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Cardiovascular diseases (CVDs) and cancer continue to be the primary cause of mortality worldwide and their pathomechanisms are a complex and multifactorial process. Insufficient oxygen availability (hypoxia) plays critical roles in the pathogenesis of both CVDs and cancer diseases, and hypoxia-inducible factor 1 (HIF-1), the main sensor of hypoxia, acts as a central regulator of multiple target genes in the human body. Accumulating evidence demonstrates that mitochondria are the major target of hypoxic injury, the most common source of reactive oxygen species during hypoxia and key elements for inflammation regulation during the development of both CVDs and cancer. Taken together, observations propose that hypoxia, mitochondrial abnormality, oxidative stress, inflammation in CVDs, and cancer are closely linked. Based upon these facts, this review aims to deeply discuss these intimate relationships and to summarize current significant findings corroborating the molecular mechanisms and potential therapies involved in hypoxia and mitochondrial dysfunction in CVDs and cancer.

Background: Vitamin D exerts multiple beneficial effects in humans, including neuronal, immune, and bone homeostasis and the regulation of cardiovascular functions. Recent studies correlate vitamin D with cancer cell growth and survival, but meta-analyses on this topic are often not consistent. Methods: A systematic search of the PubMed database and the Clinical Trial Register was performed to identify all potentially relevant English-language scientific papers containing original research articles on the effects of vitamin D on human health. Results: In this review, we analyzed the antioxidant and anti-inflammatory effects of vitamin D against acute and chronic diseases, focusing particularly on cancer, immune-related diseases, cardiomyophaties (including heart failure, cardiac arrhythmias, and atherosclerosis) and infectious diseases. Conclusions: Vitamin D significantly reduces the pro-oxidant systemic and tissue biomarkers involved in the development, progression, and recurrence of chronic cardiometabolic disease and cancer. The overall picture of this review provides the basis for new randomized controlled trials of oral vitamin D supplementation in patients with cancer and infectious, neurodegenerative, and cardiovascular diseases aimed at reducing risk factors for disease recurrence and improving quality of life.

The psychological impact of the Covid 19 pandemic on cancer patients, a population at higher risk of fatal consequences if infected, has been only rarely evaluated. This study was conducted at the Departments of Oncology of four hospitals located in the Verona area in Italy to investigate the psychological consequences of the pandemic on cancer patients under active anticancer treatments. A 13-item ad hoc questionnaire to evaluate the psychological status of patients before and during the pandemic was administered to 474 consecutive subjects in the time frame between April 27 th and June 7 th 2020. Among the 13 questions, 7 were considered appropriate to elaborate an Emotional Vulnerability Index ( EVI ) that allows to separate the population in two groups (low versus high emotional vulnerability) according to observed median values. During the emergency period, the feeling of high vulnerability was found in 246 patients (53%) and was significantly associated with the following clinical variables: female gender, being under chemotherapy treatment, age ≤ 65 years. Compared to the pre-pandemic phase, the feeling of vulnerability was increased in 41 patients (9%), remained stably high in 196 (42%) and, surprisingly, was reduced in 10 patients (2%). Overall, in a population characterized by an high level of emotional vulnerability the pandemic had a marginal impact and only a small proportion of patients reported an increase of their emotional vulnerability.

Background: Immune checkpoint inhibitors (ICI) plus radiotherapy (RT) have been suggested as an emerging combination in non-small cell lung cancer (NSCLC) patients. However, little is known about the magnitude of its benefits and potential clinical predictors. Objective: To assess the effects of this combination on the increase in overall and progression-free survival. Data sources: The MEDLINE and CANCERLIT (1970–2020) electronic databases were searched, and the reference lists of included studies were manually searched. Study selection: Studies were included if they were comparative studies between combination ICI-RT and ICI or RT alone in advanced or metastatic NSCLC patients. Overall survival (OS) was analyzed according to the treatment strategy. Data extraction: Data on population, intervention, and outcomes were extracted from each study, in accordance with the intention-to-treat method, by two independent observers and combined using the DerSimonian method and Laird method. Results: Compared to ICI or RT alone, ICI-RT significantly increased the 1-year and 3-year OS RR by 0.75 (95% CI 0.64–0.88; p = 0.0003) and 0.85 (95% CI 0.78–0.93; p = 0.0006), respectively. Furthermore, there was a statistically significant benefit on 1- and 3-year progression-free survival (RR 0.73 (95% CI, 0.61–0.87; p = 0.0005) and RR 0.82 (95% CI 0.67–0.99; p = 0.04), respectively). Conclusions: In patients with advanced or metastatic NSCLC, combination ICI-RT increases 1- and 3-year OS and progression-free survival compared to ICI or RT alone.

Introduction. This study aims to conduct a cost-effectiveness analysis comparing two primary treatment approaches: radical prostatectomy versus radiotherapy plus androgen deprivation therapy (ADT) in patients with Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. Patients and Methods. Data were extracted from two published retrospective cohort studies. Using survival data from two retrospective studies, we reconstructed Kaplan–Meier curves, overlaid them for comparative metasurvival analysis, and developed a cost-function model to assess economic implications alongside clinical outcomes. The primary outcomes included biochemical recurrence-free survival (FFBF) at 2 and 5 years; the area under the survival curve; total cost per treatment strategy; and cost per recurrence-free patient at 5 years. Results. At 5 years, the estimated FFBF was 83% for radiotherapy vs. 28% for prostatectomy. Radiotherapy yielded an AUC of 80.7, while prostatectomy showed 41.9. Radiotherapy yielded a cost of 21,211 € per FFBF patient compared to 113,730 € for prostatectomy. Conclusion. Our study demonstrates that radiotherapy combined with ADT, when selected based on mpMRI stratification, may represent a cost-efficient alternative, pending prospective validation. To radical prostatectomy in patients with PI-RADS 5 prostate cancer, with a favourable cost–benefit profile.

PurposeAbdominal recurrences of gastrointestinal malignancies are common. Evidence in clinical studies has shown that re-irradiation (Re-I) is tolerable and efficient in different tumor locations. In contrast, little clinical data are available on normal long-term Re‑I tolerance doses. A systematic review of upper abdominal Re‑I was performed with the aim of exploring the cumulative dose, toxicity, and outcomes.MethodsA computerized search was undertaken in MEDLINE, EMBASE, OVID, and the Cochrane database. Only studies reporting toxicity and/or outcomes were taken into consideration. To improve the comparability of the different Re‑I regimens and assess the relationship between Radiotherapy (RT) dose and toxicity, the equivalent dose in 2‑Gy fractions was calculated according to the linear quadratic model.ResultsSixteen studies met the inclusion criteria, with the total patients numbering 408. Median follow-up Re‑I ranged from 5.9 to 45 months. The median time elapsed since previous RT treatment was 15 months (2–162 months). Re‑I prescription doses were variable (22.5 Gy in 3 fractions to 126.5 Gy with 125I). Cumulative doses calculated for acute- and late-responding tissues ranged from 67.25 to 136 Gy and 30.3 to 188.38 Gy, respectively. Comprehensively, the pooled ≥G3 toxicity was 12% (95%CI: 7.6–19%). The overall 1‑year survival and local recurrence-free survival rates were 53.7% (95%CI: 45.6–63.2%) and 66.5% (95% CI: 58.7–75.4%), respectively. Pain improvement was reported in 66.9% of patients.ConclusionDue to limited evidence as a result of the retrospective design of the majority of the studies, our review suggests that upper abdominal Re‑I is effective in terms of local control and palliation, with a moderate rate of severe toxicities.

The discovery of immune checkpoint inhibitors (ICIs) such as programmed cell death protein 1 (PD-1) inhibitors, nivolumab and pembrolizumab, and programmed cell death ligand 1 (PD-L1) inhibitors, atezolizumab and durvalumab, has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). Concurrent radiotherapy (RT) is of particular interest with regard to the potential role for this combination in many settings. The purpose of this commentary is to evaluate the potential for the combination of immune checkpoint inhibitors and radiotherapy, including analysis of studies that have considered this combination in various settings.

Resistance to chemotherapy still remains a major challenge in the clinic, impairing the quality of life and survival rate of patients. The identification of unconventional chemosensitizing agents is therefore an interesting aspect of cancer research. Resveratrol has emerged in the last decades as a fascinating molecule, able to modulate several cancer-related molecular mechanisms, suggesting a possible application as an adjuvant in cancer management. This review goes deep into the existing literature concerning the possible chemosensitizing effect of resveratrol associated with the most conventional chemotherapeutic drugs. Despite the promising effects observed in different cancer types in in vitro studies, the clinical translation still presents strong limitations due to the low bioavailability of resveratrol. Recently, efforts have been moved in the field of drug delivery to identifying possible strategies/formulations useful for a more effective administration. Despite the necessity of a huge implementation in this research area, resveratrol appears as a promising molecule able to sensitize resistant tumors to drugs, suggesting its potential use in therapy-refractory cancer patients.

Purpose To assess toxicity and clinical outcome, in breast cancer patients treated with external beam partial breast irradiation (PBI) consisting of 35 Gy in 7 daily fractions (5 Gy/fraction). Materials and Methods Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old or over and treated with breast conservative surgery for early stage invasive carcinoma. Results Seventy-three patients were analyzed. Median follow-up was 40 months. The proposed schedule was well tolerated. No Grade 3 toxicity was documented. Late toxicity was assessable for all the treated patients. Two patients (2.7%) developed Grade 2 pain 6 months after PBI. Four patients (5%) developed asymptomatic fat necrosis. Grade 2 fibrosis was observed in 5 patients (6.7%). No correlation was found between early and late toxicity and the type of adjuvant systemic therapy (no therapy vs. hormonal therapy vs. chemotherapy). No statistical correlation between dosimetric parameters and toxicity was found. Patients who developed Grade 2 radiation fibrosis had not higher radiation volumes to the untreated normal breast than those without fibrosis. Cosmesis was judged good/excellent in the majority of the cases (93%). One patient relapsed locally, and one developed distant metastases, corresponding to a 5-year local control and distant metastases-free survival of 98% and 96.7%, respectively. Conclusions 35 Gy in 7 daily fractions is an effective and well-tolerated regimen to deliver PBI.