tbuckley/cabot-search huggingface dataset:
Small business technology transfer (STTR) phase I study (1 R41 MD006148-01) of an automated voice response (AVR) system to improve symptom management in neuro-oncology patients.
Authors: Sajeel A. Chowdhary, Barbara Ann Given, Charles W Given, Cindy Majeske, Paul D Decker, Brian Decker
Journal: Journal of Clinical Oncology (2012)

e12500 Background: This STTR Phase 1 study focused on enhancing and improving the technology of a prior AVR system (Grant #R01 CA30724) to manage symptoms in cancer patients. Neuro-Oncology patients were enrolled to test our proof of concept (POC). Methods: Previous AVR function was replicated using Asterisk software enhancing the branching logic, configurability and operational capacity on multiple operating systems; limitations of the previous AVR. Eligibility criteria: access to a telephone; actively on chemotherapy. Nurse recruiters provided detailed information about the study and answered questions. Following signed consent patients provided a preferred phone number and chose a day and time of the week to receive AVR calls. Patients received a Symptom Management Guide (SMG) at time of consent. Patients were contacted a total of 4 times over a 4 week period by the AVR. At each contact patients were asked to rate 17 symptoms on a scale of 1-9 for severity and interference with 4 domains of quality of life on a 1-5 scale. Patient’s reporting a 4 or higher severity level were directed by the AVR to reference their SMG for self-care strategies to manage their symptoms. At the end of the study patients completed a satisfaction survey. Results: Ten patients were enrolled. The AVR placed 38 of 40 scheduled calls. No errors in survey branching were evident with confirmation. Patient satisfaction surveys were completed with 70% of patients. One patient did not complete any scheduled calls and was not contacted, two patients were unreachable. All patients reported satisfaction. 86% reported they would recommend this system to their oncology provider. 71% felt it was helpful in individualized monitoring of symptoms between visits. 57% liked knowing their symptom(s) were being checked regularly. One indicated the system was too overwhelming. Complaints included: not being able to change responses (1) and not allowing them to answer questions as fast as they wanted (2). Conclusions: Patient satisfaction results and system performance confirmed that the POC was feasible and that this system should be studied in larger groups of oncology patients.
Meta-analysis of clinical outcomes to second-line endocrine therapy for visceral and non-visceral metastases.
Authors: John Forsyth Russell Robertson, Christine Campbell, Angelo Di Leo, Stephen R. D. Johnston, Judith Bliss, Ian Bradbury
Journal: Journal of Clinical Oncology (2015)

568 Background: A previous meta-analysis reported that patients with hormone receptor-positive visceral metastases (VMs) who respond to 1st-line endocrine therapy (ET) benefit for as long as those with only non-VMs. Here, we assess outcomes in the 2nd-line setting. Methods: We meta-analyzed five phase 3 RCTs of 2nd-line ETs for hormone receptor-positive breast cancer (anastrozole, exemestane and fulvestrant 500 and 250 mg; Table). All reported objective response rate (ORR), CBR, time to progression (TTP) and duration of clinical benefit (DoCB). Results: Combined ORR was similar for non-VMs (10%) vs VMs (9.2%) (Peto method p=0.485); only CONFIRM was an exception (ORR: 5.4% [non-VMs] vs 13.2% [VMs]); Tarone’s test for heterogeneity: p=0.0014). CBR for non-VMs (38.8%) vs VMs (31.9%) was significantly different (Peto method p< 0.001); Tarone’s test: p=0.068. Combined median DoCB was 420 days (non-VMs) vs 338 days (VMs) (odds ratio, 0.79; 95% CI, 0.68-0.91; Yusuf-Peto method p=0.001); Tarone’s test: p=0.028. The odds ratio of TTP (non-VMs vs VMs) was 0.71 (0.65-0.77) (Yusuf-Peto method p=0.001); Tarone’s test: p=0.022. Conclusions: VMs and non-VMs had similar ORRs. Approximately a third of patients with VMs (31.9%) achieve clinical benefit, 7% less than non-VMs (38.8%). VMs which achieve clinical benefit have prolonged periods of disease control, the median being almost 1 year. ET remains the well-tolerated treatment of choice for hormone responsive disease in the 2nd-line setting until newer agents, alone or in combination with ET, exhibit better efficacy than ET monotherapy. 0020 0021 EFECT CONFIRM SOFEA Combined Total, N 343 345 681 736 723 2828 Non-visceral 202 181 292 333 297 1305 (46.1%) CBR, n (%) 95 (47.0) 75 (41.4) 69 (23.6) 165 (49.6) 102 (34.3) 506 (38.8) ORR, n (%) 38 (18.8) 34 (18.8) 18 (6.2) 18 (5.4) 23 (7.7) 131 (10.0) Median TTP, d 174 210 147 253 162 173 Median DoCB, d 418 446 254 459 430 420 Visceral 141 164 389 403 426 1523 (53.9%) CBR, n (%) 54 (38.3) 61 (37.2) 103 (26.5) 148 (36.7) 120 (28.2) 486 (31.9) ORR, n (%) 19 (13.5) 27 (16.5) 21 (5.4) 53 (13.2) 20 (4.7) 140 (9.2) Median TTP, d 91 87 85 139 104 101 Median DoCB, d 306 272 273 491 362 338 d, days. ET Treatment groups are combined for all studies.
Quality of life (QOL) in esophageal cancer patients treated with tri-modality therapy: Is the CROSS protocol better?
Authors: Rachel Woo, Edwin Chan, Catherine Vanderwater, Charles Cho, Jason Wong, Wei Xu, Qihuang Zhang, Geoffrey Liu, Beibei Zhang, Agnes Cheung, Alex Lee, Pravin Philip Chacko, Ehab Fadhel, Zahra Kassam
Journal: Journal of Clinical Oncology (2017)

132 Background: To investigate the impact of trimodality therapy on QOL in esophageal cancer patients and compare the CROSS regimen to neoadjuvant cisplatin/5FU. Methods: In a non-randomized, prospective cohort study, patients undergoing neoadjuvant chemoradiation (CRT) and esophagectomy between June 2012 and Nov 2015, with esophageal adenocarcinoma or squamous cell cancer, T1-4N0-3 (AJCC 7 th Ed.), completed the EORTC-QLQ-C30 at baseline, end of RT, 6 months, and then annually. A 10-point difference in QOL scores was considered clinically significant. Results: Of 35 patients, 13 received cisplatin/5FU concurrent with 45-50 Gy/25fr; 22 received carboplatin/paclitaxel with 41.4 Gy/23fr (CROSS). Median follow up was 16 months (range 2-49). Questionnaire compliance ranged from 75-100%. Median differences (MD) for physical, role, cognitive, social, &amp; global function, and fatigue, nausea/vomiting (N/V), pain, appetite, &amp; constipation were clinically worse at the end of RT. Statistical worsening was found at the end of RT for global (MD -17, p = 0.001), physical (-17, p = 0.001), role (-33, p = 0.001), &amp; social function (-17, p = 0.003), and for fatigue (28, p = 0.001), N/V (17, p = 0.003), pain (17, p = 0.01), dyspnea (0, p = 0.015), sleep disorder (0, p = 0.049) &amp; appetite (33.3, p = 0.001). Clinical worsening persisted on several domains at 6 months. All scores at 1 year improved at least to baseline, except role functioning (-17, p = 1.0) and appetite (33, p = 0.5) which were clinically, but not statistically worse. No significant difference in QOL was found between cisplatin/5FU and CROSS groups at baseline or end of RT. At 6 months median scores were statistically significantly better for pain, fatigue, role, social, and global functioning in the CROSS group. Global QOL at 1 year remained significantly better in the CROSS group. Higher baseline global QOL was associated with improved OS (p = 0.04) and DFS (p = 0.02). Conclusions: QOL worsened across several domains until 6 months post-RT. Most scores returned to baseline or improved at 1 year except for role functioning and appetite. A larger cohort or controlled trial is needed to confirm our findings of a better long term QOL with the CROSS regimen.
A randomized phase II study of GDC-0980 versus everolimus in metastatic renal cell carcinoma (mRCC) patients (pts) after VEGF-targeted therapy (VEGF-TT).
Authors: Thomas Powles, Stephane Oudard, Bernard J. Escudier, Janet Elizabeth Brown, Robert E. Hawkins, Daniel E. Castellano, Alain Ravaud, Michael D. Staehler, Brian I. Rini, Wei Lin, Bridget O'Keeffe, Michelle Byrtek, Mark Lackner, Jill M Spoerke, Joseph A. Ware, Rui Zhu, Robert J. Motzer
Journal: Journal of Clinical Oncology (2014)

4525 Background: GDC-0980 (G) is a potent oral dual pan-PI3K and mTOR (TORC1/2) inhibitor that has been evaluated in multiple solid tumors in Phase I and II. Everolimus (E) inhibits TORC1 and is active in mRCC post VEGF-TT. This study is the first to dirctly test if a PI3K/mTOR inhibitor may improve efficacy over a TORC1 inhibitor. Methods: Clear cell mRCC pts who progressed on or after VEGF-TT were randomized (1:1) to G (40 mg QD) or E (10 mg QD), stratified by MSKCC score and time to progression on first VEGF-TT (≤ or > 6 months). The primary endpoint was progression-free survival (PFS); secondary endpoints included safety, overall survival (OS), objective response rate (ORR); and pharmacokinetic (PK) and biomarker correlation with safety and efficacy were exploratory. Results: Eighty-five pts were randomized (G 42:E 43). After 62 events (G 32:E 30), stratified analysis revealed the median PFS was significantly shorter for G than E (3.7 vs. 6.1 mo: HR 2.04 [95%CI: 1.18-3.54; p<0.01]) and did not favor G for any stratification subgroup. Median OS was not significantly different but trended in favor of E (11.9 vs. 14.6 mo: HR 1.73 [95%CI: 0.87-3.43; p=0.12]). ORR was 7.1% for G and 11.6% for E. Patients treated with G had greater incidence of Grade 3-4 adverse events (AEs) and were more likely to discontinue treatment because of an AE (G 31%:E 12%). G was associated with substantially more high-grade hyperglycemia (G 40%:E 7%) and rash (G 24%:E 5%). PK analyses of G suggest a relationship between exposure and safety (rash and hyperglycemia), but no clear exposure-efficacy relationship. Retrospective biomarker analyses from archived tissue revealed a relationship between VHL mutation status (by NGS) and outcome with E but not G. High HIF1A protein expression was associated with better outcome in both arms. Conclusions: This study was unable to demonstrate that inhibition of PI3K/TORC1/TORC2 with GDC-0980 provides any benefit over inhibition of TORC1 alone with everolimus. This may be due to the high rate of AEs associated with potent pathway inhibition. VHL mutation and HIF1A expression may be predictive of mTOR inhibitor benefit, though future prospective validation is required. Clinical trial information: NCT01442090.
Prognostic impact of changes in circulating tumor cells (CTC) in metastatic breast cancer (MBC).
Authors: Markus Wallwiener, Andreas D. Hartkopf, Sabine Riethdorf, Martin Sprick, Christoph Wolfram Domschke, Sarah Schott, Irene Baccelli, Caroline Modugno, Birgitt Schoenfisch, Barbara Burwinkel, Frederik Marme, Joerg Heil, Christof Sohn, Klaus Pantel, Andreas Trumpp, Andreas Schneeweiss
Journal: Journal of Clinical Oncology (2013)

11012 Background: To prospectively assess the prognostic value of CTC counts at baseline and after one cycle of therapy and their kinetics for response, progression-free (PFS), and overall survival (OS) in MBC. Methods: MBC patients underwent CTC enumeration (CellSearch, Veridex) at baseline (CTC BL ), after one cycle of a new line of therapy (CTC 1C ), and at progression (CTC PD ). CTC status was classified as negative (neg (−)) or positive (pos (+)) for &lt;5 and ≥5 CTC/7.5 ml peripheral blood, respectively. CTC kinetics (CTC KIN ) from CTC BL to CTC 1C were classified as favorable if CTCs remained neg (neg&gt;neg) or became neg (pos&gt;neg), or as unfavorable (neg&gt;pos or pos&gt;pos). Tumor response was assessed every 2–3 months using RECIST criteria. CTC status and kinetics were associated with outcome using log-rank and Fisher’s exact tests. Results: Of 326 patients enrolled (median age (range) at first diagnosis: 50 (23–81) years), 115/326 (35%) were CTC BL +, 51/162 (31%) were CTC 1C +, and 39/108 (36%) were CTC PD +. Median follow-up was 15.9 months (mos). Median PFS and OS were significantly reduced in CTC BL + compared to CTC BL − patients (PFS, 4.3 vs. 7.1 mos, p = .019; OS, 15.0 mos vs. not reached (nr), p &lt;.001) and for CTC 1C + compared to CTC 1C − patients (p &lt;.001 for PFS and OS). CTC KIN were predictive of progressive disease as best response (neg&gt;neg, 33%; pos&gt;neg, 38%; pos&gt;pos, 60%; neg&gt;pos, 75%; p = .040). PFS and OS for patients with unfavorable CTC KIN were significantly shorter than for favorable CTC KIN (PFS, 3.7 vs. 6.8 mos, p &lt;.001; OS, 7.8 mos vs. nr, p &lt;.001). Conclusions: CTC at baseline, CTC after one cycle and CTC kinetics are highly predictive of outcome in MBC. Serial CTC enumeration could serve as a useful adjunct to standard diagnostic tests in tailoring therapy. Further details of CTC PD will be presented at the meeting. Clinical trial information: S-295/2009.
Distress in older adult cancer patients approaching end of life.
Authors: Elizabeth Ann Kvale, Gabrielle Betty Rocque, Kerri S. Bevis, Aras Acemgil, Richard A. Taylor, Wendy Demark-Wahnefried, Kelly Kenzik, Yufeng Li, Karen Meneses, Michelle Martin, Mona Fouad, Edward E. Partridge, Maria Pisu
Journal: Journal of Clinical Oncology (2015)

9548 Background: Lay health navigators are able to address various issues that cause distress in older cancer survivors by administering and responding to distress thermometers (DT). Methods: Lay navigators in the UAB Patient Care Connect Program assist cancer patients ≥ 65 years old with traditional Medicare insurance at 12 cancer centers in Alabama, Mississippi, Georgia, Florida, and Tennessee. Navigators documented distress levels, causes of distress, and requests for intervention.. Distress screening data from the final DT administered prior to death were used to describe care gaps for older adults with advanced cancer. Results: DTs were collected on a representative sample of 1060 patients who were evenly divided with respect to gender and 18% minority. Median number of days from date of last DT to date of death was 42(1-544). Distress score ≥ 4 were observed in 43% of patients;10% reported scores ≥ 8. Forty four percent of patients attributed distress to physical symptoms such as pain and fatigue. Twenty two percent indicated mobility issues contributed while 15% indicated informational needs related to their illness or treatment. Patients were more likely to ask for help from navigators with informational issues related to their illness (63%) or hospice (75%) than mobility (35%) or physical symptoms (33%). Conclusions: Through distress screening lay navigators are able to help older adults with advanced cancer with informational or logistical needs and advocate for proactive assistance with issues related to symptom burden. The project described was supported by Grant Number 1C1CMS331023 from the Department of Health and Human Services, Centers for Medicare & Medicaid Services. The contents of this abstract are solely the responsibility of the authors and do not necessarily represent the official views of the U.S. Department of Health and Human Services or any of its agencies.
Prognostic impact of the 21-gene recurrence score in patients presenting with stage IV breast cancer.
Authors: Tari A. King, Jaclyn P Lyman, Mithat Gonen, Amy Voci, Marina De Brot, Camilla Boafa, Amy Pratt Sing, Eun-Sil Shelley Hwang, Michael Alvarado, Minetta C. Liu, Judy Caroline Boughey, Kandace P. McGuire, Catherine H. Van Poznak, Lisa K. Jacobs, Ingrid M. Meszoely, Helen Krontiras, Gildy Babiera, Larry Norton, Monica Morrow, Clifford Hudis
Journal: Journal of Clinical Oncology (2013)

507 Background: The 21-gene Recurrence Score (OncotypeDX Breast Cancer Assay) predicts outcome and benefit from chemotherapy (CT) in early stage ER+ BC treated with adjuvant endocrine therapy. We evaluated the association between Recurrence Score (RS), time to progression (TTP), and overall survival (OS) in patients with stage IV BC enrolled in TBCRC 013. Methods: TBCRC 013 is a registry study evaluating surgery of the primary tumor in pts presenting with Stage IV BC. From 7/09 - 4/12, 128 evaluable pts were enrolled in two cohorts (A: metastases (mets) with intact primary tumor (n=112); B: mets within 3 months of primary surgery (n=16)). This study includes 110 pts with pre-treatment primary tumor samples available for analysis. Clinical variables, TTP and OS were correlated with RS using long-rank, Kaplan-Meier and Cox regression. Results: Median pt age was 52yrs (21-79) and median tumor size 3.1cm (0.7-15). 82 (80%) were ER+, 83 (81%) Her2(-) and 51 (46%) had bone-only mets. Cohorts A and B did not differ. At a median follow-up of 26 mos (1-47), median TTP is 19 mos (95%CI16-25) and surgery is not associated with OS. 102 samples qualified for RS. 23 (23%) had low RS&lt;18, 29 (28%) intermediate RS, 18-30; and 50 (49%) high RS≥31. Age, tumor size or site of 1 st mets was not associated with RS. Risk groups were prognostic for TTP in ER+ pts and for 2 yr OS in ER+Her2- pts (Table). In Cox models continuous RS was also prognostic for TTP in ER+ pts (HR 3.5; for 50 point difference (PD) 95%CI 1.5-8.1, p=0.003) and for OS in ER+Her2- pts (HR 21.4, for 50 PD 95%CI 2.2-204.4, p=0.008). In MVA, adjusting for clinical variables, RS remained prognostic for TTP in ER+ pts (p=0.01). Further analysis of surgery in this trial is ongoing. Conclusions: The 21-gene RS is independently prognostic for TTP in ER+ Stage IV BC. RS is also prognostic for OS in ER+Her2- BC, suggesting that a high RS may be a surrogate for endocrine resistance and could be used to select pts with ER+ Stage IV BC for CT. A randomized trial to address this hypothesis is warranted. Clinical trial information: NCT00941759. [Table: see text]
EGFR mutation testing methods in clinical practice in Central Europe: findings from the insight observational study
Authors: W. Olszewski, H. Popper, I. Kern, L. Mullauer, R. Dziadziuszko, P. Berzinec, Ladislav Dušek, T. Cufer, P. Bajcic, Zbyněk Bortlíček, Lucia Copáková, B. Dome, J. Chorostowska-Wynimko, Blanka Robešová, Vítězslav Kolek, Miloš Pešek, R. Ramlau, W. Eisterer, L. Medvecova, P. Krawczyk, J. Mazal, J. Pirker
Journal: Journal of Thoracic Oncology (2013)
Circulating tumor (ct)-DNA alterations in advanced urothelial carcinoma: Association with outcomes and evolution with therapy.
Authors: Petros Grivas, Rebecca J Nagy, Gregory Russell Pond, Sumati Gupta, Jue Wang, Ulka N. Vaishampayan, Sumanta K. Pal, Mehmet Asim Bilen, Gurudatta Naik, Pooja Ghatalia, Dharmesh Gopalakrishnan, Pedro Barata, Richard B. Lanman, AmirAli Talasaz, Guru Sonpavde
Journal: Journal of Clinical Oncology (2017)

334 Background: Cell-free ctDNA may be potentially actionable, prognostic for outcomes and evolve after therapy. We conducted a retrospective study to evaluate these issues and shed light on UC biology. Methods: Patients (pts) with advanced UC who underwent ctDNA analysis for potentially actionable alterations using Guardant360 were identified. Data were requested for prognostic factors, current and prior therapies, TTF (time to treatment failure) and overall survival (OS). A 70-gene ctDNA next generation sequencing panel from a CLIA-licensed, CAP-accredited laboratory (Guardant Health, Inc.) offers complete exon sequencing for 29 cancer genes, critical exons in 39 genes and amplifications (16 genes), fusions (6 genes) and indels (3 genes) harvested from 10 mL of peripheral blood. Alterations were reported and association of non-synonymous potentially functional alterations with outcomes and prior therapy was examined. Results: There were 217 pts with 238 samples. ctDNA was detectable in 212 (89%) samples. Median age was 62 (range 39-91). The most common recurrent somatic mutations were in TP53 (n = 122, 57%) ARID1A (n = 47, 22%), NF1 (n = 35, 16%), FGFR2, FGFR3, and BRCA1 (n = 30, 14% each), MET (n = 27, 13%), ERBB2 (n = 25, 12%), PIK3CA (n = 24, 11%), and EGFR (n = 22, 10%). Most common genes with increased copy numbers were ERBB2 (n = 19, 9%) and RAF1 (n = 18, 8%). Clinical data were available for 64 pts, of whom 38 (59%) had prior chemotherapy. FGFR1 alterations noted in 3 of those pts (5%, 2 functional, 1 amplification) were associated with shorter OS (HR 2.95, p = 0.05). Pts with prior chemotherapy showed trend towards frequent alterations in DNA repair genes (45% vs. 23%, p = 0.11). Serial ctDNA profiling of 21 pts receiving therapy revealed the clonal evolution of mutations in BRCA2, NF1 and GATA3. Conclusions: ctDNA was very frequently detected in pts with advanced UC, and alterations were similar to those previously seen in muscle-invasive UC tumor tissue. FGFR1 alterations predicted for unfavorable outcome and DNA repair gene alterations evolved commonly after chemotherapy. Drugs exploiting these targets such as FGFR1 and PARP inhibitors may warrant exploration as salvage therapy in selected pts.
Pharmacodynamic separation (PDS) of gemcitabine (Gem) and the epidermal growth factor receptor (EGFR) inhibitor erlotinib (E) in patients (Pts) with advanced pancreatic cancer: Phase II results.
Authors: Thomas John Semrad, Heinz-Josef Lenz, I-Yeh Gong, Michael S. Tanaka, Courtney Eddings, Nichole Mahaffey, Philip C. Mack, Laurel Beckett, Primo Lara
Journal: Journal of Clinical Oncology (2013)

e15073 Background: Continuously dosed E given concurrently with Gem results in only a modest survival improvement in pts with advanced pancreatic cancer. Preclinical data suggest that there is antagonism between chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) when these are delivered concurrently due to cell cycle effects. Work by our group and others has shown that EGFR TKIs induce cytostasis due to G1 arrest, which reduces subsequent cell cycle phase-dependent activity of chemotherapy. We tested a PDS approach for E + Gem as a means of overcoming the hypothesized negative interaction of EGFR TKIs and chemotherapy. Methods: Pts with measurable, previously untreated locally advanced unresectable/metastatic pancreatic cancer with adequate organ function and PS 0-2 were eligible. Tumor tissue was collected for molecular studies. PDS Regimen: Gem 1000 mg/m2 IV days 1, 8, 15, and E 150 mg/day on days 2-5, 9-12, 16-26 of each 28-day cycle. Primary endpoint was PFS; secondary endpoints included response rate (RR) and safety. To have 80% power at 5% significance, 70 pts were planned to detect an increase of PFS from 3.75 to 5.25 months. The study was terminated due to funding considerations. Results: 30 pts enrolled with median age 67 years (range 46-84); PS: 0 (23%), 1 (47%), and 2 (30%); locally advanced (13%) &amp; metastatic (87%). Median PFS was 2.07 months (95% CI; 1.87 – 5.50 months). Median OS was 5.67 months (95% CI; 2.83 – 11.87 months). Median cycles completed were 2 (range 0-8). Two pts withdrew consent in the first cycle without progression and were not evaluable for response. RR was 11% (3 PRs); DCR was 46%. Grade 3/4 adverse events occurred in 63% of pts; the most common were neutropenia (23%), fatigue (13%), anemia (10%), thrombocytopenia (10%), rash (10%), nausea (10%), and diarrhea (10%). Conclusions: Although Gem and E in a PDS dose-schedule was feasible &amp; tolerable in pts with advanced pancreatic cancer, no signal for increased efficacy was seen (compared to historic controls) in this molecularly unselected cohort. Correlative studies to identify potential molecular biomarkers of benefit are ongoing and will be presented. Clinical trial information: NCT00810719.