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.
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 息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