Portec trial ppt

PORTEC TRIAL

1. PORTEC TRIAL DR SAILENDRA NARAYAN PARIDA SENIOR RESIDENT DEPT.OF RADIOTHERAPY MAULANA AZAD MEDICAL COLLEGE

2. The Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) trial (1990-1997) was among the first to randomly compare pelvic external-beam radiotherapy(EBRT) to no additional treatment (NAT). Between 1990 and 1997, 715 patients P elvic external-beam radiotherapy (EBRT) or no additional treatment (NAT ) Median follow-up was 13.3 years .

3. ELIGIBILITY CRITERIA INCLUSION CRITERIA Women of any age with a WHO performance score 0 to 2 Endometrial adenocarcinoma stage I, grade 1 with deep (50%) myometrial invasion ; grade 2 with any invasion; or grade 3 with superficial (50 %) invasion were eligible . EXCLUSION CRITERIA History of invasive cancer(except for basal cell carcinoma of the skin) Previously received chemotherapy,hormonal therapy, or radiotherapy. The interval between surgery and radiotherapy had to be less than 8 weeks. INFORMED CONSENT WAS OBTAINED FROM ALL PATIENTS.

4. PRIMARY ENDPOINTS Locoregional recurrence and overall survival. SECONDARY ENDPOINTS Treatment morbidity and survival after relapse.

5. Surgery consisted of total extrafascial hysterectomy and bilateral salpingo-oophorectomy without lymphadenectomy (only biopsy of any suspicious lymph nodes)

6. RADIOTHERAPY TECHNIQUE Pelvic EBRT was administered with the target volume including Parametrial tissues Proximal two thirds of the vagina Lymphatic drainage regions along the internal iliac vessels up to the promontory. The superior field border was at the L5-S1 disc. Total dose was 46 Gy with 2 Gy daily fractions,5 fractions per week,23#. The median energy used was 10 MV photons. The radiotherapy technique consisted of anteroposterior-posteroanterior fields in 101 patients, a four-field box technique in 177 patients , and a three-field technique in 61 patients.

7. FOLLOW UP Patients were followed in their regional hospitals at least until 7 years after treatment. LRRs were defined as vaginal and/or pelvic recurrences. Distant failures included para -aortic lymph node metastases; abdominal relapses; liver, lung, and bone metastases; and diffuse metastatic disease . All statistical analyses were performed by using SPSS version 17.0

8. The risk factors identified were grade 3 age 60 years or older deep myometrial invasion . Patients with at least two of these three risk factors were designated high intermediate risk (HIR ). Patients with HIR features had a 20% risk of locoregional recurrence ( LRR) after NAT, which was reduced to 5% with EBRT.

9. RESULTS FIFTEEN-YEAR OUTCOMES The outcome analysis was done on data frozen on March 1, 2009. Of the 714 evaluable patients, 48 patients were lost to follow-up (41 of them were lost after5 years of follow-up ). Median follow-up for patients alive was 13.3 years (range, 2.8 to 18.5 years ).

10. LRRS AT 15 YEARS 5.8% - EBRT Group 15.5% - NAT Group Among 50 LRRS in the NAT arm, 37 (74%) were located in the vagina.

11. OS RATE AT 15 YEARS 52% - EBRT Group 60% - NAT Group P=0.14

12. TOXICITY PROFILE

13. URINARY SYMPTOMS Compared with patients in the NAT arm, patients treated with EBRT reported significantly higher levels of urinary urgency (P=0.001), and of urinary incontinence, a higher need to remain close to the toilet,and more limitations in daily activities due to bladder symptoms.

14. BOWEL SYMPTOMS P atients treated with EBRT reported increased levels of diarrhea , fecal leakage, and more limitations in daily activities due to bowel symptoms(P=0.006).

15. There were no significant differences in vaginal symptoms, body image, lymphedema , lower back pain, or menopausal symptoms between the groups.

16. CONCLUSION PORTEC-1 trial (1990-1997) was among the first to randomly compare pelvic external beam radiotherapy(EBRT) to no additional treatment (NAT). It showed that EBRT provides a highly significant improvement of local control but without a survival advantage. It was concluded that in view of the absence of survival benefit, EBRT would be justified only for patients at relatively high risk of recurrence. Pelvic EBRT for Endometrial carcinoma is associated with long-term urinary and bowel symptoms , leading to lower physical functioning , even 15 years after treatment.

17. LIMITATIONS Impact of low-grade toxicity on HRQL are lacking in these trials, and follow-up of reported toxicity generally does not exceed 5 years . Conformal techniques are not used.

18. Randomised trial undertaken in 19 Dutch radiation oncology centres 427 patients with stage I or IIA endometrial carcinoma with features of high-intermediate risk were randomly assigned by a computer-generated system. The primary endpoint was vaginal recurrence. Secondary endpoints were locoregional recurrence (pelvic or vaginal, or both) distant metastases overall and disease-free survival treatment-related toxic effects and quality of life

19. The randomised PORTEC-2 trial was started to investigate whether VBT would be equally effective as EBRT in reduction of vaginal recurrence, with fewer treatment related toxic effects and improved quality of life . The study was undertaken between May 27, 2002, and Sept 25, 2006 . C linically suspicious pelvic or pariaortic lymph nodes were removed, but no routine lymphadenectomy was done.

20. ELIGIBILITY CRITERIA Patients with endometrial adenocarcinoma were eligible for the trial on the basis of the following features of H igh-intermediate risk : Age greater than 60 years Stage 1C grade 1 or 2 disease Stage 1B grade 3 disease Stage 2A disease,any age (apart from grade 3 with greater than 50% myometrial invasion)

21. HIGH RISK Non endometrioid type carcinoma IC grade 3 S tage IIB or higher.

22. EXCLUSION CRITERIA Serous or clear cell carcinoma Staging lymphadenectomy interval between surgery and radiotherapy more than 8 weeks History of previous malignant disease Previous radiotherapy,hormonal therapy,or chemotherapy P revious diagnosis of Crohn’s disease or ulcerative colitis.

23. RADIOTHERAPY TECHNIQUE The clinical target volume for EBRT consisted of The proximal half of the vagina Parametrial tissues Internal and external iliac lymph node region and the caudal part of the common iliac lymph node chain(up to 1 cm below the level of the promontory ) The planning target volume consisted of the clinical target volume with a 1 cm three dimensional margin . A dose of 46 Gy , with 2 Gy fractions, 5 times per week , was prescribed to the planning target volume.

24. Computerised treatment planning was done with three-dimensional conformal or multiple field techniques Brachytherapy was delivered with a vaginal cylinder, with the reference isodose covering the proximal half of the vagina. The dose was specified at 5mm distance from the surface of the cylinder .

25. BRACHYTHERAPY SCHEDULE DOSE FOR HDR 21 Gy in 3 fractions of 7 Gy , 1 week apart DOSE FOR LDR 30 Gy at 50–70 cGy /h DOSE FOR MDR 28 Gy at 100 cGy /h in 1 session

26. FOLLOW UP Patients were assessed by their radiation oncologist 2–4 weeks after completion of radiotherapy. F ollow-up visits to the gynaecologist and radiation oncologist were planned every 3 months in the first 2years, every 6 months until year 5, and then every year, up to 10 years.

27. All statistical analyses were done with SPSS(version 16.0 ). Data were frozen for analysis on May 19, 2009

28. No significant difference in 5-year locoregional recurrence, despite a higher rate of pelvic recurrence after VBT . No significant difference in OS and DFS

29. No significant difference in vaginal recurrence More pelvic recurrence with VBT than with EBRT

30. NO SIGNIFICANT DIFFERENCE IN LRR AND OS AT 5 YEARS

31. TOXIC EFFECTS G.I.TOXICITY Grade 1 and 2 gastrointestinal ( EORTC-RTOG small/large intestine) toxic effects increased significantly at completion of EBRT compared with VBT (EBRT 53·8 %[ 112/208] vs 12·6% [27/215]). This difference decreased with further follow-up and lost statistical significance after 24 months For patients assigned to VBT, gastrointestinal toxic effects remained at baseline level. MUCOSAL TOXICITY From 6 months onwards, grade 1–2 mucosal atrophy increased , with significantly more grade 2 atrophy after VBT than after EBRT

32. PORTEC-2 shows that patients at high intermediate risk, about 30% of all patients with endometrial cancer, can be safely treated with vaginal brachytherapy alone, with fewer side effects and improved quality of life. EBRT will thus be used only for the 15% of patients with high-risk or advanced disease.

33. CONCLUSION VBT is very effective in ensuring local control keeping to a minimum the risk of vaginal recurrence. VBT achieves excellent vaginal control and rates of locoregional recurrence. Overall survival , and disease-free survival that are similar to EBRT Quality of life and gastrointestinal toxic effects are significantly better with VBT. VBT should be the adjuvant treatment of choice for patients with endometrial carcinoma of high intermediate risk.

34. LIMITATIONS Number of patients is low that under powers the study Change in grade I and grade II diseases in central pathological review. 44% to 79% in grade I 44% to 9% in grade II 13% In Retrospect were ineligible for trial It did not consider LVSI in risk factors It underscored the role of pathologists in the diagnosis of carcinoma endometrium

35. PORTEC-3 Randomized Phase III Trial Comparing Concurrent Chemoradiation and Adjuvant Chemotherapy with Pelvic Radiation Alone in High Risk and Advanced Stage Endometrial Carcinoma:PORTEC-3 An international Intergroup trial Recruitment ended in Dec 31, 2013 Data not yet published. PORTEC-3, CKTO 2006-04, CME P06.031, version 12 April 2012

36. PORTEC-4 Postoperative Radiation Therapy for Endometrial Carcinoma Multicenter Randomised Phase III Trial Comparing Vaginal Brachytherapy (Two Dose Schedules) with Observation after Surgery A Dutch Gynaecological Oncology Group trial Recruitment will continue upto 5 years Result not yet published PORTEC-4, KWF-CKS UL2011-5336; CME P11.185; version 1.5.1, 09 May 2013

37. THANK YOU

38. THE LANCET • Vol 355 • April 22, 2000