Salivary proteomic biomarkers of oral squamous cell carcinoma

Objectives. The aim of the present study is to investigate the presence of proteomic signatures of Oral Squamous Cell Carcinoma (OSCC) in saliva and their use as potential biomarkers for early and non-invasive diagnosis, as well as prognostication. Methods. Saliva from 45 OSCC patients and 30 healthy controls was analysed by SELDI-TOF mass spectrometry and ProteinChip\uae technology. Proteomic profiles were tested with differential expression analysis and fold change of protein peaks, principal component analysis, Spearman rank correlation test and hierarchical clustering in order to identify a list of peaks of interest representative of controls, N- and N+ cases. Those peaks were used in a supervised artificial neural network in order to classify samples according to the following conditions: controls vs OSCC, controls vs N-, and controls vs N+. Results. When compared with controls, four peaks (i.e. 6913, 11948, 13287 and 27280 m/z) were significantly altered in both N- group and N+ group; four peaks (i.e. 3353, 3433, 3482 and 4136 m/z) were selectively altered in Ngroup; eight peaks were selectively altered in N+ group (i.e. 4038, 7133, 11755, 13746, 13841, 14264, 16807, 17127 m/z). Those peaks were capable to classify 100% of cases and controls, thus being potential diagnostic and prognostic biomarkers for OSC

Secondary malignancies after high-dose chemotherapy in germ cell tumor patients: A 34-year retrospective study of the European Society for Blood and Marrow Transplantation (EBMT)

We aimed to assess the incidence and risk factors of secondary malignancy (SM) in the young adult patients who received high-dose chemotherapy (HDCT) for germ cell tumors (GCT). The EBMT database was interrogated. Criteria for patient selection included adult male GCT and HDCT administered in any line of therapy. Cumulative incidence methods were used to estimate the time-to-SM diagnosis. Univariable Fine and Gray proportional hazard regression evaluated risk factors of SM occurrence. From 1981 to 2015, 9153 autografts were identified. Among 5295 patients, 59 cases of SM, developed after a median follow-up of 3.8 years, were registered. Of these patients, 23 (39%) developed hematologic SM, 34 (57.6%) solid SM (two patients had uncoded SM). Twenty-year cumulative incidence of solid versus hematologic SM was 4.17% (95% CI: 1.78-6.57) versus 1.37% (95% CI: 0.47-2.27). Median overall survival after SM was significantly shorter for patients who developed hematologic SM versus solid SM (8.6 versus 34.4 months, p = 0.003). Age older than 40 years at the time of HDCT was significantly associated with hematologic, but not solid, SM development (p = 0.004 versus p = 0.234). SM occurrence post-HDCT showed different patterns of incidence and mortality in GCT. These data may be important to optimize patient selection, counseling and follow-up after HDCT

Predictors of CD34+ cell mobilization and collection in adult men with germ cell tumors: implications for the salvage treatment strategy

BACKGROUND: High-dose chemotherapy with tandem or triple carboplatin and etoposide course is currently the first curative choice for relapsing GCT. The collection of an adequate amount of hematopoietic (CD34(+)) stem cells is a priority. PATIENTS AND METHODS: We analyzed data of patients who underwent HDCT at 2 referral institutions. Chemotherapy followed by myeloid growth factors was applied in all cases. Uni- and multivariable models were used to evaluate the association between 2 prespecified variables and mobilization parameters. Analyses included only the first mobilizing course of chemotherapy and mobilization failures. RESULTS: A total of 116 consecutive patients underwent a mobilization attempt from December 1995 to November 2012. Mobilizing regimens included cyclophosphamide (CTX) 7 gr/m(2) (n = 39), cisplatin, etoposide, and ifosfamide (PEI) (n = 42), paclitaxel, cisplatin, and gemcitabine (TPG) (n = 11), and mixed regimens (n = 24). Thirty-seven percent were treated in first-line, 50% (n = 58) in second-line, 9.5% (n = 11) and 3.4% (n = 4) in third- and fourth-line settings, respectively. Six patients did not undergo HDCT because they were poor mobilizers, 2 in first- and second-line (1.9%), and 4 beyond the second-line (26.7%). In the multivariable model, third-line or later setting was associated with a lower CD34(+) cell peak/μL (P = .028) and a lower total CD34(+)/kg collected (P = .008). The latter was also influenced by the type of mobilizing regimen (P < .001). CONCLUSION: A decline in significant mobilization parameters was found, primarily depending on the pretreatment load. Results lend support to the role of CD34(+) cell mobilization in the therapeutic algorithm of relapsing GCT, for whom multiple HDCT courses are still an option, and potentially a cure

Clinical Outcomes of Patients With Metastatic Urothelial Carcinoma After Progression to Immune Checkpoint Inhibitors: A Retrospective Analysis by the Meet-Uro Group (Meet-URO 1 Study)

Background: Immune checkpoint inhibitors (ICIs) are currently the standard of care for metastatic urothelial cancer (mUC) after the failure of previous platinum-based chemotherapy. The choice of further therapy after ICI progression is a new challenge, and scarce data support it. We aimed to examine the outcomes of mUC patients after progression to ICI, especially when receiving chemotherapy. Methods: Data were retrospectively collected from clinical records of mUC patients whose disease progressed to anti-programmed death 1 (PD-1)or programmed death ligand 1 (PD-L1) therapy at 14 Italian centers. Patients were grouped according to ICI therapy setting into SALVAGE (ie, ICI delivered ⩾ second-line therapy after platinum-based chemotherapy) and NAÏVE (ie, first-line therapy) groups. Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared among subgroups. Cox regression assessed the effect of treatments after progression to ICI on OS. Objective response rate (ORR) was calculated as the sum of partial and complete radiologic responses. Results: The study population consisted of 201 mUC patients who progressed after ICI: 59 in the NAÏVE cohort and 142 in the SALVAGE cohort. Overall, 52 patients received chemotherapy after ICI progression (25.9%), 20 (9.9%) received ICI beyond progression, 115 (57.2%) received best supportive care only, and 14 (7.0%) received investigational drugs. Objective response rate to chemotherapy in the post-ICI setting was 23.1% (28.0% in the NAÏVE group and 18.5% in the SALVAGE group). Median PFS and OS to chemotherapy after ICI-PD was 5 months (95% confidence interval [CI]: 3-11) and 13 months (95% CI: 7-NA) for the NAÏVE group; 3 months (95% CI: 2-NA) and 9 months (95% CI: 6-NA) for the SALVAGE group, respectively. Overall survival from ICI initiation was 17 months for patients receiving chemotherapy (hazard ratio [HR] = 0.09, p &lt; 0.001), versus 8 months for patients receiving ICI beyond progression (HR = 0.13, p &lt; 0.001), and 2 months for patients who did not receive further active treatment (p &lt; 0.001). Conclusions: Chemotherapy administered after ICI progression for mUC patients is advisable irrespective of the treatment line

Gender Asymmetry in Okun's Law in the Four PIGS Countries

AbstractCentred on the four PIGS countries (Portugal, Italy, Greece and Spain) and using the quarterly data from Q2/1998 until Q4/2014, the paper investigates whether there exists gender asymmetries in Okun's law and whether male unemployment reacts identically to economic fluctuations as female unemployment does. Whilst the trend components of output, male and female unemployment are estimated with the aid of the HP filter, Okun's relationships are modelled in the SVAR framework assuming that cyclical fluctuations of the economy and the labour market with both male and female labour force are endogenous. It is established that gender is indeed a factor that makes the respective segments of the labour market respond slightly differently to changes in real output

Prognostic impact of progression to induction chemotherapy and prior paclitaxel therapy in patients with germ cell tumors receiving salvage high-dose chemotherapy in the last 10 years: A study of the European Society for Blood and Marrow Transplantation Solid Tumors Working Party

Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P&lt;0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel

Biological therapeutic advances for the treatment of advanced urothelial cancers

In recent years, diagnostic and therapeutic advances have contributed to a reduction in mortality rates of patients with metastatic urothelial carcinoma (mUC). Immune checkpoint inhibitors have demonstrated efficacy and safety as both first-line and first-line switch maintenance therapy for mUC. For platinum-refractory patients, in addition to immunotherapy, other targeted agents (antibody–drug conjugates and fibroblast growth factor receptor inhibitors) have been approved after demonstrating a clinically relevant advantage in overall response rate, progression-free survival, and overall survival compared to standard of care. Sequential treatment strategies are finally feasible for patients with advanced urothelial carcinoma. This review will summarize the results of the most important phase II–III clinical trials for first-line, switch maintenance, second-line, and subsequent lines of therapy, and describe the most promising clinical trials currently ongoing in these treatment scenarios