Mairéad Geraldine McNamara1, Andre Lopes2, Harpreet Wasan3, David Malka4, David Goldstein5, Jenny Shannon6, Takuji Okusaka7, Jennifer J Knox8, Anna Dorothea Wagner9, Thierry André10, David Cunningham11, Markus Moehler12, Lars Henrik Jensen13, Dieter Koeberle14, Tanios Bekaii-Saab15, John Bridgewater16, Juan W Valle17. 1. Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester M20 4BX, UK. Electronic address: Mairead.McNamara@christie.nhs.uk. 2. Cancer Research UK & UCL Cancer Trials Centre, London WCIE 6BT, UK. 3. Imperial Healthcare, London WI2 ONN, UK. 4. Institut Gustave Roussy, Villejuif, France. 5. Prince of Wales Clinical School, University of New South Wales, NSW 2052, Australia. 6. University of Sydney, NSW 2006, Australia. 7. National Cancer Center Hospital, Tokyo 104-0045, Japan. 8. Princess Margaret Cancer Centre, Toronto M5G 2M9, Canada. 9. Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland. 10. Sorbonne université and Hôpital Saint-Antoine, 75012 Paris, France. 11. Royal Marsden Hospital, UK. 12. Universitätsmedizin Mainz, 55122 Mainz, Germany. 13. Vejle University Hospital, Vejle 7100, Denmark. 14. Leiter Medizinische Klinik, Chefarzt Onkologie, St. Claraspital, CH - 4016 Basel, Switzerland. 15. Mayo Clinic, Phoenix, AZ 85054, USA. 16. UCL Cancer Institute, London WCIE 6BT, UK. 17. Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester M20 4BX, UK.
Abstract
BACKGROUND & AIMS: Whether all patients with advanced biliary tract cancer (aBTC) should be included in prospective trials, irrespective of the anatomic site of origin, is debated. Herein, we aimed to assess the survival impact of anatomic site of origin in prospective clinical trials of aBTC using landmark survival analysis. METHODS: Patients enrolled into prospective first-line aBTC clinical trials (Jan 97-Dec 15) were included. Overall survival (OS) was analysed using Cox proportional hazard regression; landmark survival (LS) and 95% CIs were calculated. RESULTS: Overall, 1,333 patients were included: median age 63 years (range 23-85); 46% male; 84% ECOG-PS0/1; 25% with locally advanced disease, 72% with metastatic, 3% not reported (NR). Patients were treated with mono-chemotherapy (23%), cisplatin/gemcitabine (36%), other combinations (39%), or NR (2%). Median OS was 10.2 months (95% CI 9.6-10.9). All sites (treatment-adjusted) had decreased risk of death vs. gallbladder cancer (GBC) (p <0.001). This reduced risk vs. GBC was maintained in those receiving cisplatin/gemcitabine for extrahepatic cholangiocarcinoma (p<0.001) and intrahepatic cholangiocarcinoma (IHC, p<0.001), but not in cholangiocarcinoma-not specified (CCA-NS, p = 0.82) or ampullary carcinoma (p = 0.96). One-year OS rates amongst patients who survived beyond 1, 2, 3 and 4 years post-trial registration were 37%, 45%, 61%, and 63%, respectively. For patients who survived 1 year, those receiving combination therapy vs. mono (p = 0.008) (acknowledging potential selection bias) and those with IHC and CCA-NS vs. GBC had better LS (both p <0.05). Metastatic disease was associated with shorter LS than locally advanced disease (p = 0.002). ECOG-PS and gender were not associated with LS (p >0.05, p = 0.08 respectively). CONCLUSIONS: GBC is associated with worse OS than other BTC sites and should be considered as a stratification factor in clinical trials. LS rates enable adjusted prognostication for aBTC survivors. LAY SUMMARY: Patients with gallbladder cancer have worse overall survival compared to those with biliary tract cancers of different primary origin. Thus, gallbladder cancer should be considered as a stratification factor in future clinical trials. Landmark survival rates enable adjusted prognosis prediction for patients with advanced biliary tract cancer who survive for some time.
BACKGROUND & AIMS: Whether all patients with advanced biliary tract cancer (aBTC) should be included in prospective trials, irrespective of the anatomic site of origin, is debated. Herein, we aimed to assess the survival impact of anatomic site of origin in prospective clinical trials of aBTC using landmark survival analysis. METHODS:Patients enrolled into prospective first-line aBTC clinical trials (Jan 97-Dec 15) were included. Overall survival (OS) was analysed using Cox proportional hazard regression; landmark survival (LS) and 95% CIs were calculated. RESULTS: Overall, 1,333 patients were included: median age 63 years (range 23-85); 46% male; 84% ECOG-PS0/1; 25% with locally advanced disease, 72% with metastatic, 3% not reported (NR). Patients were treated with mono-chemotherapy (23%), cisplatin/gemcitabine (36%), other combinations (39%), or NR (2%). Median OS was 10.2 months (95% CI 9.6-10.9). All sites (treatment-adjusted) had decreased risk of death vs. gallbladder cancer (GBC) (p <0.001). This reduced risk vs. GBC was maintained in those receiving cisplatin/gemcitabine for extrahepatic cholangiocarcinoma (p<0.001) and intrahepatic cholangiocarcinoma (IHC, p<0.001), but not in cholangiocarcinoma-not specified (CCA-NS, p = 0.82) or ampullary carcinoma (p = 0.96). One-year OS rates amongst patients who survived beyond 1, 2, 3 and 4 years post-trial registration were 37%, 45%, 61%, and 63%, respectively. For patients who survived 1 year, those receiving combination therapy vs. mono (p = 0.008) (acknowledging potential selection bias) and those with IHC and CCA-NS vs. GBC had better LS (both p <0.05). Metastatic disease was associated with shorter LS than locally advanced disease (p = 0.002). ECOG-PS and gender were not associated with LS (p >0.05, p = 0.08 respectively). CONCLUSIONS:GBC is associated with worse OS than other BTC sites and should be considered as a stratification factor in clinical trials. LS rates enable adjusted prognostication for aBTC survivors. LAY SUMMARY:Patients with gallbladder cancer have worse overall survival compared to those with biliary tract cancers of different primary origin. Thus, gallbladder cancer should be considered as a stratification factor in future clinical trials. Landmark survival rates enable adjusted prognosis prediction for patients with advanced biliary tract cancer who survive for some time.
Authors: Mairéad G McNamara; John Bridgewater; Daniel H Palmer; Olusola Faluyi; Harpreet Wasan; Alkesh Patel; William D Ryder; Safia Barber; Chathunissa Gnanaranjan; Essam Ghazaly; T R Jeff Evans; Juan W Valle Journal: Oncologist Date: 2020-12-03
Authors: Stephen P Hack; Wendy Verret; Sohail Mulla; Bo Liu; Yulei Wang; Teresa Macarulla; Zhenggang Ren; Anthony B El-Khoueiry; Andrew X Zhu Journal: Ther Adv Med Oncol Date: 2021-07-31 Impact factor: 8.168
Authors: Felix Thol; Simon Johannes Gairing; Carolin Czauderna; Thomas Thomaidis; Thomas Gamstätter; Yvonne Huber; Johanna Vollmar; Johanna Lorenz; Maurice Michel; Fabian Bartsch; Lukas Müller; Roman Kloeckner; Peter Robert Galle; Marcus-Alexander Wörns; Jens Uwe Marquardt; Markus Moehler; Arndt Weinmann; Friedrich Foerster Journal: JHEP Rep Date: 2021-12-16