Survivors Of Pediatric Hodgkin Lymphoma Research Articles

Barriers to long-term follow-up in pediatric Hodgkin lymphoma survivors.

Pediatric Hodgkin lymphoma (HL) survivors have an increased risk of late effects following treatment. Barriers at the patient, provider, and payor level adversely affect adherence to long-term follow-up. We conducted a retrospective chart review of HL survivors diagnosed from 1999 to 2014 at Texas Children's Hospital. HL survivors were considered lost to follow-up if there were no documented visits to Texas Children's Cancer Center Long-Term Survivor (LTS) clinic for 2 or more years after their last LTS clinic visit. Univariate and multivariable logistic regression analyses were conducted to explore factors contributing to loss to follow-up. Reasons for not attending subsequent LTS visits were assessed by phone interviews in a subset of lost to follow-up patients. There were 120 HL survivors who had at least one LTS clinic visit in this timeframe; 64 (53%) were classified as lost to follow-up, and of these, 23 (36%) were interviewed. Eleven (47%) indicated that the reason for failure to follow-up was lack of or inadequate insurance, and seven (30%) stated they were unaware of the importance of continued follow-up. Loss to follow-up was associated with lack of insurance, earlier diagnosis, and lack of comorbidities in univariate analyses. Only earlier year of diagnosis (odds ratio [OR] 0.84, 95% confidence interval [CI]: 0.7-0.9, p=.01) and lack of insurance (OR 22.2, 95% CI: 4-123, p<.001) were associated with loss to follow-up in multivariable analyses. Insurance status and awareness of the need for long-term follow-up care are key factors associated with loss to follow-up in survivors of HL. Targeted education and low-cost options for survivorship care are potential strategies for improving adherence to long-term follow-up care in HL survivors.

Excellent results of screening for subsequent breast cancers in long-term survivors of childhood Hodgkin's lymphoma-Results of a population-based study.

Subsequent breast cancer (SBC) represents a major complication in childhood cancer survivors and screening for SBC in survivors after incidental irradiation of breasts is recommended. In this article, we report the results and discuss benefits of SBC screening in female pts treated for Hodgkin's lymphoma (HL) in Slovenia in a period of 45 years. Between 1966 and 2010, 117 females were treated for HL under the age of 19 in Slovenia. One hundred five of them survived for 5 years and were included in our study. They were 3-18 (med. 15) years old at diagnosis and followed for 6-52 (med. 28) years. Eighty-three percent of them had chest RT with a median dose of 30 Gy. Ninety-seven (92%) of 105 pts were regularly followed according to the international guidelines including yearly screening mammography/breast MRI in those who received chest RT. We diagnosed 10 SBCs in eight pts 14-39 (med. 24) years after diagnosis at the age of 28-52 (med. 42) years. At 40 years of follow-up, cumulative incidence of SBCs in females who got chest RT was 15.2%. Seven of eight patients (with 9 SBCs) got chest RT with 24-80 (med. 36) Gy at the age of 12 to 18 (median 17) years. Two patients in this group got bilateral SBC. One patient got invasive SBC after being treated with ChT containing high-dose of anthracyclines without chest RT at the age of 13. All eight invasive SBCs were invasive ductal cancers, HER2 receptors negative, all but one with positive hormonal receptors. Six invasive cancers were of stage T1N0, one T1N1mi, only one, diagnosed before era of screening, was of T2N1. None of 8 pts died of SBC. After introduction of regular breast screening in our female patients, who received chest RT in childhood, all SBCs were of early stage and no patients died of SBC. Survivors of pediatric HL should be informed about the risk of late sequelae of treatment for HL, including SBC. Regular follow-up with breast cancer screening and breast self-examination is of vital importance in those treated with chest RT.

Survivors of Pediatric HL May Age More Quickly.

A study of long-term survivors of pediatric Hodgkin lymphoma presented at the 2022 American Society of Hematology Annual Meeting and Exposition shows that they have an increased risk for cognitive impairment and early death when compared with individuals who never had the disease. The results suggest that they may experience accelerated aging and that assessing the biomarker for epigenetic age acceleration could be critical in addressing long-term effects of treatment on survivors of cancer.

Epigenetic Age Acceleration and Neurocognitive Function Among Long-Term Survivors of Pediatric Hodgkin Lymphoma: A Report from the St. Jude Lifetime Cohort

Introduction: Long-term survivors of pediatric Hodgkin lymphoma (HL) are at elevated risk for cardiopulmonary morbidity, cognitive impairment, and premature mortality. This pattern of late effects suggests accelerated aging, which may signal risk for premature onset of dementia.7 The relation between biological aging and neurocognitive function has not been examined in survivors of pediatric cancer. Methods: This study included 215 survivors of pediatric HL (50% female, mean[sd] 39[9] years old, 25[9] years from diagnosis) and 282 community controls (51% female, mean[sd] 36[10] years old) of European ancestry from the St. Jude Lifetime Cohort. Participants completed a comprehensive neuropsychological battery and provided a blood sample. Genome-wide methylation data were generated with peripheral blood mononuclear cell-derived DNA using Infinium Methylation EPIC BeadChip arrays. Epigenetic age was calculated according to Levin's clock and epigenetic age acceleration (EAA) was defined as the residual from regressing the epigenetic age on chronological age (higher EAA suggested older biological age relative to chronological age). Linear regression, adjusted for sex, compared EAA in HL and controls, and compared neurocognitive z-score in those in the third or second tertile of EAA to the first tertile, adjusted for sex, age at diagnosis, and high-dose methotrexate. Results: Survivors of HL (mean EAA 95% confidence interval [CI] 64.2 (3.6, 4.8) had significantly greater EAA compared to community controls (control mean EAA 95%CI -3.5 (-4.1, -2.9); mean difference b =7.7 years, 95% CI 6.8 to 8.5; p<0.001). Among HL, EAA was associated with worse visual-motor processing speed, with those in the second tertile performing, on average, 0.42 standard deviations worse (b = -0.42, 95% CI -0.71 to -0.13, p=0.005) and those in the third tertile performing 0.55 standard deviations worse (b = -0.55, 95%CI -0.84 to -0.25, p<0.001) than HL survivors in the first tertile (Table 1). Those in the second and third tertiles also performed worse on short-term memory compared to those in the first tertile (second b = -0.42, 95% CI -0.74 to -0.10, p=0.011; third b = -0.59, 95% CI -0.90 to -0.27, p<0.001). The third tertile of EAA was also associated with worse performance in verbal learning (p=0.007) and long-term verbal recall (p=0.005). Lastly, those in the second or third tertiles performed 0.4 standard deviations worse, on average, than the first tertile on a measure of executive function (verbal fluency; second b = -0.40 95%CI -0.76 to -0.03 p=0.035; third b = -0.39, 95%CI -0.75 to -0.03, p=0.036). Conclusions: Survivors of pediatric HL experience significant EAA that is associated with deficits in visual-motor processing speed, short- and long-term memory, and verbal fluency. EAA may be a useful biomarker to not only identify survivors at risk for accelerated cognitive aging but also to gauge preclinical response to interventions designed to improve cognitive function. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Advanced glycation end products and their related signaling cascades in adult survivors of childhood Hodgkin lymphoma: A possible role in the onset of late complications

Hodgkin lymphoma (HL) is today one of the most curable pediatric cancers. Despite survival rates now exceeding 90%, survivors of pediatric HL are still at higher risk to develop late effects of cancer therapy. Premature aging has been proposed as a paradigm to explain the onset of long-term complications in these subjects. High levels of advanced glycation end products (AGEs), together with chronic inflammation and oxidative unbalance, have been shown to be among the main factors contributing to aging. The present study aims to evaluate glycoxydation, inflammatory status, and oxidative stress in plasma and peripheral blood mononuclear cells (PBMC) obtained from 20 adult survivors of pediatric HL and 40 age- and sex-matched healthy controls. After the isolation of PBMC and the collection of plasma, we performed the analyses of gene expression by qRT-PCR and measured inflammatory and oxidative-stress markers. AGEs plasma levels, expressed as Nϵ-carboxymethyl-lysine and methylglyoxal hydroimidazolone, were markedly higher in HL survivors than in healthy subjects. HL survivors also showed a condition of higher oxidative stress, as demonstrated by an increased expression of NADPH oxidase on PBMC. Antioxidant defenses, evaluated in terms of alpha-tocopherol, GSSG/GSH ratio and catalase plasma levels, were strongly impaired in survivors. This pro-oxidative condition led to the over-expression of both NLRP3 and NFkB genes in PBMC and, consequently, to increased plasma levels of interleukin(IL)-1β and IL-6. Finally, the expression of the receptors for AGEs in PBMC confirmed the dysregulated AGE pathways. Data show AGEs accumulation in survivors of pediatric HL. The consequent activation of the receptor for AGEs leads to the persistent activation of intracellular signaling toward inflammation. These results suggest that the co-existence of AGEs accumulation, unbalanced oxidative status, and inflammation could play a role in the onset of late complications in HL survivors.

Late effects in pediatric Hodgkin lymphoma survivors after uniform treatment with ABVD with or without radiotherapy.

ABVD (doxorubicin, bleomycin,vinblastine, and dacarbazine) is not a standard regimen in children due to concerns regarding late effects. However, no studies have evaluated long-term toxicities of ABVD in children. Total 154 pediatric Hodgkin lymphoma (HL) survivors uniformly treated with ABVD were clinically followed up as per institutional protocol. All participants were evaluated for cardiac, pulmonary, and thyroid function abnormalities by multigated acquisition scan (MUGA) scan, spirometry with diffusion capacity of lung for the uptake of carbon monoxide (DLCO), and thyroid profile test, respectively, at a single time point. Predictors of toxicity were also analyzed. The median duration of follow-up of the cohort was 10.3years (6.04-16.8). No secondary malignant neoplasm (SMN) or symptomatic cardiac/pulmonary toxicities were detected. Nine patients (5.9%) had left ventricular ejection fraction (LVEF) <55%. Subclinical and overt hypothyroidism were observed in 78 (50.6%) and 16 (10.4%) survivors, respectively. Abnormal spirometry and reduced DLCO was observed in 43.2% and 42.0% survivors, respectively. Receiving neck radiation was significantly associated with thyroid dysfunction (odds ratio [OR] 16.04, p<.001); age ≥10years predicted reduced DLCO (OR 4.12, p=.001). Sixty-three and 33 patients had one and two late adverse effects, respectively; receiving neck radiation predicted development of multiple late effects (proportional OR 4.72, p<0.001). Cumulative dose of chemotherapy did not predict toxicity. Overall, ABVD appears safe in children at a relatively short follow-up. Long-term safety data are required before it can be adopted for treating pediatric HL patients. Children receiving neck radiation require close follow-up.

Outcomes within Five Years from Diagnosis in Pediatric Hodgkin Lymphoma Patients Following Contemporary Therapy

Background: Survival rates for pediatric Hodgkin lymphoma (HL) exceed 95% with contemporary therapy. To reduce long-term morbidity while maintaining excellent survival, risk-adapted therapy including tailored use of radiation has been developed. Studies of 5-year survivors and cohorts treated in the 1970s-1990s have shown pediatric HL survivors are at increased risk for treatment-related chronic health conditions, including subsequent malignancies, cardiopulmonary disease, thyroid dysfunction, and infertility. However, little is known about chronic conditions associated with contemporary therapy presenting during the first 5 years from diagnosis (early outcomes). The purpose of this study was to analyze survival and early outcomes of pediatric HL patients treated with contemporary therapy.Methods: We conducted a retrospective review of HL patients diagnosed <21 years of age and treated at our institution from 2011-2014. Three patients treated with surgery only were excluded. Three-year overall (OS) and event-free (EFS) survival were calculated with Kaplan Meier statistics using SAS 9.4. Results of screening (per Children's Oncology Group and Institutional Fertility Preservation Screening Guidelines) for targeted toxicities that developed between 2 and 5 years from diagnosis were identified and graded per CTCAE criteria. Censoring occurred at date of death, 5 years after diagnosis, or December 31, 2016. Data from the last collection point were used for prevalence calculations in cases with multiple evaluations. Descriptive statistics were calculated for the cohort.Results: We identified 62 patients (52% male; 39% non-Hispanic white; mean age at diagnosis 13.6 ± 3.6 years) with a median time since diagnosis of 3.3 years (range 0.06-5.0). Initial treatment included: 49 (79%) chemotherapy only and 13 (21%) multimodality treatment. Chemotherapy comprised ABVE-PC (56%), BEACOPP (19%), COPP/ABV (16%), or other (8%). Four patients with relapsed/refractory disease received salvage treatment including chemotherapy (n=1), multimodality therapy (n=1), or multimodality treatment including stem cell transplant (SCT; n=2). One patient remained on treatment at the time of censoring.The 3-year OS across all stages was 98.4% with an EFS of 91.9% (89.7% chemotherapy only, 100% multimodality treatment). The one mortality was due to toxic death during chemotherapy.At our institution, patients are referred to survivor clinic at 2 years from completion of therapy. Of the 44 patients eligible for survivor clinic, 35 (80%) attended during the study period, 5 (11%) were seen after the study period, 3 (7%) were lost to follow-up, and 1 (2%) was followed by the primary oncologist only. Early outcomes for patients who received exposure-based screening are listed in Table 1. No patients developed pulmonary dysfunction greater than CTCAE Grade 1, hyperthyroidism, thyroid nodules, cardiac dysfunction, or a subsequent neoplasm during the study period.Anti-mullerian hormone (AMH) below the normal range was found in all 8 evaluated females who received procarbazine-based regimens (BEACOPP or COPP/ABV; 6 received chemotherapy alone, 2 received chemotherapy with supradiaphragmatic radiation). All 8 females who received ABVE-PC with or without radiation (1 abdominal) had normal AMH levels. No males had abnormal gonadotropins.Conclusions: With the incorporation of novel agents in HL therapy, defining the baseline early outcomes of contemporary regimens is germane to future comparative medicine initiatives. This study is the first to evaluate early outcomes in pediatric HL survivors. While the cohort is young, the results indicate contemporary chemotherapy and a lower rate of radiation therapy utilization leads to excellent 3 year survival rates with minimal early toxicities. Females treated with procarbazine-based regimens are at increased risk for diminished ovarian reserve compared to those receiving ABVE-PC and should be prioritized for fertility preservation approaches prior to initiation of therapy. We plan to further expand our experience to include patients diagnosed since 2005 and evaluate the relationship between cumulative alkylating agent exposure and female gonadal dysfunction.[Chemotherapy abbreviations: (A) Adriamycin, (B) Bleomycin, (C) Cyclophosphamide, (E) Etoposide, (O) Vincristine, (P) Prednisone, (P) Procarbazine, (V) Vinblastine] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pulmonary dysfunction in pediatric Hodgkin Lymphoma survivors Praneetha M, R. Seth, Aditya Gupta , Jagdish P Meena, Sumita Gupta, S K Kabra

Pulmonary dysfunction in pediatric Hodgkin Lymphoma survivors Praneetha M, R. Seth, Aditya Gupta , Jagdish P Meena, Sumita Gupta, S K Kabra

Clinical and subclinical cardiac late effects in pediatric Hodgkin's lymphoma survivors.

Cardiac late effects are responsible for a significant burden of mortality and morbidity among pediatric Hodgkin's lymphoma (HL) survivors (HLS). The aim of our study was to assess clinical and subclinical cardiac sequelae in a cohort of childhood HLS treated in the 1980s with doxorubicin, bleomycin, vinblastine, and dacarbazine (the ABVD regimen) and limited-field radiotherapy (RT). We retrospectively examined a series of HLS treated from 1979 to 1989. We searched for subtle cardiac abnormalities in a subgroup of asymptomatic individuals, who underwent rest and exercise echocardiography at least 20 years after completing their therapies. Their cardiac assessment included physical examination, electrocardiogram (ECG), and resting and postexercise echocardiograms. On thorough cardiac assessment a mean of 21 years after their diagnosis, none of the 53 unselected asymptomatic HLS showed physical signs or significant ECG abnormalities during or after the stress echo test. Twenty-two (41%) of the 53 patients revealed valvular abnormalities, with mitral regurgitation in 28%, aortic regurgitation in 9%, and both in 4%. No significant myocardial dysfunction as a result of previous combined doxorubicin treatment and chest RT was identified. Only 2 individuals had mild pericardial alterations. The present study shows that long-term cardiac effects are common in HLS treated with the ABVD regimen and RT. The most frequent complications observed in this sample were essentially coronary artery disease and valvular abnormalities. None of the survivors in this sample showed overt congestive heart failure, a finding in contrast with larger studies.

Predictors of fatigue and poor sleep in adult survivors of childhood Hodgkin's lymphoma: a report from the Childhood Cancer Survivor Study.

Survivors of pediatric Hodgkin's lymphoma (HL) are at risk for a number of debilitating late effects. Excessive fatigue and poor sleep quality are primary complaints of HL survivors. Understanding the emotional and physical factors that influence fatigue and sleep quality may provide opportunities for intervention to improve health-related quality of life for HL survivors. Data from 751 adult survivors of childhood HL who participated in the Childhood Cancer Survivor Study (CCSS) from 2000-2002 were analyzed. Multivariable logistic regression analyses investigated the demographic, psychological, and physical variables that predicted clinically significant levels of poor sleep quality, fatigue, and excessive daytime sleepiness. Survivors' self-reported level of emotional distress, pain, and physical functioning limitations did not differ from population norms. Clinically elevated levels of emotional distress (OR 8.38, 95% CI 4.28-16.42) and pain (OR 3.73, 95% CI 2.09-6.67) increased the risk for endorsing elevated levels of fatigue. Survivors with elevated levels of emotional distress (OR 6.83, 95% CI 2.71-15.90) and pain (OR 5.27, 95% CI 1.78-15.61) were more likely to report poor sleep quality. Pain (OR 2.11, 95% CI 1.39-3.34) was related to excessive daytime sleepiness. Emotional and physical factors are associated with elevated levels of fatigue, excessive daytime sleepiness, and poor sleep quality in survivors of pediatric HL. This is consistent with findings from research conducted with non-cancer survivors. These results suggest that interventions designed to target sleep and fatigue difficulties in the general population may be well suited for pediatric HL survivors as well.

Cumulative burden of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma: an analysis from the St Jude Lifetime Cohort Study

BackgroundThe magnitude of cardiovascular morbidity among survivors of pediatric, adolescent, and young adult Hodgkin lymphoma is not known. Using medically ascertained data, we applied the cumulative burden metric to compare chronic cardiovascular health conditions among Hodgkin survivors and general population controls.MethodsAmong 670 survivors treated at St. Jude Children’s Research Hospital, who survived ≥10 years and became 18 years old, 348 were clinically assessed in the St. Jude Lifetime Cohort Study (SJLIFE). Age-sex-frequency-matched SJLIFE community-controls (n=272) were used for comparison. All SJLIFE participants underwent evaluation for 22 chronic cardiovascular health conditions. Direct assessments, combined with retrospective clinical reviews, were used to assign severity to conditions using a modified Common Terminology Criteria of Adverse Events (CTCAE) grading schema. Occurrences and CTCAE-grades of the conditions for 322 eligible non-SJLIFE participants were accounted for by multiple imputation. The mean cumulative count (treating death as a competing risk) was used to estimate cumulative burden.FindingsAt 50 years of age, the cumulative incidence of survivors experiencing at least one grade 3-5 cardiovascular condition was 45.5%. The survivor cohort experienced, on average, 430·6 (95% confidence interval, 380·7-480·6) grade 1-5 and 100·8 (77·3-124·3) grade 3-5 cardiovascular conditions per 100 survivors. At age 50, the grade 1-5 and 3-5 cumulative burdens of community-controls were appreciably lower at 227·4/100 (192·7-267·5) and 17·0/100 (8·4-27·5), respectively. Myocardial infarction and structural heart defects were the major contributors to the excess grade 3-5 cumulative burden among survivors. Higher cardiac radiation dose (≥35 Gy) was associated with an increased grade 3-5 cardiovascular burden.InterpretationThe true impact of cardiovascular morbidity among pediatric Hodgkin lymphoma survivors is reflected in the cumulative burden. 50-year-old Hodgkin survivors will experience over two times the number of chronic cardiovascular health conditions compared community-controls and, on average, have one severe/life-threatening/fatal cardiovascular condition. The cumulative burden metric provides a more comprehensive approach to evaluating overall morbidity and will assist clinical researchers when designing future trials and refining general practice screening guidelines.

A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohort and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography-based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9Gy (68.6%) and 17.6Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.

Pediatric Hodgkin Lymphoma.

Hodgkin lymphoma (HL) is one of the most curable pediatric and adult cancers, with long-term survival rates now exceeding 90% after treatment with chemotherapy alone or combined with radiotherapy (RT). Of note, global collaboration in clinical trials within cooperative pediatric HL study groups has resulted in continued progress; however, survivors of pediatric HL are at high risk of potentially life-limiting second cancers and treatment-associated cardiovascular disease. Over the last three decades, all major pediatric and several adult HL study groups have followed the paradigm of response-based treatment adaptation and toxicity sparing through the reduction or elimination of RT and tailoring of chemotherapy. High treatment efficacy is achieved using dose-dense chemotherapy. Refinement and reduction of RT have been implemented on the basis of results from collaborative group studies, such that radiation has been completely eliminated for certain subgroups of patients. Because pediatric staging and response criteria are not uniform, comparing the results of trial series among different pediatric and adult study groups remains difficult; thus, initiatives to harmonize criteria are desperately needed. A dynamic harmonization process is of utmost importance to standardize therapeutic risk stratification and response definitions as well as improve the care of children with HL in resource-restricted environments.

Breast cancer detection among young survivors of pediatric Hodgkin lymphoma with screening magnetic resonance imaging.

BACKGROUNDFemale survivors of pediatric Hodgkin lymphoma (HL) who have received chest radiotherapy are at increased risk of breast cancer. Guidelines for early breast cancer screening among these survivors are based on little data regarding clinical outcomes. This study reports outcomes of breast cancer screening with MRI and mammography (MMG) after childhood HL.METHODSWe evaluated the results of breast MRI and MMG screening among 96 female survivors of childhood HL treated with chest radiotherapy. Outcomes measured included imaging sensitivity and specificity, breast cancer characteristics, and incidence of additional imaging and breast biopsy.RESULTSMedian age at first screening was 30 years, and the median number of MRI screening rounds was 3. Ten breast cancers were detected in 9 women at a median age of 39 years (range, 24-43 years). Half were invasive and half were preinvasive. The median size of invasive tumors was 8 mm (range, 3-15 mm), and none had lymph node involvement. Sensitivity and specificity of the screening modalities were as follows: for MRI alone, 80% and 93.5%, respectively; MMG alone, 70% and 95%, respectively; both modalities combined, 100% and 88.6%, respectively. All invasive tumors were detected by MRI. Additional investigations were required in 52 patients, (54%), and 26 patients (27%) required breast biopsy, with 10 patients requiring more than 1 biopsy.CONCLUSIONSScreening including breast MRI with MMG has high sensitivity and specificity in pediatric HL survivors, with breast cancers detected at an early stage, although it is associated with a substantial rate of additional investigations. Cancer 2014;120:2507–2513. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.Screening female survivors of pediatric Hodgkin Lymphoma for breast cancer with MRI and mammography detected tumors at an earlier stage than prior studies of mammography alone, although a substantial proportion of women required additional tests for benign imaging findings. The 5-year cumulative incidence of invasive or preinvasive tumors after initiating screening was 10.8%.

Longitudinal Evaluation of Health Status in Aging Pediatric Hodgkin Lymphoma Survivors: Report from the Childhood Cancer Survivor Study

Longitudinal Evaluation of Health Status in Aging Pediatric Hodgkin Lymphoma Survivors: Report from the Childhood Cancer Survivor Study

Pulmonary outcomes in patients with Hodgkin lymphoma treated with involved field radiation

Abnormalities in pulmonary function tests (PFT) and clinical symptoms have been reported in up to one third of patients with Hodgkin lymphoma (HL) treated with irradiation. The purpose of this study is to describe the prevalence of pulmonary complications in HL patients treated using contemporary protocols. Eligible patients at Children's Hospital Los Angeles from 1999 to 2009 were identified from the radiation oncology database. Clinical features, radiographic findings, PFT, and radiation details were retrospectively ascertained. The median age at diagnosis of 65 patients with HL was 13.6 years and the median follow-up was 3.7 years. The median prescribed radiation dose was 21 Gy. The prevalence of clinical symptoms was low: chronic cough (3%), dyspnea (9.2%), and supplemental oxygen requirement (1.5%). Radiological interstitial lung changes were observed in 31% of the patients. PFT results following irradiation were available in 38 patients. Forced expiratory volume in 1 second (FEV1) and forced expiratory flow 25-75% (FEF25-75%) were decreased in 13% and 11% of patients respectively. Residual volume (RV) was elevated in 21%. Total Lung capacity (TLC) was decreased in 8%. Age at irradiation (P = 0.004), maximum lung dose (P = 0.03), and volume of lung receiving >25 Gy were associated with development of adverse pulmonary outcomes on univariate analysis. On multivariate analysis, older age was associated with worse outcomes. In survivors of pediatric HL, involved field irradiation was accompanied by a low prevalence of pulmonary symptoms but substantial subclinical dysfunction. Older age at irradiation was associated with worse pulmonary outcomes.

Pediatric Hodgkin Lymphoma: on the road to a 'radiotherapy-free' cure rate?-Commentary on a report on final results of the Multinational Trial GPOH-HD95.

During the last four decades, the treatment of children and adolescents affected by classic Hodgkin Lymphoma (HL) has achieved continuous and dramatic improvements in response and survival rates, from uniform fatality up to curability for 90% of patients (1). This success has occurred mainly in economically advantaged countries due to constant participation of children in clinical trials, the administration of pediatric cancer care in specialized centers and the continuous efforts in refining treatment intensities against the gradually discovered profiles of subacute and delayed complications of radiotherapy (RT) and multiagent chemotherapy (2,3). As a matter of fact, due to active growth and development at the time of treatment, youngsters and children may suffer of impaired growth of soft tissue and bones, and have a greater sensitivity as compared to adults, in developing thyroid and gonadal dysfunction, cardiopulmonary toxicity, and secondary neoplasms (4). In a large series including 1,876 pediatric HL survivors, the estimated cumulative incidence rates of total (grade 1 to 5) and severe grade (grade 3 to 5) chronic medical conditions were 75% and 40%, respectively, at 25 years follow-up (5).

Performance-based physical function in long-term survivors of Hodgkin lymphoma.

9532 Background: Survivors of pediatric Hodgkin lymphoma (HL) are at increased risk for late effects including loss of physical function, which may interfere with an active lifestyle. The aims of these analyses were to describe the prevalence of physical performance limitations, and to determine associations between treatment exposures and long-term functional loss. Methods: Clinical assessment including measures of ankle flexibility and strength, quadriceps strength, and walking endurance were completed in HL survivors 10+ years from diagnosis. Those with ankle motion < 5 degrees of dorsiflexion (required for foot clearance during walking), and isokinetic strength or distances on the six minute walk in the lowest 10th percentiles of age/sex predicted norms were classified as having severe limitations. The prevalence of severe loss was calculated for each measure. Associations between HL treatment and functional loss were evaluated in regression models. Results: Among the first 196 eligible HL participants randomly recruited to participate in a large cohort study, 188 (median age 40 (26-61) years; median time since diagnosis 26 (11-45) years) completed the performance measures. Severe limitations were present in ankle motion for 29.0%, ankle strength for 22.3%, quadriceps strength for 21.8%, and endurance for 31.9% of survivors. Among those with severe limitations, 53.3% had limitations on 2+ performance measures. Those treated with vinca alkaloids had mean ankle dorsiflexion age/sex specific z-scores of -0.35±1.0 vs. 0.19±1.3 (p=0.007) among those not exposed. Mean quadriceps z-scores were -0.45±1.0 among those exposed to vinca alkaloids vs. -0.29±0.97 (p=0.01) among those not exposed. After adjusting for anthracycline and radiation exposure, those treated were 2.4 (95% CI 1.1-5.2) times more likely than those not treated with glucocorticoids to have poor endurance. Conclusions: Severe physical performance limitations are present in 20-30% of long-term HL survivors. Exposure to vinca alkaloids and glucocorticoids are associated with decreased strength and walking ability, respectively. Losses in lower extremity motion and strength, and in sustained walking ability, may provide targets for intervention.

Pediatric Hodgkin lymphoma survivors at negligible risk for significant bone mineral density deficits

We hypothesized that pediatric Hodgkin lymphoma (HL) survivors would have bone mineral density (BMD) deficits compared to their peers because of osteotoxic chemotherapy during the time of greatest BMD accretion. We retrospectively reviewed records of HL survivors returning for follow-up between 1990 and 2002. Of the 133 eligible survivors, 109 who underwent quantitative computed tomography (QCT) comprised the study group. QCT-determined BMD Z-scores were correlated with patient characteristics and therapeutic exposures by Wilcoxon rank sum or Chi-square tests. Logistic regression models were used to explore risk factors for diminished BMD. The study cohort was half male (50.5%) and 85.3% reported their race as white. Participants were representative of all survivors potentially eligible for study, except that more study participants were female, had hypothyroidism, and had received cyclophosphamide. Median age at diagnosis was 15.1 years (range, 3.1-20.7 years); median time between diagnosis and QCT was 7.5 years (range, 5.0-12.4 years). The proportion of HL survivors with BMD below the mean did not significantly differ from the general population (P = 0.503). However, those with BMD -1.5 SD and BMD -2.0 SD or lower (14.7% and 7.3%, respectively) exceeded that in the general population (6.7% and 2.3%, respectively; P < 0.001 for both degrees of severity). Males, diagnosed at 14 years or older, were at 6.5 times higher risk than females (OR 95% CI: 1.24-34.14; P = 0.027) for BMD deficits. Overall, pediatric HL survivors had negligible BMD deficits. Male gender was associated with an increased risk of developing BMD deficits.

Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma

Survivors of Hodgkin lymphoma and other patients who receive neck irradiation are at increased risk of thyroid cancer. Ultrasonography provides an inexpensive and non-invasive method of thyroid screening, but the clinical significance of thyroid nodules detected by ultrasound screening is uncertain. We reviewed the demographics, clinical characteristics, method of detection, and outcome of patients who developed thyroid nodules after treatment for pediatric Hodgkin lymphoma at our institution. One radiologist reviewed all imaging studies. Sixty-seven children treated for Hodgkin lymphoma from 1962 to 2001 developed thyroid nodules. The study group represented 9,024 person-years of follow-up after the diagnosis of Hodgkin lymphoma and 581 person-years after diagnosis of a thyroid nodule. A median of 10.5 years (range, 0.2-24.8 years) elapsed between the diagnoses of Hodgkin lymphoma and thyroid nodule(s). All but one patient had received neck irradiation for Hodgkin lymphoma, with a median thyroid radiation dose of 35 Gy (range, 12-45 Gy). Thyroid nodules were found to be malignant in seven patients (10%), at a median of 16.2 years (range, 8.4-23.7 years) after diagnosis of Hodgkin lymphoma. Only one malignancy was found through screening ultrasonography. All patients with thyroid cancer remained disease-free at 0.4-16.2 years of follow-up. Thyroid nodules are common in Hodgkin lymphoma survivors treated with neck irradiation, but the majority of these lesions have an indolent clinical course and do not undergo malignant transformation. Only patients with a palpable mass or clinical symptoms need more extensive evaluation, including Doppler-flow ultrasonography and fine-needle aspiration.