bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parenchymal sparing surgery for colorectal liver metastases: The need for a common definition.
Authors: Desjardin Marie , Evrard Serge , Brouste Véronique , Desolneux Gregoire , Fonck Marianne , Bechade Dominique , Bonhomme Benjamin , Becouarn Yves 
Published: September 2018

e15013 Background: Colorectal cancer metastases (CRLM) are major public health issue. Recently, surgeons have advocated the use of parenchymal sparing surgery (PSS) however, a common definition of the concept is lacking.To clarify and try to validate the concept of PSS to treat CRLM through the available retrospectives studies, including ours. Methods: Retrospective analysis of a cohort of patients treated by combined resections and intra-operative ablation (IOA) based on PSS, prospectively recorded in a database from 2003 to 2015 in a regional referral cancer center. All the patients benefited from the same strategy, constituting a homogenous series.PSS consists of using resection or IOA in order to spare the healthy parenchyma. One-stage is favored over two-stage surgery and use of portal vein embolization was restricted to the minimum.Post-operative complications were the primary endpoint with a special focus on post-operative liver failure. Liver toxicities and overall survival were also scrutinized. Results: Three hundred and eighty-seven patients underwent a PSS out of which 348 patients received a median of 9 pre-operative cycles of oxaliplatin or irinotecan with targeted therapies for half of them. Resection was major in 128 patients, combined with IOA in 137 patients and IOA alone in 50 cases. Thirty-eight patients had a PVO by strict necessity. The 5yr-overall survival was 50.3%. Seventy-eight patients had a complication > grade 3 out of which 10 patients died. Nine patients had a liver failure (LF) grade B and C and four died. There was no difference in post-operative complications comparing minor and major resections, validating our PSS definition. Chemotherapy and liver toxicity were not related to more post-operative complications. Only one patient died from a primitive LF. Conclusions: With PSS, healthy liver is no more a target. Routine use of chemotherapy does not impair the results and severe LFs are rare. PSS is the optimal strategy to treat CRLM. Definition of PSS cannot be based just on the retrived volume but on the ratio Tumor burden/Healthy liver. A major hepatectomy can be a PSS and a minor may not be one. That is why PSS defintion must be clarify especially for further prospective validations.
Effect of tumor location in metastatic colorectal cancer to response anti-EGFR and anti-VEGF treatment: One center study.
Authors: Ozkan Metin , Dogan Ender , Ucar Mahmut , Sakalar Teoman , Alghareeb Ahmet , Ozaslan Ersin , Inanc Mevlude 
Published: September 2018

e15023 Background: Colorectal cancer is the one of the most common malignancy in western countries. In addition to standart treatment antiEGFR and antiVEGF agents have improved PFS and overall survival. Current studies showed that the colorectal cancers have heterogenous characteristics. The Colon is divided into two parts as a right and left colon according to embrological origin. Recent years supposed that right and left located colorectal tumors may not response samely to anti egfr and anti vegfr therapies. We performed a retrospective study in our clinic to answer this questions. Methods: Study Population and data collection: Between January 2005 and December 2016, all metastatic colorectal cancer patients (n = 285) who received anti-EGFR and anti- VEGF agent with chemotherapy on initial treatment at the Erciyes University Medical Oncology Department were retrospectively reviewed. We included patients with diagnosed metastatic colorectal cancer and who received at least 1 dose of antiEGFR-based or antiVEGFR-based triplet bio-chemotherapy as their first-line treatments. Study population was divided into two groups as right and left colon. Results: A total of 251 patients met the inclusion criteria: 55 patients classified as a right colon cancer (RCC) and 196 patients classified as a left colon cancer (LCC) . 16 patients in RCC group received anti-EGFR-based triplet and 39 patients in RCC group received antiVEGF-based triplet; 76 patients in LCC group received anti-EGFR-based triplet and 120 patients in LCC group received antiVEGF-based triplet as first-line bio-chemotherapy. There were no differences between the patients received antiEGFR and antiVEGF therapy in RCC group (PFS,antiEGFR vs anti VEGF, 7 vs 8 months,P = 0.378; OS, 21 vs 19 months, P = 0.876). There were no differences between the patients received antiEGFR and antiVEGF therapy in LCC group (PFS,antiEGFR vs anti VEGF, 10 vs 10 months,P = 0.202; OS, 27 vs 24 months, P = 0.656). Conclusions: Our study shows that there were no significiant difference between the metastatic colorectal cancer patients received antiEGFR and antiVEGF treatment in LCC and RCC.
Safety analysis of regorafenib prior to selective internal radiation therapy (SIRT) using 90Y resin microspheres for the treatment (tx) of patients (pts) with refractory metastatic colorectal cancer (mCRC) with liver metastases (mets).
Authors: Kennedy Andrew S. , Shipley Dianna , Blakely L. Johnetta , Hemphill Michael Brian , Shih Kent C. , Mainwaring Mark G. , Peyton James D. , Zubkus John D. , Wright David Donald , Bendell Johanna C. , Singh Jaswinder 
Published: September 2018

e15040 Background: SIRT (or radioembolization) has been successfully used in the tx of mCRC patients with liver mets who are not surgical candidates. The addition of the multi-kinase inhibitor, regorafenib to SIRT is an attractive option as anti-tumor and maintenance tx for refractory CRC. Here we present the safety analysis of the 1st of 2 cohorts of our Phase II, open-label study comparing the safety of the combination of SIRT and regorafenib where chemotherapy occurs either before or after SIRT. Methods: mCRC pts with evidence of liver mets not treatable by surgical resection or local ablation were tx with 160 mg regorafenib QD PO on days 1-21 of a 28-day cycle followed by a 1 week (wk) washout then SIRT infusion (SIR-Spheres; Sirtex, North Sydney, Australia). Liver function was evaluated 2 wks and 4 wks after SIRT, and regorafenib was re-initiated if liver function was normal. Pts were evaluated for safety, and restaged on wk 6 and 12 following SIRT. The primary objective was to evaluate the safety of this tx schema. Results: 25 pts were enrolled from 7/15 to 8/16: median age 56 yrs, 48% male; 88% colon cancer, 12%, rectal cancer; 48% KRASmt, 4% BRAFmt. 68% of pts had prior systemic therapy for metastatic disease and 80% of pts had prior CRC surgeries. Pts received a median 11 wks regorafenib. 3 pts received regorafenib, but not SIRT due to disease progression. The median activity of SIRT delivered to the liver was 38 mCi and the median lung shunt fraction was 4%. The median tumor volume treated was 76 mL. The most common tx-related adverse events (AEs) were fatigue (60% all grades [G]; 8% G3/4), decreased appetite (32% all G; 0 G 3/4), and nausea (32%, all G; G 3/4). There were 4 tx-related serious AEs (bowel perforation, intractable abdominal pain, portal hypertension, and diarrhea) and no tx-related deaths. The overall response rate was 4%. The median PFS was 4 months and the median OS was 12 months. Conclusions: The treatment of mCRC pts with liver mets with regorafenib followed by SIRT infusion was found to be tolerable in this pt population. Further efficacy analysis of this treatment schema is merited. Clinical trial information: NCT02195011.
Angiogenesis inhibitor bevacizumab and symptomatic anal ulcers in metastatic colorectal cancer patients: A single center experience.
Authors: Battaglin Francesca , Bergamo Francesca , Salmaso Beatrice , Murgioni Sabina , Intini Rossana , Saadeh Luca , Cavallin Francesco , Manai Chiara , Urbano Federica , Lonardi Sara , Lacognata Carmelo , Aliberti Camillo , Zagonel Vittorina , Castoro Carlo , Scarpa Marco 
Published: September 2018

e15042 Background: Chemotherapy (CT) associated with angiogenesis inhibitor bevacizumab (bev) is a standard first line treatment in metastatic colorectal cancer (mCRC). Among adverse events related to bev, anal canal ulcers have never been extensively described. The aim of our study was to evaluate symptomatic anal ulcers development and its impact on clinical practice and proctologic management. Methods: We retrospectively reviewed clinical records of 601 consecutive mCRC patients (pts) undergoing first line CT from January 2010 to December 2015 at our Institute. Pts’ characteristics, treatments and proctology reports were analyzed. Anal pain was graded in a semi-quantitative scale. Vascularization of the anal canal was compared with contrast MRI in 5 pts treated with bev and 5 healthy controls. Non parametric statistics was performed. Results: Fifty out of 601 pts reported perianal complaints during treatment and underwent proctologic evaluation. Among those, 16 were found to have an anal ulcer. Symptomatic anal ulcers occurred only in pts receiving CT plus bev (16 out of 384, 4.2%) while none was observed in 217 pts treated with other regimens (p = 0.009). The peak incidence was 4-8 weeks after treatment start. Vascularization of anal canal was significantly lower in pts treated with bev (p = 0.03). Hypertension and hemorrhoids were associated with a lower risk of anal ulcer occurrence (p = 0.009 and p = 0.036) while a previous neoadjuvant pelvic CT-RT was not associated with a higher risk. Pain intensity was severe. All attempts at symptomatic treatment with topical and sistemic drugs only led to transient benefit. Pts with symptomatic anal ulcers suspended their first line therapy significantly earlier than other pts (HR = 0.30, 95%CI 0.07-0.80). Conclusions: Symptomatic anal ulcer in mCRC pts treated with CT plus bev is a common adverse event in our series. It can compromise oncologic treatment and pts’ quality of life. We recommend an early proctologic evaluation in case of anal symptoms with the aim to prevent and timely manage such complication in pts treated with bev. A more extensive analysis is ongoing considering subsequent treatment lines and other angiogenesis inhibitors.
Phase II trial of modified FOLIRI plus Panitumumab as first-line treatment in elderly patients with RAS wild-type metastatic colorectal cancer.
Authors: Karampeazis Athanasios , Vamvakas Lampros , Kentepozidis Nikolaos K. , Kotsakis Athanasios , Kalbakis Kostas , Xynogalos Spyros , Sougklakos Ioannis , Emmanouilides Christos E. , Voutsina Alexandra , Hatzidaki Dora , Georgoulias Vassilis 
Published: September 2018

e15053 Background:The role of combination chemotherapy plus anti-EGFR treatment in older patients with metastatic colorectal cancer (mCRC) is unclear. We conducted an open label phase II trial in order to evaluate the safety and efficacy of modified FOLFIRI plus panitumumab as first-line treatment in elderly patients with RAS wild-type mCRC. Methods: Patients ≥70 years old with unresectable all-RAS wild-type mCRC were treated with Panitumumab 6mg/kg as 60min iv infusion followed by Irinotecan 130mg/m2 as 90min iv infusion, Leucovorin 400mg/m2 as 2h iv infusion and 5-Fluorouracil 400mg/m2 as bolus iv infusion on day 1 and 5-Fluorouracil 1.200 mg/m2 as continuous iv infusion for 46h, every 2 weeks. Sample size calculation was based on the minimax Simon two-step design: The null hypothesis was that the overall response rate (ORR) is ≤ 30% versus the alternative hypothesis of ORR ≥ 50% (α = 0.05, power 80%). Results: Forty-six patients were enrolled in the study. Two patients did not receive treatment because they were RAS mutant. Median age for the 44 treated patients was 76 years (range 70-88). Males were 32 and the PS was 0, 1 and 2 in 25%, 70.5% and 4.5% of patients, respectively. Rectal cancer accounted for 25% while 15.9% of patients had the primary tumour in situ. Twenty-one partial responses were observed for an ORR of 47.7% (95%CI: 32.9%-62.5%) while seven patients (15.9%) had stable disease. After a median follow-up of 36.0 months, the median progression-free survival was 6.1 months (95%CI: 3.6-8.7) and the median overall survival was 20.9 months (95%CI: 11.7-30.1). Grade 3-4 neutropenia was recorded in 4 (9%) and grade 3-4 diarrhea in 9 (20.4%) patients while one patient had a grade 4 bowel perforation. One patient experienced grade 3 mucositis, two patients grade 3 skin toxicity and two patients grade 3 fatigue. There were no toxic deaths while one patient died due to bowel obstruction and one due to postoperative complications after removal of the primary tumor. Conclusions: The modified FOLFIRI plus panitumumab combination presented significant efficacy with manageable toxicity in elderly patients with mCRC.
The risk of malnutrition in patients with rectal carcinoma: An analysis of 9789 patients.
Authors: Meissner Carl , Fahlke Joerg , Otto Ronny , Kahl Christoph , Ptok Henry , Asperger Walter , Lippert Hans , Ridwelski Karsten 
Published: September 2018

e15059 Background: The problem of under-nutrition and lack of nutrition is increasingly placed in the focus of operational discipline. Many of them are deficient in malnutrition before being hospitalized. In surgical therapy, the prevention of postoperative complications is of utmost importance. Due to a preoperative condition of malnutrition, the complication rate may increase and thus the associated increased treatment therapy costs per patient. The consequence, of course, is also a diminished postoperative treatment quality of the treating clinic. Methods: Prospective Multicentre Observational Study: "Quality Assurance Study of Rectal Cancer from 2010-2014 of the" An-Institute for Quality Assurance in Operative Medicine "at the Otto-von-Guericke-University Magdeburg, was screened for Nutritional Risk Screening (NRS 2002) Kondrup J et al Results: 9789 primary data records from 2010 to 2014 were included. With the help of the NRS screening, a total score in the form of a scoring system is possible. The sum of 3 points or more identifies a patient with a food-related risk and should be a cause for further diagnosis and therapy. The median of all rectal carcinoma patients was NRS = 3. 53.9% of the patients had an NRS score of > = 3. In morbidity, the complications in colorectal cancer patients with NRS > = 3 points are significantly increased. Also in the case of general complications (such as pneumonia, urinary tract infection, etc.) the rate increases with a larger NRS score. Conclusions: If the risk of malnutrition is small in patients with a colon carcinoma, the morbidity is low.
Outcomes of concurrent chemoradiotherapy for anal cancer in Brazil.
Authors: Azeredo Andressa Cardoso , Silva Bruna Castilhos 
Published: September 2018

e15073 Background: The incidence of anal cancer has increased in the last 30 years and concurrent chemoradiotherapy has been the standard treatment for anal cancer for many decades, since it is a curative treatment in most cases. Although, data from real life outcomes in brazilian patients is lacking. Methods: From October 2001 to November 2016, all the pacientes who were treated with concomitant 5-FU and mitomycin or more recently cisplatin plus radiation at Hospital de Clínicas de Porto Alegre, an academic hospital from South Brazil were identified by electronic database. Medical records were reviewed and demographic data, tumor and treatment characteristics were collected. OS and PFS were estimated by Kaplan-Meier curves. Statistical analysis was performed with SPSS 22. Results: Fifty one patients were analysed for this review. Patient characteristics revealed a mean age of 53 ± 9.03 years, 69% female, with predominantly histology being squamous cell carcinoma (90%). 92% (47) received chemoradiotherapy as a definitive treatment. The chemoterapy regimen used was 5-FU and mitomycin in 69% (35) of the patients and 5-FU plus cisplatin was used in 16 patients (31%). The standard chemoterapy regimen was changed because of lack of supply of mitomycin in our country. Approximately 66% of the patients achieved a complete response while 4 patients (7%) had persistent disease after treatment and 7% had disease progression during treatment. On multivariable analysis, the lymph node status and the size of the tumor were independently associated with worst results. The estimated median PFS was 78 months and the median OS was 92 months. Conclusions: To our knowledge, this is the first report of patients from Brazil treated with concurrent chemoradiation for anal canal cancer. Although we have a delay in the diagnosis and many patients present with locally advanced disease, the CR rate and prognosis are consistent with data from previous studies. We need a longer follow-up to confirm these data and also verify if there will be different outcomes because of the change in the chemoterapy regimen.
Study of circulating tumor DNA (ctDNA) of RAS-wild metastatic colorectal cancer (mCRC) as a tool for on-site mutation screening: A prospective study.
Authors: Sawada Takeshi , Nakamura Keishi , Takahashi Naoki , Kubota Eiji , Sugiyama Manabu , Nakano Shunsuke , Ichijo Toshimitsu , Sakai Rie , Numai Daisuke , Nakanishi Hiroyoshi , Inagaki Satoko , Wakita Shigenori , Ota Ryosuke , Hasatani Kenkei , Tsuji Kunihiro , Doyama Hisashi , Izawa Naoki , Tsuyada Akihiro 
Published: September 2018

e15077 Background: Clinical use of ctDNA has been become an important criterion for patient care. The transfer of this knowledge and technology from top clinical labs to local hospitals is still distant. With the goal of a robust, precise, simple and cost-effective genomic test, we designed a prospective study featuring high-sensitive mutation screening of ctDNA from RAS-wild mCRC with digital PCR (dPCR) technology. This approach allows detection of 85 hotspot mutations of KRAS, NRAS, BRAF and PIK3CA, which are present in approximately 60% of CRC, and is clinically important information for anti-EGFR treatment. Methods: 18 “ RAS-wildtype” mCRC patients, initially diagnosed with PCR-rSSO (RASKET) using CRC FFPE samples, were recruited. After extracting ctDNA from patient plasma, dPCR analysis was conducted with LBx Probes. Results: Mutations in KRAS, NRAS, BRAF and PIK3CA, were detected in 5 samples ( KRAS in 3 samples, NRAS in 1 sample, BRAF in 1 sample, and PIK3CA in 2 samples). In a patient undergoing treatment with panitumumab, two different KRAS clones were detected, indicating possible clonal evolution under drug pressure. Interestingly, we also encountered another patient who had never received anti-EGFR antibodies, but who tested RAS mutation-positive at a level below the detection sensitivity of PCR-rSSO. Conclusions: Our dPCR screening with ctDNA was able to identify mutations successfully in a previously-diagnosed “ RAS-wild” mCRC group. Based on these results, we designed the following test, which with <0.1% mutation sensitivity, would be useful for 1) predicting the efficacy of anti-EGFR antibodies prior to treatment; 2) predicting early emergence of acquired resistance to EGFR blockade; and 3) monitoring disease progression during treatment. [Table: see text]
Dietary fiber intake and risks of proximal and distal colon cancers: A systematic review and meta-analysis.
Authors: Ma Yu , Huang Peilin , Hu Mingyue , Ling Sunkai , Li Yuan , Chen Baoan , Xu Yueshuang 
Published: September 2018

e15080 Background: Epidemiological studies have suggested that intake of dietary fiber is associated with decreased risk of colon cancer, however, these findings are inconsistent in that dietary fiber intake is differentially associated with risks of proximal colon and distal colon cancers. To address this, we conducted a systematic review and meta-analysis. Methods: Pubmed database were searched to identify relevant cohort studies up to December 2016 to examine the association between dietary fiber and risks of proximal colon and distal colon cancers, respectively. A random-effects model was used to compute summary risk estimates. Results: 11 prospective cohort studies were identified and included in the analysis. We observed that the risk of proximal colon cancer was 14% lower among the highest dietary fiber intake compared with the lowest intake (RR = 0.86, 95% confidence interval [CI] = 0.78 to 0.95). A similar result was also found for distal colon cancer (RR = 0.79, 95% CI = 0.71 to 0.87). Conclusions: In current analysis, we show that dietary fiber intake is associated inversely with risks of both proximal and distal colon cancers.
Serum microRNA expression during neoadjuvant chemoradiation for rectal cancer.
Authors: Lim Stephanie Hui-Su , Ip Emilia , Chua Wei , Ng Weng , Henderson Christopher , Shin J-S , Harris Benjamin Howell Lole , Barberis Alessandro , Cowley Mark , De Souza Paul L. , Spring Kevin 
Published: September 2018

e15081 Background: Changes in microRNA (miRNA) expression during treatment for locally advanced rectal cancer (LARC) may provide insight into disease biology and potentially act as predictive biomarkers. We investigated 112 miRNAs in serum during neoadjuvant chemoradiation for LARC. Methods: Serum was collected at baseline, week 3 and at completion of chemoradiation from 40 prospectively recruited patients with LARC. Responders were classed as tumour regression grade (AJCC classification) 0 or 1 and non-responders as 2 or 3. Serum was also collected from 20 healthy controls. RNA extraction was performed using the Norgen total RNA purification kit. Reverse transcription and pre-amplification were performed according to Taqman OpenArray MicroRNA Panels manufacturer's instructions. QuantStudio12K platform was used for miRNA array qPCR. The delta-delta-Ct method was used to identifiy differentially expressed miRNAs, normalised against U6 snRNA. Analysis was performed in R using paired t-statistics and the Benjamini-Hochberg False Discovery Rate for multiple hypothesis testing adjustment, with q < 0.05 for significance. Enriched KEGG pathways were identified using DIANA, based on verified gene targets of each miRNA from Tarbase. Results: Four miRNAs (miR-125b-1, miR-1183, miR-130a, miR-375) were differentially expressed in baseline patient samples compared to controls. From baseline to completion of treatment, three of these - miR-125b-1, miR-1183, miR-130a were downregulated by more than 2-fold. Comparing responders and non-responders, miR-130a was significantly downregulated in the non-responders only. Conclusions: miR-125b-1, miR-1183 and miR-130a are significantly downregulated in patients with LARC during chemoradiation. These miRNAs are known to target key colorectal cancer genes such as ATM and CHEK1, which have been implicated in chemoradiation resistance. miR-130a warrants further investigation as a predictive biomarker, being downregulated in patients with a poor response to therapy. Work is ongoing, investigating these miRNA targets in the solid tissue in these patients. To our knowledge, this is the first study to profile potentially predictive miRNA changes during chemoradiation in LARC.