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1.
Immunotherapy ; 13(17): 1379-1386, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34743545

RESUMO

Recent studies have shown that immune-related adverse events (irAEs), occurring even after the discontinuation of immune checkpoint inhibitors (ICIs), may be associated with favorable disease outcomes, particularly in patients with melanoma and lung cancer. However, a few clinical cases have been described on the correlation between irAEs and ICIs efficacy in renal cell carcinoma (RCC) patients. This study reports the clinical case of a metastatic RCC patient who has experienced severe immune-related renal toxicity after 19 months of nivolumab use. Despite immunotherapy discontinuation, the patient has maintained clinical benefit and disease progression-free for 3 years. We examined the correlation between the occurrence and the severity of irAEs, treatment discontinuation and clinical benefits. The evidence on ICI retreatment following ICI discontinuation due to irAEs was also reviewed.

3.
Cancers (Basel) ; 13(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34771680

RESUMO

In recent years, the treatment landscape of urothelial carcinoma has significantly changed due to the introduction of immune checkpoint inhibitors (ICIs), which are the standard of care for second-line treatment and first-line platinum-ineligible patients with advanced disease. Despite the overall survival improvement, only a minority of patients benefit from this immunotherapy. Therefore, there is an unmet need to identify prognostic and predictive biomarkers or models to select patients who will benefit from ICIs, especially in view of novel therapeutic agents. This review describes the prognostic and predictive role, and clinical readiness, of clinical and tumour factors, including new molecular classes, tumour mutational burden, mutational signatures, circulating tumour DNA, programmed death-ligand 1, inflammatory indices and clinical characteristics for patients with urothelial cancer treated with ICIs. A classification of these factors according to the levels of evidence and grades of recommendation currently indicates both a prognostic and predictive value for ctDNA and a prognostic relevance only for concomitant medications and patients' characteristics.

4.
Immunotherapy ; 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34784782

RESUMO

Background: Few data are available regarding the effectiveness of immune checkpoint inhibitors in advanced upper tract urothelial carcinoma (UTUC) patients. Methods: To provide a real-world experience with anti-PD-1/PD-L1-based therapy in UTUC patients, we involved an Italian network in a multicenter retrospective analysis. Results: A total of 78 UTUC patients were enrolled. The median follow-up was 25.1 months. The median progression-free survival (mPFS) was 2.2 months (95% CI 1.8-2.6), and the median OS (mOS) was 6.0 months (95% CI 3.6-8.4). The Sonpavde score (including performance status > 0, hemoglobin < 10 g/dl, liver metastases, time from prior chemotherapy ≥ 3 months) split the patients into three groups (0 vs 1 vs 2-4 factors), efficiently predicting the OS and PFS outcome at the multivariate analyses (p < 0.0001). Conclusion: The prognosis of unselected UTUC patients is still unsatisfactory. The Sonpavde score was validated for the first time in an UTUC population, as a useful tool for the treatment decision-making process.

5.
Cancers (Basel) ; 13(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638258

RESUMO

Prostate cancer (PCa) therapy has been recently revolutionized by the approval of new therapeutic agents in the metastatic setting. However, the optimal therapeutic strategy in such patients should be individualized in the light of prognostic and predictive molecular factors, which have been recently studied: androgen receptor (AR) alterations, PTEN-PI3K-AKT pathway deregulation, homologous recombination deficiency (HRD), mismatch repair deficiency (MMRd), and tumor microenvironment (TME) modifications. In this review, we highlighted the clinical impact of prognostic and predictive molecular factors in PCa patients' outcomes, identifying biologically distinct subtypes. We further analyzed the relevant methods to detect these factors, both on tissue, i.e., immunohistochemistry (IHC) and molecular tests, and blood, i.e., analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Moreover, we discussed the main pros and cons of such techniques, depicting their present and future roles in PCa management, throughout the precision medicine era.

7.
Nat Rev Clin Oncol ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561632

RESUMO

Protein tyrosine kinases of the human epidermal growth factor receptor family, including EGFR and HER2, have emerged as important therapeutic targets in non-small-cell lung, breast and gastroesophageal cancers, and are of relevance for the treatment of various other malignancies (particularly colorectal cancer). Classic activating EGFR exon 19 deletions and exon 21 mutations, and HER2 amplification and/or overexpression, are predictive of response to matched molecularly targeted therapies, translating into favourable objective response rates and survival outcomes. By comparison, cancers with insertion mutations in exon 20 of either EGFR or HER2 are considerably less sensitive to the currently available tyrosine kinase inhibitors and antibodies targeting these receptors. These exon 20 insertions are structurally distinct from other EGFR and HER2 mutations, providing an explanation for this lack of sensitivity. In this Review, we first discuss the prevalence and pan-cancer distribution of EGFR and HER2 exon 20 insertions, their biology and detection, and associated responses to current molecularly targeted therapies and immunotherapies. We then focus on novel approaches that are being developed to more effectively target tumours driven by these non-classic EGFR and HER2 alterations.

8.
Cancer Invest ; : 1-12, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34409906

RESUMO

BACKGROUND: The impact of systemic anticancer treatments on SARS-CoV-2-related mortality is still debatable. METHODS: By a retrospective analysis of patients with non-small-cell lung cancer (NSCLC) treated with first-line Pembrolizumab or in combination with chemotherapy (ChT) during the first surge of the pandemic. RESULTS: The adjusted risk of death was higher in patients treated with ChT + Pembrolizumab (HR 4.6, 1.2-17.4, p = 0.02). The SARS-CoV-2-related mortality rate was higher in patients treated with ChT + Pembrolizumab (p = 0.03), ≥70 years (p = 0.03) and current smokers (p = 0.17). CONCLUSIONS: The addition of ChT to immunotherapy could be associated with increased risk of mortality and higher SARS-CoV-2-related mortality rate.

9.
Transl Lung Cancer Res ; 10(7): 3385-3400, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430374

RESUMO

Objective: This review aims to summarize the possibilities of recently discovered molecular diagnostic techniques in lung cancer, by evaluating their impact on diagnosis, monitoring, and prognosis in oligometastatic disease. Background: Oligometastatic non-small cell lung cancer (OM-NSCLC) is currently defined based on morphological rather than biological features. Major advances in the detection of molecular biomarkers in cell-free tumoral DNA and the models of oncogene addiction make as feasible an early diagnosis and guide the therapeutic decision-making progress to improve the prognosis. Methods: This narrative review EXAMINES current approaches of diagnosis, monitoring, and prognosis of OM-NSCLC and describes the fast-evolving therapeutic scenario of this disease. We provide an overview of the powerful capability of liquid biopsy techniques applied to blood and fluid and we focus on the technological advancement of circulant biomolecular factors in OM NSCLC pathology, starting from apparently simpler models such as oncogene addicted tumors to evaluate themselves in the light of treatment with immune-checkpoint inhibitors. Conclusions: A better understanding of spatial and temporal evolution of oligometastatic diseases would contribute to a more accurate diagnosis and tailored treatment. Data from prospective clinical trials in the early stage of disease, coupled with knowledge of genetic characteristics of lung tumors, are warranted. These efforts would lead to improving the possibility to eradicate the residual disease in these low burden tumoral settings, thus enhancing the definitive cure perspectives.

10.
Clin Med Insights Oncol ; 15: 11795549211021667, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290538

RESUMO

Background: Immune checkpoint inhibitors (ICIs) are currently the standard of care for metastatic urothelial cancer (mUC) after the failure of previous platinum-based chemotherapy. The choice of further therapy after ICI progression is a new challenge, and scarce data support it. We aimed to examine the outcomes of mUC patients after progression to ICI, especially when receiving chemotherapy. Methods: Data were retrospectively collected from clinical records of mUC patients whose disease progressed to anti-programmed death 1 (PD-1)or programmed death ligand 1 (PD-L1) therapy at 14 Italian centers. Patients were grouped according to ICI therapy setting into SALVAGE (ie, ICI delivered ⩾ second-line therapy after platinum-based chemotherapy) and NAÏVE (ie, first-line therapy) groups. Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared among subgroups. Cox regression assessed the effect of treatments after progression to ICI on OS. Objective response rate (ORR) was calculated as the sum of partial and complete radiologic responses. Results: The study population consisted of 201 mUC patients who progressed after ICI: 59 in the NAÏVE cohort and 142 in the SALVAGE cohort. Overall, 52 patients received chemotherapy after ICI progression (25.9%), 20 (9.9%) received ICI beyond progression, 115 (57.2%) received best supportive care only, and 14 (7.0%) received investigational drugs. Objective response rate to chemotherapy in the post-ICI setting was 23.1% (28.0% in the NAÏVE group and 18.5% in the SALVAGE group). Median PFS and OS to chemotherapy after ICI-PD was 5 months (95% confidence interval [CI]: 3-11) and 13 months (95% CI: 7-NA) for the NAÏVE group; 3 months (95% CI: 2-NA) and 9 months (95% CI: 6-NA) for the SALVAGE group, respectively. Overall survival from ICI initiation was 17 months for patients receiving chemotherapy (hazard ratio [HR] = 0.09, p < 0.001), versus 8 months for patients receiving ICI beyond progression (HR = 0.13, p < 0.001), and 2 months for patients who did not receive further active treatment (p < 0.001). Conclusions: Chemotherapy administered after ICI progression for mUC patients is advisable irrespective of the treatment line.

11.
Cancers (Basel) ; 13(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064232

RESUMO

Lung cancer represents the most common form of cancer, accounting for 1.8 million deaths globally in 2020. Over the last decade the treatment for advanced and metastatic non-small cell lung cancer have dramatically improved largely thanks to the emergence of two therapeutic breakthroughs: the discovery of immune checkpoint inhibitors and targeting of oncogenic driver alterations. While these therapies hold great promise, they face the same limitation as other inhibitors: the emergence of resistant mechanisms. One such alteration in non-small cell lung cancer is the Kirsten Rat Sarcoma (KRAS) oncogene. KRAS mutations are the most common oncogenic driver in NSCLC, representing roughly 20-25% of cases. The mutation is almost exclusively detected in adenocarcinoma and is found among smokers 90% of the time. Along with the development of new drugs that have been showing promising activity, resistance mechanisms have begun to be clarified. The aim of this review is to unwrap the biology of KRAS in NSCLC with a specific focus on primary and secondary resistance mechanisms and their possible clinical implications.

12.
Ther Adv Med Oncol ; 13: 17588359211019642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046089

RESUMO

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS - mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.

13.
Cancers (Basel) ; 13(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800236

RESUMO

Small cell lung cancer (SCLC) is one of the deadliest thoracic neoplasms, in part due to its fast doubling time and early metastatic spread. Historically, cytotoxic chemotherapy consisting of platinum-etoposide or anthracycline-based regimens has demonstrated a high response rate, but early chemoresistance leads to a poor prognosis in advanced SCLC. Only a fraction of patients with limited-disease can be cured by chemo-radiotherapy. Given the disappointing survival rates in advanced SCLC, new cytotoxic agents are eagerly awaited. Unfortunately, few novel chemotherapy drugs have been developed in the latest decades. This review describes the results and potential application in the clinical practice of novel chemotherapy agents for SCLC.

14.
Clin Genitourin Cancer ; 19(5): 396-404, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33849811

RESUMO

INTRODUCTION: Immunotherapy is effective in a small percentage of patients with cancer and no reliable predictive biomarkers are currently available. Artificial Intelligence algorithms may automatically quantify radiologic characteristics associated with disease response to medical treatments. METHODS: We investigated an innovative approach based on a 3-dimensional (3D) deep radiomics pipeline to classify visual features of chest-abdomen computed tomography (CT) scans with the aim of distinguishing disease control from progressive disease to immune checkpoint inhibitors (ICIs). Forty-two consecutive patients with metastatic urothelial cancer had progressed on first-line platinum-based chemotherapy and had baseline CT scans at immunotherapy initiation. The 3D-pipeline included self-learned visual features and a deep self-attention mechanism. According to the outcome to the ICIs, a 3D deep classifier semiautomatically categorized the most discriminative region of interest on the CT scans. RESULTS: With a median follow-up of 13.3 months (95% CI, 11.1-15.6), the median overall survival was 8.5 months (95% CI, 3.1-13.8). According to disease response to immunotherapy, the median overall survival was 3.6 months (95% CI, 2.0-5.2) for patients with progressive disease; it was not yet reached for those with disease control. The predictive accuracy of the 3D-pipeline was 82.5% (sensitivity 96%; specificity, 60%). The addition of baseline clinical factors increased the accuracy to 92.5% by improving specificity to 87%; the accuracy of other architectures ranged from 72.5% to 90%. CONCLUSION: Artificial Intelligence by 3D deep radiomics is a potential noninvasive biomarker for the prediction of disease control to ICIs in metastatic urothelial cancer and deserves validation in larger series.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Inteligência Artificial , Humanos , Imunoterapia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/tratamento farmacológico
15.
Immunotherapy ; 13(8): 645-652, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823647

RESUMO

Immune checkpoint inhibitors have improved the treatment landscape of different tumors and one of the emerging issues is the reintroduction of immunotherapy after discontinuation. Scarce evidence is currently available and different definitions have been used. The case of a patient with pretreated advanced urothelial cancer, who responded to immunotherapy retreatment after long-term benefit from the previous course, is reported. Based on a review of the different clinical scenarios, a definition of immunotherapy retreatment was proposed, as rechallenge or reintroduction, based on the reasons of discontinuation of the previous course. Clinical factors potentially associated with clinical benefit from immunotherapy retreatment are discussed, even though ad hoc studies are needed to assess the efficacy and safety of the different immunotherapy retreatment strategies.

16.
Crit Rev Oncol Hematol ; 159: 103241, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33545355

RESUMO

BACKGROUND: Advanced upper tract urothelial carcinoma (UTUC) has different molecular and genetic features from the commonest carcinoma of the bladder, suggesting a possible different sensitivity to immune-checkpoint inhibitors (ICI). METHODS: A systematic review and meta-analysis of all relevant clinical studies including advanced UTUC patients treated with ICI was conducted according to PRISMA guidelines. RESULTS: Six prospective trials for a total 2537 patients, including 396 (15.6 %) with advanced UTUC, were eligible for the analysis. In UTUC patients, the pooled ORR was 21.2 % (95 % CI, 12.5 %-33.7 %); the risk of death was reduced by 24 % over the standard platinum-based chemotherapy, but this was not statistically significant (hazard ratio = 0.76; 95 % confidence interval, 0.41-1.40; p = 0.37, χ2 = 3.28, p = 0.07; I2 = 70 %). CONCLUSIONS: The current evidence does not support a statistically significant effect from ICI over the standard treatment for advanced UTUC patients. Properly performed pre-planned subgroup analyses from randomized clinical trials are eagerly awaited.


Assuntos
Carcinoma de Células de Transição , Inibidores de Checkpoint Imunológico , Carcinoma de Células de Transição/tratamento farmacológico , Humanos , Estudos Prospectivos
18.
Clin Lung Cancer ; 22(2): e180-e192, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33162330

RESUMO

BACKGROUND: Real-world data have suggested a detrimental effect of steroid use in patients with advanced non-small-cell lung cancer (NSCLC) receiving immunotherapy. However, previous studies included heterogeneous cohorts of patients receiving different lines of treatment with several immuno-oncology agents and various combinations of chemotherapy and immuno-oncology agents. PATIENTS AND METHODS: A comprehensive clinicopathologic database of patients with NSCLC and programmed cell death ligand 1 >50% treated with frontline pembrolizumab monotherapy was constructed in 14 centers in Italy, Spain, Greece, and Switzerland. A multivariate analysis adjusting for the established prognostic factors was performed using a Cox regression model. RESULTS: For the 265 eligible patients, the median age at diagnosis was 67 years, 66% were male, 90% were current or former smokers, 18% had had an Eastern Cooperative Oncology Group performance status of 2 or 3. Of the NSCLC subtypes, 64% were adenocarcinoma and 25% were squamous cell. Of the patients, 18% had had brain metastases at diagnosis and 24% had received steroids before or during pembrolizumab treatment. The median time to progression was 4.4 months with and 13.7 months without steroid use (hazard ratio [HR], 2.55; 95% confidence interval [CI], 1.69-3.85; log-rank P < .001). The median survival was 22.5 months for the whole cohort, 7.7 months for the steroid group, and not reached for the non-steroid group (HR, 3.64; 95% CI, 2.34-5.68; log-rank P < .001). On multivariate analysis accounting for all established prognostic variables, steroid use was still independently associated with a high risk of progression (HR, 1.864; 95% CI, 1.179-2.949; P = .008) and death (HR, 2.292; 95% CI, 1.441-3.644; P < .001) CONCLUSIONS: In patients with advanced NSCLC and programmed cell death ligand 1 expression > 50% receiving frontline pembrolizumab monotherapy, any use of steroids before or during treatment was associated with an 86% increase in the risk of progression and a 2.3-fold increase in the risk of death, even accounting for palliative indication-related bias, including the presence of central nervous system metastasis. The use of steroids for palliative indications should be restricted to absolutely necessary for patients receiving immuno-oncology monotherapy.

19.
Lung Cancer ; 150: 123-131, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33130353

RESUMO

OBJECTIVES: In the most of cases, for non-small cell lung cancer (NSCLC) patients who progressed to previous immune checkpoint inhibitors (CKI) administered as first- or as second-line therapy, chemotherapy (CT) remains the only viable options in the absence of "druggable" mutations. We aimed to explore the efficacy of salvage chemotherapy after immunotherapy (SCAI) in advanced NSCLC patients. MATERIALS AND METHODS: We designed a retrospective, multicenter study, involving 20 Italian centers, with the primary objective of describing the clinical outcome of advanced NSCLC patients treated with SCAI at the participating institutions from November 2013 to July 2019. The primary endpoint of the study was represented by overall survival (OS), defined as the time from CT initiation to death. Secondary outcome endpoints of the SCAI (progression free survival, PFS, objective response rate, ORR and toxicity) and explorative biomarkers (lactate dehydrogenase, LDH, and neutrophil-to-lymphocyte ratio, NLR during immunotherapy) were also analyzed. RESULTS: In our study population of 342 NSCLC patients, SCAI obtained a median OS of 6.8 months (95 % confidence interval, CI 5.5-8.1), median PFS of 4.1 months (95 % CI 3.4-4.8) and ORR of 22.8 %. A "Post-CKI score" was constructed by combining significant predictors of OS at the multivariate analyses (sex, ECOG PS, disease control with prior immunotherapy), Harrell'C was 0.65, (95 % CI:0.59-0.71). CONCLUSIONS: Despite the late-line settings, our findings support the hypothesis that previous immunotherapy might increase the sensitivity of the tumor to the subsequent chemotherapy. The "Post-CKI score" was clinically effective in successfully discriminating three distinct prognostic subgroups of patients after the failure of CKI, representing a possibly useful tool for the tailored decision-making process of advanced treatment-line settings in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
20.
J Immunother ; 43(9): 299-306, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991393

RESUMO

The authors conducted a multicenter retrospective study on the outcome of programmed death-ligand 1 tumor proportion score≥50% advanced non-small cell lung cancer patients treated with first-line pembrolizumab according to the presence/absence of brain metastases. A total of 282 patients were included, of whom 56 had brain metastases that were treated with upfront local radiation therapy in 80.3% of cases. The overall response rate was 39.2% and 44.4% in patients with and without brain metastases (P=0.48), respectively, while intracranial response rate and intracranial disease control rate were 67.5% and 85.0%, respectively. The median time-to-treatment failure (TTF) and overall survival (OS) were 4.2 and 9.9 months versus 10.8 and 26.5 months for patients with and without brain metastases (P=0.06 and 0.05, respectively). Drug discontinuation rate due to treatment-related adverse events was 10.7% and 10.2% in patients with and without brain metastases, respectively. Multivariate analysis showed that baseline steroids was an independent predictor for a worse OS (P<0.001), while performance status (PS)≥2 was an independent predictor for a poorer TTF (P<0.001) and OS (P<0.001). In patients with brain metastases, only PS ≥2 was predicted for a worse TTF (P=0.02) and OS (P=0.03). Pembrolizumab has activity against brain metastases from non-small cell lung cancers with programmed death-ligand 1≥50%. Presence of brain metastases per se does not appear to be prognostic, and PS ≥2 seems to be the only factor associated with a worse outcome in patients with brain metastases.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/etiologia , Gerenciamento Clínico , Feminino , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/etiologia , Masculino , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento
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