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BACKGROUND: This study investigated the effect of adjuvant sublingual immunotherapy (SLIT) on inhaled corticosteroid (ICS) dose in patients with pollinosis-associated asthma. METHODS: We retrospectively evaluated patients with cedar pollinosis-associated asthma who initiated pharmacotherapy with or without adjuvant SLIT therapy from December 2014 to December 2016 and who continued treatment for 3 years. Changes in ICS dose (fluticasone propionate or its equivalent), antihistamine use, leukotriene antagonist use and intranasal corticosteroid (INCS) use over the 3-year period were compared. RESULTS: The study included 36 and 35 patients in the add-on SLIT and standard treatment groups, respectively. At 3 years, the add-on SLIT group showed a significant decline in ICS dose (p = 0.024). Although leukotriene antagonist use and INCS use did not differ between the two groups, the percentage of patients using antihistamines at 3 years was significantly lower in the add-on SLIT group than in the standard treatment group (p = 0.009); one in three patients on adjuvant SLIT therapy was able to discontinue ICS treatment. Patients who discontinued ICS treatment were younger (44.6±13.3 years vs. 55.0±14.1 years, p = 0.042), had a higher FEV1% predicted (109.9±14.4 vs. 94.8±18.6, p = 0.02), and were on a lower treatment step (2.1±0.7 vs. 3.0±0.8, p = 0.002) than those who did not. CONCLUSION: The addition of SLIT to standard pharmacotherapy resulted in a significant reduction in ICS dose at 3 years.
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Asma , Cryptomeria , Rinite Alérgica Sazonal , Imunoterapia Sublingual , Corticosteroides , Asma/tratamento farmacológico , Humanos , Estudos Retrospectivos , Rinite Alérgica Sazonal/tratamento farmacológicoRESUMO
BACKGROUND: Dissociated responses (DR) are phenomena in which some tumors shrink, whereas others progress during treatment of patients with cancer. The purpose of the present study was to evaluate the frequency and prognosis of DR in non-small cell lung cancer (NSCLC) patients treated with anti-programmed cell death-1/ligand 1 (anti-PD-1/L1) inhibitors. METHODS: This retrospective study included NSCLC patients who received anti-PD-1/L1 inhibitor as second- or later-line treatment. We excluded patients without radiological evaluation. In patients who showed progressive disease (PD) according to the RECIST 1.1 at the initial CT evaluation, we evaluated all measurable lesions in each organ to identify DR independently of RECIST 1.1. We defined DR as a disease with some shrinking lesions as well as growing or emerging new lesions. Cases not classified as DR were defined as 'true PD'. Overall survival was compared between patients with DR and those with true PD using Cox proportional hazards models. RESULTS: The present study included 62 NSCLC patients aged 27-82 years (median: 65 years). DR and true PD were observed in 11 and 51 patients, respectively. The frequency of DR in NSCLC patients who showed PD to anti-PD-1/L1 was 17.7%. Median overall survival was significantly longer in patients with DR versus true PD (14.0 vs. 6.6 months, respectively; hazard ratio for death: 0.40; 95% confidence interval: 0.17-0.94). CONCLUSIONS: Patients with DR exhibited a relatively favorable prognosis.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodosRESUMO
PURPOSE: Chemoradiotherapy (CRT) is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Recently, anti-PD-1 antibody therapy became a key treatment for stage IV NSCLC as the combination of immune checkpoint inhibitors (ICIs) and platinum doublet chemotherapy. However, the efficacy and toxicity of anti-PD-1 therapy for recurrence after CRT in stage III NSCLC are not well examined. METHODS: Patients who received anti-PD-1 therapy for recurrence after CRT were identified in our clinical database. The safety and efficacy of anti-PD-1 therapy were retrospectively analyzed. RESULTS: From March 1, 2013 to April 30, 2018, there were 20 patients who received anti-PD-1 therapy for recurrence after CRT. The median duration from CRT to initial anti-PD-1 therapy was 9.3 months. 12 patients (60%) were alive and 7 patients (35%) were still receiving anti-PD-1 therapy at the data cutoff point (median follow-up, 13.5 months). The ORR for anti-PD-1 therapy was 45.0%. Median progression-free survival (PFS) and overall survival (OS) from initiation of anti-PD-1 therapy was 8.4 months and 26.2 months, respectively. PFS in patients who had a short interval from last CRT to initial anti-PD-1 therapy seemed to have better outcomes (duration from last CRT to initial anti-PD-1 therapy < 9.3 months vs. ≥ 9.3 months; median PFS, 17.0 months vs. 4.9 months). Grade 3 or 4 immune-related adverse events occurred in 5% of patients. Only grade 1 pneumonitis was observed. CONCLUSION: The efficacy of anti-PD-1 therapy for recurrence after CRT in stage III NSCLC might better than in stage IV NSCLC. The duration from CRT to initial anti-PD-1 therapy might be related to efficacy.
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Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
A 56-years-old woman, who had undergone a complete resection for atypical meningioma (grade 2 of World Health Organization classification)8 years before was admitted to our hospital to treat a mass on the right middle lobe detected by chest X-ray. The mass was resected successfully by video-assisted thoracoscopic surgery and pathological diagnosis of the tumor was a metastatic atypical meningioma. We experienced a rare case of extracranial pulmonary metastasis of meningioma. Grade 2 meningioma is thought to have malignant potential of local recurrence and extracranial metastasis compared to grade 1 meningioma, so long-term observation may be necessary after resection of atypical meningioma.
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Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Neoplasias Meníngeas/patologia , Meningioma/secundário , Meningioma/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Pneumonectomia , Resultado do TratamentoRESUMO
Nivolumab plus ipilimumab is one of the first-line treatments for advanced non-small-cell lung cancer (NSCLC), but the safety and efficacy in patients on hemodialysis (HD) is unclear. We herein report a patient with NSCLC on HD in whom nivolumab and ipilimumab were initiated. We observed general deterioration and enlarged lesions, followed by a long-term response. The patient developed secondary hypoadrenocorticism, an immune-related adverse event that was easily controlled. Nivolumab plus ipilimumab can be used safely for patients with NSCLC on HD. Long-term effectiveness can be observed after initial progression, so we should carefully assess the response.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Nivolumabe/uso terapêutico , Ipilimumab/uso terapêutico , Antígeno B7-H1 , Neoplasias Pulmonares/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
PURPOSE: For patients with locally advanced non-small-cell lung cancer (LA-NSCLC) that progressed after definitive chemoradiotherapy (CRT) and durvalumab consolidation therapy, no subsequent standard treatment exists. The type of treatment selected for each timing of disease progression and its efficacy have not been investigated. METHODS: We retrospectively enrolled patients with LA-NSCLC or inoperable NSCLC that progressed after definitive CRT and durvalumab consolidation therapy at 15 Japanese institutions. Patients were classified into the following: Early Discontinuation group (disease progression within 6 months after durvalumab initiation), Late Discontinuation group (disease progression from 7 to 12 months after durvalumab initiation), and Accomplishment group (disease progression from 12 months after durvalumab initiation). RESULTS: Altogether, 127 patients were analyzed, including 50 (39.4%), 42 (33.1%) and 35 (27.5%) patients from the Early Discontinuation, Late Discontinuation, and Accomplishment groups, respectively. Subsequent treatments were Platinum plus immune checkpoint inhibitors (ICI) in 18 (14.2%), ICI in 7 (5.5%), Platinum in 59 (46.4%), Non-Platinum in 35 (27.6%), and tyrosine kinase inhibitor in 8 (6.3%) patients. In the Early Discontinuation, Late Discontinuation, and Accomplishment groups, 4 (8.0%), 7 (16.7%), and 7 (20.0%) patients were receiving Platinum plus ICI; 21 (42.0%), 22 (52.4%), and 16 (45.7%) were receiving Platinum, and 20 (40.0%), 8 (19.0%), and 7 (20.0%) were receiving Non-Platinum, respectively. No significant difference in progression-free survival was observed in the timing of disease progression. CONCLUSION: In patients with LA-NSCLC hat progressed after definitive CRT and durvalumab consolidation therapy, subsequent treatment may change depending on the timing of disease progression.
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Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Quimioterapia de Consolidação , Estudos Retrospectivos , Estadiamento de Neoplasias , Quimiorradioterapia , Progressão da DoençaRESUMO
BACKGROUND: The therapeutic efficacy of cytotoxic anticancer drugs has been reported to be enhanced after immune checkpoint inhibitors (ICI) in non-small cell lung cancer; however, it is unclear whether the same is applicable for small cell lung cancer (SCLC). We evaluated the efficacy of second-line amrubicin (AMR) following first-line platinum-based chemotherapy and ICI combination therapy (chemo-ICI) in SCLC. PATIENTS AND METHODS: We retrospectively enrolled consecutive patients with SCLC treated with AMR as a second-line following chemo-ICI as first-line between July 2019 and April 2021 from 16 institutions throughout Japan. We investigated the therapeutic effectiveness, safety, and efficacy-enhancing variables of AMR. RESULTS: Overall, 89 patients treated with AMR after first-line chemo-ICI were analyzed. The overall response rate (ORR) was 29.2% (95% confidence intervals [CI], 20.1-39.8) and median PFS (m PFS) was 2.99 months (95% CI, 2.27-3.65). Patients who relapsed more than 90 days after receiving first-line platinum combination therapy (sensitive relapse) exhibited greater ORR (58.3% vs. 24.7%, p = 0.035) and m PFS (5.03 vs. 2.56 months, p = 0.019) than patients who relapsed in <90 days (refractory relapse). Grade 3 or higher adverse events were mainly hematological toxicity. CONCLUSIONS: Our study suggested that the therapeutic effect of AMR was not enhanced after ICI on SCLC. However, AMR may be effective in cases of sensitive relapse after chemo-ICI. There was no increase in severe toxicity associated with AMR after ICI.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/induzido quimicamente , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Antineoplásicos/uso terapêutico , Resultado do Tratamento , RecidivaRESUMO
Introduction: Malignant pleural effusion (MPE) is associated with poor treatment outcome in patients with NSCLC receiving immune checkpoint inhibitors (ICIs). ICIs and chemotherapy (ICI/Chemo) combination therapy is currently the standard therapy for NSCLC, and some ICI/Chemo regimens for nonsquamous (non-Sq) NSCLC contain bevacizumab (BEV), which is effective for controlling MPE and may enhance immune response. This study aimed to determine the optimal first-line treatment for this clinical population. Methods: We retrospectively enrolled consecutive patients with non-Sq NSCLC with MPE who received ICI/Chemo or pembrolizumab monotherapy. Treatment outcomes were analyzed in patients with programmed death-ligand 1 (PD-L1) tumor proportion score more than or equal to 50% who were administered ICI/Chemo or pembrolizumab monotherapy (PD-L1 high cohort) and in patients with any PD-L1 status, treated with ICI/Chemo with or without BEV (ICI/Chemo cohort). We used propensity score matching (PSM) to reduce bias. Results: PD-L1 high and ICI/Chemo cohorts included 143 and 139 patients, respectively. In PD-L1 high cohort, 37 patients received ICI/Chemo. With PSM, the median progression-free survival was significantly longer in the ICI/Chemo group than in the pembrolizumab group (11.1 versus 3.9 mo, respectively, p = 0.0409). In the ICI/Chemo cohort, 23 patients received BEV. With PSM, no significant difference occurred in median progression-free survival between BEV and non-BEV groups (6.1 versus 7.4 mo, p = 0.9610). Conclusion: ICI/Chemo seemed more effective than pembrolizumab monotherapy for patients with non-Sq NSCLC with MPE. Nevertheless, the synergistic effect of BEV with ICI/Chemo may be limited. Further studies are needed to clarify the key factor in the tumor-induced immunosuppression environment in these patients.
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PURPOSE: This study aimed to determine the incidence and clinical course of epidermal growth factor receptor (EGFR)-mutated lung cancer with histologic transformation (HT). PATIENTS AND METHODS: We conducted a multicentre, retrospective, cohort study of patients with advanced EGFR-mutated lung cancer who received EGFR-tyrosine kinase inhibitors (TKIs) between 2012 and 2019. The primary outcome was the incidence of HT. The secondary outcome was treatment efficacy in patients with HT. RESULTS: In total, 6356 patients were enrolled. In 2624 patients, the histological type was proven by rebiopsy after acquiring resistance to EGFR-TKIs. Among them, 74 patients had HT (incidence rate: 2.8% [95% confidence interval: 2.3%-3.5%]). The median progression-free survival after EGFR-TKIs and first-line therapy after confirming HT was 10.4 and 4.4 months, respectively, which was not significantly different between patients with transformation to high-grade neuroendocrine carcinoma and those with transformation to another subtype of non-small cell lung cancer. Overall survival after confirming HT was 12.2 months. Twenty-seven patients received immune checkpoint inhibitors: 6 and 21 received immune checkpoint inhibitors before and after confirming HT, respectively. No patients achieved 1-year progression-free survival. The median progression-free survival after immune checkpoint inhibitor therapy after confirming HT was 1.6 months. CONCLUSION: HT occurred in approximately 3% of EGFR-mutated patients who developed resistance to EGFR-TKIs. Cytotoxic agents are likely to be effective in patients with HT. However, the therapeutic effectiveness of immune checkpoint inhibitors was limited in these patients. Given the rarity of HT and absence of prospective trials, our findings are important to inform the treatment of these patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases , Estudos RetrospectivosRESUMO
BACKGROUND: The efficacy of anti-programmed cell death-1/ligand 1 antibody monotherapy (anti-PD-1/PD-L1 monotherapy) in patients with active brain metastases (BMs) is not established. Here, we aimed to evaluate the efficacy of anti-PD-1/PD-L1 monotherapy in non-small cell lung cancer (NSCLC) patients with active BMs. METHODS: This retrospective study included NSCLC patients treated with second-line or later-line anti-PD-1/PD-L1 monotherapy between December 2015 and August 2019. Patients were classified into those with or without active BMs, including symptomatic BMs requiring systemic steroids and untreated BMs. The progression-free survival (PFS) and overall survival (OS) of the patients with and without active BMs were compared. Intracranial and extracranial tumor responses were evaluated in patients with active BMs. RESULTS: We analyzed 197 patients who had received anti-PD-1/PD-L1 monotherapy. Among them, 24 had active BMs. Among those without active BMs, 145 had no BMs and 28 had treated asymptomatic BMs. The PFS and OS of patients with active BMs were significantly shorter than those of patients without active BMs (1.3 vs. 2.7 months; P < 0.001, and 4.5 vs. 16.3 months; P = 0.001 respectively). For patients with active BMs, the intracranial and extracranial response rates were 13.3% and 26.7%, respectively. On multivariate analysis, active BMs, poor performance status (PS), and EGFR/ALK positivity were significant factors associated with shorter PFS. Active BMs and poor PS were significant factors associated with shorter OS. CONCLUSIONS: This study suggested that anti-PD-1/PD-L1 monotherapy was not effective for NSCLC patients with active BMs. Further studies on immunotherapy are needed for patients with active BMs. KEY POINTS: Significant findings of the study: The present study showed that anti-PD-1/PD-L1 antibody monotherapy was not effective for non-small cell lung cancer patients with active brain metastases. Intracranial and extracranial response rates were 13.3% and 26.7%, respectively. WHAT THIS STUDY ADDS: Further studies on immunotherapy are needed for patients with active BMs.
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Antígeno B7-H1/uso terapêutico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Anaplastic lymphoma kinase (ALK) fusion genes are found in 3%-5% of non-small cell lung cancers (NSCLCs). ALK inhibitors show a very high response rate to ALK-positive NSCLCs. However, the emergence of acquired resistance is inevitable. In this study, we investigated the drugs for overcoming resistance especially compound mutations after sequential treatment with crizotinib, alectinib, and lorlatinib. METHOD: Next-generation sequencing (NGS) and Sanger sequencing were performed on a liver biopsy tissue obtained from a clinical case. Ba/F3 cells in which mutant EML4-ALK were overexpressed were prepared, and cell viability assay and immunoblotting were performed to check the sensitivity of five independent ALK inhibitors. RESULTS: I1171S + G1269A double mutation was identified by NGS and Sanger sequencing on a liver biopsy tissue from a patient who relapsed on lorlatinib treatment. Ceritinib and brigatinib-but not other ALK inhibitors-were active against the compound mutations in the cell line model. CONCLUSIONS: With the sequential ALK inhibitors treatment, cancer cells accumulate new mutations in addition to mutations acquired previously. The identified compound mutation (I1171S + G1269A) was found to be sensitive to ceritinib and brigatinib, and indeed the patient's tumor partially responded to ceritinib. KEY POINTS: ALK compound mutation was found in a clinical sample that was resistant to lorlatinib after sequential ALK-tyrosine kinase inhibitor (TKI) treatment. Ceritinib and brigatinib are potential overcoming drugs against ALK I1171S + G1269A double mutation.
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Quinase do Linfoma Anaplásico/antagonistas & inibidores , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Apoptose , Carbazóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células , Crizotinibe/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Compostos Organofosforados/uso terapêutico , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonas/uso terapêutico , Células Tumorais CultivadasRESUMO
BACKGROUND/AIM: STK11/LKB1 mutation has been suggested as a poorly responding candidate biomarker of the anti-programmed cell death-1 (PD-1) antibody; however, the association between STK11/LKB1 expression and the effects of anti-PD-1 antibodies is uncertain. The aim of the study was to correlate the efficacy of pembrolizumab monotherapy and STK11/LKB1 expression in untreated patients with non-small-cell lung carcinoma (NSCLC) and high PD-ligand 1 expression. PATIENTS AND METHODS: From February 2017 to January 2020, we retrospectively analyzed 30 previously untreated patients with NSCLC and a tumor proportion score (TPS) ≥50% treated with pembrolizumab monotherapy. STK11/LKB1 expression in tumor tissue was evaluated by immunohistochemistry. RESULTS: Twenty-three (76.7%) of the 30 patients were classified with low-STK11/LKB1 expression. The median progression-free survival and overall survival of patients with low-STK11/LKB1 expression was shorter than those with high-STK11/LKB1 expression, although the results were not statistically significant. The disease progression rate for the low-STK11/LKB1 group was higher than that of the high-STK11/LKB1 group. CONCLUSION: STK11/LKB1 expression, as measured by immunohistochemistry, could be a useful biomarker associated with the efficacy of pembrolizumab monotherapy for patients with NSCLC and a TPS ≥50%.
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Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Quinases Proteína-Quinases Ativadas por AMP , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas Serina-Treonina Quinases/genética , Estudos RetrospectivosRESUMO
OBJECTIVES: Vascular endothelial growth factor-A (VEGF-A) plays important roles in tumor immune suppression and thus correlates with the efficacy of anti-programmed cell death-1/ligand 1 (anti-PD-1/PD-L1) antibodies. We aimed to determine the association between change in plasma VEGF-A levels and the efficacy of chemotherapy combined with anti-PD-1/PD-L1 antibodies (chemo-PD1) in non-small cell lung cancer (NSCLC) patients. METHODS: We included NSCLC patients treated with chemo-PD1. Plasma VEGF-A levels were measured at baseline (Pre) and days 7 (D7) and 14 (D14) after the initiation of chemo-PD1. Continuous VEGF-A decrease was determined by comparing Pre with the median value of maximum change rate of posttreatment VEGF-A as cutoff. Patients whose change rates of VEGF-A at both D7 and D14 were consistently lower than the cutoff value were classified into the VEGF-A decrease group, whereas those whose VEGF-A at D7 or D14 were higher than the cutoff level were classified into the VEGF-A no-decrease group. The primary outcome was progression-free survival (PFS). RESULTS: A total of 32 patients were evaluated. The median Pre VEGF-A levels was 49 (range, 13-257). The median change rate of VEGF-A at D7 and D14 was -25.6% (range, -77.5-376.9) and -42.3% (range, -100-138.5) respectively. The cutoff value of posttreatment VEGF-A change rate was -9.3%. The PFS was significantly longer in the VEGF-A decrease group than that in the VEGF-A no-decrease group (median, not reached vs 2.4 months; p = 0.017). CONCLUSIONS: Continuous decrease of plasma VEGF-A levels during treatment may be associated with the efficacy of chemo-PD1.
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Antígeno B7-H1/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Docetaxel (DTX) efficacy increases in patients with non-small cell lung cancer (NSCLC) who had received anti-programmed cell death-1/ligand 1 (anti-PD-1/L1) therapy. However, the effect of ramucirumab (Ram) on DTX efficacy following anti-PD-1/L1 therapy is unknown. Here, we aimed to evaluate the effect of Ram on DTX efficacy following anti-PD-1/L1 therapy. MATERIALS AND METHODS: This retrospective study included 99 patients with NSCLC, who were divided into those who had (pre-ICI group) or had not (no-ICI group) received anti-PD-1/L1 antibody before DTX. Both groups were then treated with DTX or DTX plus Ram (DTX/Ram). Patient characteristics were compared between the DTX and DTX/Ram groups and adjusted with inverse probability of treatment weighting using propensity scores and the following confounding variables: age, sex, performance status, smoking status, histology, driver mutation, and line of treatment. We compared DTX/Ram and DTX in terms of efficacy in both the pre-ICI and no-ICI groups. RESULTS: In the pre-ICI group, 18 and 21 patients received DTX and DTX/Ram, respectively. In the no-ICI group, 35 and 25 patients received DTX and DTX/Ram. In the no-ICI group, progression-free survival (PFS) and overall survival (OS) were not significantly different between DTX/Ram- and DTX-treated patients (median PFS, 2.6 versus 1.6 months; pâ¯=â¯0.30, median OS; 8.2 versus 8.0 months; pâ¯=â¯0.30). In the pre-ICI group, PFS was significantly longer in DTX/Ram-treated than in DTX-treated patients (median, 5.9 versus 2.8 months; pâ¯=â¯0.03). Hazard ratio for disease progression or death was 0.75 (95% confidence interval, 0.20-0.96). The OS of DTX/Ram-treated patients tended to be longer than that of DTX-treated patients (median, 19.8 versus 8.6 months; pâ¯=â¯0.10). CONCLUSIONS: DTX efficacy following anti-PD-1/L1 therapy may be enhanced by Ram. Further studies are needed to validate the efficacy of inhibiting the vascular endothelial growth factor pathway following anti-PD-1/L1 therapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Monoclonais Humanizados , Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular , RamucirumabRESUMO
BACKGROUND: This study aimed to determine whether the neutrophil-to-lymphocyte ratio (NLR) reflected poor treatment benefits in patients with tumor proportion score (TPS) ≥50% and who under went first-line pembrolizumab monotherapy. PATIENTS AND METHODS: This study retrospectively analyzed patients with untreated stage III/IV or recurrent non-small cell lung cancer (NSCLC) with TPS ≥50% and who received pembrolizumab monotherapy at two hospitals between February 2017 and April 2019. The NLR was calculated from pre-treatment complete blood counts. RESULTS: A total of 51 previously untreated patients with NSCLC who had TPS ≥50% and who underwent pembrolizumab monotherapy were evaluated. Multivariate analysis revealed that high NLR, Eastern Cooperative Oncology Group performance status (PS) ≥2, stage IV or recurrent cancer, and TPS=50-74% were significantly and independently associated with poor progression-free survival. Moreover, high NLR and PS ≥2 were significantly associated with short overall survival. CONCLUSION: A high pre-treatment NLR was associated with significantly short progression-free and overall survival in previously untreated patients with NSCLC with high expression of programmed cell-death ligand 1 treated with pembrolizumab monotherapy.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Contagem de Leucócitos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Regulação para CimaRESUMO
Interstitial lung disease (ILD) has rarely been reported as a manifestation of giant cell arteritis (GCA). We herein report a unique case of GCA in a 76-year-old woman who presented with ILD as an initial manifestation of GCA. Ten years before admission, she had been diagnosed with granulomatous ILD of unknown etiology. Corticosteroid therapy induced remission. One year after the cessation of corticosteroid therapy, she was admitted with a persistent fever. After admission, she developed left oculomotor paralysis. Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) proved extremely useful in establishing the diagnosis. Our case promotes awareness of GCA as a possible diagnosis for granulomatous ILD with unknown etiology.