Pancreatic ductal adenocarcinoma is a highly aggressive malignancy with a poor prognosis. Effective treatment with acceptable outcomes is yet to be found, with chemo- and radioresistance comprising major impediments towards this goal. Although upfront surgery is the established therapeutic approach for resectable and borderline resectable disease, neoadjuvant treatment has recently monopolized the interest in clinical trials. This also applies to locally advanced pancreatic adenocarcinomas that could potentially be rendered operable. Chemotherapy and chemoradiotherapy are the most utilized therapeutic modalities in the neoadjuvant setting, while immunotherapy and targeting agents have been gaining significant attention. This critical review focuses on the clinical experience gained from retrospective and phase II/III randomized trials, reporting on the outcomes of neoadjuvant chemotherapy and chemoradiotherapy for pancreatic adenocarcinoma. Moreover, the ongoing trials, including those that involve immunotherapy and targeting agents, are summarized.
Neoadjuvant chemotherapy (NACT) for certain breast cancer (BC) subtypes confers significant tumor regression rates and a survival benefit for patients with a complete pathologic response. Clinical and preclinical studies have demonstrated that immune-related factors are responsible for better treatment outcomes, and thus, neoadjuvant immunotherapy (IO) has emerged as a means to further improve patient survival rates. Innate immunological “coldness”, however, of specific BC subtypes, especially of the luminal ones, due to their immunosuppressive tumor microenvironment, hinders the efficacy of immune checkpoint inhibitors. Treatment policies aiming to reverse this immunological inertia are, therefore, needed. Moreover, radiotherapy (RT) has been proven to have a significant interplay with the immune system and promote anti-tumor immunity. This “radiovaccination” effect could be exploited in the neoadjuvant setting of BC and significantly enhance the effects of the already established clinical practice. Modern stereotactic irradiation techniques directed to the primary tumor and involved lymph nodes may prove important for the RT-NACT-IO combination. In this review, we provide an overview and critically discuss the biological rationale, clinical experience, and ongoing research underlying the interplay between neoadjuvant chemotherapy, anti-tumor immune response, and the emerging role of RT as a preoperative adjunct with immunological therapeutic implications in BC.
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