Phase II trial of nivolumab monotherapy and biomarker screening in patients with chemo-refractory germ cell tumors.

OBJECTIVES: Germ cell tumors are highly susceptible to chemotherapy; however, there is a lack of established treatments for consistently relapsing germ cell tumor. Therefore, in this phase II study, we evaluated the efficacy and safety of nivolumab for relapsed germ cell tumor. METHODS: Seventeen adult patients (median age 34 years) with refractory primary germ cell tumor after second-line or higher chemotherapy were enrolled. Nivolumab was administered over 30 min at 240 mg/body every 2 weeks until disease progression or intolerable adverse event occurrence. The primary endpoint was the overall response rate. RESULT: We performed a biomarker analysis of programmed death ligand-1 expression and genomic sequencing. Tumor histology revealed nonseminoma and seminoma in 14 and three patients, respectively. Patients were pretreated with a median of three chemotherapy lines, and three patients received high-dose chemotherapy. The median number of nivolumab doses was 3 (range 2-46). One patient showed a partial response and three showed stable disease. Responses were durable in one patient with a partial response and one patient with stable disease (median 90 and 68 weeks, respectively). Nivolumab was well-tolerated, with only two Grade 3 adverse events observed. Programmed death ligand-1 expression was not associated with objective responses. Genomic sequencing revealed a high tumor mutation burden in a patient with a durable partial response. While a small subset of chemorefractory germ cell tumors may respond to nivolumab, programmed death ligand-1 is unreliable to measure response. CONCLUSIONS: Tumor mutation burden is a potential biomarker for future testing of germ cell tumor response.

How far is the left circumflex coronary artery from the mitral annulus?

INTRODUCTION: The relationship between the distance from the mitral annulus to the left circumflex coronary artery (LCX) and iatrogenic LCX injury has been questioned. This study was designed to determine the high-risk sites of LCX injury with an anatomical approach using multiple detector-computed tomography (MDCT) scanning taken before mitral valve annuloplasty (MVA). The purpose of this study is to prevent LCX injury in patients unable to receive MDCT before mitral valve surgery. METHODS: In 2018, we performed MVA on 59 patients, 52 of whom had undergone preoperative MDCT scanning. We retrospectively analyzed the MDCT images of these 52 patients and measured the shortest distance from the mitral annulus to the LCX in three dimensions. Also, we divided the mitral annulus into 12 clockwise areas (A0-A11) to identify the exact location. RESULTS: The site of closest proximity and their numbers of patients were as follows: A6, 1 patient; A8, 2 patients; A9, 32 patients; and A10, 17 patients. Nine (17.3%) of the 52 patients had the shortest distance of less than 2 mm. The shortest distance according to the dominance of coronary artery showed no significant difference (p = 0.81). CONCLUSION: The site of closest proximity from the mitral annulus to the LCX was concentrated on the A8 to A10 areas and it is an interesting result that as many as 17% of patients have their coronary arteries less than 2 mm away from the annulus.