Late Effects of Treatment for Childhood Cancer (PDQ®): Treatment - Health Professional Information [NCI] - Subsequent Neoplasms
Table 1. Selected Syndromes of Inherited Cancer Predispositiona continued...
DNA repair polymorphisms
DNA repair mechanisms protect somatic cells from mutations in tumor suppressor genes and oncogenes that can lead to cancer initiation and progression. An individual's DNA repair capacity appears to be genetically determined. A number of DNA repair genes contain polymorphic variants, resulting in large interindividual variations in DNA repair capacity. Evaluation of the contribution of polymorphisms influencing DNA repair to the risk of SN represents an active area of research.
Screening and Follow-up for Subsequent Neoplasms
Vigilant screening is important for those at risk. Because of the relatively small size of the pediatric cancer survivor population and the prevalence and time to onset of therapy-related complications, undertaking clinical studies to assess the impact of screening recommendations on the morbidity and mortality associated with the late effect is not feasible. However, well-conducted studies on large populations of childhood cancer survivors have provided compelling evidence linking specific therapeutic exposures and late effects. This evidence has been used by several national and international cooperative groups (Scottish Collegiate Guidelines Network, Children's Cancer and Leukaemia Group, Children's Oncology Group [COG]) to develop consensus-based clinical practice guidelines to increase awareness and standardize the immediate care needs of medically vulnerable childhood cancer survivors. The COG Guidelines employ a hybrid approach that is both evidence-based (utilizing established associations between therapeutic exposures and late effects to identify high-risk categories) and grounded in the collective clinical experience of experts (matching the magnitude of the risk with the intensity of the screening recommendations). The screening recommendations in these guidelines represent a statement of consensus from a panel of experts in the late effects of pediatric cancer treatment.
In regard to screening for malignant SNs recommended by the COG Guidelines, certain high-risk populations of childhood cancer survivors merit heightened surveillance due to predisposing host, behavioral, or therapeutic factors.
- Screening for leukemia: t-MDS/AML usually manifests within 10 years following exposure. Recommendations include monitoring with annual complete blood count for 10 years after exposure to alkylating agents or topoisomerase II inhibitors.
- Screening after radiation exposure: Most other SNs are associated with radiation exposure. Screening recommendations include careful annual physical examination of the skin and underlying tissues in the radiation field. Specific comments about screening for more common radiation-associated SNs follow:
- Screening for early-onset skin cancer: Annual dermatological exam should focus on skin lesions and pigmented nevi in the radiation field. Survivors should be counseled about their increased risk of skin cancer, the potential exacerbation of risk through tanning, and the benefits of adhering to behaviors to protect the skin from excessive ultraviolet radiation exposure.
- Screening for early-onset breast cancer: Since outcome after breast cancer is directly linked to stage at diagnosis, close surveillance resulting in early diagnosis should confer survival advantage. Mammography, the most widely accepted screening tool for breast cancer in the general population, may not be the ideal screening tool by itself for radiation-related breast cancers occurring in relatively young women with dense breasts; hence, the American Cancer Society recommends including adjunct screening with magnetic resonance imaging (MRI). Many clinicians are concerned about potential harms related to radiation exposure associated with annual mammography in these young women. In this regard, it is important to consider that the estimated mean breast dose with contemporary standard two-view screening mammograms is about 3.85 mGy to 4.5 mGy.[55,56,57] Thus, 15 additional surveillance mammograms from age 25 to 39 years would increase the total radiation exposure in a woman treated with 20 Gy of chest radiation to 20.05775 Gy. The benefits of detection of early breast cancer lesions in high-risk women must be balanced by the risk predisposed by a 0.3% additional radiation exposure. To keep young women engaged in breast health surveillance, the COG Guideline recommendations for females who received radiation with potential impact to the breast (i.e., radiation doses of 20 Gy or higher to the mantle, mediastinal, whole lung, and axillary fields) include monthly breast self-examination beginning at puberty; annual clinical breast examinations beginning at puberty until age 25 years; and a clinical breast examination every 6 months, with annual mammograms and MRIs beginning 8 years after radiation or at age 25 years (whichever occurs later).
- Screening for early-onset colorectal cancer: Screening of those at risk for early-onset colorectal cancer (i.e., radiation doses of 30 Gy or higher to the abdomen, pelvis, or spine) should include colonoscopy every 5 years beginning at age 35 years or 10 years following radiation (whichever occurs later).
- Friedman DL, Whitton J, Leisenring W, et al.: Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 102 (14): 1083-95, 2010.
- Mertens AC, Liu Q, Neglia JP, et al.: Cause-specific late mortality among 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 100 (19): 1368-79, 2008.
- Armstrong GT, Liu W, Leisenring W, et al.: Occurrence of multiple subsequent neoplasms in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 29 (22): 3056-64, 2011.
- Travis LB, Rabkin CS, Brown LM, et al.: Cancer survivorship--genetic susceptibility and second primary cancers: research strategies and recommendations. J Natl Cancer Inst 98 (1): 15-25, 2006.
- Bhatia S, Sklar C: Second cancers in survivors of childhood cancer. Nat Rev Cancer 2 (2): 124-32, 2002.
- Berger C, Trombert-Paviot B, Casagranda L, et al.: Second malignant neoplasms following childhood cancer: a study of a recent cohort (1987-2004) from the childhood cancer registry of the Rhône-Alpes region (ARCERRA) in France. Pediatr Hematol Oncol 28 (5): 364-79, 2011.
- Nottage K, Lanctot J, Li Z, et al.: Long-term risk for subsequent leukemia after treatment for childhood cancer: a report from the Childhood Cancer Survivor Study. Blood 117 (23): 6315-8, 2011.
- Bhatia S, Yasui Y, Robison LL, et al.: High risk of subsequent neoplasms continues with extended follow-up of childhood Hodgkin's disease: report from the Late Effects Study Group. J Clin Oncol 21 (23): 4386-94, 2003.
- Bhatia S, Sather HN, Pabustan OB, et al.: Low incidence of second neoplasms among children diagnosed with acute lymphoblastic leukemia after 1983. Blood 99 (12): 4257-64, 2002.
- Vardiman JW, Harris NL, Brunning RD: The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 100 (7): 2292-302, 2002.
- Hijiya N, Hudson MM, Lensing S, et al.: Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. JAMA 297 (11): 1207-15, 2007.
- Hijiya N, Ness KK, Ribeiro RC, et al.: Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues. Cancer 115 (1): 23-35, 2009.
- Szczepanski T, van der Velden VH, Waanders E, et al.: Late recurrence of childhood T-cell acute lymphoblastic leukemia frequently represents a second leukemia rather than a relapse: first evidence for genetic predisposition. J Clin Oncol 29 (12): 1643-9, 2011.
- Thirman MJ, Larson RA: Therapy-related myeloid leukemia. Hematol Oncol Clin North Am 10 (2): 293-320, 1996.
- Pedersen-Bjergaard J, Philip P: Balanced translocations involving chromosome bands 11q23 and 21q22 are highly characteristic of myelodysplasia and leukemia following therapy with cytostatic agents targeting at DNA-topoisomerase II. Blood 78 (4): 1147-8, 1991.
- Bassal M, Mertens AC, Taylor L, et al.: Risk of selected subsequent carcinomas in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol 24 (3): 476-83, 2006.
- Neglia JP, Robison LL, Stovall M, et al.: New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 98 (21): 1528-37, 2006.
- Perkins JL, Liu Y, Mitby PA, et al.: Nonmelanoma skin cancer in survivors of childhood and adolescent cancer: a report from the childhood cancer survivor study. J Clin Oncol 23 (16): 3733-41, 2005.
- Ronckers CM, Sigurdson AJ, Stovall M, et al.: Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation dose response and its modifiers. Radiat Res 166 (4): 618-28, 2006.
- Majhail NS, Brazauskas R, Rizzo JD, et al.: Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning. Blood 117 (1): 316-22, 2011.
- Watt TC, Inskip PD, Stratton K, et al.: Radiation-related risk of basal cell carcinoma: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 104 (16): 1240-50, 2012.
- Braam KI, Overbeek A, Kaspers GJ, et al.: Malignant melanoma as second malignant neoplasm in long-term childhood cancer survivors: a systematic review. Pediatr Blood Cancer 58 (5): 665-74, 2012.
- Kenney LB, Yasui Y, Inskip PD, et al.: Breast cancer after childhood cancer: a report from the Childhood Cancer Survivor Study. Ann Intern Med 141 (8): 590-7, 2004.
- Travis LB, Hill D, Dores GM, et al.: Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma. J Natl Cancer Inst 97 (19): 1428-37, 2005.
- Travis LB, Hill DA, Dores GM, et al.: Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease. JAMA 290 (4): 465-75, 2003.
- van Leeuwen FE, Klokman WJ, Stovall M, et al.: Roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin's disease. J Natl Cancer Inst 95 (13): 971-80, 2003.
- O'Brien MM, Donaldson SS, Balise RR, et al.: Second malignant neoplasms in survivors of pediatric Hodgkin's lymphoma treated with low-dose radiation and chemotherapy. J Clin Oncol 28 (7): 1232-9, 2010.
- Inskip PD, Robison LL, Stovall M, et al.: Radiation dose and breast cancer risk in the childhood cancer survivor study. J Clin Oncol 27 (24): 3901-7, 2009.
- Dores GM, Anderson WF, Beane Freeman LE, et al.: Risk of breast cancer according to clinicopathologic features among long-term survivors of Hodgkin's lymphoma treated with radiotherapy. Br J Cancer 103 (7): 1081-4, 2010.
- van Santen HM, Tytgat GA, van de Wetering MD, et al.: Differentiated thyroid carcinoma after 131I-MIBG treatment for neuroblastoma during childhood: description of the first two cases. Thyroid 22 (6): 643-6, 2012.
- Sklar C, Whitton J, Mertens A, et al.: Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 85 (9): 3227-32, 2000.
- Sigurdson AJ, Ronckers CM, Mertens AC, et al.: Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer Survivor Study): a nested case-control study. Lancet 365 (9476): 2014-23, 2005 Jun 11-17.
- Bhatti P, Veiga LH, Ronckers CM, et al.: Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the childhood cancer survivor study. Radiat Res 174 (6): 741-52, 2010.
- Neglia JP, Friedman DL, Yasui Y, et al.: Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study. J Natl Cancer Inst 93 (8): 618-29, 2001.
- Neglia JP, Meadows AT, Robison LL, et al.: Second neoplasms after acute lymphoblastic leukemia in childhood. N Engl J Med 325 (19): 1330-6, 1991.
- Taylor AJ, Little MP, Winter DL, et al.: Population-based risks of CNS tumors in survivors of childhood cancer: the British Childhood Cancer Survivor Study. J Clin Oncol 28 (36): 5287-93, 2010.
- Faraci M, Morana G, Bagnasco F, et al.: Magnetic resonance imaging in childhood leukemia survivors treated with cranial radiotherapy: a cross sectional, single center study. Pediatr Blood Cancer 57 (2): 240-6, 2011.
- Vinchon M, Leblond P, Caron S, et al.: Radiation-induced tumors in children irradiated for brain tumor: a longitudinal study. Childs Nerv Syst 27 (3): 445-53, 2011.
- Tucker MA, D'Angio GJ, Boice JD Jr, et al.: Bone sarcomas linked to radiotherapy and chemotherapy in children. N Engl J Med 317 (10): 588-93, 1987.
- Hawkins MM, Wilson LM, Burton HS, et al.: Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer. J Natl Cancer Inst 88 (5): 270-8, 1996.
- Le Vu B, de Vathaire F, Shamsaldin A, et al.: Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during childhood. Int J Cancer 77 (3): 370-7, 1998.
- Henderson TO, Whitton J, Stovall M, et al.: Secondary sarcomas in childhood cancer survivors: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 99 (4): 300-8, 2007.
- Henderson TO, Rajaraman P, Stovall M, et al.: Risk factors associated with secondary sarcomas in childhood cancer survivors: a report from the childhood cancer survivor study. Int J Radiat Oncol Biol Phys 84 (1): 224-30, 2012.
- van Leeuwen FE, Klokman WJ, Stovall M, et al.: Roles of radiotherapy and smoking in lung cancer following Hodgkin's disease. J Natl Cancer Inst 87 (20): 1530-7, 1995.
- Tukenova M, Diallo I, Anderson H, et al.: Second malignant neoplasms in digestive organs after childhood cancer: a cohort-nested case-control study. Int J Radiat Oncol Biol Phys 82 (3): e383-90, 2012.
- Henderson TO, Oeffinger KC, Whitton J, et al.: Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study. Ann Intern Med 156 (11): 757-66, W-260, 2012.
- Nottage K, McFarlane J, Krasin MJ, et al.: Secondary colorectal carcinoma after childhood cancer. J Clin Oncol 30 (20): 2552-8, 2012.
- Andersson A, Enblad G, Tavelin B, et al.: Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma. Br J Cancer 98 (5): 1001-5, 2008.
- Hisada M, Garber JE, Fung CY, et al.: Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 90 (8): 606-11, 1998.
- Strahm B, Malkin D: Hereditary cancer predisposition in children: genetic basis and clinical implications. Int J Cancer 119 (9): 2001-6, 2006.
- Collins A, Harrington V: Repair of oxidative DNA damage: assessing its contribution to cancer prevention. Mutagenesis 17 (6): 489-93, 2002.
- Landier W, Bhatia S, Eshelman DA, et al.: Development of risk-based guidelines for pediatric cancer survivors: the Children's Oncology Group Long-Term Follow-Up Guidelines from the Children's Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol 22 (24): 4979-90, 2004.
- Diller L, Medeiros Nancarrow C, Shaffer K, et al.: Breast cancer screening in women previously treated for Hodgkin's disease: a prospective cohort study. J Clin Oncol 20 (8): 2085-91, 2002.
- Saslow D, Boetes C, Burke W, et al.: American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 57 (2): 75-89, 2007 Mar-Apr.
- Berrington de Gonzalez A, Berg CD, Visvanathan K, et al.: Estimated risk of radiation-induced breast cancer from mammographic screening for young BRCA mutation carriers. J Natl Cancer Inst 101 (3): 205-9, 2009.
- Young KC, Burch A, Oduko JM: Radiation doses received in the UK Breast Screening Programme in 2001 and 2002. Br J Radiol 78 (927): 207-18, 2005.
- Spelic DC: Updated Trends in Mammography Dose and Image Quality. Silver Spring, Md: U.S. Food and Drug Administration, 2006. Available online. Last accessed April 01, 2013.