Pulmonary complications in survivors of childhood and adolescent cancer

A report from the Childhood Cancer Survivor Study

Authors


  • The following are CCSS Institutions and Investigators: University of California-San Francisco, San Francisco, CA (Arthur Ablin, M.D. [Institutional Principal Investigator]); University of Alabama, Birmingham, AL (Roger Berkow, M.D. [Institutional Principal Investigator]); International Epidemiology Institute, Rockville, MD (John Boice, Sc.D. [Member CCSS Steering Committee]); University of Washington, Seattle, WA (Norman Breslow, Ph.D. [Member CCSS Steering Committee]); University of Texas Southwestern Medical Center, Dallas, TX (George R. Buchanan, M.D. [Institutional Principal Investigator]); Dana-Farber Cancer Institute, Boston, MA (Lisa Diller, M.D. [Institutional Principal Investigator], Holcombe Grier, M.D. [Former Institutional Principal Investigator], and Frederick Li, M.D. [Member CCSS Steering Committee]); Texas Children's Center, Houston, TX (Zoann Dreyer, M.D. [Institutional Principal Investigator]); Children's Hospital and Medical Center, Seattle, WA (Debra Friedman, M.D., M.P.H. [Institutional Principal Investigator] and Thomas Pendergrass, M.D. [Former Institutional Principal Investigator]); Roswell Park Cancer Institute, Buffalo, NY (Daniel M. Green, M.D. [Institutional Principal Investigator and Member CCSS Steering Committee]); Hospital for Sick Children, Toronto, Ontario, Canada (Mark Greenberg, M.B., Ch.B. [Institutional Principal Investigator]); St. Louis Children's Hospital, St. Louis, MO (Robert Hayashi, M.D. [Institutional Principal Investigator] and Teresa Vietti, M.D. [Former Institutional Principal Investigator]); St. Jude Children's Research Hospital, Memphis, TN (Melissa Hudson, M.D. [Institutional Principal Investigator and Member CCSS Steering Committee]); University of Michigan, Ann Arbor, MI (Raymond Hutchinson, M.D. [Institutional Principal Investigator]); Stanford University School of Medicine, Stanford, CA (Michael P. Link, M.D. [Institutional Principal Investigator] and Sarah S. Donaldson, M.D. [Member CCSS Steering Committee]); Children's Hospital of Philadelphia, Philadelphia, PA (Anna Meadows, M.D. [Institutional Principal Investigator and Member CCSS Steering Committee] and Bobbie Bayton [Member CCSS Steering Committee]); Children's Hospital, Oklahoma City, OK (John Mulvihill, M.D. [Member CCSS Steering Committee]); Children's Hospital, Denver, CO (Brian Greffe [Institutional Principal Investigator] and Lorrie Odom, M.D. [Former Institutional Principal Investigator]); Children's Health Care-Minneapolis, MN (Maura O'Leary, M.D.[Institutional Principal Investigator]); Columbus Children's Hospital, Columbus, OH (Amanda Termuhlen, M.D. [Institutional Principal Investigator], Frederick Ruymann, M.D. [Former Institutional Principal Investigator], and Stephen Qualman, M.D. [Member CCSS Steering Committee]); Children's National Medical Center, Washington, DC (Gregory Reaman, M.D. [Institutional Principal Investigator] and Roger Packer, M.D. [Member CCSS Steering Committee]); Children's Hospital of Pittsburgh, PA (A. Kim Ritchey, M.D. [Institutional Principal Investigator] and Julie Blatt, M.D. [Former Institutional Principal Investigator]); University of Minnesota, Minneapolis, MN (Leslie L. Robison, Ph.D.[Institutional Principal Investigator and Member CCSS Steering Committee], Ann Mertens, Ph.D.[Member CCSS Steering Committee], Joseph Neglia, M.D., M.P.H. [Member CCSS Steering Committee], Mark Nesbit, M.D.[Member CCSS Steering Committee], and Stella Davies, M.D., Ph.D.[Member CCSS Steering Committee]); Children's Hospital of Los Angeles, Los Angeles, CA (Kathy Ruccione, R.N., M.P.H. [Institutional Principal Investigator]); Memorial Sloan-Kettering Cancer Center, New York, NY (Charles Sklar, M.D.[Institutional Principal Investigator and Member CCSS Steering Committee]); National Cancer Institute, Bethesda, MD (Malcolm Smith, M.D. [Member CCSS Steering Committee] and Martha Linet, M.D. [Member CCSS Steering Committee]); Mayo Clinic, Rochester, MN (W. Anthony Smithson, M.D. [Institutional Principal Investigator] and Gerald Gilchrist, M.D. [Former Institutional Principal Investigator]); University of Texas M. D. Anderson Cancer Center, Houston, TX (Louise Strong, M.D. [Institutional Principal Investigator and Member CCSS Steering Committee] and Marilyn Stovall, Ph.D. [Member CCSS Steering Committee]); Riley Hospital for Children, Indianapolis, IN (Terry A. Vik, M.D. [Institutional Principal Investigator] and Robert Weetman, M.D. [Former Institutional Principal Investigator]); Fred Hutchinson Cancer Center, Seattle, WA (Yutaka Yasui, Ph.D. [Institutional Principal Investigator] and John Potter, M.D., Ph.D. [Former Institutional Principal Investigator and Member CCSS Steering Committee]); and University of California-Los Angeles, Los Angeles, CA (Lonnie Zeltzer, M.D. [Institutional Principal Investigator and Member CCSS Steering Committee]).

Abstract

BACKGROUND

The Childhood Cancer Survivor Study is a resource that was designed to investigate long-term effects among 5-year survivors of childhood and adolescent malignancies. Previous studies have shown that exposure to chemotherapy and/or radiation can compromise pulmonary function in these survivors of childhood cancer.

METHODS

Using information obtained from questionnaires from 12,390 childhood cancer survivors and 3546 randomly selected siblings, the authors evaluated the rate of first occurrence of 15 selected pulmonary conditions in three periods: during therapy, from the end of therapy to 5 years postdiagnosis, and ≥ 5 years postdiagnosis. Multivariate analyses were used to determine the relative risks with 95% confidence intervals of reported pulmonary conditions by exposure to the following treatment variables: radiation therapy to the chest, bleomycin, cyclophosphamide, busulfan, lomustine (CCNU), and/or carmustine (BCNU).

RESULTS

Compared with siblings, survivors had a statistically significant increased relative risk (RR) of lung fibrosis, recurrent pneumonia, chronic cough, pleurisy, use of supplemental oxygen, abnormal chest wall, exercise-induced shortness of breath, bronchitis, recurrent sinus infection, and tonsillitis for all three periods. During the period of ≥ 5 years postdiagnosis, statistically significant associations were present for lung fibrosis and chest radiation (RR, 4.3; P = 0 001); for supplemental oxygen use and chest radiation (RR, 1.8; P < 0.001), BCNU (RR, 1.4; P = 0.05), bleomycin (RR, 1.7; P = 0.001), busulfan (RR, 3.2; P = 0.002), CCNU (RR, 2.1; P < 0.001), and cyclophosphamide (RR, 1.5; P = 0.01); for recurrent pneumonia and chest radiation (RR, 2.2; P = 0.001) and cyclophosphamide (RR, 1.6; P = 0.04); for chronic cough and chest radiation (RR, 2.0; P < 0.001), bleomycin (RR, 1.9; P < 0.001), and cyclophosphamide (RR, 1.3; P = 0.004); and for pleurisy and chest radiation (RR, 1.4; P = 0.02) and busulfan (RR, 5.1; P = 0.02). Chest radiation was associated with a 3.5% cumulative incidence of lung fibrosis at 20 years after diagnosis.

CONCLUSIONS

For self-report of pulmonary conditions, treatment-related factors that continue to manifest > 5 years after diagnosis and treatment are important determinants of risk. Continued follow-up of childhood cancer survivors is needed to evaluate the impact of pulmonary conditions on quality of life. Cancer 2002;95:2431–41. © 2002 American Cancer Society.

DOI 10.1002/cncr.10978

Ancillary