bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of overall and disease-specific survivals following adjuvant radiotherapy with neo-adjuvant radiotherapy for rectal cancer
Authors: Ahmed I. , Howard M. , Rehman Z. , Ofar F. , Marley P. , O’Doherty E. , Martin M. J. 
Published: August 2020

e15008 Background: Preoperative radiotherapy is the preferred treatment for stage II-III rectal cancer. This arose following publication of the results of the German Rectal Cancer Study Group. It demonstrated a statistically significantly reduced local recurrence rate, and reduced toxicity for preoperative treatment compared with postoperative treatment. However, it failed to demonstrate improved overall survival. This study used the Surveillance, Epidemiology, and End Results (SEER) Program to compare overall and disease specific survival in rectal cancer patients treated with preoperative versus those receiving postoperative radiotherapy. Methods: 14,553 patients were identified with stage II-III rectal cancer, treated with either preoperative (5,136 patients) or postoperative radiotherapy (9,417 patients). Kaplan-Meier survival analyses and Cox multivariate analyses were used to compare 5 and 10 year overall and disease specific survival rates. Cause of death (COD) recorded as ‘Rectum and Rectosigmoid Junction’ was used to calculate rectal-specific survival. CODs recorded as ‘Colon excluding Rectum’ and ‘Rectum and Rectosigmoid Junction’ were used for colorectal-specific survival. Results: Kaplan-Meier analysis failed to demonstrate any statistical significant differences in survival figures. Cox multivariate analysis returned hazard ratios for overall survival of 1.207 (95% CI 1.122 - 1.298) and 1.180 (95% CI 1.103 - 1.263) at 5 and 10 years respectively for preoperative radiotherapy when compared with postoperative radiotherapy. For rectal-specific survival, 5 and 10 year hazard ratios of 1.381 (95% CI 1.239 - 1.539) and 1.342 (95% CI 1.210 - 1.489) respectively were obtained. Colorectal-specific survival returned 5 and 10 year hazard ratios of 1.222 (95% CI 1.124 - 1.329) and 1.193 (95% CI 1.101–1.292) respectively. Conclusions: Preoperative radiotherapy is the preferred treatment for stages II-III rectal cancer. This is because of its decreased risk of local recurrence and more optimal toxicity profile. However, this study suggests that preoperative radiotherapy is associated with poorer survival when compared with postoperative radiotherapy in the treatment of stage II-III rectal cancer. No significant financial relationships to disclose.
Evaluation of the potential association of preoperative chemotherapy with steatohepatitis in surgical patients with hepatic colorectal metastases
Authors: Artinyan A. , Castillo E. , Foster B. , Wagman L. 
Published: August 2020

e15009 Background: The treatment of hepatic colorectal cancer metastases is increasingly multi-modal. Preoperative chemotherapy may be associated with steatohepatitis, which may increase morbidity in patients undergoing resection. Our objective was to determine if preoperative chemotherapy is associated with steatohepatitis and to determine which agents confer the greatest risk. Materials and Methods: 149 patients who had undergone liver resection or biopsy for hepatic colorectal cancer metastases were identified from an institutional database. Surgical specimens were assessed for percent steatosis and the presence of steatohepatitis as defined by the Kleiner score. The medical record was reviewed for details of preoperative chemotherapy and post-operative course. The association of preoperative chemotherapy with steatosis and steatohepatitis was assessed. Preoperative non-contrast CT scans were reviewed for evidence of steatosis as determined by the radiographic liver/spleen (L/S) ratio. The association of the L/S ratio with the presence of steatohepatitis was determined. Post-operative outcome was compared in patients with and without steatohepatitis. Results: The mean age of the population was 60.8 ±11.6 years, 56% of patients were male, and 37% of patients received preoperative chemotherapy. Steatohepatitis was identified in 45.7% of specimens. There was no statistically significant difference in the rate of steatohepatitis (59% vs. 50%, p=0.49) or percent steatosis (37% vs. 32%, p=0.29) with or without preoperative chemotherapy. No individual agent predicted a greater risk of steatohepatitis or a greater degree of steatosis. There was no significant difference in the L/S ratio in patients with or without steatohepatitis (p=NS). In patients undergoing liver resection, there was no difference in total ICU stay, blood loss, total surgery time or total length of stay between the steatohepatitis and non-steatohepatitis groups. Conclusions: Although steatohepatitis remains a potential complication of systemic chemotherapy in surgical patients with hepatic colorectal metastases, the risk and impact of chemotherapy associated steatohepatitis have not been significant in our patient population. No significant financial relationships to disclose.
Efficacy and safety of cetuximab, oxaliplatin, and capecitabine as first-line therapy for metastatic colorectal cancer (mCRC): Results of a phase II study
Authors: Barroso S. A. , Sanches E. , Ferreira M. , Passos M. , Sá A. , Nabiço R. , Sotto-Mayor C. , Espírito Santo J. , San- Bento R. 
Published: August 2020

e15013 Background: To date, few studies have investigated the use of cetuximab in combination with oxaliplatin and capecitabine in the first-line treatment of mCRC. We therefore conducted an uncontrolled, open-label, multicenter study to evaluate the efficacy and safety of this combination in this setting. Methods: Patients (pts) received intravenous (iv) oxaliplatin 130 mg/m2 (3h day 1) plus capecitabine 1,000 mg/m2 twice daily (days 1–14) every 3 weeks (XELOX) and cetuximab 400 mg/m2 iv week 1 then 250 mg/m2 weekly over 8 cycles. Treatment was continued until disease progression (PD), unacceptable toxicity or completion of therapy. Pts were followed until death. The primary endpoint was overall response rate (ORR). A sample size of 45 pts was necessary to obtain a 95% confidence interval (CI) for ORR with a maximum width of 15% assuming an ORR of 50–80%. Results: From Sept 2005-Jan 2007, 49 pts were enrolled (ITT population): 67% male, mean age 60 (range: 44–75) years, 56.3% ECOG PS 0. Of 42 pts evaluable for ORR, 4 (9.5%) achieved a complete response, 31 (73.8%) a partial response, 6 (14.3%) had stable disease and 1 (2.4%) had PD. The ORR was 83.3% (95% CI: 72.0–94.6%). Median time to progression was 9 months (95% CI: 7.1–10.9 months). Of the 49 pts evaluable for safety, 27 (55.1%) had at least one grade 3/4 toxicity, 42 (85.7%) had acne-like rash (8 pts [16.3%] grade 3). Most common grade 3/4 toxicities included diarrhea (n=9;18.4%) and changes in potassium (n=6;12.2%). 24 (3.4%) AEs led to dose reductions (12 unrelated, 10 unlikely and 2 definitely related to cetuximab), 56 (7.8%) led to a dose delay (12 unrelated, 28 unlikely, 8 possibly, 6 probably, 2 definitely related to cetuximab) and 2 (0.3%) led to infusion rate reduction (not treatment related). 27 (55.1%) pts discontinued therapy: 10 (20.4%) due to AEs, 7 (14.3%) PD, 10 (20.4%) other reasons. 33 (67.3%) pts died: 30 (61.2%) due to PD, 2 (4.1%) intercurrent event/disease, 1 (2.0%) acute pancreatitis. The results according with the HGFR evaluation by IHC will be presented. Conclusions: In this first-line mCRC study, 83.3% of pts treated with cetuximab, oxaliplatin and capecitabine achieved an overall response. This combination appears to be a highly active and well-tolerated regimen. No significant financial relationships to disclose.
Hepatic resection of initially unresectable liver metastases from colorectal cancer after hepatic arterial infusion of oxaliplatin and systemic 5-fluorouracil and leucovorin
Authors: Goere D. , Dsehais I. , de Baere T. , Boige V. , Malka D. , Bonnet S. , Dromain C. , Elias D. , Ducreux M. 
Published: August 2020

e15015 Background: About 80% of patients (pts) presenting colorectal liver metastases (CRLM) are initially unresectable. A subgroup will become eligible for surgery after chemotherapy administration. Efficacy of hepatic arterial infusion (HAI) of oxaliplatin with systemic 5-Fluorouracil and leucovorin (LV5FU2) in with unresectable CRLM was previously demonstrated. This study was performed to evaluate the resection rate of pts with initially unresectable CRLM after oxaliplatin HAI and systemic LV5FU2. Methods: Patients treated in our hospital with oxaliplatin HAI and systemic LV5FU2 for unresectable CRLM from May 1999 to May 2007 were analyzed. Inclusion criteria were : unresectable CRLM, no extensive extrahepatic disease, HAI performed in our hospital, minimal follow up of 24 months. Eighty-seven pts were selected from a prospective database Results: Hepatic arterial infusion was delivered after previous systemic chemotherapy failure in 69 pts (80%). Main criterion for unresectability was massive liver involvement (80%). CRLM were synchronous and bilateral in respectively 85% and 90% of pts. The median number of oxaliplatin HAI cycles was 8 (0- 25). Thirty-one pts experienced technical problems with the arterial catheter, which was responsible for HAI withdrawal in seven. A total of 23 pts (26.4%) were operated, leading to resection and/or radiofrequency ablation of CRLM in 21 pts. No post-operative mortality was observed and the morbidity rate was 30%. The 3-year overall survival for patients operated was 72.5% versus 12% for non operated pts (p<0.0001). After a median follow-up of 75 months [24–118], intra-hepatic recurrence occurred in 10 pts. Conclusions: Hepatic artery infusion of oxaliplatin and systemic LV5FU2 increase the resectability rate in pts with advance CRLM even after previous systemic chemotherapy failure. Future studies combining oxaliplatin HAI and recent IV chemotherapy are needing to achieve an increase disease-free survival. No significant financial relationships to disclose.
KRAS mutation profile in colorectal cancer patients in Brazil: A cohort of 989 individuals
Authors: Zalis M. G. , Vieira F. M. , Zalcberg-Renault I. , Bonamino M. H. , Ferreira C. G. , Oliveira S. 
Published: August 2020

e15017 Background: KRAS mutation is common event in colorectal cancer occurring in around 40% of the patients. It is well- known that patients harboring the KRAS mutation do not derive benefit from cetuximab. However data available KRAS mutation profile is limited to Caucasian and Asian individuals and there is a lack of data in the population from Latin America. Brazilian population has a heterogeneous genetic background and this may have pharmacogenetic implications (Suarez-Kurtz, 2006). Methods: Between July and November 2008, we analyzed 989 consecutive patient samples sent to our laboratory for KRAS genotyping as a screening for cetuximab use. DNA was extracted from paraffin-embedded tissue, exons 1 were amplified by PCR and submitted to automatic sequencing. Codons 12 and 13 were analyzed. Results: The median age was 59 years and 53% of the patients were male and 47% female. The percentage of wild-type and mutated KRAS was 62 and 38%, respectively. Among the 375 mutated cases, 87% were in codon 12 versus 13% in codon 13. Mutation Gly12Asp was the most common being detected in 39% of the mutated cases. Due to the sample size a comparison among patients from different regions of Brazil was possible. However, no significant difference was observed in relation to the type or percentage of patients harboring the KRAS mutation. Interestingly, a significant difference in the percentage of mutated KRAS patients was observed between male and female (41 versus 35%, p= 0.05). Conclusions: The profile of KRAS mutation in the Brazilian population is similar to that reported for Caucasian and Asian populations. This is one of the largest cohorts of KRAS genotyping in colorectal cancer patients ever reported. To the best of our knowledge our data is the first to put forward the issue of a potential difference in the mutation rate according to gender. The observed higher incidence of KRAS-mutation in male than female deserves further investigation. No significant financial relationships to disclose.
A phase II study of capecitabine, irinotecan, and bevacizumab (XELIRI-A) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC)
Authors: Chen E. X. , Welch S. , Krzyzanowska M. , MacKay H. , Knox J. , Feld R. , Petronis J. , Blatter C. , Wang L. , Moore M. J. 
Published: August 2020

e15019 Background: Capecitabine (XEL), irinotecan (IRI) and bevacizumab (A) are all active agents in the treatment of mCRC. However, combining these agents has proven to be problematic due to overlapping toxicities. Optimal dosing strategies for this combination remain unclear. This study prospectively evaluated toxicity and efficacy of the XELIRI-A combination with dose modification. Methods: This was a single-institution, open-label phase II clinical trial. Eligible pts include those with previously untreated metastatic CRC, adequate organ function and ECOG performance status 0–2. IRI (200 mg / m2) and A (7.5 mg / kg) were given on day 1, and XEL (1000 mg / m2 p.o. BID) was given on days 1–14 of every 21-day cycle. The dose of XEL was reduced to 750 mg / m2 BID for pts age ≥ 65. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, time to progression, overall survival and toxicity. Results: 50 pts (ECOG PS 0:1 = 27:23; male:female= 34:16) were enrolled over 19 months. Median age was 58 (range: 35–72). 7 pts had prior adjuvant chemotherapy. A total of 360 cycles were administered, with a median of 6 (range: 1–16). To date, 20 confirmed PR, 3 unconfirmed PR, and 20 SD by RECIST criteria were observed (ORR= 40%, disease control rate 86%). The median PFS was 11.1 months (95% CI: 9.2 months - not reached), and the 1-year progression-free rate was 49%. 7 pts have gone on to have metastatectomy. The most frequently reported related grade 3 or 4 adverse events were neutropenia (6), hand-foot syndrome (6), and diarrhea (5). One death was seen on study, and 1 pt had treatment-emergent grade 3 hypertension. Conclusions: XELIRI-A at doses studied appears to be well- tolerated. Results are favorable compared to those from previous studies. XELIRI-A at reduced doses is safe and effective as first-line treatment for mCRC. [Table: see text]
New CT treatment response score for predicting survival in patients with metastatic colorectal carcinoma: A pilot study
Authors: Fora A. , Fakih M. , Scheib S. , Hanna T. , Raczyk C. , Hutson A. , Gottlieb R. 
Published: August 2020

e15026 Background: To develop a methodology that results in an optimized CT Treatment Response Score (CTRS) for prediction of survival using quantified changing lesion features. Methods: We evaluated the overall survival (OS) predictive value of a new methodology to assess CT scan-based responses versus RECIST guidelines in a homogenous metastatic colorectal cancer population. All patients (pts) with MCRC treated with cetuximab and irinotecan (cet & irino) between 2005 and 2008 in our Center after failure of prior oxaliplatin and fluoropyrimidine were included in this analysis. Other inclusion criteria included: at least 6 weeks of cet & irino and serial CT scans on cet & irino including baseline performed in our Center. 38 pts (22 men, 16 women, mean age = 62, range = 28–91 ) were included. CT scans were interpreted by 2 trained physician assistants initially independently with differences resolved by consensus. Parameters evaluated included change in tumor size using standard RECIST and visual based (VB) assessment, VB assessment of enhancement, and interval development of new lesions.VB scoring used Likert-type scales to code reader confidence as to change in an imaging characteristic (size, enhancement) and the presence/absence of a characteristic (new lesions). The most predictive parameters for OS were used to generate the CTRS with an overall range of -2 (definite tumor decrease) to +2 (definite tumor increase). Results: The optimal CTRS resulted from combining VB assessment of change in size of existing lesions and new lesion development. This resulted in prediction of survival with a Cox Hazard Ratio of 1.639 (p = 0.0008). Using a threshold value of 0 to generate good (scores ≤ 0) and poor (scores > 0) response groups resulted in probabilities of survival at 8 months (ms) of 75% (16 pts) and 32% (22 pts), median survival times of 13.3 ms (95% CI = 10.94 ms, 17.81 ms) and 5.06 ms (95% CI = 3.84 ms, 8.77 ms), respectively. CTRS was easier to perform and appeared to be more predictive of OS outcome than RECIST. Conclusions: The methodology results in a single CTRS with transparent for others to test and understandable in terms of predicting survival for pts and caretakers. This methodology needs validation in a larger patient data set and across various tumors and lines of treatment. No significant financial relationships to disclose.
Histological hepatic changes in patients undergoing liver resection for colorectal metastasis: A retrospective cohort study
Authors: Allegro S. M. , Rowsell C. , Law C. , Ko Y. 
Published: August 2020

e15034 Background: Patients with colorectal cancer (CRC) with liver metastases (LM) have a poor prognosis and the only potential cure is surgical resection. Neoadjuvant chemotherapy (NC) in this setting can increase the success of resection and can potentially improve survival. However, chemotherapy can be associated with hepatic toxicity which may influence postoperative morbidity. Methods: Consecutive patients who underwent hepatectomy for CRC with LM from 1999–2005 at a single institution (OCC) were retrospectively reviewed. Data on baseline characteristics, chemotherapy regimens, operative outcomes and pathology were collected. Results: 107 patients underwent hepatectomy for CRC LM. Median age was 62 years (range 24–84). 53 (53%) patients had positive lymph nodes (primary tumor) and 51 (48%) had with synchronous LM. 46 (43%) patients had a solitary LM and 90 (84%) underwent major resection (>4 segments). 63 (59%) patients received NC. 96% received a 5FU-based regimen. The majority of patients (55%) received 6–12 cycles of NC. The median time between NC and surgery was 6.5 weeks. Patients receiving NC before surgery were younger (mean 59.5 versus 65.5 years, p=0.0056). NC was more often administered in patients with positive primary lymph node status (72%,versus 40%, p=0.0014) and with multiple (versus solitary) LM (75% versus 37%, p=0.0001). Patients more often received NC with synchronous (versus metachronous) LM (90% versus 30%, p<0.0001). Operative and postoperative courses were not significantly different in patients with NC, including hemodynamic instability, postoperative complications, transfusion requirements (red blood cell and platelets) and mortality. Pathological analysis of the resected liver segments reviewed mild (<30%) steatosis in 58% of patients. Most specimens did not reveal lobular inflammation (56%) or ballooning (87%). Sinusoidal injury was most often graded as 1 (33%). There were no significant increased rates of liver toxicity in patients with NC. Conclusions: This study demonstrates that neoadjuvant chemotherapy, although associated with increased steatosis is not associated with increased perioperative morbidity and mortality with liver resection. No significant financial relationships to disclose.
Use of genotype subset selections of multi-UGT1As polymorphisms to predict severe neutropenia and tumor responses of metastatic CRC patients received FOLFIRI regimen
Authors: Hazama S. , Okuyama Y. , Kato T. , Okayama N. , Hinoda Y. , Sakamoto J. , Mishima H. , Fujita Y. , Hamamoto Y. , Oka M. 
Published: August 2020

e15038 Introduction: The pharmacogenetics of irinotecan indicate that a common polymorphism in the uridine diphosphate glucuronosyltransferase 1As (UGT1As) gene predict severe toxicity. However the tumor response to irinotecan is variable and unpredictable. Methods: Two multi-center phase II studies of FOLFIRI (FLIGHT-1 and FLIGHT-2 study) were conducted for patients with metastatic colorectal cancer (CRC) in Japan. FLIGHT-1 study was first-line chemotherapy, and FLIGHT-2 study was FOLFOX-refractory second-line chemotherapy. 103 patients have been enrolled in these studies (53 patients in FLIGHT-1 and 50 patients in FLIGHT-2) from 20 institutions by April 2007 from November 2005. Seventy one patients were analyzed UGT1As polymorphisms, UGT1A1*28 (TA6>TA7), UGT1A1*6 (G>A), UGT1A1*60 (T>C), UGT1A7 (N129K; T>G), UGT1A7 (-57 T>G), UGT1A9*22 (T10>T9). Results: Out of 71 patients, 34 had G3/4 neutropenia or leukopenia, and 23 had tumor responses (CR +PR). G3/4 neutropenia was more frequent in patients with *6, N129K(G), -57(G), *22 allele than patients without these allele (p<0.05). Other polymorphism was not the predictive factor for toxicity and tumor response, independently. On the other hand, genotype subset selection of multi-UGT1As polymorphisms was useful to predict severe toxicities and tumor responses. Only 7 patients of 22 patients with TA6/TA6 and T10/T10, or TA6/TA7 and -57(T/T), or *6(G/G) and *60(T/T) had grade3/4 toxicity. Similarly, high risk group of toxicity or high and low tumor responses groups was also predicted by genotype subset selections. Conclusions: Genotype subset selections of multi-UGT1As polymorphisms were the excellent predictor for severe toxicities and tumor responses of metastatic CRC patients received FOLFIRI regimen. No significant financial relationships to disclose.
Circulating microRNAs as potential blood-based biomarkers for detection of colorectal cancer
Authors: Chajut A. , Benjamin S. , Gilad S. , Goren Y. , Dan H. , Zion O. , Kushnir M. , Kundel Y. , Niv Y. , Brenner B. 
Published: August 2020

e15040 Background: Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. While there is a strong correlation between stage and prognosis in this disease, current screening methods for CRC have significant limitations, and newer technological approaches are desired. Circulating nucleic acids in body fluids have been studied as a source for diagnostic information and for cancer screening, yet the potential of microRNAs, a family of small non-coding regulatory RNAs, has not yet been thoroughly explored. Here we investigated the utility of microRNAs as potential serum biomarkers for early detection of CRC. Methods: We developed protocols for extracting and quantifying microRNA levels in serum. Serum levels of more than 350 microRNAs were measured using qRT-PCR on samples from 10 healthy controls and 10 CRC patients. Most microRNAs showed consistent levels across different individuals. A subset of microRNAs had significant differences in abundance between the two groups and was studied on a larger cohort of 118 patients and controls. Results: We initially identified a subset of microRNAs that showed significant differential abundance between sera of CRC patients and controls. Measuring the serum levels of 22 microRNAs on a cohort of 118 patients and controls, we showed that levels of circulating microRNAs can be very informative in the identification of CRC. Conclusions: The results demonstrate the potential of the microRNA processing and analysis methods that we developed. Certain microRNAs were found in different amounts in sera of CRC patients compared to healthy controls. Thus, circulating microRNAs represent promising candidates for diagnostic biomarkers in CRC. [Table: see text]