tbuckley/cabot-search huggingface dataset:
An interdisciplinary model of collaboration between medical staff (MS), hospital quality improvement (QI), and continuing medical education (CME) departments to promote education and practice changes in the prevention of venous thromboembolism (VTE) in cancer patients (pts).
Authors: Lucille A. Leong, Mary Mendelsohn, Crystal J. Saavedra, Robert Morgan
Journal: Journal of Clinical Oncology (2014)

215 Background: Venous thromboembolism (VTE) is a leading cause of morbidity/mortality in cancer pts. VTE is increasing and is the second cause of death in cancer pts, behind only cancer itself. In 2010 of the 186 unique hospitalized cancer pts at our institution with VTE, 25% were medical and 75% surgical. Gaps in clinician knowledge/practice of VTE prevention were evident. Methods: A interdisciplinary approach across clinical and administrative specialties was undertaken, with collaboration between: medical/surgical oncologists, MS leaders, pharmacists, nursing, and hospital departments of QI, information technology, and CME, to educate a target group of 120 cancer clinicians in VTE prophylaxis. In 2/2013 - 2/2014 multiplatform educational initiatives were utilized to reach physicians, advance practice/ward nurses and pharmacists: didactic lectures, Key Opinion Leader visiting professorships, online vignettes, VTE FAQ emails from MS QI leaders, small group sessions, e-learning modules. System changes such as standardized VTE prophylaxis order sets tailored for each service and strategically placed visual cues were also used. Results: Almost 3 times as many unique learners participated in these activities as were targeted. Learner satisfaction, knowledge acquisition and competency were high. Compliance with use of standardized order sets improved from 65 to 95% among the MS. Claims by clinicians of pt contraindications to prophylaxis were audited and found valid. Despite these improvements, incidence of VTE has not dropped, reflecting a national trend. Conclusions: With intensive and interdisciplinary effort, progressin clinician knowledge and performance in VTE prophylaxis can be made. This effort required considerable input from physician champions (eg., surgical oncologists with overlapping roles of clinician, QI advocate, and departmental leader, and medical oncologists with roles of clinician, CME and MS leader). This is a promising model for other QI initiatives. Supported by Unihealth educational grant.
EBV(+) Diffuse Large B Cell Lymphoma Is Infrequent in Upper Central United States and Lacks Unique Clinical Characteristics or Adverse Prognosis Compared to EBV (−) Counterparts: Results From University of Iowa/Mayo Clinic SPORE
Authors: Usha Perepu, Ahmet Dogan, Matthew J Maurer, Cristine Allmer, Carrie A. Thompson, Stephen M Ansell, Sergei I Syrbu, Susan L Slager, Thomas E. Witzig, George J. Weiner, Thomas M. Habermann, James R Cerhan, Brian K Link
Journal: Blood (2012)
A phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory metastatic colorectal cancer.
Authors: Michael J. Overman, Cathy Eng, Bryan K. Kee, David R. Fogelman, Christine Fark, Rick Hippert, Scott Holter, Jean-Pierre Issa, Stanley R. Hamilton, Scott Kopetz
Journal: Journal of Clinical Oncology (2012)

450 Background: Hypermethylation of promoter CpG islands (CIMP) has been strongly implicated in chemotherapy resistance and both clinical and preclinical studies have shown the ability to restore platinum sensitivity with the reversal of hypermethylation. CIMP is implicated in the pathogenesis of a subset of colorectal cancers termed CIMP-high. We sought to explore the safety and efficacy of the hypomethylator, azacitidine, in combination with CAPOX. Methods: We report the results of the phase I portion of a prospective phase I/II study in fluoropyrimidine and oxaliplatin refractory metastatic colorectal cancer (mCRC). The primary objectives were to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of this combination. Two dose levels were explored with a standard 3+3 design of azacitidine (75 mg/m2, SQ D1-5), oxaliplatin (90 and 110 mg/m2 IV D2), and capecitabine (1500 mg/m2/d, PO divided BID, D1-14) every 3 weeks, followed by an expansion of 6 patients at the MTD to evaluate for delayed hematological toxicity. The phase II portion is restricted to patients with CIMP-high (≥ 2/6 methylation-specific PCR markers: hMLH1, P16, P14, MINT1, MINT2, and MINT31). Results: 15 pts [M/F 8/7, median age: 60 yrs (range: 34-73), ECOG PS 0/1: 1/14] were enrolled from 8/2010 to 4/2011. Prior progression on fluoropyrimidine/oxaliplatin-based treatment met RECIST criteria in 13 pts. All pts were evaluable for toxicity and 13 for response. Twelve pts were treated at the highest dose level with no DLTs. Common grade 3-4 treatment-related toxicities were: neutropenia in 5 (33%), diarrhea in 2 (13%), oxaliplatin hypersensitivity reaction in 2 (13%). Best response was SD in 7 pts (54%) with a median duration of SD of 3.2 months (range: 2.2-6.9 months). Two pts remain on treatment. Two of 14 tested pts had CIMP-high tumors and both had progressive disease. Conclusions: Azacitidine and CAPOX was well tolerated in an unenriched oxaliplatin-refractory mCRC population. The recommended phase II dose of azacitidine with CAPOX is 75mg/m2, D1-5. Enrollment in the phase II cohort continues in fluoropyrimidine and oxaliplatin refractory CIMP-high metastatic colorectal cancer.
Bortezomib-Associated Peripheral Neuropathy: Relationship Between Clinical Neurophysiologic Evidence in Previously Untreated Multiple Myeloma Patients and Preclinical Characterization in a Mouse Model.
Authors: Paul G. Richardson, Jordi Bruna, Anthony A. Amato, Esther Udina, Constantine S. Mitsiades, Patrick Y. Wen, E. Tessa Hedley-Whyte, Anne Louise Oaklander, Johan Monbaliu, An Vynckier, Lee Silverman, Kenneth C. Anderson, Xavier Navarro
Journal: Blood (2009)
Use of telemedicine to expand access to survivorship care.
Authors: Kelli Kristine Cole-Vadjic, Jennie Robertson Crews
Journal: Journal of Clinical Oncology (2016)

26 Background: PeaceHealth St Joseph Cancer Center (PHSJCC) provides medical and radiation oncology services in northwest Washington. PeaceIsland Medical Center (PIMC) is an affiliated medical center that provides medical oncology services in the nearby San Juan islands. Survivorship appointments for Survivorship Care Plan (SCP) delivery are available at PHSJCC but have not been available at PIMC. Telemedicine services were previously established for medical oncology appointments for patients at PIMC with a provider at PHSJCC. Methods: Since January of 2015, patients who are eligible for survivorship services are identified by their medical oncologist or nurse upon completion of chemotherapy at PIMC. They are scheduled for a 1 hour survivorship telemedicine appointment with the survivorship physician assistant (PA). The patients attend the appointment at PIMC with a nurse present there to assist with logistics and deliver survivorship appointment materials. The PA is at PHSJCC and conducts the appointment through visual and audio telemedicine equipment. During the telemedicine appointment the SCP is reviewed and delivered, educational materials are provided and discussed, and referrals are initiated as needed based on a standardized patient distress screening questionnaire. Patients who complete radiation therapy at PHSJCC but live in the San Juan islands are now also being identified and scheduled for survivorship telemedicine appointments at PIMC. Results: Patients who live in a small island community where survivorship services were not available are now able to receive a survivorship appointment with SCP delivery through telemedicine. Between January and July of 2015, 6 patients were identified for survivorship appointment eligibility upon completion of chemotherapy at PIMC. 3 of these patients have completed a survivorship telemedicine appointment, 2 are currently scheduled, and 1 declined to schedule. Although qualitative surveys have not yet been conducted, the patients who completed survivorship telemedicine appointments offered generally positive feedback about the experience. Conclusions: Telemedicine is an effective way to deliver SCPs in geographic areas where patients do not otherwise have access to survivorship care.
FLT3-positive acute myeloid leukemia: Does timed sequential induction therapy influence outcome?
Authors: D. Rifai, M. L. Larson, M. C. Keller, P. Venugopal
Journal: Journal of Clinical Oncology (2011)

6544 Background: Mutations of FLT3, ITD, or TKD, occur in 30% of AML, making them the most common in AML. FLT3-ITD has been correlated with higher WBC counts and bone marrow (BM) blast counts and decreased disease-free survival (DFS) and overall survival (OS). Median OS has been reported as 2.8-6.4 months (mo) in FLT3-ITD+ vs. 10-14.9 mo in FLT3-ITD wild-type (WT). To date, no treatment regimen has been shown to impact the outcome of FLT3+ patients (pts). Various studies have shown that type and intensity of therapy or use of a reinforced induction regimen could influence the outcome of FLT3-ITD+ pts. We retrospectively studied the outcome of pts with FLT3+ AML treated with a regimen based on timed sequential therapy concept. Methods: 33 pts were treated with 2 doses of cytarabine 2 gm/m2 IVPB 12 hours apart followed by 1 dose of mitoxantrone 30 mg/m2 IVPB on days 1 and 5. For pts ≥ 70 years, cytarabine was reduced to 1.5 gm/m2. Study end points were overall response rate (ORR), DFS, and OS. Results: 19 pts were FLT3-WT, 9 were FLT3-ITD+ and 5 were FLT3-TKD+. Median age was 50 years in the FLT3-WT group (30-73), 50 in the ITD+ group (30-72) and 51 in the TKD+ group (36-66). Cytogenetics, NPM status, peripheral WBC count, Peripheral Blast% & BM Blast% are summarized in the table. ORR (CR + CRi) was 78.9% in the FLT3-WT group and 100% in both FLT3+ groups. Median DFS for FLT3-WT pts was 7.1 mo (0.4 – 17.6), 9.9 mo in the ITD group (0.9-33.7) and 6.6 mo in the TKD group (2.3-14.8). Median OS for FLT3-WT pts was 8.7 mo (0.6 – 57.9), 14.2 mo in the ITD group (2.2-41.5) & 8 mo in the TKD group (3.3-18.7). Conclusions: This regimen was highly effective in achieving remission in FLT3-ITD+ AML resulting in improved survival. The lack of unfavorable cytogenetics in this group may have influenced the outcome. This regimen appears to be promising for FLT3+ pts, and further studies are needed. All Pts FLT3-WT FLT3-ITD FLT3-TKD Median age 50 50 50 51 Favorable cytogenetics 7 4 1 2 Intermediate cytogenetics 19 9 8 2 Unfavorable cytogenetics 7 6 0 1 NPM (# positive/# tested) 7 / 13 2 / 5 5 / 6 0 / 2 Median peripheral WBC # 20.19 17.14 49.27 74.02 Median peripheral blast% 23 3 59 47.55 Median BM aspirate blast% 68.5 68 85 37.5 ORR 87.9% 78.9% 100% 100% Median DFS (mo) 7.1 7.1 9.9 6.6 Median OS (mo) 9.8 8.7 14.2 8
Mathematical Modeling of Molecular Relapse Kinetics in NPM1c+, PML-Rara+, RUNX1-RUN1T1+, and CBFB-MYH11+ Acute Myeloid Leukemias
Authors: Hans Beier Ommen, Susanne Schnittger, Jelena V Jovanovic, Ingrid Beier Ommen, Henrik Hasle, Mette Oestergaard, David Grimwade, Peter Hokland
Journal: Blood (2008)
Copy number alterations of DNA mismatch repair (MMR) genes as novel prognostic markers in localised prostate cancer (CaP).
Authors: Melvin Chua, Emilie Lalonde, Osman Mahamud, Alejandro Berlin, Alan Dal Pra, Michèle Orain, Valerie Picard, Helene Hovington, Alain Bergeron, Yves Fradet, Bernard Têtu, Alice Meng, Junyan Zhang, Gaetano Zafarana, Julie Livingstone, Melania Pintilie, Theodorus van der Kwast, Michael Fraser, Paul Boutros, Robert G. Bristow
Journal: Journal of Clinical Oncology (2016)

96 Background: To investigate the prognostic significance of CNA of genes involved in the MMR pathway in localised CaP. Methods: We studied CNA of genes involved in MMR, namely MSH2, MSH3, MSH6, MLH1, PMS2, in 284 patients with intermediate-risk CaP (Toronto cohort), and compared our findings against three public databases (MSKCC and Cambridge cohorts) that included 375 low- to high-risk CaP. The Toronto cohort comprised of 143 and 141 individuals who underwent image-guided radiotherapy (IGRT) and radical prostatectomy (RadP), respectively, while all patients from the public databases underwent RadP. Information on genome-wide copy number alterations (Toronto) was obtained using Affymetrix Oncoscan array. Biochemical relapse-free survival (bRFS) was assessed for clinical outcome. Results: CNA of MSH2, MSH3, MSH6, MLH1, PMS2 were observed in 3.9% (n = 11), 7.7% (n = 22), 3.9% (n = 11), 4.6% (n = 13) and 13.0% (n = 37) of the Toronto cohort, respectively. Distinct patterns of allelic gain and loss were observed for the gene set; gains only for MLH1 and PMS2, and losses only, in all but 1 case, for MSH2, MSH3 and MSH6. In the Toronto cohort, allelic losses of MSH2, MSH3 and MSH6 were determined to be prognostic for poorer bRFS in IGRT patients (HR 2.04, 95% CI 1.01, 4.12, p = 0.048), but not for patients who underwent RadP (HR 1.08, 95% CI 0.49, 2.39, p = 0.84); while gains in MLH1 and PMS2 were not prognostic in either IGRT or RadP patients. A pooled analysis of these genes for all RadP patients from the Toronto and public databases (n = 516) did however indicate that allelic losses of MSH2, MSH3 and MSH6 were significant predictors of poorer bRFS (HR 2.48, 95% CI 1.64-3.77, p &lt; 0.001), but not MLH1 and PMS2 gains. On multi-variable modelling that includes percent genome aberration and pre-treatment PSA levels, allelic losses of MSH2, MSH3 and MSH6remained significant predictors of bRFS for the pooled RadP cohort (HR 1.96, 95% CI 1.27, 3.01, Wald's p &lt; 0.001), but not for IGRT patients (HR 1.50, 95% CI 0.72, 3.12, p = 0.28). Conclusions: We identified a distinct pattern of copy number loss of MSH2, MSH3 and MSH6 genes in localised CaP that appears to be a novel biomarker of failure to definitive treatment.
Phase I/II trial of TS-1 plus carboplatin in patients with advanced non-small cell lung cancer: Final report of a Central Japan Lung Study Group Trial-CJLSG0402
Authors: H. Saka, C. Kitagawa, M. Yamamoto, R. Suzuki, H. Taniguchi, M. Ichikawa, K. Shimokata
Journal: Journal of Clinical Oncology (2008)

19056 Background: TS-1 (S-1), a novel oral fluoropyrimidine derivative, is active against advanced non-small cell lung cancer (NSCLC). A response rate of 22% was reported in a monotherapy trial (Br J Cancer 2001). In combination with cisplatin, TS-1 demonstrated a response rate of 47% in NSCLC (Clin Cancer Res 2004). To develop a clinically relevant combination, we investigated TS-1 plus carboplatin in patients (pts) with advanced NSCLC in a phase I/II setting. Methods: Chemo-naïve pts in stages IIIB and IV were enrolled with ages under 75, PS (ECOG) of 0 or 1, and with adequate bone marrow and major organ functions. Post-surgical relapses and asymptomatic brain metastases were allowed. In the phase I part, the doses of TS-1 were increased 60, 70, 80 mg/m2 orally from day 1 to 14, with the fixed dose of CBDCA (AUC=6 mg/mL min) on day 1. This regimen was repeated every 3 weeks. The phase II study was followed to evaluate response rate as the primary endpoint. Results: In the phase I part, the recommended dose was determined to be level 2 (TS-1 dose, 70 mg/m2). Twenty-six measurable pts were enrolled in the phase II analysis. The median age was 66 years (range, 51–74 years), median PS was 1 (n=16), and weight losses were less than 5% in most of the pts (n=21). Three pts had stage IIIB, 21 pts had stage IV, and 2 pts had relapsed disease. Adenocarcinoma (n=19) was the dominant histology. The median courses of chemotherapy delivered were 3, and the actual dose of TS-1 taken was 95.2% of planned. Response rate was 38% (n=26) in all enrolled pts. Grade 4 leukopenia, neutropenia, anemia and thrombocytopenia were observed in 0, 0, 22, 39% respectively. No Grade 4 non-hematological toxicity was observed. No toxic death was reported. The median survival time for all pts was 13.1 months. Conclusions: The antitumor effect was promising. A randomized phase III trial has been underway. No significant financial relationships to disclose.
Disconnect between earlier presentation patterns and application of curative treatments in HCC.
Authors: Susanna Varkey Ulahannan, Austin G. Duffy, Jonathan K Kish, Katherine McGlynn, Osama E. Rahma, Tim F. Greten, Sean Altekruse
Journal: Journal of Clinical Oncology (2014)

187 Background: In the U.S., a greater proportion of small hepatocellular carcinomas are being diagnosed. The extent to which patients with small HCCs are receiving potentially curative therapies is unclear. Methods: Receipt of liver transplantation, resection, radiofrequency ablation, and other or unspecified surgery/ablation as first therapy was examined among HCC cases in the NCI SEER18 cancer registries during the years 2000 to 2010. Survival of HCC by treatment modality was also examined. Results: The diagnosis of small tumors (≤5 cm) significantly increased between 2000 and 2010, surpassing diagnosis of larger tumors beginning in 2005. Among patients diagnosed during 2007-2010 with complete data available, 57% had small tumors and more than three quarters had a single tumor, however fewer than one third received surgical or ablative treatment. Incidence rates of resection, ablation and transplantation (therapies with curative intent) increased 17.6% per year between 2000 and 2005, then decreased by -2.9% per year through 2010. Resection was the leading treatment followed by radiofrequency ablation and transplantation. The number of patients treated with curative intent decreased as tumor size or tumor number increased; 42% of patients with single tumors ≤5 cm in size were treated with curative intent compared to 20% with single tumors &gt;5 cm. While radiofrequency ablation was used to treat small tumors, resection was used to treat both small and large tumors. Patients who received transplants had the best five-year survival rate (71%), followed by patients who received resection (42%) and radiofrequency ablation (30%). Five-year survival of patients who did not receive surgery or ablation was 6%. Conclusions: Despite more patients being diagnosed with small tumors, the US-SEER database analysis demonstrates a recent decrease in the use of curative treatments. Treatment guidelines suggest that early diagnosis HCC cases are eligible for treatment with curative intent. Investigations of reasons for the limited treatment are recommended with the goal of improving outcomes.
A phase II study of <sup>99m</sup>Tc-trofolastat (MIP-1404) SPECT/CT to identify and localize prostate cancer in high-risk patients undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (EPLND) compared to histopathology: An interim analysis.
Authors: Kevin Mark Slawin, William J. Ellis, Peter Tenke, Steven Joniau, Boris Y. Alekseev, Istvan Buzogány, Sergey Mishugin, Eric A. Klein, R. Jeffrey Karnes, Douglas Scherr, Bertram E. Yuh, David Frasier Jarrard, Edouard John Trabulsi, Josef Stolz, John Babich, Hagop Youssoufian, Nancy Stambler, Thomas Armor, Robert Joseph Israel
Journal: Journal of Clinical Oncology (2014)

94 Background: Technetium (Tc99m) trofolastat (USANC) is a novel urea-based small molecule SPECT radiotracer with utility in imaging overexpression of PSMA in prostate cancer (PCa). Unlike earlier agents targeting PSMA, this ligand is rapidly internalized and retained in tumors. We conducted an open-label, multicenter phase 2 study in the US and Europe (NCT01667536). An interim analysis was performed at approximately 50% accrual. Methods: Patients (pts) with confirmed adenocarcinoma of the prostate scheduled for RP with EPLND at high risk for disease outside of the prostate gland were eligible. High risk pts were ≥cT3 or Kattan nomogram score ≥130. Within 30 days of screening, pts required a bone scan and pelvic MRI. After enrollment, pts received trofolastat followed by whole-body planar and SPECT/CT imaging 3 to 6 hrs later. Pts then underwent RP with EPLND within 21 days. SPECT/CT images were evaluated centrally by 3 readers blinded to clinical information and compared to on-site pathology assessments using a common scoring template. The primary endpoint was the ability of trofolastat to detect PCa within the gland. Secondary endpoints included detection of extent and location within the gland, pelvic lymph nodes and comparative performance against MRI. Results: 84 pts were enrolled to date from 16 centers. Interim data is available for 54 pts. A majority (≥2/3) of SPECT/CT readers correctly identified the presence or absence of primary PCa in 51/54 (94%, 85-98 95% CI) patients including 2 true-negative cases treated with neoadjuvant enzalutamide. Sensitivity and specificity were 94% (84-98 95% CI) and 100% (34-100 95% CI) respectively. Conclusions: Based on the interim data available, trofolastat has accurately detected primary prostate carcinoma within the gland with high sensitivity and specificity in high-risk pts prior to surgery. Updated results, analyses of secondary endpoints, pelvic lymph nodes, and comparative performance vs. MRI from this ongoing study will be presented. Clinical trial information: NCT01667536. [Table: see text]
25-hydroxy vitamin D (VitD) and associated variables as predictors of breast cancer (BC) risk and tamoxifen benefit in NSABP-P1.
Authors: E. Amir, R. S. Cecchini, P. A. Ganz, J. P. Costantino, S. Beddows, N. Hood, P. J. Goodwin
Journal: Journal of Clinical Oncology (2011)

1528 Background: Observational studies suggest that host lifestyle factors are associated with BC risk. Evidence is strong for obesity after menopause, but less convincing for VitD. Obesity and low VitD are associated with insulin resistance, inflammation and elevated adipocytokines such as leptin. We have examined associations of obesity, VitD and these related factors with BC risk. Methods: A nested case control study of the NSABP-P1 trial was conducted. Cases were participants who developed invasive BC. Control participants (≤4 per case) did not develop invasive or non-invasive BC during follow-up and were matched for age, race, 5-year Gail score and geographic location of clinical center as a surrogate for latitude. Fasting serum banked at trial enrolment was assayed for 25-hydroxy VitD, insulin, leptin and C-reactive protein (CRP), a marker of inflammation. Associations between study variables and the risk of invasive BC were evaluated using conditional logistic regression with adjustment for baseline factors including tamoxifen treatment and body mass index (BMI). Results: 231 cases were matched with 856 controls. Mean age was 54 and 45% were postmenopausal. There were significant (p<0.05) negative correlations for VitD (mean 57.9 nmol/L + 25.3)with insulin, CRP and leptin (Spearman’s rho =−0.23,−0.15,−0.22). There were positive correlations for BMI (mean 27.2 kg/m2 + 5.7) and these variables (rho = 0.58, 0.54, 0.79). Higher BMI was associated with higher BC risk [odds ratio (OR) 1.45 (≥25 vs. <25 kg/m2), 95% confidence interval (CI) 1.06-2.00, p=0.02]. Tamoxifen treatment (vs. placebo) was protective (OR 0.44, 95% CI 0.32-0.61 p<0.001). VitD deficiency (<72 nmol/L or 30 ng/mL) did not influence BC risk (OR 1.05 95% CI 0.73-1.53, p=0.76). When evaluated as continuous variables, insulin, CRP and leptin levels were not associated with BC risk (OR 0.88 [p=0.34], OR 0.97 [p=0.68] and OR 1.05 [p=0.70]). There were no significant interactions between treatment and BMI or serum variables. Conclusions: Higher BMI is associated with a greater BC risk. Serum levels of VitD, insulin, CRP and leptin are not independent predictors of BC risk or tamoxifen benefit in this high risk population.