Differential effects of radiotherapy on growth and endocrine function among acute leukemia survivors: A childhood cancer survivor study report†
Corresponding Author
Eric J. Chow MD, MPH
Department of Pediatrics, Seattle Children's Hospital and University of Washington, Seattle, Washington
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
Fred Hutchinson Cancer Research Center, PO Box 19024, Mailstop M4-C308, Seattle, WA 98109-1024.===Search for more papers by this authorWei Liu PhD
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
Search for more papers by this authorKumar Srivastava PhD
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
Search for more papers by this authorWendy M. Leisenring ScD
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
Search for more papers by this authorRobert J. Hayashi MD
Department of Pediatric Hematology/Oncology, Washington University School of Medicine, St. Louis, Missouri
Search for more papers by this authorCharles A. Sklar MD
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York
Search for more papers by this authorMarilyn Stovall PhD
Department of Radiation Physics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Search for more papers by this authorLeslie L. Robison PhD
Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee
Search for more papers by this authorK. Scott Baker MD, MS
Department of Pediatrics, Seattle Children's Hospital and University of Washington, Seattle, Washington
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
Search for more papers by this authorCorresponding Author
Eric J. Chow MD, MPH
Department of Pediatrics, Seattle Children's Hospital and University of Washington, Seattle, Washington
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
Fred Hutchinson Cancer Research Center, PO Box 19024, Mailstop M4-C308, Seattle, WA 98109-1024.===Search for more papers by this authorWei Liu PhD
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
Search for more papers by this authorKumar Srivastava PhD
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
Search for more papers by this authorWendy M. Leisenring ScD
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
Search for more papers by this authorRobert J. Hayashi MD
Department of Pediatric Hematology/Oncology, Washington University School of Medicine, St. Louis, Missouri
Search for more papers by this authorCharles A. Sklar MD
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York
Search for more papers by this authorMarilyn Stovall PhD
Department of Radiation Physics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Search for more papers by this authorLeslie L. Robison PhD
Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee
Search for more papers by this authorK. Scott Baker MD, MS
Department of Pediatrics, Seattle Children's Hospital and University of Washington, Seattle, Washington
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington
Search for more papers by this authorConflict of interest: Nothing to declare.
Abstract
Background
The differential effects of cranial radiotherapy (CRT), spinal radiotherapy (SRT), and total body irradiation (TBI) on growth and endocrine outcomes have rarely been examined in combination among childhood acute leukemia survivors.
Procedure
Self-reported height/weight, hypothyroidism, and pregnancy/live birth were determined among acute lymphoblastic and myeloid leukemia survivors (n = 3,467) participating in the Childhood Cancer Survivor Study, an ongoing cohort study of 5-year survivors of pediatric cancers diagnosed from 1970 to 1986.
Results
Compared with no radiotherapy, risk estimates were consistent across outcomes (adult short stature, hypothyroidism, absence of pregnancy/live birth) with CRT treatment associated with 2–3-fold increased risks, TBI associated with 5–10 fold increased risks, and CRT + TBI associated with >10 fold increased risks. Exposure to any SRT further increased risk of these outcomes 2–3-fold. Changes in body composition were more nuanced as CRT only was associated with an increased risk of being overweight/obese (OR 1.6, 95% CI 1.3–1.9) whereas TBI only was associated with an increased risk of being underweight (OR 6.0, 95% CI 2.4–14.9).
Conclusions
Although patients treated with CRT + TBI were at greatest risk for short stature, hypothyroidism, and a reduced likelihood of pregnancy/live birth, those treated with either modality alone had significantly increased risks as well, including altered body composition. Any SRT exposure further increased risk in an independent fashion. Pediatr Blood Cancer 2013; 60: 110–115. © 2012 Wiley Periodicals, Inc.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| pbc_24198_sm_SupplTabs.doc41.5 KB | Supplemental Tables |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1
Hudson MM,
Neglia JP,
Woods WG, et al.
Lessons from the past: Opportunities to improve childhood cancer survivor care through outcomes investigations of historical therapeutic approaches for pediatric hematological malignancies.
Pediatr Blood Cancer
2011; DOI: 10.1002/pbc.23385.
10.1002/pbc.23385 Google Scholar
- 2 Chemaitilly W, Sklar CA. Endocrine complications in long-term survivors of childhood cancers. Endocr Relat Cancer 2010; 17: R141–R159.
- 3 Margolin JF, Steuber CP, Poplack DG. Acute lymphoblastic leukemia. In: PA Pizzo, DG Poplack, editors. Principles and practice of pediatric oncology, 5th edition. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 538–590.
- 4 Hill-Kayser CE, Plastaras JP, Tochner Z, et al. TBI during BM and SCT: Review of the past, discussion of the present and consideration of future directions. Bone Marrow Transplant 2011; 46: 475–484.
- 5 Pasquini MC, Wang Z. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR Summary Slides 2011; http://www.cibmtr.org/ReferenceCenter/SlidesReports/SummarySlides/index.html. Accessed December 31, 2011.
- 6 Robison LL, Mertens AC, Boice JD, et al. Study design and cohort characteristics of the Childhood Cancer Survivor Study: A multi-institutional collaborative project. Med Pediatr Oncol 2002; 38: 229–239.
- 7 Robison LL, Armstrong GT, Boice JD, et al. The Childhood Cancer Survivor Study: A National Cancer Institute-supported resource for outcome and intervention research. J Clin Oncol 2009; 27: 2308–2318.
- 8 Stovall M, Weathers R, Kasper C, et al. Dose reconstruction for therapeutic and diagnostic radiation exposures: Use in epidemiological studies. Radiat Res 2006; 166: 141–157.
- 9 Centers for Disease Control and Prevention. 2000; CDC Growth Charts for the United States. http://www.cdc.gov/GROWTHcharts/. Accessed December 31, 2011.
- 10 National Health Interview Study. http://www.cdc.gov/nchs/nhis.htm. Accessed December 31, 2011.
- 11 Armenian SH, Sun CL, Kawashima T, et al. Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: A report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS). Blood 2011; 118: 1413–1420.
- 12 Robison LL, Nesbit ME Jr, Sather HN, et al. Height of children successfully treated for acute lymphoblastic leukemia: A report from the Late Effects Study Committee of Childrens Cancer Study Group. Med Pediatr Oncol 1985; 13: 14–21.
- 13 Sklar C, Mertens A, Walter A, et al. Final height after treatment for childhood acute lymphoblastic leukemia: Comparison of no cranial irradiation with 1800 and 2400 centigrays of cranial irradiation. J Pediatr 1993; 123: 59–64.
- 14 Cohen A, Rovelli A, Bakker B, et al. Final height of patients who underwent bone marrow transplantation for hematological disorders during childhood: A study by the Working Party for Late Effects-EBMT. Blood 1999; 93: 4109–4115.
- 15 Chow EJ, Friedman DL, Yasui Y, et al. Decreased adult height in survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study. J Pediatr 2007; 150: 370–375.
- 16 Dalton VK, Rue M, Silverman LB, et al. Height and weight in children treated for acute lymphoblastic leukemia: Relationship to CNS treatment. J Clin Oncol 2003; 21: 2953–2960.
- 17 Vilela MI, Viana MB. Longitudinal growth and risk factors for growth deficiency in children treated for acute lymphoblastic leukemia. Pediatr Blood Cancer 2007; 48: 86–92.
- 18 Giorgiani G, Bozzola M, Locatelli F, et al. Role of busulfan and total body irradiation on growth of prepubertal children receiving bone marrow transplantation and results of treatment with recombinant human growth hormone. Blood 1995; 86: 825–831.
- 19 Huma Z, Boulad F, Black P, et al. Growth in children after bone marrow transplantation for acute leukemia. Blood 1995; 86: 819–824.
- 20 Sanders JE, Guthrie KA, Hoffmeister PA, et al. Final adult height of patients who received hematopoietic cell transplantation in childhood. Blood 2005; 105: 1348–1354.
- 21 Warner JT, Evans WD, Webb DK, et al. Body composition of long-term survivors of acute lymphoblastic leukaemia. Med Pediatr Oncol 2002; 38: 165–172.
- 22 Janiszewski PM, Oeffinger KC, Church TS, et al. Abdominal obesity, liver fat, and muscle composition in survivors of childhood acute lymphoblastic leukemia. J Clin Endocrinol Metab 2007; 92: 3816–3821.
- 23 Garmey EG, Liu Q, Sklar CA, et al. Longitudinal changes in obesity and body mass index among adult survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study. J Clin Oncol 2008; 26: 4639–4645.
- 24 Chow EJ, Pihoker C, Hunt K, et al. Obesity and hypertension among children after treatment for acute lymphoblastic leukemia. Cancer 2007; 110: 2313–2320.
- 25 Razzouk BI, Rose SR, Hongeng S, et al. Obesity in survivors of childhood acute lymphoblastic leukemia and lymphoma. J Clin Oncol 2007; 25: 1183–1189.
- 26 Withycombe JS, Post-White JE, Meza JL, et al. Weight patterns in children with higher risk ALL: A report from the Children's Oncology Group (COG) for CCG 1961. Pediatr Blood Cancer 2009; 53: 1249–1254.
- 27 Kohler JA, Moon RJ, Wright S, et al. Increased adiposity and altered adipocyte function in female survivors of childhood acute lymphoblastic leukaemia treated without cranial radiation. Horm Res Paediatr 2011; 75: 433–440.
- 28 Nysom K, Holm K, Michaelsen KF, et al. Degree of fatness after allogeneic BMT for childhood leukaemia or lymphoma. Bone Marrow Transplant 2001; 27: 817–820.
- 29 Chow EJ, Simmons JH, Roth CL, et al. Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic leukemia treated with total body irradiation. Biol Blood Marrow Transplant 2010; 16: 1674–1681.
- 30 Mostoufi-Moab S, Ginsberg JP, Bunin N, et al. Body composition abnormalities in long-term survivors of pediatric hematopoietic stem cell transplantation. J Pediatr 2012; 160: 122–128.
- 31 Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640–1645.
- 32 Nieder ML, McDonald GB, Kida A, et al. National Cancer Institute -National Heart, Lung and Blood Institute/pediatric Blood and Marrow Transplant Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: Long-term organ damage and dysfunction. Biol Blood Marrow Transplant 2011; 17: 1573–15784.
- 33 Chow EJ, Friedman DL, Stovall M, et al. Risk of thyroid dysfunction and subsequent thyroid cancer among survivors of acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 2009; 53: 432–437.
- 34 Sanders JE, Hoffmeister PA, Woolfrey AE, et al. Thyroid function following hematopoietic cell transplantation in children: 30 years' experience. Blood 2009; 113: 306–308.
- 35 Boulad F, Bromley M, Black P, et al. Thyroid dysfunction following bone marrow transplantation using hyperfractionated radiation. Bone Marrow Transplant 1995; 15: 71–76.
- 36 Bakker B, Oostdijk W, Bresters D, et al. Disturbances of growth and endocrine function after busulphan-based conditioning for haematopoietic stem cell transplantation during infancy and childhood. Bone Marrow Transplant 2004; 33: 1049–1056.
- 37 Slatter MA, Gennery AR, Cheetham TD, et al. Thyroid dysfunction after bone marrow transplantation for primary immunodeficiency without the use of total body irradiation in conditioning. Bone Marrow Transplant 2004; 33: 949–953.
- 38 Ishiguro H, Yasuda Y, Tomita Y, et al. Long-term follow-up of thyroid function in patients who received bone marrow transplantation during childhood and adolescence. J Clin Endocrinol Metab 2004; 89: 5981–5986.
- 39 Berger C, Le-Gallo B, Donadieu J, et al. Late thyroid toxicity in 153 long-term survivors of allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. Bone Marrow Transplant 2005; 35: 991–995.
- 40 Green DM, Whitton JA, Stovall M, et al. Pregnancy outcome of female survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Am J Obstet Gynecol 2002; 187: 1070–1080.
- 41 Green DM, Kawashima T, Stovall M, et al. Fertility of male survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. J Clin Oncol 2010; 28: 332–339.
- 42 Green DM, Kawashima T, Stovall M, et al. Fertility of female survivors of childhood cancer: A report from the childhood cancer survivor study. J Clin Oncol 2009; 27: 2677–2685.
- 43 Salooja N, Szydlo RM, Socie G, et al. Pregnancy outcomes after peripheral blood or bone marrow transplantation: A retrospective survey. Lancet 2001; 358: 271–276.
- 44 Carter A, Robison LL, Francisco L, et al. Prevalence of conception and pregnancy outcomes after hematopoietic cell transplantation: Report from the Bone Marrow Transplant Survivor Study. Bone Marrow Transplant 2006; 37: 1023–1029.
- 45 Sanders JE, Hawley J, Levy W, et al. Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation. Blood 1996; 87: 3045–3052.
- 46 Rovo A, Tichelli A, Passweg JR, et al. Spermatogenesis in long-term survivors after allogeneic hematopoietic stem cell transplantation is associated with age, time interval since transplantation, and apparently absence of chronic GvHD. Blood 2006; 108: 1100–1105.
- 47 Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N Engl J Med 1999; 341: 427–434.
- 48 Louie AD, Robison LL, Bogue M, et al. Validation of self-reported complications by bone marrow transplantation survivors. Bone Marrow Transplant 2000; 25: 1191–1196.
- 49 Wilcox AJ, Weinberg CR, O'Connor JF, et al. Incidence of early loss of pregnancy. N Engl J Med 1988; 319: 189–194.
