tbuckley/cabot-search huggingface dataset:
Long-term patterns in race-specific, distant metastasis-free survival following radiation treatment for prostate cancer.
Authors: Jennifer Cullen, Charlton A Smith, Huai-Ching Kuo, Inger L. Rosner, Yongmei Chen, Lauren Hurwitz, Sean Stroup, Timothy C. Brand, Joseph Sterbis, Christopher Porter, Kevin R. Rice, William Skinner, Anthony Victor D'Amico, Grace L. Lu-Yao
Journal: Journal of Clinical Oncology (2018)

5077 Background: Racial differences in prostate cancer (PCa) outcomes are widely observed, irrespective of risk stratum at diagnosis. The primary study aim was to compare distant metastasis-free survival (DMFS) for African American (AA) and Caucasian American (CA) military health care beneficiaries undergoing radiation therapy (RT) for PCa over 20+ years. Methods: A retrospective cohort study of Center for Prostate Disease Research Multi-Center National Database enrollees was conducted. Eligibility requirements included a diagnosis with biopsy-confirmed PCa between January 1, 1989 and December 31, 2013, primary treatment ( < 6 months post-diagnosis) with external beam radiation therapy (EBRT) or brachytherapy (BRY), and ≥2 years follow-up. EBRT combined CT-based, 3D conformal, and intensity modulated RT (IMRT). DMFS was compared across race using Kaplan Meier (KM) estimation curve analysis, stratified by treatment type (EBRT vs. BRY). Multivariable (MV) Cox Proportional Hazards (PH) analysis was used to model DMFS as a function of race, stratified by treatment type (EBRT vs. BRY), controlling for clinical covariates. Results: Of the 4,299 eligible men who had primary RT, 2,022 (77.6%) had EBRT and 583 (22.4%) had BRY (N = 2605). Among EBRT patients, 28% were AA and 66% were CA. For BRY patients, 18% were AA and 77% were CA. Median follow up times and ages were 6.7 and 69.8 years for EBRT patients and 6.9 and 65.4 years for BRY, respectively. In KM analysis race did not predict DMFS for EBRT group (p = 0.56) but there were significant racial differences among BRY group (p = 0.013). Table 1 shows DMFS estimates by race and treatment group. In MV Cox PH models, race did not predict DMFS among EBRT patients (p = 0.695); however, among BRY group, AA men had a 4.7-fold increased probability of developing distant metastasis compared to CA men (p = 0.045), controlling for age at RT, year of treatment, and NCCN risk stratum. Conclusions: In this racially diverse, equal access health care system, comparable DMFS was observed across patient race over this 20+ years for EBRT but not BRY patients who had significantly poorer DMFS. Subsequent work will examine cancer-specific survival, comorbidity, and prostate volume.
Epigenetic Therapy with Panobinostat Combined with Bicalutamide Rechallenge in Castration-Resistant Prostate Cancer
Authors: Anna C. Ferrari, Joshi J. Alumkal, Mark N. Stein, Mary-Ellen Taplin, James Babb, Ethan S. Barnett, Alejandro Gomez-Pinillos, Xiaomei Liu, Dirk Moore, Robert DiPaola, Tomasz M. Beer
Journal: Clinical Cancer Research (2018)

This study assesses the action of panobinostat, a histone deacetylase inhibitor (HDACI), in restoring sensitivity to bicalutamide in a castration-resistant prostate cancer (CRPC) model and the efficacy and safety of the panobinostat/bicalutamide combination in CRPC patients resistant to second-line antiandrogen therapy (2ndLAARx).The CWR22PC xenograft and isogenic cell line were tested for drug interactions on tumor cell growth and on the androgen receptor (AR), AR-splice variant7, and AR targets. A phase I trial had a 3 × 3 panobinostat dose-escalation design. The phase II study randomized 55 patients to panobinostat 40 mg (A arm) or 20 mg (B arm) triweekly ×2 weeks with bicalutamide 50 mg/day in 3-week cycles. The primary endpoint was to determine the percentage of radiographic progression-free (rPF) patients at 36 weeks versus historic high-dose bicalutamide.In the model, panobinostat/bicalutamide demonstrated synergistic antitumor effect while reducing AR activity. The dose-limiting toxicity was not reached. The probability of remaining rPF exceeded protocol-specified 35% in the A arm and 47.5% and 38.5% in the B arm. The probabilities of remaining rPF were 47.5% in the A arm and 38.5% in the B arm, exceeding the protocol-specified threshold of 35%. A arm/B arm: adverse events (AE), 62%/19%; treatment stopped for AEs, 27.5%/11.5%; dose reduction required, 41%/4%; principal A-arm grade ≥3 AEs, thrombocytopenia (31%) and fatigue (14%).The 40 mg panobinostat/bicalutamide regimen increased rPF survival in CRPC patients resistant to 2ndLAARx. Panobinostat toxicity was tolerable with dose reductions. Epigenetic HDACI therapy reduces AR-mediated resistance to bicalutamide in CRPC models with clinical benefit in patients. The combination merits validation using a second-generation antiandrogen.
Improvement of EGFR testing under multidisciplinary care: A retrospective chart analysis.
Authors: Margaret Griffin Crawford, Jun Zhang, Hussein Hamad, Srijana Rai
Journal: Journal of Clinical Oncology (2018)

e18874 Background: Testing for epidermal growth factor receptor (EGFR) gene mutation have been standard of care for patients with metastatic lung adenocarcinoma since 2013. We reviewed if case discussion in Multidisciplinary Thoracic Tumor Board (MDTB) would improve the rate of EGFR testing. Methods: 189 patients with metastatic lung adenocarcinoma were identified in Harris Health System Lung Cancer Database from 2012-2016. Patients’ charts were reviewed to determine if MDTB discussion at any point during patient care would improve EGFR mutation testing. Results: We reviewed charts for 189 patients. 54 of the 189 patients (28.6%) were discussed in MDTB at any given time. 44 of the 54 patients (81.4%) were tested for EGFR mutation, and 10 patients were not tested. Of these, one patient was discussed in 2012 prior to testing being standard, 5 patients died or opted for hospice care, one patient did not undergo biopsy due to failure to show up for the appointment and one patient who underwent bone biopsy and had sampling error. Two patients were not tested even though discussed at MDTB. 79 of 135 (58.5%) patients who were not discussed in MDTB had EGFR testing performed. Compared to patients who were not discussed in MDTB, patients who were discussed in MDTB were more likely to be tested for EGFR mutation, 58.5% versus 81.4%. Conclusions: From our observation, patients who had MDTB discussion had a higher chance of EGFR testing. Since EGFR tyrosine kinase inhibitor is the standard first-line treatment for stage IV EGFR mutated lung adenocarcinoma, EGFR testing is imperative for providing quality oncologic care. We recommend MDTB discussion on every newly diagnosed lung cancer case in clinical practice.
Genomic profiling of melanomas of unknown primary.
Authors: Keith Ryan Wells, Jennifer Hintzsche, Carol M Amato, William Robinson
Journal: Journal of Clinical Oncology (2017)

e21048 Background: Approximately 2-10% of metastatic melanoma patients present without an identifiable primary melanocytic lesion. These melanomas of unknown primary (MUP) are clinically classified into stage III or stage IV based upon extent of spread of metastatic disease. Previous studies, evaluating MUP using a limited sequencing of BRAF, NRAS, and KIT, have shown a similar frequency of mutations as cutaneous samples. Methods: We identified and performed retrospective chart review on 43 patients treated at the University of Colorado who presented with a melanoma of unknown primary. We excluded patient who presented with a preceding pigmented lesion treated with excision or cryotherapy without a histological diagnosis. After informed consent, DNA was extracted from the tumor samples of these 43 patients. Whole exome sequencing (WES) was performed with exome capture on an Illumina HiSeq sequencer. Results: Our cohort showed a male predominance at 58.1%. The median age at diagnosis was 50.6 years. In our cohort, 93% were Caucasian, while 4.7% were Hispanic and 2.3% were of unknown ethnic origin. 9.3% of patient had a family history of melanoma. Sun exposure was documented in 39.5% of patients and its presence was associated with an increased survival (Median OS of 3.7 vs 1.3 years, p = 0.026). Patients with stage III melanoma had an increased survival (Median OS of 6.8 vs 1.3 years, p = 0.013). Genomic analysis showed mutational pattern similar to cutaneous melanoma with 50% harboring a BRAF mutation, 12% with an NRAS mutation, and 19% carrying an NF1 variant. We found mutational signatures for each tumor and classified each against a larger cohort of cutaneous, mucosal and acral melanomas. Conclusions: We present the genomic data of a large cohort of MUP. The mutational profile of MUP is consistent with other cutaneous melanomas.
Possible predictive value of G8 score and the drug concentrations for efficacy and toxicity of trifluridine/tipiracil for elderly patients with advanced colorectal cancer: A multicenter, phase II study (T-CORE1401).
Authors: Masanobu Takahashi, Makio Gamoh, Hisatsugu Ohori, Yasuhiro Sakamoto, Yasushi Tsuji, Michio Kuroki, Masahiro Takahashi, Hiroko Yaegashi, Hiroaki Yamaguchi, Takuhiro Yamaguchi, Hideki Shimodaira, Takashi Yoshioka, Chikashi Ishioka
Journal: Journal of Clinical Oncology (2018)

e15516 Background: The RECOURSE trial showed that trifluridine/tipiracil, or TAS-102, compared with placebo, prolonged overall survival (OS) of patients with colorectal cancer who were refractory to standard chemotherapy. We conducted this study to assess whether trifluridine/tipiracil was effective for elderly patients with advanced colorectal cancer. Methods: This trial was a single-arm, open-label, multicenter, Japanese phase II study, conducted by Tohoku Clinical Oncology Research and Education Society (T-CORE). Elderly patients, aged 65 years or more, with fluoropyrimidine-refractory advanced colorectal cancer, were treated with trifluridine/tipiracil, 35 mg/m2 twice daily, days 1-5 and 8-12, every 4 weeks. Primary endpoint was progression-free survival (PFS). Secondary endpoints were OS, overall response rate (ORR), toxicities, associations between the efficacies and geriatric assessment screening score, and associations between toxicities and plasma concentrations of the drug. Results: A total of 30 patients were enrolled from 7 hospitals in Japan. Mean age was 73 years. Median PFS was 2.3 months (95% CI 1.9―4.3 months). Median OS was 5.7 months (95%CI 3.7―8.9 months). ORR was 0%, and stable disease was observed in 57%. Grade 4 neutropenia was observed in 13%. Most frequently observed grade 3 non-hematologic toxicity was anorexia (13%). Patients with the higher G8 score (14 or more) showed longer PFS than those with lower G8 score (median, 2.0 vs 3.8 months, p = 0.008). Patients with grade 3 or 4 neutropenia showed higher maximum trifluridine concentration than those with grade 1 or 2 (mean, 2,945 vs 2,107 ng/ml, p = 0.036). Conclusions: The primary endpoint was met. This phase II trial supported that trifluridine/tipiracil is an effective and well-tolerable option in elderly patients with advanced colorectal cancer. In addition, using geriatric assessment screening tools and/or monitoring drug concentrations in plasma might be helpful for predicting efficacy and toxicities in elderly patients treated with this drug. Clinical trial information: UMIN000017589.
Determinants of bone and blood lead levels among teenagers living in urban areas with high lead exposure.
Authors: P Farias
Journal: Environmental Health Perspectives (1998)

Although lead has been extensively studied in children, its sources and effects remain unclear in adolescents. This study examined the relation of blood and tibia bone lead levels to lead determinants. One hundred adolescents living in Mexico City and surrounding suburbs were studied. Blood lead was measured by atomic absorption spectroscopy, and tibia lead was measured by a K X-ray Fluorescence (KXRF) instrument. Blood lead ranged from 1.8 to 29.2 microgram/dl, with a mean of 7.4 microgram/dl. Bone lead ranged from &lt;1 to 44.82 microgram Pb/g bone mineral, with a mean of 4.8 microgram Pb/g. Predictors of bone lead included higher traffic density near the home, mother's smoking history, and time spent outdoors. Predictors of log-transformed blood lead included bone lead levels, male sex, use of lead-glazed ceramics, and living in Mexico City. Bone lead remained a significant predictor of blood lead after adjusting for covariates in a final multivariate regression model. In our final model, a rise in bone lead from the middle of the lowest quintile to the middle of the highest quintile (a difference of 21.6 microgram Pb/g) was associated with an increase in blood lead of 1.2 microgram/dl. Our data suggest that in addition to current sources of environmental lead exposure, bone lead accumulated over time constitutes a moderate source of circulating lead during adolescence and may account for some of the adverse health effects documented in recent studies.
TCT-188 Culprit Lesion Harbouring Calcified Nodule Predicts A Higher Target Lesion Revascularization Rate after PCI with 2ndGeneration Drug-eluting Stent in ACS Patients: Findings from Serial Coronary Angiography Study
Authors: Hiroki Sugane, Yu Kataoka, Hiroki Nakano, Fumiyuki Otsuka, Yasuhide Asaumi, Teruo Noguchi, Satoshi Yasuda
Journal: Journal of the American College of Cardiology (2018)
Impact of the influenza vaccination on cancer patients undergoing therapy with immune checkpoint inhibitors (ICI).
Authors: Ragisha Gopalakrishnan, Douglas Buckner Johnson, Sally York, Michael N. Neuss, Travis John Osterman, David D. Chism, Kristin Kathleen Ancell, Ingrid A. Mayer, Vandana Gupta Abramson, Mia Alyce Levy, Kenneth Wyman, Jill Gilbert, Nishita Reddy, David S. Morgan, Kimryn Rathmell, Leora Horn
Journal: Journal of Clinical Oncology (2018)

3053 Background: Immune checkpoint inhibitors (ICI) are standard of care for many cancer patients (pts). There have been conflicting reports on the effect of the influenza (flu) vaccines (flu-V) on pts being treated with ICI, and some suggest that flu-V may impact survival outcomes in ICI treated pts. Methods: We conducted a retrospective review of patients at Vanderbilt Ingram Cancer Center treated with ICI from 2010-2017. Data collected included age, gender, race, cancer type, comorbidities, type of ICI (single v. combo), time of drug administration, time of flu-V, rate of flu prodromal, rate of admissions for flu related complications, rate of immune related adverse events (irAE) and admissions, and the impact of flu-V on PFS and OS. Statistical analysis was performed using Graph PAD prism and SPSS. Results: 534 patients were included, 72.1% received flu vaccine. Median age was 54, 76% male, 64.1% stage IV. Cancer types included were lung (37%), melanoma (34%), GU (18%), breast 7.2%, and lymphoma (3.4%). 93% received single agent ICI. Vaccinated and unvaccinated pts (37.4 v. 42.6, p = 0.067) developed equal rates of irAEs. Unvaccinated pts who developed irAEs were more likely to develop pneumonitis (37.23 v. 17.17, p = 0.023) and more likely to be admitted than vaccinated pts (41.53% v. 23.2% p = 0.016). Unvaccinated pts were less likely to experience flu prodrome (32.2 % v 43.7%, p = 0.067), but were more likely to be admitted for influenza related complications (62.4% 23.2 %, p = 0.032). Most common reason for admission was sepsis. Flu-V did not change PFS (vaccinated 47.2 m vs. unvaccinated 43.2 m, p = 0.0621) but improved OS (vaccinated 72 months v. 62 months unvaccinated, p < 0.001). In multivariate analysis, age and abstaining from flu-V were predictive for developing irAEs. Type and stage of malignancy, # of prior lines of therapy, type of ICI, and timing of flu-V was not predictive for developing for irAE. Conclusions: Our results suggest that seasonal flu vaccination is safe and beneficial for patients on ICI and reduces the rate of hospital admissions from flu related and irAEs. Furthermore, our study also demonstrates that vaccination with influenza may improve OS in patients receiving ICI.
Phase 1 study of intraperitoneal infusion of autologous monocytes with peginterferon alfa-2b and interferon gamma-1b in women with recurrent or refractory ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
Authors: Ana Tablante Nunes, Daniel Green, Irene Ekwede, Kathryn Zoon, Christina M. Annunziata
Journal: Journal of Clinical Oncology (2017)

TPS3092 Background: Monocytes can differentiate into classic M1 macrophages inhibiting tumor proliferation and promoting natural killer (NK) cell differentiation. We previously demonstrated that the combination of human monocytes, human interferon alfa-2b (IFNα-2b), and interferon gamma-1b (IFNγ 1b) act synergistically against tumor cells in vitro and in mouse models, providing a long and durable response. Additionally, monocytes, IFNα and IFNγ have been individually shown in early phase clinical trials to be safely administered intraperitoneally. As ovarian cancer is largely confined to the peritoneal cavity, it is likely that the administration of IFNs and monocytes intraperitoneally will create a strong anti-tumor environment and can overcome the immunosuppressive environment of epithelial ovarian cancer. We hypothesize that the monocyte and interferon administration will be tolerable to women with relapsed ovarian cancer. Methods: A Phase 1 single arm study to determine the maximum tolerated dose of intraperitoneal monocytes and pegylated IFNα-2b and IFNγ-1b is currently enrolling patients with recurrent or refractory ovarian cancer, fallopian tube cancer or primary peritoneal cancer without standard therapy options. Autologous monocytes obtained through apheresis 24 hours prior will be mixed with pegylated IFNα-2b and IFNγ-1b in a 3 + 3 dose escalation and administered intraperitoneally once every 28 days. Results: As of February 2017 we are enrolling our first cohort of patients and are evaluating for dose limiting toxicities. Conclusions: This is a novel therapy that if successful, may be efficacious alone or used to create a backbone on which to add novel agents such as SMAC mimetics or PD-L1 blockade, in order to increase immune-mediated killing of ovarian cancer. Clinical trial information: NCT 02948426.
Combination of accessible laboratory parameters to predict complications following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A single center experience with 240 procedures.
Authors: Celso Abdon Mello, Renata Takahashi, Fabio Oliveira Ferreira, Samuel Aguiar, Ademar Lopes
Journal: Journal of Clinical Oncology (2016)

e15669 Background: Metabolic and inflammatory markers are used to monitoring the consequences of surgical trauma. Our purpose was to evaluate laboratory changes and its association with postoperative complications following Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CS-HIPEC). Methods: pH, bicarbonate, coagulation, lactate, C-reactive protein-CRP, white blood cell-WBC count, neutrophil-lymphocyte ratio and platelets count were retrospectively evaluated in different moments of the perioperative period: (1) Preoperative; (2) Pre-HIPEC; (3) Post-HIPEC; (4) ICU admission; (5) 1st postoperative day; (6) 3rd postoperative day. We also analyzed the association between the findings and postoperative complications severity grade (NCI CTCAE v3.0), divided into two groups: 1–no/minor complication and 2–major complication. Repeated measures ANOVA test was used and statistical significance was assigned for p < 0.05. Results: Data from 240 CS-HIPEC procedures were evaluated (Mar/2001-Jul/2014). Morbidity and mortality rates were 62.9% and 2.5%, respectively. Minor and major complication rates were 38.7% and 24.2%, respectively. In the group of patients with major complications, we found lower levels of Neutrophil-lymphocyte ratio (preoperative); inferior mean values of leukocytes (9240 vs. 9410; p = 0.021) and neutrophils (9000 vs. 9210; p = 0.021) at ICU admission and 1st postoperative day; higher mean values of lactate (26.04 vs. 21.24; p = 0.002) at 1st postoperative day and higher mean values of CRP (15.95 vs. 10.78; p = 0.004) at 3rd postoperative day. In general, we observed a decrease in platelets level, an increase of INR and a tendency to acidosis as consequence of the HIPEC. Conclusions: Laboratory changes in metabolic and inflammatory parameters can be helpful tools to predict the risk of complications following CS-HIPEC. Lower levels of Neutrophil-lymphocyte ratio (preoperative), lower levels of white blood cell count (postoperative) and higher levels of lactate and CRP (postoperative) were associated to the risk of major complications.
Abstract 19451: Preoperative Brain MRI Findings in d-Transposition of the Great Arteries and Relation to Timing of Diagnosis
Authors: Jacqueline G Weinberg, Jonathan Murnick, Jessica L Carpenter, John T Berger, Kami Skurow-Todd, Anita Krishnan, Catherine Limperopoulos, Mary T Donofrio
Journal: Circulation (2015)

Introduction: Congenital heart disease is known to be associated with alterations in fetal cerebral blood flow and brain development. Instability in the fetal/neonatal periods may lead to injury. We sought to assess the prevalence of preoperative brain injury in neonates with d-transposition of the great arteries (d-TGA) and the relationship to prenatal/postnatal variables and outcomes. Methods: We performed a single center retrospective analysis of neonates with d-TGA who had preoperative brain MRI from 2009-2014. Patients with other cardiac and/or extracardiac anomalies were excluded. Prenatal/postnatal clinical variables were recorded and correlated to brain MRI findings. Results: A total of 45 neonates with d-TGA were identified of which 23 (51%) were diagnosed prenatally. The average gestational age was 38 weeks (range 33-41). All underwent an arterial switch procedure with 100% survival. Those diagnosed prenatally were more likely to be born within 5 miles of the tertiary pediatric center (96% vs. 5%, p&lt;0.001), had lower incidence of hypoxia (lowest PaO2 25.3 vs 21.1, p=0.02), shorter time to cardiac intensive care unit admission (85 vs 1025 minutes, p=0.002), and shorter time to balloon atrial septostomy (295 vs 1456 minutes, p=0.007). Brain MRI was abnormal in 14 (31%); 9/23 (39%) with a prenatal and 5/22 (23%) with a postnatal diagnosis. The most common abnormality was small or punctate ischemic white matter lesions (N=14). Three patients had evidence of deep grey matter injury. Those with brain MRI abnormalities had a lower average gestational age (37 vs 39 weeks, p=0.02) and were less likely to have had a balloon atrial septostomy (79% vs 93%, p=0.03). Brain MRI findings were not associated with preoperative acidosis, hypoxia, need for inotropes, time to admission to cardiac intensive care unit, or surgical procedural variables. Conclusions: Neonates with d-TGA had similar incidence of preoperative brain injury by MRI whether diagnosed pre or postnatally. Brain injury was associated with lower gestational age and lack of balloon septostomy. Further work is needed to determine any association between prenatal diagnosis and type/severity of brain injury, as well as other in utero factors relating to brain development that may play a role.