Adult Hodgkin Lymphoma Survivors Research Articles

Treatments affecting splenic function as a risk factor for valvular heart disease in Childhood Cancer Survivors: A DCCSS-LATER study.

Splenectomy might be a risk factor for valvular heart disease (VHD) in adult Hodgkin lymphoma survivors. As this risk is still unclear for childhood cancer survivors (CCS), the aim of this study is to evaluate the association between treatments affecting splenic function (splenectomy and radiotherapy involving the spleen) and VHD in CCS. CCS were enrolled from the DCCSS-LATER cohort, consisting of 6,165 five-year CCS diagnosed between 1963 and 2002. Symptomatic VHD, defined as symptoms combined with a diagnostic test indicating VHD, was assessed from questionnaires and validated using medical records. Differences in the cumulative incidence of VHD between CCS who received treatments affecting splenic function and CCS who did not were assessed using the Gray test. Risk factors were analyzed in a multivariable Cox proportional hazards model. The study population consisted of 5,286 CCS, with a median follow-up of 22 years (5-50 years), of whom 59 (1.1%) had a splenectomy and 489 (9.2%) radiotherapy involving the spleen. VHD was present in 21 CCS (0.4%). The cumulative incidence of VHD at the age of 40 years was significantly higher in CCS who received treatments affecting splenic function (2.7%, 95% confidence interval (CI) 0.4%-4.9%) compared with CCS without (0.4%, 95% CI 0.1%-0.7%) (Gray's test, p=0.003). Splenectomy was significantly associated with VHD in a multivariable analysis (hazard ratio 8.6, 95% CI 3.1-24.1). Splenectomy was associated with VHD. Future research is needed to determine if CCS who had a splenectomy as part of cancer treatment might benefit from screening for VHD.

Doxorubicin Exposure and Breast Cancer Risk in Survivors of Adolescent and Adult Hodgkin Lymphoma.

Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages. We assessed BC risk in a cohort of 1,964 female 5-year HL survivors, treated at age 15-50 years in 20 Dutch hospitals between 1975 and 2008. We calculated standardized incidence ratios, absolute excess risks, and cumulative incidences. Doxorubicin exposure was analyzed using multivariable Cox regression analyses. After a median follow-up of 21.6 years (IQR, 15.8-27.1 years), 252 women had developed invasive BC or ductal carcinoma in situ. The 30-year cumulative incidence was 20.8% (95% CI, 18.2 to 23.4). Survivors treated with a cumulative doxorubicin dose of >200 mg/m2 had a 1.5-fold increased BC risk (95% CI, 1.08 to 2.1), compared with survivors not treated with doxorubicin. BC risk increased 1.18-fold (95% CI, 1.05 to 1.32) per additional 100 mg/m2 doxorubicin (Ptrend = .004). The risk increase associated with doxorubicin (yes v no) was not modified by age at first treatment (hazard ratio [HR]age <21 years, 1.5 [95% CI, 0.9 to 2.6]; HRage ≥21 years, 1.3 [95% CI, 0.9 to 1.9) or chest RT (HRwithout mantle/axillary field RT, 1.9 [95% CI, 1.06 to 3.3]; HRwith mantle/axillary field RT, 1.2 [95% CI, 0.8 to 1.8]). This study shows that treatment with doxorubicin is associated with increased BC risk in both adolescent and adult HL survivors. Our results have implications for BC surveillance guidelines for HL survivors and treatment strategies for patients with newly diagnosed HL.

T064: Doxorubicin exposure and breast cancer risk in adolescent and adult Hodgkin lymphoma survivors

Figure 1: Doxorubicin dose-response plot. Dose-response curve for continuous doxorubicin dose and breast cancer risk, adjusted for age at HL treatment, chest radiotherapy and gonadotoxic treatment. Adjusted HRs for doxorubicin dose categories are added. Background: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy at a young age have a strongly increased risk of breast cancer (BC). Recent studies in childhood cancer survivors have shown that doxorubicin may also increase BC risk. So far, the association between doxorubicin and BC risk has not been examined in cancer survivors treated at adolescent/adult ages. Methods: We assessed BC risk in a cohort of 1964 female five year HL survivors, treated at ages 15–50 years in 20 Dutch hospitals between 1975 and 2008. Cumulative BC incidence was estimated in the presence of death as a competing risk. Treatment factors were time-dependently included in the multivariable Cox regression analysis, focusing on the effect of doxorubicin exposure on BC risk. Results: HL survivors were treated at a median age of 27.8 years (interquartile range (IQR) 21.9–35.2 years). After a median follow-up of 18.3 years (IQR 12.9–24.7) years, 200 women had developed invasive BC (n=190) and/or ductal carcinoma in situ (n=49). The 30-year cumulative incidence was 19.4% (95% confidence Interval (CI) 16.6–22.3%). Among patients treated with chemotherapy (n=1113), receipt of doxorubicin-containing chemotherapy increased from 32.6% in 1975–1986 to 84.5% in 1998–2008. In multivariable analysis a cumulative dose of >200 mg/m2 was associated with increased BC risk (HR 1.7; 95% CI 1.1–2.4), compared to patients not treated with doxorubicin. BC risk increased 19% (HR 1.19; 95% CI 1.1–1.3) per additional 100 mg/m2 doxorubicine (ptrend=0.003). Receipt of mantle or axillary field irradiation or gonadotoxic therapy did not modify the association between doxorubicin and BC risk. Among patients who received >200 mg/m2 doxorubicin, the HR was 1.6 (95% CI 1.1–2.5) for patients treated with and 2.0 (95% CI 0.9–4.2) for patients treated without mantle or axillary field irradiation (Pinteraction=0.35). Gonadotoxic treatment (>8.4 g/m2 procarbazine or pelvic irradiation) significantly decreased the risk of BC. Conclusion: This study shows that doxorubicin is associated with an increased BC risk among adolescent and adult HL survivors. Now that radiotherapy doses and volumes have decreased and doxorubicin increasingly forms the backbone of HL treatment, the potential association of doxorubicin with increased BC risk is an important issue.

Clinicopathologic features of breast cancers diagnosed in women treated with prior radiation therapy for Hodgkin lymphoma: Results from a population-based cohort.

Childhood and young adult survivors of Hodgkin lymphoma (HL) are at elevated risk of developing breast cancer, yet little data exist on the tumor characteristics that develop in this high-risk patient population. The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify breast cancers diagnosed between 1990 and 2016 in women who had received prior radiation therapy for HL at age 30years or younger. Clinicopathologic features of subsequent breast cancers (breast cancer after radiation therapy for HL [BC-HL]) were examined and compared with breast cancers diagnosed in women who had no prior malignancy (breast cancer with no prior malignancy [BC-NPM]). In total, 321 breast cancers were identified in 257 women who had a history of radiation therapy for HL. The median age at HL diagnosis was 22years (interquartile range, 18-26years), and nearly all patients in the BC-HL group (97.9%) were diagnosed ≥8years after radiation therapy. Overall, 56 patients in the BC-HL group (21.8%) developed bilateral breast cancer. Compared with women who had BC-NPM, those who had BC-HL were younger (43 vs 60years; P<.001) and were less likely to present with ductal carcinoma in situ (8.4% vs 14.9%; P=.001). On multivariable analysis that included adjustment for age, invasive BC-HL was associated with smaller (≤2cm) tumor size (odds ratio, 1.64; 95% CI, 1.25-2.15) and upper outer quadrant tumors (odds ratio, 1.37; 95% CI, 1.04-1.81) compared with BC-NPM. In a subset analysis of 102 women who had HER2/neu status available, the distribution of biologic subtype was not significantly different between BC-HL and BC-NPM (P=.16). Breast cancers in women who previously received radiation therapy for HL are characterized by earlier onset disease, although most remain estrogen receptor-positive and have early stage disease at presentation. Women who have had radiation therapy for Hodgkin lymphoma at a young age are at increased risk of developing early onset breast cancer; however, most of these breast cancers are sensitive to hormones (estrogen receptor-positive) and are diagnosed at early stages. Because these breast tumors are estrogen receptor-positive, medications that prevent breast cancer by blocking the effect of or lowering hormone levels (also termed endocrine prevention) may be useful in this group of high-risk women.

Long-Term Outcomes Following Myocardial Infarction in Young Adult Survivors of Hodgkin Lymphoma: The YOUNG-MI Registry

Long-Term Outcomes Following Myocardial Infarction in Young Adult Survivors of Hodgkin Lymphoma: The YOUNG-MI Registry

Vo2peak in Adult Survivors of Hodgkin Lymphoma: Rate of Decline, Sex Differences, and Cardiovascular Events

BackgroundAdult survivors of Hodgkin lymphoma (HL) are at increased risk of cardiovascular (CV) events secondary to mediastinal radiation therapy (RT). ObjectivesIn this group of patients, we assessed the association between cardiopulmonary exercise testing (CPET), as determined by percent-predicted peak Vo2 (ppVo2peak), and clinical outcomes, as well as the rate of ppVo2peak decline and sex differences. MethodsAll survivors of HL who were >10 years post chest RT and who underwent ≥1 CPET were enrolled from a single center. Traditional CV and treatment risk factors, along with CV events, were ascertained. ResultsA total of 64 patients (67% female; median age 51 years [range 26 to 70 years]) with a median follow-up time after RT of 23 years (range 11 to 41 years), and 141 CPET studies, were included. Median initial ppVo2peak was 91% (range 58% to 138%). ppVo2peak in survivors declined by 7.5 percentage points every 10-year period after RT, as compared with age- and sex-based norms (P = 0.001), even after adjusting for hypertension and history of anthracycline. Both male and female patients had a similar rate of ppVo2peak decline. However, women had a lower ppVo2peak at all times, and they developed abnormal ppVo2peak (≤85%) on average earlier than men (24.1 years vs 47.0 years after RT). Patients with abnormal ppVo2peak vs normal ppVo2peak (>85%), had an increased risk of CV events (59% vs 16%). Abnormal ppVo2peak was independently associated with the risk of CV events (adjusted HR: 6.37; 95% CI: 2.06-19.80; P = 0.001). ConclusionsPercent-predicted Vo2peak in long-term survivors of HL who were treated with chest RT progressively declined as compared with population- and sex-based norms. Importantly, women developed abnormal ppVo2peak more than 2 decades earlier than male survivors. Abnormal ppVo2peak was associated with an increased risk of CV events in this group of patients.

Clinicopathologic features of breast cancers diagnosed in females treated with prior radiation therapy for Hodgkin lymphoma: Results from a population-based cohort.

567 Background: Childhood and young adult survivors of Hodgkin Lymphoma are at an increased risk of developing breast cancer, although little data exist on the characteristics and biologic subtype of breast cancers that develop in this high-risk population. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all histologically confirmed breast cancers diagnosed between 1990-2016 in women treated with prior radiation therapy for Hodgkin Lymphoma ≤ 30 years of age. Clinicopathologic features of subsequent breast cancers (BC-HL) were examined and compared to breast cancers diagnosed in women with no prior malignancy (BC-NPM). The association between prior chemotherapy use and biologic subtype of BC-HL was evaluated. Results: We identified 321 breast cancers diagnosed in 257 women with a history of radiation therapy for Hodgkin Lymphoma. The median age at Hodgkin Lymphoma diagnosis was 22 years (range, 12-30 years), and nearly all BC-HL (97.9%) were diagnosed 8 or more years after radiation therapy. Overall, 56 (21.8%) BC-HL patients developed bilateral breast cancer, of which 28 (50%) were synchronous. When compared to women with BC-NPM, women with BC-HL were significantly younger at time of diagnosis (median age, 43 years vs. 60 years, p&lt;0.001) and less likely to present with ductal carcinoma in situ (8.4% vs. 14.9%, p=0.001). Patients with invasive BC-HL were more likely to have high grade (43.8% vs. 32.9%, p&lt;0.001), estrogen receptor (ER) negative breast cancer (27.7% vs. 18.2%, p&lt;0.001), although pathologic tumor size, nodal status, and stage were not significantly different from those with BC-NPM. Compared to women with BC-NPM, the majority of operable BC-HL patients underwent surgical management with mastectomy (86.5% vs. 42.5%, p&lt;0.001). In subset analysis of 102 women for which HER2 status was available, BC-HL were HER2+ in 18.7% of patients. Distribution of biologic subtype between BC-HL and BC-NPM are shown in the table below. In BC-HL patients, prior chemotherapy exposure was not associated with substantial differences in the proportion of ER+HER2- breast cancers (65.8% vs. 63.5%, p=0.82). Conclusions: Breast cancers in women treated with radiation therapy for Hodgkin Lymphoma are characterized by earlier onset and more aggressive biologic features, although the majority remain estrogen sensitive and early stage at presentation. Further studies are warranted to evaluate the use of preventive strategies in this high-risk patient population.[Table: see text]

Cardiac Morbidity in Adolescents and Young Adult Survivors of Hodgkin Lymphoma

Cardiac Morbidity in Adolescents and Young Adult Survivors of Hodgkin Lymphoma

Use of recommended posttreatment services for adolescent and young adult survivors of Hodgkin lymphoma.

Hodgkin lymphoma (HL) is a leading cancer diagnosis for adolescents and young adults (AYAs), with an overall 5-year survival rate of >80%. However, to the authors' knowledge, little is known regarding posttreatment patterns of care. In the current study, the authors characterized the use of guideline-recommended services in a cohort of AYA survivors of HL in Kaiser Permanente Southern California. Patients with HL who were diagnosed between ages 15 and 39 years between 2000 and 2010 were identified. The authors calculated the number of patients who received recommended short-term care within 2 years after treatment cessation for those who remained enrolled and alive from 2001 through 2015. Use of recommended late-effects screening for breast cancer and cardiovascular disease was examined. Logistic regression was used to evaluate the association between receipt of recommended care and patient, cancer, and treatment characteristics. A total of 354 patients were identified, with a mean age at the time of diagnosis of 26 years (standard deviation, 6.9 years). Approximately 12% of patients had stage I disease, 59% had stage II disease, 17% had stage III disease, and 13% of patients had stage IV disease. Nearly all patients received chemotherapy (95%), 51% received radiotherapy, and 5% received care from a pediatric oncologist. Overall, approximately 49% of patients received recommended short-term care. Of those patients eligible for cardiovascular screening at 10 years posttreatment (60 patients), 53% received at least 1 screening. Of those patients eligible for breast cancer screening (21 patients), approximately 50% underwent at least 1 screening. Regression results indicated that those patients treated by a pediatric oncologist were >3 times as likely to receive recommended short-term care. The results of the current study highlight gaps in the delivery of posttreatment care to AYA survivors of HL. By determining areas in need of improvement, these findings can guide the development of tailored interventions with which to improve care.

Accelerated atherosclerosis, hyperlipoproteinemia and insulin resistance in long-term survivors of Hodgkin lymphoma during childhood and adolescence.

Long-term survivors of Hodgkin lymphoma during childhood or adolescence (HL survivors) are at high risk of developing treatment-related late cardiovascular sequelae. In our study we evaluated the presence of modifiable cardiovascular risk factors (hypertension, hyperlipoproteinemia, hyperinsulinemia, obesity), endothelial and inflammatory markers (E-selectin, PAI-1, hs-CRP) and atherosclerotic changes in the common carotid arteries. Assessment was performed in 80 young adult Hodgkin lymphoma long-term survivors at more than 10 years after the potentially cardiovascular toxic anticancer treatment (median age at evaluation 34.7 years; range 24.1-40.9 years). The HL survivors were compared with 83 age- and gender-matched healthy volunteers. The HL survivors showed unfavorable lipid profiles compared to those of healthy controls: triglycerides (p=0.01), total cholesterol (p=0.0004), low density lipoprotein cholesterol (p=0.005). In HL survivors, we found a higher prevalence of hypertension (p=0.004) and insulin resistance - HOMA-IR (p=0.0002). Ultrasonographic examination of both common carotid arteries revealed a higher prevalence of atherosclerotic plaques (p=0.0009) and higher carotid intima-media thickness (p<0.0001) in HL survivors. Markers of oxidative stress (advanced oxidation protein products, oxidized low-density lipoprotein), inflammation (hs-CRP) and endothelial dysfunction (E-selectin, PAI-1) were also higher in HL survivors (p<0.0001, p=0.0002, p=0.0031, p=0.0087, p=0.004, respectively). Adult survivors of Hodgkin lymphoma during childhood and adolescence need closer follow-up with screening of metabolic syndrome components, unfavorable lifestyle factors and early management of these risk factors.

Employment status and health related quality of life among Hodgkin-lymphoma survivors\u2019\u2013 results based on data from a major treatment center in Hungary

BackgroundDue to risk and response adapted treatment strategies, more than 80% of newly diagnosed classical Hodgkin lymphoma (HL) patients can be cured, and become long-term survivors. However, a high proportion of survivors suffer from treatment-related long-term side effects such as secondary malignancy, organ failure, persistent fatigue and psychological distress. The aim of this study was to evaluate psychological distress and its risk factors among our HL survivors.MethodsOne hundred sixty-three (50% female) adult HL survivors were contacted between January 1, 2012 and march 31, 2015 in our outpatient centre. The patients were asked to complete a standardized, validated, self-administered Hungarian questionnaire with demographic questions and the following scales: Hospital anxiety and depression scale (HADS14), general health questionnaire (GHQ12), sense of coherence (SOC13) perceived stress scale (PSS4), dysfunctional attitude scale (DAS17). Disease and treatment data were acquired from hospital records.ResultsMajority of HL survivors are in early adulthood, our most important goal should be to return them to normal life after their lymphoma is cured. The employment status at the time of survey seemed to be crucial so patients were divided into either active (n = 93) or inactive (n = 47) group. Retired survivors (n = 19) were excluded from the subgroup analysis. Psychological distress was significantly lower in active patients. Multiple logistic regression analysis showed significant differences between the inactive and active subgroups, such as age at diagnosis (≥30 years or below, p = 0.001), education level (below college vs. college, p = 0.032) and treatment related long-term side effects (yes vs. no, p < 0.001). Predictors for treatment-related long-term side effects are female gender (p = 0.011), chemotherapy protocol (ABVD vs. other, p < 0.001).ConclusionsOur data suggest that employment status and treatment-related long-term side effects play a critical role in the health related quality of life outcome among Hungarian HL survivors.

Use of recommended post-treatment services for adolescent and young adult Hodgkin lymphoma survivors.

107 Background: Adolescent and young adult (AYA) Hodgkin lymphoma survivors are at high risk for long-term and late effects. Post-treatment guidelines are available from the National Comprehensive Cancer Network (NCCN) and others; however, adherence to these guidelines is unknown. The purpose of this study was to identify AYA Hodgkin survivors from an integrated health care system and examine use of post-treatment services. Methods: We identified patients diagnosed between 2000 and 2010, ages 15 to 39. We identified use of NCCN recommended services (oncology visits, labs, CT) and non-recommended services (PET scan, CT after first year). Multivariate logistic regression was used to identify associations between receipt of recommended services within first 12 months post-treatment (oncology visits, labs, CT) and patient (gender, race/ethnicity) and cancer characteristics (stage, diagnosis age, diagnosis year). Results: We identified 354 patients (see table). Almost all had recommended oncology visits within the first 5 years (96%); 70% received recommended labs. Two-thirds received a recommended CT scan within 12 months post- treatment. However, 47% received a non-recommended CT in year 2 and 35% in year 3, and 33% received a non-recommended PETs. Overall, 48% received all recommended care within the first 12 months. Diagnosis year was significant in regression, with those diagnosed 2000-2005 less likely to receive recommended care than those diagnosed 2006-2010 (OR = 0.007, p &lt; .0001). Conclusions: Less than half of patients received recommended care within the first year post-treatment. These results will inform development of effective programs to meet survivors’ needs. Next steps include exploring risk-stratified patterns of care in long-term survivors. [Table: see text]

Late mortality, secondary malignancy and hospitalisation in teenage and young adult survivors of Hodgkin lymphoma: report of the Childhood/Adolescent/Young Adult Cancer Survivors Research Program and the BC Cancer Agency Centre for Lymphoid Cancer

Late complications affecting Hodgkin lymphoma (HL) survivors are well described in paediatric and adult-based publications. This study determined the late morbidity and mortality risk for 442 teenage and young adult (TYAs) 5-year HL survivors, diagnosed at 15-24 years of age between 1970 and 1999, identified from the British Columbia Cancer Registry. Treatment details were abstracted from charts. Survivors and a matched comparison cohort were linked to provincial administrative health datasets until December 2006 and regression analysis was performed, providing risk ratios regarding mortality, secondary malignancy and morbidity causing hospitalisation. Sixty (13·6%) survivors experienced late mortality with excess deaths from secondary cancer [standardised mortality ratio (SMR) 18·6; 95% confidence interval (CI) 11-29·4] and non-malignant disease (SMR 3·6; 95% CI 2·2-5·5). Excess secondary cancers (standardised incidence ratio 7·8; 95% CI 5·6-10·5) were associated with radiotherapy [Hazard ratio (HR) 2·7; 95% CI 1-7·7] and female gender (HR 1·8; 95% CI 1-3·4). Of 281 survivors treated between 1981 and 1999, 143 (51%) had morbidity resulting in hospitalisation (relative risk 1·45; 95% CI 1·22-1·73). Hospitalisation significantly increased with combined modality therapy, chemotherapy alone and recent treatment era. TYA HL survivors have excess risk of mortality and secondary malignancy continuing 30 years from diagnosis. Radiotherapy is associated with secondary malignancy and current response-adapted protocols attempt to minimise exposure, but late morbidity causing hospitalisation remains significant.

Exercise and Fatigue in Adolescent and Young Adult Survivors of Hodgkin Lymphoma: A Report from the Children's Oncology Group.

Fatigue is a significant problem for adolescent and young adult (AYA) Hodgkin lymphoma (HL) survivors. The relationship between exercise and fatigue is complex. This study explored the trajectory of and the relationship between exercise and fatigue over 36 months post-therapy in a cohort of 103 AYA-aged HL survivors treated on Children's Oncology Group (COG) study AHOD0031. Descriptive statistics and generalized estimating equations were used in this secondary data analysis. Exercise and fatigue improved over time but were unrelated; amount of exercise at end of therapy predicted amount of exercise at 12 (p = 0.02) and 36 (p = 0.0008) months post-therapy.

Physical Fitness In Survivors Of Childhood Hodgkin Lymphoma

PURPOSE: Survival rates following a diagnosis of childhood Hodgkin Lymphoma (HL) have surpassed 90%. However, cancer therapies increase the risk for late effects, potentially limiting survivor’s abilities to participate in physical activity (PA). This analysis evaluated objective markers of physical fitness among adult survivors of HL and compared them to matched peers without a history of childhood cancer. METHODS: Participants included HL survivors (n=340, 53.5% male, 84.4% Caucasian) from the St. Jude Lifetime Cohort and a comparison group members (n=340) without a history of cancer, frequency matched on age, sex and race. Participants completed physical fitness testing including anthropometrics, vital signs, isokinetic quadriceps and isometric hand grip strength, low back and hamstring flexibility (sit and reach test), and cardiorespiratory endurance (six minute walk test). Survivors also completed the Medical Outcomes Survey Short-Form-36 (SF-36). Linear regression was used to compare HL survivor to peers, and to evaluate associations between fitness and score on the SF-36, adjusting for age and sex. RESULTS: Survivors and comparison group members were a mean age of 37±8 and 36±9 years respectively. Survivors were a mean age of 14±4 years at diagnosis and had survived, on average 23±8 years. Survivors and the comparison group were overweight (28.0 ± 5.6 vs. 28.4±5.6 kilograms/meter squared respectively). Resting heart rate (HR) and respirations (RR) were higher among survivors than among comparison group members (HR 82.0±10.4 vs. 73.1±10.5 beats per minute, p < 0.001; RR 18.2±1.5 17.8±1.5 breaths per minute, p <0.001). Performance on the sit and reach test (29.5±6.6 vs. 25.4±6.8 centimeters, p < 0.001) and six minute walk test (586±83.7 vs. 618.4±82.1 meters, p < 0.001) were lower among HL survivors than among comparison group members. There were no differences in mean strength values between groups. Survivors who walked < 490 meters on the six minute walk test scored 10.31 ± 1.36 points lower on the physical component summary scale of the SF-36 than those who walked ≥490 meters. CONCLUSION: Survivors of childhood HL have impaired performance on several cardiorespiratory fitness markers when compared to peers which influences quality of life and may make it difficult to participate in regular PA.

Late morbidity and mortality in patients with Hodgkin's lymphoma treated during adulthood.

Survivors of Hodgkin's lymphoma (HL) treated as adults are at risk for late effects of therapy. However, the burden of late morbidity and mortality among adults treated for HL remains incompletely characterized. Vital status and, for deceased, cause of death were determined for 746 adults treated on a first-line trial at a single center from 1975 to 2000. Survivors completed a detailed survey describing their physical and mental health. A severity score (grades 1-4, ranging from mild to life-threatening or disabling) was assigned to self-reported conditions. At a median follow-up of 22 years, 227 of patients (30.4%) had died, 107 (47.1%) from HL, 120 (52.9%) from other causes, including second primary malignancies (SPMs) (n = 52) and cardiovascular disease (n = 27). Across the duration of follow-up, all-cause and SPM-specific risk of death remained higher than predicted by normative data. Among survivors, late morbidity survey data are available for 238 patients (45.9%). Ninety-four-point-one percent of respondents reported at least one morbidity, and 47.5% reported at least one grade 3 or 4 morbidity; 20.2% reported two or more grade 3 morbidities. Commonly reported morbidities included cardiovascular (54.6%), endocrine (68.5%), pulmonary disease (21.4%), and nonfatal second malignancy (23.1%). Anxiety, depression, and fear of recurrence were frequently reported. Among a large cohort of patients treated for HL with extensive follow-up, risk of late mortality from causes other than HL and prevalence of late medical morbidity are high. Guidelines for prevention, screening, and management of late effects in adult survivors of HL are needed.

Impaired vascular function in asymptomatic young adult survivors of Hodgkin Lymphoma following mediastinal radiation

Mediastinal radiation can accelerate atherosclerosis in Hodgkin lymphoma survivors (HLS), and early detection is optimal. Peripheral arterial tonometry (PAT), a non-invasive measure of endothelial function, is a surrogate marker of sub-clinical atherosclerosis. The objective of our study was to evaluate endothelial function in HLS and controls using PAT and to determine the influence of mediastinal radiation. Cross-sectional evaluation was performed on 26 HLS aged 12-30 years who were a minimum of 2 years from therapy, and their healthy age and gender matched controls. Evaluation included assessment for cardiovascular risk factors and completion of the Habitual Activity Estimation Score (HAES) questionnaire to assess activity level. Endothelial Function was measured using PAT hyperemia ratios (PAT-HR). HLS and controls were similar for baseline variables (mean age 23.3 +/- 5 yrs vs. 23.4 +/- 4.8 yrs, p = 0.92). HLS were on average 6.7 +/- 4.6 yrs post treatment. No differences in endothelial function or cardiovascular risk factors were observed between HLS and controls. However, impaired endothelial function, as evidenced by lower PAT-HR (1.67 +/- 0.39 vs. 2.03 +/- 0.37, p < 0.01) was seen in HLS (n = 13) who received mediastinal radiation (mean radiation dose 2,600 +/- 840 cGy) compared to controls. Impaired endothelial function was preferentially observed in HLS who received mediastinal radiation, while no difference was observed between the HLS and control groups overall. This finding, assessed using a non invasive test of endothelial function, confirms that mediastinal radiation is an additional cardiovascular risk factor in this young cohort of patients. Further studies of endothelial function in this patient population are warranted.

Late mortality and morbidity of patients with Hodgkin lymphoma treated in adulthood

8547 Background: Increased late mortality and morbidity have been observed among adult survivors of Hodgkin lymphoma (HL) treated in childhood, but are less well characterized for patients treated in adulthood. Methods: We investigated the late mortality and morbidity of adult patients treated at our center from 1975 to 2000. The study population consisted of all patients treated on one of 6 consecutive first-line trials of combined modality therapy (CMT), one of which included a chemotherapy-only arm. Cause-specific mortality was determined by chart review and National Death Index. Survival was estimated using the method of Kaplan-Meier, and cause-specific mortality using competing risk methodology. Self-report surveys were distributed to surviving patients to assess the prevalence of late morbidity; severity of morbidity was scored based on a published adaptation of the Common Terminology Criteria for Adverse Events. Results: 746 patients were eligible for assessment. At time of survey, 227 patients (30.4%) had died: 107 deaths from HL, 100 from causes other than HL, and 20 from unknown cause ( Table 1 ). 20-year OS for the cohort was 71%. Cumulative risk of death due to HL is surpassed by causes other than HL by 22 years post-treatment. Among the 521 survivors, survey data were available for 233 (44.7%), with a median follow-up of 21.6y. Late morbidity was common: 94% reported any morbidity, 48% reported at least one severe (grade 3/4) late morbidity and 22% reported two or more severe late morbidities. The most prevalent severe morbidities included second primary malignancy (SPM) (17%), cardiovascular (CV) (18%) and neurologic (18%) disease. Conclusions: Among adults treated on trials of CMT, by 22y post-treatment the risk of death due to HL is surpassed by risk of death due to other causes. Survivors of HL treated during adulthood experience substantial late morbidity. These findings underscore the importance of efforts directed at prevention of and early intervention for late morbidity in adult survivors of HL. [Table: see text] No significant financial relationships to disclose.