tbuckley/cabot-search huggingface dataset:
A phase 1b/2, multicenter, open-label trial to evaluate the safety of talimogene laherparepvec (T-VEC) injected into primary and metastatic liver tumors alone and in combination with pembrolizumab (pembro) (MASTERKEY-318).
Authors: J. Randolph Hecht, Aleix Prat, Miklos Pless, Antonio Cubillo, Aitana Calvo, Steven Raman, Jason Alan Chesney, Chunxu Liu, Emily Chan
Journal: Journal of Clinical Oncology (2018)

TPS3105 Background: Combining the intralesional oncolytic immunotherapy T-VEC with systemic immunotherapy may enhance the systemic efficacy of both agents through complementary mechanisms of action. The open-label MASTERKEY-318 study (ClinicalTrials.gov, NCT02509507) was designed to evaluate the safety of intrahepatic injection of T-VEC, with or without intraveneous (IV) pembro, in pts with liver metastases (met) from solid tumors (non-HCC; from breast cancer [BC], colorectal cancer [CRC], gastroesophageal cancer [GEC], melanoma, non-small cell lung cancer [NSCLC], or clear cell renal cell carcinoma [RCC]) or from primary hepatocellular carcinoma (HCC). The study consists of 2 parts. Methods: In Part 1, the safety of administering increasing concentrations (Initial 106 plaque forming unit [PFU]/mL followed 3 weeks (wk) later by 107 PFU/mL or 108 PFU/mL q3 wk) and volumes of T-VEC will be determined in the monotherapy and combination (combo) cohorts. The primary objective for Part 1 is to evaluate the maximum tolerated volume and concentration (MTV and MTC) of injection of T-VEC into tumors in the liver alone and in combo (MTC only) with systemic pembro (200 mg IV q3 wk) as measured by incidence of dose limiting toxicities. Once the MTC is determined, Part 2 will evaluate the efficacy and safety of the T-VEC/pembro combo in the respective tumor types. For Part 2, the primary objective is objective response rate and incidence of treatment-emergent and treatment-related adverse events. Key eligibility criteria include age ≥18 years, confirmed BC, CRC, GEC, melanoma, NSCLC, or RCC with liver met or HCC. Generally, non-HCC pts must have received ≥1 prior standard of care systemic therapy for their locally advanced or metastatic disease. However, for the combo cohorts, pts with melanoma or NSCLC do not need to have received prior therapy. Pts must have measurable liver tumors suitable for injection, an Eastern Cooperative Oncology Group performance status of 0 or 1, and life expectancy ≥5 months. MASTERKEY-318 will enroll up to 244 pts from ~50 sites. 21 pts have enrolled onto the monotherapy cohorts so far. Clinical trial information: NCT02509507.
Abstract 11576: Factors Associated With Coronary Artery Disease Progression Assessed by Serial Coronary Computed Tomography Angiography
Authors: Gabriel C Camargo, Tamara Rothstein, Maria Eduarda Derenne, Leticia Sabioni, Isadora R Calafate, Carolina A Xavier, Livia G Marcomini, Ronaldo S Lima, Ilan Gottlieb
Journal: Circulation (2013)

Introduction: Computed tomography coronary angiography (CCTA) allows for non-invasive coronary artery disease (CAD) phenotyping. Factors related to CAD progression are epidemiologically valuable. Objective: Identify factors associated with CAD progression in patients who underwent sequential CCTA testing. Methods: This is a retrospective study comprising a database of 5055 CCTA exams performed between May-2003 and Mar-2013 using 64 and 256-slice scanners, in which 382 individuals had sequential CCTA testing. Those with surgical revascularization or submitted to a percutaneous coronary intervention (PCI) between studies were excluded due to limitations in native vessel analysis and progression quantification, respectively. CAD progression was defined as any increase in the previously established segment stenosis score (calculated using the number of diseased segments and stenosis severity) in all coronary segments without stents (reestenosis was excluded from analysis). All studies were analyzed by a reade...
Dacomitinib (daco) versus gefitinib (gef) for first-line treatment of advanced NSCLC (ARCHER 1050): Final overall survival (OS) analysis.
Authors: Tony Mok, Ying Cheng, Xiangdong Zhou, Ki Hyeong Lee, Kazuhiko Nakagawa, Seiji Niho, Min Young Lee, Rolf Gerhard Linke, Rafael Rosell, Jesus Corral Jaime, Maria Rita Migliorino, Adam Pluzanski, Eric I Sbar, Tao Wang, Jane Liang White, Yi-Long Wu
Journal: Journal of Clinical Oncology (2018)

9004 Background: In the ongoing phase 3 ARCHER 1050 study, first-line treatment with daco significantly improved the primary endpoint of progression-free survival, duration of response, and time to treatment failure vs gef in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC) (Wu et al, Lancet Oncol, 2017). Here, we present the OS results. Methods: Pts with newly diagnosed stage IIIB/IV or recurrent NSCLC harboring an EGFR mutation (exon 19 del or exon 21 L858R ± exon 20 T790M) and without central nervous system metastasis were randomized 1:1 to oral daco 45 mg/day or oral gef 250 mg/day. Pts were stratified by race and EGFR mutation type. Results: As of 17 February 2017, a total of 220 deaths (48.7%) occurred over a median follow-up of 31.3 months (mo): 103 (45.4%) in the daco arm (n = 227) and 117 (52.0%) in the gef arm (n = 225). Daco showed a significant improvement in OS compared to gef (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.582–0.993; 2-sided P = 0.044 based on stratified analysis). Median OS (95% CI) was 34.1 mo (29.5–37.7) with daco vs 26.8 mo (23.7–32.1) with gef. Survival rates at 30 mo were 56.2% with daco and 46.3% with gef. The table shows preliminary OS subgroup analyses by race and EGFR mutation type, with >55% of pts being censored in some subsets. OS subgroup analyses were consistent with the primary OS analysis across most baseline characteristics. Conclusions: In pts with advanced EGFR mutation-positive NSCLC, daco is the first to show a significant improvement in OS in a phase 3 trial compared with a standard-of-care tyrosine kinase inhibitor. Daco should be considered as one of the standard treatment options for these pts. Clinical trial information: NCT01774721. Daco (n = 227) Gef (n = 225) Daco vs Gef, HR (95% CI) 2-Sided P Value n Median OS, mo (95% CI) n Median OS, mo (95% CI) Race Non-East Asian 57 29.5 (20.7–NR) 49 20.6 (16.1–25.5) 0.721 (0.433–1.201) 0.2073 Asian 170 34.2 (30.1–NR) 176 29.1 (25.2–NR) 0.812 (0.595–1.108) 0.1879 EGFR mutation status at randomization Exon 19 del 134 34.1 (30.1–NR) 133 NR (25.0–NR) 0.880 (0.613–1.262) 0.4862 Exon 21 L858R 93 32.5 (25.5–NR) 92 23.2 (19.6–28.6) 0.707 (0.478–1.045) 0.0805 NR, not reached
The neutrophil to lymphocyte ratio as a prognostic factor among a diverse population with advanced pancreatic cancer.
Authors: Michael Shusterman, Erin Jou, Andreas Kaubisch, Jennifer W. Chuy, Lakshmi Rajdev, Justin Tang, Nitin Ohri, Santiago Aparo, Sanjay Goel
Journal: Journal of Clinical Oncology (2017)

e15729 Background: The neutrophil to lymphocyte ratio (NLR), a marker of systemic inflammatory response, has been suggested as a prognostic marker in patients with pancreatic adenocarcinoma (PAC). Black and Hispanic patients have been underrepresented in studies evaluating the significance of NLR in PAC. We investigated the prognostic significance of NLR in patients with advanced PAC treated at the Montefiore-Einstein Center for Cancer Care (MECCC) in the Bronx, NY. Methods: We included patients who were chemotherapy naive and treated for unresectable or metastatic PAC at MECCC between 2006 and 2015. Demographics, clinical characteristics and treatment data were collected. Overall survival was determined by the Kaplan-Meier method and Cox proportional-hazards models were built to assess survival differences adjusting for clinically relevant and statistically significant variables. Results: 201 patients were included in the study. Median age was 65 (range 32, 90). 52% were male. 41 were White (19%), 71 Black (33%), 71 Hispanic (33%), and 33 Other (15.3%). 66 (30.6%) had unresectable disease and 135 (62.5%) metastatic disease. An NLR ≥ 4 was associated with a worse OS compared to an NLR ≤ 4 (median 10 vs. 16.4 months; HR 1.895; 95% CI 1.390, 2.585; P &lt; 0.0001). Predictors of worse OS on univariate analysis were ever smoker status (HR 1.365; P = 0.05), metastatic disease (HR 1.736; P = 0.001), and albumin ≤ 3.5 g/dL (HR 2.558; P&lt; 0.0001). An NLR ≥ 4 on multivariate analysis remained significantly associated with worse OS (HR 1.665; 95% CI 1.188, 2.334; P = 0.003) after adjusting for age, gender, ever smoker status, metastatic disease, and albumin. Conclusions: In a cohort with significant minority patient representation, an NLR ≥ 4 was associated with significantly worse overall survival in patients with advanced pancreatic cancer. An elevated NLR in advanced PAC may be an important independent predictor to risk stratify patients and predict poor OS in future analyses.
TCT-853 Thrombus Aspiration in Patients With ST-Elevation Myocardial Infarction Presenting Late After Symptom Onset – Long-term Clinical Outcome of a Randomized Trial
Authors: Anne Freund, Sandra Schock, Thomas Stiermaier, Suzanne de Waha, Philipp Lurz, Holger Thiele, Steffen Desch
Journal: Journal of the American College of Cardiology (2018)
Clinicopathological, genomic and immunological features of hyperprogressive disease during PD-1 blockade in gastric cancer patients.
Authors: Yosuke Togashi, Takahiro Kamada, Akinori Sasaki, Yoshiaki Nakamura, Shota Fukuoka, Yasuko Tada, Akihito Kawazoe, Kohei Shitara, Hiroyoshi Nishikawa
Journal: Journal of Clinical Oncology (2018)

4106 Background: Hyperprogressive disease (HPD) during PD-1 blockade reported in several cancer types is a big hurdle for applying cancer immunotherapy, whereas there is no report in gastric cancer (GC) and the detailed clinicopathological, genomic, and immunological features remain to be determined. Methods: To clarify clinicopathological, genomic, and immunological features of hyperprogressive disease during PD-1 blockade in patients with advanced GC, 36 patients with advanced GC who received nivolumab from October 2017 to December 2017 and underwent at least one imaging evaluation of their clinical responses were enrolled in this study. Tumor DNA/RNA samples and tumor-infiltrating lymphocyte (TIL) were also analyzed using next-generation sequencing and flow-cytometry assay, respectively. Results: Among 36 patients, four patients (11.1%) experienced hyperprogressive disease, and their prognosis was very poor with three of four patients died within very short period after the initial administration of nivolumab (range 20 to 65 days). Three and two among four patients were subjected to genome analyses and TIL analyses, respectively. One patient had an MDM2 gene amplification as was previously reported, whereas the other patients did not have any MDM2 gene family alterations. Immunological analyses in two patients revealed that effector regulatory T (eTreg) cells with proliferative capacity (Ki67+CD45RA-FOXP3highCD4+ T cells) were markedly increased in TILs from pre-treatment to hyperprogressive disease state, whereas those in non-hyperprogressive disease patients showed significant reduction. Especially, one patient without MDM2 gene amplification contained enormously high frequency of Ki67+eTreg cell-infiltration in the tumor at HPD state. Conclusions: HPD during PD-1 blockade is observed in gastric cancer as well as other cancer types and the prognosis is very poor. High regulatory T cell-infiltration and MDM2 family gene alterations might contribute to HPD, which should be taken care during the treatment with anti-PD-1 antibodies.
Carfilzomib-associated cardiovascular adverse events: A systematic review and meta-analysis.
Authors: Adam Justin Waxman, Suparna Chandra Clasen, Alfred L. Garfall, Joseph R. Carver, Dan T. Vogl, Rupal O'Quinn, Adam D. Cohen, Edward Allen Stadtmauer, Bonnie Ky, Brendan M. Weiss
Journal: Journal of Clinical Oncology (2017)

8018 Background: The incidence and nature of cardiovascular adverse events (CVAEs) with carfilzomib (CFZ) in multiple myeloma (MM) remain incompletely defined. We performed the first systematic review and meta-analysis of CFZ CVAEs. Methods: PubMed was queried for the keywords “carfilzomib,” “Kyprolis,” and “PX-171.” Phase 1-3 clinical trials of carfilzomib in MM with evaluable toxicity data were included. CVAEs were defined as heart failure, hypertension, ischemia, and arrhythmia. All-grade and grade ≥3 CVAEs and study characteristics were recorded. Summary incidence rates and relative risks (for randomized trials) with 95% confidence intervals were calculated using the logistic-normal random-effects model. Subgroup analyses were performed using study level covariates. Results: 514 studies were reviewed. 2623 MM patients from 25 eligible studies were included. Incidence rates are summarized in the table. All grade and grade ≥3 CVAEs were seen in 16.8% and 7.6 %, respectively. Phase 2 or 3 studies, carfilzomib doses ≥45mg/m 2 , and longer infusion length were study characteristics associated with high-grade cardiac AEs (p&lt;0.05). Median age &gt;65, prior MM therapies, and concurrent MM therapies were not associated with CVAEs (p&gt;.05). For the three randomized trials, the relative risk of all-grade and grade ≥3 CVAEs were 1.75 and 2.25, respectively (p&lt;0.001). Conclusions: CFZ is associated with a significant incidence of CVAEs, including heart failure, hypertension, ischemia, and arrhythmia. Phase I studies may be underdetecting CVAEs. Future studies are needed to: identify patients at high-risk for CVAEs, develop optimal monitoring strategies, and explore therapies to mitigate these risks. [Table: see text]
Quantitative multiplex immunofluorescence (qmIF) and genomic evaluation of tumor microenvironment (TME) to identify candidate biomarkers in stage II/III melanoma.
Authors: Robyn Denise Gartrell, Douglas Kanter Marks, Thomas D Hart, Yan Lu, Camden L Esancy, Zoe Blake, Bret Taback, Basil Horst, Yvonne M. Saenger
Journal: Journal of Clinical Oncology (2018)

9580 Background: Biomarkers are needed to risk stratify for adjuvant trials in early stage melanoma. Features of the immune infiltrate within the TME are hypothesized to be prognostic, but quantification methods are not standardized for clinical practice. Expression profiling of stage II/III melanoma shows that Th1 genes have prognostic value. Combination of genomic and qmIF analyses of the TME may identify prognostic immune biomarkers. Methods: We performed qmIF analysis on 104 primary melanoma tumors (stage II-III) diagnosed at Columbia University Medical Center from 2000-2012. Tissue was stained for DAPI (nuclei), CD3 (T cell), CD8 (cytotoxic T cell (CTL)), CD68 (Mj), SOX10 (tumor), HLA-DR (activation) and Ki67 (proliferation). Phenotyping was performed with inForm software. High/low density cut-offs were defined by Classification and Regression Tree Analysis (CART) and Receiver Operating Characteristic (ROC) curves. For 64 patients (pts), with known of cause of death, KM curves were calculated. mRNA expression analysis for 63 immune genes (NanoString) was performed on 44 of 64 pts for whom sufficient tissue was available. Results: On qmIF, we find that high CTL and low Mj infiltration, particularly when located in the stroma, correlates with disease specific survival (DSS) (p = 0.004 and p < 0.001, respectively). Of greatest significance, when combined, low stromal CTL/Mj ratio correlates with death from melanoma using ROC (AUC = 0.724, p = 0.026). By AUC cutoff, low CTL/Mj ratio predicts poor DSS (p = 0.003) and overall survival (OS) (p = 0.008). On multivariable cox analysis, low CTL/Mj was independently associated with DSS (p = 0.002) and OS (p = 0.020). Genomic analysis identified increased expression of CXCL9, CXCR3, CCL5 and CD37 in non-recurrent pts (p < 0.050 after bonferoni correction) which did not correlate with CTL/Mj ratio. Conclusions: Multiparameter phenotyping of stage II/III melanoma pts shows that stromal CTL/Mj ratio strongly correlates with survival. mRNA analysis shows that high Th1 gene expression correlates with non-recurrence. Combination of qmIF and mRNA analysis may be useful in stratifying pts to receive immunotherapy.
Financial toxicity in children, adolescent, and young adult cancer patients and their families: A large national registry analysis from the family reach foundation.
Authors: Lori S. Muffly, Carla Tardif, Jonas de Souza
Journal: Journal of Clinical Oncology (2016)

6615 Background: Although financial toxicity is an increasingly recognized side effect of a cancer diagnosis and treatment, little is known about the characteristics of children, adolescent, and young adult (AYA) cancer patients and caregivers who seek financial assistance. We sought to describe patient demographics and causes of financial burden in a large national sample of children and AYA patients and families who applied for financial support. Methods: Cancer patients aged < 1 to 39 years who were receiving active cancer treatment and had applied for a financial grant to the Family Reach Foundation between 2010-2015 were included in the analysis. Descriptive statistics characterized the study population; chi2 test was used to evaluate differences between groups. Results: 2198 children, adolescents, and young adults (69% < 15 years; 24% 15-24 years; 7% 25-40 years) from 48 U.S. states are included. 28%, 13%, 11%, and 30% were Hispanic, African American, Multiracial, and Caucasian non-Hispanic, respectively. Family income was < $24,250 in 44%, and 29% were living in a single parent household. Cancer diagnoses included those common to children and AYAs: acute leukemia (36%), sarcoma (13%), brain (14%), lymphoma (9%). The mean grant funded was $1163 (range $0-$6461). Causes of financial need were characterized as non-medical costs (e.g. rent, mortgage, food, auto payments) or medical costs (e.g. uncovered medical expenses, health insurance premiums/copays, travel to hospital, lodging). The majority (92%) of financial burden was non-medical costs, with rent/mortgage accounting for 62%. Medical costs accounted for a greater proportion of financial burden in patients and families of AYA cancer patients (12%) as compared to families of childhood cancer patients (6%); p < 0.001. Conclusions: In this large national sample of pediatric and AYA cancer patients seeking financial support, the costs of daily living predominate as important drivers of financial toxicity. Future research should focus on interventions to relieve the varied causes of financial distress associated with childhood and AYA cancer.
Costs associated with adverse events for systemic therapies in metastatic melanoma.
Authors: Ying Qiu, Zhiyi Li, Jackson Tang, Kris Grzegorzewski, Syed Mahmood, Tyler Whisman, Syed Quadri, Alex Z Fu
Journal: Journal of Clinical Oncology (2016)

9560 Background: Current systemic therapies of metastatic melanoma (MM) include immunotherapy, target therapy (if BRAF mutated), high-dose IL-2, and chemotherapy, all of which are associated with different toxicity and adverse events (AEs). A comprehensive understanding of the costs of AEs will enable more accurate comparisons among the treatments and better management of costs. Methods: Two retrospective cohort studies were independently conducted using IMS PharMetrics Plus databases and MarketScan commercial and Medicare supplemental databases. Patients included those aged ≥ 18 years who had ≥ 1 metastatic melanoma diagnosis and ≥ 1 claim for any systemic therapies from July 1, 2004 to June 30, 2015. AEs were identified based on ICD-9-CM diagnosis/procedure codes. Incremental cost per AE was determined by comparing the 30-day expenditures between patients with the AE event and patients without the event using a generalized linear model. Propensity score with inverse probability of treatment weighted method was used to adjust for baseline demographic and clinical differences. Results: 1,654 patients from PharMetrics were included. Mean age was 61.2 years (SD ± 11.4); mean baseline Charlson comorbidity index was 8.0 (SD ± 2.3); 59% were male. 1,329 patients included from MarketScan had similar characteristics. The adjusted 30-day incremental costs by AE category in 2015 US$ are summarized below in the table. Conclusions: Incremental AE costs associated with systemic therapies of mm are substantial. AE Category Incremental Costs PharMetrics MarketScan $ 95% CI $ 95% CI Cardiovascular 16,083 (15,640, 16,526) 15,430 (15,052, 15,809) CNS/ psychiatric 21,277 (20,748, 21,806) 18,739 (18,255, 19,222) Gastrointestinal 18,534 (18,061, 19,007) 15,648 (15,173, 16,122) Hematologic/lymphatic 14,997 (14,652, 15,342) 15,538 (15,134, 15,941) Metabolic /nutritional 12,340 (11,851, 12,829) 17,251 (16,825, 17,677) Pain 12,928 (12,553, 13,303) 16,104 (15,691, 16,518) Skin/subcutaneous tissue 11,016 (10,717, 11,315) 10,597 (10,319, 10,875) Respiratory 17,338 (16,850, 17,826) 17,064 (16,620, 17,508) General/administration site 14,227 (13,829, 14,625) 13,371 (13,018, 13,724) Other 15,065 (14,643, 15,487) 15,381 (14,950, 15,812)
Tumor volume as a prognostic factor in patients (pts) with locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) treated with induction chemotherapy (IC).
Authors: Daniel Moore Freitas Palhares, Fernando Coutinho Batista, Ana Lima Veneziani, Marcos Duarte Mattos, Augusto Elias Mamere, Renato Castro Capuzzo, Carlos Roberto Santos, Andre Lopes Carvalho, Luciano De Souza Viana, Alexandre Arthur Jacinto
Journal: Journal of Clinical Oncology (2017)

e17507 Background: Tumor volume and the ratio of volumetric change have been demonstrated to have a prognostic role in head and neck cancers during definitive treatment in LAHNSCC. The aim of this study was to evaluate the prognostic value of tumor volume assessment during IC. Methods: We retrospectively assessed the tumor volume of 58 pts with LAHNSCC included in a prospective phase II trial which evaluated the safety of a non–5-fluorouracil-based IC (paclitaxel; cisplatin) followed by chemoradiotherapy (cisplatin; 70Gy/35fx) during 2009-2012. The volume of primary tumor (P rim V), all suspicious lymph nodes (L N V) and their sum (S um V) were determined on tomography before (CT 1 ) and after (CT 2 ) IC using a radiotherapy treatment planning system and the ratio of volumetric change was calculated for each variable (P rim V%, L N V% and S um V%). Results: The median follow-up time, the progression free survival (PFS) and the overall survival (OS) was 78,1, 19,3 and 22,5 months, respectively. Fifty-four pts were men, mean age 55,3±8,3y. Most had oropharynx (53%) and stage IV (72%) cancer. The median volume (cm 3 ) was P rim V 1 = 25,5, L N V 1 = 7,5, S um V 1 = 40,7, P rim V 2 = 10,9, L N V 2 = 3,0, S um V 2 = 18,8 and median ratio of change (%) was P rim V% = 55, L N V% = 51 and S um V% = 54. Volume wa s associated with resectability (P rim V 1, AUC ROC curve = 0,66 , p = 0,04; L N V 1 , AUC = 0,85, p &lt; 0,001; S um V 1 , AUC = 0,86, p &lt; 0,001). Pts with S um V% reduction &gt; 35% had better PFS (median 84,0 vs 10,1 months, 3y 52% vs 29%; HR = 0,39, p = 0,01) and OS (median 45,5 vs 17,0 months, 48% vs 21%; HR = 0,49, p = 0,04). On univariate analysis the PFS was correlated with T (p = 0,004), N (p = 0,01), stage (p = 0,03), primary site (p = 0,01), resectability (HR = 0,32, p = 0,001), P rim V 1 (p = 0,002), S um V 1 (p = 0,001), P rim V 2 (p = 0,02), L N V 2 (p = 0,04), S um V 2 (p = 0,004), P rim V% (p = 0,04), L N V% (p = 0,003) and S um V% (p = 0,04) and OS was associated with T (p = 0,04), N (p = 0,02), stage (p = 0,04), primary site (p = 0,01), resectability (HR = 0,29, p &lt; 0,001) P rim V 1 (p = 0,003), L N V 1 (p = 0,002) and S um V 1 (p &lt; 0,001). Conclusions: Tumor volume and the volumetric response during IC were associated with prognosis in LAHNSCC in the present study. Clinical trial information: NCT00959387.
TCT-227 Outcomes with Drug-coated balloons in Small-Vessel Coronary Artery Disease.
Authors: Michael Megaly, Michael Rofael, Marwan Saad, Ahmed Rezq, Mariam Tawadros, Louis Kohl, Ankur Kalra, Mehdi Shishehbor, Peter Soukas, J. Dawn Abbott, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2018)