bluuebunny/crossref_metadata_2025_split huggingface dataset:
TOPO1 expression in primary and metastatic GI cancers.
Authors: Castro Michael , Feldman Rebecca , Reddy Sandeep K. 
Published: February 2017

643 Background: Irinotecan failed in Stage III colon cancer, but succeeds in Stage IV, to prolong survival. We propose that TOPO1 over-expression is a phenomenon of metastatic disease, and perhaps part of the epithelial-mesenchymal-transition (EMT) associated with metastatic phenotypes. Methods: 5029 colorectal (CRC), 3016 pancreatic, 848 gastric and 309 small bowel adenocarcinoma (SBA) patients were included in the study and tested centrally at a CLIA laboratory (Caris Life Sciences, Phoenix, AZ). A threshold of ≥ 2+ and ≥ 30% (intensity and percent staining) and TOPO1 (1D6) clone was utilized. TOPO1 was examined in primary and metastatic specimens. Two-tailed Fisher’s exact test was performed to test where proportions of positive results were different by subgroup (p ≤ 0.05). Results: See table below. Conclusions: The EMT associated with the transition from primary to invasive metastatic disease appears to include upregulation of TOPO1, in some GI cancers, including CRC, pancreatic and gastric cancer. The paradoxical failure of adjuvant irinotecan in stage III, the epithelial phase of the cancer, may be due to a smaller fraction of patient's whose cancers express this biomarker of response in that setting. A re-examination of irinotecan makes sense for a portion of stage III patients whose cancer expresses high levels of TOPO1 in the primary lesion. The recent superiority with regard to response rate and survival or FOLFOXIRI over FOLFOX alone in the stage IV setting raises renewed interest in whether patients with non-metastatic disease could derive a superior cure rate if suitably selected for FOLFOXIRI with a biomarker approach. At the same time, a large number of patients fail to express TOPO1 in the metastatic setting and perhaps should be spared irinotecan-based approaches including the use of FOLFOXIRI. [Table: see text]
Clinical trial experience with uridine triacetate for 5-fluorouracil toxicity.
Authors: Ma Wen Wee , Saif Wasif M. , El-Rayes Bassel F. , Fakih Marwan , Cartwright Thomas H. , Posey James , von Borstel Reid , Bamat Michael K. 
Published: February 2017

655 Background: Life-threatening or lethal 5-FU toxicity occurs due to infusion pump/reservoir errors and 5-FU dosage miscalculations. Additionally, DPD-deficient patients often experience serious or lethal toxicity. Regardless of DPD status, some patients demonstrate severe, early-onset toxicities (as early as during 5-FU infusion) such as encephalopathy or cardiotoxicity. Uridine triacetate is an orally bioavailable prodrug of uridine, a direct antagonist of 5-FU, that competitively inhibits 5-FU incorporation in normal tissues and can counter 5-FU toxicity, reducing morbidity and mortality due to toxicity. Methods: 135 patients at excess risk of 5-FU toxicity due to overdose or accidental capecitabine ingestion (n = 111); or DPD deficiency and/or who showed rapid onset of severe toxicities (n = 24) have been treated with uridine triacetate under emergency IND or expanded access protocols. Patients were to receive uridine triacetate granules (10g q6h for 20 doses) up to 96h after the termination of 5-FU therapy. Clinical endpoints included survival compared with historical controls, time to resumption of chemotherapy, and safety. Results: A total of 130/135 (96%) patients treated with uridine triacetate recovered fully (within 30 days after receiving uridine triacetate), including rapid reversal of cardiotoxicity (EKG abnormalities, chest pain, etc) and neurotoxicity (altered mental status, ataxia, etc). Of the 111 overdose patients, 24 had a pump malfunction; 49 dose error; 5 had accidental capecitabine ingestion (2 adults/3 peds); 33 unknown. No patient who received uridine triacetate within 96 h after stopping 5-FU died. Comparatively, 38 of the 47 historical controls (81%) with 5-FU overexposure died. Of the 106 overdose patients with a diagnosis of cancer, 40 (37.7%) resumed chemotherapy within 30 days (median 20.0 days post-5-FU), highly indicative of rapid recovery from toxicity. Overall compliance was 92.5% (mean 18.3/20 doses). Mild, infrequent adverse events (diarrhea/nausea/vomiting) were attributed to uridine triacetate. Conclusions: In this study, uridine triacetate was a safe and effective life-saving antidote for 5-FU overexposure, and facilitated rapid resumption of chemotherapy. Clinical trial information: NCT01432301.
Oncologic outcome of lateral pelvic lymph node metastasis in locally advanced rectal cancer.
Authors: Kim HyungJin , Kim Gun , Yoo Ri Na , Kye Bong-Hyeon , Cho Hyeon-Min 
Published: February 2017

661 Background: Lateral pelvic lymph node (LPLN) metastasis is a major cause of recurrence in patients with rectal cancer. This study investigates the oncologic outcome based on LPLN status after neoadjuvant chemoradiotherapy (nCRT). Methods: Between January 2009 and February 2013, 141 patients with rectal cancer received nCRT followed by curative radical surgery in our hospital. 16 patients were identified with LPLN before nCRT. These patients were categorized to two groups according to nCRT response evidenced by post-nCRT imaging studies with 5mm criteria. Group 1 included 7 patients who showed disappearance of LPLN after nCRT. Group 2 consisted of the patients identified with LPLN after nCRT. Results: The mean follow-up period was 35.6 ± 12.8 months. The mean overall survival (OS) period and 3-year OS rate for the patient with LPLN before nCRT was 56.0 ± 2.6 months and 93.3%, respectively. The mean relapse free survival period and 3-year RFS rate for the patient with LPLN before nCRT was 32.6 ± 5.7 months and 47.1%, respectively. The risk factors associated with RFS were ypN stage (P = 0.031), tumor location (P = 0.002), and postoperative CEA level (P = 0.022). Comparing RFS between Group 1 and 2, Group 1 tended to demonstrate longer RFS (P = 0.058). Analyzing oncologic outcome of two groups compared to the cohort population, group 1 showed similar oncologic outcome with ypTNM stage II. Group 2 demonstrated a tendency of worse oncologic outcome than ypTNM stage III (Group 1 vs. ypII P = 0.761 and Group 2 vs. ypIII P = 0.135). Conclusions: Preoperative LPLN status after nCRT seems to influence oncologic outcome in rectal cancer patient. If patients with LPLN metastasis before nCRT exhibit persistent LPLN metastasis after nCRT, they may require additional treatment.
Resection of non-regional lymph node metastasis in patients with colorectal cancer.
Authors: Bailey Christina Edwards , Idrees Kamran , Parikh Alexander A. 
Published: February 2017

664 Background: Approximately 20% of patients with colorectal cancer (CRC) present with metastatic disease-most commonly to the liver or lungs. Successful resection of these metastatic foci leads to significant long-term survival. Less commonly, patients present with isolated metastasis to non-regional lymph nodes (NRLN) and little is known regarding the role of resection in these patients. The primary aim of this study is to evaluate the outcomes of patients with CRC who undergo resection of NRLN metastasis. Methods: A retrospective cohort study of patients diagnosed with CRC and NRLN metastasis was performed using the Surveillance, Epidemiology, and End Results database (2004-2012). Demographic and clinical factors were compared for patients who underwent resection of NRLN metastasis and those who had not. Kaplan-Meier and log-rank analysis was used for survival analysis. Logistic regression analysis was used to assess factors associated with resection of NRLN metastasis. Results: A total of 22,848 patients presented with metastatic CRC and underwent primary tumor resection. Of these, 786 (3.4%) presented with isolated NRLN metastasis and 78 (9.9%) underwent NRLN resection. Patients who underwent resection were more likely to be male, have rectal cancers, and poorly or undifferentiated grade tumors. Median overall survival (OS) was significantly improved for patients who underwent resection compared to those who did not (36 vs. 28 months, p = 0.036). In patients with colon cancer (N = 602), median OS was 33 vs. 21 months (p = 0.042) for those who underwent resection compared to those who did not, whereas in patients with rectal cancer (N = 184), the median OS was 45 vs. 38 months (p = 0.977), respectively. In multivariate analysis, rectal cancer (OR 1.84, 95% CI 1.08 to 3.13) and poorly or undifferentiated grade tumors (OR 1.64, 95% CI 1.01 to 2.66) were associated with increased resection of NRLN. Conclusions: Resection of NRLN metastasis in patients with CRC is associated with an overall survival benefit, particularly among patients with colon cancer. Further studies are needed to identify which specific patient subgroups would best benefit from this resection strategy.
Characterization of a novel regulator of AKT/mTOR signaling in gastric cancer.
Authors: Singh Shikha Satendra 
Published: February 2017

68 Background: Gastric cancer (GC) is a leading cause of cancer-related death with poor prognosis and “one-size fits all approach”. Dysregulation of PI3K/Akt/mTOR pathway is a common event in GC with PIK3CAmutations reported to correlate with poor prognosis. With prognosis far from satisfactory, we aimed to identify novel surrogate biomarkers. We hypothesize the role of DP103, a DEAD-box RNA helicase, as a novel surrogate biomarker for GC by regulating the PI3K/Akt/mTOR pathway. Additionally, we shed light on high DP103 GC cells responding to Akt/mTOR dual inhibitor treatment, indicating its potential role as a surrogate biomarker for GC treatment. Methods: Tissue microarray data from GC cohorts were used in correlation analysis between DP103 and PIK3CA expression. Effect of DP103 knockdown was assessed on functions downstream of PI3K/Akt/mTOR pathway including apoptosis, autophagy and cell invasion. Next, DP103 depletion studies were done and PI3K/Akt/mTOR pathway proteins were assessed. Further, immunoprecipitation studies assessed for DP103 interacting partners from PI3K/Akt/mTOR pathway in GC. Results: Herein, we provide clinical evidence of DP103 upregulation in GC patients’ tissues compared to normal gastric tissues. Additionally, we showed a positive correlation between DP103 and PIK3CA expression in GC patients’. DP103 knockdown resulted in decrease in cell invasion and an increase in apoptosis and autophagy. Further, decrease in phosphorylation of PI3K/Akt/mTOR pathway proteins was observed with DP103 depletion. Mechanistically, we discovered a novel physical interaction between DP103 and PI3K in GC. Conclusions: Here we summarized, current understanding of DP103 regulating PI3K/Akt/mTOR pathway in GC and discuss potential use as a new surrogate biomarker for better clinical application.
Quality of life (QoL) and therapy management in metastatic colorectal cancer (mCRC) patients treated with FOLFIRI and aflibercept in Germany, Switzerland, and Austria (GSA): Interim results of the noninterventional QoLiTrap-study.
Authors: Hofheinz Ralf , Thaler Josef , Von Moos Roger 
Published: February 2017

681 Background: QoLiTrap (AIO-LQ-0113) is a non-interventional study to assess the QoL and clinical outcomes of mCRC patients treated with Aflibercept and Folfiri in Germany, Austria and Switzerland. This interim analysis shows the first results of the study. Methods: QoL is assessed by EORTC-QLQ C30 questionnaires that are filled in by the patients at baseline and before every therapy cycle. Clinical data (overall survival, progression-free survival (PFS), response to treatment, therapeutic sequences) are reported by participating physicians. Results: The first 277 patients who completed at least baseline and 2 additional EORTC questionnaires were included in this analysis. Median cycle number at the time of analysis was 6 (including patients still on therapy). Therapeutic sequences comprised treatment with Bevacizumab (B) (48%), anti-EGFR (13%), both (13%) or no biological (14%) before Aflibercept (A) (n.d.: 12%). Median PFS was similar in B (PFS: 6.6 months, CI[5.4;8.9]) and anti-EGFR (PFS: 7 months, CI[4.7,12.1]) pre-treated patients. Complete or partial remission was observed in 22%, Stable Disease in 52% and Progressive Disease in 26% of all patients with evaluated response (n=144). Main grade 3-5 adverse events were hypertension (15.9%) and diarrhea (6%). Only minor changes in EORTC global health score were observed from baseline (57.50; sd: 20.39; n=277) to cycle 6 (52.27; sd: 20.6; n=114). Conclusions: In clinical practice A is used in various therapeutic sequences in GSA. This interim analysis provides encouraging results with a tumor control rate of 74% in patients with response documentation and similar median PFS values for B and anti-EGFR pretreated patients. The decline in global health status was moderate. No unexpected safety signals were observed. This study is supported by Sanofi. Clinical trial information: AIO-LQ-0113.
Bevacizumab effectiveness and primary tumor location in metastatic colorectal cancer patients.
Authors: He Wen-zhuo , Yang Qiong , Jiang Chang , Liao Fang-xin , Liu Shou-sheng , Xia Liang-ping 
Published: February 2017

683 Background: There is currently no consensus about whether bevacizumab effectiveness is associated with the primary tumor location of metastatic colorectal cancer (mCRC). The aim of this study was to assess whether the primary tumor location was a predictor for bevacizumab treatment. Methods: From 2004 to 2013, 740 patients with mCRC treated with oxaliplatin / 5-FU / leucovorin (mFOLFOX6) or irinotecan / 5-FU / leucovorin (FOLFIRI) (CT group) and 244 patients treated with bevacizumab plus mFOLFOX6 or FOLFIRI (CT + B group) as first-line setting were included from Sun yat-sen university cancer center. Right-side colon cancers included those occurring in the cecum, ascending colon or transverse colon. Left-side colon cancers included those from descending or sigmoid colon. The primary outcome was overall survival (OS). Kaplan-Meier curves with log-rank tests were used to detect difference. All statistical tests were two sided. Results: 222 right-side colon, 259 left-side colon and 259 rectal cancer patients were included in CT group while 78 right-side colon, 86 left-side colon and 80 rectal cancer patients were included in CT + B group. Patients in CT + B group had similar OS compare with CT group only when the primary tumor located at right-side colon (median OS was 19.6 months for CT + B group versus 19.5 months for CT group, P = 0.269). For left-side colon cancer, significantly longer OS were observed in CT + B than CT group (22.3 months versus 21.9 months, P = 0.014). For rectal cancer patients, those in CT + B group also had longer OS than CT group (25.9 months versus 21.1 months, P = 0.005). Conclusions: Our data suggested that patients with right-side colon cancer could not get survival benefit from the addition of bevacizumab to first-line chemotherapy. Further data from randomized trials are needed to test our hypothesis. [Table: see text]
Characterization of KRAS, NRAS, and BRAF testing and timing among mCRC patients treated at community cancer centers in the United States.
Authors: Lowe Kimberly , Kelsh Michael Anthony , McCarl Kevin , Bohac Gerry C. 
Published: February 2017

695 Background: The requirement to establish RAS status prior to administration of an EGFR inhibitor has increased the need to understand which patients are tested for RAS and the length of time it takes for the treating oncologist to receive the RAS test result. Our objective was to evaluate factors that may influence RAS testing among patients with metastatic colorectal cancer (mCRC) and the turn-around time for RAS testing among patients who are treated at community cancer centers in the United States (U.S.). Methods: The sample includes 1550 patients in the Oncology Services Comprehensive Electronic Records (OSCER) database who were diagnosed with mCRC between 1/1/2011 and 8/31/2015. Patient demographics and clinical characteristics were evaluated at the time of mCRC diagnosis. The median number of days and interquartile range (IQR) between the following dates was summarized: diagnosis for mCRC, tissue collection for biomarker testing, tissue was received by the lab for biomarker testing, and biomarker results returned to the oncologist. Results: The frequency of RAS testing was as follows: KRAS (n = 964; 62%), NRAS (n = 116; 7%), BRAF (n = 231; 15%), all three simultaneously (n = 94, 6%). There were significant differences in KRAS testing by age and type of insurance, with young (p < 0.001) and commercially-insured (p = 0.01) patients more likely to receive testing. The median number of days and IQR between specimen collection and diagnosis of mCRC was as follows: KRAS (0; 0 to 443), NRAS (0; -18.5 to 362), and BRAF (-3; -474 to 0). The median number of calendar days between the date the specimen was collected and the date it was received by the lab was as follows: KRAS (19; 1 to 303), NRAS (34.5, 8 to 518), and BRAF (29; 2 to 428). The median number of days between the date the specimen was received by the lab and the date the result was returned to the oncologist was as follows: KRAS (7; 5 to 13), NRAS (10; 7 to 15), and BRAF (8; 6 to 14). Conclusions: Many patients had a specimen collected for biomarker testing at the time of mCRC diagnosis and the results were generally returned to the treating oncologist within one week of it arriving at the lab.
Evaluation of hypersensitivity reactions to oxaliplatin in gastrointestinal malignancies.
Authors: Markey Kelly , Gatewood Tyra , Valone Tiffany , Strosberg Jonathan R. 
Published: February 2017

709 Background: Oxaliplatin is an important component of therapy for multiple gastrointestinal cancers. The incidence of hypersensitivity reaction (HSR) to oxaliplatin is approximately 10%, and about 3% are serious in nature (Grade 3 or 4). Data on management of hypersensitivity reactions is limited to small case series, with scarce information on the success rates of rechallenging patients who have previously reacted. Methods: We conducted a retrospective review of patients who had a documented hypersensitivity (HSR) to oxaliplatin utilizing our internal adverse event reporting system from January 1, 2007 until December 31, 2012. Results: 44 patients met inclusion criteria for this study. The majority had a grade 1 or 2 reaction (n = 36 or 81.82%). Seven patients had a grade 3 reaction and one patient experienced a grade 4 reaction. 29 patients were rechallenged with oxaliplatin during subsequent courses. Infusion durations were extended in 79% of cases, and additional premedications were administered in 90%. Two patients were treated with a desensitization protocol, which consisted of serial dilutions of oxaliplatin (given over approximately 8 hours) with a two-stage premedication regimen. With these measures, seventeen of the twenty-nine patients (66%) were able to receive 3 or more additional infusions, thirteen (45%) received 5 or more additional infusions, and 4 (14%) we able to receive 10 or more additional infusions. Conclusions: Our review of hypersensitivity reactions to oxaliplatin demonstrates that the majority of patients experience mild (Grade 1 or 2) reactions and are able to be successfully rechallenged in subsequent courses with modifications in the infusion rate and premedications. The use of these treatment strategies may prevent premature discontinuation of an important backbone drug for the treatment of gastrointestinal malignancies.
Dihydro pyrimidine dehydrogenase deficiency in patients treated with capecitabine-based regimens: A retrospective tertiary care centre experience.
Authors: Sahu Arvind , Ostwal Vikas S. , Ramaswamy Anant 
Published: February 2017

712 Background: Capecitabine is an integral part of treatment of gastrointestinal cancers. Dihydropyrimidine dehydrogenase (DPD) enzyme is rate limiting in the metabolism of capecitabine, deficiency of which leads to myelsuppression, mucositis, diarrhea, hand foot syndrome (HFS) and rarely, death. Data regarding the toxicity of capecitabine in patients with DPD deficiency in the Indian context is scarce. Methods: 506 patients were treated with capecitabine containing regimens with a dose range of 1250 mg/m2/day to 2000 mg/m2/day during the period from June 2013 to May 2015 in the Gastrointestinal Medical Oncology Unit of our institution. Patients with Grade 3/4 toxicities requiring in-patient care (life threatening complications) were planned for DPD activity testing by Peripheral Blood PCR sequencing. Results: 27 patients developed Gr 3/4 toxicities during cycle 1 of capecitabine. It included mucositis in 22 (81.5 %), diarrhea in 25 (92.6%), HFS in 10 (37%) and myelosuppression in 4 (14.8%). 19 were found to be DPD deficient with 5 patients negative for DPD mutation. 3 patients did not do the DPD analysis as advised. Homozygous mutations were seen in 9 (33.3%) and heterozygous mutations in 10 (27%) of patients. More than one mutation was seen in 10 patients (37%). The relative frequencies of mutation were Exon 14 (44.4%), Exon 2 (25.9%), Exon 13 (25.9%), Exon 6 (11.1%) and Exon 18 (7.4 %). Post Cycle 1 of capecitabine, the drug was stopped in 5 patients (18.5%), regimen changed in 2 (7.4%) and dose reduction by 50% of the drug was done in the remaining patients. Despite dose reduction and change in therapy during Cycle 2, patients still had Grade 3/4 toxicities including mucositis in 7(25.9%), diarrhoea in 10 (37%), HFS in 7 (25.9 %) and myelosuppression in 6 (22%) of patients. Conclusions: Capecitabine can also lead to severe toxicities in DPD-deficient patients. Dose reduction of capecitabine in DPD deficient patients may not completely ameliorate the future risk of life – threatening complications. Screening for DPD deficiency prior to administration of capecitabine in toxicity prone nutritionally deficient Indian patients should be further evaluated based on this data.
Pathologic complete response rates after neoadjuvant treatment in rectal cancer: An analysis of the NCDB.
Authors: Lorimer Patrick D. , Kirks Russell C. , Boselli Danielle , Crimaldi Anthony Joseph , Hill Joshua S. , Salo Jonathan C. 
Published: February 2017

713 Background: Pathologic complete response (pCR) of rectal cancer following neoadjuvant therapy is associated with decreased local recurrence and increased overall survival. The present study utilizes a large national dataset to identify predictors of pCR in rectal cancer. Methods: The NCDB was queried for patients with non-metastatic rectal cancer (2004-2011) who underwent neoadjuvant therapy (regional radiation dose 4500 cGy, boost dose 540 cGy) followed by surgical resection. Generalized linear mixed models were used to analyze the probability of pCR by hospital volume with adjustments for demographic, socioeconomic, staging, and tumor characteristics. Hospitals were separated into groups based on the number of resections performed per year <2, 2-5, and 5+. To account for clustering of cases at individual hospitals, a random effect was used at the hospital level and covariates were included as fixed effects. Results: 7,859 patients met inclusion criteria from 951 participating hospitals. Generalized linear mixed models demonstrated that the odds of achieving pCR was independently associated with more recent diagnosis, female gender, private insurance, smaller tumor size, lower grade, lower clinical T-classification, increasing interval between the end of radiation and surgery, and treatment at higher volume institutions (Table). Conclusions: The incidence of pCR was associated with favorable tumor factors (size, grade, T classification), demographics (insurance status) as well as treatment factors (time between radiation and surgery and institutional volume). With the data available, it is not clear what is driving the higher rates of pCR at high volume institutions. Research specifically targeted at understanding processes which are associated with pCR in high volume institutions is needed so that similar results can be achieved across the spectrum of facilities caring for patients in this population. [Table: see text]