rtincaovary-160504111103 (1).pptx RADIATION ONCOLOGY

CA OVARY

1. RADIOTHERAPY IN CARCINOMA OVARY 1

2. INTRODUCTION 2 Contemporary strategies Surgical exploration Staging, and cytoreduction Chemotherappy- most often platinum and paclitaxel based adjuvant chemotherapy Radiation therapy, known since 1912 to induce long term remission in certain patients with ovarian cancer. RT has largely been excluded from routine use now.

3. What NCCN says… 3

4. RADIATION IN PRIMARY OVARIAN CANCER 4 Methods- Localized pelvic radiation Abdominopelvic radiation Intraperitoneal radiocolloids In reviewing the utility of primary irradiation as a sole treatment modality in ovarian cancer, it is useful to discuss its role, separately in, Early stage Advanced stage

5. SIGNIFICANCE OF RT 5 Is there conclusive evidence that radiation therapy induces tumor cell kill in patients with ovarian cancer? Residuum Study End Point <2 cm >2 cm Dembo % 10 yr relapse free 38% 6% Martinez % 15 yr freedom from relapse 50% 14% Fuller % 10 yr relapse free 62% 0% Weiser % 10 yr survival 42% 10% Goldberg 6 yr survival fraction 0.41 — Thomas G. Dembo A: Integrating radiation therapy into the management of ovarian cancer. Cancer 71:1710–8, 1993

6. CT Vs RT How do the results of APRT compare with those achieved with conventional chemotherapy? No head to head trials between APRT Vs Paclitaxel based chemotherapy. 6

7. CT Vs RT How do the results of APRT compare with those achieved with conventional chemotherapy? No head to head trials between APRT Vs Paclitaxel based chemotherapy. 7

8. Someone had thought for 8 Prospective evaluation of APRT versus cisplatin chemotherapy Stage IA/B grade 2 or 3; stage IC through FIGO Stage IIA/B through EORTC END POINTS= SURVIVAL and QOL. However, because the survival rate in this subgroup of patients is 80% or better at 5 years, conclusions regarding these endpoints are years off. A. Files et al , European Journal of Cancer Part A. 1997;33(1):12- 19.

9. CT+RT 9 N= 28 Stage III or IV epithelial ovarian carcinoma. 4 X Cyclophosphamide and Hexamethylmeamine A/W 4 X concurrent cisplatin, whole abdominal radiotherapy, and intraperitoneal Misonidazole. The entire treatment program lasted 6 months. This outcome was no different than the previous experience with combination chemotherapy(NONCISPLATIN) performed by the same group. CR 50% RESPONSE RATE 61% pCR 18% MEDIAN SURVIVAL 15.2 MONTHS

10. WART AS CONSOLIDATION THERAPY 10 Rationale- 40% to 60% of patients achieving a pCR after chemotherapy ultimately recur and succumb. Consolidation Regimens Additional intravenous chemotherapy Intraperitoneal chemotherapy Intraperitoneal radiocolloids Intraperitoneal immunoconjugates ( Cederkrantz E et al, Int J Radiat Oncol Biol Phys. 2015 Nov 1;93(3):569- 76. ) Hormones High dose chemotherapy Abdominopelvic RT would be a reasonable choice to affect this recurrence rate, if given after primary induction chemotherapy. ( Fuks Z et al.Int J Radiat Oncol Biol Phys 8: 903, 1982 . & Mychalaczak B. Hematol Oncol Clin North Am 6: 895, 1992. Thomas G. Gynecol Oncol 51: 97, 1993 )

11. Game changer 11 Introduction of Cisplatin almost closed the trials of radiotherapy in Ovarian carcinoma. In this Platinum era, very few prospective trials are there for RT as consolidation therapy. Benefit from consolidation depends on residual tumor size.

12. Swedish Norwegian Ovarian Cancer Study In this latter stratification, no difference in survival was demonstrated. In the former, however, a significant improvement in disease free survival was noted for abdominal pelvic radiation therapy, although follow up is premature. N= 172 4 X CDDP & DOXO SECOND LOOK LAPARO- TOMY RESIDUAL NON or MICRO MACRO (74) CHEMO 12 APRT OBSER APRT CHEMO

13. BenBaruch and colleagues In this trial, no significant difference was observed between the treatment arms initially; however, in this updated report with now 5years of minimum followup, a nonsignificant trend to poorer survival was seen in the APRT arm In addition, these authors report that survival after secondary recurrence was reduced significantly in those patients receiving APRT as their initial salvage regimen. BenBaruch et al. Eur J Gynecol Oncol 15: 272, 1994 N= 37 SECOND LOOK LAPARO- TOMY INTRAPERITONEAL CDDP , THIOSULPHATE 13 APRT (N= 19)

14. Pickel et al ( Gynecol Oncol 68:119 (abstract 192), 1998 ) Of the 64 patients randomized, 58 had stage III or IV disease at presentation. PFS at 10 years was significantly higher in APRT arm (50% vs. 30%, p = 0.012). OS at 10 years was significantly higher (62% vs. 38%, p = 0.029) in the APRT arm. Subset analysis of the stage III/IV patients was comparable. N= 64 FIGO- IC  IV MAXIMAL CYTOREDUCTIO N 6 X CARBO EPIRUBICIN PREDNIMUSTINE NO RESIDUAL APRT 14 OBSER

15. Recently 15

16. A retrospective analysis n= 27 for IFRT, n= 14 for NIFRT (control cohort) Tumour volume- directed IFRT for localized extraperitoneal recurrences (either as consolidation after cytoreductive surgery (CRS) or as attempted salvage if unresectable) All patients were heavily pretreated with multiple chemotherapy Involved field radiation therapy was primarily with external beam (median dose, 50.4 Gy). Technique- 3- dimensional conformal techniques in over half the patients with the remaining receiving 2-dimensional RT. Local recurrence- free survival (LRFS) was defined as freedom from in- field recurrences and was considered as a measure of effectiveness of radiotherapy 16

17. 17

18. Of 27 patients, 17 had optimal CRS before RT. 18 None of the NIFRT patients survived beyond 5 years from initiation of salvage chemotherapy. Yahara et al , maximal benefit in tumour size less than 3 cm. ( J Radiat Res . 2013;54:322–329 ) 5 years 10 years LRFS 70% 60% OS 30% 19% DFS 33% 20%

19. Conclusion on WPRT as Consolidation therapy 19 Toxicity in this setting is significant. Patients without any residual disease will have more benefit. It will be very premature to comment on survival data from these trials. Presented data are still inconclusive, in spite that we can try IFRT in highly selected patients.

20. Salvage WPRT in Epithelial Ovarian Cancer 20 Reddy et al . IntJ Radiat Oncol Biol Phys 27: 879, 1993 Cases who have failed to one or more chemotherapeutic regimens. (N= 30) 2 groups- with microscopic(n=16) and with macroscopic(n=14) residual disease. Subjected to WART (2500 cGy) f/b pelvic and paraaortic boost (2500 cGy) Only 2 patients were unable to complete the planned therapy. Another 26% of the patients required interruption of the therapy secondary to hematologic toxicity but eventually completed the treatment.

21. With an overall median follow- up of 14 months 56% of the patients remain alive. Two- year actuarial survival and recurrence- free survival rates are 47 and 32%, respectively. The survival and recurrence- free survival rates for the group with microscopic residual disease- -61 and 33%, respectively-- are better than those for the patients with macroscopic residual disease- - 36 and 18%. The abdominopelvic cavity was the first site of failure. In spite of the higher doses, pelvic failure alone or as a component occurred in 54% of the patients. Small bowel obstruction necessitating surgical intervention as a complication of therapy was seen in 13% of the patients. 21 Conclusion Whole abdominal radiation is unlikely to benefit those patients with macroscopic disease , and only those patients with localized microscopic pelvic disease stand to gain from this treatment.

22. Indications of RT 22 In good risk patients with stage I, grade I disease, adjuvant RT not required. For patients with macroscopic disease in the abdomen and bulky disease in the pelvis (gross stage III and IV), RT is not a curative form of treatment. Maximum benefit of post op RT is in patients with small volume (< 2 cm) residuum in the pelvis and without macroscopic disease in abdomen in salvage. As a consolidative treatment in bulky post op residuum cases. In palliative intent in cases of refractory or recurrent cases and also in cases of metastases.

23. Radiotherapy 23 Now it is a history for routine use, unless otherwise specified. Target - Whole abdominal cavity and pelvis. Patient position- Supine/ Prone Portals- AP/PA Field borders for WART Superior- 1.5 to 2 cm (above diaphragm) Inferior- inferior border of obturator foramen Lateral- whole peritoneum with a margin of subcutaneous tissue Techniques Moving strip technique (MST) ( Delclos, 1963 ) Martinez technique/ Open field technique ( Martinez et al. J Clin Oncol 3:901- 902, 1985 ) Modified Martinez technique.

24. Techniques MST Dose Small fraction size 100- 125 cGy daily is ideal for whole abdominal field. ( Princess Margaret Hospital, Toronto, Canada, 1976 ) At PMH- 2500- 2750 cGy WART f/b 2000- 2250 cGy boost to Pelvis. 25- 30 Gy in 20# over 4 weeks + Pelvic Boost 20 Gy/ 10# over 2 weeks. Both kidneys are shielded from posteriorly with 2 HVL and right half of liver is shielded with 1 HVL from both AP/PA. 24

25. Techniques MARTINEZ Doses WART- 30 Gy in 20 # over 4 weeks the Pelvic boost in phase I, 9 Gy in 5#, in Phase II (T- Field) 12 Gy in 8# Full thickness kidney shield applied posteriorly after 10 Gy and a 50% transmission block for liver after 15 Gy in both AP/PA. Total liver dose 22.5 Gy in 23 #, total kidney dose 20 Gy in 20 #. 25

26. Techniques 26 Modified Martinez Field and borders remain the same. Except that the para- aortic boost field is omitted. Used in cases with suspected bowel compromise WART- 22 Gy/17# Diaphragmatic boost- 15 Gy Pelvic Boost- 24 Gy by 4 field or box technique

27. Radiotherapy Pelvic field borders- Superior- L5- S1 junction Inferior- lower border of obturator foramen Laterally- 1.5 cm beyond the true boney pelvis. 27

28. Complications of RT 28 Acute- Small bowel symptoms Nausea & vomiting Bone marrow suppression Late- Adhesions Perforation Peritonitis

29. RADIOACTIVE CHROMIC PHOSPHATE (P- 32) 29 Pure beta emitter. Improved tumour penetration. Less hazard to treating personnel. Has been used since early 1950s. Intraperitoneally at a dose of 10 to 20 mCi mixed in 1 to 2L of saline. Before instillation of the active P- 32, a technetium scan usually is performed to determine whether distribution of the colloid in the abdominal cavity is satisfactory.

30. Radioactive Chromic Phosphate in Primary Therapy 30 Several investigators have studied this therapy in combination with other modalities, such as chemotherapy (nonplatinum) or pelvic radiation. because of significant complications, they have concluded that this agent is best considered singly. Soper J, Wilkinson R, Bandy L et al: Intraperitoneal chromic phosphate P32 as salvage therapy for persistent carcinoma of the ovary after surgical restaging. Am J Obstet Gynecol 156: 1153, 1987

31. As consolidation therapy 31 It is clear that volume of residual disease is an important predictor of response. No much improvement in survival. Toxicity is high, some require surgical intervention.

32. Palliative therapy 32 For stage IV patients, and in metastatic cases Dose and field depends on the site of the disease.

33. Reference 33 1. 2. NCCN version Devita Clinical Oncology 10 th edition 5. Text book of Radiation Oncology, principles and practice- Rath & Mohanty