Kyohei Kaburaki

Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation.

Background: Germline alterations in the proapoptotic protein Bcl-2–like 11 (BIM) can have a crucial role in tumor response to treatment. To determine the clinical utility of detecting BIM deletion polymorphism in non–small-cell lung cancer positive for epidermal growth factor receptor (EGFR) mutation, we examined outcomes of patients with and without BIM alterations. Methods: We studied 70 patients with EGFR mutation-positive non–small-cell lung cancer who were treated with an EGFR tyrosine kinase inhibitor between January 2008 and January 2013. BIM deletion was analyzed by polymerase chain reaction in 58 samples of peripheral blood and 24 formalin-fixed paraffin-embedded slides of surgical specimens (20 of lung tissue and four of brain tissue); both blood and tissue specimens were available for 12 patients. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM deletion. Results: BIM deletion was present in 13 of 70 patients (18.6%). There were no significant differences between patients with and without BIM deletion in clinical characteristics, rate of response to EGFR tyrosine kinase inhibitor, or incidence of adverse events. Patients with BIM deletion had significantly shorter progression-free survival (PFS) than those without BIM deletion (median, 227 versus 533 days; p < 0.001). Multivariate Cox regression analysis showed that BIM deletion was an independent indicator of shorter PFS (hazard ratio, 3.99; 95% confidence interval, 1.864–8.547; p < 0.001). Conclusions: Polymerase chain reaction successfully detected BIM deletion in samples of peripheral blood and formalin-fixed paraffin-embedded slides of surgical specimens. BIM deletion was the most important independent prognostic factor in shorter PFS.

Miliary Tuberculosis that Developed after Intravesical Bacillus Calmette-Guerin Therapy

As a treatment for superficial transitional cell carcinoma, Bacillus Calmette-Guerin (BCG) intravesical instillation can rarely cause unpredictable systemic side effects. We describe a patient admitted due to continuous pyrexia and general fatigue. He was previously treated with intravesical BCG. Laboratory data indicated a hepatic disorder, and chest computed tomography revealed extensive bilateral miliary nodules. Transbronchial lung biopsy specimens showed several small noncaseating granulomas. The diagnosis was unsolved on the basis of acid fast staining, polymerase chain reaction and microbiological cultures, so we considered the possibility of BCG side effect-induced granuloma. Two months after treatment with antituberculous agents and corticosteroids, his clinical symptoms were improved.

New risk scoring system for predicting acute exacerbation of interstitial pneumonia after chemotherapy for lung cancer associated with interstitial pneumonia

BACKGROUND Fatal acute exacerbation (AE) of interstitial pneumonia (IP) sometimes occurs after chemotherapy for lung cancer. We developed and evaluated a scoring system for assessing AE risk after chemotherapy in patients with lung cancer associated with IP. METHODS A review of medical records identified 109 patients with primary lung cancer associated with IP who had received chemotherapy at our center during the period from June 2007 through September 2017. We developed a model to score AE risk after chemotherapy in this patient group, and logistic regression was used to evaluate the model. RESULTS The anticancer agent score was determined by using AE rates reported in past studies. The risk score was calculated with the following formula: (1 × anticancer agent score) + (3 × smoking history [>70 pack-years]) + (4 × history of steroid use) + (3 × %diffusing capacity of lung carbon monoxide [<50%]). Patients were then classified into three groups. The AE incidence rate was 12% for a risk score of 0-5, 47% for a score of 6-10, and 66.7% for a score of ≥11. The sensitivity of the scoring system was 78.6% and specificity was 67.8%. CONCLUSIONS The present scoring system was able to identify IP patients at high risk for AE after chemotherapy for lung cancer associated with IP.

A feasibility study of bevacizumab and vinorelbine in patients with previously treated advanced non‑squamous non-small‑cell lung cancer

The aim of this prospective study was to evaluate the efficacy and feasibility of bevacizumab combined with vinorelbine therapy in patients with previously treated non-squamous non-small-cell lung cancer (nonSq-NSCLC). Patients who had received at least one prior chemotherapy course were eligible for this study. The patients were treated with vinorelbine (25 mg/kg on days 1 and 8) and bevacizumab (15 mg/kg on day 1), which was repeated every 3 weeks until the development of progressive disease or unacceptable toxicity. Between June, 2011 and January, 2013, 15 patients were enrolled. The response and disease control rates were 26.7 and 73.3%, respectively. The median progression-free survival was 2.1 months and the median overall survival was 34.1 months. Grade 3-4 phlebitis occurred in 3 patients. Therefore, the combination of vinorelbine and bevacizumab was found to be effective in patients with previously treated nonSq-NSCLC, but physicians must be aware of the risk of phlebitis associated with this regimen.