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Saikat Mandal

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Open access Aug 2026

Trends and Disparities in Mortality Involving Pancreatic Cancer and Pulmonary Embolism in the United States, 1999–2024: A CDC WONDER Analysis

Background: U.S. mortality trends involving pancreatic cancer and pulmonary embolism (PE) and whether PE is becoming increasingly represented among pancreatic cancer deaths remain incompletely characterized. Methods: We analyzed CDC WONDER Multiple Cause of Death data for adults aged ≥ 25 years from 1999 through 2024. Deaths were included in the primary analysis when pancreatic cancer and PE were both recorded as underlying or contributing causes. Age-adjusted mortality rates (AAMRs) were evaluated using Joinpoint Regression Program version 6.0.1. Forecasting and additional weighted log-linear and segmented regression analyses were performed in R version 4.5. Additional analyses evaluated race/ethnicity, the proportion of pancreatic cancer underlying-cause deaths with PE recorded, and sensitivity to the COVID-19 years. Results: Overall, 18,243 deaths involved both pancreatic cancer and PE. The AAMR increased from 0.19 per 100,000 in 1999 to 0.55 in 2024. Mortality increased by 2.65% annually during 1999–2016 and by 8.54% annually during 2016–2024, with a significantly steeper post-2016 slope (p < 0.001). Rates were consistently higher among males and non-Hispanic Black individuals. Hispanic or Latino mortality increased significantly during 2011–2024, whereas estimates for Asian or Pacific Islander individuals were too sparse or frequently suppressed to support reliable longitudinal trend analysis. Among deaths with pancreatic cancer as the underlying cause, the proportion with PE recorded increased from 1.00% in 1999 to 2.85% in 2024, with significantly faster growth after 2016 (p < 0.001). Excluding 2020–2021 did not materially alter the post-2016 increase. Conclusions: Mortality involving pancreatic cancer and PE increased substantially in the United States, and PE was recorded in a growing proportion of pancreatic cancer deaths. These death-certificate data identify an increasing population-level burden but cannot establish causality or demonstrate the effectiveness of specific clinical interventions.

A. Dhali, J. Biswas, Ali Shan Hafeez et al. · 0 citations
Review Open access Aug 2026

Tissue and blood-based predictive biomarkers in hepatocellular carcinoma immunotherapy: synthesis of 2023–2026 evidence and a proposed clinical integration framework

Atezolizumab-bevacizumab and durvalumab-tremelimumab have established immunotherapy as a first-line standard of care in advanced hepatocellular carcinoma (HCC). Yet, objective response rates (ORRs) remain confined to approximately 15-20%, and no validated predictive biomarker exists for patient selection. Unlike melanoma and lung cancer, conventional markers, including programmed death-ligand 1, microsatellite instability-high status, and tumor mutational burden, have not demonstrated reliable predictive value in HCC. Prior narrative reviews comprehensively catalogued the biomarker landscape through 2022 but predate a wave of clinically significant publications. This narrative review synthesizes evidence published between 2020 and 2026, with particular emphasis on 2023–2026 data, within a unified clinical framework not provided by prior reviews. We critically evaluate tissue-based biomarkers, including the AI-derived Atezolizumab-Bevacizumab Response Signature-Pathology model, spatial multiplex immunohistochemistry, and β-catenin mutational profiling; blood-based biomarkers encompassing circulating tumor DNA for minimal residual disease detection and peripheral immune phenotyping; and serum indices including the CRAFITY score and neutrophil-to-lymphocyte ratio. Hepatitis B virus etiology and non-alcoholic steatohepatitis are discussed as biological modifiers of biomarker performance. We propose an original biomarker-guided clinical algorithm, a comparative clinical readiness table, and a disease-continuum biomarker timeline as practical tools for clinicians and trialists. Prospective biomarker-enrichment trials represent the most critical next step toward clinical translation.

Ashish Sharma, J. Tan, Rajvardhan Sisodia et al. · 0 citations

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