Immunotherapy or Chemoimmunotherapy in Older Adults With Advanced Non-Small Cell Lung Cancer.

Importance: Immune checkpoint inhibitor (ICI) plus chemotherapy combination treatment (ICI-chemotherapy) is now a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alterations, but there are few data on ICI-chemotherapy for patients 75 years and older. Objective: To inform the choice of first-line drugs in clinical practice and assess the safety and efficacy of ICI-chemotherapy combination treatment in older adult patients with previously untreated advanced NSCLC. Design, Setting, and Participants: This retrospective cohort study included 58 centers in Japan. The cohort consisted of patients 75 years and older with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC. Patients started first-line systemic therapy between December 2018 and March 2021. Those receiving first-line molecular targeted drugs were excluded. The data were analyzed from February 2022 to October 2022. Exposures: Systemic therapy. Main Outcomes and Measures: The main outcomes were overall survival (OS), progression-free survival (PFS), and safety. Results: A total of 1245 patients (median [range] age, 78 [75-95] years; 967 [78%] male) with NSCLC were included in the cohort. Programmed death ligand-1 (PD-L1) expression of less than 1% occurred in 268 tumors (22%); 1% to 49% in 387 tumors (31%); 50% and higher in 410 tumors (33%), and unknown expression in 180 tumors (14%). Median OS was 20.0 (95% CI, 17.1-23.6) months for the 354 patients receiving ICI-chemotherapy (28%); 19.8 (95% CI, 16.5-23.8) months for the 425 patients receiving ICI alone (34%); 12.8 (95% CI, 10.7-15.6) months for the 311 patients receiving platinum-doublet chemotherapy (25%); and 9.5 (95% CI, 7.4-13.4) months for the 155 patients receiving single-agent chemotherapy (12%). After propensity score matching, no differences in OS and PFS were found between the patients receiving ICI-chemotherapy vs ICI alone. Each group consisted of 118 patients. For PD-L1 expression of 1% and higher the OS hazard ratio (HR) was 0.98 (95% CI, 0.67-1.42; P = .90), and the PFS HR was 0.92 (95% CI, 0.67-1.25; P = .59). Significance was also not reached when separately analyzed for lower or higher PD-L1 expression (1%-49% or ≥50%). However, grade 3 or higher immune-related adverse events occurred in 86 patients (24.3%) treated with ICI-chemotherapy and 76 (17.9%) with ICI alone (P = .03). Conclusions and Relevance: In this study, ICI-chemotherapy combination treatment did not improve survival and increased the incidence of grade 3 and higher immune-related adverse events compared with ICI alone in patients 75 years and older. Based on these results, ICI alone may be recommended for older adult patients with PD-L1-positive NSCLC.

Clinical characteristics of rheumatoid arthritis patients complicated with pulmonary nontuberculous mycobacterial disease: A cross-sectional case series study.

OBJECTIVES: Pulmonary nontuberculous mycobacterial disease (pNTM) is a common pulmonary complication of rheumatoid arthritis (RA), but their association has rarely been researched. We aimed to reveal the clinical characteristics of RA with pNTM. METHODS: Among all the RA patients who visited Tenri hospital from April 2017 to March 2018, we enrolled those fulfilling the 2007 ATS/IDSA diagnostic criteria of pNTM, and sex- and age- matched control group at a ratio of 1:5. Demographic characteristics were compared between the two groups. RESULTS: Among 865 RA patients, 35 (4.0%) patients were complicated with pNTM. RA patients with pNTM had significantly lower BMI and higher rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity. Bronchiectasis was the most frequent lesion, followed by clusters of small nodules, patchy consolidation and cavity. Multivariable logistic regression analysis revealed bronchiectasis as a strong independent associated factor of pNTM. Treatment for pNTM was needed in 14 of the 35 (40%) RA patients with pNTM and sputum negative conversion was accomplished in 11 of the 14 cases (78.6%). CONCLUSIONS: RA patients with lower BMI, RF/ACPA positivity, and bronchiectasis were associated with pNTM. Treatment for pNTM may attain sputum negative conversion and radiological improvement in patients with RA.

Prediction of forced vital capacity with dynamic chest radiography in interstitial lung disease.

PURPOSE: The pulmonary function test (PFT) has played an essential role in diagnosing and managing interstitial lung disease (ILD) but has its contraindications and difficult conditions to perform. Therefore, the present study aimed to evaluate dynamic chest radiography (DCR) ability to predict forced vital capacity (FVC) and other PFT parameters of ILD patients. METHOD: The prospective observational study included 97 patients who underwent DCR at Tenri Hospital (Tenri, Japan) between June 2019 and April 2020. Twenty-five patients with stable disease status underwent DCR twice to evaluate test-retest reliability using the intraclass correlation coefficient. From the lung field areas measured by DCR, lung volumes at maximum inspiration (V.ins) and expiration (V.exp) were estimated. Correlation coefficients between the measured values of DCR and PFT parameters were calculated. Multilinear models for predicting FVC and other PFT parameters were developed. RESULTS: Intraclass correlation coefficients between first and second measurements of V.ins and V.exp were 0.94 (95% CI: 0.89-0.97, p < 0.001) and 0.88 (95% CI: 0.78-0.94, p < 0.001), respectively. The correlation coefficient between V.ins and FVC was 0.86 (95% CI: 0.79-0.90, p < 0.001). A multilinear model for predicting FVC was developed using V.ins, V.exp, age, sex, and body mass index as predictor variables, wherein the adjusted coefficient of determination was 0.814. CONCLUSIONS: Lung volumes measured by DCR correlated with the lung function of ILD patients. Prediction models with high predictive power and internal validity were developed, suggesting that DCR can predict FVC and other PFT parameters of ILD patients.

A case report of pulmonary Botrytis sp. infection in an apparently healthy individual.

BACKGROUND: Botrytis species are well known fungal pathogens of various plants but have not been reported as human pathogens, except as allergenic precipitants of asthma and hypersensitivity pneumonitis. CASE PRESENTATION: The asymptomatic patient was referred because of a nodule revealed by chest X-ray. Computed tomography (CT) showed a cavitary nodule in the right upper lobe of the lung. He underwent wedge resection of the nodule, which revealed necrotizing granulomas and a fungus ball containing Y-shaped filamentous fungi, which was confirmed histopathologically. Culture of the specimen yielded white to grayish cotton-like colonies with black sclerotia. We performed multilocus gene sequence analyses including three single-copy nuclear DNA genes encoding glyceraldehyde-3-phosphate dehydrogenase, heat-shock protein 60, and DNA-dependent RNA polymerase subunit II. The analyses revealed that the isolate was most similar to Botrytis elliptica. To date, the pulmonary Botrytis sp. infection has not recurred after lung resection and the patient did not require any additional medication. CONCLUSIONS: We report the first case of an immunocompetent patient with pulmonary Botrytis sp. infection, which has not recurred after lung resection without any additional medication. Precise evaluation is necessary for the diagnosis of pulmonary Botrytis infection because it is indistinguishable from other filamentous fungi both radiologically and by histopathology. The etiology and pathophysiology of pulmonary Botrytis infection remains unclear. Further accumulation and analysis of Botrytis cases is warranted.

Pseudoprogression in Previously Treated Patients with Non-Small Cell Lung Cancer Who Received Nivolumab Monotherapy.

INTRODUCTION: Nivolumab is effective in the treatment of previously treated patients with advanced NSCLC. However, its radiological evaluation is challenging because of atypical patterns of response such as pseudoprogression. We examined the characteristics and outcomes of previously treated patients with NSCLC who were treated with nivolumab and experienced development of pseudoprogression. METHODS: We conducted a 15-center retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab monotherapy. For the patients who showed pseudoprogression, we defined progression-free survival 1 (PFS1) as the time to Response Evaluation Criteria in Solid Tumors-defined first progressive disease and progression-free survival 2 (PFS2) as the time to Response Evaluation Criteria in Solid Tumors-defined second progressive disease or death. RESULTS: Among the 542 patients included, 20% and 53% showed a typical response and progression, respectively. Of the 14 (3%) patients who showed pseudoprogression, most (n = 10) showed a response within 3 months of nivolumab treatment. The median PFS1 and PFS2 were 1.0 and 7.3 months, respectively. The median PFS2 was significantly shorter in the patients who showed pseudoprogression than the PFS of the patients with a typical response (p < 0.001). In contrast, patients showing pseudoprogression had significantly longer overall survival than did patients showing typical progression (p = 0.001). CONCLUSIONS: Pseudoprogression was uncommon, and the duration of response in patients who showed pseudoprogression was shorter than that in patients who showed a typical response. However, the survival benefit of pseudoprogression was markedly better than that of typical progression. Further research is required to elucidate the characteristics of and mechanisms underlying pseudoprogression.

Efficacy and safety of nivolumab in previously treated patients with non-small cell lung cancer: A multicenter retrospective cohort study.

INTRODUCTION: Nivolumab has been shown to be effective and safe in previously treated patients with advanced non-small cell lung cancer (NSCLC). However, little is known regarding its performance in real-world (i.e., non-trial) settings. Furthermore, nivolumab efficacy is unknown in patients who are ineligible for clinical trials or who are categorized into small subgroups in such trials. METHODS: We conducted a 15-center, observational, retrospective cohort study of patients with advanced NSCLC who received nivolumab monotherapy between January and December 2016. RESULTS: Of 613 patients included in our study, 141 had poor performance status (PS) and 106 were EGFR mutation - or ALK rearrangement-positive. The response and disease control rates were 20% and 44%, respectively; the estimated 1-year progression-free survival (PFS) was 18%. Multivariate analysis identified never smoking, poor PS, and EGFR mutation/ALK rearrangement as independent negative predictors of PFS. The most frequently reported grade ≥3 adverse event was pneumonitis (5% of patients). Severe pneumonitis (grade ≥3) occurred significantly earlier than mild pneumonitis (1.6 vs. 2.3 months, P = 0.031). Patients with pneumonitis achieved higher response rates and longer PFS than those without (37% vs. 18%, and 5.8 vs. 2.1 months, respectively; P = 0.002). CONCLUSIONS: Smoking status, PS, and EGFR mutation/ALK rearrangement were independent predictors of PFS. Our study elucidated nivolumab's efficacy in previously underreported patient populations; i.e., those with poor PS and/or with driver oncogenes. We also found that pneumonitis is not infrequent, and carries key implications for outcomes. These data should be useful for improving the clinical courses of nivolumab-treated patients with NSCLC.

Nontuberculous mycobacteria in diffuse panbronchiolitis.

BACKGROUND AND OBJECTIVE: Nontuberculous mycobacterial (NTM) lung disease secondary to cystic fibrosis (CF) has been reported, but there is limited data about NTM prevalence in non-CF bronchiectasis. We retrospectively investigated the prevalence of NTM associated with diffuse panbronchiolitis (DPB), a disorder also characterized by reduced mucociliary clearance with bronchiectasis. METHODS: We reviewed mycobacterial cultures, patient characteristics and computed tomography findings of 33 patients with DPB between January 2000 and December 2012. Prevalence was based on at least one positive NTM culture. RESULTS: Mean patient age was 51.5 years. During a mean 162.8-month follow-up, the prevalence of NTM in sputum was 21.2% (seven patients). Of the seven positive patients, six had Mycobacterium avium complex, one had M. kansasii and M. chelonae co-cultured with M. avium complex. Three patients were positive twice, and two had positive smears. The mean time from DPB diagnosis to the first positive result was 194.6 months. NTM-positive patients tended to have lower forced expiratory volume in 1 s (% predicted) than NTM-negative patients (50.0% vs 77.3%, P = 0.03), but there were no radiological or clinical differences between the two groups. CONCLUSIONS: Our observations suggest that NTM is found more often in DPB. Defects of mucociliary clearance may predispose individuals to NTM infection.

[An analysis of the correlation between guidelines-concordant treatment and the treatment outcome on nursing and healthcare-associated pneumonia patients].

BACKGROUND: The nursing and healthcare-associated pneumonia (NHCAP) guidelines recommend broad-spectrum antibiotics usage when the presence of multidrug resistant pathogens is anticipated. However, it has not been proved that guidelines-concordant treatment improves the outcome. PURPOSE: To clarify the impact of guidelines-concordant treatment on the outcome of NHCAP patients. METHOD: This was a single-center, medical record based retrospective study. The outcomes of NHCAP patients who were treated with guidelines-concordant antibiotics were compared with those of the patients who were not so treated. Then, along with other parameters such as pneumonia severity or patient backgrounds, we analyzed what parameters affected the outcome of NHCAP. RESULT: Two hundred and twenty-six admissions were analyzed. Guidelines-concordant treatment did not show significant correlation with 30 days mortality, in-hospital mortality or treatment failure. A multivariate analysis showed a significant correlation between the treatment outcome and no parameters other than "Classified into severe-group of community-acquired pneumonia". Even in the analysis limited to the patients who were actually proved to possess drug-resistant pathogens, the antibiotic coverage of the pathogens did not show any correlation with the outcomes. CONCLUSION: NHCAP guidelines-concordant treatment might not improve the patient outcome.

Successful chemotherapy for small-cell lung cancer in an elderly patient undergoing continuous ambulatory peritoneal dialysis.

A standard treatment has not yet been established for elderly small-cell lung cancer patients, especially when they have end-stage renal disease. We report the first case of successful chemoradiotherapy in an elderly small-cell lung cancer patient undergoing continuous ambulatory peritoneal dialysis. A 77-year-old Japanese man on continuous ambulatory peritoneal dialysis was diagnosed as having limited disease small-cell lung cancer. He received four monthly cycles of chemotherapy consisting of carboplatin at 240 mg/m(2) on day 1 and etoposide at 40 mg/m(2) on days 1 and 3. He underwent additional hemodialysis on days 1 and 3, while continuous ambulatory peritoneal dialysis continued as usual on the other days. Following chemotherapy, he underwent hyperfractionated radiotherapy to a total dose of 45 Grey, resulting in complete remission of the disease. A pharmacokinetic study showed an area under the concentration-time curve of carboplatin of 3.41 to 4.88 mg.min/mL, increasing gradually over the first three cycles, while etoposide did not show this gradual increase. The increased area under the concentration-time curve of carboplatin may have reflected a worsened renal function during chemotherapy. Despite dose reductions and favorable areas under the concentration-ime curve of carboplatin, the patient suffered grade 3-4 hematological toxicities, necessitating transfusions and a further dose reduction. The patient died of recurrent small-cell lung cancer 19 months after diagnosis.