bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prechemoradiotherapy/nadir ratio of white blood-cell count to predict tumor response and survival in locally advanced rectal cancer.
Authors: Lee Joo Hwan , Kim Sung Hwan , Lee Jong Hoon , Sung Soo Yoon , Jang Hong Seok 
Published: January 2019

783 Background: Predicting treatment response of preoperative chemoradiotherapy (CRT) in patients with rectal cancer is important for physicians to guide a patient to the relevant treatment. We evaluate the change of white blood cell (WBC) count before and during CRT if it is associated with susceptibility to the CRT and affects tumor response. Methods: Medical records of 641 patients with rectal cancer who received preoperative CRT followed by curative surgery were retrospectively reviewed. Complete blood cell counts were measured weekly before and during the radiation therapy. We assessed the pre-CRT/nadir ratio of WBC count for the treatment response to CRT and recurrence-free survival. Results: The enrolled patients were divided into two groups of high WBC ratio (HWR) and low WBC ratio (LWR) with the cutoff value of 0.49, which was found by receiver operating characteristic curve (Sensitivity, 0.38 and 1-Specificity, 0.22; p=0.007). In 641 patients, 490 (76.4%) were HWR group and 151 (23.6%) were LWR group. Complete pathologic response rates were 12.2% in HWR group and 23.8% in LWR group, respectively (p=0.001). Downstaging rates of each group were 37.8% and 48.3%, respectively (p=0.02). In the logistic regression analysis, CEA level over 5ng/ml (Adjusted OR 0.566, 95% CI 0.351-0.912; p=0.019) and HWR (Adjusted OR 0.412, 95% CI 0.256-0.663; p=0.001) were significant adverse factors of the pathologic complete response. The 5-year recurrence-free survival rate was significantly higher in LWR group than in HWR group (67.6% and 83.3%; p=0.001). Conclusions: Low WBC ratio predicts a good tumor response to the preoperative CRT, and is significantly associated with an improved recurrence-free survival in rectal cancer.
Risk of peritoneal carcinomatosis in pT4 and perforated colorectal cancer.
Authors: Gutierrez Sanz Lourdes Gutierrez , Muñoz-Rodríguez Joaquin M , Movilla Arsenio S , Alonso Isabel , Serrano Ángel , Pérez-Viejo Estibalitz , Penacoba Cecilia , Ruiz-Casado Ana 
Published: January 2019

787 Background: Peritoneal carcinomatosis has a dismal prognosis with shorter overall survival than other isolated metastases. In selected patients, HIPEC shows encouraging results. However, early diagnosis continues to be a challenge. COLOPEC trial has been designed to determine the effectiveness of HIPEC in pT4 and perforated colon cancer expecting 25% of peritoneal carcinomatosis in the control arm. A routine second-look procedure in a pilot trial addressed to high-risk patients revealed peritoneal carcinomatosis in 13.3 % in the pT4 group and 50% in the perforation group. Methods: The aim of our study is to describe the risk of clinical/radiological peritoneal relapse in a high-risk population.This is a retrospective study. 711 patients diagnosed with colorectal cancer between 2012 and 2014 according to the hospital – based registry hospital, were reviewed. Patients with stage IV at diagnosis were excluded. 95 cases were considered as high-risk patients. We categorized different classes for pT4 (only), perforation (only) and pT4 + perforation. Results: Peritoneal carcinomatosis was identified during the follow-up in 19 (20 %) of patients initially diagnosed with pT4, perforated colorectal cancer or both. Conclusions: Whereas the risk of peritoneal carcinomatosis in patients with an only risk factor (pT4 or perforation) is 0-15%, it increases up to 33% (one in three patients) when both pT4 and perforation coexist. It is important to collect this information in the clinical record and considering it for the decision-making process. Second-look procedures should not be performed out of the setting of clinical trials. Some patients considered as high-risk patients in old series could have a good prognosis nowadays. [Table: see text]
Use of FDG PET scanning to evaluate 5-FU myocardial toxicity as a global metabolic effect rather than vascular spasm.
Authors: Dean Andrew Peter , Higgs Dom , Robins Peter , Stobie Paul , Craven Philip , Daly Ciara , Carija Samantha 
Published: January 2019

792 Background: This is the first ever case series which presents a series of PET images that conclusively demonstrate reversible abnormal myocardial glucose utilisation in 7 patients with normal coronary arteries occurring during 5-FU infusions. Fluoropyrimidine induced myocardial toxicity is estimated to occur in 9% of cases, with some instances proving fatal. Traditionally some hypothesised coronary artery spasm as the mechanism of action behind such events and an animal study suggesting dysfunction of the Krebs cycle, with depletion of high-energy phosphate compounds, was largely ignored. Having observed abnormal myocardial FDG uptake in a patient with chest pain undergoing FDG PET scanning, we prospectively evaluated a further 6 patients presenting with cardiac symptoms whilst receiving infusional 5-FU. Methods: Over an eighteen-month period, 7 patients experienced cardiac like chest pain during 5FU infusion. All were investigated for cardiac ischaemia as per institutional protocol (serial troponin, ECGs and coronary artery imaging), as well as FDG PET scanning to assess FDG uptake in the myocardium. Results: All 7 cases showed reduced FDG uptake throughout the myocardium, with the ventricular blood pool demonstrating a higher affinity for FDG than the myocardium itself. All 7 cases showed normal physiological uptake of FDG in the myocardium on previous and subsequent PET imaging. Imaging of the myocardium and coronary arteries in all cases showed no structural vascular disease. Conclusions: All cases demonstrated a global pattern of reduced FDG myocardial uptake that could not be isolated to a single coronary territory. Angiography or myocardial perfusion scanning demonstrated no significant coronary artery disease, and there were no features consistent with coronary artery spasm found on ECG. This supports the hypothesis that 5FU inhibits physiological myocardial glucose utilisation, thus acting as a direct myocardial toxin. We believe our findings warrant further investigation into the metabolic effects of 5FU on myocardial tissue.
Tumor bulk to predict clinical outcomes of anti-EGFR therapy in treatment refractory metastatic colorectal cancer independent of sidedness.
Authors: Kratz Jeremy D. , LoConte Noelle K. , Lubner Sam Joseph , Mulkerin Daniel , Uboha Nataliya Volodymyrivna , Deming Dustin A. 
Published: January 2019

795 Background: Epidermal growth factor receptor (EGFR) antibodies, cetuximab (C) and panitumumab (P) have shown improvement in clinical outcomes for distinct molecular profiles in metastatic colorectal cancer (mCRC). In the first line setting, EGFR targeting of left-sided tumors has shown favorable clinical outcomes when compared to right-sided tumors. Here we examined the efficacy of EGFR therapy in the treatment refractory setting as well as the impact of tumor bulk on clinical outcomes. Methods: A retrospective cohort of 72 patients (pts) with KRAS wild-type mCRC were identified who received either C or P in the late-line setting. Tumor measurements were performed per RECIST v1.1. Disease bulk was defined as single lesion with longest diameter or lymph node with short axis > 3.5 cm. Right colon primary was defined proximal to splenic flexure. Results: In pts with treatment refractory right-sided disease the response rate (RR) was 16.7%, progression free survival (PFS) was 3.7 months (mo), and overall survival (OS) was 14.0 mo. This was compared to left sided disease with RR of 26.0%, PFS 6.2 mo (p < 0.05), and OS 15.0 mo. In the non-bulky cohort the RR was 32.4%, PFS 7.9 mo, and OS 18.4 mo. In the bulky cohort the RR was 5.3% (p < 0.01), PFS 4.0 mo (p < 0.02), and OS 6.6 mo. In the right-sided non-bulky cohort there was a RR of 33% v. 0% in the right-sided bulky cohort. In the left-sided non-bulky cohort there was a RR of 32.3% v. 7.7% in the bulky cohort (p < 0.05). Conclusions: These data indicate that tumor bulk can predict clinical outcomes for anti-EGFR targeting. In the late line setting, pts with left-sided cancers overall trended towards improvements in clinical outcomes, consistent with prior understanding in first line setting. Despite a limited cohort size, response was observed in pts with non-bulky right-sided disease. There was limited-to-no benefit of anti-EGFR targeting with right-sided bulky disease. Left-sided non-bulky patient received the greatest benefit from anti-EGFR targeting. Future prospective studies of targeted therapeutics should incorporate tumor bulk and sidedness when assessing clinical outcomes and tumor biology.
Results from an institutional universal reflex testing program for MSI/MMR in colorectal cancer.
Authors: Franke Aaron J , Gaffar Maira , Feely Michael , Starr Jason Scott , Parekh Hiral D. , Tan Sanda , Iqbal Atif , Allegra Carmen Joseph , George Thomas J. 
Published: January 2019

796 Background: In colorectal cancer (CRC), clinical guidelines and immunotherapy treatment selection requires knowledge of tumor DNA mismatch repair gene deficiencies (dMMR) or accumulation of microsatellite repeats through genomic errors (MSI-H). Tumors harboring dMMR/MSI-H are found in 15- 20% of early stage CRC while the prevalence is ~5% in metastatic disease. Reflex testing of CRC to identify these important subsets has been proposed as a system-solution to improve identification. We present a large, single-institutional database of CRC reflexively profiled for MSI/MMR status at the University of Florida (UF). Methods: Beginning in 2009, stage IV CRC underwent reflex testing for MSI/MMR status. Earlier stage CRC testing began in subsequent years. For all new CRC diagnosed at UF, concurrent testing for dMMR by IHC (MLH1, PMS2, MSH2, MSH6), MSI by PCR (Promega MSI kit) and NGS is performed with appropriate positive and negative controls. IHC protein loss is confirmed by second GI pathologist. MSI is not performed if inadequate adjacent normal tissue. We conducted a retrospective analysis of all CRC samples analyzed between 2009 and 2017. Clinical data was collected from the EMR. This study was approved by the UF IRB. Results: A total of 388 new CRC cases were reflex tested (16% Stage I, 23% Stage II, 35% Stage III, and 25% Stage IV). Median age at diagnosis was 63 yrs (range: 17-98 yrs), 51% male and 79% white. Both MMR and MSI were performed in 244 (63%) tumors with 100% concordance when concurrently tested. dMMR/MSI-H incidence (20% in overall population) decreased with stage: I/II (31%), III (18%) and IV (~9%) and was associated with BRAF V600E mut in 36/76 cases (47%). Importantly, in pts < 50 yrs, 13% of stage IV patients were dMMR/MSI-H. Conclusions: Reflex testing of MMR/MSI status in CRC is feasible with concordant results. Routine testing results in identification of dMMR/MSI-H at or higher than published rates. Notable findings include the high prevalence in those with sporadic CRC and/or younger than 50 yrs. Continued impact analysis of this approach is warranted to maximize IO therapy offering.
CYTO-CHIP: Cytoreductive surgery versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: A propensity-score analysis from BIG RENAPE and FREGAT working groups.
Authors: Bonnot Pierre Emmanuel , Piessen Guillaume , Pocard Marc , Meunier Bernard , Bereder Jean Marc , Abboud Karine , Marchal Frederic , Quenet Francois , Goere Diane , Msika Simon , Arvieux Catherine , Pirro Nicolas , Wernert Romuald , RAT Patrick , Pezet Denis , Lefevre Jérémie , Courvoisier Thomas , Kianmanesh Reza , Meeus Pierre , Glehen Olivier ,   BIG-RENAPE and FREGAT Working Groups
Published: January 2019

8 Background: Gastric cancer with peritoneal carcinomatosis (PC) is considered by most as an end-stage disease. Poor outcomes are achieved with palliative chemotherapy. Aggressive combination of cytroreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) are still debated in this indication. Purpose: to assess the impact of HIPEC on survival and postoperative outcomes after complete CRS compared with CRS alone (CRSa) Methods: Data from 277 consecutive patients treated for gastric cancer with PC in 19 French centers from 1989 to 2014 were collected. 180 patients who underwent CRS and HIPEC were compared to 97 treated by CRSa. Extension of PC was assessed by the Peritoneal Cancer Index (PCI). Only patients treated by complete CRS were included (CC-0 or CC-1). To assess the effect of HIPEC and to account for confounding factors, a Cox proportional hazards regression model with inverse probability of treatment weighting (IPTW) based on propensity score was used. Multivariate models and sensitivity analyses were also performed. Results: After propensity weighting, groups were similar except for the PCI that remained higher in the HIPEC group (median: 6 v 2, P = .003). However, there was no difference in the completeness of CRS (CC-0: 76.7% v 83.5 %, P = .904). HIPEC was associated with improved overall survival (OS) on both multivariate and IPTW models. On IPTW analysis, median OS was 18.8 v 12.1 months. 3- and 5-years OS were 26.21% and 19.87% v 10.82% and 6.43% (HR, 1.66; 95% CI, 1.17-2.37; P = .005). 3- and 5-years disease-free survival were 20.40% and 17.05% v 5.87% and 3.76% (P = .001). Mortality rate (7.4% v 10.1%, P = .820) and grade 3-4 morbidity (53.7% v 55.3%, P = .496) at 90 days were similar. Surgical morbidity was 37.1% v 38.8% in CRSa group. Conclusions: Compared to CRSa, HIPEC was associated with increased OS and potential disease eradication for gastric cancer with PC, without additional morbidity. This treatment, when optimal CRS can be achieved, should be considered as the gold standard since outcomes remain grim with chemotherapies. Clinical trail information: NCT03253939
Quality of life at baseline in the international open-label early-access program of trifluridine/tipiracil in previously treated metastatic colorectal cancer (phase IIIb).
Authors: Falcone Alfredo , Taieb Julien , Price Timothy Jay , Seitz Jean Francois , Wyrwicz Lucjan , Becquart Martin , Moreno Shanti , Mounedji Nadjat , Van Cutsem Eric 
Published: January 2019

803 Background: Pivotal phase 3 RECOURSE trial evaluated efficacy and safety of trifluridine/tipiracil (FTD/TPI, also known TAS-102) in metastatic colorectal cancer (mCRC) without collecting quality of life (QoL) data (Mayer et al. N Engl J Med 2015;372:1909-19). We set up a phase IIIb open-label, early access program to confirm safety and to assess QoL in mCRC in real-world practice (EudraCT Number: 2016‐002311‐18). First patient (pt) was enrolled in Oct 2016; enrolment is ongoing. Methods: Eligible pts had histologically confirmed mCRC previously treated with, or not considered candidates for, available therapies. Other inclusion criteria include Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. Pts planned to receive FTD/TPI (35 mg/m2 bid) orally on days 1–5 and days 8–12 of each 28-day cycle. Pts health-related QoL were measured with the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) and the EuroQol 5-dimension, 3-level (EQ-5D) questionnaires and visual analogue scale (VAS). For the EORTC QLQ-C30 global health status, EQ-5D utility values and VAS, scores could range to a maximum of 100 representing a better health-related QoL. EORTC QLQ-C30 and EQ-5D were considered non evaluable when responses were missing for one third or at least one of the dimensions, respectively. QoL was measured at baseline, every 4 weeks on treatment, and at treatment discontinuation. Results: A total of 298 pts from 7 countries had received at least 1 dose of treatment as of 7 March 2017. Among 271 patients, 39.5% and 60.1% had respectively ECOG PS 0 and 1 at baseline except 1 pt was enrolled with ECOG PS 2. Out of these 298 pts, 263, 261 and 258 were evaluable at baseline for EORTC QLQ-C30 global health status, EQ-5D utility values and VAS, respectively. These means were 62.4 (standard deviation [SD] 21.3), 73.6 (SD 20.3) and 66.1 (SD 19.1), respectively. Conclusions: Analysis of pt QoL in the real-world practice shows it may be substantially deteriorated in heavily pretreated pts with advanced mCRC in spite of having an ECOG PS of 0/1. Preliminary safety /efficacy and QoL results are expected in summer 2018. Clinical trial information: 2016-002311-18.
Adjuvant therapy use and outcomes of stage II and III colorectal cancer (CRC): Comparison of young and elderly patients (pts) in a large, contemporary, population-based Canadian database.
Authors: Samawi Haider , Tilley Derek , Cheung Winson Y. 
Published: January 2019

807 Background: The incidence of CRC increases significantly with age. Despite the benefits associated with adjuvant therapy, older pts are frequently treated less aggressively due to perceived poor tolerance to treatment, comorbidity, or limited life expectancy. We aim to examine the impact of chronological age on use of perioperative therapies in a contemporary cohort of pts and determine differences in outcomes based on age. Methods: Adult pts who underwent surgical resection for stage II or III CRC in Alberta, Canada from 2004 to 2015 were analyzed. Pts were stratified based on pre-specified age sub-groups. Overall survival (OS) and cancer specific survival (CSS) were assessed using the Kaplan-Meier method and compared with the log-rank test. A Cox proportional hazards model was constructed to evaluate the impact of age on outcomes. Results: We identified 8,538 pts of whom 56% were men, 53% had stage III disease, and 26% had rectal cancer. Older pts were more likely diagnosed with right-sided tumors, earlier stage, and higher Charlson comorbidity index (CCI) (all p <.01). Chemotherapy (CT) use decreased significantly with advancing age, even in recent years (Table). Older rectal cancer pts were also less likely to receive radiation (p <.01). Elderly age was the strongest predictor for not using CT, after adjusting for sex, stage, tumor location, and CCI. On multivariate Cox regression, older age was associated with inferior OS and CSS, but CT improved outcomes. Conclusions: Despite evidence of benefit and prior studies recommending treatment of elderly, the current cohort of older pts with resected stage II and III CRC continue to undergo perioperative therapy less commonly than their younger counterparts. [Table: see text]
Facility variation in clinical staging of rectal adenocarcinoma and its contribution to underutilization of neoadjuvant therapy.
Authors: Swords Douglas S. , Skarda David E. , Stoddard Gregory J. , Kim H. Tae , Sause William T. , Scaife Courtney L. 
Published: January 2019

810 Background: Studies of the National Cancer Database (NCDB) found that neoadjuvant therapy (NAT) for clinical stage II-III rectal adenocarcinoma is underutilized, but they reclassified patients without clinical staging by pathologic stage. Methods: Study of patients < 80 with resected clinically non-metastatic rectal adenocarcinoma in the 2010-2014 NCDB. Reliability-adjusted (RA) facility rates of clinical staging were calculated. Then, patients with clinical stage I, unknown clinical/pathologic stage 0-1 and NAT contraindications/refusal were excluded. Multivariable Poisson regression was used to examine predictors of NAT. Multiple imputation was used to account for missing data. RA facility NAT rates were calculated. Variance partitioning was used to examine causes of omission of NAT. Results: Of 26220 patients with clinical stage II-III or unknown clinical/pathologic stage II-III, 3634 (14%) were not clinically staged. RA facility clinical staging rates ranged from 17%-99%. NAT was delivered to 20415/22586 (90%) patients who were clinical stage II-III vs. 1372/3634 (38%) of those without clinical staging. Of 4443 patients who did not receive NAT, 2262 (51%) did not have clinical staging. Treatment at facilities with higher volume and clinical staging rates was associated with delivery of NAT. RA facility NAT rates ranged from 33%-96%. Patient factors explained 15% of variance in facility NAT rates, type/volume 16%, and facility clinical staging rates 23%. Conclusions: A single process (omission of clinical staging) is present in half of cases omitted NAT (Pareto principle). Facility NAT rates vary 3-fold, and facility clinical staging rates explain much of the variation in use of NAT. Efforts to increase utilization of clinical staging are warranted. [Table: see text]
The significance and long-term clinical outcome of preoperative chemoradiotherapy using S-1 plus Irinotecan for locally advanced rectal cancer.
Authors: Kimura Kei , Beppu Naohito , Tsukamoto Kiyoshi , Yamano Tomoki , Noda Masafumi , Ikeda Masataka , Tomita Naohiro 
Published: January 2019

819 Background: Preoperative chemoradiotherapy regimen using S-1 plus Irinotecan is still under clinical investigation. The aim of this study was to investigate the significance and the long-term outcomes of this regimen for locally advanced rectal cancer. Methods: Between 2009 and 2016, 81 patients underwent radical surgery after preoperative chemoradiotherapy. Radiotherapy was administered in total 45Gy with 1.8Gy/day for 25 days. S-1 was administered orally in a fixed daily dose of 80mg/m2 on days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan was infused with dose of 80 mg/m2 on days 1, 8, 22, and 29. 6-9 weeks after the completion of the treatment, radical surgery was performed. The median follow-up was 35.3 months. Results: Of the 81 patients, 76 (93.8%) completed treatment of chemoradiotherapy. Relative dose intensity of CPT-11 was 92.8%, S-1 was 90.1%. 79 (97.5%) patients completed the radiotherapy. 18 patients (22.2%) had ≧Grade 3 hematologic toxicity (leukopenia; 15 patients, neutropenia; 16 patients ). 23 patients (28.3%) had ≧Grade 3 nonhematologic toxicity (diarrhea). In terms of the surgical procedure, 73 of 81 patients (90.1%) underwent sphincter-preserving surgery including 42 patients intersphincteric resection, and 8 patients (9.9%) underwent abdominoperineal resection. The tumor regression grade of 1/2/3(pCR) was 30/39/12(14.8%). In terms of long-term survival, 3-year local relapse-free survival rate was 96.7%, the recurrence-free survival rate was 71.6% and 3-year overall survival rate was 94.9%. Conclusions: Preoperative chemoradiotherapy using combined with Irinotecan as secondary drugs may result safe and feasible and accomplished favorable downstaging. This regimen was considered to be effective in patients with locally advanced rectal cancer.