tbuckley/cabot-search huggingface dataset:
Administration of chemotherapy via median cubital vein without implantable central venous access port for metastatic colorectal cancer: Port-free chemotherapy.
Authors: Yoichiro Yoshida, Naoya Aisu, Masayasu Naito, Syu Tanimura, Takamitsu Sasaki, Shinsuke Takeno, Seiichiro Hoshino, Ai Mogi, Toshihiro Tanaka, Kazuo Tamura, Yuichi Yamashita
Journal: Journal of Clinical Oncology (2014)

651 Background: Repeated venous punctures are usually required in cancer patients for application of chemotherapy. Central venous catheters and implantable port systems have substantially facilitated the problem of vascular access. Safe and easy-to-handle port systems have become an integral part of daily clinical routine in oncology. However, there are several serious complications associated with central venous ports (CV-ports). With the recent development of capecitabine plus oxaliplatin (XELOX) therapy involving oral administration of drug preparations, etc., implantation of a CV-port can be avoided. The present study was undertaken to evaluate the safety of administration of chemotherapy via median cubital vein without CV port for metastatic colorectal cancer. Methods: The study included 144 patients who received XELOX + bevacizumab (BV) therapy and XELOX therapy for metastatic colorectal cancer without implantation of a CV-port. Results: Eighty-five patients experienced vascular pain, but it was transient. The drip infusion route had to be switched to the opposite side because of vascular pain in only 1 of the 144 patients. No patients required CV-port implantation or postponement of treatment due to adverse events caused by administration of the drug via the peripheral vein. Grade 3 or higher hemotoxicity was noted in 12.5%, and grade 3 or higher nonhematological toxicity was noted in 17.4%. Conclusions: We may be able to perform port-free-chemotherapy via median cubital vein for patients with colorectal cancer. We can avoid the serious complications associated with CV-port.
Outcomes after major cancer surgery: Can we predict them using parsimonious models?
Authors: Neha Goel, William H. Ward, Lyudmila DeMora, Samuel Manstein, Marc C. Smaldone, Jeffrey M. Farma, Christina Chu, Alexander Kutikov, David Chen, Miriam Lango, Rosalia Viterbo, John A. Ridge, Eric A. Ross, Robert Uzzo, Nestor F. Esnaola
Journal: Journal of Clinical Oncology (2018)

811 Background: Major cancer surgery is associated with significant risks of morbidity/mortality. Retrospective studies have demonstrated an association between Surgical Apgar Score (SAS) and postoperative risk of serious complications (SC). This study prospectively evaluated the predictive value of SAS to predict SC, as well as other adverse postoperative outcomes and length of stay (LOS), both singly and in combination with parsimonious measures of “fitness for surgery” (American Society of Anesthesiology [ASA] classification) and surgical complexity (work relative value units [wRVU]). Methods: Demographic, comorbidity, procedure, intraoperative, and outcome data was collected prospectively for 442 cancer patients undergoing elective major surgery between 2014-17. ASA and wRVU were assigned preoperatively; SAS was calculated postoperatively. Logistic regression was used to analyze association of ASA versus (vs) wRVU vs SAS vs ASA/wRVU/SAS (combined) with perioperative outcomes, including SC, return to the operating room (ROR), not being discharged to home, and unplanned readmission; areas under receiver operator characteristic curves were calculated to assess predictive accuracy. Accelerated failure time models were used to analyze associations with LOS and compared using Harrell’s concordance index. Results: Predictive accuracy of SAS for SC was modest (AUC0.655) and not improved when controlling for ASA and wRVU (both of which had poor predictive accuracy for SC). Both wRVU (AUC 0.634) and SAS (AUC 0.663) had modest predictive accuracies for ROR, whereas the predictive accuracy of ASA (AUC 0.749) surpassed that of wRVU (AUC 0.630) for not being discharged to home. All 3 measures were poor at predicting readmission. In contrast, the predictive accuracy of ASA, wRVU, and SAS for LOS was highest when combined (AUC 0.699). Conclusions: Commonly used, simple measures of comorbidity/functional status and surgical complexity can help predict risk of ROR and not being discharged to home (respectively), whereas only SAS has sufficient (albeit modest) discriminatory ability to predict risk of SC. All three measures are too coarse to predict unplanned readmission, but when used in combination, can help predict LOS.
Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma
Authors: R.I. Haddad, E. Massarelli, J.J. Lee, H.Y. Lin, K. Hutcheson, J. Lewis, A.S. Garden, G.R. Blumenschein, W.N. William, R.R. Pharaon, R.B. Tishler, B.S. Glisson, C. Pickering, K.A. Gold, F.M. Johnson, G. Rabinowits, L.E. Ginsberg, M.D. Williams, J. Myers, M.S. Kies, V. Papadimitrakopoulou
Journal: Annals of Oncology (2018)

BackgroundThe survival advantage of induction chemotherapy (IC) followed by locoregional treatment is controversial in locally advanced head and neck squamous cell carcinoma (LAHNSCC). We previously showed feasibility and safety of cetuximab-based IC (paclitaxel/carboplatin/cetuximab—PCC, and docetaxel/cisplatin/5-fluorouracil/cetuximab—C-TPF) followed by local therapy in LAHNSCC. The primary end point of this phase II clinical trial with randomization to PCC and C-TPF followed by combined local therapy in patients with LAHNSCC stratified by human papillomavirus (HPV) status and T-stage was 2-year progression-free survival (PFS) compared with historical control.Patients and methodsEligible patients were ≥18 years with squamous cell carcinoma of the oropharynx, oral cavity, nasopharynx, hypopharynx, or larynx with measurable stage IV (T0–4N2b–2c/3M0) and known HPV by p16 status. Stratification was by HPV and T-stage into one of the two risk groups: (i) low-risk: HPV-positive and T0–3 or HPV-negative and T0–2; (ii) intermediate/high-risk: HPV-positive and T4 or HPV-negative and T3–4. Patient reported outcomes were carried out.ResultsA total of 136 patients were randomized in the study, 68 to each arm. With a median follow up of 3.2 years, the 2-year PFS in the PCC arm was 89% in the overall, 96% in the low-risk and 67% in the intermediate/high-risk groups; in the C-TPF arm 2-year PFS was 88% in the overall, 88% in the low-risk and 89% in the intermediate/high-risk groups.ConclusionThe observed 2-year PFS of PCC in the low-risk group and of C-TPF in the intermediate/high-risk group showed a 20% improvement compared with the historical control derived from RTOG-0129, therefore reaching the primary end point of the trial.
Content of estrone and estrogen metabolites in tissues of hysterocarcinoma, adenomyosis, and hysteromyoma tissue.
Authors: Nataliya Chernikova, Elena Frantsiyants, Tatiyana Moiseyenko, Ekaterina Komarova, Meri Adamyan, Ivan Nikitin
Journal: Journal of Clinical Oncology (2014)

e22214 Background: The significance of autocrine tumor growth regulation and the role of hyperestrogenism in pathogenesis of hyperplastic processes of women's reproductive organs has not been determined so far. Methods: The IFA method was used for determining the content of estrone (E1) and estradiol (E2) in the hysterocarcinoma tissue (HC, n=25), adenomyosis of uterus (A, n=26), myoma tissue (M, n=30) as independent variants and in 29 patients having the combination of the above.The patients were aged 35-49, all women were in the reproductive period. The control was visually unchanged uterine body tissue. Results: Under A the levels of E1and E2 were 1.3 and 2 times higher than the value of the intact tissue, respectively. Under M the level of E1 was 1.6 times as high as that of the intact tissue, with the content of E2 being the same. On the contrary, under the HC, the level of E1 was 1.6 times lower as compared to the indicator in the intact skin, but, similarly, with E2 normal. If the three processes (HC, A and M) are combined, the content of E2 was on average 2 times higher than the norm as for all tissues studied. Under HC, A and M combined, the level of E1 was reduced in the A and M tissues in 2.4 and 2.5 times, respectively, while it was reduced in 1.2 in the HC tissue. Under the independent A and HC, E1/E2 was lower than the norm on average in 1.6 times and it was 69% higher than the norm under the independent M. In the combination process occurs unification E1/E2: decreased an average of 5.8 times compared to intact tissue Conclusions: It has been demonstrated that independently developing HC, adenomyosis and uterine myoma are featured by the individual local hormonogenesis. The results obtained allow concluding that under combined pathology the hyperplastic processes influence each other, which is most brightly reflected by the unifying of E1/E2 ratio.
Mesothelin expression as a predictive biomarker of breast cancer outcomes.
Authors: Yun Rose Li, Rena R Xian, Amy Ziober, Jose Conejo-Garcia, Carl H. June, Paul J. Zhang, Julia C. Tchou
Journal: Journal of Clinical Oncology (2014)

11119 Background: Mesothelin, previously-shown to be expressed in triple negative breast cancer (TNBC) tumors, is a potential therapeutic target and prognostic marker in breast cancer. Methods: We analyzed clinical data from two cohorts: a 141 patient-cohort treated between 2009 and 2011 at the UPHS (discovery) and the 844 patient-cohort from The Cancer Genome Atlas (TCGA) (validation). Mesothelin expression was quantified by immunohistochemistry (IHC) (discovery) or RNA transcript levels by whole-transcriptome sequencing (validation). Results: Median follow up for our discovery cohort was 3.54 years. Univariate analyses demonstrated that tumor size (HR=1.30, 95% CI 1.115-1.515, p < 4.58 x10-4), number of positive axillary lymph nodes (HR=1.131; 95% CI 1.06-1.21; p-value < 9.20 x10-5), tumor stage (HR (Grade III to I) = 21.294, 95% CI 2.69-168.69, p < 3.40 x10-5), at least one lymph node removed (HR=1.07, 95% CI 1.021-1.116, p< 2.45 x10-3), and most importantly, mesothelin expression (HR= 2.377; 95% CI 1.12-5.02; p < 3.01 x10-3) were associated with both overall and disease-specific survival. We used a Cox-proportional hazard (Cox-PH) model to adjust for the only other independent predictors of survival, namely axillary lymph nodes involved and tumor size, and stratifying by African American race, we found a significant association between mesothelin expression and overall and disease-specific survival in the discovery cohort (HR = 3.138, 85% CI 1.38-7.10, p < 6.14 x10-3). Using the TCGA dataset, we confirmed that, over a median follow-up of 16.0months, patients with mesothelin-expressing tumors had poorer overall survival (HR=1.463; 95% CI 1.053-2.033; p<0.021). On Cox-PH analysis, mesothelin-positivity was independently predictive of poorer survival, after adjusting for the number of involved axillary lymph nodes and tumor size (HR = 1.688; 95% CI 1.174-2.425; p<4.67x10-3). Conclusions: Our results suggest that mesothelin is a prognostic breast tumor marker and that its expression in a large proportion in TNBC holds promise that existing targeted therapy directed against mesothelin may be effective for the treatment of TNBC. Further work is needed to elucidate the mechanistic role of mesothelin in breast cancer.
Molecular profiling of HER2-positive colorectal cancer for identification of multiple potential drug targets.
Authors: William Jeffery Edenfield, Ki Y Chung, Zoran Gatalica, Gargi Dan Basu
Journal: Journal of Clinical Oncology (2014)

e14508 Background: Colorectal adenocarcinoma (CRC) is a clinically and genetically heterogeneous disease driven by multiple pathways including the HER2 receptor tyrosine kinase pathway. This study was undertaken to assess the frequency of HER2 abnormalities in colorectal cancer patients and to determine the molecular profile of HER2 over-expressing colorectal tumors. Methods: A database of 4,110 consecutive CRC patients was analyzed for demographics (sex, age, geography, site of tumor) and predictive biomarkers. Multiplatform testing included gene sequencing for up to 44 genes by NGS or Sanger, immunohistochemistry (up to 28 genes) and gene amplification by CISH or FISH (up to 8 genes). Results: The incidence of HER2 overexpression was 1.8% (81 out of 4,110) in CRC patients and there was 97% concordance between HER2 protein expression and gene amplification based on overall population. HER2 mutations were only present in 11% (2/19) of HER2 over-expressing CRC patients and did not correlate with either protein or gene copy number. One patient with a HER2 mutation harbored 2 synchronous APC mutations and a KRAS and SMAD4 gene mutation suggesting tumor aggressiveness. The most frequent genetic alteration in the HER2 over-expressing patient cohort was P53 (74%, 14/19) followed by APC (63%, 12/19). SMAD4 mutation was detected in 21% (4/19) and KRAS mutation was detected in 14% (9/64) of cases. Other RAS mutations were absent. Additional genes involved in downstream HER2 signaling through the PI3K /AKTpathway were frequently aberrant, including PTEN loss of expression (54%, 43/79), and PIK3CA mutation (14%, 4/29) and FBXW7 mutation (10%, 2/19). cMET was overexpressed in 47% (16/34) of cases, however, without correlative gene amplification or mutation. Conclusions: Multiplatform molecular profiling of the HER2 over-expressing subset of colorectal cancer provides additional treatment options as well as clinical trials to consider. Many of the actionable targets (PTEN loss and cMET positivity) were detected using IHC and would have been missed if NGS alone had been used. This study is by far the largest data set of HER2 overexpressing CRC patients profiled in a centralized laboratory with standardized testing.
Combined epiregulin (EREG) and amphiregulin (AREG) expression levels as a biomarker of prognosis and panitumumab benefit in <i>RAS</i>-wt advanced colorectal cancer (aCRC).
Authors: Jenny F. Seligmann, Faye Elliott, Susan Richman, Bart Jacobs, Gemma Hemmings, Jenny Barrett, Sabine Tejpar, Philip Quirke, Matthew T. Seymour
Journal: Journal of Clinical Oncology (2014)

3520 Background: RNA expression of epiregulin (EREG) ligands EREG and/or amphiregulin (AREG) has shown correlation with the efficacy of EGFR-targeted therapy in advanced colorectal cancer (aCRC). This finding requires validation, and interaction with MEK-AKT pathway mutations clarified. We examined both ligands and mutations in patients (pts) in a large randomised trial of panitumumab. The a priori hypothesis was that high expression of either AREG or EREG, in RAS-wild type (wt) pts, would predict panitumumab benefit. Methods: AREG and EREG expression and RAS (KRAS and NRAS) and BRAF mutations were assessed in archival tumor from 323 pts randomised to irinotecan (Ir) or irinotecan/panitumumab (IrPan) as second-line treatment of aCRC (PICCOLO trial, Lancet Oncol 14: 749-759). A predefined dichotomous model classified ligand expression as “high” (either EREG or AREG in top tertile for mRNA level) or “low” (neither EREG nor AREG in top tertile). Prognostic effect was assessed, then predictive effect by testing interaction with drug impact. The primary population was RAS-wt (n=220); primary endpoint was progression-free survival (PFS). Results: High ligand expression was not a significant prognostic marker for PFS (HR 0.93, 95% CI 0.68-1.27, p=0.64) or overall survival (OS) (HR 0.79, 95% CI, 0.58-1.09, p=0.15). However, it was significantly predictive. For RAS-wt pts with high ligand expression, median PFS was 8.3 months (IrPan) vs 4.4 months (Ir) (HR=0.62, 95%CI 0.49-0.78, p<0.001). Conversely, RAS-wt pts with low expression gained no benefit: 3.2 months (IrPan) vs. 4 months (Ir) (HR=0.97, 95%CI 0.8-1.17, p=0.73). The ligand-treatment interaction was p=0.01. Less effect was seen on the secondary endpoints response rates (interaction p=0.09) and overall survival (interaction p=0.11). Ligand expression was markedly lower in BRAF-mutated than all-wt tumours (p<0.001), however ligand expression remained predictive of panitumumab effect following adjustment for BRAF. Conclusions: The hypothesis was confirmed: high ligand expression predicts panitumumab benefit on PFS in RAS-wt pts; there was no evidence of benefit with low ligand expression. Optimisation of the ligand model for clinical use is needed, however this work confirms that EREG and AREG are potentially useful biomarkers for anti-EGFR therapy.
Combining Next Generation Proteomics Platforms with Drug Sensitivity Resistance Testing AllowsÂ Identification of Physiologically Distinct Sub-ClonesÂ That Can Inform Therapeutic and Drug Development Strategies
Authors: Despina Bazou, Muntasir M Majumder, Ciara Tierney, Sinead O'Rourke, Pekka Anttila, Raija Helena Silvennoinen, Caroline A Heckman, Paul Dowling, Peter O'Gorman
Journal: Blood (2018)
The revised AJCC staging (7th edition) and prognostic stratification in esophagogastric adenocarcinoma.
Authors: Haris Zahoor, James D. Luketich, Benny Weksler, Dan G. Winger, Neil A. Christie, Ryan M. Levy, Michael K. Gibson, Katie Sue Nason
Journal: Journal of Clinical Oncology (2014)

4038 Background: AJCC esophageal staging assigns prognostic groups based on tumor, node, and metastasis classifications. In 2010, AJCC 7th ed. separated adenocarcinoma from squamous cell histology and added tumor grade and number of involved regional nodes. Our study aim was to compare survival prognostication for esophagogastric adenocarcinoma between AJCC 7 and AJCC 6th ed. stage groupings. Methods: We abstracted pathology and survival for surgically resected esophagogastric adenocarcinoma patients (n=836; 1997 to 2011); 256 received induction therapy. AJCC stage was assigned; overall survival in months (esophagectomy to death or most recent alive contact) was analyzed. Discriminatory ability and homogeneity, by stage, was assessed with Kaplan-Meier (KM) curves. Monotonicity comparisons were evaluated with linear trend chi-squared tests. Overall survival was compared using Cox regression and Akaike Information Criterion (AIC) was used to assess model fit. Results: Compared to AJCC 6, AJCC 7 restaged 165 patients (Table). KM log-rank statistic indicated stronger differentiation in AJCC 7 curves compared to AJCC 6 (166.128 vs 185.523 overall). Cox likelihood ratio (162.957 vs. 173.951 overall) and AIC (4831.011 vs 4820.016 overall) indicate better model fit to the survival data for AJCC 7 versus AJCC 6, overall and for induction subgroups (data not shown). As stage group increases, stronger linear trends for survival were observed at 24, 36, and 60 months using AJCC7 stage groupings, overall and for induction subgroups, compared to AJCC 6. Conclusions: AJCC 7 stage groupings demonstrate superior homogeneity, discriminatory ability, and monotonicity compared to AJCC 6. Incorporating the extent of nodal disease, and tumor grade into the revised AJCC 7 stage classification improves prognostic stratification of surgically resected esophagogastric adenocarcinoma patients, including patients who received induction therapy. Patients upstaged or downstaged comparing AJCC 6 to AJCC 7. Upstaged Number of patients IIa to IIb 77 IIb to IIIa 29 IIb to IIIc 10 Downstaged Number of patients IIa to Ib 32 IVa to IIb 1 IVa to IIIa 3 IVa to IIIb 3 IVa to IIIc 10
The role of nutritional intervention in advanced stage pancreatic ductal adenocarcinomas (PDAC).
Authors: Ashley Baldwin, Rachel Winston, Robert P. Whitehead, Toufic Kachaamy, Sharon Day, Madappa N. Kundranda
Journal: Journal of Clinical Oncology (2014)

e20668 Background: PDAC is the 4th leading cause of death in the US; with a 5-yr survival of <10%. Newer chemotherapy regimens have contributed to increased survival but nutritional decline and weight-loss plays a key role in the patient’s (pts) inability to tolerate effective chemotherapy. The Patient Generated Subjective Global Assessment (PG-SGA) is a validated clinical tool to assess nutritional status. We examined the association of important nutritional variables with changes in the modified PG-SGA score from baseline up to week 6 and week 12. Methods: Retrospective chart review of PDAC pts treated between 2008-2013 was performed. The change from baseline PG-SGA scores to the incorporation of 10 active nutritional interventions including enzymes, calcitriol, Omega-3 and appetite stimulants (collectively termed as Nutrient Score) was measured. Correlation coefficients using the Pearson correlation method was performed. Regression analyses was performed to determine their association with the change in PG-SGA and survival analyses performed to determine the PG-SGA impact on patient survival. Results: Baseline demographics of 165 pts; median age 58yrs; 63% had prior systemic therapies and 77% had ECOG 1-2. Mean PG-SGA at baseline was 5.4.Time from diagnosis to initial presentation at our cancer center was 6.7 months. At weeks 6 and 12; increase in weight was associated with improvement in PG-SGA scores. No significant correlation observed between total Nutrient Score and change in PG-SGA at weeks 6 (P=0.684) and 12 (P=0.371). However there was improved survival among patients with improved PG-SGA scores at weeks 6 (HR=1.175, P<0.001) and week 12 (HR=1.337, P<0.001). The median survival time (mOS) from initial visit to the cancer center was 7.8 months while starting from initial diagnosis the mOS was 13.5 months. Conclusions: Global nutritional status measured by PG-SGA predicted improved survival in patients with PDAC. Whether the improvements noted were due to other nutritional factors versus successful anti-neoplastic therapy (which improved GI function); or a combination is unclear. Future studies need to be conducted to tease out and determine contributory factors towards the improvement in PG-SGA scores.
Abstract 16065: The STS-Score Outperforms the EuroSCORE In Predicting Outcome Following Transcatheter Aortic Valve Implantation
Authors: Henrik Fox, Kathrin Hemann, Johannes Weber, Margarita Sirotina, Florian Seeger, Anton Moritz, Andreas M Zeiher, Volker Schächinger, Mirko Doss, Horst Sievert, Stephan Fichtlscherer, Ralf Lehmann
Journal: Circulation (2012)

BACKGROUND: Transcatheter aortic valve implantation (TAVI) was developed as new innovative therapy for inoperable patients and high-risk patients as an alternative to traditional aortic valve repla...
Anti-CD123 Targeted Therapy with Talacotuzumab in Advanced MDS and AML after Failing Hypomethylating Agents - Final Results of the Samba Trial
Authors: Anne Sophie Kubasch, Freya Schulze, Katharina S. Götze, Jan Krönke, Katja Sockel, Jan Moritz Middeke, Fatiha Chermat, Silke Gloaguen, Martin Puttrich, Carmen Weigt, Katja Jersemann, Pierre Fenaux, Richard F. Schlenk, Aristoteles Giagounidis, Lionel Ades, Anna Mies, Uta Oelschlaegel, Uwe Platzbecker
Journal: Blood (2018)