PMID- 36495588 OWN - NLM STAT- MEDLINE DCOM- 20230407 LR - 20240411 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 41 IP - 11 DP - 2023 Apr 10 TI - The Advanced-Stage Hodgkin Lymphoma International Prognostic Index: Development and Validation of a Clinical Prediction Model From the HoLISTIC Consortium. PG - 2076-2086 LID - 10.1200/JCO.22.02473 [doi] AB - PURPOSE: The International Prognostic Score (IPS) has been used in classic Hodgkin lymphoma (cHL) for 25 years. However, analyses have documented suboptimal performance of the IPS among contemporarily treated patients. Harnessing multisource individual patient data from the Hodgkin Lymphoma International Study for Individual Care consortium, we developed and validated a modern clinical prediction model. METHODS: Model development via Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines was performed on 4,022 patients with newly diagnosed advanced-stage adult cHL from eight international phase III clinical trials, conducted from 1996 to 2014. External validation was performed on 1,431 contemporaneously treated patients from four real-world cHL registries. To consider association over a full range of continuous variables, we evaluated piecewise linear splines for potential nonlinear relationships. Five-year progression-free survival (PFS) and overall survival (OS) were estimated using Cox proportional hazard models. RESULTS: The median age in the development cohort was 33 (18-65) years; nodular sclerosis was the most common histology. Kaplan-Meier estimators were 0.77 for 5-year PFS and 0.92 for 5-year OS. Significant predictor variables included age, sex, stage, bulk, absolute lymphocyte count, hemoglobin, and albumin, with slight variation for PFS versus OS. Moreover, age and absolute lymphocyte count yielded nonlinear relationships with outcomes. Optimism-corrected c-statistics in the development model for 5-year PFS and OS were 0.590 and 0.720, respectively. There was good discrimination and calibration in external validation and consistent performance in internal-external validation. Compared with the IPS, there was superior discrimination for OS and enhanced calibration for PFS and OS. CONCLUSION: We rigorously developed and externally validated a clinical prediction model in > 5,000 patients with advanced-stage cHL. Furthermore, we identified several novel nonlinear relationships and improved the prediction of patient outcomes. An online calculator was created for individualized point-of-care use. FAU - Rodday, Angie Mae AU - Rodday AM AUID- ORCID: 0000-0002-8671-3401 AD - Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA. FAU - Parsons, Susan K AU - Parsons SK AUID- ORCID: 0000-0003-0282-6490 AD - Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA. FAU - Upshaw, Jenica N AU - Upshaw JN AUID- ORCID: 0000-0001-5801-5481 AD - Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA. AD - The CardioVascular Center and Advanced Heart Failure Program, Tufts Medical Center, Boston, MA. FAU - Friedberg, Jonathan W AU - Friedberg JW AD - James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY. FAU - Gallamini, Andrea AU - Gallamini A AUID- ORCID: 0000-0002-2054-7412 AD - Research and Clinical Innovation Department, Antoine Lacassagne Cancer Center, Nice, France. FAU - Hawkes, Eliza AU - Hawkes E AUID- ORCID: 0000-0002-0376-2559 AD - Australasian Lymphoma and Related Diseases Registry, Monash University, Melbourne, Australia. FAU - Hodgson, David AU - Hodgson D AUID- ORCID: 0000-0003-4687-4582 AD - Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. FAU - Johnson, Peter AU - Johnson P AUID- ORCID: 0000-0003-2306-4974 AD - Faculty of Medicine, School of Cancer Sciences, University of Southampton, United Kingdom. FAU - Link, Brian K AU - Link BK AUID- ORCID: 0000-0001-5084-0698 AD - Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA. FAU - Mou, Eric AU - Mou E AUID- ORCID: 0000-0002-9865-4517 AD - Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA. FAU - Savage, Kerry J AU - Savage KJ AUID- ORCID: 0000-0002-5835-9863 AD - Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada. FAU - Zinzani, Pier Luigi AU - Zinzani PL AUID- ORCID: 0000-0002-2112-2651 AD - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seragnoli" Dipartimento di Medicina Specialistica, Diagnostica Sperimentale Universita di Bologna, Bologna, Italy. FAU - Maurer, Matthew AU - Maurer M AUID- ORCID: 0000-0002-1867-0526 AD - Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN. FAU - Evens, Andrew M AU - Evens AM AUID- ORCID: 0000-0002-6900-1824 AD - Division of Blood Disorders, Rutgers Cancer Institute New Jersey, New Brunswick, NJ. LA - eng GR - UG1 CA233230/CA/NCI NIH HHS/United States GR - P30 CA086862/CA/NCI NIH HHS/United States GR - K08 HL146959/HL/NHLBI NIH HHS/United States GR - 9619/CRUK_/Cancer Research UK/United Kingdom GR - U10 CA180888/CA/NCI NIH HHS/United States GR - U10 CA180820/CA/NCI NIH HHS/United States GR - P50 CA097274/CA/NCI NIH HHS/United States GR - R01 CA262265/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20221210 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 SB - IM EIN - J Clin Oncol. 2024 Mar 1;42(7):862. PMID: 38207253 MH - Adult MH - Humans MH - Middle Aged MH - Aged MH - *Hodgkin Disease/drug therapy MH - Prognosis MH - Models, Statistical MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Survival Analysis MH - Retrospective Studies PMC - PMC10082254 COIS- The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Andrew M. Evens Honoraria: Seattle Genetics, Pharmacyclics, Research to Practice, Miltenyi Biotec, Epizyme, Novartis, MorphoSys, Cota Healthcare, Curio Science, Targeted Oncology, WebMD, AbbVie/Pharmacyclics, HMP, Takeda, Patient Power, PER, OncLive Clinical Congress Consultants, HUTCHMED, Incyte, MorphoSys, Daiichi Sankyo/Astra Zeneca Consulting or Advisory Role: Seattle Genetics, Novartis, Pharmacyclics, Miltenyi Biotec, Epizyme, MorphoSys, Cota Healthcare, AbbVie, Incyte, MorphoSys Speakers' Bureau: Research to Practice, Curio Science Travel, Accommodations, Expenses: Seattle Genetics, Novartis, Curio Science No other potential conflicts of interest were reported. EDAT- 2022/12/11 06:00 MHDA- 2023/04/07 10:18 PMCR- 2024/04/10 CRDT- 2022/12/10 17:12 PHST- 2023/04/07 10:18 [medline] PHST- 2022/12/11 06:00 [pubmed] PHST- 2022/12/10 17:12 [entrez] PHST- 2024/04/10 00:00 [pmc-release] AID - JCO.22.02473 [pii] AID - 10.1200/JCO.22.02473 [doi] PST - ppublish SO - J Clin Oncol. 2023 Apr 10;41(11):2076-2086. doi: 10.1200/JCO.22.02473. Epub 2022 Dec 10.