tbuckley/cabot-search huggingface dataset:
Real-world comparative economics of a 12-gene assay for prognosis in stage II colon cancer.
Authors: Tiffany Yu, Steven R. Alberts, Robert J. Behrens, Lindsay A. Renfro, Geetika Srivastava, Gamini S. Soori, Shaker R. Dakhil, Rex B. Mowat, J. Phillip Kuebler, George P. Kim, Miroslaw Mazurczak, John C. Hornberger
Journal: Journal of Clinical Oncology (2013)

3640 Background: Prior economic analysis of a 12-gene assay (Oncotype DX), compared with patterns of care reported in the NCCN database of patients with stage II, T3, DNA mismatch repair proficient (MMR-P) colon cancer, predicted that the assay would save medical costs and improve patient well-being (Hornberger et al. Value Health 2012). This study assessed the validity of those findings with actual adjuvant chemotherapy (aCT) recommendations. Methods: Outcomes and costs were estimated for patients with stage II, T3, MMR-P colon cancer using a Markov model. A study of 141 patients from 17 sites in the Mayo Clinic Cancer Research Consortium collected data on aCT recommended before and after knowledge of the 12-gene assay results (Srivastava et al. abstract). Quality-adjusted life years (QALY) and medical resource use after recurrence were computed using guideline-validated state-transition probability estimation methods. Risk of progression and incidence of adverse events with different aCT regimens were based on published literature. Drug and administration costs for aCT were obtained from 2012 Medicare fee schedules. One-way sensitivity analyses were conducted to evaluate parameter influence on economic impact. Results: After receiving the 12-gene assay results, physician recommendations in favor of aCT decreased 22% (95% CI 11%-32%; McNemar test p&lt;0.001) from 73 (52%) to 42 (30%) patients. Oxaliplatin aCT and 5-FU monotherapy recommendations each declined 11%. Average aCT costs decreased $3,228 for drugs, $750 for administration, and $3,168 for adverse events management. Overall, average total direct medical costs decreased $1,683. The net effect on average patient well-being was a gain of 0.102 QALYs. Total change in medical costs is most influenced by the cost of death due to colon cancer, time-preference discount rate, and the change in aCT recommendations. Savings are expected to persist even if the cost of oxaliplatin dropped by &gt;75% due to generic substitution. Conclusions: The 12-gene assayhas been shown to alter aCT recommendations for patients with stage II, T3, MMR-P colon cancer. This study provides real-world confirmation that these aCT changes reduce direct medical costs and improve patient well-being.
Factors associated with biopsy progression on active surveillance.
Authors: Christopher J Welty, Janet E. Cowan, Hao Nguyen, Katsuto Shinohara, Nannette Perez, Kirsten L Greene, Maxwell V. Meng, Matthew R. Cooperberg, Peter Carroll
Journal: Journal of Clinical Oncology (2014)

19 Background: Active surveillance (AS) is a treatment strategy for prostate cancer (CaP) involving monitoring of men diagnosed with low-risk CaP to reduce overtreatment. We report factors associated with disease progression while on AS in a large, single institution cohort. Methods: We retrospectively reviewed the data of men enrolled in the University of California at San Francisco (UCSF) AS cohort between 1990 and 2012. Strict eligibility criteria were prostate-specific antigen (PSA) less than 10ng/ml, Stage less than cT3, Gleason grade 6 or less, 33% or less of biopsy cores positive, and 50% or less of any single biopsy core positive. Men who did not meet these criteria but elected AS were followed as well. Surveillance consisted of quarterly PSA testing, reimaging with TRUS at provider discretion, and annual prostate biopsy. Biopsy progression was defined as upgrade to at least Gleason 7 or increase in volume more than 33% cores. Factors associated with progression while on active surveillance were determined through multivariate Cox proportional hazards regression. Results: Of 1,009 men enrolled in AS at UCSF, 758 men have consented to participate in research to date and have been followed on AS for a median of 57 months. Of these, 518 (68%) met strict criteria for AS while 240 (32%) did not. The median number of repeat biopsies was three (IQR 2-4). At 5 years after diagnosis, 53% were progression-free and 40% of patients received local therapy. Overall survival was 94% among those not AS eligible and 100% among those AS eligible at 5 years. There were no CaP-related deaths. In multivariate analysis, only PSA density (PSAD) and later year of diagnosis were positively associated with the risk of both biopsy progression (HR 1.62, 95% CI 1.36-1.92, p&lt;0.01 and HR 1.17, 95% CI 1.10-1.25, p&lt;0.01, respectively) and receiving treatment (HR 1.39, 95% CI 1.20-1.60, p&lt;0.01 and HR 1.18, 95% CI 1.14-1.23, p&lt;0.01, respectively). White race was associated with receiving treatment (HR 1.92, 95% CI 1.35-2.74, p&lt;0.01) but not with disease progression. Conclusions: The majority of men who enrolled in this active surveillance cohort remained on AS after a median follow up of 57 months. While higher PSAD was associated with biopsy progression, additional predictive tools would improve selection and counseling of men for AS.
Impact of comorbidities on surgical outcomes following mastectomy in elderly breast cancer patients: An analysis of the NSQIP database.
Authors: Simone Mays, Tracy-Ann Moo, Rache M. Simmons
Journal: Journal of Clinical Oncology (2015)

88 Background: Approximately 4% of women age 70 will develop breast cancer during the next ten years. There is limited data on surgical outcomes in elderly patients undergoing treatment for breast cancer. This study examines complications following mastectomy in elderly patients and determines how comorbidities impact those outcomes. Methods: The American College of Surgeons National Surgery Quality Improvement Program database was used to examine complications and comorbidities in breast cancer patients 70 or older undergoing mastectomy from 2007-2012. The relationship between complication and comorbidity was characterized using descriptive statistics and Wilcoxon rank-sum test. Variable frequencies were compared using Chi-square or Fisher’s exact test with a statistically significant two-sided p-value set at 0.05. Results: We identified 12,026 patients 70 or older who underwent mastectomy. The 30-day overall morbidity rate was 4.22%. Myocardial infarction (MI) was associated with history of bleeding disorder and cerebral vascular accident (CVA) (P &lt; 0.05). Prior CVA, transient ischemic attack and MI were associated with post-operative CVA (p &lt; 0.05). Chronic obstructive pulmonary disease and steroid use impacted post-operative pneumonia (p &lt; 0.05). Bleeding disorder, hypertension, and steroid use impacted urinary tract infection occurrence (p &lt; 0.05). Diabetes increased the rate of wound dehiscence (p = 0.001). Conclusions: The 30-day morbidity rate of elderly breast cancer patients undergoing mastectomy is low. Although the complication rate is low, certain comorbidities increase the risk of specific complications. Appropriate measures should be taken to optimize comorbidities in elderly patients to further minimize adverse outcomes.
Association of changes in biomarkers with treatment with cabozantinib (Cabo) in metastatic castration-resistant prostate cancer (mCRPC): A post-hoc analysis of the 100mg nonrandomized expansion cohort of a randomized discontinuation trial.
Authors: Raya Leibowitz-Amit, Melania Pintilie, A. Douglas Laird, Dana T. Aftab, Raanan Berger, Kim N. Chi, Anthony M. Joshua
Journal: Journal of Clinical Oncology (2015)

196 Background: Cabo, an oral inhibitor of receptor tyrosine kinases (RTK) including MET and VEGFR2, showed activity in early clinical studies in mCRPC, and is being investigated in phase 3 trials. Our primary aim was to retrospectively study the potential association between plasma concentrations of known markers of hypoxia, RTK cell signaling, inflammation, bone metabolism, chemo-attraction and epithelial-mesenchymal transition with response to Cabo in patients (pts) who received 100mg daily as part of a phase 2 non-randomized expansion cohort (NCT00940225). Methods: Our cohort of mCRPC pts with available plasma samples comprised of 81 pts with bone lesions assessed for bone scan response (BSR, defined as ≥30% decrease in lesion area compared to baseline). Thirty three pts also had measurable disease and were assessed for RECIST response. Plasma samples were available for all pts at baseline, at 6 weeks and at time of best response. Levels of 27 plasma biomarkers were measured in duplicate using ELISA. Spearman correlation coefficients were calculated for the association between response and biomarker levels at each time point. Results: Sixty six of 81 pts (81%) had a BSR, and 6 of 33 pts (18%) had a partial response by RECIST. No significant associations were found between the levels of any of the biomarkers at baseline or subsequent time points and either BSR or response by RECIST. Over time, the plasma concentrations of soluble VEGFR2 were significantly decreased during treatment with Cabo, consistent with the known effects of VEGFR inhibition on soluble VEGFR2. The plasma concentrations of nine markers (VEGFA, CA9, clusterin, FLT3L, Gas6A, Bone Alkaline phosphatase, and the soluble forms of the RTKs MET, IGF1R and AXL) were significantly increased during treatment with Cabo irrespective of response. Conclusions: These results demonstrate that metabolic alterations occur following treatment with Cabo in pts with mCRPC. Changes in certain biomarkers during treatment with Cabo could suggest potential co-targeting approaches with Cabo or other RTK inhibitors in mCRPC.
Disparities in outcomes in Hispanic patients with non-small cell lung cancer (NSCLC): Evaluation of differences of predictive biomarker expression.
Authors: L. E. Raez, R. E. Ochoa, J. C. Villasboas, G. Walker, J. E. Gomez, A. Belalcazar, K. Danenberg, J. J. Hu, E. S. Santos
Journal: Journal of Clinical Oncology (2011)

e21041 Background: Disparities in survival of Hispanic (H) and Non-Hispanic (NH) patients (pts) with NSCLC independent of stage, age or sex have been described by us [Raez: JCO 27:15s, 2009 s; abs 8080] and others. EGFR mutation has prognostic and predictive value of response to TKI, while ERCC1, RRM1, EML4-ALK and TS might have similar significance. Our hypothesis is that differences in expression of these biomarkers (BM) between these two groups could explain disparities in the treatment outcome. Methods: Tumor samples from advanced NSCLC pts were analyzed for BM expression. BMs were tested by using ResponseDx test: RNA expression of ERCC1, TS, and RRM1 was analyzed by RT-PCR and PCR analysis of DNA was used to determine K-RAS and EGFR mutation status. Objective response was assessed after 2 cycles of therapy. Fisher’s exact test was used for comparisons. Results: Tumors from 58 pts were evaluated for BM expression. Median age was 67.5 (44-87y), men were 64% and former or current smokers 71%. 31 pts (53%) were H and 27 (47%) NH (Caucasian 42%). TS was overexpressed (OE) in 21 of 30 pts (70%), with no variation by ethnicity. OE of ERCC1 was found in 16 of 33 pts (48.3%), and occurred less often among H pts than NH, 37.5% v. 58.8%, (p=0.303). OE of RRM1, which was found in 17 of 25 pts (68%), was more common among H pts than NH, 83.3% v. 53.8%, (p=0.202). Mutated EML4-ALK was seen in 2 (7.4%) of 27 pts, one each from H and a NH pt. Mutated EGFR occurred in 6 (18.8%) of 32 pts with no evidence of variation by ethnicity. K-RAS mutation (10/33 pts, 30.3%) was more common in H pts than NH, 37.5 v 23.5%, (p=0.465). An overall response rate of 24.5% (1 CR/12 PR) was higher among H pts than NH, 33.3% v 13.0% (p=0.115). Disease control (CR/PR/SD) was achieved in 42 (79.2%) pts, and the rate among H pts was significantly higher than among NH, 93.3% v 60.9%, p=0.006. Conclusions: H pts were significantly less likely than NH to develop disease progression within the first two treatment cycles. Of the 7 markers considered, only ERCC1 and RRM1 indicate association with ethnicity. A larger study is needed to establish significance of marker-ethnicity associations and to investigate the effect of these factors on treatment response.
Follow-up decisions and care after BRCA testing.
Authors: Hadeel Assad, Maliha Naseer, Samira Ahsan
Journal: Journal of Clinical Oncology (2014)

52 Background: Women with a deleterious mutation in BRCA 1/2 genes have an increased lifetime risk of developing breast and ovarian cancer. A spectrum of risk reducing and early detection strategies exist including clinical and radiographic surveillance, hormonal therapy, and prophylactic surgery. Methods: We studied the pattern of clinicopreventive inclination among patients undergoing BRCA testing in our genetics center via a telephone based questionnaire. Differences in sociodemographic and clinical characteristics were identified using independent sample t-test and Fisher exact test. Results: A total of 320 individuals were seen at the genetics center between October 2007 and February 2013. Twenty-nine were eligible of which 25 agreed to participate; 20 were found to be BRCA positive and 5 were true negatives. Most participants (&gt; 75%) informed family members they were undergoing BRCA testing and all women shared the result of their deleterious mutation. An average of 2.2 (SD: 1.28) subsequent family members were tested which led to the discovery of 1.33 (SD: 1.15) new deleterious BRCA mutation carriers. Of the 20 BRCA positive patients, 13 opted for prophylactic surgery of which 5 underwent prophylactic oophorectomy (PO), 4 had prophylactic mastectomy (PM), and another 4 combined PO with PM. The remaining chose increased surveillance. Hormonal therapy was used as a preventive program in 6 women, 4 combined it with prophylactic surgery. Data subanalysis revealed BRCA carriers who opted for prophylactic surgery were more likely to be white (&gt; 75%), younger, multiparous, live in Detroit suburbs, and have a personal history of cancer (92% versus 83%, respectively). Screening and surveillance practices were variable in timing and modality. Conclusions: 65 % of women with deleterious BRCA mutation underwent prophylactic surgery as their cancer risk reducing method. Decisions regarding adopting least to most aggressive measures remain highly influenced by personal history of cancer as well as individual socioeconomic characteristics. Understanding factors that affect women’s decisions to adopt various risk reduction strategies will aid both mutation carriers and clinicians to decide on optimal management.
Frequency and distinctive spectrum of <i>KRAS</i> mutations in never smokers with lung adenocarcinoma
Authors: G. J. Riely, M. G. Kris, J. L. Marks, A. Li, D. A. Chitale, E. R. Riedel, M. Hsu, W. Pao, V. A. Miller, M. Ladanyi
Journal: Journal of Clinical Oncology (2008)

8006 Background: KRAS mutations are found in ∼ 25% of lung adenocarcinomas in Western countries and, as a group, are strongly associated with cigarette smoking. These mutations are predictive of poor prognosis in resected disease as well as resistance to treatment with erlotinib or gefitinib. In KRAS, transversions (substituting the purine G with a pyrimidine) are more common than transitions (substituting the purine G with A) and identify a molecular signature for the carcinogenic effects of cigarette smoke. Methods: We determined the frequency and type of KRAS codon 12 and 13 mutations and characterized their association with cigarette smoking history in patients with lung adenocarcinomas. Comparisons were made using Fisher's exact test. Results: KRAS mutational analysis was performed on 482 lung adenocarcinomas, 81 (17%) of which were obtained from patients who had never smoked cigarettes. KRAS mutations were found in 15% (12/81; 95% CI 8%-24%) of tumors from never smokers. Twenty-two% (69/316; 95% CI 17%-27%) of tumors from former smokers, and 25% (21/85; 95% CI 16%-35%) of tumors from current smokers had KRAS mutations. The frequency of KRAS mutation was not associated with age, gender, or smoking history. The number of pack years of cigarette smoking did not predict an increased likelihood of KRAS mutations. When the type of KRAS mutation was examined, never smokers were significantly more likely than former or current smokers to have a transition mutation (G–>A) rather than the transversion mutations known to be smoking related (G–>T or G–>C; p<0.0001). Conclusions: Based upon our data, KRAS mutations are not rare among never smokers with lung adenocarcinoma and such patients have a distinct KRAS mutation profile. The etiologic and biological heterogeneity of KRAS mutant lung adenocarcinomas is worthy of further study. Mutation Nucleotide Former/current Never Total G12A GGT–>GCT 13 0 13 G12C GGT–>TGT 38 0 38 G12V GGT–>GTT 20 1 21 G13C GGC–>TGC 2 0 2 G13D GGC–>GAC 1 0 1 G12D GGT–>GAT 15 10 25 G12S GGT–>AGT 1 1 2 Total 90 12 No significant financial relationships to disclose.
Development of Osteonecrosis Is Associated with Difference in Upregulation of Antithrombin, Protein C and Protein S after Four Weeks of Dexamethasone during Induction Treatment in Childhood Acute Lymphoblastic Leukemia.
Authors: Mariel L. te Winkel, Rob Pieters, Inge M. Appel, Marry M. Van Den Heuvel
Journal: Blood (2007)
Completeness and accuracy of survivorship care plans (SCPs) prepared via two methods: Electronic health record (EHR) auto-population versus manual data entry.
Authors: Amye Tevaarwerk, Jamie L Zeal, Mindy Gribble, Kevin A Buhr, Douglas Wiegmann, Tamara Koehn, Mary E Sesto, William Gray Hocking
Journal: Journal of Clinical Oncology (2016)

62 Background: To improve care for side effects and coordinate follow up, SCPs should correctly and thoroughly report details regarding diagnosis and treatment. However, literature is lacking regarding SCP accuracy and completeness. We audited SCPs for errors and omissions, as part of a clinical trial conducted at two cancer centers. Methods: SCPs were prepared for Stage 0-3 breast cancer patients by 1 of 2 methods, which was based on the standard of care at each center: 1) EHR-based: auto-populated using data entered into the EHR by oncologists for clinical use. SCP finalized by oncologist or advanced practice provider; and 2) Manual entry: prepared by an RN using manual transfer of clinical data into software program. Each participant’s clinical data was abstracted from her chart, with audit and cross-check against each SCP. In the case of discrepancies, oncologists reviewed the chart and adjudicated the “correct” information, as well as completeness and error. Omissions were defined by missing SCP information required per IOM recommendations; errors were defined as data reported in the SCP that did not match the chart. Results: Two sites enrolled 128 women between 11/2013-12/2014; 80 received EHR-based vs 41 manual SCPs. Omissions: 24 (30%) EHR-based versus 6 (15%) manual SCPs contained at least 1 omission. Omissions included failure to provide some dates and specific axillary surgery type (sentinel vs axillary) for EHR-based SCPs and failure to specify receptors for manual SCPs. Errors: 7 (9%) EHR-based versus 19 (46%) manual SCPs contained at least one error. The majority of EHR-based SCP errors were minor discrepancies in dates. Errors in manual SCPs included chemotherapy regimen, incorrect receptors, incorrect stage and axillary surgeries; stage and surgery errors were affected by poor fit with templated SCP fields. Conclusions: Little is known about SCP accuracy and completeness. Manually prepared SCPs may have a higher rate of errors while EHR-based SCPs may have more omissions. Differences in preparation (site, training of preparer) could also account for these differences. In an era of required SCP provision, measures of SCP quality should be considered.
Exploring multidisciplinary practice patterns in the management of muscle invasive bladder cancer (MIBC) across the U.S. and Canada in 2015.
Authors: Lauren Christine Harshman, Matthew Kaag, Jason A. Efstathiou, Andrea B. Apolo, Jean H. Hoffman-Censits, Walter Michael Stadler, Evan Y. Yu, Bernard H. Bochner, Eila C. Skinner, Tracy Downs, Anne E Kiltie, Dean F. Bajorin, Khurshid Guru, William U. Shipley, Gary D. Steinberg, Noah M. Hahn, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2016)

368 Background: Effective treatment of MIBC requires a multidisciplinary (multiD) approach including surgical, radiation, and chemotherapeutic modalities, which are further supported by pathology, radiology, nursing, social work, nutrition, pharmacy, and psychologic expertise. As surgical and bladder preservation approaches have not been directly compared, practice patterns are heterogeneous. Our primary objective was to catalogue the different styles of multiD approaches or lack thereof in the management of MIBC. Secondary objectives were to assess physician interest, capture examples of successful approaches, and describe barriers to implementation. Methods: We conducted an international online survey regarding the type of multiD approach and available resources used by clinicians managing MIBC. We collaborated with the Bladder Cancer Advocacy Network and the Genitourinary Medical Oncologists of Canada to reach a wide variety of academic and community practices. Results: Of the 101 clinicians surveyed, most practiced at NCI designated comprehensive cancer centers (46%) or Canadian academic institutions (29%). The median number of cases per month was 5 (0-40).Of the different multiD styles, sequential (separate) visits on different days was the most common (60%) followed by sequential same day (41%), concurrent (one visit with all providers, 23%), and none (5%). However, most preferred a sequential same day (44%) or concurrent (28%) approach. Although most academic practices had some form of multiD approach, reported barriers for implementing the preferred strategy were lack of clinic space (63%), funding (46%), staff (46%), and time (34%). The majority felt a multiD approach enriched their practice. Conclusions: Most surveyed practitioners at academic centers integrate a multiD strategy in the management of MIBC. The major barriers are not attitudinal but rather insufficient resources and time. Thus, most physicians employ a sequential rather than a concurrent approach. Future goals include developing strategies to overcome these obstacles and integrating these results with patient preferences to optimize the management of MIBC patients.