Kathleen A Meeske1,2, Lingyun Ji3, David R Freyer1,2, Paul Gaynon1,2, Kathleen Ruccione1,2, Anna Butturini4, Vassilios I Avramis1,2, Stuart Siegel1,2, Yousif Matloub5, Nita L Seibel6, Richard Sposto1,3. 1. Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California. 2. Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California. 3. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. 4. Agensys, Inc., Santa Monica, California. 5. Division of Hematology-Oncology, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio. 6. Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland.
Abstract
BACKGROUND: Epidemiologic studies find sex-based differences in incidence, survival, and long-term outcomes for children with cancer. The purpose of this study was to determine whether male and female patients differ with regard to acute treatment-related toxicities. PROCEDURES: We reviewed data collected on the Children's cancer group (CCG) high-risk acute lymphoblastic leukemia (ALL-HR) study (CCG-1961), and compared male and female patients' toxicity incidence and related variables in the first four phases of treatment. Similar analyses were performed with standard-risk ALL (ALL-SR) patients enrolled in CCG-1991. RESULTS: Among ALL-HR patients, females had significantly more hospital days, delays in therapy, grade 3 or 4 toxicities (e.g., gastrointestinal, liver), and supportive care interventions (e.g., transfusions, intravenous antibiotics) than males. Females were significantly more likely to have died of treatment-related causes than males (Hazard ratio = 2.8, 95%CI = 1.5-5.3, P = 0.002). Five months after beginning the treatment, the cumulative incidence of treatment-related deaths was 2.6% for females and 1.2% for males. Similar disparities were found among ALL-SR patients, with females experiencing significantly more hospital days and treatment-related toxicities than males. CONCLUSIONS: This study complements cancer survivorship studies that also report an increase in treatment-related late effects among females. Risk profiles appear to be different for male and female patients, with females having greater risk of developing both acute and long-term treatment-related toxicities. The underlying biological mechanisms for these sex differences are poorly understood and warrant further study in order to determine how sex-based outcome disparities can be addressed in future clinical trials and practice.
BACKGROUND: Epidemiologic studies find sex-based differences in incidence, survival, and long-term outcomes for children with cancer. The purpose of this study was to determine whether male and female patients differ with regard to acute treatment-related toxicities. PROCEDURES: We reviewed data collected on the Children's cancer group (CCG) high-risk acute lymphoblastic leukemia (ALL-HR) study (CCG-1961), and compared male and female patients' toxicity incidence and related variables in the first four phases of treatment. Similar analyses were performed with standard-risk ALL (ALL-SR) patients enrolled in CCG-1991. RESULTS: Among ALL-HR patients, females had significantly more hospital days, delays in therapy, grade 3 or 4 toxicities (e.g., gastrointestinal, liver), and supportive care interventions (e.g., transfusions, intravenous antibiotics) than males. Females were significantly more likely to have died of treatment-related causes than males (Hazard ratio = 2.8, 95%CI = 1.5-5.3, P = 0.002). Five months after beginning the treatment, the cumulative incidence of treatment-related deaths was 2.6% for females and 1.2% for males. Similar disparities were found among ALL-SR patients, with females experiencing significantly more hospital days and treatment-related toxicities than males. CONCLUSIONS: This study complements cancer survivorship studies that also report an increase in treatment-related late effects among females. Risk profiles appear to be different for male and female patients, with females having greater risk of developing both acute and long-term treatment-related toxicities. The underlying biological mechanisms for these sex differences are poorly understood and warrant further study in order to determine how sex-based outcome disparities can be addressed in future clinical trials and practice.
Authors: Eduard H Panosyan; Nita L Seibel; Sagrario Martin-Aragon; Paul S Gaynon; Ioannis A Avramis; Harland Sather; Janet Franklin; James Nachman; Lawrence J Ettinger; Mei La; Peter Steinherz; Lewis J Cohen; Stuart E Siegel; Vassilios I Avramis Journal: J Pediatr Hematol Oncol Date: 2004-04 Impact factor: 1.289
Authors: A C Mertens; Y Yasui; J P Neglia; J D Potter; M E Nesbit; K Ruccione; W A Smithson; L L Robison Journal: J Clin Oncol Date: 2001-07-01 Impact factor: 50.717
Authors: Renée L Mulder; Dorine Bresters; Malon Van den Hof; Bart Gp Koot; Sharon M Castellino; Yoon Kong K Loke; Piet N Post; Aleida Postma; László P Szőnyi; Gill A Levitt; Edit Bardi; Roderick Skinner; Elvira C van Dalen Journal: Cochrane Database Syst Rev Date: 2019-04-15
Authors: Marina Curra; Amanda F Gabriel; Maria Beatriz C Ferreira; Marco Antonio T Martins; André T Brunetto; Lauro J Gregianin; Manoela Domingues Martins Journal: Support Care Cancer Date: 2021-04-12 Impact factor: 3.603
Authors: Amy M Berkman; Clark R Andersen; Branko Cuglievan; David C McCall; Philip J Lupo; Susan K Parsons; Courtney D DiNardo; Nicholas J Short; Nitin Jain; Tapan M Kadia; J A Livingston; Michael E Roth Journal: Cancer Epidemiol Biomarkers Prev Date: 2022-06-01 Impact factor: 4.090
Authors: Carmen L Wilson; Wassim Chemaitilly; Kendra E Jones; Sue C Kaste; Deo Kumar Srivastava; Rohit P Ojha; Yutaka Yasui; Ching-Hon Pui; Leslie L Robison; Melissa M Hudson; Kirsten K Ness Journal: J Clin Oncol Date: 2016-03-21 Impact factor: 44.544
Authors: Wasil Jastaniah; Naglla Elimam; Khalid Abdalla; Aeshah A AlAzmi; Aml M Elgaml; Ahmad Alkassar; Mustafa Daghistani; Sami Felimban Journal: Exp Hematol Oncol Date: 2018-11-19