tbuckley/cabot-search huggingface dataset:
Association of surgical quality metrics and hospital-level overall survival for patients with head and neck squamous cell carcinoma.
Authors: David W. Schoppy, Yifei Ma, Kim Felder Rhoads, Michelle M Chen, Brian Nussenbaum, Ryan K. Orosco, Eben Lloyd Rosenthal, Vasu Divi
Journal: Journal of Clinical Oncology (2017)

206 Background: Both negative margins and lymph node yields ≥ 18 from neck dissections in patients with head and neck mucosal squamous cell carcinomas (SCC) have been correlated with improved overall survival. It is unclear whether these patient-level metrics are applicable at the hospital level, and what compliance rates hospitals would need to achieve to show an improvement in survival. Methods: The National Cancer Database (NCDB) was used to identify patients who underwent primary surgery that included a neck dissection for mucosal SCC of the oral cavity, oropharynx, larynx, and hypopharynx. The percentage of patients at each institution with negative margins on primary resection and lymph node yields ≥ 18 from a neck dissection was quantified. A multivariate Cox proportional hazard regression was used to determine the association between hospital compliance rates with these metrics and overall survival. Results: There were 65,097 patients at 1,087 hospitals in the NCDB who underwent a neck dissection for mucosal SCC of the head and neck. A total of 221 hospitals (20%) had lymph node yields of 18 or higher in ≥ 80% of patients, and 137 hospitals (12.6%) achieved negative margins in ≥ 90% of patients. Patients treated at hospitals that attained the combined quality metric of ≥ 80% compliance rate with lymph node counts and a ≥ 90% compliance rate with negative margins, showed a significant improvement in overall survival (hazard ratio [HR] 0.93; 95% CI 0.89 to 0.98). This benefit in survival was independent of the patient level improvement seen from having negative margins (HR 0.73; 95% CI 0.70 to 0.75) and a lymph node count ≥ 18 (HR 0.85; 95% CI 0.83 to 0.88). Treatment at high volume or academic teaching hospitals was not independently associated with improved survival once the model controlled for margin status and lymph node count. Conclusions: Patients with head and neck mucosal SCC experience better survival when treated at hospitals achieving a combined quality metric based on lymph node counts and negative margin rates. National tracking of these modifiable quality metrics may identify facilities that would benefit from quality improvement measures.
Multicentre phase II study of imatinib mesylate in patients with recurrent glioblastoma: An EORTC: NDDG/BTG Intergroup Study
Authors: E. Raymond, A. Brandes, A. Van Oosterom, C. Dittrich, P. Fumoleau, B. Coudert, C. Twelves, C. De Balincourt, D. Lacombe, M. Van Den Bent
Journal: Journal of Clinical Oncology (2004)

1501 Background: Autocrine activation of PDGFα&β receptors yields strong mitogenic effects and activates tumor angiogenesis in malignant gliomas. Preclinical data showed tumor growth inhibition of ras and v-sis transformed BALB/c, 3T3U87 and U343 human glioma xenografts in mice using imatinib mesylate. Methods: To assess the antitumor activity (measured by response and 6-month PFS) and the safety of imatinib mesylate (Glivec) in patients (pts) with histologically proven, CT-scan or MRI documented measurable recurrent glioblastoma, stable/decreasing doses of steroids, no more than one prior chemotherapy regimen, and no surgery or radiotherapy within 3 months prior to enrollment were entered. Imatinib mesylate was given until tumor progression at the daily dose of 600mg (group A) and 800mg (group B) in two cohorts of pts. A Fleming one sample/one stage testing procedure was used. Results: A total of 51 pts (M/F: 26/25; median age: 54, range: 27–68; PS 0/1/2: 18/26/7) were entered. 33 pts had been exposed to chemotherapy, 50 to radiotherapy, and 45 had prior resection. 19 pts were entered in group A (70 cycles) and 32 in group B (113 cycles). Grade 3–4 neutropenia was reported in 5 pts (1 in group A and 4 in group B) and was associated with fever in 3 pts. Dose reduction:5 pts (4 in group A, 1 in group B); dose interruption: 21 pts (11 in group A, 10 in group B) pts. Grade 3–4 non hematological toxicity consisted of edema (1 pt), skin rash (2 pts), and reversible ALT elevation (4 pts). One patient presented an intratumoral hemorrhage associated with a documented tumor progression (considered not related to treatment). Three pts (2 in group A and 1 in group B) experienced confirmed partial responses that lasted 10, 10, and 12+ months. Responses slowly occurred after 3, 6 and 7 months of drug exposure. Prolonged ≥6-months tumor stabilizations were reported in 5 pts (1 in group A and 4 in group B). Conclusion: Imatinib mesylate as single agent displays promising antitumor activity and good safety profile in patients with recurrent glioblastoma. This study is currently extended to patients with malignant oligodendroglioma and anaplastic astrocytoma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
Circulating Tumor DNA as Biomarkers for Cancer Detection
Authors: Xiao Han, Junyun Wang, Yingli Sun
Journal: Genomics Proteomics & Bioinformatics (2017)

Detection of circulating tumor DNAs (ctDNAs) in cancer patients is an important component of cancer precision medicine ctDNAs. Compared to the traditional physical and biochemical methods, blood-based ctDNA detection offers a non-invasive and easily accessible way for cancer diagnosis, prognostic determination, and guidance for treatment. While studies on this topic are currently underway, clinical translation of ctDNA detection in various types of cancers has been attracting much attention, due to the great potential of ctDNA as blood-based biomarkers for early diagnosis and treatment of cancers. ctDNAs are detected and tracked primarily based on tumor-related genetic and epigenetic alterations. In this article, we reviewed the available studies on ctDNA detection and described the representative methods. We also discussed the current understanding of ctDNAs in cancer patients and their availability as potential biomarkers for clinical purposes. Considering the progress made and challenges involved in accurate detection of specific cell-free nucleic acids, ctDNAs hold promise to serve as biomarkers for cancer patients, and further validation is needed prior to their broad clinical use.
Cardiac effects of Dovitinib in first-line metastatic renal cell carcinoma: Sub-analysis of a phase II clinical trial.
Authors: Michael Kuan-Ching Lee, Rob Doughty, Reuben James Broom, Kerin Thompson, Steven Duffey, Georgia Wilson, Christine Crooks, Mark James McKeage, Fritha J. Hanning, Peter C.C. Fong
Journal: Journal of Clinical Oncology (2015)

e15605 Background: Dovitinib is an anti-VEGFR tyrosine kinase inhibitor (TKI) which also inhibits FGFR-1,-2,-3 and PDGFRβ. VEGFR inhibitors are known to cause cardiotoxicity. We sought to assess the cardiac effects of dovitinib in subjects with metastatic clear-cell renal cell carcinoma (mCCRCC). Methods: The 30 treatment naïve patients with mCCRCC enrolled in this single-arm, single-site, phase II study received dovitinib at 500mg 5 days on/2 days off until progression. Cardiac evaluation included; ECG (Wks 0,4,7), echocardiogram (Wks 0,12,24), lipid profile (Wks 0,4), high-sensitivity troponin T (Wks 0,4, every 6 Wks). Results: At baseline, all patients had a normal LVEF (mean 66.1% SD6.1%). At 12 Wks, the mean change in LVEF was -1.1% (SD 8.6%, p = 0.3). 13 of 18 patients that remained on treatment at 24 Wks had echocardiograms - these showed a mean drop in LVEF of -4.2% (SD 8%, p = 0.049). No patient suffered a clinical cardiac event nor symptoms. Of the five patients with positive high sensitivity troponin at baseline (range 15-49ng/L) and the three that became positive, all had insignificant rises ( < 10ng/L or < 50% change). At 4 Wks, there was a significant rise in triglycerides (change of 1.26mmol/L SD 0.36mmol/L p = 0.0002) and significant decrease in HDL (change 0.26mmol/L SD 1.71mmol/L p = 0.0001). Conclusions: Dovitinib has sub-clinical cardiac effects not dissimilar to those observed with other anti-VEGFR TKIs. Routine use of high-sensitivity troponin T may not identify subjects who need echocardiogram surveillance on anti-VEGFR therapies. Clinical trial information: ACTRN12612000140853.
Accounting for Patient Preferences Regarding Life-Sustaining Treatment in Evaluations of Medical Effectiveness and Quality
Authors: Allan J. Walkey, Amber E. Barnato, Renda Soylemez Wiener, Brahmajee K. Nallamothu
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Section:ChooseTop of pageAbstract <<Influence of Patient Pref...Influence of Patient Pref...Strategies to Incorporate...Eliciting PreferencesDocumenting PreferencesRetrieving PreferencesAdhering to PreferencesAccounting for Preference...ReferencesCITING ARTICLES
Role of African American genetic polymorphisms in prostate cancer
Authors: M. P. Mims, J. Maran, S. M. Leal, T. G. Hayes, M. Ittmann, T. Wheeler, Y. Guan, J. T. Prchal
Journal: Journal of Clinical Oncology (2004)

4710 Background: In the U.S., African-American men have an incidence of prostate cancer that is substantially higher than any other ethnic group and is not clearly related to poor access to medical care. We proposed that common African-American genetic polymorphisms such as G6PD A+, G6PD A-, African polymorphism of b5R, α thalassemia, and sickle trait could influence the development and course of this malignant disease. These polymorphisms bear on capacity to respond to oxidative stress, and thus may impact expression of many genes that subsequently influence abnormal growth. We hypothesized that African-Americans who inherit these polymorphisms may be susceptible to these effects in general and development of prostate cancer in particular. Methods: We developed rapid methods for genotyping patients for each of these polymorphisms using small amounts of blood or tissue. Forty-five African-American patients with prostate cancer and 45 healthy African-American men were genotyped for the above conditions. Results: Conclusions: Although the results are not significant, possibly due to small sample size, the data suggest an association between African American polymorphisms of the housekeeping enzymes cytochrome b5R and G6PD and risk of developing prostate cancer. The results also seem to show that the G6PDA+ mutation (which results in no significant hemolysis) may be protective. Neither of the purely red cell disorders tested was associated with risk of developing prostate cancer. One could speculate that deficiencies of the ubiquitious intracellular enzymes cytochrome b5R and G6PD modify response to oxidative stress and might be associated with the development of prostate cancer. The study will be expanded to achieve adequate power to evaluate any link of these polymorphisms to prostate cancer. If associations are found, then antioxidant strategies could be devised to minimize the risk and lower the incidence of prostate cancer. No significant financial relationships to disclose.
Pre-existing hypertension is an independent prognostic factor in metastatic renal cell carcinoma (mRCC) patients treated with sunitinib (SU).
Authors: Lisa Derosa, Hassane Izzedine, Gwenael Le Teuff, Laurence Albiges, Bernard Escudier
Journal: Journal of Clinical Oncology (2014)

4573 Background: Hypertension (HTN), one of the most frequent side effects of VEGF inhibitors, has been related with outcome in mRCC. We aimed to investigate the prognostic value of history of pre-existing HTN (HTN-PRE) and pre-existing medications with angiotensin system inhibitors (ASI-PRE). Methods: mRCC patients (pts) treated with SU as first line therapy at Gustave Roussy from April 2004 to January 2014 with available data about HTN-PRE and pre-existing concomitant medications were included. Overall survival (OS) and progression free-survival (PFS) were compared with the log rank test and hazard ratios (HR) and 95% confidence interval (CI) estimated through a multivariable Cox model adjusted on age, gender, histology and IMDC prognostic groups. Results: 213 pts with a 44 (95%CI=31-60) months median follow-up received SU as first line treatment. Most pts were male (78%), 59 years median age (28-86), had clear-cell histology (87%) and intermediate IMDC risk (61%). 84 pts (39%) had HTN-PRE including 54 (64%) receiving ASI-PRE. Pts with HTN-PRE received ASI-PRE more often than pts without (64% vs 6%, p<0.001). The total number of deaths and PFS events was 59% and 85%. Pts with HTN-PRE had a longer OS (median: 32 vs 23 months, p=0.03) and longer PFS (median: 12 vs 9 months, p<0.02) with respectively HR of 0.59 [0.39-0.89], p=0.01 for OS and HR of 0.66 [0.48-0.91], p=0.01 for PFS. In HTN-PRE subgroup, pts with ASI-PRE had a better OS but similar PFS than pts without ASI-PRE with HR of 0.45 [0.23-0.89], p=0.02 and HR of 0.72 [0.41-1.26], p=0.24, respectively. Conclusions: HTN-PRE is an independent prognostic factor in pts with mRCC treated with SU. The mechanism of action of ASI in SU treated pts deserves further evaluation.
A novel dosing schedule with gemcitabine, vinorelbine, and carboplatin for advanced non-small cell cancer of the lung
Authors: R. Sadasivan
Journal: Journal of Clinical Oncology (2004)

7368 Background: Lung Cancer remains a leading cause of cancer death worldwide. Patients with stages IIIB and IV non-small cell cancer of the lung have a very poor outcome. Current treatment with chemotherapy using various two-drug regimens has shown limited benefits. Three-drug regimens have considerable toxicities. Understanding drug synergy between Gemcitabine and Carboplatin, and between Vinorelbine and Carboplatin, we have pioneered a novel dosing schedule that combines the three drugs on a fractionated weekly schedule. Methods: A phase II trial of this novel dosing schedule of a three-drug regimen using a fractionated weekly schedule is reported. Patients received weekly treatments with Gemcitabine, Vinorelbine, and Carboplatin for a duration of 26 weeks. Patients who met eligibility requirements which included stage IIIB and IV disease; performance status 0–2; ability to give consent; and adequate renal, hepatic, and cardiac function were enrolled on the protocol. Patients who developed anemia were eligible for Darbepoetin or Epoetin. Patients who developed neutropenia (ANC < 1,000) were given a week off treatment. To date, 26 patients with stages IIIB and IV have been enrolled in this single institution study. All patients had histologic confirmation of a non-small cell cancer of the lung. Chemotherapy treatments consisted of Gemcitabine 800mg/m2 /week, Vinorelbine 15mg/m2 /week and Carboplatin AUC=2/week. Results: 6 patients (23%) are in complete remission; 11 patients (42%) have partial remission; 7 patients (27%) have stable disease, and 2 patients (8%) have failed treatment. The protocol is closed to accrual, but median survival has not been reached. Toxicities include neutropenia 50% (grade 3–4), anemia 40% (grade 3–4), and neuropathy 16% (grade 3–4). Conclusion: This novel regimen, which utilizes drug synergy, is well tolerated and holds promise for further study in a phase III trial. No significant financial relationships to disclose.
Gaps in integrating genetic testing into management of breast cancer.
Authors: Steven J. Katz, Sarah T. Hawley, Reshma Jagsi, Allison W. Kurian
Journal: Journal of Clinical Oncology (2017)

160 Background: Genetic testing for breast cancer risk is evolving rapidly, with surging use of multiple-gene panels. However, little is known about the extent to which testing is effectively integrated into management after diagnosis of breast cancer. Methods: A population-based sample of 3930 patients diagnosed with breast cancer in 2014-15 and identified by two SEER registries (Georgia and Los Angeles) were sent surveys 2 months after surgery and responses merged to SEER data. A subgroup at higher pre-test risk of pathogenic mutation carriage (vs average risk) was defined according to testing guidelines. Results: Among 2502 eligible patients with unilateral breast cancer (response rate 70%), 666 (27%) reported genetic testing. The Table shows wide variability in patient report of which professional ordered the test and discussed the results. Few (18-21%) patients had testing ordered by a genetic counselor and approximately half (57% high-risk, 42% average-risk) discussed results with one. One third of patient received testing after they had surgery. In a multivariable model adjusted for age, race, education, pre-test risk of mutation carriage, stage, co-morbidities and study site, the only factor significantly associated with delayed testing was insurance status: Compared to private insurance, patients were more likely to be tested after surgery if they had Medicare (OR 2.1, 95% CI 1.1-4.2) or no insurance (OR 3.0, CI 1.6-5.3). Conclusions: There is wide variability in which professionals order genetic testing and discuss results. Many breast cancer patients who receive genetic testing never see a genetic counselor. Many patients do not get tested early enough to consider the results in surgery management. These findings suggest enormous challenges in personalizing communication about genetic testing after diagnosis of breast cancer. [Table: see text]
Work productivity in rhinitis using cell phones: The <scp>MASK</scp> pilot study
Authors: J. Bousquet, M. Bewick, S. Arnavielhe, E. Mathieu‐Dupas, R. Murray, A. Bedbrook, D. P. Caimmi, O. Vandenplas, P. W. Hellings, C. Bachert, J. M. Anto, K. C. Bergmann, C. Bindslev‐Jensen, S. Bosnic‐Anticevich, J. Bouchard, G. W. Canonica, N. H. Chavannes, A. A. Cruz, R. Dahl, P. Demoly, G. De Vries, P. Devillier, A. Fink‐Wagner, W. J. Fokkens, J. Fonseca, N. A. Guldemond, T. Haahtela, B. Hellqvist‐Dahl, J. Just, T. Keil, L. Klimek, M. L. Kowalski, P. Kuna, V. Kvedariene, D. Laune, D. Larenas‐Linnemann, J. Mullol, A. M. Pereira, P. Carreiro‐Martins, E. Melén, M. Morais‐Almeida, L. Nogueira‐Silva, R. E. O'Hehir, N. G. Papadopoulos, G. Passalacqua, F. Portejoie, D. Price, D. Ryan, B. Samolinski, A. Sheikh, F. E. R. Simons, O. Spranger, A. Todo Bom, P. V. Tomazic, M. Triggiani, A. Valero, E. Valovirta, A. Valiulis, M. van Eerd, M. Wickman, I. Young, T. Zuberbier
Journal: Allergy (2017)

Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS-work >50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.
Development of a complex patient identification process for the CMS’ Oncology Care Model.
Authors: Naralys Sinanis, Osama Abdelghany, Michael Strait, Catherine A. Lyons, Kerin B. Adelson
Journal: Journal of Clinical Oncology (2017)

32 Background: The CMS’ Oncology Care Model (OCM) provides practices with enhanced monthly payments for beneficiaries with cancer receiving chemotherapy. While the program will distribute a retrospective beneficiary list, practices need to track and identify eligible patients upfront to initiate care management and financial counseling processes and to bill for the enhanced payment. The eligibility criteria require information that many practices do not have. We describe a stepwise approach to patient identification that can be used by other OCM practices. Methods: We ran a report that identified patients with Medicare who received an OCM-eligible drug. We classified drugs into four categories: IV chemo confirmed by our own billing, oral specialty tracked and/or filled by our specialty pharmacy, general prescriptions filled at offsite pharmacies, and oral drugs billed under Medicare Part B. Because patients on general oral drugs receive 11 refills when first prescribed, we could not rely on a new prescription to trigger enrollment; we created a candidate list of patients who received oral prescriptions in the last year. Our pharmacists manually checked QS1, to verify Medicare Part D status and Surescripts to confirm that patients filled their prescription. Results: The build took time to validate due to disparate data and incomplete insurance information. 1039 IV chemo, 249 oral chemo, 196 oral Medicare Part B, were definitively eligible. 2991 with general prescriptions made the oral candidate list, which required additional verification of last visit date, Medicare Part D status, and prescription fill date. Approximately 70% of our patients have Medicare Part D and over 90% filled their prescription. We billed IV for July and August and are awaiting final confirmation of drug fill before billing the patients from the oral categories. Conclusions: The patient identification process was more complex than expected. Implementation required a multi-disciplinary effort with extensive collaboration across several departments as well as a time-intensive manual insurance and drug fill-verification process. Opportunities exist to automate Medicare Part D verification using our real-time eligibility software.