Neutrophils in pancreatic ductal adenocarcinoma: bridging preclinical insights to clinical prospects for improved therapeutic strategies.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a dismal five-year survival rate of less than 10%. Neutrophils are key components of the innate immune system, playing a pivotal role in the PDAC immune microenvironment. AREAS COVERED: This review provides a comprehensive survey of the pivotal involvement of neutrophils in the tumorigenesis and progression of PDAC. Furthermore, it synthesizes preclinical and clinical explorations aimed at targeting neutrophils within the milieu of PDAC, subsequently proposing a conceptual framework to propel further inquiry focused on enhancing the therapeutic efficacy of PDAC through neutrophil-targeted strategies. PubMed and Web of Science databases were utilized for researching neutrophils in pancreatic cancer publications prior to 2024. EXPERT OPINION: Neutrophils play roles in promoting tumor growth and metastasis in PDAC and are associated with poor prognosis. However, the heterogeneity and plasticity of neutrophils and their complex relationships with other immune cells and extracellular matrix also provide new insights for immunotherapy targeting neutrophils to achieve a better prognosis for PDAC.

Surgical and local control outcomes after sequential short-course radiation therapy and chemotherapy for rectal cancer.

Background: Total neoadjuvant therapy (TNT) is an accepted approach for the management of locally advanced rectal cancer (LARC) and is associated with a decreased risk of development of metastatic disease compared to standard neoadjuvant therapy. However, questions remain regarding surgical outcomes and local control in patients who proceed to surgery, particularly when radiation is given first in the neoadjuvant sequence. We report on our institution's experience with patients who underwent short-course radiation therapy, consolidation chemotherapy, and surgery. Methods: We retrospectively reviewed surgical specimen outcomes, postoperative complications, and local/pelvic control in a large cohort of patients with LARC who underwent neoadjuvant therapy incorporating upfront short-course radiation therapy followed by consolidation chemotherapy. Results: In our cohort of 83 patients who proceeded to surgery, a complete/near-complete mesorectal specimen was achieved in 90 % of patients. This outcome was not associated with the time interval from completion of radiation to surgery. Postoperative complications were acceptably low. Local control at two years was 93.4 % for all patients- 97.6 % for those with low-risk disease and 90.4 % for high-risk disease. Conclusion: Upfront short-course radiation therapy and consolidation chemotherapy is an effective treatment course. Extended interval from completion of short-course radiation therapy did not impact surgical specimen quality.

Circulating Tumor DNA to Predict Radiographic and Pathologic Response to Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

Despite advances in treatment and response assessment in locally advanced rectal cancer (LARC), it is unclear which patients should undergo nonoperative management (NOM). We performed a single-center, retrospective study to evaluate post-total neoadjuvant therapy (TNT) circulating tumor DNA (ctDNA) in predicting treatment response. We found that post-TNT ctDNA had a sensitivity of 23% and specificity of 100% for predicting residual disease upon resection, with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 47%. For predicting poor tumor regression on MRI, ctDNA had a sensitivity of 16% and specificity of 96%, with a PPV of 75% and NPV of 60%. A commercially available ctDNA assay was insufficient to predict residual disease after TNT and should not be used alone to select patients for NOM in LARC.