tbuckley/cabot-search huggingface dataset:
A prospective, multicenter, observational study of bevacizumab in combined with chemotherapy as first-line or second-line treatment in Chinese metastatic colorectal cancer.
Authors: Shukui Qin, Yanhong Deng, Feng Bi, Tian Shu Liu, Yunpeng Liu, Suzhan Zhang, Jianming Xu, Shu Yongqian, Nong Xu, Changping Wu, Xin Wang, Haijun Zhong, Jifeng Feng, Yulong He, Jianwei Yang
Journal: Journal of Clinical Oncology (2016)

e15012 Background: Bevacizumab (BV) was approved in February 2010 in China with indication of combined with 5-FU for metastatic colorectal cancer (mCRC). Post-marketing surveillance of patients (Pts) who received BV was required because of limited clinical data, especially safety profile in China. In order to understand practical use of BV and guide clinical practice in China, we have studied safety and efficacy of BV combined with chemotherapy (CT) in 1st- or 2nd-line treatment for Pts with mCRC. Methods: The current study is a prospective observational study conducted in 24 Chinese cancer centers. Pts were treated with BV plus CT for mCRC as 1st- or 2nd-line therapy. The primary objective was to investigate the safety profile of these treatments. Results: 606 Pts (median age 56.6 years (22–81); ECOG PS 0-1: 76.7%) were treated with BV plus CT as 1st- line (n = 453) or 2nd- line (n = 153) therapy.The median cycles on BV treatment were 5 (3.0 – 8.0) cycles. The incidence of any AEs (grade ≥ 3 ) was 16.8%. In which grade ≥ 3 AEs related to BV were reported in 10.9% of Pts. AE of special interest (grade ≥ 3) included hypertension (1.8%), proteinuria (0.8%), GI perforation (0.5%), bleeding (3.3%), arterial TE (0.3%), venous TE (1.0%), fistula formation (0.8%) and wound healing complications (0.2%). The safety profile was similar between 1st- and 2nd-line therapies. The ORR and median PFS were 18.3% (95% CI, 15.3%–21.6%) and 9.1 months (95% CI, 8.1–9.8), respectively. The one-year PFS rate and one-year survival rate were 33.1% and 68.8%, respectively. The ORR in KRAS wild-type and mutant Pts were 15.9% (95% CI, 9.0–25.2) and 9.5% (95% CI, 4.7–16.8), respectively. The median PFS was 9.8 months (95% CI, 6.7–12.3) in KRAS wild-type Pts and 8.6 months (95% CI, 6.2–9.9) in KRAS mutant Pts. Conclusions: The safety profile of BV containing regimen in China seemed comparable with those reported from other pivotal studies or Chinese registration study (ARTIST). BV combined with standard CT is effective as observed in our registry. However, due to the short treatment cycles, the ORR in this observational study is not good as previous studies. Clinical trial information: NCT01319877.
P01.050 Circulating MACC1 transcript plasma levels in glioblastoma patients segregate together with prognostic markers and treatment response
Authors: C Hagemann, N Neuhaus, M Dahlmann, A F Kessler, D Kobelt, P Herrmann, M Eyrich, B Freitag, B Freitag, T Linsenmann, C M Monoranu, R Ernestus, M Löhr, U Stein
Journal: Neuro-Oncology (2018)

IDH1-mutation and MGMT-promoter methylation are established prognostic markers in glioblastoma multiforme (GBM); however, invasive procedures are needed to obtain the required tumor tissue. Metastasis-associated in colon cancer-1 (MACC1) has been established as a prognostic plasma marker for several solid cancer entities. Here, we evaluated circulating MACC1 transcripts for prediction of clinical outcome and therapy response in GBM. Plasma samples were collected from 45 GBM patients (31 IDH1 wildtype (wt), 5 IDH1R132H, 9 unspecified) before surgery. The patients’ clinical course was followed for 24 months. Samples from 15 healthy volunteers served as controls. MACC1-transcript levels, determined by qRT-PCR, were correlated with patient overall survival (OS) and clinical data of known prognostic significance. Cut-off values for Kaplan-Meier analyses were determined by ROC calculations. Cluster analyses were performed. MACC1 transcripts were higher in patients plasma compared to healthy controls (P<0.0001). Low MACC1 levels clustered together with other favorable markers, especially IDH1R132H. MACC1 levels correlated with patient prognosis in conjunction with the IDH mutation status: patients with IDH1R132H mutation and low MACC1 levels showed the most favorable outcome (mean OS 21.2 months (m), SD=2.5; 95% CI 16.3–26.1), IDH1wt and high MACC1 patients had the worst prognosis (mean OS 8.6 m, SD=1.6; 95% CI 5.5–11.8), while those with IDH1wt and low MACC1 were intermediate (mean OS 14.9 m, SD=2.1; 95% CI 10.8–19.1). No patients displayed IDH1R132H and high MACC1 levels. Patients with low MACC1 levels receiving standard therapy (operation and radiochemotherapy according to Stupp) (n=29) survived longest (mean OS 17.6 m, SD=1.9; 95% CI 13.9–21.3). Patients with high MACC1 showed shorter OS (mean OS 10.3 m, SD=2.3; 95% CI 5.9–14.8). The worst prognosis had patients not receiving the standard regimen (n=16), independently of their MACC1 levels (MACC1 low: 5.2 m, SD=1.8; 95% CI 1.6–8.8; MACC1 high: 5.5 m, SD=1.5; 95% CI 2.6–14.8). The inclusion of circulating MACC1 transcript levels into the prognostic workup might improve the accuracy of outcome prediction and help to define more precise risk categories of GBM patients.
Effects of commonly used chronic medications on the outcomes of ipilimumab therapy in patients with metastatic melanoma.
Authors: Jarrett Failing, Heidi D. Finnes, Lisa A. Kottschade, Jacob B Allred, Svetomir Markovic
Journal: Journal of Clinical Oncology (2016)

e21038 Background: Ipilimumab can induce long-term survival in up to 20% of patients with metastatic melanoma, however response comes with high rates of immune-related adverse events (irAEs). Concurrent chronic medications may impact the patient’s immune system, possess anti-melanoma properties, and potentially affect clinical outcomes (efficacy and/or toxicity). This retrospective study sought to describe the influence of 12 classes of concomitant chronic medications used by metastatic melanoma patients undergoing therapy with ipilimumab. Methods: Retrospective study of 159 adults who received ipilimumab for metastatic melanoma at Mayo Clinic in Rochester, MN from March 1, 2011 through December 31, 2014. Data on patient characteristics, best tumor response, irAEs, progression, death, and use of chronic medications (statins, metformin, beta blockers, ACE/ARBs, calcium channel blockers, aspirin, NSAIDs, H1 and H2 receptor antagonists, proton pump inhibitors, antidepressants, and vitamin D supplements) were abstracted from the electronic medical record. For the analysis of best tumor response and irAEs, a case-control analysis was employed. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan Meier method and Cox Proportional Hazard modeling. Results: Of the 12 concomitant medication classes, only proton pump inhibitors (PPIs) were found to have an increased odds of experiencing a partial response (PR) or complete response (CR) to ipilimumab (OR, 3.73; CI 1.26-11.04; p = .02). While not significant, PPI use trended towards improved OS and PFS (HR, 0.44; CI 0.17-1.15; p = .09; and HR, 0.6; CI 0.34-1.06; p = .08; respectively). Likewise, H2 antagonist use may result in an increased odds of PR or CR (OR, 5.27; CI 0.99-28.1; p = .05). No medication class was associated with increased risk of grade 3/4 irAEs. Conclusions: Patients on PPIs may be more likely to experience a PR/CR following ipilimumab therapy. Due to the small sample size and retrospective nature of this work, these finding are only descriptive and support further study. Other classes of chronic medications did not produce statistically significant effects for any of the measured outcomes.
Somatic tumor profiling of DNA mismatch repair (MMR) deficient endometrial cancers (EC).
Authors: Karen Anne Cadoo, Deborah DeLair, Diana Mandelker, Magan Trottier, Carolyn Stewart, Christina Tran, Yelena Kemel, Michael Francis Walsh, Felicia Scharf, David Michael Hyman, Vijai Joseph, Mark E. Robson, Nadeem Abu-Rustum, Kenneth Offit, David B. Solit, Michael F. Berger, Carol Aghajanian, Zsofia Kinga Stadler
Journal: Journal of Clinical Oncology (2017)

e17121 Background: Approximately 20% of EC have loss of MMR ( MSH2, MSH6, MLH1, PMS2) protein expression by immunohistochemistry (IHC). The majority have somatic MLH1/PMS2 loss, driven by MLH1 promoter hypermethylation. For the remaining patients (pts), germline testing for Lynch Syndrome (LS) is recommended. However, half do not have a corresponding germline mut. This is considered “Lynch-like syndrome” (LLS) &amp; clinical management is challenging. We sought to determine if tumor profiling could identify somatic mut potentially underpinning loss of protein expression. Methods: Per institutional standard, all EC, regardless of age or family history undergo reflex LS screening with IHC for MMR protein expression. Pts consented to IRB approved protocols. Tumor-normal sequencing was performed via custom next-generation sequencing panel (MSK-IMPACT). Electronic medical records were reviewed. Results: 16 pt have completed tumor sequencing, median age 53 (35-83), 6 (38%) &lt; 50 yrs at diagnosis. 2 had personal history of additional cancer (DCIS, ovary), none had first degree relative with colon or EC. A mix of EC histologies was represented: 10 endometrioid (all grades), 2 clear cell, 4 mixed. There were no serous cancers. There were median 58 mut (9-546), 14 (88%) had hyper or ultra mutated EC. 5 EC were driven by somatic POLE mut (3 known hotspot, 1 likely pathogenic), all ultra-mutated phenotype, resulting in multiple somatic MSH6 muts with isolated IHC MSH6 loss. 4 EC had MSH2/MSH6 IHC loss with corresponding double somatic mut in MSH2. 5 had one somatic mut corresponding to the MMR protein loss, assessment of LOH in these cases is pending. Two cases are unexplained: 40 yo with IHC MLH1 loss, 47mut; 69 yo, IHC MSH6 loss, 12 mut. In this cohort of LLS, somatic muts were frequently observed in ARID1A (13,81%), PTEN (10,63%) &amp; PIK3CA(9,56%), in keeping with non serous histologies. Conclusions: In line with our prior report that pt with LLS had benign personal &amp; family cancer histories compared with LS pts, we have identified that in 56% of LLS EC either POLE mut or double somatic MMR mut likely underpins the MMR IHC loss. As such, in these LLS EC cases, somatic tumor profiling may help to rule out LS. Further testing is ongoing to increase cohort size.
A phase II randomized study to evaluate a new psychosocial intervention (PI) plus early palliative care (PC) in the reduction of depression of advanced cancer patients (ACP): The PREPArE trial.
Authors: Carlos Eduardo Paiva, Thamires Monteiro do Carmo, Cleyton Zanardo de Oliveira, Maria Salete de Angelis Nascimento, Milena Ruas de Siqueira, Marielle Borges, Bianca Sakamoto Ribeiro Paiva
Journal: Journal of Clinical Oncology (2016)

e21626 Background: The benefits of early integration of PC in oncology have been demonstrated. However, patients continue to receive late referrals to PC. Patients and health professionals may perceive PC as 'a place to die,' and this stigma is a barrier to timely referrals. Interventions to improve PC acceptability are needed. Our aims were to evaluate the feasibility and potential efficacy of a new PI plus early PC in the reduction of depression of ACPs. Methods: ACPs without depression and/or anxiety diagnosis and starting palliative chemotherapy were recruited from the outpatient oncology clinics and were randomized into one of the following treatment arms: Arm A, 5-wk PIs based on cognitive behavioral therapy plus early PC; Arm B, early PC only; and Arm C, standard oncologic care. The impact of these interventions on emotional symptoms was evaluated in this planned interim analysis. The Hospital Anxiety and Depression Scale (HADS), the Patient Health Questionnaire (PHQ-9), the Edmonton Symptom Assessment System (ESAS), and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-Pal were completed at baseline, 45 and 90 days after randomization. Mixed-ANOVA and Cohen’s d effect size (ES) were calculated. Results: 696 pts were screened; 103 were potentially eligible; and 40 refused to participate. 19, 22 and 22 pts were included in Arms A, B, and C, respectively. Baseline characteristics were well balanced between groups. 16 (84%) pts from Arm A participated in at least 3 psychosocial sessions. Interaction between baseline scores of depression (PHQ-9, HADS-D), anxiety (HADS-A), emotional functioning and ESAS-emotional and treatment arms were all non-significant. Based on ES analysis, a trend for benefit of Arm A over Arm B was observed for HADS-A (ES = 0.17), ESAS-emotional (ES = 0.21) and emotional functioning (ES = 0.66), but not regarding depression scores. Conclusions: Although a large number of ACPs needed to be screened, the intervention was considered feasible. It was not useful for the prevention of depression; however, a potential benefit in the reduction of anxiety levels was observed. Clinical trial information: NCT02133274.
OS5.4 Oligodendrogliomas in pediatric and teenage patients only rarely exhibit molecular markers and patients have excellent survivals
Authors: A K CHAN, Y X Li, A Aibaidula, H K Ng
Journal: Neuro-Oncology (2018)

Although oligodendrogliomas appear histologically similar in adult and pediatric patients, the latter have only been rarely studied and most of those studies did not have long follow-up. We examined 55 oligodendroglial tumors from pediatric and teenage patients for their biomarkers with formalin-fixed paraffin-embedded tissues and studied their survival status. None of the tumors harbored 1p/19q codeletion or IDH mutation. Mutations in TERTp (4%), BRAF (11%), FGFR1 (3%) and H3F3A (5%), fusions of BRAF (8%) and FGFR1 (8%) were found sparingly and almost all in a mutually exclusive manner. Molecular events were exclusively found in tumors with classic oligodendroglial histology. Survival analysis showed remarkably excellent prognosis compared to the adult counterparts. 5-year overall survival was 95% in our cohort with median follow-up of 8.1 years and in nine patients with follow-up more than 10 years, the 10-year overall survival was 100%. The 5-year and 10-year progression-free survivals of our cohort were 89 and 77%, respectively. FGFR1 fusion seemed to confer a poor prognosis in pediatric oligodendrogliomas. Patients receiving adjuvant chemotherapy (p=0.046) or harboring Grade II histology (p<0.001) had longer interval to recurrence. Our study demonstrated the distinct indolent clinical course of pediatric and teenage oligodendrogliomas compared to the adult tumors. Molecular markers commonly seen in adult oligodendrogliomas and other pediatric low-grade gliomas were only rarely seen. Since there is no clinical or molecular evidence suggesting that pediatric “oligodendrogliomas” are the same as adult oligodendrogliomas albeit histologic similarity, a case can be made for their separation from adult oligodendrogliomas in the next WHO classification.
Validation of Risk Score in Predicting Early Readmissions in Decompensated Cirrhotic Patients: A Model Based on the Administrative Database
Authors: Khalid Mumtaz, Abdulfatah Issak, Kyle Porter, Sean Kelly, James Hanje, Anthony J. Michaels, Lanla F. Conteh, Ashraf El‐Hinnawi, Sylvester M. Black, Marwan S. Abougergi
Journal: Hepatology (2018)

Early readmission in patients with decompensated liver cirrhosis leads to an enormous burden on health care use. A retrospective cohort study using the 2013 and 2014 Nationwide Readmission Database (NRD) was conducted. Patients with a diagnoses of cirrhosis and at least one feature of decompensation were included. The primary outcome was to develop a validated risk model for early readmission. Secondary outcomes were to study the 30‐day all‐cause readmission rate and the most common reasons for readmission. A multivariable logistic regression model was fit to identify predictors of readmissions. Finally, a risk model, the Mumtaz readmission risk score, was developed for prediction of 30‐day readmission based on the 2013 NRD and validated on the 2014 NRD. A total of 123,011 patients were included. The 30‐day readmission rate was 27%, with 79.6% of patients readmitted with liver‐related diagnoses. Age &lt;65 years; Medicare or Medicaid insurance; nonalcoholic etiology of cirrhosis; ≥3 Elixhauser score; presence of hepatic encephalopathy, ascites, variceal bleeding, hepatocellular carcinoma, paracentesis, or hemodialysis; and discharge against medical advice were independent predictors of 30‐day readmission. This validated model enabled patients with decompensated cirrhosis to be stratified into groups with low (&lt;20%), medium, (20%‐30%), and high (&gt;30%) risk of 30‐day readmissions. Conclusion: One third of patients with decompensated cirrhosis are readmitted within 30 days of discharge. The use of a simple risk scoring model with high generalizability, based on demographics, clinical features, and interventions, can bring refinement to the prediction of 30‐day readmission in high‐risk patients; the Mumtaz readmission risk score highlights the need for targeted interventions in order to decrease rates of readmission within this population.
Whole body diffusion-weighted MRI in metastatic breast cancer patients: A single centre’s experience.
Authors: Priya V. Joshi, Anwar R. Padhani, Ewan Chapman, Chandana Jaliya Jayasekera, Mei-Lin Ah-See
Journal: Journal of Clinical Oncology (2016)

e23133 Background: Despite the known increased accuracy of whole body MRI (WB-MRI) for detecting skeletal metastases, its impact on patient management in comparison to standard imaging with CT scans remains unexplored. [1]We evaluate a single centre experience of WB-MRI in the setting of bone predominant metastatic breast cancer (MBC) to evaluate its impact on patient care, in routine clinical practice. Methods: A retrospective audit was performed of MBC patients treated at Luton and Dunstable (L&D) Hospital over a 59-month period (Feb 2011 to Dec-2015). Patient records were used to assess the impact of WB-MRI compared to CT scans, on treatments received, per time-point. Results: 93 patients were identified. 17 patients were excluded: 3 belonged to other teams; 14 did not have metastatic disease, therefore 76 patients were included. The median patient age at first WB-MRI was 54 years (range 31-87 years). The majority of patients had bone-predominant MBC (66/76, 86.8%). 343 WB-MRI scans were performed, with a median number of 3 scans per patient (range 1-17). 115 WB-MRI were performed with a concurrent (median 1 day, range 0-41 days) CT scan of the chest, abdomen and pelvis (CT-CAP); 108 paired WB-MRI & CT-CAP scans were reviewed. In 62 of 108 paired scans (57.4%) demonstrated comparable disease, not requiring management change at 54 time-points. In 46 of 108 paired scans (44.6%), CT-CAP and WB-MRI were discordant in their findings; WB-MRI showed disease progression not reported on CT-CAP. This resulted in 22 (20.3%) time-points requiring management change (18/22 bone, 7/22 liver, 6/22 CNS and 6/22 other sites). Conclusions: For an unselected patient group with bone-predominant MBC, serial WB-MRI detects disease progression not seen by CT scans; resulting in management changes in approximately 20% when CT and WB-MRI scan are compared. Further research comparing WB-MRI with standard-of-care imaging is required to assess the lead time to progression for the competing modalities, and whether the earlier detection of progression results in improved outcomes. [1] Woolf DK, Padhani AR, Makris A. Assessing response to treatment of bone metastases from breast cancer: what should be the standard of care? Ann Oncol. 2015;26:1048-57
A systematic review and meta-analysis of randomized controlled trials to evaluate the risk of health-related quality of life and metabolic events in patients with advanced breast cancer treated with everolimus.
Authors: Somedeb Ball, Kyaw Zin Thein, Muhammad Saad Khan, Sriman Swarup, Anita Sultan, Fred L. Hardwicke, Nicholas C. D'Cunha, Catherine Jones
Journal: Journal of Clinical Oncology (2018)

e22219 Background: Activation of PI3K/AKT/mTOR signaling pathway was shown to involve in breast cancer (BC) progression. Everolimus (E) is an oral mTOR inhibitor and has employed in patients with BC. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of health-related quality of life (HRQOL) and metabolic events. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through January 2018 were queried. Phase 3 RCTs that mention HRQOL and metabolic events as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: A total of 1992 patients with advanced BC were eligible for analysis. Studies compared E+ paclitaxel(P) + Herceptin(H) vs P+H, E+ exemestane(Ex) vs Ex, E+ vinorelbine(V)+ H vs V+H. The RR of all-grade side effects were as follows: fatigue, 1.07 (95% CI: 0.93-1.23, p = 0.33); asthenia, 1.61 (95% CI: 0.95-2.73, p = 0.07); decreased appetite, 2.01 (95% CI: 1.46-2.78, p < 0.001); pyrexia, 1.64 (95% CI: 1.34-2.01, p < 0.001); insomnia, 1.17 (95% CI: 0.91-1.50, p = 0.21); rash, 2.46 (95% CI: 1.18-5.10, p = 0.01); bone pain, 1.18 (95% CI: 0.78-1.79, p = 0.41); hyperglycemia, 2.79 (95% CI: 1.46-5.32 p = 0.002); and hypertriglyceridemia, 2.19 (95% CI: 1.42-3.36, p < 0.001). The RR of high-grade side effects were as follows: fatigue, 2.81 (95% CI: 1.71-4.62, p < 0.001); decreased appetite, 2.25 (95% CI: 0.67-7.50, p = 0.18); pyrexia, 1.54 (95% CI: 0.67-3.50, p = 0.30); rash, 1.27 (95% CI: 0.23-7.00, p = 0.77); bone pain, 1. 89 (95% CI: 0.41-8.71, p = 0.41); hyperglycemia, 3.44 (95% CI: 1.46-8.06 p = 0.004); and hypertriglyceridemia, 1.91 (95% CI: 0.70-5.16, p = 0.20). Conclusions: Patients on everolimus experienced a significant increase in all-grade rash, pyrexia and decreased appetite as well as high-grade fatigue. They also contributed to all grades of hyperglycemia and all-grade hypertriglyceridemia. Timely recognition and proper supportive care may enhance patients' quality of life.
TCT-861 Predicting Left Ventricular Outflow Tract Obstruction from Transcatheter Mitral Valve Replacement Despite Anterior Mitral Leaflet Resection: the Skirt NeoLVOT
Authors: Jaffar Khan, Adam Greenbaum, Toby Rogers, Vasilis Babaliaros, Robert Lederman
Journal: Journal of the American College of Cardiology (2018)