tbuckley/cabot-search huggingface dataset:
A retrospective cohort study evaluating the safety and efficacy of TAS-102 in patients with metastatic colorectal cancer (HGCSG1503): Analysis of cases of prior regorafenib.
Authors: Atsushi Ishiguro, Satoshi Yuki, Hiroshi Nakatsumi, Takuro Saiki, Yasushi Tsuji, Kazuteru Hatanaka, Hiroki Yoshita, Shinya Minami, Tomoyuki Ohta, Kazunori Eto, Junta Nakajima, Michio Nakamura, Kazuhiro Suzuki, Masahiko Koike, Kanji Kato, Miki Tateyama, Chiaki Asada, Mari Sekiguchi, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2018)

832 Background: The J003 trial and RECOURSE trial revealed the safety and efficacy of TAS-102 for patients with metastatic colorectal cancer (mCRC). In March 2014, TAS-102 was approved in Japan. However, in these pivotal trials, there were few cases in which regorafenib was administered as prior treatments, and also there were few reports on the effectiveness and safety of TAS-102 after administration of regorafenib. Methods: We retrospectively analyzed the clinical data of 126 patients who received TAS-102 after administration of regorafenib in the multi-institutional retrospective study (HGCSG1503). This study was analyzed by CTCAE v4.0 for adverse events (AEs), RECIST v1.1 for response rate (RR)/disease control rate (DCR), and Kaplan-Meier method for progression free survival (PFS) and overall survival (OS). Results: Patients characteristics were as follows; male/female 75/51, median age 66.5 (range 38-84), ECOG PS (0/1/2/3) 48/64/12/2, KRAS Exon2 wild/mutant 64/60 (2 patients; KRAS Exon2 was not tested). The initial starting dose was 70 mg/m2 (n = 100, 79.4%) and reduced dose (n = 26, 20.6%). Dose reductions were required in 30 patients (30.9%). The common ≥grade 3 AEs were neutrophil count decreased (45.1%), white blood cell decreased (34.9%), and anemia (28.6%). RR and DCR were 0% and 36.5%, respectively. Median PFS and OS were 2.1 and 5.7 months. In the analysis on the relationship between ECOG PS 0-1 and PS 2-3, median PFS was 2.2 vs. 1.4 months (HR 2.187, p = 0.008), and MST was 6.5 vs. 2.7 months (HR 2.424, p = 0.002). Conclusions: In this analysis, TAS-102 after administration of regorafenib in the real-world clinical practice showed similar efficacy and safety to the pivotal clinical trials, except for patients with PS 2-3. Clinical trial information: 000020551.
The Relationship Between Common Variant Schizophrenia Liability and Number of Offspring in the UK Biobank
Authors: Valentina Escott-Price, Antonio F. Pardiñas, Enrique Santiago, James Walters, George Kirov, Michael J. Owen, Michael C. O’Donovan
Journal: American Journal of Psychiatry (2019)

Schizophrenia is associated with a marked reduction in reproductive success, yet alleles that are common contribute substantially to the liability of the disorder. Among several possible explanations for this, it has been postulated that individuals who carry risk alleles but are unaffected are at some reproductive advantage, offsetting the effects of negative selection among those who are affected. The authors sought to test this hypothesis, isolating the effects of risk alleles on fecundity from the effects that are contingent on expressing schizophrenia.The burden of schizophrenia risk alleles, as indexed by a polygenic risk score (PRS), carried by 139,679 participants in the UK Biobank study who did not have schizophrenia was compared with the number of offspring of these individuals.Higher schizophrenia liability in study subjects without manifest disorder was weakly but significantly associated with having more children (B=0.006, 95% CI=0.002, 0.010). The relationship was dependent on sex, with a positive correlation between number of children and liability among females (B=0.011, 95% CI=0.006, 0.016), whereas among males, higher liability was associated with being childless (odds ratio=0.96, 95% CI=0.94, 0.98). The negative effect on number of children associated with schizophrenia itself was twofold to 15-fold greater than the positive effect associated with PRS in unaffected individuals.These findings suggest that a complex relationship between liability and fecundity is consistent with sexual selection. Although the overall pattern of a weak positive correlation with liability may contribute to the persistence of schizophrenia risk alleles, these results indicate that the negative selection acting on individuals affected by schizophrenia in the general population is larger than any advantage conferred by genetic loading in unaffected individuals.
18F-fluoro-ethyl-tyrosine (18F-FET) uptake kinetics and maximum tumor to brain ratio (TBRmax) as predictors of glioma grade-first experience.
Authors: Maciej Harat, Bogdan Malkowski, Tomasz Wiśniewski, Roman Makarewicz
Journal: Journal of Clinical Oncology (2014)

e13025 Background: Gliomas grading scale is predictve for treatment methods and outcome. Unfortunately not all lesions suggestive of gliomas are able to be resected or biopsied. The value of 18F-FET in differential diagnosis of brain tumors remains unsettled. The purpose of this study was to explore diagnosis potential of 18F-FET in low and high grade gliomas. Methods: Twenty-two patients harbouring suspected low(LG; n=13) or high (HG; n=10) grade glioma were examined with 18F-FET PET. Consequently resection or biopsy of the tumour were performed. Comparisons were made between the histology of the specimens and standard and dynamic parameters of 18F-FET uptake. For standard estimation we analyze maximum tumor uptake(SUV) and maximum tumor to brain uptake ratio(TBRmax=SUVmax/Background). For 18F-FET kinetics evaluation we analyze absolute difference and ratio of TBRmax in two consecutive measurments: 10 (TBR10) and 60 (TBR60) minutes post 18F-FET injection. Results: Statistically significant differences were found between LG and HG group in three parameters of standard evaluation: TBR10 (1,76 +/-1,17 vs 3,21 +/- 1,41; p=0,015), TBR60 (1,69 +/- 1,08 vs 2,63 +/- 0,98; p=0,047) and SUV60 (Me 2,3 vs Me 3,7; p=0,038). ROC curve analysis shows, that TBR10 is the most promising parameter to distinguish LG and HG groups (AUC 0,799; SN 55,6%/; SP 92,3%; opt. threshold 3,23). Moreover, TBR value below the thresholds for LG and above for HG measure in both time periods (TBR10 and TBR60 ) improve accuracy. Uptake kinetics evaluation reveal very low sensitivity among whole spectrum of glioma tumors. Conclusions: Based on studied material we conclude that 18F-FET PET is valuable tool in differential diagnosis but unable to replace histopatological grading. SUV 10/60 and TBR 10/60 are comparable parameters. However TBR may be more useful, especially when we evaluate it 10 and 60 minutes post injection. Further analysis provide on more patients are expected.
Initial Results of the Phase 2 Treatment Naive Cohort in a Phase 1b/2 Study of Obinutuzumab, Ibrutinib, and Venetoclax in Chronic Lymphocytic Leukemia
Authors: Kerry A. Rogers, Ying Huang, Amy Stark, Farrukh T. Awan, Kami J. Maddocks, Jennifer A. Woyach, Thomas Whitlow, John C. Byrd, Jeffrey A. Jones
Journal: Blood (2017)
Treatment summaries and care plans for post-treatment cancer survivors: Association of quality of life with empowerment.
Authors: Ellen Ingalls Beckjord, Stephanie Nutt, Gijsberta J. Van Londen, Dana H. Bovbjerg, Carissa A. Low, Amy Lowery, Donna M. Posluszny, John E. Schmidt, Sarah R. Arvey, Ruth Rechis
Journal: Journal of Clinical Oncology (2014)

9520 Background: We developed a conceptual framework based on Self-Determination Theory that suggests providing treatment summaries (TSs) or care plans (CPs) will positively impact quality of life (QOL) via positive impact on empowerment. We tested this framework with data from the 2012 LIVESTRONG Survey. Methods: 5,274 post-treatment cancer survivors (average age = 51; average 7.3 years post-diagnosis) responded to an online survey (fielded June-December 2012) that asked about receipt of a TS, follow-up instructions (FUI), and a CP. QOL was operationalized as a score (1-10) on the Distress Thermometer. Empowerment was measured with three items on confidence in getting support; ability to discuss concerns openly with a doctor; and ability to improve mood. Multivariate logistic and linear regressions modeled the odds of receiving a TS, FUI, or CP and the relationships between TS, FUI, or CP and QOL and empowerment adjusting for sociodemographic and medical characteristics. Results: 92% received FUI; 52% received a TS; and 17% received a CP. Women, those further from diagnosis, and those without insurance had lower odds of receiving a TS, FUI, or CP. White survivors were less likely than non-Whites to receive a TS or CP but were more likely to get FUI. Survivors who received more treatment were less likely to get a TS but more likely to get FUI or a CP. TS, FUI, and CP were all positively associated with survivors’ empowerment; TS and FUI were associated with better QOL. Sequential regressions showed that the relationships between TS or FUI and QOL were mediated by a positive association between TS or FUI and empowerment. Conclusions: These analyses supported our framework linking post-treatment information interventions (TS, FUI) to better QOL via positive associations with empowerment. Some survivors are more likely to report receipt of a TS, FUI, or CP than others; the association between receipt and shorter times since diagnosis may reflect practice changes. As TSs and CPs become more common, research should examine cost- and time-effective methods TS and CP development and delivery and their impact on empowerment, QOL, and health behaviors over time.
Serum Vascular Endothelial Growth Factor D in Cystic Lung Disease
Authors: Ali Ataya, Leonard Riley, Mark L. Brantly
Journal: JAMA (2019)

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Immunohistochemically determined EGFR mutations in NSCLC.
Authors: Nina Turnsek, Izidor Kern, Aleksander Sadikov, Mitja Rot, Karmen Stanic, Matjaz Zwitter, Tanja Cufer
Journal: Journal of Clinical Oncology (2014)

8096 Background: ActivatingEGFR mutations (EGFRmu), especially exon 19 deletions (del 19) and L858R point mutation in exon 21 are best predictors of response to TKI therapy in advanced non-small cell lung cancer (NSCLC) and are routinely detected by PCR. Data on immunohistochemically (IHC) determined EGFRmu are scarce. We evaluated the concordance between PCR and IHC determined del 19 and L858R EGFRmu and their predictive value in a Slovenian cohort of NSCLC patients. Methods: IHC using mutation specific antibodies for E746-A750 deletion in exon 19 and for L858R in exon 21 (Ventana Medical Systems) was performed on 137 formalin-fixed tissue specimens. These specimens had PCR predetermined EGFRmu status: 37/137 (27.0%) specimens with del 19, 40/137 (29.1%) with L858R, 31/137 (22.6%) with other mutations, and 29/137 (21.2%) EGFRwt specimens (Therascreen EGFR 28 Mutation Kit Qiagen). IHC staining reaction was assessed by two independent evaluators as positive or negative. 81 EGFRmu patients that received EGFR TKI for advanced disease were included in the survival analysis. Results: With PCR results set as gold standard, the sensitivity, specificity, positive and negative predictive value for the del 19-specific antibody were 67.6%, 99.0%, 96.2%, and 89.2%, respectively, while for the L858R-specific antibody were all 100% (Table). The median overall survival (mOS) of patients treated by TKI differs significantly for PCR+ and IHC+ patients (n=50) compared to PCR+ alone patients (n=31) (33.8 months vs. 17.1 months, respectively; p= 0.024). Conclusions: Both mutation-specific antibodies are highly specific, and could be used as a first-step method for EGFRmu screening. Results, including survival (mOS), are indicating that IHC positive patients could directly receive TKI therapy, while IHC negative cases should be submitted for further molecular testing. Results for del 19-specific antibody. PCR Del 19+ Del 19- Total IHC Del 19+ 25 1 26 Del 19- 12 99 111 Total 37 100 137 Results for L858R-specific antibody. PCR L858R+ L858R- Total IHC L858R+ 40 0 40 L858R- 0 97 97 Total 40 97 137
Risk of severe diarrhea associated with ipilimumab in cancer patients.
Authors: Robert Charles Hendler, Shenhong Wu
Journal: Journal of Clinical Oncology (2014)

9634 Background: Ipilimumab is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody, which augments T-cell activation and proliferation and is thought to indirectly affect the T-cell mediated anti-tumor immune response. It has been approved by the FDA for treatment of unresectable or metastatic melanoma, and several trials have also shown promising results regarding ipilimumab's role in the treatment of other types of cancer. Ipilimumab has been associated in some individual studies with an increased rate of diarrhea, a serious adverse event associated with morbidity and treatment discontinuation. However the overall incidence and risk of diarrhea to ipilimumab is unknown. Objective: To conduct a systematic review of relevant clinical trials, and perform a meta-analysis to determine risk of diarrhea with ipilimumab. Methods: Articles from PubMed from January 1998 to November 2013 and abstracts presented at the American Society of Clinical Oncology up to 2013 were searched to identify relevant studies. The incidence and relative risk (RR) of diarrhea and its 95% Confidence Intervals were calculated using random effects or fixed effects models depending on the heterogeneity of included studies. Results: There were a total of 1571 patients across 10 clinical trials included in this meta-analysis. The overall incidence of all-grade diarrhea was 41.6% (95% CI: 33.6-50.0%). The overall incidence of high-grade diarrhea was 8.4% (95% CI: 5.5-12.7%). In comparison with controls, ipilimumab significantly increased the risk of all-grade diarrhea with an RR of 1.63 (95% CI: 1.37-1.97, P<0.001) and high-grade diarrhea with an RR of 2.19 (95% CI: 1.11-4.34, P=0.025). Conclusions: There was a significant risk of severe diarrhea in cancer patients treated with ipilimumab.
Preclinical evaluation of PARP inhibitors in combination with DNA-damaging agents in a Ewing sarcoma orthotopic xenograft model.
Authors: Elizabeth Stewart, David Ross Goshorn, Michael A. Dyer, Anang Shelat, Cori Bradley, Alberto S. Pappo, Amos Loh
Journal: Journal of Clinical Oncology (2014)

10073 Background: Ewing sarcoma (EWS) is an aggressive malignancy of childhood with a dismal prognosis in patients with metastatic or recurrent disease. Previous research demonstrated EWS cell lines with the EWS-FLI1 translocation be sensitive to Poly (ADP ribose) polymerase inhibitors (PARPi). Although phase 1 clinical trials have failed to demonstrate significant single agent efficacy for EWS, preclinical studies suggest increased efficacy with the addition of DNA damaging agents to PARPi. We examined the PARPi BMN 673, olaparib, and veliparib in combination with irinotecan and temozolomide (TMZ) in a clinically relevant EWS orthotopic xenograft model. Methods: EWS orthotopic xenografts were created by injecting EW-8 luciferase labeled cells into the femur of CD-1 nude mice. Mice were randomized to the following treatment groups (see Table.) Allometric doses were administered on a clinically relevant schedule for two cycles. Complete response (CR), stable disease (SD), and progressive disease (PD) were determined using bioluminescence. Results: The addition of TMZ and irinotecan to BMN 673 and olaparib (Groups 1, 2) showed significant disease response in comparison to irinotecan and TMZ alone (Group 4). Mice that received BMN 673 had the best response with 100% achieving CR. Mice that received olaparib (Group 2) had a 50% CR and 50% SD. Groups 3, 4, and 5 all had 80% PD and 20% SD. Conclusions: The addition of the PARP inhibitors BMN 673 and olaparib to irinotecan and TMZ provides significant disease response and stabilization in an orthotopic xenograft model of EWS. These drug combinations may be effective in the treatment of pediatric patients with EWS. Ongoing pharmacokinetic and preclinical studies will be performed to determine if efficacy is likely to be achieved within the therapeutic window of this patient population. Group 1 (n = 5) Irinotecan + TMZ + BMN 673 Group 2 (n = 4) Irinotecan + TMZ + Olaparib Group 3 (n = 5) Irinotecan + TMZ + Veliparib Group 4 (n = 5) Irinotecan + TMZ Group 5 (n = 5) Placebo
Psychiatric morbidity and suicidal behaviour in psoriasis
Authors: R. Parisi, R.T. Webb, C.E. Kleyn, M.J. Carr, N. Kapur, C.E.M. Griffiths, D.M. Ashcroft
Journal: British Journal of Dermatology (2019)

Psoriasis is a long‐term skin disorder that currently does not have a cure. Many people with psoriasis also suffer from social or emotional problems, called psychosocial comorbidities. Suggested explanations for mental illness in people with psoriasis include the considerable impact that psoriasis has on people's quality of life, mainly related to how their skin looks and how this impacts on their lives. It is thought that the psychological burden in people with psoriasis may lead to elevated risk of self‐harm and suicide. This study, from the UK, examined this theory by comparing medical data from 56,961 people with psoriasis and 876,919 without. This data showed higher prevalence of alcohol misuse, bipolar disorder, depression, anxiety disorders, self‐harm, and psychotropic drug (for mental health) prescription in people with psoriasis. However, while there was a 15% increase in self‐harm risk in the psoriasis group versus the general population, the overall risk of suicide in people with psoriasis was 40% lower compared to peers without the condition. The risk of suicide varied according to age: it was 60% lower among individuals with psoriasis diagnosed at age 40 or over, compared to people without the disease of the same age group, whereas if the diagnosis occurred prior to age 40 years there was no difference in risk between the two groups. Healthcare professionals caring for patients with psoriasis should continue to monitor and tackle effectively the psychological needs of these individuals.
Abstract 14971: Trends and Predictors of Implantable Cardioverter Defibrillator Implantation After Sudden Cardiac Arrest: Insight From The National Inpatient Sample
Authors: Muhammad Bilal Munir, Fahad Alqahtani, Sami Aljohani, Ashwin Bhirud, Sujal Modi, Mohamad Adnan Alkhouli
Journal: Circulation (2017)

Background: Implantable cardioverter defibrillators (ICD) improve survival and have a class IA indication in patients who experienced sudden cardiac arrest (SCA) provided no reversible cause is ide...
Absolute risk and cost of management of toxicities of newly approved anticancer drugs: A meta-analysis.
Authors: Saroj Niraula, Eitan Amir, Francisco Emilio Vera Badillo, Bostjan Seruga, Alberto Ocana, Ian Tannock
Journal: Journal of Clinical Oncology (2014)

e17556 Background: Frequency of rare but serious adverse events (AEs) caused by new anticancer drugs, and costs associated with their management, are poorly documented. The type of anticancer drug can influence the prevalence of such AEs and associated costs. Methods: We identified anticancer drugs andpivotal trials supporting their registration by Food and Drug Administration during 2000-2011. Twelve frequent, grade III-IV AEs were weighted and pooled in a meta-analysis. Incremental drug prices, and costs for management of AEs were estimated according to target-specificity of new agents and control treatment used in the trials. Results: We identified 41 studies (27,500 patients; 6,000 events) involving 19 experimental drugs. Agents directed against a specific molecular target on cancer cells had trend towards lower incidence of grade III-IV toxicities than the controls (median relative risk [RR]=0.7, p=0.2), whereas less-specific targeted agents, including angiogenesis-inhibitors (median RR=3.4, p<0.001), and chemotherapeutic agents (median RR=1.6, p<0.01) were more toxic. Risk was increased regardless of whether control arm contained active treatment (RR=2.1, p<0.001) or placebo (RR=3.0, p<0.001). Median incremental drug-price for experimental agents was $6000/patient/month. Cost of toxicity management was lower than controls if experimental agents were specific but was higher for less-specific targeted agents and chemotherapies. Conclusions: Newly approved anticancer drugs are associated with increased toxicity except for agents with a specific molecular target on cancer cells. Management of toxicity leads to a relatively small increase in overall cost of treatment. Frequency of toxicity and associated costs are likely higher in less selected patients treated in general oncologic practice.
Relation between irinotecan-induced cholinergic syndrome and prognosis of colorectal cancer patients.
Authors: Hiroyuki Fujii, Taizo Hirata, Takuya Mura, Yuko Okada, Hirotaka Tashiro
Journal: Journal of Clinical Oncology (2018)

859 Background: It is well known that a cetuximab induced rash is strongly associated with improved survival of colorectal cancer patients. Irinotecan Induced Cholinergic Syndrome (IICS), manifesting in such events as early diarrhea and diaphoresis, is a notorious adverse effect of irinotecan. In this study, we reveal the relation between IICS and prognosis of colorectal cancer patients and examine the validity of IICS as a surrogate marker for the efficacy of irinotecan. Methods: We retrospectively reviewed data from 52 colorectal cancer patients who were treated with a chemotherapeutic regimen that included irinotecan at Kure Medical Center between 2012 and 2017. First, to assess the relation between adverse events and efficacy of irinotecan, patients who experienced IICS (n = 11) and did not experience IICS (n = 41) were analyzed from the aspect of overall survival (OS), progression-free survival (PFS), sex, age, dose, performance status (PS) and previous chemotherapy (PC). Kaplan-Meier survival curves were drawn for OS and PFS, and compared by means of a log-rank test. Secondly, to determine the response rate of butylscopolamine for IICS, we injected butylscopolamine 20mg into the irinotecan infusion bag and administered both agents through the intravenous line together to 11 patients who experienced IICS. Results: The presence of IICS was associated with a prolonged median OS (589 vs. 280 days, log-rank p = 0.0282; adjusted hazard ratio (HR) 0.27, 95% confidence interval [CI] 0.06-0.79, p = 0.0140), and prolonged median PFS (317 vs. 154 days, log-rank p = 0.1474; adjusted HR 0.56, 95% CI 0.22-1.25, p = 0.1635). There was no statistically significant difference between the two groups in terms of sex, age, dose, PS and PC. Ten patients of 11 patients who were administered butylscopolamine, experienced complete or partial improvement of IICS. The response rate was nearly 90%. Conclusions: The presence of IICS is associated with an improved OS for colorectal cancer patients and tends to have a positive correlation with PFS. IICS is a viable surrogate biomarker of the antitumor efficacy of irinotecan. As a prophylaxis of IICS, mixing butylscopolamine into the irinotecan infusion bag was remarkably effective.