Disseminated non-tuberculous mycobacterial infection caused by Mycobacterium obuense in an immunocompromised patient: a case report.

BACKGROUND: Mycobacterium obuense (M. obuense) is a rapidly growing mycobacterium (RGM) which has been considered nonpathogenic. Here, we report a case of disseminated non-tuberculous mycobacterial (NTM) infection caused by M. obuense in an immunocompromised patient. CASE PRESENTATION: A 16-year-old boy was referred to our hospital due to acute myeloid leukemia. During the treatment of leukemia, the patient exhibited continuous fever, and diffuse miliary nodules with random distribution were found on chest computed tomography. Repeated examinations of bacterial culture tests revealed sputum and urine samples to be smear-positive for acid-fast bacillus, and blood culture from a peripherally inserted central catheter line showed the growth of NTM. The NTM species was identified as M. obuense by mass spectrometry and confirmed by genome sequencing. Combination therapy with amikacin, rifampicin, azithromycin, and moxifloxacin significantly improved the patient's symptoms and radiological findings. CONCLUSION: We report a case of disseminated NTM infection caused by M. obuense for which combination anti-microbial therapy was effective. An immunocompromised host indwelling catheter is at risk of RGM bloodstream infections. Although relatively rare, M. obuense may be considered as a potential pathogen causing infectious diseases, especially in high-risk patients.

Sequencing strategies with ramucirumab and docetaxel following prior treatments for advanced non-small cell lung cancer: a multicenter retrospective cohort study.

OBJECTIVES: Ramucirumab (RAM) and docetaxel (DOC) are commonly used after first-line therapy for advanced non-small cell lung cancer (NSCLC). Therefore, we aimed to elucidate sequencing strategies of RAM and DOC following prior treatments, including immune checkpoint inhibitor (ICI), cytotoxic agent (CTx) alone, bevacizumab (BEV), and tyrosine kinase inhibitor (TKI). METHODS: We recruited patients with NSCLC who received RAM and DOC and compared the groups with and without prior ICI, CTx alone, BEV, and TKI, respectively. By tumor response to such treatments, the patients were further classified into "complete response (CR) + partial response (PR)," "stable disease," and "progressive disease" groups, respectively. We compared RAM and DOC efficacy among these groups. RESULTS: In total, 237 patients were registered. In the group with prior ICI, the objective response rate and disease control rate were significantly higher than those without prior ICI (p = 0.012 and 0.028, respectively), and the median progression-free survival (PFS) was also significantly longer (p = 0.027). There were no significant differences in PFS between the groups with and without CTx alone, BEV, and TKI. Multivariate analysis revealed that prior ICI was an independent factor associated with better PFS. Furthermore, the prior ICI group with CR + PR significantly prolonged PFS compared to the group without prior ICI (p = 0.013). CONCLUSION: RAM and DOC may be preferably administered after ICI, rather than after CTx alone, BEV, or TKI, and, furthermore, enhanced if the prior ICI has a favorable tumor response.

Real-world impact of antifibrotics on prognosis in patients with progressive fibrosing interstitial lung disease.

OBJECTIVE: No studies have demonstrated the real-world efficacy of antifibrotics for progressive fibrosing interstitial lung disease (PF-ILD). Therefore, we evaluated the efficacy of antifibrotics in patients with PF-ILD. METHODS: We retrospectively reviewed the medical records of patients with ILD from January 2012 to July 2021. Patients were diagnosed with PF-ILD if they had ≥10% fibrosis on high-resolution CT (HRCT) and a relative forced vital capacity (FVC) decline of either ≥10% or >5% to <10% with clinical deterioration or progression of fibrosis on HRCT during overlapping windows of 2 years and with a %FVC of ≥45%. We compared FVC changes and overall survival (OS) between patients with and without antifibrotics. FVC changes were analysed using generalised estimating equations. We used inverse probability weighting (IPW) and statistical matching to adjust for covariates. RESULTS: Of the 574 patients, 167 were diagnosed with PF-ILD (idiopathic pulmonary fibrosis (IPF), n=64; non-IPF, n=103). Antifibrotics improved the FVC decline in both IPF (p=0.002) and non-IPF (p=0.05) (IPW: IPF, p=0.015; non-IPF, p=0.031). Among patients with IPF, OS was longer in the antifibrotic group (log-rank p=0.001). However, among patients with non-IPF, OS was not longer in the antifibrotic group (p=0.3263) (IPW and statistical matching: IPF, p=0.0534 and p=0.0018; non-IPF, p=0.5663 and p=0.5618). CONCLUSION: This is the first real-world study to show that antifibrotics improve the FVC decline in PF-ILD. However, among patients with non-IPF, we found no significant difference in mortality between those with and without antifibrotics. Future studies must clarify whether antifibrotics improve the prognosis of non-IPF.

Efficacy and safety of ramucirumab and docetaxel in previously treated patients with squamous cell lung cancer: a multicenter retrospective cohort study.

OBJECTIVE: Ramucirumab plus docetaxel (RAM/DOC) therapy is currently the standard for previously treated advanced non-small cell lung cancer (NSCLC), irrespective of histology. However, in the clinical trial, only the first-line platinum-based chemotherapy refractory patients were enrolled and the eligible criteria was strict to avoid hemoptysis, especially in squamous cell NSCLC (Sq). Thus, the efficacy and safety data on ramucirumab for Sq in real-world settings after immune checkpoint inhibitors monotherapy or combination therapy approved as novel first-line therapy is lacking. METHODS: We retrospectively analyzed previously treated patients with advanced NSCLC who underwent RAM/DOC therapy at four institutions. Clinical data on the initiation of RAM/DOC were collected from medical records. Treatment outcomes were assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Incidence of pulmonary hemorrhage was assessed according to the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Overall, 237 patients with NSCLC were included and 38 (16%) had squamous cell carcinoma. There were no significant differences in median progression-free survival and overall survival between Sq and non-Sq patients (5.8 months vs. 4.3 months, P = 0.0937; 15.2 months vs. 13.4 months, P = 0.714, respectively). Of all patients, 13 (5%) developed pulmonary hemorrhage. According to histological analysis, there was no significant difference in pulmonary hemorrhage proportion between Sq and non-Sq cohorts (2/38 vs. 11/199, respectively, P = 0.947). CONCLUSIONS: For previously treated patients with Sq, the efficacy and safety of RAM/DOC therapy were confirmed in a real-world setting and were similar to non-Sq.

Efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer: A multicenter retrospective cohort study.

OBJECTIVE: Ramucirumab (RAM) plus Docetaxel (DOC) is one of the standard treatments after first-line treatment failure in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the efficacy and safety of RAM plus DOC in older patients. We aimed to clarify these and elucidate the prognostic factors. MATERIALS AND METHODS: In this multicenter retrospective study, conducted at four medical facilities in Japan, we evaluated the efficacy and safety data for two groups (<65 and ≥ 65 years). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and log-rank test. Multivariate analysis was performed to reveal the prognostic factors for better PFS and OS. Patient characteristics and adverse events (AEs) in both groups were compared using the Mann-Whitney's U and Fisher's exact tests for categorical variables. RESULTS: A total of 237 patients were included, of whom 43% (n = 103), and 57% (n = 134) were aged <65, and ≥ 65 years. Median OS was 12.2 (95% CI: 9.4-15.0), and 14.8 months (95% CI: 10.8-18.8), respectively, and there were no significant differences between the groups (p = 0.534). Multivariate analysis identified DOC dose reduction (none vs performed, HR: 2.66, 95% CI: 1.62-4.35, p < 0.001) as an independent prognostic factor for OS in older patients, and a similar result was shown for the PFS. Grade ≥ 3 all AEs were identified in 42.7% and 56.7% of younger and older patients, respectively, and there was a significant difference between the groups (p = 0.033); however, the difference between the groups disappeared with primary DOC dose reduction (p = 0.526). CONCLUSION: The efficacy of RAM plus DOC administration in older, pretreated patients with advanced NSCLC was comparable to those of younger patients, whereas RAM plus DOC should be cautiously administered to older patients because of severe toxicity. Moreover, appropriate DOC dose reduction may be recommended for increased survival benefit and safety in such patients.

Impact of docetaxel plus ramucirumab on metastatic site in previously treated patients with non-small cell lung cancer: a multicenter retrospective study.

BACKGROUND: Docetaxel (DOC) plus ramucirumab (RAM) has been recommended as an optimal therapy for previously treated patients with non-small cell lung cancer (NSCLC). In a clinical setting, there are few reports about DOC plus RAM, therefore its effect on factors such as Eastern Cooperative Oncology Group (ECOG) performance status (PS) and metastatic sites is still unknown. METHODS: We recruited NSCLC patients who received DOC plus RAM in four medical facilities in Japan from June 2016 to March 2020. We retrospectively investigated the overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) of DOC plus RAM and conducted univariate and multivariate analyses using PFS as a dependent factor. Patients were followed up until June 30, 2020. RESULTS: A total of 237 patients were consecutively enrolled. For all patients, the ORR, DCR, and median PFS were 25.2%, 63.9%, and 4.5 months, respectively. The ORR and DCR for malignant pleural effusion (MPE), lung metastasis, and liver metastasis were 7.7% and 53.8%, 30.3% and 77.5%, and 48.6% and 71.4%, respectively. In the multivariate analysis, MPE, lung metastasis, and liver metastasis were not prognostic factors for poor PFS. However, ECOG-PS 2 or more [hazard ratio (HR): 1.66, 95% confidence interval (CI): 1.14-2.40, P=0.008] and brain metastasis (HR: 1.71, 95% CI: 1.23-2.37, P=0.001) were significant and independent factors associated with shorter PFS. CONCLUSIONS: DOC plus RAM could be an optimal therapy for previous treated NSCLC patients with lung and liver metastasis, and furthermore, should be used carefully for patients with poor ECOG-PS or brain metastasis. KEYWORDS: Docetaxel and ramucirumab; non-small cell lung cancer (NSCLC); metastatic site; poor performance status.

A case of simultaneous occurrence of hepatitis and pancreatitis during the combination immunochemotherapy for non-small cell lung carcinoma.

Immune checkpoint inhibitors (ICIs) improved the prognosis of patients with advanced lung cancers. The combination therapy of cytotoxic drugs and ICI is approved as first-line chemotherapy in non-small-cell lung cancer (NSCLC) and extensive disease small-cell lung cancer (ED-SCLC). It has been reported various immune-related adverse events (irAEs). We herein report a 65-year-old man with NSCLC who developed hepatitis and pancreatitis simultaneously during the combination immunochemotherapy. In the treatment of hepatitis and pancreatitis, the clinical course was different. In this report, the importance of accurate diagnosis through detailed examination and treatment priority depending on the severity of the symptoms is indicated.