tbuckley/cabot-search huggingface dataset:
Utilization of advanced molecular analyses in lung cancer: A country perspective—Young Research Group.
Authors: H. Ibrahim Petekkaya, Huseyin Abali
Journal: Journal of Clinical Oncology (2017)

e18027 Background: Molecular and genetic analyses in cancer treatment are continuously evolving, and taking part in patient management. This study evaluated the clinical practices of medical oncologists in Turkey for utilization of these methods in lung cancer patients. Methods: All medical oncologists registered to Turkish M.Oncology Society were called to participate an online survey about their practice patterns of using molecular and genetic analyses for the management of lung cancer patients. Survey included 19 questions for demographic data, work environment, knowledge about the molecular and genetic analyses, and barriers to use these methods. Results: A total of 188 medical oncologists (M/F: 117/71; mean age 39.3±6.7) were participated. The key findings: Work environment: Academia 49%; others 51% Checking mutations in adenocancer: 88.4% Molecular analyses available at home institution: 61.4% Checking EGFR, EML-ALK, ROS-1 in NSCLC: 75.7% Non-specifically checking markers: 58.2% Checking markers only for locally advanced/metastatic disease at diagnose: 75.1% Obtaining analyze results in: 8-14 days 45%; 15-21 days 31.2% Obtaining a positive EGFR/ALK report after initiating chemo: re-evaluate patient after 2/3 cycles 68.3%; stop chemo and shift to targeted therapy 20.6%; continue full-regimen 12.2% Maintenance therapy after response regardless of mutation: 36% If targeted therapy initiated regardless of mutation, the preferred 1 st step cytotoxic chemo regimen in metastatic adenocancer: cisplatin+pemetrexed 50.2% Analyzing mutation from primary lung biopsy: 95.8% Re-biopsy if sample was inadequate: 91.5% Secondary biopsy for: EGFR/ALK discordance 38.1%; progression under treatment 46%; young patient 22.2%; never-smoker 34.9%; test-negative but presumed to be clinically-positive patient 46.6% Conclusions: Majority of the medical oncologists in Turkey use molecular and genetic analyses in clinical practice. But, the limited availability and the lags in obtaining results lead oncologists to initiate treatment primarily based on clinical findings. Once these methods become more available, targeted therapies and consequent favorable outcomes will increase in oncology practice.
Prospective phase II multi-center study of individualized axitinib (Axi) titration for metastatic renal cell carcinoma (mRCC) after treatment with PD-1 / PD-L1 inhibitors.
Authors: Moshe Chaim Ornstein, Sumanta K. Pal, Laura S. Wood, Kimberly D Allman, Allison Martin, Jorge A. Garcia, Timothy D. Gilligan, Donna Company, Thomas Olencki, Kimryn Rathmell, Brian I. Rini
Journal: Journal of Clinical Oncology (2018)

4517 Background: Standard of care treatment in mRCC after checkpoint inhibitor (CPI) therapy includes VEGFR TKIs, though no prospective data have been published. Axitinib (Axi) is a VEGF-R inhibitor with prior clinical data supporting increased efficacy with dose titration. The existing titration schema of 5mg BID to 7mg BID to 10mg BID every 4 weeks, however, can lead to toxicity due to the magnitude of dose increases. A prospective, multi-center phase II trial of Axi given on an individualized dosing algorithm in mRCC after treatment with CPI was conducted (NCT02579811). Methods: Patients (pts) with clear cell mRCC, adequate organ function and measurable disease whose most recent therapy was anti PD-1 / PD-L1 treatment were eligible. Pts were treated with Axi 5mg BID starting dose with upward dose titration in 1mg BID increments (e.g. 5mg BID to 6mg BID, up to 10mg BID max dose) every 14 days if there was no grade (G) 2 Axi-related mucositis, diarrhea, hand-foot-syndrome, or fatigue. If G2 adverse events (AEs) occurred, pts took a 3-day break then resumed the same dose. Recurrent G2 AEs despite treatment breaks or G3/4 AEs resulted in dose reduction in 1mg BID increments. The primary outcome was progression free survival (PFS) with 38 pts needed to improve PFS from 6.5 months (based on retrospective data of TKI post-CPI) to 9.5 months (a = 0.10; power 80%). Results: The trial has completed accrual (n = 38): 74% male, median age 64, 89% KPS ≥80%, 16%/66%/19% IMDC favorable/intermediate/poor risk, 94% prior nephrectomy, 71% ≥ 2 prior therapies. Most recent therapy was 89% anti PD-1 (63% nivolumab monotherapy; 17% ipilimumab/nivolumab; 9% other) or 11% anti PD-L1 (6% atezolizumab; 3% bevacizumab/atezolizumab; 3% durvalumab). In evaluable pts, the estimated median is PFS 9.2 months, with 54% of pts still on Axi. The ORR is 38.7% (best response PR 38.7%, SD 48.3%, and PD 12.9%). The median highest dose per pt was 6mg BID (range, 5-9) and 44% of pts required dose reduction to < 5mg BID. There were no unexpected toxicities related to Axi. Conclusions: Axitinib on an individualized titration schema resulted in robust clinical efficacy after checkpoint inhibitor therapy. Clinical trial information: NCT02579811.
Association of TGF-β responsive signature with anti-tumor effect of vactosertib, a potent, oral TGF-β receptor type I (TGFBRI) inhibitor in patients with advanced solid tumors.
Authors: Vicki Leigh Keedy, Todd Michael Bauer, Jeffrey Melson Clarke, Herbert Hurwitz, Insun Baek, Ilho Ha, Chan-Young Ock, Su Youn Nam, Mina Kim, Neunggyu Park, Jung Yong Kim, Seong-Jin Kim
Journal: Journal of Clinical Oncology (2018)

3031 Background: Stromal signature regulated by TGF-β pathway is one of the major mechanisms of tumor immune surveillance, leading to resistance to immune checkpoint inhibitors (ICI). Moreover, TGF-β responsive signatures (TBRS) of stromal cells have been associated with poor prognosis. Vactosertib (TEW-7197) is a potent, highly selective, oral inhibitor of TGFBR1. The safety, anti-tumor effect of vactosertib and its association with TBRS levels were evaluated in patients with advanced solid tumors. Based on in-house TCGA analysis, high fibroblast TBRS (F-TBRS) levels were seen in pancreatic, lung, colorectal (CMS4 subtype), and stomach (GS subtype) cancers in association with poor prognosis (adjusted hazard ratio 1.27; P = 1.06 x 10-8). Methods: 29 patients were enrolled in a phase I modified 3+3 dose-escalating study (NCT02160106) and received vactosertib once daily at the dose range of 30~340 mg for 5 days with 2 days off. RNA sequencing of pre-treatment tumor samples in 16 patients were analyzed to evaluate F-TBRS levels defined as geometric mean values of 171 corresponding gene expressions. Results: Vactosertib was safe and well tolerated, and the maximum tolerated dose was not determined. The most common treatment-related AE (TRAE) was fatigue, while G3/4 abdominal pain, AST elevation, and pulmonary edema were each reported in one patient, respectively. One DLT of stroke was seen at 100mg QD. In per-protocol analysis, 6 out of 17 patients who received ≥140 mg achieved stable disease (35.3%) and showed higher F-TBRS levels than those with progressive disease. Conclusions: Vactosertib, a potent and highly selective oral TGFBR1 inhibitor, showed excellent safety with the current dosing schedule. Furthermore, since high F-TBRS levels are well recognized as one of the main mechanisms related to resistance to ICI, vactosertib would be an ideal therapeutic strategy in combination with ICIs or conventional anti-tumor therapies for solid tumors with high F-TBRS levels. Clinical trial information: NCT02160106.
TCT-490 Right Atrial Pressure Predicts Mortality in Cardiogenic Shock: Insights from the Cardiogenic Shock Working Group Registry
Authors: Kevin Morine, Shiva Annamalai, Lena Jorde, Allen Razavi, Robert Pedicini, Michele Esposito, Kyle Gobeil, Jaime Hernandez-Montfort, Arthur Reshad Garan, Claudius Mahr, Navin Kapur
Journal: Journal of the American College of Cardiology (2018)
The effect of routine early palliative care (PC) consultation on aggressiveness of care at the end of life (EOL) in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Hiral D. Parekh, Katherine Tullio, Paul Elson, Mellar P. Davis, Vamsidhar Velcheti, James Stevenson, Marc A. Shapiro, Cheryl M Carrino, Nathan A. Pennell
Journal: Journal of Clinical Oncology (2016)

e21688 Background: Early integration of PC for patients (pts) with advanced NSCLC improves quality of life, decreases aggressive care at the EOL, and possibly improves survival. In 2011 the Cleveland Clinic instituted routine referral to PC for advanced NSCLC pts at the time of initial assessment. We investigated the real world effects of early PC intervention on aggressiveness of care at the EOL in NSCLC pts before and after this policy. Methods: In a retrospective cohort study, 242 metastatic NSCLC pts cared for at the Cleveland Clinic in 2009-10 (pre-PC) and 2013-14 (post-PC) were reviewed through the tumor registry and electronic medical record. Primary endpoint was % pts receiving aggressive EOL care: chemotherapy within 14 days of death, no hospice care, or admission to hospice 3 days or less before death. Outcomes were also compared in pts who saw PC early ( < 60 days from initial visit) compared to late ( > 60 d) or no PC. Fisher's exact test was used for factors with 2 levels, chi-square test and Cochran-Armitage trend test for categorical factors with > 2 levels, Wilcoxon rank sum test for measured factors, and log rank test for survival. Results: See table below. Conclusions: NSCLC pts treated in 2013-14 were referred to PC significantly sooner and more often than pts in 2009-10 due to routine early PC referrals. Post-PC pts had significantly less chemo in the last 2 wks of life than pre-PC, as did pts with any PC compared to those with no PC. Although there was no significant difference in aggressive care between the 2 eras, there was a trend toward less aggressive care with early PC intervention compared to those with late or no PC (p = .08). All 2009- 10 (n = 105) 2013- 14 (n = 137) P value No PC (n = 93) Late PC > 60d (n = 50) Early PC < 60d(n = 74) P value Age (median) 63 62 63 0.20 64 59 63 0.04 Sex (% fem) 50 50 49 0.89 51 48 51 0.93 Systemic tx % 84 88 82 0.07 87 92 81 0.04 # PC visits, median (range) 1 (0- 15) 0 (0- 14) 2 (0- 15) < 0.0001 0 2 (1- 14) 4 (1- 15) 0.01 Median time to first PC visit (wks) 5.5 31.1 4 < 0.0001 0 33.1 5.6 < 0.0001 Hospice % 63 66 59 0.32 55 62 68 0.11 Systemic tx within 2 wks of death % 12 17 7 0.04 18 5 7 0.05 Median Survival from Dx (mos) 10.9 9.4 11.75 0.25 10.9 15.8 9.2 0.07 Aggressive EOL care % 42 44 41 0.77 50 43 35 0.08
TCT-137 Five-Year Clinical Outcomes for Resolute Zotarolimus-Eluting Stents in Total Occlusions
Authors: Robert Yeh, Henning Kelbaek, Franz-Josef Neumann, Patrick Serruys, Stephan Windecker, Jorge Belardi, Bo Xu, Shubin Qiao, Minglei Liu, Sigmund Silber
Journal: Journal of the American College of Cardiology (2018)
Healthcare resource utilization and costs associated with non-adherence to oral targeted therapies for patients with hematologic malignancies.
Authors: Krish Patel, Shaum Kabadi, Vinjamuri Sai Sudhir, Francine Leech, Kushan Thakkar, Joanna Huang, John M. Pagel
Journal: Journal of Clinical Oncology (2018)

e19564 Background: Oral targeted therapies (OTT) have provided significant benefit to patients with hematologic malignancies (HM). Although it is known that non-adherence to OTT is associated with greater healthcare resource utilization/costs (HCRU), most studies have focused on a single malignancy. Methods: A retrospective cohort study was conducted using a US-based payer claims database. Eligible patients had a diagnosis of a hematologic malignancy and received OTT between 1/1/2011 and 09/30/2016. Adherence was evaluated by the medication possession ratio (MPR), defined as sum of the days' supply for all fills of a given OTT in the follow-up period divided by the number of days in the same period. A patient was classified as adherent if the 12-month fixed MPR ≥ 0.8. Descriptive statistics and generalized linear models were used to evaluate the association between non-adherence and HCRU. Results: Of 2,399 patients meeting inclusion criteria, 60% adherent and 40% were non-adherent. Patients had a median age of 61 years and median Charlson Comorbidity Index of 2. Mean (SD) monthly inpatient and outpatient encounters for adherent patients were 0.02 (0.07) and 0.86 (1.00), respectively, and were 0.08 (0.13) and 1.71 (2.14) for non-adherent patients. Adherent patients had lower costs than non-adherent patients across all medical care settings. After adjusting for baseline characteristics, adherent patients had 69% lower medical costs compared to non-adherent patients (OR = 0.31; 95% CI 0.27-0.36). Conclusions: Better adherence to oral targeted therapies was associated with lower total HCRU in a contemporary cohort of patients across multiple HM. Monthly Costs for Adherent and Non-Adherent Patients on an OTT (All P < 0.01) Care Setting Adherent (N = 1436) Non-Adherent (N = 963) Mean SD Mean SD Inpatient Admissions 565 2173 2587 5606 Emergency Department Visits 41 159 81 388 Outpatient Office Visits 906 1950 2932 5921 Outpatient Other Visits 500 1107 941 2067 Skilled Nursing Facility Visits 15 164 63 461 Subtotal Medical Costs (Excluding Rx) 2069 3953 6758 1096 Outpatient Prescriptions 8475 2348 4736 2839 Total Monthly Cost 10544 4688 11494 10431
Adjuvant chemotherapy in the elderly population with locally advanced rectal cancer: A single-centre retrospective review.
Authors: Shiru Lucy Liu, Nathan William Dana Lamond, Christine Orr, Corey Sean Bricks, Wilma M Hopman, Nazik Hammad, Ravi Ramjeesingh
Journal: Journal of Clinical Oncology (2016)

e15080 Background: The role of adjuvant chemotherapy (aCTX) in the elderly population with locally advanced rectal cancer (LARC) previously treated with neoadjuvant chemoradiation (nCTX+RAD) followed by surgery is poorly understood and controversial. We have evaluated the association between aCTX and overall survival (OS) in elderly LARC patients ( > 65 years old) compared to non-elderly LARC (NELARC). Methods: This study comprised of a single-center retrospective analysis of 156 LARC patients diagnosed between 2005 and 2011 from Kingston, Ontario, Canada. All patients received nCTX+RAD followed by surgery and were followed until January 2015. Baseline characteristics were collected. Survival analysis was performed using Kaplan-Meier and Cox-regression statistics. Results: 76 patients were identified as being NELARC. More elderly patients were found to have cardiac comorbidities than NELARC (69% vs 31%), though rates of other comorbidities were similar. There were no differences in other demographic or pathological characteristics amongst the two groups. Elderly patients (with or without aCTX) had a lower 5-year OS compared to NELARC (63.8% vs 84.2%; p = 0.0006). While a significant survival advantage associated with aCTX was not identified within the elderly population, there was a numeric advantage (5yr OS with aCTX 68.4%, no aCTX 61.9%, p = 0.64). In cox-regression analysis, receipt of aCTX was a statistically significant variable associated with improved OS in both age groups (LARC: HR = 0.34, CI 0.14-0.83, p = 0.018; NELARC: HR = 0.17, CI 0.06-0.49, p = 0.001). Conclusions: As expected, elderly patients have inferior OS when compared to NELARC. Despite this, the current hypothesis generating data suggest that aCTX is significantly associated with survival regardless of patient age.
Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer
Authors: P. A. Bunn, K. Kelly
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer Get access Paul A. Bunn, Jr., Paul A. Bunn, Jr. University of Colorado Cancer CenterDenver, Colo Correspondence to : Paul A. Bunn, Jr., M.D., University of Colorado Cancer Center, 4200 E. Ninth Ave., Box B-188, Denver, CO 80262. Search for other works by this author on: Oxford Academic PubMed Google Scholar Karen Kelly Karen Kelly University of Colorado Cancer CenterDenver, Colo Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 3, February 1995, Pages 161–163, https://doi.org/10.1093/jnci/87.3.161 Published: 01 February 1995
Cardiometabolic risk in childhood cancer survivors: A Children's Oncology Group study.
Authors: Emma Lipshultz, Eric Jessen Chow, David Doody, Lisa M. Kopp, Sanjeev Aggarwal, Saro Armenian, Barbara Asselin, K. Scott Baker, Smita Bhatia, Louis S. Constine, David Robert Freyer, Caroline Laverdiere, Cindy L. Schwartz, Steven E. Lipshultz, Lynda M. Vrooman
Journal: Journal of Clinical Oncology (2018)

10056 Background: Childhood cancer survivors (CCS) are at increased risk of cardiovascular (CV) disease. We assessed the burden of potentially modifiable cardiometabolic risk factors among young adult CCS vs population-matched controls. Methods: CCS who enrolled on Pediatric Oncology Group protocols 9404, 9425, 9426, and 9754 from 1996-2001 with acute lymphoblastic leukemia/lymphoma, Hodgkin lymphoma, and osteosarcoma were prospectively assessed for prevalence of obesity, hypertension, dyslipidemia, diabetes, and lifestyle habits (smoking, physical activity) in CCS vs an age-, sex-, and ethnicity-matched 2013 NHANES population. We then estimated Framingham and PDAY general CV risk scores for both groups, and for CCS we also estimated CV risk scores published by the Childhood Cancer Survivor Study (CCSS). Results: Compared with NHANES (n = 591), CCS (n = 109; 43% female, mean age 28y; 16y since diagnosis; mean doxorubicin dose 286 mg/m2; 39% chest radiation, mean 23 Gy; 54% dexrazoxane exposed) had similar rates of obesity (26 vs 30%, p = .73), hypertension (35 vs 31% p = .46), hyperglycemia (12 vs 18%; p = .17), dyslipidemia (49 vs 46%; p = .55), and metabolic syndrome (ATP3 criteria: 12 vs 17%; p = .19). More CCS met Centers for Disease Control & Prevention’s guidelines for physical activity (69 vs 45%; p < .001) and fewer reported a history of smoking (27 vs 45%; p = .002). Results were similar among CCS recruited from sites with > 50 vs < 50% participation in this analysis. Because of lifestyle differences, Framingham and PDAY risk scores were generally higher for NHANES vs CCS. Applying the CCSS risk scores, 39% of CCS were at moderate risk of ischemic heart disease, and > 95% at moderate or high risk for heart failure corresponding to a 9-12% predicted incidence of these conditions by age 50. Conclusions: Young adult CCS exhibited similar cardiometabolic profiles as NHANES. With more favorable lifestyle habits, CCS had lower predicted CV risk per general risk models but a high proportion had moderate or greater risk of CV disease predicted by the CCSS risk models. Further analyses are needed to determine the impact of dexrazoxane on CCS-specific CV risk. However, the favorable lifestyle habits of this cohort provide cause for optimism.
Genetic variants of R-spondin genes to predict clinical outcome in mCRC patients (pts) treated with first line FOLFIRI and bevacizumab (FOLFIRI/BEV) in FIRE-3 cohort.
Authors: Yan Ning, Sebastian Stintzing, Wu Zhang, Dongyun Yang, Diana L. Hanna, Satoshi Okazaki, Martin D. Berger, Yuji Miyamoto, Jordan David West, Mitsukuni Suenaga, Marta Schirripa, Afsaneh Barzi, Volker Heinemann, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2016)

3586 Background: The secreted Wnt agonists of the R-spondin (RSPO) family, RSPO1-4, play important roles as Wnt coactivators by interacting with LGR receptors, leading to stabilization of Frizzles at the cell surface and resulting in various Wnt-related cellular and biological processes, including tumorigenesis. The novel Rspo-Wnt-VegfC-Vegfr3 pathway has been reported as bypass angiogenic pathway during tumor angiogenesis. Also, genomic alterations of RSPO genes were found in CRC. Therefore, we tested whether polymorphisms (SNPs) in RSPO1 (rs4074961, rs1134025), RSPO2 (rs601558, rs555008) and RSPO3 (rs1892172, rs10457487) could predict clinical outcome in mCRC pts treated with first line FOLFIRI/BEV enrolled in FIRE3 trial. Methods: Genomic DNA was isolated from tissue samples of 295 pts treated with first-line FOLFIRI/BEV in FIRE-3 trial. Median follow up: 39.6 mos; Median PFS: 11.3 mos. and Median OS: 25 mos. PCR-based DNA sequencing was used to determine SNPs. Results: Our data showed that RSPOs snps predict clinical outcome by pts tumor location and KRAS status. In left-side tumor pts, the RSPO2 rs555008 T/T genotype was significantly associated with shorter OS [23.7 (18.4-27.5) mos] compared to any G allele [31.9 (25-40) mos] in both univariate (P = 0.011) and multivariate analyses (P = 0.05). The RSPO3 rs10457487 any C [11.7 (10.1-13) mos] was associated with longer PFS compared to A/A [9.1 (7.5-10.1) mos] in both univariate (P = 0.009) and multivariate analyses (P = 0.024). For KRAS wild type pts, the RSPO2 rs555008 T/T was significantly associated with shorter OS [22.3 (17.5-26.4) mos] compared to any G allele [28.4 (22.7-35) mos] in univariate (P = 0.011). The RSPO3rs10457487 any C allele was significantly associated with longer PFS [10.8 (9.7-12) mos] compared to A/A [9.1 (7.6-10.1) mos] in univariate (P = 0.025) and had a similar trend in multivariate analyse (P = 0.08). Conclusions: This study provides the first evidence that RSPO2 rs555008 and RSPO3 rs10457487 could be prognostic markers for OS and PFS in mCRC pts treated with first line FOLFIRI/BEV. The significant correlation with outcomes was dependent on tumor location and KRAS status.
Effect of EGFR C797S/G mutation on osimertinib resistance in Chinese patients with non-small-cell lung cancer.
Authors: Keke Nie, Zhongfa Zhang, Chunling Zhang, Ketao Lan, Youxin Ji
Journal: Journal of Clinical Oncology (2018)

e21171 Background: To identify the optimal targets mutated genes after resistant to osimertinib treatment in Chinese patients with non-small-cell lung cancer. Methods: Study patients were all advanced lung adenocarcinoma, acquired resistance to osimertinib as a second or third line treatment. After resistant to osimertinib treatment, tumor tissues were collected by core needle biopsy. DNA was extracted from 15 x 5 um sliced section of formalin-fixed paraffin-embedded (FFPE) material and NGS was done and 1021 genes were tested. Results: A total of 11 Chinese patients were studied, 6 female and 5 male, median age 66-year old. 11 patients had harboring 66 kinds of point mutations, 2 altered gene copies, 2 genes amplifications, and 1 EML4-ALK gene fusion. There’s no MET or HER2 amplification, no SCLC transformation found in this cohort. All 11 patients still maintained initial EGFR 19 del or L858R activating mutations, 8 (72.7%) patients kept EGFR T790M mutations. 7 (63.6%) patients acquired EGFR C797S and/or C797G mutation, while 6 of them kept EGFR T790M mutation. Furthermore, these 6 patients had their EGFR T790M mutation and EGFR C797S and/or C797G mutation in the same allele. 3 patients had lost T790M mutation was treated back with gefitinib; one of them had stable disease for 3 months, the other two just started. 1 patient had EML4-ALK gene fusion as well as EGFR 19 del, T790M and C797G mutations, progressed with 1 month crizotinib orally, but had partial response with two-cycle of bargatinib plus cetuximab treatment. 2 patients died because of disease progression, and the other 5 patients were in chemotherapy or BSC at last follow-up. Conclusions: EGFR C797S/G mutation and it presented on the same allele with EGFR T790M was the most common mutation feature and played a key role in osimertinib resistance of Chinese patients of NSCLC. Patients’ tumor cells losing T790M mutation and maintaining EGFR activating mutation might be benefit from first-generation EGFR-TKI treatment. Bargatinib in combination with cetuximab in the management of patients harboring EGFR T790M with C797S/G in the same allele concomitant with ALK rearrangement need to be studied in the future.