Adjuvant chemoRT for Cholangiocarcinoma Edgar Ben-Josef, M.D. Eli - - PowerPoint PPT Presentation

Adjuvant chemoRT for Cholangiocarcinoma

Edgar Ben-Josef, M.D. Eli Glatstein Professor of Radiation Oncology Vice-Chair for Translational Research

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Rationale for Radiotherapy in CC and Gallbladder Cancer w Direct: along the biliary tree and radially w Nodal: w Perihilar and periportal nodes w Along the common bile duct to the retropancreaticoduodenal lymph nodes w Local regional failure rates are high w Hilar ~40% w Distal ~25% w Gallbladder ~20-40% w Isolated LRF is ~10-15%

Disease Spread Patterns of First Failure

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Lack of Evidence is not Evidence of Lack (of Effect)

w No prospective randomized trials are available that examined the effect of adjuvant radiotherapy. w Numerous retrospective studies of adjuvant therapy have shown mixed results w Horgan et al JCO 2011

• Meta-analysis 20 series
• Adjuvant chemotherapy, radiotherapy, or CRT compared with

curative-intent surgery alone

• IHCC, EHCC, Gallbladder cancer
• Twenty studies involving 6,712 patients
• Those receiving CT or CRT derived statistically significant

benefit (OR, 0.39, 0.61, respectively); No benefit for RT alone.

• The greatest benefit for AT was in those with +LN disease

(OR, 0.49) and R1 disease (OR, 0.36)

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Rationale for radiotherapy in cholangiocarcinoma (SEER)

EHCC

Shinohara ET, et al. Radiotherapy is associated with improved survival in adjuvant and palliative treatment of IHCC/EHCC. Int J Radiat Oncol Biol Phys. 2008/2009

IHCC

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SWOG S0809

Eligibility:

• Phase II trial of adjuvant chemo followed by chemoRT
• EHCC and GB Cancer
• Stage pT2-4 or N+ or R1
• S/P radical resection; performance status 0 to 1

Treatment:

• Chemotherapy (gemcitabine and capecitabine x 4 cycles)
• Chemoradiation

– 45 Gy to regional LNs, 54-59.4 Gy to tumor bed – 3DCRT or IMRT – Concurrent capecitabine

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SWOG 0809

Results: – 79 patients

○ R0, n = 54; R1, n = 25 ○ Hilar CC 49%, Distal 17%, GBCA, 32%

– 2-year OS 65% (67% R0; 60% R1 patients) – Median overall survival was 35 months – Grade 3 and 4 adverse effects were observed in 52% and 11% of patients, respectively (neutropenia 44%) Conclusion:

• Well tolerated, efficacious regimen option

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DFS and Overall Survival by resection margin

SWOG 0809 Komaya et.al Surgery 2018 SWOG 0809 Komaya et.al Surgery 2018

Hilar

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Recurrence After Curative Resection of Perihilar CC

w 402 patients (R0, n = 340; R1, n = 62) resected 2001- 2012 w Minimal use of adjuvant therapy, mostly in R1 pts

Komaya et. Al., Surgery 2018

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OS and DFS by disease site

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Gallbladder Cancer Patterns of (first) Failure

w 70 patients s/p radical cholecystectomy and LN dissection; T2 or higher w Median F/U 23 months w Locoregional – 41% (isolated LR 19%) w Distant (with or without LR) – 40%)

Kim TG., Radiation Oncology J 2017 35(4):359-367

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Adjuvant Chemoradiotherapy is Associated with Improved Survival for Patients with Resected Gallbladder Carcinoma

Kim et al., Ann Surg Oncol (2018) 25:255–264

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Conclusions

w Locoregional relapse rates are high after curative resection of CC and GB cancer w Adjuvant radiotherapy improves local control and survival

• Retrospective reviews, meta analyses, large

database analysis, a single phase 2 study (no prospective phase 3 data) w Some adjuvant chemotherapy regimens improve DFS (capecitabine) w One modality does not exclude the other – there is no reason not to use both

The 15th Annual Meeting of the International Society of Gastrointestinal Oncology

The 2018 Gastrointestinal Oncology Conference