tbuckley/cabot-search huggingface dataset:
Comprehensive genomic profiling (CGP) of advanced stage esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinomas (EAC) to reveal similarities and differences.
Authors: Kai Wang, Juliann Chmielecki, Siraj M. Ali, Julia Andrea Elvin, Roman Yelensky, Doron Lipson, Vincent A. Miller, Philip J. Stephens, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2015)

7 Background: ESCC and EAC are relatively rare malignancies in the US with EAC more common than ESCC. Using a sensitive CGP assay, we compared the genomic profiles of ESCC and EAC focused on the search for therapy targets. Methods: DNA was extracted from 40u of FFPE sections from 54 clinically advanced ESCC and 234 EAC. CGP was performed on hybridization-captured, adaptor ligation based libraries to a median coverage depth of 652X for 3,230 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. The results were evaluated for all classes of genomic alterations (GA) including point mutations, short INDELs, copy number alterations and fusions/rearrangements. Clinically relevant genomic alterations (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: All ESCC and EAC were at an advanced stage (Stage III/IV) at the time of CGP and had similar gender and age (median 63 yrs) distribution. 54 (100%) of ESCC and 233 (99.6%) of EAC featured GA on profiling with 397 GA in ESCC (7.4/sample) and 1,317 GA (5.6/sample) in EAC. The frequency of clinically relevant GA in ESCC (2.7/sample; 93% of cases) and EAC (2.7/sample; 92% of cases) were identical. EAC featured a greater number of CRGA (72) than ESCC (46). CRGA more frequently altered in EAC than ESCC included KRAS (23% vs 7%) and ERBB2 (23% vs 4%). CRGA more frequently identified in ESCC than EAC included PIK3CA (28% vs 10%), PTEN (13% vs 4%) and NOTCH1 (22% vs 3%). Other GA that were significantly different in the 2 tumor types included SMAD4 (14% EAC vs 0% ESCC), RB1 (19% ESCC vs 2% EAC), SOX2 (17% ESCC vs 1% EAC) and NFE2L2(19% ESCC vs 0% EAC). HPV-16 was detected in 2 (4%) and HPV-18 in 1 (2%) of ESCC. HPV was not detected in EAC. Conclusions: ESCC and EAC share high frequencies of total GA and CRGA. However, KRAS and ERBB2 are far more frequently altered in EAC than ESCC and mTOR pathway genes (PIK3CA and PTEN) more frequently altered in ESCC than EAC. CGP shows significant promise to identify CRGA in both ESCC and EAC and drive the potential use of clinical outcome altering targeted therapies in both major types of esophageal cancer.
Resilience among older (≥ 65 years) cancer patients undergoing ambulatory chemotherapy treatment.
Authors: M. A. de Souza, O. C. Junior, A. F. Ferreira Filho, I. M. Tavares Cavalcante, A. H. Friedrich, N. Marmitt, F. Ramminger, D. L. Da Silva
Journal: Journal of Clinical Oncology (2010)

e19676 Background: Resilience is a positive characteristic that enhances individual and group adaptation, helping in the adjustment and maintenance of psychological balance during periods of stress and/or misfortune. Most research on older cancer patients (OCP) has focused on physical aspects with relatively little attention to resilience and its assessment. The objective of this study is to evaluate and describe resilience scores (RS) in a population of OCP undergoing chemotherapy treatment on ambulatorial basis. Methods: A resilience questionnary was applied to 38 patients (20 women), with ≥ 65 years undergoing ambulatory chemotherapy treatment. Individual RS were measured by the Wagnild and Young Scale, validated for portuguese language from Brazil. Possible scores range from 25 to 175 with higher scores reflecting higher resilience. The study was approved by the Ethics Comitte and all patiens signed the informed consent form. Results: The mean age was 72 ± 5 years (range 65-82). Mean RS was 141 ± 22 (range 45-175), with individual scores displaying a statistically normal distribution by the Kolmogorov- Smirnov test (P = 0.4). The most common neoplasm were: colon (8), breast (7), lung (6) and prostate (4). Metastatic disease was present in 23 pts (60%). The intent of treatment was palliative in 22 (58%) pts and curative in 16 (42%). No statistical differences in mean RS were detected between pts receiving palliative (mean RS 141) versus curative (140) intention treatment (P = 0.54), nor in pts with metastatic (mean RS 140) as compared non-metastatic pts (142) (P = 0.63). Mean RS scores for men and women were 145 and 138 (P = 0.64). Conclusions: Our ambulatory OCP had a statistically normal distribution of resilience scores. Mean resilience scores were similar between subgroups of pts defined as metastatic versus non-metastatic and palliative versus curative treatment intention. Further research is necessary to confirm and further explore these results. No significant financial relationships to disclose.
Role of surgical resection among chemotherapy-treated patients with colorectal cancer stage IV disease: A survival analysis.
Authors: B. S. Lin, A. Ziogas, T. E. Seery, M. J. Stamos, J. A. Zell
Journal: Journal of Clinical Oncology (2011)

3564 Background: Advances in systemic chemotherapy have provided significant survival improvements in patients with stage IV colorectal cancer (CRC). The benefit of surgery to remove the primary tumor among these patients is controversial. The purpose of this study was to analyze CRC-specific survival (CRC-SS) and overall survival (OS) associated with surgical resection of primary tumor among chemotherapy-treated CRC patients with stage IV disease. Methods: 12,239 chemotherapy-treated CRC patients with stage IV disease in the California Cancer Registry between 1989 and 2008 were analyzed. Patients with contraindications to undergo surgery were excluded. Patients were stratified into surgery and no-surgery groups. Estimates of median CRC-SS and OS were generated using the Kaplan-Meier method. Multivariate CRC-SS and OS analyses were performed using Cox proportional-hazard ratios adjusted for age, gender, race/ethnicity, histology, primary tumor site, surgery, and socioeconomic status. Results: Surgical resection of the primary tumor was performed in 76.6% of patients (9,373 of 12,239); partial colectomy was the most frequent type of surgery performed (44.0%). Median age was similar in both surgery and no-surgery groups, 64.0 (range 11-94) vs. 64.0 (range 15-97) years. Proximal/transverse colon was the most likely primary tumor site in the surgery group (45.1%); rectum was the most likely primary tumor site in the no-surgery group (35.6%). Patients undergoing resection had higher median CRC-SS and OS rates, 18 vs. 9 months (P <0.0001) and 17 vs. 8 months (P <0.0001) respectively. In the multivariate model, surgical resection of the primary tumor was associated with a statistically significant improvement in both CRC-SS (HR 0.44; 95% CI 0.42-0.46; P < 0.0001) and OS (HR 0.42; 95% CI 0.40-0.44; P < 0.0001). The benefit was seen in both colon cancer (CRC-SS HR 0.40; 95% CI 0.37-0.43; P <0.0001; OS HR 0.39; 95% CI 0.36-0.41; P < 0.0001) and rectal cancer (CRC-SS HR 0.45; 95% CI 0.41-0.49; P <0.0001; OS HR 0.45; 95% CI 0.41-0.48; P < 0.0001). Conclusions: Surgical resection of primary tumor provided significant improvements in both CRC-SS and OS among stage IV chemotherapy-treated CRC patients.
Quality of life in patients treated with stereotactic radiosurgery following resection of brain metastases.
Authors: C. Turner, D. Stacy, B. Collett, J. Lipani, S. Williamson, K. Hill, M. Ali, L. Howard, A. Stroink, K. Kattner, E. Nardone, J. Seibly
Journal: Journal of Clinical Oncology (2011)

e19726 Background: This multi-institutional study analyzes QOL in pts tx with stereotactic r(SRS) to the tumor bed following gross total resection (GTR) of brain mets. Health-related qualify of life (HRQL) is defined as
How to implement Institute of Medicine (IOM) 2013 recommendations on supportive oncology in community setting.
Authors: Christine B. Weldon, Julia Rachel Trosman, Rosa Berardi
Journal: Journal of Clinical Oncology (2015)

172 Background: The IOM 2013 report recommends supportive oncology services from diagnosis through survivorship and end of life. We examined what community institutions need in order to implement IOM recommendations. Funded by the Coleman Foundation. Methods: We conducted a survey of 35 institutions in a large urban area (13 cancer centers; 14 stand-alone cancer support centers, and 8 hospices) on institutional needs in implementing IOM recommendations. Results: Survey response rate was 100%. Respondents agreed on 8 of the top 10 priorities across the three organization types (Table). Local inter-institutional collaboration leveraging respective resources and facilitating care consistency across sites was the most frequently noted need. It was followed by the need for stratified care processes based on patient need and improved supportive oncology reimbursement. Priorities differed between Cancer Centers and other institution types on Consolidated screening tools* (p = .05, .09) and Care process for family / caregiver** (p = .006, .04). Conclusions: Supportive oncology care processes and tools are needed to implement IOM recommendations in the community. Our findings inform a roadmap for practical collaborative implementation of the IOM recommendations. Differing priorities across cancer institution types should be further explored and addressed within the roadmap. [Table: see text]
Analysis of recurrence after resection of pancreatic neuroendocrine tumors.
Authors: Naeem A Newman, Gary N. Mann, Mrinal Shukla, Katrina R Swett, Edward A. Levine, John Bergquist, James Oh Park, Venu Gopal Pillarisetty, Jonathan G Sham, Perry Shen
Journal: Journal of Clinical Oncology (2013)

304 Background: Outcomes after recurrence of resected pancreatic neuroendocrine tumors (PNETs) are not well described. Our aim is to assess the rate and sites of recurrence and its effect on clinical outcomes. Methods: Retrospective chart review of patients (n= 80) who underwent surgical resection of PNETs at two institutions. Patients were treated from September 2002 to July 2010. Charts were reviewed for disease recurrence, date, site, and treatment of recurrence. Results: There were a total of 14 (17.5%) recurrences. The most common site of recurrence was the liver (10 patients, 71.4%). The most common treatment of recurrences was chemotherapy (5 patients, 35.7%). The 1, 3, and 5 year disease-free survival (DFS) was 90.9%, 82.7%, and 72.5% respectively. Median recurrence free survival (RFS) was 127 months. The median follow-up for all PNET patients was 25.8 months (range 1 to 140 months). Three-year survival was 97%. Local, distant, and combined recurrences occurred in 7.5%, 12.5%, and 5% of all patients, respectively. Multivariate analysis found AJCC stage (p=0.03) to be an independent predictor for DFS. Median follow-up of patients after they were found to have a recurrence was 13.8 months. Three-year survival for those with and without recurrence was 96.3% and 100%, respectively (p=0.36). Conclusions: AJCC stage is a significant predictor of recurrence after resection of PNETs with hepatic metastases being most common. Survival of patients with recurrence is not significantly different from patients without recurrence and is likely due to the indolent nature of the disease.
Phase I dose-escalation study of ALN-VSP02, a novel RNAi therapeutic for solid tumors with liver involvement.
Authors: A. Cervantes, M. Alsina, J. Tabernero, J. R. Infante, P. LoRusso, G. Shapiro, L. G. Paz-Ares, R. Falzone, J. Hill, J. Cehelsky, A. White, I. Toudjarska, D. Bumcrot, R. Meyers, G. Hinkle, N. Svrzikapa, D. W. Sah, A. Vaishnaw, J. Gollob, H. A. Burris
Journal: Journal of Clinical Oncology (2011)

3025 Background: ALN-VSP02 is a RNA interference (RNAi) therapeutic comprised of lipid nanoparticle-formulated small interfering RNAs (siRNAs) targeting the expression of vascular endothelial growth factor (VEGF)-A and kinesin spindle protein (KSP). Methods: A multi-center, open label, phase I dose-escalation trial of ALN-VSP02 administered as a 15-minute iv infusion q2 wks was initiated in patients (pts) with advanced solid tumors and at least one measurable liver lesion. Main objectives included evaluation of safety/tolerability and assessment of PK/PD. Results: Thirty-one pts were enrolled across 7 dose levels (0.1-1.5 mg/kg); median age 57 yrs, all with multiple prior therapies. A total of 140 doses were administered, mean of 4.5 (range 1-17). Treatment was generally well-tolerated, with no dose-dependent trends in clinical or laboratory adverse events. One on-study death (liver failure in a pt with near complete replacement of the liver by tumor) deemed possibly related to treatment occurred at 0.7 mg/kg. Low-grade acute infusion reactions occurred in 10% of pts and were managed with slowing of infusion. Dose-limiting toxicities at doses >0.7 mg/kg included 1 episode each of reversible grade 3 thrombocytopenia (1.25 mg/kg) and hypokalemia (1.5 mg/kg). Plasma PK showed dose-proportional AUC and Cmax. Post-treatment biopsies from 10 pts (7 liver and 3 extrahepatic tumors) showed pharmacologically relevant concentrations (0.3-142 ng/g tissue) of both siRNAs. Molecular evidence of RNAi-mediated VEGF mRNA cleavage was shown in liver (n=2 at 0.4 mg/kg) and in an extrahepatic tumor (ovarian cancer at 1.25 mg/kg) through use of the 5’ RACE assay on tumor biopsies. Additional evidence for an anti-VEGF effect with ALN-VSP02 included a decrease in Ktrans of at least 40% by DCE-MRI in 56% of evaluable pts. Among 27 pts evaluable for response, 8.3% (1 of 12) at doses ≤ 0.4 mg/kg had stable disease (SD) for at least 2 mo compared to 46.6% (7/15) with SD (n=6) or PR (n=1, endometrial cancer with liver metastases) at doses ≥ 0.7 mg/kg. Conclusions: ALN-VSP02 is well-tolerated and has antitumor activity. Pharmacodynamic data are consistent with an anti-VEGF effect, and 1.25 mg/kg q2wks is the recommended phase II dose.
Time-Related Interpretation of Molecular Response Levels According to Long Term Overall and Progression-Free Survival of CML Patients on First-Line Imatinib Treatment
Authors: Martin C. Müller, Benjamin Hanfstein, Michael Lauseker, Philipp Erben, Ulrike Proetel, Susanne Schnittger, Hans-Jochem Kolb, Stefan W. Krause, Christoph Nerl, Dominik Heim, Gabriela M. Baerlocher, Joerg E. A. Schubert, Hermann Einsele, Matthias Hänel, Jolanta Dengler, Christiane Falge, Lothar Kanz, Andreas Neubauer, Michael Kneba, Frank Stegelmann, Michael Pfreundschuh, Cornelius F. Waller, Markus Pfirrmann, Jörg Hasford, Wolf-Karsten Hofmann, Rüdiger Hehlmann, Susanne Saussele, Andreas Hochhaus
Journal: Blood (2011)
Disease flare after tyrosine kinase inhibitor (TKI) discontinuation in patients with <i>EGFR</i>-mutant lung cancer and acquired resistance.
Authors: J. E. Chaft, G. R. Oxnard, V. A. Miller, M. G. Kris, C. S. Sima, G. J. Riely
Journal: Journal of Clinical Oncology (2011)

e18001 Background: Treatment of oncogene-addicted malignant neoplasms with targeted kinase inhibitors is biologically and clinically different than treatment with cytotoxic chemotherapy. We have observed that some patients (pts) with acquired resistance to EGFR TKI (initial response followed by RECIST disease progression) have accelerated progression of disease after discontinuation of EGFR TKI. The risk of a serious disease flare after discontinuing erlotinib or gefitinib in EGFR-mutant lung cancer despite acquired resistance has not been systematically evaluated. Methods: We identified pts with EGFR-mutant lung adenocarcinoma enrolled in 6 trials for treatment of acquired resistance which mandated TKI discontinuation prior to treatment. Disease flare was defined as symptomatic progression of disease leading to hospitalization or death during the washout period. All pts met consensus criteria for acquired resistance (Jackman, JCO, 2010). Results: 55 pts were eligible, (age range: 27-82, women: 76%). Baseline EGFR mutations were exon 19 deletions (36) and L858R (19). The median time on TKI before discontinuation was 19 months (range 7-78). 12 pts (22%; 95% CI 13-35%) experienced a disease flare after discontinuation of EGFR TKI. The median time to disease flare from discontinuation of TKI was 8 days (range 3-21). Of these 12, all were hospitalized and 3 died. Flare was associated with a preceding shorter initial time to progression on TKI, median 9 vs. 13 months, p=0.015 (Wilcoxon). There was no association between disease flare and EGFR sensitizing mutation, presence of secondary T790M mutation, sites of disease, or performance status. Conclusions: In pts with EGFR-mutant lung cancer with acquired resistance to EGFR TKI, discontinuation of erlotinib or gefitinib prior to initiation of an alternative treatment is associated with a clinically significant risk of accelerated disease progression. There is a need to identify clinical and molecular characteristics that predict this phenomenon. Future clinical trials targeting this patient population should eliminate or minimize protocol-mandated washout periods. Funded by NIH T32 CA009207, P01 CA129243.
Analysis of predictive and prognostic value of clinical and pathological factors in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT): Bologna multidisciplinary rectal cancer group study (BMRG-B01-Study).
Authors: Sara Pini, Francesca Di Fabio, Claudio Ceccarelli, Bruno Iacopino, Ferdinando Lecce, Dajana Cuicchi, Giampaolo Ugolini, Francesco Varrese, Alessandra Guido, Fabiola Lorena Rojas Llimpe, Stefania Giaquinta, Carmine Pinto
Journal: Journal of Clinical Oncology (2013)

421 Background: Preoperative fluoropyrimidine based CRT is standard treatment in LARC patients. The aim of this study was to evaluate prognostic and predictive role of clinical and pathological factors in this setting Methods: Between December 2001 and January 2012 we evaluated 149 pts with cT3-T4 N-/+ rectal adenocarcinoma located ≤12 cm from the anal margin. Preoperative CRT consisted of radiotherapy 50.4 Gy in 28 daily fractions + 5-fluorouracil or capecitabine +/- oxaliplatin. Rectal surgery with total mesorectal excision was performed 6-8 weeks after the end of neoadjuvant treatment. Pathological examination of surgical specimens included TRG according to the Dworak criteria. TS, EGFR, Ki-67, p53, Bcl-2, MLH1 and MSH2 were immunohistochemically determined in pre-treatment biopsies and surgical specimens. For immunohistochemistry evaluation serial sections of formalin-fixed, paraffin-embedded tissues were stained with specific antibodies using a biotin-free ready-to-use amplification system Results: After a median follow-up of 60 months (2-122) we observed 4.7% local recurrences, 12.7% distant recurrences, and 13.4% deaths. In surgical specimens TRG 1, 2, 3 and 4 were observed respectively in 22.5%, 35.3%, 25.6% and 16.6% of patients. ypN and TRG were independent prognostic factors of DFS (p=0.020, p=0.027). CRM and TRG were independent prognostic factors of OS (p=0.016, p=0.010). High pre-treatment biopsy expression of TS was associated with poor TRG (0-1) (p=0.007); high biopsy expression of Ki-67 was associated with good TRG (2-4) (p=0.039); decrease between pre-treatment biopsy and surgical specimen of Ki-67 (Δ Ki-67 ≥ 0) was associated with good TRG (2-4) (p=0.02). Decrease in Ki-67 (Δ Ki-67 ≥ 0) was associated with good DFS (p=0.011) and confirmed by multivariate analysis as an independent prognostic factor (p=0.035). Conclusions: In our analysis ypN, CRM and TRG were independent prognostic factors; baseline expression of TS, Ki-67 and decrease in Ki-67 were predictive of TRG; decrease in Ki-67 was an independent prognostic factor of DFS.
Pathways of care for adolescents with cancer in France.
Authors: E. Desandes, S. Bonnay, C. Berger, L. Brugieres, F. Isfan, V. Laurence, L. Mignot, D. Olive-Sommelet, I. Tron, J. Clavel, B. Lacour
Journal: Journal of Clinical Oncology (2011)

6058 Background: In France pathways of care for adolescent cancer patients are different between pediatric and adult medical background. Health care professionals need to have a population-based view of their treatment modalities in order to implement facilities required in any center dedicated to their care, and to promote change in the usual models of care, with a special attention on their medical and psychosocial management. Methods: Using a population-based registration, we report care pathways of patients aged from 15 to 19 years, diagnosed with cancer from 2006 to 2007, living in 6 French Regions, representing 41% of the French population. Results: The median times (inter-quartile range) of the 595 included adolescents for diagnosis and treatment for all cancers were respectively 8 weeks (3-17), and 3 days (0-16). First physicians met by the patients were mostly general practitioners (59%). 19% of patients were firstly seen on emergency wards. Most of the patients (70%) were treated in an adult environment. For leukemia patients and for patients aged from 15 to 17 years, proportion treated in pediatric oncology reached respectively 56% and 47%. Management decisions were taken within the context of a multi-disciplinary team in 54% of cases, but few of were had input of both pediatric and adult clinicians. 27% of patients were included in randomized clinical trials or non randomized studies : percentage depended on the tumor type (leukemia 55%, bone tumors 52%, soft-tissue sarcoma 36%, lymphoma 33%) and on the number of trials opened at the study period. 15% of patients were included in pediatric studies, 7% in adult studies, and 5% in studies including both adults and children. Conclusions: Our study is the first large French population-based for 15-19 years cancer patients. According to the 2nd French Cancer Strategic Action Plan, our objective is to identify health institutions and practices ensuring an appropriate and optimal care for these patients, to improve education of health professionals in the adolescent and young adult oncology field, and to promote effective collaboration between pediatric and adult health providers, specific research programs, as well as transition of care between pediatric and adult teams, and the organization of long term follow-up.
Treatment target development in muscle-invasive bladder cancer.
Authors: Mick D. Brown, Richard Robinson, Claire Hart, Noel W. Clarke
Journal: Journal of Clinical Oncology (2014)

328 Background: Outcome for many patients with high-grade muscle invasive bladder cancer (MIBC) remains poor despite aggressive therapy. This study used novel marker approaches to evaluate putative treatment targets, correlating cell line models of bladder cancer with a large scale MIBC tissue microarray (TMA) linked to long-term post-treatment outcomes. Methods: The TMA was constructed from 497 cystectomy specimens from patients with comprehensively documented disease outcome (minimum 5 years follow-up). TMA sections were stained for putative targets using DAB-based IHC. Cellular expression of CYR61 and CTGF was quantified (after targets had been identified using the genetic search programme, Oncomine) using Definiens automated image-analysis (AIA) software. Putative TMA based-targets studied were also evaluated in J82 and T24 bladder cancer cell-lines by siRNA knockdown during proliferation, time course stimulation and Boyden chamber MatrigelÒ invasion assays. Results: CTGF was increased significantly in both cell lines following stimulation with the cMET ligand HGF. siRNA knockdown of CTGF and CYR61 reduced cell proliferation and invasion towards HGF and FCS significantly (p&lt;0.01). AIA demonstrated high sensitivity and specificity (82.5% and 99.8% respectively) for identifying tumour cells. There was no intra-observer variability (ICC=1). CYR61 was associated with significantly improved survival following cystectomy, median 15.2 versus 40.0 months for intermediate/high versus negative/low expression respectively (p=0.004). Conclusions: AIA is robust tool for use in IHC based research. CTGF is an important component of the cMET axis in MIBC. CTGF and in particular CYR61 are promising treatment targets and warrant further investigation in the management of this disease.