Neighborhood factors associated with late effects among survivors of adolescent and young adult cancer.

PURPOSE: The purpose of this study is to evaluate the associations between neighborhood income, education, and neighborhood racial composition (measured as a low percentage of white residents) and risk of developing cardiovascular diseases (CVD), diabetes (DM), and severe depression among survivors of AYA cancer and matched non-cancer peers. METHODS: Two-year survivors of AYA cancers diagnosed at age 15-39 yrs at Kaiser Permanente Southern California (diagnosed 2000-2012) and individually matched (1:13) non-cancer subjects were included. The development of CVD, DM, and severe depression was ascertained via electronic health records. Neighborhood characteristics were obtained from census-based geocoded data. Cox regression evaluated associations between neighborhood characteristics and the health outcomes of interest among both the cancer survivors and the non-cancer comparison cohort and effect modification by cancer survivor status on these relationships. RESULTS: Among cancer survivors (n = 6774), living in mostly non-white neighborhoods, was associated with risk of CVD (hazard ratio (HR) = 1.54 (95% CI 1.00-2.36)), while lower education level (HR = 1.41 (95% CI 1.02-1.94)) was associated with risk of severe depression. None of the neighborhood characteristics were associated with risk of DM. Effect modification was found for neighborhood education and risk of DM and severe depression. CONCLUSION: When jointly considered, cancer survivors who resided in the most disadvantaged neighborhoods were at the highest risk of developing these health outcomes compared to other subgroups. IMPLICATIONS FOR CANCER SURVIVORS: Our findings may inform screening strategy and addressing social determinants of health among AYA cancer survivors.

Chronic Comorbidities Among Survivors of Adolescent and Young Adult Cancer.

PURPOSE: To describe the incidence, relative risk, and risk factors for chronic comorbidities in survivors of adolescent and young adult (AYA) cancer. METHODS: This retrospective cohort study included 2-year survivors of AYA cancer diagnosed between age 15 and 39 years at Kaiser Permanente Southern California from 2000 to 2012. A comparison cohort without cancer was individually matched (13:1) to survivors of cancer on age, sex, and calendar year. Using electronic medical records, all participants were followed through December 31, 2014, for chronic comorbidity diagnoses. Poisson regression was used to evaluate the association between cancer survivor status and risk of developing each comorbidity. The associations between cumulative exposure to chemotherapy and radiation therapy and selected comorbidities were examined for survivors of cancer. RESULTS: The cohort included 6,778 survivors of AYA cancer and 87,737 persons without a history of cancer. The incidence rate ratio (IRR) for survivors of cancer was significantly increased for nearly all comorbidities examined. IRR ranged from 1.3 (95% CI, 1.2 to 1.4) for dyslipidemia to 8.3 (95% CI, 4.6 to 14.9) for avascular necrosis. Survivors of AYA cancer had a 2- to 3-fold increased risk for cardiomyopathy, stroke, premature ovarian failure, chronic liver disease, and renal failure. Among survivors of cancer, significant associations between chemotherapy and radiation therapy exposures and late effects of cardiomyopathy, hearing loss, stroke, thyroid disorders, and diabetes were observed from the multivariable analyses. Forty percent of survivors of AYA cancer had multiple (≥ 2) comorbidities at 10 years after index date, compared with 20% of those without cancer. CONCLUSION: Risk of developing comorbidities is increased in survivors of AYA cancer compared with the general population. Specific cancer treatment exposures were associated with risk of developing different comorbidities. These findings have important implications for survivorship care planning and patient education.

Incidence, Risk Factors, and Mortality Associated With Second Malignant Neoplasms Among Survivors of Adolescent and Young Adult Cancer.

Importance: Detailed data describing the epidemiology of second malignant neoplasms (SMN) are needed for survivors of adolescent and young adult (AYA) cancer to inform the development of age-appropriate survivorship care guidelines. Objective: To describe the incidence, risk factors, and mortality for SMN in survivors of AYA cancer. Design, Setting, and Participants: This retrospective matched cohort study included 10 574 two-year survivors diagnosed with cancer between January 1, 1990, and December 31, 2012, at age 15 to 39 years in an integrated health care delivery system in Southern California. A comparison cohort without a history of cancer was individually matched 13:1 to survivors of AYA cancer by age, sex, and calendar year. Data analysis was completed in July 2018. Exposures: Secondary malignant neoplasm risk factors of interest included age, stage, and calendar year at first cancer diagnosis; sex; race/ethnicity; radiation therapy; and chemotherapy. Main Outcomes and Measures: Diagnoses of SMN were ascertained using cancer registries from the National Cancer Institute Surveillance, Epidemiology, and End Results Program through December 31, 2014. Poisson regression was used to evaluate the association between cancer survivor status and developing SMN and risk factors for SMN, while risk of all-cause mortality by SMN status was examined in Cox regression. Results: A total of 10 574 survivors of AYA cancer (6853 [64.8%] female; median [range] age, 33 [15-39] years; 622 with SMN) and 136 683 participants in the comparison cohort (88 513 [64.8%] female; median [range] age, 33 [15-39] years; 3437 with first cancer) were included. In survivors of AYA cancer, 20-year cumulative incidence of SMN was 12.5%. The incidence rate ratio (IRR) of developing SMN in survivors of AYA cancer was 2.6 (95% CI, 2.4-2.9) compared with the comparison cohort. Survivors of breast cancer, melanoma, and testicular cancer had substantially elevated risk for SMN of the same organ (IRR, 5.6 [95% CI, 4.6-6.8], 11.2 [95% CI, 7.3-17.2], and 16.2 [95% CI, 6.8-38.4], respectively). Among survivors of AYA cancer, older age (IRR for age 30-39 years, 1.79 [95% CI, 1.21-2.65]), female sex (IRR, 1.31 [95% CI, 1.09-1.57]), white race/ethnicity (IRR for Asian race, 0.61 [95% CI, 0.43-0.87]), advanced stage at first cancer diagnosis (IRR for stage II, 1.29 [95% CI, 1.11-1.65]), and use of radiotherapy (IRR, 1.50 [95% CI, 1.26-1.79]) were associated with increased risk of SMN. Survivors of AYA cancer who developed SMN had an all-cause mortality rate 7.2 (95% CI, 6.1-8.5) times greater than survivors without SMN. Conclusions and Relevance: This study suggests that SMN risk is elevated in survivors of AYA cancer and varies across survivor subgroups. Survival following SMN may be significantly compromised. These data may form the basis for identifying individuals at high risk, as well as informing screening for SMN.

Amygdala damage impairs eye contact during conversations with real people.

The role of the human amygdala in real social interactions remains essentially unknown, although studies in nonhuman primates and studies using photographs and video in humans have shown it to be critical for emotional processing and suggest its importance for social cognition. We show here that complete amygdala lesions result in a severe reduction in direct eye contact during conversations with real people, together with an abnormal increase in gaze to the mouth. These novel findings from real social interactions are consistent with an hypothesized role for the amygdala in autism and the approach taken here opens up new directions for quantifying social behavior in humans.