Exploring the feasibility of a combined exercise program for patients with advanced lung or pancreatic cancer

Objective: This study aims to assess the safety, feasibility, and potential benefits of a combined aerobic and resistance exercise intervention for patients diagnosed with advanced pancreatic or lung cancer. Methods: A prospective, single-arm study was conducted, enrolling patients with advanced lung or pancreatic cancer. Participants engaged in a 12-week exercise intervention comprising personalized bi-weekly aerobic and resistance training tailored to individual baseline conditions. The primary study outcomes focused on safety (absence of serious adverse events) and feasibility. Secondary outcomes included assessments of functional capacity using the "Six minutes walking test", strength measured through handgrip and leg press tests, anthropometric measures including body mass index and waist-hip ratio, quality of life (QoL), and changes in blood parameters. Results: The study involved twelve patients (mean age 57.66 ​± ​7.40 years), with seven having pancreatic cancer and five having lung cancer. The recruitment rate was 50%, and assessment adherence was 100%, with an 84% adherence to the exercise program and no dropouts. No exercise-related adverse events were recorded, while three non-severe, non-exercise-related adverse events were observed: treatment-related dermatitis (Grade 2), axillary lymphadenopathy (Grade 2), and migraine (Grade 1). Significant enhancements in functional capacity, emotional well-being, and social functioning within the QoL domains were observed. Anthropometric measures, specifically waist-hip ratio and body mass index, remained stable. Conclusions: The findings suggest that a tailored 12-week exercise intervention is both feasible and safe for patients with advanced lung or pancreatic cancer. This intervention appears to enhance functional capacity, specific aspects of QoL, and contribute to maintaining body weight

Exercise and bone health in cancer: enemy or ally?

Simple Summary Patients with cancer may face bone metastases and osteoporosis due to cancer or treatments, leading to a high risk of developing skeletal-related events. Skeletal-related events may negatively affect patients' quality and length of life. Although physical exercise has been recognized as a potential adjunctive strategy in the cancer setting, it is often not recommended to patients with bone health impairments due to safety concerns. In the present review, we explore the effects of exercise on safety profile, bone health, and the impact on functional outcomes in patients with cancer affected by bone metastasis, osteoporosis/osteopenia, or at high risk of losing bone. Moreover, the underlying mechanisms of the beneficial effect of exercise on bone are explored, and considerations about exercise prescription are discussed. Bone health is often threatened in cancer patients. Bone metastasis and osteoporosis frequently occur in patients with cancer and may lead to different skeletal-related events, which may negatively affect patients' quality of life and are associated with high mortality risk. Physical exercise has been recognized as a potential adjunctive strategy in the cancer setting to improve physical function as well as treatment-related side effects. Nevertheless, exercise is often not recommended to patients with bone health impairments due to safety concerns. In the current review, we aimed, through a comprehensive review of the evidence, to explore the impact of exercise in terms of safety profile, bone outcomes, and the effects on other outcomes in patients with cancer affected by bone metastasis or at high risk of losing bone. Additionally, we explored the potential mechanisms by which exercise may act on bone, particularly the impact of mechanical load on bone remodeling. Finally, considerations about exercise prescription and programming in these populations are also discussed

Exceptional Response in BRAF p.V600E-Mutant Enteric-Type Adenocarcinoma of the Lung With Cutaneous Spread: A Case Report

Background: Enteric-type adenocarcinoma of the lung (lung-ETAC) is a rare form of lung cancer with histologic similarities to colorectal cancer, with aggressive behavior and unfavorable prognosis. Case presentation: An 81-year-old man presented with discolored skin lesions on the chest and abdomen. After comprehensive evaluation, including skin biopsy and molecular profiling, the patient was diagnosed with having lung-ETAC with a BRAF p.V600E mutation. Treatment with dabrafenib and trametinib initially resulted in positive results, with improvement in skin lesions and overall clinical condition. Nevertheless, approximately 6 months after, the disease had progression with new skin lesions reappearing. Conclusions: We reported a unique case of a patient with BRAF p.V600E-mutant lung-ETAC with metastatic skin lesions achieving complete cutaneous response after targeted treatment with dabrafenib and trametinib, highlighting the potential for targeted therapy in patients with lung-ETAC harboring a BRAF p.V600E mutation

A Feasibility Study Investigating an Exercise Program in Metastatic Cancer Based on the Patient-Preferred Delivery Mode

Background: Feasibility of exercise in patients with metastatic cancer is still a challenge. This study aimed to determine the feasibility and preliminary efficacy of an exercise intervention based on a patient-preferred delivery mode in patients affected by metastatic cancer. Materials and methods: Forty-four patients with a confirmed diagnosis of metastatic cancer were recruited in a 3-month exercise program. Whereas the exercise program consisted of aerobic and resistance activities performed twice a week, the participants may choose the mode of delivery: home based, personal training, or group based. The primary endpoint was the feasibility, defined by recruitment rate, attendance, adherence, dropout rate, tolerability (comparing the session RPE with the target RPE), and safety (using the Common Terminology Criteria for Adverse Events, version 5.0). Secondary endpoints included cardiorespiratory fitness (six minutes walking test), muscle strength (handgrip strength test and isometric leg press test), flexibility (the back scratch and chair sit and reach tests), anthropometric parameters (body mass index and waist-hip ratio), quality of life (EORTC QLQ C-30 questionnaire), and amount of physical exercise (Godin's Shepard Leisure Time Exercise Questionnaire). Descriptive statistics, Student t test, and Wilcoxon signed rank test were used to analyze data. Results: The study recruitment rate was 81%. Out of 44 recruited patients, 28 chose the personal training program, 16 chose the home-based program, and none chose the group-based program. Nine dropouts occurred (20%), 6 in the personal training program, and 3 in the home-based intervention. The median attendance rate was 92%, adherence was 88%, tolerability was 100%, and 9 nonsevere adverse events were registered during the exercise sessions. An increase in cardiorespiratory fitness (P < .001) and flexibility (P = .011 for chair sit and reach; P = .040 for back scratch) was observed at the end of the intervention, while no changes in anthropometric values and muscle strength were detected. Different quality-of-life domains were improved following the intervention, including physical (P = .002), emotional (P < .001), and role functioning (P = .018), fatigue (P = .030), and appetite loss (P = .005). Conclusion: A 3-month exercise program based on a patient-preferred delivery mode is feasible in patients with metastatic cancer and may improve physical function and quality of life. Trial registration: NCT04226508

The Renaissance of KRAS Targeting in Advanced Non-Small-Cell Lung Cancer: New Opportunities Following Old Failures

: Non-small cell lung cancer (NSCLC) represents the perfect paradigm of 'precision medicine' due to its complex intratumoral heterogeneity. It is truly characterized by a range of molecular alterations that can deeply influence the natural history of this disease. Several molecular alterations have been found over time, paving the road to biomarker-driven therapy and radically changing the prognosis of 'oncogene addicted' NSCLC patients. Kirsten rat sarcoma (KRAS) mutations are present in up to 30% of NSCLC (especially in adenocarcinoma histotype) and have been identified decades ago. Since its discovery, its molecular characteristics and its marked affinity to a specific substrate have led to define KRAS as an undruggable alteration. Despite that, many attempts have been made to develop drugs capable of targeting KRAS signaling but, until a few years ago, these efforts have been unsuccessful. Comprehensive genomic profiling and wide-spectrum analysis of genetic alterations have only recently allowed to identify different types of KRAS mutations. This tricky step has finally opened new frontiers in the treatment approach of KRAS-mutant patients and might hopefully increase their prognosis and quality of life. In this review, we aim to highlight the most interesting aspects of (epi)genetic KRAS features, hoping to light the way to the state of art of targeting KRAS in NSCLC

Cross-sectional survey evaluating the psychological impact of the COVID-19 vaccination campaign in patients with cancer: The VACCINATE study

The COVID-19 pandemic has profoundly impacted on cancer patients' psychological well-being and clinical status. We assessed the levels of anxiety, depression, and distress and the attitude towards COVID-19 vaccination in cancer patients, accepting vaccination at the Verona University Hospital and Camposampiero Hospital in the Veneto region. Self-reported questionnaires were administered to patients undergoing COVID-19 vaccination between March and May 2021 (first and second dose). Twenty-seven items were investigated: i) demographics/clinical characteristics; ii) anxiety, depression, and distress (Hospital Anxiety and Depression Scale-HADS-and Distress Thermometer-DT); iii) four specific items regarding awareness about infection risks, interference with anticancer treatments, and vaccine side effects. Sixty-two and 57% of the patients who accepted to be vaccinated responded to the survey in the two participating Hospitals, respectively. Mean age was 63 years (SD: 12 years; range 19-94 years), women were slightly more prevalent (57.6%), most participants were married (70%), and either worker or retired (60%). Borderline and clinical levels of anxiety were recorded in 14% and 10% of respondents; borderline and clinical levels of depression in 14% and 8%; and moderate and severe distress levels in 33% and 9%. Overall, there was high confidence that vaccination would reduce the risk of contracting COVID-19 (70%), which would make patients feel less worried about contracting the infection (60%). Fear that vaccine-related side effects would interfere with anticancer treatment and/or global health status was low (10% and 9% for items 3 and 4, respectively) and significantly associated with baseline levels of anxiety, depression, and distress at multivariate analysis. Results did not differ between the Verona and Camposampiero cohorts. During the COVID-19 vaccination campaign, adult cancer patients demonstrated high levels of confidence towards vaccination; baseline levels of anxiety, depression, and distress were the only significant predictors of reduced confidence

Safety of extended interval dosing immune checkpoint inhibitors:a multicenter cohort study

BACKGROUND: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown. METHODS: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival were also described. RESULTS: A total of 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 (41%) patients developed any grade and 17 (3%) G3 or G4 irAEs; after switching to ED, any grade and G3 or G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR] = 0.83, 95% confidence interval [CI] = 0.64 to 0.99; P = .047), whereas no difference for G3 or G4 events was noted (aOR = 1.55, 95% CI = 0.81 to 2.94; P = .18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3 or G4 irAEs during ED. Patients with irAEs during ED had improved overall survival (adjusted hazard ratio [aHR] = 0.53, 95% CI = 0.34 to 0.82; P = .004 after switching; aHR = 0.57, 95% CI = 0.35 to 0.93; P = .025 upfront). CONCLUSIONS: Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials.</p

Analisi della cascata di trasduzione di MET e di EGFR in pazienti con carcinoma gastrico e della giunzione gastroesofagea radicalmente operato in stadio II e III

In Europa, l’adenocarcinoma gastrico è la sesta neoplasia con più alta incidenza (11.7 casi/100.000 abitanti) e la quinta per mortalità (8.4 decessi/100.000). Sebbene vi sia una riduzione progressiva degli adenocarcinomi dello stomaco distale, stiamo osservando un sostanziale incremento di quelli insorti a livello della giunzione esofago-gastrica. Circa 1/3 degli adenocarcinomi gastrici sono diagnosticati in stadio II o III di malattia. La resezione chirurgica è il trattamento di scelta per questi pazienti ma è curativa solo in una parte dei casi. Infatti, la sopravvivenza a 5 anni dei pazienti in stadio II e III è inferiore al 20%. Pertanto, l’aggiunta di un trattamento chemioterapico perioperatorio, con composti del platino in aggiunta ad una fluoropirimidina ed epirubicina, si è dimostrato efficace nel prolungare la sopravvivenza globale e la sopravvivenza libera da progressione. Tuttavia, è necessaria una più accurata selezione dei pazienti che possano beneficiare di un trattamento adiuvante e lo sviluppo di schemi di chemioterapia più efficaci. I farmaci a bersaglio molecolare di recente introduzione nella ricerca clinica oncologica sembrano dare promettenti risultati. Pertanto, abbiamo valutato l’overespressione dei recettori di membrana HER2, EGFR e MET e delle molecole implicate nella trasduzione del segnale AKT1 e phospho-mTOR. Lo scopo dello studio era quello di valutare il ruolo prognostico di questi markers. Novantadue pazienti con adenocarcinoma gastrico o della giunzione gastroesofagea radicalmente operati in stadio II e III sono stati selezionati retrospettivamente. L’overespressione di questi markers è stata valutata tramite indagine immunoistochimica e l’iperespressione di HER-2, nei casi 2+ all’immunositochimica, tramite la metodica FISH. L’overespressione di HER-2 è stata osservata nel 13% delle neoplasie, prevalentemente in quelle di tipo intestinale (p=0.039), e si associa ad un trend per una migliore overall survival e disease free survival. L’overespressione di EGFR è presente nell’11% dei casi e rappresenta un fattore prognostico negativo indipendente. Il 32% degli adenocarcinomi overesprime MET e questo sembra associato ad un trend per una peggiore sopravvivenza. Per quanto riguarda le proteine implicate nella via di trasduzione del segnale, l’overespressione di AKT1 è stata ritrovata nell’8% dei casi, con evidenza di un trend non statisticamente significativo per una ridotta overall survival ed di un’associazione significativa con le neoplasie insorte a livello del piloro (p=0.038) e con quelle scarsamente/non differenziate (p=0.001), mentre l’overespressione di phospho-mTOR è risultata presente nel 48% dei pazienti senza associazione significativa con una ridotta sopravvivenza ma con evidenza di un trend, non statisticamente significativo, per una ridotta disease free survival. In 17 pazienti l’overespressione di AKT1 e quella di EGFR sono risultate mutualmente esclusive ed identificano un sottogruppo a prognosi peggiore

Infections and Immunotherapy in Lung Cancer: A Bad Relationship?

Infectious diseases represent a relevant issue in lung cancer patients. Bacterial and viral infections might influence the patients&rsquo; prognosis, both directly affecting the immune system and indirectly impairing the outcome of anticancer treatments, mainly immunotherapy. In this analysis, we aimed to review the current evidence in order to clarify the complex correlation between infections and lung cancer. In detail, we mainly explored the potential impact on immunotherapy outcome/safety of (1) bacterial infections, with a detailed focus on antibiotics; and (2) viral infections, discriminating among (a) human immune-deficiency virus (HIV), (b) hepatitis B/C virus (HBV-HCV), and (c) Sars-Cov-2. A series of studies suggested the prognostic impact of antibiotic therapy administration, timing, and exposure ratio in patients treated with immune checkpoint inhibitors, probably through an antibiotic-related microbiota dysbiosis. Although cancer patients with HIV, HBV, and HCV were usually excluded from clinical trials evaluating immunotherapy, some retrospective and prospective trials performed in these patient subgroups reported similar results compared to those described in not-infected patients, with a favorable safety profile. Moreover, patients with thoracic cancers are particularly at risk of COVID-19 severe outcomes and mortality. Few reports speculated about the prognostic implications of anticancer therapy, including immunotherapy, in lung cancer patients with concomitant Sars-Cov-2 infection, showing, to date, inconsistent results. The correlation between infectious diseases and immunotherapy remains to be further explored and clarified in the context of dedicated trials. In clinical practice, the accurate and prompt multidisciplinary management of lung cancer patients with infections should be encouraged in order to select the best treatment options for these patients, avoiding unexpected toxicities, while maintaining the anticancer effect

Immune Checkpoint Inhibitors and Radiotherapy in NSCLC Patients: Not Just a Fluke

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