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Gastric cancer remains a considerable health burden throughout the world. The Cancer Genome Atlas (TCGA) analysis has recently unveiled 4 genotypes of gastric cancer with data not ready to change treatment strategy yet. A multimodality approach to therapy is the cornerstone of screening, diagnosing, staging, treating and supporting patients with gastric cancer. The evidence‐based approach to localized gastric cancer (>cT1b) is to use an either preoperative or postoperative strategy to maximize the benefit of surgery. The focus of future research is to optimize chemotherapy regimens, determine the role of radiation therapy and investigate the effect of treatment timing. In metastatic gastric cancer, biologic therapies have been introduced targeting markers shown to be prognostic. The results of ongoing randomized controlled phase 3 trials using targeted and immunotherapy agents, either in combination or alone, have the potential to alter the current treatment landscape of advanced gastric cancer. A multimodality approach to therapy is critical for patients with gastric cancer. One of the most challenging and exciting field that appears promising is the potential of host's immune system to inhibit signaling pathways.

Background and Objectives: Childhood obesity is a global public health concern with long-term and serious health implications. An important factor for childhood obesity is maternal gestational diabetes mellitus (GDM), which in turn impacts maternal and offspring long-term health. This study aimed to investigate the associations between maternal GDM and childhood weight status and multiple anthropometric and sociodemographic factors and perinatal outcomes. Materials and Methods: A total of 5348 children aged 2–5 years old and their paired mothers took part in the study. Questionnaires were utilized to evaluate the sociodemographic factors and perinatal outcomes as well as smoking habits, educational level, economic status, age, and parity status. Children’s anthropometric parameters were measured, and maternal medical history, preterm birth records, and anthropometric measures during pregnancy were retrieved by their medical records. Results: Overall, 16.4% of the children aged at 2–5 years were overweight, and 8.2% of them were affected by obesity, leading to a total 24.6% of children with overweight/obesity. Further, 5.5% of the enrolled mothers were diagnosed with gestational diabetes mellitus. GDM doubles the probability of childhood overweight/obesity at ages 2–5 years old independently of multiple confounding factors. Pre-pregnancy overweight and obesity, older maternal age, and smoking are risk factors for GDM, while GDM additionally increases the risk of preterm birth. Children of mothers that developed GDM were at greater risk of overweight or obesity, with the association between GDM and offspring’s weight status being independent of confounding factors. Conclusions: GDM is a severe public health issue with prolonged complications for both the mother and their children. Public health approaches and programs need to promote the negative role of pre-pregnancy weight and smoking status as well as the significance of a good glycemic control throughout gestation in women of childbearing age.

Hippo pathway with its main molecule YAP is a crucial pathway for development, tissue homeostasis, wound healing, tissue regeneration, and cancer. In this review, we discuss the multiple effects of the YAP/Hippo pathway in the immune system and cancer. We analyzed a series of effects: extracellular vesicles enhanced immunity through inhibition of LATS1/2, ways of modulation of the tumor microenvironment, YAP- and TAZ-mediated upregulation of PDL1, high expression of YAP and PDL1 in EGFR-TKI-resistant cells, enhanced YAP activity in inflammation, and the effect of the Hippo pathway on T cells, B cells, Tregs, macrophages, and myeloid-derived suppressor cells (MDSCs). These pleiotropic effects render the YAP and Hippo pathway a key pathway for exploitation in the future, in order to enhance our immunotherapy treatment strategies in oncology.

This study compared the risks for developing second primary cancers and cardiotoxicity following radiotherapy for thymoma. Three different 3D-CRT, IMRT, and VMAT plans were generated with 6 MV photons for 12 females with thymoma. Dose-volume histogram data were employed to estimate the second cancer risks using a mechanistic non-linear model. The radiation doses to the heart and cardiac substructures were combined with linear models to assess the probability of cardiotoxicity. The mean lifetime risk for lung, esophageal, thyroid, left breast, and right breast cancer induction was 4.34–4.49%, 0.30–0.31%, 0.05–0.07%, 2.06–2.30%, and 2.04–2.34%, respectively, depending upon the radiotherapy technique. The relative risk for major cardiac events, including myocardial infarction, coronary revascularization, and death, was 1.43–1.55, whereas that for chronic heart failure was 1.20–1.29. The IMRT and VMAT significantly reduced the risk for cardiotoxicity with respect to 3D-CRT (p ≤ 0.023). Small but significant reductions were observed for most organ-specific cancer risks with IMRT compared to conformal treatment (p ≤ 0.008). Similar decreases were detected only for esophageal and thyroid cancer with VMAT (p ≤ 0.033). No difference was found in the probability for radiation-induced lung cancer with the three techniques (p ≥ 0.06). Healthcare professionals may use these data to select the appropriate radiotherapy technique and restrict the risk of late effects.

Background During these last years, new agents have dramatically improved the survival of the metastatic patients. Oligometastases represent a continuous field of interest in which the integration of metastases-directed therapy and drugs could further improve the oncologic outcomes. Herein a narrative review is performed regarding the main rationale in combining immunotherapy and target therapies with SBRT looking at the available clinical data in case of oligometastatic NSCLC, Melanoma and Kidney cancer. Material and method Narrative Review regarding retrospective and prospective studies published between January 2009 to November 2019 with at least 20 patients analyzed. Results Concerning the combination between SBRT and Immunotherapy, the correct sequence of remains uncertain, and seems to be drug-dependent. The optimal patients’ selection is crucial to expect substantial benefits to SBRT/Immunotherapy combination and, among several factors. A potential field of interest is represented by the so-called oligoprogressed disease, in which SBRT could improve the long-term efficacy of the existing target therapy. Conclusions A low tumor burden seems to be the most relevant, thus making the oligometastatic disease represent the ideal setting for the use of combination therapies with immunological drugs.

For patients diagnosed with cancer who have previously received an organ transplant, radiotherapy represents a challenging clinical scenario without well established care algorithms. Immunosuppressive therapy can be a cause for concern among clinicians treating this category of patients. Potential immune modulation following irradiation could affect recipient organ tolerance and the outcomes of the transplantation itself. The main aim of this systematic review was to define the safety and effectiveness of radiotherapy in patients diagnosed with cancer who have previously received an organ transplant. We searched PubMed and Embase for articles published between Jan 1, 1995, and April 30, 2020 for studies in patients who had undergone radiotherapy for post-transplantation malignancies. The Review is framed by the PICO (population, intervention, control, and outcomes) criteria, and primarily focuses on modern treatment techniques.

Background There is no clear evidence on whether radiotherapy (RT) improves treatment result in patients with retroperitoneal sarcomas (RPS). Methods A systematic literature search was performed using PubMed, Scopus and CENTRAL databases. Data were retrieved from published comparatives studies in patients with RPS undergoing surgery alone or RT plus surgery. The primary endpoints were the 5-year OS and the median OS. The secondary endpoints were the recurrence-free survival (RFS) and the R0-resection rate. Continuous outcomes were calculated by means of weighted mean difference (WMD). Results Ten out of 374 articles were analyzed. The median OS and the 5-year survival were significantly increased in patients treated with RT and surgery, compared to patients treated with surgery alone (p < 0.00001, p < 0.001). Median RFS was significantly increased in patients treated with either preoperative (p < 0.001) or postoperative (p = 0.001) RT compared to patients that underwent surgery alone. Finally, median R0-resection rate was similar between the two groups (p = 0.56). Conclusion RT along with radical surgery could be the standard of care in at least a subgroup of patients with RPS.

Background Primary invasive Extramammary Paget’s vulvar disease is a rare tumor that is challenging to control. Wide surgical excision represents the standard treatment approach for Primary invasive Extramammary Paget’s vulvar disease. The goal of the current study was to analyze the appropriate indications of radiotherapy in Primary invasive Extramammary Paget's vulvar disease because they are still controversial. Discussion We searched the Cochrane Gynecological Cancer Group Trials Register, Cochrane Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE database up to September 2015. Radiotherapy was delivered as a treatment in various settings: i) Radical in 28 cases (range: 60–63 Gy), ii) Adjuvant in 25 cases (range: 39–60 Gy), iii) Salvage in recurrence of 3 patients (63 Gy) and iv) Neoadjuvant in one patient (43.3 Gy). A radiotherapy field that covered the gross tumor site with a 2–5 cm margin for the microscopic disease has been used. Radiotherapy of the inguinal, pelvic or para-aortic lymph node should be considered only for the cases with lymph node metastases within these areas. Summary Radiotherapy alone is an alternative therapeutic approach for patients with extensive inoperable disease or medical contraindications. Definitive radiotherapy can be used in elderly patients and/or with medical contraindications. Adjuvant radiotherapy may be considered in presence of risk factors associated with local recurrence as dermal invasion, lymph node metastasis, close or positive surgical margins, perineal, large tumor diameter, multifocal lesions, extensive disease, coexisting histology of adenocarcinoma or vulvar carcinoma, high Ki-67 expression, adnexal involvement and probably in overexpression of HER-2/neu. Salvage radiotherapy can be given in inoperable loco-regional recurrence and to those who refused additional surgery.

Background: Malnutrition in esophageal and pharyngeal cancer patients constitutes a common and serious concern, which significantly reduces patients’ prognoses. Cancers of the esophagus and the pharynx can considerably impair feeding in patients, resulting in severe undernutrition. This is a scoping review that intends to critically analyze the most well-designed clinical studies investigating the potential beneficial impact of diverse nutritional assessment tools on the prognosis of patients with esophageal and pharyngeal cancers. Methods: The most accurate and remarkable scientific databases were comprehensively explored utilizing relative keywords to detect clinical studies that investigate whether nutritional status may affect disease prognosis. Results: Several assessment tools have evaluated and highlighted the potential beneficial impact of nutritional status on disease progression and patients’ prognosis in both esophageal and pharyngeal cancers. Regarding esophageal cancer, CONUT, PNI, PG-SGA, and NRS-2002 are more commonly used, while albumin is also frequently evaluated. Regarding pharyngeal cancers, fewer studies are currently available. PNI has been evaluated, and its significance as a factor for shorter survival’ times has been highlighted. The Comprehensive Nutritional Index has also been evaluated with positive results, as well as NRS 2002, GPS, and body-weight status. However, there is currently a lack of studies with an adequate number of women with cancer. An international literature gap was identified concerning follow-up studies with adequate methodology. Conclusions: Nutritional status may significantly affect disease progression and patients’ survival, highlighting the significance of a great nutritional status in individuals with esophageal and pharyngeal cancers. Further large-scale and well-designed prospective surveys should be performed to verify the potential beneficial effects of adequate nourishment in people suffering from cancer of the esophagus and pharynx.

Background/Objectives: Epidermal growth factor receptor (EGFR) plays a vital role in cell proliferation and survival, with its overexpression linked to various malignancies, including non-small cell lung cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (TKIs) are a key therapeutic strategy, acquired resistance and relapse remain challenges. This study aimed to synthesize and evaluate novel rhenium-based complexes incorporating EGFR TKIs to enhance anticancer efficacy, particularly in radiosensitization. Methods: We synthesized a rhenium tricarbonyl complex (Complex 2) and its 99mTc analog (Complex 2’) by incorporating triphenylphosphine instead of bromine as the monodentate ligand and PF6− as the counter-ion, resulting in a positively charged compound that forms cationic structures. Cytotoxicity and EGFR inhibition were evaluated in A431 cells overexpressing EGFR using MTT assays, Western blotting, and flow cytometry. Radiosensitization was tested through MTT and clonogenic assays. The 99mTc complex’s radiochemical yield, stability, and lipophilicity were also assessed. Results: Complex 2 exhibited significant cytotoxicity with an IC50 of 2.6 μM and EGFR phosphorylation inhibition with an IC50 of 130.6 nM. Both complex 1 and 2 induced G0/G1 cell cycle arrest, with Complex 2 causing apoptosis. Radiosensitization was observed at doses above 2 Gy. Complex 2’ demonstrated high stability and favorable lipophilicity (LogD7.4 3.2), showing 12% cellular uptake after 30 min. Conclusions: Complexes 2 and 2’ show promise as dual-function anticancer agents, offering EGFR inhibition, apoptosis induction, and radiosensitization. Their potential as radiopharmaceuticals warrants further in-depth investigation in preclinical models.