{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T14:38:13Z","timestamp":1772203093476,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Platinum-based chemotherapy represents the standard first-line treatment for biliary tract cancers (BTC). Deficits in genes involved in the homologous recombination (HR) and DNA damage response (DDR) may confer higher sensitivity to platinum agents.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We retrospectively included patients affected by BTC from 2 Italian institutions. Inclusion criteria consist of the receipt of platinum-based chemotherapy in the metastatic setting and the availability of comprehensive genomic profiling using next-generation sequencing (NGS). Patients were included in the HRD-like group if demonstrated oncogenic or likely oncogenic alterations in HR-\/DDR-genes. Clinical endpoints were compared between the HRD-like group and the non-HRD-like group.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Seventy-four patients were included, of whom 25 (33%) in the HRD-like group and 49 (66%) in the non-HRD group. With a median follow-up of 26.04 months (interquartile-range [IQR] 9.41-29.27) in the HRD-like group and of 22.48 months (IQR 16.86-40.53) in the non-HRD group, no PFS difference emerged, with a mPFS of 5.18 months in the HRD-like group compared to 6.04 months in the non-HRD group (hazard ratio [HR], 1.017, 95% CI 0.58-1.78; P\u2005=\u2005.95). No differences were observed in DCR (64% [95 CI 45%-83%] vs 73% [95 CI 61%-86%]; P\u2005=\u2005.4), and CBR (45% [95% CI 28%-73%] vs 50% [95% CI, 37%-68%]; P\u2005=\u2005.9) between the HRD-like group and non-HRD groups, respectively. Median OS did not statistically differ between the HRD-like group and non-HRD group (26.7 vs 18.0 months, respectively; HR, 0.670, 0.33 to 1.37, P\u2005=\u2005.27).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>HR-\/DDR-genes, when assessed with regular tumor-only NGS panels, provide limited clinical validity to identify patients with BTC more likely to benefit from platinum-based chemotherapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyae125","type":"journal-article","created":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T20:07:10Z","timestamp":1717272430000},"page":"707-715","source":"Crossref","is-referenced-by-count":4,"title":["Deleterious alterations in homologous recombination repair genes and efficacy of platinum-based chemotherapy in biliary tract cancers"],"prefix":"10.1093","volume":"29","author":[{"given":"Carmen","family":"Belli","sequence":"first","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS , Milan 20141 , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1026-3923","authenticated-orcid":false,"given":"Luca","family":"Boscolo Bielo","sequence":"additional","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS , Milan 20141 , Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan , Milan 20122 , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Repetto","sequence":"additional","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS , Milan 20141 , Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan , Milan 20122 , Italy"},{"name":"Early Drug Development Service, Memorial Sloan-Kettering Cancer Center , New York 10065 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edoardo","family":"Crimini","sequence":"additional","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS , Milan 20141 , Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan , Milan 20122 , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raimondo","family":"Scalia","sequence":"additional","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS , Milan 20141 , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Diana","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Ospedale del Mare , Naples 80147 , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Orefice","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Ospedale del Mare , Naples 80147 , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana","family":"Ascione","sequence":"additional","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS , Milan 20141 , Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan , Milan 20122 , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Pellizzari","sequence":"additional","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS , Milan 20141 , Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan , Milan 20122 , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Fusco","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, University of Milan , Milan 20122 , Italy"},{"name":"Division of Pathology, IEO, European Institute of Oncology IRCCS , Milan 20141 , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Barberis","sequence":"additional","affiliation":[{"name":"Division of Pathology, IEO, European Institute of Oncology IRCCS , Milan 20141 , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Daniele","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Ospedale del Mare , Naples 80147 , 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