Second Cancer Risk Up to 40 Years after Treatment for Hodgkin’s Lymphoma

Schaapveld, Michael; Aleman, Berthe M.P.; Eggermond, Anna M. van; Janus, Cécile P.M.; Krol, Augustinus D.G.; Maazen, R.W.M. van der; Roesink, Judith M.; Raemaekers, John; Boer, Jan Paul de; Zijlstra, Josée M.; Imhoff, Gustaaf W. van; Petersen, Eefke; Poortmans, Philip; Beijert, Max; Lybeert, Marnix L.M.; Mulder, Ina; Visser, Otto; Louwman, Marieke W. J.; Krul, Inge M; Lugtenburg, Pieternella J.; Leeuwen, Flora E. van

doi:10.1056/nejmoa1505949

Cited by 519 publications

(564 citation statements)

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“…HL treatment (Figure 1), 9 with a 40-year cumulative incidence of second cancer estimated at 43.6% (Figure 2). 9 The largest standardized incidence ratios (SIRs) are observed for leukemia (SIR 5 10-30), followed by connective tissue, pleura and thyroid cancer, and non-HL (SIR 5 6-20).…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8] Common late effects include second and subsequent malignant neoplasms (SMNs), several cardiovascular diseases (CVDs), thyroid dysfunction, subfertility, premature menopause, and fatigue. [7][8][9][10][11][12][13][14][15][16][17] In addition to this wide range of physical late effects, many HL survivors face psychosocial problems that may or may not be linked to specific treatments, but significantly reduce their quality of life. These include impaired memory and concentration, depression and anxiety, sexual problems, and problems with employment and insurances.…”

Section: Introductionmentioning

confidence: 99%

“…14,21,22 In a recent study that included HL patients treated from 1965 to 2000, 9 the excess risk of second malignancy remained significantly increased beyond 35 years after Conflict-of-interest disclosure: The authors declare no competing financial interests.…”

Section: Introductionmentioning

confidence: 99%

“…9 The largest standardized incidence ratios (SIRs) are observed for leukemia (SIR 5 10-30), followed by connective tissue, pleura and thyroid cancer, and non-HL (SIR 5 6-20). 9,12,21,23 Moderately increased risks (SIR 5 2-7) are observed for a large number of solid tumors, such as cancers of the lung, breast, stomach, esophagus, colon/rectum, cervix, mouth and pharynx, and melanoma. 9,12,[23][24][25] Absolute excess risk (AER) is the best risk measure to express burden of disease.…”

Section: Introductionmentioning

confidence: 99%

“…9,12,21,23 Moderately increased risks (SIR 5 2-7) are observed for a large number of solid tumors, such as cancers of the lung, breast, stomach, esophagus, colon/rectum, cervix, mouth and pharynx, and melanoma. 9,12,[23][24][25] Absolute excess risk (AER) is the best risk measure to express burden of disease. HL patients experience an excess of about 85 to 125 malignancies per 10 000 patients per year, over and above the background rate.…”

Section: Introductionmentioning

confidence: 99%

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Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment

Leeuwen

2016

Hematology

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108

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Long-term survivors of Hodgkin lymphoma (HL) experience several late adverse effects of treatment, with second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) being the leading causes of death in these patients. Other late effects have also been identified, such as pulmonary dysfunction, endocrinopathies (thyroid dysfunction, infertility), neck muscle atrophy, and persistent fatigue. HL survivors have two-to fourfold increased risks to develop SMNs and CVD compared with the general population. With respect to SMNs, radiotherapy is associated with 1.5-to 15-fold increased risk of solid malignancies. The relative risk (RR) of solid tumors increases steadily with increasing follow-up time from 5 to 15 years since radiotherapy, and remains elevated for at least 40 years. The RR of solid SMNs increases strongly with younger age at first treatment. Risks of lung, breast, and gastrointestinal (GI) cancers increase with higher radiation dose. Alkylating agent chemotherapy, especially procarbazine, does not only increase risk of leukemia but also of solid malignancies, in particular, cancers of the lung and GI tract. In contrast, gonadotoxic chemotherapy decreases the risk of radiation-associated breast cancer, through induction of premature menopause. Smoking appears to multiply the radiation-and chemotherapy-associated risks of lung cancer. Both radiotherapy and chemotherapy for HL may cause cardiovascular toxicity. Radiotherapy increases the risk of coronary heart disease, valvular heart disease, congestive heart failure (HF), and pericarditis, whereas anthracycline-containing chemotherapy increases the risks of HF and valvular heart disease. Cardiovascular toxicity following radiotherapy is usually observed from 5 to at least 35 years after therapy, whereas anthracycline-related toxicity is already observed during treatment, up to at least 25 years. The joint effects of anthracyclines, radiotherapy, and conventional cardiovascular risk factors (eg, hypertension, smoking, and physical inactivity) appear to be additive rather than multiplicative. HL survivors need lifelong risk-based screening for selected SMNs and CVDs. Furthermore, preventive strategies should include lifestyle and drug-based interventions to minimize exposure to conventional risk factors for cancer and CVD. Learning Objectives• Know treatment-related risk factors for the development of second malignancy and CVDs after HL • Be aware of the content of use surveillance guidelines for HL survivors, aimed at reduction of morbidity and mortality from second malignancy and CVDs

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment

Leeuwen

2016

Hematology

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108

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Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015

Turcotte

Liu

Yasui

et al. 2017

JAMA

193

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IMPORTANCE Cancer treatments are associated with subsequent neoplasms in survivors of childhood cancer. It is unknown whether temporal changes in therapy are associated with changes in subsequent neoplasm risk.OBJECTIVE To quantify the association between temporal changes in treatment dosing and subsequent neoplasm risk.DESIGN, SETTING, AND PARTICIPANTS Retrospective, multicenter cohort study of 5-year cancer survivors diagnosed before age 21 years from pediatric tertiary hospitals in the United States and Canada between 1970-1999, with follow-up through December 2015.EXPOSURES Radiation and chemotherapy dose changes over time.MAIN OUTCOMES AND MEASURES Subsequent neoplasm 15-year cumulative incidence, cumulative burden, and standardized incidence ratios for subsequent malignancies, compared by treatment decade. Multivariable models assessed relative rates (RRs) of subsequent neoplasms by 5-year increments, adjusting for demographic and clinical characteristics. Mediation analyses assessed whether changes in rates of subsequent neoplasms over time were mediated by treatment variable modifications. RESULTS Among 23 603 survivors of childhood cancer (mean age at diagnosis, 7.7 years; 46% female) the most common initial diagnoses were acute lymphoblastic leukemia, Hodgkin lymphoma, and astrocytoma. During a mean follow-up of 20.5 years (374 638 person-years at risk), 1639 survivors experienced 3115 subsequent neoplasms, including 1026 malignancies, 233 benign meningiomas, and 1856 nonmelanoma skin cancers. The most common subsequent malignancies were breast and thyroid cancers. Proportions of individuals receiving radiation decreased (77% for 1970s vs 33% for 1990s), as did median dose (30 Gy [interquartile range, 24-44] for 1970s vs 26 Gy [interquartile range, 18-45] for 1990s). Fifteen-year cumulative incidence of subsequent malignancies decreased by decade of diagnosis (2.1% [95% CI, 1.7%-2.4%] for 1970s, 1.7% [95% CI, 1.5%-2.0%] for 1980s, 1.3% [95% CI, 1.1%-1.5%] for 1990s). Reference absolute rates per 1000 person-years were 1.12 (95% CI, 0.84-1.57) for subsequent malignancies, 0.16 (95% CI, 0.06-0.41) for meningiomas, and 1.71 (95% CI, 0.88-3.33) for nonmelanoma skin cancers for survivors with reference characteristics (no chemotherapy, splenectomy, or radiation therapy; male; attained age 28 years). Standardized incidence ratios declined for subsequent malignancies over treatment decades, with advancing attained age. Relative rates declined with each 5-year increment for subsequent malignancies (RR, 0.87 [95% CI, 0.82-0.93]; P < .001), meningiomas (RR, 0.85 [95% CI, 0.75-0.97]; P = .03), and nonmelanoma skin cancers (RR, 0.75 [95% CI, 0.67-0.84]; P < .001). Radiation dose changes were associated with reduced risk for subsequent malignancies, meningiomas, and nonmelanoma skin cancers.CONCLUSIONS AND RELEVANCE Among survivors of childhood cancer, the risk of subsequent malignancies at 15 years after initial cancer diagnosis remained increased for those diagnosed in the 1990s, although the risk was lower compar...

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Assessment of Secondary Sarcomas Among Patients With Cancer of the Abdomen or Pelvis Who Received Combinations of Surgery, Radiation, and Chemotherapy vs Surgery Alone

et al. 2020

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Key Points Question What is the rate of secondary sarcoma among patients with nonmetastatic cancer of the prostate, bladder, colon, rectum or anus, cervix, uterus, or testis who were treated with combinations of surgery, radiation, or chemotherapy compared with patients treated with surgery alone and with the general population? Findings In this cohort study of 173 580 patients, the rate of secondary sarcoma among patients treated with radiotherapy was increased compared with patients who had surgery alone and with the general population. The risk was highest among those who received both chemotherapy and radiotherapy. Meaning This study provides further evidence to support the association of radiotherapy with secondary sarcoma; the finding of an increase in risk with combination radiotherapy and chemotherapy, in particular, merits further study.

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Second Cancer Risk Up to 40 Years after Treatment for Hodgkin’s Lymphoma

Cited by 519 publications

References 30 publications

Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment

Long-term risk of second malignancy and cardiovascular disease after Hodgkin lymphoma treatment

Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015

Assessment of Secondary Sarcomas Among Patients With Cancer of the Abdomen or Pelvis Who Received Combinations of Surgery, Radiation, and Chemotherapy vs Surgery Alone

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