A Case of Immune Aplastic Anemia during Combined Treatment with Atezolizumab and Chemotherapy for Non-Small Cell Lung Cancer.

Immune check point inhibitors (ICIs) have durable antitumor effects. However, autoimmune toxicities, termed immune-related adverse events, occur in some patients. We report a case of severe immune aplastic anemia (AA) in a patient with non-small cell lung cancer who was receiving atezolizumab with bevacizumab/carboplatin/paclitaxel. Although the cancer has not recurred, his bone marrow is depleted and he did not respond to immunosuppressive therapy. He has survived for 1.5 years with blood transfusions and infection control. Immune AA associated with ICIs is rare, and a treatment has not yet been established. This case report provides information on the management and treatment response of patients with AA caused by ICIs. Further studies should investigate the mechanism and pathogenesis of immune AA caused by ICIs.

Thyroid transcription factor-1 (TTF-1) expression and the efficacy of combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapy in non-squamous non-small cell lung cancer.

Background: Thyroid transcription factor-1 (TTF-1) is expressed in approximately 70% of lung adenocarcinomas and is one of the most reliable makers to distinguish primary lung adenocarcinoma from metastatic disease. TTF-1-negative status is a poor prognostic factor, and TTF-1-negative lung adenocarcinoma is associated with poor efficacy of immune checkpoint inhibitor (ICI) monotherapy. However, the relationship between TTF-1 expression and the efficacy of ICI plus chemotherapy is still unclear. Methods: We performed a retrospective analysis of 129 consecutive patients with advanced non-squamous non-small cell lung cancer (NS-NSCLC) treated with ICI monotherapy or ICI plus chemotherapy between January 2016 and December 2021. The expression of programmed death ligand-1 (PD-L1) and TTF-1 was also determined in cases for which no previous data were available. We then evaluated the association between TTF-1 expression status and treatment efficacy. Results: Of the 129 cases, 33 were TTF-1-negative and 96 were positive. In the ICI monotherapy group (N=70), progression-free survival (PFS) was not significantly different between TTF-1-positive and negative patients (median 3.6 vs. 3.8 months, P=0.27); however, in patients with wild-type epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), a trend for worse PFS was observed in TTF-1-negative cases compared with those that were TTF-1-positive (median 3.8 vs. 4.5 months, P=0.088). Moreover, long-term efficacy of ICI monotherapy (>2 years) was not observed in the TTF-1-negative group. TTF-1-negative patients tended to have worse overall survival (OS) than TTF-1-positive patients (median 15.6 vs. 19.5 months, P=0.13). In the ICI plus chemotherapy group (N=59), TTF-1-negative patients tended to have better PFS and similar OS compared with TTF-1-positive patients (median 9.9 vs. 9.6 months, P=0.14; median 32.3 vs. 18.9 months, P=0.78). Long-term efficacy was generally observed in TTF-1-negative patients treated with atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP) (median PFS 22.5 months, median OS not reached). Conclusions: ICI monotherapy is generally less efficacious in TTF-1-negative NS-NSCLC patients, and clinicians should consider ICI plus chemotherapy in these cases. Our study suggests that ABCP is an optimal regimen for TTF-1-negative NS-NSCLC.

A remarkable response to combination chemotherapy with nivolumab and ipilimumab in a patient with primary pulmonary choriocarcinoma: a case report.

Background: Primary pulmonary choriocarcinoma (PPC) is a rare malignancy, and only 41 PPC cases have been reported in males up to 2021. Due to its rarity, no standardized treatments for PPC have been established. Cytotoxic chemotherapy has limited efficacy, and the prognosis of advanced PPC is notably poor. Immune checkpoint inhibitors (ICIs) are expected to provide long-term survival for PPC patients, but only a few cases have been reported. The optimal treatment for PPC has not been determined. Case Description: Here, we report a 72-year-old male with post-surgery relapsed PPC, presenting with multiple pulmonary nodules and an intracardiac mass. The OncomineTM Dx target test showed no mutation of cancer-relevant genes, and programmed death-ligand 1 (PD-L1) expression was negative (0%) in the 22C3 assay. He received a combination of carboplatin, paclitaxel, nivolumab, and ipilimumab which is widely used as a first-line treatment for advanced non-small-cell lung cancer (NSCLC). Two months after treatment began, computed tomography (CT) showed multiple lung nodules and an intracardiac mass reduction, which has been sustained for 12 months. Grade 3 febrile neutropenia and grade 2 rash were observed, however, these adverse events were manageable. Conclusions: This is the first case of postoperative relapse PPC that has been successfully treated with the combination of chemotherapy, nivolumab, and ipilimumab. This therapy may be a promising option for advanced PPC.

Minimal effective dose of maintenance steroid therapy for relapse of cryptogenic organizing pneumonia.

BACKGROUND: Long-term maintenance steroid therapy (MST) is frequently required for repeated relapses of cryptogenic organizing pneumonia (COP); however, the optimal minimal dose has not been clarified. Therefore, this study evaluated the minimal MST dose required to prevent repeated relapses and identify relapse predictors. METHODS: We retrospectively reviewed the medical records of patients with steroid-treated COP and compared background factors between the non-relapse and relapse groups. We also reviewed the treatment course in the relapse group and determined the minimal effective steroid dose based on the MST dose at relapse events and the current relapse prevention dose. RESULTS: In total, 48 patients were identified, including 27 (56%) in the non-relapse group and 21 (44%) in the relapse group. Receiver operating characteristic curve analysis identified prednisolone at 5 mg/day as the optimal cut-off value in the relapse group. Relapse-free time in patients with relapsed COP was significantly longer in the MST dose ≥5 mg/day group than in the <5 mg/day group (log-rank P = 0.003; hazard ratio, 0.19; 95% confidence interval [CI], 0.04-0.60). Multivariate logistic regression analysis demonstrated that a high eosinophil percentage and CD4/CD8 ratio in bronchoalveolar lavage fluid (BALF) were predictors of relapse (odds ratio [OR], 1.12; 95% CI, 1.02-1.23; P = 0.008 and OR, 3.87; 95% CI, 1.29-11.6; P = 0.008, respectively). CONCLUSIONS: Our results indicate that 5 mg/day of prednisolone may be the minimal effective dose for preventing repeated relapses, and a high BALF eosinophil percentage and CD4/CD8 ratio are independent predictors of relapse.

Development of eosinophilic pneumonia from eosinophilic bronchiolitis without asthma: A case report.

Eosinophilic bronchiolitis is a disease concept reported in Japan in 2001, that presents with bronchiolitis accompanied by eosinophilia in the blood and lungs. In 2013, hypereosinophilic obliterative bronchiolitis, as a group of disease presenting with eosinophilic bronchiolitis, was proposed in France. The relationship between eosinophilic bronchiolitis and other eosinophil-related diseases has not been clarified. Herein, we report the case of a 56-year-old female patient with eosinophilic bronchiolitis without asthma, which developed into eosinophilic pneumonia. Treatment with oral prednisone improved the respiratory function. According to the clinicopathological findings in this case, eosinophilic bronchiolitis may be a different disease from asthma.

Indoor/outdoor radon decay products associated aerosol particle-size distributions and their relation to total number concentrations.

The activity size distributions of indoor and outdoor radioactive aerosol associated with short-lived radon decay products were observed at Nagoya, Japan, for some periods from 2010 to 2012, following the indoor observation by Mostafa et al. [Mostafa, A. M. A., Tamaki, K., Moriizumi, J., Yamazawa, H. and Iida, T. The weather dependence of particle size distribution of indoor radioactive aerosol associated with radon decay products. Radiat. Prot. Dosim. 146: (1-3), 19-22 (2011)]. The tendency of smaller indoor activity median aerodynamic diameter (AMAD) after rainfalls showed in the previous study was not consistently obtained, while the consistent tendency of less indoor radioactive particles with diameters in the accumulation mode was observed again after rainfalls. The indoor aerosols showed activity size distributions similar to the outdoor ones. Non-radioactive aerosol particle concentrations measured with a laser particle counter suggested a somewhat liner relationship with AMAD.