bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of adding oxaliplatin to fluoropyrimidines in the adjuvant colon cancer: Experience in Ramon y Cajal University Hospital.
Authors: Martinez Saez Olga , Barquín García Arantzazu Martínez , Villamayor Delgado Maria , Saavedra Serrano Cristina , Corral de la Fuente Elena , Serrano Domingo Juan José , Martín Huertas Roberto , Reguera Puertas Pablo , LONGO FEDERICO , Pachon Vanessa , Rodríguez Garrote Mercedes , Guillen Carmen , Carrato Alfredo , Ferreiro Monteagudo Reyes 
Published: January 2019

815 Background: The addition of oxaliplatin to fluorouracil and leucovorin as adjuvant therapy for patients with stage II and III colon cancer (CC) has been analyzed in two large, randomized trials, MOSAIC and C-07 trials. The updated results of these studies showed that the addition of oxaliplatin enhances overall survival by approximately 5% in patients with stage III disease but has no effect in patients with stage II disease. Methods: We retrospectively included patients with stage II and III CC that were operated between 2009 and 2014 in the Ramón y Cajal University Hospital from Madrid. We perform a multivariable Cox model analysis to estimate the benefit of the chemotherapy stratifying by oxaliplatin in each stage. The model was further adjusted by including the following confounders: ECOG-PS, number of removed nodes, perforation, obstruction, grade and age. Stata 13.1 was used to analyze the data. Results: 564 patients were identified (281 stage II and 283 stage III). 305 did not receive any chemotherapy, 61 received monotherapy with fluoropyrimidines (FP) and 198, FP and oxaliplatin. The median follow-up in the entire cohort was 49 months. Globally, adjuvant chemotherapy (either with FP alone or with the combination with oxaliplatin) showed no benefit in DFS (HR of 1.18 and 0.98, respectively). The benefit in OS was significant either for FP alone (HR: 0.46, p: 0.029) and for the combination treatment (HR: 0.41, p: 0.001). Patients with stage II treated with FP in monotherapy showed no benefit, neither in DFS nor OS (HR for DFS: 2.2, p: 0.1; HR for OS: 0.5, p: 0.22). The benefit was neither seen with the addition of oxaliplatin (HR for DFS: 2, p: 0.11; HR for OS: 0.85, p: 0.7). Stage III patients treated with FP presented a HR for DFS of 0.76 (p: 0.5) and a HR for OS of 0.42 (p: 0.087). The HR for DFS with oxaliplatin was 0.53 (p: 0.07). A significant improvement in OS was observed, with a HR of 0.22 (p < 0.001). Conclusions: The addition of oxaliplatin in the adjuvant treatment of stage III patients showed a trend towards improvement in DFS and a significant benefit in OS compared to not receiving chemotherapy. On the contrary, patients with stage II did not benefit from this treatment, neither in DFS nor OS.
Relation between the size of nonmetastatic lymph nodes and outcomes in patients with stage III colorectal cancer.
Authors: Okada Kazutake , Sadahiro Sotaro , Miyakita Hiroshi , Saito Gota , Tanaka Akira , Suzuki Toshiyuki 
Published: January 2019

822 Background: In stage II colon cancer, retrieval of less than 12 lymph nodes (LNs) is a risk factor for recurrence. We previously reported that the great long-axis diameter of the largest retrieved lymph nodes (maximum LNs) is associated with a higher number of retrieved LNs and better outcomes (Int J Colorectal Dis 2015). We examined whether the long-axis diameter of maximum LNs is a prognostic factor in node-positive stage III colorectal cancer. Methods: The study group comprised 260 patients (pts) with stage III disease who underwent curative resection from 2005 through 2014. Pts who underwent laparoscopic or emergency surgery were excluded. The long-axis diameter was measured on H-E stained specimens and one non-metastatic LN with the greatest long-axis diameter was selected. The cut-off value (COV) for the long-axis diameter was determined by using receiver ROC curves with recurrence or overall mortality as events. Results: Tumors were located in right colon in 86 pts (33%), left colon in 104 pts (40%), and rectum in 70 pts (27%). In pts with rectal cancer, 49 (70%) received chemoradiotherapy (CRT). The mean long-axis diameter was 8.0 ± 3.5 mm. Factors related to the long-axis diameter were tumor location (right colon 9.5 ± 3.8 mm, left colon 7.7 ± 3.4 mm, rectum 6.6 ± 2.4 mm, p < 0.001), CRT (absent 8.4 ± 3.6 mm, present 6.3 ± 2.3 mm, p < 0.001), TNM stage (IIIA 6.6 ± 3.0 mm, IIIB 8.0 ± 3.5 mm, IIIC 8.8 ± 3.7 mm, p = 0.025), and the number of retrieved LNs (less than 12, 6.5 ± 2.9 mm; 12 or more, 9.0 ± 3.5 mm, p < 0.001). The COV for the long-axis diameter from the ROC curves was 8.0 mm. A long-axis diameter of ≥8.0 mm (106 pts 41%) were associated with significantly better outcomes than a long-axis diameter of < 8.0 mm (154 pts 59%) (5y RFS: < 8.0 mm 57%, ≥8.0 mm 70%, p = 0.012). On multivariate analysis, sex (female/male, HR 0.61, p = 0.019), venous invasion (absent/present, HR 0.58, p = 0.042), TNM stage (IIIB/IIIA, HR 3.19, p = 0.021; IIIC/IIIA, HR 3.47, p = 0.033), and the long-axis diameter (≥8.0 mm/ < 8.0 mm, HR 0.55, p = 0.005) were independent prognostic factors. Conclusions: In pts with stage III colorectal cancer, the long-axis diameter of maximum LNs was a prognostic factor. The size of maximum LNs might thus reflect the tumor immunity of the host.
A phase II trial of the effect of perindopril on hand foot syndrome (HFSR) incidence and severity in patients receiving regorafenib with refractory metastatic colorectal carcinoma (mCRC).
Authors: Melosky Barbara L. , Lim Howard John , Davies Janine , Gill Sharlene , Kollmannsberger Christian K. , Ho Maria , Vandt Solomon A. , Renouf Daniel John 
Published: January 2019

824 Background: Regorafenib is an oral multi-kinase inhibitor (MKI), with a demonstrated overall survival benefit in mCRC refractory to standard therapy ( PMID 23177514). The most common grade 3 adverse event (AE) reported in this trial was HFSR, with 47% of patients (pts) experiencing HFSR of all grades, and 17% with grade 3 severity. The pathogenesis of regorafenib-induced HFSR is not well established, but may be related to alterations in the capillary endothelium. Perindopril is an Angiotensin Converting Enzyme (ACE) Inhibitor indicated for the treatment of hypertension, and may also play a role in preventing endothelial dysfunction ( PMID 17140552). We hypothesized that perindopril may prevent or reduce the severity of regorafenib-induced HFSR. Methods: In this single center Phase II, open label trial, 34 pts with refractory mCRC were planned to be treated with regorafenib (160 mg/day) and perindopril (4 mg/day) with both agents given 3 weeks on and 1 week off. An interim analysis was planned after 10 evaluable pts. The primary objective was to assess the proportion of pts with any grade HSFR toxicity. Secondary endpoint included time to development of worst (grade 3) HSFR toxicity, proportion of all grades of hypertension and all grade toxicities, and progression free survival. All toxicities were evaluated using CTCAE v4.03. Results: 12 pts were accrued over a 9 month time period, and 10 pts were considered evaluable as they completed one cycle of treatment. Pt characteristics included (6 M/ 6F, mean age 62, ECOG PS 0 (25%)/ 1 (75%). A planned interim analysis was performed after 10 evaluable pts had completed their first cycle of study treatment. 5/10 (50%) experienced Grade 3 HFSR, and based on the statistical plan it was deemed highly unlikely that perindopril would lead to reduced levels of regorafenib induced HSFR compared with regorafenib alone thus enrolment was stopped. The most frequent other grade 3 toxicities included hypertension (16.7%), and increased AST (16.7%). Conclusions: The addition of perindopril to regorafenib did not appear to reduce HSFR incidence and severity in pts with refractory mCRC. Clinical trial information: NCT02651415.
Contemporary multi-modal management of colorectal cancer: Evolving patterns of care in an Irish cohort.
Authors: Greally Megan , Harrold Emily , Fenlon Helen M , Eaton Donna , McCarthy Jim , Redmond Karen C , Conneely John B , McEntee Gerry P , Brannigan Ann E , Shields Conor J , Mulsow Jurgen , Gallagher David James , Carney Desmond N. , Higgins Michaela Jane , Kelly Catherine Margaret , McCaffrey John 
Published: January 2019

827 Background: The last 15 years have seen significant improvements in the outcomes of patients (pts) with CRC. More effective systemic therapy (Rx) and wider use of surgery (Sx) in stage IV disease (Dx) are key drivers of this. We evaluated the impact of intense surveillance in concert with greater use of metastasectomy and improved systemic Rx on CRC outcomes. Methods: This is a retrospective review of the clinical, radiologic and histological records for consecutive pts with CRC who were referred to the multi-disciplinary CRC team from 2003-2016. Pts with stage I/II Dx were included when referred for adjuvant Rx for high-risk features. We recorded pt characteristics, Rx received and outcomes. Survival was assessed using Kaplan-Meier analysis. Results: We identified 600 pts. Median age was 65 (22-97 years). 71.2% (n=427) of pts had left sided CRC and 25.7% (n=154) had right sided Dx. 211 pts (35.2%) had de novo metastatic Dx. 163 of 389 pts (41.9%) with stage II/III disease relapsed. Median Dx-free interval was 16 months. Of 163 relapses, 121 (74%) were detected by radiologic surveillance and 14 (9%) by rise in CEA. Symptomatic relapse occurred in 20 pts (12%). Median overall survival (OS) was significantly improved in pts with relapse detected by CT, PET/CT or CEA rise (54, 53 and 54 months respectively) vs pts with symptomatic relapse (4 months, p<0.001). Metastasectomy rates were higher in pts with image-detected relapse ( p=0.017). Median OS for pts with stage IV CRC who received any Rx was 27 months. Pts with right sided Dx had shorter median OS vs pts with left sided Dx (24 months vs 40 months, p=0.002). 195 pts (52.8%) underwent metastasectomy; median OS was 71 months vs 16 months in those who did not undergo Sx. 84 pts (14%) with stage IV CRC are currently Dx-free after Sx. Median OS was improved with increasing lines of Rx. Survival in pts receiving best supportive care was 5 months vs 17, 25, 34, 38 and 42 months for pts receiving 2, 3, 4 and 5 lines of Rx respectively ( p<0.001). Conclusions: CRC outcomes are improving with effective multi-disciplinary care, close surveillance, sequencing of systemic Rx and judicious use of salvage Sx following relapse. Our findings support long-term benefit for surgical metatastectomy in stage IV CRC.
Predictive value of primary tumor location (TL) in patients (pts) with pan-RAS wild-type (wt) metastatic colorectal cancer (mCRC) receiving chemotherapy (CTX) ± cetuximab or panitumumab (C/P): An updated meta-analysis.
Authors: Wang Zi-Xian , He Ming-ming , Wang Ying-Nan , Wang Feng , Xu Rui-hua 
Published: January 2019

830 Background: Previous evidence suggests that TL may be predictive of the efficacy of C/P versus bevacizumab. This meta-analysis was aimed to evaluate the efficacy of CTX plus C/P versus CTX only as a first-line (1L) or second-line (2L) treatment for RAS wt right- and left-sided mCRC (R- and L-mCRC) in randomized controlled trials (RCTs). Methods: A systematic literature review was performed of PubMed and oncology congress websites (2000–present). RCTs studying the additional efficacy of C/P to CTX in RAS wt R- and L-mCRC were included. Assessed outcomes included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Random-effects meta-analytic models were used in the presence of significant heterogeneity ( I2> 50%). Otherwise, fixed-effects models were performed. Random-effects meta-regression models were used to evaluate the interaction between TL and the efficacy of C/P. Results: A total of three 1L RCTs (CRYSTAL, PRIME, and TAILOR) and one 2L RCT (20050181) were included (325 pts with R-mCRC and 1214 with L-mCRC). Pooled estimates of the efficacy of C/P are summarized in the table. In both R- and L-mCRC pts, the addition of C/P to CTX significantly improved PFS and ORR. A significant OS benefit from C/P was observed in L-mCRC but not R-mCRC pts. No significant interaction was detected between TL and the efficacy of C/P on PFS, OS, and ORR ( P= 0.69, 0.09, and 0.22, respectively). Conclusions: Adding C/P to CTX clearly benefits RAS wt L-mCRC pts in terms of PFS, OS, and ORR. Considering the improvements in PFS and ORR versus CTX only, anti-EGFR agents remain an option for pts with RAS wt R-mCRC. [Table: see text]
A retrospective cohort study evaluating the safety and efficacy of TAS-102 in patients with metastatic colorectal cancer (HGCSG1503): Analysis of cases of prior regorafenib.
Authors: Ishiguro Atsushi , Yuki Satoshi , Nakatsumi Hiroshi , Saiki Takuro , Tsuji Yasushi , Hatanaka Kazuteru , Yoshita Hiroki , Minami Shinya , Ohta Tomoyuki , Eto Kazunori , Nakajima Junta , Nakamura Michio , Suzuki Kazuhiro , Koike Masahiko , Kato Kanji , Tateyama Miki , Asada Chiaki , Sekiguchi Mari , Sakata Yuh , Komatsu Yoshito 
Published: January 2019

832 Background: The J003 trial and RECOURSE trial revealed the safety and efficacy of TAS-102 for patients with metastatic colorectal cancer (mCRC). In March 2014, TAS-102 was approved in Japan. However, in these pivotal trials, there were few cases in which regorafenib was administered as prior treatments, and also there were few reports on the effectiveness and safety of TAS-102 after administration of regorafenib. Methods: We retrospectively analyzed the clinical data of 126 patients who received TAS-102 after administration of regorafenib in the multi-institutional retrospective study (HGCSG1503). This study was analyzed by CTCAE v4.0 for adverse events (AEs), RECIST v1.1 for response rate (RR)/disease control rate (DCR), and Kaplan-Meier method for progression free survival (PFS) and overall survival (OS). Results: Patients characteristics were as follows; male/female 75/51, median age 66.5 (range 38-84), ECOG PS (0/1/2/3) 48/64/12/2, KRAS Exon2 wild/mutant 64/60 (2 patients; KRAS Exon2 was not tested). The initial starting dose was 70 mg/m2 (n = 100, 79.4%) and reduced dose (n = 26, 20.6%). Dose reductions were required in 30 patients (30.9%). The common ≥grade 3 AEs were neutrophil count decreased (45.1%), white blood cell decreased (34.9%), and anemia (28.6%). RR and DCR were 0% and 36.5%, respectively. Median PFS and OS were 2.1 and 5.7 months. In the analysis on the relationship between ECOG PS 0-1 and PS 2-3, median PFS was 2.2 vs. 1.4 months (HR 2.187, p = 0.008), and MST was 6.5 vs. 2.7 months (HR 2.424, p = 0.002). Conclusions: In this analysis, TAS-102 after administration of regorafenib in the real-world clinical practice showed similar efficacy and safety to the pivotal clinical trials, except for patients with PS 2-3. Clinical trial information: 000020551.
First line treatment of metastatic colorectal cancer: Are clinical trial results reproducible in real-life practice?
Authors: Lewin Ron , Gal Omer , Sulkes Aaron , Gordon Noa , Ben-Aharon Irit , Purim Ofer , Perel Gali , Kundel Yulia , Moore Assaf , Ulitsky Olga , Brenner Baruch 
Published: January 2019

836 Background: Treatment of metastatic colorectal cancer (mCRC) has greatly advanced over the past decade, based on data from randomized controlled trials (RCTs). This raises the question whether results of RCTs, performed on selected patients (pts), do reflect outcomes in real-life practice. The aim of this study was to summarize our experience in the treatment of mCRC and compare it to data reported in RCTs. Methods: A retrospective single-institution study on consecutive mCRC pts treated with first-line bevacizumab-containing regimens in our institute between 2006 and 2014. Results: The study included 300 pts, of whom 54% were males. Median age was 67 years (range 28-90), 26% aged ≥ 75 years. ECOG performance status was ≤1 in 93%. The primary tumor site was right colon in 37%, left colon in 40%, rectal in 23% and 1% of pts had synchronous tumors. RAS status was available in 60%, of whom 55% had wild-type alleles. 46% of pts had a single metastatic site, including 27% with liver-limited disease, and 54% had multiple metastatic sites. Irinotecan-based chemotherapy was used in 66%, oxaliplatin-based chemotherapy in 29% and flouropyrimidine monotherapy in 5%. Curative metastasectomy during 1st line treatment was performed in 29%. Grade ≥3 hematological and non-hematological toxicities were reported in 24% and 38% of pts, respectively. Second and third line treatments were administered to 75% and 66% of pts, respectively; 73% of pts received both irinotecan and oxaliplatin through their treatment course and 76% of those with wild-type RAS were treated with anti-EGFR therapy. Overall response rate and disease control rate were 69% and 89%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 17 and 28 months, respectively. In a sub-group analysis on "RCT-like population", excluding pts ≥ 75 years, ECOG PS ≥ 3 and/or mutated/unknown RAS status, median PFS and OS were 15 and 29 months, respectively. Conclusions: The results of this study suggest that, if adhered to international clinical guidelines, outcomes reported in RCTs are indeed reproducible in routine clinical practice in unselected real-life pts. Additional data, with more pts and longer follow-up, will be presented.
Rectal cancer in the elderly: A review of treatment variances between younger and older patients.
Authors: Corrigan Lynda , O'Leary Connor Gerard , Kroes Jeska , Calvert Paula , O'Connor Miriam , Martin Petra , Cooke Fiachra , Horgan Anne M. 
Published: January 2019

839 Background: Rectal cancer (RC) treatment involves multiple modalities with tolerability a concern for some older patients (pts). However, fit older pts have outcomes similar to those of younger pts. We examined the treatment of RC in older pts compared to younger counterparts. Methods: Pts diagnosed with early stage and locally advanced RC from January 2014 to January 2016 were identified from a prospectively maintained electronic database. Characteristics were ascertained through retrospective analysis of pt records. Associations between categorical variables was tested using chi- square. Results: 116 pts diagnosed with RC were identified. Median age was 67 (range 36- 95). 47 (41%) were ≥ 70 years old. Stage distribution is summarised in the Table. Eight pts with stage I disease had rectal polyp cancers, fully resected at endoscopy. 108 were discussed at multidisciplinary meeting (MDM). Treatment (tx) recommendations based on clinical stage and ultimate tx received are outlined in the Table. Clinical Stage and MDM Outcomes Older pts were less likely to receive recommended NACRT than those < 70 (52% and 85% respectively). All pts ≥ 70 who received NACRT completed a full course successfully. Older pts were less likely to proceed to curative resection than younger pts (76% and 94% respectively). Average length of hospital stay was longer in pts ≥ 70: 22.9 vs. 16.6 days in pts < 70. Hospital readmission within 30 days in ≥ 70 vs. < 70 was 9% and 3% respectively. There was no statistical difference in the likelihood of receiving AC based on age. 25% of older pts required dose reductions of AC; 38% did not complete the planned number of cycles. Conclusions: While most older pts tolerated NACRT without significant toxicity, post- operative recovery and tolerability of AC varies widely. Comprehensive geriatric assessment may be useful in guiding tx decisions, and ensuring best outcomes, in this heterogeneous group.[Table: see text]
Early outcomes in patients with locally advanced rectal cancer following total neoadjuvant therapy.
Authors: Friedrich Tyler , Goodman Karyn A. , Leong Stephen , Herter Whitney , Davis Sarah Lindsey , Vogel Jon , Gleisner Ana , Meguid Cheryl Lauren , Purcell William T. , McCarter Martin , Cowan Michelle , Schefter Tracey E. , Messersmith Wells A. , Lieu Christopher Hanyoung 
Published: January 2019

848 Background: The current standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation followed by surgery, and then adjuvant chemotherapy. An alternative approach currently being offered to patients at University of Colorado is total neoadjuvant therapy (TNT), in which patients receive all of their planned treatment, including systemic chemotherapy, preoperatively. Methods: Records of patients from the University of Colorado multidisciplinary colorectal clinic between 2/2015 and 5/2017 were retrospectively reviewed. Treatment plans for included patients involved 8 cycles of preoperative chemotherapy with FOLFOX (5-fluoruracil, oxaliplatin, leucovorin), followed by chemoradiation with concurrent capecitabine, and then resection. Patient data collected includes demographic information, initial staging, chemotherapy and radiation received, adverse effects, surgical outcomes, and clinical and pathological response to treatment. Results: At the time of our analysis, 14 patients have completed TNT and undergone surgical resection, with either abdominoperineal resection or low anterior resection (LAR), at the University of Colorado. Patients ranged in age from 39 to 74 years (mean age 56) with 8 patients (57%) female sex. All 14 patients received 5-fluorouracil with all 8 cycles, though 4 (29%) required omission of oxaliplatin by cycle 8. Toxicities from preoperative treatment were as expected, without significant delays in surgery. Of the 14 patients, 4 (29%) showed a pathologic complete response (grade 0, no residual tumor) on their surgical pathology, with 8 (57%) having either grade 0 or 1 (minimal residual tumor) response. Of the 5 patients who underwent LAR with diverting loop ileostomies, mean time to ostomy reversal was 53.6 days (range 49-61). No patients developed clinically-apparent metastatic disease during preoperative therapy. Conclusions: The use of preoperative chemotherapy in addition to standard chemoradiation for locally advanced rectal cancer is well-tolerated, results in a high rate of pathologic complete response, and allows for early reversal of diverting ileostomies.
The estrogenic hormone effect in gastric cancer.
Authors: Jang Youjin , Mok Youjae 
Published: January 2019

85 Background: Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. A few of studies have examined the expression of ER in gastric cancer. However, considerable controversy is raised as to the expression level of ER and its prognostic value in gastric cancer. In the present study, the expression profile of ERα, ERβ was determined in gastric cancer cell lines according Lauren classification and evaluate that the treatment effect of selective estrogen receptor modulator. Methods: Using four cell lines established from human gastric carcinomas according Lauren classification, check endogenous ERα, ERβ expression levels with RT-PCR. The SERM treatment effect were detected MTT test. Using immunohistochemical detection, the present study analyzed the clinical relevance of ERα, ERβ expression in tumor cells in 197 patients who underwent curative radical surgery and who were observed on long-term follow-up. Results: Endogenous ERα was high expression not intestinal cancer cell lines but in diffuse cancer cell line. Endogenous ERβ was high expression both type cancer cell line than normal gastrointestinal cell lines. According MTT assay, only raloxifene among SERM was significant treatment effect. In immonohistochemial study of gastric tissue, ERα negative and ERβ positive was associated with good prognosis. Conclusions: ERβ may be partly involved in gastric carcinogenesis and ERβ antagonist might be new therapeutic drug for gastric cancer.