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BACKGROUND: Although polypharmacy has been described among cancer patients, very few studies have focused on those with lung cancer. We aimed to assess whether polypharmacy and comorbidity have an impact on systemic parenteral treatment administration and survival among lung-cancer patients. METHODS: In this retrospective monocenter cohort study, we included patients hospitalized in thoracic oncology for the first time between 2011 and 2015. The Elixhauser score was used to assess comorbidity and polypharmacy was estimated with a threshold of at least five prescribed medications. The Fine and Gray competitive risk model was used to estimate the impact of polypharmacy and comorbidity on systemic parenteral treatment administration within the first two months of hospitalization. The effect of comorbidity and polypharmacy on overall survival was evaluated by Cox proportional hazards analysis. RESULTS: In total, 633 patients were included (71% men), with a median age of 66 years. The median Elixhauser score was 6 and median overall survival was four months. Among the patients, 24.3% were considered to be receiving polypharmacy, with a median number of medications of 3, and 49.9% received systemic parenteral treatment within two months after hospitalization. Severe comorbidity (Elixhauser score > 11), but not polypharmacy, was independently associated with a lower rate of systemic parenteral treatment prescription (SdHR = 0.4 [0.3;0.6], p < 0.01) and polypharmacy, but not a high comorbidity score, was independently associated with poorer four-month survival (HR = 1.4 [1.1;1.9], p < 0.01) CONCLUSIONS: This first study to evaluate the consequences of comorbidity and polypharmacy on the care of lung-cancer patients shows that a high comorbidity burden can delay systemic parenteral treatment administration, whereas polypharmacy has a negative impact on four-month survival.
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Neoplasias Pulmonares , Masculino , Humanos , Idoso , Feminino , Estudos Retrospectivos , Estudos de Coortes , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Comorbidade , PulmãoRESUMO
BACKGROUND: The comorbidity burden has a negative impact on lung-cancer survival. Several comorbidity scores have been described and are currently used. The current challenge is to select the comorbidity score that best reflects their impact on survival. Here, we compared seven usable comorbidity scores (Charlson Comorbidity Index, Age adjusted Charlson Comorbidity Index, Charlson Comorbidity Index adapted to lung cancer, National Cancer Institute combined index, National Cancer Institute combined index adapted to lung cancer, Elixhauser score, and Elixhauser adapted to lung cancer) with coded administrative data according to the tenth revision of the International Statistical Classification of Diseases and Related Health Problems to select the best prognostic index for predicting four-month survival. MATERIALS AND METHODS: This cohort included every patient with a diagnosis of lung cancer hospitalized for the first time in the thoracic oncology unit of our institution between 2011 and 2015. The seven scores were calculated and used in a Cox regression method to model their association with four-month survival. Then, parameters to compare the relative goodness-of-fit among different models (Akaike Information Criteria, Bayesian Information Criteria), and discrimination parameters (the C-statistic and Harrell's c-statistic) were calculated. A sensitivity analysis of these parameters was finally performed using a bootstrap method based on 1,000 samples. RESULTS: In total, 633 patients were included. Male sex, histological type, metastatic status, CCI, CCI-lung, Elixhauser score, and Elixhauser-lung were associated with poorer four-month survival. The Elixhauser score had the lowest AIC and BIC and the highest c-statistic and Harrell's c-statistic. These results were confirmed in the sensitivity analysis, in which these discrimination parameters for the Elixhauser score were significantly different from the other scores. CONCLUSIONS: Based on this cohort, the Elixhauser score is the best prognostic comorbidity score for predicting four-month survival for hospitalized lung cancer patients.
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Neoplasias Pulmonares , Humanos , Masculino , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Teorema de Bayes , Comorbidade , Prognóstico , Pacientes , Mortalidade HospitalarRESUMO
The purpose of immune checkpoint inhibitor (ICI)-based therapies is to help the patient's immune system to combat tumors by restoring the immune response mediated by CD8+ cytotoxic T cells. Despite impressive clinical responses, most patients do not respond to ICIs. Therapeutic vaccines with autologous professional antigen-presenting cells, including dendritic cells, do not show yet significant clinical benefit. To improve these approaches, we have developed a new therapeutic vaccine based on an allogeneic plasmacytoid dendritic cell line (PDC*line), which efficiently activates the CD8+ T-cell response in the context of melanoma. The goal of the study is to demonstrate the potential of this platform to activate circulating tumor-specific CD8+ T cells in patients with lung cancer, specifically non-small-cell lung cancer (NSCLC). PDC*line cells loaded with peptides derived from tumor antigens are used to stimulate the peripheral blood mononuclear cells of NSCLC patients. Very interestingly, we demonstrate an efficient activation of specific T cells for at least two tumor antigens in 69% of patients irrespective of tumor antigen mRNA overexpression and NSCLC subtype. We also show, for the first time, that the antitumor CD8+ T-cell expansion is considerably improved by clinical-grade anti-PD-1 antibodies. Using PDC*line cells as an antigen presentation platform, we show that circulating antitumor CD8+ T cells from lung cancer patients can be activated, and we demonstrate the synergistic effect of anti-PD-1 on this expansion. These results are encouraging for the development of a PDC*line-based vaccine in NSCLC patients, especially in combination with ICIs.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Leucócitos Mononucleares/patologia , Linfócitos T CD8-Positivos , Antígenos de Neoplasias , Células DendríticasRESUMO
BACKGROUND: At intensive care unit (ICU) admission, the issue about prognosis of critically ill cancer patients is of clinical interest, especially after ICU discharge. Our objective was to assess the factors associated with 3- and 6-month survival of ICU cancer survivors. METHODS: Based on the French OutcomeRea™ database, we included solid cancer patients discharged alive, between December 2005 and November 2013, from the medical ICU of the university hospital in Grenoble, France. Patient characteristics and outcome at 3 and 6 months following ICU discharge were extracted from available database. RESULTS: Of the 361 cancer patients with unscheduled admissions, 253 (70%) were discharged alive from ICU. The main primary cancer sites were digestive (31%) and thoracic (26%). The 3- and 6-month mortality rates were 33 and 41%, respectively. Factors independently associated with 6-month mortality included ECOG performance status (ECOG-PS) of 3-4 (OR,3.74; 95%CI: 1.67-8.37), metastatic disease (OR,2.56; 95%CI: 1.34-4.90), admission for cancer progression (OR,2.31; 95%CI: 1.14-4.68), SAPS II of 45 to 58 (OR,4.19; 95%CI: 1.76-9.97), and treatment limitation decision at ICU admission (OR,4.00; 95%CI: 1.64-9.77). Interestingly, previous cancer chemotherapy prior to ICU admission was independently associated with lower 3-month mortality (OR, 0.38; 95%CI: 0.19-0.75). Among patients with an ECOG-PS 0-1 at admission, 70% (n = 66) and 61% (n = 57) displayed an ECOG-PS 0-2 at 3- and 6-months, respectively. At 3 months, 74 (55%) patients received anticancer treatment, 13 (8%) were given exclusive palliative care. CONCLUSIONS: Factors associated with 6-month mortality are almost the same as those known to be associated with ICU mortality. We highlight that most patients recovered an ECOG-PS of 0-2 at 3 and 6 months, in particular those with a good ECOG-PS at ICU admission and could benefit from an anticancer treatment following ICU discharge.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Neoplasias/mortalidade , Alta do Paciente/estatística & dados numéricos , Idoso , Feminino , Seguimentos , França , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
The use of complementary and alternative medicine at least once during or after cancer treatment has increased over the past years from an estimated 25% in the 1970s and 1980s to more than 32% in the 1990s and to 49% after 2000. The risk of herb-drug interaction is therefore increasingly recognized as a public health problem. To the best of our knowledge, we report here the first case of interaction between ginger and anticancer drug, with serious consequences for the patient. There is an urgent need regarding complementary and alternative medicine: Both clinicians and patients should be aware of the potential interactions between herbs and prescribed drugs.
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Antineoplásicos , Crizotinibe , Interações Ervas-Drogas , Zingiber officinale , Antineoplásicos/farmacocinética , Crizotinibe/farmacocinética , HumanosRESUMO
BACKGROUND: The study objective was to assess the influence of neutropenia on outcome of critically ill cancer patients by meta-analysis of individual data. Secondary objectives were to assess the influence of neutropenia on outcome of critically ill patients in prespecified subgroups (according to underlying tumor, period of admission, need for mechanical ventilation and use of granulocyte colony stimulating factor (G-CSF)). METHODS: Data sources were PubMed and the Cochrane database. Study selection included articles focusing on critically ill cancer patients published in English and studies in humans from May 2005 to May 2015. For study selection, the study eligibility was assessed by two investigators. Individual data from selected studies were obtained from corresponding authors. RESULTS: Overall, 114 studies were identified and authors of 30 studies (26.3% of selected studies) agreed to participate in this study. Of the 7515 included patients, three were excluded due to a missing major variable (neutropenia or mortality) leading to analysis of 7512 patients, including 1702 neutropenic patients (22.6%). After adjustment for confounders, and taking study effect into account, neutropenia was independently associated with mortality (OR 1.41; 95% CI 1.23-1.62; P = 0.03). When analyzed separately, neither admission period, underlying malignancy nor need for mechanical ventilation modified the prognostic influence of neutropenia on outcome. However, among patients for whom data on G-CSF administration were available (n = 1949; 25.9%), neutropenia was no longer associated with outcome in patients receiving G-CSF (OR 1.03; 95% CI 0.70-1.51; P = 0.90). CONCLUSION: Among 7512 critically ill cancer patients included in this systematic review, neutropenia was independently associated with poor outcome despite a meaningful survival. Neutropenia was no longer significantly associated with outcome in patients treated by G-CSF, which may suggest a beneficial effect of G-CSF in neutropenic critically ill cancer patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026347 . Date of registration: Sept 18 2015.
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Neoplasias/mortalidade , Neutropenia/complicações , Estado Terminal/mortalidade , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Neutropenia/mortalidade , Avaliação de Resultados em Cuidados de Saúde/métodos , Respiração Artificial/métodosRESUMO
Plasma circulating cell-free (cf)DNA is of interest in oncology because it has been shown to contain tumour DNA and may thus be used as liquid biopsy. In nonsmall cell lung cancer (NSCLC), cfDNA quantification has been proposed for the monitoring and follow-up of patients. However, available studies are limited and need to be confirmed by studies with larger sample sizes and including patients who receive more homogenous treatments. Our objective was to assess the predictive and prognostic value of plasma cfDNA concentration in a large series of patients with NSCLC and treated with a standard chemotherapy regimen.We included samples from lung cancer patients recruited into the Pharmacogenoscan study. The cfDNA of 218 patients was extracted and quantified by fluorometry before and after two or three cycles of platinum-based chemotherapy. The association between baseline and post-chemotherapy concentrations and treatment response, assessed by RECIST (response evaluation criteria in solid tumours) or patient survival was analysed.Patients with high cfDNA concentrations (highest tertile) at baseline had a significantly worse disease-free and overall survival than those with lower concentrations (lowest and middle tertiles) (median overall survival 10 months (95% CI 10.7-13.9) versus 14.2 months (95% CI 12.6-15.8), respectively; p=0.001). In multivariate analysis, increased baseline concentration of cfDNA was an independent prognostic factor. However, we did not find any association between cfDNA concentration and response to treatment.cfDNA may be a biomarker for the assessment of prognosis in NSCLC. However, total concentration of cfDNA does not appear to predict chemotherapy response.
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Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , DNA/sangue , Neoplasias Pulmonares/sangue , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores/sangue , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , DNA de Neoplasias/sangue , Feminino , Fluorometria , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , PrognósticoRESUMO
The decision-making process for the intensity of care delivered to patients with lung cancer and organ failure is poorly understood, and does not always involve intensivists. Our objective was to describe the potential suitability for intensive care unit (ICU) referral of lung cancer in-patients with organ failures. We prospectively included consecutive lung cancer patients with failure of at least one organ admitted to the teaching hospital in Grenoble, France, between December 2010 and October 2012. Of 140 patients, 121 (86%) were evaluated by an oncologist and 49 (35%) were referred for ICU admission, with subsequent admission for 36 (73%) out of those 49. Factors independently associated with ICU referral were performance status ⩽2 (OR 10.07, 95% CI 3.85-26.32), nonprogressive malignancy (OR 7.00, 95% CI 2.24-21.80), and no explicit refusal of ICU admission by the patient and/or family (OR 7.95, 95% CI 2.39-26.37). Factors independently associated with ICU admission were the initial ward being other than the lung cancer unit (OR 6.02, 95% CI 1.11-32.80) and an available medical ICU bed (OR 8.19, 95% CI 1.48-45.35). Only one-third of lung cancer patients with organ failures were referred for ICU admission. The decision not to consider ICU admission was often taken by a non-intensivist, with advice from an oncologist rather than an intensivist.
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Cuidados Críticos/organização & administração , Neoplasias Pulmonares/terapia , Seleção de Pacientes , Encaminhamento e Consulta , Idoso , Tomada de Decisões , Progressão da Doença , Feminino , França , Humanos , Unidades de Terapia Intensiva , Masculino , Oncologia/organização & administração , Pessoa de Meia-Idade , Admissão do Paciente , Projetos Piloto , Prognóstico , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: Response Evaluation Criteria in Solid Tumors (RECIST) are widely used to assess the effect of chemotherapy in patients with cancer. We hypothesised that the change in unidimensional tumour size handled as a continuous variable was more reliable than RECIST in predicting overall survival (OS). METHODS: The prospective Pharmacogenoscan study enrolled consecutive patients with non-small-cell lung cancer (NSCLC) at any stage seen between 2005 and 2010 at six hospitals in France, given chemotherapy. After exclusion of patients without RECIST or continuous-scale tumour size data and of those with early death, 464 patients were left for the survival analyses. Cox models were built to assess relationships between RECIST 1.1 categories or change in continuous-scale tumour size and OS. The best model was defined as the model minimising the Akaike Information Criterion (AIC). RESULTS: OS was 14.2 months (IQR, 7.3-28.9 months). According to RECIST 1.1, 146 (31%) patients had a partial or complete response, 245 (53%) stable disease, and 73 (16%) disease progression. RECIST 1.1 predicted better OS than continuous-scale tumour in early (<6 months) predicted survival analyses (p = 0.03) but the accuracy of the two response evaluation methods was similar in late (≥6 months) predicted survival analyses (p = 0.15). CONCLUSION: In this large observational study, change in continuous-scale tumour size did not perform better than RECIST 1.1 in predicting survival of patients given chemotherapy to treat NSCLC. TRIAL REGISTRATION: NCT00222404.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , França , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento , Carga TumoralRESUMO
OBJECTIVE: In many countries, the first line response to an emergency call is decided by the emergency dispatch center EMS clinician. Our main objective was to compare the pre-hospital response to calls received from cancer and non-cancer patients. We also compared the reasons for calling, for each group. METHODS: We conducted a retrospective cohort study of data collected between January 1, 2016 and December 31, 2020, from emergency dispatch center records of the Isère county, France. Statistical tests were conducted after matching one cancer patient with two non-cancer patients, resulting in a cohort of 44,022 patients. We used multivariate logistic regression to determine the impact of patient cancer status on the medical decision taken in response to the emergency call. RESULTS: Overall, data on 849,110 patients were extracted, including 16,451 patients with a diagnosis of cancer and 29,348 non-cancer patients. In the matched cohort, cancer was associated with a higher odd of having a mobile intensive care unit (MICU) [odds ratio (OR)=2.02 (1.81-2.26), p<0.001] or an ambulance being dispatched to the patient's home or other location [OR=2.36 (2.24-2.48), p<0.001]. The two most frequent medical responses were to send an ambulance (58.6%) and giving advice only (36.8%). The five main reasons for the emergency call for the cancer group were cardiovascular disease symptoms (13.5%), respiratory problems (10.6%), digestive disorders (10.4%), infections (8.9%) and neurological disorders (6.0%). CONCLUSION: An MICU or an ambulance was more often dispatched for cancer patients than for others. Considering that cancer is a very frequent comorbidity in Western countries, knowledge of the patient's cancer status should be sought and taken into consideration when a patient seeks emergency help.
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Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/complicações , Neoplasias/epidemiologia , França/epidemiologia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Unidades de Terapia Intensiva/estatística & dados numéricos , Ambulâncias/estatística & dados numéricos , Bases de Dados Factuais , Serviços Médicos de Emergência/estatística & dados numéricos , Adulto , Despacho de Emergência Médica/estatística & dados numéricos , Unidades Móveis de Saúde/estatística & dados numéricos , Modelos Logísticos , Idoso de 80 Anos ou mais , Operador de Emergência Médica/estatística & dados numéricosRESUMO
BACKGROUND: Most lung cancers are diagnosed at an advanced stage and therefore have a poor prognosis. One major challenge is to choose the most adapted sampling technique to obtain a rapid pathological diagnosis so as to start treatment as early as possible. A growing number of techniques have been developed in recent years. This study sought to assess the diagnostic efficiency of each, along with the respective duration of the diagnostic pathways. METHODS: This retrospective, bicentric, observational study enrolled patients with inoperable lung cancer (stage III or IV) diagnosed in 2018-2019. Diagnostic efficiency was assessed based on the different examinations performed to achieve a precise diagnosis (pathology, immunohistochemistry, and/or molecular biology). The time between the first medical contact and treatment initiation was also assessed. RESULTS: Overall, 625 patients were included (median age 67 years; men 67 %; adenocarcinoma 55 %). The most frequent examinations were bronchial endoscopy (n = 469, 75 %), followed by metastasis biopsy (n = 137, 21.9 %) and guided transthoracic core-needle biopsy (TCNB) (n = 116, 18.6 %). 372 patients had only one procedure (59.5 %), mainly bronchial endoscopy (n = 217, 34.7 %) and metastasis biopsy (n = 71, 11 %). The most efficient examination was thoracic surgery (surgical pleural biopsy, (n = 32, 100 %); mediastinoscopy (n = 26, 96.3 %); surgical pulmonary biopsy (n = 14, 93.3 %). The second most efficient examination was metastasis biopsy (n = 126, 94 %) followed by guided TCNB (n = 108, 93.1 %). The median time from first medical contact to first examination was 4 days (interquartile range 25 %-75 % 1-8). The median time from first medical contact to pathological result was 17 days (10-34). The median time from first medical contact to treatment start was 48 days (30-69). CONCLUSIONS: In order to make an accurate and rapid diagnosis of lung cancer, it is crucial to choose the most appropriate technique. Bronchial endoscopy remains the first-line examination for central lesions, as it is efficient and easily accessible. Guided TCNB and metastasis biopsy are the preferred techniques for peripheral lesions. The choice of the diagnostic technique should be part of a multidisciplinary approach and a dedicated pathway to optimize initial management.
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Arcagen (NCT02834884) is a European prospective study aiming at defining the molecular landscape of rare cancers for treatment guidance. We present data from the cohort of rare thoracic tumors. Patients with advanced pleural mesothelioma (PM) or thymic epithelial tumors (TET) underwent genomic profiling with large targeted assay [>300 genes, tumor mutational burden (TMB), microsatellite instability (MSI) status] on formalin-fixed paraffin-embedded (FFPE) or plasma samples. EORTC molecular tumor board (MTB) advised for biomarker-guided treatments. 102 patients recruited from 8 countries between July 2019 and May 2022 were evaluable: 56 with PM, 46 with TET (23 thymomas, 23 thymic carcinomas). Molecular profiling was performed on 70 FFPE samples (42 PM, 28 TET), and 32 cases on ctDNA (14 PM, 18 TET), within a median turnaround time of 8 days from sample reception. We detected relevant molecular alterations in 66 out of 102 patients (65%; 79% PM, 48% TET), 51 of 70 FFPE samples (73%; 90% PM, 46% TET), and 15 of 32 plasma samples (47%; 43% PM, 50% TET). The most frequently altered genes were CDKN2A/B, BAP1, MTAP in PM and TP53, CDKN2A/B, SETD2 in TET. The TMB was low (mean 3.2 Muts/MB), 2 PM had MSI-high status. MTB advised molecular-guided treatment options in 32 situations, for 17 PM and 15 TET patients (75% clinical trial option, 22% off-label drug or compassionate use, 3% early access program). Molecular testing and MTB discussion were feasible for patients with rare thoracic cancers and allowed the broadening of treatment options for 30% of the cases.
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The issue of limiting life-sustaining treatments for intensive care unit (ICU) patients is complex. The ethical principles applied by ICU staff when making treatment-limitation decisions must comply with the law of their country. Until 2011, the law in Taiwan prohibited the withdrawal of mechanical ventilation. Consequently, patients with severe underlying diseases could receive prolonged mechanical ventilation. In a study conducted by Shih and colleagues in patients with cancer in Taiwan, continuous mechanical ventilation for more than 21 days was associated with poor outcomes, particularly in the subgroups of patients with metastases, lung cancer, or liver cancer. These results highlight the need for appropriate legislation regarding the withdrawal of life-sustaining treatments in patients, especially those for whom no effective cancer treatments are available.
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Expectativa de Vida/tendências , Neoplasias/mortalidade , Neoplasias/terapia , Respiração Artificial/mortalidade , Respiração Artificial/tendências , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: The COVID 19-pandemic has led physicians to change their approach to treating non-small cell lung cancer (NSCLC) to reduce hospital stays for patients. OBJECTIVES: We aimed to assess the toxicity and efficacy of extended interval (EI) dosing of immune checkpoint inhibitors (ICIs) compared to standard dosing (SD). METHODS: In this retrospective two-center study, we included patients with stage III/IV NSCLC who were treated with ICIs with or without maintenance pemetrexed during the month before March 2020. Adverse events and efficacy were collected until June 2021. Toxicity and survival were assessed using multivariate Cox models. RESULTS: Among the 134 patients identified (8 stage III and 126 stage IV; 66 first line and 60 second or subsequent lines), 70.9% received EI dosing. In the EI group, 12.6% of patients developed grade 3 or 4 immune-related adverse events versus 15.4% in the SD group (P- value = 0.8). Treatment was definitively discontinued due to toxicity in 9 patients in the EI group and in 5 in the SD group (P-value =0.5). Overall survival was not associated with dosage regimen or toxicity analyzed as a time-dependent variable. CONCLUSIONS: Our study suggests that EI dosing of ICIs did not affect toxicity and overall survival in lung cancer patients.
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COVID-19 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Pandemias , Estudos Retrospectivos , COVID-19/epidemiologiaRESUMO
INTRODUCTION: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment in recent years, but have led to the emergence of new so-called immune-related adverse events (irAE). The objective of this study was to determine whether cancer type is a potential predictive factor of irAEs. METHODS: This retrospective study included patients who had started an ICI treatment between 2019 and 2020 at the Grenoble Alpes University Hospital. A logistic regression model and a Fine and Gray survival model with death as a competing risk were used to identify variables associated with grade≥2 irAEs and grade≥2 irAEs-free survival. RESULTS: Of the 512 patients included, 160 (31.2%) had a grade≥2 irAE. Grade≥2 irAEs were less frequent in head and neck cancer compared to other cancers. Ipilimumab (odds ratio [OR]: 6.05; 95% confidence interval [CI]: 2.81-13.7), treatment duration (OR: 1.01; 95% CI: 1.01-1.02), and history of autoimmune disease (OR: 6.04; 95% CI: 2.45-16.5) were independently associated with grade≥2 irAEs. With death as a competing risk, grade≥2 irAEs-free survival was independently improved with treatment duration (subdistribution hazard ratio [sdHR]: 0.93; 95% CI: 0.92-0.94), ipilimumab (sdHR: 0.24; 95% CI: 0.1-0.59) and history of autoimmune disease (sdHR: 0.23; 95% CI: 0.08-0.69) whereas it was poorer for patients with performance status≥2 (sdHR: 2.04; 95% CI: 1.5-2.76) and an older age (sdHR: 1.02; 95% CI: 1.00-1.03). CONCLUSION: Ipilimumab and history of autoimmune disease were both associated with the presence of grade≥2 irAEs and grade≥2 irAEs-free survival. The different cancer groups were not.
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Antineoplásicos Imunológicos , Doenças Autoimunes , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Ipilimumab/efeitos adversos , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversosRESUMO
Most patients with lung cancer are smokers and are of advanced age. They are therefore at high risk of having age- and lifestyle-related comorbidities. These comorbidities are subject to treatment or even polypharmacy. There is growing evidence of a link between lung cancer, comorbidities and medications. The relationships between these entities are complex. The presence of comorbidities and their treatments influence the time of cancer diagnosis, as well as the diagnostic and treatment strategy. On the other hand, cancer treatment may have an impact on the patient's comorbidities such as renal failure, pneumonitis or endocrinopathies. This review highlights how some comorbidities may have an impact on lung cancer presentation and may require treatment adjustments. Reciprocal influences between the treatment of comorbidities and anticancer therapy will also be discussed.
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BACKGROUND: Although short- and long-term survival in critically ill patients with cancer has been described, data on their quality of life (QoL) after an intensive care unit (ICU) stay are scarce. This study aimed to determine the impact of an ICU stay on QoL assessed at 3 months in patients with solid malignancies. METHODS: A prospective case-control study was conducted in three French ICUs between February 2020 and February 2021. Adult patients with lung, colorectal, or head and neck cancer who were admitted in the ICU were matched in a 1:2 ratio with patients who were not admitted in the ICU regarding their type of cancer, curative or palliative anticancer treatment, and treatment line. The primary endpoint was the QoL assessed at 3 months from inclusion using the mental and physical components of the Short Form 36 (SF-36) Health Survey. The use of anticancer therapies at 3 months was also evaluated. RESULTS: In total, 23 surviving ICU cancer patients were matched with 46 non-ICU cancer patients. Four patients in the ICU group did not respond to the questionnaire. The mental component score of the SF-36 was higher in ICU patients than in non-ICU patients: median of 54 (interquartile range: 42-57) vs. 47 (37-52), respectively (p = 0.01). The physical component score of the SF-36 did not differ between groups: 35 (31-47) vs. 42 (34-47) (p = 0.24). In multivariate analysis, no association was found between patient QoL and an ICU stay. A good performance status and a non-metastatic cancer at baseline were independently associated with a higher physical component score. The use of anticancer therapies at 3 months was comparable between the two groups. CONCLUSION: In patients with solid malignancies, an ICU stay had no negative impact on QoL at 3 months after discharge when compared with matched non-ICU patients.
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Neoplasias , Qualidade de Vida , Adulto , Humanos , Estudos de Casos e Controles , Estudos Prospectivos , Unidades de Terapia Intensiva , Neoplasias/terapiaRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICI) have revolutionized the management of cancer. They can induce immune-related adverse events (irAE) leading to intensive care unit (ICU) admission. We aimed to describe irAEs for ICU admissions in solid cancer patients treated with ICIs. METHODS: This prospective multicenter study was conducted in France and Belgium. Adult patients with solid tumor and treated with systemic ICIs within the last 6 months, requiring non-programmed ICU admission were included. Patients admitted for microbiologically documented sepsis were excluded. Imputability of irAEs in ICU admissions was described according to the WHO-UMC classification system at ICU admission and at ICU discharge. The use of immunosuppressant treatment was reported. RESULTS: 115 patients were eligible. Solid tumor was mainly lung cancer (n = 76, 66%) and melanoma (n = 18, 16%). They were mainly treated with an anti-PD-(L)1 alone (n = 110, 96%). Main ICU admission reasons were acute respiratory failure (n = 66, 57%), colitis (n = 14, 13%), and cardiovascular disease (n = 13, 11%). ICU admission was considered "likely" associated with irAE for 48% (n = 55) of patients. Factors independently associated with irAE were a good ECOG performance status (PS) (ECOG-PS of 0 or 1 vs. ECOG-PS of 2-3, odds ratio [OR] = 6.34, 95% confidence interval [95% CI] 2.13-18.90, and OR = 3.66, 95% CI 1.33-10.03, respectively), and a history of irAE (OR = 3.28, 95% CI 1.19-9.01). Steroids were prescribed for 41/55 (75%) patients with ICU admission "likely" related to irAE. Three patients were subsequently treated with immunosuppressants. CONCLUSION: IrAEs accounted for half of ICU admissions in cancer patients receiving ICIs. They could be treated with steroids. Identifying the imputability of irAEs in ICU admissions remains a challenge.
RESUMO
BACKGROUND: Previous reports showed limited efficacy of immune checkpoint inhibitors as single-agent treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation or ALK/ROS1 fusion. We aimed at evaluating the efficacy and safety of immune checkpoint inhibitor combined with chemotherapy and bevacizumab (when eligible) in this patient subgroup. METHODS: We conducted a French national open-label multicentre non-randomised non-comparative phase II study in patients with stage IIIB/IV NSCLC, oncogenic addiction (EGFR mutation or ALK/ROS1 fusion), with disease progression after tyrosine kinase inhibitor and no prior chemotherapy. Patients received platinum, pemetrexed, atezolizumab, bevacizumab (PPAB cohort) or, if not eligible to bevacizumab, platinum-pemetrexed-atezolizumab (PPA cohort). The primary end-point was the objective response rate (RECIST v1.1) after 12 weeks, evaluated by blind independent central review. RESULTS: 71 patients were included in PPAB cohort and 78 in PPA cohort (mean age, 60.4/66.1 years; women 69.0%/51.3%; EGFR mutation, 87.3%/89.7%; ALK rearrangement, 12.7%/5.1%; ROS1 fusion, 0%/6.4%, respectively). After 12 weeks, objective response rate was 58.2% (90% confidence interval [CI], 47.4-68.4) in PPAB cohort and 46.5% (90% CI, 36.3-56.9) in PPA cohort. Median progression-free survival and overall survival were 7.3 (95% CI 6.9-9.0) months and 17.2 (95% CI 13.7-NA) months in PPAB cohort and 7.2 (95% CI 5.7-9.2) months and 16.8 (95% CI 13.5-NA) months in PPA cohort, respectively. Grade 3-4 adverse events occurred in 69.1% of patients in PPAB cohort and 51.4% in PPA cohort; Grade 3-4 atezolizumab-related adverse events occurred in 27.9% and 15.3%, respectively. CONCLUSION: Combination approach with atezolizumab with or without bevacizumab and platinum-pemetrexed achieved promising activity in metastatic EGFR-mutated or ALK/ROS1-rearranged NSCLC after tyrosine kinase inhibitor failure, with acceptable safety profile.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Pemetrexede , Platina/uso terapêutico , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genéticaRESUMO
INTRODUCTION: Immunotherapy has transformed the treatment paradigm of several cancers. Hospital-at-home (HAH) care is an innovative healthcare model in which treatments are delivered at home under the supervision of a hospital, which likely applies to cancer immunotherapy. For this home-care option, official treatment guidelines are still lacking. We therefore sought to create guidance and recommendations on how to administer immune response checkpoint inhibitor therapies and other monoclonal antibodies used in cancer treatment in the context of HAH setting. METHODS: A multidisciplinary group of healthcare professionals with expertise in managing cancer patients and prescribing immunotherapy in HAH settings was set up. RESULTS: Based on the survey results and working group discussions, six major components were identified: (1) existing HAH organization in France; (2) underlying framework; (3) flowchart; (4) patient pathway before, the day of, and after immunotherapy; (5) healthcare personnel training; (6) patient therapeutic education. The detailed specifications for each component are provided herein, along with an illustrative flowchart. The prerequisites for home administration of cancer immunotherapies are summarized in Table 1. DISCUSSION: This paper seeks to facilitate the implementation of cancer immunotherapy within HAH settings for the healthcare professionals concerned.