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.

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.

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.].

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.

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.

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.

Feasibility of a novel exercise program for patients with breast cancer offering different modalities and based on patient preference.

PURPOSE: Exercise improves quality of life and reduces the side effects of cancer therapies. Nevertheless, attendance to exercise programs remains a challenge for patients. This study explored the feasibility of an exercise program in which women with breast cancer may be allowed to choose among three exercise delivery modalities. METHODS: Forty-seven patients with breast cancer (stage I-IV) participated in a 12-week combined aerobic and resistance training program. The exercise modality was chosen by patients according to their preferences and needs among three options: the personal training program, the home-based program, or the group-based program. Exercise prescription was similar between the three modalities. Whereas the primary endpoint was feasibility, assessed through recruitment rate, attendance, adherence, dropout rate, tolerability, and safety, secondary endpoints included health-related skills and quality of life. RESULTS: Out of 47 recruited patients, 24 chose the home-based program, 19 the personal training program, and four the group-based program. Six dropouts (13%) were registered, and no severe adverse events were recorded. The median program attendance was 98% for personal training programs, 96% for home-based programs, and 100% for group-based programs, whereas compliance resulted in more than 90% in each modality. At postintervention, a significant increase in cardiorespiratory fitness, lower body flexibility, and body weight was observed. Different quality-of-life domains were improved following the intervention, including physical and social functioning, fatigue, and appetite loss. No significant changes in other parameters were detected. CONCLUSIONS: An exercise prescription based on a patient-preferred delivery modality showed high feasibility in women with breast cancer.

The biomarkers ATLAS: An audit on 1100 non-small cell lung cancer from an Italian knowledge-based database.

AIMS: To date, precision medicine has revolutionized the clinical management of Non-Small Cell Lung Cancer (NSCLC). International societies approved a rapidly improved mandatory testing biomarkers panel for the clinical stratification of NSCLC patients, but harmonized procedures are required to optimize the diagnostic workflow. In this context a knowledge-based database (Biomarkers ATLAS, https://biomarkersatlas.com/) was developed by a supervising group of expert pathologists and thoracic oncologists collecting updated clinical and molecular records from about 80 referral Italian institutions. Here, we audit molecular and clinical data from n = 1100 NSCLC patients collected from January 2019 to December 2020. METHODS: Clinical and molecular records from NSCLC patients were retrospectively collected from the two coordinating institutions (University of Turin and University of Naples). Molecular biomarkers (KRAS, EGFR, BRAF, ROS1, ALK, RET, NTRK, MET) and clinical data (sex, age, histological type, smoker status, PD-L1 expression, therapy) were collected and harmonized. RESULTS: Clinical and molecular data from 1100 (n = 552 mutated and n = 548 wild-type) NSCLC patients were systematized and annotated in the ATLAS knowledge-database. Molecular records from biomarkers testing were matched with main patients' clinical variables. CONCLUSIONS: Biomarkers ATLAS (https://biomarkersatlas.com/) represents a unique, easily managing, and reliable diagnostic tool aiming to integrate clinical records with molecular alterations of NSCLC patients in the real-word Italian scenario.

Osimertinib in Patients With Treatment-Naive EGFR-Mutant Non-small Cell Lung Cancer: Overall Survival, Post-progression Management and Budget Impact Analysis in Real-World.

INTRODUCTION: The observational multicenter prospective FLOWER study (NCT04965701) confirmed effectiveness and safety of osimertinib in the real-world (RW) management of untreated EGFR-mutant advanced non-small cell lung cancer (aNSCLC) patients. METHODS: Herein, we report updated survival data, post-progression management, cost/effectiveness and budget impact (BI) of osimertinib compared with a RW population receiving gefitinib or erlotinib. RESULTS: Overall, 189 Caucasian patients receiving first-line osimertinib were included. After a follow-up of 20.7 months, 74(39.2%) patients discontinued osimertinib, median time-to-treatment discontinuation (mTTD) was 27.9 months, overall survival 36.8 months. At progression, tissue biopsy was performed in 29 (56.9%), liquid biopsy in 15 (29.4%) and both in 7 (13.7%) cases. The most frequent resistant mechanism was MET amplification (N = 14, 29.8%). At data cutoff, 13 (6.9%) patients were continuing osimertinib beyond progression; 52 (67.5%) received second-line treatment; no further treatments were administered in 25 (32.5%) cases. Thirty-three (63.4%) patients received chemotherapy, 12(23.1%) TKIs combination. Cost-effectiveness analysis showed a total cost per patient based on RW mTTD of 98,957.34€, 21,726.28€ and 19,637.83€ for osimertinib, erlotinib and gefitinib, respectively. The incremental cost-effectiveness ratio (ICER)/month for osimertinib was 359,806.0€/life-year-gained (LYG) and 197,789.77€/LYG compared to erlotinib and gefitinib. For osimertinib, the BI-gap between RW-TTD and theoretical-TTD was 16,501.0€ per patient. CONCLUSIONS: This updated analysis confirms the effectiveness of osimertinib in RW. Although the ICER of osimertinib seems not cost-effective, additional costs for the management of disease progression to old generation TKIs were not considered in this study. The BI-gap suggests RW mTTD as a more reliable measure for expense estimation.

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.

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.

Characterization of two transcriptomic subtypes of marker-null large cell carcinoma of the lung suggests different origin and potential new therapeutic perspectives.

Pulmonary large cell carcinoma (LCC) is an undifferentiated neoplasm lacking morphological, histochemical, and immunohistochemical features of small cell lung cancer, adenocarcinoma (ADC), or squamous cell carcinoma (SCC). The available molecular information on this rare disease is limited. This study aimed to provide an integrated molecular overview of 16 cases evaluating the mutational asset of 409 genes and the transcriptomic profiles of 20,815 genes. Our data showed that TP53 was the most frequently inactivated gene (15/16; 93.7%) followed by RB1 (5/16; 31.3%) and KEAP1 (4/16; 25%), while CRKL and MYB genes were each amplified in 4/16 (25%) cases and MYC in 3/16 (18.8%) cases; transcriptomic analysis identified two molecular subtypes including a Pure-LCC and an adenocarcinoma like-LCC (ADLike-LCC) characterized by different activated pathways and cell of origin. In the Pure-LCC group, POU2F3 and FOXI1 were distinctive overexpressed markers. A tuft cell-like profile and the enrichment of a replication stress signature, particularly involving ATR, was related to this profile. Differently, the ADLike-LCC were characterized by an alveolar-cell transcriptomic profile and association with AIM2 inflammasome complex signature. In conclusion, our study split the histological marker-null LCC into two different transcriptomic entities, with POU2F3, FOXI1, and AIM2 genes as differential expression markers that might be probed by immunohistochemistry for the differential diagnosis between Pure-LCC and ADLike-LCC. Finally, the identification of several signatures linked to replication stress in Pure-LCC and inflammasome complex in ADLike-LCC could be useful for designing new potential therapeutic approaches for these subtypes.

Surface CD52, CD84, and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors.

Precise molecular characterization of circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is hampered by their mixed composition of mature and immature cells and lack of specific markers. Here, we focus on mature CD66b+CD10+CD16+CD11b+ PMN-MDSCs (mPMN-MDSCs) from either cancer patients or healthy donors receiving G-CSF for stem cell mobilization (GDs). By RNA sequencing (RNA-seq) experiments, we report the identification of a distinct gene signature shared by the different mPMN-MDSC populations under investigation, also validated in mPMN-MDSCs from GDs and tumor-associated neutrophils (TANs) by single-cell RNA-seq (scRNA-seq) experiments. Analysis of such a gene signature uncovers a specific transcriptional program associated with mPMN-MDSC differentiation and allows us to identify that, in patients with either solid or hematologic tumors and in GDs, CD52, CD84, and prostaglandin E receptor 2 (PTGER2) represent potential mPMN-MDSC-associated markers. Altogether, our findings indicate that mature PMN-MDSCs distinctively undergo specific reprogramming during differentiation and lay the groundwork for selective immunomonitoring, and eventually targeting, of mature PMN-MDSCs.

Association Between Lung Immune Prognostic Index and Durvalumab Consolidation Outcomes in Patients With Locally Advanced Non-Small-Cell Lung Cancer.

INTRODUCTION: The LIPI, based on pretreatment derived neutrophils/[leukocytes-neutrophils] ratio (dNLR) and LDH, is associated with immune checkpoint inhibitors (ICI) outcomes in advanced non-small-cell lung cancer (NSCLC). We aimed to assess baseline LIPI correlation with durvalumab consolidation outcomes in the locally advanced setting. MATERIAL AND METHODS: Multicentre retrospective study (330 patients) with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and December 2020; 65 patients treated with chemo-radiotherapy only. Baseline LIPI characterized 3 groups: good (dNLR≤3+LDH≤ULN), intermediate (dNLR>3/LDH>ULN) and poor (dNLR>3+LDH>ULN). Primary endpoint was overall survival (OS). RESULTS: In the durvalumab cohort, median age was 67 years, 95% smokers, 98% with a performance status of 0-1; 60% had nonsquamous histology and 16% a PD-L1 expression <1%. Radiotherapy was delivered concurrently in 81%. LIPI was evaluable in 216 patients: 66% good, 31% intermediate, 3% poor. LIPI significantly correlated with median OS (median follow-up: 19 months): 18.1 months vs. 47.0 months vs. not reached in poor, intermediate and good LIPI groups, respectively (P = .03). A trend between objective response rate and LIPI groups was observed: 0% vs. 41% vs. 45%, respectively (P = .05). The pooled intermediate/poor LIPI group was associated with shorter OS (HR 1.97; P = .03) and higher risk of progressive disease (OR 2.68; P = .047). Survivals and response were not influenced in the control cohort. CONCLUSION: Baseline LIPI correlated with outcomes in patients with locally advanced NSCLC treated with durvalumab consolidation, but not in those who only received chemo-radiotherapy, providing further evidence of its prognostic and potential predictive role of ICI benefit in NSCLC.

Sotorasib in KRASp.G12C mutated advanced NSCLC: Real-world data from the Italian expanded access program.

BACKGROUND: Sotorasib showed a significant improvement of progression free survival (PFS), safety and quality of life over docetaxel in patients with KRASp.G12C-mutated advanced non-small-cell lung cancer (NSCLC) within the CodeBreak-200 study. Here we report real-world efficacy and tolerability data from NSCLC patients who received sotorasib within the Italian expanded access program (EAP). METHODS: Sotorasib (960 mg, orally, once daily) was available on physician request for KRASp.G12C mutant advanced NSCLC patients. Clinical-pathological and molecular data were collected from the Italian ATLAS real-world registry. Patients underwent CT-scan and responses were evaluated by RECIST criteria. Efficacy and tolerability outcomes have been assessed. RESULTS: A total of 196 advanced NSCLC patients were treated across 30 Italian centers. Median age was 69 years old (range 33-86). Most patients were male (61 %), former (49 %) or current smokers (43 %), with ECOG-PS 0/1 (84 %) and adenocarcinoma subtype (90 %). 45 % and 32 % of patients received sotorasib in 2nd and 3rd line, respectively. Overall, response rate was 26 % and the median duration of response was 5.7 months (95 % CI: 4.4-7.0). Median PFS and OS were 5.8 months (95 % CI: 5 - 6.5) and 8.2 months (95 % CI: 6.3 - 9.9). Grade 3-4 TRAEs occurred in 16.5 % of patients, with Grade ≥ 3 liver enzyme increase and TRAEs-related discontinuation reported in 12 % and 4.6 % of cases. CONCLUSION: Real-world data from the Italian EAP confirm the tolerability and effectiveness of sotorasib in patients with KRASp.G12C-mutated advanced NSCLC and highlight the value of the national ATLAS network as source of real-world evidence driving the clinical management of NSCLC patients.

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.

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.

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.