jueves, 6 de junio de 2019

Childhood Hodgkin Lymphoma Treatment (PDQ®) 6/6 —Health Professional Version - National Cancer Institute

Childhood Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version - National Cancer Institute
National Cancer Institute

Childhood Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version


Special Considerations for the Treatment of Children With Cancer

Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:
  • Primary care physicians.
  • Pediatric surgeons.
  • Radiation oncologists.
  • Pediatric medical oncologists and hematologists.
  • Rehabilitation specialists.
  • Pediatric nurse specialists.
  • Social workers.
  • Child life professionals.
  • Psychologists.
(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[2] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients and their families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.
References
  1. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
  2. Corrigan JJ, Feig SA; American Academy of Pediatrics: Guidelines for pediatric cancer centers. Pediatrics 113 (6): 1833-5, 2004. [PUBMED Abstract]

Late Effects From Childhood/Adolescent Hodgkin Lymphoma Therapy

Childhood and adolescent survivors of Hodgkin lymphoma may be at risk of developing numerous late complications of treatment related to radiation, specific chemotherapeutic exposures, and surgical staging.[1,2] Adverse treatment effects may impact the following:
In the past 30 to 40 years, pediatric Hodgkin lymphoma therapy has changed dramatically to proactively limit exposure to radiation and chemotherapeutic agents, such as anthracyclines, alkylating agents, and bleomycin. When counseling individual patients about the risk of specific treatment complications, the era of treatment should be considered.
Table 10 summarizes late health effects observed in Hodgkin lymphoma survivors, followed by a limited discussion of the common late effects. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for a full discussion of the late effects of cancer treatment in children and adolescents.)
Table 10. Treatment Complications Observed in Hodgkin Lymphoma Survivors
Health EffectsPredisposing TherapyClinical Manifestations
ReproductiveAlkylating agent chemotherapyHypogonadism
Gonadal irradiationInfertility
ThyroidRadiation impacting thyroid glandHypothyroidism
Hyperthyroidism
Thyroid nodules
CardiovascularRadiation impacting cardiovascular structuresSubclinical left ventricular dysfunction
Cardiomyopathy
Pericarditis
Heart valve dysfunction
Conduction disorder
Coronary, carotid, subclavian vascular disease
Myocardial infarction
Stroke
Anthracycline chemotherapySubclinical left ventricular dysfunction
Cardiomyopathy
Congestive heart failure
Subsequent neoplasms or diseaseAlkylating agent chemotherapyMyelodysplasia/acute myeloid leukemia
EpipodophyllotoxinsMyelodysplasia/acute myeloid leukemia
RadiationSolid benign and malignant neoplasms
Oral or dentalAny chemotherapy in a patient who has not developed permanent dentitionDental maldevelopment (tooth or root agenesis, microdontia, root thinning and shortening, enamel dysplasia)
Radiation impacting oral cavity and salivary glandsSalivary gland dysfunction
Xerostomia
Accelerated dental decay
Periodontal disease
PulmonaryRadiation impacting the lungsSubclinical pulmonary dysfunction
BleomycinPulmonary fibrosis
MusculoskeletalRadiation of musculoskeletal tissues in any patient who is not skeletally matureGrowth impairment
GlucocorticosteroidsBone mineral density deficit
Multiple sclerosis
ImmuneSplenectomyOverwhelming post-splenectomy sepsis

Male Gonadal Toxicity

Important concepts related to male gonadal toxicity include the following:
  • Gonadal irradiation and alkylating agent chemotherapy may produce testicular Leydig cell or germ cell dysfunction, with risk related to cumulative dose of both modalities.
  • Hypoandrogenism associated with Leydig cell dysfunction may manifest as lack of sexual development; small, atrophic testicles; and sexual dysfunction. Hypoandrogenism also increases the risk of osteoporosis and metabolic disorders associated with chronic disease.[3,4]
  • Testicular Leydig cells are relatively resistant to treatment toxicity compared with testicular germ cells. Survivors who are azoospermic after gonadal toxic therapy may maintain adequate testosterone production.[5-7]
  • Infertility caused by azoospermia is the most common manifestation of gonadal toxicity. Some pubertal male patients will have impaired spermatogenesis before they begin therapy.[8,9]
  • The prepubertal testicle is likely equally or slightly less sensitive to chemotherapy compared with the pubertal testicle. Pubertal status is not protective of chemotherapy-associated gonadal toxicity.[6,7]
  • Chemotherapy regimens that do not include alkylating agents such as ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine), ABVE (doxorubicin [Adriamycin], bleomycin, vincristine, etoposide), OEPA (vincristine [Oncovin], etoposide, prednisone, doxorubicin [Adriamycin]), or VAMP (vincristine, doxorubicin [Adriamycin], methotrexate, prednisone) are not associated with male infertility.
  • ABVE-PC (prednisone and cyclophosphamide) and OEPA-COPDAC (cyclophosphamide, vincristine, prednisone, dacarbazine) are titrated to limit alkylating agent dose to below the usual threshold associated with male sterility. Investigations evaluating germ cell function in relation to single alkylating agent exposure suggest that the incidence of permanent azoospermia will be low if the cyclophosphamide dose is less than 7.5 g/m2.[7,10]
  • Chemotherapy regimens that include more than one alkylating agent, usually procarbazine in conjunction with cyclophosphamide (i.e., COPP [cyclophosphamide, vincristine (Oncovin), prednisone, procarbazine]), chlorambucil, or nitrogen mustard (MOPP) confer a high risk of permanent azoospermia if treatment exceeds three cycles.[11,12]
(Refer to the Testis section in the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information.)

Female Gonadal Toxicity

Ovarian hormone production is linked to the maturation of primordial follicles. Depletion of follicles by alkylating agent chemotherapy can potentially affect both fertility and ovarian hormone production. Because of their greater complement of primordial follicles, the ovaries of young and adolescent girls are less sensitive to the effects of alkylating agents than are the ovaries of older women. In general, girls maintain ovarian function at higher cumulative alkylating agent doses compared with the germ cell function maintained in boys.
Important concepts related to female gonadal toxicity include the following:
  • Most females treated with contemporary risk-adapted therapy will have menarche (if prepubertal at treatment) or regain normal menses (if pubertal at treatment) unless pelvic radiation therapy is given without oophoropexy. Current regimens used in pediatric oncology are tailored to minimize the risk of ovarian failure. Data presented below related to pediatric treatment before 1987 [13,14] or adult trials in Europe (European Organisation for Research and Treatment of Cancer H1–H9 trials) [15] are not likely reflective of the expected reproductive outcomes in the current era.
  • Ovarian transposition to a lateral or medial region from the planned radiation volume may preserve ovarian function in young and adolescent girls who require pelvic radiation therapy for lymphoma.[16] Ovarian transposition did not appear to modify risk of premature ovarian insufficiency in a cohort of 49 long-term survivors of Hodgkin lymphoma enrolled in the St. Jude Lifetime Cohort Study treated with gonadotoxic therapy who underwent ovarian transposition before pelvic radiation therapy.[17]
  • The risk of acute ovarian failure and premature menopause is substantial if treatment includes combined-modality therapy with alkylating agent chemotherapy and abdominal or pelvic radiation or dose-intensive alkylating agents for myeloablative conditioning before hematopoietic cell transplantation.[13,14] The risk of ovarian failure after treatment with contemporary regimens using lower cumulative doses of cyclophosphamide without procarbazine is anticipated to be lower.
  • In the Childhood Cancer Survivor Study (CCSS), investigators observed that Hodgkin lymphoma survivors were among the highest risk groups for acute ovarian failure and early menopause. In this cohort, the cumulative incidence of nonsurgical premature menopause among survivors treated with alkylating agents and abdominal or pelvic radiation approached 30%.[13,14] These patients were treated before 1986, usually with substantially higher doses of alkylating agents than are used in current regimens in the Children's Oncology Group, EuroNet, or other consortiums.
  • A German study demonstrated that parenthood for female survivors of Hodgkin lymphoma was similar to that of the general population, although parenthood was lower for survivors who received pelvic radiation therapy.[18]
(Refer to the Ovary section in the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information.)

Thyroid Abnormalities

Abnormalities of the thyroid gland, including hypothyroidism, hyperthyroidism, and thyroid neoplasms have been reported to occur at a higher rate among survivors of Hodgkin lymphoma than in the general population.
  • Hypothyroidism. Risk factors for hypothyroidism include increasing dose of radiation, female sex, and older age at diagnosis.[19-21] CCSS investigators reported a 20-year actuarial risk of 30% of developing hypothyroidism in Hodgkin lymphoma survivors treated with 3,500 cGy to 4,499 cGy of radiation and 50% for subjects whose thyroid received 4,500 cGy or more of radiation.
    Hypothyroidism develops most often in the first 5 years after treatment, but new cases have been reported to emerge more than 20 years after the diagnosis.[20]
  • Hyperthyroidism. Hyperthyroidism has been observed after treatment for Hodgkin lymphoma, with a clinical picture similar to that of Graves disease.[22] Higher radiation dose has been associated with greater risk of hyperthyroidism.[20]
  • Subsequent neoplasms. Thyroid neoplasms, both benign and malignant, have been reported with increased frequency after neck irradiation. The incidence of nodules varies substantially across studies (2%–65%) depending on the length of follow-up and detection methods used.[19-21]
    The relative risk (RR) of thyroid cancer is increased among Hodgkin lymphoma survivors (approximately 18-fold for the CCSS Hodgkin lymphoma cohort compared with the general population).[21] Risk factors for the development of thyroid nodules in Hodgkin lymphoma survivors reported by CCSS include time since diagnosis of more than 10 years (RR, 4.8; 95% confidence interval [CI], 3.0–7.8), female sex (RR, 4.0; 95% CI, 2.5–6.7), and radiation dose to thyroid higher than 25 Gy (RR, 2.9; 95% CI, 1.4–6.9).[21] The absolute risk of thyroid cancer is relatively low, with approximately 1% of the CCSS Hodgkin cohort developing thyroid cancer, with a median follow-up of approximately 15 years.[21]
    A single-institution Hodgkin lymphoma survivor cohort that included both adult and pediatric cases showed a cumulative incidence of thyroid cancer at 10 years from diagnosis of 0.26%, increasing to approximately 3% at 30 years from diagnosis. In this cohort, age younger than 20 years at Hodgkin lymphoma diagnosis and female sex were significantly associated with thyroid cancer.[23]
(Refer to the Thyroid Gland section in the PDQ summary on Late Effects of Treatment for Childhood Cancer summary for more information.)

Cardiac Toxicity

Hodgkin lymphoma survivors exposed to doxorubicin or thoracic radiation therapy are at risk of long-term cardiac toxicity. The effects of thoracic radiation therapy are difficult to separate from those of anthracyclines because few children undergo thoracic radiation therapy without the use of anthracyclines. The pathogenesis of injury differs, however, with radiation primarily affecting the fine vasculature of the heart, and anthracyclines directly damaging myocytes.[24-26]
Survivors of childhood Hodgkin lymphoma older than 50 years will experience more than two times the number of chronic cardiovascular health conditions and nearly five times the number of more severe (grades 3–5) cardiovascular conditions compared with community controls and, on average, have one severe, life-threatening, or fatal cardiovascular condition.[27]
Cardiac mortality is higher for survivors of adolescent Hodgkin lymphoma than for survivors of young adult Hodgkin lymphoma. This was demonstrated in the Teenage and Young Adult Cancer Survivor Study cohort, with standardized mortality ratios (SMR) of 10.4 (95% CI, 8.1–13.3) for those diagnosed at age 15 and 19 years, compared with an SMR of 2.8 (95% CI, 2.3–3.4) for those diagnosed at age 35 to 39 years.[28]

Radiation-associated cardiovascular toxicity

  • Late effects of radiation to the heart may include the following:[29-32]
    • Delayed pericarditis.
    • Pancarditis including pericardial and myocardial fibrosis, with or without endocardial fibroelastosis.
    • Cardiomyopathy.
    • Coronary artery disease.[26,32]
    • Functional valve injury.[26,33]
    • Conduction defects.
    The risks to the heart are related to the amount of radiation delivered to different depths of the heart, volume and specific areas of the heart irradiated, total and fractional irradiation dose, age at exposure, and latency period.
  • Modern radiation techniques allow a reduction in the volume of cardiac tissue incidentally exposed to higher radiation doses. It is anticipated that this will reduce the risk of adverse cardiac events.
  • Austrian-German investigators evaluated the development of cardiac disease (via patient self-report supplemented by physician report) in a cohort of 1,132 pediatric Hodgkin lymphoma survivors monitored for a median of 20 years. The 25-year cumulative incidence of heart disease increased with higher mediastinal radiation doses: 3% (unirradiated), 5% (20 Gy), 6% (25 Gy), 10% (30 Gy), and 21% (36 Gy). Valve defects were most common, followed by coronary artery disease, cardiomyopathy, rhythm disorders, and pericardial abnormalities.[33]
  • In a study of adult survivors of Hodgkin lymphoma, vigorous exercise lowered the risk of cardiovascular events, independent of the treatment received.[34]

Anthracycline-related cardiac toxicity

  • Late complications related to anthracycline injury may include subclinical left ventricular dysfunction, cardiomyopathy, and congestive heart failure.[26]
  • Increased risk of doxorubicin-related cardiomyopathy is associated with female sex, cumulative doses higher than 200 mg/m2 to 300 mg/m2, younger age at time of exposure, and increased time from exposure.[35]
  • Prevention or amelioration of anthracycline-induced cardiomyopathy is important because the continued usage of anthracyclines is required in cancer therapy in more than one-half of children with newly diagnosed cancer.[36,37]
  • Dexrazoxane (a bisdioxopiperazine compound that readily enters cells and is subsequently hydrolyzed to form a chelating agent) has been shown to prevent heart damage in adults and children treated with anthracyclines.[38] Studies suggest that dexrazoxane is safe and does not interfere with chemotherapeutic efficacy. Dexrazoxane has been associated with increased hematologic toxicity and typhlitis in children with Hodgkin lymphoma receiving ABVE-PC chemotherapy.[39]
  • A number of trials have studied the risk of subsequent neoplasms following dexrazoxane administration and none have found a significant association with subsequent neoplasms.[40,41] However, one study found a borderline statistical increase in subsequent neoplasms in patients randomly assigned to receive dexrazoxane that was attributed to the administration of three topoisomerase inhibitors (doxorubicin, etoposide, and dexrazoxane) within 2 to 3 hours of each other.[42]
  • Studies of cancer survivors treated with anthracyclines have not demonstrated the benefit of enalapril in preventing progressive cardiac toxicity.[43,44]
(Refer to the Late Effects of the Cardiovascular System section in the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information.)

Subsequent Neoplasms

A number of series evaluating the incidence of subsequent neoplasms in survivors of childhood and adolescent Hodgkin lymphoma have been published.[45-54]; [55][Level of evidence: 3iii] Many of the patients included in these series received high-dose radiation therapy and high-dose alkylating agent chemotherapy regimens, which are no longer used.
  • Subsequent neoplasms comprise two distinct groups:[56,57]
    • Myelodysplasia and acute myeloid leukemia (AML) that are chemotherapy related.
      Subsequent hematological malignancy (most commonly AML and myelodysplasia) is related to the use of alkylating agents, anthracycline, and etoposide and exhibit a brief latency period (<10 a="" cancer="" from="" href="https://www.cancer.gov/types/lymphoma/hp/child-hodgkin-treatment-pdq?cid=eb_govdel#cit/section_7.58" primary="" style="border: 0px; box-sizing: border-box; color: #2b7bba; font: inherit; margin: 0px; padding: 0px; text-decoration-line: none; vertical-align: baseline;" the="" years="">58
] This excess risk is largely related to cases of myelodysplasia and subsequent AML. A single-study experience suggests that there could be an increase in malignancies when multiple topoisomerase inhibitors are administered in close proximity.[42] Clinical trials using dexrazoxane in childhood leukemia have not observed an excess risk of subsequent neoplasms.[42,59,60]
Chemotherapy-related myelodysplasia and AML are less prevalent following contemporary therapy because of the restriction of cumulative alkylating agent doses.[61,62]
  • Solid neoplasms that are predominately radiation related.
    Solid neoplasms most often involve the skin, breast, thyroid, gastrointestinal tract, lung, and head and neck, with risk increasing with radiation dose.[52,54,63]; [55][Level of evidence: 3iii] The risk of a solid subsequent neoplasm escalates with the passage of time after diagnosis of Hodgkin lymphoma, with a latency of 20 years or more. (Refer to the Thyroid Abnormalities section of this summary for more information about subsequent thyroid neoplasms.)
    Breast cancer is the most common therapy-related solid subsequent neoplasm after Hodgkin lymphoma:
    • The absolute excess risk of breast cancer ranges from 18.6 to 79 per 10,000 person-years, and the cumulative incidence ranges from 12% to 26%, 25 to 30 years after radiation exposure.[51,64-66]
    • High risk of breast cancer has been found to increase as early as 8 years from radiation exposure, is rare before age 25 years, and continues to increase with time from exposure. Importantly, breast cancer in female childhood cancer survivors typically develops at least 25 years earlier than that of primary breast cancer in the general population and often years before the implementation of population-based screening.[51]
    • The cumulative incidence of breast cancer by age 40 to 45 years ranges from 13% to 20%, compared with a 1% risk for women in the general population.[51,64,66,67] This risk is similar to what is observed for women with a BRCAgene mutation, where, by age 40 years, the cumulative incidence of breast cancer ranges from 10% to 19%.[68]
    • The risk of breast cancer in female survivors of Hodgkin lymphoma is directly related to the dose of radiation therapy received over a range from 4 Gy to 40 Gy.[69] Female patients treated with both radiation therapy and alkylating agent chemotherapy have a lower RR of developing breast cancer than women receiving radiation therapy alone.[52,70] CCSS investigators also demonstrated that breast cancer risk associated with breast irradiation was sharply reduced among women who received 5 Gy or more to the ovaries.[71] The protective effect of alkylating chemotherapy and ovarian radiation is believed to be mediated through induction of premature menopause, suggesting that hormone stimulation contributes to the development of radiation-induced breast cancer.[72]
  • Hereditary syndromes, other than high-risk breast cancer syndromes, may modify the effect of radiation exposure on breast cancer risk after childhood cancer.[73]
  • A study of women survivors who received chest radiation for Hodgkin lymphoma showed that one of the most important factors in obtaining breast cancer screenings per guidelines was recommendation from their treating physician.[74] Standard guidelines for routine breast screening are available. The COG guidelinesrecommend annual screening with magnetic resonance imaging and mammograms for women beginning 8 years after treatment or at age 25 years, whichever is later.[74]
    • (Refer to the Subsequent Neoplasms section in the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information.)
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    48. Metayer C, Lynch CF, Clarke EA, et al.: Second cancers among long-term survivors of Hodgkin's disease diagnosed in childhood and adolescence. J Clin Oncol 18 (12): 2435-43, 2000. [PUBMED Abstract]
    49. Wolden SL, Lamborn KR, Cleary SF, et al.: Second cancers following pediatric Hodgkin's disease. J Clin Oncol 16 (2): 536-44, 1998. [PUBMED Abstract]
    50. Sankila R, Garwicz S, Olsen JH, et al.: Risk of subsequent malignant neoplasms among 1,641 Hodgkin's disease patients diagnosed in childhood and adolescence: a population-based cohort study in the five Nordic countries. Association of the Nordic Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology. J Clin Oncol 14 (5): 1442-6, 1996. [PUBMED Abstract]
    51. 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. [PUBMED Abstract]
    52. Constine LS, Tarbell N, Hudson MM, et al.: Subsequent malignancies in children treated for Hodgkin's disease: associations with gender and radiation dose. Int J Radiat Oncol Biol Phys 72 (1): 24-33, 2008. [PUBMED Abstract]
    53. Swerdlow AJ, Higgins CD, Smith P, et al.: Second cancer risk after chemotherapy for Hodgkin's lymphoma: a collaborative British cohort study. J Clin Oncol 29 (31): 4096-104, 2011. [PUBMED Abstract]
    54. Chowdhry AK, McHugh C, Fung C, et al.: Second primary head and neck cancer after Hodgkin lymphoma: a population-based study of 44,879 survivors of Hodgkin lymphoma. Cancer 121 (9): 1436-45, 2015. [PUBMED Abstract]
    55. Holmqvist AS, Chen Y, Berano Teh J, et al.: Risk of solid subsequent malignant neoplasms after childhood Hodgkin lymphoma-identification of high-risk populations to guide surveillance: A report from the Late Effects Study Group. Cancer : , 2018. [PUBMED Abstract]
    56. Reulen RC, Frobisher C, Winter DL, et al.: Long-term risks of subsequent primary neoplasms among survivors of childhood cancer. JAMA 305 (22): 2311-9, 2011. [PUBMED Abstract]
    57. 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. [PUBMED Abstract]
    58. Le Deley MC, Leblanc T, Shamsaldin A, et al.: Risk of secondary leukemia after a solid tumor in childhood according to the dose of epipodophyllotoxins and anthracyclines: a case-control study by the Société Française d'Oncologie Pédiatrique. J Clin Oncol 21 (6): 1074-81, 2003. [PUBMED Abstract]
    59. Lipshultz SE, Scully RE, Lipsitz SR, et al.: Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial. Lancet Oncol 11 (10): 950-61, 2010. [PUBMED Abstract]
    60. Barry EV, Vrooman LM, Dahlberg SE, et al.: Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane. J Clin Oncol 26 (7): 1106-11, 2008. [PUBMED Abstract]
    61. Koontz MZ, Horning SJ, Balise R, et al.: Risk of therapy-related secondary leukemia in Hodgkin lymphoma: the Stanford University experience over three generations of clinical trials. J Clin Oncol 31 (5): 592-8, 2013. [PUBMED Abstract]
    62. Schellong G, Riepenhausen M, Creutzig U, et al.: Low risk of secondary leukemias after chemotherapy without mechlorethamine in childhood Hodgkin's disease. German-Austrian Pediatric Hodgkin's Disease Group. J Clin Oncol 15 (6): 2247-53, 1997. [PUBMED Abstract]
    63. Daniëls LA, Krol AD, Schaapveld M, et al.: Long-term risk of secondary skin cancers after radiation therapy for Hodgkin's lymphoma. Radiother Oncol 109 (1): 140-5, 2013. [PUBMED Abstract]
    64. 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. [PUBMED Abstract]
    65. Ng AK, Bernardo MV, Weller E, et al.: Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors. Blood 100 (6): 1989-96, 2002. [PUBMED Abstract]
    66. Taylor AJ, Winter DL, Stiller CA, et al.: Risk of breast cancer in female survivors of childhood Hodgkin's disease in Britain: a population-based study. Int J Cancer 120 (2): 384-91, 2007. [PUBMED Abstract]
    67. Henderson TO, Amsterdam A, Bhatia S, et al.: Systematic review: surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer. Ann Intern Med 152 (7): 444-55; W144-54, 2010. [PUBMED Abstract]
    68. Easton DF, Ford D, Bishop DT: Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 56 (1): 265-71, 1995. [PUBMED Abstract]
    69. Alm El-Din MA, Hughes KS, Finkelstein DM, et al.: Breast cancer after treatment of Hodgkin's lymphoma: risk factors that really matter. Int J Radiat Oncol Biol Phys 73 (1): 69-74, 2009. [PUBMED Abstract]
    70. 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. [PUBMED Abstract]
    71. 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. [PUBMED Abstract]
    72. De Bruin ML, Sparidans J, van't Veer MB, et al.: Breast cancer risk in female survivors of Hodgkin's lymphoma: lower risk after smaller radiation volumes. J Clin Oncol 27 (26): 4239-46, 2009. [PUBMED Abstract]
    73. Morton LM, Sampson JN, Armstrong GT, et al.: Genome-Wide Association Study to Identify Susceptibility Loci That Modify Radiation-Related Risk for Breast Cancer After Childhood Cancer. J Natl Cancer Inst 109 (11): , 2017. [PUBMED Abstract]
    74. Oeffinger KC, Ford JS, Moskowitz CS, et al.: Breast cancer surveillance practices among women previously treated with chest radiation for a childhood cancer. JAMA 301 (4): 404-14, 2009. [PUBMED Abstract]

    Changes to This Summary (05/29/2019)

    The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
    General Information About Childhood Hodgkin Lymphoma
    Added presence of a pleural effusion as a pretreatment factor associated with an adverse outcome (cited McCarten et al. as reference 36 and level of evidence 2A).
    Added text to state that pleural effusions have been shown to be an adverse prognostic finding in patients treated for low-stage Hodgkin lymphoma. The risk of relapse was 25% in patients with an effusion, as opposed to less than 15% in patients without an effusion. Patients with effusions were more often older and had nodular-sclerosing histology.
    Treatment of Newly Diagnosed Children and Adolescents with Hodgkin Lymphoma
    Added text to state that pleural effusions have been shown to be an adverse prognostic finding in patients treated for low-stage Hodgkin lymphoma. The risk of relapse was 25% in patients with an effusion, as opposed to less than 15% in patients without an effusion. Patients with effusions were more often older and had nodular-sclerosing histology (cited McCarten et al. as reference 23 and level of evidence 2A).
    Added text to state that most patients treated with four cycles of the ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide) regimen achieved a rapid early response with a complete response status and demonstrated excellent event-free survival and overall survival without involved-field radiation therapy. This finding suggests that the dose-dense, response-based protocol therapy designed for patients with classical Hodgkin lymphoma may have been more intensive than necessary for patients with lymphocyte-predominant Hodgkin lymphoma.
    This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

    About This PDQ Summary

    Purpose of This Summary

    This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood Hodgkin lymphoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

    Reviewers and Updates

    This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
    Board members review recently published articles each month to determine whether an article should:
    • be discussed at a meeting,
    • be cited with text, or
    • replace or update an existing article that is already cited.
    Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
    The lead reviewers for Childhood Hodgkin Lymphoma Treatment are:
    • Louis S. Constine, MD (James P. Wilmot Cancer Center at University of Rochester Medical Center)
    • Alan Scott Gamis, MD, MPH (Children's Mercy Hospital)
    • Thomas G. Gross, MD, PhD (National Cancer Institute)
    • Melissa Maria Hudson, MD (St. Jude Children's Research Hospital)
    • Kenneth L. McClain, MD, PhD (Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital)
    • Arthur Kim Ritchey, MD (Children's Hospital of Pittsburgh of UPMC)
    • Malcolm A. Smith, MD, PhD (National Cancer Institute)
    Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

    Levels of Evidence

    Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

    Permission to Use This Summary

    PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”
    The preferred citation for this PDQ summary is:
    PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Hodgkin Lymphoma Treatment. Bethesda, MD: National Cancer Institute. Updated . Available at: https://www.cancer.gov/types/lymphoma/hp/child-hodgkin-treatment-pdq. Accessed . [PMID: 26389170]
    Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

    Disclaimer

    Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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    • Updated: May 29, 2019
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