Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma

Abstract

BACKGROUND.Estimates of radiation‐related second cancer risk among Hodgkin lymphoma survivors are largely based on radiation therapy (RT) fields and doses no longer in use, and these estimates do not account for differences in normal tissue dose among individual patients. This study gives individualized estimates for the risks of lung and female breast cancer expected with contemporary involved‐field RT and low‐dose (20 Gy) RT for mediastinal Hodgkin lymphoma.METHODS.Three RT plans were constructed for 37 consecutive patients with mediastinal Hodgkin lymphoma: 35 Gy mantle RT, 35 Gy involved‐field RT (IFRT), and 20 Gy IFRT. For each of the 111 RT plans, individual‐level dosimetry data were incorporated into a cell initiation/inactivation/proliferation model to estimate the excess relative risk (ERR) and cumulative incidence of radiation‐induced second cancer.RESULTS.ERR estimates were compatible with results of epidemiological studies. Compared with 35 Gy mantle radiation therapy, 35 Gy IFRT was predicted to reduce the 20‐year ERRs of breast and lung cancer by 63% and 21%, respectively, primarily because of lower normal tissue doses with the omission of axillary RT. Low‐dose (20 Gy) IFRT was associated with a 77% and 57% decrease in these ERRs. Patient‐specific differences in normal tissue dose with IFRT led to 11‐fold and 3.6‐fold variations among individual's estimates of breast and lung cancer ERR, respectively.CONCLUSIONS.Contemporary IFRT is predicted to substantially reduce risk of secondary breast and lung cancer compared with mantle RT, with considerable variation in risk among individuals. Individualized prospective risk estimates could facilitate patient‐specific counseling and the development of more effective RT techniques. Cancer 2007. © 2007 American Cancer Society.

The UK national breast cancer screening programme for survivors of Hodgkin lymphoma detects breast cancer at an early stage

“…At The Christie, as elsewhere, the use of a mantle field for the treatment of women requiring SRT for HL has declined over time. In a recent report, a switch from a 35-Gy mantle field to involved field radiotherapy (IFRT) at the same total dose reduced the estimated 20-year excess RR of BC by 63% (Hodgson et al, 2007). This model is consistent with meta-analysis data of clinical trials demonstrating an odds ratio of 3.25 (P ¼ 0.04) for the development of BC for women treated with extended field vs IFRT (Franklin et al, 2006).…”

“…Thus, the NRASP strategy seems to be capable of detecting BC at an early clinical stage, whereas the range of immunophenotypes suggests that these tumours are not of a universally good prognosis. Although new radiotherapy techniques and treatment strategies have the potential to reduce the future burden of late effects, the population of women reviewed in the NRASP has a mean age approaching that at which BC was diagnosed in the 23 affected women, suggesting that there remains a significant cohort at an increased risk of BC (and other malignancies) in whom continued vigilance is required (Tinger et al, 1997;Hodgson et al, 2007).…”

The addition of radiotherapy to chemotherapy does not improve outcome of early stage Hodgkin’s lymphoma patients: a retrospective long-term follow-up analysis of a regional Italian experience

“…Nonetheless, radiotherapy, especially when administered in extended field has been associated with an increased risk of second neoplasia [13,15,17]. In our series, a second tumor was diagnosed in four patients who had been exposed to RT, even though a clear relationship with RT was only found in two of the cases.…”

“…It therefore became interesting to determine whether combined modality therapy (chemotherapy + radiotherapy, CT + RT) might improve the results as compared to radiotherapy [8][9][10][11][12]. Moreover, the late risk of developing second tumors and coronary heart disease after chest radiotherapy led to reconsider the application of involved or extended field radiotherapy in front line treatment [13][14][15][16][17]. Over the last decade, some trials have explored the possibility of treating HL patients with CT alone [18][19][20].…”

Efficacy of dose escalation on TCP, recurrence and second cancer risks: a mathematical study

“…To validate our mathematical framework clinically, one can use the DVH data and evaluate TCP, relapse and second cancer risk for patients with HL. The estimation of second cancer risk based on DVH data has been previously carried out by Hodgson et al 26 This work can be extended, upon the availability of clinical data for primary tumours such as the differential DVHs and the relapse data for patients with HL, to validate our modelling results. Additionally, we would also like to extend our model to include tissue recovery and repair owing to radiation therapy.…”