tbuckley/cabot-search huggingface dataset:
A phase II randomized, multicentric clinical trail comparing recombinant human endostatin plus intensity-modulated radiotherapy versus concurrent chemoradiotherapy in locally advanced low-risk nasopharyngeal carcinoma.
Authors: Min Kang, Shaomin Lin, Haisheng Zhu, Sihui Liao, Haixin Huang, Bin Yu, Hongqian Wang, Meilian Liu, Jinxian Zhu, Guang Huang, Yutao Qin, Zhuxin Wei, Qinghua Du, Kai Hu, Tingting Zhang, Pingting Zhou, Xueyin Liao, Rensheng Wang
Journal: Journal of Clinical Oncology (2017)

6063 Background: A prospective, randomized, and multicentric phase II study was performed to evaluate the short-term efficacy and safety of Endostar plus intensity-modulated radiotherapy (IMRT) versus concurrent chemoradiotherapy(CCRT) in locally advanced low-risk nasopharyngeal carcinoma(NPC). Methods: From September 2014 to August 2016, 120 patients with low-risk NPC at stages III-IVa from 9 centers were randomly divided into experimental group (Endostar plus radiotherapy (ERT); n = 60) and control group (CCRT; n = 60). ERT patients were given Endostar (7.5 mg/m 2 /day) by continuous intravenous infusion (CIV) from 5 days before radiotherapy for consecutive 10 days for 2 cycles with an interval of 14 days. Then, ERT patients received 2 cycles of 10 days of maintenance treatment with Endostar after radiotherapy. The CCRT patients were given cisplatin (100 mg/m 2 ) on days 1, 22, and 43 for 3 cycles. Immediate and 3-month efficacy and adverse effects were evaluated between the two groups. ClinicalTrials registration number was NCT02237924. Results: All patients were eligible for toxicity and response analysis. Regarding immediate efficacy, the complete response(CR) rates were 45.0% for ERT arm and 33.3% for CCRT arm in nasopharynx (P = 0.190), and 43.3% for ERT arm and 36.7% for CCRT arm in regional nodes (P = 0.456). Three months after RT, the CR rates were 71.2% for ERT arm and 60.0% for CCRT arm in nasopharynx (P = 0.151), and 74.6% for ERT arm and 63.3% for CCRT arm in regional nodes (P = 0.172). The rate and severity of leukopenia, hemoglobin reduction and thrombocytopenia in ERT arm were significantly lower than CCRT arm (P &lt; 0.01). The occurrence rates of Xerostomia, oral mucositis, nausea / vomiting, constipation and weight loss in ERT arm were significantly lower than those in CCRT arm (P &lt; 0.01). Conclusions: The present study demonstrates that ERT has similar short-term efficacy on locally advanced low-risk NPC compared with CCRT, but the acute adverse effects of ERT are fewer, and the compliance and tolerability of patients are better. Clinical trial information: NCT02237924.
P04.34 Low-dose irradiation increases recruitment and effector function of tumor-specific T cells in experimental gliomas
Authors: X Zhang, K Sahm, J Sonner, K Jähne, M Breckwoldt, M Piechutta, P Häring, F Winkler, W Wick, M Platten
Journal: Neuro-Oncology (2018)

One major challenge in glioma immunotherapy is to ensure homing of peripherally activated adaptive immune cells to the tumor while retaining their effector function. For systemic tumors, local irradiation has been shown to induce a proinflammatory chemokine and cytokine milieu which facilitates tumor infiltration of effector immune cells. Within the CNS, molecular mechanisms mediating the irradiation-induced modulation of leukocyte function are only poorly understood but essential to exploit radiotherapy as immunological adjuvant for malignant gliomas. To assess the influence of radiotherapy on the outcome of T-cell-based immunotherapeutic approaches for brain tumors we have created a syngeneic murine GL261-glioma model over-expressing the major histocompatibility complex (MHC) class I-restricted model-antigen glycoprotein-100 (gp100), which is expressed in about 50% of human glioblastomas. Low-dose glioma irradiation (4x2Gy) resulted in increased numbers of vaccination-induced and adoptively transferred gp100-specific tumor-infiltrating T cells. Cytotoxic T cells displayed an activated phenotype and combined radioimmunotherapy significantly inhibited growth of established gliomas. In vivo two-photon-microscopy and correlative ultramicroscopy of ex vivo cleared whole brains demonstrated co-localization of fluorescently labeled tumor blood vessels with adoptively transferred T cells after radiotherapy. Of note, chemokine arrays and immunohistochemical analyses suggested the induction of CXCL10 in the tumor tissue as an important mechanism of irradiation-mediated recruitment of antigen-specific T cells to gliomas. Low-dose glioma irradiation promotes infiltration of vaccination-induced or adoptively transferred tumor-specific cytotoxic T cells and thus synergizes with T cell-based immunotherapies.
A randomized study of enzalutamide in patients with localized prostate cancer undergoing active surveillance (ENACT).
Authors: Neal D. Shore, Srinivas Vourganti, Jonathan L. Silberstein, Bruce A. Brown, Samuel Wilson, Courtney M.P. Hollowell, Matthew Cooperberg, Gwendoline Shang, Neil Eric Fleshner
Journal: Journal of Clinical Oncology (2017)

TPS5097 Background: Prostate cancer (PC) patients (pts) who select active surveillance (AS) are a heterogeneous population with varying risks for disease progression. Studies have estimated that approximately 31–42% of pts electing AS have experienced disease progression (pathological or therapeutic) over 1.8 and 2.3 years. There is no evidence-based pharmacological intervention which has effectively lessened this progression event. Pharmacological intervention with enzalutamide (ENZ), an androgen receptor inhibitor approved for treatment of metastatic castration-resistant PC, may lessen this progression. The aims of this study are to evaluate the efficacy of ENZ versus AS alone for delaying time to progression in pts with clinically localized PC undergoing AS. This study examines the effects of ENZ on progression in a subset of pts with low- or intermediate-risk PC who would otherwise elect an AS protocol. Methods: This is a multicenter, randomized, open-label study (NCT02799745). Eligibility criteria include histologically confirmed prostate adenocarcinoma within 6 months of screening, low or intermediate risk PC (T1c−T2c, prostate-specific antigen [PSA] &lt; 20, N0, M0, Gleason score ≤7 [3+4 pattern only]), Eastern Cooperative Oncology Group status ≤2 and estimated life expectancy &gt; 5 years. Exclusion criteria include any prior PC intervention. Pts will be randomized to receive open-label oral ENZ 160 mg/day once daily or to AS during the 1-year study treatment period. After the first year, all pts will be followed for one additional year with no other intervention. All pts will undergo prostate biopsy at 1 and 2 years. The primary end point is time to PC progression (pathological or therapeutic). Secondary end points include safety, incidence of negative biopsies for cancer at 1 and 2 years, percentage of cancer positive cores at 1 and 2 years, time to PSA progression, incidence of secondary rise in serum PSA, and quality-of-life questionnaires. Exploratory end points include biomarker assessment and genomic analysis. Study enrolment commenced in June 2016, with study completion expected in March 2019. Planned total enrolment is 222 pts from ~60 United States/Canadian sites. Clinical trial information: NCT02799745.
<i>Crebbp</i> Loss Drives Small Cell Lung Cancer and Increases Sensitivity to HDAC Inhibition
Authors: Deshui Jia, Arnaud Augert, Dong-Wook Kim, Emily Eastwood, Nan Wu, Ali H. Ibrahim, Kee-Beom Kim, Colin T. Dunn, Smitha P.S. Pillai, Adi F. Gazdar, Hamid Bolouri, Kwon-Sik Park, David MacPherson
Journal: Cancer Discovery (2018)

, encoding an acetyltransferase, is among the most frequently mutated genes in small cell lung cancer (SCLC), a deadly neuroendocrine tumor type. We report acceleration of SCLC upon
PS2 CheckMate 227: Nivolumab + Ipilimumab vs Chemotherapy as 1L Treatment for Advanced NSCLC With High Tumor Mutational Burden
Authors: C. Mathias, M. Reck, M. Hellmann, S. Ramalingam, J. Brahmer, K. O'Byrne, P. Bhagavatheeswaran, F. Nathan, H. Borghaei, L. Paz-Ares
Journal: Journal of Thoracic Oncology (2018)
The NantOmics Pharmacogenomics Test: An integrative panomic approach to pharmacogenomics screening.
Authors: Camille Schwartz, John Little, Charles Joseph Vaske, Stephen Charles Benz, Patrick Soon-Shiong, Shahrooz Rabizadeh, J Zachary Sanborn
Journal: Journal of Clinical Oncology (2018)

2575 Background: Numerous oncology drugs have pharmacogenomics warnings on their FDA labels, yet pharmacogenomics screening is not routinely applied in clinical practice. Pharmacogenomics testing is used to reduce the chance of drug-induced toxicities, improve patient outcomes, and reduce treatment costs by tailoring therapies to the patient’s genotype. Here we present the NantOmics Pharmacogenomics test, which screens for pharmacogenomics variants related to 19 gene-drug pairs with CPIC guidelines and FDA label indications. Methods: Pharmacogenomics screening was performed on whole genome and whole exome sequencing data of FFPE tumors and matched normals from 1,879 oncology patients. Patients were screened using a panel of 31 germline markers in 11 genes linked to toxicities from 14 cancer therapies. The test has been validated on 10 cell lines from the CDC GeT-RM, on a set of synthetic data, as well as on a cohort of patients previously genotyped by an independent CLIA-validated PCR-based panel. Results: Of the 1879 patients screened, 96.4% contained a variant with a pharmacogenomics recommendation. Furthermore, 6.8% of patients had genomic variants associated with severe or life-threatening drug toxicities. For all alleles in our clinical panel, we observed similar allele frequencies to those reported in the ExAC database. In all validation studies, we were able to demonstrate that the test detects each variant in our panel, and correctly determines patient genotype in all studied cases. Conclusions: The NantOmics pharmacogenomics test is able to accurately detect pharmacogenomic variants in oncology patients. Observed allele frequencies correspond well to known population frequencies, and validation studies demonstrated that the test detects each variant in our panel, and correctly determines patient genotype in all studied cases. Given the high percentage of patients with potentially treatment-altering genomic variants, these results underscore the need for more routine pharmacogenomics screening in the oncological setting.
Phase 1 study of olaratumab as monotherapy and in combination with doxorubicin, vincristine/irinotecan, or high-dose ifosfamide in pediatric patients with relapsed or refractory solid tumors: Part A results.
Authors: Steven G. DuBois, Brenda Weigel, Theodore Willis Laetsch, Margaret Macy, Donna Elise Levy, Gary Mo, Jennifer A. Wright, Leo Mascarenhas
Journal: Journal of Clinical Oncology (2018)

10541 Background: Olaratumab (O), a PDGFRα antagonist, is a targeted human IgG1 monoclonal antibody that specifically binds PDGFRα, blocking PDGF-AA, -BB, and -CC binding and receptor activation, and has improved survival outcomes in adults with advanced sarcoma. Methods: This ongoing Phase 1, multicenter, dose-escalation study (NCT02677116) enrolled patients (pts) aged < 18 years, with a diagnosis of relapsed or refractory solid tumors, to 2 dose levels (Parts A and B) of O combined with fixed doses of standard chemotherapy with doxorubicin (D), vincristine/irinotecan (VI), or high-dose ifosfamide (I). Pts in Part A received 1 cycle (21 days) of O monotherapy at 15mg/kg IV on Days 1 and 8 followed by O + (D, VI, or I) for subsequent 21-day cycles. Each combination arm was complete when 6 pts received 2 full cycles. The primary objective of Part A was to determine the safety and tolerability of O 15mg/kg + (D, VI, or I) based on any dose-limiting toxicity (DLT) and O serum exposure matching between adult and pediatric pts. Results: Pts enrolled by O + chemotherapy regimen (n) were D (11), VI (10), and I (9). One pt (3.3%) experienced a DLT during the DLT period (Cycles 1 and 2), which consisted of grade (G) 4 elevated ALT while on O monotherapy. No ≥G3 infusion- or cardiac-related treatment emergent adverse events (AEs) occurred. Treatment-related AEs (TRAEs) ≥G3 reported in ≥2 pts are presented (Table). Serum concentrations of O in pediatric pts were within expected ranges based on adult exposure. Conclusions: Based on Part A results,O 15mg/kg as monotherapy or in combination with D, VI, or I is tolerable in pediatric pts with relapsed or refractory solid tumors. Part B of this trial is currently enrolling. Clinical trial information: NCT02677116.TRAE, n (%) O + D O + VI O + I G3 G4 G3 G4 G3 G4 ALT increased 0 0 1 (10.0) 0 0 1 (11.1) Anemia 1 (9.1) 0 1 (10.0) 1 (10.0) 3 (33.3) 0 Leukopenia 0 2 (18.2) 0 1 (10.0) 0 3 (33.3) Lymphopenia 0 1 (9.1) 1 (10.0) 0 1 (11.1) 4 (44.4) Neutropenia 0 3 (27.3) 2 (20.0) 1 (10.0) 1 (11.1) 1 (11.1) Thrombocytopenia 0 1 (9.1) 0 1 (10.0) 3 (33.3) 1 (11.1) Vomiting 0 0 1 (10.0) 0 1 (11.1) 0
Patient survival on the dose escalation phase of the Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) against WHO grade IV malignant glioma (MG) clinical trial compared to historical controls.
Authors: Annick Desjardins, John H. Sampson, Katherine B. Peters, Gordana Vlahovic, Dina Randazzo, Stevie Threatt, James Emmett Herndon, Susan Boulton, Denise Lally-Goss, Frances McSherry, Eric S Lipp, Allan H. Friedman, Henry S. Friedman, Darell D. Bigner, Matthias Gromeier
Journal: Journal of Clinical Oncology (2016)

2061 Background: The live attenuated oral (SABIN) serotype 1 poliovirus vaccine was modified to contain a heterologous internal ribosomal entry site stemming from human rhinovirus type 2, creating PVSRIPO. PVSRIPO recognizes CD155, an oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy. We report the survival results of the dose-finding portion evaluating PVSRIPO delivered intratumorally by convection-enhanced delivery (CED) compared to a historical control group of patients (pts) treated at Duke. Methods: Eligible pts on trial were adults with recurrent supratentorial WHO grade IV MG; solitary tumor 1-5cm in diameter; ≥ 4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; KPS ≥ 70%; and positive anti-polio titer. A historical group of adult recurrent WHO grade IV mg pts treated at Duke between 1/01/07-12/15/14 was retrospectively identified based on presence of a solitary tumor 1-5cm in diameter, KPS ≥ 70%, and absence of clinical decline which would have prevented enrollment on the PVSRIPO trial. Results: Fifteen pts were treated in the dose escalation phase, dose levels 1-5 (1 each at dose levels 1 and 3, 7 at level 2, 2 at level 4, and 4 at level 5), while 124 pts were identified as historical controls. Patient characteristics were similar for age, gender, KPS, prior number of progressions, steroid dosage at enrollment, and prior bevacizumab failure; however, 80% of PVSRIPO pts versus 58.9% of control pts had a gross total resection at diagnosis. As of 1/15/16, a median OS of 12.6 months was observed for the PVSRIPO group versus 10.5 months for the historical controls, with 23.3% of PVSRIPO pts alive at 24 months versus 13.7% of historical controls. Conclusions: Infusion of PVSRIPO via CED seems to have a survival advantage when compared to historical control pts treated at the same institution, with a higher proportion of patients alive at 24 months. Reported pts were not treated at what was identified as the optimal dose of PVSRIPO (dose level -1). It is predicted that the pts treated at the optimal dose will have a greater increase in survival. Clinical trial information: NCT01491893.
More hospital doctors are opting to retire early
Authors: Tom Moberly
Journal: BMJ (2018)

Hospital doctors in England and Wales are increasingly choosing to take early retirement, show figures released to The BMJ by the NHS Business Services Authority.

The number of hospital doctors claiming their NHS pension on grounds of voluntary early retirement rose from 164 in 2008 to 397 in 2018 (fig 1). The number retiring on ill health grounds rose from …
Multidrug-Resistant <i>Campylobacter jejuni</i> Outbreak Linked to Puppy Exposure — United States, 2016–2018
Authors: Martha P. Montgomery, Scott Robertson, Lia Koski, Ellen Salehi, Lauren M. Stevenson, Rachel Silver, Preethi Sundararaman, Amber Singh, Lavin A. Joseph, Mary Beth Weisner, Eric Brandt, Melanie Prarat, Rick Bokanyi, Jessica C. Chen, Jason P. Folster, Christy T. Bennett, Louise K. Francois Watkins, Rachael D. Aubert, Alvina Chu, Jennifer Jackson, Jason Blanton, Amber Ginn, Kirtana Ramadugu, Danielle Stanek, Jamie DeMent, Jing Cui, Yan Zhang, Colin Basler, Cindy R. Friedman, Aimee L. Geissler, Samuel J. Crowe, Natasha Dowell, Staci Dixon, Laura Whitlock, Ian Williams, Michael A. Jhung, Megin C. Nichols, Sietske de Fijter, Mark E. Laughlin
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Campylobacter causes an estimated 1.3 million diarrheal illnesses in the United States annually (1). In August 2017, the Florida Department of Health notified CDC of six Campylobacter jejuni infections linked to company A, a national pet store chain based in Ohio. CDC examined whole-genome sequencing (WGS) data and identified six isolates from company A puppies in Florida that were highly related to an isolate from a company A customer in Ohio. This information prompted a multistate investigation by local and state health and agriculture departments and CDC to identify the outbreak source and prevent additional illness. Health officials from six states visited pet stores to collect puppy fecal samples, antibiotic records, and traceback information. Nationally, 118 persons, including 29 pet store employees, in 18 states were identified with illness onset during January 5, 2016-February 4, 2018. In total, six pet store companies were linked to the outbreak. Outbreak isolates were resistant by antibiotic susceptibility testing to all antibiotics commonly used to treat Campylobacter infections, including macrolides and quinolones. Store record reviews revealed that among 149 investigated puppies, 142 (95%) received one or more courses of antibiotics, raising concern that antibiotic use might have led to development of resistance. Public health authorities issued infection prevention recommendations to affected pet stores and recommendations for testing puppies to veterinarians. This outbreak demonstrates that puppies can be a source of multidrug-resistant Campylobacter infections in humans, warranting a closer look at antimicrobial use in the commercial dog industry.
Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin lymphoma (HL): Impact of cycle 2 PET result on modified progression-free survival (mPFS).
Authors: Robert W. Chen, Stephen M. Ansell, Andrea Gallamini, Joseph M. Connors, Kerry J. Savage, Graham P. Collins, Andrew Grigg, Anna M. Sureda, Nilanjan Ghosh, Tatyana Feldman, Alexander Fosså, Evren Ozdemir, Fritz Offner, Gerald Engley, Keenan Fenton, Shih-Yuan Lee, Hina Jolin, Ashish Gautam, Martin Hutchings
Journal: Journal of Clinical Oncology (2018)

7539 Background: The ECHELON-1 trial demonstrated improved outcomes for patients (pts) with advanced HL who received frontline A+AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) vs ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), with 2-year mPFS rates of 82% and 77%, respectively. Here we report a post-hoc analysis of mPFS outcomes and clinical characteristics by Cycle 2 PET (PET2) status per independent review facility (IRF). Methods: Pts were randomized 1:1 to A+AVD or ABVD on Days 1 and 15 for up to six 28-day cycles. PET scans were conducted at the end of Cycle 2 and end of treatment. PET2 results guided an optional switch to alternative therapy at the treating physician’s discretion for pts with a Deauville score of 5. A switch to alternate therapy was not considered an event. The primary endpoint, mPFS, was defined as time to progression, death, or absence of a complete response with subsequent anticancer therapy, per IRF. Results: PET2 negativity rates (Deauville ≤3) were 89% (588/664 pts) in the A+AVD arm and 86% (577/670) with ABVD. Baseline characteristics were well-balanced across arms, with no significant differences in PET2– vs PET2+ pts in either arm. PET2 positivity rates (Deauville ≥4) were 7% (47/644) in the A+AVD arm and 9% (58/670) with ABVD; 5 total pts with a Deauville score of 5 switched to alternative frontline therapy. Subgroup analyses showed a favorable treatment effect for both subgroups in favor of A+AVD (Table 1), with 2-year mPFS (PET2– vs PET2+) of 85.2 vs 57.5% in the A+AVD arm, and 80.9 vs 42.0% in the ABVD arm. Outcomes for PET2+ pts were relatively poor in both arms, as previously reported. Conclusions: Overall, ECHELON-1 demonstrated a treatment effect in favor of A+AVD over ABVD. This post-hoc analysis showed a similar treatment effect on mPFS consistently in favor of A+AVD regardless of PET2 status. Clinical trial information: NCT01712490.Summary of mPFS by PET2 Status. 2-year mPFS (per IRF), % HR P-value A+AVD ABVD Overall 82.1 77.2 0.77 0.035 95% CI 78.8–85.0 73.7–80.4 0.603–0.983 N 664 670 PET2– 85.2 80.9 0.774 0.070 95% CI 81.9–88.0 77.3–84.0 0.586–1.022 N 588 577 PET2+ 57.5 42.0 0.609 0.089 95% CI 41.0–70.9 28.6–54.8 0.341–1.088 N 47 58
Abstract 19132: Home Monitoring is Associated With Fewer Gastrointestinal Bleeding Events Following Left Ventricular Assist Device Implantation
Authors: Jana Svetlichnaya, MItchell A Psotka, Michele Kassemos, Krystal Kobasic, Kelly McClure, Sonia Sharma, Yuri Nam, Van N Selby, Munir Janmohamed, Teresa De Marco, Georg M Wieselthaler, Liviu Klein
Journal: Circulation (2016)

Introduction: Patients (pts) treated with a continuous flow left ventricular assist device (LVAD) are at increased risk for both bleeding and thromboembolic events. Maintenance of oral anticoagulat...
Markers of response to PD-1 inhibition.
Authors: Thijo Jeroen Nicolaas Hiltermann, Lucie Hijmering-Kappelle, Harry J.M. Groen
Journal: Journal of Clinical Oncology (2017)

e14505 Background: Nivolumab (Nivo) has a durable tumour response in 20 % of patients. While a PD-L1 IHC complementary diagnostic has been approved, there is a need to identify a predictive biomarker with greater diagnostic accuracy. Serum biomarkers predicted by the cancer immunogram (Blake Science 2016) and response to Nivo defined by a clinical benefit ≥6 month (DR) and response by CR, PR or SD according to RECIST v1.1 are shown. Methods: Advanced NSCLC pts progressing after 1L platinum-based chemotherapy were treated with Nivo. Baseline blood markers drawn: CRP, absolute lymphocyte count, plasma glucose and LDH. Kaplan-Meier used to estimate survival data. Cox regression was used to predict associations with possible (bio-) markers and survival (age, gender, ECOG PS, histology, presence of brain metastasis, CRP, LDH, glucose, lymphocyte count). Results: Patient characteristics see table. 20% showed a DR with CR (n = 3), PR (n = 31 of 33) and SD (n = 9 of 20). Only ECOG PS was associated with OS and PFS. Soluble biomarkers were not. When tumour response (RECIST or DR) was added to the regression model ECOG PS was no longer significant but responses were. HR for PFS for DR was 0.07 (0.03-0.14) and HR according to the classical RECIST1.1 was 0.22 (0.16-0.32). HR for OS for DR 0.09 (0.03-0.21) and for classical RECIST1.1 0.26 (0.17-0.40). Conclusions: Serum blood markers at baseline were not associated with survival. Response to treatment as DR seems a stronger predictor for survival than RECIST. 45% of pts with SD had a DR. [Table: see text]