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Background Within the classification of pathological scars, scars after a burn that degenerate into squamous cell carcinoma, are called Marjolin's Ulcer. They generally present with nodules or plaques with irregular margins and surface, heterogeneous in color, painless, which present a slow growth mainly in a burn scar. These lesions are more frequent in patients with fair skin, being the main risk factor chronic exposure to sunlight. When Marjolin's ulcers occur, they appear many years after the burn and are characterized by being aggressive with a poor prognosis. A case report from a 58-year-old male, with a history of a third-degree burn for 3 years on the back and abdomen presented a plaque on a scar on his back of 8 years of evolution which had presented recurrent infections. Keywords: Marjolin ulcer, flap reconstruction

Supplementary Figure/Table Legends from A Phase I/II Trial of Belinostat in Combination with Cisplatin, Doxorubicin, and Cyclophosphamide in Thymic Epithelial Tumors: A Clinical and Translational Study

Table S1: Dose escalation schema; Table S2: Disease and treatment characteristics and outcomes of patients who underwent multimodality therapy; Table S3: Cycle 1 pharmacokinetic parameters of belinostat.

Mean plasma concentration vs. time curve at belinostat 250 mg/m2.

Purpose: This phase I/II study sought to determine the safety and maximum tolerated dose (MTD) of a novel schedule of belinostat, a histone deacetylase inhibitor (HDAC) administered before and in combination with cisplatin (P), doxorubicin (A), and cyclophosphamide (C) in thymic epithelial tumors (TET). Antitumor activity, pharmacokinetics, and biomarkers of response were also assessed.Experimental Design: Patients with advanced, unresectable TET received increasing doses of belinostat as a continuous intravenous infusion over 48 hours with chemotherapy in 3-week cycles. In phase II, belinostat at the MTD was used.Results: Twenty-six patients were enrolled (thymoma, 12; thymic carcinoma, 14). Dose-limiting toxicities at 2,000 mg/m2 belinostat were grade 3 nausea and diarrhea and grade 4 neutropenia and thrombocytopenia, respectively, in two patients. Twenty-four patients were treated at the MTD of 1,000 mg/m2 with chemotherapy (P, 50 mg/m2 on day 2; A, 25 mg/m2 on days 2 and 3; C, 500 mg/m2 on day 3). Objective response rates in thymoma and thymic carcinoma were 64% (95% confidence interval, 30.8%-89.1%) and 21% (4.7%–50.8%), respectively. Modulation of pharmacodynamic markers of HDAC inhibition and declines in regulatory T cell (Treg) and exhausted CD8+ T-cell populations were observed. Decline in Tregs was associated with response (P = 0.0041) and progression-free survival (P = 0.021). Declines in TIM3+ CD8+ T cells were larger in responders than nonresponders (P = 0.049).Conclusion: This study identified the MTD of belinostat in combination with PAC and indicates that the combination is active and feasible in TETs. Immunomodulatory effects on Tregs and TIM3+ CD8+ T cells warrant further study. Clin Cancer Res; 20(21); 5392–402. ©2014 AACR.

Supplementary Figures S1-S2; Supplementary Tables S1-S3.

Purpose: Sorafenib, a multikinase inhibitor targeting Raf and VEGFR, has shown activity in unselected patients with non–small-cell lung cancer (NSCLC). At present there are no validated biomarkers indicative of sorafenib activity.Experimental Design: Patients received sorafenib 400 mg BID daily to determine activity and tolerability and to measure its biological effects. KRAS mutation status (N = 34), angiogenesis markers (VEGF, bFGF, FLT-1, PLGF-1) and imaging with DCE-MRI (dynamic contrast enhanced MRI) to determine early changes in tumor vascular characteristics were evaluated. Three parameters Ktrans, Kep, and Ve were measured by DCE-MRI at baseline and day 14 of cycle 1. Cytokine analysis was done on days 0, 14, 28, and 54.Results: Thirty-seven patients with previously treated stage IV NSCLC were enrolled in this single-center phase II trial. In 34 evaluable patients, 2 had partial responses and 20 had stable disease for 3 to 17 months, a disease control rate of 65%. The median progression-free survival (PFS) was 3.4 months, and median overall survival (OS) was 11.6 months. Toxicity was consistent with the known side effects of sorafenib. KRAS (32%) and EGFR mutations (22%) showed no correlation with response, PFS, or OS. Kep, was significant in predicting an improvement in OS (P = 0.035) and PFS (P = 0.029). Cytokine analysis demonstrated an improved OS for bFGF day 0 (6 pg/mL; P = 0.042), whereas a PFS benefit was seen with bFGF at day 28 (6; P = 0.028).Conclusions: KRAS and EGFR mutational status showed no correlation with response, PFS, or OS. Radiologic and cytokine changes may act as biomarkers indicative of early angiogenesis inhibition. Clin Cancer Res; 17(5); 1190–9. ©2011 AACR.

Relative changes (mean and standard deviation) in the number of CTLA4-expressing Tregs with treatment (A). Overall survival of patients with pre-treatment CTLA4 expressing-Treg numbers above and below the median (B).

Supplemetary Methods from A Phase I/II Trial of Belinostat in Combination with Cisplatin, Doxorubicin, and Cyclophosphamide in Thymic Epithelial Tumors: A Clinical and Translational Study

Relative changes (mean and standard deviation) in γ-H2AX expression in CD3+ (A) and CD14+ (B) cells and by microscopy (C) before and after treatment. Figure S2C shows representative images of γ-H2AX foci incidence in PBMCs from one patient pre-treatment (C1D1), cycle 1 day 2 (C1D2), cycle 1 day 3 (C1D3), and cycle 2 day 1 pre-treatment (C2D1). Green, γ-H2AX; red, DNA stained with propidium iodide.

Climate change is one of the world's major problems and concerns the entire human population as its effects are global in scope. Climate change is driven by the greenhouse effect, which is generated by greenhouse gases (GHG). The construction industry is important in the development of a country, both economically and culturally, since it is through it that the infrastructure needs required for a nation's economic and social activities are met. Urban environments are composed of various structures that favor economic, social and any other activities of interest within the existing population; such urban environment is mainly connected by a system that is constituted by asphalt pavements of flexible or rigid type. This project analyzes the environmental impacts generated during the construction process of an asphalt pavement corresponding to the Real de Sevilla III subdivision, located in Obregon City, Sonora, Mexico, applying the Simapro 9.0 Software, obtaining a result of 12.618 Kg CO2 eq/m2 and 1,140, 863.493 Kg-CO2/fractionation generated by its main materials and activities and equipment consumptions.

RESUMEN Bacillus subtilis como promotor de crecimiento en el cultivo de Capsicum frutescens “ají tabasco”, en Moyobamba En los últimos años, el cultivo de Capsicum frutescens “ají tabasco” aumentó considerablemente junto al uso de agroquímicos que incrementan la polución ambiental, no obstante, escasas son las alternativas eco amigables para minimizar y controlar los químicos sin alterar la producción, ante ello se desarrolló la investigación empleando la bacteria Bacillus subtilis. El objetivo general fue “Evaluar la influencia del Bacillus subtilis como promotor de crecimiento en el cultivo de Capsicum frutescens “ají tabasco”, en Moyobamba”. El área de investigación fue una parcela demostrativa ubicada en el centro de producción del IESTP “Alto Mayo”, del distrito y provincia de Moyobamba de la región San Martín. El periodo de ejecución estuvo comprendido entre el 21/10/2021 al 20/06/2022 resultando un total de 8 meses. La población y muestra fue de 48 plantas de ají tabasco y el diseño experimental de bloques al azar con cuatro tratamientos y tres bloques, los cuales fueron T1: 150 mL de BS + 850 mL de H2O, T2: 200 mL de BS + 800 mL de H2O, T3: 250 mL de BS + 750 mL de H2O y T4: 1 L de H2O (testigo). Se midieron los niveles de altura y longitud de hojas, pre y post aplicación del inoculante a los 30, 60 y 90 días, el método de aplicación de los tratamientos fue por aspersión y las mediciones fueron obtenidas en campo, utilizando materiales como wincha metálica y una ficha de recolección de datos; por otro lado, con un nivel de significancia del 5% se aplicaron los estadísticos de análisis de varianza y prueba de Duncan. Como resultados se encontraron que antes de la aplicación de los tratamientos no existió diferencias significativas en la altura y longitud de hojas de las plantas de ají tabasco, mientras que post aplicación de tratamientos existió diferencias significativas en la media de las variables estudiadas, de los cuales a los 30, 60 y 90 días se obtuvieron mayores y menores niveles de altura y medias con T3 y T4 respectivamente, determinando además con un nivel de confianza del 95% que el tratamiento óptimo a los 30, 60 y 90 días fue T3 (250 mL de BS + 750 mL de H2O) para ambas variables. Se concluye que existe efecto de Bacillus subtilis para promover el crecimiento del cultivo de Capsicum frutescens “ají tabasco”, a nivel de altura y longitud de hojas. Bacillus subtilis as a growth promoter for Capsicum frutescens "tabasco chili" cultivation in Moyobamba. In recent years, the cultivation of Capsicum frutescens "tabasco chili" has increased considerably along with the use of agrochemicals that increase environmental pollution, however, there are few eco-friendly alternatives to minimize and control chemicals without altering production. In response to this, the research was carried out using the bacterium Bacillus subtilis. The general objective was "To evaluate the influence of Bacillus subtilis as a growth promoter in the cultivation of Capsicum frutescens " tabasco chili" in Moyobamba". The research area was a demonstration plot located in the production center of the IESTP "Alto Mayo", in the district and province of Moyobamba in the San Martin region. The execution period was from 10/21/2021 to 06/20/2022 for a total of 8 months. The population and sample consisted of 48 tabasco chili peppers plants and the experimental design was randomized blocks with four treatments and three blocks, which were T1: 150 mL of BS + 850 mL of H2O, T2: 200 mL of BS + 800 mL of H2O, T3: 250 mL of BS + 750 mL of H2O and T4: 1 L of H2O (control). The height and length of leaves were measured pre and post inoculant application at 30, 60 and 90 days. The application method of the treatments was by spraying and the measurements were obtained in the field, using materials such as a metal winch and a data collection sheet. Analysis of variance and Duncan's test were applied at a significance level of 5%. As results, it was found that before the application of the treatments there were no significant differences in the height and leaf length of the tabasco chili plants. After the application of the treatments there were significant differences in the average of the variables under study, of which at 30, 60 and 90 days the highest and lowest levels of height and average were obtained with T3 and T4, respectively. It was also determined with a confidence level of 95% that the optimal treatment at 30, 60 and 90 days was T3 (250 mL of BS + 750 mL of H2O) for both variables. It is concluded that there is an effect of Bacillus subtilis to promote the growth of Capsicum frutescens " tabasco chili", at the level of height and leaf length.

After weeks under lockdown, metropolitan areas fighting the spread of COVID-19 aim to balance public health goals with social and economic standards for well-being. Mathematical models of disease transmission seeking to evaluate mitigation strategies must assess the possible impacts of social distancing, economic lockdowns and other measures. However, obscure relations between model parameters and real-world phenomena complicate such analyses. Here, we use a high-resolution metapopulation model of Guadalajara (GDL, Western Mexico) to represent daily mobility patterns driven by economic activities and their relation to epidemic growth. Given the prominence of essential activities in the city’s economy, we find that strategies aiming to mitigate the risk of out-of-home interactions are insufficient to stop the catastrophic spread of COVID-19. Using baseline reproduction numbers R0 = [2.5, 3.0] in the absence of interventions, our simulations suggest that household transmission alone can make Rt ∼ 1, and is estimated to drive 70 ±15% of current epidemic growth. This sets an upper bound for the impact of mobility-based interventions, which are unlikely to lower Rt below 1.3 and must be complemented with aggressive campaigns for early case detection and isolation. As laboratory testing and health services become insufficient to meet demand in GDL and most other cities, we propose that cities facilitate guidelines and equipment to help people curb spreading within their own homes. Postponing these actions will increase their economic cost and decrease their potential returns.Author summaryPublic health strategies to mitigate the spread of COVID-19 in metropolitan areas have focused on preventing transmission in schools, work sites and other public spaces. Here, we use a demographically- and spatially-explicit model of Guadalajara (GDL, Western Mexico) to represent economic lockdowns and their impact on disease spread. Our findings suggest that viral exposure within households accounts for 70±15% of the epidemic’s current growth rate. This highlights the importance of early case detection and isolation as necessary measures to prevent the spread of COVID-19 between strangers and close contacts alike.

Cognitive radio is a technique that was originally created for the proper use of the radio electric spectrum due its underuse. A few methods were used to predict the network traffic to determine the occupancy of the spectrum and then use the ‘holes’ between the transmissions of primary users. The goal is to guarantee a complete transmission for the second user while not interrupting the trans-mission of primary users. This study seeks the multifractal generation of traffic for a specific radio electric spectrum as well as a bio-inspired route estimation for secondary users. It uses the MFHW algorithm to generate multifractal traces and two bio-inspired algo-rithms: Ant Colony Optimization and Max Feeding to calculate the secondary user’s path. Multifractal characteristics offer a predic-tion, which is 10% lower in comparison with the original traffic values and a complete transmission for secondary users. In fact, a hybrid strategy combining both bio-inspired algorithms promise a reduction in handoff. The purpose of this research consists on deriving future investigation in the generation of multifractal traffic and a mobility spectrum using bio-inspired algorithms.

Background Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)–programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stag...

El artículo que se presenta es el resultado de discusiones teóricas que emergieron desde la propia creación del área de investigación “Desigualdades sociales y políticas de equidad”, del Programa FLACSO-Cuba, donde la multiplicidad de miradas y disciplinas ha enriquecido el debate, motivado por la ampliación de las desigualdades sociales en Cuba en las últimas décadas. En primer lugar se presenta una aproximación al contexto cubano actual, luego se analizan diferentes referentes teóricos sobre desigualdades sociales, pobreza, exclusión social, vulnerabilidad social y ambiental, políticas sociales para la inclusión y la equidad, en lo concerniente a su pertinencia para la realidad cubana. The article presented is the result of theoretical discussions that emerged from the creation of the research area "Social inequalities and political equity", of the FLACSO-Cuba Program, where the multiplicity of views and disciplines has enriched the debate, motivated by the expansion of social inequalities in Cuba in recent decades. In the first place an approximation to the current Cuban context is presented, then different theoretical referents about social inequalities, poverty, social exclusion, social and environmental vulnerability, social policies for inclusion and equity are analyzed, as far as their pertinence for the reality Cuban.

In non-small cell lung cancer (NSCLC), platelet-derived growth factor receptor (PDGFR) mediates angiogenesis, tissue invasion, and tumor interstitial pressure. Olaratumab (IMC-3G3) is a fully human anti-PDGFRα monoclonal antibody. This Phase II study assessed safety and efficacy of olaratumab+paclitaxel/carboplatin (P/C) versus P/C alone for previously untreated advanced NSCLC.Patients received up to six 21-day cycles of P 200mg/m131 patients were: 67 with olaratumab+P/C and 64 with P/C; 74% had nonsquamous NSCLC. Median PFS was similar between olaratumab+P/C and P/C (4.4 months each) (HR 1.29; 95% CI [0.86-1.93]; p=0.21). Median OS was similar between olaratumab+P/C (11.8 months) and P/C (11.5 months) (HR 1.04; 95% CI [0.68-1.57]; p=0.87). Both arms had similar toxicity profiles. All evaluable cases were PDGFR-negative by immunohistochemistry. Tumor stroma PDGFR expression was evaluable in 23/131 patients, of which 78% were positive.The addition of olaratumab to P/C did not result in significant prolongation of PFS or OS in advanced NSCLC. Olaratumab studies in other patient populations, including soft tissue sarcoma (NCT02783599), pancreatic cancer (NCT03086369), and pediatric malignancies (NCT02677116) are underway.

Purpose Epidermal growth factor receptor (EGFR) mutations confer sensitivity to EGFR tyrosine kinase inhibitors in patients with advanced non–small-cell lung cancer (NSCLC). There are limited and conflicting reports on the frequency of EGFR mutations in Latinos. Patients and Methods Samples from 642 patients with NSCLC from seven institutions in the United States and Latin America were assessed for EGFR mutations (exons 18 to 21) at Clinical Laboratory Improvement Amendments-certified central laboratories. Results EGFR mutation analysis was successfully performed in 480 (75%) of 642 patients; 90 (19%) were Latinos, 318 (66%) were non-Latino whites, 35 (7%) were non-Latino Asians, 30 (6%) were non-Latino blacks, and seven (2%) were of other races or ethnicities. EGFR mutations were found in 21 (23%) of 90 Latinos with varying frequencies according to the country of origin; Latinos from Peru (37%), followed by the United States (23%), Mexico (18%), Venezuela (10%), and Bolivia (8%). In never-smoker Latinos and Latinos with adenocarcinoma histology, EGFR mutation frequencies were 38% and 30%, respectively. There was a significant difference in the frequency of EGFR mutations among the different racial and ethnic subgroups analyzed (P < .001), with non-Latino Asians having the highest frequency (57%) followed by Latinos (23%), non-Latino whites (19%), and non-Latino blacks (10%). There was no difference between Latinos (23%) and non-Latinos (22%; P = .78) and Latinos and non-Latino whites (P = .37). Patients from Peru had an overall higher frequency of mutations (37%) than all other Latinos (17%), but this difference only exhibited a trend toward significance (P = .058). Conclusion There was no significant difference between the frequency of EGFR mutations in NSCLC in Latinos and non-Latinos.

BACKGROUND. Seribantumab (MM‐121) is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3/ErbB3) to block heregulin (HRG/NRG)‐mediated ErbB3 signaling and induce receptor downregulation. This open‐label, randomized phase 1/2 study evaluated safety and efficacy of seribantumab plus erlotinib in advanced non‐small cell lung cancer (NSCLC). Here, we report the activity of seribantumab plus erlotinib, versus erlotinib alone, in patients with EGFR wild‐type tumors and describe the potential predictive power of HRG. MATERIALS AND METHODS. Patients with EGFR wild‐type NSCLC were assigned randomly to receive seribantumab + erlotinib or erlotinib alone. Patients underwent pretreatment core needle biopsy and archived tumor samples were collected to support prespecified biomarker analyses. RESULTS. One hundred twenty‐nine patients received seribantumab + erlotinib (n = 85) or erlotinib alone (n = 44). Median estimated progression‐free survival (PFS) in the unselected intent‐to‐treat (ITT) population was 8.1 and 7.7 weeks in the experimental and control arm, respectively (hazard ratio [HR], 0.822; 95% confidence interval [CI], 0.37–1.828; p = 0.63), and median estimated overall survival was 27.3 and 40.3 weeks in the experimental and control arm, respectively (HR, 1.395; 95% CI, 0.846 to 2.301; p = .1898) In patients whose tumors had detectable HRG mRNA expression, treatment benefit was observed in the seribantumab + erlotinib combination (HR, 0.35; 95% CI, 0.16–0.76; p = .008). In contrast, in patients whose tumors were HRG negative, the HR was 2.15 (95% CI, 0.97–4.76; p = .059, HRG‐by‐treatment interaction, p value = .0016). CONCLUSION. The addition of seribantumab to erlotinib did not result in improved PFS in unselected patients. However, predefined retrospective exploratory analyses suggest that detectable HRG mRNA levels identified patients who might benefit from seribantumab. An ongoing clinical trial of seribantumab, in combination with docetaxel, is underway in patients with advanced NSCLC and high HRG mRNA expression (NCT02387216). IMPLICATIONS FOR PRACTICE. The poor prognosis of patients with non‐small cell lung cancer (NSCLC) underscores the need for more effective treatment options, highlighting the unmet medical need in this patient population. The results of this study show that a novel biomarker, heregulin, may help to identify patients with advanced NSCLC who could benefit from treatment with seribantumab. On the basis of the observed safety profile and promising clinical efficacy, a prospective, randomized, open‐label, international, multicenter phase II trial (SHERLOC, NCT02387216) is under way to investigate the efficacy and safety of seribantumab in combination with docetaxel in patients with heregulin‐positive advanced adenocarcinoma.

Purpose We conducted a basket clinical trial to assess the feasibility of such a design strategy and to independently evaluate the effects of multiple targeted agents against specific molecular aberrations in multiple histologic subtypes concurrently. Patients and Methods We enrolled patients with advanced non–small-cell lung cancer (NSCLC), small-cell lung cancer, and thymic malignancies who underwent genomic characterization of oncogenic drivers. Patients were enrolled onto a not-otherwise-specified arm and treated with standard-of-care therapies or one of the following five biomarker-matched treatment groups: erlotinib for EGFR mutations; selumetinib for KRAS, NRAS, HRAS, or BRAF mutations; MK2206 for PIK3CA, AKT, or PTEN mutations; lapatinib for ERBB2 mutations or amplifications; and sunitinib for KIT or PDGFRA mutations or amplification. Results Six hundred forty-seven patients were enrolled, and 88% had their tumors tested for at least one gene. EGFR mutation frequency was 22.1% in NSCLC, and erlotinib achieved a response rate of 60% (95% CI, 32.3% to 83.7%). KRAS mutation frequency was 24.9% in NSCLC, and selumetinib failed to achieve its primary end point, with a response rate of 11% (95% CI, 0% to 48%). Completion of accrual to all other arms was not feasible. In NSCLC, patients with EGFR mutations had the longest median survival (3.51 years; 95% CI, 2.89 to 5.5 years), followed by those with ALK rearrangements (2.94 years; 95% CI, 1.66 to 4.61 years), those with KRAS mutations (2.3 years; 95% CI, 2.3 to 2.17 years), those with other genetic abnormalities (2.17 years; 95% CI, 1.3 to 2.74 years), and those without an actionable mutation (1.85 years; 95% CI, 1.61 to 2.13 years). Conclusion This basket trial design was not feasible for many of the arms with rare mutations, but it allowed the study of the genetics of less common malignancies.

Summary Background Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7–22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2–4·8), and median duration of response was not reached (95% CI 8·31–not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7–10·9). 20 (17%) of 117 patients reported grade 3–4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. Funding Bristol-Myers Squibb.

Purpose: This phase I/II study sought to determine the safety and maximum tolerated dose (MTD) of a novel schedule of belinostat, a histone deacetylase inhibitor (HDAC) administered before and in combination with cisplatin (P), doxorubicin (A), and cyclophosphamide (C) in thymic epithelial tumors (TET). Antitumor activity, pharmacokinetics, and biomarkers of response were also assessed. Experimental Design: Patients with advanced, unresectable TET received increasing doses of belinostat as a continuous intravenous infusion over 48 hours with chemotherapy in 3-week cycles. In phase II, belinostat at the MTD was used. Results: Twenty-six patients were enrolled (thymoma, 12; thymic carcinoma, 14). Dose-limiting toxicities at 2,000 mg/m2 belinostat were grade 3 nausea and diarrhea and grade 4 neutropenia and thrombocytopenia, respectively, in two patients. Twenty-four patients were treated at the MTD of 1,000 mg/m2 with chemotherapy (P, 50 mg/m2 on day 2; A, 25 mg/m2 on days 2 and 3; C, 500 mg/m2 on day 3). Objective response rates in thymoma and thymic carcinoma were 64% (95% confidence interval, 30.8%-89.1%) and 21% (4.7%–50.8%), respectively. Modulation of pharmacodynamic markers of HDAC inhibition and declines in regulatory T cell (Treg) and exhausted CD8+ T-cell populations were observed. Decline in Tregs was associated with response (P = 0.0041) and progression-free survival (P = 0.021). Declines in TIM3+ CD8+ T cells were larger in responders than nonresponders (P = 0.049). Conclusion: This study identified the MTD of belinostat in combination with PAC and indicates that the combination is active and feasible in TETs. Immunomodulatory effects on Tregs and TIM3+ CD8+ T cells warrant further study. Clin Cancer Res; 20(21); 5392–402. ©2014 AACR.