bluuebunny/crossref_metadata_2025_split huggingface dataset:
A central review of resectability of optimally unresectable colorectal liver metastases following neoadjuvant chemotherapy (KSCC0802).
Authors: Takatsuki Mitsuhisa , Eguchi Susumu , Tokunaga Shoji , Emi Yasunori , Oki Eiji , Uchida Shinji , Sakoda Masahiko , Kakeji Yoshihiro , Shirabe Ken , Akagi Yoshito , Beppu Toru , Baba Hideo , Ueno Shinichi , Natsugoe Shoji , Ogata Yutaka , Maehara Yoshihiko ,   Kyushu Study Group of Clinical Cancer
Published: March 2020

e14633 Background: Kyushu Study group of Clinical Cancer (KSCC) conducted the phase II study that evaluated the neoadjuvant chemotherapy for optimally-unresectable colorectal liver-limited metastases (KSCC0802, Samura et al, J Clin Oncol 30:4s, 2012). We carried out a central review for the purpose of obtaining an objective assessment of how resectability changed during treatment. Methods: We reviewed the CT or MRI images before and after protocol treatment, according to the method of CELIM study. A surgical review was done by five independent hepatobiliary special surgeons from five different centers. A resectability was reviewed based on radiological images only. Individual surgeons were blinded to the time when the CT scan was taken. The surgeons voted for (1) curative resection, (2) exploratory laparotomy with aim of resection (3) borderline resectable with chemotherapy preferred first, (4) unresectable, (5) non-evaluable. Patients were considered resectable if 50% (non-evaluable is excluded) or more of surgeons voted for categories (1) and (2), and images were considered evaluable if more than three surgeons voted with categories (1)–(4). Results: In KSCC0802 study, of the 40 pts. enrolled from Sept. 9 2008 to Aug. 10 2010. The number of cases to intent operation after chemotherapy was 17 (42.5%), and the actual liver resectability was 16/40 (40.0 %). The number of R0 cases was 10 pts. . In total, 77 images were presented for this central review. Only three follow-up scans were not available. Following review, 17 (42.5%) of 40 patients were judged to be resectable after chemotherapy, compared with 14 (35.0%) patients at baseline. Of 36 cases in which both imaging studies were available to be evaluated before and after chemotherapy, 7 cases (19.4%) judged as unresectable before chemotherapy were finally determined as resectable after chemothrerapy. Conclusions: With the central review by 5 independent liver surgeons, the resectability was fairly determined before and after chemotherapy. mFOLFOX6 with Bevacizumab regimen is safe and effective for unresectable liver limited-metastases from colorectal cancer, and might be to lead the liver resectability. Clinical trial information: UMIN000001308.
Preclinical model for combined effects of metformin and vitamin D3 on colitis-associated colon neoplasia.
Authors: Li Wan , Wang Qi-Long , Li Hong-Xia , Li Chun-Yang , Berger Nathan A. , Li Li , Wu Yongjie 
Published: March 2020

e14634 Background: Metformin and vitamin D each has been shown to have anti-colon carcinogenic effects in pre-clinical and epidemiologic studies. We tested the potential synergistic effects of Metformin and vitamin D3 against colorectal neoplasia in a DMH-DSS induced colitis-associated colon neoplasia mouse model. Methods: We randomized 182 5-week old ICR male mice into 7 groups: 1) normal controls; 2) DMH controls; 3) DSS controls; 4) DMH + DSS controls; 5) vitamin D3 (3 dosage groups), 6) metformin (3 dosage groups), and 7) vitamin D3 + metformin (3 dosage combinations). After 20 weeks of treatment, the mice were sacrificed and colon tissues were harvested and examined for multiplicity of adenoma/cancer, volume of each tumor, number and score of aberrant crypt foci (ACF). Results: Compared to the DMH + DDS controls, combination of vitamin D3 (200 IU/kg/day) and metformin (240 mg/kg/day) statistically significantly reduced the average number of adenoma/cancer per mouse formed (6.20 ± 3.68 vs. 2.20 ± 2.12, p<0.01), volume (mm3 ) of tumor (115.46 ± 107.32 vs. 31.05 ± 38.26, p< 0.05), number of ACF (0.46 ± 0.88 vs. 2.58 ± 1.93, p <0.01), and ACF score (5.00 ± 3.26 vs. 1.23 ± 2.04, p <0.01). Western blot and IHC show that vitamin D3 potentiates metformin in activating AMPK (phos-AMPK: 0.53 ± 0.01 vs. 0.70 ± 0.03, p < 0.01), inhibiting AKT (phos-AKT: 0.39 ± 0.10 vs. 0.15 ± 0.04, p < 0.01), S6P (phos-S6P: 0.36 ± 0.03 vs. 0.14 ± 0.04, p <0.01), cyclin D1 (0.24 ± 0.02 vs. 0.06 ± 0.02, p <0.01), ?-catenin (0.808 ± 0.142 vs. 0.010 ± 0.001, p < 0.01), and VDR (0.182 ± 0.045 vs. 0.488 ± 0.081). Combination treatment also statistically significantly increases serum levels of IGFBP-3, with little effect on IGF-1, IGFBP-1 or IL-1?. Conclusions: Metformin and vitamin D3 synergistically inhibit the development of colorectal neoplasia in a colitis-associated mouse colon carcinogenesis model. Further study of the underlying mechanisms is warranted.
Downstaging after preoperative chemoradiation as a prognostic marker for recurrence after curative surgery in locally advanced rectal cancer.
Authors: Lee Jieun , Lee Myung Ah , Kim Sang Woo , Kim Jun Ki , Oh Seong Taek , Kang Won Kyung , Jang HongSeok 
Published: March 2020

e14650 Background: 5-fluorouracil (5-FU) based preoperative concurrent chemoradiation (CCRT) with surgery is the standard treatment for resectable rectal cancer. Chemotherapy after surgery improves local control, but there are some debates for the role in 5-FU based adjuvant chemotherapy. This study was aimed to analyze the tumor recurrence pattern in locally advanced rectal cancer, and the relationship between clinicopathologic factors with tumor recurrence. Methods: One hundred forty-nine patients with locally advanced rectal cancer, receiving preoperative 5-FU based CCRT (radiation dose: 5040 cGy) with total mesorectal excision (TME), followed by adjuvant 5-FU based chemotherapy were enrolled. Sex ratio was 95:54. Median age was 61 (range 37~83). Medical records were reviewed retrospectively. Clinicopathologic factors, oncologic outcomes (tumor recurrence, disease free survival (DFS)) were assessed. Results: Median follow-up duration was 25.3 months (range 5.2~66.2). Median DFS was 19.3 months (range 0~63.4). Thirty-five (23%) patients showed recurrence after surgery. Among tumor recurrence, 86% of patients were presented with distant metastases. Absence of T or N downstaging after 5-FU CCRT was significantly correlated with tumor recurrence (P=0.032 and P=0.011 by Fisher’s exact test, respectively) and longer DFS (P=0.003 and P<.001 by Kaplan-Meier survival curve, respectively). Lymphatic invasion, neural invasion after 5-FU CCRT showed correlation with recurrence (HR=6.37, 95% CI; 2.74-14.84, P<.001; HR=4.9, 95% CI; 1.85-12.97, P=0.002, respectively). In contrast, vascular invasion was not associated with tumor relapse after 5-FU CCRT followed by surgery. Conclusions: The absence of T or N downstaging, the presence of lymphatic or perineural invasion in pathology was associated with tumor recurrence. In spite of 5-FU based adjuvant chemotherapy, distant metastases were more prevalent. In patients with the possibility of distant metastases, more aggressive adjuvant chemotherapy-including platinum agents-should be considered.
Serum iron levels potential biomarker in FOLFOX/FOLFIRI with or without molecularly targeted drug therapy.
Authors: Ochiai Takumi , Nishimura Kazuhiko , Watanabe Tomoo , Kitajima Masayuki , Nakatani Akinori , Sato Tsuyoshi , Kishine Kennji , Okubo Satoshi , Futagawa Shunji , Nagaoka Isao 
Published: March 2020

e14651 Background: We reported an increase in serum iron levels during therapy with FOLFOX or FOLFIRI ± molecularly targeted drugs and a correlation between prognosis and transition of those levels in advanced colorectal cancer (CRC) patients (ASCO; 2009: #e15110, 2011: #e14141, 2012: #e14004). The aims of this prospective cohort study were to establish serum iron levels as a new biomarker in advanced CRC patients undergoing therapy based on this correlation and investigate the mechanism of this increase in serum iron levels. Methods: Eighty-one advanced CRC patients were treated; all died between Dec. 2005 and Nov. 2012; none received radiotherapy; 9 of these patients were undergoing treatment between Sep. 2012 and Nov. 2012. Serum iron levels were measured at before and 48 hr after treatment. Taking the median rate of increase in serum iron levels as the cut-off value in each therapy, the patients were categorized into cohort I (increase rate over cut-off value in at least one therapy) or cohort II (increase rate under cut-off value in all therapies). Prognosis was evaluated between the two. Hepcidin (Hepc), Interleukin-6 (IL-6) and soluble transferrin receptor (sTfR) were measured at before and 48 hr after treatment. Results: No significant bias in patient characteristics (including in frequency or type of regimen) was observed between the two cohorts. Serum iron levels transiently increased after treatment (p<0.001), then returning to baseline within 2 weeks. Median survival time (MST) in cohort I (n: 50) and cohort II (n: 31) was 437 and 378 days, respectively, with MST significantly better in cohort I (p=0.0417). Multivariate analysis identified Dukes’ stage, recurrence type, and serum iron level as independent risk factors for overall survival (OS). Hepc significantly increased after treatment (p<0.001), with no significant change in IL-6 or sTfR. Conclusions: Serum iron levels offer potential as an extremely useful and convenient biomarker for OS in CRC patients. While Hepc significantly increased, no significant decrease was observed in sTfR after treatment. This suggests that serum iron levels increased as a result of a treatment-induced reduction in iron consumption by bone marrow.
Benefit-risk evaluation of ziv-aflibercept in combination with irinotecan-fluoropyrimidine-based chemotherapy (FOLFIRI) from the VELOUR trial using multicriteria decision analysis (MCDA).
Authors: Macarulla Teresa , Wu Jasmanda , Phillips Larry , Iqbal Sheikh Usman , Kripas Chris , Gu Zheng , Freedman Amy , Bhargava Pankaj , Van Cutsem Eric 
Published: March 2020

e14656 Background: In the VELOUR trial, in metastatic colorectal cancer (mCRC) patients, ziv-aflibercept (Afl) combined with FOLFIRI demonstrated significant improvements in median overall survival (OS) by 1.44 mos and median progression-free survival (PFS) by 2.23 mos when compared with FOLFIRI + placebo. We utilized a systematic approach to evaluate the benefit/risk profile of the regimen in the target disease population. Objectives: To evaluate favorable and unfavorable effects of Afl in combination with FOLFIRI in patients with mCRC previously treated with an oxaliplatin-based regimen using the MCDA method. Methods: Data from VELOUR were used to compare the 2 treatment arms (Afl + FOLFIRI vs placebo + FOLFIRI). An 8-step process based on the MCDA was used to construct a value tree that displayed evaluation criteria for favorable and unfavorable effects, determined score, assigned weight for each criteria, and then combined weights and scores for each treatment arm to derive an overall value. Sensitivity analysis was also conducted. Results: The final value tree comparing the 2 treatment arms had 2 branches representing favorable and unfavorable effects. Favorable effects criteria included survival probability at 12, 18, and 24 mos, median OS, median PFS, and overall response rate. Unfavorable effects criteria included 11 anti-VEGF- and FOLFIRI-associated adverse events (AEs), as well as deaths and treatment discontinuation due to AEs. The survival rate at 24 mos had the highest weight (100), followed by median OS (95). For unfavorable effects, diarrhea had the highest weight (15), followed by arterial thromboembolism (ATE) (12). AEs seen with Afl + FOLFIRI were generally manageable; their clinical impact did not outweigh the benefits. The overall value combining favorable and unfavorable effects for Afl + FOLFIRI was 53 vs 40 for placebo + FOLFIRI. Conclusions: Results from this quantitative benefit-risk analysis indicate that the benefit-risk balance for ziv-aflibercept in combination with FOLFIRI is favorable compared with FOLFIRI alone in adults with mCRC previously treated with an oxaliplatin-based regimen. Clinical trial information: NCT00561470.
Leucovorin shortage: Impact on leucovorin/levoleucovorin usage and tx choices in colon cancer patients treated in the United States.
Authors: Katler Ann , Wang Zhaohui , Bergstrom Kimberly A. 
Published: March 2020

e14668 Background: 5FU + leucovorin (LV) containing regimens are the most commonly used regimens for colorectal cancer (CRC). A LV shortage in the U.S. beginning Apr 2010 became critical by fall 2011. In May ’11, levoleucovorin (LLV) was approved to treat CRC in the U.S. LV replacement by LLV incurs a 34 fold cost increase. This study examines if the LV shortage impacted colon cancer (CC) regimen selection and LV/LLV usage in the adjuvant and 1st line tx. Methods: Data obtained via web-based, drug dispensing technology was used to identify 3 groups of adult CC patients starting adjuvant or first-line tx within a 6 month period: Group 1 (Q2,Q3 2009), Group 2 (Q2,Q3 2010) and Group 3 (Q4, 2011 – Q1, 2012). Regimen selection and LV usage were examined from tx onset through completion. Results: Adjuvant and first-line tx administered by 545 practices across 47 states was examined and including 2,502 pts, 2,551 pts, and 2,689 pts in Groups 1, 2, and 3 respectively. The median pt age was 66. 77% of pts in each group received FOLFOX for adjuvant tx. Approx 7% of pts in Groups 1 and 2 received capecitabine-containing regimens compared to 9.9% in Group 3. 58% of pts in Group 1, 51% in Group 2 and 56% in Group 3 received mFOLFOX6 or mFOLFIRI + bevacizumab for first-line tx. Use of 5FU + LV or LLV-containing regimens remained constant in all 3 groups. The Table summarizes LV/LLV usage in LV-containing regimens planned for ’09 - Q1 of ‘12. Lower LV dosing and relative dose intensity (RDI), fewer LV administrations and increased LLV usage are seen for the time period reviewed. Conclusions: Based on data examined from 2009-Q1 2012, while no significant impact on regimen selection was observed, the LV shortage significantly decreased LV and raised LLV usage (and cost) in the adjuvant and first-line tx for colon cancer. [Table: see text]
Six years of experience in citoreductive surgery and the application of HIPEC-oxaliplatin.
Authors: Nikolic Srdjan , Zegarac Milan , Djurisic Igor , Martinovic Aleksandar , Kocic Milan , Tomasevic Zorica 
Published: March 2020

e14676 Background: In this abstract we present six years of experience in citoreductive surgery and intraperitoneal chemotherapy (HIPEC) as treatment for patients with peritoneal carcinosis of colorectal carcinoma. Methods: In six years time 61 patient has been operated. Age distribution was from 27 to 76 and median age was 55. Male/female distribution was 18.13%/81.87%. All patients have been treated with intraperitoneal Oxaliplatin with dose of 410mg/m2 in 2 liters of perfusions. In 93.44% cases R0 resection was done and R1 in 3.28%. There was no patient with R2 resection. In 13.1% cases there was Grade I postoperative complication Adjuvant chemotherapy has been applied to 67.21% of operated patients and most had FOLFOX protocol. By the end of this research we still follow up 55,74 % of patients as 44.26% had lethal outcome. Results: Median (95% CI )overall survival(OS) was 51 month(22+ months) . Disease free survival (DFS) was 23 months (16+ months ) . One, two and six years OS was 78.6% ,58.7% and 50.5% One , two and six years DFS was 68.3%, 46.7% and 38.1%. The research has shown that factors such as patient age, sex, preoperative symptoms, synchronous and metachronous carcinosis had no statistically relevant influence on OS. There was statistic relevance in DFS for patients who developed peritoneal carcinosis within 12 months after primary tumor resection(p=0.03) Carcinosis node size has no statistical relevance on OS(p=0.24) and DFS(p=0.64). Involving of left subdiaphragmal region significantly reduces OS(p=0.0022) , but has no statistically relevant influence on DFS(p=0.49). Involving of left iliacal region was on boundary of statistical relevance on OS(p=0.05). Involving of right subdiaphragmal regions statistically significantly reduces OS(p=0.04) , and has no influence on DFS. Involving of small intestine has statistical relevance on OS(p=0.01) As the most important prognosis factor we highlight the peritoneal cancer index (PCI). Patients with PCI less then 13 have statistically better OS (p<0.01) and also statistically better DFS (p<0.05). Conclusions: Our results show that citoreductive surgery followed up by HIPEC with Oxaliplatin should always be considered for patients with colorectal cancer carcinosis.
The impact of multidisciplinary cancer conferences (MCC) on the treatment of metastatic rectal cancer (MRC) at the Ottawa Hospital Cancer Centre (TOHCC).
Authors: Di Valentin Tanya , Asmis Timothy R. , Auer Rebecca Ann C. 
Published: March 2020

e14686 Background: There is significant controversy surrounding the management of surgically resectable MRC. The use and timing of neoadjuvant chemotherapy, pelvic radiation, and relative risks and benefits of a combined surgical resection are areas of debate among surgeons, medical, and radiation oncologists. The TOHCC multidisciplinary Cancer Conferences (MCC) provide an opportunity to discuss these cases and propose treatment plans for these patients. Methods: We conducted a retrospective chart review of all the cases of MRC which were discussed at MCC at the TOHCC from November 2007 until October 2009. Information collected included patient demographics, site of metastases, the treatment they received prior to their case being discussed at MCC (past surgeries, chemotherapy, radiotherapy), the treatment plan discussed at MCC, treatment actually administered post MCC discussion, and patient outcome at 6 months. Results: Forty-two patients with MRC were reviewed. The most common sites of metastases were liver (45.2%) and lung (31%). Once diagnosed with metastatic disease, prior to the MCC, patients had received the following treatments alone or in combination: chemotherapy (33.3%), radiotherapy (21.4%), surgery (19.0%), no treatment (n=57.1%). After their case was presented, 38 patients (90.5%) received the treatment recommended at the MCC , while 4 (9.5%) did not. Treatment post MCC included: chemotherapy (neoadjuvant: 38.1%; adjuvant: 23.8%; palliative: 28.6%), radiotherapy (neoadjuvant: 14.3%; adjuvant: 7.1%; palliative: 7.1%) and surgery (31.0%). Conclusions: There is no standardized approach to the management of MRC. Given its complexity, many cases are reviewed at MCC, which allow coordination for multidisciplinary care of these patients. The results of this study suggest that in a majority of cases, the recommendations brought forth at MCC are indeed acted upon. Given that these meetings have a significant impact on the treatment plan and outcome of patients with MRC, they should represent the standard of care when treating this disease.
Chemokine receptor CXCR4: What is its role in gastrointestinal cancer?
Authors: Lombardi Lucia 
Published: March 2020

e14687 Background: Multiple metastasis is the predominant cause of colorectal cancer (CC) and pancreatic cancer (PC) related mortality. Chemokines receptors have been implicated in cancer metastatic process by directing the migration of tumour cells to sites of metastasis. However, their clinical relevance in gastrointestinal cancer has not been defined. The aim of our study was to evaluate the possible role of CXCR4 as prognostic factor in CC and PC. Methods: Quantitative determination of CXCR4 in serum samples were collected before and after surgery from 36 CC and 23 PC patients later treated with adjuvant (Ad) therapy or for metastatic (Meta) disease (19 Ad-and 17 Meta-CC; 15Ad-PC and 8 Meta-PC) and from 31 healthy controls (HC) enrolled as controls group, was performed by means of ELISA. Relative expression levels of CXCR4 in matched-pairs of tumour and adjacent normal tissue samples collected from the same 36 CC and 15 Ad-PC patients, were determined by means of qRT-PCR using the QuantiFast SYBR Green PCR kit. Results: Compared to HC, pre-operative CXCR4 serum levels were increased in both CC and PC patients. Post-operative serum levels were higher than those observed pre-operatively in 42% and 47% of patients with Ad- and Meta-CC, respectively. Conversely, in 53% and 50% of patients with Ad- and Meta-PC, CXCR4 serum levels decreased after surgical treatment. Furthermore, higher levels of CXCR4 were associated with advanced stages and in PC with lymph nodes involvement. In addition, CXCR4 was over-expressed in tumor compared to normal tissue in 42% and 41% of patients with Ad- and Meta-CC, and in 73% of patients with Ad-PC. In relation to clinical phenotype, all these patients had stage T3N1 disease in both disease. Conclusions: Our data showed that CXCR4 levels may be associated with tumor stage and disease progression in CC and PC patients. Further studies with larger samples size, might confirm the role for CXCR4 as prognostic factor and/or marker of patients’ response to therapy.
An overview of clinical and economic outcomes of U.S. veteran colorectal cancer patients.
Authors: Baser Onur , Fritschel Elyse , Li Lu , Zhang J , Wang Li 
Published: March 2020

e14689 Background: Colorectal cancer is the second leading cause of cancer-related death in the United States. While studies have shown that conditions such as diabetes are associated with shorter disease-free survival in colon cancer patients, fewer U.S. Department of Veterans Affairs (VA)-specific studies have been conducted focusing on colorectal cancer outcomes (Centers for Disease Control and Prevention. Colorectal (colon) cancer. www.cdc.gov/cancer/colorectal. Extermann M. Interaction between comorbidity and cancer. Cancer Control. 2007; 14(1): 13-22). This study aimed to describe the comorbidity profile and economic outcomes of colorectal cancer patients in the VA population. Methods: A retrospective study of patients diagnosed with colorectal cancer during the study period of October 1, 2005 to September 30, 2010 was conducted using the Veterans Health Administration datasets. All colorectal cancer patients were identified using International Classification of Disease 9thRevision Clinical Modification (ICD-9-CM) diagnosis codes 153.xx and 154.xx. Descriptive statistics were calculated as means ± standard deviation (SD) and percentages using SAS version 9.3 software. Results: In diagnosed colorectal cancer patients (n=62,200), common comorbidities included hypertension (n=18,309, 29.44%) and diabetes (n=10,891, 17.51%). Other minor comorbidities included hyperlipidemia and benign neoplasm of the colon. The average Fecal Occult Blood Test result (found in 12.21% of colorectal cancer veterans) was 96.37. Outpatient services were utilized by 99.71% of colorectal cancer patients, followed by pharmacy (91.94%) and inpatient visits (31.15%). Costs for outpatient ($10,637, SD=$17,125), pharmacy ($2,704, SD=$9,773), and inpatient services ($16,032, SD=$53,078) contributed to follow-up health care expenditures. Conclusions: Despite frequent outpatient utilization, inpatient costs have the greatest impact on the considerable health care cost incurred by lung cancer veterans. The presence of comorbid conditions may further complicate colorectal cancer treatment, though further characterization requires further research.