Background: Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. Patients and methods:In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m 2 on days 1 and 8, and oxaliplatin 100 mg/m 2 on day 1) or XELOX (capecitabine 1000 mg/m 2 , twice daily, on days 1-14 and oxaliplatin 130 mg/m 2 on day 1) as first-line treatment, given every 3 weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate.Results: In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3 months for the GEMOX group and 5.8 months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was À12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P¼0.171) and median overall survival (P¼0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P<0.001). Conclusion:XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs.Trial Registration: This study was registered in ClinicalTrials.gov (number NCT01470443).

Positron emission tomography (PET) has been found useful in monitoring response to treatment of malignant lymphoma. We investigated the ability of interim PET to monitor response to standard dose R-CHOP chemotherapy in chemotherapy-naïve patients with diffuse large B-cell lymphoma (DLBCL). Between March 2004 and April 2009, 155 DLBCL patients treated with R-CHOP and available for interim and post-treatment PET/CT were identified and included in this analysis. Response, progression-free survival (PFS), and overall survival (OS) were compared between interim PET/CT-negative and positive group, and among three patient groups which were categorized based on their interim and post-treatment PET/CT: those with early metabolic complete response (mCR), delayed mCR, and never mCR. Interim PET/CT-negative patients (n=100) showed superior CR rates to interim PET/CT-positive patients (n=55; 93% vs 62%, P<0.001). However, there was no difference in PFS (P=0.07) and OS (P=0.24) between interim PET/CT-negative and positive group. We categorized patients into three groups, with 100 (64%) in the early mCR group, 35 (23%) in the delayed mCR group, and 20 (13%) in the never mCR group. Early mCR and delayed mCR group did not differ significantly in PFS (P=0.84) or OS (P=0.20). However, the survival outcome in the never mCR group was significantly inferior to the combined early and delayed mCR group. The result from this study suggests that interim PET/CT might be an inappropriate tool for designing risk-adaptive therapy in chemotherapy-naïve DLBCL patients treated with R-CHOP. Prospective trials should be performed to clearly determine the role of interim PET/CT.

Surgical resection of residual lesions after disease control with imatinib is likely to be beneficial to patients with recurrent or metastatic GISTs.

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These data suggest that infused CD34+ cell count is predictive of kinetics of lymphocyte recovery after ASCT and is an independent prognostic factor for OS and EFS after ASCT in patients with NHL.

We investigated the feasibility of i.v. BU, CY and etoposide (BUCYE), followed by auto-SCT (ASCT) in patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The planned treatment consisted of induction chemotherapy with five cycles of high-dose MTX and two cycles of high-dose cytarabine followed by conditioning with BUCYE (BU 3.2 mg/m 2 , day À7 to day À5; CY 50 mg/kg, day À3 to day À2 and etoposide 200 mg/m 2 , twice a day, days À5 and À4) and then ASCT. Between

In subsets of gastrointestinal stromal tumors (GISTs), mutations of the KIT and PDGFRA receptor tyrosine kinases correlate with tumor prognosis and response to tyrosine kinase inhibitors (TKIs). Determining genotypes in TKI-resistant GISTs is challenging due to the potential risks and limitations of repeated biopsies during the course of treatment. We prospectively collected plasma samples from three GIST patients harboring KIT mutations that were detected in tissue DNA. The plasma samples were then analyzed for mutations in KIT, PDGFRA, and BRAF via next-generation sequencing. We were able to identify primary KIT mutations in all plasma samples. Additional mutations, including KIT exon 17 S821F and PDGFRA exon 18 D842V, were detected in the patient-matched plasma samples during follow-up and appeared to result in decreased sensitivity to TKIs. Our results demonstrate an approach by which primary and secondary mutations are readily detected in blood-derived circulating tumor DNA from patients with GIST. These mutations can be used as biomarkers for prediction of treatment response. The identification of a resistance mutation in plasma DNA will allow early change to alternative TKIs or dose escalation of imatinib for optimal patient management.

Background: Peripheral T-cell lymphomas (PTCLs) are uncommon and their frequency is regionally heterogeneous. Several studies have been conducted to evaluate the clinical features and treatment outcomes of this disease entity, but the majority of these were conducted in limited areas, making it difficult to comprehensively analyze their relative frequency and clinical features. Furthermore, no consensus treatment for PTCLs has been established. Therefore, we conducted an Asia-specific study to understand the relative frequency of PTCLs and assess treatments and their outcomes in Asian patients.Methods: We performed a multinational, multicenter, prospective registry of adult patients with PT-CLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated.Findings: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57%) had stage III or IV. Extranodal natural killer (NK)/T-cell lymphoma was the most common subtype ( n = 139,28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL, n = 120,24.7%), PTCL-not otherwise specified (PTCL-NOS, n = 101,20.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n = 34,6.9%), and ALK-negative ALCL ( n = 30,6.2%). The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6-31.6) and 83.6 months (95% CI, 56.7-110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to one another.Interpretation: This multinational, multicenter study identified the relative frequency of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently used.