Radiotherapy For Hodgkin Lymphoma Research Articles

Effect of organ size and position on out-of-field dose distributions during radiation therapy

Mantle field irradiation has historically been the standard radiation treatment for Hodgkin lymphoma. It involves treating large regions of the chest and neck with high doses of radiation (up to 30 Gy). Previous epidemiological studies on the incidence of second malignancies following radiation therapy for Hodgkin lymphoma have revealed an increased incidence of second tumors in various organs, including lung, breast, thyroid and digestive tract. Multiple other studies, including the Surveillance, Epidemiology and End Results, indicated an increased incidence in digestive tract including stomach cancers following mantle field radiotherapy. Assessment of stomach dose is challenging because the stomach is outside the treatment field but very near the treatment border where there are steep dose gradients. In addition, the stomach can vary greatly in size and position. We sought to evaluate the dosimetric impact of the size and variable position of the stomach relative to the field border for a typical Hodgkin lymphoma mantle field irradiation. The mean stomach dose was measured using thermoluminescent dosimetry for nine variations in stomach size and position. The mean doses to the nine stomach variations ranged from 0.43 to 0.83 Gy when 30 Gy was delivered to the treatment isocenter. Statistical analyses indicated that there were no significant differences in the mean stomach dose when the stomach was symmetrically expanded up to 3 cm or shifted laterally (medial, anterior or posterior shifts) by up to 3 cm. There was, however, a significant (P > 0.01) difference in the mean dose when the stomach was shifted superiorly or inferiorly by ⩾2.5 cm.

Long-Term Survival Among Patients With Hodgkin's Lymphoma Who Developed Breast Cancer: A Population-Based Study

The increased risk of breast cancer (BC) among women receiving chest radiotherapy for Hodgkin's lymphoma (HL) is well-established. However, there are no large population-based studies that describe overall survival (OS) and cause-specific survival (CSS) compared with women with first primary BC. For 298 HL survivors who developed BC (HL-BC group) and 405,223 women with a first or only BC (BC-1 group), actuarial OS and CSS were compared, accounting for age, BC stage, hormone receptor status, sociodemographic status, radiation for HL, and other variables. All patients were derived from the population-based Surveillance, Epidemiology, and End Results program. OS among patients with HL-BC was significantly inferior that of to patients with BC-1: 15-year OS was 48% versus 69% (P < .0001) for localized BC, and 33% versus 43% (P < .0001) for regional/distant BC. Patients with HL-BC had a significantly increased seven-fold risk (P < .0001) of death from other cancers (ie, not HL or BC) compared with patients with BC-1. Mortality from heart disease among patients with HL-BC with either localized or regional/distant disease was also significantly increased (hazard ratio = 2.22, P = .04; and hazard ratio = 4.28, P = .02, respectively) compared with patients with BC-1. Although 10-year BC-CSS was similar for patients with HL-BC and BC-1 with regional/distant disease, it was inferior for patients with localized BC (82% v 88%, respectively; P = .002). Women with HL may survive a subsequent diagnosis of BC, only to experience significant excesses of death from other primary cancers and cardiac disease. Greater awareness of screening for cardiac disease and subsequent primary cancers in patients with HL-BC is warranted.

Multiple soft tissue masses in a young female patient presenting six years after radiation therapy for Hodgkin disease

Desmoid fibromatosis is a rare soft tissue tumor, that while often occurring sporadically, is also thought to be related to tissue trauma, hormonal factors, familial adenomatous polyposis syndromes or a late reaction to radiation treatment. Here, it is presented in a young adult who received radiation therapy for Hodgkin lymphoma. Cross-sectional and sagittal images using plain radiography, CT and MR are shown, demonstrating the heterogeneous appearance of these lesions and locally invasive pattern of growth.

Risk-Adapted Therapy With Three or Six Cycles of Doxorubicin/Bleomycin/Vinblastine/Dacarbazine Plus Involved-Field Radiation Therapy in Hodgkin Lymphoma, Based on Prognosis at Diagnosis and Early Response: Results From the GATLA Study

Doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) plus involved-field radiation therapy (IFRT) is the gold-standard treatment for early and advanced stages of Hodgkin lymphoma (HL). We evaluated the outcomes of patients according to prognosis at diagnosis and over time to determine who achieved complete remission (CR). Treatment-naive patients under the age of 75 years at all stages of HL were eligible. The favorable group (FG) contained patients with stage IA-IIIA disease without bulky areas who achieved CR after the third cycle of ABVD. They received only IFRT at 25 Gy. Patients in the unfavorable group (UG) exhibited stages IIIB and IV HL. The UG also included all patients with bulky disease and the subset of the FG without CR after 3 cycles of ABVD, ie, slow responders (FGSR). The UG received 6 cycles of ABVD plus IFRT at 30 Gy to bulky areas at diagnosis or to those areas remaining positive after the third cycle of ABVD. In total, 584 patients were evaluable: 285 of them belonged to the FG, and 299 to the UG. Rates of CR were 98% and 85% for the FG and the UG, respectively (P < .001). Sixty patients in the FG received 6 cycles of ABVD because they had not achieved CR after 3 cycles (ie, the FGSR subgroup). The 5-year event-free survival rate was 89% for the FG, 66% for the FGSR, and 72% for the UG (P < .001). The overall survival at 5 years was significantly better for the FG (98%) than for the FGSR (87%) and the UG (88%; P < .001). Patients from the FG demonstrated excellent outcomes compared with those from the FGSR and UG, despite receiving less chemotherapy and fewer doses of IFRT.

Long-term survival among 298 Hodgkin lymphoma (HL) patients who develop breast cancer (BC): A population-based study.

1502 Background: The markedly increased risk of BC among women receiving chest radiotherapy for HL is well established. However, no large, population-based studies exist that describe overall survival (OS) and cause-specific survival (CSS) compared to women with a first primary BC. Methods: For 298 HL survivors who developed BC (HL-BC patients) and 405,223 women with a first or only BC (BC-1 patients), actuarial OS and CSS were compared, accounting for age, BC stage, hormone receptor status, sociodemographic status, radiation for HL and other variables. All patients were derived from the population-based Surveillance, Epidemiology, and End Results program. Results: Compared with BC-1 patients, the HL-BC group was significantly younger at BC diagnosis (p < 0.0001), had a greater likelihood of high grade BC (p > 0.02), and greater likelihood of estrogen negative BC (p < 0.004) and progesterone receptor negative BC (p > 0.005 for localized BC and p > 0.06 for regional BC). HL-BC patients were > 1.5 times (p < 0.0001) more likely to undergo mastectomy (rather than breast conserving surgery) compared with BC-1 pts, and were > 2 times (p < 0.0001) less likely to have received radiation than BC-1 patients. Fifteen-year OS among HL-BC patients was significantly inferior to BC-1 patients: 48% versus 69% respectively (p<0.0001) for localized BC, and 33% versus 43% (p < 0.0001) for regional/distant BC. HL-BC patients had a significantly increased 7-fold risk (p < 0.0001) of death from other cancers (i.e., not HL or BC) compared to BC-1 patients. Mortality due to heart disease among HL-BC patients with either localized or regional/distant disease was also significantly increased (hazard ratio 2.22, p > 0.04; and hazard ratio 4.28, p > 0.02 respectively) compared to BC-1 patients. While 10-year BC CSS was similar for HL-BC and BC-1 patients with regional/distant disease, it was inferior for patients with localized BC (82% versus 88% respectively (p > 0.002). Conclusions: Women with HL may survive a subsequent diagnosis of BC only to experience significant excesses of death from other primary cancers and cardiac disease. Greater awareness of screening for cardiac disease and subsequent primary cancers in HL-BC patients is warranted. No significant financial relationships to disclose.

9224 Role of salvage radiation therapy in Hodgkin Lymphoma with relapsed or progressive disease despite autologous stem cell transplant

9224 Role of salvage radiation therapy in Hodgkin Lymphoma with relapsed or progressive disease despite autologous stem cell transplant

Involved-Node and Involved-Field Volumetric Modulated Arc vs. Fixed Beam Intensity-Modulated Radiotherapy for Female Patients With Early-Stage Supra-Diaphragmatic Hodgkin Lymphoma: A Comparative Planning Study

A comparative treatment planning study was performed to compare volumetric-modulated arc (RA) to conventional intensity modulated (IMRT) for involved-field (IFRT) and involved-node (INRT) radiotherapy for Hodgkin lymphoma (HL). Plans for 10 early-stage HL female patients were computed for RA and IMRT. First, the planning target volume (PTV) coverage and organs at risk (OAR) dose deposition was assessed between the two modalities. Second, the OAR (lung, breast, heart, thyroid, and submandibular gland) dose-volume histograms were computed and compared for IFRT and INRT, respectively. For IFRT and INRT, PTV coverage was equally homogeneous with both RA and IMRT. By and large, the OAR irradiation with IFRT planning was not significantly different between RA and IMRT. For INRT, doses computed for RA were, however, usually lower than those with IMRT, particularly so for the lung, breast, and thyroid. Regardless of RA and IMRT modalities, a significant 20-50% decrease of the OAR computed mean doses was observed with INRT when compared with IFRT (Breast D(Mean) 1.5 +/- 1.1 vs. 2.6 +/- 1.7 Gy, p < 0.01 and 1.6 +/- 1.1 vs. 2.9 +/- 1.9 Gy, p < 0.01 for RA and IMRT, respectively). RA and IMRT results in similar level of dose homogeneity. With INRT but not IFRT planning, the computed doses to the PTV and OAR were usually higher and lower with RA when compared to IMRT. Regardless of the treatment modality, INRT when compared with IFRT planning led to a significant decrease in OAR doses, particularly so for the breast and heart.

Synchronous and metachronous bilateral breast cancer: Are the risks greater in women with a history of radiation for Hodgkin lymphoma?

607 Background: Women with a history of radiation therapy (RT) for Hodgkin lymphoma (HL) have an elevated risk of breast cancer (BC). The characteristics, treatment and outcomes of these cancers, compared with sporadic breast cancers, are not well described. In particular, rates of synchronous and metachronous bilateral BC may be greater in patients with a history of RT for HL. Methods: Women diagnosed with BC between 1980 and 2006 following RT for HL were identified retrospectively from 8 institutions in North America. Each patient in this cohort was matched with 3 BC patients with no history of HL, from the same institution, by age at BC diagnosis, year of BC diagnosis and race. Information on patient and tumor characteristics, disease recurrence and new contralateral tumors was obtained from medical records. Analysis of metachronous contralateral breast cancer (CBC) was limited to women with a breast at risk, and adjusted hazard ratios (HRs) for CBC were estimated using Cox proportional hazards regression. Results: 253 BC patients with a history of RT for HL were matched with 741 patients with sporadic BC. The median interval between HL and first BC diagnosis was 19 years. Median age at BC diagnosis was 44 years and median follow-up was 5 years from BC diagnosis. Synchronous bilateral BC was diagnosed in 6% of the HL survivors and 2% of the matched patients with sporadic BC. Among women with unilateral disease, 21% of HL survivors and 3% of sporadic BC patients had a bilateral mastectomy. Overall 64 women with a breast at risk developed metachronous CBC. BC patients with a history of RT for HL had a greater rate of metachronous CBC (adjusted hazard ratio 3.3, 95% CI 2.1–5.8), controlling for patient, tumor and treatment characteristics. In addition, those who received chemotherapy for BC were less likely to develop CBC (adjusted HR 0.51, 95% CI 0.31–0.85), and those with a family history of BC in a 1st degree relative were more likely to develop CBC (adjusted HR 1.8, 95% CI 1.1–3.0). Conclusions: Women who develop BC after RT for HL have more than 3 times the risk of CBC than similar women with sporadic BC. Our findings support close follow-up for CBC in BC patients with a history of RT for HL and may inform decisions about prophylactic mastectomy in this population. No significant financial relationships to disclose.

Risk of radiation‐related salivary gland carcinomas among survivors of Hodgkin lymphoma

AbstractBACKGROUND.Radiotherapy for Hodgkin lymphoma (HL) increases the risk of salivary gland carcinomas (SGC). To the authors' knowledge, however, the magnitude of the risk has not been assessed to date.METHODS.The risks of SGC among 20,928 1‐year survivors of HL who were diagnosed between 1973 and 2003 were evaluated in 11 population‐based cancer registry areas of the Surveillance, Epidemiology, and End Results (SEER) program. Observed‐to‐expected ratios (O/E) were assessed by radiation treatment, sex, age at the time of HL diagnosis, calendar year of diagnosis, attained age, time since HL diagnosis, histologic type of SGC, and site of occurrence in the major salivary glands.RESULTS.Among 11,047 HL patients who received radiotherapy as part of their initial treatment for HL, 21 developed subsequent invasive SGC (O/E = 16.9; 95% confidence interval [95% CI], 10.4‐25.8). The risk of radiation‐related SGC was highest for younger HL patients (age &lt;20 years) (O/E = 45.5; 95% CI, 12.4‐116.5) and among 10‐year survivors (O/E = 23.9; 95% CI, 13.1‐40.1), with risks remaining elevated for at least 2 decades after irradiation. Significant differences in risk by histologic type were observed, with a particularly high risk of developing mucoepidermoid carcinomas (O = 14; O/E = 44.2 [95% CI, 24.2‐74.2]) and adenocarcinomas (O = 4; O/E = 30.6 [95% CI, 8.3‐78.2]) noted.CONCLUSIONS.HL patients treated with radiotherapy experienced a significantly increased risk of SGC, particularly when exposed at young ages or for at least 2 decades after exposure. Although the results of the current study reflect the late effects of former HL treatment approaches, they point to the importance of long‐term follow‐up and a heightened awareness of SGC risk in this population. Cancer 2008. Published 2008 by the American Cancer Society.

Quality of Radiotherapy Reporting in Randomized Controlled Trials of Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma: A Systematic Review

Standards for the reporting of radiotherapy details in randomized controlled trials (RCTs) are lacking. Although radiotherapy (RT) is an important component of curative therapy for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), we postulated that RT reporting may be inadequate in Phase III HL and NHL trials. We searched PubMed and the Cochrane registry for reports of RCTs involving RT and either HL or NHL published between 1998 and 2007. We screened 133 titles and abstracts to identify relevant studies. We included a total of 61 reports. We assessed these reports for the presence of six quality measures: target volume, radiation dose, fractionation, radiation prescription, quality assurance (QA) process use, and adherence to QA (i.e., reporting of major or minor deviations). Of 61 reports, 23 (38%) described the target volume. Of the 42 reports involving involved-field RT alone, only 8 (19%) adequately described the target volume. The radiation dose and fractionation was described in most reports (54 reports [89%] and 39 reports [64%], respectively). Thirteen reports specified the RT prescription point (21%). Only 12 reports (20%) described using a RT QA process, and 7 reports (11%) described adherence to the QA process. Reporting of RT in HL and NHL RCTs is deficient. Because the interpretation, replication, and application of RCT results depend on adequate description and QA of therapeutic interventions, consensus standards for RT reporting should be developed and integrated into the peer-review process.

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

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. 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. 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. 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.

Radiotherapy of Hodgkin Lymphoma: Indications, New Fields, and Techniques

In recent years, radiotherapy in patients with Hodgkin lymphoma has evolved considerably because of sophisticated imaging technologies and radiation delivery techniques. Even more recently, a new radiation field concept has emerged to ensure better normal tissue protection while preserving an excellent clinical outcome. The role of radiation therapy is also rapidly changing because the concept of a risk-adapted treatment strategy, in which combined-modality treatments were the order of the day, is now expanding into a concept of response-adapted treatments.

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Cardiovascular calcifications after radiation therapy for Hodgkin lymphoma: computed tomography detection and clinical correlation

To study cardiovascular calcifications, detected by computed tomography, in patients following mediastinal radiation for Hodgkin lymphoma, and correlate them with clinical findings. Fifteen patients, <or=55 years, with computed tomography detected cardiovascular calcifications after mediastinal radiotherapy for Hodgkin lymphoma were identified during a 10-year period. Calcifications were evaluated for site and extent and were correlated with clinical data including symptoms and signs of heart disease, angiographic and surgical findings. Accelerated calcifications were detected in the coronary arteries (n=11), in the aorta (n=11), and in the aortic valve and the mitral apparatus (n=8). Calcifications were more extensive when radiation was given at a young age. Clinical evidence of cardiovascular disease included coronary events in three patients, valvular dysfunction in two, pericarditis in two and complete atrioventricular block in one. Seven patients had no cardiac symptoms. Early cardiovascular calcifications can be radiation associated. Such calcifications may represent radiation-induced atherosclerosis and can be detected by computed tomography even in asymptomatic patients. The implication of our findings is that spiral computed tomography may serve as a non-invasive modality to detect accelerated cardiovascular calcifications in high-risk asymptomatic patients who survived Hodgkin lymphoma.

Breast cancer risk following radiotherapy for Hodgkin lymphoma: modification by other risk factors

AbstractThe importance of genetic and other risk factors in the development of breast cancer after radiotherapy (RT) for Hodgkin lymphoma (HL) has not been determined. We analyzed data from a breast cancer case-control study (105 patients, 266 control subjects) conducted among 3 817 survivors of HL diagnosed at age 30 years or younger in 6 population-based cancer registries. Odds ratios (ORs) and excess relative risks (ERRs) were calculated using conditional regression. Women who received RT exposure (≥ 5 Gy radiation dose to the breast) had a 2.7-fold increased breast cancer risk (95% confidence interval (CI) 1.4-5.2), compared with those given less than 5 Gy. RT exposure (≥ 5 Gy) was associated with an OR of 0.8 (95% CI, 0.2-3.4) among women with a first- or second-degree family history of breast or ovarian cancer, and 5.8 (95% CI, 2.1-16.3) among all other women (interaction P = .03). History of a live birth appeared to increase the breast cancer risk associated with RT among women not treated with ovarian-damaging therapies. Breast cancer risk following RT varied little according to other factors. The additional increased relative risk of breast cancer after RT for HL is unlikely to be larger among women with a family history of breast or ovarian cancer than among other women.

Biophysical analysis of the acute toxicity of radiotherapy in Hodgkin’s lymphoma—a comparison between extended field and involved field radiotherapy based on the data of the German Hodgkin Study Group

To determine biophysical parameters from the complication probability data during and after radiotherapy of Hodgkin's lymphoma (HL), based on the number of gastrointestinal side effects that were found in the multicenter HD8 trial of the German Hodgkin Lymphoma Study Group. Between 1993 and 1998, 1204 patients with newly diagnosed, histology-proven HL in clinical Stages I/IIA/IIB with defined risk factors and stage IIIA without risk factors were enrolled into the multicenter HD8 study. Patients were randomized to receive two cycles of COPP (cyclophosphamide, vincristine, procarbazine, prednisone) alternating with two cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by radiotherapy (RT) of 30 Gy extended field plus 10 Gy to bulky disease (Arm A) or 30 Gy involved field plus 10 Gy to bulky disease (Arm B). For 910 patients, the rates of acute gastrointestinal side effects during and after RT could be determined. Comparison showed differences between Arms A and B (Grade 1-2: 16.6 vs. 3.9; Grade 3-4: 0.9 vs. 0.2; p < 0.001). From the dose-volume histograms for a "standard patient" (volume intestine 2300 cm3), we determined the normal tissue complication probability (NTCP) (V, D, m, n, TD50), the biophysical parameter TD50, and n (volume dependent) in such a manner that the observed NTCP in Arm A in cases of supradiaphragmatic involvement only and in cases of infradiaphragmatic involvement correlated with the calculated values. Of 1,204 patients randomized, 1,064 patients were informative for the comparison of study arms. The median observation time was 54 months. The overall survival for all eligible patients was 91%, and freedom from treatment failure was 83%. Survival rates at 5 years after start of RT revealed no differences in terms of freedom from treatment failure (85.8% in Arm A, 84.2% in Arm B) and overall survival (90.8% and 92.4%). There were also no differences between the two arms in terms of complete remission, progressive disease, relapse, death, and secondary neoplasias. In contrast, acute side effects, including leukopenia, thrombocytopenia, nausea, gastrointestinal toxicity, and pharyngeal toxicity, were more frequent in the extended field arm. Concerning gastrointestinal toxicity, the different radiation treatment volumes resulted in different NTCPs. On the basis of these findings, values of n = 0.09 and TD50 = 32 Gy were derived. However, this biophysical model is sensitive to variations of the parameters. A deviation of 1% of TD50 results in a deviation of 10% of the NTCP. Radiotherapy volume reduction from extended field to involved field after two cycles of COPP/ABVD chemotherapy gives similar results and less toxicity in patients with early-stage, unfavorable HL. Biophysical parameters could be determined from the complication probability data after RT of HL. Because of the exponential dependence, this biophysical model is unstable. It represents a "start model" until further data can be incorporated.

Pathologic Quiz Case: A 13-Year-Old Adolescent Girl With an Abdominal Mass 2 Months After Radiation for Hodgkin Lymphoma

Pathologic Quiz Case: A 13-Year-Old Adolescent Girl With an Abdominal Mass 2 Months After Radiation for Hodgkin Lymphoma

Pathologic quiz case: a 13-year-old adolescent girl with an abdominal mass 2 months after radiation for Hodgkin lymphoma. Epithelioid angiosarcoma.

Pathologic quiz case: a 13-year-old adolescent girl with an abdominal mass 2 months after radiation for Hodgkin lymphoma. Epithelioid angiosarcoma.

439 Late effects of radiotherapy for Hodgkin lymphoma and future prospects for treatment reduction

439 Late effects of radiotherapy for Hodgkin lymphoma and future prospects for treatment reduction

Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of hodgkin lymphoma treated with radiation therapy.

The majority of patients with Hodgkin lymphoma are young and highly curable. This necessitates concern for prevention, diagnosis, and optimal management of potential treatment-related complications. To identify and quantify the incidence of and factors contributing to long-term cardiac and vascular complications after radiation therapy for Hodgkin lymphoma. Retrospective study comparing patients treated from 1962 to 1998 at a university-based referral center with a matched general population. Four hundred fifteen consecutive patients who fulfilled the inclusion criteria of a minimum 2-year follow-up (median, 11.2 years) and whose radiation fields included the heart or carotid or subclavian arteries. Multivariable analyses of potential risk factors and observed-to-expected ratios for cardiac valve surgery, coronary artery bypass graft surgery, percutaneous coronary intervention, or both based on Surveillance, Epidemiology, and End Results (SEER) and National Hospital Discharge Survey (NHDS) data. Forty-two patients (10.4%) developed coronary artery disease at a median of 9 years after treatment, 30 patients (7.4%) developed carotid and/or subclavian artery disease at a median of 17 years after treatment, and 25 patients (6.2%) developed clinically significant valvular dysfunction at a median of 22 years. The most common valve lesion was aortic stenosis, which occurred in 14 valves. The observed-to-expected ratio for valve surgery was 8.42 (95% confidence interval [CI], 3.20-13.65) and the observed-to-expected ratio for coronary artery bypass graft surgery or percutaneous coronary intervention was 1.63 (95% CI, 0.98-2.28). At least 1 cardiac risk factor was present in all patients who developed coronary artery disease. The only treatment-related factor associated with the development of coronary artery disease was utilization of a radiation technique that resulted in a higher total dose to a portion of the heart (relative risk, 7.8; 95% CI, 1.1-53.2; P =.04). No specific treatment-related factor was associated with carotid or subclavian artery disease or valvular dysfunction. Freedom from any cardiovascular morbidity was 88% at 15 years and 84% at 20 years. Among patients treated with radiation therapy for Hodgkin lymphoma, there are statistically higher than expected rates of valve surgery and coronary revascularization procedures over the next 10 to 20 years. Coronary vascular disease is associated with higher radiation doses and traditional coronary heart disease risk factors. Noncoronary vascular disease and clinically important valvular dysfunction are less well understood complications at 15 to 20 years after radiation, requiring surveillance and further study.