Transcript CA Esophagus – Role of Chemoirradiation
CA Esophagus
–
Chemoirradiation Role of
WH Chan Pamela Youde Nethersole Eastern Hospital
Ca Esophagus
Incidence: 4.5 cases per 100,000 in one year in Europe 1 8th commonest cause of cancer death in 2011 in HK (4.8 per 100,000) 2 Squamous cell carcinoma Adenocarcinoma 1.
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Esophageal Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. M. Stahl; C. Mariette; K. Haustermans; A. Cervantes & D. Arnold, on behalf of the ESMO Guidelines Working Groups. Annals of Oncology 24 (Supplement 6), vi51-vi56, 2013 Hong Kong Cancer Registry
Surgery
High morbidity and mortality Worsened physical function, social function, long lasting deterioration in health-related quality of life 3 Recurrence Complete Resection may not be possible 3. Meta-analysis shows clinically relevant and long-lasting deterioration in health-related quality of life after esophageal cancer surgery. M. Jacobs; R.C. Macefield; R.G. Elbers; M.A.G. Sprangers. Qual Life Res (2014) 23: 1155-1176
• 286 patients had surgery alone • Median FU period: 49 months • 30-day mortality: 3.7% • Recurrence: - Stage I: 7.1%; Stage II/III/IV: 50.5% • 5 year disease free survival: - Stage I: 76.3%; Stage II/III/IV: 30.8%
Chemoirradiation
Introduced in 1980s 5-FU, cisplatin Radiation of 40-50 Gy Improves survival, complete resection rate Surgically not fit patient ?Increase surgical morbidity
20 RCTs were included 9 comparing neoadjuvant CRT vs surgery 8 comparing neoadjuvant chemotherapy vs surgery 3 comparing definitive CRT vs surgery
Neoadjuvant CRT vs surgery alone
9 RCTs included 1099 patients: 554 received neoadjuvant CRT, 545 received surgery alone Mean age 60.8
Surgery performed 2-8 weeks after CRT (mean 3 weeks) Median FU time: 10-98 months
R0 resection rate
p-value = 0.043
Morbidity
p-value = 0.363
30-day mortality
p-value = 0.692
Overall survival
p-value = 0.008
Conclusion
Neoadjuvant chemoradiotherapy improved R0 resection and overall survival, but does not increase post-op morbidity or mortality
Definitive chemoRT vs surgery
3 RCTs included All squamous cell carcinoma 512 patients: 252 received definitive chemoRT; 260 received surgery
Morbidity
p-value = 0.332
30-day mortality
p-value = 0.007
Overall survival
Conclusion
Definitive chemoRT has lower 30-day mortality compared with surgery, but overall survival is similar
Neoadjuvant chemotherapy vs surgery
Neoadjuvant chemotherapy improved R0 resection rate, but no improvement in overall survival
Definitive chemoirradiation
Efficacy Tolerance and toxicity Any new regimen
Traditionally is radiotherapy + 5-FU + cisplatin Cisplatin is difficult to administer as requiring prolonged hydration, nephrotoxic, emetogenic
Study period 2004-2011 Exclusion: Metastasis Contraindication to chemoRT: tracheoesophageal fistula, recent AMI, etc 131 patients in FOLFOX; 128 patients in 5 FU + cisplatin
Regimen
Radiotherapy: 50Gy in 25 fractions Chemotherapy: FOLFOX: 6 cycles (each cycle 2 days), one cycle every 2 week, first 3 cycles concurrent with RT 5-FU + cisplatin: 4 cycles (each cycle 4 days), first 2 cycles with RT Completion rate: FOLFOX: 90/131 (68.7%) 5-FU + cisplatin: 96/128 (75%)
No difference in progression free or overall survival Median survival: FOLFOX 20.2 months 5-FU + cisplatin 17.5 months P = 0.70
Morbidity
FOLFOX group: More paraesthesia, sensory neuropathy, elevation of liver enzyme 5-FU + cisplatin group: More mucositis, alopecia, renal impairment
Mortality
1 in FOLFOX group (0.76%): pneumopathy plus denutrition 6 in 5-FU + cisplatin group (4.69%): 5 neutropenic sepsis, 1 cardiac ischemia p-value = 0.066
Conclusion
FOLFOX is a more convenient option, similar efficacy to 5-FU + cisplatin, with probably lower mortality
New development
Retrospective review 204 patients: 75 had neoadjuvant chemoRT, 129 had surgery alone Propensity score matching: 75 patients in each group with similar demographics and tumor staging 41.4 Gy, Paclitaxel and carboplatin
Neoadjuvant chemoRT had better disease free and overall survival
Locoregional recurrence Complete Response Distant recurrence
Neoadjuvant chemoRT could improve disease free survival, overall survival and locoregional recurrence free survival Not improved distant recurrence free survival
Future Development
Any method to predict complete response to chemoRT EGFR inhibitors, HER-2 receptor inhibitors Adjuvant agents to reduce distant metastases
Conclusion
Neoadjuvant chemoirradiation improves survival of CA esophagus without increasing post-op morbidities Definitive chemoRT is an effective alternative to patients who are not fit for surgery New agents are needed to improve the complete response rate and survival of patients
Reference
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Esophageal Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. M. Stahl; C. Mariette; K. Haustermans; A. Cervantes & D. Arnold, on behalf of the ESMO Guidelines Working Groups. Annals of Oncology 24 (Supplement 6), vi51 vi56, 2013 Meta-analysis shows clinically relevant and long-lasting deterioration in health-related quality of life after esophageal cancer surgery. M. Jacobs; R.C. Macefield; R.G. Elbers; M.A.G. Sprangers. Qual Life Res (2014) 23: 1155-1176 Meta-analysis of neoadjuvant treatment modalities and definitive non-surgical therapy for esophageal squamous cell cancer. M. Kranzfelder; T. Schuster; H. Geinitz; H. Friess; P. Buchler. British Journal of Surgery 2011; 98: 768-783 Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with esophageal cancer (PRODIGE5/ACCORD17): final results of a randomized phase 2/3 trial. Thierry Conroy; Marie-Pierre Galais; Antonie Adenis. Lancet Onco 2014; 15: 305-14 Different Recurrence Pattern After Neoadjuvant Chemoradiotherapy Compared to Surgery Alone in Esophageal Cancer Patients. Justin K. Smit, MD; Sahin Guler, Bsc; John Th. M. Plukker, MD, PhD. Annals of Surgical Oncology (2013) 20; 4008-4015
Thank You
Staging method: CT scan, PET, EUS 752 clinical staging of T2N0 disease 482 underwent surgery directly 27.4% confirmed T2N0 disease 25.9% downstaged 46.7% upstaged