tbuckley/cabot-search huggingface dataset:
A phase II study of panobinostat with lenalidomide and weekly dexamethasone in myeloma.
Authors: Ajai Chari, Hearn J. Cho, Samir S. Parekh, Amishi Dhadwal, Katarzyna Garcia, Gillian Morgan, Natalie Belostotsky, Crystle Carter, Donna Catamero, Juliet Escalon, Daniel Verina, Moon-Hee Yum, Lisa La, Elaine Chan, Jude Gullie, Sundar Jagannath
Journal: Journal of Clinical Oncology (2015)

8528 Background: Preclinical data support deacetylation of oncogenic proteins/histones with the pan histone deacetylase inhibitor (HDACi) panobinostat (pan), which renders MM cells more susceptible to other anti-MM agents. Clinically, pan added to btz & dex in the PANORMA 1 phase III study resulted in both improved CR & PFS by 3.9 months. However, grade 3/4 diarrhea also increased from 8 to 25%. Though the MTD of pan-len-dex was attained in a phase 1b study of Rel Ref MM (Mateos et al, ASCO ‘10), 4 day pulses of dex *3 per cycle was toxic. We modified that regimen; pan 20 mg D1, 3, 5, 15, 17, 19 + len 25 mg qd D1-21 + dex 40 mg D1, 8, 15 in 28 day cycle. Methods: Pts with RRMM with PD, measurable disease, & adequate PS/heme/organ function were eligible. Use of QTc prolonging agents & prior HDACIs were prohibited. Evaluation of the ORR was the primary objective & safety, DOR, OS, & PFS were secondary objectives. Results: 20 evaluable pts median 64 yo (45% > 65 yo) with 3 median lines of Rx over 4 years were enrolled. 13 (65%) were high molecular risk, 16(75%) were len- refr, & 35, 45, 30% were refr to each: pom, btz, & cfz. Responses include 1 CR, 3 VGPRs, 5 PRs, 8 MRs, & 2 SD, for an ORR of 45%, CBR of 85 % and a median PFS of 7.5 mos. In the 16 len-refr pts, there were 3 VGPRs, 3 PRs, 7 MRs, with a median PFS of 6.5 mos. Grade 3/4 toxicities (regardless of drug attribution) were primarily heme, with neutropenia (55%), thrombocytopenia (40%) and anemia (5%) respectively. Grade 3/4 nonheme AEs included infections in 4 (1 while neutropenic), 3 diarrhea (transient) & 2 PEs and 1 pt each with: neck pain, QTc prolongation, fatigue, & weight loss. Pts requiring dose reductions of len/pan respectively were 4/2 for ANC, 2/1 for plts, & 1 len for fatigue, & 1 pan for asymptomatic T wave inversions. No doses were held or reduced for GI toxicities. Conclusions: In RRMM, the completely oral pan len dex demonstrates durable responses, even in high risk len-refr pts, indicating the essential role of pan in attaining responses. In notable contrast to PANORMA 1 there were no significant GI toxicities & primarily expected heme toxicities. Updated results of planned 27 pts, including correlatives, will be presented at the annual meeting. Clinical trial information: NCT01651039.
Re: Liselotte M.S. Boevé, Maarten C.C.M. Hulshof, André N. Vis, et al. Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomized Clinical Trial: Data from the HORRAD Trial. Eur Urol 2019;75:410–8
Authors: Fabiana Gregucci, Alba Fiorentino
Journal: European Urology (2018)
Effect of Developmentally Adapted Cognitive Processing Therapy for Youth With Symptoms of Posttraumatic Stress Disorder After Childhood Sexual and Physical Abuse
Authors: Rita Rosner, Eline Rimane, Ulrich Frick, Jana Gutermann, Maria Hagl, Babette Renneberg, Franziska Schreiber, Anna Vogel, Regina Steil
Journal: JAMA Psychiatry (2019)

Despite the high prevalence, evidence-based treatments for abuse-related posttraumatic stress disorder (PTSD) in adolescents have rarely been studied.To examine whether developmentally adapted cognitive processing therapy (D-CPT) is more effective than a wait-list condition with treatment advice (WL/TA) among adolescents with PTSD related to childhood abuse.This rater-blinded, multicenter, randomized clinical trial (stratified by center) enrolled treatment-seeking adolescents and young adults (aged 14-21 years) with childhood abuse-related PTSD at 3 university outpatient clinics in Germany from July 2013 to June 2015, with the last follow-up interview conducted by May 2016. Of 194 patients, 88 were eligible for randomization.Participants received D-CPT or WL/TA. Cognitive processing therapy was enhanced by a motivational and alliance-building phase, by including emotion regulation and consideration of typical developmental tasks, and by higher session frequency in the trauma-focused core CPT phase. In WL/TA, participants received treatment advice with respective recommendations of clinicians and were offered D-CPT after 7 months.All outcomes were assessed before treatment (baseline), approximately 8 weeks after the start of treatment, after the end of treatment (posttreatment), and at the 3-month follow-up. The primary outcome, PTSD symptom severity, was assessed in clinical interview (Clinician-Administered PTSD Scale for Children and Adolescents for DSM-IV [CAPS-CA]). Secondary outcomes were self-reported PTSD severity, depression, borderline symptoms, behavior problems, and dissociation.The 88 participants (75 [85%] female) had a mean age of 18.1 years (95% CI, 17.6-18.6 years). In the intention-to-treat analysis, the 44 participants receiving D-CPT (39 [89%] female) demonstrated greater improvement than the 44 WL/TA participants (36 [82%] female) in terms of PTSD severity (mean CAPS-CA scores, 24.7 [95% CI, 16.6-32.7] vs 47.5 [95% CI, 37.9-57.1]; Hedges g = 0.90). This difference was maintained through the follow-up (mean CAPS-CA scores, 25.9 [95% CI, 16.2-35.6] vs 47.3 [95% CI, 37.8-56.8]; Hedges g = 0.80). Treatment success was greatest during the trauma-focused core phase. The D-CPT participants also showed greater and stable improvement in all secondary outcomes, with between-groups effect sizes ranging from 0.65 to 1.08 at the posttreatment assessment (eg, for borderline symptoms, 14.1 [95% CI, 8.0-20.2] vs 32.0 [95% CI, 23.8-40.2]; Hedges g = 0.91).Adolescents and young adults with abuse-related PTSD benefited more from D-CPT than from WL/TA. Treatment success was stable at the follow-up and generalized to borderline symptoms and other comorbidities.German Clinical Trials Register identifier: DRKS00004787.
THU-301-Weight loss significantly reduces the risk of chronic kidney disease development in patients with non-alcoholic fatty liver disease
Authors: Young Eun Chon, Seong Gyu Hwang, Mi Na Kim, Hana Park, Joo Ho Lee, Yeonjung Ha, Shin-Wook Kang, Hyung-Jong Kim, Yu Bum Choi, Mi Jung Lee
Journal: Journal of Hepatology (2019)
THU-493-Reciprocal changes in ARID1A and EZH2 are associated with cholangiocarcinoma development in a mouse model of caroli disease with high Yap expression
Authors: Eleanna Kaffe, Carlo Spirli, Romina Fiorotto, Valeria Mariotti, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco
Journal: Journal of Hepatology (2019)
How patients prefer to learn that they have cancer: Results of a survey on patients’ preference for communication in prostate cancer using the MPP-d (German version of the <i>Measure of Patients’ Preferences</i>).
Authors: Axel S. Merseburger, Karl Scheithe, Christiane Colling
Journal: Journal of Clinical Oncology (2015)

e20591 Background: Most physicians report that discussing bad news about cancer is a difficult issue in daily practice. The aim of this survey was to assess preferences regarding the communication of bad news in patients with prostate cancer (PCa) in Germany. Methods: The MPP-D consists of 46 questions that are rated by the patient on a 5-step Likert-scale ranging from 1=‘not important at all' (low), to 5=‘absolutely important and should be done by each physician’ (high). About 1,400 questionnaires were issued to PCa patients by 68 office-based urologists. Results: In total, 709 patients were included. Mean age was 72.2 years (43–92), 50.4% of the patients were 70 to 80 years old. Timepoint of PCa diagnosis was a median 4.0 years ago (1–44). Nearly all patients (98.7%) came from Central, Western or Northern Europe. As professional background, 68.8% of patients had completed an apprenticeship, 37.9% a higher education (college, academy, university), 10.2% had another or no professional education. The highest patient preference ratings for delivery of bad news were associated with privacy (mean: 4.1 points), expertise (mean: 4.0 points) and completeness of information (mean: 4.0 points). Thus, bad news should preferably be delivered in person by a doctor who is up-to-date on research and provides all relevant information on the disease and treatment options. The lowest ratings were for emotional support (mean: 3.2 points), information about psycho-social support options (mean: 3.2 points) and involvement of family (mean: 2.8 points). Differences in subgroup analyses by age, duration of PCa and professional education were noted for a subscale of involvement of family, where this was less important for younger, highly educated patients who recently have been diagnosed than for other patients. Conclusions: Communication by physicians about diagnosis, disease and treatment has a major impact on patient acceptance of disease and quality of life. Thus, identifying patients’ needs is essential in optimizing the physician–patient relationship and communications.
Randomized translational study of 5-HT3 receptor antagonists for evaluation of chemotherapy-induced nausea and vomiting (CINV) related biomarker and prevention of CINV using questionnaires.
Authors: Yukari Tsubata, Yusuke Mori, Mika Nakao, Yoshihiro Amano, Takamasa Hotta, Naoya Koba, Megumi Hamaguchi, Tamio Okimoto, Kiyotaka Miura, Teppei Hoshino, Miki Ohe, Shunichi Hamaguchi, Akihisa Sutani, Yukikazu Awaya, Hiroyasu Takeyama, Takashige Kuraki, Masayuki Itakura, Takeshi Isobe
Journal: Journal of Clinical Oncology (2015)

e20695 Background: CINV are frequent adverse events during cancer treatments. Inadequate control of CINV impairs quality of life (QOL) and may compromise adherence to treatment. The subjective evaluation using short self-report tools has not been well studied. Besides, the association between emetic biomarkers and CINV is unknown clearly. We assessed the efficacy of palonosetron (PAL) comparing from granisetron (GRA) for acute and late phase of CINV using MASCC antiemesis tools (MAT) and The functional living index-emesis (FLIE) questionnaires following administration of highly (HEC) and moderately emetic chemotherapy (MEC). In addition, we analyzed the relation to serum levels of emetic biomarkers (5-HIAA, substance P, ghrelin) in preventing CINV. Methods: This is a randomized study in 70 patients naïve to chemotherapy. The patients were randomized 1:1 to either PAL or GRA treatment groups. The primary endpoint was score of late phase in MAT and FLIE questionnaires. The patients were evaluated by themselves the MAT and FLIE questionnaires at acute and late phases. Plasma concentration of biomarkers were measured at day 1 and 3. All data were statistically assessed using Student’s t-test or the Mann Whitney U test. This trial was registered with UMIN 000005268. Results: The patient characteristics (Median age was 68 years, about 80 and 20% were lung cancer and breast cancer, respectively.) in both groups were well balanced. The proportion of patients with a complete response and total control were similar in both groups. However there were no statistical differences in score of questionnaires, the mean values in PAL had higher compared with GRA both acute and delayed phase. The value of ghrelin on day 1 were significantly higher (p = 0.001) for GRA compared with PAL. Conclusions: According to the result of questionnaire scoring, PAL may preserve QOL by all regimens. Many patients still suffered from CINV and impaired QOL. We needs to investigate the QOL using various questionnaire. The blood concentration of the ghrelin which is an appetite increase hormone may be related to the type and dosage of 5-HT3RA. Clinical trial information: UMIN 000005268.
FRI-365-Efficacy of combined partial hepatectomy and cyst fenestration on health-related quality of life in polycystic liver disease
Authors: Lucas H.P. Bernts, Myrte Neijenhuis, Marie E. Edwards, Rory L. Smoot, David M. Nagorney, Joost Ph Drenth, Marie C. Hogan
Journal: Journal of Hepatology (2019)
FRI-004-Cirrhosis status at diagnosis, non-Caucasian descent, treatment response and age determine long term survival in autoimmune hepatitis
Authors: Maaike Biewenga, Martine Baven-Pronk, Aad van den Berg, Karin van Nieuwkerk, Gerd Bouma, Henk Van Buuren, Bart Van Hoek
Journal: Journal of Hepatology (2019)
Elderly patients treated with afatinib in clinical practice: Results from the prospective non-interventional study GIDEON
Authors: W. Brückl, E. Laack, C. Kortsik, H. Schaefer, M. Reck, A. Maerten, C. Hoffmann
Journal: Annals of Oncology (2019)

Background: Elderly patients are often underrepresented in clinical trials, leading to uncertainties in the treatment of these patients in the clinical routine. Methods: The prospective non-interventional study GIDEON allows analyzing a German real world patient collective treated with afatinib according to label. This analysis focusses on patients older than 70 years. Results: Patients older than 70 years account for 44% of the GIDEON study population (n = 67). Main EGFR mutation in this population was Del.19 (n = 43, 64%), followed by L858R und rare mutations (both n = 12, 18%). Brain metastases at baseline were detected in 22% of patients (n = 15). Afatinib dose was reduced in 55% (n = 37) of all patients older than 70 years and in 58% of patients younger than 70 years. The percentage of patients who received a starting dose of afatinib lower than 40mg was higher in the elderly population (n = 25, 37%) compared to patients younger than 70 years (18%). Main Afatinib related side effects of grade 3 or higher were independent of age, with diarrhea (18% in patients <70 years and 15% in patients ≥70 years) as the most frequent adverse drug reactions. Overall response rate was 78% and disease control rate was 93% in the elderly population. PFS rate at one year was 62%. Conclusions: With 44% of the whole study population, elderly patients (>70 years) are well represented in GIDEON. Therefore, these data provide important information for the routine clinical use of afatinib in these patients. With an overall response rate of 78% and a PFS-rate of 62% after one year, these data support the use of afatinib in elderly patients. Adverse drug reactions of grade 3 or more were not significantly higher in the elderly group. Clinical trial identification: NCT02047903. Legal entity responsible for the study: Boehringer Ingelheim. Funding: Boehringer Ingelheim. Disclosure: W. Brückl: Fees for consulting and/or lectures: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Chugai, Lilly, MSD, Pfizer, Roche, Stratifyer. M. Reck: Honoraria for lectures and consultancy: Hoffmann-La Roche, Lilly, Amgen, Boehringer Ingelheim, Abbot, AstraZeneca, Celgene, BMS, MSD, Merck, Novartis, Pfizer. A. Maerten, C. Hoffmann: Employee: Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Notable variation of molecular testing in metastatic lung cancer in the Netherlands
Authors: C. Kuijpers, M. Van den Heuvel, L. Overbeek, A. Van Lindert, R. Damhuis, S. Willems
Journal: Annals of Oncology (2019)

Background: Adequate and timely testing for molecular alterations in NSCLC is necessary to enable treatment with tyrosine kinase inhibitors (TKI) when a certain mutation or rearrangement is present. On a nationwide basis, we aimed to assess the performance of molecular testing for EGFR and/or KRAS mutation, and ALK and ROS rearrangement in a cohort of metastatic NSCLC. Methods: All stage IV non-squamous NSCLC from 2013 and 2015 were identified from the Netherlands Cancer Registry and matched to the Dutch Pathology Registry (PALGA). Using information extracted from pathology reports, proportions of tumors tested for EGFR and/or KRAS and ALK, and in 2015 also for ROS, within 3 months after diagnosis, were determined, and variation between 48 laboratories was assessed. In a best practice session with 4 laboratories with highest testing proportions, we tried to identify a process for the best possible flow and highest possible testing proportions. Results: In total, 6,619 tumors were included (2013: n = 3,195; 2015: n = 3,424). In 2013, EGFR and/or KRAS testing was performed in 73.1% (variation between laboratories 30.6% to 91.7%) and was significantly higher in 2015: 78.9% (40.0% to 91.0%). Of the EGFR/KRAS wildtype (wt) tumors, 49.5% underwent ALK testing in 2013 (6.3% to 100%) and 77.4% in 2015 (32.5% to 100%), which was significantly higher. ROS testing was performed for 50.9% (0% to 100%) of the EGFR/KRAS wt tumors from 2015. In 2015, 6, 7 and 13 laboratories tested significantly less often for EGFR/KRAS, ALK and ROS, respectively, than the national proportion. Insufficient tissue was the most stated reason for not testing. The best practice session showed that, among other, dedicated specialized personnel, good communication with short lines, and a work culture of critical openness and honesty are essential for adequate molecular testing. Conclusions: Although molecular testing proportions were significantly higher in 2015, improvement remains possible in some laboratories/hospitals, considering that some patients were possibly unjustly not eligible for TKI. Feedback on molecular testing performance was sent to individual laboratories, so they can review, and, if needed, improve their practice. Legal entity responsible for the study: University Medical Centre Utrecht. Funding: AstraZeneca, Pfizer, Roche. Disclosure: C. Kuijpers, S. Willems: Funding: AstraZeneca, Pfizer, Roche (these companies had no role in study design, analyses and reporting). All other authors have declared no conflicts of interest.
p53-targeted lincRNA-p21 acts as a tumor suppressor by inhibiting JAK2/STAT3 signaling pathways in head and neck squamous cell carcinoma
Authors: Shufang Jin, Xi Yang, Jiayi Li, Wenyi Yang, Hailong Ma, Zhiyuan Zhang
Journal: Molecular Cancer (2019)

Long intergenic noncoding RNA p21 (lincRNA-p21) is considered a target of wild-type p53, but little is known about its regulation by mutant p53 and its functions during the progression of head and neck squamous cell carcinoma (HNSCC). RNAscope was used to detect the expression and distribution of lincRNA-p21. Chromatin immunoprecipitation and electrophoretic mobility shift assays were performed to analyze the transcriptional regulation of lincRNA-p21 in HNSCC cells. The biological functions of lincRNA-p21 were investigated in vitro and in vivo. RNA immunoprecipitation and pull-down assays were used to detect the direct binding of lincRNA-p21. Lower lincRNA-p21 expression was observed in HNSCC tissues and indicated worse prognosis. Both wild and mutant type p53 transcriptionally regulated lincRNA-p21, but nuclear transcription factor Y subunit alpha (NF-YA) was essential for mutant p53 in the regulation of lincRNA-p21. Ectopic expression of lincRNA-p21 significantly inhibited cell proliferation capacity in vitro and in vivo and vice versa. Moreover, the overexpression of lincRNA-p21 induced G1 arrest and apoptosis. Knockdown NF-YA expression reversed tumor suppressor activation of lincRNA-p21 in mutant p53 cells, not wild-type p53 cells. A negative correlation was observed between lincRNA-p21 and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in HNSCC tissues. High lincRNA-p21 expression inhibited Janus kinase 2 (JAK2)/STAT3 signal activation and vice versa. Further, we observed direct binding to STAT3 by lincRNA-p21 in HNSCC cells, which suppressed STAT3-induced oncogenic potential. Our results revealed the transcriptional regulation of lincRNA-p21 by the mutant p53/NF-YA complex in HNSCC. LincRNA-p21 acted as a tumor suppressor in HNSCC progression, which was attributed to direct binding to STAT3 and blocking of JAK2/STAT3 signaling.
LBO-02-Elafibranor, a peroxisome proliferator-activted receptor alpha and delta agonist demonstrates favourable efficacy and safety in patients with primary biliary cholangitis and inadequate response to ursodeoxycholic acid treatment
Authors: PD Dr. Schattenberg Jörn, Albert Parés, Kris V. Kowdley, Michael Heneghan, Stephen Caldwell, Daniel Pratt, Alan Bonder, Prof. Gideon M. Hirschfield, MB Bchir, Cynthia LEVY, John Vierling, David Jones, Sophie Megnien, Remy Hanf, David Magrez, Pascal BIRMAN, VELIMIR LUKETIC
Journal: Journal of Hepatology (2019)
Efficacy and safety of adding the retinoid tamibarotene or placebo to paclitaxel/carboplatin for advanced non-small cell lung cancer.
Authors: Oscar Arrieta, Daniel J. Levitt, Kelly B. Pendergrass, Oleg Gladkov, Igor Bondarenko, Minish Mahendra Jain, Scott Wieland
Journal: Journal of Clinical Oncology (2015)

e19034 Background: The results of studies to evaluate adding retinoids to chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) have been mixed. The retinoid all-trans retinoid acid (ATRA) appears to improve efficacy in NSCLC patients, while bexarotene, a rexinoid, does not. Tamibarotene (T) is a potent retinoid with fewer side effects than ATRA. We evaluated the efficacy and safety of adding T or placebo (Pb) to paclitaxel (P) and carboplatin (C) in patients with stage IIIb (+ pleural effusion) or IV non-small cell lung cancer. Methods: Patients with either stage IIIb (with pleural effusion) or stage IV NSCLC (both adeno- and squamous carcinomas), no prior chemotherpy, satisfactory neutrophil, platelet and red cell numbers, ECOG < / = 2, satisfactory liver, cardiac and renal function, peripheral neuropathy < grade 2, triglycerides < 1000 mg/dL, Hb1Ac < 5.7 and no active CNS metastases were eligible. Patients were randomized to receive P (200 mg/m2) and C (AUC = 6) every 3 weeks, and either T (6 mg/m2) or matching Pb daily for up to 6 cycles. Patients with stable disease or an objective response could continue to receive either T or Pb until progression. CT scans were obtained on Days 50, 113 and every 2 months to progression or death. Scans were read by a blinded radiology review organization (RECIST 1.1). Results: 127 randomized patients were analyzed by intent-to-treat criteria (59 Pb/P/C; 68 T/P/C). Median PFS for Pb/P/C was 9.2 months (95% CI 6.8-12.7) and for T/P/C it was 5.7 months (95% CI 2.8-7.9), p = 0.088; HR 1.54 (0.85- ). At the time of analysis median OS for Pb/P/C was 13.8 months (9.7- ) and for T/P/C it was 13.7 months (8.9-15.8), p = 0.24; HR = 1.48 (0.68- ). The ORR for Pb/P/C was 27.0% and for T/P/C it was 19.1% (p = 0.28). Grades 3&4 adverse events were generally greater in the T/P/C cohort and included anemia (8.2 vs 3.2%); hypertrigyceridemia (17.8 vs 1.6%); thromboembolism (8.2 vs 1.6%); febrile neutropenia (4.2 vs 0%). Grades 3&4 neutropenia were similar in both arms (12.3 vs 12.7%). Conclusions: The potent retinoid tamibarotene does not improve the outcome in NSCLC patients receiving paclitaxel/carboplatin chemotherapy and is associated with increased toxicity. Clinical trial information: NCT01337154.
US authorities seek $3bn penalty in criminal charges against UK opioid maker
Authors: Owen Dyer
Journal: BMJ (2019)

The US justice department has brought a felony indictment against the UK drug maker Indivior, alleging that it misrepresented the safety of its sublingual Suboxone Film, an opioid replacement therapy designed to treat addiction.

Indivior developed Suboxone Film in 2007 to replace the Suboxone tablet whose patent was expiring, and it marketed the film as safer to keep around children and harder to misuse or divert—when there was no evidence to support that claim and good reason to suspect the opposite, the indictment alleges.1 Suboxone contains the opioid buprenorphine and the opioid blocker naloxone.

The indictment also alleges that Indivior sought to boost profits with a “Here to Help” scheme, “which Indivior used to connect patients to doctors Indivior knew were prescribing Suboxone …