In recent years, evidence has shown the potential therapeutic effects of different natural compounds for the prevention and treatment of radiotherapy-induced mucositis (RIOM). RIOM represents one of the most frequent side effects associated with anti-neoplastic treatments affecting patients’ quality of life and treatment response due to radiation therapy discontinuation. The innate radio-protective ability of natural products obtained from plants is in part due to the numerous antioxidants possessed as a part of their normal secondary metabolic processes. However, oxygen presence is a key point for radiation efficacy on cancer cells. The aim of this review is to describe the most recent evidence on radiation-induced injury and the emerging protective role of natural compounds in preventing and treating this specific damage without compromising treatment efficacy.

Aim: The aim was to investigate the use of comprehensive pretreatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18F-FDG-positron emission tomography (PET)/computed tomography (CT) scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies. Materials and methods: This study was a secondary analysis of three prospective studies of chemoradiotherapy (CRT) with or without induction chemotherapy (IC). The inclusion period was from December 2009 until February 2023. An intensified pretreatment staging was conducted for all LAPC patients. Patients without distant disease at initial staging, with borderline resectable or unresectable LAPC, were enrolled in CRT combination protocols (CRT with or without IC). IC regimens included GemOx or FOLFIRINOX for four cycles, followed by concurrent CRT with gemcitabine. The primary endpoint was the detection of occult metastatic disease, and secondary objectives included resection rate, treatment toxicity, overall survival (OS), progression-free survival (PFS), local control, and metastasis-free survival. Results: Out of the 134 LAPC patients, 33.5% were identified with metastatic disease. Of these, 23.1% had a positive exploratory laparoscopy. Additionally, 13.4% were identified as having distant metastases by 18-FDG PET/CT. The median PFS for all patients who completed CRT was 14.3 months, and the median OS was 17.2 months. Resected patients after the combined therapies demonstrated significantly improved outcomes compared tonon-resected patients (median PFS, 22.5 months vs. 9.5 months, P<0.001; median OS, 38.2 months vs. 13 months, P<0.001). Moreover, patients treated with IC followed by CRT showed significantly better outcomes compared to the upfront CRT group (median PFS, 19 months vs. 9.9 months, P<0.001; median OS, 19.3 months vs. 14.6 months, P<0.001). At univariate logistic regression analysis, the adding of IC was the only predictor for resection rate (95% CI: 0.12–1.02, P=0.05), and this data was confirmed at multivariate analysis (95% CI: 0.09–0.98, P=0.04). Hematological and gastrointestinal toxicities were observed during treatment, with manageable adverse events. Conclusions: The use of comprehensive pretreatment staging, including laparoscopy and 18F-FDG-PET/CT scan, is an effective approach in identifying occult metastatic disease in LAPC patients. Our findings offer valuable insights into accurate staging and treatment efficacy, providing evidence-based support for optimal management strategies in LAPC patients.

Aims: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. Methods: We performed a retrospective cohort study. Patients were divided according to chemotherapy regimens concurrent to radiotherapy (1-drug vs. 2-drug) and according to the time interval between the end of CRT and surgery (≤8 weeks vs. >8 weeks), as well as in relation to specific relevant clinical factors. Logistic regression was used to estimate the independent factors for pCR and downstaging. Results: 269 patients were eligible for this study. Overall, pCR and downstaging rates were 26% and 75.4%, respectively. Univariate analysis showed that female gender (p = 0.01) and time to surgery >8 weeks (p = 0.04) were associated with pCR; age > 70 years (p = 0.05) and time to surgery >8 weeks (p = 0.002) were correlated to downstaging. At multivariate analysis, interval time to surgery of >8 weeks was the only independent factor for both pCR and downstaging (p = 0.02; OR: 0.5, CI: 0.27–0.93 and p = 0.003; OR: 0.42, CI: 0.24–0.75, respectively). Conclusions: This study indicates that, in our population, an interval time to surgery of >8 weeks is an independent significant factor for pCR and downstaging. Further prospective studies are needed to define the best interval time.

Background: Pancreatic cancer, with its poor prognosis, is frequently diagnosed in elderly patients who may be ineligible for surgery or chemoradiation due to age or comorbidities. Stereotactic body radiotherapy (SBRT) offers a targeted approach by delivering precise, high-dose radiation to a limited volume in few fractions. This study aims to evaluate the efficacy and safety of SBRT in elderly pancreatic cancer patients. Methods: Patients with pancreatic cancer received SBRT using Volumetric Modulated Arc Therapy in schedules of five dose fractions tailored to the tolerance of adjacent tissues. Progression-free survival (PFS), local progression-free survival (LPFS), metastasis-free survival (MFS) and overall survival (OS) were analysed. Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Median follow-up was 9.5 months (range, 4–37.2 months). The 1-year, 2-year and 3-year LPFS rates were 88%, 73% and 54%, respectively (median not reached). Median PFS, MFS and OS were 29.6 months, 32.6 months, and 24.1 months, respectively. SBRT was well tolerated with acute and late toxicity rates of 6% and 9%, respectively. Conclusionsd: SBRT appears to be an effective and safe option for elderly pancreatic cancer patients, achieving high local control with minimal toxicity.

Backgrounds and aim: Protective effects of natural compounds have been suggested in the prevention and treatment of radiation-induced mucositis or bacterial infections. In this study, the protective effects of proanthocyanidin-rich grape seed extract (GSE) on bacterial Lipopolysaccharide (LPS) and radiation-induced epithelial barrier damage and Reactive Oxygen Species (ROS) production were investigated in an in vitro model. Methods: Human intestinal epithelial cells Caco-2, previously treated with LPS, GSE, or LPS + GSE, were irradiated with 10 Gy divided into five daily treatments. Epithelial barrier integrity and ROS production were measured before and after each treatment. Results: Irradiation, at different doses, significantly increased intestinal permeability and ROS production; pretreatment with GSE was able to significantly prevent the increased intestinal permeability (4.63 ± 0.76 vs. 15.04 ± 1.5; p < 0.05) and ROS production (12.9 ± 1.08 vs. 1048 ± 0.5; p < 0.0001) induced by irradiation treatment. When the cells were pretreated with LPS, the same results were observed: GSE cotreatment was responsible for preventing permeability alterations (5.36 ± 0.16 vs. 49.26 ± 0.82; p < 0.05) and ROS production (349 ± 1 vs. 7897.67 ± 1.53; p < 0.0001) induced by LPS exposure when added to the irradiation treatment. Conclusions: The results of the present investigation demonstrated, in an in vitro model, that GSE prevents the damage to intestinal permeability and the production of ROS that are induced by LPS and ionizing radiation, suggesting a potential protective effect of this extract on the intestinal mucosa during irradiation treatment.