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1.
Crit Rev Oncol Hematol ; 198: 104350, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38642726

RESUMEN

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.

2.
PLoS One ; 19(1): e0290792, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38271378

RESUMEN

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.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Neoplasias , Vacunación , Adulto , Femenino , Humanos , Persona de Mediana Edad , Ansiedad/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Estudios Transversales , Depresión/epidemiología , Neoplasias/complicaciones , Pandemias , Estrés Psicológico/epidemiología , Vacunación/psicología , Masculino , Adulto Joven , Anciano , Anciano de 80 o más Años
3.
Oncologist ; 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38206849

RESUMEN

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.

4.
JTO Clin Res Rep ; 4(12): 100597, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38124787

RESUMEN

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.

5.
Cancers (Basel) ; 15(21)2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37958458

RESUMEN

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.

6.
Cancers (Basel) ; 15(22)2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-38001628

RESUMEN

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.

7.
Support Care Cancer ; 31(12): 670, 2023 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-37924500

RESUMEN

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.


Asunto(s)
Neoplasias de Cabeza y Cuello , Calidad de Vida , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ejercicio Físico , Neoplasias de Cabeza y Cuello/terapia , Fuerza Muscular/fisiología , Terapia por Ejercicio/métodos
8.
J Pers Med ; 13(10)2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37888038

RESUMEN

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.

9.
Oncoimmunology ; 12(1): 2253644, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37720688

RESUMEN

Cancer cells favor the generation of myeloid cells with immunosuppressive and inflammatory features, including myeloid-derived suppressor cells (MDSCs), which support tumor progression. The anti-apoptotic molecule, cellular FLICE (FADD-like interleukin-1ß-converting enzyme)-inhibitory protein (c-FLIP), which acts as an important modulator of caspase-8, is required for the development and function of monocytic (M)-MDSCs. Here, we assessed the effect of immune checkpoint inhibitor (ICI) therapy on systemic immunological landscape, including FLIP-expressing MDSCs, in non-small cell lung cancer (NSCLC) patients. Longitudinal changes in peripheral immunological parameters were correlated with patients' outcome. In detail, 34 NSCLC patients were enrolled and classified as progressors (P) or non-progressors (NP), according to the RECIST evaluation. We demonstrated a reduction in pro-inflammatory cytokines such as IL-8, IL-6, and IL-1ß in only NP patients after ICI treatment. Moreover, using t-distributed stochastic neighbor embedding (t-SNE) and cluster analysis, we characterized in NP patients a significant increase in the amount of lymphocytes and a slight contraction of myeloid cells such as neutrophils and monocytes. Despite this moderate ICI-associated alteration in myeloid cells, we identified a distinctive reduction of c-FLIP expression in M-MDSCs from NP patients concurrently with the first clinical evaluation (T1), even though NP and P patients showed the same level of expression at baseline (T0). In agreement with the c-FLIP expression, monocytes isolated from both P and NP patients displayed similar immunosuppressive functions at T0; however, this pro-tumor activity was negatively influenced at T1 in the NP patient cohort exclusively. Hence, ICI therapy can mitigate systemic inflammation and impair MDSC-dependent immunosuppression.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Células Supresoras de Origen Mieloide , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Monocitos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico
10.
Expert Opin Biol Ther ; 23(11): 1077-1087, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36995069

RESUMEN

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.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Inmunoconjugados , Neoplasias Pulmonares , Humanos , Inmunoconjugados/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Camptotecina/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Medicina de Precisión
11.
Crit Rev Oncol Hematol ; 184: 103929, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36773668

RESUMEN

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.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Pronóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inducido químicamente , Receptores ErbB , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteína p53 Supresora de Tumor/genética
12.
J Cancer Res Clin Oncol ; 149(7): 3435-3445, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35943598

RESUMEN

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.


Asunto(s)
Neoplasias , Humanos , Estudios Transversales , Neoplasias/terapia , Neoplasias/psicología , Ejercicio Físico , Encuestas y Cuestionarios , Consejo
13.
Asia Pac J Oncol Nurs ; 10(Suppl 1): 100298, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38197044

RESUMEN

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.

14.
Cancers (Basel) ; 14(24)2022 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-36551564

RESUMEN

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.

15.
Semin Oncol ; 49(5): 389-393, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36184311

RESUMEN

We performed an updated meta-analysis to explore the role of maintenance therapy in SCLC. Clinical trials with randomization to maintenance/consolidation (V) placebo or observation or best supportive care in SCLC, both extended and limited disease were searched from January 2009 to March 2022. The hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) with the relative 95% confidence interval (CI) were extracted from each study. Summary HR was calculated using random- or fixed-effects models, depending on the heterogeneity of the included studies. A total of 9 studies were identified. Neither PFS nor OS were improved with maintenance/consolidation (PFS: random-effect; HR 0.93; 95% CI 0.71-1.21; P=0.10; OS: fixed-effect; HR 0.98; 95% CI 0.89-1.08; P=0.14). Among the different strategies, immunotherapy maintenance showed a significantly decreased risk of progression (V)standard of care (random-effect; HR 0.80; 95% CI 0.66-0.97; P=0.03). The current updated meta-analysis did not demonstrate a benefit of maintenance/consolidation therapy in SCLC, with only a PFS benefit for immunotherapy approach.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Quimioterapia de Consolidación , Inmunoterapia , Supervivencia sin Progresión
16.
Expert Rev Anticancer Ther ; 22(8): 785-794, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35726802

RESUMEN

INTRODUCTION: Selpercatinib is a RET selective tyrosine kinase inhibitor with nanomolar potency against diverse RET alterations, including fusions, activating point mutations, and acquired resistance mutations. Rearranged during transfection (RET) gene is a validated target in non-small-cell lung cancer (NSCLC). Selpercatinib is currently approved for adult patients with metastatic RET fusion-positive NSCLC. AREAS COVERED: This review summarizes the efficacy and safety data of selpercatinib in the treatment landscape of RET fusion-positive NSCLC. EXPERT OPINION: Globally considered, selpercatinib is an optimal treatment choice, in terms of both (systemic and intracranial) efficacy and safety, in patients affected by advanced NSCLC harboring RET fusions as a driver mechanism. Future challenges include the identification of the most appropriate placement for selpercatinib in the treatment algorithm of RET fusion-positive NSCLC (including early stages), the clarification of resistance mechanisms, as well as of its role in EGFR-mutant NSCLC undergoing progression during osimertinib driven by RET alterations.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-ret/genética , Pirazoles , Piridinas
17.
Transl Lung Cancer Res ; 10(7): 3369-3384, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34430373

RESUMEN

OBJECTIVE: In this review, we aim to collect and discuss available data about the role and composition of tumor microenvironment (TME) in oligometastatic (OMD) and oligoprogressive (OPD) non-small cell lung cancer (NSCLC). Furthermore, we aim to summarize the ongoing clinical trials evaluating as exploratory objective the TME composition, through tissue and/or blood samples, in order to clarify whether TME and its components could explain, at least partially, the oligometastatic/oligoprogressive process and could unravel the existence of predictive and/or prognostic factors for local ablative therapy (LAT). BACKGROUND: OMD/OPD NSCLC represent a heterogeneous group of diseases. Several data have shown that TME plays an important role in tumor progression and therefore in treatment response. The crucial role of several types of cells and molecules such as immune cells, cytokines, integrins, protease and adhesion molecules, tumor-associated macrophages (TAMs) and mesenchymal stem cells (MSCs) has been widely established. Due to the peculiar activation of specific pathways and expression of adhesion molecules, metastatic cells seem to show a tropism for specific anatomic sites (the so-called "seed and soil" hypothesis). Based on this theory, metastases appear as a biologically driven process rather than a random release of cancer cells. Although the role and the function of TME at the time of progression in patients with NSCLC treated with tyrosine-kinase inhibitors and immune checkpoint inhibitors (ICIs) have been investigated, limited data about the role and the biological meaning of TME are available in the specific OMD/OPD setting. METHODS: Through a comprehensive PubMed and ClinicalTrials.gov search, we identified available and ongoing studies exploring the role of TME in oligometastatic/oligoprogressive NSCLC. CONCLUSIONS: Deepening the knowledge on TME composition and function in OMD/OPD may provide innovative implications in terms of both prognosis and prediction of outcome in particular from local treatments, paving the way for future investigations of personalized approaches in both advanced and early disease settings.

18.
Int J Mol Sci ; 22(1)2020 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-33375194

RESUMEN

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.


Asunto(s)
Infecciones Bacterianas/complicaciones , COVID-19/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/terapia , Inmunoterapia , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/terapia , Virosis/complicaciones , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/patología , Síndrome de Inmunodeficiencia Adquirida/terapia , Antibacterianos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/patología , COVID-19/patología , Carcinoma de Pulmón de Células no Pequeñas/microbiología , Carcinoma de Pulmón de Células no Pequeñas/virología , VIH/efectos de los fármacos , Hepatitis B/complicaciones , Hepatitis B/inmunología , Hepatitis B/patología , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/patología , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/microbiología , Neoplasias Pulmonares/virología , Microbiota/efectos de los fármacos , Microbiota/inmunología , Tratamiento Farmacológico de COVID-19
19.
Eur J Cancer ; 135: 159-169, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32580131

RESUMEN

BACKGROUND: On February 23rd, the 1st case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed at the University Hospital Trust of Verona, Italy. On March 13th, the Oncology Section was converted into a 22-inpatient bed coronavirus disease (COVID) Unit, and we reshaped our organisation to face the SARS-CoV-2 epidemic, while maintaining oncological activities. METHODS: We tracked down (i) volumes of oncological activities (January 1st - March 31st, 2020 versus the same period of 2019), (ii) patients' and caregivers' perception and (iii) SARS-CoV-2 infection rate in oncology health professionals and SARS-CoV-2 infection-related hospital admissions of "active"' oncological patients. RESULTS: As compared with the same trimester in 2019, the overall reduction in total numbers of inpatient admissions, chemotherapy administrations and specialist visits in January-March 2020 was 8%, 6% and 3%, respectively; based on the weekly average of daily accesses, reduction in some of the oncological activities became statistically significant from week 11. The overall acceptance of adopted measures, as measured by targeted questionnaires administered to a sample of 241 outpatients, was high (>70%). Overall, 8 of 85 oncology health professionals tested positive for SARS-CoV-2 infection (all but one employed in the COVID Unit, no hospital admissions and no treatment required); among 471 patients admitted for SARS-CoV-2 infection, 7 had an "active"' oncological disease (2 died of infection-related complications). CONCLUSIONS: A slight, but statistically significant reduction in oncology activity was registered during the SARS-CoV-2 epidemic peak in Verona, Italy. Organisational and protective measures adopted appear to have contributed to keep infections in both oncological patients and health professionals to a minimum.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/prevención & control , Control de Infecciones/organización & administración , Oncología Médica/organización & administración , Neoplasias/terapia , Pandemias/prevención & control , Neumonía Viral/prevención & control , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico/normas , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Femenino , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud/psicología , Humanos , Control de Infecciones/normas , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Transmisión de Enfermedad Infecciosa de Profesional a Paciente/prevención & control , Italia/epidemiología , Masculino , Tamizaje Masivo/normas , Oncología Médica/métodos , Neoplasias/psicología , Admisión del Paciente/normas , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , Sistemas de Apoyo Psicosocial , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2
20.
ESMO Open ; 5(3): e000689, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32424067

RESUMEN

BackgroundNutritional derangements are common hallmarks of non-small-cell lung cancer (NSCLC). Nevertheless, their early detection is overlooked in clinical routine. This study aimed to evaluate nutritional status and its correlation with outcome in NSCLC patients.MethodsData regarding NSCLC patients undergoing nutritional evaluation were prospectively collected (May 2016-October 2018). Nutritional risk was assessed by Nutritional Risk Screening 2002 (NRS-2002). Bilateral psoas major muscles were measured at L3 vertebrae level with routine staging-computed tomography and changes were evaluated using Wilcoxon signed-rank test. Clinico-pathological and nutritional data were correlated to progression-free/overall survival (PFS/OS) and response rate (ORR) using a Cox and logistic regression model. Kaplan-Meier curves were compared with log-rank test.ResultsThirty-eight patients were included. The majority (65.8%) of them were at nutritional risk (NRS-2002 ≥3). At multivariate analysis for patients with advanced disease, age (HR 2.44, p=0.05), performance status (HR 2.48, p=0.043) and NRS-2002 (HR 1.74, p=0.001) were significant independent predictors for PFS and weight loss (HR 1.07, p=0.008) for OS. Patients with baseline NRS-2002 <3 had significantly longer 1-year PFS (85.7% vs 19.4%, p=0.02) and higher ORR (66.7% vs 21.4%) than those with NRS-2002 ≥3. An explorative evaluation demonstrated that NRS-2002 score significantly decreased after nutritional intervention (p=0.001) for 3 months.ConclusionBaseline nutritional risk represents a prognostic factor in NSCLC. Nutritional counselling should be applied as a fundamental tool to improve nutritional risk in a short period, ameliorating patients' outcome.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Detección Precoz del Cáncer , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Estado Nutricional , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
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