tbuckley/cabot-search huggingface dataset:
The association of serum ghrelin, GIP, insulin, and leptin levels with sleep quality and cancer-related fatigue in cancer survivors.
Authors: Po-Ju Lin, Eva Culakova, Charles E. Heckler, Michelle Christine Janelsins, Luke Joseph Peppone, Julia Ellen Inglis, Ian Kleckner, Judith O. Hopkins, Amarinthia Curtis, Benjamin Esparaz, Karen Michelle Mustian
Journal: Journal of Clinical Oncology (2018)

10122 Background: Sleep disruption leads to metabolic alterations such as increased appetite and reduced insulin sensitivity. Sleep disruption often co-occurs and is likely associated with cancer-related fatigue (CRF) in cancer survivors. Whether metabolic alterations are also associated with CRF is unknown. This preliminary data analysis assessed the association of serum metabolic markers, ghrelin, gastric inhibitory polypeptide (GIP), insulin, and leptin, with sleep quality and CRF in cancer survivors. Methods: Serum samples collected from 36 cancer survivors in an ongoing multi-center RCT examining the efficacy of yoga, health education, and cognitive behavioral therapy in reducing insomnia were analyzed at baseline and post 4-week intervention. They were selected based on changes in CRF, evaluated by Multidimensional Fatigue Symptom Inventory (MFSI), with 12 survivors in each of improved, no-change, and worse fatigue groups. Sleep quality was measured by Pittsburgh Sleep Quality Index (PSQI). Serum ghrelin, GIP, insulin, and leptin were assessed by a Luminex Multiplex Immunoassay. Spearman’s rank correlation was used to examine the association of metabolic markers with sleep and CRF. Results: Changes in PSQI were significantly correlated with changes in MFSI (r = 0.44, p < 0.01), indicating that higher sleep quality is associated with less CRF. Baseline (r = 0.35, p = 0.04) and changes in serum ghrelin (r = -0.32, p = 0.06) were correlated with changes in MFSI, suggesting that increased serum ghrelin level is associated with improvements in CRF. Baseline serum GIP (r = 0.36, p = 0.03) and leptin (r = 0.34, p = 0.04) were significantly correlated with MFSI at post-intervention, suggesting that lower baseline serum GIP and leptin levels are associated with improvements in CRF. A trend toward significant correlation was found between baseline serum insulin and changes in MFSI (r = 0.30, p = 0.08) and between changes in serum leptin and changes in PSQI (r = -0.30, p = 0.08). Conclusions: These exploratory findings suggest potential associations of metabolic markers with CRF in cancer survivors. More studies are needed to further establish the association of energy metabolism and CRF. Clinical trial information: NCT02613364.
A bi-shRNA<sup>furin</sup> and GMCSF engineered autologous tumor cell immunotherapy vs. gemcitabine + docetaxel for Ewing sarcoma and with cryoablation in Ewing family tumors.
Authors: Peter Meade Anderson, Maurizio Ghisoli, Minal A. Barve, Jonathan Benjamin Gill, Leonard H. Wexler, Guillermo DeAngulo, Kathleen Neville, Luisa Manning, Gladice Wallraven, Neil N. Senzer, Martin Birkhofer, John J. Nemunaitis
Journal: Journal of Clinical Oncology (2017)

TPS11079 Background: Vigil, an immuno-stimulatory autologous cellular therapy, uses patient tumor cells transfected with a plasmid encoding genes for GM-CSF and furin (to down regulate TGFβ 1&amp;2). A Phase I study in relapsed Ewing’s sarcoma. (N = 16) had one 9 month partial response and a two-year survival rate of 44% [1]. Rapid, durable systemic immune activation was seen in the majority of patients using an IFNƔ ELISPOT assay [2]. We seek to extend these early findings in a randomized Phase 2 study (NCT02511132). Methods: Following surgery (for Vigil manufacture), patients are randomized 1:1 to Vigil (1 x 10 7 cells/ml by monthly intradermal injection), or to chemotherapy with gemcitabine 675mg/m2 IV D1 and D8 and docetaxel 75 mg/m2 IV D8 every 21 days. Key eligibility criteria include: Age &gt; 2, histologically documented metastatic Ewing's, refractory or intolerant to ≥2 prior lines of chemotherapy, and availability of at least 4 doses of manufactured Vigil. Patients with bone only disease are ineligible. The primary objective is to compare the overall survival of patients treated with Vigil vs. chemotherapy. The sample size of 62 patients assumes a one-year survival rate of 25% in the chemotherapy group vs. 60% in the Vigil group, corresponding to a hazard ratio of 0.383 favoring Vigil. Results: As of January 2017, thirteen patients have been randomized at 10 centers in the U.S. The design allows for reduction in disease burden prior to surgery using modalities like SBRT and interventional radiology. Toxicity of Vigil has been low compared to chemotherapy. Time to disease progression is being assessed in patients who crossover to Vigil after progressing on chemotherapy. Systemic control of metastatic lesions using cryoablation is also being assessed in other patients (e.g. DSRCT liver metastases) using a separate IND. Conclusions: Although associated with systemic immune activation, additional means to reduce disease burden such as SBRT and cryoablation can possibly improve patient health and augment Vigil efficacy. References: 1.Ghisoli M, Barve M, et al. Mol Ther. 2016 Apr 25 2. Oh J, Barve M, et al. Gynecologic Oncology 2016; 143: 504–510. Clinical trial information: NCT02511132.
The feasibility of using small biopsy samples from lung cancer for targeted next-generation sequencing.
Authors: Hee Kyung Kim, Bo Mi Ku, Hansang Lee, Mi Hwa Heo, Joo Hyun Hong, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2017)

e20584 Background: As the genomic based personalized medicine has been advanced, biomarker analysis using targeted next-generation sequencing (NGS) becomes crucial diagnostic approach for treatment of lung cancer. Most patients of lung cancer are diagnosed on small biopsy specimen, but the feasibility of the small tissue samples for targeted NGS has not been evaluated. We aimed to investigate the feasibility of using small tissue samples of lung cancer for targeted NGS. Methods: The medical records of the patients who underwent biopsy and targeted NGS were reviewed. Two types of panel for targeted NGS were used which were AmpliSeq Cancer Hotspot panel v2 and Oncomine Focus Assay. Results: A total of 603 biopsy specimens of lung cancer were analyzed from April 2014 to October 2016. The sites of biopsy were lung or bronchus (51.2%), lymph node (26.2%), Pleura (2.3%), liver (2.5%), Brain (1.7%) and the others (adrenal gland, bone, muscle, spleen, stomach, thymus). Percutaneous transthoracic core needle biopsy (PTCNB) was most frequently used method for acquisition of tissue (24.9%). The other methods of biopsy were bronchoscopy (14.4%), endobronchial ultrasound (EBUS, 23.8%), Video-assisted transthoracic surgery (VATS, 9.9%) and so on. The types of tissue samples were formalin-fixed, paraffin-embedded (FFPE, 80.6%) and fresh tissue (19.4%). All of these samples, 398 cases (66.0%) were successfully analyzed using targeted, NGS. In 34% of analysis failure cases, 23.5% were not adequate for DNA or RNA extraction and 10.5% had amount not to be enough. On multivariate analysis, PTCNB was more likely to fail than other methods of biopsy such as bronchoscopy, EBUS (HR 2.31, 95% CI 1.4-3.8, p = 0.001). Conclusions: The biopsy of lung cancer for targeted NGS was taken from a variety of sites via different methods, and the type of tissue samples was mostly FFPE. Considering the yield of our study, small biopsy specimens could be used to investigate genomic characteristics of lung cancer via targeted NGS.
Multicenter phase II trial of pembrolizumab (pembro) in previously-treated metastatic esophageal cancer.
Authors: Peter C. Enzinger, Nadine Jackson McCleary, Nora Horick, James M. Cleary, Douglas Adam Rubinson, Bridget Fitzpatrick, Christopher Graham, Jeffrey W. Clark, Anuj K. Patel, Eirini Pectasides, Kimberly Perez, Matthew B. Yurgelun, Christopher G. Azzoli, Andrea Catherine Enzinger, Justin F. Gainor, Benjamin L. Schlechter, Jeffrey A. Meyerhardt, Kimmie Ng, Adam Joel Bass, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2018)

e16072 Background: There are limited treatment (tx) options for metastatic esophageal cancer patients (pts). We sought to determine the safety and efficacy of pembro among US pts with previously treated metastatic esophageal cancer. Methods: Eligible pts had metastatic esophageal cancer, or Sievert type 1 GEJ adenocarcinoma (ADC), ECOG of 0 or 1, and had progressed on at least 1 line of therapy. Squamous cell carcinoma (SCC) pts were enrolled on a compassionate use basis. Fresh baseline biopsy for PD-L1 and correlatives was required; patients could enroll regardless of PD-L1 status. Pembro was given at 200mg q3 weeks. Pts were restaged q9 weeks with RECIST v1.1 by independent review. Primary endpoint was overall response rate (ORR = CR+PR) among ADC pts. Results: Of 45 pts enrolled, 39 had ADC and 6 had SCC, 36 were men, median age was 62 (range 34-78), 14 pts had received 1 prior line of therapy, 17 had received 2, 10 had received 3, and 4 had received 4. 13 pts were PD-L1 positive, 25 were negative, 6 unevaluable, 1 pending. Among 44pts (1 too early), 4 PR's (9.1%) were observed, 3 with ADC and one with SCC. Duration of response was 10.6+ mo, 6.2 mo, 5.8 mo, and 2.3 mo, with PD-L1 H-scores of 220, 10, 6, and 0, respectively. 9 pts (20%) had stable disease. 11 pts discontinued pembro prior to restaging but are included in this analysis. Only 3 pts (7%) had grade 3-4 toxicity attributed to pembro: one grade 3 pneumonitis, one grade 4 myasthenia gravis, and one grade 3 joint pain. There were no treatment related deaths. We are currently evaluating immunologic correlates of response, profiling pre-treatment biopsies and on-treatment biopsies using flow cytometry and gene expression analysis. Conclusions: Pembro is active in US pts with previously treated metastatic esophageal cancer. The safety profile is similar to other studies with this agent. Supported by Merck & Co, Inc. Clinical trial information: NCT02971956.ORR N = Percent 95% CI All 44 9.1 2.5-21.7 ADC 38 7.9 1.7-21.4 SCC 6 16.7 0.4-64.1 PFS N = Months 95% CI All 45 1.97 1.84-2.73 ADC 39 1.97 1.84-2.14 SCC 6 2.99 1.71- OS N = Months 95% CI All 45 5.03 3.02- ADC 39 4.67 2.73- SCC 6 Too early
A randomized phase II/III study comparing stereotactic body radiotherapy (SBRT) versus conventional palliative radiotherapy (CRT) for patients with spinal metastases (NCT02512965).
Authors: Arjun Sahgal, Sten Myrehaug, Kristopher Dennis, Mitchell Liu, Edward Chow, Rebecca Wong, James B. Butler, Jeffrey Noah Greenspoon, Michael G Fehlings, Pejman Maralani, Laura Masucci, Young Lee, Michael Donald Brundage, Stanley K. Liu, Keyue Ding, Maaike Hum, Wendy R. Parulekar
Journal: Journal of Clinical Oncology (2017)

TPS10129 Background: Innovative radiotherapy technology and modern imaging capabilities enable the use of Stereotactic Body Radiotherapy (SBRT) to treat patients with spinal metastases to optimize tumour control and palliation compared to standard conventional radiotherapy. No randomized clinical trial evidence exists directly comparing the two treatment strategies. Methods: SC.24 is a Canadian Cancer Trials Group randomized phase II/III study comparing standard conventional radiotherapy (20 Gy/5fr) to SBRT (24 Gy/2fr) in patients with solid tumours and MRI documented, painful spinal metastases suitable for RT. The primary accrual objective for the phase II portion of the study was met in January 2017 and the study continues as a randomized phase III study with a primary outcome measure of complete pain response at 3 months post radiotherapy. Secondary objectives include: measurement of complete pain response at 6 months; radiation site progression free survival at 3 and 6 months; adverse event profile, health related QOL and compliance with RT QA measures. Biobanking for future correlative studies is included in study design. Statistical design: The statistical assumptions for the phase III study include estimated complete pain response rates of 10% and 30% for the CRT and SBRT treatment arms respectively. Using a two sided alpha = 0.05 and power = 80% the sample size for the phase III study is 152, taking into account a 5% drop out rate. Conduct to Date: Study activation: July 2015. Accrual to date: 58. Supported by CCSRI grant 021039 Clinical trial information: NCT02512965.
TCT-642 The Comparative Effectiveness and Safety of Cangrelor vs. In- lab Glycoprotein IIb/IIIa Inhibitor (GPI) in Patients Undergoing Percutaneous Coronary Intervention: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2)
Authors: Saifullah Siddiqui, Milan Seth, Devraj Sukul, Ryan Madder, Maged Rizk, Eric Walchak, Cyril Ruwende, Frank Saltiel, Mark Zainea, Hameem Changezi, Hitinder Gurm
Journal: Journal of the American College of Cardiology (2018)
Retrospective study of complete remission imatinib-free metastatic gastro-intestinal stromal tumors (GIST).
Authors: Elise Nassif, Louise De Forceville, Arthur Geraud, Justine Gantzer, Charles Honoré, Sarah Naomie Dumont, Olivier Mir, Thierry De Baere, Jean-Yves Blay, Axel Le Cesne
Journal: Journal of Clinical Oncology (2018)

e23512 Background: Imatinib (IM) treatment should be continued indefinitely in advanced GIST since treatment interruption is generally followed by rapid tumor progression in almost all cases, even when lesions have been previously surgically excised. Methods: All patients with advanced GIST treated in two institutions where IM was definitively interrupted were retrospectively reviewed. Results: Nine patients met eligibility criteria. All patients treated with IM (400 mg daily dose) underwent loco-regional approaches on residual tumor masses with surgery, radiofrequency ablation (RFA) or a combination of these two modalities. Seven patients had oligo-metastatic liver and/or peritoneal diseases and two patients had more diffuse peritoneal sarcomatosis. The mean duration of IM before local treatment was 34.5 months (range 0 to 106). Three patients were treated with RFA, 3 with surgery and 3 with a combination of both. Combined modality treatment was for all 3 patients a two-step procedure with initial surgery, followed by RFA of a single hepatic nodule with a mean interval of 103 months between local treatments. IM was rechallenged in all but one patient, according to this patient’s own decision. IM was definitively stopped after an IM mean duration of 35.3 months (range 0 to 112) after local treatment. After a mean follow-up of 58.3 months after definitive IM interruption, 6 patients have a persistent complete remission and 3 patients presented a new progression at 78, 17 and 14 months. Amongst patients who relapsed, two patients had initial surgery followed by RFA and one patient had RFA alone. The mean treatment-free interval for the three relapsed patients was 36.6 months and relapses occurred only in new metastatic sites. The mean treatment-free interval for the 6 patients with persistent remission is 69.2 months. All patients are alive at the time of analysis. Conclusions: IM discontinuation after destruction of metastases is not consistently associated with short-term relapse in patients with complete remission. Treatment discontinuation can be discussed in rare cases after informed discussion with the patient.
A phase Ib trial of pembrolizumab (Pembro) following adoptive cell therapy (ACT) in patients with platinum-resistant ovarian cancer; The ACTIVATE (Adoptive Cell Therapy InVigorated to Augment Tumor Eradication) trial.
Authors: Josee-Lyne Ethier, Luisa Bonilla, Sarah Boross-Harmer, Genevieve Bouchard-Fortier, Jane Cipollone, Blaise A. Clarke, Neesha C. Dhani, Alexandra Maria Easson, Norman Franke, David Paul Goldstein, Stephanie Lheureux, Habeeb Majeed, Taymaa May, Michael Reedijk, Marjan Rouzbahman, Sam Saibil, Patricia Ann Shaw, Pamela S Ohashi, Linh T. Nguyen, Marcus O. Butler
Journal: Journal of Clinical Oncology (2018)

TPS5611 Background: ACT is based on the in vitro expansion of T cells with anti-tumor activity, followed by transfer of large numbers of T cells back to the patient. T cells for ACT can be obtained from tumor-infiltrating lymphocytes (TILs), which represent a source of tumor-specific T cells. Evidence supports that epithelial ovarian carcinoma (OC) is immunogenic and has the potential to respond to immunotherapy. Pembro, a PD-1 monoclonal antibody, was shown to have activity in metastatic ovarian cancer with a response rate of 11.5% (Varga, ASCO 2015;33:5510). There is limited data regarding the efficacy of combining ACT with PD-1/PD-L1 inhibitors. However, ACT may synergize with checkpoint inhibitors to overcome immunosuppression within the tumor microenvironment, and dramatic clinical responses have been observed anecdotally. Based on these observations, a Phase 1b study of ACT followed by Pembro in advanced OC was initiated. Methods: This is a single-centre, non-randomized trial of Pembro following ACT using TILs in platinum-resistant OC. Key inclusion criteria include progression within 6 months of last platinum dose and tumor suitable for harvest. Patients undergo preparative lymphodepleting chemotherapy, followed by a single TIL infusion. Therapy with Pembro 200 mg q3 weeks is initiated once toxicities grade 2 or higher have resolved. The primary objective is safety, and the regimen will be deemed feasible if at least 80% of enrolled patients receive ACT with TILs and ≥2 doses of Pembro without unacceptable toxicity. Secondary objectives include evaluation of response rate, overall and progression free survival. The study will enroll 12 patients to determine whether the proportion of patients in whom the treatment regimen is tolerable, P, is less than or equal to 0.50 or is greater than or equal to 0.80. If the number of patients for whom treatment is feasible is 8 or more, the hypothesis that P ≤ 0.50 is rejected with a target error rate of 0.20. Enrollment is currently ongoing, with TIL preparation underway for 10 patients and plan to initiate treatment in 3 of these over the next 3 months. Clinical trial information: NCT03158935.
Association between DNA level aberrations and immune cell infiltration in breast cancer.
Authors: Anton Mikhailovich Safonov, Tingting Jiang, Giampaolo Bianchini, James Platt, Weiwei Shi, David L. Rimm, Lajos Pusztai, Christos Hatzis
Journal: Journal of Clinical Oncology (2016)

3078 Background: What causes high versus low, or absent, immune cell infiltration in breast cancer is unknown. The goals of this analysis were to examine if total mutation load, neoantigen load, copy number variations (CNV), gene-level or pathway level somatic mutations or germline polymorphisms (SNP) are associated with the level of immune infiltration measured by immune metagene expression levels. Methods:: We used RNA-Seq, DNA copy number, mutation and germline SNP data from the TCGA representing 627 ER+, 207 HER2+ and 191 TNBC cancers. 13 published immune metagenes were used in correlation and multivariate linear regression analyses performed separately for the 3 major clinical subtypes. P-values were adjusted for multiple comparisons and permutation testing was used to assess false discovery rates. Results: Overall mutation, neoantigen and amplification, or deletion loads did not correlate strongly with any of the immune metagenes in any subtype (Spearman coefficient 0.2). In ER+ cancers, mutations in MAP2K4 and TP53 were associated with lower and higher levels of immune infiltration, respectively. In TNBC, mutations in MYH9 and HERC2 were associated with lower immune infiltration. None were found in HER2+ cancers. Three SNPs (rs425757, rs410232, rs470797) in the exonic regions of the FHPR1 and MLP genes were associated with low immune infiltration in ER+ cancers, none in the other subtypes. Two amplicons in TNBC and 3 amplicons in HER2+ cancers were associated with lower immune infiltration. We also identified alterations in several biological pathways that were associated with immune infiltration in different breast cancer subtypes. At the individual patient level, each pathway was affected at different genes and through distinct genomic mechanisms. Conclusions: Immune infiltration in breast cancer is not driven by a single global metric of genomic aberrations such as mutation, neoantigen or CNV loads, or by a few recurrent aberrations but by multiple different gene and pathway level associations that each affect small subsets of patients within each subtype.
Survival outcomes in sarcomatoid renal cell carcinoma.
Authors: Taha Al-Juhaishi, Laura Alder, Asit K. Paul
Journal: Journal of Clinical Oncology (2018)

e16559 Background: Sarcomatoid Renal Cell Carcinoma (sRCC) is a rare disease found in approximately 5% of all RCCs. It is considered to be an aggressive variant with average survival of less than 12 months. In this study, we sought to determine the epidemiologic factors and therapeutic interventions affecting survival in this rare disease using a large national database. Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to identify all adult patients (≥18 years) diagnosed with sRCC between 2004 and 2013. Multiple variables were explored including age, gender, race, marital status, year of diagnosis, tumor stage and laterality, and different treatment interventions (surgery, chemotherapy, radiotherapy). Overall survival was estimated using the Kaplan-Meier method, and compared using the Log-Rank test. Cox proportional hazards models were used for adjusted survival analyses. Results: A total of 1600 patients were included in the analysis. Median age was 62.9 [51-75] years, and the majority were male (67.6%) and Caucasian (68.8%). The majority of patients (N = 1163; 72.7%) underwent nephrectomy, followed by systemic therapy (N = 505; 31.6%) and radiation therapy (N = 268; 16.8%). At a median follow-up of 62 [56.3-67.7] months, 1230 (77%) patients had died. Median overall survival was 8 [7.2 – 8.8] months. Factors associated with increased mortality included: Age above 65 years (HR 1.28 [1.13-1.44], P < 0.001), locally invasive tumor (T4) (HR 2.90 [1.15-7.29], P = 0.024), lymph node involvement (HR 1.62 [1.38 – 1.89], P < 0.001 for N1 disease; and HR 1.47 [1.22 – 1.77], P < 0.001 for N2 disease), and distant metastases (HR 2.44 [2.10 – 2.83], P < 0.001). On multivariate analysis; nephrectomy was found to be associated with significant survival benefit (HR 0.37 [0.30-0.44], P < 0.001) followed by systemic therapy (HR 0.63 [0.55-0.72], P < 0.001). Conclusions: sRCC is a rare disease with overall very poor prognosis. Old age and higher tumor stage are predictors of mortality on univariate analysis. Nephrectomy significantly decreased overall mortality.
Doctor who charged for locum work while employed to do research job is suspended for 12 months
Authors: Clare Dyer
Journal: BMJ (2018)

A junior doctor who received an eight month suspended prison sentence after being convicted of fraud for double billing his NHS employer has been suspended for 12 months by a medical practitioners tribunal.

Chun Ooi, 31, who represented himself, managed to persuade the Manchester tribunal to reject the General Medical Council’s (GMC) recommendation to strike him off the UK medical register.

Ooi, a Malaysian citizen who qualified at Dundee University, told the tribunal that his goal had been to learn as much medicine as possible in Britain before returning to practice in Malaysia. In February 2016 he took a job as a clinical research fellow in the internal medicine and dermatology departments at Cardiff and Vale University Health Board. The job was supposed to involve both research in dermatology and clinical work in …