Purpose: No standard treatment exists for platinum-refractory, recurrent/metastatic nasopharyngeal cancer (NPC). This phase II study (NCT02605967) evaluated progression-free survival (PFS) of spartalizumab, an antiprogrammed cell death protein-1 (PD-1) monoclonal antibody, versus chemotherapy, in NPC.Patients and Methods: Patients with nonkeratinizing recurrent/metastatic NPC who progressed on/after platinum-based chemotherapy were enrolled. Spartalizumab was dosed 400 mg once every 4 weeks, and chemotherapy was received per investigator's choice.Results: Patients were randomized to receive either spartalizumab (82 patients) or chemotherapy (40 patients). The most common spartalizumab treatment-related adverse events were fatigue (10.3%) and pruritus (9.3%). Median PFS in the spartalizumab arm was 1.9 months versus 6.6 months in the chemotherapy arm (P = 0.915). The overall response rate in the spartalizumab arm was 17.1% versus 35.0% in the chemotherapy arm. Median duration of response was 10.2 versus 5.7 months in the spartalizumab versus chemotherapy arms, respectively. Median overall survival was 25.2 and 15.5 months in the spartalizumab and chemotherapy arms, respectively. Tumor RNA sequencing showed a correlation between response to spartalizumab and IFNγ, LAG-3, and TIM-3 gene expression.Conclusions: Spartalizumab demonstrated a safety profile consistent with other anti–PD-1 antibodies. The primary endpoint of median PFS was not met; however, median overall survival and median duration of response were longer with spartalizumab compared with chemotherapy.

Introduction. Despite advances in breast cancer systemic treatment, new prognostic and predictive factors are still needed. Tissue inhibitor of metalloproteinase-1 (TIMP-1), a physiologic inhibitor of matrix metalloproteinases (MMPs), can act in both pro- and antitumoral effects. As role of TIMP-1 in breast cancer is controversial, we aimed to determine the prognostic significance of TIMP-1 in breast cancer.Methods. A single center-based case-control study was applied. Primary breast cancers from women with early stage disease treated with standard adjuvant therapy were analyzed by gene expression microarrays and immunohistochemistry for TIMP-1.Results. At the optimized cut-point, patients with high TIMP-1 RNA levels had a significantly shorter time to relapse, with a hazard ratio (HR) of 1.64 (P=0.04), but without significant differences in overall survival (HR 1.29,P=0.37). Although cytoplasmic overexpression of TIMP-1 protein was not correlated with early relapse (HR 1.0,P=0.92), there was a tendency for short overall survival in patients with high expression (HR 1.41,P=0.21).Conclusions. Our data indicate that elevated TIMP-1 RNA levels are independently prognostic for early recurrence, and there is a tendency for association of high cytoplasmic TIMP-1 protein levels with short survival in primary breast cancer.

Background Small-cell carcinomas (sccs) of the genitourinary (gu) tract are rare systemic diseases, and there is no standard treatment strategy for patients with this malignancy. The objectives of the present study were to report the management and outcome of patients with scc of the gu tract treated at a tertiary-care institution from 1982 to 2009. Methods In a chart review of all patients diagnosed with scc of the gu tract between 1982 and 2009, data on demographics, clinical and pathologic characteristics, treatment, and patient outcomes were collected. Results The 58 patients identified had scc in the following primary sites: urinary bladder (n = 35), prostate (n = 17), and upper urinary tract (n = 6). In 38 patients (66%), the scc was of pure histology; in the remainder, histology was mixed. Overall, 28 patients had limited-stage disease; 24 had extensive-stage disease; and staging was unknown in 6 patients. Median survival for the entire cohort was 7.5 months, with extensive-stage disease being identified as a poor prognostic factor (survival was 22.0 months for limited-stage patients and 4.1 months for extensivestage patients, p < 0.001). Based on site, prostate patients fared worst, with a median survival of only 5.1 months. Compared with best supportive care, treatment was associated with better outcomes (median survival: 12.3 months vs. 2.3 months, p < 0.0001). Conclusions Small-cell cancer of the GU tract is an aggressive cancer, with a poor prognosis overall. Although there is no standard of care, patients should be treated using a multimodality approach analogous to that used in the treatment of small-cell lung cancer.

The necessity of prophylactic percutaneous endoscopic gastrostomy (PPEG) before concurrent chemoradiation (CCRT) in head and neck cancer (HNC) patients remains uncertain. We evaluated the utilization rate of PPEG tube. Weight changes and tube dependence were also assessed. This prospective cohort study evaluated the utilization rate of PPEG tube in patients with newly diagnosed HNC undergoing CCRT. Baseline characteristics, nutrition status, and weight loss data were collected and compared between use and non-use groups. 110 patients (94.8%) used PPEG tube (70 fully-used and 40 partially-used groups). Non-users had a tendency to lose weight more than partially and fully-used groups; 9.13%, 3.42%, and 1.95%, respectively (p = 0.085). Fully-used group had significantly longer time of tube dependence than partially-used group, 7.0 months versus 4.9 months (p = 0.012). The type of PPEG tube use (full use or partial use) and presence of dysphagia were significantly related to tube dependence. The time ratio of tube dependence for partially-used patients versus fully-used patients was 0.82 (95% CI: 0.68-0.99) (p = 0.039). The time ratio for patients with symptoms of dysphagia was 1.29 (95% CI: 1.02-1.63) (p = 0.032). At the end of CCRT, 96.6% of patients agreed that PPEG tube was necessary. We recommend PPEG for patients undergoing CCRT. Partial use of PPEG with continuous oral intake as tolerated is strongly encouraged to maintain weight, and to reduce risk of tube dependence. Future study to evaluate effective swallowing exercise is warranted.

Germ cell tumor with somatic malignant transformation is an uncommon phenomenon occurring about 7% of all mediastinal teratomas. Among all transformed component, sarcoma appears to be the most frequent histology, followed by primitive neuroectodermal tumor (PNET) and adenocarcinoma. To our knowledge, there were 3 cases of colonic-type adenocarcinoma arising in a primary teratoma have been reported to date. However, none of them received chemotherapy directed to transformed histology given localized disease at presentation. We, therefore, report here the first case of patient who achieved good response from chemotherapy directed to transformed histology, which confirms the importance of chemotherapy regimen used.