This study evaluated treatment outcomes of 89 Saudi women with uterine cancers who received postoperative radiotherapy between 2007-2012. It found:
1. Five-year locoregional control rates were 80.9% for endometrial cancer, 87.1% for carcinosarcoma, and 100% for leiomyosarcoma.
2. Distant metastases control at 5 years was 69.3% for endometrial cancer, 16.3% for carcinosarcoma, and 45% for leiomyosarcoma.
3. Overall survival at 5 years was 71.1% for endometrial cancer, 16.3% for carcinosarcoma, and 60%
2. 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,
3. 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).
4. 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
5. 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
6. METHODS AND MATERIALS:
Medical records review.
2007 and 2012
FIGO IB- IVA
TAH-BSO +/- PLND.
All uterine cancers who received PORT post TAHBSO.
45-50.4 Gy in 25-28 fractions+HDR .
Data :
The safety profile,
Pathology & Radiology
Locoregional control (LRC)
Distant metastases control (DMC)
Overall survival (OS)
7. 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 .
8. Adjuvant chemotherapy:
Indications :
Papillary serous
Clear cell types
Carcinosarcoma
FIGO III, IVA endometrial cancers.
Before starting radiation therapy.
4 cycles of Paclitaxal (175mg/m2) and Carboplatin
(350 mg/m2) every 21 days.
9. 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.
10. 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
12. RESULTS:
LRC :
80.9%, for leiomyosarcoma
87.1% for carcinosarcoma
100%, for endometrial carcinoma
DMC :
69.3% for endometrial
45% for leiomyosarcoma
16.3% for carcinosarcoma
13. RESULTS:
Five-year OS rates :
71.1%, for endometrial
60% for leiomyosarcoma
16.3%, for carcinosarcoma
Acute grade 3 and 4 proctitis/enteritis
seen only in 4 patients (4.5%) and late
toxicities were minimal.
14. 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
15. Factors
Locoregional
recurrence
OR (95% CI)
Distant
metastasis
OR (95% CI)
Overall survival
OR (95% CI)
Age (>50 vs.<50)* 0.9 (0.9-1.50) 1.1(0.8-2.0) 1.1 (0.9-1.9)
Cormorbids ( Yes vs. No)* 0.8 (0.6-0.99) 0.8 (0.7-1.1) 1.8 (1.1-2.3)
BMI kg/m2
( > 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
16.
17.
18.
19.
20.
21.
22. 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.
23. Locoregional control, distant control and
overall survival rates
Endometrial 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)
24. 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.
25. 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.
26. 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 .
27. 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,
28. 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 .
