Home-based lifestyle intervention for breast cancer survivors: A surprising improvement in the quality of life during the first year of COVID-19 pandemic.

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: NCT04818359). 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.

A home-based lifestyle intervention program reduces the tumorigenic potential of triple-negative breast cancer cells.

Translational research for the evaluation of physical activity habits and lifestyle modifications based on nutrition and exercise has recently gained attention. In this study, we evaluated the effects of serum samples obtained before and after a 12-week home-based lifestyle intervention based on nutrition and exercise in breast cancer survivors in terms of modulation of the tumorigenic potential of breast cancer cells. The home-based lifestyle intervention proposed in this work consisted of educational counselling on exercise and nutritional behaviors and in 12 weeks of structured home-based exercise. Triple-negative breast cancer cell line MDA-MB-231 was cultured in semi-solid medium (3D culture) with sera collected before (PRE) and after (POST) the lifestyle intervention program. Spheroid formation was evaluated by counting cell colonies after 3 weeks of incubation. Results show a slight but significant reduction of spheroid formation induced by serum collected POST in comparison to those obtained PRE. Moreover, statistical analyses aimed to find physiologic and metabolic parameters associated with 3D cell proliferation revealed the proliferative inducer IGF-1 as the only predictor of cell tumorigenic potential. These results highlight the importance of lifestyle changes for cancer progression control in a tertiary prevention context. Translational research could offer a useful tool to identify metabolic and physiological changes induced by exercise and nutritional behaviors associated with cancer progression and recurrence risk.

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research.

INTRODUCTION: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). METHODS AND OBJECTIVES: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. CONCLUSION: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project.

Effect of a lifestyle intervention program's on breast cancer survivors' cardiometabolic health: Two-year follow-up.

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.

KRAS4A and KRAS4B in liquid biopsy of metastatic lung adenocarcinoma patients treated with Pembrolizumab or chemotherapy plus Pembrolizumab.

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.

Changes in gut microbiota composition after 12 weeks of a home-based lifestyle intervention in breast cancer survivors during the COVID-19 lockdown.

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.

The DianaWeb cohort during the first COVID-19 lockdown: changes in eating behaviour in women with breast cancer.

BACKGROUND AND AIM OF THE WORK: Home confinement during the first wave of COVID-19 subverted people's routines and generated a lot of stress among individuals. In addition to the 'pure' mental health consequences-a major public health concern, itself-this stressful situation led to a risk of worsening eating behaviours. The aim of this study was to investigate the potential deterioration of dietary habits in a cohort of women with breast cancer (BC). METHODS: We used data from 781 women with BC enrolled in the DianaWeb project. We used validated questionnaires to collect data concerning socio-demographic/anthropometric parameters, quality of life (QoL), lifestyle and the change in dietary habits before and during the lockdown period (December 2019 and June 2020). RESULTS: Data showed that psychiatric treatment, QoL and health perception significantly affected the food choices of the cohort (p = 0.048, p=0.002, and p=0.001, respectively), decisively contributing to a worsening in their eating behaviour. Moreover, sedentary behaviour during the lockdown also influenced food choice (p = 0.010): individuals who increased their sedentary behaviour were more likely to decrease their intake of recommended foods (p = 0.033). CONCLUSIONS: In summary, emotional state and mood-here investigated as QoL and health perception-definitely affected dietary habits in women with BC in the first COVID-19 lockdown. Given the centrality of correct eating behaviour in BC management, psychological aspects should not be contemplated merely as confined mental health matters but should be definitely taken into consideration also as factors that seriously affect an individual's healthy lifestyle.

Movement and health beyond care, MoviS: study protocol for a randomized clinical trial on nutrition and exercise educational programs for breast cancer survivors.

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.

Effects of a Home-Based Lifestyle Intervention Program on Cardiometabolic Health in Breast Cancer Survivors during the COVID-19 Lockdown.

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.

Special Attention to Physical Activity in Breast Cancer Patients during the First Wave of COVID-19 Pandemic in Italy: The DianaWeb Cohort.

Recent evidence highlights that physical activity (PA) is associated with decreased recurrence risk, improved survival and quality of life for breast cancer (BC) patients. Our study aimed to explore patterns of increased/decreased PA, and sedentary behaviors among BC women of the DianaWeb cohort during the first wave of COVID-19 pandemic, and examined the association with residential locations, work changes, different modality used to increase PA, and quality of life. The study analyzed the questionnaires completed by the 781 BC women (age 54.68 ± 8.75 years on both December 2019 and June 2020. Results showed a decrease of 22%, 57%, and 26% for walking activity, vigorous activity, and total PA, respectively. Sitting/lying time increased up to 54.2% of the subjects recruited. High quality of life was associated with lower odds of being sedentary (p = 0.003). Our findings suggest that innovative health management fostering compliance with current guidelines for PA and active behavior should be implemented, especially in unpredictable emergency conditions.

Cancer Related Anemia: An Integrated Multitarget Approach and Lifestyle Interventions.

Cancer is often accompanied by worsening of the patient's iron profile, and the resulting anemia could be a factor that negatively impacts antineoplastic treatment efficacy and patient survival. The first line of therapy is usually based on oral or intravenous iron supplementation; however, many patients remain anemic and do not respond. The key might lie in the pathogenesis of the anemia itself. Cancer-related anemia (CRA) is characterized by a decreased circulating serum iron concentration and transferrin saturation despite ample iron stores, pointing to a more complex problem related to iron homeostatic regulation and additional factors such as chronic inflammatory status. This review explores our current understanding of iron homeostasis in cancer, shedding light on the modulatory role of hepcidin in intestinal iron absorption, iron recycling, mobilization from liver deposits, and inducible regulators by infections and inflammation. The underlying relationship between CRA and systemic low-grade inflammation will be discussed, and an integrated multitarget approach based on nutrition and exercise to improve iron utilization by reducing low-grade inflammation, modulating the immune response, and supporting antioxidant mechanisms will also be proposed. Indeed, a Mediterranean-based diet, nutritional supplements and exercise are suggested as potential individualized strategies and as a complementary approach to conventional CRA therapy.

The role of autologous stem cell transplantation in the treatment of diffuse large B-cell lymphoma.

Diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) accounting for approximately 30% of new lymphoma diagnoses in adult patients. Complete remissions (CRs) can be achieved in 45% to 55% of patients and cure in approximately 30-35% with anthracycline-containing combination chemotherapy. The ageadjusted IPI (aaIPI) has been widely employed, particularly to "tailor" more intensive therapy such as high-dose therapy (HDT) with autologous hemopoietic stem cell rescue (ASCT). IPI, however, has failed to reliably predict response to specific therapies. A subgroup of young patients with poor prognosis exists. To clarify the role of HDT/ASCT combined with rituximab in the front line therapy a longer follow-up and randomized studies are needed. The benefit of HDT/ASCT for refractory or relapsed DLBCL is restricted to patients with immunochemosensitive disease. Currently, clinical and biological research is focused to improve the curability of this setting of patients, mainly young.

A case of nodular sclerosis Hodgkin's lymphoma repeatedly relapsing in the context of composite plasma cell-hyaline vascular Castleman's disease: successful response to rituximab and radiotherapy.

We report the case of an Epstein-Barr virus (EBV)- and human immunodeficiency virus-serum negative patient suffering from repeatedly relapsing classical Hodgkin's Lymphoma (cHL) associated with a histological picture of plasma cell-hyaline vascular (PC-HV) form of Castleman's disease (CD). The CD30- and CD15-positive, Reed-Sternberg/Hodgkin cells, only occasionally expressed the CD20 molecule, but not leukocyte common antigen and latent membrane protein-1. Single-strand polymerase chain reaction failed to detect human herpesvirus 8 or EBV in the involved tissues. At the time of second relapse in July 2005, the clinical picture was characterized by a palpable right hypogastric mass, disclosed at physical exam, in the absence of other enlarged peripheral lymph nodes, subjective symptoms or laboratory profile alterations. Combined hybrid-(18)F-fluorodeoxyglucose positron emission-computerized tomography (18F-FDG PET/CT) showed increased radionuclide uptake in multiple external iliac lymph nodes [standardized uptake value (SUV) of 7.4] and non-palpable left supraclavicular lymph nodes (SUV of 5.8). Relapsing cHL in the context of mixed PC-HV CD was documented in two of three surgically excised abdominal lymph nodes never previously enlarged or involved by any lymphoproliferative disease. Because of the limited disease extension and failure to induce continuous remission with previous conventional chemoradiotherapy, the patient was treated with six rituximab injections. This immunotherapy induced significant reduction in size of supraclavicular lymph nodes as evident at ultrasound (US) scan (<1 vs. 2.5 cm, post- vs. pretherapy), which was confirmed by the 18F-FDG PET/CT in October 2005, despite no modification in SUV of 4.2. 18F-FDG PET/CT also disclosed no radionuclide uptake by abdominal lymph nodes. Thus, a second course of four additional rituximab injections was given and subsequent 18F-FDG PET/CT indicated persistent, but reduced incorporation of radionuclide compared to the pretherapy value (SUV of 2.7) in the supraclavicular area and confirmed a normal metabolic activity in the iliac external lymph nodes. Because of uncertain persistent disease in the supraclavicular nodal site, involved-field radiotherapy (RT) was delivered in that area as consolidation treatment. After completion of rituximab and RT for 16 and 14 months respectively, US and 18F-FDG PET/CT exams were indicative of complete remission. This case is in concordance with previously published data suggesting that rituximab immunotherapy might be a valid option in the treatment of CD and also have a role in the management of relapsing cHL.