Post-operative Radiotherapy for Esophageal Cancer
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The document discusses evidence from randomized trials and studies on the use of postoperative radiotherapy and chemoradiotherapy for esophageal cancer. It summarizes several key trials that have shown postoperative radiotherapy improves overall survival for stage III and node-positive esophageal cancer patients by decreasing locoregional recurrence rates. The largest trial discussed found that postoperative chemoradiotherapy improved both overall and relapse-free survival compared to surgery alone for gastric adenocarcinoma patients. Non-randomized studies also suggested benefits of postoperative chemoradiotherapy over radiotherapy alone or surgery alone for esophageal squamous cell carcinoma.
Post-operative Radiotherapy for Esophageal Cancer
- 1. Post-operative Radiotherapy for Esophageal Cancer Parag Sanghvi, M.D., M.S.P.H. Department of Radiation Medicine Esophageal Care Conference
- 2. Background 5 year OS for locally advanced esophageal cancers (T3 or above, N+) is dismal
- 3. Preoperative ChemoRT vs. Post-operative ChemoRT This has not been studied in a randomized trial head to head Prefer pre-operative chemoRT Allows for tumor downstaging R0 resection Complete pathologic response improves survival Feasibility and Patient compliance ? Earlier control of micro-metastatic disease Only 1 of 6 randomized trials have shown OS benefit to neoadjuvant chemoRT (Walsh)
- 5. Post-operative RT+/- Chemotherapy Data is primarily from Asia and Europe Most randomized trials have looked at Surgery + RT vs. Surgery alone No randomized trial has compared post-operative concurrent chemoRT to either chemotherapy or RT alone
- 6. Indications for Post-operative RT Standard Indications Positive Margins Gross Residual Disease Less Clear + LN + ECE on adenopathy
- 7. Current NCCN Guidelines for Post-operative Therapy
- 8. Randomized Trials Teniere et al Surg Gynecol Obstet . Aug 1991; 173(2): 123-30 ( France ) S+ RT vs. S Fok et al Surgery . Feb 1993; 113(2) 138-47 ( Hong Kong ) S + RT vs. S Xiao et al The Annals of Thoracic Surgery Feb 2003; 75(2): 331-336 ( China ) LN + S+ RT vs. S Macdonald et al NEJM . Sept 2001; 345:725-730 ( USA ) GE junction S + CRT vs. S
- 9. French trial – Post-operative Radiation for Esophageal SCCA 221 patients treated with “curative” resection Squamous cell histology; mid/distal location Post-op RT 45-55 Gy vs. Observation Post-op RT did not improve OS 5 y OS 19% (38% if node -; 7% if node + Locoregional failure decreased after RT: 30 % 15% Benefit significant in node negative patients: 35% LR failure vs. 10%
- 10. Hong Kong Trial – Postoperative RT for Esophageal cancer Single institution randomized trial, 130 patients Curative Resection 60 patients 30 S+ RT vs. 30 S Palliative Resection 70 patients 35 S + RT vs. 35 S RT dose/technique unknown
- 11. Hong Kong Trial - Results Overall Median Survival, All patients S + RT 8.7 months vs. S 15.2 months (p=0.02) Local Recurrence, Palliative Surgery patients S+ RT 20% vs. S 46 % (p=0.04) Local Recurrence, Curative Surgery S+RT 10% vs. S 13% Complications S+RT 37% vs. S 6% (p<0.0001) Intra-thoracic recurrence, All patients S+RT 4 patients vs. S 13 patients (p=0.01)
- 12. Chinese trial – Post-operative radiation for Esophageal SCCA Randomized to post-operative RT vs. observation; 495 patients 275 S, 220 S+ RT Most of mid thoracic esophagus (67%), T3 (69%) and 48% had + LN Margin status unknown
- 13. Chinese Trial – RT parameters RT Extended Field RT Included bilateral SCV, mediastinal and peri-gastric LN 60 Gy
- 14. Chinese Trial - Results 5 y OS S+ RT 41.3 % vs. S 37.1 % (p=0.45) LN – S+RT 52.8 % vs. S 51% (p=0.95) LN+ S+RT 29.2 % vs. S 14.7% (p=0.07) Stage II S+ RT 50.3 % vs. S 51.3 % (p=0.63) Stage III OS S+ RT 35.1% vs. S 13.1 % (p=0.003)
- 15. Chinese trial - Results Stage III
- 16. Chinese trial - Results LN + patients
- 17. Chinese Trial - Sites of Failure
- 18. Conclusions Post-operative RT improves OS in Stage III and potentially LN + patients Post-operative RT decreases risk of intra-thoracic LN recurrence and anastomotic recurrence
- 19. Macdonald trial – Post-operative chemoRT for GE junction/stomach adenoCA Randomized to post-operative chemoradiation vs. observation 556 patients; 20% GE junction tumors Stage IB – IV M0, negative margins Adenocarcinoma histology D2 dissection recommended 10% D2; 36% D1; 54% D0
- 20. Macdonald Trial - Treatment Schema Chemotherapy d 28 ChemoRT 2 cycles additional chemotherapy Chemotherapy 5FU + Leucovorin RT – 45 Gy/25 fx Tumor bed + Regional LN + 2 cm margin 64% completed chemoRT as planned
- 21. Macdonald Trial – Tumor Characteristics
- 22. Macdonald Trial Results 5 year Median Survival S+ CRT 36 months vs. S 27 months 3 y OS S+ CRT 50% vs. S 41% (p= 0.005) 3 y RFS S + CRT 48% vs. S 31% (p <0.001)
- 23. Macdonald Trial – Overall Survival
- 24. Macdonald Trial – Relapse Free Survival
- 25. Macdonald Trial – Sites of Relapse
- 26. Macdonald Trial - Conclusions Add chemoRT for GE junction adenoCA T3 or higher + LN + margins, + residual disease ? Selected T2 cases
- 27. Non Randomized Trials Liu HC et al. World J. Gastroenterology . 2005; 11(34): 5367-5372 S+ CRT vs. S + RT Bedard EL et al. Cancer Jun 2001; 91(12): 2423-2430 N1 patients S + CRT vs. S
- 28. Taiwan Study – Postoperative ChemoRT vs. RT for esophageal SCCA 60 patients; 30 patients in each arm T3/T4 N0/N1 M0 thoracic esophageal SCCA Surgery included En-bloc esophagectomy – sub-total resection of esophagus with bilateral 10 cm adjacent soft-tissue margin followed by proximal gastrectomy/porta hepatis LN dissection Cervical LN sampling Prospectively enrolled into post-operative chemoRT vs. RT alone
- 29. Taiwan study – RT parameters Treatment started within 3 weeks of surgery RT 40 Gy AP/PA followed by 15-20 Gy 3 D boost standard 1.8 Gy/fx Margins Sup / Inf 5 cm Elsewhere 3 cm Mean dose 58.32 Gy (50.4 – 59.4 Gy)
- 30. Taiwan study - Chemotherapy Chemotherapy 6 weekly cycles CDDP 30 mg/m2 during RT 4 weeks after chemoRT, additional adjuvant chemotherapy 4 cycles of CDDP 20mg/m2 + 5 FU 1000mg/m2 X 5 days bolus infusion
- 31. Taiwan study - Patient Characteristics
- 32. Taiwan study - Patient Characteristics
- 33. Taiwan Study - Results ChemoRT 30/30 received planned dose RT 15/30 received planned dose concurrent chemo; 10 received 4/6 weekly cycles; 5 received <4 cycles 15/30 received adjuvant chemotherapy RT 24/30 received planned dose RT Median follow-up 18 months
- 34. Taiwan Study - Results ChemoRT Mean survival 31.9 months 3 y/o OS 70% 3 y/o LRF 40% 3 y/o DF 27% RT Mean survival 20.7 months 3 y/o OS 33.7% 3 y/o LRF 60% 3 y/o DF 57% Treatment modality and tumor grade were significant on multi-variate analysis
- 35. Taiwan Study - Results
- 36. Taiwan Study - Results
- 37. Taiwan Study - ChemoRT complications Complications Anastomotic Stricture 36% Chronic Aspiration 33% Pneumonia 20%
- 38. Taiwan Study - Conclusions ChemoRT showed improved OS compared to RT alone in T3 or higher patients Improved overall survival compared to historical data for surgery alone
- 39. Canadian Study – Postoperative chemoRT in patients with N+ esophageal cancer Retrospective review of N1 patients – chemo RT vs. surgery alone; 70 patients 39 pts to chemoRT arm vs. 31 patients to surgery alone; in final analysis 38 pts. ChemoRT & 28 pts. Surgery alone Thoracic & GE junction tumors AdenoCA & Squamous histology T1-T4, all N1 Transhiatal esophagectomy
- 40. Canadian Study - Treatment Schema 2 cycles of chemotherapy RT with 3 rd & 4 th cycle of chemotherapy Chemotherapy CDDP 60 mg/m2 Continuous infusion 5-FU Epirubicin 50 mg/m2 in last 6 patients RT 50 Gy (36 Gy AP/PA followed by 14 Gy 3D planning)
- 41. Canadian Study - Patient Characteristics Patient characteristics and tumor characteristics well balanced between two groups No data on # LN + or ECE status provided
- 42. Canadian Study –Tumor Characteristics
- 43. Canadian Study - Results Median follow-up 19 months Surgery + ChemoRT Median DFS – 10.2 months Local Recurrence 13% Median Time to LR 22.2 months Median OS 47.5 months 5 y OS 48% Surgery Median DFS – 10.6 months Local Recurrence 35% Median Time to LR 9.5 months Median OS 14.1 months 5 y OS 0%
- 44. Canadian Study – Overall Survival
- 45. Canadian Trial - Conclusion Benefit of ChemoRT in node + patients
- 46. Additional abstracts Kurtzman SM et al. (ASTRO 1995) 192 patients Esophageal adenoCA Post-op RT with 5FU/Leucovorin & γ -Interferon 39% 3 y OS
- 47. Additional abstracts Kang HJ et al (ASCO 1992) Phase 2 trial ChemoRT 40-50 Gy CDDP + 5 FU 47% 20 month survival rate 93% LCR
- 48. What about post-op chemotherapy alone? 2 randomized Japanese trials Ando N et al. J of Thoracic and Cardiovascular Surgery . 1997; 114;204-205 Randomized study; 205 patients S + C vs. S alone Chemo – 2 cycles of Cisplatin (70 mg./m2) + Vindesine 5 y OS S + C 48.1 % vs. S 44.9% (p = NS) Ando N et al. JCO. Dec 2003; 21(24): 4592-4596 Randomized study; 242 patients Thoracic SCCA S+C vs. S alone Chemo – 2 cycles of Cisplatin (80 mg/m2) + 5 FU (800mg/m2/5 day infusion) 5 y OS 61 vs. 52 % (p=0.13);5 y DFS 55% vs. 45% (p=0.04); 5 y DFS in N + patients 52% vs. 38% (p=0.04) Significant nodal failure in S + C patients; role of RT??
- 49. Overall Conclusions Treatment decisions need to be individualized Pre-operative chemoRT preferable when needed Recognize the morbidity of neoadjuvant chemoRT; consider surgery first in resectable patients with marginal performance status Post-operative chemoRT for + margins, residual gross disease + LN locally advanced disease (T3 or higher) with – margins, - LN?
- 50. Acknowledgements Dr. John Holland Dr. Charles Thomas Dr. Tasha Mcdonald