Background: Multiple primary malignant tumors (MPMTs) involving the digestive tract pose diagnostic and therapeutic challenges, with survival differences between synchronous and metachronous forms not well defined. This study assessed predictors of overall survival (OS) in patients in whom at least one tumor originated in the digestive tract or accessory organs. Methods: We retrospectively reviewed 1920 oncology cases (January 2020–June 2023) from St. Nicholas Hospital, Romania. Of 118 patients with MPMTs, 45 had ≥1 digestive tract tumor. They were classified as synchronous (2 months) as per the SEER rules. Clinical, pathological, treatment, and follow-up data were analyzed; OS was evaluated using Kaplan–Meier and Cox regression. Results: Fifteen patients (33%) had synchronous tumors and 30 (67%) had metachronous tumors. Overall, 17 of 45 patients (37.8%) died by the last follow-up. The restricted mean survival time (RMST) was 31.3 months for those with synchronous vs. 68.3 months for those with metachronous tumors (HR = 2.49, 95% CI 0.95–6.50, p = 0.062; log-rank p = 0.053). Curative treatment of the first tumor was associated with markedly improved survival (RMST 58.2 vs. 29.4 months; HR = 20.5, 95% CI 3.68–114, p < 0.001). In the multivariable Cox regression analysis, advanced primary nodal stage (N2–N3) remained independently associated with reduced survival (adjusted HR 3.86, 95% CI 1.04–14.3, p = 0.044). The adjusted effect of synchronous vs. metachronous classification was attenuated (adjusted HR 2.22, 95% CI 0.84–5.86, p = 0.10). Conclusions: In this single-center, hypothesis-generating cohort, synchronous digestive-tract MPMTs were associated with shorter unadjusted survival than metachronous tumors, but advanced nodal stage and limited feasibility of curative therapy were the dominant independent predictors of poor outcome. Given the small sample size and retrospective design, these findings should be interpreted as preliminary and warrant validation in larger, multicenter cohorts.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, marked by late diagnosis, limited responsiveness to conventional therapies, and an immunosuppressive tumor microenvironment. While immunotherapy has transformed treatment paradigms in several cancers, its efficacy in PDAC has been minimal. Oncolytic viruses and therapeutic cancer vaccines have emerged as promising immunotherapeutic strategies designed to stimulate robust, tumor-specific immune responses and reshape the immune landscape. However, despite encouraging preclinical data, clinical translation in PDAC has been largely disappointing. This review critically evaluates the design, delivery, and efficacy of oncolytic virotherapy and cancer vaccines in PDAC, examining barriers such as stromal desmoplasia, immune exclusion, and tumor heterogeneity. We also explore combination strategies integrating checkpoint inhibitors, chemotherapy, radiotherapy, and stromal modulation to overcome resistance. Ultimately, the viability of these approaches hinges on a clearer understanding of their mechanistic limitations and the refinement of delivery platforms. These factors will determine whether oncolytic viruses and cancer vaccines can be successfully repositioned within the therapeutic arsenal or warrant reevaluation in the evolving landscape of PDAC treatment.

Background: Triple primary malignant tumors (TPMTs) are extremely rare and represent a major diagnostic and therapeutic challenge. Their frequency has increased with advances in cancer detection and longer patient survival. Case presentation: We report the case of a 76-year-old male diagnosed with three synchronous primary malignancies involving the liver, left kidney, and right lung. Imaging revealed a hepatic mass with arterial enhancement and portal washout, a large left renal mass, and a cavitated pulmonary nodule. Histopathological and immunohistochemical evaluation confirmed three distinct tumors: well-differentiated hepatocellular carcinoma, chromophobe renal cell carcinoma, and invasive non-mucinous lung adenocarcinoma. A multidisciplinary oncology board recommended surgical resection of the liver and kidney lesions and stereotactic body radiotherapy for the lung tumor. The patient underwent hepatectomy and nephrectomy but experienced severe postoperative complications leading to multi-organ failure and death. Results of the systematic review: A systematic search identified 83 relevant cases of triple primary malignancies after full-text eligibility assessment. None of the 159 articles included after primary screening described a synchronous association of primary liver, kidney, and lung cancers. Conclusions: This case highlights the importance of thorough diagnostic assessment and individualized, multidisciplinary management in patients with multiple synchronous malignancies. To our knowledge, this is the first reported case of synchronous hepatocellular carcinoma, chromophobe renal cell carcinoma, and lung adenocarcinoma.