Anna S Holmqvist1,2, Yanjun Chen3, Jennifer Berano Teh4, Canlan Sun4, Jillian M Birch5, Cor van den Bos6, Lisa R Diller7, Kimberley Dilley8, Jill Ginsberg9, Laura T Martin10, Rajaram Nagarajan11, Paul C Nathan12, Joseph P Neglia13, Monica Terenziani14, David Tishler15, Anna T Meadows16, Leslie L Robison17, Odile Oberlin18,19, Smita Bhatia3,20. 1. Department of Clinical Sciences, Lund University, Lund, Sweden. 2. Pediatric Oncology and Hematology, Skane University Hospital, Lund, Sweden. 3. Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, Alabama. 4. Department of Population Sciences, City of Hope, Duarte, California. 5. Pediatric and Familial Cancer Research Group, Cancer Research UK, Royal Manchester Children's Hospital, Manchester, United Kingdom. 6. Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands. 7. Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 8. Division of Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 9. Center for Childhood Cancer Research, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. 10. Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio. 11. Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 12. Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada. 13. Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota. 14. Pediatric Oncology Unit, IRCCS Foundation National Cancer Institute, Milan, Italy. 15. Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California. 16. The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 17. Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee. 18. Department of Pediatrics, Gustave Roussy Institute, Villejuif, France. 19. Department of Biostatistics, Gustave Roussy Institute, Villejuif, France. 20. Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.
Abstract
BACKGROUND: Survivors of Hodgkin lymphoma (HL) in childhood have an increased risk of subsequent malignant neoplasms (SMNs). Herein, the authors extended the follow-up of a previously reported Late Effects Study Group cohort and identified patients at highest risk for SMNs to create evidence for risk-based screening recommendations. METHODS: The standardized incidence ratio was calculated using rates from the Surveillance, Epidemiology, and End Results program as a reference. The risk of SMN was estimated using proportional subdistribution hazards regression. The cohort included 1136 patients who were diagnosed with HL before age 17 years between 1955 and 1986. The median length of follow-up was 26.6 years. RESULTS: In 162 patients, a total of 196 solid SMNs (sSMNs) were identified. Compared with the general population, the cohort was found to be at a 14-fold increased risk of developing an sSMN (95% confidence interval, 12.0-fold to 16.3-fold). The cumulative incidence of any sSMN was 26.4% at 40 years after a diagnosis of HL. Risk factors for breast cancer among females were an HL diagnosis between ages 10 years and 16 years and receipt of chest radiotherapy. Males treated with chest radiotherapy at age <10 years were found to be at highest risk of developing lung cancer. Survivors of HL who were treated with abdominal/pelvic radiotherapy and high-dose alkylating agents were found to be at highest risk of developing colorectal cancer and females exposed to neck radiotherapy at age <10 years were at highest risk of thyroid cancer. By age 50 years, the cumulative incidence of breast, lung, colorectal, and thyroid cancer was 45.3%, 4.2%, 9.5%, and 17.3%, respectively, among those at highest risk. CONCLUSIONS: Survivors of childhood HL remain at an increased risk of developing sSMNs. In the current study, subgroups of survivors of HL at highest risk of specific sSMNs were identified, and evidence for screening provided.
BACKGROUND: Survivors of Hodgkin lymphoma (HL) in childhood have an increased risk of subsequent malignant neoplasms (SMNs). Herein, the authors extended the follow-up of a previously reported Late Effects Study Group cohort and identified patients at highest risk for SMNs to create evidence for risk-based screening recommendations. METHODS: The standardized incidence ratio was calculated using rates from the Surveillance, Epidemiology, and End Results program as a reference. The risk of SMN was estimated using proportional subdistribution hazards regression. The cohort included 1136 patients who were diagnosed with HL before age 17 years between 1955 and 1986. The median length of follow-up was 26.6 years. RESULTS: In 162 patients, a total of 196 solid SMNs (sSMNs) were identified. Compared with the general population, the cohort was found to be at a 14-fold increased risk of developing an sSMN (95% confidence interval, 12.0-fold to 16.3-fold). The cumulative incidence of any sSMN was 26.4% at 40 years after a diagnosis of HL. Risk factors for breast cancer among females were an HL diagnosis between ages 10 years and 16 years and receipt of chest radiotherapy. Males treated with chest radiotherapy at age <10 years were found to be at highest risk of developing lung cancer. Survivors of HL who were treated with abdominal/pelvic radiotherapy and high-dose alkylating agents were found to be at highest risk of developing colorectal cancer and females exposed to neck radiotherapy at age <10 years were at highest risk of thyroid cancer. By age 50 years, the cumulative incidence of breast, lung, colorectal, and thyroid cancer was 45.3%, 4.2%, 9.5%, and 17.3%, respectively, among those at highest risk. CONCLUSIONS: Survivors of childhood HL remain at an increased risk of developing sSMNs. In the current study, subgroups of survivors of HL at highest risk of specific sSMNs were identified, and evidence for screening provided.
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