tbuckley/cabot-search huggingface dataset:
Comparison of three different molecular methods to detect mutations in <i>KRAS</i>, <i>NRAS</i>, <i>BRAF</i> and <i>PIK3CA</i> in metastatic colorectal cancer samples (mCRC): Interim analysis of a Spanish cohort.
Authors: Cristina Santos, Valentín Navarro-Perez, Maria Elena Elez Fernandez, Bartomeu Massuti, Manuel Valladares Ayerbes, Jose Maria Vieitez de Prado, Jose Luis Manzano Mozo, Javier Gallego Plazas, Cristina Gravalos Castro, Alfredo Carrato, Mar Varela, Maria Jose Safont, Vicente Alonso, Esther Falco, M. Pilar Escudero, Xavier Sanjuan, Josep Tabernero, Gabriel Capella, Ramon Salazar, Enrique Aranda
Journal: Journal of Clinical Oncology (2015)

e14613 Background: Mutational analysis of RAS in mCRC has demonstrated an improvement in patient selection for anti-EGFR drugs. The techniques for the detection of point mutations have an analytical sensitivity of 1-5%. Even more sensitive techniques can detect 0.05-0.1% mutated alleles, although it is not clear the impact on anti-EGFR treatment benefit. Objective: The aim of our study was to compare the sensitivity to detect point mutations in KRAS, NRAS, BRAF and PIK3CAby cobas, therascreen assays and Digital PCR (Fluidigm), and their predictive value to anti-EGFR and bevacizumab (bev) treatments in terms of progression free survival. 600 patient level datasets treated with chemotherapy and anti-EGFR or bev were pooled from several mCRC trials and retrospective series from the TTD/RTICC Spanish network. Methods: Interim analysis of mutational studies of tumor samples from 249 (out of 600) mCRC mostly treated in clinical trials with bev (37.4%), cetuximab (12.6%) or panitumumab (49.9%) is reported. Invalid rates and turnaround time (TAT) were assessed for each platform. Concordance and predictive capability were evaluated using kappa and Harrel’s C index. Results: There were no invalid results for Digital PCR and only one for cobas and therascreen each. The average time for DNA extraction per 24 samples was 21.5 hrs for cobas Kit and 23 hrs for QIAamp DNA mini Kit. The average time for testing all genes per 24 samples was 14 hrs for cobas, 35 hrs for therascreen and 65 hrs for Digital PCR. There was a very good concordance between cobas and therascreen in the KRAS mutation analysis (kappa index: 0.87 (95% CI, 0.8-0.94)). The best platforms in terms of Harrel’s C index for all patients were KRAScriteria by cobas and Digital PCR (both with 0.53). Conclusions: Concordance in the KRAS mutation analysis between platforms is good with a TAT favoring cobas assay. Mutations (n,% & kappa) Cobas Kappa Therascreen Kappa Digital PCR Kappa Digital PCR/Cobas KRAS (exon2/3) 64(25.70%) 0.87 60(24.1%) 0.6 88(35.34%) 0.7 RAS extended (exon2/3/4) 90(36.14%) 0.78 81(32.53%) 0.58 111(44.58%) 0.64 Any mutation 120(48.2%) 0.70 106(46.57%) 0.52 124(49.8 %) 0.60
Does the use of complementary and alternative medicine (CAM) influence survival in glioblastoma multiforme?
Authors: Prakash Ambady, Tara Morrison
Journal: Journal of Clinical Oncology (2012)

e12509 Background: Glioblastoma multiforme (GBM) is a devastating CNS tumor with an incidence of around 14,000 per year in the USA. Patients often independently adopt complementary and alternative medicines (CAM) in addition to the recommended surgery and chemoradiation due to the poor prognosis of the disease despite maximal therapy. We try to document the most frequently used supplement therapies and identify differences in side effect profiles, and survival rates (PFS and OS) between groups of patients taking standard therapy versus standard therapy with CAM Methods: This is a retrospective single institution study. We reviewed charts of 25 GBM patients seen in Neuro-Oncology Clinic at Fox Chase Cancer Center between September 2010 and September 2011. All patients received standard chemoradiation. Information regarding the age, sex, use of CAM, performance status at diagnosis, side effect profile, PFS and OS was obtained. Results: 9/25 (36%) patients reported using CAM. The most frequently used supplement was the homeopathic medication Ruta-6 followed by curcumin, hydroxychloroquine, melatonin and green tea extract. The mean PFS were 14 vs 17 months in the CAM vs non-CAM groups. OS rates were 17 vs 20.5 months in the CAM vs non-CAM groups. There were no statistically significant differences between the groups. In addition, no differences in side effects were noted. Conclusions: Most neuro-oncologists are eventually confronted with questions about CAM in the treatment of GBM.Considering the limited therapeutic options available for GBM and the multiple options that CAM offers, this retrospective study provides insight into the most frequently used supplements and compares the benefits and their side effect profiles. Information regarding the use of CAM was based on voluntary disclosure at the time of documentation. Information about genetic markers was not always available. Larger prospective studies are required to elucidate any meaningful clinical differences between the groups.
Access to Children’s Oncology Group phase I clinical trials: Racial/ethnic dissimilarities in participation.
Authors: Ajay K. Nooka, Madhusmita Behera, Sagar Lonial, Margie Dixon, Biljana Georgievska, Suresh S. Ramalingam, Rebecca D. Pentz
Journal: Journal of Clinical Oncology (2014)

e17527 Background: Phase I clinical trials involve the rational introduction of new therapies to humans for the first time ever, and also to evaluate the safety of their combination with established agents. Prior studies have highlighted racial/ethnic inequalities in enrollment in clinical trials. The current study evaluates the representation of racial/ethnic/age group/gender in pediatric (ages birth to 19 years) phase I clinical trials. Methods: We evaluated 1,348 children with 128 diagnoses enrolled in Children’s Oncology Group (COG) and Pediatric Brain Tumor Consortium (PBTC) phase I clinical trials in United States from 02/28/2000 until 12/29/2008. The observed (O) to expected (E) proportions were calculated by following established methodology and using the representative population from Surveillance, Epidemiology, and End Results (SEER) 18 data including 27,266 children with the same ICD-0-3 diagnostic codes. Patients were analyzed by race/ethnicity, age category, sex, and cancer type [solid or lympho-hematopoietic (LH)]. SPSS version 21.0 (Chicago, IL) was used for analysis. Results: Under-representation in phase I trials was seen for LH tumors (9% O vs. 37% E) compared to solid tumors. Although representation was fairly proportional by gender and age, as well as by racial/ethnic group, significantly under-represented subgroups were Hispanics (11.4% O vs. 27% E), and ages 0 to 4 years (12% O vs. 36.5% E). Age groups 5 to 9 years were overrepresented (30% O vs. 18.5% E). By the tumor type, the most significantly under-represented groups were ages 0 to 4 years and Hispanics for both solid (11% O vs 34.4% E and 11% O vs 23.6% E) and LH (16.0% O vs 40% E and 18.0% O vs 33% E) cancers), respectively. Age group 5 to 9 years with solid tumors (30.4% O vs 17% E) was overrepresented. Conclusions: Although gender, racial/ethnic groups are proportionally represented in phase 1 trials, some specific subgroups including the Hispanic children, and age groups 0 to 4 years are under-represented and may benefit from focused accrual.
Phase II neoadjuvant trial with carboplatin and eribulin mesylate in patients with triple-negative breast cancer.
Authors: Sara E. Barnato, Jacqueline Sara Jeruss, Kevin P. Bethke, Nora M. Hansen, Seema Ahsan Khan, Jamie H. Von Roenn, Steven T. Rosen, William John Gradishar, Kalliopi P. Siziopikou, Caitlin Meservey, Virginia G. Kaklamani
Journal: Journal of Clinical Oncology (2012)

TPS1134 Background: Several neoadjuvant trials have been conducted in triple negative breast cancer (TNBC) with platinum agents with pathologic complete response (pCR) ranging from 16%-32%. Eribulin mesylate, a nontaxane microtubule dynamics inhibitor, has clinical activity as monotherapy in breast cancer and other solid tumors. A recent phase I trial found the combination of eribulin mesylate with carboplatin was well tolerated and showed activity in advanced solid tumors. The recommended dose for future trials was eribulin mesylate 1.1 mg/m 2 and carboplatin AUC6. We proposed a neoadjuvant phase II trial with the combination of carboplatin and eribulin in patients with TNBC. Methods: This is a non-randomized, open-label, multi-center, phase II clinical trial of eribulin and carboplatin enrolling histologically-confirmed TNBC patients. Our primary endpoint is to determine the pCR in TNBC patients treated with the combination of carboplatin and eribulin. Secondary endpoints include determination of the clinical response rate, toxicity evaluation and measurement of stem cell and TLE3 as a biomarker of response to eribulin therapy. To obtain an alpha of 0.10 and a power of 0.90, a sample size of 30 patients is required to detect a pCR rate &gt;=30%. 10 of the planned 30 patients have been enrolled to date. Treatment will be given every 3 weeks for a total of 4 cycles of therapy. There will be an initial safety run-in to evaluate the appropriate dose of eribulin in this population. The first 10 patients will receive eribulin at 1.4 mg/m 2 (intravenously over 2-5 minutes) followed by carboplatin AUC=6 (intravenously over 30 minutes). After the 10th patient has been enrolled, the study will be temporarily suspended pending review; toxicity will be assessed for these first 10 patients (cycle 1 only) to assess whether this dose of eribulin will be used for the remaining patients or if a reduction to a dose of 1.1 mg/m 2 will be required. Definitive surgery will be performed 3-8 weeks after completion of therapy, which will conclude the duration of the study. Clinical Trial Registry Number NCT01372579.
Impact of body surface area (BSA) on efficacy of gefitinib in patients with non-small cell lung cancer (NSCLC).
Authors: Kenichiro Kudo, Katsuyuki Hotta, Hiroshige Yoshioka, Kei Kunimasa, Kazuya Tsubouchi, Masahiro Iwasaku, Isao Oze, Eiki Ichihara, Mitsune Tanimoto, Katsuyuki Kiura
Journal: Journal of Clinical Oncology (2013)

e19167 Background: Drug dosing of chemotherapeutic agents has traditionally been based on an estimated BSA to reduce the pharmacokinetic inter-patient variability. However, the approved dose of gefitinib was fixed at 250 mg/body/day. Our preliminary retrospective study showed a potential association between BSA and progression-free survival (PFS) in the gefitinib monotherapy in advanced NSCLC [ASCO 2012, #2607]. Here, we investigated the influence of BSA on efficacy of gefitinib, using data from a prospective cohort of NSCLC patients receiving gefitinib. Methods: The subjects were 154 consecutive, EGFR-tyrosine kinase inhibitor (TKI)-naïve NSCLC patients who were to receive gefitinib monotherapy between 2007 and 2012. Baseline BSA was estimated by height and weight in each patient. The association between BSA and survival time was assessed using log-rank test and stepwise multivariate Cox proportional hazard model. Results: Median BSA of the subjects was 1.42 m 2 (range: 0.98-1.95). At the cutoff level in BSA of 1.50 m 2 , overall survival (OS) and PFS in the large BSA group were not different from those in the small BSA group in the univariate analysis, which was also shown in multivariate analysis (hazard ratio: 1.12, 95% confidence interval: 0.66-1.92 and 1.67, 0.86-3.44, respectively). Among subjects with EGFR-mutant tumors (n=125; 81%), BSA had no association with OS, but patients with larger BSA had significantly worse PFS in the multivariate analysis (1.59, 1.01-2.51). The association of BSA with PFS was highly sensitive to increase or decrease in the cutoff level of BSA: BSA ≥ 1.45 m 2 vs. &lt;1.45 m 2 , [1.18, 0.80-1.75]; BSA ≥ 1.55 m 2 vs. &lt;1.55 m 2 , [1.75, 1.11-2.78]; BSA ≥ 1.60 m 2 vs. &lt;1.60 m 2 , [1.32, 0.82-2.11]. Conclusions: In this cohort, PFS was significantly associated with BSA in EGFR-mutant NSCLC when BSA level was cut off by around the median score. Our findings might suggest the need for further investigation of dose finding PK/PD study stratified by BSA level in gefitinib therapy in EGFR-mutant NSCLC.
Factors influencing recurrence following anatomic lung resection for non-small cell lung cancer.
Authors: Rodney Jerome Landreneau, Ghulam Abbas, Omar Awais, Arjun Pennathur, Jill Siegfried, David O Wilson, James D. Luketich, Matthew J. Schuchert
Journal: Journal of Clinical Oncology (2012)

7074 Background: Anatomic lung resection provides the patient with the best chance for cure in the setting of early-stage non-small cell lung cancer (NSCLC). Despite complete (R0) resection, up to 20-30% of patients will develop recurrent disease. In the current study, we analyze the impact of surgical and pathologic variables upon recurrence patterns following anatomic lung resection for clinical stage I NSCLC. Methods: A total of 1,192 patients (394 segmentectomies, 805 lobectomies) with clinical stage I NSCLC were evaluated. The primary outcome variable was recurrence. Multivariate analysis was performed based upon clinical (age, gender, comorbidities), surgical (operation, approach, surgical margin) and pathological (pleural invasion, tumor size and histology) variables. Predictors of recurrence were identified by proportional hazards regression. Differences in recurrence patterns between groups are illustrated by log rank tests applied to Kaplan-Maier estimates. Results: A total of 243 recurrences (20.3%) were recorded at a mean follow-up of 35.6 months (71 locoregional, 172 distant). There was no significant difference in recurrence patterns when comparing segmentectomy and lobectomy. Multivariate analysis demonstrated that a margin:tumor ratio &lt; 1, angiolymphatic invasion and the presence of only mild-moderate tumor inflammation were predictors of recurrence risk. Conclusions: Recurrence following anatomic lung resection is influenced predominantly by pathological variables (tumor size, angiolymphatic invasion, tumor inflammation). Optimization of surgical margin in relation to tumor size may improve outcomes. Extent of resection (segmentectomy vs. lobectomy) does not appear to have an impact on recurrence-free survival when adequate margins are obtained. These data have implications regarding the potential use of adjuvant therapy in selected Stage I patients at high risk for recurrence. [Table: see text]
Variables impacting the number of palliative chemotherapy lines administered to patients with advanced non-small cell lung cancer (NSCLC) in a common daily practice setting.
Authors: Diana Marcela Roa-Garcia, Silvia Muñoz, Neus Baste, Francia Holguin, Elia Sais, Cristina Urbano, Nuri Quer, Silvia Guerra, Silvia Cufi, Alejandro Vazquez-Martin, Cristina Oliveras-Ferraros, Bruna Corominas-Faja, Javier A. Menendez, Joan Brunet, Adelaida Garcia-Velasco, Angel Izquierdo, Rut Porta, Joaquim Bosch-Barrera
Journal: Journal of Clinical Oncology (2013)

e19159 Background: Palliative chemotherapy (CT) can increase survival and quality of life for advanced non-small cell lung cancer (NSCLC) patients (pts). It has been observed in phase III clinical trials that not all pts are able to receive second or further lines of CT. We have analyzed the number of CT lines that pts with advanced NSCLC do in our institution and factors that could have an impact on it. Methods: All pts treated during 2010 for advanced NSCLC in our institution were analyzed (n=124). Quantitative data were compared by Student’s t test. Overall survival (OS) was estimated by Kaplan-Meier analysis and differences were assessed with the log-rank test. Results: Most pts (75.8%) were men. Median age was 66 years. The 67.7% of patients received up to 2 lines of CT, 38.7% 3 lines, 15.3% 4 lines, 8% 5 lines, and 2.4% received up to 6 lines. The higher the number of lines of CT were administered, the higher the median of OS obtained from one line of CT to up to six lines respectively (4.4 vs 10.9 vs 15.6 vs 19.2 vs 31.1 vs 54.3 months, p&lt;0.0001). Women presented a higher median of OS than men (18.7 vs 12.1 months, p=0.015), but without a significant higher number of CT lines (2.6 vs 2.17, p=0.159). Adenocarcinoma pts (54.0%) received greater numbers of CT lines than squamous cell carcinoma pts (26.6%) (2.54 vs 1.58, p=0.007), with a trend towards significant increase in the median OS (14.7 vs 11.6 months, p=0.072). Pts receiving cisplatin-based CT as first line (40.3%) received more lines of treatment than carboplatin-based (46.0%) (2.88 vs 2.04, p=0.001) and were also younger (59.6 vs 65.8 years, p=0.003), but these differences did not have a statistically significant impact on median OS (14.0 vs 11.6 months, p=0.375). Conclusions: In our series, pts with adenocarcinoma histology and cisplatin-based first line treatment received a higher number of lines of CT. Women had better median OS. The number of lines of CT received may have an impact on median OS.
Cystic fibrosis patients in Canada live nearly a decade longer than those in US, study finds
Authors: Michael McCarthy
Journal: BMJ (2017)

Patients in Canada who have cystic fibrosis live almost 10 years longer than their counterparts in the US, a study by Canadian and US researchers has found.1

They wrote in Annals of Internal Medicine , “The risk for death was consistently lower in Canada after accounting for several patient demographic and clinical factors and persisted in patients with severe clinical phenotypes.”

Lead author Anne L Stephenson, of St Michael’s Hospital in Toronto, and colleagues reviewed data on 5941 patients who were followed on the Canadian Cystic Fibrosis Registry …
International comparison on the factors influencing reimbursement of expensive cancer drugs.
Authors: Carol Sunghye Lim, Soonil Kwon, Yun-Gyoo Lee, Youngil Koh, Dae Seog Heo
Journal: Journal of Clinical Oncology (2013)

6614 Background: Reimbursement policy for expensive cancer drugs is heterogeneous and inconsistent among countries. We compared the pattern of publically funded drug programs of ten countries. Methods: We investigated reimbursement policies of 19 indications with expensive cancer drugs (nilotinib, dasatinib, imatinib, pemetrexed, bevacizumab, sunitinib, temsirolimus, lapatinib, crizotinib, erlotinib, cetuximab, sorafenib and lenalidomide) in ten countries (Australia, Canada, England, France, Germany, Japan, Korea, Sweden, Taiwan, and the United States). Microarray analysis methodology is adopted to cluster the countries according to the pattern of reimbursement, based on incremental cost effectiveness ratio (ICER) and other variables of 19 indications. The earlier a country starts reimbursement for the indication, the higher reimbursement score (RS) is assigned to the country. Fairness index (FI) was determined for each country, depending on whether reimbursement decision follows ICER sequence. Results: Except for US, Japan and France were more likely to reimburse the indications (16/19), whereas Sweden and UK were less likely to reimburse them (5/19 and 6/19, respectively). From array analysis, we observed three separate groups: 1) France and Germany, 2) Korea and Japan, 3) UK, Sweden, Canada, Taiwan and Austrailia. The details of analysis will be presented. Regarding FI, Sweden (0.75), France (0.73) and UK (0.71) were the countries with high FI, in which health system was financed by general taxation and health technology assessment (HTA) was performed by government agency. Korea (0.34), Taiwan (0.40) and Germany (0.46) were the countries with low FI, in which social health insurance was financed by payroll tax or premium rather than general taxation. HTA was performed by non-government agency (Germany) or recently established government agency (2007 in Taiwan and 2009 in Korea) in these countries. Conclusions: Reimbursement policies for expensive cancer drugs are variable among the nations. Countries where health system is funded by general taxation and HTA is performed by government agency showed consistency of reimbursement policy based on ICER.
Efficacy and safety of olaparib monotherapy in a subgroup of patients with a germline <i>BRCA1/2</i> mutation and advanced ovarian cancer from a Phase II open-label study.
Authors: Susan M. Domchek, Ronnie Shapira-Frommer, Rita K. Schmutzler, M. William Audeh, Michael Friedlander, Judith Balmaña, Gillian Mitchell, Georgeta Fried, Salomon M. Stemmer, Ayala Hubert, Ora Rosengarten, Niklas Loman, Jane D. Robertson, Helen Mann, Bella Kaufman
Journal: Journal of Clinical Oncology (2015)

5529 Background: Olaparib (Lynparza), an oral PARP inhibitor, has demonstrated antitumor activity in patients (pts) with BRCA-mutated(m) ovarian cancer. Data from the overall cohort of pts in this Phase II study (NCT01078662) have been reported (Kaufman et al. JCO 2014). Presented here are data from a subgroup of pts with germline (g)BRCAm ovarian cancer, stratified by prior lines of chemotherapy (< 3 or ≥ 3) and platinum sensitivity. Methods: Pts were treated with olaparib 400 mg twice daily (bid; capsule formulation) monotherapy until disease progression according to RECIST v1.1. Objective response rate (ORR) and duration of response (DoR) were assessed for pts with measurable disease at baseline (n=167). Safety and tolerability were assessed for all pts (n = 193). Results: Of the pts with measurable disease at baseline, 30 and 137 had received < 3 and ≥ 3 prior lines of chemotherapy, respectively. Adverse events (AEs) most commonly causally related to olaparib were nausea (107/193 pts, 55%), fatigue (99 pts, 51%) and anemia (60 pts, 31%; grade ≥ 3 in 36/193 [19%]). Twenty pts (10%) had a serious AE causally related to olaparib. Two pts developed leukemia and one pt myelodysplastic syndrome; all three had been heavily pretreated. Conclusions: Olaparib 400 mg bid (capsule form) monotherapy demonstrated notable antitumor activity in gBRCAm pts with advanced ovarian cancer, including heavily pretreated, platinum-resistant pts. No new safety signals were identified. Clinical trial information: NCT01078662. Platinum sensitivity Confirmed responders, n/N ORR, % (95% CI) Median DoR, mths (95% CI) Confirmed responders, n/N ORR, % (95% CI) Median DoR, mths (95% CI) < 3 prior lines ≥ 3 prior lines Total 14/30 47 (28, 66) 6.2 (3.9, 9.2) 46/137 34 (26, 42) 7.9 (5.6, 9.6) Sensitive* 6/9 67 (30, 93) 5.7 (3.7, 9.2) 17/38 45 (29, 62) 8.2 (5.6, 13.5) Resistant 4/8 50 (16, 84) 8.3 (3.9, NC) 22/77 29 (19, 40) 8.0 (4.8, 14.8) Refractory 0/1 0 (0, 98) 0 2/14 14 (2, 43) 6.4 (5.4, 7.4) Unknown 4/12 33 (10, 65) 5.4 (3.8, 6.8) 5/8 63 (24, 91) 7.9 (4.7, NC) *Platinum sensitive but ineligible to receive further platinum-based chemotherapy; n, response; N, total pts with measurable disease; NC, not calculated