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.

Successful Treatment with Definitive Concurrent Chemoradiotherapy Followed by Durvalumab Maintenance Therapy in a Patient with Tracheal Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma (ACC) is a rare type of malignant tracheal tumor originating from the secretory glands. Complete surgical resection is the current standard of care for tracheal ACC. However, there have been few case reports of chemoradiotherapy for unresectable tracheal ACC. We herein report a 28-year-old man with unresectable tracheal ACC who received concurrent chemoradiotherapy (CCRT) followed by maintenance therapy with durvalumab. CCRT was completed with a good response and safety, and the patient is currently receiving durvalumab as maintenance therapy. Durvalumab after CCRT can be a treatment option for patients with unresectable tracheal ACC.

Alectinib-Induced Severe Hemolytic Anemia in a Patient with ALK-Positive Non-Small Cell Lung Cancer: A Case Report.

Alectinib is a selective anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor as standard therapy for ALK-rearranged non-small cell lung cancer (NSCLC). Hemolytic anemia is considered as a rare but significant adverse event with alectinib. Here, we report a case of a 73-year-old female with lung adenocarcinoma, harbouring an ALK fusion gene, who received alectinib as second-line therapy and developed gradually progressive grade 4 (6.4 g/dL) drug-induced hemolytic anemia (DIHA) after complete response. We discontinued alectinib and performed a blood transfusion for the severe anemia. The anemia improved with no recurrence of lung adenocarcinoma over 10 months. Regular hematologic monitoring and the possibility of DIHA should be considered in case of progressive hemolytic anemia during alectinib treatment.

Successful Treatment with Short-Term Steroid Against Severe Hepatitis Confirmed by Liver Biopsy in a Patient with Advanced Squamous-Cell Lung Cancer Receiving a Combination of Pembrolizumab, Carboplatin, and Nab-Paclitaxel: A Case Report.

Pembrolizumab is an immune checkpoint inhibitor (ICI) that targets programmed death-1. Although ICIs have shown efficacy in the treatment of lung cancer, they have also been reported to cause a variety of immune-related adverse events (irAEs). Hepatotoxicity is a known irAEs, but currently, there is not enough information on its pathological characteristics and treatment. We report the case of a 70-year-old man with advanced squamous-cell lung cancer who developed severe grade 4 hepatitis on day 8 after receiving carboplatin, nab-paclitaxel, and pembrolizumab as fourth-line therapy. We treated him with steroid therapy the day after a liver biopsy was performed to investigate his pathological features, which led to a rapid and remarkable improvement. Confirmation of immune-related hepatotoxicity by pathological findings allowed the early tapering and discontinuation of steroid therapy. Performing a liver biopsy and verifying histological characteristics are needed for successful treatment with short-term steroids when drug-induced hepatitis caused by anti-cancer therapy including pembrolizumab is considered.