Since non-anthracycline-based chemotherapy with L-asparaginase has improved survival outcomes in patients with extranodal natural killer/T-cell lymphoma (ENKTL), the incidence of central nerve system (CNS) relapse can be different when compared with previous reports. In this research, we sought to identify the incidence of and predictors for CNS relapse and to evaluate the necessity of CNS prophylaxis with intermediate-dose MTX (ID-MTX). The records of 399 patients in the training cohort and 253 patients in the validation cohort with ENKTL who received non-anthracycline-based chemotherapy were reviewed. Patients were divided into two groups according to whether the chemotherapy regimen included ID-MTX above 2 g/m². A new CNS-PINK model was developed using one-point powerful predictors of CNS relapse [the prognostic index of natural killer lymphoma (PINK); HR: 2.908; P = .030 and extranodal involvement (≥ 2); HR: 4.161; P = .001] and was calculated as a sum of scores. The high-risk group of CNS-PINK was defined as 2 points. The cumulative incidence of CNS relapse was different between the CNS-PINK risk groups in the training (P < .001) and validation cohort (P = .038). Patients in the high-risk CNS-PINK group who received SMILE or SMILE-like regimens with ID-MTX (S-ID-MTX) displayed a lower incidence rate of CNS relapse than did those who received other regimens without ID-MTX in the training cohort (P = .029). The CNS-PINK was demonstrated its strong predictability of CNS relapse in ENKTL patients. The effect of S-ID-MTX for preventing CNS events in high-risk CNS-PINK patients should be verified by future studies.

We investigated the size-based isolation and enumeration of circulating tumor cells (CTCs) using a centrifugal microfluidic device equipped with a fluid-assisted separation technology (FAST) disc. We further assessed the correlations among CTCs, cancer antigen-125 (CA125) levels, and clinical course of the disease in a prospective analysis of 47 serial blood samples collected at multiple time-points from 13 ovarian cancer patients. CTCs were isolated from whole blood using the FAST disc and were classified as epithelial cell adhesion molecule (EpCAM)/cytokeratin+, CD45−, and 4′,6-diamidino-2-phenylindole (DAPI)+. Mean CTC count at baseline was 20.2; 84.62% of patients had more than one CTC at baseline and had decreased CTCs counts after surgery and chemotherapy. The CTC counts in eight patients with complete responses were <3. CTC counts were correlated with CA125 levels in three patients without recurrence; they were elevated in three patients with recurrence and normal CA125 concentrations. CTC counts and CA125 levels showed high concordance with directional changes (increasing 71.4%; non-increasing 75.0%). CTC counts showed higher associations with clinical status, sensitivity (100.0% vs. 60.0%), positive predictive value (55.6% vs. 42.9%), and negative predictive value (100.0% vs. 87.5%) than CA125 levels. CTC counts were better associated with treatment response and recurrence than CA125 levels.

Despite comprehensive genomic analyses, no targeted therapies are approved for bladder cancer. Here, we investigate whether a single and combination therapy with targeted agents exert antitumor effects on bladder cancer cells through genomic alterations using a three-dimensional (3D) high-throughput screening (HTS) platform. Seven human bladder cancer cell lines were used to screen 24 targeted agents. The effects of 24 targeted agents were dramatically different according to the genomic alterations of bladder cancer cells. BEZ235 (dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor) showed antitumor effects against most cell lines, while AZD2014 (mTOR inhibitor) had an IC50 value lower than 2 μM in 5637, J82, and RT4 cell lines. AZD5363 (protein kinase B (AKT) inhibitor) exerted antitumor effects on 5637, J82, and 253J-BV cells. J82 cells (PI3KCA and mTOR mutations) were sensitive to AZD5363, AZD2014, and BEZ235 alone or in AZD5363/AZD2014 and AZD5363/BEZ235 combinations. Although all single drugs suppressed cell proliferation, the combination of drugs exhibited synergistic effects on cell viability and colony formation. The synergistic effects of the combination therapy on the PI3K/Akt/mTOR pathway, apoptosis, and EMT were evident in Western blotting. Thus, the 3D culture-based HTS platform could serve as a useful preclinical tool to evaluate various drug combinations.

Introduction: Current standard chemotherapy for biliary tract cancer (BTC) has limited survival benefits, and the need for targeted therapies is increasing. This study investigated the genetic profiles and clinical implications of BRCA mutations in patients with advanced BTC. Methods: Targeted high-throughput sequencing was performed on samples obtained from 25 patients with advanced BTC who had received palliative first-line platinum-based chemotherapy. Results: Of the 25 patients, 16 (64.0%) were younger than 65 years of age and 16 (64.0%) were male. The BTC cases consisted of intrahepatic cholangiocarcinoma (9, 36.0%), extrahepatic cholangiocarcinoma (5, 20.0%), and gallbladder cancer (11, 44.0%). The median overall survival (OS) and progression-free survival (PFS) of all patients were 11.9 months (95% confidence interval [CI]: 9.2–14.6) and 5.6 months (95% CI: 3.8–7.3), respectively. Genomic alterations in TP53 (52.0%), BRCA (36.0%), ATM (32.0%), ERBB2 (24.0%), NOTCH1 (20.0%), and FGFR3 (20.0%) were frequently reported. TP53 and ATM mutations were associated with OS (TP53: hazard ratio [HR] 2.719, 95% CI: 1.074–6.881, p = 0.035; ATM: HR 2.780, 95% CI: 1.091–7.082, p = 0.032). Patients with BRCA mutations had a slightly improved PFS compared to those with intact BRCA (6.7 months [range, 2.7–10.7 months] vs. 5.3 months [range, 3.6–7.0 months], p = 0.090). However, there was no significant difference in OS between groups (BRCA mutant vs. intact: 10.6 months [range, 3.6–17.6 months] vs. 11.9 months [range, 7.5–16.3 months], p = 0.252). BRCA mutations were significantly associated with PFS in the multivariate analysis (HR 0.150, 95% CI: 0.034–0.655, p = 0.012). Conclusion: This study demonstrated that BRCA mutations might have a role as predictive biomarkers for palliative first-line platinum-based chemotherapy in patients with advanced BTC.

Background: Biliary tract cancers (BTC) have a poor prognosis even after curative resection because of frequent local and distant recurrences. Therefore, the importance of adjuvant therapy in BTC has been advocated to improve outcomes. However, the choice of adjuvant therapy is still controversial. The aim of this study was to compare the effects of adjuvant concurrent chemoradiotherapy (CCRT) and chemotherapy on resected BTC. Methods: We analyzed 92 patients who had curatively resected BTC and had received adjuvant CCRT or chemotherapy from January 2000 to December 2017 at Keimyung University Dongsan Medical Center. Results: Of the patients, 46 received adjuvant CCRT and 46 received adjuvant chemotherapy. The median recurrence-free survival (RFS) for the adjuvant CCRT and chemotherapy groups were 13.8 and 11.2 months (p = 0.014), respectively. The median overall survival (OS) for the adjuvant CCRT and chemotherapy groups were 30.1 and 26.0 months (p = 0.222), respectively. Adjuvant CCRT had significantly better RFS and numerically higher OS than did chemotherapy. For subgroups with no lymph node (LN) involvement (RFS p = 0.006, OS p = 0.420) or negative resection margins (RFS p = 0.042, OS p = 0.098), adjuvant CCRT led to significantly longer RFS and numerically higher OS than did chemotherapy. For multivariate analysis, the pattern of adjuvant treatment (chemotherapy vs. CCRT, p = 0.004, HR 2.351), histologic grade (poor vs. well, p = 0.023, HR 4.793), and LN involvement (p = 0.028, HR 1.912) were the significant prognostic factors for RFS. Conclusions: Our study demonstrated the superiority of adjuvant CCRT over chemotherapy for improving RFS in curatively resected BTC.

Purpose: To assess the efficacy and safety of docetaxel rechallenge in the salvage setting in metastatic castration-resistant prostate cancer (mCRPC) patients. Materials and Methods: Clinicopathologic data from patients treated with docetaxel rechallenge were collected from a single-center cancer registry. Among 227 patients who received first-line docetaxel for mCRPC between January 2011 and June 2019, 23 undergo rechallenge docetaxel after failure to androgen receptor targeting agents and/or cabazitaxel treatment. Endpoints included radiologic progression-free survival (PFS), treatment duration, and prostate-specific antigen (PSA) response and safety. Results: Overall, 30%, 44%, 13%, and 13% of patients received docetaxel rechallenge as either the third, fourth, fifth, or sixth-line therapy, respectively, at a median of 23.6 months after stopping first-line docetaxel. With first-line docetaxel and rechallenge, median treatment duration was 6.4 and 3.3 months, respectively. With docetaxel rechallenge, PSA response was 35% (95% confidence interval [CI], 15% to 54%) and median PFS was 4.5 months (95% CI, 1.9 to 7.1 months). The median OS was 24.3 months (95% CI, 4.6 to 44.0 months). There were 7 severe adverse events (grade 3 or more) including anemia (8.7%), neutropenia, thrombocytopenia, leukopenia, diarrhea, and nausea (4.3% each). Conclusions: Docetaxel rechallenge showed meaningful anti-tumor activity with acceptable toxicity in heavily pretreated patients with mCRPC.