Showing papers by "Nickhill Bhakta published in 2016"

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.

Abstract: Summary Background The magnitude of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma is not known. Using medically ascertained data, we applied the cumulative burden metric to compare chronic cardiovascular health conditions in survivors of Hodgkin's lymphoma and general population controls. Methods For this study, participant data were obtained from two ongoing cohort studies at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE) and the St Jude Long-term Follow-up Study (SJLTFU). SJLIFE is a cohort study initiated on April 27, 2007, to enable longitudinal clinical evaluation of health outcomes of survivors of childhood cancer treated or followed at St Jude Children's Research Hospital, and SJLTFU is an administrative system-based study initiated in 2000 to collect outcome and late toxicity data for all patients treated at the hospital for childhood cancer. The patient cohort for our study was defined as patients treated at St Jude Children's Research Hospital who reached 18 years of age and were at least 10 years post-diagnosis of pathologically confirmed primary Hodgkin's lymphoma. Outcomes in the Hodgkin's lymphoma survivors were compared with a sample of SJLIFE community control participants, aged 18 years or older at the time of assessment, frequency-matched based on strata defined by 5-year age blocks within each sex, who were selected irrespective of previous medical history. All SJLIFE participants underwent assessment 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) version 4.03 grading schema. Occurrences and CTCAE grades of the conditions for 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. Findings Of 670 survivors treated at St Jude Children's Research Hospital, who survived 10 years or longer and reached age 18 years, 348 were clinically assessed in the St Jude Lifetime Cohort Study (SJLIFE); 322 eligible participants did not participate in SJLIFE. Age and sex frequency-matched SJLIFE community controls (n=272) were used for comparison. At age 50 years, the cumulative incidence of survivors experiencing at least one grade 3–5 cardiovascular condition was 45·5% (95% CI 36·6–54·3), compared with 15·7% (7·0–24·4) in community controls. The survivor cohort at age 50 experienced a cumulative burden of 430·6 (95% CI 380·7–480·6) grade 1–5 and 100·8 (77·3–124·3) grade 3–5 cardiovascular conditions per 100 survivors; these numbers were appreciably higher than those in the control cohort (227·4 [192·7–267·5] grade 1–5 conditions and 17·0 [8·4–27·5] grade 3–5 conditions per 100 individuals). Myocardial infarction and structural heart defects were the major contributors to the excess grade 3–5 cumulative burden in survivors. High cardiac radiation dose (≥35 Gy) was associated with an increased proportion of grade 3–5 cardiovascular burden, whereas increased anthracyline dose was not. Interpretation The true effect of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma is reflected in the cumulative burden. Survivors aged 50 years will experience more than two times the number of chronic cardiovascular health conditions and nearly five times the number of more severe (grade 3–5) cardiovascular conditions compared with community controls and, on average, have one severe, life-threatening, or fatal cardiovascular condition. The cumulative burden metric provides a more comprehensive approach for assessing overall morbidity compared with currently used cumulative incidence based analytic methodologies, and will assist clinical researchers when designing future trials and refining general practice screening guidelines. Funding US National Cancer Institute, St Baldrick's Foundation, and American Lebanese Syrian Associated Charities.

Pulmonary Function after Treatment for Childhood Cancer. A Report from the St. Jude Lifetime Cohort Study (SJLIFE).

Abstract: Rationale: The relationship between treatment-related impairment of pulmonary function in adult survivors of childhood cancer and subsequent physical function has not been studied.Objectives: In this prospective evaluation of 606 adult survivors of childhood cancer, we sought to determine the risk factors for, as well as the functional impact of, clinically ascertained pulmonary function impairment.Methods: We measured FEV1, FVC, total lung capacity (TLC), and single-breath diffusing capacity of the lung for carbon monoxide corrected for hemoglobin (DlCOcorr), expressing the results as percent predicted and lower limit of normal (LLN) values, and we also assessed functional exercise capacity (6-minute-walk distance). Lung radiation exposure was expressed as the estimated percentage of lung tissue that received at least 10 Gy (V10). Associations of clinical and treatment factors with pulmonary function measures were assessed using log-binomial regression to calculate relative risks and 95% confidence inter...

Absence of Basal Cell Carcinoma in Irradiated Childhood Cancer Survivors of Black Race: A Report from the St. Jude Lifetime Cohort Study.

Abstract: Background: Cancer survivors exposed to therapeutic radiation are at increased risk for basal cell carcinoma (BCC). Despite the notable influence of race on rates of BCC in the general population, the same is not clearly defined in previously irradiated cancer survivors. We investigated the influence of race on the development of BCC in adult survivors of childhood cancer. Methods: Using a retrospective cohort study, outcomes were collected through June 30, 2015, for 1,746 irradiated childhood cancer survivors participating in the St. Jude Lifetime Cohort Study (SJLIFE), comprising a total of 33,147 person-years of follow-up. Subsequent neoplasms identified in survivors through self-report and prospective clinical assessment were validated by pathology reports. Expected numbers of each type of radiation-associated neoplasm, including BCC, were calculated for irradiated black survivors based on rates in irradiated white survivors, accounting for primary cancer diagnosis, diagnosis year, attained age, and sex. Results: On the basis of the rate of BCC in previously irradiated white survivors, 56.1 BCCs were expected among 237 black survivors, yet none observed. In contrast, the observed-to-expected ratio of non-BCC radiation-associated neoplasms (melanoma, brain, breast, thyroid cancer) was 0.88 (30 observed/34.2 expected, 95% confidence interval, 0.59–1.25). Conclusions: We identified an unexpected absence of BCC in irradiated black survivors in SJLIFE. We observe a similar absence of BCC in black individuals among two additional cohorts treated with irradiation for childhood cancer. Impact: Black survivors are at a substantially reduced or absent risk for BCC from therapeutic radiation for reasons not yet fully understood. Cancer Epidemiol Biomarkers Prev; 25(9); 1356–60. ©2016 AACR.

Cumulative burden of chronic disease in adult survivors of childhood cancer: The St. Jude Lifetime (SJLIFE) cohort.

Abstract: 10523Background: A substantial proportion of childhood cancer survivors develop chronic health conditions However, the cumulative burden (CB) of multiple organ system morbidity among survivors has