A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

Koh, Eng‐Siew; Tran, Tim; Heydarian, M.; Sachs, Rainer K.; Tsang, Richard W.; Brenner, David J.; Pintilie, Melania; Xu, Tengteng; Chung, June Key; Paul, Narinder; Hodgson, David C.

doi:10.1186/1748-717x-2-13

Cited by 128 publications

(98 citation statements)

References 31 publications

(78 reference statements)

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“…Involved field radiotherapy has been reported to give a median MHD of 17.2 Gy for prescribed doses of 35 Gy and involved node radiotherapy leads to even lower doses (median MHDs of 7.7-12.0 Gy for prescribed doses of 36 Gy). [33][34][35] Also, anthracycline doses are nowadays frequently lower than the doses received by the majority of patients in our study. Therefore, patients treated today are likely to be at a substantially lower risk of treatment-related HF than the patients included in this study.…”

Section: Discussionmentioning

confidence: 66%

Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines

Nimwegen

Ntentas

Darby

et al. 2017

Blood

175

163

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Key Points• Risk of HF increases following cardiac radiation doses above 20 Gy.• Anthracyclines increase HF rate by threefold independently of radiation.Hodgkin lymphoma (HL) survivors treated with radiotherapy and/or chemotherapy are known to have increased risks of heart failure (HF), but a radiation dose-response relationship has not previously been derived. A case-control study, nested in a cohort of 2617 five-year survivors of HL diagnosed before age 51 years during 1965 to 1995, was conducted. Cases (n 5 91) had moderate or severe HF as their first cardiovascular diagnosis. Controls (n 5 278) were matched to cases on age, sex, and HL diagnosis date. Treatment and follow-up information were abstracted from medical records. Mean heart doses and mean left ventricular doses (MLVD) were estimated by reconstruction of individual treatments on representative computed tomography datasets. Average MLVD was 16.7 Gy for cases and 13.8 Gy for controls (P difference 5 .003). HF rate increased with MLVD: relative to 0 Gy, HF rates following MVLD of 1-15, 16-20, 21-25, and ‡26 Gy were 1.27, 1.65, 3.84, and 4.39, respectively (P trend < .001). Anthracyclinecontaining chemotherapy increased HF rate by a factor of 2.83 (95% CI: 1.43-5.59), and there was no significant interaction with MLVD (P interaction 5 .09). Twenty-five-year cumulative risks of HF following MLVDs of 0-15 Gy, 16-20 Gy, and ‡21 Gy were 4.4%, 6.2%, and 13.3%, respectively, in patients treated without anthracycline-containing chemotherapy, and 11.2%, 15.9%, and 32.9%, respectively, in patients treated with anthracyclines. We have derived quantitative estimates of HF risk in patients treated for HL following radiotherapy with or without anthracycline-containing chemotherapy. Our results enable estimation of HF risk for patients before treatment, during radiotherapy planning, and during follow-up. (Blood. 2017;129(16):2257-2265 Medscape Continuing

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Section: Discussionmentioning

confidence: 66%

Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines

Nimwegen

Ntentas

Darby

et al. 2017

Blood

175

163

View full text Add to dashboard Cite

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“…On the other hand, two studies [26,30] showed a wide increased BC risk in case of exclusive mantle radiotherapy, but with a reduced risk by irradiation of mediastinum only or associated subdiaphragmatic RT, as well as CT use. Indeed, mediastinal RT alone (without axillary field such as in classical 'mantle" field) spares approximately 50% of the breast tissues [31] (especially upper external quadrants, the most common size of BC onset). On the other hand, both CT (especially with alkylating agents) and supradiaphragmatic RT induce a high rate of permanent menopause, which is a well-known protective factor against BC, whereas the role of splenectomy or subsequent BC risk is discussed.…”

Section: Specific Survival According To Surgerymentioning

confidence: 99%

“…In all cases, it is important to give clear information to women and physicians on the long-term breast cancer risk, in order to perform a regular screening and facilitate diagnosis of in situ or very small invasive cancers, with a favourable long-term prognosis [48,49]. Finally, we can hope that optimal combinations of CT and involved field RT will reduce the absolute risk of secondary BC in young patients [26,31,50,51].…”

Section: Specific Survival According To Surgerymentioning

confidence: 99%

Breast cancer occurred after Hodgkin's disease: Clinico-pathological features, treatments and outcome: Analysis of 214 cases

Cutuli

Kanoun

Lara

et al. 2012

Critical Reviews in Oncology/Hematology

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“…f) For solid tumors, no spatial properties are taken into account. Effects of doseinhomogeneity can be taken into account with dose-volume histograms (Koh et al, 2007) but spatial factors during tumor progression are more complicated [e.g. (Enderling et al, 2007)].…”

Section: Some Weaknesses Of the Iip Modelsmentioning

confidence: 99%

Second cancers after fractionated radiotherapy: Stochastic population dynamics effects

Sachs

Shuryak

Brenner

et al. 2007

Journal of Theoretical Biology

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When ionizing radiation is used in cancer therapy it can induce second cancers in nearby organs. Mainly due to longer patient survival times, these second cancers have become of increasing concern. Estimating the risk of solid second cancers involves modeling: because of long latency times, available data is usually for older, obsolescent treatment regimens. Moreover, modeling second cancers gives unique insights into human carcinogenesis, since the therapy involves administering well characterized doses of a well studied carcinogen, followed by long-term monitoring.In addition to putative radiation initiation that produces pre-malignant cells, inactivation (i.e. cell killing), and subsequent cell repopulation by proliferation can be important at the doses relevant to second cancer situations. A recent initiation/inactivation/proliferation (IIP) model characterized quantitatively the observed occurrence of second breast and lung cancers, using a deterministic cell population dynamics approach. To analyze if radiation-initiated pre-malignant clones become extinct before full repopulation can occur, we here give a stochastic version of this IIP model. Combining Monte Carlo simulations with standard solutions for time-inhomogeneous birth-death equations, we show that repeated cycles of inactivation and repopulation, as occur during fractionated radiation therapy, can lead to distributions of pre-malignant cells per patient with variance ≫ mean, even when pre-malignant clones are Poisson-distributed. Thus fewer patients would be affected, but with a higher probability, than a deterministic model, tracking average pre-malignant cell numbers, would predict. Our results are applied to data on breast cancers after radiotherapy for Hodgkin disease. The stochastic IIP analysis, unlike the deterministic one, indicates: a) initiated, pre-malignant cells can have a growth advantage during repopulation, not just during the longer tumor latency period that follows; b) weekend treatment gaps during radiotherapy, apart from decreasing the probability of eradicating the primary cancer, substantially increase the risk of later second cancers.

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A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

Cited by 128 publications

References 31 publications

Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines

Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines

Breast cancer occurred after Hodgkin's disease: Clinico-pathological features, treatments and outcome: Analysis of 214 cases

Second cancers after fractionated radiotherapy: Stochastic population dynamics effects

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