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.

Effect of exercise across the head and neck cancer continuum: a systematic review of randomized controlled trials.

PURPOSE: This study aims to systematically explore the impact of physical exercise as supportive therapy for head and neck cancer. METHODS: A systematic search on PubMed/MEDLINE, Cochrane, and SPORTDiscus was conducted. Randomized controlled trials exploring the effects of a physical exercise intervention in comparison with usual care on outcomes in patients with head and neck cancer were selected. The RoB 2 tool was used to determine the study quality. The extracted data are reported as qualitative synthesis. RESULTS: Among the 527 records examined, nine studies were included. No trials investigating exercise as prehabilitation were found, whereas eight studies involving 452 patients with head and neck cancer were conducted during anticancer treatment. Most trials did not report improvements in body mass index or body composition, while 2/4 and 3/5 investigations found a significant increase in muscle strength and cardiorespiratory fitness, respectively. Regarding the patients' reported outcomes, 4 out of 7 studies observed enhancements in some domains of quality of life, and two trials out of 3 detected an amelioration in fatigue following the exercise intervention. Analyzing the exercise programs, it seems that combining aerobic and resistance training could be more beneficial compared to a single type of full-body exercise in counteracting physical decline and controlling symptoms in the anticancer therapy phase. One trial has investigated the effect of resistance exercise on patients who had terminated the anticancer treatments, reporting significant improvements in lean mass, muscle strength, and quality of life. CONCLUSION: Exercise may be a promising approach in patients with head and neck cancer. Future studies are needed to consolidate these results.

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' 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.

The frontier of neoadjuvant therapy in non-small cell lung cancer beyond PD-(L)1 agents.

INTRODUCTION: While surgical resection is the cornerstone of treatment for resectable lung cancer, neoadjuvant/adjuvant chemotherapy has shown limited improvement in survival rates over the past decades. With the success of immune checkpoint inhibitors (ICIs) in advanced NSCLC, there is growing interest in their application in earlier stages of the disease. Recent approvals for neoadjuvant/adjuvant ICIs in stage II-IIIA NSCLC highlight this shift in treatment paradigms. AREAS COVERED: In this review, we aim to explore available data regarding alternative agents beyond the PD-(L)1 inhibitors, such as monoclonal antibodies against CTLA4, LAG3, TIGIT, antiangiogenic drugs, and novel therapies (antibody drug conjugates, bispecific antibodies) in neoadjuvant/perioperative regimens. EXPERT OPINION: Novel agents and combinations (with or without ICI or/and chemotherapy), guided by molecular profiling and immune phenotyping, showed promise in improving surgical and survival outcomes. Crucial is, also in early setting, to identifying biomarkers predictive of treatment efficacy in order to personalize neoadjuvant/perioperative treatment strategies.

Integrating nutrition, physical exercise, psychosocial support and antiemetic drugs into CINV management: The road to success.

Over the years, advancements in antiemetic drugs have improved chemotherapy-induced nausea and vomiting (CINV) control. However, despite the antiemetics therapies, in a relevant number of adult patients (∼30 %), CINV is still persistent, leading to several complications, such as electrolyte imbalances, anorexia, and treatment discontinuation. Supportive care interventions have gained credibility in cancer care, helping to improve patients' psycho-physical condition, quality of life, and managing symptoms, including CINV. Physical exercise and tailored nutritional counseling have demonstrated benefits in reducing the severity of nausea and vomiting. Psychological intervention has been postulated as a key approach in controlling anticipatory nausea/vomiting, as well as acupuncture/acupressure has been shown to decrease nausea and vomiting after chemotherapy treatments. In the current review, we aim to provide a clinical update on current prophylactic and delayed antiemetic guidelines for CINV and an overview of the non-pharmacological interventions tested for alleviating CINV in patients with cancer.

What is the role of physical exercise in the era of cancer prehabilitation? A systematic review.

PURPOSE: Exercise before surgery, as part of prehabilitation, aiming to enhance patients' functional and physiological capacity, has become widespread, necessitating an in-depth understanding. METHODS: A systematic search was conducted on Pubmed, Cochrane, and Scopus to examine the effect of exercise as prehabilitation, alone or in combination with other interventions, in patients with cancer. Interventional studies applying a single-arm, randomized controlled, or nonrandomized design were included. RESULTS: A total of 96 studies were included, and categorized according to cancer types, i.e., gynecological, breast, urological, gastrointestinal and lung cancer. For each cancer site, the effect of exercise, on physical fitness parameters and postoperative outcomes, including length of hospital stay and postoperative complications, was reported. CONCLUSION: Exercise as prehabilitation may have an important role in improving physical fitness, postoperative outcomes, and accelerating recovery, especially in certain types of malignancies.

Exploring the Association between Health-Related Physical Fitness and Quality of Life in Patients with Cancer: A Cross-Sectional Study.

Whereas an exercise intervention effectively improves patients' quality of life, little information is available about the contribution of each physical fitness component. This study aims to explore the association between physical fitness components and the quality-of-life domain in patients with cancer. Between September 2021 and August 2023, 160 patients with mixed cancer types visiting the Oncology Unit were selected on a consecutive basis according to selection criteria. They underwent a comprehensive baseline assessment including the six-minute walking test, the handgrip strength test, the isometric leg press test, the back scratch, sit and reach tests, their waist-hip ratio, and their body mass index. The European Organization for Research and Treatment of Cancer Quality of Life and Core Questionnaire was used to measure the quality of life. The sample size was based on the use of regression models to study associations between clinical characteristics and fitness outcomes. All of the analyses were performed using the SPSS v.25 statistical package. Patients had a mean age of 58 years, 68% were female, 42% were affected by breast cancer, and all were receiving anticancer treatments. Higher functional capacity was associated with better global health status (p < 0.0001) and physical (p < 0.0001), role (p < 0.0001), emotional (p = 0.026), and social function (p = 0.016) and inversely linked with fatigue (p = 0.001). Lower-limb flexibility was significantly associated with all of the domains except for role and social functions. The waist-hip ratio was inversely associated with physical function (p < 0.0001) and positively related to fatigue (p = 0.037). Exercise programs aiming to improve the quality of life in cancer should be addressed to optimize these fitness components.

Prognostic impact of Interleukin-8 levels in lung cancer: A meta-analysis and a bioinformatic validation.

BACKGROUND: High interleukin-8 (IL-8) levels have been linked to poor prognosis in lung cancer, but conclusive data are lacking. MATERIALS AND METHODS: A comprehensive search was conducted on April 1st, 2023, from electronic databases, focusing on studies with IL-8 expression evaluations and the availability of hazard ratio (HR) and 95% confidence intervals (CI) for overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) or adequate data for their estimation. Then, we examined IL-8 and CXCR1 RNA-seq data from The Cancer Genome Atlas (TCGA) dataset, and we correlated these data with OS. RESULTS: Among 2655 produced records, 10 manuscripts involving both non-small cell lung cancer and small cell lung cancer, were included in the analysis. Two manuscripts and one study included two and three different cohorts, respectively, for a total of 14 cohorts of patients. Overall, 4 cohorts evaluated IL-8 levels in patients treated with chemotherapy, 3 cohorts immunotherapy, 2 cohorts surgical patients and 4 cohorts other treatments; 1 cohort was removed, as the type of treatments was lacking. The 12 cohorts included in the OS analysis revealed that patients with high IL-8 levels have a lower OS probability, as compared to patients with low IL-8 levels (HR=1.75, 95 % CI 1.36-2.26). No significant difference between patients with high and low IL-8 levels was observed in the 8 cohorts available for PFS analysis. Sensitivity analysis according to treatment revealed significant PFS and OS differences for patients treated with chemotherapy or immunotherapy. Analysis of RNA-seq data from TCGA, confirmed the correlation between high IL-8 and CXCR1 expression and worse OS in patients with resected lung cancer. CONCLUSION: To the best of our knowledge, this study represents the first meta-analysis demonstrating a negative prognostic impact of high IL-8 level in lung cancer, particularly in patients treated with chemotherapy and/or immunotherapy.

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

[This corrects the article DOI: 10.1371/journal.pone.0290792.].

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.

Characterizing the immune tumor microenvironment in ALK fusion-positive lung cancer: state-of-the-art and therapeutical implications.

INTRODUCTION: Approximately 5% of non-small cell lung cancer (NSCLC), exhibits anaplastic lymphoma kinase (ALK) rearrangements. EML4-ALK fusions account for over 90% of ALK rearrangements in NSCLC. The advent of treatment targeting ALK has significantly improved survival rates in patients with advanced ALK-positive NSCLC. However, the emergence of resistance mechanisms and the subsequent progression disease inevitably occurs. The tumor immune microenvironment (TIME) plays a pivotal role in lung cancer, influencing disease development, patient's outcomes, and response to treatments. AREAS COVERED: The aim of this review is to provide a comprehensive characterization of the TIME in ALK rearranged NSCLC and its intrinsic plasticity under treatment pressure. EXPERT OPINION: Recognizing the fundamental role of the TIME in cancer progression has shifted the paradigm from a tumor cell-centric perspective to the understanding of a complex tumor ecosystem. Understanding the intricate dynamics of the TIME, its influence on treatment response, and the potential of immunotherapy in patients with ALK-positive NSCLC are currently among the primary research objectives in this patient population.

Tissue- and liquid-biopsy based NGS profiling in advanced non-small-cell lung cancer in a real-world setting: the IMMINENT study.

Introduction: To date, for all non-small cell lung cancer (NSCLC) cases, it is recommended to test for driver alterations to identify actionable therapeutic targets. In this light, comprehensive genomic profiling (CGP) with next generation sequencing (NGS) has progressively gained increasing importance in clinical practice. Here, with the aim of assessing the distribution and the real-world frequency of gene alterations and their correlation with patient characteristics, we present the outcomes obtained using FoundationOne (F1CDx) and FoundationLiquid CDx (F1L/F1LCDx) NGS-based profiling in a nationwide initiative for advanced NSCLC patients. Methods: F1CDx (324 genes) was used for tissue samples, and F1L (70 genes) or F1LCDx (324 genes) for liquid biopsy, aiming to explore the real-world occurrence of molecular alterations in aNSCLC and their relationship with patients' characteristics. Results: Overall, 232 advanced NSCLC patients from 11 Institutions were gathered [median age 63 years; never/former or current smokers 29.3/65.9%; adenocarcinoma/squamous 79.3/12.5%; F1CDx/F1L+F1LCDx 59.5/40.5%]. Alterations were found in 170 different genes. Median number of mutated genes per sample was 4 (IQR 3-6) and 2 (IQR 1-3) in the F1CDx and F1L/F1LCDx cohorts, respectively. TP53 (58%), KRAS (22%), CDKN2A/B (19%), and STK11 (17%) alterations were the most frequently detected. Actionability rates (tier I and II) were comparable: 36.2% F1CDx vs. 34% ctDNA NGS assays (29.5% and 40.9% F1L and F1LCDx, respectively). Alterations in KEAP1 were significantly associated with STK11 and KRAS, so as TP53 with RB1. Median tumor mutational burden was 6 (IQR 3-10) and was significantly higher in smokers. Median OS from metastatic diagnosis was 23 months (IQR 18.5-19.5) and significantly lower in patients harboring ≥3 gene mutations. Conditional three-year survival probabilities increased over time for patients profiled at initial diagnosis and exceeded those of individuals tested later in their clinical history after 12 months. Conclusion: This study confirms that NGS-based molecular profiling of aNSCLC on tissue or blood samples offers valuable predictive and prognostic insights.

Antibody-drug conjugates (ADCs) targeting TROP-2 in lung cancer.

INTRODUCTION: The advent of antibody-drug conjugates (ADCs) represents a renewed strategy in the era of precision oncology. Several epithelial tumors harbor overexpression of the trophoblast cell-surface antigen 2 (TROP-2), which represents a predictor of poor prognosis and a promising target for anticancer therapy. AREAS COVERED: In this review, we aim to collect the available preclinical and clinical data regarding anti-TROP-2 ADCs in lung cancer obtained through extensive literature research and screening of the available abstract/posters presented at recent meetings. EXPERT OPINION: Anti-TROP-2 ADCs represent an innovative upcoming weapon against both non-small cell lung cancer and small cell lung cancer subtypes, pending the results of several ongoing trials. The proper combination and placement of this agent throughout the lung cancer treatment pathway, the identification of potentially predictive biomarkers of benefit, as well as the optimal management and impact of peculiar toxicity (i.e. interstitial lung disease) are the next questions to be answered.

Unlocking New Horizons in Small-Cell Lung Cancer Treatment: The Onset of Antibody-Drug Conjugates.

Small-cell lung cancer (SCLC) is a highly aggressive disease, accounting for about 15% of all lung cancer cases. Despite initial responses to chemoimmunotherapy, SCLC recurs and becomes resistant to treatment. Recently, antibody-drug conjugates (ADCs) have emerged as a promising therapeutic option for SCLC. ADCs consist of an antibody that specifically targets a tumor antigen linked to a cytotoxic drug. The antibody delivers the drug directly to the cancer cells, minimizing off-target toxicity and improving the therapeutic index. Several ADCs targeting different tumor antigens are currently being evaluated in clinical trials for SCLC. Despite the negative results of rovalpituzumab tesirine (Rova-T), other ADCs targeting different antigens, such as B7-H3, seizure-related homolog 6 (SEZ6), and CEACAM5, have also been investigated in clinical trials, including for SCLC, and their results suggest preliminary activity, either alone or in combination with other therapies. More recently, sacituzumab govitecan, an anti-TROP2 ADC, demonstrated promising activity in lung cancer, including SCLC. Furthermore, an anti-B7-H3 (CD276), ifinatamab deruxtecan (DS7300A), showed a high response rate and durable responses in heavily pretreated SCLC. Overall, ADCs represent an intriguing approach to treating SCLC, particularly in the relapsed or refractory setting. Further studies are needed to determine their efficacy and safety and the best location in the treatment algorithm for SCLC. In this review, we aim to collect and describe the results regarding the past, the present, and the future of ADCs in SCLC.

Adjuvant Targeted Therapy in Solid Cancers: Pioneers and New Glories.

Targeted therapy (TT) has revolutionized cancer treatment, successfully applied in various settings. Adjuvant TT in resected early-stage gastrointestinal stromal tumors (GIST), melanoma, non-small cell lung cancer (NSCLC), and breast cancer has led to practice-changing achievements. In particular, standard treatments include BRAF inhibitors for melanoma, osimertinib for NSCLC, hormone therapy or HER2 TT for breast cancer, and imatinib for GIST. Despite the undeniable benefit derived from adjuvant TT, the optimal duration of TT and the appropriate managing of the relapse remain open questions. Furthermore, neoadjuvant TT is emerging as valuable, particularly in breast cancer, and ongoing studies evaluate TT in the perioperative setting for early-stage NSCLC. In this review, we aim to collect and describe the large amount of data available in the literature about adjuvant TT across different histologies, focusing on epidemiology, major advances, and future directions.

Willingness, preferences, barriers, and facilitators of a multimodal supportive care intervention including exercise, nutritional and psychological approach in patients with cancer: a cross-sectional study.

PURPOSE: Supportive care, including exercise, nutritional and psychological support, is becoming increasingly important in cancer given their impact on 'patients' quality and quantity of life. The purpose of this study was to explore willingness, preferences barriers and facilitators for a multimodal intervention in patients with cancer. METHODS: An anonymous questionnaire was proposed on randomly selected days to the patients visiting the cancer outpatients' facilities at the Oncology Unit of the University Hospital of Verona. The questionnaire investigated willingness, preferences, barriers, and facilitators associated with participation in a multimodal program designed for patients with cancer. Exercise level was estimated using two open questions, nutritional risk was identified using the Nutritional Risk Screening 2002, while distress was evaluated with the Distress Thermometer. RESULTS: Based on 324 participants, 65% were interested in starting a multimodal intervention. Patients declared to prefer to receive instructions from dedicated experts, with a face-to-face approach, and during the anticancer treatment. Treatment-related side effects were the major obstacles for a multimodal program, while the availability of a specialized staff as exercise kinesiologists, dietitians, and psycho-oncologists was found to be an important facilitator for increasing 'patients' participation. CONCLUSION: Patients patients with cancer are interested in participating in a multimodal supportive care program specifically designed for them. Information from this study may help to design a tailored multimodal intervention for patients with cancer.

Meta-analysis of the prognostic impact of TP53 co-mutations in EGFR-mutant advanced non-small-cell lung cancer treated with tyrosine kinase inhibitors.

PURPOSE: To assess the prognostic impact of TP53 mutations in EGFR-mutant advanced NSCLC patients treated with TKIs. METHODS: Studies exploring the clinical outcomes of EGFR mutant/TP53 wild-type versus EGFR/TP53 co-mutant patients treated with TKIs were selected. Data were cumulated by adopting a fixed and random-effect model. RESULTS: Overall, 29 trials were eligible. The PFS analysis showed that TP53 co-mutant group has shorter PFS versus EGFR mutant/TP53 wild-type group (HR = 1.67, 95% CI 1.51-1.83, heterogeneity I2 =20%, p = 0.18). Patients affected by EGFR/TP53 co-mutant NSCLC have a higher chance of shorter OS versus EGFR mutant/TP53 wild type (HR= 1.89, 95% CI 1.67-2.14, heterogeneity I2 = 21%; p = 0.19). The subgroup analysis showed no significant difference between first-second versus third-generation TKIs in both PFS and OS (p = 0.31, p = 0.08). CONCLUSIONS: TP53 mutations represent a clinically relevant mechanism of resistance to EGFR-TKIs, regardless of their generation. A personalized therapeutical approach should be explored in dedicated clinical trials.

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 â€‹± â€‹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.

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.

Plasmacytoid Dendritic Cell, Slan+-Monocyte and Natural Killer Cell Counts Function as Blood Cell-Based Biomarkers for Predicting Responses to Immune Checkpoint Inhibitor Monotherapy in Non-Small Cell Lung Cancer Patients.

The advent of immune checkpoint inhibitors (ICIs), for instance, programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockers, has greatly improved the outcome of patients affected by non-small cell lung cancer (NSCLC). However, most NSCLC patients either do not respond to ICI monotherapy or develop resistance to it after an initial response. Therefore, the identification of biomarkers for predicting the response of patients to ICI monotherapy represents an urgent issue. Great efforts are currently dedicated toward identifying blood-based biomarkers to predict responses to ICI monotherapy. In this study, more commonly utilized blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and the lung immune prognostic index (LIPI) score, as well as the frequency/number and activation status of various types of circulating innate immune cell populations, were evaluated in NSCLC patients at baseline before therapy initiation. The data indicated that, among all the parameters tested, low plasmacytoid dendritic cell (pDC), slan+-monocyte and natural killer cell counts, as well as a high LIPI score and elevated PD-L1 expression levels on type 1 conventional DCs (cDC1s), were independently correlated with a negative response to ICI therapy in NSCLC patients. The results from this study suggest that the evaluation of innate immune cell numbers and phenotypes may provide novel and promising predictive biomarkers for ICI monotherapy in NSCLC patients.