{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:02:09Z","timestamp":1785308529980,"version":"3.55.0"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients enrolled in phase I oncology clinical trials are expected to survive more than 3 months, yet up to 15% may die before this threshold. Several prognostic scores have been developed to identify patients unlikely to derive benefit from trial participation. We aimed to compare the prognostic performance of five described scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study included 844 patients treated with immunotherapy in phase I trials at Cl\u00ednica Universidad de Navarra (2016-2023). Prognostic scores (RMH, GRIm, LIPI, PIPO, ROPRO) were calculated according to their original definitions. Discriminative performance was assessed using Harrell\u2019s C-index, 3-month AUC, and time-dependent AUC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Median OS was 9.08 months. All scores demonstrated statistically significant prognostic stratification. C-index values were: RMH 0.58, GRIm 0.55, LIPI 0.66, PIPO 0.63, and ROPRO 0.69. AUC at 3 months was highest for ROPRO (0.76). However, no score identified a subgroup with a median OS below 3 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>All five scores stratified prognosis but failed to select patients with OS below 3 months. These findings challenge their use as rigid exclusion criteria and support their role as stratification factors. New models integrating dynamic clinical or molecular biomarkers are needed to improve patient selection in phase I immunotherapy trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1849425","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T04:20:51Z","timestamp":1784521251000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic value of existing scoring systems for early mortality in phase I immunotherapy trials: a head-to-head real-world cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Paloma","family":"Sangro","sequence":"first","affiliation":[{"name":"Liver Unit and HPB Oncology Area, Cancer Center Cl\u00ednica Universidad de Navarra (CCUN)","place":["Madrid, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en el \u00c1rea tem\u00e1tica de Enfermedades Hep\u00e1ticas (CIBERHED)","place":["Pamplona, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA)","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Landa-Magdalena","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit for Oncology. Oncology Department. CCUN","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Sogbe","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en el \u00c1rea tem\u00e1tica de Enfermedades Hep\u00e1ticas (CIBERHED)","place":["Pamplona, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA)","place":["Pamplona, Spain"]},{"name":"Liver Unit and HPB Oncology Area, CCUN","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Zumarraga","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit for Oncology. Oncology Department. CCUN","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Matos","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit for Oncology. Oncology Department. CCUN","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano","family":"Ponz-Sarvise","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit for Oncology. Oncology Department. CCUN","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Crespo","sequence":"additional","affiliation":[{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Oncolog\u00eda de Gipuzkoa","place":["San Sebasti\u00e1n, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Esperanza","family":"Rodriguez-Ruiz","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit for Oncology. Oncology Department. CCUN","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vilalta-Lacarra","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit for Oncology. Oncology Department. CCUN","place":["Pamplona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Casta\u00f1\u00f3n","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trial Unit for Oncology. Oncology Department. CCUN","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.molonc.2014.07.025","article-title":"Early phase clinical trials to identify optimal dosing and safety","volume":"9","author":"Cook","year":"2015","journal-title":"Mol Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.04.017","article-title":"90-days mortality rate in patients treated within the context of a phase-I trial: How should we identify patients who should not go on trial","volume":"44","author":"Arkenau","year":"2008","journal-title":"Eur J Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-007-9088-x","article-title":"Prognostic factors among cancer patients with good performance status screened for phase I trials","volume":"26","author":"Penel","year":"2008","journal-title":"Invest New Drugs"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604218","article-title":"Clinical outcome and prognostic factors for patients treated within the context of a phase I study: The Royal Marsden Hospital experience","volume":"98","author":"Arkenau","year":"2008","journal-title":"Br J Cancer"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2017.07.027","article-title":"Prospective validation of a prognostic score for patients in immunotherapy phase I trials: The Gustave Roussy Immune Score (GRIm-Score)","volume":"84","author":"Bigot","year":"2017","journal-title":"Eur J Cancer"},{"key":"B6","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1001\/jamaoncol.2017.4771","article-title":"Association of the Lung Immune Prognostic Index with immune checkpoint inhibitor outcomes in patients with advanced non\u2013small cell lung cancer","volume":"4","author":"Mezquita","year":"2018","journal-title":"JAMA Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.05.040","article-title":"Phase I prognostic online (PIPO): A web tool to improve patient selection for oncology early phase clinical trials","volume":"155","author":"Matos","year":"2021","journal-title":"Eur J Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.07.013","article-title":"An enhanced prognostic score for overall survival of patients with cancer derived from a large real-world cohort","volume":"31","author":"Becker","year":"2020","journal-title":"Ann Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1200\/jco.21.02125","article-title":"Ethical considerations for phase I trials in oncology","volume":"40","author":"Bittlinger","year":"2022","journal-title":"J Clin Oncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12885-017-3925-x","article-title":"Colorectal cancer liver metastases - a population-based study on incidence, management and survival","volume":"18","author":"Engstrand","year":"2018","journal-title":"BMC Cancer"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1849425\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:12:35Z","timestamp":1785305555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1849425\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":10,"alternative-id":["10.3389\/fonc.2026.1849425"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1849425","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"article-number":"1849425"}}