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Role of primary chemoradiation in esophageal carcinoma

Role of primary chemoradiation in esophageal carcinoma. ANDREW NG PRINCE OF WALES HOSPITAL. Cancer of the esophagus. Often presenting as advanced disease 40-50% stage III disease among pre-operative cases Poor 5-year survival after primary resection 10-15% for stage III tumors

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Role of primary chemoradiation in esophageal carcinoma

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  1. Role of primary chemoradiation in esophageal carcinoma ANDREW NG PRINCE OF WALES HOSPITAL

  2. Cancer of the esophagus • Often presenting as advanced disease • 40-50% stage III disease among pre-operative cases • Poor 5-year survival after primary resection • 10-15% for stage III tumors • Esophagectomy remains a major undertaking • Mortality 4-10% • Morbidity 26-41%

  3. Neo-adjuvant chemoradiation • Advent of neo-adjuvant chemoradiation • Chemotherapy to treat micro-metastasis • Radiotherapy for improved local control • Many RCTs compare neoadjuvant chemoRT to surgery alone • Limited by small sample size • Nearly all suggest no benefit

  4. Neo-adjuvant chemoradiation Neo-adjuvant chemoRT: 623 Surgery alone:586 • Val Gebski et. al: Lancet Oncol 2007;8:226-34

  5. Neo-adjuvant chemoradiation n = 366 • Improvement in median overall survival after neo-adjuvant chemoRT • 24 months to 49.4 months (Hazard ratio of 0.657; p=0.003) • Improvement in rate of clear resection margins • 92% to 69% (p<0.001) • Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer • - Van Hagen et. al.: NEJM 2012; 355:2074-84

  6. Primary chemoradiation Advent of primary chemoradiation in advanced tumors • High rates of complete response to neo-adjuvant treatment • ~25% with complete patho-histologic remission • High operative mortality after neo-adjuvant chemoRT • 10 -16% • Good survival after primary chemoRT • 27% 5 year survival • In comparison with primary radiotherapy

  7. Primary chemoradiation • Chemoradiation with curative intent • Higher doses of radiotherapy • Total dose of over 50Gy • Prolonged course of chemotherapy • usually Cisplatin and 5-Fluorouracil • Mostly studies involve advanced disease • Stage III disease

  8. Primary chemoRT vs Surgery alone

  9. Primary chemoRT vs Surgery alone 2 year Overall survival: Esophagectomy: 54.5% Chemoradiation 58.3% n = 81 Chiu P. W. Y. et. al: J Gastrointest Surg 2005;9:794-802

  10. Primary chemoRT vs Surgery alone Median disease free survival Esophagectomy: 24 months ChemoRT: 20 months n = 81 Chiu P. W. Y. et. al: J Gastrointest Surg 2005;9:794-802

  11. Primary chemoRTversus NeoadjuvantchemoRT

  12. Primary chemoRT versus NeoadjuvantchemoRT n = 172 • Overall survival at 2 years similar between groups • NeoAdjv: 39.9%; ChemoRT: 35.4% • Median survival similar • NeoAdjv: 16.4; ChemoRT: 14.9 Stahl M. et. al: J Clin Oncol 2005; 23:2310-2317 Primary chemoRT Neoadjuvant chemoRT

  13. Primary chemoRT versus NeoadjuvantchemoRT • 2 year freedom from progression significantly better in surgery arm • Neoadjv: 64%; ChemoRT: 40.7%;Hazard ratio for ChemoRT vs Neoadjv: 2.1, p=0.003 n = 172 Stahl M. et. al: J Clin Oncol 2005; 23:2310-2317 Primary chemoRT Neoadjuvant chemoRT

  14. Primary chemoRT versus NeoadjuvantchemoRT Tumor response found to be an independent prognostic factor in cases of SCC of the esophagus • Patients with tumor response had 3 year survival of >50% regardless of treatment group • Non-responders • After surgery: 3 year survival of 17.9% • After chemoRT group: 3 year survival of 9.4% Stahl M. et. al: J Clin Oncol 2005; 23:2310-2317

  15. Primary chemoRTversus NeoadjuvantchemoRT

  16. Primary chemoRT versus NeoadjuvantchemoRT 259 patients randomized:129 arm A130 to arm B 66Gy 30Gy 57% responders to induction 45Gy 46Gy Bedenne L et. al.: J Clin Oncol 2007; 25:1160-1168

  17. Primary chemoRT versus NeoadjuvantchemoRT • Similar two year survival • Surgery: 34% • ChemoRT: 40% • Hazard ratio of ChemoRT vs Surgery: 0.9, p=0.44 • Similar median survival • Surgery: 17.7m • ChemoRT: 19.3m Bedenne L et. al.: J Clin Oncol 2007; 25:1160-1168

  18. Primary chemoRT versus NeoadjuvantchemoRT More locoregional relapse after primary chemoradiation (p=0.0014) • Surgery: 33.6% • ChemoRT: 43.0%

  19. Morbidity and mortality

  20. Morbidity and mortality • Treatment related mortality significantly higher in surgery group • 12.8% vs 3.5% (p=0.03) • Stahl M. et. al: J Clin Oncol 2005; 23:2310-2317 • 9% vs 1% (p=0.002) in 3 months from randomization • Bedenne L et. al.: J Clin Oncol 2007; 25:1160-1168 Mortality from chemoRT due to neutropenic infections Mortality from surgery due to complications including leaking anastomosis, pneumonia

  21. Mortality and morbidity Bedenne L et. al.: J Clin Oncol 2007; 25:1160-1168

  22. Quality of Life

  23. Quality of life 2-year follow-up subgroup Bonnetain et. al.: Ann Onc 2006; 17: 827–834

  24. Conclusion • Primary chemoRT for locally advanced Ca esophagus is at least as good as surgery alone • Overall survival • Locoregional control • When compared to neo-adjuvant chemoRT followed by surgery, primary chemoRT provides • Possibly similar overall survival • Inferior locoregional control

  25. Remaining questions • Optimal timing and dosage of primary chemoRT • Variance between trials • Role in Adenocarcinomas • Role in early esophageal tumors • Monitoring response - when to abandon? • Role of induction chemoRT

  26. The End

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