tbuckley/cabot-search huggingface dataset:
Attitudes of medical oncologists across Canada toward CYP2D6 genotype testing: A Web-based survey.
Authors: S. Nasim, D. Cole, K. Hill, E. Warner
Journal: Journal of Clinical Oncology (2011)

e16552 Background: The clinical relevance of CYP2D6 genotype testing (CYPT) in breast cancer patients on tamoxifen (TAM) remains controversial due to conflicting reports. The aim of our survey was to evaluate knowledge, variations in physician attitudes and practice patterns among Canadian medical oncologists towards CYPT. Methods: The survey was electronically mailed to all medical oncologists practicing in Canada identified through the Canadian Association of Medical Oncology membership directory. Only oncologists treating newly diagnosed breast cancer patients (BCO) were invited to complete the survey which included demographics, a knowledge question, test availability and cost, and four case scenarios to assess response to hypothetical CYPT results. Results: 97/ 300 (32%) oncologists responded including 48 (49.5%) BCO and 49(50.5%) non BCO. While 98% (48) BCO were aware of CYPT, only 28% thought CYPT should be done routinely. 67% had access to test facilities, 50% had no patients and another 44% less than 10% of patients on TAM had CYPT, the most common reason being lack of evidence for CYPT relevance (81%). Although knowledge of CYP2D6 inhibitors was excellent only 62% routinely asked about inhibitors. In hypothetical scenarios involving CYPT in patients on TAM: 1) for peri-menopausal poor metabolizer 24% would continue TAM. 2) For pre-menopausal woman on strong antidepressant only 9% would recommend CYPT and with extensive metabolizer result 65% would continue TAM but change antidepressant and 26% would continue tamoxifen. 3) For 75 year old who had not tolerated an aromatase inhibitor with reduced metabolism ability 79% would continue current dose of tamoxifen. 4) For young ultrarapid metabolizer 30% were not sure regarding correct management. Conclusions: CYPT is infrequent in oncology practice in Canada and physicians are reluctant to change management based on test results. There are no consensus guidelines on correct management of patients on tamoxifen according to genotype status. If well designed prospective trials confirm a link between CYP2D6 activity and prognosis of patients on adjuvant tamoxifen further studies will be needed to determine the optimal management for each genotype.
Association of TLR9 polymorphism with overall survival in metastatic colorectal cancer patients treated with FOLFIRI plus bevacizumab enrolled in FIRE3.
Authors: Satoshi Okazaki, Sebastian Stintzing, Volker Heinemann, Shu Cao, Wu Zhang, Dongyun Yang, Yan Ning, Satoshi Matsusaka, Martin D. Berger, Jordan D. West, Yuji Miyamoto, Mitsukuni Suenaga, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2016)

498 Background: Toll-like receptors (TLRs) play crucial roles in carcinogenesis and evolution of the tumor microenvironment. TLR9 dependent stimulation is known to cause antitumor activity not only by activating anti-tumor immunity but also by interfering with angiogenesis. We tested the hypothesis that genetic variations in TLR9 will be associated with clinical outcome in metastatic colorectal cancer (mCRC) patients treated with bevacizumab based chemotherapy. Methods: Genomic DNA was isolated from tissue samples from 301 mCRC patients enrolled in the FIRE3 trial and treated in first-line with FOLFIRI plus bevacizumab. Three single nucleotide polymorphisms (SNPs) in the TLR9 gene, rs187084 A/G, rs352140 C/T, and rs5743836 T/C, were analyzed by PCR-based direct sequencing. These SNPs were tested for the association with tumor response, progression free survival (PFS), and overall survival (OS). Subgroup analyses by gender, tumor location, and Kras status were also analyzed. Results: The patients carrying variant genotype (T/C or C/C) for rs5743836 showed a strong trend toward shorter OS compared to those with a wild-type T/T genotype (median: 21.2 vs. 24.8 months, HR: 1.35, P = 0.069). This difference remained statistically significant in the multivariate analysis (HR: 1.53, 95%CI: 1.09-2.15, P = 0.014). In the subgroup of Kras-mutant type, the variants (T/C and C/C) were significantly associated with worse PFS (8.1 vs. 11.3 months, HR 2.06, p = 0.043) and OS (16.4 vs. 25.1 months, HR: 2.44, p = 0.012), which retained statistical significance in the multivariate analysis. No association with clinical outcome was observed for rs187084 and rs352140. Conclusions: Our findings suggest that TLR9 polymorphism of rs5743836 is a prognostic marker of mCRC patients, especially of those with Kras-mutant type, who were treated with FOLFIRI plus bevacizumab.
Treatment of stage IV NSCLC with chemotherapy in a community setting based on ECOG PS.
Authors: Rahul Singh, Jillian Saucier, Andrew Michael Schreiber
Journal: Journal of Clinical Oncology (2014)

62 Background: ECOG Performance Status (PS) plays a pivotal role in the decision to treat patients with NSCLC Stage IV. The current ASCO guidelines for offering cytotoxic chemotherapy in stage IV NSCLC state that a PS of ≤2 can be considered for intravenous treatment. The goal of our retrospective evaluation was to evaluate treatment patterns based on ECOG PS in a community setting. Methods: An IRB-retrospective chart review of all stage IV NSCLC patients at our institution between 1/1/2008 and 1/1/2013 was conducted. A total of 150 patients with NSCLC and an ECOG of ≤2 were randomly selected and reviewed from the cancer registry (12 were excluded for undocumented ECOG PS status). 138 patients were included. The data was analyzed using X 2 test of independence, Fisher’s exact, and students T-Test all run by SAS 9.1. Results: Of the 138 patients observed, 92 (66.7%) had an ECOG PS of 0, 16 (11.6%) were PS 1 and 30 (21.7%) were PS 2. There were no significant differences in ECOG PS based on race, gender or payer status. Patients with a PS of 2 received chemotherapy (N=1/30, p &lt;0.0001) significantly less than those with PS 0-1 (N=54/108, p &lt;0.0001). Those with PS 2 were more likely to have additional comorbidities as well (N=23/30, p&lt;0.0001) versus patients with a PS 0 or 1. Chemotherapy was not offered to 76.7% of patients with a PS of 2 (N= 23/30, p &lt;0.0001). Conclusions: In our community setting cytotoxic chemotherapy was offered significantly less in patients with ECOG PS of 2 compared to those with 0 and 1. While it is more likely that patients with better PS will be offered treatment, this significant difference reflects practice that differs from ASCO’s guidelines. It is suspected the disparity in offering treatment depending on the PS of 2 vs 0-1 likely was due to many cofounding variables as well as provider and patient preference. Another disparity noted was that of undocumented ECOG PS. As the system of healthcare is switching to an electronic based system one proposed theory would be to add the quality measure ECOG PS as an additional vital sign in an oncologist progress note, with a prompt to consider chemotherapy in patients with PS ≤2 and not to consider in PS 3 or 4. This could greatly benefit the medical oncologist in considering possible treatment.
Use of adjuvant chemotherapy in young women with node-negative ER+ breast cancer: Refining the use of recurrence score—A decision analysis
Authors: C. E. Woodall, N. P. Reuter, C. R. Scoggins, R. C. Martin, K. M. McMasters, J. B. Hargis, A. B. Chagpar
Journal: Journal of Clinical Oncology (2008)

11547 Background: Current guidelines recommend young women with early ER+ breast cancer with intermediate recurrence scores (RS) receive “consideration” for adjuvant chemotherapy. To guide clinical decision making in this setting, a formal decision analysis was performed to identify the RS at which the benefit of chemotherapy outweighs its risks of adverse events and reduced health- related quality of life. Methods: A decision tree was constructed around the choice of adjuvant chemotherapy with hormone therapy vs. hormone therapy alone for a 40-year old patient with a LN-, ER+ tumor (TreeAge Pro). The probability of long-term adverse events resulting from chemotherapy was estimated from clinical trial data. Standard gamble utilities for the terminal states of relapse after 10 years were obtained from the literature and direct estimation. The probability of relapse was estimated using Adjuvant! Online; a sensitivity analysis was performed over a range of RS from 18–30. The threshold probability of relapse was correlated with the RS at which the decision point of indifference was met. Results: The 10-year risk of death from other causes was 1.9%. The risk of serious toxicities with long term complications was set at 4%. At a RS of 18, the 10-year risk of relapse on tamoxifen alone was 10.9%, vs. 6.2% with combined therapy. At a RS of 30, the 10-year risk of relapse on tamoxifen alone was 19.8%, vs. 11.6% with combined therapy. Setting the average absolute difference in 10-year relapse between tamoxifen vs. combination at 6.5%, one way sensitivity analysis found tamoxifen therapy alone to be a superior strategy when the probability of 10-year relapse on tamoxifen alone was < 12.5%. This corresponded to a RS of 21. Conclusions: These data support the addition of chemotherapy to tamoxifen adjuvant therapy in young patients with ER+ node-negative tumors with RS of 21 or greater. Patients with lower RS may be better treated with tamoxifen alone. No significant financial relationships to disclose.
Consistent tumor measurement reporting in serial CT scans: A pilot study.
Authors: Terri P. Wolf, Dana Ann Little, Scott Christensen, Natasha Perkins
Journal: Journal of Clinical Oncology (2014)

99 Background: Oncologists in community cancer centers affiliated with the UC Davis Cancer Care Network reported quality concerns with inconsistently measured lesions on serial Computed Tomography (CT) scan reports. Radiologic imaging is an important tool in diagnosis, staging, and assessment of response to therapy in cancer treatment cancer. Accurate assessment of oncologic therapeutic efficacy is dependent on reliable radiology and report quality. The primary objective of this pilot study was to validate oncologist concerns about tumor measurement consistency in radiology reports through an audit. The secondary objective was to identify areas for quality improvement and establish process and time requirements for auditing. Two of four affiliated cancer centers (CC1 and CC2) were selected for a pilot assessment. Methods: CC1 and CC2 identified charts with CT scans in the audit timeframes. Auditors reviewed charts for serial CT scans and measureable disease in the audit date range and created a list of eligible charts. Auditors randomized the list and a sample of 61 (CC1) and 66 (CC2) charts were audited. Auditors reviewed CT orders, radiology reports for consistent lesion measurement, comparison to previous scan, addenda, service dates, radiology facilities, reading radiologist, and medical provider placing order. Results: This audit demonstrated deficiencies with lesion measurement consistency at both CC1 and CC2. At CC1 64% of radiology reports were consistently measured and at CC2 57% were consistently measured. Both CC1 and CC2 had identifiable areas for process and quality improvement. The audit required 86 hours at CC1 and 83 hours at CC2. The audit identified deficiencies in order clarity and information flow from the cancer center to the reading radiologist. At CC1 a radiologist reviewed the audited charts and reported an 85% concurrence with the auditors. A literature search did not provide benchmarks for measurement consistency in radiology reports. Conclusions: Oncologists complaints were verified regarding lesion measurement inconsistencies. This pilot demonstrated the need for quality oversight and implementation of standardized measurement (RECIST) criteria and tumor logs in the non-clinical trial environment.
A phase 2 study of the Aurora A kinase (AAK) tyrosine kinase inhibitor (TKI) alisertib (MLN8237) in patients (pts) with pretreated urothelial cancer (UC).
Authors: Andrea Necchi, Daniele Raggi, Salvatore Lo Vullo, Luigi Mariani, Patrizia Giannatempo, Giuseppina Calareso, Elena Togliardi, Nicola Nicolai, Federica Perrone, Giuseppe Pelosi, Roberto Salvioni, Filippo G. De Braud
Journal: Journal of Clinical Oncology (2016)

382 Background: Progress in developing effective salvage therapies for UC is warranted. AAK overexpression has been described in UC and spindle checkpoint (SC) dysregulation is a common feature. Alisertib is an orally available, selective TKI of AAK. Methods: A single-group, Ph2 trial was conducted with Alisertib 50 mg orally BID for 7 days, with 14d rest until disease progression (PD) (NCT01653028). The primary endpoint was RECIST 1.1 objective response-rate (ORR), and ≥ 3/20 responses were required (H0 ≤ 5%, H1 ≥ 20%, α = 5%/β = 20%) to move to a randomized trial of paclitaxel plus either Alisertib or placebo. Eligibility included failure of ≤ 2 platinum-based regimens. Cox regression analyses were done. Targeted sequencing of pts is being performed through the Ion AmpliSeq Comprehensive Cancer Panel (Life Technologies). Results: From 10/2014 to 04/2015, 22 pts were enrolled (20 evaluable for response), 8 (36.4%) in 2 nd line and 14 (63.6%) &gt; 2 nd line. 8 (36.4%) had an ECOG-PS 1-2, 3 (13.6%) had Hb &lt; 10mg/dl, 9 (40.9%) had liver metastases. 2 PR (ORR: 10%), 7 stable disease (SD) and 11 PD were recorded. Median FUP was 6.3 mos (IQR: 4.5-8.0). 6m-PFS was 18.2% (95%CI: 7.5-44.1), including 2 pts with 9.7 and 9.5 mos FUP (still ongoing, both &gt; 2 nd line). Median PFS was 1.8 mos (IQR: 1.3-3.4), but median OS was not reached (6m-OS: 63.6%, 95%CI: 46.4-87.3). Hb &lt; 10gr/dl was significantly associated with shorter PFS and OS multivariably (p = 0.031 and p = 0.033). AAK-IHC expression did not correlate with outcome. Tissue of pt with 9.7 month SD harbored a missense mutation of mTOR (E1813D*) and the nonsense mutation Q527STOP* of TSC1, together with HER3 and TAF1Lmissense mutations. Grade 3-4 adverse events (AE) were: 54.5% alopecia, 41% mucositis, 36.4% fatigue, 18% neutropenia (14% febrile neutropenia). There were 2 treatment-related deaths (septic shock). Conclusions: Preliminary data suggest the possibility for sustained disease control in about 20% of pts, including very long term PR/SD. Hb ≥ 10 and mutations of TSC1/mTOR (TAF1L?) might be the clinical and biological markers for patient enrichment design with SC inhibitors like Alisertib, although the incidence of AE is a major concern. Clinical trial information: NCT01653028.
The psychosocial matrix: A community-derived evaluative tool for designing quality psychosocial cancer care.
Authors: Laura Pence Forsythe, Julia Howe Rowland, Lynne Padgett, Karyl Blaseg, Scott Siegel, Chad M Dingman, Theresa A. Gillis
Journal: Journal of Clinical Oncology (2012)

250 Background: Although the Institute of Medicine provided a vision for effective psychosocial care for cancer survivors, guidance regarding the essential components of comprehensive care or progressive steps for implementing each component is limited. This abstract presents a unique tool for self-assessing capacity to provide quality psychosocial care to cancer survivors and results of the first full-scale implementation of this tool. Methods: The psychosocial workgroup of the National Cancer Institute Community Cancer Centers Program (NCCCP) developed the Psychosocial Care Matrix Assessment Tool which covers 7 domains (e.g., distress screening, patient-provider communication, evaluation of psychosocial programs). All NCCCP sites (16 enrolled in 2007, 14 enrolled in 2010) completed the matrix in 2010 regarding their capacity for psychosocial care at entry into NCCCP (baseline), after two years of NCCCP participation (2007 sites only), and within the coming year (future aspirations). Results: At baseline, matrix responses reflected few or no systematic processes in place for most components of psychosocial care. However, reported capacity to deliver specific components improved at two years post-NCCCP entry for the 2007 sites and in all sites’ future aspirations. For example, about 80% of all sites reported no or inconsistent distress screening at baseline. After two years, 48% of the 2007 sites reported consistent screening with a standardized tool or consistent screening plus a comprehensive interview. Nearly all 2007 sites (89%) aspired to provide consistent screening plus comprehensive interview with 50% also hoping to add systematic follow-up screenings. The majority of 2010 sites (71%) aspired to provide consistent screening with a standardized tool. Conclusions: The psychosocial matrix tool was found to be useable and valuable. At the NCCCP sites, some aspects of psychosocial care (e.g., communicating the importance of psychosocial care) are more readily implemented than others (e.g., follow-up after a positive distress screen). With growing demand on cancer centers to meet new metrics of quality care, the psychosocial matrix can help identify and develop steps to address gap areas.
Thirty-day mortality rate in oncology patients treated with palliative radiotherapy.
Authors: Brian Stewart Bingham, Tomas Dvorak, Christopher G. Morris, Anamaria R Yeung
Journal: Journal of Clinical Oncology (2016)

172 Background: Thirty-day mortality is a well-established metric for surgical specialties, but there are limited data available for 30-day mortality after radiation therapy. Our aim was to specifically identify the 30-day mortality of patients treated with palliative radiotherapy for the purposes of establishing a baseline to improve upon. Methods: We retrospectively reviewed the medical records of all patients treated with external-beam radiotherapy (EBRT) from January 1, 2012, to December 31, 2012, who died within 30 days of their last delivered radiation fraction. Patient age, sex, primary disease site, treatment site, fractions planned, and fractions delivered were recorded. Among all patients treated with palliative intent, age (&gt; 70 and &lt; 70 years) and sex were assessed for increased risk of 30-day mortality using a Fisher’s Exact test. Results: Of the 877 patients who received EBRT, 262 were treated palliatively and 615 were treated with curative intent. Of the 262 patients treated palliatively, 33 died within 30 days of the last delivered fraction, resulting in a palliative 30-day mortality rate of 12.6%. Of these 33 patients, the most common primary disease sites were lung (15%), pancreas (12%), and head/neck (12%), and the most common treatment sites were metastases to bone (37%) and brain (24%). In cases of palliative 30-day mortality, 10 or fewer fractions were prescribed 90% of the time and 83% of patients received more than half of their prescribed fractions. Among all patients treated with palliative intent, age (p = 0.0576) and sex (p = 0.5572) were not significantly associated with higher rates of 30-day mortality. Conclusions: We have established a baseline palliative radiation 30-day mortality rate at 12.6%, with the majority of patients receiving less than or equal to 10 radiation fractions and completing most if not all of their intended fractions. This analysis suggests institutional practices that are in line with other published patterns of care, and illustrates how clinical characteristics and 30-day mortality rate can be used to better understand palliative radiotherapy outcomes at a single treatment center.
Improving screening and prophylaxis of Hepatitis B in immunosuppressed patients.
Authors: Mary Mitsuko Ichiuji, Violeta Rabrenovich, David M. Baer, Joanne E. Schottinger
Journal: Journal of Clinical Oncology (2016)

139 Background: Kaiser Permanente (KP) is an integrated health care delivery system that provides clinical services to over 10 million members in nine states and the District of Columbia. Since 2007, KP oncology community collaborates at the national level to systematically improve safety and quality of care. Our improvements are accelerated by rapid adoption of evidence based protocols, leveraging of EMR and integration of quality improvement methods into clinical operations. Methods: KP created a team that included oncologists, hepatologists, rheumatologist, pharmacy, and quality improvement experts to evaluate safety of existing practice. Based on internal findings, we decided to focus on screening and prophylaxis of Hepatitis B in immunosuppressed patients. Hepatitis B primary infection can be self-limited with viral elimination and lasting immunity or can result in a state of chronic infection with persistent viremia. Hepatitis B can be reactivated with, or after withdrawal of, immune suppressive cancer therapy. Reactivation can result in clinical hepatitis, treatment interruptions, and not infrequently death from fulminant hepatitis. The goal of this initiative is to save lives (i.e. track % patients on chemotherapy who were not tested for Hepatitis B surface Antigen and Hepatitis B core Antibody and for those with a positive test, to determine if they received appropriate prophylaxis). Results: The multidisciplinary group initiated interventions: 1) Defined the patient safety measure of a rate of patients on anti-CD 20 therapies who had a Hepatitis B test prior to therapy; 2) Completed a baseline analyses and shared results with KP regions for appropriate actions; 3) Created an alert and incorporated into KP oncology/ rheumatology Beacon module; 4) Developed KP National screening and prophylaxis resource for hepatitis B in immunosuppressed patients; 5) Developed capacity for ongoing monitoring. Conclusions: We determined a need to educate clinicians and to standardize recommendations for screening and prophylaxis of Hepatitis B in patients receiving Anti-CD20 therapy. Changes were instituted in the Beacon protocols to check baseline labs. Ongoing surveillance using a safety net will be developed.
Clinicopathologic significance of hypoxia-inducible factor 1α, p53, and vascular endothelial growth factor expression and preoperative serum vascular endothelial growth factor level in gastric cancer
Authors: H. Kwon, S. Oh, S. Kim, J. Jang, M. Kim, K. Kim, S. Kim, J. Jeong, H. Kim
Journal: Journal of Clinical Oncology (2008)

4576 Backgrounds: Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1α (HIF-1α), p53, and vascular endothelial growth factor (VEGF) are all important factors in the mechanisms inherent to tumor progression. In this work, we have investigated the clinicopathologic significance of HIF-1α, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer. Methods: We immunohistochemically assessed the HIF-1α, p53, and VEGF expression patterns in 114 specimens of gastric cancer. Additionally, we determined the levels of preoperative serum VEGF (sVEGF). Results: The positive rates of p53 and HIF-1α (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1α were correlated positively with the depth of invasion (p=0.015, p=0.001, respectively). Preoperative sVEGF and p53 levels were correlated significantly with lymph node involvement (p=0.005, p=0.040, respectively). VEGF overexpression was more frequently observed in the old age group (≥ 60 years old) and the intestinal type (p=0.013, p=0.014, respectively). However, correlations between preoperative sVEGF level and tissue HIF, VEGF, and p53 were not observed. The median follow- up duration after operation was 24.5 months. HIF-1α was observed to be a poor prognostic factor of disease recurrence or progression (p=0.002). Conclusion: p53, HIF-1α and preoperative sVEGF might be markers of depth of invasion or lymph node involvement. HIF-1α expression was a poor prognostic factor of disease progression in patients with gastric cancers. No significant financial relationships to disclose.