Predictive classifier for intensive treatment of head and neck cancer.


Journal

Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236

Informations de publication

Date de publication:
15 12 2020
Historique:
received: 31 03 2020
revised: 24 05 2020
accepted: 10 06 2020
pubmed: 6 10 2020
medline: 21 5 2021
entrez: 5 10 2020
Statut: ppublish

Résumé

This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer. This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events. The classifier was externally validated on the MACH-NC data set. The study tested for interactions between the ω score and treatment effects on overall survival (OS). Factors associated with a higher ω score were a younger age, a better performance status, an oral cavity site, higher T and N categories, and a p16-negative/unknown status. The effect of AFX on OS was greater in patients with high ω scores (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99) and medium ω scores (HR, 0.91; 95% CI, 0.84-0.98) versus low ω scores (HR, 0.97; 95% CI, 0.90-1.05; P for interaction = .086). The effect of chemotherapy on OS was significantly greater in patients with high ω scores (HR, 0.81; 95% CI, 0.75-0.88) and medium ω scores (HR, 0.86; 95% CI, 0.78-0.93) versus low ω scores (HR, 0.96; 95% CI, 0.86-1.08; P for interaction = .011). LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment.

Sections du résumé

BACKGROUND
This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer.
METHODS
This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events. The classifier was externally validated on the MACH-NC data set. The study tested for interactions between the ω score and treatment effects on overall survival (OS).
RESULTS
Factors associated with a higher ω score were a younger age, a better performance status, an oral cavity site, higher T and N categories, and a p16-negative/unknown status. The effect of AFX on OS was greater in patients with high ω scores (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99) and medium ω scores (HR, 0.91; 95% CI, 0.84-0.98) versus low ω scores (HR, 0.97; 95% CI, 0.90-1.05; P for interaction = .086). The effect of chemotherapy on OS was significantly greater in patients with high ω scores (HR, 0.81; 95% CI, 0.75-0.88) and medium ω scores (HR, 0.86; 95% CI, 0.78-0.93) versus low ω scores (HR, 0.96; 95% CI, 0.86-1.08; P for interaction = .011).
CONCLUSIONS
LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment.

Identifiants

pubmed: 33017867
doi: 10.1002/cncr.33212
doi:

Types de publication

Journal Article Meta-Analysis Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5263-5273

Subventions

Organisme : UC San Diego Head and Neck Cancer Center
Organisme : Programme d'Actions Intégrées de Recherche
ID : 2011-1-VADS-04
Organisme : Ligue National Contre le Cancer, Institut National du Cancer
ID : PHRC-K 10-02-58
Organisme : Ligue National Contre le Cancer, Institut National du Cancer
ID : PHRC-K-15-189

Informations de copyright

© 2020 American Cancer Society.

Références

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Auteurs

Kaveh Zakeri (K)

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Federico Rotolo (F)

Ligue Nationale Contre le Cancer Meta-Analysis Plateform, Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Centre d'Etude des Supports de Publicite, Institut National de la Santé et de la Recherche Médicale U1018, Université Paris Sud, Université Paris-Saclay, Villejuif, France.

Benjamin Lacas (B)

Ligue Nationale Contre le Cancer Meta-Analysis Plateform, Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Centre d'Etude des Supports de Publicite, Institut National de la Santé et de la Recherche Médicale U1018, Université Paris Sud, Université Paris-Saclay, Villejuif, France.

Lucas K Vitzthum (LK)

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.

Quynh-Thu Le (QT)

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.

Vincent Gregoire (V)

Radiation Oncology Department, Centre Léon Bérard, Lyon, France.

Jens Overgaard (J)

Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.

Allan Hackshaw (A)

Cancer Research United Kingdom and University College London Cancer Trials Centre, Cancer Institute, University College London Hospital, London, United Kingdom.

Björn Zackrisson (B)

Department of Radiation Sciences-Oncology, Umeå University, Umeå, Sweden.

Mahesh K B Parmar (MKB)

Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom.

Barbara A Burtness (BA)

Yale University, New Haven, Connecticut.

Maria Grazia Ghi (MG)

Oncology Unit 2, Istituto Oncologico Veneto-IRCCS, Padua, Italy.

Giuseppe Sanguineti (G)

Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Brian O'Sullivan (B)

Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.

Catherine Fortpied (C)

Headquarters, European Organisation for Research and Treatment of Cancer, Brussels, Belgium.

Jean Bourhis (J)

Department of Radiotherapy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Hanjie Shen (H)

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.

Jonathan Harris (J)

NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, Pennsylvania.

Stefan Michiels (S)

Ligue Nationale Contre le Cancer Meta-Analysis Plateform, Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Centre d'Etude des Supports de Publicite, Institut National de la Santé et de la Recherche Médicale U1018, Université Paris Sud, Université Paris-Saclay, Villejuif, France.

Jean-Pierre Pignon (JP)

Ligue Nationale Contre le Cancer Meta-Analysis Plateform, Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Centre d'Etude des Supports de Publicite, Institut National de la Santé et de la Recherche Médicale U1018, Université Paris Sud, Université Paris-Saclay, Villejuif, France.

Loren K Mell (LK)

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.

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