INTRODUCTION:Pembrolizumab, a monoclonal antibody targeting programmed death-1 (PD-1), improves outcomes in metastatic lung adenocarcinoma (MLA) expressing programmed death ligand-1 (PD-L1). Single nucleotide polymorphisms (SNPs) in the PDCD1 gene may impair PD-1 signaling and reduce the efficacy of pembrolizumab. We evaluated the impact of rs11568821 C>T, rs10204525 C>T, rs7421861 A>G, rs2227981 G>A, and rs41386349 G>A on progression-free survival (PFS) in non-oncogene-addicted MLA patients treated with pembrolizumab-based regimens. MATERIALS AND METHODS:Patients were prospectively enrolled: those expressing PD-L1 ⩾50% received pembrolizumab monotherapy, whereas those expressing PD-L1 <50% received pembrolizumab plus platinum-pemetrexed chemotherapy. Associations between SNPs and PFS (primary endpoint) were assessed using univariate and multivariable Cox models. Secondary endpoints included response rate and overall survival (OS). RESULTS:Among 141 evaluable patients, 71 received pembrolizumab and 70 received combination therapy. Median PFS was 20 months (95% confidence interval [CI], 13-27) overall, 25 months (95% CI, 16-34) with pembrolizumab, and 13 months (95% CI, 8-23) with combination therapy. Rs7421861 was significantly associated with PFS: 23 months (95% CI, 13-40) in A/A, 20 months (95% CI, 12-29) in A/G, and 6 months (95% CI, 3-11) in G/G patients. In multivariable analysis, G/G genotype showed the strongest effect (HR 2.85; 95% CI, 1.53-5.29; p = 0.001). Most G/G carriers (12/13) had stable or progressive disease, and OS was also inferior. DISCUSSION:The rs7421861G-allele is associated with poorer outcomes in pembrolizumab-treated MLA patients and warrants further validation.

Obesity-related biomarkers such as insulin-like growth factor-1 (IGF-1) may help identify high-risk breast cancer survivors (BCS) who could benefit from lifestyle interventions (LIs). However, the effect of LIs on modulation of IGF-1 levels in BCS remains inconclusive. Fifty inactive BCS were randomized into a control group (CG, n = 26) and an intervention group (IG, n = 24). Both groups received recommendations on exercise and the Mediterranean diet; the IG additionally followed a supervised 3-month aerobic exercise program (MoviS trial, NCT04818359). Associations between baseline and LI-induced changes (∆) in IGF-1, IGF binding protein-1 (IGFBP1) and IGFBP3 levels, along with anthropometric, metabolic, and fitness parameters, were assessed using linear and quadratic models. Both groups increased physical activity (MET min/week) and Mediterranean diet adherence (MeDiet score) after the LI, while maximal oxygen uptake (V̇O2max) increased only in the IG. Reductions in BMI, fat mass, insulin levels, HOMA-IR index, total and LDL cholesterol were observed in both groups and were associated with increased IGFBP1 and decreased IGFBP3 levels. Mean IGF-1 levels remained unchanged in both groups. Baseline IGFBP1 was inversely correlated with IGF-1, LDL, BMI, fat mass, and insulin, while baseline IGFBP3 was positively correlated with IGF-1, insulin, and HOMA-IR. Baseline IGF-1 levels were negatively correlated with ∆ IGF-1: participants with IGF-1 ≤ 94.7 ng/mL showed increases, whereas those with IGF-1 ≥ 173.3 ng/mL exhibited decreases post-intervention. Similar trends were found for IGFBP3 but not for IGFBP1. A three-dimensional quadratic model revealed a U-shaped relationship between baseline IGF-1, ∆ IGF-1, and ∆ V̇O2max: improvements in V̇O2max were associated with IGF-1 increase in participants with low baseline IGF-1 and decrease in those with high levels. Conversely, an inverted U-shaped relationship was found between baseline IGF-1, ∆ IGF-1, and ∆ fat mass. These findings underscore the importance of accounting for IGFBP modulation and baseline heterogeneity in IGF-1 levels when evaluating the efficacy of LIs targeting the IGF-1 system in high-risk BCS. Trial registration ClinicalTrials.gov NCT04818359. Registration Date 26 March 2021.

Introduction The COVID-19 pandemic induced an extraordinary impact on public mental health to a degree not completely understood, especially in vulnerable populations such as breast cancer (BC) survivors. In this study, we described the short- (after 3-month) and long- (after 12-month) term effects of a multidisciplinary home-based lifestyle intervention in Italian women BC survivors during the first year of COVID-19 pandemic. Materials and methods In total, 30 Italian BC survivors with risk factors for recurrence took part in the ongoing MoviS trial (protocol: NCT 04818359). Between January 2020 and January 2021, a 3-month lifestyle intervention based on psychological counseling, nutrition, and exercise was carried out. Participants were asked to fill out psychological questionnaires for the assessment of quality of life (QoL) indicators (European Organization for Research and Treatment of Cancer QoL, EORTC-QLQ-C30) and psychological health measures such as fatigue (Brief Fatigue Inventory, BFI), distress (Distress Thermometer, DT and Psychological Distress Inventory, PDI), cancer-related fatigue (Verbal Rating Scale, VRS), and mood states (Profile of Mood States Questionnaire, POMS). IBM SPSS Statistical Software version 27.0 and R Project for Statistical Computing version 4.2.1 were used to process data. All participants were assessed at four time points: T0 (baseline), T1 (3-month), and follow-up at T2 and T3 (6- and 12-month, respectively) to measure primary (quality of life indicators) and secondary (psychological health) outcomes. Friedman non parametric test and Wilcoxon signed rank test (with Bonferroni correction) were conducted to investigate the statistically significant differences in psychometric scores and between assessment times. Results Compared to baseline (T0), at T1 most of the QoL indicators (i.e., symptoms of fatigue and general health) were improved ( p < 0.017) with the exception of a worsening in participants’ social functioning ability. Also, perception of severity of fatigue, distress, cancer-related fatigue, depression, and anger enhanced. Compared to baseline (T0), at T3 we mainly observed a stable condition with T0-T1 pairwise comparison, however other secondary outcomes (i.e., fatigue mood state, confusion, and anxiety) significantly improved. Discussion Our preliminary findings support the proposal of this lifestyle intervention for BC survivors. Despite the home-confinement due to the COVID-19 pandemic, the intervention surprisingly improved QoL indicators and psychological health of the participants.

Background Clinical and experimental studies indicate that the tumor protein p53 (TP53) gene loss of function due to missense mutations (MMs) may confer sensitivity to anti-angiogenics. This effect seems to be linked to cross-talk mechanisms among TP53, vascular endothelial growth factor (VEGF), and VEGF receptors. We investigated whether specific TP53 MMs are associated with clinical outcomes of patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy plus Bevacizumab. The study focused on KRAS-mutated, liver-only mCRC cases as a homogeneous subgroup that may represent a relevant setting for exploring this association.Materials and methods MMs were identified on primary tumors. MMs were classified by mutant-specific residual transcriptional activity scores (TP53RTAS) as transcriptionally inactive (TP53inactive = TP53RTAS 0%) or active (TP53active = TP53RTAS >= 1%) and used for stratifying patients in progression-free survival (PFS), response rate, and overall survival (OS) analyses.Results The study population consisted of 62 patients. MMs were found in 39 cases (62%) with 16 having TP53inactive and 23 TP53active MMs. Patients with TP53inactive MMs showed better PFS in comparison with the remaining groups (wild-type and TP53active). This effect was retained in the multivariate model. A similar clinical impact was observed in the OS analysis. There was a significant difference in the overall response rate and rate of post-treatment resection of liver metastases between the TP53inactive and the wild-type or TP53active MMs cases.Conclusions Specific TP53 MMs may identify sub-groups of patients who benefit from Bevacizumab-based systemic therapy and these findings could lead to novel tailored treatment strategies in this setting. This study investigated the possible clinical impact of TP53 missense mutations in patients with KRAS-mutated metastatic colorectal cancer undergoing first-line chemotherapy plus bevacizumab.

KRAS is involved in the stability and expression of PD-L1. We investigated the expression of circulating mRNA (cmRNA) of KRAS4A and KRAS4B and the possible impact on progression-free survival (PFS) of patients with metastatic lung adenocarcinoma treated with immunotherapy. Patients without driver mutations undergoing Pembrolizumab (P) or P plus chemotherapy (PC) were prospectively accrued for liquid biopsy analysis of KRAS4A, KRAS4B, and PD-L1 cmRNA. Both KRAS isoforms were also studied for association with PD-L1 cmRNA. Of 56 patients, 28 received P and 28 PC. Patients with high levels of both KRAS isoforms showed significantly better PFS. The median PFS for KRAS4A was 29 months (95% CI 22–29 months) and KRAS4B 24 months (95% CI 13–29 months), respectively. The median PFS of patients with low levels of both isoforms was 12 months (95% CI 6–15 months for KRAS4A and 95% CI 5–20 months for KRAS4B). High KRAS4A retained a significant positive association with PFS in the multivariate model. An exploratory analysis in treatment subgroups found a positive association between high KRAS4A and KRAS4B with PFS in patients treated with P. PD-L1 cmRNA was significantly higher in patients with high KRAS isoforms levels and this effect was pronounced for high KRAS4A carriers. KRAS4A deserves further investigation as a potential marker for defining patients who may benefit the most from immune checkpoint inhibitors therapy and improving personalized cancer immunotherapeutic strategies.

Background:Breast cancer (BC) is the second-leading cause of cancer-related death worldwide. This study aimed to investigate the effects of a 12-week home-based lifestyle intervention (based on nutrition and exercise) on gut microbial composition in twenty BC survivors of the MoviS clinical trial (protocol: NCT04818359).Methods:Gut microbiota analysis through 16S rRNA gene sequencing, anthropometrics, Mediterranean Diet (MD) adherence, and cardiometabolic parameters were evaluated before (Pre) and after (Post) the lifestyle intervention (LI).Results:Beneficial effects of the LI were observed on MD adherence, and cardiometabolic parameters (pre vs post). A robust reduction of Proteobacteria was observed after LI, which is able to reshape the gut microbiota by modulating microorganisms capable of decreasing inflammation and others involved in improving the lipid and glycemic assets of the host. A significant negative correlation between fasting glucose and Clostridia_vadinBB60 (r = -0.62), insulin and homeostatic model assessment (HOMA) index and Butyricicoccus genera (r = -0.72 and -0.66, respectively), and HDL cholesterol and Escherichia/Shigella (r = -0.59) have been reported. Moreover, positive correlations were found between MD adherence and Lachnospiraceae_ND3007 (r = 0.50), Faecalibacterium (r = 0.38) and Butyricimonas (r = 0.39).Conclusion:These data suggest that adopting a healthy lifestyle, may contribute to ameliorate several biological parameters that could be involved in the prevention of cancer relapses through the modulation of gut microbiota.

Pre-clinical studies indicate that the KRAS pathway enhances the stability and expression of PD-L1. We investigated the expression of the circulating mRNA (cmRNA) levels of KRAS4A and KRAS4B isoforms and their possible impact on progression-free survival (PFS) of patients with metastatic lung adenocarcinoma treated with Pembrolizumab (P) by liquid biopsy. Patients with metastatic lung adenocarcinoma without driver mutations undergoing P or P plus chemotherapy (PC) were prospectively accrued to analyze KRAS4A, KRAS4B and PD-L1 cmRNA levels by liquid biopsy. Receiver operating characteristic curves (ROC) calculated the Youden index to define the optimum cut-off values for binary classification of patients and PFS analysis. Both the KRAS isoforms were also studied for association with the PD-L1 cmRNA levels. RT-PCR is the method used for expression analysis. In 56 fully assessable patients, 28 received P and 28 patients PC. Patients with high (H) KRAS4A cmRNA and HKRAS4B cmRNA levels showed significantly better PFS than patients classified with low (L). The median PFS of patients with H KRAS4A cmRNA and H KRAS4B cmRNA levels was 29 months (95% CI 22-29 months) and 24 months (95% CI 13-29 months), respectively. The median PFS of patients with L KRAS4A cmRNA and L KRAS4B cmRNA expression was 12 months (95% CI 6-15 months) and 12 months (95% CI 5-20 months), respectively. H KRAS4A cmRNA retained a significant positive association with PFS in the multivariate model. The mean expression values of PD-L1 cmRNA levels were significantly higher in patients with H KRAS4A cmRNA and H KRAS4B cmRNA levels. Moreover, an exploratory analysis in treatment subgroups found a positive association between H KRAS4A cmRNA and H KRAS4B cmRNA levels with PFS in patients treated with P. Our results suggest the KRAS4A isoform deserves further investigation as a potential marker for defining patients who may benefit the most from immune checkpoint inhibitors therapy. Progresses in this field are desirable to improve personalized cancer immunotherapeutic strategies.

Background: FLOT perioperative chemotherapy represents the standard of care in non-metastatic gastric cancer patients. Signet-ring cell positivity is associated with a worse prognosis in patients with gastric cancer treated with chemotherapy. Comparison between FLOT perioperative chemotherapy vs. surgery followed by adjuvant chemotherapy based on signet-ring cell positivity is lacking. The aim of the analysis was to compare perioperative FLOT with adjuvant chemotherapy in gastric cancer patients stratified by signet-ring cell positivity. Methods: We conducted a retrospective multicenter analysis based on disease-free survival (DFS) and overall survival (OS) in patients with gastric cancer who received perioperative chemotherapy with a FLOT regimen and compared their survival with a historical cohort of patients treated with adjuvant chemotherapy, matched by cT and cN stage and by tumor histological features. Results: Seventy-six patients were enrolled and 24 (32%) were signet-ring cell positive. At a median follow-up time of 39 months, the median DFS was 26.3 months and the median OS was 37.3 months. Signet-ring cell positivity was associated with a shorter OS (median OS: 20.4 vs. 46.9 months, HR: 3.30, 95%CI: 1.56–6.99, p = 0.0018) and DFS (mDFS: 15.2 vs. 38.6 months, HR: 3.18, 95%CI: 1.55–6.54, p = 0.0016). This was confirmed by multivariate analysis for DFS (Exp(B): 2.55) and OS (Exp(B): 2.68). After propensity score matching, statistically significant shorter DFS (HR: 3.30, 95%CI: 1.50–7.35, p = 0.003) and OS (HR: 5.25, 95%CI: 2.18–12–68, p = 0.0002) were observed for patients with signet-ring cell positivity who received perioperative treatment vs. those who received surgery followed by adjuvant chemotherapy. Conclusions: Signet-ring positivity was associated with shorter DFS and OS in patients who received perioperative treatment with FLOT compared with surgery followed by adjuvant therapy. These data suggest that for patients with signet-ring cell histology, FLOT perioperative treatment might not always be the best choice of treatment, and further research should be focused on this group of patients.

The purpose of this study is to assess the cardiometabolic responses of a lifestyle intervention (LI) conducted at home among breast cancer (BC) survivors during the two years of COVID-19 pandemic. A 3-month LI focused on diet and exercise was performed on thirty BC survivors (women; stages 0-II; non-metastatic; aged 53.5–7.6 years; non-physically active) with a risk factor related to metabolic/endocrine diseases. Anthropometrics, cardiorespiratory fitness (V̇O2max), physical activity level (PAL), adherence to the Mediterranean diet, and several biomarkers (i.e., glycemia, insulin, insulin resistance [HOMA-IR] index, triglycerides, high- [HDL] and low- [LDL] density lipoproteins, total cholesterol, progesterone, testosterone, and hs-troponin) were evaluated before and 3 months, 6 months, 12 months, and 24 months after the LI. Beneficial effects of the LI were observed on several variables (i.e., body mass index, waist circumference, Mediterranean diet adherence, PAL, V̇O2max, glycemia, insulin, HOMA-IR index, LDL, total cholesterol, triglycerides, testosterone) after 3 months. The significant effect on Mediterranean diet adherence and V̇O2max persisted up to the 24-month follow-up. Decreases in HOMA-IR index and triglycerides were observed up to 12 months, however did not persist afterward. This study provides evidence on the positive association between LI and cardiometabolic health in BCSs during the pandemic period.

The purpose of this study is to assess the cardiometabolic responses of a lifestyle intervention (LI) conducted at home among breast cancer (BC) survivors during the two years of COVID-19 pandemic. A 3-month LI focused on diet and exercise was performed on thirty BC survivors (women; stages 0-II; non-metastatic; aged 53.6 ± 7.6 years; non-physically active) with a risk factor related to metabolic/endocrine diseases. Anthropometrics, cardiorespiratory fitness (V˙ O2max), physical activity level (PAL), adherence to the Mediterranean diet (MeDiet modified questionnaire), and several biomarkers (i.e., glycemia, insulin, insulin resistance [HOMA-IR] index, triglycerides, high- [HDL] and low- [LDL] density lipoproteins, total cholesterol, progesterone, testosterone, and hs-troponin) were evaluated before and 3-, 6-, 12-, and 24-month after the LI. Beneficial effects of the LI were observed on several variables (i.e., body mass index, waist circumference, MeDiet, PAL, V˙ O2max, glycemia, insulin, HOMA-IR index, LDL, total cholesterol, triglycerides, testosterone) after 3-month. The significant effect on Mediterranean diet adherence and V˙ O2max persisted up to the 24-month follow-up. Decreases in HOMA-IR index and triglycerides were observed up to 12-month, however did not persist afterward. This study provides evidence on the positive association between LI and cardiometabolic health in BC survivors.

Abstract Background Breast cancer (BC) is the most common invasive cancer in women, and exercise can significantly improve the outcomes of BC survivors. MoviS (Movement and Health Beyond Care) is a randomized controlled trial aimed to evaluate the potential health benefits of exercise and proper nutritional habits. This study aims to assess the efficacy of aerobic exercise training in improving quality of life (QoL) and health-related factors in high-risk BC. Methods One hundred seventy-two BC survivor women, aged 30–70 years, non-metastatic, stage 0–III, non-physically active, 6–12 months post-surgery, and post chemo- or radiotherapy, will be recruited in this study. Women will be randomly allocated to the intervention arm (lifestyle recommendations and MoviS Training) or control arm (lifestyle recommendations). The MoviS training consists of 12 weeks of aerobic exercise training (2 days/week of supervised and 1 day/week of unsupervised exercise) with a progressive increase in exercise intensity (40–70% of heart rate reserve) and duration (20–60 min). Both arms will receive counseling on healthy lifestyle habits (nutrition and exercise) based on the World Cancer Research Fund International (WCRF) 2018 guidelines. The primary outcome is the improvement of the QoL. The secondary outcomes are improvement of health-related parameters such as Mediterranean diet adherence, physical activity level, flexibility, muscular fitness, fatigue, cardiorespiratory fitness (estimated maximal oxygen uptake), echocardiographic parameters, heart rate variability (average of the standard deviations of all 5 min normal to normal intervals (ASDNN/5 min) and 24 h very low and low frequency), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein). Discussion This trial aims to evaluate if supervised exercise may improve QoL and health-related factors of BC survivors with a high risk of recurrence. Findings from this project could provide knowledge improvement in the field of exercise oncology through the participation of a multidisciplinary team that will provide a coordinated program of cancer care to improve healthcare quality, improve prognosis, increase survival times and QoL, and reduce the risk of BC recurrence. Trial registration ClinicalTrials.gov NCT04818359 . Retrospectively registered on March 26, 2021

Rationale: A better overall diet may improve survival after breast cancer (BC) diagnosis. Association between better post-diagnosis diet quality and lower levels of chronic inflammation has been shown. Thus, anti-inflammatory dietary patterns, as the Mediterranean diet (MD), may play an essential role in modifying inflammation and reducing risk of comorbidities and recurrence in BC survivors (BCS). Methods: Food intake and indices of glycemic variability of 15 BCS women without diabetes were analyzed using food diary and continuous glucose monitoring devices. Dietary habits were assessed in relation to principles of the MD and Healthy Eating Plate, through a qualitative analysis of food diaries. Results: Patients' eating habits do not align with the MD principles. Grain consumption is inadequate, and only 23% of those with adequate consumption choose whole grains. Fruit and vegetable intake is insufficient, as none of the participants consume the recommended five servings per day. While 66% of fruit portions respect seasonality, the percentage rises to 85% for vegetables. Milk, dairy products, and nuts are inadequately consumed by all. Fish and white meat consumption is generally sufficient, but processed meats, snacks, and sweets are overconsumed. Only 47% of the population adequately consumes legumes, with an average weekly intake of 1.5 servings. In addition, subjects consuming a nutritionally balanced meal in accordance with the Healthy Eating Plate exhibit a significantly attenuated postprandial glycemic response within the subsequent two hours compared to those consuming an unbalanced meal. Conclusion: Findings underscore the fundamental role of diet and the need to raise awareness among BCS regarding the importance of adopting a proper dietary regimen and implementing effective meal management strategies, enhancing their overall health outcomes and quality of life. Disclosure of Interest: None declared

The main hypothesis on the positive effects of exercise in oncological patients has been focusing on lowering the basal systemic levels of cancer risk factors such as insulin-like growth factor-1 (IGF-1) and its binding proteins (IGFBP). However, there is a paucity of data and a remarkable heterogeneity when considering the response of the IGF-1 system to exercise in breast cancer survivors (BCS). In this study we tested the hypothesis that aerobic exercise training might normalize the IGF-1 system in BCS patients with normal to high level of IGF-1. Non physically active BCS women (n=30, age 52.7 ± 7.6 years), enrolled in the MoviS ‘Movement and Health Beyond Care’ study (clinicaltrial.gov identifier: NCT04818359), at high metabolic and hormonal risk of BC recurrences performed 3-month aerobic training (2 d/week of supervised and 1 d/week of unsupervised exercise) with increase of exercise intensity (40-70% HRR) and duration (20-60 min). Circulating IGF-1 and IGFBP3 levels were measured before and after the intervention. VO2max increased by 10.1 % (mL·min-1·kg−1: before=30.7±5.7, after=33.4±6.8; p<0.001) while body mass index (kg/m2: before=26.0±5.0, after=25.5±4.7; p=0.035), glycemia (mg/dL: before=100.8±11.4, after=91.7±11.0; p<0.001) and insulin resistance (HOMA-IR score: before =2.07±1.54, after =1.53±1.11; p=0.005) decreased after training. Mean IGF-1 level did not change after training (ng/mL: before=164.3±70.9, after=166.8±57.6) while IGFBP3 level decreased (μg/mL: before=6.1±1.4, after=4.2±1.5). There was a negative correlation between pre-training IGF-1 levels and individual changes in IGF-1 after training (r=- 0.62, p<0.001). Accordingly, the IGF-1 coefficient of variation (CV) decreased after training (%: before=43.2, after=34.5). Finally, the correlation between IGF-1 and IGFBP3 levels was reduced after training (r: before=0.74, after 0.45, p<0.001). The exercise intervention modulates the IGF-1 system lowering the circulating IGF-1 variability, the IGFBP3 level and the relationship between IGF-1 and IGFBP3 among BCS patients.

Background: MoviS: 'Movement and health beyond care' is an ongoing randomized controlled trial aiming to educate breast cancer (BC) survivors on the benefits of exercise and proper nutrition habits. Methods: The study included thirty women (17.4% of the total planned cohort of 172 patients) with stage 0-III non-metastatic BC (age: 53.5±7.6 yrs;BMI: 25.3±4.9 kg/ m2) randomly allocated to the Intervention Arm (IA;supervised exercise training: “MoviS Training”) or control arm. The MoviS Training consists of 12 weeks of aerobic exercise (2 d/week of supervised and 1 d/week of unsupervised exercise) which intensity and duration gradually increased from 40 to 70% of heart rate reserve and from 20 to 60min, respectively. Both arms received nutritional and lifestyle counselling based on WCRF 2018 guidelines through the DIANA-Web platform and motivational interviewing. As the planned protocol was changed due to nationwide lockdown to contain the spread of COVID-19, IA performed home-based exercise sessions, which were remotely supervised using heart rate monitors. Heart rate variability (HRV;by 24-Holter monitoring), cardiac function indexes (by echocardiography with speckle tracking imaging), and cardiorespiratory fitness (by estimated maximal oxygen uptake [VO2max]) were evaluated at baseline and after the intervention period. Results: There were no adverse events during training. Baseline evaluation revealed no systolic disfunction (mean LVEF 60.4±4.5%) and a mild reduction (values 3 -18%) in global longitudinal strain in 26% of patients. HRV improved in both time and frequency domains: ASDNN/5min (50.6±14.4 to 55.2±16.7 msec, p=0.033);very low frequency (VLF) (1597±967 to 1881±963 msec, p=0.04);low frequency (LF) (613±404 to 731±542 msec, p=0.004);total power (2627±1393 to 3034±1669 msec, p=0.034). HRV parameters tended to improve to a greater extent in IA group (Coefficient of Variation: ASDNN/5min 13.7% vs 4.6%, LF 27% vs 10%, total power 26.5% vs 5.1%). Cardiorespiratory fitness level increased significantly in both groups (VO2max from 30.7±5.7 to 33.9±6.6mL/kg/min, p<0.001). Conclusion: During COVID-19 lockdown, short-term remotely supervised exercise training and recommendations on a healthy lifestyle lead to a significant improvement in HRV parameters and cardiorespiratory fitness in BC survivors.

Purpose: The confinement and lockdown imposed by the COVID-19 pandemic have produced restrictions in the lifestyle of Italian citizens with variations in their psychological well-being.The aim of the study was to identify changes and relationship with socio-demographic parameters.Methods: An online survey was administered to 1383 subjects (1007 females and 307 males) working in the University of Florence, Italy.Three validated questionnaires were used for the survey: the Global Physical Activity Questionnaire, the Med Diet Score and the Psychological General Well-Being Index-A.All the subjects were asked to complete the questionnaires twice, in order to attain a picture of the habits before and a later time point during confinement.Results: Our results show that work-related physical activity was decreased, along with an increase in sedentary behaviour (from 07:22 ± 03:20 to 08:49 ± 03:41 h:min; p \ 0.001, ES = 0.38), whereas recreational physical activity was increased (vigorous exercise varied from 568.5 ± 838.6 to 833.7 ± 1263.0 METs; p \ 0.002, ES = 0.25).Eating habits changed according to the place where meals were eaten, with an increased habit for breakfast and snacks and a slight increase in alcohol consumption.Psychological well-being decreased (Index from 21.4 ± 3.9 to 18.0 ± 5.3; p \ 0.001, ES = 0.723), especially in terms of vitality and positive thinking.The socio-demographic variables affecting these variations were mostly represented by age, gender and working conditions.Conclusions: Young age and self-employment conditions can be considered factors for the changes in daily habits induced by confinement that may affect psychological well-being.

During the lockdown period due to COVID 19, total hospital admissions drastically decreased, mainly for the fear of contagion. In the first days of lockdown, our hospital decided to separate the pathway of COVID 19 positive/suspicious patients and COVID 19 free patients, to avoid the spread of the disease. After arriving in the pre-triage camping tend, vital parameters and temperature were measured to all patients and a questionnaire was submitted to identify subjects at risk of COVID-19 contact. After the immediate pre-triage, patients were separated into suspected/ positive and negative, a rapid serological test (10minutes) and oral-pharyngeal antigen swab (20minutes) were executed, at the result of these two exams, the patients were sent on a COVID-free pathway or in dedicated area of hospitalization for COVID patients. To guarantee the best possible assistance for urgent pathologies, our hospital has equipped the COVID structure with the necessary diagnostic methods including CT and a dedicated angiograph for neuroradiology, vascular radiology and interventional cardiology, to allow the execution of coronary angiography and angioplasty in patients with STEMI and NSTEMI. A team dedicated to the COVID operating room consisting of a doctor, 2 nurses and a technician and was available 24/24 hours for any emergencies. From March 4 to today, the operating room has been used for a definitive pacemaker implant in a patient with complete AV block, 13 STEMI patients came from 'Rete IMA ', our regional emergency medical system (our hospital is the provincial HUB) or in hospital with their own means of transport or transported by 118. Of these 13 patients, 4 died during the hospital stay. Since March 2020, the pathways for cardiological patients with acute pathologies have been differentiated, minimizing the possibility of contact between the two populations and always guaranteeing hospital users the best treatment indicated for the various emergency/ urgent pathologies. The reduction in the number of ACS is around 30% (the reduction for unstable angina and NSTEMI is greater), but the complexity of cases has increased, we have seen an increase in heart attacks with complications (cardiogenic shock, ruptures) compared to the same period of the last year. Probably the late presentation (sometimes even a few days after the onset of symptoms) makes these patients particularly at risk of complications, pre and post-procedural.

This study aimed to evaluate the cardiometabolic effects of a home-based lifestyle intervention (LI) in breast cancer survivors (BCSs) during the COVID-19 lockdown. In total, 30 BCSs (women; stages 0–II; non-metastatic; aged 53.5 ± 7.6 years; non-physically active; normal left ventricular systolic function) with a risk factor for recurrence underwent a 3-month LI based on nutrition and exercise. Anthropometrics, Mediterranean diet adherence, physical activity level (PAL), cardiorespiratory fitness (VO2max), echocardiographic parameters, heart rate variability (average standard deviation of NN intervals (ASDNN/5 min) and 24 h very- (24 hVLF) and low-frequency (24 hLF)), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein (hs-CRP)) were evaluated before (T0) and after (T1) the LI. After the LI, there were improvements in: body mass index (kg/m2: T0 = 26.0 ± 5.0, T1 = 25.5 ± 4.7; p = 0.035); diet (Mediet score: T0 = 6.9 ± 2.3, T1 = 8.8 ± 2.2; p < 0.001); PAL (MET-min/week: T0 = 647 ± 547, T1 = 1043 ± 564; p < 0.001); VO2max (mL·min−1·kg−1: T0 = 30.5 ± 5.8, T1 = 33.4 ± 6.8; p < 0.001); signs of diastolic dysfunction (participants: T0 = 15, T1 = 10; p = 0.007); AS-DNN/5 min (ms: T0 = 50.6 ± 14.4, T1 = 55.3 ± 16.7; p = 0.032); 24 hLF (ms2: T0 = 589 ± 391, T1 = 732 ± 542; p = 0.014); glycemia (mg/dL: T0 = 100.8 ± 11.4, T1 = 91.7 ± 11.0; p < 0.001); insulin resistance (HOMA-IR score: T0 = 2.07 ± 1.54, T1 = 1.53 ± 1.11; p = 0.005); testosterone (ng/mL: T0 = 0.34 ± 0.27, T1 = 0.24 ± 0.20; p = 0.003); hs-CRP (mg/L: T0 = 2.18 ± 2.14, T1 = 1.75 ± 1.74; p = 0.027). The other parameters did not change. Despite the home-confinement, LI based on exercise and nutrition improved cardiometabolic health in BCSs.

e16571 Background: Current data support the angiogenic potential of cancer cells with mutant p53 and VEGF-A up-regulation in solid tumors. These findings have renewed interest in the p53 role as a predictive/prognostic factor in cancer therapy. We investigated TP53 mutations in gastric adenocarcinoma (GA) samples of metastatic patients (pts) who underwent anti-angiogenic Paclitaxel-Ramucirumab (PR) therapy. The analysis was also performed in a control group of pts who received first-line chemotherapy (CT) with platinum derivates and fluoropyrimidines. Methods: TP53 mutations were identified by next-generation sequencing in 110 GA primary tumors of two retrospective metastatic series including 48 pts who were treated with second-line PR and 62 pts who received first-line CT with Cisplatin or Oxaliplatin plus 5-Fluorouracil or Capecitabine. Detected TP53 mutations were classified for TP53 mutant-specific residual transcriptional activity scores ( TP53 RTAS) (Fischer NW et al JCI Insight 2018). TP53 RTAS results were used for stratifying pts in survival analyses. Primary end-point was overall survival (OS). Results: In the PR group, TP53 mutations were detected in 29 out of 48 tumor samples (60.4%) with 10 having TP53 RTAS 0%-to-<1%. In the CT group, TP53 mutations were found in 40 out of 62 tumor samples (64.5%) with 11 having TP53 RTAS 0%-to-<1%. In the PR group, the 10 cases with a TP53 mutation causing no residual or minimal activity ( TP53 RTAS 0%-to-<1%) showed better OS in comparison with pts in the remaining groups (wild-type and TP53 RTAS > 1%). This effect was retained in the multivariate model analysis (Hazard Ratio = 0.29, 95% confidence interval 0.17-0.85, p = 0.02). An opposite effect was seen in the CT group with the worst OS in carriers of TP53 RTAS 0%-to-<1% mutations (Hazard Ratio = 2.64, 95% confidence interval 1.17-5.95, p = 0.02). Notably, in the whole group of 110 pts, TP53 mutations (any type) occurred more frequently in the intestinal-type GA group (p = 0.02). Conclusions: Additional studies are warranted to explore the favorable role of TP53 mutations in cancer pts undergoing anti-angiogenic therapies. TP53 mutations frequently occur in GA and these findings would lead to novel tailored therapy strategies in this lethal disease.