RESUMEN
ICONIC is a multicenter, open-label, nonrandomized phase II clinical trial aiming to assess the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in cancer patients who have obtained disease stability with pembrolizumab administered as per standard-of-care. The primary end point is objective response rate, and the secondary end points are safety, survival and disease control rate. Translational research is an exploratory aim. The planned sample size is 27 patients. The study combination will be considered worth investigating if at least four objective responses are observed. If the null hypothesis is rejected, ICONIC will be the first proof of concept of the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in oncology.
ICONIC is a multicenter, open-label, nonrandomized, phase II clinical trial aiming to evaluate the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in cancer patients who have obtained disease stability with pembrolizumab administered as per standard-of-care. Considering that no clinical trials have been conducted thus far to assess the safety of the association between immune checkpoint inhibitors and carbon ion radiotherapy, the current clinical study will provide controlled data about the safety of this unprecedented therapeutic combination. Clinical Trial Registration: NCT05229614 (ClinicalTrials.gov).
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Carcinoma de Pulmón de Células no Pequeñas , Radioterapia de Iones Pesados , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Radioterapia de Iones Pesados/efectos adversos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase II como Asunto , Estudios de Factibilidad , Prueba de Estudio ConceptualRESUMEN
BACKGROUND: Nutritional support, including nutritional counseling and oral nutritional supplements (ONS), has been recommended as a first-line strategy in patients with non-small cell lung cancer (NSCLC). Evidence on the efficacy of immunonutrition during immunotherapy in these patients is positive, but still limited some secondary endpoints, such as treatment toxicity and tolerance. We hypothesize that early systematic provision of ONS with a high-protein-high calorie mixture containing immunonutrients (Impact®) in addition to nutritional counseling, compared to nutritional counseling alone, is beneficial to patients with NSCLC receiving immunotherapy with or without chemotherapy. We designed the present study to evaluate the efficacy of early systematic provision of ONS enriched with immunonutrients compared to nutritional counseling alone, in patients with NSCLC undergoing immunotherapy. Study endpoints were: treatment response (primary endpoint: progression-free survival), treatment tolerance and toxicity, body weight, body composition, protein-calorie intake, quality of life, fatigue, muscle strength and immunological profile. METHODS: This is a pragmatic, multicentre, randomized (1:1), parallel-group, open label, controlled, pilot clinical trial (N = 180). DISCUSSION: The improvement of efficacy of nutritional support in oncology still deserves many efforts. Immunonutrition represents a promising approach also in patients with NSCLC, but evidence on its efficacy on clinical outcomes during immunotherapy is still inconclusive. The present pilot study, which guarantees early high-quality nutritional care (assessment and treatment) to all patients in agreement with current guidelines and recommendations, could represent one of the first proofs of efficacy of early oral immunonutrition in patients with cancer undergoing immunotherapy. Further large randomized trials addressing the improvement of supportive care could be hypothesized, accordingly. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov Identifier: NCT05384873.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Calidad de Vida , Proyectos Piloto , Suplementos Dietéticos , Neoplasias Pulmonares/terapia , Consejo , InmunoterapiaRESUMEN
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural layers. MPM has a strong association with asbestos, mainly caused by exposure to its biopersistent fibers in at least 80% of cases. Individuals with a chronic exposure to asbestos might develop disease with a 20-40-year latency with few or no symptoms. Such has been the case in the Italian regions of Piedmont and Lombardy, where industrial production of materials laden with asbestos, mainly cements, has been responsible for the onset of a large epidemic. Since 2018, a multidisciplinary team at San Matteo hospital in Pavia has been collecting data on over 100 patients with MPM. The main goal of this project is to define and describe an integrated profile for each MPM case at diagnosis by using data mining and partition analysis. METHODS: Here we bring together exhaustive epidemiologic, histologic and radiologic data of 88 MPM patients that came to our observation and draw correlations with predictive and prognostic significance. RESULTS: The median overall survival (OS) was 15.6 months. Most patients presented with pleural effusion, irrespective of disease stage. Quite unexpectedly, no statistically significant association was demonstrated between OS and TNM disease stage at diagnosis. Although average OS is similar in male and female patients, partition analysis of data underlined a significant differential hierarchy of predictor categories based on patient gender. In females with no smoking history, full chemotherapeutic regimens are associated with better outcomes. Moreover, concerning second line treatments, vinorelbine emerged as the most advantageous choice for female patients, whereas in the male subgroup no statistically significant difference resulted between gemcitabine and vinorelbine. CONCLUSION: A multidisciplinary approach to MPM is mandatory to define better therapeutic approaches, personalize the management and improve patient outcomes.
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Mesotelioma Maligno/epidemiología , Mesotelioma Maligno/terapia , Neoplasias Pleurales/epidemiología , Neoplasias Pleurales/terapia , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Masculino , Mesotelioma Maligno/mortalidad , Neoplasias Pleurales/mortalidad , Análisis de SupervivenciaRESUMEN
Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.
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Mesotelioma Maligno/patología , Mesotelioma Maligno/terapia , Terapia Combinada , Sistemas de Liberación de Medicamentos/métodos , Humanos , Inmunoterapia/métodos , Mesotelioma/patología , Mesotelioma/terapia , Neoplasias Pleurales/patología , Neoplasias Pleurales/terapia , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/terapia , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/fisiologíaRESUMEN
BACKGROUND: Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. METHODS: The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. FINDINGS: Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68·0 years (61·8-75·0) and the majority had an Eastern Cooperative Oncology Group performance status of 0-1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1·88, 95% 1·00-3·62), being a current or former smoker (4·24, 1·70-12·95), receiving treatment with chemotherapy alone (2·54, 1·09-6·11), and the presence of any comorbidities (2·65, 1·09-7·46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3·18, 95% CI 1·11-9·06) was associated with increased risk of death. INTERPRETATION: With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference. FUNDING: None.
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Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Sistema de Registros/estadística & datos numéricos , Neoplasias Torácicas/epidemiología , Anciano , Betacoronavirus , COVID-19 , Causas de Muerte , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/patología , Estudios Transversales , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/mortalidad , Neumonía Viral/patología , Factores de Riesgo , SARS-CoV-2 , Neoplasias Torácicas/mortalidad , Neoplasias Torácicas/patología , Neoplasias Torácicas/terapiaRESUMEN
PURPOSE: Data from two noninferiority trials of a dexamethasone-sparing regimen were assessed for the impact of acute nausea and vomiting on delayed outcome in patients undergoing moderately emetogenic chemotherapy (MEC) or anthracycline plus cyclophosphamide (AC). METHODS: Chemo-naive patients were randomized to receive palonosetron (0.25 mg IV) plus dexamethasone (8 mg IV) on day 1 of chemotherapy, or the same regimen followed by oral dexamethasone on days 2 and 3 in the MEC (n = 237) and AC (n = 380) cohorts. Patients were divided into two groups according to whether or not they experienced vomiting and/or moderate-to-severe nausea during the acute phase (high- and low-risk groups, respectively). Primary efficacy endpoint was the complete protection (CP) against delayed vomiting and moderate-to-severe nausea. Patient's satisfaction (0-100 mm visual analog scale) was also analyzed. RESULTS: Among the 209 low-risk patients undergoing MEC, delayed CP occurred in 82.9% of those who received single-dose dexamethasone and 89.8% of those who received 3-day dexamethasone (P = 0.165). Of the 271 low-risk patients undergoing AC, CP was achieved in 71.7 % of those treated with single-dose dexamethasone and 84.2% treated with 3-day dexamethasone (P = 0.019). In spite of these observations, the patient satisfaction data was not influenced by dexamethasone regimen. In both cohorts, occurrence of acute vomiting or moderate-to-severe nausea was the key independent-predictor for delayed vomiting or nausea, respectively. CONCLUSIONS: The dexamethasone-sparing regimen provides adequate delayed protection in patients undergoing MEC who are at low risk for delayed symptoms, and can still be discussed for low-risk AC patients as the daily difference in control is modest. Additional dexamethasone doses can be customized on the basis of occurrence or absence of acute symptoms in the first cycle of MEC and even AC.
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Antieméticos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Dexametasona/uso terapéutico , Náusea/inducido químicamente , Vómitos/inducido químicamente , Adulto , Anciano , Antineoplásicos Hormonales/administración & dosificación , Estudios de Cohortes , Dexametasona/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Aberrant cyclin-dependent kinase 2 (CDK2) activation has been identified as a main resistance mechanism to CDK4/6 inhibition in hormone-receptor positive (HR+) breast cancer. Additionally, consistent preclinical evidence states its crucial role in MYC and CCNE1 overexpressed cancer survival, such as triple-negative breast cancers (TNBC), thus representing an appealing and relatively unexplored target treatment opportunity. Despite emerging initial results of novel CDK2 inhibitors (CDK2i) activity, a comprehensive outcomes collection is currently absent from the scientific literature. We aim to provide an overview of ongoing clinical trials involving CDK2i in the context of metastatic breast cancer (mBC), either as monotherapy or in combination with other agents. The review extends beyond CDK2i to encompass novel emerging CDK4 inhibitors, combined CDK2/4/6 inhibitors, and the well-known pan-CDK inhibitors including those specifically directed at CDK2. Delving into the results, we critically appraise the observed clinical efficacy and offer valuable insights into their potential impact and future applications.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/patología , Quinasa 2 Dependiente de la Ciclina , Quinasa 4 Dependiente de la Ciclina , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Puntos de Control del Ciclo Celular , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Quinasa 6 Dependiente de la CiclinaRESUMEN
BACKGROUND: Immunotherapy represented a turning point for treating extensive small-cell lung cancer (ES-SCLC). Although, many issues remain debated. METHODS: A group of Italian medical and radiation oncologists with expertise in managing patients with ES-SCLC developed a list of statements divided in six areas of interest. The Delphi method was used to assess the consensus on the defined list of statements. RESULTS: 32 statements were included in the final list to be voted by the Delphi panel, and 26 reached a consensus on the agreement. A prompt involvement of a multidisciplinary team is a priority to provide an integrated treatment strategy. First-line recommended treatment is immunotherapy in combination with platinum-based chemotherapy and etoposide for four cycles followed by maintenance immunotherapy. CONCLUSIONS: While awaiting new data from clinical trials and real-world studies, these recommendations can represent a useful tool to guide the management of ES-SCLC patients in daily practice.
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Consenso , Técnica Delphi , Inmunoterapia , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/terapia , Carcinoma Pulmonar de Células Pequeñas/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Inmunoterapia/métodos , Italia/epidemiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Manejo de la EnfermedadRESUMEN
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.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Calidad de Vida , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Italia/epidemiología , Proteínas Proto-Oncogénicas p21(ras)/genética , MutaciónRESUMEN
INTRODUCTION: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). METHODS AND OBJECTIVES: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. CONCLUSION: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project.
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Productos Biológicos , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Inteligencia Artificial , Investigación Biomédica Traslacional , Estudios Prospectivos , Estudios Retrospectivos , Leucocitos Mononucleares , Biomarcadores , Terapias en Investigación , Productos Biológicos/uso terapéuticoRESUMEN
OBJECTIVE: The effectiveness of palonosetron without delayed dexamethasone dosing against emesis was investigated in patients scheduled to receive the corticosteroid-containing combination of doxorubicin and paclitaxel (AT) for 3 cycles. METHODS: Chemo-naïve women with breast cancer receiving doxorubicin (60 mg/m(2)) and paclitaxel (200 mg/m(2)) were eligible. Patients received palonosetron 0.25 mg intravenously before chemotherapy, however, all patients also received a premedication consisting of prednisone (25 mg orally the evening before therapy) and hydrocortisone (250 mg intravenously just before paclitaxel). The primary end point was complete control (CC; no vomiting, no rescue anti-emetics, and no more than mild nausea) during the overall phase (days 1-5) following cycle 1. RESULTS: Seventy-six patients were enrolled and evaluable (median age 50 years). Fifty-six patients (74%; 95% CI 62-83%) achieved overall CC. Acute (day 1) and delayed (days 2-5) CC rates were 78 and 74%, respectively. No vomiting rates for the acute, delayed and overall phases were 85, 85 and 83%, respectively. An exploratory analysis showed only a small decrease in the probability of achieving CC between cycle 1 (74%) and cycle 3 (66%). CONCLUSION: The dexamethasone-sparing strategy prevented emesis in more than 70% of breast cancer patients receiving their initial cycle of AT chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Isoquinolinas/uso terapéutico , Náusea/prevención & control , Quinuclidinas/uso terapéutico , Antagonistas de la Serotonina/uso terapéutico , Vómitos/prevención & control , Adulto , Anciano , Antieméticos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estreñimiento/inducido químicamente , Dexametasona/uso terapéutico , Doxorrubicina/administración & dosificación , Femenino , Cefalea/inducido químicamente , Humanos , Isoquinolinas/efectos adversos , Persona de Mediana Edad , Náusea/inducido químicamente , Paclitaxel/administración & dosificación , Palonosetrón , Quinuclidinas/efectos adversos , Antagonistas de la Serotonina/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Vómitos/inducido químicamente , Adulto JovenRESUMEN
AIM: Data from two randomized trials were pooled to further characterize the effectiveness of palonosetron combined with dexamethasone in the setting of highly emetogenic chemotherapy. PATIENTS & METHODS: The analysis included 1411 patients who were randomized to receive palonosetron or ondansetron/granisetron intravenously on day 1 plus either 1-day or 3-day dexamethasone dosing. The primary end point was complete response (no vomiting and no rescue antiemetics over days 1-5) in cycle one. Data across the studies were analyzed by the Mantel-Haenszel method. RESULTS: The vast majority of patients received either cisplatin (62%) or anthracycline plus cyclophosphamide (34%). The palonosetron regimen provided a 12 percentage-point improvement in the rate of overall complete response compared with the control regimen (49.2 vs 37.3%; odds ratio: 1.65; 95% CI: 1.33-2.04; p < 0.0001). The frequency of no delayed nausea at all daily periods was consistently higher in the palonosetron group. CONCLUSION: The current analysis confirmed that palonosetron plus dexamethasone improved control of highly emetogenic chemotherapy-induced nausea and vomiting throughout 5 days postchemotherapy to a significantly greater extent than the combination including older 5-HT3 antagonists.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/uso terapéutico , Isoquinolinas/uso terapéutico , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Neoplasias/complicaciones , Quinuclidinas/uso terapéutico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Palonosetrón , Resultado del TratamientoRESUMEN
INTRODUCTION/BACKGROUND: This single-arm, phase 2, multi-center, study aims to assess the safety and efficacy of a regimen of induction chemo-immunotherapy followed by de-intensified, hypo-fractionated thoracic radiotherapy (RT) given concurrently with durvalumab and maintenance durvalumab in patients with unresectable, stage III NSCLC. MATERIAL AND METHODS: we will enroll 45 patients with unresectable stage III NSCLC, any PD-L1, deemed ineligible for concurrent CRT by a thoracic oncology multidisciplinary team, and candidate to sequential chemoradiation followed by durvalumab. RESULTS: Primary endpoint is safety, defined by the incidence of grade 3 and 4 possibly related adverse events (PRAEs) within 6 months from the initiation of treatment. The secondary objectives are PFS and OS (median and 12 months). Ancillary endpoints are molecular response evaluated by cfDNA isolation baseline, after chemo-immuno RT and at progression, and radiomics analysis on CT scans at baseline and before maintenance. CONCLUSION: DEDALUS phase 2 trial explores the safety and efficacy of a novel sequence of chemo-radiation (with de-intensified RT) plus the anti-PD-L1 agent durvalumab in patients with stage III unresectable NSCLC who are candidates to sequential chemoradiation plus maintenance immunotherapy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapia , Inmunoterapia , Quimioradioterapia , Quimioterapia de Inducción , Carcinoma de Pulmón de Células no Pequeñas/terapiaRESUMEN
BACKGROUND AND RATIONALE: Novel coronavirus-related disease (COVID-19) has profoundly influenced hospital organization and structures worldwide. In Italy, the Lombardy Region, with almost 17% of the Italian population, rapidly became the most severely affected area since the pandemic beginning. The first and the following COVID-19 surges significantly affected lung cancer diagnosis and subsequent management. Much data have been already published regarding the therapeutic repercussions whereas very few reports have focused on the consequences of the pandemic on diagnostic procedures. METHODS: We, here, would like to analyze data of novel lung cancer diagnosis performed in our Institution in Norther Italy where we faced the earliest and largest outbreaks of COVID-19 in Italy. RESULTS: We discuss, in detail, the strategies developed to perform biopsies and the safe pathways created in emergency settings to protect lung cancer patients in subsequent therapeutic phases. Quite unexpectedly, no significant differences emerged between cases enrolled during the pandemic and those before, and the two populations were homogeneous considering the composition and diagnostic and complication rates. CONCLUSIONS: By pointing out the role of multidisciplinarity in emergency contexts, these data will be of help in the future for designing tailored strategies to manage lung cancer in a real-life setting.
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COVID-19 , Neoplasias Pulmonares , Humanos , Biopsia con Aguja Fina/métodos , Pandemias , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X , Prueba de COVID-19RESUMEN
BACKGROUND: Growing evidence suggests that sublobar resections offer more favorable outcomes than lobectomy in early-stage lung cancer surgery. However, a percentage of cases that cannot be ignored develops disease recurrence irrespective of the surgery performed with curative intent. The goal of this work is thus to compare different surgical approaches, namely, lobectomy and segmentectomy (typical and atypical) to derive prognostic and predictive markers. PATIENTS AND METHODS: Here we analyzed a cohort of 153 NSCLC patients in clinical stage TNM I who underwent pulmonary resection surgery with a mediastinal hilar lymphadenectomy from January 2017 to December 2021, with an average follow-up of 25.5 months. Partition analysis was also applied to the dataset to detect outcome predictors. RESULTS: The results of this work showed similar OS between lobectomy and typical and atypical segmentectomy for patients with stage I NSCLC. In contrast, lobectomy was associated with a significant improvement in DFS compared with typical segmentectomy in stage IA, while in stage IB and overall, the two treatments were similar. Atypical segmentectomy showed the worst performance, especially in 3-year DFS. Quite unexpectedly, outcome predictor ranking analysis suggests a prominent role of smoking habits and respiratory function, irrespective of the tumor histotype and the patient's gender. CONCLUSIONS: Although the limited follow-up interval cannot allow conclusive remarks about prognosis, the results of this study suggest that both lung volumes and the degree of emphysema-related parenchymal damage are the strongest predictors of poor survival in lung cancer patients. Overall, these data point out that greater attention should be addressed to the therapeutic intervention for co-existing respiratory diseases to obtain optimal control of early lung cancer.
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We investigated the association of T1/T2 mapping values with programmed death-ligand 1 protein (PD-L1) expression in lung cancer and their potential in distinguishing between different histological subtypes of non-small cell lung cancers (NSCLCs). Thirty-five patients diagnosed with stage III NSCLC from April 2021 to December 2022 were included. Conventional MRI sequences were acquired with a 1.5 T system. Mean T1 and T2 mapping values were computed for six manually traced ROIs on different areas of the tumor. Data were analyzed through RStudio. Correlation between T1/T2 mapping values and PD-L1 expression was studied with a Wilcoxon-Mann-Whitney test. A Kruskal-Wallis test with a post-hoc Dunn test was used to study the correlation between T1/T2 mapping values and the histological subtypes: squamocellular carcinoma (SCC), adenocarcinoma (ADK), and poorly differentiated NSCLC (PD). There was no statistically significant correlation between T1/T2 mapping values and PD-L1 expression in NSCLC. We found statistically significant differences in T1 mapping values between ADK and SCC for the periphery ROI (p-value 0.004), the core ROI (p-value 0.01), and the whole tumor ROI (p-value 0.02). No differences were found concerning the PD NSCLCs.
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IMPORTANCE: After the PACIFIC trial, concurrent chemo-radiotherapy followed by consolidation therapy with durvalumab for 1 year (limited to PD-L1 tumour proportion score ≥ 1% in the EMA region) is the firmly established standard of care treatment for unresectable NSCLC patients. Several relevant questions are emerging with the growing use of this approach, posing novel challenges in clinical practice. Treatment of oncogene-addicted NSCLCs, management of mediastinal disease recurrence after surgery and the optimal management of patients progressing during or after durvalumab are now some of the most clinically relevant issues. OBSERVATIONS: Patients with unresectable NSCLC harbouring EGFR and HER2 mutations or ALK/ROS1/RET /NTRK1,2,3 rearrangements are unresponsive to immunotherapy. Importance of knowing the tumour genotyping (NGS, preferable DNA and RNA) from the earliest stages of NSCLC, also for the possible use of immunotherapy both in the adjuvant and perioperative setting. In case of mediastinal disease recurrence after surgery, re-biopsy is essential to re-determine the histological and biological characteristics of the disease and the distinction of recurrence in curable and non-curable disease is of pivotal important for the optimal management of subsequent treatments. CONCLUSIONS AND RELEVANCE: Treatment of stage III NSCLC has always been controversial and challenging: Multidisciplinary approach is mandatory and defining resectability is a critical issue. Chemo-radiotherapy followed by maintenance Durvalumab is now the standard of treatment. Herein, we provide a comprehensive overview of the key challenges and open questions that we are currently facing in clinical practice, in unresectable stage III and in early-stage NSCLC, identifying the knowledge gaps and the possible solutions.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Oncólogos de Radiación , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas , Recurrencia Local de Neoplasia , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapiaRESUMEN
Pleural mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. Here, we review all these aspects to underline the progress being made in its investigation and to emphasize how much work remains to be carried out to improve prognosis and treatment.
RESUMEN
BACKGROUND: The non-inferiority of palonosetron plus 1-day versus 3-day dexamethasone in preventing chemotherapy-induced nausea and vomiting (CINV) due to moderately emetogenic chemotherapy (MEC) has been previously demonstrated. OBJECTIVE: The objectives of this prespecified post hoc analysis were to demonstrate the non-inferiority hypothesis in an adjusted model for known risk factors (age, gender, alcohol consumption, and type of MEC [anthracycline plus cyclophosphamide (AC)-based versus other MEC]) for CINV and to explore the impact on antiemetic outcome of these risk factors. METHODS: Chemonaive patients (n = 324) with solid tumors were randomized to receive palonosetron 0.25 mg IV plus dexamethasone 8 mg IV on day 1 of chemotherapy or the same regimen followed by oral dexamethasone 8 mg on days 2 and 3. The primary end point was complete response (CR, no emesis and no rescue antiemetics) during the 5-day study period. A modified intention-to-treat approach was used for multivariable analysis. RESULTS: Non-inferiority of the 1-day regimen was confirmed even after adjusting for risk factors (risk difference -4.4%, 95% CI -14.1% to 5.4%; P = .381). Only age less than 50 years (P = .044) independently predicted a poor outcome of antiemetic treatment. However, most of the younger patients were women (1-day regimen 81.8%, 3-day regimen 88.4%) who underwent AC-based chemotherapy (1-day regimen 61.1%, 3-day regimen 71.0%). There were no significant between-treatment differences in the CR rate according to risk factors. CONCLUSION: This analysis confirmed that the 1-day regimen provides a valid treatment option for prevention of CINV in delayed, non-AC-based MEC.
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Antieméticos/administración & dosificación , Dexametasona/administración & dosificación , Isoquinolinas/administración & dosificación , Náusea/prevención & control , Quinuclidinas/administración & dosificación , Agonistas de Receptores de Serotonina/administración & dosificación , Vómitos/prevención & control , Factores de Edad , Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Dexametasona/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Isoquinolinas/uso terapéutico , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Palonosetrón , Quinuclidinas/uso terapéutico , Factores de Riesgo , Agonistas de Receptores de Serotonina/uso terapéutico , Vómitos/inducido químicamenteRESUMEN
Surgery is part of a multimodal therapeutic approach to malignant pleural mesothelioma (MPM) although its real beneficial effect is still controversial. The optimal precise sequence of treatments within the trimodality is unclear, and should be decided upon a multidisciplinary consensus for each individual patient. Here, we analyzed the perioperative data of 19 MPM patients who underwent extended pleurectomy/decortication (EPD) with curative intent. The mean age at diagnosis was 67 years; 11 males and eight females. Ten patients were diagnosed with MPM via medical thoracoscopy (MT), and nine via video-assisted thoracoscopic surgery (VATS). The vast majority of cases harbored epitheliod forms. We compared neoadjuvant chemotherapy (NCT) followed by surgery (11 cases) versus surgery followed by adjuvant chemotherapy (ACT, 8 cases) within a 3-year period. All patients had extended pleurectomy/decortication and none had an extended pneumonectomy. Analysis of survival curves suggested that the short-term outcomes are better with upfront EDP followed by ACT if compared to EDP preceded by NCT. Although limited, the data highlighted the safety and feasibility of EPD, with manageable postoperative complications and no major burden for the patients.