tbuckley/cabot-search huggingface dataset:
Use, misuse, and overuse of white cell growth factors (GF) in community oncology practices in southeastern United States.
Authors: William J. Hrushesky, Dinah Faith Q Huff, Carol Anthony, Laura Rose Bobolts, Melissa Armitage, Sharon Davis, Charles L. Bennett, William S. Shimp, Anna E. Schorer, Marc L. Fishman, Cristalle Dobies, Danielle Fishman, Val Fishman, Robert Walton, Jurgen Kogler
Journal: Journal of Clinical Oncology (2014)

9654 Background: Level 1 data, multiple national guidelines, and ASCO Choosing Wisely policy recommend that GFs be employed if the risk of febrile neutropenia (FN) exceeds 20%. Virtually every common chemotherapy regimen has been documented to put cancer patients at low (<10%) or intermediate (10-20%) or high risk (>20%) for FN. Oncology analytics (OA) screens all requests for GFs. If low risk regimens are employed, their use is challenged serially by: 1. electronically in initial request interaction, 2. informational fax bearing all relevant data, and 3. oncologist-to-oncologist peer review. We hypothesize that these agents are being overused in the community oncology setting among 2,800 practices we advise in the southeastern united states. Methods: During the 10 months between April 2013 and Jan 2014, we reviewed 1,700 requests for GFs: 894 for pegfilgrastim, 725 for filgrastim, and 62 for other GFs. Results: 355 of the 890 pegfilgrastim requests (40%) were made for patients receiving low-risk chemotherapy regimens; 455 (50%) intermediate risk, and 91 (10%) high risk regimens. Record reviews, educational faxes, and peer-to-peer reviews were serially instituted for all GF requests for low risk regimens. 113 (12%) of these were withdrawn or rescinded resulting in diminished cost of 2.1 million dollars in those 10 months. Conclusions: This ongoing pre-approval process results in more guidelines-compliant cancer care and diminishes waste.
Effective routine electronic symptom screening and use of evidence to improve cancer symptom management in Ontario, Canada.
Authors: Sean Molloy, Esther Green, Jose Pereira, Reena Tabing, Carol Anne Sawka
Journal: Journal of Clinical Oncology (2013)

e20507 Background: Improving symptom management is a critical component of high quality care. Cancer Care Ontario (CCO) is working to improve through a standardized approach to symptom screening and assessment that leverages electronic tools along the cancer journey. Methods: CCO has developed a web-based application that allows patients to report their symptoms using the Edmonton Symptom Assessment System (ESAS). ESAS is a validated screening tool that asks patients to rate the severity of nine common cancer symptoms. The use of ESAS promotes a common language among patients and providers and across care settings. To support clinicians in determining follow-up to scores, CCO has developed symptom management guides. The guides represent current evidence and best practices and are available in various formats to help the care team assess and manage a patient’s cancer-related symptoms. Results: Since the program’s introduction in 2007, over 1.6 million ESAS screens have been performed across the province. In November 2012, over 53% of all Regional Cancer Centre patients were screened representing over 23,000 patients and nearly 35,000 ESAS screens. Symptom assessments collected from 45,000 cancer patients revealed that 75% of patients reported fatigue as a concern, 57% reported anxiety and 53% reported pain. Patients have indicated that they value this approach. Results from a 2012 survey of 3,320 patients show that 93% thought that indicating their symptom severity is important as it helps their health care providers know how they are feeling. Evidence from chart audit reviews demonstrates that symptom screening is linked to higher rates of documented clinical interventions but further research is needed to analyze its impact on outcomes. Conclusions: Lessons learned include the importance of leadership at all levels, clinician engagement in change, point of care decision support tools and the importance of engaging patients in the management of their symptoms. Patients are overwhelmingly in support of this approach to cancer symptom screening and their involvement is critical to its expansion across all settings of care.
Survival rates in patients with primary metastatic breast cancer over a 10-year period: A retrospective analysis based on individual patient data from a multicenter data bank.
Authors: Jana Barinoff, Philipp Harter, Florian Heitz, Christine Dittmer, Sherko Kuemmel, Rita Hils, Fatemeh Lorenz-Salehi, Alexander Traut, Andreas du Bois
Journal: Journal of Clinical Oncology (2013)

1577 Background: Approximately 6% of patients with breast cancer have distant metastases at the time of the initial diagnosis. The aim of this analysis was to examine the overall survival rate over time and to investigate the effect of new therapy options. Methods: This retrospective analysis was performed based on the data bank of the Clinic for Gynaecological Oncology/ Dr. Horst Schmidt Klinik, Wiesbaden and the Clinic for Gynaecological Oncology and Senology/ Kliniken Essen Mitte, Essen. The patients with primary metastatic breast cancer (pmBC) who were diagnosed and treated at the accredited breast cancer centres of these clinics were enrolled between 1998 and 2007. The date of diagnosis was used to define 2 specifically chosen 5-year periods: 1998–2002 and 2003–2007. The follow-up time was on average 76 months. The Breslow Test was used to evaluate changes in the median survival time and to detect factors associated with the increase in survival rates. Results: Two hundred sixteen patients with complete baselines were analysed. Ninety patients were diagnosed between 1998 and 2002, and 126 patients received their diagnosis of pmBC between 2003 and 2007. The tumour-biological factors were the same in both groups, whereas the therapeutic concepts were different—the later group (2003–2007) received more aromatase inhibitors, taxane-based chemotherapy and trastuzumab. This finding resulted in an increased median survival time from 31 months in the years 1998–2002 to 44 months in the group with the first diagnosis between 2003 and 2007. Conclusions: Primary metastatic breast cancer occurred at constant rates over last 10 years. The tumour findings did not change in the time between the two examined groups; however, the treatment options in the 2003–2007 group included newly approved therapies. The time period of the first diagnosis was detected as a risk factor for overall survival. Those patients diagnosed in the more recent time frame had a significantly improved survival rate. The establishment of new therapy options may explain this finding.
Creating a national collaborative strategy to enhance trial accrual in NCI’s National Clinical Trials Network (NCTN) in the era of precision medicine.
Authors: Andrea Denicoff, Holly A Massett, Grace E. Mishkin, Rick Bangs, Jordan Berlin, Miriam B. Bischoff, Frank DeSanto, Anne Duli, Laura E. Horvath, Michael S. Katz, Ruth Lambersky, Bhupinder Singh Mann, Worta J. McCaskill-Stevens, Nita Seibel, Sharon Hartson Stine, Wade Williams, Margaret M. Mooney, Jeffrey S. Abrams
Journal: Journal of Clinical Oncology (2015)

6589 Background: NCI launched the NCTN on March 1, 2014 to reinvigorate the publically funded cancer trials system. As precision medicine (PM) trials increasingly require screening large numbers of patients to identify a subset of patients whose tumors contain specific molecular targets, national accrual strategies are needed. We report findings from a Network-wide interactive meeting held in Dec, 2014 to explore accrual to PM and adolescent and young adult (AYA) trials. Methods: NCI convened a 2-day meeting of NCTN grantees and NCI staff, with 75 representatives from Groups, Patient Advocates & Lead Academic Participating Sites (LAPS), to discuss accrual in the era of PM. Accrual challenges and strategies were identified via a mixed method approach: pre-meeting worksheets, trial case studies, group and breakout sessions and a priority ranking activity. Findings were triangulated to determine next steps to maximize future accrual. Results: Key themes identified included the need to streamline trial communication and promotion, emphasize accrual feasibility during trial design and review, better address minority and underserved populations, increase the efficiency and clarity of regulatory processes, and incentivize and enhance participation in trials by investigators and sites. Consensus was reached on the need for a cross-NCTN forum to collaborate on accrual for specific challenging trials and address broader accrual issues. Key themes and recommendations for the forum will be elaborated on in light of PM and AYA trials. Conclusions: A new NCTN Accrual Core Team (ACT) will be formed to collaboratively address identified cross-cutting themes that have implications for accrual to trials. Next steps that may be addressed by ACT include identifying ways to target messaging to promote trials to key groups (including investigators, research teams, and patients), developing templates for trial education, facilitating the pooling of resources currently replicated by sites such as Medicare Coverage Analyses, standardizing trial tools and processes, and developing metrics to monitor accrual enhancement efforts.
A phase I study of cabozantinib plus nivolumab (CaboNivo) and ipilimumab (CaboNivoIpi) in patients (pts) with refractory metastatic urothelial carcinoma (mUC) and other genitourinary (GU) tumors.
Authors: Andrea B. Apolo, Amir Mortazavi, Mark N. Stein, Sumanta K. Pal, Nicole N. Davarpanah, Howard L. Parnes, Yangmin M. Ning, Deneise C Francis, Lisa M Cordes, Paul Monk, Tiffany Lancaster, Rene Costello, Swati Nanda, Donald P. Bottaro, John Joseph Wright, Howard Streicher, Seth M. Steinberg, Marilise Berninger, Liza Lindenberg, William L. Dahut
Journal: Journal of Clinical Oncology (2017)

293 Background: We report the safety and clinical activity of CaboNivo and CaboNivoIpi in pts with mUC and other GU tumors. Methods: Part I included 4 dose levels (DLs) (Cabo PO daily and Nivo IV q2wk): DL1 Cabo40/Nivo1, DL2 Cabo40/Nivo3, DL3 Cabo60/Nivo1, DL4 Cabo 60/Nivo3. Part II included 3 DLs (Cabo PO daily, plus NivoIpi IV q3 wk x 4 doses then Nivo q2wk): DL5 Cabo 40/Nivo1/Ipi1, DL6 Cabo40/Nivo3/Ipi1, DL7 Cabo 60/Nivo3/Ipi 1. Tumors were assessed for overall response rate (ORR) by RECIST 1.1. Adverse events (AEs) were graded (G) by NCI-CTCAE v4.0. Results: From 7/22/15-10/14/16, 40pts [mUC N=14/(plasmacytoid N=1); bladder urachal N=4; bladder squamous cell carcinoma (bSCC) N=2; germ cell tumor (GCT) N=4; castrate-resistant prostate cancer (CRPC) N=9/(neuroendocrine prostate N=1); sarcomatoid renal cell carcinoma (sRCC) N=1; trophoblastic tumor N=1); sertoli cell tumor N=1; and penile SCC N=4] were treated. Median age was 58 (range 31-77); 36 (90%) were male. AEs related to study drugs with [1] CaboNivo included G3 hyponatremia 4/24 (17%), hypophosphatemia 4/24 (17%), lipase increase 3/24 (13%), dehydration 2/24 (8%), diarrhea 2/24 (8%), fatigue 2/24 (8%), HTN 2/24 (8%), thromboembolic event 1/24 (4%), rash 1/24 (4%), chest pain 1/24 (4%), amylase increase 1/24 (4%), hyperthyroid 1/24 (4%), proteinuria 1/24 (4%), thrombocytopenia 1/24 (4%); and G4 pyelonephritis 1/24 (4%); [2] CaboNivoIpi included G3 hypophosphatemia 2/16 (13%), lipase increase 2/16 (13%), fatigue 1/16 (6%), ALT increase 1/16 (6%), and HTN 1/16 (6%). There were 2/40 (5%) G3 immune-related AEs: 1 aseptic meningitis/CaboNivo; and 1 colitis/CaboNivoIpi. There were no G5 toxicities, or DLTs. 38 pts were evaluable for response. ORR was 12/38 (32%): 1 CR (bSCC); 11 PRs (5 mUC, 1 sRCC, 1 urachal, 1 bSCC, 1 CRPC, 2 penile). SD 20/38 (53%); 9/11 responses were ongoing and 26/39 (67%) pts remain on study. Conclusions: CaboNivo and CaboNivoIpi were well tolerated with no DLTs. Responses were seen at all DLs. The recommended dose for Part I is Cabo40/Nivo3 and for Part II is Cabo40/Nivo3/Ipi1. Rare tumors such as bSCC, urachal, and penile cancer demonstrated responses. Clinical trial information: NCT02496208.
Feasibility and acceptability of implementing an electronic patient reported outcome (e-PRO) dysphagia screening tool for routine multidisciplinary care.
Authors: Kishan Shani, Michael Borean, Judy Chen, Yuchen Li, M. Catherine Brown, Ashlee Vennettilli, Anthea Lau, Dennis Zheng, Qin Kuang, Kevin Boyd, Yvonne Leung, David Cella, Helen Mackay, Gail Elizabeth Darling, Rebecca Wong, Deval Patel, Wei Xu, Geoffrey Liu, Doris Howell
Journal: Journal of Clinical Oncology (2017)

155 Background: In Ontario, Canada, longitudinal patient self-reporting of 9 common cancer symptoms and a global health scale (Edmonton Symptom Assessment System, ESAS) is mandated and used clinically as a screening tool for multidisciplinary precision care (chemo/rads/surg). However, a common GI symptom, dysphagia, is not assessed in the same setting. Methods: Mostly gastro-esophageal cancer outpatients (some head and neck and lung cancer patients undergoing radiation were also included for generalizability) received one of two versions (V1, V2) of the dysphagia screening tool based on PRO-CTCAE-derived language. The tool included two screening questions, which when answered affirmatively, led to more comprehensive dysphagia/odynophagia questioning. The survey was introduced on iPads with V1. An assessment of acceptability through patient survey was additionally included in V2, and the duration of survey completion was recorded. Exploratory in-depth interviews were conducted with oncologists to assess usability in the clinic setting. Results: Of 101 approached and eligible, 79 consented, and 66 completed the survey. Median completion time was 2.12 ± 0.80 min. 95% were happy to complete survey on a touchscreen tablet, 88% did not find completion of survey time-consuming, and 91% found completion of survey useful in order to tell the clinician how they feel physically and emotionally. The prevalence of dysphagia based on screening question #1 (“difficulty upon swallowing?”) was 38% (25/66), while for screening question #2 (“pain upon swallowing?”) prevalence was 18% (12/66). Five interviewed physicians found the survey to be clinically informative, not burdensome in terms of time consumption, and felt it would be a valuable addition to outpatient clinics. One recurring suggestion was to combine the two screening questions into one. Results were similar across GI, head and neck, and lung cancer sites. Conclusions: The e-PRO dysphagia screening tool is acceptable and feasible for patients, and useful for clinicians. Next, a modified one-question dysphagia tool will be assessed in the multidisciplinary care of gastro-esophageal cancer patients.
Phase III trial of stem cell transplantation compared to melphalan and dexamethasone in the treatment of immunoglobulin light chain amyloidosis (AL).
Authors: Morie A. Gertz, Martha Lacy, Angela Dispenzieri, Francis Buadi, David Dingli, Suzanne R. Hayman, Shaji Kumar, Nelson Leung, John Anthony Lust, S. Vincent Rajkumar, Stephen J. Russell, VeraJean Suman, William J. Hogan
Journal: Journal of Clinical Oncology (2015)

8595 Background: Autologous stem cell transplant is widely performed for the management of select patients with AL amyloidosis in the United States. There are no phase III trials that document improved overall survival. This phase III trial allowed patients to select between melphalan and dexamethasone or autologous stem cell transplantation. Methods: Eighty-nine patients with biopsy-proven AL amyloidosis elected to receive melphalan and dexamethasone (n = 34) or stem cell transplantation (n = 54). Patients were selected to exclude those for whom cardiac involvement would not have permitted safe autologous stem cell transplantation. Results: Allowing patients to select their preferred treatment resulted in an imbalance of patients between the two arms. Patients that selected melphalan and dexamethasone were younger, were more likely to be ECOG performance status less than 2, and had a higher amyloid stage defined by increasing degrees of cardiac amyloidosis. Patients receiving melphalan and dexamethasone had a three-year progression-free survival of 29% and overall survival of 58.8%. Patients receiving stem cell transplant had a three-year progression-free survival of 51.7% and overall survival of 83.6%. An attempt to match patients between the two arms, in terms of risk, produced 24 matched triplets with no difference in hematologic response. Conclusions: This trial, which did not meet its accrual goals, failed to demonstrate a survival advantage for matched patients undergoing autologous stem cell transplantation. Clinical trial information: NCT00477971.Differences between those who chose SCT and those who chose melphalan with dexamethasone. Arm A n = 33 Arm B n = 52 Median Age (25th-75th percentile) 63 years (58-67) 57 years (53-61) p < 0.001 Male 17 (51.5%) 37 (71.2%) p = 0.067 ECOG performance status 0-1 2 24 (72.7%) 9 (27.3%) 48 (92.3%) 4 (7.7%) p = 0.015 Risk group low high 20 (60.6%) 13 (39.4%) 37 (71.2%) 15 (28.8%) p = 0.350 AL stage I II III 4 (12.1%) 19 (57.6%) 10 (30.3%) 25 (48.1%) 21 (40.4%) 6 (11.5%) p = 0.002 Heart as dominant disease site yes no 22 (66.7%) 11 (33.3%) 18 (34.6%) 34 (65.4%) p = 0.007
A propensity-matched analysis of laparoscopic versus open distal pancreatectomy for pancreatic adenocarcinoma.
Authors: Mustafa Raoof, Sinziana Dumitra, Philip HG Ituarte, Yanghee Woo, Susanne Warner, Gagandeep Singh, Yuman Fong, Laleh Golkar Melstrom
Journal: Journal of Clinical Oncology (2017)

376 Background: Laparoscopic-assisted distal pancreatectomy (LDP) has improved perioperative outcomes over open distal pancreatectomy (ODP). Concerns regarding failure to achieve proper oncologic resection and compromised survival remain. Methods: Using the National Cancer Database (NCDB), we analyzed patients undergoing distal pancreatectomy for resectable pancreatic adenocarcinoma over a four-year period (2010-2014). Propensity score nearest-neighbor 1:1 matching (PSM) was performed between LDP and ODP patients based on age, sex, race, insurance, hospital volume, comorbidities, T-stage, N-stage, grade, neoadjuvant therapy, adjuvant therapy. Primary outcome was overall survival. Results: Of the 1,947 eligible patients, 605 (31%) underwent LDP. After PSM two well-balanced groups of 544 patients each were analyzed. There was a trend towards improved overall survival (OS) in patients undergoing LDP as compared to ODP (HR: 0.83, 95% CI 0.68-1.0; Median OS 29 vs. 23 months, p = 0.06). Patients undergoing ODP had a higher margin positive rate compared to those undergoing LDP (21.1% vs. 14.9%, p-value = 0.007). Overall conversion rate was 27%. Patients undergoing ODP had comparable outcomes to LDP in regards to median time to chemotherapy (50 vs. 48 days, p-value = 0.96); median nodes examined (12 vs. 12, p-value = 0.61); 30-day mortality (1.6% vs. 1.1%, p-value = 0.43); 90-day mortality (3.5% vs. 2.4%, p-value = 0.28); 30-day readmission rate (8.6% vs. 9.4%, p-value = 0.67). However, the median length of stay was shorter in the LDP group (6 vs. 7 days, p = 0.0001). Conclusions: In the absence of randomized trials, this is the largest comparative study demonstrating LDP as an acceptable alternative ODP, associated with a lower margin positive rate and shorter length of stay, and with no detriment in long term survival.
Intratumoral heterogeneity of intrahepatic cholangiocarcinoma.
Authors: Dirk Walter, Claudia Döring, Magdalena Feldhahn, Florian Battke, Sylvia Hartmann, Ria Winkelmann, Markus Schneider, Katrin Bankov, Andreas Schnitzbauer, Stefan Zeuzem, Martin-Leo Hansmann, Jan Peveling-Oberhag
Journal: Journal of Clinical Oncology (2017)

335 Background: No personalized therapy regimens could demonstrate a benefit in survival in intrahepatic cholangiocarcinoma (iCCA). Since genetic heterogeneity might influence single biopsy based targeted therapy or the outcome of clinical trials, aim of the present study was to investigate intratumoral heterogeneity of iCCA by whole exome sequencing. Methods: Samples from tumor center and tumor periphery of large iCCA lesions as well as a control from healthy liver tissue were obtained from 4 patients and whole exome sequencing was performed. Mutations that occurred only in the tumor center or periphery were defined as private, whereas mutations present in both samples were regarded as common. Results: A mean of 3 non-synonymous private mutations (range 0-13) per sample compared to 31.8 common mutations per sample (range 23-39) was identified. Mean percentage of non-synonymous private mutations per sample was 12% (range 0-57). In all samples of patient 1-3 as well as the central sample of patient 4 ≤ 10% private mutations were found, whereas 57% of private mutations were identified in the peripheral sample of patient 4. In this sample, a private mutation in the DNA mismatch repair protein MSH6 as well as a spatial loss of expression of MSH6 could be identified most likely causing the high amount of private mutations. No substantial intratumoral heterogeneity was found in copy number variation analysis apart from a heterozygous duplication of chromosome 6p of patient 4. Conclusions: iCCA show a small but distinct intratumoral heterogeneity. Somatic mutations in mismatch repair proteins might contribute significantly to increased spatial tumor burden and thereby can have crucial impact on clinical management.
Clinical validation of mutational analysis of <i>EGFR</i> and <i>KRAS</i> in fine needle aspiration and small core needle biopsies using a real-time PCR method.
Authors: Maria D. Lozano, Tania Labiano, Jose Ignacio Echeveste, Myriam Montanana, Nerea Gomez, Mercedes Aguirre, Felice Shieh, Teresa Ramos, Javier Zulueta, Alfonso Gurpide, Jose Luis Perez-Gracia, Salvador Martin-Algarra
Journal: Journal of Clinical Oncology (2013)

e19027 Background: About 75% of NSCLC is diagnosed at an advanced stage, thus analysis is often performed from small samples. There is a growing need for multiple biomarker testing when tissue is limited. We evaluated two real-time PCR based assays to assess EGFR and KRAS mutation status in limited tissue specimens and compared results to a lab validated method. Methods: 117 NSCLC patient samples (46 CNB, 71 FNA) were tested for EGFR and KRAS mutations using a single section. DNA was extracted directly from one stained smear in FNA samples (without pre-processing) and one 5-micron section in CNB using the cobas DNA Sample Preparation Kit. Sixty samples were also analyzed for both genes by direct sequencing using the same DNA. Eleven patients had matched CNB and FNA samples. Results: We tested 68 ADCs, 38 SqCCs, 8 NSCLC-NOS, 2 ADCs in situ non-mucinous, and 1 large cell carcinoma (Table). Median DNA concentrations for CNB and FNA were 14.17 ng/ul and 3.75 ng/ul. The failure rate for the cobas were 1.7% (EGFR), 6.8 % (KRAS) in FNA samples, and 0% for CNB. The failure rate for EGFR sequencing was 13.1% (FNA), 16.4% (CNB), and 0% for KRAS. The 11 patients with FNA and CNB showed concordant results between cobas and sequencing. One patient had two mutations; one (L782F) was detected only by sequencing. No discordant findings were seen other than invalid results comparing both systems. Conclusions: Assessment of mutations in limited tissue samples of CNB and FNA using a single section performed on the cobas EGFR and KRAS test is feasible and reliable. There was a lower invalid rate for EGFR testing on cobas test compared to Sanger sequencing. The cobas tests have rapid turnaround time to results, require limited input DNA, and are easier to use compared to sequencing. Still, it is mandatory that pathologists maintain careful quality control of the samples. [Table: see text]