Rec ref gct
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This document discusses management of recurrent and refractory germ cell tumors. It finds that while poor-risk germ cell tumors have only a 45% long-term survival with initial chemotherapy, salvage regimens can achieve disease-free status in around 50% of cases. High-dose chemotherapy followed by stem cell transplant also shows promise, with some studies finding long-term survival rates of 30-50%. Post-chemotherapy surgery can further increase long-term survival rates to over 50% for those with residual tumors. However, late relapses occurring more than two years later generally have a poorer prognosis and lower response to chemotherapy.
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Rec ref gct
- 1. Management of recurrent and refractory germ cell tumors
- 2. • Good risk GCTs achieve a very good long term cure approaching 95% • Poor-risk GCTs require four cycles of BEP that attains an approximately 45% long-term disease-free survival • A significant proportion are either refractory to the platinum first line chemo regimens,,or the relapse early
- 3. Standard guidelines for advanced disease
- 4. Management for residual disease
- 5. What does the NCCN say?
- 6. Therapy for early relapse and refractory disease Salvage regimens…
- 7. VeIP/VIP
- 8. Results.. • N : 135 • 49.6 % pts achieved dis. free status after chemotherapy ( with or without surgery for residual) • 32% are alive • 23.7% are continually free of disease • All pts had a minimal f/u of 6 yrs from entry into study
- 9. Variable No of pts Percentage % Assessable 56 n/a Response CR 20 36 IR 36 64 Status.. Alive disease free 19 34 Alive with disease 4 7 Dead 33 59 Alive, continuously disease free 13 23
- 10. • N : 189 ( 1985 to 2012) • CR: 18.5% • Marker normalization: 35.4% • 2yr PFS: 34.3% • 5yr OS: 42.1%
- 16. Prognostic factors with salvage chemo
- 19. Outcomes with second-line salvage therapy for recurrent germ cell tumors. Sonpavde G et al. The Oncologist 2007;12:51-61 ©2007 by AlphaMed Press
- 20. Role of HDCT and auto BMT?
- 22. • Pts included: – Those , who received high dose chemotherpay as salvage and has not progressed within 4 weeks after the last dose • Stem cells were harvested with GCSF stimulation • High dose chemo was given with – Carboplatin 700mg/m2 – Etoposide 750mg/m2 – On days -5, -4 and -3 of stem cell infusion
- 26. German data.. • N : 74pts • ORR : 63% with CR in 31% • EFS of sensitive disease at 2 yrs: 50% • Only one pt of 23 who had refractory disease had 7mo event free survival • OS at 2 yrs: 44%
- 27. Other European data.. • N: 150 • Median follow up : 55months • EFS: 29% • OS: 29%
- 28. • N: 80 • 3 # TIP followed by HDCT • 70% responded to TIP • 66% responded to HDCT • 3 yr OS: 30% • 3 yr EFS: 25%
- 29. Italian experience. • N : 84 • Median follow up 46months • DFS rates: – Good risk: 69% – Int. risk: 13% – Poor risk: 0%
- 30. High dose chemo: blessing or a curse??
- 31. Design.. • 280 pts • Pts refractory to platinum based chemo were excluded four cycles of cisplatin, ifosfamide and etoposide (or vinblastine) three such cycles followed by transplant
- 34. Roles of surgery?? • N: 125 pts who underwent postchemotherapeutic resention • Mean f/u: 120monthns • 57% long term survivors who had raised TM • Conslusion: salvage surgery results in long term survival of more than 50%
- 35. • N : 16pts • Six patients (37%) are alive and free of disease at a mean of seventy-four months following surgery (range 20 to 145 months). • Five had RP disease only. • Ten patients died of disease at a mean of eight months postoperatively (range 5 to 21 months).
- 38. • N: 114 • 5 yr OS: 53.9% • Sixty-one patients (53.5%) are alive with a medium follow-up of 72 months • Retroperitoneal pathology revealed – germ cell cancer in 53.5% of patients, – teratoma in 34.2% of patients, and – fibrosis in 12.2% of patients, with – 5-year survival rates of 31.4%, 77.5%, and 85.7%, respectively (P < .0001).
- 39. Surgery after HDCT and auto BMT • Complete resection in 93% pts • Pts with viable tumor had poor survival comapred to teratomas or fibrosis
- 41. Therapy of late relapses • Defn: relapses occurring after 2 yrs and in the absence of a second primary tumor • Typically chemo refractory • Different disease biology
- 42. • N: 83 • Indiana university • Available specimens were investigated for expression of the transcription regulator FoxD3 and apurinic/apyrimidinic endonuclease and the presence of chromosome 12 abnormalities.
- 43. Results… • Forty-three of 49 patients who underwent surgery were rendered disease free (NED), and 20 (46.5%) remain continuously NED • Thirty-two patients received chemotherapy, but only six (18.8%) obtained a complete remission. • Eighteen of these 32 patients were successfully rendered NED by postchemotherapy surgery, and 12 remain continuously NED.
- 44. Overall.. • 69 of the 81 treated patients (85.2%) ultimately achieved an NED state, and – 38 (46.9%) remain continuously NED with median follow-up from LR therapy of 24.5 months (range, 1 to 83 months), – whereas nine other patients are currently NED after therapy for subsequent relapses – Conclusion on moleular markers could not be made i/v/o low no. of samples tested
- 45. • Follow up of 530pts • 25 cases of late relapse identified • Risk was lower with good risk pts
- 49. • Median survival 23.9mo • Median follow up 50.3months • Only 9 survivors • CRs were observed with only TIP regimen
- 50. To summarize.. • Refractory disease and early relapse to be managed in same lines with salvage chemo +/- surgery • HDCT with auto BMT also has shown promising results • Later relapse: – Poor prognosis – Surgical resection whenever feasible – Chemo has poor outcomes
Editor's Notes
- #20: Outcomes with second-line salvage therapy for recurrent germ cell tumors