Comprehensive Clinical and Genetic Characterization of Hyperprogression Based on Volumetry in Advanced Non–Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitor

IntroductionHyperprogressive disease (HPD), characterized by accelerated tumor progression, has been proposed as a new pattern of progression after immune checkpoint inhibitor (ICI) treatment. The aim of this study was to describe the characteristics of HPD and investigate its predictive markers.MethodsClinical and radiological findings of 335 patients with advanced NSCLC treated with ICI monotherapy were retrospectively analyzed. Radiological data were quantitatively and longitudinally analyzed for tumor size and volume by comparing baseline and follow-up computerized tomography results. The findings were matched with individual genomic profiles generated by deep sequencing of 380 genes.ResultsAmong 135 patients with progressive disease (PD), as assessed by the Response Evaluation Criteria in Solid Tumors version 1.1 criteria, 48 (14.3% of all patients and 35.6% of those with PD) and 44 (13.1% of all patients and 32.6% among those with PD) were found to have HPD by volumetry (HPD_V) and assessed by RECIST 1.1 (HPD_R), respectively. Patients with HPD_V were associated with significantly inferior overall survival (OS) versus that of patients without HPD_V with PD (median OS = 4.7 months [95% confidence interval: 3.5–11.9)] versus 7.9 months [95% confidence interval: 6.0–13.5] [p = 0.004]); OS did not differ between patients without and without HPD_R. HPD_V status was an independent factor in OS. A derived neutrophil-to-lymphocyte ratio greater than 4 and lactate dehydrogenase level greater than the upper limit of normal were significantly associated with HPD_V. Moreover, we identified coinciding KRAS and serine/threonine kinase 11 gene (STK11) mutations in the cohort of patients with HPD_V (three of 16), whereas none were found in the cohort of patients without HPD_V (zero of 28).ConclusionsDefining HPD treated with ICI on the basis of volumetric measurement is more precise than is defining it on the basis of one-dimensional analysis. Pre-ICI derived neutrophil-to-lymphocyte ratio, lactate dehydrogenase level, and concurrence of STK11 and KRAS mutations could thus be used as potential biomarkers for HPD prediction.     

Retrospectively validating the results of the ACOSOG Z0011 trial in a large Asian Z0011-eligible cohort

Breast Cancer Research and Treatment - The Z0011 trial demonstrated that axillary dissection (ALND) could be omitted during breast-conserving therapy for cT1-2N0 breast cancers with 1–2...     

A retrospective analysis of re‐exploration after living donor right lobe liver transplantation: incidence,causes, outcomes,and risk factors

Despite technical difficulties, right lobe liver grafting is preferred in living donor liver transplantation because of the graft size. Re‐exploration after living donor right lobe liver transplantation (LRLT) has never been separately analyzed. We aimed to analyze the incidence, causes, outcomes, and risk factors of re‐exploration after LRLT. We reviewed medical records of 1016 LRLT recipients from October 2003 to July 2017 and identified recipients who underwent re‐exploration within hospital stay. Separate analyses were also performed according to cause of re‐exploration. The overall incidence of re‐exploration was 17.0% (173/1016). The most common cause of re‐exploration was bleeding (50%). Overall re‐exploration was associated with clinical outcome, but different results were shown on analyses according to cause of re‐exploration. Risk factors of re‐exploration were underlying hepatocellular carcinoma and operative duration [Odds ratio (OR), 1.49; 95% confidence interval (CI), 1.05–2.12; P = 0.03, and OR, 1.002; 95% CI, 1.001–1.004; P = 0.0023, respectively]. Re‐exploration after LRLT is relatively common, and is strongly associated with mortality and graft failure.