which warrant a national level obesity
awareness campaign.
Our results did not support the incorporation of sequential chemotherapy in adjuvant care of early endometrial carcinoma due to poor LRC .
Five Years Treatment Outcomes of Postoperative Radiotherapy in Saudi Women with Uterine CancersIntroduction:PORTEC-1 trialUterine sarcomas :PURPOSE: METHODS AND MATERIALS: Postoperative Radiation therapy techniques:Adjuvant chemotherapy:Toxicity and Response evaluation: RESULTS: Slide Number 11RESULTS: RESULTS: Slide Number 14Slide Number 15Slide Number 16Slide Number 17Slide Number 18Slide Number 19Slide Number 20Slide Number 21Toxicity profileLocoregional control, distant control and overall survival ratesEndometrial carcinoma:Carcinosarcoma:Leiomyosarcoma:Discussion:Discussion:Conclusion: