Citations

The NCCN Guidelines for Survivorship include screening, evaluation, and treatment recommendations for common physical and psychosocial problems resulting from adult-onset cancer and its treatment and provide a framework for coordination of survivorship care. They also include recommendations to help cancer survivors enhance their wellness and maintain a healthy lifestyle. These NCCN Guidelines Insights summarize the panel’s current recommendations and recent updates regarding physical activity, nutrition, and weight management for cancer survivors.

Thymomas and thymic carcinomas are rare mediastinal tumors that originate in the thymus. Patients with thymoma may experience symptoms associated with autoimmune paraneoplastic diseases (such as myasthenia gravis), which typically do not occur in patients with thymic carcinoma. The NCCN Guidelines for Thymomas and Thymic Carcinomas provide guidance for the diagnosis, treatment, and surveillance of patients with thymoma and thymic carcinoma. Involvement of a multidisciplinary team with experience treating thymomas and thymic carcinomas is highly recommended.

Numerous factors including social determinants of health, knowledge gaps, economic challenges, workforce limitations, and health system deficiencies are associated with significant disparities in access to health care services and health outcomes for people with epilepsy (PWE). The American Epilepsy Society (AES) and the International League Against Epilepsy—North America (ILAE-NA) established a joint task force to explore and develop recommendations to address health care disparities experienced by PWE. The task force gathered foundational knowledge through meetings, public and patient organization comments and discussions to develop consensus recommendations. We enumerate the recommendations and discuss the rationale behind them to reduce disparities in epilepsy care through comprehensive research, inclusive clinical practices, robust advocacy, and targeted educational initiatives. While our recommendations are focused on the United States, we acknowledge that similar barriers and limitations exist for PWE globally and that these also need to be addressed within their local domains and with attention to unique factors therewithin.

Abstract Background High-grade gliomas (HGG) have a poor prognosis despite aggressive treatment. Severe, persistent lymphopenia occurring in HGG patients after concurrent chemoradiation is associated with worse survival. NT-I7, a long-acting interleukin-7 analog, has been shown to increase CD4 and CD8 counts in healthy, septic, and HIV-positive adults. This multi-institutional, NCI-funded dose-escalation trial is the first to evaluate NT-I7 safety and activity in HGG patients with severe treatment-related lymphopenia (TRL) and the effect of co-administered glucocorticoids. Methods Eligible HGG patients had CD4 counts <300 cells/mm3 after 5 weeks of standard chemoradiation and were receiving either ≤0.75 or ≥4 mg/day of dexamethasone. Patients received a single intramuscular dose of NT-I7 (60 or 360 µg/kg) post-chemoradiation, followed by safety evaluation and multi-parameter, longitudinal monitoring of lymphocyte populations and immunologic function. Results NT-I7 was well tolerated in all 12 patients (median age 64; median CD4 count 161 cells/mm³) before the study closed prematurely. Absolute lymphocyte counts doubled in 83% (10/12; 95% CI: 51.6%-97.9%) of patients, and CD4 counts doubled in 42% (5/12; 95% CI: 15.2%-72.3%) of patients. Glucocorticoid use did not significantly affect CD4 or lymphocyte increases. Correlative immune profiling revealed increased Ki67 expression in CD4 (P < .005) and CD8 (P < .05) after one week, along with the expansion of CD4 and CD8 T-cell subsets and CD56 + natural killer cells. Conclusions NT-I7 is well tolerated and effectively increases lymphocyte and CD4 counts in severe TRL patients, regardless of glucocorticoid use, suggesting its potential to mitigate TRL and improve outcomes in HGG.

Cancer cachexia is a multifactorial syndrome involving muscle and fat wasting, inflammation, and metabolic dysfunction. Across cancer subtypes, pancreatic cancer has one of the highest cachexia incidence rates at ∼80%. Given the advanced age of most pancreatic cancer patients, we sought to query cancer-associated muscle wasting using an age-matched murine model. We found that histamine and histamine decarboxylase (HDC) activity were specifically elevated in the muscles of aged tumor-bearing mice. We further found that (1) wasting stimuli induced histamine production and enhanced HDC activity; (2) exogenous histamine was sufficient to induce atrophy-associated gene expression; (3) inhibition of HDC activity by α-fluoromethylhistidine (FMH) protected against atrophy; (4) treatment of tumor-bearing mice with FMH rescued muscle wasting; and (5) a calcineurin inhibitor was able to rescue histamine-associated increases in calcium/atrogene signaling. In summary, we present a novel metabolic pathway that has significant implications for the treatment of cachectic cancer patients.

LBA3509 Background: Systemic inflammation has been implicated in colon cancer progression. We examined whether intake of a proinflammatory diet is associated with survival among patients (pts) with stage III colon cancer. Methods: This prospective cohort study was nested within a randomized phase III trial of adjuvant therapy in pts with stage III colon cancer who had undergone curative-intent resection. EDIP score – a validated tool to classify the inflammatory nature of diets – was derived as a cumulative exposure using data from food-frequency questionnaires completed within 6 weeks of randomization and 14-16 months (mo) after randomization. Cox proportional hazards regression was used to assess the associations of EDIP with disease-free survival (DFS) and overall survival (OS). Results: Of 1625 included pts, the mean (SD) age was 60.9 (10.5) years (yrs). Compared to pts in the lowest EDIP quintile, pts in the highest quintile (a more inflammatory diet) were younger (58.7 ± 10.8 vs 61.3 ± 9.5 yrs old) and more likely to be female (64.0% vs 48.9%) and have worse performance status (ECOG 1-2: 35.7% vs 19.4%). Pts in the highest quintile were less likely to be White (76.6% vs 92.0 %) and more likely to be Black (15.4% vs 3.7%). Baseline aspirin use, assigned chemotherapy (3 mo vs 6 mo), and assigned pharmacotherapy (celecoxib vs placebo) were not significantly different across EDIP quintiles. Compared with pts in the lowest EDIP quintile, pts in the highest quintile had significantly worse OS (multivariable hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26-2.77, P trend =0.01), but not DFS (HR 1.36, 95% CI 0.99-1.86, P trend =0.22). Diet and physical activity jointly influenced OS. Those with lower EDIP scores (quintiles 1-4, 80% of the study population) and higher physical activity (≥9 MET-h/wk) had the best OS (HR 0.37, 95% CI 0.25-0.53) compared with pts in the highest EDIP quintile (20% of the study population) and lower physical activity (<9 MET-h/wk) ( P interaction <0.001). The association between higher EDIP and OS was consistent when analyzed by celecoxib and placebo treatment arms ( P interaction 0.54). The relationship between EDIP and OS did not differ significantly according to aspirin use, with HR 1.60 (95% CI 0.71-3.60) among aspirin users and HR 2.01 (95% CI 1.27-3.16) among aspirin non-users ( P interaction 0.06). Conclusions: Our findings suggest that greater intake of a proinflammatory dietary pattern is associated with worse OS in pts with stage III colon cancer. Regular physical activity may attenuate the association, and further investigation of diet and physical activity intervention is warranted. Support: U10CA180821, U10CA180882, U24CA196171, U10CA180863, CCS 707213, UG1CA233234, U10CA180820, U10CA180868, U10CA180888; https://acknowledgments.alliancefound.org. Pfizer; ClinicalTrials.gov Identifier: NCT01150045.