tbuckley/cabot-search huggingface dataset:
Conservative management following clinical complete response to neoadjuvant chemotherapy for muscle-invasive bladder cancer: Contemporary outcomes of a multi-institutional prospective cohort study.
Authors: Patrick M Mazza, George W. Moran, Gen Li, Dennis J. Robins, Justin T. Matulay, Harry W. Herr, Christopher B. Anderson, James M. McKiernan
Journal: Journal of Clinical Oncology (2018)

4522 Background: Neoadjuvant platinum-based chemotherapy (NAC) followed by radical cystectomy (RC) is the gold standard treatment for muscle-invasive bladder cancer (MIBC). High morbidity and mortality associated with RC and favorable survival outcomes seen in patients who exhibit a clinical complete response (cCR) to NAC and forego RC has encouraged interest in conservative management of MIBC. We report the outcomes of patients from two institutions who experienced a cCR to NAC and opted for surveillance only. Methods: Prospective enrollment and retrospective review of patients occurred at Columbia University Medical Center (CUMC) and Memorial Sloan Kettering Cancer Center (MSKCC) to produce two distinct, IRB-approved databases of MIBC patients who underwent “radical” TURBT (complete resection down to muscularis propria) followed by NAC, exhibited a cCR, and opted for surveillance only from 2001-2017. A cCR was defined as negative “radical” TURBT, urine cytology, and cross-sectional imaging. Patients were followed at 3-6 month intervals with cystoscopy ± biopsy, urine cytology, and cross-sectional imaging, with databases continually updated. Results: The 148 patient cohort included 119 (80%) men and 29 women of median age 62 (32-88) years and follow-up 55 (5-145) months. NAC regimens were 31% MVAC, 63% gemcitabine and cisplatin, and 6% other platinum-based regimens. Of the 148, 71 (48%) recurred in the bladder—16 (11%) with MI disease and 55 with non-muscle invasive (NMI). Salvage RC prevented cancer-specific death in 9 of 12 (75%) patients who accepted RC after MI relapse and 13 of 14 (93%) after NMI relapse. 5-year disease-specific, overall, cystectomy-free, and recurrence-free survival rates for the entire cohort were 90%, 86%, 76%, and 64%. Conclusions: The favorable outcomes observed in this large, multi-institutional cohort support the efficacy of surveillance only for carefully selected and closely monitored MIBC patients. Future studies should aim to improve patient selection by identifying biomarkers predictive of invasive relapse and developing novel imaging methods for its detection.
Abstract 20071: Patients with Human Immunodeficiency Virus on Chronic Treatment Have Increased Carotid Artery Wall Thickness on Magnetic Resonance Imaging
Authors: Troy M LaBounty, W. David Hardy, Fan Zhaoyang, Roya Yumul, Debiao Li, Rohan Dharmakumar, Antonio H Conte
Journal: Circulation (2014)

Introduction: Patients with human immunodeficiency virus (HIV) infection have an elevated risk of stroke. Hypothesis: Subjects with HIV on chronic highly active antiretroviral therapy (HAART) have ...
Phase II clinical trial of eribulin (E) in advanced/recurrent cervical cancer.
Authors: Jocelyn Garcia, Yvonne Gail Lin, Stan Louie, Paulette Fauceglia, Denice D Tsao-Wei, EunJeong Yoo, Marcia Ciccone, Crystal Adams, Laurie Leigh Brunette, KOJI MATSUO, Huyen Q. Pham, Annie A. Yessaian, Susan G. Groshen, Grace Facio, Kristy Watkins, Laila I. Muderspach, Agustin A. Garcia, Lynda D. Roman
Journal: Journal of Clinical Oncology (2018)

5526 Background: Eribulin (E), a Halichondrin B analog from the marine sponge H. okadai has clinical efficacy in pretreated metastatic breast cancer patients (pts) and preclinical antitumor activity in squamous cell carcinoma (SCC). We conducted a 2-stage Phase 2 study of E in pts with advanced/recurrent CC to examine its clinical activity and evaluate potential predictors of response. Methods: Pts with advanced/recurrent CC after ≤1 prior CT regimens, measurable disease and ECOG performance status ≤2 were treated with E (1.4mg/m2 IV day 1 and 8, every 21 days) with tumor assessments every 2 cycles. Primary endpoint was 6-month progression-free survival PFS6; secondary were best overall response (RECISTv1.1), toxicity (CTCAEv4.03) and overall survival (OS); and exploratory were associations of tumor and serum GRP78 as well as apoptosis/proliferation markers, unfolded protein response markers and tubulin sub-types with clinical activity. 30 evaluable pts would ensure 80% power when the true PFS6= 26% with a 1-sided α ≤0.1 (Ho: PFS6= 10%). A prespecified futility analysis gating stage 2 was set if 0/15pts showed at least SD at 6 months. Immunohistochemistry was performed on archival tumor samples and serial serum GRP78 levels were quantified by ELISA. Results: 32 pts were enrolled, median age 51 years (range 29-76), 22 had SCC, the median number of cycles was 4 (range 1-29). 26 pts had received prior pelvic irradiation. 29 pts had received prior CT with cisplatin/gemcitabine (12) and cisplatin/paclitaxel/bevacizumab (12) as the most common regimens. 6/32 pts (18.8%) achieved > PFS6; median PFS is 2.6 months (95%CI: 1.2, 4.2). Median OS is 6.6 months (95% CI: 4.4, 12.7). Two pts were inevaluable for response having received less than 2 cycles. Among the 30 evaluable pts, 6 (20%) had a partial response and 11 (37%) had stable disease (clinical benefit rate 57%). 2 pts remain on study having received 21 and 29 cycles. Grade 3/4 adverse events occurring in > 10 % of pts are anemia (12pts), neutropenia (7pts) and leukopenia (6pts). 1 pt was removed from study due to paresthesia after 7 cycles. Analysis of correlative predictors of response is ongoing. Conclusions: Eribulin shows evidence of activity in recurrent/advanced CC with a favorable toxicity profile. Clinical trial information: NCT01676818.
Single institution experience of posterior reversible encephalopathy syndrome (PRES) associated with high risk pediatric ALL induction therapy: Is there a role of pharmaco-ethnicity.
Authors: Nupur Mittal, Murali Nagarajan, Peter Heydemann
Journal: Journal of Clinical Oncology (2017)

e22005 Background: PRES, a rare complication of childhood leukemia treatment occurs in up to 5% patients in small series and &lt; 1% of patients on the current COG high risk leukemia protocol. Hypertension, chemotherapy and cortical spreading depression have been implicated in the pathophysiology. It is important to recognize the characteristic radiologic findings, manage appropriately and reintroduce chemotherapy since delays can be unfavorable for high risk ALL patients. Pharmaco-ethnicity may determine variation in drug responsiveness and neurotoxicity in children with ALL. Ethnic Differences in occurrence of PRES in pediatric ALL have not been reported. Methods: 12 children (1-20 yrs) diagnosed with ALL between 2011-2016 were retrospectively reviewed for the occurrence of PRES, demographics, chemo-therapy received, clinical features, radiology and management. All literature on PRES in pediatric leukemia on Pubmed was reviewed. Results: 5/12 (42%) children (avg 8.5 yrs) developed PRES during days 10-29 of induction. 80% of the patients that developed and 45% of those that did not develop PRES were Hispanic. All the patients that developed and 3/7 that did not develop PRES were high risk ALL. All patients received vincristine, 4/5 daunorubicin and intrathecal methotrexate and 1/5 peg asparaginase in the 1 week before the event. MRI findings confirmed the diagnosis of PRES in all patients. All patients were in remission based on MRD and spinal fluid cytology. 3/5 patients had clinical and electroencephalographic seizures and hypertension at the time of the event. All patients had complete neurologic recovery. Conclusions: Hispanic ethnicity, high risk ALL and exposure to vincristine ,daunomycin and intrathecal methotrexate during induction were associated with PRES in our cohort . Ethnicity emerged as a new association possibly contributing to the increased incidence of PRES in our cohort compared to historical cohorts. Larger studies to understand the importance of pharmcoethnicity in PRES will help in individualization of chemotherapy with the goal of improving the tolerability and effectiveness of chemotherapy.
Analysis of racial differences in histologic subtype and survival in renal cell carcinoma at an urban academic cancer center.
Authors: Kevin Wong, Michael Shusterman, Benjamin Adam Gartrell
Journal: Journal of Clinical Oncology (2017)

e16571 Background: Black patientswithrenal cell carcinoma (RCC) have a unique distribution of histological subtypes and historic worse survival compared to white patients. Little is known about RCC in Hispanics. We investigated histologic and survival differences between racial groups treated for RCC at the Montefiore-Einstein Cancer Center (MECC) in Bronx, NY. Methods: We included via the Cancer Registry 1010 patients who underwent RCC resection at MECC between 2000 and 2015. Demographics, clinical characteristics and pathology reports were collected. Logistic regression and Cox proportional hazards models were built to evaluate the association of histology and survival with clinically and statistically significant risk factors in Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic (H) patients. Results: 233 patients were NHW (23.1%), 383 NHB (37.9%), 174 H (17.2%), and 220 other race (21.8%). Median age was 61 (range 22, 91). 58% were male. Histology was 529 (52%) clear cell (CC), 255 (25%) papillary (P), 100 (10%) chromophobe, and 126 (12.5%) other. P was more common in NHB (60.5%) compared to NHW (17%) and less common in H (6.3%) patients (P &lt; 0.0001). On multivariate logistic analysis, patients with P vs. CC were more likely to be NHB (OR 5.06; 95% CI 2.92, 8.76; P &lt; 0.0001) and less likely to have a body mass index &gt; 30 (BMI, OR 0.49; 95% CI 0.32, 0.76, P = 0.001) adjusting for age, race, gender, hypertension (HTN), and end stage renal disease (ESRD). Adjusting for above covariates there were no significant differences for C vs. CC. There was no difference in disease free survival (DFS) for NHB vs. NHW (HR 0.93; 95% CI 0.44, 1.94; P = 0.841) or H vs. NHW (HR 1.29; 95% CI 0.62, 2.71; P = 0.495) patients adjusting for age, gender, histology, ESRD, and BMI. There was no difference in overall survival (OS) for NHB vs. NHW (HR 0.97; 95% CI 0.57, 1.65; P = 0.908) or H vs. NHW (HR 1.37; 95% CI 0.79, 2.38; P = 0.256) patients adjusting for the same covariates. Conclusions: In this cohort of patients with RCC, P histology and lower BMI were significantly associated with NHB race. Unlike historic cohorts there was no significant difference in DFS or OS in NHB compared to NHW patients.
A biomarker-directed phase 2 trial of SY-1425, a selective retinoic acid receptor alpha agonist, in adult patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
Authors: Rachel J. Cook, Eytan Stein, David P. Steensma, Mikkael A. Sekeres, Dale L. Bixby, David Rizzieri, Joseph G. Jurcic, Carlos Enrique Vigil, Robert Redner, Gail J. Roboz, Michael R. Savona, Michael R. McKeown, Kristin Stephens, David A. Roth, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2017)

TPS7071 Background: SY-1425 (tamibarotene) is an orally available, synthetic retinoid approved in Japan for the treatment of relapsed/refractory (R/R) APL. SY-1425 is a more potent and selective retinoic acid receptor alpha (RARα) agonist with improved pharmacologic properties compared to all-trans retinoic acid (ATRA) including increased half-life and lack of metabolism by CYP26A1 resulting in extended relative exposures. SY-1425 binding to RARα relieves pathogenic repression of myeloid differentiation. Super-enhancers associated with RARA and upregulation of RARA expression correlate with increased sensitivity to SY-1425 in vitro and predict for response to SY-1425 with induced differentiation and reduced proliferation in RARA-high PDX AML models, but not in RARA-low models. SY-1425 also induces the RARα target gene DHRS3 in RARA-high AML cell lines. This study is designed to demonstrate pharmacodynamic (PD) and clinical effects of SY-1425 in non-APL AML and MDS patients (pts) positive for the RARA super-enhancer associated biomarker or exploratory RARA pathway biomarker, IRF8. Methods: This study is enrolling pts with R/R AML, R/R higher-risk MDS, newly-diagnosed AML ≥60 yrs unlikely to respond to or tolerate standard therapy, and transfusion dependent lower-risk MDS pts without del 5q who are unlikely to respond to or have failed ESAs. Pts must be biomarker positive based on centralized testing of tumor cells from blood. All pts receive SY-1425 at 6 mg/m 2 /day PO with continuous twice daily dosing. Primary objectives are to characterize the activity of SY-1425 by ORR in AML and higher-risk MDS pts or transfusion independence in lower-risk MDS pts. Secondary objectives include event-free and relapse-free survival, duration of response, overall survival, hematologic improvement and safety. PD evaluation includes induction of DHRS3 and expression of myeloid differentiation markers. Target enrollment is 80 pts. This trial opened in September 2016. Through a protocol amendment, SY-1425 treatment in combination with azacitidine will also be evaluated. ClinicalTrials.gov identifier: NCT02807558.
Enhancing targeted therapy of tumors with activating FGFR alterations.
Authors: Bruno Bockorny, Maria Rusan, Federica Piccioni, Li Tan, Adam Joel Bass, Peter S. Hammerman
Journal: Journal of Clinical Oncology (2017)

e23134 Background: Emerging evidence points to the Fibroblast Growth Factor Receptor (FGFR) kinase family as a promising target in multiple cancer types including lung squamous cell carcinoma, cholangiocarcinoma, gastric, bladder and breast cancer. Although several FGFR kinase inhibitors have entered clinical trials, single agent clinical efficacy has been modest and resistance invariably occurs. A comprehensive understanding of the molecular basis of resistance to FGFR inhibitors is urgently needed to enable the successful application of anti-FGFR therapy in the clinic. Methods: We utilized a systematic genome-wide open reading frame (ORF) screen to identify genes whose upregulation confers resistance to the FGFR inhibitors BGJ398 and FIIN-3 in FGFR1-amplified H2077 lung cancer cells. In an orthogonal approach, we established resistant clones of FGFR1-amplified and FGFR3-translocated cell lines by chronic exposure to BGJ398, and characterized these by high-throughput gene expression analysis. Results: We identified 34 candidate genes, including expected findings such as a mutant KRAS allele and MET overexpression. Intriguingly, we also identified novel candidate resistance mechanisms involving the genes of the TAM family, which encode the transmembrane receptors Tyro3, Axl and Mertk. These tyrosine kinases may serve as a secondary target to augment FGFR therapy. We validated that the TAM family confers resistance to FGFR inhibitors in different FGFR dependencies including FGFR1-amplified lung cancer, FGFR2-amplified gastric and colon cancer and FGFR 3-translocated bladder cancer, with AXL having the greatest rescue. Notably, gene profiling of resistant clones also implicates the TAM family, with both receptors and their ligands upregulated in the majority cases. Moreover, concurrent TAM blockade augments the response to FGFR inhibition in vitro and provides a promising therapeutic strategy to overcome resistance. Conclusions: TAM kinases are important mediators of resistance to FGFR inhibitors and the dual blockade of FGFR and TAM provides a novel approach to enhance the efficacy of anti-FGFR therapy.
Phosphorylated signal transducer and activator of transcription–3 (p-STAT3) expression concordance in paired primary and metastatic colorectal cancers (mCRC): Updated analysis.
Authors: Daniel Yokom, E. Celia Marginean, Derek J. Jonker, Allen M. Gown, Shelly Sud, Timothy R. Asmis, Manijeh Daneshmand, Horia Marginean, Rachel Anne Goodwin
Journal: Journal of Clinical Oncology (2017)

e15137 Background: p-STAT3 is a transcription factor which is associated with poor prognosis in multiple cancers. Overexpression of p-STAT3 by immunohistochemistry (IHC) in tumors of patients with mCRC is associated with more aggressive disease and decreased survival. Concordance of p-STAT3 expression in primary and metastatic tumors was assessed to determine the temporal heterogeneity of expression and correlation with clinical outcomes. Methods: Patients with tissue available from both primary and liver metastases were identified retrospectively. Tissue microarrays (TMA) were constructed using 2 x 2mm cores. Nuclear p-STAT3 expression intensity by IHC was graded as absent, low, or high. Primary outcome was concordance of p-STAT3 expression between primary and metastatic sites. Secondary outcome was correlation of p-STAT3 expression with disease outcomes. Results: 91 patients were identified: 55% were male, median age at diagnosis was 63, 60% had left-sided disease and 81% of metastases were synchronous. Expression of p-STAT3 in primary tumors was 23% high, 47% low and absent in 30% compared to 29% high, 50% low, and 21% absent in metastases. Concordant expression was observed in 23% of patients whereas it increased in 46% and decreased in 31% from primary to metastasis. Pearson’s correlation was 0.119 indicating a weak concordance. After a median follow-up of 7 years, 50 of 91 patients died. One-year and 5-year survival rates were 92% and 44% respectively, while the median overall survival (mOS) was 4.7 years [95%CI 3.1-6.4]. No significant prognostic correlation between primary or metastatic p-STAT3 expression and mOS was found. Conclusions: There was low concordance of p-STAT3 expression in primary and metastatic tumors of patients with mCRC. Tumor staining heterogeneity due to sampling of small cores included in TMA and predominance of synchronous metastases may play a role. Further research in the use of p-STAT3 as a biomarker in patients with mCRC is needed.
Upfront autologous stem cell transplantation (ASCT) versus novel agent-based therapy for multiple myeloma (MM): A randomized phase 3 study of the European Myeloma Network (EMN02/HO95 MM trial).
Authors: Michele Cavo, Antonio Palumbo, Sonja Zweegman, Meletios A. Dimopoulos, Roman Hajek, Lucia Pantani, Meral Beksac, Ruth Wester, Hans E. Johnsen, Ulf-Henrik Mellqvist, Maria Teresa Petrucci, Christoph Driessen, Francesco Di Raimondo, Rossella Troia, Annalisa Pezzi, Bronno van der Holt, Ka Lung Wu, Heinz Ludwig, Francesca Gay, Pieter Sonneveld
Journal: Journal of Clinical Oncology (2016)

8000 Background: The role of upfront ASCT for newly diagnosed (ND) MM (NDMM) patients (pts) has been questioned in the novel agent era. Methods: A phase 3 study was designed to compare [random (R) 1] 4 cycles of bortezomib-melphalan-prednisone (VMP) vs high-dose melphalan (HDM) and single or double ASCT (this latter limited to centers applying a tandem ASCT policy) as intensification therapy following induction with bortezomib-cyclophosphamide-dexamethasone and subsequent collection of peripheral blood stem cells. Consolidation therapy with bortezomib-lenalidomide-dexamethasone vs no consolidation (R2) was planned after VMP and HDM, followed by lenalidomide maintenance until progression or toxicity in both treatment arms. Primary study end point was progression-free survival (PFS) from R1. A first prespecified interim analysis was performed in January 2016 when at least 33% of the required events had been observed. Results are herein reported. Results: From February 2011 through April 2014, 1503 pts aged ≤65 years with symptomatic NDMM were registered. Of these, 1308 pts were eligible for R1 and 1266 who were randomized (1:1 ratio; stratification by ISS stage) to VMP (512 pts) or HDM (1±2 ASCT) (754 pts) were analyzed. Median follow up from R1 was 24 months. PFS was significantly prolonged in pts randomized to HDM (HR=0.76; 95% CI=0.61-0.94; P=0.010), a benefit retained across predefined pt subgroups, including those with revised ISS stage III (HR=0.52; CI=0.32-0.84; P=0.008) and high-risk cytogenetics [t(4;14) ± del(17p) ± del(1p) ± 1q gain] (HR=0.72; CI=0.54-0.97; P=0.028). Superior rate of ≥ very good partial response was observed with HDM (84%) vs VMP (74%) (odds ratio=1.90; CI=1.42-2.54; P<0.0001). In a Cox regression analysis, randomization to HDM (HR=0.61, CI=0.45-0.82; P=0.001) was confirmed to be an independent predictor of prolonged PFS. Overall survival was not yet mature and no difference between the treatment groups was evident. Conclusions: Upfront ASCT still remains the preferred treatment for younger NDMM pts. Further follow-up of the study is needed. Clinical trial information: NCT01208766.
Retrospective correlational study between dyslipidemia and prostate cancer characteristics.
Authors: Korkor Sackey, Larisa Schwartzman, Stephen P. Shapero, Steven A. Lewis, Debora S. Bruno
Journal: Journal of Clinical Oncology (2017)

e16569 Background: Numerous studies have suggested metabolic syndrome’s association with advanced prostate cancer and patient outcomes but the data has not been conclusive. The goal of our research project was to analyze the relationship between lipid profiles and prostate cancer characteristics that predict outcomes in our patient population. Methods: A retrospective study was conducted on patients with a new diagnosis of prostate cancer seen at MetroHealth Medical Center (MHMC) between the years of 2009-2014. 427 electronic medical records of patients with stages I-III prostate cancer were reviewed. Dependent variables were pathological TNM stage, Gleason score (GS) and Prostate-Specific Antigen (PSA) level at time of diagnosis. Independent variables included components of the lipid profile (highest triglycerides, highest and lowest HDLs), body mass index, hypertension, diabetes and use of lipid lowering agents. Patients who did not have lipid panels available were excluded from final evaluation. Results: A total of 363 patients met inclusion criteria. The median age was 63, with African Americans accounting for 56% of all cases. The average BMI was 28.6 consistent with overweight and at time of prostate cancer diagnosis, 23% of patients had diabetes and 69% had hypertension. 68% of patients had stage I disease at time of diagnosis and no correlations were noted between TNM stage, GS or PSA at diagnosis with any of the components of the lipid profile, hypertension, hemoglobin A1c or use of lipid lowering medication. African Americans were noted to have higher PSA at diagnosis than other races (p &lt; 0.0001). Conclusions: Of patients with stage I-III prostate cancer diagnosed between 2009-2014 at MHMC, 85% were screened for dyslipidemia. Preliminary analysis of our data did not establish a correlation between dyslipidemia and prostate cancer characteristics. However, by limiting our study to only patients with lipid profiles, a subset of patients and their characteristics were not analyzed. This could explain the results noted in our study. Further studies are needed in our population to investigate which factors affect prostate cancer characteristics so better screening and interventions can be developed.