tbuckley/cabot-search huggingface dataset:
Phase II neoadjuvant and immunologic study of B7-H3 targeting with enoblituzumab in localized intermediate- and high-risk prostate cancer.
Authors: Eugene Shenderov, Angelo Demarzo, Karim Boudadi, Mohamad Allaf, Hao Wang, Carolyn Chapman, Christian Pavlovich, Trinity Bivalacqua, Tanya Skelton O'Neal, Rana Harb, Rehab Abdallah, Charles G. Drake, Drew M. Pardoll, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2018)

TPS5099 Background: B7-H3 is part of the B7 superfamily and is an immune checkpoint expressed on multiple tumor types. B7-H3 inhibition limits tumor growth by enhancing cytotoxic T lymphocyte function through engagement with an unknown receptor. B7-H3 is highly expressed in prostate cancer (PCa) and is negatively correlated with both biochemical recurrence and metastasis. Enoblituzumab is a humanized Fc-optimized B7-H3–targeting antibody that induces antibody-dependent cellular cytotoxicity (ADCC). To date, approximately 180 patients have received Enoblituzumab monotherapy in a phase I study, with good tolerability. To determine the anti-tumor, immunological and biological effects of B7-H3 inhibition in high-risk localized PCa, we are currently conducting a neoadjuvant and pharmacodynamic phase II study (NCT02923180). We hypothesize that neoadjuvant enoblituzumab treatment will be feasible, safe, and will produce a robust antitumor immune responses that will correlate with clinical outcomes in high-risk prostate patients undergoing prostatectomy. Methods: In this investigator-initiated single-center, single-arm, open-label phase II neoadjuvant trial we plan to enroll 32 patients with localized PCa (16/32 accrued). Patients must have clinical stage T1c–T3b, N0, M0 disease and Gleason sum 7-10. Eligible patients undergo a pre-treatment prostate biopsy and receive enoblituzumab at a dose of 15mg/kg IV weekly for 6 doses beginning 50 days prior to radical prostatectomy. Fourteen days after the last dose of enoblituzumab, prostate glands are harvested at the time of radical prostatectomy, and prostate tissue is examined for the secondary pharmacodynamic endpoints. The primary co-endpoints are (1) to characterize safety and tolerability of enoblituzumab treatment in the neoadjuvant setting, and (2) to estimate clinical benefit based on PSA0 response (PSA < 0.1 ng/mL) 12 months after radical prostatectomy. Secondary endpoints include evaluation of anti-tumor effects consistent with enoblituzumab's proposed mechanism of action (apoptosis, proliferation), ADCC markers, and assessment of immunologic correlates (CD8, FOXP3, PD-L1 expression). Clinical trial information: NCT02923180.
Changes in oncological outcomes: Comparision of conventional and minimally invasive esophagectomy over ten years.
Authors: Misbah Khan, Anam Muzaffar, Aamir Ali Syed, Shahid Khattak, Muhammad Ijaz Ashraf, Namra Urooj, Ali Raza Khan
Journal: Journal of Clinical Oncology (2016)

e15524 Background: Minimally invasive esophagectomy is becoming a routine for resectable esophageal cancer. Aim of this retrospective study is to evaluate oncologic adequacy of the procedure at our centre. Methods: Out of 1252 registered esophageal adeno and squamous cell cancer patients from July 2006 to July 2015, 206 patients who had a surgical resection with curative intent and a complete medical record for all variables were evaluated thru our hospital medical record system( HIS). Patients were allocated into 3 groups; conventional open OE 87, total minimally invasive MIE 91and Hybrid 28. Primary outcomes are tumor recurrence, disease free survival over a minimum follow-up of 1 year and, adequacy of pathological specimen in terms of number of lymph nodes harvested and clear longitudinal < 1cm and circumferential( > 1mm) resection margins. Secondary end point is to look for trends in the oncologic clearance in each group over ten years. Results: Groups were found to be homogenous in terms of gender, histological type and grade, neoadjuvant and adjuvant therapy and initial radiological T and pathological N stage(p > 0.05). Overall there was no significant difference (p > 0.05) between groups (OE vs. MIE vs. Hybrid), for median number of lymphnodes retrieved(13 vs.14 vs.15), resection margin positivity (55.8% vs. 35.7% vs 44% for patients with residual disease N = 103;50%) or recurrence(45.2% vs. 37.3% vs. 25%). Disease free Kaplan Meier Survival over a mean follow-up of 2.3 years was higher in the OE group( 13.8months vs 9.7 MIE and 11.8 hybrid ) without a statistical significance. Learning curve for comparable oncologic clearance was 1 year. Conclusions: Minimally invasive esophagectomy are found to be oncologically adequate as compare to their conventional analogue Uni-Variate Multi-Variate Analysis Esophagectomy compared to OE Odds ratio 95% CI p Adjusted odds ratio 95% CI p Margin + MIE -0.82 (0.2- 1.02) 0.054 -0.48 (0.08- 4.8) 0.65 Hybrid -0.5 (0.2- 2.6) 0.53 -0.73 (0.14- 1.64) 0.243 Recurrence MIE 0.72 (0.34- 1.54) 0.4 0.25 (0.06- 1.04) 0.06 Hybrid 0.40 (0.13- 1.25) 0.12 0.8 (0.07- 8.9) 0.9 Lymphnodes harvest N < 10 MIE -0.30 (0.4- 1.5) 0.40 -0.31 (0.3- 1.9) 0.53 Hybrid -0.5 (0.21- 1.81) 0.4 -0.76 (0.11- 2.1) 0.32
TCT-765 Effect of PSP and other Elements of Technique on 3 Year Outcomes Among Metallic Everolimus-Eluting Stent-Treated Patients in the ABSORB Trials
Authors: Stephen Ellis, Dean Kereiakes, Patrick Serruys, Yoshinobu Onuma, Takeshi Kimura, Runlin Gao, Ovidiu Dressler, Thomas McAndrew, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Investigation of <i>PIK3CA</i> gene mutation in Indian breast cancer and its correlation with clinicopathological findings.
Authors: Simi Bhatia
Journal: Journal of Clinical Oncology (2018)

e13512 Background: Mutations in PIK3CA gene represent one of the most common genetic alterations seen in approximately 18-40% of breast carcinomas. More than 80% of the PIK3CA mutations occur at two “hotspots” in exon 9 and exon 20, which encode the helical (E542K and E545K) and kinase (H1047R) domains, respectively. Methods: In this study, we evaluated PIK3CA mutation in 185 Indian breast cancer patients by direct DNA sequencing. Tumor histology, tumor grade and other histological findings were evaluated as per Scarff-Bloom-Richardson classification. Immunohistochemically analyses using antibodies against estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) were performed following optimized laboratory protocol. Results: Histopatholgical examination of the tumors revealed that bulk of the cases were ductal in origin (n = 178, 96.1%), followed by lobular (n = 5, 2.7%) and other (n = 2, 1.2%) category. Furthermore, ~ 50% of tumors were classified as grade III, 47% as grade II and only 3.3% as grade I. Tumor sub typing with IHC analysis for ER, PR, and HER2 antibody revealed that 63.2%, 49.2% and 28.2% of the cases showed positive expression for the respective markers. PIK3CA mutations were observed in 23.2% (43/185) of breast tumor samples. PIK3CA mutations were more frequent exon 30 (76.8%) than in exon 9 (23.2%). Sequencing analysis revealed mutations at codon 542 and 545 (E542K, E545K, E545A and E545G) in the helical domain, and two different amino acid substitutions at codon 1047 (H1047R and H1047L) in the kinase domain. PIK3CA mutations were more frequent in older patients, smaller size tumors, ductal carcinomas, grade II tumors, lymph node-positive tumors and non-DCIS tumors. In addition, PIK3CA mutations were common in ER, PR and HER2 positive cases (30 %), and a comparatively low frequency was noted in triple-negative. Conclusions: To our knowledge, this is the largest study to evaluate PIK3CA mutation in Indian breast cancer patients. The frequency and distribution pattern of PIK3CA mutations is similar to global reports. PIK3CA mutation seems to be commonly seen in hormone positive tumors and relatively low in triple negative breast tumors.
Examining progression free survival (PFS), overall survival (OS), and toxicities of palbociclib in a geriatric population.
Authors: Katherine Clifton, Jaime Kimmel, Jennifer Keating Litton, Debu Tripathy, Meghan Sri Karuturi
Journal: Journal of Clinical Oncology (2018)

10039 Background: A recent FDA pooled analysis of patients treated with CDK4/6 inhibitors showed a trend towards improved PFS in the geriatric population, although this was not statistically significant. The study found more grade 3-4 events in the geriatric population, however the overall adverse event rate was low. The objective of this study was to analyze PFS, OS, dose reductions, dose delays and toxicity in a geriatric population receiving palbociclib as standard of care. Methods: Patients with metastatic breast cancer receiving palbociclib in any line of therapy were identified from a cohort of 845 pts at MDACC. Clinical, demographic, comorbidities, recurrence and survival data were collected. Dose delays, dose reductions, and toxicities were retrospectively extracted from the medical record. Data was analyzed using Fischer's exact test for categorized variables and T test/Wilcoxon rank-sum test for continuous variables. PFS and OS were analyzed using the Kaplan Meier method. Results: 605 pts who met eligibility criteria were included. Pts receiving palbociclib on clinical trial were excluded. 160 pts were ≥ 65 years-old and 92 pts were ≥ 70 years-old. Pts ≥ 70 had a significantly increased number of dose reductions (p = 0.03) and dose delays (p = 0.02) compared to the younger pts. Pts ≥ 70 had significantly lower baseline GFR (p < 0.0001) and higher Charleston Comorbidity index (p < 0.0001). There was no significant increase in toxicity rate, including neutropenic fever, infections, or hospitalizations, in the ≥ 70 cohort (p = 0.3). The ≥ 70 cohort had a significantly improved PFS as compared to the younger cohort (p = 0.02). This was also true when an age cut-off of ≥ 65 was used (p = 0.009). There was no difference in OS in either cohort (age ≥70 p = 0.4, age ≥ 65 p = 0.9). Conclusions: Palbociclib was well tolerated in the geriatric population. Interestingly, the geriatric population was found to have improved PFS. Palbociclib has been shown to restore senescence signaling. Further studies are warranted to investigate if palbociclib may work synergistically with already enhanced senescence pathways in the geriatric population.
A phase I single arm, open label clinical trial evaluating safety of MAGE-A10c796T in subjects with advanced or metastatic head and neck, melanoma, or urothelial tumors (NCT02989064).
Authors: David S. Hong, Marcus O. Butler, Ryan J. Sullivan, Connie L. Erickson-Miller, Trupti Trivedi, Karen Chagin, Arundathy N. Bartlett-Pandite, Rafael G. Amado
Journal: Journal of Clinical Oncology (2017)

TPS3098 Background: MAGE-A10 is a cancer/testis antigen that has been identified in 42, 26 and 17% of urothelial, melanoma and head and neck tumors, respectively. This study will evaluate the safety and antitumor activity of genetically engineered affinity enhanced autologous MAGE-A10 c796 T cells directed towards a MAGE-A10 peptide expressed on tumors in the context of HLA *02:01 and/or *02:06. Methods: This first-in-human T cell dose escalation study utilizes a modified 3+3 design to evaluate safety, including dose limiting toxicities (DLT). Secondary objectives include anti-tumor activity (overall response, duration of response, time to response, PFS, OS) and translational research assessments. Patients are screened under a separate protocol (NCT02636855). Those who are HLA*02:01 and/or *02:06 positive and have inoperable or metastatic (advanced) urothelial cancer, melanoma, or squamous cell head and neck tumors with MAGE-A10 expression and meet all other entry criteria are eligible for treatment. Patients must have received standard of care therapies and have progressive disease. Following apheresis, the T cells are isolated and expanded with CD3/CD28 beads, transduced with a lentiviral vector containing the MAGE-A10 c796 TCR, and infused into the subject (Day 1) after receiving lymphodepleting chemotherapy (fludarabine 30 mg/m 2 /day and cyclophosphamide 600 mg/m 2 /day, on days -7, -6 and -5). The DLT observation period will be during the first 30 days following the infusion of MAGE-A10 c796 T for each patient in all groups. Up to 10 patients will be enrolled at the target dose. Disease assessments will be conducted at week 6, 12, 18 and 24, and then every 3 months until confirmation of disease progression. On study tumor biopsies and blood samples will be evaluated to compare the pre- and post-T cell infusion immune profile for association with treatment outcome. Clinical trial information: NCT02989064. [Table: see text]
TCT-477 Prevalence and Clinical Impact of Baseline QRS Duration in Patients With Severe Aortic Stenosis Two Years After Aortic Valve Replacement in the PARTNER II Trial
Authors: Leon Gustavo Macedo, Ioanna Kosmidou, Maria Alu, Fabien Praz, Tamim Nazif, Susheel Kodali, Vinod Thourani, Wilson Y. Szeto, Chandan Devireddy, Samir Kapadia, Raj Makkar, Martin Leon
Journal: Journal of the American College of Cardiology (2018)
Does coaching goals of care discussion skills make a difference?
Authors: Nina A. Bickell, Kerin B. Adelson, Jason Parker Gonsky, Sofya Pintova, Benjamin Philip Levy, Jenny J. Lin, Rebeca Franco, Natalia Egorova, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2017)

6586 Background: Advanced cancer patients often have a poor understanding of their cancer prognosis. Goals of Care (GoC) discussions provide information about the cancer, its treatment &amp; prognosis and elicit patient values. Little is known about the best ways to enhance patient understanding, clarify values and move GoC discussions earlier in the disease process. We report the effect of coaching oncologists on GoC discussions. Methods: We recruited oncologists &amp; their advanced cancer patients with &lt; 2 year prognosis to a RCT testing a coaching model communication skills training. Patients were surveyed after their post-imaging visit. We define GoC discussions as patient report that their doctor talked about their cancer prognosis and clarified things most important to them given their disease. Outcome variables assess the impact of GoC on patients’ knowledge on what to expect and clarity of values. Results: We enrolled 22/25 (88%) oncologists and 70% of eligible patients of whom 96 (55%) completed a survey. On average, doctors were 44 yrs old (32-66) and in practice 14.5 yrs (5-40). Patients’ mean age was 62 yrs (20-95), 40% females, 58% white, 24% Latino &amp; 22 % black. Overall, 2/3 of patients reported their treatment’s goal was to cure their cancer; 14% reported cure to be unlikely. Patients felt more knowledgeable (79% vs 21%; p = 0.02) when their doctors discussed treatments, side effects &amp; quality of life. When patients were asked about things important to them, they report being a bit clearer about their values (65% vs 35%; p = 0.16). Compared to controls, intervention patients felt more knowledgeable (78% v 63%; p = 0.17) but did not feel clearer about their values (60% v 54%; p = 0.59). Multivariate modeling found that poor health literacy (OR = 0.2; 95%CI: 0.07-0.82), having a GoC discussion (OR = 10.2; 1.7-63.1) and being in the intervention group (OR = 8.8; 1.4-55.2) significantly affected knowledge (model c = 0.88; p &lt; 0.01). However, discussing what’s important to patients did not help patients feel clearer about their values (OR = 2.7; 0.6-12.2; model c = 0.82; p &lt; 0.05). Conclusions: Using a coaching model to teach oncologists communication skills may improve patients’ understanding of what to expect with their cancer but does not impact their clarity of values. Clinical trial information: NCT02374255.
Relapse-free survival (RFS) of clinical T2-4N0 urothelial bladder carcinoma (UBC) after radical cystectomy (RC), with or without perioperative chemotherapy (POC): Endpoints for clinical trial design.
Authors: Marco Bandini, Alberto Briganti, Elizabeth R. Plimack, Guenter Niegisch, Evan Y. Yu, Aristotelis Bamias, Neeraj Agarwal, Srikala S. Sridhar, Cora N. Sternberg, Ulka N. Vaishampayan, Christine Theodore, Jonathan E. Rosenberg, Joaquim Bellmunt, Matt D. Galsky, Francesco Montorsi, Andrea Necchi
Journal: Journal of Clinical Oncology (2018)

4535 Background: Recent data suggests that the full benefit of neoadjuvant therapy may not be captured via pathologic complete response rates. Improved relapse-free survival (RFS) may identify active agents acting though novel mechanisms. Methods: Within RISC and San Raffaele databases (1990-2016), we identified 973 cT2-4N0 UBC patients (pts), from 27 centers in the U.S., Europe, Israel, and Canada. A Cox-based nomogram predicting 12-m RFS was built including pt (gender, race), tumor characteristics (histology, pT, pN and surgical margin status [SMS]), and administration of neoadjuvant or adjuvant chemotherapy (CT). Multiple imputation was performed to handle missing data. Validation (2000 bootstrap resamples) was internally tested. Calibration and prognostic ability was assessed comparing estimated versus observed 12-m RFS. Results: Overall, 577 (59.3%) and 236 (24.3%) pts had cT2 and cT3-T4, respectively (T unknown and imputated in 160, 16.4%). 125 (12.8%) had mixed UC+other histologies. 275 pts (28.3%) received neoadjuvant CT, 165 (17%) adjuvant CT. On multivariable analyses, pT (p < 0.002), pN (p < 0.001) and SMS (p = 0.005) were associated with higher rate of recurrence. Conversely, use of adjuvant CT (HR = 0.63, p < 0.001) was associated with lower rate of recurrence. Results were confirmed in sensitivity analyses after removing 61 (6.2%) non-cisplatin POC. Overall, 405 (41.6%) pts relapsed and 375 (38.5%) died. Median RFS and overall survival were 44 months (95%CI, 36-65) and 57 months (95%CI, 50-90), respectively. In POC-treated pts, nomogram-predicted 12-m RFS rates were 91.6% (95%CI, 87-96), 79.7% (95%CI, 73-88) and 53.0% (95%CI, 44-63), across the nomogram-derived tertiles. In pts who did not receive POC, these estimates were 89.8%, 74.8%, and 47.0%, respectively. The bootstrapped c-index of the nomogram was 78% (95%CI: 74-81). Conclusions: Nomogram-predicted 12-m RFS may provide data to base future clinical trial designs of novel agents in the perioperative setting.
Abstract 21208: Association Between Serum Collagen and Myocardial Fibrosis Assessed by Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis
Authors: Bharath Ambale Venkatesh, Chetan Shenoy, Myron Gross, Otto A Sanchez, Jorge R Kizer, Eliseo Guallar, Joachim Ix, Russell Tracy, Colin O Wu, David R Jacobs, Dnaiel A Duprez, David A Bluemke, Joao A Lima
Journal: Circulation (2017)

Introduction: C-terminal telopeptide of procollagen type I (ICTP) and N-terminal propeptide of procollagen type III (PIIINP) are two of the major collagen turnover markers representing collagen degradation and synthesis. Cardiac magnetic resonance (CMR) using delayed enhancement (DE) and T1 mapping, provides a tool for detection and quantification of focal scar and diffuse interstitial myocardial fibrosis. Hypothesis: Levels of the serum biomarkers of ICTP and PIIINP at baseline are associated with the presence of myocardial scar and diffuse interstitial fibrosis at the 10-year follow-up. Methods: Of 3000 participants in a case(CVD)-cohort study that measured PIIINP and ICTP in baseline, 827 subjects with had CMRI at follow-up. Participants were initially aged 45-84 years and free of clinical CVD. Baseline serum PIIINP and ICTP concentrations were assayed using radio-immunoassay. DE-CMRI assessed myocardial scar at 10-year follow-up, with T1 mapping indices of extracellular volume fraction (ECV), pre-contrast T1, and T1 at 25 minutes post-contrast measuring diffuse interstitial fibrosis. Logistic (DE scar vs. absence as a dichotomous outcome) or linear (continuous values of T1 indices as outcomes) multivariable regression analysis with ICTP and PIIINP levels weighted for the design as continuous exposures were performed with adjustment for ACC-AHA ASCVD risk score and glomerular filtration rate at baseline (Model 1) and follow-up (Model 2). Results: Mean (SD) ICTP was 3.1 ± 0.9 μg/L; PIIINP was 5.4 ± 1.3 μg/L; ECV was 27.3 ± 3.1 %; and T1 at 25’ was 517 ± 42 ms. Among 827 participants, 68 had myocardial scar. Increased ICTP and PIIINP levels at baseline were associated with the presence of myocardial scar at follow-up (Table 1). ICTP showed no association with T1 mapping indices. Conclusions: Increased levels of collagen turnover markers were independently associated with the presence of myocardial scar 10 years later, but not with diffuse interstitial fibrosis.
P04.17 Cancer cell lines response to tumor treating fields: results of a meta-analysis
Authors: G Lavy Shahaf, M Giladi, R Schneiderman, A Kinzel, U Weinberg, E Kirson, Y Palti
Journal: Neuro-Oncology (2018)

Tumor Treating Fields (TTFields) therapy, an approved modality for the treatment of glioblastoma, is currently being investigated in many other indications. These alternating electric fields were shown to exert an inhibitory effect in numerous cancer cell lines with some variability in the response of different cell lines. The goal of the present study is to compare cell lines characteristics based on their response pattern to TTFields. TTFields were applied for 72 hours at their optimal frequency with the same nominal intensity (1.7 V/cm) to forty different human cancerous cell lines. Cell survival and clonogenicity were determined. Functional analysis of differentially expressed genes and mutations associated with response to TTFields was performed based on data from the Cancer Cell Line Encyclopedia (CCLE) database. Sensitivity to TTFields was compared with pharmacological profiling (CCLE). The inhibitory response to TTFields was found to be distributed around an average of 50% with a cytotoxic effects ranging between 14% and 86% reductions in cell counts, and a clonogenic effect ranging between no effect and 88% reduction in the number of colonies. In line with TTFields anti-mitotic properties, a correlation between treatment efficacy and cell doubling time was demonstrated. Yet, few cell lines demonstrated enhanced treatment efficacy despite long doubling time suggesting other factors may also be involved in the response to treatment. Functional analysis of cell line gene expression and mutation data revealed enriched pathways related to DNA damage repair response such as the BRCA1 repair pathway which validate previous data obtained using different methodologies. Other pathways which were found to be associated with sensitivity to TTFields include: cell migration, hypoxia signaling, oxidative stress. Pharmacological profiling based on IC50 values, revealed increased sensitivity to: Lapatinib, PHA-665752 and PLX-4720 within the group of cell lines which were less sensitive to TTFields. This multi parameter, large scale comparison of cancerous cell line response to TTFields demonstrate the broad effectiveness of TTFields in various cell lines and define the optimal frequency to be applied for each cell line. The data suggest that beside their anti-mitotic properties, TTFields may have effects on other cellular pathways. The pharmacological profiling may offer a rational for combining specific agents with TTFields in cells which are less sensitive to the electric fields.