RESUMO
BACKGROUND: Monitoring the progression of idiopathic pulmonary fibrosis (IPF) using CT primarily focuses on assessing the extent of fibrotic lesions, without considering the distortion of lung architecture. OBJECTIVES: To evaluate three-dimensional average displacement (3D-AD) quantification of lung structures using deformable registration of serial CT images as a parameter of local lung architectural distortion and predictor of IPF prognosis. MATERIALS AND METHODS: Patients with IPF evaluated between January 2016 and March 2017 who had undergone CT at least twice were retrospectively included (n = 114). The 3D-AD was obtained by deformable registration of baseline and follow-up CT images. A computer-aided quantification software measured the fibrotic lesion volume. Cox regression analysis evaluated these variables to predict mortality. RESULTS: The 3D-AD and the fibrotic lesion volume change were significantly larger in the subpleural lung region (5.2 mm (interquartile range (IQR): 3.6-7.1 mm) and 0.70% (IQR: 0.22-1.60%), respectively) than those in the inner region (4.7 mm (IQR: 3.0-6.4 mm) and 0.21% (IQR: 0.004-1.12%), respectively). Multivariable logistic analysis revealed that subpleural region 3D-AD and fibrotic lesion volume change were independent predictors of mortality (hazard ratio: 1.12 and 1.23; 95% confidence interval: 1.02-1.22 and 1.10-1.38; p = 0.01 and p < 0.001, respectively). CONCLUSIONS: The 3D-AD quantification derived from deformable registration of serial CT images serves as a marker of lung architectural distortion and a prognostic predictor in patients with IPF.
RESUMO
PURPOSE: Panel-based comprehensive genomic profiling (CGP) is used in clinical practice worldwide; however, large real-world data (RWD) of patients with advanced small intestine cancer have not been characterized. We investigated differences in the prevalence of clinically relevant alterations across molecularly defined or age-stratified subgroups. PATIENTS AND METHODS: This was a collaborative biomarker study of RWD from CGP testing (Foundation Medicine, Inc). Hybrid capture was conducted on at least 324 cancer-related genes and select introns from up to 31 genes frequently rearranged in cancer. Overall, 1,364 patients with advanced small intestine cancer were available for analyses and were stratified by age (≥40 years/<40 years), microsatellite instability (MSI) status, tumor mutational burden (TMB) status (high ≥10/low <10 Muts/Mb), and select gene alterations. The frequency of alterations was analyzed using a chi-square test with Yate's correction. RESULTS: Genes with frequent alterations included TP53 (59.8%), KRAS (54.8%), APC (27.7%), and CDKN2A (22.4%). Frequent genes with amplifications were MYC (6.7%), MDM2 (5.9%), GATA6 (5.5%), and CCND1 (3.4%). Patients younger than 40 years had significantly lower frequency of APC mutations than those 40 years and older (10.4% v 28.7%; P = .0008). Druggable genomic alterations were detected in 22.3% of patients: BRAF V600E (1.2%), BRCA1 (1.8%), BRCA2 (3.2%), ERBB2 amplification (3.2%), KRAS G12C (3.3%), NTRK1/2/3 fusion (0.07%), MSI-high (7.0%), and TMB-high (12.2%), with no significant differences in the frequency according to age (<40 years v ≥40 years; 22.1% v 22.3%). TMB of 10-20 Mut/Mb was observed in 4.8% of patients, and TMB ≥20 Mut/Mb was seen in 7.3% of the cohort. CONCLUSION: RWD from clinical panel testing revealed the genomic landscape in small intestine cancer by subgroup. These findings provide insights for the future development of treatments in advanced small intestine cancer.
Assuntos
Neoplasias Intestinais , Intestino Delgado , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Neoplasias Intestinais/genética , Idoso , Idoso de 80 Anos ou mais , Genômica , Adulto Jovem , Mutação , Instabilidade de MicrossatélitesRESUMO
Various symptoms emerge as immune-related adverse events of immune checkpoint inhibitor (ICI). A 73-year-old woman, a non-smoker, receiving chemotherapy including atezolizumab for lung adenocarcinoma, presented with fever, bilateral parotid swelling and sicca syndrome after four courses of chemotherapy. Because the lesions were not localized, the diagnosis was ICI-related sialadenitis rather than infectious. Prednisolone improved salivary gland swelling quickly. Six months after the last administration of ICI, there was no obvious progression of lung cancer. To our knowledge, this is the first case of sialadenitis caused by atezolizumab. ICI-related sialadenitis may be a good prognostic marker for lung cancer.
RESUMO
Herein, we report a case of 72-year-old man who had L858R EGFR-mutated lung adenocarcinoma. Chest computed tomography revealed a large lung mass that had completely replaced the right upper lobe. Although the mass dramatically shrank after initiating chemotherapy, non-malignant pleural effusion appeared. Because diffuse pleural thickening and shrinking of the thoracic cage gradually became apparent, the patient was diagnosed with trapped lung. Despite the stabilization of his lung cancer, he experienced severe dyspnea and significant weight loss, ultimately leading to a decreased performance status. Chest physicians should recognize that trapped lung can develop as a sequela of dramatic tumor shrinkage in lung cancer.
RESUMO
Pleuroparenchymal fibroelastosis (PPFE) is characterized by fibrosis involving the pleura and subpleural lung parenchyma, predominantly in the upper lobes. As PPFE appears to occur in patients with heterogeneous etiologies, the disease course is thus also heterogenous, with some patients showing rapid progression while others have slow progression. Therefore, it is very difficult to predict prognosis with PPFE. Needless to say, this problematic matter has influenced the treatment strategy of PPFE patients. In fact, until now no evidence has been shown for use in creating an appropriate management algorithm for PPFE. We speculate that "uncoordinated breathing" is the most important reason for dyspnea in PPFE patients. Because monitoring of physique and not just pulmonary function and radiological evaluation is also very important, particularly in PPFE patients, this review focused on the characteristics of PPFE through an overview of previous studies in this field, and we proposed an algorithm as precision medicine based on the current evidence. Multiple views by the pulmonologist are needed to standardize a clinical algorithm that is necessary to correctly assess PPFE patients under the premise of maintenance of physique by providing appropriate nutritional care and pulmonary rehabilitation.
RESUMO
BACKGROUND: According to international diagnostic guidelines for hypersensitivity pneumonitis (HP), cases with both nonfibrotic and fibrotic lesions are classified by the predominant feature. Therefore, some cases with nonfibrotic HP, have inflammatory lesions alone, while others have a mixture of fibrosis and inflammation. We investigated the impact of slight fibrotic lesions in nonfibrotic HP. METHODS: This retrospective study included nonfibrotic HP cases with <10% of lung distortion on high-resolution CT. We divided the cases into two groups: those with pure ground glass opacities (GGOs) without lung distortion and those with slight lung distortion of <10%. RESULTS: In this study, 37 cases were included. The mean baseline forced vital capacity (FVC) was 109% in the pure GGO group and 96% in the slight lung distortion group (p = 0.038). After 1 year, the reticular shadows appeared or increased more in the slight lung distortion group than in the pure GGO group (16% vs. 8%, p = 0.030). The time to medication initiation was significantly shorter in the slight lung distortion group than in the pure GGO group (p = 0.044). %FVC decreased by ≥ 5% from diagnosis in no cases with the pure GGO and in two cases with the slight lung distortion (-11.0% for 9.5 years and -10.7% for 1.3 years, respectively). CONCLUSIONS: The slight distortion group exhibited a higher rate of worsening and new appearance of reticular shadows after 1 year and a shorter time to first medication compared to the pure GGO group.
RESUMO
PURPOSE: We aimed to identify computed tomography (CT) radiomics features that are associated with cellular infiltration and construct CT radiomics models predictive of cellular infiltration in patients with fibrotic ILD. MATERIALS AND METHODS: CT images of patients with ILD who underwent surgical lung biopsy (SLB) were analyzed. Radiomics features were extracted using artificial intelligence-based software and PyRadiomics. We constructed a model predicting cell counts in histological specimens, and another model predicting two classifications of higher or lower cellularity. We tested these models using external validation. RESULTS: Overall, 100 patients (mean age: 62 ± 8.9 [standard deviation] years; 61 men) were included. The CT radiomics model used to predict cell count in 140 histological specimens predicted the actual cell count in 59 external validation specimens (root-mean-square error: 0.797). The two-classification model's accuracy was 70% and the F1 score was 0.73 in the external validation dataset including 30 patients. CONCLUSION: The CT radiomics-based model developed in this study provided useful information regarding the cellular infiltration in the ILD with good correlation with SLB specimens.
RESUMO
Background: In compatible with fibrotic hypersensitivity pneumonitis (HP) of the computed tomography (CT) classification using the American Thoracic Society (ATS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) HP guidelines, the lung fibrosis pattern was classified as either a usual interstitial pneumonia (UIP) pattern or a diffuse ground-glass opacity (GGO) pattern with subtle fibrosis. We investigated whether patients with the same imaging classification had different disease progression. We also attempted to reclassify these patients using the CHEST HP guidelines. Methods: Patients with fibrotic HP who had compatible CT pattern in the ATS/JRS/ALAT classification were investigated retrospectively. Results: With 62 patients in the UIP pattern group and 25 patients in the diffuse GGO pattern group, 87 patients with fibrotic HP had compatible pattern on CT. Annual forced vital capacity changes in the UIP pattern group and diffuse GGO pattern group were -2.7% and +3.3% (P=0.004), respectively. The 5-year survival rates in the UIP pattern group and diffuse GGO pattern group were 86% and 100% (P=0.02). In UIP pattern group in the ATS/JRS/ALAT classification, 27% patients were classified as typical fibrotic HP pattern in the CHEST guidelines. In the diffuse GGO pattern group, 52% patients were classified as typical pattern of fibrotic HP. In the CHEST guidelines, more patients in the GGO pattern were classified as typical pattern compared with those in the UIP pattern (P=0.02). Conclusions: The two patterns in compatible with fibrotic HP of CT classification using the ATS/JRS/ALAT HP guidelines had different disease progression. Typical patterns were more frequent in the CHEST guidelines than the ATS/JRS/ALAT guidelines.
RESUMO
BACKGROUND: Evaluation of the antigen responsible for fibrotic hypersensitivity pneumonitis (HP) is challenging. Serum immunoglobulin (Ig) G testing against HP-associated antigens is performed. Although single-serum IgG testing has been investigated, multiple-serum IgG testing has not yet been studied. METHODS: This study included patients who underwent histopathological examination and positive inhalation challenge test as well as those with moderate or high HP guideline confidence level. Serum IgG testing against pigeon serum was conducted twice using two methods: enzyme linked-immunosorbent assay (ELISA) and ImmunoCAP. The association between changes in serum IgG antibody titers and changes in forced vital capacity (FVC) and other parameters was investigated. RESULTS: In this study, 28 patients (mean age, 64.5 years; mean FVC, 85.3%) with fibrotic avian HP were selected, of whom 20 and 8 underwent surgical lung biopsy and transbronchial lung cryobiopsy, respectively. Of the 28 patients, 19 had been keeping birds for more than 6 months. A correlation was observed between the annual changes in serum IgG antibody titers by ELISA and changes in relative FVC (r = - 0.6221, p < 0.001). Furthermore, there was a correlation between the annual changes in serum IgG antibody titers by ImmunoCAP and changes in relative FVC (r = - 0.4302, p = 0.022). Multiple regression analysis revealed that the change in serum IgG antibody titers by both ELISA and ImmunoCAP also influenced the relative FVC change (p = 0.012 and p = 0.015, respectively). Moreover, 13 patients were given additional treatments between the first and second blood test; however, the additional treatment group was not significantly different in relative FVC change compared to the group with no additional treatment (p = 0.982). CONCLUSIONS: In patients with fibrotic avian HP, the annual changes in serum IgG testing were correlated with FVC changes, highlighting the importance of serum IgG testing over time.
Assuntos
Pulmão do Criador de Aves , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Imunoglobulina G/sangue , Idoso , Pulmão do Criador de Aves/imunologia , Pulmão do Criador de Aves/diagnóstico , Pulmão do Criador de Aves/sangue , Animais , Capacidade Vital , Columbidae , Pulmão/patologia , Pulmão/fisiopatologia , Estudos Longitudinais , Alveolite Alérgica Extrínseca/sangue , Alveolite Alérgica Extrínseca/imunologia , Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/patologiaRESUMO
We present a case of lung adenocarcinoma with malignant pleural effusion. Nineteen days after pleurodesis using minocycline and OK-432 (picibanil), pembrolizumab monotherapy was initiated. Four days later, the patient experienced a persistent cough. Chest computed tomography showed that ground-glass opacity appeared on the same side as pleurodesis and spread bilaterally thereafter, which was diagnostic of immune checkpoint inhibitors (ICI)-related pneumonitis. As he presented a severe respiratory failure, corticosteroid therapy was administered. Two weeks later, respiratory failure completely resolved and the abnormal shadows dramatically improved. Our results indicate that severe ICI-related pneumonitis can develop within a short period after pleurodesis.
RESUMO
Non-small cell lung cancer (NSCLC) patients are often complicated by other respiratory diseases, including interstitial pneumonia (IP), chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB), and the management of which can be problematic. NSCLC patients with IP sometimes develop fatal acute exacerbation induced by pharmacotherapy, and the establishment of a safe treatment strategy is desirable. For advanced NSCLC with IP, carboplatin plus nanoparticle albumin-bound paclitaxel is a relatively safe and effective first-line treatment option. Although the safety of immune checkpoint inhibitors (ICIs) for these populations remains controversial, ICIs have the potential to provide long-term survival. The severity of COPD is an important prognostic factor in NSCLC patients. Although COPD complications do not necessarily limit treatment options, it is important to select drugs with fewer side effects on the heart and blood vessels as well as the lungs. Active TB is complicated by 2-5% of NSCLC cases during their disease course. Since pharmacotherapy, especially ICIs, reportedly induces the development of TB, the possibility of developing TB should always be kept in mind during NSCLC treatment. To date, there is no coherent review article on NSCLC with these pulmonary complications. This review article summarizes the current evidence and discusses future prospects for treatment strategies for NSCLC patients complicated with IP, severe COPD, and TB.
RESUMO
Effective treatment for advanced lung cancer and idiopathic interstitial pneumonia (IIP) remains an unmet medical need. The relationship between chemotherapy's effectiveness in advanced lung cancer and the risk of acute exacerbation of IIP is poorly investigated. There is limited evidence that patients who experience an acute exacerbation of IIPs during cytotoxic chemotherapy have poorer outcomes than those who do not. Among 1004 patients with advanced lung cancer and IIPs enrolled in our published multi-centre retrospective study from 110 Japanese institutions, 708 patients (male: female, 645:63; mean age, 70.4) received first-line chemotherapy. The occurrence of chemotherapy-triggered acute exacerbations of IIPs and overall survival (OS) were analysed. The OS between groups of patients with and without the occurrence of acute exacerbation was compared at four landmark time points (30, 60, 90, and 120 days), starting from the first-line chemotherapy, using the landmark method. The incidence of acute exacerbation in patients who received first-line chemotherapy with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was more frequent in NSCLC patients than in SCLC (4.2% vs 12.6%; odds ratio [OR]: 3.316; 95% confidence interval [CI] 1.25-8.8). Median survival time was 9.9 months (95% CI 9.2-10.7). Patients who experienced acute exacerbation had significant worse survival outcomes than those who did not at various time points (30 days, hazard ratio [HR]: 5.191, 95% CI 2.889-9.328; 60 days, HR: 2.351, 95% CI 1.104-5.009; 90 days, HR: 2.416, 95% CI 1.232-4.739; and 120 days, HR: 2.521, 95% CI 1.357-4.681). Acute exacerbation during first-line chemotherapy can predict poor survival.Trial Registration number: UMIN000018227.
Assuntos
Pneumonias Intersticiais Idiopáticas , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Idoso , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Pneumonias Intersticiais Idiopáticas/tratamento farmacológico , Pneumonias Intersticiais Idiopáticas/mortalidade , Estudos Retrospectivos , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Prognóstico , Progressão da Doença , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Resultado do Tratamento , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Idoso de 80 Anos ou maisRESUMO
Importance: Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events. Objective: To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis. Design, Setting, and Participants: Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023. Interventions: Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks. Main Outcomes and Measures: The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported. Results: Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group). Conclusions and Relevance: Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. Trial Registration: ClinicalTrials.gov Identifier: NCT03955146.
Assuntos
Anticorpos Monoclonais Humanizados , Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Masculino , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Pessoa de Meia-Idade , Idoso , Capacidade Vital , Adulto , Método Duplo-Cego , Idoso de 80 Anos ou mais , Progressão da Doença , Fator de Crescimento do Tecido ConjuntivoRESUMO
BACKGROUND: In previous Japanese subgroup/subset analyses of the global INBUILD trial, nintedanib reduced the annual rate of forced vital capacity (FVC) decline and the risk of disease progression in patients with progressive fibrosing interstitial lung diseases (PF-ILDs). This exploratory subset analysis assessed the effect of nintedanib on symptoms and impacts of pulmonary fibrosis in Japanese patients with PF-ILDs, including those with usual interstitial pneumonia (UIP)-like fibrotic pattern on high-resolution computed tomography (HRCT). METHODS: This analysis included Japanese patients who received at least one dose of study treatment in the randomized, double-blind, placebo-controlled INBUILD trial. The Living with Pulmonary Fibrosis (L-PF) questionnaire was used to assess pulmonary fibrosis symptoms and impacts (higher scores indicated greater impairment) at baseline and weeks 12-52. RESULTS: In total, 108 Japanese patients (nintedanib: n = 52; placebo: n = 56) were included; 84 patients had UIP-like fibrotic pattern on HRCT. In the total Japanese subgroup and in those with UIP-like fibrotic pattern, numerically greater increases in L-PF total, symptoms total, symptoms fatigue domain, and impacts scores were observed in the placebo group than in the nintedanib group at all timepoints, starting from week 12. A numerically greater increase in the symptoms dyspnea domain score was observed with placebo versus nintedanib starting from week 36. Throughout the study, the symptoms cough domain score increased in the placebo group but decreased in the nintedanib group. CONCLUSIONS: Our findings demonstrate that nintedanib has the potential to reduce the worsening of symptoms and impacts of pulmonary fibrosis in Japanese patients with PF-ILDs.
Assuntos
Progressão da Doença , Indóis , Doenças Pulmonares Intersticiais , Qualidade de Vida , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Duplo-Cego , População do Leste Asiático , Indóis/uso terapêutico , Indóis/administração & dosagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Fibrose Pulmonar/tratamento farmacológico , Inquéritos e Questionários , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Capacidade VitalRESUMO
BACKGROUND: Panel-based comprehensive genomic profiling is used in clinical practice worldwide; however, large real-world datasets of patients with advanced gastric cancer are not well known. OBJECTIVE: We investigated what differences exist in clinically relevant alterations for molecularly defined or age-stratified subgroups. METHODS: This was a collaborative biomarker study of a real-world dataset from comprehensive genomic profiling testing (Foundation Medicine, Inc.). Hybrid capture was carried out on at least 324 cancer-related genes and select introns from 31 genes frequently rearranged in cancer. Overall, 4634 patients were available for analyses and were stratified by age (≥ 40/< 40 years), microsatellite instability status, tumor mutational burden status (high 10 ≥ /low < 10 Muts/Mb), Epstein-Barr virus status, and select gene alterations. We analyzed the frequency of alterations with a chi-square test with Yate's correction. RESULTS: Genes with frequent alterations included TP53 (60.1%), ARID1A (19.6%), CDKN2A (18.2%), KRAS (16.6%), and CDH1 (15.8%). Differences in comprehensive genomic profiling were observed according to molecularly defined or age-stratified subgroups. Druggable genomic alterations were detected in 31.4% of patients; ATM (4.4%), BRAF V600E (0.4%), BRCA1 (1.5%), BRCA2 (2.9%), ERBB2 amplification (9.2%), IDH1 (0.2%), KRAS G12C (0.7%), microsatellite instability-high (4.8%), NTRK1/2/3 fusion (0.13%), PIK3CA mutation (11.4%), and tumor mutational burden-high (9.4%). CDH1 alterations and MET amplification were significantly more frequent in patients aged < 40 years (27.7 and 6.2%) than in those aged ≥ 40 years (14.7 and 4.0%). CONCLUSIONS: Real-world datasets from clinical panel testing revealed the genomic landscape in gastric cancer by subgroup. These findings provide insights for the current therapeutic strategies and future development of treatments in gastric cancer.
Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Genômica/métodos , Idoso , Terapia de Alvo Molecular/métodosRESUMO
Microsatellite instability (MSI) is a valuable biomarker for immune checkpoint inhibitors. We report the first case of MSI-high thymoma successfully treated with pembrolizumab. This patient had pleural dissemination and was treated with two cytotoxic chemotherapy regimens including carboplatin and paclitaxel combination therapy and pemetrexed, which did not have the desired effect. Because MSI status was high by using the surgical specimen, pembrolizumab was administered as 3rd line chemotherapy. After three courses, the pleural lesions dramatically shrunk, which confirmed a partial response. Although MSI-high thymoma is rare, our results suggest the necessity to evaluate MSI status in patients with thymoma.
Assuntos
Anticorpos Monoclonais Humanizados , Instabilidade de Microssatélites , Timoma , Neoplasias do Timo , Humanos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Timoma/tratamento farmacológico , Timoma/genética , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/genética , Neoplasias do Timo/patologia , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Masculino , Carboplatina/administração & dosagem , Pessoa de Meia-Idade , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , FemininoRESUMO
Amikacin liposome inhalation suspension (ALIS) is known to cause drug-related pneumonitis, which has been described as "hypersensitivity pneumonitis (HP)". However, its clinical and pathological characteristics have never been reported. We retrospectively evaluated 18 patients treated with ALIS. Three (16.7%) patients developed HP-pattern pneumonitis on high-resolution computed tomography. Serum eosinophil counts were elevated up to above 1000/µL in these three patients, which decreased with ALIS discontinuation only. Of note, the specimen obtained by transbronchial lung cryobiopsy in one patient revealed a mild degree of lymphocyte and eosinophil infiltration. Rather, the findings of acute lung injury such as an edematous thickening of the alveolar walls, and an accumulation of foamy degenerative macrophages in the alveolar lumina was prominent. A pulmonary alveolar proteinosis reaction was also observed. HP-pattern pneumonitis due to ALIS may pathologically correspond to acute lung injury and a pulmonary alveolar proteinosis reaction despite increasing serum eosinophil counts.
Assuntos
Amicacina , Eosinófilos , Lipossomos , Humanos , Masculino , Amicacina/administração & dosagem , Amicacina/efeitos adversos , Administração por Inalação , Idoso , Feminino , Estudos Retrospectivos , Eosinófilos/patologia , Pessoa de Meia-Idade , Suspensões , Tomografia Computadorizada por Raios X , Alveolite Alérgica Extrínseca/induzido quimicamente , Contagem de Leucócitos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/diagnóstico por imagemRESUMO
Non-small-cell lung cancer (NSCLC) with comorbid interstitial pneumonia (IP) is a population with limited treatment options and a poor prognosis. Patients with comorbid IP are at high risk of developing fatal drug-induced pneumonitis, and data on the safety and efficacy of molecularly targeted therapies are lacking. KRAS mutations have been frequently detected in patients with NSCLC with comorbid IP. However, the low detection rate of common driver gene mutations, such as epidermal growth factor receptor and anaplastic lymphoma kinase, in patients with comorbid IP frequently results in inadequate screening for driver mutations, and KRAS mutations may be overlooked. Recently, sotorasib and adagrasib were approved as treatment options for advanced NSCLC with KRASG12C mutations. Although patients with comorbid IP were not excluded from clinical trials of these KRASG12C inhibitors, the incidence of drug-induced pneumonitis was low. Therefore, KRASG12C inhibitors may be a safe and effective treatment option for NSCLC with comorbid IP. This review article discusses the promise and prospects of molecular-targeted therapies, especially KRASG12C inhibitors, for NSCLC with comorbid IP, along with our own clinical experience.
RESUMO
A 73-year-old man visited our hospital for persistent cough. Chest high-resolution CT (HRCT) showed infiltration shadows in lower lobes and diffuse ground glass opacities in the upper lobes. Blood tests showed elevated white blood cell, C-reactive protein, surfactant protein D, and Krebs von den Lungen-6 levels. After an antigen avoidance test, his HRCT and blood test findings improved; we diagnosed him with hypersensitivity pneumonitis (HP). A culture of the rotting interior walls within his home revealed Paecilomyces, which we believe caused his HP. Given the few patients with Paecilomyces-induced HP, systematic approach was important to identify the inciting antigen.
RESUMO
Invasive mucinous adenocarcinoma (IMA) of the lung is a rare variant of adenocarcinoma characterized by abundant intracytoplasmic mucin within the tumor. Although IMA has poor sensitivity to conventional chemotherapy regimens used for non-small cell lung cancer, we observed a better response to the bevacizumab (BEV) regimen. In this retrospective study, we aimed to investigate the response to BEV-combined regimens in patients with IMA. Among 16 consecutive patients diagnosed with IMA between January 2016 and December 2020 at our institution and treated with systemic chemotherapy, seven patients were treated with BEV-combined regimens. The overall response rate to BEV-combined regimens was 85.7%, with six patients showing a partial response. The median progression-free survival was 6.1 months. One patient experienced respiratory failure, which was improved after administration of BEV-combined regimen. BEV-combined systemic therapy may have a favorable effect on advanced or recurrent IMA of the lung.