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BACKGROUND:Cancer is a leading cause of death in both the USA and India. During Prime Minister Narendra Modi's State Visit to Washington, DC in June 2023, the two governments announced several cooperation commitments. One such commitment was the establishment of the US-India Cancer Dialogue, initiating a structured bilateral effort to address shared cancer challenges. The aim of this article is to outline the preparatory steps and proceedings of the inaugural joint meeting of the US-India Cancer dialogue that took place in New Delhi in August 2024. MATERIALS AND METHODS:This manuscript reports the outcomes of a structured bilateral consensus development process designed to identify priority areas for collaboration between the USA and India. Following the announcement, a high-level virtual consultation convened government, scientific, and clinical leaders to identify shared priority areas. A US-based meeting hosted by the American Society of Clinical Oncology (ASCO) refined technical workstreams, including prevention, early detection, therapeutics, clinical trials, and implementation science. Continued coordination among the US National Cancer Institute, the White House Office of Science and Technology Policy, and India's Department of Biotechnology formalized the bilateral agenda RESULTS: Over 2 days, the in-person Dialogue identified priority areas for bilateral collaboration, including expansion of human papillomavirus (HPV) vaccination and cervical cancer screening, advancement of artificial intelligence (AI)-enabled early detection technologies, improved access to immunotherapies and chimeric antigen receptor T cell (CAR-T) therapies, strengthened genomics and data-sharing infrastructure, expanded clinical trial capacity, and enhanced survivorship and palliative care. CONCLUSIONS:This collaboration establishes a durable framework to accelerate innovation, expand equitable access, and reduce preventable cancer deaths across both nations.
BACKGROUND:Methotrexate-based chemoradiotherapy is effective in primary central nervous system lymphoma (PCNSL) but carries a risk of severe neurotoxicity. In a single-arm study, a regimen with methotrexate, procarbazine, vincristine, and cytarabine was combined with rituximab (R-MPV-A) and substantially reduced doses of whole-brain radiotherapy (LD-WBRT), resulting in excellent progression-free survival (PFS) and overall survival (OS). Because R-MPV-A had never been tested without radiation, we sought to evaluate the efficacy of R-MPV-A with and without LD-WBRT, as well as determining if such low radiotherapy doses influenced disease control and/or neurotoxicity. METHODS:Patients were randomized to receive R-MPV-A alone (Chemo arm) or combined with LD-WBRT (ChemoRT arm), given at 2,340 cGy (180cGy X13). Primary endpoint was intent-to-treat (ITT) PFS. A sample size of 89 would provide 80% power to detect a hazard ratio (HR) of 0.63 (one-sided alpha = 0.15). RESULTS:Ninety-one patients were randomized, with 44 analyzed in the ChemoRT and 46 in the Chemo arm. Median age was 66 and 59.5, respectively. R-MPV-A was well tolerated, achieving a complete response rate of 92.3% (ChemoRT) and 76.3% (Chemo). After median follow-up of 4.6 years, median PFS was not reached (ChemoRT) vs 2.1 years (Chemo), HR = 0.47 (P = .007; 95% CI, 0.26-0.87). The 2-year PFS was 78.7% vs 54%, respectively. Differences in OS did not reach statistical significance (HR = 0.71; P = .33). Neuropsychological evaluation showed no differences in cognitive outcomes, with several tests favoring ChemoRT. CONCLUSIONS:R-MPV-A is a highly efficacious and safe regimen with or without LD-WBRT. LD-WBRT contributes to disease control and increases PFS in PCNSL.
BACKGROUND: The evidence linking long-term exposure to air pollution and the development of chronic obstructive pulmonary disease (COPD) is still controversial. Furthermore, most studies have investigated associations with particulate matter (PM) and nitrogen dioxide (NO2), disregarding their emission source and other relevant air pollutants, such as ultrafine particles (UFP) and elemental carbon (EC). OBJECTIVES: This study aimed to assess associations between long-term residential exposure to PM2.5, NO2, UFP, and EC and the risk of COPD, distinguishing the effects of air pollution from local traffic and other sources. METHODS: We pooled data from two large Danish cohorts, the Diet, Cancer, and Health cohort and the Danish National Health Survey. For all participants (N = 159,769), we estimated long-term air pollution exposure to total, local traffic, and other contributions, based on complete address histories. We used Cox proportional hazards models to estimate associations between 10-year time-weighted averaged air pollution and incident COPD, adjusting for demographic, socioeconomic, and lifestyle factors, including smoking. We evaluated the possible modification of these associations by sex, smoking status, and previous asthma diagnosis. RESULTS: Long-term exposures to PM2.5, NO2, UFP, and EC were associated with higher risk of COPD. The highest hazard ratio (HR) per interquartile range of total contributions was observed for PM2.5 (HR: 1.11 [95% confidence interval: 1.05, 1.17]), followed by NO2 (1.08 [1.04, 1.13]), UFP (1.05 [0.99, 1.11]), and EC (1.02 [1.00, 1.05]), after full adjustment. PM2.5 from other sources than local traffic was more strongly associated with COPD than PM2.5 from local traffic, while for UFP and EC, the contributions from local traffic seemed to be the most harmful. Effect modification analyses showed stronger associations among women, never smokers, and those with an asthma diagnosis. DISCUSSION: Our findings suggest that air pollution from local traffic and other sources contributes to COPD risk, with variations depending on the pollutant type. Further research is needed to validate these findings across different populations and geographical settings.
ABSTRACT:Newly diagnosed mantle cell lymphoma (MCL) is commonly treated with rituximab (R), combined with anthracycline-based chemotherapy, with or without autologous stem cell transplantation (ASCT). Although R maintenance (RM) in clinical trials has been shown to prolong overall survival (OS), its impact at the population level remains largely unknown. This study evaluated the effect of RM on the outcome of patients with MCL. Patients aged ≥18 years, who were diagnosed with MCL between 1989 and 2020 were identified using the Netherlands Cancer Registry and were categorized into periods that reflected R and RM implementation (1989-2000, 2001-2014, 2015-2020). The treatment strategies were categorized as R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone); R-CHOP, followed by high-dose cytarabine (intensive) and ASCT; and other. The primary end point was 5-year OS. A multivariable analysis (MVA) was performed using Cox regression. Among 4751 patients, the 5-year relative survival (RS) improved from 38% (1989-2000) to 47% (2001-2014) and 60% (2015-2020) (P< .01), irrespective of age (≤65 years: 32% vs >65 years: 20% increase over time). Patients with progression within 12 months had a 2-year OS rate of 25%. Since 2014, RM implementation reached 80% in younger patients and 50% in older patients. RM was associated with improved OS, especially for patients in partial remission (PR) after induction treatment with R-CHOP. In the MVA of patients treated with R-CHOP, RM was independently associated with reduced mortality (hazard ratio, 0.69; 95% confidence interval, 0.53-0.90). The RS in MCL improved by >20% in 30 years. Early disease progression remains associated with poor outcome. RM was associated with improved survival, especially among patients who achieved PR following R-CHOP.
The interaction between the gut microbiota and the central nervous system has been recognized as a significant mechanism in the pathophysiology of depression and stress; research identifying specific microbial patterns associated with these disorders is summarized in this review, highlighting dysbiotic shifts that exacerbate neuroinflammation, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, and neurotransmitter imbalances. Microbiota compositions typically exhibit decreased diversity in stress-induced states, such as prolonged psychological stress or exposure to environmental stressors. Both proinflammatory taxa, such as Proteobacteria, overgrow, while beneficial genera, including Lactobacillus and Bifidobacterium, are depleted. These changes are linked to increased cortisol levels, compromised intestinal barrier integrity, leaky gut, and ensuing systemic inflammation that penetrates the blood-brain barrier and promotes depressive and anxiety-related traits. Reduced short-chain fatty acid (SCFA)-producing bacteria and decreased alpha-diversity indices are two recurring patterns observed in metagenomic analyses of individuals with clinical depression. To sustain neuroplastic deficits in areas such as the hippocampus and prefrontal cortex, these microbial imbalances mechanistically interfere with serotonin synthesis, gamma-aminobutyric acid (GABA) modulation, and the expression of brain-derived neurotrophic factor (BDNF). Probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary interventions are among the approaches that target microbiota restoration and show therapeutic promise in reducing symptoms. In managing stress and depression, this story highlights microbiota patterns as modifiable processes, rather than merely serving as biomarkers. The goal of this review is to examine the impact of the microbiota on depressive disorders and the underlying mechanisms that may provide novel therapeutic approaches.
