tbuckley/cabot-search huggingface dataset:
The role of microRNA profiling in peripheral blood in predicting early progression to sunitinib in renal cell carcinoma.
Authors: A. Gámez-Pozo, L. M. Antón Aparicio, C. Bayona, P. Borrega, I. Gallegos, R. García Domínguez, T. de Portugal, M. Ramos, R. M. Perez Carrion, I. Sánchez-Navarro, A. Benguría, A. Dopazo, R. Madero, J. A. Fresno-Vara, M. V. Bolos, E. Espinosa
Journal: Journal of Clinical Oncology (2011)

e15039 Background: Sunitinib is a standard therapy for metastatic renal-cell carcinoma, but markers that identify patients who will not benefit from the drug are needed. In this study, we applied high-throughput MicroRNA (miRNA) expression profiling in peripheral blood samples to identify predictive biomarkers. Methods: This multicentre prospective study included patients with clear-cell metastatic kidney cancer and no previous therapy. A blood sample was collected before therapy initiation. Patients received sunitinib 50 mg/day in cycles 4-w-on/2w-off and then grouped according to their response (progression in ≤6 months vs. remaining patients). MiRNAs were isolated from peripheral blood samples using LeucoLOCK (Ambion) and miRNesay (Quiagen) kits. MiRNA profiling was performed using Human miRNA Microarray Release 14.0 (Agilent). Boosting for classification with classical Akaike Information criterion was applied to filter miRNA expression data according to progression results. Twelve predictive models for 1, 2, 3 or 4 variables were built using a Binary Logistic Regression with the Fisher's scoring as optimization technique. Predictive accuracy for calibration was assessed by boostrap (R2) and by the Hosmer-Lemeshow test. Discriminant power was assessed by the AUC for data training and leave-one-out cross-validation for ROC curves. Results: At the time of the analysis, 44 patients have been enrolled and 37 are available for response. Median age was 62, 78% of patients had prior nephrectomy and median follow-up is 9 months. There were 4 complete and 13 partial responses, whereas disease remained stable in 9 (>6 months in 6 of them) and progressed in 11. Peripheral blood samples from 37 patients were analyzed for novel predictive biomarkers. MicroRNA profiling data show that 29 miRNAs were differentially expressed between patients with early progression versus the other patients. Several predictive models comprising 1, 2, and 3 different miRNAs were generated and evaluated. Conclusions: MicroRNA profiling in peripheral blood may be a reliable way to identify lack of response to sunitinib in patients with metastatic renal-cell carcinoma.
Analysis of metabolic response (MR) by positron emission tomography (PET) compared with tumor response by computed tomography (CT) from MPACT, a phase III trial comparing <i>nab</i>-paclitaxel (<i>nab</i>-P) plus gemcitabine (G) versus G alone for patients (pts) with metastatic adenocarcinoma of the pancreas.
Authors: Ramesh K. Ramanathan, Daniel D. Von Hoff, Malcolm J. Moore, Luis Teixeira, Salvatore Siena, Josep Tabernero, David Goldstein, Xinyu Wei, Brian Lu
Journal: Journal of Clinical Oncology (2014)

254^ Background: In the MPACT trial, nab-P + G demonstrated superior efficacy vs G alone for the treatment of metastatic pancreatic cancer (PC). Pts with an MR (according to EORTC criteria) had a 5-month improvement in median overall survival (OS) vs those without an MR (13 vs 8 months for nab-P + G and 12 vs 7 months for G alone). This analysis examines the relationship between MR by PET and tumor response by CT. Methods: Previously untreated pts (N = 861) with metastatic PC were randomized 1:1 to receive nab-P 125 mg/m 2 + G 1000 mg/m 2 on days 1, 8, and 15 every 4 wk or G alone 1000 mg/m 2 weekly for 7 wk followed by 1 wk of rest (cycle 1) and then days 1, 8, and 15 every 4 wk (cycle ≥ 2). Tumor responses were evaluated every 8 wk by CT using RECIST v1.0. CT-documented disease progression led to treatment discontinuation. PET scans were evaluated at baseline, wk 8, and wk 16. Results: In 257 pts with a PET scan at baseline, 252 (98%) had ≥ 2 PET-avid lesions. The rate of MR (complete [CMR] or partial [PMR]) was higher for nab-P + G vs G alone (63% vs 38%; P &lt; 0.0001). The ORRs by CT (complete response + partial response [CR/PR]) in the same pts were 31% for nab-P + G vs 11% for G. In a pooled-treatment-arm analysis (n = 255), 130 pts (51%) had an MR by PET, and 54 (21%) had a CR or PR by CT. Among pts with an MR by PET, 32% had a CR or PR, 43% had stable disease, and 16% had progressive disease (PD) by CT. Pts who had an MR by PET in the absence of a CR or PR by CT (n = 88) had a median OS of 10 months (table). Conclusions: Rates of MR by PET in this trial were &gt; 2-fold the response rates by CT, suggesting that PET may be a more sensitive marker of tumor response. Of the pts without a CR or PR by CT, those with an MR by PET had a longer median OS vs those without one. A set of pts who had PD by CT exhibited an MR by PET. Thus, PET may identify a set of pts who may benefit from continued treatment despite PD by CT. Further research is needed to explore the radiological and clinical characteristics of these pts. Clinical trial information: NCT00844649. [Table: see text]
Distance to nearest radiation facility and treatment choice in early stage breast cancer.
Authors: Sahaja Acharya, Jeff M. Michalski, Stephanie Mabry Perkins
Journal: Journal of Clinical Oncology (2015)

73 Background: Breast conserving surgery followed by breast radiation (RT), collectively termed breast conserving therapy (BCT), is a recommended alternative to mastectomy (MT) for early stage breast cancer. Limited access to RT may result in more extensive surgical treatment. The purpose of this study is to assess the association between distance to nearest RT facility and MT use in a modern cohort of BCT eligible women. Methods: Women with Stage 0 – II breast cancer eligible for BCT diagnosed from 2004 – 2010 were identified from a US state registry. Distance from patient census tract to nearest RT facility census tract was calculated. Multivariate logistic regression was used to identify explanatory variables that significantly influenced MT use, adjusting for age, poverty, insurance, race, Hispanic ethnicity, marital status, diagnosis year, distance to nearest RT facility, T stage, N stage, ER/PR status and grade. Results: Of the 24,994 eligible women, 25.4% (n = 6,346) underwent MT and 74.6% (n = 18,648) underwent a breast conserving surgery. 32% of patients lived in a census tract that was &gt; 5 miles from a RT facility. MT use increased with increasing distance to RT facility (24.5% at ≤ 5 miles, 26.5% at &gt; 5 to &lt; 15 miles, 29.5% at 15 to &lt; 40 miles and 43% at ≥ 40 miles, p &lt; 0.001). The likelihood of MT was independently associated with increasing distance to RT facility (Odds Ratio [OR]: 1.02 for every mile increase, 95% Confidence Interval [CI]: 1.01 – 1.02, p &lt; 0.001). Compared to patients living ≤ 5 miles away from a RT facility, patients living 15 - &lt; 40 miles away were 1.3 times more likely to be treated with MT (OR: 1.31, 95% CI: 1.15 – 1.51, p &lt; 0.001), and those living ≥ 40 miles away were more than twice as likely to be treated with MT (OR: 2.29, 95% CI: 1.51 – 3.45, p &lt; 0.001). When restricting the sample to women with T1 disease (n = 16,656), distance to RT facility remained a significant explanatory variable for MT use on multivariate analysis (p &lt; 0.001). Conclusions: MT use in a modern cohort of women eligible for BCT is independently associated with increasing distance to RT facility. Measures to improve RT access should be explored to ensure universal opportunity for BCT.
Role of trimodality therapy versus dual-modality in T3N0 rectal cancer patients.
Authors: H. J. Lim, R. Woods, B. S. Johal
Journal: Journal of Clinical Oncology (2011)

597 Background: Adjuvant radiation (R) and chemotherapy (C) is generally recommended for patients (pts) with pT3N0 rectal cancer, although there is no data to support the use of adjuvant chemotherapy. This study examines the whether there is benefit with trimodality therapy vs. dual modality in this population. Methods: The BCCA Colorectal Cancer Outcomes Unit database was used to identify referred pts with pT3N0 rectal carcinoma diagnosed between 2000-2004. The data from this cohort has been previously reported (Johal et al. ASCO Annual Meeting 2007) During this period, “short course” R (25Gy/5, surgery within 10 days) was recommended for resectable cT3 tumors followed by 6 months of C. If not treated pre-operatively (pre-op), guidelines specified post-op “long course” (45Gy/25) R and C. Three treatment groups were identified: Surgery alone (S), S and R (SR), and S, R and C (SRC). Eligible pts had complete surgical resection with or without total mesorectal Excision (TME). Pts treated with “downstaging” pre-op long course R, with S and C only (13 pts) or with R2 resection were excluded. Locoregional Recurrence (LR) and Distant Recurrence (DR) rates determined. Reasons for non-treatment were determined by chart review. Due to the heterogeneity between the groups, a univariate and multivariate analysis was performed. Results: The patient characteristics have been previously reported. 5-yr LR was similar between SR and SRC (3.84 %vs. 6.34% p=0.474). 5-yr DR were 24.81% (SR), and 17.56% (SRC) p=0.0354 and 5 yr OS 68.4% (SR), and 86% (SRC) p=.0002. On multivariate analysis, chemotherapy did impact on OS with a HR of 0.532, p=0.0462. Conclusions: Treatment of pT3N0 rectal cancer was variable in clinical practice despite established guidelines. There was significant heterogeneity with respect to comorbid medical conditions between groups receiving SR and SRC which limits comparability between groups. However, those patients who received tri-modality therapy experienced less distant relapse and an increase in overall survival. No significant financial relationships to disclose.
Creating infrastructure to manage the maintenance of certification part IV (MOC IV) program at an academic cancer center.
Authors: Caitlin C. Donohue, Julie M. Porter, Andrew David Norden, Carole Kathleen Dalby, Suzanne Davidson, Joseph O. Jacobson
Journal: Journal of Clinical Oncology (2014)

160 Background: The American Board of Medical Specialties (ABMS) authorizes Portfolio Sponsor organizations to internally review and approve MOC IV quality improvement projects for their physicians. Dana-Farber Cancer Institute (DFCI) became the first cancer center Portfolio Sponsor in March 2013. We used the opportunity to create a central oversight and incentive structure for quality improvement projects. Methods: As part of the ABMS requirements, physicians must submit a project application, agree to meaningfully participate in a project, and personally reflect on the experience. DFCI must submit documentation of these completed requirements to the ABMS. Therefore, a multi-disciplinary team comprised of physicians, administrators, and information specialists created a user-friendly, online system to submit, track, and store MOC IV information. This web-based system is accessible via the DFCI intranet site and contains forms, feedback loops, automated emails, and reporting capabilities. Results: Three online workflows including a Project Application, a Participation Contract, and an Attestation and Personal Reflection were created. To begin the Application workflow, physicians submit an online application. A link to the application is sent to DFCI administrators with the option to return to the submitter or send the application to the Review Board. The Review Board has the option to request additional information from the submitter or approve the project to begin. Similar feedback loops are built into the other workflows as well. The submitted information is automatically saved and cataloged and can be easily queried for reporting purposes. By 2016, 25 DFCI physicians are due for board recertification and will need to earn MOC IV credit. These workflows will help this cohort and future cohorts of physicians submit information needed to earn credit. Conclusions: The physicians and administrators who have used the system enjoy the ‘save’ functionality which allows them to complete work over time, the automated emails informing them of when they have an assignment to complete, and the ease of completing web-based forms in lieu of paper-based forms.
Proto-adjuvant chemotherapy with paclitaxel (P), carboplatin (C) and gemcitabine (G) in locally advanced inoperable non-small cell lung cancer (NSCLC). A phase II study
Authors: D. Schallier, B. Neyns, C. Fontaine, J. de Mey, M. Meysman, J. van de Steene, J. de Grève
Journal: Journal of Clinical Oncology (2005)

7285 Background: Patients (pts) with locally advanced inoperable NSCLC are currently treated with concomitant or sequential chemotherapy and radiotherapy. However the outcome with current treatment is still unsatisfactory. Development of new approaches including more efficient chemotherapy combinations is warranted. Methods: Previously untreated stage IIIA-IIIB NSCLC pts (histologically proven, age > 18 yrs and written informed consent) received 3 cycles (cy) of P (175mg/m2 by 3 hour infusion on day 1), C (AUC 5mg/ml.min by 30 min infusion on day 1) and G (1000mg/m2 by 1 hour infusion on day 1 and 8) in a 3-weekly regimen followed by fractionated RT (66 Gy). Toxicity was assessed weekly during cy1 and on day 1 and day 8 of cy2 and 3. Response evaluation was performed at the end of cy3 (CT-scan). Results: The accrual has been completed and 43 pts have been enrolled and are evaluable. Pt characteristics: age: 39–77 yrs (median 66); M/F: 32/11; histology: SCC/AC/LCC/other: 17/9/10/7; KPS: 80–100% (median 90%); stage IIIA/IIIB: 17/26. 4 pts received only 1 cy and 1 pt received 2 cycles, 38 pts received the planned 3 cy. Premature termination of the chemotherapy was due to: PD: 1, pneumonia: 1, hemoptisis: 1 and Gr 3 toxicity: 2. Grade 3/4 (%) hematological toxicity consisted of: WBC: 6 (14); ANC: 23 (53); T: 5 (12) and anemia: 1 (2) Gr 3/4 (%) non-hematological toxicity: N/V: 4 (9); fatigue: 2 (5), arthralgia/myalgia (A/M): 2 (5); dermatitis: 2 (5); typhlitis: 1 (2); anaphylaxis: 1 (2); infection: 3 (7); diarrhoea: 1 (2). All pts had Gr 2 alopecia. Hematological support (transfusion, EPO, G-CSF or a combination) was needed in 13 pts. ORR on the intent to treat population was 60%. ORR was 67% (1CR + 25PR) for the 39 pts who completed the intended 3 treatment cycles, 12 were SD and 1 PD. Median TTP is 10.9 months. The median OS has not been reached (15.7+ months) Conclusions: Three cycles of P/C/G is an active and feasible induction regimen in pts with locally advanced inoperable NSCLC. Neutropenia is the main hematological toxicity. Whether this triplet regimen can improve outcome when compared to specific cisplatin doublet regimens, should be evaluated in a phase III study. No significant financial relationships to disclose.
Prognostic role of C-reactive protein levels in patients with hepatocellular carcinoma undergoing sorafenib therapy.
Authors: Jean Kyung Lee, James J. Harding, Joanne F. Chou, Marinela Capanu, Leonard Saltz, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2014)

340 Background: Markers of systemic inflammatory response including C-reactive protein (CRP) are associated with the prognosis of various malignancies including HCC. We investigated the significance of the serum CRP level as a prognostic factor in patients with advanced HCC on sorafenib therapy. Methods: The MSKCC institutional database was retrospectively queried for patients diagnosed with advanced HCC who received sorafenib therapy from 2002-2012 and had available serum CRP measurements. Patient demographics and outcomes were extracted under an IRB-approved waiver. Baseline CRP levels within 30 days of starting of sorafenib and while on sorafenib treatment were correlated with clinical outcomes. CRP levels after the initiation of sorafenib were analyzed as a time dependent covariate in a Cox regression model. Results: 51 patients had available CRP levels and received sorafenib: Median age 65 years (range 45-82); KPS 80 (70-90%); 9 females (17.6%); 32 AJCC stage IV disease (62.7%); 10 AJCC stage III (19.6%); 12 hepatitis C (23.5%), 10 hepatitis B (19.6%), 12 alcohol (23.5%), and 20 non-alcoholic steatohepatitis (39%); and 43 Child-Pugh A (84.3 %). The median time on sorafenib was 2.4 months (range 0.2-21.6). The median overall survival (OS) was 9.2 months [CI 5.8 – 13.6] and the median progression-free survival (PFS) was 2.1 months [CI 1.6 – 2.6]. 46 of 51 patients had baseline CRP levels available for analysis. Baseline CRP level was associated with OS [hazard ratio (HR) 1.2 (CI 0.996 – 1.4, p=0.056)] but not with PFS [HR 1.1 (CI 0.96-1.3, p=0.14)]. Time dependent covariate analysis demonstrated an association between CRP levels during sorafenib therapy and overall OS [HR 1.08 (CI 1.01-1.16, p=0.02)] as well as PFS [HR 1.09 (CI 1.02 – 1.16, p=0.009)]. Conclusions: Baseline CRP level prior to the start of sorafenib therapy showed a borderline significant association with OS but no association with PFS. Higher CRP levels showed a significant association with increased risk of disease progression and death for sorafenib treated HCC patients. Potential prognostic role of CRP in HCC patients undergoing sorafenib therapy is to be further studied prospectively.
A randomized, double-blind, multicenter phase II AIO trial with gemcitabine plus sorafenib versus gemcitabine plus placebo in patients with chemotherapy-naive advanced or metastatic biliary tract cancer: First safety and efficacy data.
Authors: M. H. Moehler, C. C. Schimanski, S. Kanzler, M. A. Woerns, U. Denzer, F. T. Kolligs, M. P. Ebert, A. Distelrath, M. Geissler, S. Zeuzem, F. Lammert, A. W. Lohse, M. M. Dollinger, U. Lindig, E. M. Duerr, N. Lubomierski, S. Zimmermann, M. Kabisch, S. Schadmann-Fischer, P. R. Galle
Journal: Journal of Clinical Oncology (2011)

4077 Background: Despite recent progress in chemotherapy (Valle, 2010), new therapy options are urgently needed for advanced or metastatic biliary tract cancer (mBTC). The objectives of this randomized, double-blind, multicenter phase II trial were safety and clinical activity of gemcitabine (GEM) combined with sorafenib versus placebo (Sor/Pl) as first-line therapy in mBTC. Methods: GEM (1,000 mg/m²) was given on day 1, 8, 15, 22, 29, 36, 43 in first cycle and day 1, 8, 15 of all other cycles. Sor/Pl tablets were administered as a dose of 400 mg bid orally. Preliminary incomplete data of 103 full recruited, but still blinded patients could be analysed. Since patients are still under treatment, data are shown for both groups together. Results: Out of 62 patients, 9/40/13 had gallbladder, intrahepatic or hepatic BTC, respectively. Median age was 64.5 years (range 36-93). Median size of target lesions was 80 mm (range 10-271). Median time after diagnosis was 25 days (range 1-2633). Reasons for treatment end of 47 patients were PD (27) death (7) deterioration (6) or other reasons (7). Most patients had > 1 cycle. Duration of GEM and Sor/Pl was 64 (range 1-330) and 66 days (range 8-375), respectively. 106 adverse events of 69 patients (67%) were expected as known study medication toxicities. Most frequent SAEs (grade 1-3) were health deterioration 16%, abdominal pain 12%, cholangitis 12%, pyrexia 12% and nausea 7%. In 25%, SAE outcome was death, none assessed related to sorafenib. Out of 8 SUSARs, 3 were possibly related to Sor (blurred vision; atrial fibrillation; respiratory infection) . Response were available for 46 patients. PR and SD was 7% and 63% patients, respectively. Disease control rate was 70%. Median PFS and OS calculated for 73 patients was 86 (95% CI: 67-148), and 281 days (95% CI: 160-342), respectively, with 51% for PFS and 36% for OS. Conclusions: The preliminary activity and manageable toxicity data suggest that gemcitabine combined with sorafenib/placebo can be an option as first-line therapy of advanced BTC. The role of sorafenib combined with chemotherapy warrants further investigation.
Phase II/III clinical trial with VEGFR2-epitope peptide and gemcitabine for patients with locally advanced, metastatic, or unresectable pancreatic cancer: Pegasus-PC study.
Authors: Hiroki Yamaue, Masaji Tani, Motoki Miyazawa, Kenji Yamao, Nobumasa Mizuno, Takuji Okusaka, Hideki Ueno, Narikazu Boku, Akira Fukutomi, Hiroshi Ishii, Shinichi Ohkawa, Masayuki Furukawa, Hiroyuki Maguchi, Masafumi Ikeda, Kazuto Nishio, Yasuo Ohashi, Takuya Tsunoda
Journal: Journal of Clinical Oncology (2013)

223 Background: Gemcitabine is a key drug for treating pancreatic cancer; however, with the limitation in clinical benefits, the development of another potent therapeutic was strongly called for. VEGF-receptor 2 (VEGFR2: Flk-1 and KDR) is an essential target for tumor angiogenesis, and we have executed a phase I clinical trial using gemcitabine and VEGFR2-peptide (Cancer Sci 2010). Based on promising phase I trial results, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been conducted (UMIN000001664). Methods: The eligibility criteria are: locally advanced, metastatic, or unresectable pancreatic cancer. Patients were allocated to either VEGFR2 peptide (OTS102) + gemcitabine group or placebo + gemcitabine in 2:1 ratio by dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test, with the weight proportional to cumulative death probability, was used for the statistical analysis under the time-lagged effect of immunotherapy. Sample size was estimated presuming the effects will be observed from the time point of 50% cumulative survival rate. Assuming a type I error alpha (two-sided) level of 5% and a power of 80% or more for 50%-60% reduction of hazard, sample size necessary was estimated as 100 patients for the active group and 50 patients for the placebo group. Results: No statistically significant survival time prolongation was observed in OTS102 add-on group (p = 0.92). However, the three-month landmark analysis revealed significant interaction between the treatment and reports of indurations or ulcerations (p = 0.005) in add-on group, and if patients survived for over three months, grade 1-2 patients had better survival than grade 0 (1-year survival: 47%(23/49) and 22%(9/44), respectively) in add-on group. Conclusions: Despite the lack of survival time prolongation by OTS102 add-on to gemcitabine therapy, patients experienced injection site indurations or ulcerations may have better survival, suggesting new prognostic factors for VEGFR2-epitope peptide. Our results indicate the possibility of epitope peptide used in cocktail therapies. Clinical trial information: UMIN000001664.