tbuckley/cabot-search huggingface dataset:
Phase IB study of induction chemotherapy with XELOX, followed by radiation therapy, carboplatin, and everolimus in patients with locally advanced esophageal cancer (EC).
Authors: Nabil F. Saba, Seth D Force, Charles A. Staley, Felix G Fernandez, Field F. Willingham, Pickens Allan, Kenneth Cardona, Zhengjia Chen, Dana Backlund Cardin, Eric Lambright, Jon Nesbitt, Kristin Ann Higgins, R Donald Harvey, Taofeek Kunle Owonikoko, Suresh S. Ramalingam, Dong Moon Shin, Jonathan Jay Beitler, Bassel F. El-Rayes, Jerome C Landry, Anuradha Bapsi Chakravarthy
Journal: Journal of Clinical Oncology (2017)

e15607 Background: Preclinical studies have shown synergy between everolimus, an mTOR inhibitor, radiation and platinum agents in EC. We conducted a multi-institutional phase IB trial to determine the recommended phase II dose (RP2D) of concurrent everolimus with carboplatin and radiation in non-metastatic EC pts. Methods: Patients with untreated, localized EC and ECOG performance status 0-1 were eligible. Following two cycles of induction Capecitabine/Oxaliplatin (XELOX), pts without evidence of disease progression, received concurrent chemoradiation (total dose: 50.4Gy in 28 fractions), weekly carboplatin (AUC = 2), and escalating doses of everolimus. A standard 3+3 dose escalation design was used. Results: Nineteen patients were enrolled. There were two screen failures (thrombocytopenia, metastases) and 4 pts were removed due to poor tolerance of XELOX (2 pts) or disease progression (2 pts). A total of 13 pts with stage II/III (6/7) EC completed concurrent therapy. Median age 58 (44-71yrs), 85% males; all had adenocarcinoma deemed resectable. One pt at dose level 1 (2.5 mg/QOD), was replaced due to ongoing anxiety. One of 6 pts had a DLT (bowel ischemia). At dose level 2 (2.5mg/QD), 2 out of 6 patients had a DLT (fever with neutropenia and nausea). The RP2D of everolimus was 2.5 mg QOD. Clinically relevant ≥ grade 3 toxicities included lymphopenia (25%), dehydration (12%), fatigue, leukopenia, hyponatremia, abdominal pain, vomiting (each 6%). R0 resection was achieved in 100%; a pathologic response rate (RR) of 40% and a pathologic complete response (pCR) rate of 23% were observed. The 2-year PFS and OS were 50% and 49.6% respectively. Conclusions: The RP2D of everolimus with concurrent weekly carboplatin and radiation is 2.5 mg QOD. Despite the 100% R0 resection rate, the pCR and OS rates were within the expected historical controls. (The study was funded by Novartis Pharmaceuticals) Clinical trial information: NCT01490749.
The prognostic value of blood neutrophil-to-lymphocyte ratio (NLR) factor in advanced gastrointestinal stromal tumors (GIST) treated with sunitinib after imatinib failure.
Authors: Piotr Rutkowski, Iwona Lugowska, Anna Klimczak, Elzbieta Bylina, Beata Jagielska, Pawel Teterycz
Journal: Journal of Clinical Oncology (2018)

11531 Background: Neutrophil-to-lymphocyte ratio (NLR) was shown to be prognostic in several solid malignancies. There are still limited data about predictive/prognostic value of NLR during targeted therapy of patients with advanced gastrointestinal stromal tumors (GIST). The aim of the study was to asses a clinical value of this ratio in patients with unresectable/metastatic GIST treated with sunitinib. Methods: Between 2001 and 2016, 146 of 230 patients with metastatic/unresectable GIST and fully available clinic-pathologic data who progressed on the imatinib and received sunitinib as second line treatment were included to the analysis. In all patients the NLR was assessed at the baseline, after 3 months of treatment and upon disease progression (or last observation). The cut-off value for NLR was set at median of 2.4. Kaplan-Meier survival probability estimation with in log-rank test, and Cox's proportional hazards model were used for analysis. Results: Median Progression-Free Survival (PFS) on sunitinib treatment was 12 months, 2- and 5-year rate were 27% and 5% respectively; median Overall Survival (OS) – 23 months, 2- and 5-year rate 48% and 14% respectively. NLR > 2.4 at baseline was significantly associated with poorer OS: median OS was 30.0 months (95%CI 26.7-40.6) for NLR ratio ≤2.4 vs. 16.4 months (95%CI 14.1-22.8) for NLR > 2.4 (p = 0.002); median PFS was 18.2 (95%CI 10.8-24.2) vs. 9.6 (95%CI 6.9-15.1) respectively, which was close to statistical significance (p = 0.075). In multivariate OS model adjusted for mitotic index, localization of primary tumor (stomach vs. other) and driver oncogenic primary mutation in the tumor (KIT exon 11 mutation versus other) baseline NLR > 2.4 was proven to be statistically significant (HR 1.96 95%; CI 1.31-2.91; p < 0.001). Moreover, NLR value at last observation or disease progression was also prognostic factor for OS (HR 2.37, 95% CI: 1.42-3.96, p < 0.001). Conclusions: Our results demonstrate the usefulness of NLR as a prognostic and predictive marker in patients with advanced GIST treated with sunitinib.
TCT-80 Natural change of the distal bed following percutaneous coronary intervention with drug-eluting stents for chronic total occlusion lesions
Authors: Osung Kwon, Seung-Whan Lee, Sun Hack Lee, Sangwoo Park, Tae oh Kim, Yong-Hoon Yoon, Sang Yong Om, Minsoo Kim, Hanbit Park, Sang-Cheol Cho, Euihong Ko, Kyusup Lee, Do-yoon Kang, Pil Hyung Lee, Jung-Min Ahn, Soo-Jin Kang, Duk-Woo Park, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
Olanzapine versus aprepitant in the prevention of chemotherapy induced nausea and vomiting (CINV) in breast cancer patients.
Authors: S Mukesh, Sathya M, Akshay Jk
Journal: Journal of Clinical Oncology (2017)

e21670 Background: Olanzapine has been shown to be a safe and effective agent for the prevention of CINV. This study aims to compare olanzapine with aprepitant in the prevention of CINV. Methods: This study included breast cancer patients receiving doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 chemotherapy. Female patient; age, ≥ 18; chemotherapy naïve; no nausea/ vomiting in the past 24 hours were included. Patients with seizure disorder, brain metastasis, prior use of antipsychotic agents and hypersensitivity to olanzapine were excluded. Patients were randomized into two groups. Olanzapine group received tab olanzapine 10 mg on day 1 to 3. Aprepitant group received tab.aprepitant 125mg on day 1 and 80mg on days 2-3. Both groups received inj palnosteron 0.25mg, inj dexamethasone 8mg on day 1. Use of rescue therapy for nausea or vomiting was permitted. The primary end point of the study was complete response (CR) for nausea that is no nausea in the acute (within 24 hours), delayed (days 2-5), and overall periods (0-120 hours). Secondary endpoint was CR for vomiting and no use of rescue drugs in all periods. Beginning with the first day of chemotherapy and daily through day 5, patients were asked to record daily episodes of nausea using a visual analogue scale from 0 to 10, with 0 indicating no nausea and 10 indicating a maximal level of nausea. They were asked to record daily episodes of vomiting (number and time) and the utilization of rescue therapy. Results: A total of 84 patients (42 in each arm) were evaluated and consented for the study. The median age 48 years; range 29-80; ECOG PS - 0, 1. CR for nausea was 84% for the acute period , 58% for the delayed period and 56% for the overall period for the olanzapine group. CR for nausea in aprepitant group was 69% acute period, 55% delayed period, and 55% for the overall period. CR for vomiting was 91% acute; 74% delayed; 70% overall period for olanzapine group. CR for vomiting in aprepitant group was 91% acute; 83% delayed; 83% overall period. There were no Grade 3 /4 toxicities. Conclusions: Olanzapine is better in the prevention of nausea. However aprepitant is better in the prevention of vomiting. Combination of these two agents needs to be studied in future studies.
LOCAL excision and adjuvant contact radiotherapy for EARLY PT1 and PT2 rectal cancers: Outcomes from a single centre in the United Kingdom.
Authors: Amandeep Singh Dhadda, Amy Martin, Iain Andrew Hunter
Journal: Journal of Clinical Oncology (2016)

e15132 Background: There is increasing acceptance for using local excision to treat early rectal cancers to enable organ preservation. However, those with adverse pathological features remain at significant risk of luminal and mesorectal local recurrence. Adjuvant external beam radiotherapy and luminal contact brachytherapy may be employed to reduce this risk. We present data of a series of patients treated at our centre in Hull, England, UK with prospective follow up. Methods: All patients were treated at the Queen’s Centre for Oncology, Hull, United Kingdom between September 2011 and September 2015. Patients were worked up with biopsy, MRI of liver and pelvis, CT Chest and endorectal US prior to local excision. Patients with adverse pathological features who declined or were unfit for completion radical surgery were offered 60Gy in 2 fractions to the site of excision along with external beam chemo/radiotherapy to the pelvis to treat occult mesorectal lymphadenopathy. Follow up consisted of 3 monthly flexible sigmoidoscopy and MRI liver/pelvis and 12 monthly CT Chest. Median follow-up was 26 months (range 9-54 months). Results: Between September 2011 and September 2015 a total of 22 patients were treated with local excision and adjuvant radiotherapy. Demographics of patients are shown in table 1. Median age was 71 years (range 44-87 years). There were 2 local recurrences (9%) of which 1 received successful surgical salvage. Distant recurrences were found in 1 patient (5%). Disease free and overall survival curves are shown in figs 1 and 2. Local recurrence free survival was 91% and overall survival 86% with a median follow up of 26 months. Functional outcomes were assessed using the Low Anterior Resection Score (LARS) with 81% having no LARS and 19% a major LARS (1). Conclusions: Patients with early rectal cancer who have adverse pathological features following local excision and refuse or are unfit for completion surgery may be offered adjuvant external beam and contact radiotherapy. Oncological and functional outcomes for these patients in our centre are excellent and improve on previous data when patients were not offered further adjuvant treatment (2).
Relationship of baseline tumoral IFNγ mRNA and PD-L1 protein expression to overall survival in durvalumab-treated NSCLC patients.
Authors: Brandon W Higgs, Chris Morehouse, Katie Streicher, Marlon C. Rebelatto, Keith Steele, Xiaoping Jin, Fernanda Pilataxi, Philip Z. Brohawn, John A. Blake-Haskins, Ashok Kumar Gupta, Koustubh Ranade
Journal: Journal of Clinical Oncology (2016)

3036 Background: Biomarkers may help to identify non-small cell lung cancer (NSCLC) patients (pts) more likely to have improved outcomes to anti-PD-L1 therapy. From 112 durvalumab (D)-treated pts, we previously reported that high pretreatment levels of PD-L1 protein and IFNγ mRNA expression in tumor biopsies were associated with higher objective response rates. We extend this analysis with mature survival outcome data that includes additional available pts; in addition, we examined changes in gene expression from on-treatment tumors in a subset of pts. Methods: CP1108/NCT01693562 was a nonrandomized phase 1/2 trial evaluating D in pts with advanced NSCLC or other solid tumors. As of 14 DEC 2015, 298 previously treated NSCLC pts received 10 mg/kg Q2W of D ≤12 mos with a median 16.1 mos follow up. Expression profiling of 100 immune-associated genes using Fluidigm Biomark on frozen biopsies and immunostaining for tumoral PD-L1 on fresh or archival biopsies was conducted. 157 pts (55% squamous; 54% ≥2 prior therapy lines) had matched baseline mRNA and PD-L1 data of sufficient quality. Samples with detectable levels of IFNγ mRNA were considered IFNγ+. Pts with ≥25% tumor cells stained for PD-L1 at any intensity were scored PD-L1+. Of the 157 pts, 32 pts had pre- and post-treatment tumors evaluable for 100-gene mRNA analysis. Results: Pts who were IFNγ+/PD-L1+ had a trend of longer overall survival compared to those who were IFNγ-/PD-L1-, even after adjusting for gender, age, prior therapy lines, histology, ECOG, and smoking (Table 1). Following treatment with D, the transcript most highly induced was IFNγ (~2-fold; p<0.016). Conclusions: NSCLC pts with elevated IFNγ mRNA and PD-L1 protein expression in baseline tumor biopsies may have longer survival with D treatment. D treatment induces IFNγ gene expression within the tumor microenvironment. Clinical trial information: NCT01693562.OS by IFNγ and PD-L1 status. # Pts (# events) Median in months (95% CI) Adjusted HRa; p IFNγ+/PD-L1+ 43 (11) NR (8.8, NA) 0.40; 0.016 IFNγ+/PD-L1‒ 20 (8) NR (6.5, NA) 0.38; 0.021 IFNγ‒/PD-L1+ 42 (16) 9.7 (5.1, NA) 0.64; 0.18 IFNγ‒/PD-L1‒ 52 (34) 5.9 (4.1, 10.2) NR=Not Reached; NA=Not Applicable; a Univariate log-rank p<0.05 for all adjusted p <0.05 (not shown)
Association of Leucine-Rich Glioma Inactivated Protein 1, Contactin-Associated Protein 2, and Contactin 2 Antibodies With Clinical Features and Patient-Reported Pain in Acquired Neuromyotonia
Authors: Angela Vincent, Philippa Pettingill, Rosie Pettingill, Bethan Lang, Ron Birch, Patrick Waters, Sarosh R. Irani, Camilla Buckley, Osamu Watanabe, Kimiyoshi Arimura, Matthew C. Kiernan
Journal: JAMA Neurology (2018)

Although acquired autoimmune neuromyotonia (NMT) is associated with voltage-gated potassium channel (VGKC)-complex antibodies, to date there has been no systematic study of autoantibodies to the specific antigens leucine-rich glioma inactivated protein 1 (LGI1), contactin-associated protein 2 (CASPR2), and contactin 2 together with the full clinical syndrome, particularly pain and autonomic and central nervous system involvement.To study the full spectrum of clinical features and serum autoantibodies in patients with NMT, including the effects of pain on quality of life.A cohort study of clinical features and serologic testing in 38 patients with electrophysiologically-confirmed NMT, reviewed clinically between February 2007 and August 2009, in the Universities of Sydney and Kagoshima and followed up across 2 to 4 years. Association of NMT with quality of life was researched in an independent, patient-led, online pain survey conducted from April 2012 to May 2012. Serologic analyses were performed in 2012, and final data analysis was performed in 2016.Clinical data and scores on the modified Rankin Scale (mRS), which measures disability on a range of 0 to 6, with 0 indicating normal and 6 indicating death, before and after treatments were combined with CASPR2, LGI1, and contactin 2 antibody status.Among the 38-person NMT cohort, 25 (65.8%) were male and the median (range) age was 55 (12-85) years. Twenty-three (60.5%) were Japanese and 15 (39.5%) were of white race/ethnicity. Symptomatic treatments (mainly antiepileptic drugs) were used in most patients with mild disease (12 patients with mRS <3), whereas immunotherapies were successful in most patients with mRS scores greater than 2. Autoantibodies to VGKC-complex antigens (17 patients [45%]), bound to CASPR2 (5 [13%]), contactin 2 (5 patients, 1 with CASPR2 [13%]), LGI1 (2 [5%]), or both LGI1 and CASPR2 (6 [16%]). The last group of 6 patients had high mRS scores (mean [SD], 3.8 [1.7]), thymoma (4 patients), pain (5 patients), autonomic (6 patients) and sleep (5 patients) disturbance, suggesting Morvan syndrome. The 56 responders to the independent patient-led survey reported pain that could be severe, anatomically widespread, and that often resulted in unemployment, domestic problems, and poor quality of life.The cohort study detailed underrecognized aspects of the clinical and serologic spectrum of NMT. The heterogeneity of clinical features and of specific antibodies limit associations, but the common existence of thymoma, pain, and autonomic and central nervous system features, often with both LGI1 and CASPR2 antibodies, should be better recognized to more completely address the range of comorbidities and consequences of the disease regarding quality of life.
Flu vaccination: Toronto hospitals cannot implement staff “vaccinate or mask” policy, says ruling
Authors: Owen Dyer
Journal: BMJ (2018)

A group of hospitals in Toronto, Canada, must abandon a policy of forcing healthcare workers to wear surgical masks during the flu season if they have not received the vaccine, an arbitrator has ruled.

The Ontario Nurses Association successfully argued that the requirement was unreasonable, illogical, and a breach of its collective agreement. That agreement stipulated that no nurse could be forced to accept the flu vaccination. But the “vaccinate or mask” policy mainly aimed to compel healthcare workers to accept vaccination, arbitrator William Kaplan found.

He rejected the contention of St Michael’s Hospital, the other party in the case, that this was primarily a patient safety measure. The hospital had failed to prove its case that masks reduce flu transmission, he said, calling …
Prediction of venous thromboembolism (VTE) in multiple myeloma (MM): Myeloma clot score (MCS).
Authors: Kristen Marie Sanfilippo, Tzu-Fei Wang, Suhong Luo, Kenneth Robert Carson, Theodore Seth Thomas, Brian Gage
Journal: Journal of Clinical Oncology (2018)

6585 Background: Guidelines support pharmacologic thromboprophylaxis in MM patients identified as “high-risk” for VTE. Tools for VTE risk assessment in MM are contradictory and have not been validated. Such risk stratification would allow for use of thromboprophylaxis in MM patients at high-risk of VTE while avoiding anticoagulant exposure in patients at low risk. We aimed to develop and validate a risk prediction model for VTE in MM. Methods: We identified patients starting chemotherapy for MM within the Veterans Administration between 9/1999 and 12/2013. Using a split-sample method, we randomly created derivation (2/3) and validation cohorts (1/3). Variables associated with an increased risk of VTE within 6-months of chemotherapy start (univariate p ≤ 0.05) and those with a p ≤ 0.10 and an effect consistent with prior literature were offered into a backward stepwise model. Variables were removed until remaining variables predicted VTE (p < 0.05 OR p ≤ 0.30 plus consistency with prior literature). A Myeloma Clot Score (MCS) was developed based on the parameter estimates. Results: The derivation cohort included 3036 patients of who 371 developed VTE within 6-months of starting chemotherapy. The MCS (Table 1) had a c-statistic of 0.68 in the derivation cohort and similar in the validation cohort. Incidence of VTE over the 6-month study period by score is in Table 1. In the validation cohort, the Hosmer-Lemeshow test was nonsignificant, showing adequate calibration. Conclusions: We developed and validated a risk model for predicting VTE in patients with MM starting chemotherapy. This MCS could be used to select patients who are likely to benefit from thromboprophylaxis. Multivariate model and incidence of VTE by MCS score. Incidence of VTE by MCS Score Multivariate Risk Model Covariate Hazard Ratio p value MCS Points Score Range Derivation Cohort Validation Cohort VTE before MM 2.77 < 0.001 4 ≤1 3.7% 4.4% Low-Dose Dexamethasone 2.12 < 0.001 3 2-5 10.9% 11.2% High-Dose Dexamethasone 2.61 < 0.001 4 Thalidomide 1.68 < 0.001 2 6-8 23% 25% Central Venous Catheter 1.49 0.07 2 ≥9 44% 58.8% Erythropoietin 1.38 0.01 1 BMI ³ 25 1.32 0.02 1 Diagnosis Year 1.05 < 0.001 1* Asian Race 0.45 0.26 -3 Warfarin 0.21 < 0.001 -6 *Patients diagnosed 1999-2007
Blinatumomab use in pediatric patients (pts) with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) from an open-label, multicenter, expanded access study.
Authors: Franco Locatelli, Gerhard Zugmaier, Ajay Vora, Claudia Rossig, Christina Peters, Benoit Brethon, Maureen Megan O'Brien, Laura Belton, Rupert Handgretinger
Journal: Journal of Clinical Oncology (2017)

10530 Background:Blinatumomab (blin), a bispecific T-cell engaging antibody construct, has shown antileukemia activity and tolerability in pts with r/r ALL. We further evaluated safety and efficacy of blin in the first 40 pediatric pts with r/r ALL enrolled in an expanded access study (NCT02187354). Methods: Eligible pts (28 d to &lt; 18 yrs) had ≥ 5% blasts and r/r ALL (refractory, ≥ 2 relapses or relapse after transplant [HCT]). Blin was dosed by continuous infusion (4 wks on/2 wks off) for up to 5 cycles (≥ 5 to &lt; 25% blasts: 15 µg/m 2 /d; ≥ 25% blasts: 5 µg/m 2 /d on d1−7 in cycle 1, then 15 µg/m 2 /d). The primary endpoint was incidence of treatment-emergent (TE) and treatment-related (TR) adverse events (AEs); key efficacy endpoints were complete response (CR) and minimal residual disease (MRD, by PCR or flow cytometry) in the first 2 cycles, relapse-free survival, overall survival and HCT rate. Results: Of the first40 treated pts (median age, 9 [range, 1−17] yrs), 24 (60%) had ≥ 2 relapses, 20 (50%) relapsed after HCT and 5 (13%) were primary refractory; 18 (45%) had ≥ 50% blasts and 21 (53%) had prior HCT. Safety and key efficacy outcomes are shown in the table, including 63% CR in the first 2 cycles. There were 8 relapses and 20 deaths after treatment. Regardless of causality, the most frequent TEAEs were pyrexia (78%), cytokine release syndrome (CRS; 23%) vomiting (23%) and anemia (20%); all 9 CRS events were grade (gr) 1 or 2 and 1 tumor lysis syndrome was gr 3. 10 (25%) pts interrupted treatment and 2 (5%) discontinued due to TRAEs; 13 (33%) pts had gr ≥ 3 TRAEs, including 2 of 3 neurologic events (depressed level of consciousness and headache; both gr 3); 2 fatal AEs were considered unrelated to blin. Conclusions:Here single-agent blin showed antileukemia activity in pediatric pts with high-risk r/r ALL including t(17;19) and AEs consistent with those previously reported for r/r ALL. Clinical trial information: NCT02187354. [Table: see text]