Rural-urban disparities in mortality and geriatric assessment among older adults with cancer: The cancer & aging resilience evaluation (CARE) registry.

INTRODUCTION: Rural-urban disparities persist in cancer mortality, despite improvement in cancer screening and treatment. Although older adults represent the majority of cancer cases and are over-represented in rural areas, few studies have explored rural-urban disparities in mortality and age-related impairments among older adults with cancer. MATERIALS AND METHODS: We included 962 newly-diagnosed older adults (≥60 years) with cancer who underwent geriatric assessment (GA) at their first pre-chemotherapy visit to an academic medical center in the Southeastern United States. We used Rural-Urban Commuting Area (RUCA) codes to classify residence at time of diagnosis into urban and rural areas. We used one-year survival and pre-treatment frailty as outcomes. We used Cox proportional hazards regression to evaluate the association between residence and one-year mortality, and logistic regression to evaluate the association between residence and pre-treatment frailty. All tests were two-sided. RESULTS: Median age at GA was 68.0 (interquartile rage [IQR]: 64.0, 74.0) years; most had colorectal cancer (24.3%) with advanced stage (III/IV 73.2%) disease. Overall, 11.4% resided in rural and 88.6% in urban areas. Rural areas had a higher proportion of White and less educated participants. After adjustment for age, sex, race, education, employment status, and cancer type/stage, rural residence was associated with higher hazard of one-year mortality (hazard ratio [HR] = 1.78, 95% confidence interval [CI] = 1.23, 2.57) compared to urban residence. Frailty was an effect modifier of this association (HROverall = 1.83, 95% CI = 1.27, 2.57; HRFrail = 2.05, 95% CI = 1.23, 3.41; HRNot Frail = 1.55, 95% CI = 0.90, 2.68). DISCUSSION: Among older adults with newly diagnosed cancer, rural residence was associated with reduced one-year survival, particularly among frail older adults. The rural-urban disparities observed in the current study may be due to frailty in conjunction with disparities in social determinants of health across rural and urban areas. Future studies should focus on understanding and intervening on underlying causes of these disparities.

Adoptive Cellular Therapy in Acute Myeloid Leukemia: Current Scope and Challenges.

Adoptive cellular therapies have revolutionized the management of hematologic malignancies, particularly lymphoma and multiple myeloma. These therapies targeting disease-specific antigens, such as CD19 in lymphoma and B cell maturation antigen in multiple myeloma, are efficacious and well-tolerated compared with conventional chemotherapies. Unfortunately, their potential remains unrealized in acute myeloid leukemia (AML). This is because most targetable antigens on AML cells are also expressed on healthy myeloid hematopoietic stem cells (HSC). Therefore, targeting them results in severe myeloablative effects and pancytopenia. Several strategies have been devised to overcome this barrier, including identifying AML-specific antigens, limiting CAR-T cell persistence to prevent prolonged myeloablation, and creating AML-specific antigens through manipulating HSCs prior to allogenic transplant. In this review, we discuss these strategies and the ongoing clinical trials on adoptive cellular therapies in AML, limiting our focus to chimeric antigen receptor-T cells (CAR-T) and chimeric antigen receptor-natural killer cells (CAR-NK).

Differences in Pretreatment Frailty Across Gastrointestinal Cancers in Older Adults: Results From the Cancer and Aging Resilience Evaluation Registry.

PURPOSE: Frailty predicts poor outcomes in older adults with cancer, but how it differs between different cancer types is unknown. We examined differences in pretreatment frailty between colorectal (CRC), pancreatic, and hepatobiliary cancers. METHODS: We included older adults age 60 years or older with the above cancer types enrolled in the Cancer and Aging Resilience Evaluation registry. Frailty was defined using a 44-item Cancer and Aging Resilience Evaluation frailty index constructed on the basis of the principles of deficit accumulation (including several geriatric assessment impairments encompassing malnutrition, functional status, comorbidities, anxiety, depression, cognitive complaints, health-related quality of life, falls, ability to walk one block, interference in social activities, and polypharmacy). Multivariable logistic regression models were used to examine the adjusted odds ratio (aOR) of frailty between cancer types. RESULTS: A total of 505 patients were included (mean age 70 years, 59% male): 211 (41.8%) CRC, 178 (35.2%)pancreatic cancer, and 116 (23.0%) hepatobiliary cancer. Patients with pancreatic cancer had the highest prevalence of frailty (23.3% CRC, 40.6% pancreatic, 34.3% hepatobiliary; P = .001). Both pancreatic (aOR, 2.18; 95% CI, 1.38 to 3.45), and hepatobiliary cancer (aOR, 1.73; 95% CI, 1.03 to 2.93) were independently associated with higher odds of frailty relative to CRC. Frailty was driven by higher rates of malnutrition and instrumental activities of daily living impairments in patients with pancreatic cancer and higher number of comorbidities in patients with hepatobiliary cancer. CONCLUSION: Older adults with pancreatic and hepatobiliary cancers are at high-risk of pretreatment frailty. Early interventions to improve nutritional and functional status and optimization of comorbidities may help improve outcomes.

Management of Non-Small Cell Lung Cancer: Updates from the European Lung Cancer Congress 2022.

The recently concluded European Lung Cancer Congress 2022 (ELCC22) showcased some very exciting data, with more than 200 abstracts presented during the meeting. Through this review, we focus on selected clinically relevant abstracts that in our opinion represent significant updates in the current management of non-small cell lung cancer (NSCLC). Here, we summarize the updates in surgical management, adjuvant therapy and therapy for advanced stage NSCLC and put these advances in the context of the current clinical standard of care.

Tumor lysis syndrome and infectious complications during treatment with venetoclax combined with azacitidine or decitabine in patients with acute myeloid leukemia.

Venetoclax (Ven) in combination with azacitidine or decitabine (hypomethylating agent; HMA) is the standard-of-care treatment for older (≥75 years) or intensive chemotherapy ineligible adults with newly diagnosed acute myeloid leukemia (AML). Tumor lysis syndrome (TLS) and infectious complications are two of the most concerning associated adverse events. We studied the real-world incidence and outcomes of these adverse events with HMA/Ven in AML patients. Our retrospective analysis included 106 patients (median age 70 years). Of these, 61 (58%) received HMA/Ven in frontline setting while 45 (42%) received in salvage setting. 19 (18%) met laboratory criteria for TLS, five (5%) developed clinical TLS (acute kidney injury). The median time to develop TLS was 2 days (range -2 to 4). During cycle 1, 29 patients (27%) were diagnosed with febrile neutropenia while 26 (25%) developed new infections. Median time to development of new infection was 10 days (1-25). Pneumonia was the most common infection (8%). Febrile neutropenia and/or new infection during cycle 1 was associated with poorer median overall survival compared to those without these complications (4.9 months vs 11.6 months; p = 0.03). In conclusion, incidence of TLS and infections was high in our cohort during initiation of HMA/Ven therapy. This data emphasizes the need for closer monitoring in these patients, especially during the first 7-10 days of treatment, which is often achieved in the inpatient setting.

Use of Leflunomide for Treatment of Cytomegalovirus Infection in Recipients of Allogeneic Stem Cell Transplant.

Cytomegalovirus (CMV) reactivations are common after allogeneic stem cell transplants, and pre-emptive therapy has been found to be effective. However, in India, treatment options are limited because of high cost and toxicity of ganciclovir and unavailability of cidofovir and foscarnet. Leflunomide is a cheap and easily available anti-rheumatoid arthritis drug that has been shown to have anti-CMV properties both in vitro and in vivo. It also has been used effectively for CMV reactivation after renal transplants. In this retrospective analysis, we analyzed 70 allogeneic stem cell transplants that were conducted between April 2015 and February 2017. There were 49 episodes of CMV reactivations in 43 patients in this period. Leflunomide was used in 24 episodes. It was effective in CMV clearance in 9 of the 24 episodes (38%). When the CMV copy number was <2 × 103 copies/mL, leflunomide was effective in 9 of 17 (53%) episodes, but when the copy number was >2 × 103, leflunomide was ineffective in all of the 7 episodes. This difference was statistically significant (P= .022 by Fisher exact test), suggesting that leflunomide may be more effective in clearance of CMV when copy numbers are low.