tbuckley/cabot-search huggingface dataset:
Pembrolizumab as first line therapy in patients with unresectable squamous cell carcinoma of the skin: Interim results of the phase 2 CARSKIN trial.
Authors: Eve Maubec, Marouane Boubaya, Peter Petrow, Nicole Basset-Seguin, Jean-Jacques Grob, Brigitte Dreno, Isabelle Scheer-Senyarich, Sabine Helfen, Julie De Quatrebarbes, Elodie Poirier, Lydia Deschamps, Céline Alloux, Isabelle Lopez, Soufian Cherbal, Marie Thérèse Leccia, Marie Beylot-Barry, Florent Grange, Olivier Schischmanoff, Annick Tibi, Vincent Levy
Journal: Journal of Clinical Oncology (2018)

9534 Background: Patients (pts) with advanced squamous cell carcinoma of the skin (SCCS) have a poor prognosis. Response rate (RR) of 46% with an anti PD-1 (REGN2810) was recently shown in 25 pre-treated pts. CARSKIN is an open-label, phase II study evaluating pembrolizumab (Pembro) in unresectable SCCS. We report preliminary efficacy and safety findings. Methods: Chemotherapy naive pts who had unresectable SCCS, with an ECOG PS of < 2 were eligible. Baseline PD-L1 expression was centrally assessed on tumor. Pembro kindly provided by Merck was administered IV (200 mg Q3W) for a period up to 24 mths. CT evaluation was performed at baseline, 9, 15, 24 wks and thereafter Q12W and was independently reviewed. The primary endpoint was RR at 15 wks (RECIST criteria). Using Simon two-stage design, ≥4 responses were required out of 19 pts in stage 1 to continue accrual to 39 pts. Results of stage 1 are reported. Results: Nineteen pts (6, 7 and 6 with local, regional and distant metastasis, respectively) were recruited between March and July 2017, of which 15 (79%) were male. Median age was 80 yrs (range, 61-88); 61% of pts were PS 1. Median number of Pembro infusions was 9 (range, 0-13). Median follow-up was 7 mths. Seventeen pts were evaluable for tumor response, and 19 for toxicity. RR at 15 wks in the ITT population was 42 % (95% CI: 23–63%) corresponding to 7 PR (2 unconfirmed) and 1 CR. Disease control rate at 15 wks was 58% (11/19 including 3 SD). Only 1 responder progressed. Median PFS is 7 mths and median OS is not reached. There was no Pembro-related death or SAE. One pt discontinued Pembro due to grade 2 colitis. Pembro-related AE occurred in 63% of pts, the most frequent AEs being rash (32%), pruritus (16%), fatigue (26%), dysthyroidism (10%), and diarrhea (10%). Baseline PD-L1 expression was positive in 11 cases (58%). Median PD-L1 expression (Q1-Q3) was 28% (1-75%) in responders vs 0% (0-3%) in non-responders at 15 wks (P = .15). Conclusions: As first line treatment, pembrolizumab monotherapy provided encouraging clinical activity characterized by a high RR and durable response and was well tolerated in these elderly pts. The second stage of CARSKIN is ongoing. Clinical trial information: NCT02883556.
Implementing improved pathologic nodal (pN) staging during non-small cell lung cancer (NSCLC) resection: A population-based study.
Authors: Meredith Ray, Matthew Smeltzer, Nicholas Ryan Faris, Carrie Fehnel, Cheryl Houston-Harris, Philip Ojeabulu, Olawale Akinbobola, Lynn Wiggins, David Talton, Ed Owen, Lawrence Deese, Richard Eubanks, Bradley Aaron Wolf, Todd Robbins, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2018)

e18791 Background: Poor pN staging is the main driver of poor long-term survival after NSCLC resection. We used the Reach, Effectiveness, Adoption, Implementation, Maintenance framework to study implementation of a lymph node collection kit designed to improve pN staging. We present the Effectiveness and Adoption domains. Methods: Population-based multiple baseline, staggered implementation design involving all NSCLC resections in 11 hospitals with ≥5 resections/year in 4 contiguous Dartmouth Referral Regions in E. Arkansas, N. Mississippi, W. Tennessee. Institutional baseline performance from 2009-2013 was measured retrospectively, then prospectively from 2014-2017, through introduction of the kit at roughly 3 month intervals to institutions grouped into 3 implementation cohorts from 2015 onwards. For Effectiveness we report impact on pN-staging quality; for Adoption we measured surgeon- and institutional-level penetration of kit use over time. Results: There were 1,083 pre-implementation resections, 970 post-implementation resections with and 916 post-implementation resections without the kit. Age, insurance, change in nodal status, and pT were similar across cohorts. Kit-resections attained quality benchmarks most frequently. Without the kit, post-implementation performance reverted to pre-implementation levels: National Comprehensive Cancer Network criteria (19% pre/78% post with/30% post without kit; p < 0.001); American College of Surgeons criteria (29/75/36%; p < 0.001); non-examination of lymph nodes, ie ‘pNX rate’ (10/0/10%; p < 0.001); non-examination of mediastinal lymph nodes (26/2/28%; p < 0.001). 55 surgeons performed at least one resection (16 pre/34 post adopter/5 post non-adopter). Surgeon adoption increased every year and the kit was used in 73% of resections in 2017. Only in 1 of 11 institutions has the kit never been used. In 2017 use of the kit was 0-25% in 3 hospitals, 25-50% in 3, 50-75% in 1, and 75-100% in 4 hospitals. Conclusions: Implementation of routine use of a lymph node specimen collection kit to improve pN staging of resectable NSCLC is highly feasible and effective in diverse settings.
A retrospective analysis of apatinib in advanced non-small cell lung cancer patients refractory to chemotherapy.
Authors: Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi
Journal: Journal of Clinical Oncology (2017)

e20562 Background: Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2. A phase II clinical study proved that 750 mg qd apatinib showed clinical benefit in patients with advanced non-squamous NSCLC refractory to two or more lines of chemotherapy (Zhang et al. 2012 ASCO, 7548). In this retrospective study, we assessed the efficacy of apatinib at a more frequently used dose of 500 mg qd in advanced chemo-refractory NSCLC. The preliminary clinical outcome of apatinib in patients with brain metastases was also reported. Methods: Clinical data of 25 advanced NSCLC patients who received oral apatinib 500 mg once daily as second-line and beyond therapy between August 2015 and May 2016 were reviewed. Results: The median progression-free survival (PFS) was 5.17 months (95% CI: 0.76–9.57 months). The response rate (RR) and disease control rate (DCR) were 8.0% and 68.0%, respectively. In the second-line setting (n=13), the mPFS was 7.37 months (95% CI: 0.01–14.72 months), and the RR and DCR were 0.0% and 61.5%, respectively. In the third-line and beyond setting (n=12), the mPFS was 5.17 months (95% CI: 1.78–8.55 months), and the PR and DCR were 16.7% and 75.0%, respectively. The DCR was 57.1% for 7 patients with brain metastases following apatinib administration. All patients were well tolerant to apatinib without any Grade 3 or 4 adverse events. The most common Grade 1 or 2 adverse events included hypertension (72.0%), hand-foot syndrome (24.0%), fatigue (24.0%), abnormal liver function (20.0%), nausea (12.0%) and palpitation (8.0%). Conclusions: Apatinib is effective and well tolerated in patients with advanced NSCLC, even at a dose of 500 mg qd, and might offer a new option for the treatment of such patients with brain metastases.
TCT-284 Coronary Computed Tomography Angiography-Defined Low Attenuation Plaque to Predict True Lipidic Plaque Determined by Combined Intravascular Imaging
Authors: Rafal Wolny, Mitsuaki Matsumura, Akiko Fujino, Gary Mintz, Eisuke Usui, Tetsumin Lee, Rine Nakanishi, Masahiro Hoshino, Taishi Yonetsu, Tsunekazu Kakuta, Akiko Maehara
Journal: Journal of the American College of Cardiology (2018)
Tumor regression grading after neoadjuvant chemotherapy predicts long-term outcome of stage IIIC epithelial ovarian cancer.
Authors: Mingyi Zhou, Liankun Li, Xiaobin Wang, Chunyan Wang, Danbo Wang
Journal: Journal of Clinical Oncology (2018)

5547 Background: Prognostic value of tumor regression grading (TRG) after neoadjuvant chemotherapy (NAC) in patients with FIGO stage IIIC epithelial ovarian cancer (EOC) is controversial. Methods: A total of 55 stage IIIC EOC patients who underwent interval debulking surgery (IDS) after NAC at the Department of Gynecology of Liaoning Cancer Hospital and Institute between January 2003 and September 2016 and had full information were involved this retrospective study. All the pathological sections were individually reviewed by two pathologists. TRG was determined by the ratio of viable tumor versus fibrosis, ranging from TRG 0 when no viable tumor, to TRG 5 when fibrosis was absent. TRG 1 was defined as regression more than 75%, TRG 2 was defined as regression more than 50% but less than 75%, TRG 3 was defined as regression more than 25% but less than 50%, and TRG 4 was defined as regression less than 25%. Patients were stratified into TRG 0-1-2 group and TRG 3-4-5 group according to cut-off values calculated through receiver operating characteristic (ROC) curves. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method. Univariate analyses were performed using log-rank tests. Multivariate analyses were performed using Cox regression analysis to assess the prognostic factors of TRG, which were expressed as hazard ratios (HRs). Results: Univariate and multivariate analyses suggested that TRG and residual disease (RD) were independent predictive factors of PFS, and TRG, RD and CA125 change were independent predictive factors of OS. TRG was a better prognostic factor compared with CA125 value change after NAC (area under curves [AUC] of the ROC of TRG 0.93 versus AUC of the ROC of CA125 change 0.69). The median PFS of the patients in TRG 0-1-2 group was 14.0 months longer than TRG 3-4-5 group (26.0 months versus 12.0 months, HR 2.19, 95% confidence interval [CI] 1.17-4.07, P = 0.014). The median OS of the patients in TRG 0-1-2 group was 28.6 months longer than TRG 3-4-5 group (50.4 months versus 21.8 months, HR 3.10, 95%CI 1.49-6.42, P = 0.002). Conclusions: TRG after NAC was an independent prognostic factor of patients with FIGO stage IIIC EOC.
Modulation of neutrophil gelatinase-associated lipocalin2 (NGAL, oncogene 24/p3), proinflammatory cytokines (PIC), cystatin C and lipid rafts disruption (LR) with HMG-CoA reductase inhibitor simvastatin (SV) in patients with JAK2V617F myeloprliferative neoplasms (MPN).
Authors: Eugene McPherson
Journal: Journal of Clinical Oncology (2016)

e18560 Background: MPN is a manifestation of diseases with overproduction of myoerythroid cells, platelets, BCR/abl fusion genes with prevalence to polycythemia Vera (PCV), essential thrombocythemia (ET), and myelofibrosis. These Ph-negative pts are prone to JAK2V617F mutations via paracrime DNA damages/MPN cells from their secretions of LCN2/NGAL correlation with PIC. Methods: We present a 60 YOF who was referred to our institution with respiratory failure and persistent thrombocythemia with platelets > 100K, Bone marrow aspiration/biopsy was consistent with hypercellular trilineal hematopoiesis with increased megakaryocytes/minimal fibrotic stromal background. Blood analysis was + JAK2V617F. Treatment with Hydrea, SV for dyslipidemia (HDL-C < 30). Results: Over 24 weeks, CRP trended down to 0.58 from 19.20; Cystatin C 2.80 mg/L normalize; HDL-C significantly elevated > 60; sIL2R level normalized from 29,327.4 pg/ ml to 9,442.5 pg/ ml; platelet remained below 600K; IGF-1 was normal and 182 ng/ml down from 288 ng/ ml; vWF was elevated at 226% ;apolipoprotein A1-normal and 123 mg/dL; erythropoietin > 200 mu/ mL; BNP - 115; ESR < 35; Conclusions: By regulating the cholesterol lipid rafts and dissociation of MPN cells JAK2V617 F cells secretions of LCN2/NGAL oncogene 24/p3 with disruption of lipid rafts with HMG-CoA reductase inhibitor, SV, which modulates activation of NFKb via iKB kinase (IKK) and silencing TLR 4 signals and activating STAT3 may prevent cyokine expression and promote innate immunity with suppression of MPN JAK2V617F cells clonal DNA damage and progression to myelofibrosis and leukemia in ET patients.
Effect of adjuvant therapy for stage II and III ovarian cancer in patients older than 70 years.
Authors: Samip R. Master, Richard P. Mansour, Runhua Shi
Journal: Journal of Clinical Oncology (2018)

e17557 Background: Data on safety and efficacy of adjuvant chemotherapy for stage II and III ovarian cancer in elderly patients is not clearly defined as these patients are underrepresented in clinical trials. We did a retrospective analysis of elderly patients (≥70 years) with stage II and stage III ovarian cancer to investigate adjuvant chemotherapy effect on survival in these patients. Methods: Data was analyzed from 18, 890 women (≥ 70 years of age) registered in the National Cancer Database (NCDB) who were diagnosed with Stage II and Stage III ovarian cancer between 2004 and 2013 and had follow-ups to end of 2014. The primary predictor variable was adjuvant chemotherapy, and overall survival was the outcome variable. Additional variables addressed and adjusted included age, race, Charlson Comorbidity Index and grade of tumor. Results: The mean age was 67.6 years and SCD was 10.3 years. In multivariate analysis, after adjusting for secondary predictor variables, receipt of adjuvant chemotherapy for was a statistically significant predictor of overall survival from stage II and stage III ovarian cancer. Relative to patients who did not receive adjuvant chemotherapy, the patients who got adjuvant chemotherapy had 50.3% decreased risk of mortality. Among the factors analyzed, age, race, stage, comorbidity index and grade 0f tumor were found to be significant predictors of survival. Conclusions: Among the patients with stage II and Stage III ovarian cancer over the age of 70 years, adjuvant chemotherapy lead to improved survival outcomes by 50%. In addition, stage III are 2.2 times more likely to die as compare to stage II. Poor and moderately differentiated are 58% more likely to die as compared to well differentiated ovarian cancer. Multivariate Cox regression analysis Factors Level HR Lower Upper Age 70-79 years 1 > = 80 years 1.429 1.369 1.492 Race White 1 Asian 0.932 0.798 1.087 Black 1.132 1.037 1.237 CCI 0-1 1 > 1 1.280 1.224 1.338 Stage II 1 III 2.195 2.063 2.335 Grade Well- differentiated 1 Moderately differentiated, moderately well differentiated, intermediate differentiation 1.583 1.402 1.787 Adjuvant Chemotherapy No 1 Yes 0.497 0.473 0.523
Phase II clinical trial using novel peptide vaccine cocktail as a postoperative adjuvant treatment for surgically resected pancreatic cancer patients.
Authors: Hiroki Yamaue, Motoki Miyazawa, Masahiro Katsuda, Hiroyuki Maguchi, Hiroshi Ishii, Kenji Yamao, Manabu Kawai, Seiko Hirono, Ken-Ichi Okada, Atsushi Shimizu, Yuji Kitahata
Journal: Journal of Clinical Oncology (2016)

e14587 Background: We conducted a multicenter phase II study using peptide vaccine cocktail named OCV-C01 containing epitope peptides derived from KIF20A, VEGFR1, and VEGFR2 combined with gemcitabine with the aim to estimate the disease-free survival and to explore the surrogate biomarker associated with this immunotherapy treatment. Methods: A single arm phase II study of 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy at the four Japanese high volume centers was performed. Of each 28-day treatment cycles, eligible patients received subcutaneous injection of 1mL of OCV-C01 on days, 1,8,15 and 22 for 48 weeks, and Gemcitabine was administered intravenously at a fixed dose of 1000mg/m2 on days, 1, 8 and 15 for 24 weeks. The primary endpoint was disease-free survival and secondary endpoints included safety, overall survival (OS), and immunological assays on peptide-specific CTL activity and KIF20A expression in resected pancreatic specimens. Results: The median DFS was 15.8 months (95%CI, 11.1-20.6), and the DFS rate at 18 months was 34.6% (95%CI 18.3-51.6). The median OS was still not reached and the overall survival rate at 18 month was 69.0% (95%CI 48.8-82.5). The administration of OCV-C01 was well tolerated. In the subgroup analysis of the per protocol set,there was significant differences in DFS between patients with positive CTL responses specific for KIF20A peptides and without them (p= 0.027), and between patients with positive KIF20A expression and without them (p= 0.014). In addition, all 4 patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer, and DFS of them was significantly longer than 19 patients who underwent R0 resection without KIF20A expression (p= 0.011). Conclusions: OCV-C01 combined with gemcitabine was tolerable, and DFS was favorably compared with previous data for resected pancreatic cancer. DFS of patients with positive KIF20A expression in resected pancreatic cancer specimen might be prolonged with frequent KIF20A-specific CTL response by receiving this immunotherapy treatment. Clinical trial information: UMIN000007991.
Achievement of complete remission (CR) as an endpoint for patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib.
Authors: Paolo Strati, Mariela Sivina, Ekaterina Kim, Michael J. Keating, William G. Wierda, Alessandra Ferrajoli, Hagop M. Kantarjian, Zeev Estrov, Nitin Jain, Philip A. Thompson, Jan Andreas Burger
Journal: Journal of Clinical Oncology (2018)

7522 Background: Achievement of a deep response with chemoimmunotherapy associates with prolonged survival in patients with CLL. However, it remains unclear whether this is a desirable endpoint also for patients treated with ibrutinib, who generally achieve partial remissions (PR) rather than CRs. Methods: We analyzed the characteristics and outcomes of patients with CLL enrolled in a phase 2 study (NCT02007044) of frontline or salvage continuous ibrutinib therapy, with or without 6 cycles of Rituximab, at our institution between 12/2013 and 10/2016. Progression-free survival (PFS) was defined as time from treatment initiation to disease progression and/or death secondary to CLL-related complications. Results: Two-hundred and six patients were included in this study and response was achieved in 186 (99%) of 188 evaluable patients, including PR with lymphocytosis. Six (3%) patients achieved a CR with negative minimal residual disease (MRD), 40 (21%) CR with positive MRD, 3 (2%) nodular PR, 119 (63%) PR, and 18 (10%) PR with lymphocytosis. No significant differences were observed among the baseline characteristics of the 46 patients achieving CR as compared to the 140 patients achieving PR. Achievement of CR was associated with a significantly prolonged PFS (1 event out of 46 patients, 3-year PFS 97%) as compared to PR (14 events out of 140 patients; 3-year PFS 78%)(p = 0.04). None of the baseline characteristics associated with prolonged PFS. Overall, after a median follow-up of 22 months (range, 2-37 months), median PFS was not reached and 19 patients (9%) progressed and/or died of CLL-related complications. Among patients in CR, 1 (2%) with positive MRD died of metastatic melanoma, after 19 months on treatment. Among patients in PR, 13 (8%) developed progressive CLL (1 with Richter transformation), 1 (0.5%) died of metastatic colon cancer, and 4 (1%) died of severe infections. Conclusions: This is the first study showing that achievement of CR is a desirable endpoint for patients with CLL treated with ibrutinib, associating with prolonged PFS. Our results support the development of future combination studies, aimed at achieving higher rates of CR in patients treated with ibrutinib. Clinical trial information: NCT02007044.
Abstract 17074: Melody Valve for Surgical Mitral and Tricuspid Valve Replacement in Children With Small Annuli
Authors: Breanna L Piekarski, Francesca R Pluchinotta, David Zurakowski, James M Hammel, Oliver Kretschmar, Paul J Chai, David M McMullan, Bret A Mettler, Phillip T Burch, Lale Hakami, David B Meyer, Frederic Jacques, Alessandro Frigiola, Sitaram M Emani
Journal: Circulation (2016)

Introduction: Current options for atrioventricular valve replacement are limited to mechanical valves and fixed diameter bioprostheses, with no options for annuli less than 15 mm diameter. Fixed di...
Outcomes according to involved free light chain (FLC) levels in patients with normal FLC ratio after initial therapy in light chain amyloidosis (AL).
Authors: Nidhi Tandon, Surbhi Sidana, Angela Dispenzieri, Morie A. Gertz, Martha Lacy, David Dingli, Francis Buadi, Amie L. Fonder, Suzanne R. Hayman, Yi Lisa Hwa, Miriam A. Hobbs, Prashant Kapoor, Wilson I. Gonsalves, Nelson Leung, Ronald S. Go, John Anthony Lust, Stephen J. Russell, Robert A. Kyle, S.Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2017)

8049 Background: Complete response in AL is defined as normal FLC ratio with negative serum and urine immunofixation. It is not clear if high involved serum FLC (hIFLC) in a patient with normal ratio may contribute to ongoing amyloid formation and hence affect outcomes. Methods: Data of 1308 patients (pts) with systemic AL seen within 90 days of diagnosis, at Mayo Clinic between 2006-2015, was analyzed retrospectively. Among these, 369 pts had 2 consecutive normal FLC ratio values after 1st line treatment and form the study population. Log rank test was used to estimate survival differences. Results: Among these 369 pts, pts with hIFLC at 1 st reading of normal FLC ratio (hIFLC1; n=170; 46.1%) were compared to those who did not (n=199; 53.9%). At diagnosis, the median age [61.5 vs 60.8 years (y); p=0.2], proportion of males (62.4 vs 58.3%; p=0.4), percentage of pts with renal involvement (73.5 vs 64.8%; p=0.07), in mayo stage I / II / III / IV (32.9% / 23%/ 27.3% / 16.8% vs 43.6 %/ 22.9% / 18.1% / 15.4%; p=0.1), with bone marrow plasma cells &gt;10% (24.2 vs 30%; p=0.2) and with presence of t(11; 14)(48.4 vs 60; p=0.08) was similar, while cardiac (67.5 vs 53.3%; p=0.006) and hepatic (18.2 vs 9.1%; p=0.01) involvement was higher in hIFLC1 group. The median follow-up from diagnosis was 6.1 y (95% CI; 5.6, 6.8). The median progression free survival (PFS) in pts who had hIFLC1 was lower than for those who did not; 2.6 y (95% CI; 1.9, 4.5) vs 5.2 y (95% CI; 4.6, 6.4), p&lt;0.0001, as was the median overall survival [OS; 6.7 y (95% CI; 4.5, 8.3) vs not reached (NR), p&lt;0.0001]. We performed a more stringent comparison for pts with 2 consecutive hIFLC values (hIFLC2; n=112; 30.4%) versus not (n=257; 69.6%). The median PFS (3.2 y; 95%CI; 2.2, 4.5 vs 5.6 y; 95% CI; 4.7, 7.1; p&lt;0.0001) and OS (7.8 y; 95% CI; 6.4, NR vs NR; 95%CI; 9.5, NR; p&lt;0.0001) were significantly reduced in pts with hIFLC2 versus not as well. A multivariate analysis confirmed an impact of hIFLC1 and hIFLC2 on PFS/OS independent of serum creatinine. Conclusions: In pts with systemic AL, persistent elevation of the involved FLC predicts for poor prognosis (independent of serum creatinine) even among those who achieved normal FLC ratio after 1st line treatment.