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KRAS mutations occur in approximately 30% of lung adenocarcinomas, mainly in codon 12 (83% of cases), p.G12C being the prevalent one (40%), followed by p.G12V and p.G12D (22 and 16%, respectively). Treatment options for advanced KRAS mutant non-small-cell lung cancer (KRAS-MT NSCLC) are limited to chemotherapy and immune checkpoint inhibitors (CPIs). However, clinical trials exploring specific targeted agents are expected to change the treatment landscape of this disease. Here, we describe the design and scientific rationale of the randomized, phase II, open label, RAMP-202 study, which will evaluate the efficacy and safety of VS-6766 versus VS-6766 in combination with defactinib in advanced KRAS-MT NSCLC patients after failure of prior platinum-based chemotherapy and CPI.
The alteration of KRAS gene occurs in approximately 30% of lung cancers. According to international guidelines, treatment options for patients with advanced KRAS mutant lung cancer are now limited to chemotherapy and immunotherapy. However, clinical trials are exploring how specific targeted agents are expected to change the treatment landscape of this disease. Here, we describe the design and scientific rationale of the RAMP-202 study, which will evaluate the efficacy and safety of two new biological agents for patients with KRAS mutant lung cancer. The enrolled patients were those who had failure of prior platinum-based chemotherapy and immunotherapy. Clinical Trial Registration: NCT04620330 (ClinicalTrials.gov).
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Benzamidas , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos Fase II como Assunto , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Pirazinas , SulfonamidasRESUMO
BACKGROUND LY3023414 is a selective, ATP competitive inhibitor of class I PI3K isoforms, mTORC1/2 and DNA-PK. A Phase 1 dose escalation, 200 mg twice daily (BID) of LY3023414 was the determined recommended phase 2 dose (RP2D). We report the antitumor activity and safety of LY3023414 monotherapy in patients with advanced mesothelioma.METHODS Patients enrolled had advanced malignant pleural or peritoneal mesothelioma with measurable disease, ECOG PS 0-1, were refractory or ineligible to receive standard therapies. Patients received LY3023414 200 mg BID. This dose expansion cohort is intended to evaluate preliminary antitumor activity of LY3023414 by overall response rate. Safety, tolerability and pharmacokinetics were assessed. Biomarkers associated with treatment response was an exploratory endpoint. RESULTS Forty-two patients received LY3023414 for a median duration of 11.2 weeks (range: 1.1-53.0). One patient had a confirmed partial response (PR) (ORR 2.4%). Three patients had an unconfirmed PR. Seventeen patients had stable disease (SD) (DCR 43%). Most common adverse events (AEs) included fatigue (43%), nausea (43%), decreased appetite (38%), vomiting (33%), and diarrhea (29%). AEs were mostly mild or moderate. Grade ≥ 3 AEs were reported for 21% of patients with fatigue as the most frequent event (10%). Alterations of BAP1 were identified in 11/19 patients as the most common molecular aberration, followed by SETD2 and NF2 alterations. No obvious pattern of genetic changes/mutations in single genes or pathways was associated with anti-tumor activity. CONCLUSION LY3023414 monotherapy (200 mg BID) demonstrated an acceptable and manageable safety profile with limited single-agent activity in patients with advanced mesothelioma. ClinicalTrials.gov identifier: NCT01655225; Date of registration: 19 July 2012.
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Antineoplásicos/administração & dosagem , Mesotelioma/tratamento farmacológico , Piridinas/administração & dosagem , Quinolonas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Inibidores de Fosfoinositídeo-3 Quinase/administração & dosagem , Inibidores de Fosfoinositídeo-3 Quinase/efeitos adversos , Piridinas/efeitos adversos , Quinolonas/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Resultado do TratamentoRESUMO
LESSONS LEARNED: NGR-hTNF was safely combined with doxorubicin, showing a promising antitumor activity in unselected patients with relapsed small cell lung cancer.Similar antitumor activity was observed in platinum-sensitive and platinum-resistant patient cohorts. BACKGROUND: Relapsed small cell lung cancer (SCLC) patients have limited treatment options and poor outcomes. NGR-hTNF is a vascular-targeting agent, which increases intratumoral chemotherapy penetration and T-lymphocyte infiltration. METHODS: Twenty-eight patients relapsing after at least one platinum-based regimen with a treatment-free interval shorter (n = 16; platinum-resistant) or longer (n = 12; platinum-sensitive) than 3 months received NGR-hTNF 0.8 µg/m2 plus doxorubicin 75 mg/m2 every 3 weeks. The primary endpoint of this single-arm phase II trial was progression-free survival (PFS), and safety, response rate, and survival were secondary endpoints. RESULTS: The most common grade 3-4 toxicities were neutropenia (53%) and anemia (21%). Median PFS was 3.2 months for all patients, 2.7 months for platinum-resistant patients, and 4.1 months for platinum-sensitive patients. Seven patients had partial responses (25%), including four (25%) with platinum-resistant and three (25%) with platinum-sensitive relapse. Mean changes from baseline in tumor burden (after two, four, and six cycles) did not differ between platinum-resistant (-9%, -29%, and -32%) and platinum-sensitive (-11%, -20%, and -43%) cohorts. Overall survival was associated only with baseline lymphocyte counts, with median survival times of 13.1 and 5.2 months for lymphocyte counts above or below the median, respectively. CONCLUSION: NGR-hTNF plus doxorubicin showed manageable toxicity and promising activity in patients with relapsed SCLC.
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Doxorrubicina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Fator de Necrose Tumoral alfa/uso terapêutico , Adulto , Idoso , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Proteínas Recombinantes de Fusão/efeitos adversos , Fator de Necrose Tumoral alfa/efeitos adversosRESUMO
AIM: Ceritinib was evaluated within a compassionate use program of Italian patients. PATIENTS & METHODS: 70 patients with anaplastic lymphoma kinase-positive crizotinib-refractory advanced non-small-cell lung cancer received ceritinib. RESULTS: Overall response was 40.6%, median progression-free survival was 8.2 months and median survival was 15.5 months. Dose reduction due to treatment-related adverse events occurred in 50.8% of patients starting at 750 mg/day. No significantly different progression-free survival was observed between patients who underwent any time dose reduction (n = 38) versus those who remained on the recommended dose of 750 mg/day (n = 32; p = 0.07). CONCLUSION: The efficacy of ceritinib compassionate use program resembled that of clinical trials. Dose reductions and adjustments did not appear to negatively affect clinical outcome.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Receptores Proteína Tirosina Quinases/genética , Sulfonas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios de Uso Compassivo , Crizotinibe , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Rearranjo Gênico , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Pirimidinas/efeitos adversos , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Sulfonas/efeitos adversosRESUMO
Lung cancer is the leading cause of cancer-related mortality worldwide in both sexes, expected to account, in the near future, for more than 30% of all cancer-related deaths. Recently, improvements in the systemic therapy of non-small-cell lung cancer according to histology and tumor molecular characteristics led to a progressive prolongation of survival, more clinically meaningful in selected groups of patients with tumors harboring specific genomic alterations. As the search for individualized therapeutic approaches could represent one of the potential ways to improve survival expectancy of non-small-cell lung cancer patients with advanced disease stage, the aim of this review is to discuss how currently to select the best front-line therapeutic strategy.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
PURPOSE: Treatment of homologous recombination repair-deficient (HRD)-tumors with PARP inhibitors has the potential to further increase tumor immunogenicity, suggesting a synergistic effect with immunotherapy. Here we present the preliminary results of niraparib in combination with dostarlimab for pleural mesothelioma (PM) or non-small cell lung cancer (NSCLC) harboring HRR mutations. PATIENTS AND METHODS: UNITO-001 is a phase II, prospective, study aiming to investigate the combination of niraparib plus dostarlimab in pretreated patients with HRD and programmed death ligand-1 (PD-L1) ≥1% NSCLC and/or PM. The primary endpoint is progression-free survival (PFS). RESULTS: Seventeen of 183 (10%) screened patients (12 PM and 5 NSCLC) were included. The objective response rate (ORR) was 6% [95% confidence interval (CI): 0.1-28.7] and the disease control rate (DCR) was 53% (95% CI: 27.8-77). Median PFS was 3.1 (95% CI: 2.7-N.A) and median overall survival (OS) was 4.2 (95% CI: 1.58-NA) months. The PFS was 14.1 months in one PM patient harboring a germline BAP1 mutation. The treatment duration was 9.8 months in one PM patient harboring a somatic BRCA2 mutation. The most common adverse events (AE) were grade 1-2 lymphopenia (59%), anemia (35%), hyponatremia (29%), and hypokalemia (29%). Grade ≥3 AEs were reported in 23% of the patients. CONCLUSIONS: This preliminary analysis highlighted the lack of antitumor activity for the combination of niraparib and dostarlimab in patients with PM and/or advanced NSCLC harboring BAP1 somatic mutations. A potential antitumor activity emerged for PM with germline BAP1 and/or BRCA2 somatic mutations along with a good tolerability profile.
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Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Indazóis , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Piperidinas , Neoplasias Pleurais , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Reparo de DNA por Recombinação , Estudos Prospectivos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , MutaçãoRESUMO
INTRODUCTION: Germline pathogenic mutations in TP53 gene are associated with a cancer predisposition syndrome known as Li Fraumeni syndrome. Albeit infrequently, non-small cell lung cancer, especially as oncogene-addicted disease, may be diagnosed in young patients with Li Fraumeni syndrome. CASE DESCRIPTION: We report three cases of patients affected by Li Fraumeni syndrome who developed non-small cell lung cancer with EGFR or HER2 exon 20 insertions. The first patient suffered from liposarcoma and, then, brain metastases from HER2-mutated non-small cell lung cancer: after stereotactic radiotherapy, he benefited from enrollment in a clinical trial with a HER2-targeted therapy. The second young patient was a female with personal history of rhabdomyosarcoma, diagnosed with brain metastases from EGFR-mutated non-small cell lung cancer: enrollment in a clinical trial led to a temporary clinical benefit. The last case was a female diagnosed with breast carcinoma, ovarian granulosa cell tumor and advanced EGFR-mutated non-small cell lung cancer at a young age. CONCLUSIONS: Young patients affected by oncogene-addicted non-small cell lung cancer and with a positive familial cancer history should be referred for an accurate genetic counselling to look for Li Fraumeni syndrome. The underlying molecular connection between TP53 and HER family receptor tyrosine kinases remains unclear, but an extensive molecular characterization of tumors from patients with Li Fraumeni syndrome should always be performed, to offer patients a personalized therapeutic approach.
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Environmental and occupational exposures have been associated with an increased risk of different types of cancers, although the exact mechanisms of higher carcinogenesis risk are not always well understood. Lung cancer is the leading cause of global cancer mortality, and, also, genitourinary neoplasms are among the main causes of cancer-related deaths in Western countries. The purpose of this review is to describe the main environmental and occupational factors that increase the risk of developing lung and genitourinary cancers and to investigate carcinogenesis mechanisms that link these agents to cancer onset. Further objectives are to identify methods for the prevention or the early detection of carcinogenic agents and, therefore, to reduce the risk of developing these cancers or to detect them at earlier stages.
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Lung cancer represent the leading cause of cancer mortality, so several efforts have been focused on the development of a screening program. To address the issue of high overdiagnosis and false positive rates associated to LDCT-based screening, there is a need for new diagnostic biomarkers, with liquid biopsy ncRNAs detection emerging as a promising approach. In this scenario, this work provides an updated summary of the literature evidence about the role of non-coding RNAs in lung cancer screening. A literature search on PubMed was performed including studies which investigated liquid biopsy non-coding RNAs biomarker lung cancer patients and a control cohort. Micro RNAs were the most widely studied biomarkers in this setting but some preliminary evidence was found also for other non-coding RNAs, suggesting that a multi-biomarker based liquid biopsy approach could enhance their efficacy in the screening context. However, further studies are needed in order to optimize detection techniques as well as diagnostic accuracy before introducing novel biomarkers in the early diagnosis setting.
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Safety data regarding BNT162b2 in cancer patients (CPs) are scarce. Herein we report the side effects (SEs), the adverse events (AEs), and the patient-reported outcomes (PROs) following BNT162b2 administration in CPs treated at the San Luigi Gonzaga University Hospital. All CPs who agreed to participate in our vaccination campaign received BNT162b2 and were included in the descriptive analysis. An anonymous questionnaire investigating the occurrence of SEs/AEs and PROs was administered to the study population 21 days after the first dose. Pearson's chi-squared test was used to estimate the risk of experiencing SEs/AEs according to selected variables. A total of 997 patients were included in the study: 62.0% had stage IV cancer, and 68.8% were receiving an active treatment, of whom 15.9% were receiving immunotherapy. SEs/AEs were recorded in 37.1% of cases after the first dose and in 48.5% of cases after the second dose. The most common SEs were muscle pain/local rash (27.9% and 28%, after the first and second dose, respectively). Patients older than 70 years showed lower risk of SEs/AEs, while women showed a higher risk. Before receiving the vaccine, 18.2% of patients felt fearful and/or insecure about the vaccination. After the first dose, 57.5% of patients changed their feelings positively. Our data support the short-term safety of BNT162b2 in CPs, regardless of disease stage and concurrent treatments. Overall, the vaccination showed a positive impact on quality of life.
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INTRODUCTION: US National Cancer Institute's (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) is a library of 78 symptom terms and 124 items enabling patient reporting of symptomatic adverse events in cancer trials. This multicenter study used mixed methods to develop an Italian language version of this widely accepted measure, and describe the content validity and reliability in a diverse sample of Italian-speaking patients. METHODS: All PRO-CTCAE items were translated in accordance with international guidelines. Subsequently, the content validity of the PRO-CTCAE-Italian was explored and iteratively refined through cognitive debriefing interviews. Participants (n=96; 52% male; median age 64 years; 26% older adults; 18% lower educational attainment) completed a PRO-CTCAE survey and participated in a semi-structured interview to determine if the translation captured the concepts of the original English language PRO-CTCAE, and to evaluate comprehension, clarity and ease of judgement. Test-retest reliability of the finalized measure was explored in a second sample (n=135). RESULTS: Four rounds of cognitive debriefing interviews were conducted. The majority of PRO-CTCAE symptom terms, attributes and associated response choices were well-understood, and respondents found the items easy to judge. To improve comprehension and clarity, the symptom terms for nausea and pain were rephrased and retested in subsequent interview rounds. Test-retest reliability was excellent for 41/49 items (84%); the median intraclass correlation coefficient was 0.83 (range 0.64-0.94). DISCUSSION: Results support the semantic, conceptual and pragmatic equivalence of PRO-CTCAE-Italian to the original English version, and provide preliminary descriptive evidence of content validity and reliability.
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Neoplasias , Estados Unidos , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Feminino , Autorrelato , Reprodutibilidade dos Testes , National Cancer Institute (U.S.) , Neoplasias/psicologia , Medidas de Resultados Relatados pelo Paciente , Inquéritos e Questionários , SemânticaRESUMO
INTRODUCTION: Advanced stage malignant mesothelioma (asMM) patients have poor prognosis. Several trials investigated the role of programmed cell death protein-1 (PD-1) and its ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) in pre-treated asMM. METHODS: A systematic review of the literature of clinical trials testing single-agent anti PD-1/PD-L1 ICIs in pre-treated asMM was performed. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) data were extracted. The predictive role of PD-L1 was assessed. RESULTS: We selected 13 studies including 888 patients. ORR and DCR were 18.1% (95% confidence interval [CI] 13.9-22.8%) and 55.4% (95% CI: 48.1-62.5%), respectively. Median PFS and OS ranged from 2.1 to 5.9 and from 6.7 to 20.9 months, respectively. ORR according to PD-L1 was 27.0% (95% CI: 18.7-36.2%). CONCLUSIONS: Anti-PD-(L)1 ICIs might be considered a treatment option for chemotherapy-resistant asMM, even if reliable predictive factors are still lacking.
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Neoplasias Pulmonares , Mesotelioma Maligno , Antígeno B7-H1 , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/patologia , Mesotelioma Maligno/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Intervalo Livre de ProgressãoRESUMO
BACKGROUND: Lung cancer (LC) tissue for immunological characterization is often scarce. We explored and compared T cell characteristics between broncho-alveolar lavage from tumor affected (t-BAL) and contralateral lung (cl-BAL), with matched peripheral blood (PB). METHODS: BAL and PB were collected during bronchoscopy for diagnostic and/or therapeutic purposes in patients with monolateral primary lesion. RESULTS: Of 33 patients undergoing BAL and PB sampling, 21 had histologically-confirmed LC. Most cases were locally-advanced or metastatic non-small cell LC. T cell characteristics were not significantly different in t-BAL vs. cl-BAL. Compared to PB, CD8 T cells in BAL presented features of immune activation and exhaustion (high PD-1, low IFN-g production). Accordingly, regulatory CD4 T cells were also higher in BAL vs. PB. When dichotomizing T cell density in t-BAL in high and low, we found that PD-L1 expression in LC was associated with T cell density in t-BAL. T-BAL with high T cell density had higher %IFN-g+CD8 T cells and lower %T-regs. CONCLUSION: In BAL from advanced LC patients, T cells present features of exhaustion. T cells in t-BAL could be the best surrogate of tumor-infiltrating T cell, and future studies should evaluate T cell phenotype and density as potential biomarkers for cancer immunotherapy outcome.
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Neoplasias Pulmonares , Subpopulações de Linfócitos T , Humanos , Antígeno B7-H1/metabolismo , Líquido da Lavagem Broncoalveolar , Interferon gama/metabolismo , Neoplasias Pulmonares/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Subpopulações de Linfócitos T/imunologiaRESUMO
We are witnessing a silent revolution in the treatment of early stage non-small cell lung cancer (NSCLC), with a series of practice-changing clinical trials enriching the therapeutic perspectives of lung cancer patients with potentially curable disease. The ADAURA study marked the advent of precision medicine and biomarker testing to the early stages setting. The IMPower-010 trial interrupted the negative trend of adjuvant lung cancer immunotherapy, paving the way to the application of immune-checkpoint inhibition in the resected disease. The ITACA trial definitively established no role for tailored adjuvant chemotherapy in NSCLC, while the Lung Art data questioned the efficacy of post-operative radiotherapy for pN2 resected disease. Growing evidence is supporting MRD as effective adjuvant prognostic biomarker to stratify disease's recurrence risk after radical interventions and select best candidates to the adjuvant strategies. This work summarizes the recent major breakthroughs in lung cancer adjuvant treatment, and provides a snapshot of the current real-world scenario, discussing the upcoming challenges and opportunities featuring the clinical management of early stage NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Quimioterapia Adjuvante , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares , Protocolos Antineoplásicos/classificação , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/tendências , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Estadiamento de NeoplasiasRESUMO
PURPOSE: COVID-19 cancer patients (C19-CP) represent a population at high risk for mortality, whose clinical characteristics are still unknown in the second SARS-CoV-2 wave. The aim of this retrospective study was to compare epidemiology and clinical presentation of C19-CP referring to the emergency department (ED) of our institution (San Luigi Gonzaga University Hospital, Orbassano, Turin, Italy), in a 3-week observation period of the first and second COVID-19 waves, starting from the introduction of the corresponding national lockdowns. METHODS: We retrieved ED admissions from March 9 to 29, 2020, for the first wave, and from October 24 to November 13, 2020, for the second wave. We collected clinical characteristics of consecutive patients with molecularly confirmed SARS-CoV-2 infection. We also considered untested or SARS-CoV-2-negative cancer patients referring to the ED in the reference time frames. RESULTS: C19-CP in the second wave exceeded those in the first wave despite the nonsignificant difference (39 of 576 v 8 of 163; P = .5). Compared with nononcological patients, C19-CP were older (median age 70 years [interquartile range 61-77] v 60 years [interquartile range 45-73]; P = .02) and presented more often with ≥ 2 comorbidities (40.4% v 24.3%; P = .02). Compared with nononcological patients, in C19-CP, respiratory failure (29 of 47 v 321 of 692; P = .049) and hospitalization (37 of 47 v 363 of 692; P = .0004) were higher, with comparable frequencies across the waves. Five of 24 and 10 of 27 hospitalized cancer patients in the first and second waves developed SARS-CoV-2 infection during hospitalization. CONCLUSION: C19-CP were a vulnerable population, irrespective of the COVID-19 waves. This highlights the need to prioritize vaccinations in oncological patients to safeguard and guarantee optimal anticancer care.
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COVID-19 , Neoplasias , Idoso , Controle de Doenças Transmissíveis , Serviço Hospitalar de Emergência , Hospitais Universitários , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Estudos Retrospectivos , SARS-CoV-2RESUMO
The PACIFIC trial marked a new era in the treatment of stage III unresectable NSCLC, establishing durvalumab consolidation as new standard of care worldwide, with about 14 % increase of long-term survival and half of the patients alive at 4 years. A series of intensified immune-checkpoint inhibition regimens are currently under investigation in clinical trials in order to optimize the therapeutic benefit obtained in this population, while the identification of personalized approaches as well as the development of effective treatments in the post-durvalumab progression setting represent an actual and controversial topic for clinical lung cancer research. This review describes the current real-word treatment scenario for stage III unresectable NSCLC in Italy, and provides an updated overview of the upcoming therapeutic strategies under clinical investigation, discussing the most relevant challenges and opportunities featuring the post-PACIFIC era.
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Antineoplásicos Imunológicos , Neoplasias Pulmonares , Antineoplásicos Imunológicos/uso terapêutico , Quimiorradioterapia , Humanos , Inibidores de Checkpoint Imunológico , Itália , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
BACKGROUND: Oxidative stress is a hallmark of many cancers. The increment in reactive oxygen species (ROS), resulting from an increased mitochondrial respiration, is the major cause of oxidative stress. Cell fate is known to be intricately linked to the amount of ROS produced. The direct generation of ROS is also one of the mechanisms exploited by common anticancer therapies, such as chemotherapy. METHODS: We assessed the role of NFKBIA with various approaches, including in silico analyses, RNA-silencing and xenotransplantation. Western blot analyses, immunohistochemistry and RT-qPCR were used to detect the expression of specific proteins and genes. Immunoprecipitation and pull-down experiments were used to evaluate protein-protein interactions. RESULTS: Here, by using an in silico approach, following the identification of NFKBIA (the gene encoding IκBα) amplification in various cancers, we described an inverse correlation between IκBα, oxidative metabolism, and ROS production in lung cancer. Furthermore, we showed that novel IκBα targeting compounds combined with cisplatin treatment promote an increase in ROS beyond the tolerated threshold, thus causing death by oxytosis. CONCLUSIONS: NFKBIA amplification and IκBα overexpression identify a unique cancer subtype associated with specific expression profile and metabolic signatures. Through p65-NFKB regulation, IκBα overexpression favors metabolic rewiring of cancer cells and distinct susceptibility to cisplatin. Lastly, we have developed a novel approach to disrupt IκBα/p65 interaction, restoring p65-mediated apoptotic responses to cisplatin due to mitochondria deregulation and ROS-production.
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Morte Celular/genética , Neoplasias Pulmonares/genética , Inibidor de NF-kappaB alfa/uso terapêutico , Estresse Oxidativo/genética , Humanos , Neoplasias Pulmonares/patologia , Inibidor de NF-kappaB alfa/farmacologiaRESUMO
This study investigated the clinical management of non small cell lung cancer (NSCLC) patients during the first wave of coronavirus disease 2019 (COVID-19) outbreak in Italy. A 29-questions survey was sent to 95 Italian thoracic oncologists, with 77 % of them declaring significant changes in the outpatients management and treatment. The results of this survey pointed out a significant delay of lung cancer diagnosis along with a relevant reduction of patients' accrual within clinical trials. Telemedicine emerged as a valid support for patient-healthcare interactions. Therapeutic indications followed the guidelines for adjuvant chemotherapy and concurrent chemo-radiation. Clinical indications to first-line therapies were largely confirmed, while major changes regarded the selection of second line treatment options as well as the management of elderly population. This work may represent a valid source of information to improve the clinical management of NSCLC patients during second wave of COVID-19 pandemic.
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COVID-19 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , COVID-19/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Humanos , Itália/epidemiologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Pandemias , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
Being lung cancer the main cause of cancer-related mortality worldwide, mainly dependent on tobacco consumption, fighting the tobacco epidemic and concretely acting in terms of prevention represents a current urgent need. Indeed, it has become clear that the significant reduction in tobacco consumption would result in the prevention of a large fraction of lung cancer cases and other smoking-related diseases. Women Against Lung Cancer in Europe (WALCE) is a non-profit European organisation with more than 10 years of experience, whose mission is promoting communication strategies and awareness initiatives, customized on recipients age, to aware public opinion and decision makers on damages of smoking on health and spreading accurate and updated information in order to support people affected by lung cancer and their caregivers. In this review we will provide a summary of WALCE commitment and experience in the field of smoking cessation and lung cancer prevention.
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Background: The world, and Italy on the front lines, has experienced a major medical emergency due to the novel coronavirus outbreak. Cancer patients are one of the potentially most vulnerable cohorts of people, but data about their management are still few. Patients and Methods: In this monocentric retrospective study we included all SARS-CoV-2 oncological patients accepted, between March 27th and April 19th 2020, at the Onco-COVID Unit at San Luigi Gonzaga Hospital, one of the few Italian oncological-COVID wards. Data were obtained from medical records. Results: Eighteen cancer patients with COVID-19 were included. The mean (±SD) age of patients was 67 ± 14 years, 89% were men. Seven (39%) developed infection in communities and 11 (61%) during hospitalization. Lung cancer was the most frequent type of cancer (10, 56%). Seven patients (39%) were symptomatic for COVID-19 at the time of diagnosis and symptoms began 2 (±2) days before. The most common were shortness of breath and diarrhea. Fever was present in 5 patients (28%). Among the 11 asymptomatic patients, 8 (73%) became symptomatic during the hospitalization (mean time of symptoms onset 4 days ±4). Six patients (33%) were on active anti-tumor treatment: 2 (33%) received anti-tumor therapy within 2 weeks before the infection diagnosis and 2 (33%) continued oncological treatment after SARS-CoV-2 positivity. Eight (44%) patients died within a mean of 12 days (±8) from the infection diagnosis. Conclusions: Our series confirms the high mortality among cancer patients with COVID-19. The presence of asymptomatic cases evidences that typical symptoms and fever are not the only parameters to suspect the infection. The Onco-Covid unit suggests the importance of a tailored and holistic approach, even in this difficult situation.