tbuckley/cabot-search huggingface dataset:
Rectal cancer treatment without neoadjuvant chemoradiation based on preoperative magnetic resonance imaging: Determinants of surgical quality in the German OCUM study.
Authors: Martin Ernst Kreis, Joachim Strassburg, Reinhard Ruppert, Henry Ptok, Theodor Junginger, Susanne Merkel, Paul Hermanek
Journal: Journal of Clinical Oncology (2014)

526 Background: Preoperative chemoradiation adds functional impairment to patients undergoing total mesorectal excision (TME). Surgical quality is of paramount importance to achieve low local recurrence rates in patients operated without preoperative chemoradiation when a negative circumferential margin was shown by preoperative magnetic resonance imaging (MRI). We aimed to determine surgical quality in a prospective multicenter cohort study (OCUM) in patients selected by MRI for surgery without neoadjuvant chemoradiation. Methods: Quality of TME was assessed in three categories for 282 patients from 12 hospitals enrolled for surgery without preoperative chemoradiation (Nagtegaal et al. 2005, Quirke and Morris 2007). Tumor perforation, local tumor cell dissemination and number of lymph nodes were assessed. Further, negative predictive value of MRI for histopathological involvement of the circumferential margin was determined. Results: In patients undergoing TME the muscularis propria plane (category III) was reached in 1/282 patients (0,4 %). Intraoperative tumor cell dissemination was observed in 3/282 patients (1,1 %). Total number of lymph nodes was 25 (median, range 10-79) and 79/282 patients had positive lymph nodes (28 %). The number of 12 lymph nodes recommended by UICC was not reached in one patient. Preoperative MRI correctly predicted a negative circumferential margin involvement as determined by histopathological workup in 98,9 % of patients. Conclusions: Excellent results in terms of surgical quality are possible justifying surgery without pretreatment in patients with MRI-negative circumferental margin tumors. This concept avoids additional functional impairment and reduced quality of life following preoperative chemoradiation in selected patients. Clinical trial information: NCT01325649.
Survival outcomes in patients undergoing neoadjuvant chemotherapy for upper tract urothelial cell carcinoma.
Authors: Sima P. Porten, Arlene O. Siefker-Radtke, Ashish M. Kamat, Colin P.N. Dinney, Surena F. Matin
Journal: Journal of Clinical Oncology (2013)

311 Background: High-grade upper tract urothelial carcinoma (UTUC) is frequently upstaged at surgery and has uniformly poor survival rates. Neoadjuvant chemotherapy (NAC) may provide an avenue to improve clinical outcomes in these patients prior to loss of renal function after nephroureterectomy. Methods: We performed a retrospective review of patients with high risk UTUC who received NAC followed by surgical extirpation from 2004 to 2008, a time period during which NAC was uniformly offered to patients. The study group was then compared to a historical cohort of similar risk patients who underwent initial surgical treatment from 1993-2004. Results: Of the 120 patients, 31 patients with high-risk cN0 disease received NAC, 76 had initial surgery, and 13 had surgical consolidation of clinically involved lymph nodes after chemotherapy. Those receiving NAC had an improved OS and DSS (p=0.018 and p=0.0005, respectively). The 3 and 5 year DSS for cN0 patients receiving NAC was 90% and 90% (OS 87% and 80% respectively) with median follow up of 64 months. The 3 and 5 year DSS and OS for the historical group was 70% and 62%, with median follow up of 87 months. The two groups had similar demographics and clinical features, except for a higher proportion of sessile tumor architecture in the NAC group (p=0.021). Full dose cisplatin or high dose ifosfamide based chemotherapy was given to 22 (71%) patients, while 4 (13%) received a modified dose of cisplatin, and 5 (16%) received a nephron sparing combination. Pathologic downstaging to &lt;=pT1N0 was significantly associated with NAC (65% vs 26% initial, p=0.004). The 13 patients with node positive disease at presentation received NAC followed by surgical consolidation with median OS 78 months. The 3 and 5 year DSS was 77% and 67% (OS 69% and 60% respectively). Conclusions: Neoadjuvant chemotherapy improves survival in patients with UTUC compared with historical expectations. Patients with high-risk UTUC should be considered for neoadjuvant chemotherapy especially considering the limitations of administering curative cisplatin-based chemotherapy after nephrectomy.
Use of plasma angiogenesis-related factors to investigate the association of interleukin 8 and interleukin 6 levels with efficacy of sorafenib-based antiangiogenic therapy in patients with advanced hepatocellular carcinoma (HCC).
Authors: Y. Shao, C. Hsu, C. Huang, A. Cheng
Journal: Journal of Clinical Oncology (2011)

199 Background: Anti-angiogenic agents have become the most important class of therapy for patients (pts) with advanced HCC. However, biomarkers predictive of the efficacy of anti-angiogenic therapy remain lacking. Methods: Advanced HCC pts, enrolled in a phase II study (Hsu et al: J Hepatol 2010) and its extended cohort, were treated with sorafenib plus metronomic oral tegafur/uracil until disease progression. Plasma samples were collected before treatment and 4 weeks after the start of treatment. The levels of IL-6, IL-8, IL-13, CXCL10, PDGF and VEGF-A were analyzed by multiplexed bead suspension arrays (Bio-Rad, Hercules, CA, US). Levels of VEGF-C, VEGF-D, PlGF, fibroblast growth factor 2 (FGF2), SDF1-alpha and soluble VEGF receptor 2 were determined by ELISA. The baseline levels and post-treatment changes of these plasma factors were analyzed for their associations with treatment outcomes. Results: Among 68 pts treated with the protocol treatment, 64 were enrolled to this study. There were 4 partial responder (PR) and 33 patients with stable disease (SD) according to RECIST 1.0. The disease control rate (PR+SD) was 58%. The median PFS and OS were 3.7 and 7.4 months, respectively. Patients with progressive disease, compared to those with disease control, had significant increase of post- treatment IL-6 (p = 0.016) and IL-8 (p = 0.021), borderline significant increase of post-treatment FGF2 (p = 0.078) and significant decrease of post-treatment CXCL-10 (p = 0.046). High baseline IL-8 was significantly associated with poorer PFS and OS (p = 0.002 and 0.001, respectively). More increase of post-treatment IL-6 was associated with poorer PFS and OS (p = 0.087 and 0.018, respectively). By multivariate analysis, high baseline IL-8 and more post-treatment increase of IL-6 remained independent predictors for poorer PFS and OS. Conclusions: High baseline IL-8 and more post-treatment increase of IL-6 in plasma were associated with poor treatment outcomes in advanced HCC pts treated with sorafenib-based anti-angiogenic therapy. This study was supported by the grant of NSC 98-3112-B-002-038. No significant financial relationships to disclose.
Role of thymidylate synthase (TS) polymorphisms (SNPs) as a potential prognostic factor in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (preCh-RT).
Authors: R. Vera, V. Arrazubi, A. Viúdez, D. Guerrero, M. L. Gomez Dorronsoro, F. Arias, G. Asin, E. Balen, L. Teijeira, J. Verdun, J. Suarez
Journal: Journal of Clinical Oncology (2011)

e14080 Background: Neoadjuvant concomitant fluoropyrimidine-based chemotherapy plus radiotherapy is considered a standard approach for LARC. SNPs of TS, the target for fluoropyrimidines, are recognized prognostic factors in colon cancer. The aim of this study was to evaluate the role of TS SNPs in LARC patients (pts) treated with preCh-RT. Methods: Between November 2001 and March 2009, 110 consecutive pts with stage II/III LARC were treated with neoadjuvant RT (5,040 cGy) plus fluoropyrimidine-based chemotherapy (ci 5FU:69 pts; capecitabine:41pts). Patients underwent surgery 6-8 weeks after pre Ch-RT. DNA was extracted from paraffin embedded biopsies. TS1494del6 and 5′-28bp repeat +G/C SNP polymorphisms were determined. Results: 67% were men and median age was 67 years. ypT stage was: ypT0 10%, ypT1 3%, ypT2 27%, ypT3 58% and ypT4 2%; 32% had positive nodes. Median follow-up was 45 months and relapses occurred in 20% of patients. SNPs could be determined in 98% of pt: -6bp/-6bp 10%, - 6bp/+6bp 39%, +6bp/+6bp 51% and 2R/2R 72%, 2R/3R 21%, 3R/3R 6%. The grade of pathological tumor regression was not associated with SNPs. Distant or locoregional disease relapses occurred in 40% of -6bp/-6bp pts (5FU: 42.9%; capectabine: 33.3%), 22% of patients -6bp/+6bp or +6bp/+6bp (5FU: 25.2%; capecitabine: 15.8%). The difference in disease- free survival (DFS) between the first and the second groups was statistically significant (p=0.049).Equally, a significant difference was found between -6bp/-6bp pts treated wit 5FU vs capecitabine (35m vs 16m). No relation between 5′-28bp repeat +G/C SNP polymorphism and DFS was found. Conclusions: In LARC our data suggest that the choice between 5FU or capecitabine could depends of the knowledge of TS1494del6 status.
A Web-based decision support platform to reduce non-evidence-based treatment of non-small cell lung cancer.
Authors: Stephen H. Grund, Arlene A. Forastiere, William A. Flood, Elaine Whyler, Vlad Kozlovski, Yu-Ning Wong
Journal: Journal of Clinical Oncology (2012)

71 Background: Published reports indicate 30% to 40% of oncology treatments deviate from evidence-based standards. Little is known about the extent of deviation from guidelines in lung cancer. Methods: eviti is a web-based decision support platform that incorporates all recognized guidelines (ASCO, NCI, NCCN, ASTRO, and others) and supporting literature. An automated precertification code is issued if planned treatment is evidence-based and meets payer language. Variances may be discussed in a peer-to-peer (P2P) with staff oncologists. We analyzed all treatment plans submitted for patients with stage I to IV NSCLC between 1/1/2011 and 5/10/2012 to understand reasons for non-compliance with practice guidelines. There were seven payers with a total of 650,000 covered lives encompassing 43 states. Results: 561 treatment plans were submitted. 241 (43%) received an automatic code, and another 256 (46%) were given preauthorization codes after submission of medical records. 117 treatment plans required a P2P. 26% of cases that required a P2P resulted in a change to evidence based treatment (31 cases or 5% of total cases submitted). 64 (11%) did not meet evidence-based standards and did not receive a code for pre-certification. The most common deviations were: 1. Non-evidence-based therapeutic regimen 59% (38 cases); 2. Use of supportive drugs not consistent with guidelines 23% (15 cases); 3. Non-evidence-based variation in dose and/or schedule of chemotherapy 6% (4 cases). In 7 cases the payer declined payment despite recommendation for coverage. 139 submitted treatment plans were for second line or greater and 88 were for third line or greater. Conclusions: After review for medically justified deviations and peer to peer discussions, decision support for automated pre-certification based on adherence to evidence-based standards reduced non-standard treatment plans from 30 to 11%. A Web-based, point-of-care decision-support that connects payers and providers can reduce unwarranted deviation from evidence-based standards, reducing variability and improving quality. Any such tool should promote compliance with evidence-based cancer care but allow flexibility for medically justified variances.
Predicting hospital readmissions in the oncology population.
Authors: Sarah Thirlwell, Kristine A. Donovan, Mary Turney, C. Edward Emnett, Amber Lamoreaux, Diane G. Portman
Journal: Journal of Clinical Oncology (2016)

177 Background: The 30-day readmission rate is established as an important indicator of quality of care. The LACE index is commonly used in the general medical setting to predict readmission but its ability to predict readmission with sensitivity and specificity in the oncology population has not yet been examined. At our cancer center, palliative care (PC) consultation is associated with an increased risk for readmission but it is not an element in the LACE index. Methods: We sought to characterize the operating characteristics of the LACE Index using receiver operating characteristics analyses to predict unplanned readmissions to our cancer center over a 6-week period beginning March 2016. Data was gathered from chart review to calculate a total LACE score for each unplanned admission. Logistic regression was used to examine the individual components of the LACE index and whether a PC consult improved the performance of the index. Results: A total of 329 patients with unplanned admissions were included. Fifty-nine (17.9%) were readmitted within 30 days of discharge. There was no difference between the median LACE scores of those readmitted compared to those who were not (Md = 10.0; p = .93). Receiver operating characteristic (ROC) curve analyses of LACE scores yielded an area under the curve estimate relative to 30-day readmissions of .45 indicative of poor overall accuracy. ROC analyses also showed that the previously established LACE cutoff score of 10 had sensitivity of .54 and specificity of .57 relative to readmissions. The positive predictive value was .81 and the negative predictive value was .18. In logistic regression analysis, only direct referral center/emergency department visits were an independent predictor of readmission, with a c-statistics of .64 for readmission. The inclusion of a PC consult did not improve the performance of the index. Conclusions: The LACE Index performed poorly in predicting 30-day readmission in the oncology setting; the inclusion of whether a PC consult took place did not improve the index’s utility. Further research is required to create a new tool or enhance existing indices to predict readmission in the oncology population.
Low-grade micropapillary urothelial carcinoma: Does it exist? A SEER analysis of management and outcomes.
Authors: Srinivas Vourganti, Andrew Harbin, Eric A. Singer, Brian Shuch, Adam R. Metwalli, Piyush K. Agarwal
Journal: Journal of Clinical Oncology (2013)

315 Background: Micropapillary Urothelial Bladder Carcinoma (MPBC) is a rare aggressive variant histology of bladder cancer. Management of non-muscle invasive (NMI) MPBC is controversial, as bladder sparing strategies routinely used when managing TCC have resulted in worse outcomes. In order to better understand its behavior, we reviewed all MPBC pts in the SEER database and compared them with TCC pts. Methods: Data was collected from SEER 17. Age, sex, race, grade, stage, treatment, and cause of death were collected. Kaplan-Meier (KM) and Cox proportional hazards (CPH) models were performed. Results: From 2001-2008, 120 pts with MPBC were identified, 0.1% of all bladder cancer. Mean age was 70.3 yrs, 76.7% were male, and 90.8% were Caucasian. No difference in age, sex, or race was detected between MPBC and TCC pts. MPBC presented with more high grade (HG) disease (86.1% vs. 38.7%, p&lt;0.0001) and with higher stage (40.8% NMI vs. 90.4% NMI, p &lt; 0.0001). KM analysis demonstrated that NMI MPBC had significantly worse overall survival (OS) than NMI TCC (not controlling for grade, p&lt;0.0001). Low grade (LG) NMI MPBC pts had worse OS and cancer specific survival (CSS) as compared to LG TCC pts (p=0.0037, p&lt;0.0001 respectively), and did no better than HG NMI MPBC pts. No difference was detected between HG NMI MPBC and HG NMI TCC pts. A CPH model controlling for stage, grade, treatment, age, race, and sex detected no significant survival difference in MPBC vs. TCC (HR 1.04, p=0.7966). For NMI MPBC (n=49), only 4 pts underwent definitive therapy (2 had cystectomy and 2 received EBRT). During the median follow-up period of 31 months, no cancer specific deaths occurred in this group of pts. However, in those not receiving definitive therapy (n=45), 7 cancer specific deaths occurred (15.6%). Conclusions: MPBC is a rare variant with high stage and grade presentation. Controlling for stage and grade, no difference could be detected in survival between MPBC and TCC. However, LG NMI MPBC behaved similarly to both HG MPBC and HG TCC in regards to survival outcomes. We propose that all MPBC (regardless of grade) be managed as HG disease, and that strong consideration for definitive therapy should be given even in the setting of NMI disease.
EML4-ALK in NSCLC: The OSU Experience.
Authors: E. M. Bertino, W. Zhao, M. A. Villalona-Calero, N. F. Abdel Karim, K. Shilo, G. A. Otterson
Journal: Journal of Clinical Oncology (2011)

e18014 Background: EML4-ALK gene translocation is a novel carcinogenic change described in NSCLC in 2007. Prior studies report this translocation in 1-11% of screened patients (pts) and an association with never/light smoking, male sex, absence of EGFR or KRAS mutations, and adenocarcinoma histology. Compared to other NSCLC pts, ALK positive pts have similar responses to platinum chemotherapy, resistance to erlotinib, and no difference in OS. 82 ALK positive NSCLC pts were treated on a phase I trial of crizotinib (ALK inhibitor) with an ORR of 57% with 46 PRs and 1 CR. Phase II/III trials of crizotinib in selected pts are ongoing. We report the experience with EML4-ALK translocation NSCLC pts at the Ohio State University Comprehensive Cancer Center. Methods: ALK translocation screening was performed using FISH on pts with adenocarcinoma or light/never smokers, who were EGFR/KRAS mutation negative. FISH analysis was performed with LSI ALK dual color break-apart probe; a positive result was 10% or more tumor cells splitting ALK-ba signals. IHC using clone 4A5 and Clone SP8 was also used to detect ALK protein expression in 19 pts. Results: Over 12 months, 283 NSCLC pts were screened for EGFR and KRAS. 202 pts were negative for both and were screened for ALK. 30 pts (14.9%) were positive (18 men, 12 women) with a median age of 59. Most pts were never or light smokers (14 never, 5 light). Adenocarcinoma was the most common histology (22 pts); however 5 pts had adenosquamous, 2 had squamous, and 1 had small cell histology. Average survival was 25.4 months; 5 patients survived 5+ years (65-85 months). 24 pts received platinum-based chemotherapy, 11 received erlotinib, and 18 received pemetrexed. Three pts had prolonged response to single agent pemetrexed (11- 36 cycles) and 1 pt had prolonged response to weekly paclitaxel (37 cycles). Conclusions: EML4-ALK is emerging as an important target for a subpopulation of lung cancer pts. Our single institution experience raises several important questions. The results warrant further considerationof screening all adenocarcinoma variants including adenosquamous, and the activity of pemetrexed in this population. The finding of ALK translocation in a small cell pt is intriguing. ALK testing with IHC is an ongoing area of study.
Alteration of candidate circulating microRNA cancer biomarkers by blood sample processing.
Authors: Heather H. Cheng, Hye Son Yi, Muneesh Tewari, Colin C. Pritchard
Journal: Journal of Clinical Oncology (2012)

8 Background: Circulating, cell-free microRNAs (miRNAs) are promising candidates as cancer biomarkers due to their association with cancer, stability in plasma and serum, and easy and sensitive detection using standard PCR-based methods. However, little is known about optimal conditions for collecting and processing blood specimens for miRNA biomarker measurements, or what effects blood processing has on miRNA levels. We systematically evaluated the effect of specimen processing differences on miRNA expression levels, an essential step in developing circulating miRNAs as robust cancer biomarkers. Methods: Matched plasma and serum samples drawn at a single timepoint from 3 healthy individuals were processed with increasing stringency to remove platelets (PLTs) and cell debris by differential centrifugation or 0.22µM filtration to produce: PLT-rich plasma, standard plasma, PLT-poor plasma, filtered plasma, serum, and filtered serum samples. PLTs were quantified by Coulter Counter. MiRNA expression profiling of differently processed samples was performed using Exiqon miRCury LNA qPCR panels with TaqMan qPCR confirmation. Results: Of 369 miRNAs profiled for expression after increasingly stringent sample processing, 150 (41%) showed a difference in cycle threshold (ΔCt) of ≥5 (≥30-fold), and 23 miRNAs showed a ΔCt of ≥10 (≥1,000-fold). For example, expression of miR-142-3p, a proposed biomarker for lung and esophageal cancers, ranged from a Ct of 19.9±2.4 to 30.8±0.8 (1,800-fold difference, p&lt;10 -5 ). A minority of miRNAs (34/369) showed a ΔCt ≤2 (≤4-fold) between differently processed samples, suggesting expression of this subset is relatively unaffected by processing differences. Differences attributable to processing were reproducible, with a majority of miRNAs with ΔCt ≥5 overlapping between the 3 individuals. Conclusions: Blood-sample processing substantially and reproducibly affects about half of circulating miRNAs, while a minority of miRNAs are relatively unaffected. In pursuing circulating miRNAs as cancer biomarkers, focusing efforts on miRNAs less affected by processing and ensuring adherence to standardized processing protocols will minimize confounding effects.
Pretreatment neutrophil/lymphocyte ratio (NLR) prior to steroids as a prognostic factor in metastatic castrate refractory prostate cancer (mCRPC) patients treated with taxanes.
Authors: David Chan, Jennifer Mary McLachlan, Megan Crumbaker, Gavin M. Marx
Journal: Journal of Clinical Oncology (2015)

273 Background: The neutrophil/lymphocyte ratio (NLR) has been demonstrated to be a prognostic factor in multiple malignancies. Prior analyses have demonstrated conflicting results in correlation between NLR and overall survival (OS) in mCRPC. Prednisone and dexamethasone, commonly used in chemotherapy regimens for prostate cancer, have been demonstrated to affect neutrophils and hence NLR. We investigated the correlation between pre-dexamethasone NLR and OS in patients with mCRPC. Methods: We performed a retrospective single-center study of patients with mCRPC who received taxane-based chemotherapy (docetaxel or cabazitaxel) between 9/2005 and 12/2012. Patients were included if blood test results were available between 3 and 28 days prior to commencement of chemotherapy. Baseline demographics and NLR were correlated with OS using a Cox proportional hazards model. Results: 42 patients were included, 9 of whom were still alive, with median age 70 and median follow-up 23.1 months. Median OS was 24.1 months. 36 were commenced on docetaxel-based chemotherapy and 6 on cabazitaxel-based chemotherapy. Considering NLR as a categorical variable, OS was significantly better in patients with NLR&lt;5 (n=28) compared to those with NLR&gt;5 (n=14), with median OS 32mo vs 15.4mo and HR 2.155 (95% CI 1.072-4.332, p=0.0007 by log-rank test). In multivariate analyses, NLR (p=0.008) and age (p=0.048) were independent predictors of overall survival. In sensitivity analyses, when including NLRs within 48 hours of chemotherapy initiation, the correlation between NLR and OS was only marginally significant (p=0.048). Conclusions: HighNLR is an adverse prognostic marker for decreased overall survival in mCRPC patients undergoing taxane-based chemotherapy. Previous conflicting results regarding its value may be related to the effect of steroids on NLR.