tbuckley/cabot-search huggingface dataset:
A multicentric single-arm phase II clinical trial to evaluate safety and efficacy of the combination of olaparib and PLD for platinum resistant ovarian primary peritoneal carcinoma and fallopian tube cancer patients: The GEICO-1601 ROLANDO trial—A trial in resistant ovarian cancer with olaparib and pegylated liposomal doxorubicin.
Authors: Jose Alejandro Perez-Fidalgo, Uriel Bohn, Elisa Calvo, Yolanda Garcia Garcia, Eva Mª Guerra, Maria Iglesias, Luis Manso, Ana Santaballa, Antonio González-Martín
Journal: Journal of Clinical Oncology (2018)

TPS5610 Background: Olaparib is a PARP-inhibitor that has demonstrated efficacy in ovarian cancer in both platinum-sensitive and platinum-resistant relapse. BRCA mutations have been identified as an important predictive factor for response to olaparib, however in Study 19 progression free survival (PFS) was also improved in BRCA wildtype (BRCAwt) patients (1). A preclinical study showed synergism between doxorubicin and olaparib in 2D and 3D models of ovarian cancer (2). The combination of pegylated liposomal doxorubicin (PLD) 40 mg/m2 and olaparib 400 mg bid (capsule formulation) was considered tolerated and suitable in a phase I trial (3). Methods: This is a multicenter single arm phase II trial in women with platinum-resistant relapsed ovarian cancer. Patients receive Pegilated liposomal doxorubicin (PLD) 40 mg/m2 every 28 days and olaparib 300 mg bid tablets for 6 cycles followed by olaparib 300 mg bid maintenance until toxicity or disease progression. Primary endpoint is progression-free survival at 6 months (PFS6m). Secondary endpoints are PFS, overall-survival, response rate, quality of life, and growth modulation index. Key inclusion criteria are: 1) Serous or endometrioid ovarian cancer 2) Platinum-resistant relapse (between 28 days and 6 months after last platinum-containing chemotherapy (CT)) 3) Previous PLD is allowed if administered as part of a platinum-sensitive recurrence and > 6 months before inclusion 4) BRCA mutant patients are eligible after only 1 previous CT line, 5) BRCAwt or unknown are eligible after at least 2 previous platinum sensitive lines 6) no more than 3 CT lines are allowed, 7) Hemoglobin > 10 g/dl and 8) left ventricle ejection fraction > 50%. Sample size calculation assumed that PFS6m 40% or higher would be of interest for further investigation; with 90% power and a 2-sided alpha error 0.05 the number of patients needed will be 32 patients. Enrolment was initiated in December 2017 and the first patient has been enrolled. Clinical trial information: NCT03161132.
Carbapenem-Sparing Therapy for Extended-Spectrum β-Lactamase–Producing <i>E coli</i> and <i>Klebsiella pneumoniae </i>Bloodstream Infection
Authors: Mary K. Hayden, Sarah Y. Won
Journal: JAMA (2018)

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Apatinib in advanced alveolar soft part sarcoma: Evidence of efficacy and safety.
Authors: Li Min, Yong Zhou, Fan Tang, Yi Luo, Wenli Zhang, Rui Shi, Hong Duan, Chongqi Tu
Journal: Journal of Clinical Oncology (2018)

e23521 Background: Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma with high metastatic potential and poor prognosis, and it mainly affects young patients. As ASPS is resistance to chemotherapy, antiangiogenic agent sunitinib is the only therapeutic option recommended by NCCN Guidelines Version 2017. Previous studies have suggested that apatinib, an oral VEGFR-2 inhibitor, is safe and effective in some sarcomas. The aim of this study was to evaluate the efficacy and safety of apatinib for advanced ASPS. Methods: This retrospective series analyzed 6 advanced ASPS patients who received apatinib from 2015 to 2017 at West China Hospital, Sichuan University. Among the 6 patients, there were 1 patient with unresectable local tumor and 5 patients with multiple unresectable lung metastases. Apatinib 500mg was administered once daily. Five of the 6 patients had no previous exposure to other antiangiogenic agents. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Toxicities were also evaluated according to the National Cancer Institute Common Toxicity Criteria version 4.0 (CTC4.0). Results: The mean age of the six patients was 26±5 years old. Until Nov. 6 2017, 4 patients continued using apatinib, 1 patients stopped because of CR, the other patient stopped because of surgery. The median dosing time was 8.8 months (4.5-11.93 months). Of the 6 patients, 1 patient achieved complete response and 5 patients achieved partial response. The clinical benefit was recorded in total 6 patients, the objective response rate and disease control rate are both 100%. The common adverse events were as follows: hand-foot syndrome (66.7%), diarrhea (50%), grey hair (33.3%), hypertension (16.7%) and albuminuria (16.7%). There were no grade 3/4 adverse events. No patients experienced dosage reduction. Conclusions: Apatinib showed promising antitumor activity in patients with ASPS with tolerated adverse effects, when treated as first-line or second line treatment.
Randomized controlled trial to test the efficacy of trans-tympanic injections of a sodium thiosulfate gel to prevent cisplatin-induced ototoxicity.
Authors: Francois Meyer, Viannique Rolland, Isabelle Bairati, Matthieu Guitton, André Fortin, Mathieu Côté
Journal: Journal of Clinical Oncology (2017)

e17560 Background: The hearing loss due to cisplatin cochlear damage is frequent and severe. Antioxidants, such as sodium thiosulfate (STS), can neutralize the effects of cisplatin, but, when administered systemically, they decrease its efficacy. In animal experiments, STS deposited in the middle ear reached the cochlea and reduced cisplatin ototoxicity. We conducted a randomized controlled trial to test the efficacy of trans-tympanic injections of a STS gel to prevent cisplatin-induced ototoxicity. Methods: Eligible participants were patients with symmetrical hearing treated for a locally advanced head and neck cancer with chemoradiation including 3 cisplatin cycles (100 mg/m 2 ). For each participant, one randomly selected ear received the injections while the other ear did not. On the eve of each cisplatin treatment, a trans-tympanic injection deposited 0.1 ml of an immediately prepared STS-hyaluronate gel (0.5 M) on the round window. The main outcome was assessed blindly using the shift of hearing threshold in decibels (dB) from before chemoradiation to one month thereafter for pure-tone air conduction at 0.5-14 kHz frequencies. Adverse effects were noted according to CTCAE. Assuming a lower hearing loss of 7.0 dB for the treated ears, 0.90 power and 0.05 two-sided statistical significance, 25 patients were needed. The main outcome was assessed in a mixed linear model with hearing threshold shift as dependent variable and intervention, frequency and radiation dose to the cochlea as independent variables. Results: From January to December 2015, 13 patients were randomized. The trial was stopped in June 2016 for poor accrual. The average loss of hearing over all frequencies was 1.5 dB less for the treated ears than for the control ears. The difference was not statistically (p = 0.56) nor clinically significant, but was consistently in favor of the treated ears for all frequencies between 3 and 10 kHz. The intervention adverse effects were mild. Conclusions: Our trial suggests that STS deposited in the middle ear reached the cochlea but was not clinically effective. More work is needed to improve the efficacy of trans-tympanic administration of cisplatin antidotes. Clinical trial information: NTC02281006.
A large, multicenter, retrospective study to identify a cutoff of MGMT methylation status by quantitative pyrosequencing approach in patients (PTS) with glioblastoma (GBM).
Authors: Giuseppe Lombardi, Luisa Bellu, Veronica Villani, Simona Rizzato, Marco Russo, Mariantonia Carosi, Elisa De Carlo, Lorena Biasini, Marina Paola Gardiman, Pasquale Fiduccia, Ardi Pambuku, Alessandro Della Puppa, Miran Skrap, Franco Servadei, Domenico D'Avella, Carmine Maria Carapella, Mario Caccese, Roberta Bertorelle, Andrea Pace, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2018)

2012 A LARGE, MULTICENTER, RETROSPECTIVE STUDY TO IDENTIFY A CUT-OFF OF MGMT METHYLATION STATUS BY QUANTITATIVE PYROSEQUENCING APPROACH IN PATIENTS (PTS) WITH GLIOBLASTOMA (GBM). Background: MGMT promoter methylation status representsan important prognostic factor for GBM PTS in terms of progression free survival (PFS) and overall survival (OS). Quantitative pyrosequencing approach is a valid alternative to methylation-specific PCR but a cut-off value in still unclear. We performed a large, multicenter, retrospective study to identify a real cut-off value to discriminate its impact on clinical outcome in terms of PFS and OS. Methods: Retrospectively, from italian neuro-oncology centers, we collected GBM PTS from 2005 to 2016 with assessment of MGMT promoter methylation by pyrosequencing approach evaluating CpG islands from 74 to 83. Other inclusion criteria were: confirmed histological diagnoses of GBM, ECOG PS ≥2, treatment with concomitant radiation therapy and temozolomide. Kaplan-Maier method was used to estimate the survival curves and ROC curve for defining cut-off value for PFS and OS. Results: 376 GBM PTS were enrolled;median age was 62 ys (25-86); ECOG PS was 0 in 129 PTS, 1 in 160 PTS, 2 in 87 PTS; 212 PTS (58%) had a complete resection. 67 PTS (18%) received a second surgery. Median PFS and OS was 8.6 and 14.3 months. The optimal cut-off value to identify a strong prognostic value of MGMT methylation status in terms of PFS and OS, was 26% (sensitivity 72%, specificity 61%, accuracy 71%) and 24% of methylation (sensitivity 72%, specificity 61%, accuracy 71%), respectively. On multivariate analyses, corrected for age, KPS, type of surgery and second surgery, the MGMT cut-off values remained significantly correlated to longer PFS (HR = 0.5, 95%CI 0.4-0.7) and OS (HR = 0.47, 95% CI 0.3-0.6). Conclusions: From this large, multicenter study, we identify, by pyrosequencing approach, a strong prognostic value of MGMT methylation, in terms of PFS and OS. This value could be used as stratification factor in prospective clinical trials.
Abstract 19313: Characteristics of CPR Performance Metrics Early vs Late in Pediatric In-hospital Resuscitations
Authors: Elena Insley, Elaine Gilfoyle, Todd Sweberg, Jordan Duval-Arnould, Dana E Niles, Ivie Esangbedo, Tia Raymond, Ichiro Watanabe, Annemarie Silver, Vinay M Nadkarni
Journal: Circulation (2017)

Introduction: Compliance with CPR performance metrics during pediatric in-hospital cardiac arrest (IHCA) is associated with outcome. The evolution of CPR performance over time (early vs. late) has ...
ZUMA-2: Phase 2 multicenter study evaluating efficacy of kte-C19 in patients with relapsed/refractory mantle cell lymphoma.
Authors: Michael Wang, Frederick Lundry Locke, Javier Munoz, Andre Goy, Houston Eccleston Holmes, Tanya Siddiqi, Ian Flinn, Peter A McSweeney, Patrick Michael Reagan, Brian Thomas Hill, Caron A. Jacobson, David A. Rizzieri, Leonard T. Heffner, Samantha Mary Jaglowski, David Bernard Miklos, Paul Shaughnessy, Sherry Unabia, John M. Rossi, Yizhou Jiang, Rajul K. Jain
Journal: Journal of Clinical Oncology (2018)

TPS3102 Background: Mantle cell lymphoma (MCL) is an aggressive B cell malignancy, and accounts for ≈6% of non-Hodgkin lymphomas. Despite high initial response rates, MCL is generally considered incurable, as almost all patients (pts) eventually progress (Cheah et al. J Clin Oncol. 2016). Bruton tyrosine kinase (BTK) inhibition can lead to high rates of prolonged responses in relapsed/refractory (R/R) MCL, as noted with ibrutinib (Wang et al. NEJM. 2013) and acalabrutinib (Wang et al. Lancet. 2017). However, many pts develop ibrutinib-resistance and outcomes to salvage regimens (including investigational agents) are poor with a response rate of 32% and median overall survival of 8.4 months (Cheah et al. Ann Oncol. 2015). This phase 2, multicenter, open-label study examines efficacy and safety of KTE-C19, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in pts with R/R MCL who have progressed on prior chemotherapy, an anti-CD20 antibody, and a BTK inhibitor. Methods: ZUMA-2 (NCT02601313) is enrolling pts with R/R MCL sequentially into 2 separate dose level cohorts (~40 pts each). After leukapheresis and manufacturing, pts will receive conditioning chemotherapy with fludarabine 30 mg/m2/d and cyclophosphamide 500 mg/m2/d × 3 d and then receive a single infusion of KTE-C19 cells at a dose of 0.5 × 106 CAR T cells/kg. The primary endpoint is objective response rate by Independent Review Committee assessment; secondary and exploratory endpoints include duration of response, progression-free survival, overall survival, incidence of adverse events and levels of CAR T cells and cytokines in blood. Eligible adult pts with pathologically confirmed R/R MCL and an ECOG of 0-1 must have received ≤ 5 prior therapies that must have included an anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy, and ibrutinib or acalabrutinib. Pts who received allogenic stem cell transplant or prior CD19-directed therapy or those with clinically significant infection or a history of central nervous system lymphoma or central nervous system disorders are not eligible. Accrual is ongoing. Clinical trial information: NCT02601313.
Assessment of State, Local, and Territorial Zika Planning and Preparedness Activities — United States, June 2016–July 2017
Authors: Bhavini Patel Murthy, Sara Vagi, Rodel Desamu-Thorpe, Rachel Avchen
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

The emergency response to Zika virus disease required coordinated efforts and heightened collaboration among federal, state, local, and territorial public health jurisdictions. CDC activated its Emergency Operations Center on January 21, 2016, with seven task forces to support the national response. The State Coordination Task Force, which functions as a liaison between jurisdictions and federal operations during a response, coordinated the development of CDC Guidelines for Development of State and Local Risk-based Zika Action Plans, which included a Zika Preparedness Checklist (1). The checklist summarized recommendations covering topics from the seven task forces. In July 2016, CDC's Office of Public Health Preparedness and Response (OPHPR) awarded $25 million in supplemental funding to 53 jurisdictions (41 states, eight territories, and four metropolitan areas) to support Zika preparedness and response activities. In December 2016, CDC awarded an additional $25 million to 21 of the 53 jurisdictions at the greatest risk for seeing Zika in their communities based on the presence of the mosquito responsible for spreading Zika, history of local transmission, or a high volume of travelers from Zika-affected areas. The additional $25 million was part of the $350 million in Zika supplemental funding provided to CDC by Congress in 2016* (2,3). Funded jurisdictions reported progress through the checklist at five quarterly points throughout the response. Data were analyzed to assess planning and response activities. Among the 53 jurisdictions, the percentage that reported having a Zika virus readiness, response, and recovery plan increased from 26% in June 2016 to 64% in July 2017. Overall, Zika planning and response activities increased among jurisdictions from June 2016 to July 2017. The recent Zika virus outbreak underscores the importance of strengthening state, local, and territorial health department capacity for rapid response to emerging threats.
Phase I/II study of BSK01, an artificial intelligence-driven, peptide-pulsed, mature DC immunotherapy for solid and hematological malignancies.
Authors: Leonardo Mirandola, Zahra Timsah, Diane Duyen Thuy Nguyen, Robert Bresalier, Naval Guastad Daver, Maurizio Chiriva-Internati
Journal: Journal of Clinical Oncology (2018)

TPS3136 Background: Despite advances in understanding the biology of hematologic malignancies (HM) and solid malignancies (SM), and the availability of new treatment options, many patients with HM and SM remain incurable. Since the majority of cancer patients display a defective immune response to tumor antigens, the ex vivo activation of dendritic cells (DC), through their exposure to tumor associated antigens, is an attractive and active area of investigation. The choice of the target antigen and the identification of immuno-dominant and immunogenic peptides to drive powerful and specific cellular responses against tumor cells are crucial for the success of cancer vaccines. We have developed a powerful artificial intelligence (AI) computational platform, K.A.I., capable of collecting, normalizing, and analyzing data from multiple data sources, and to prioritize target antigens and immuno-dominant peptides for any given malignancy. Methods: Currently, we are conducting 4 clinical trials for solid and hematologic malignancies, both in the consolidation and refractory settings. We hypothesize that treatment of patients with HM or metastatic SM using autologous DC pulsed with immuno-dominant tumor-specific peptide antigens will result in antigen-specific CD4+ T-cell and/or CD8+ CTL responses without significant toxicities. We also hypothesize that the responses generated against specific antigens may translate into clinical anti-tumor activity. Primary Objective: Phase I (6 subjects). To determine safety of intradermal/subcutaneous DC vaccine therapy, low-dose cyclophosphamide and GM-CSF, in patients with metastatic SM or HM. Secondary Objective: Phase II (up to 17 subjects). To determine immune responses associated with intradermal/subcutaneous DC vaccine therapy, low-dose cyclophosphamide and GM-CSF, in patients with metastatic SM or HM who demonstrate a response, or whose disease remains stable, after conventional first-line systemic therapy, or who have failed conventional systemic therapy. The study population is currently drawn from patients at various clinical institutions following contractual agreements. Clinical trial information: NCT02709993; NCT02705703; NCT02224599; NCT02223312.
Impact of histologic type on survival in primary testicular lymphomas.
Authors: Taha Al-Juhaishi, Victor Y. Yazbeck
Journal: Journal of Clinical Oncology (2018)

e19545 Background: Primary testicular lymphoma (PTL) is a rare disease accounting for 1-2% of extranodal non-Hodgkin lymphomas (NHL), and less than 5% of testicular malignancies. PTL is considered the most common testicular neoplasm in men above 60 years. In this study, we sought to explore the impact of histologic type on survival. Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients (≥18 years) diagnosed with PTL between 1983 and 2013. B-cell and T-cell lymphomas of all stages were included. Overall survival was estimated using the Kaplan-Meier method, and compared using Log-Rank test. Cox proportional hazards models were used for adjusted survival analyses Results: Total of 1072 patients were included. Median age was 67 years (53-81), and majority were Caucasian (n = 841, 79%). Diffuse large B cell lymphoma was the most common histology (DLBCL, N = 962, 89.7%), followed by Burkitt (BL, N = 21, 2%) and follicular (FL, N = 19, 1.8%). 48 patients (4.5 %) were reported as unspecified histology (B-NHL, NOS).1034 (96.5%) patients had surgery, 805 (75%) had chemotherapy and 410 (38%) had radiation. At a median follow-up of 7 years (3.3-11.6), 570 (53%) patients had died. Median overall survival was 5.9 [5.2 – 6.6.; 95% CI] years. Survival was different by histological type (table, P = 0.029). Compared with DLBCL, BL (HR 2.05 [1.12 - 3.76], P = 0.021) and precursor NHL (HR 2.24 [1.12 – 4.48], P = 0.023) were associated with higher mortality, independent of other variables. In a multivariate model; surgery (HR 0.57 [0.37 – 0.87], P < 0.001), chemotherapy (HR 0.60 [0.49 – 0.73], P < 0.001), and radiotherapy (HR 0.62 [0.51 – 0.76], P < 0.001) were all associated with lower mortality. Conclusions: PTL is rare and affects the elderly. DLBCL is the most common type while BL and precursor NHL have the highest mortality. All treatment modalities (surgery, chemo- and radiotherapy) were associated with improved outcomes Survival by Histology Type Number (%) Median Survival (years) 1-year survival 5-year survival DLBCL 962 (89.7) 6.3 84% 56% BL 21 (2.0) 1.3 57% 43% CLL/SLL 3 (0.3) 5.9 67% 67% FL 19 (1.8) 5.9 89% 56% Precursor NHL 10 (0.9) 2.5 70% 10% MZL 4 (0.4) 2.8 75% 50% Mantle Cell 3 (0.3) 4.8 67% 33% T-cell 2 (0.2) 0.7 50% unknown Overall 1024 5.9 83% 55%