bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arterial stiffness to predict hypertensive response to antiangiogenic drugs.
Authors: Giroux Julie , Alivon Maureen , Briet Marie , Boudou-Rouquette Pascaline , Ropert Stanislas , Cessot Anatole , Durand Jean-Philippe , Boutouyrie Pierre , Laurent Stephane , Goldwasser Francois 
Published: March 2020

e13589 Background: Targeting angiogenesis with anti-VEGF receptors is a new approach for cancer treatment. The most common side effect is arterial hypertension. We hypothesize that pre-existing large artery remodeling with increased arterial stiffness is a determinant of blood pressure (BP) increase under antiangiogenic (AAD) and that AAD may alter mechanical properties of large arteries independently of BP increase. Methods: 49 patients (mean age=57[15] years, mean bSBP=128[22] mmHg and mean DBP=75[11] mmHg; treated for a cancer with an indication to start AAD (Sorafenib, Sunitinib or Bevacizumab) were included in this longitudinal study. Arterial evaluation was assessed at baseline (BL) before the introduction of AAD and every two weeks for 2 months (V1 to V4) with aortic stiffness (PWV) and central BP measurements by aplanation tonometry (SphygmoCor), carotid distensibility with high resolution echotracking system (ArtLab). Results: 43% of the patients developed hypertension between BL and V1. Using linear mixed model analysis with random effects, PWV significantly increased between BL and V1 (BL-V1, adjusted slope 0.89 m/s, F value=6.8, p=0.04) after adjustment to age and mean BP, carotid distensibility decreased significantly during follow-up (BL-V1, adjusted slope= -4.4, p=0.04; BL-V2, adjusted slope= -5.23, p=0.001) after adjustment to age and mean BP. The determinants of BP increase were studied between BL and V1 since anti-hypertensive drugs were introduced after V1. Using multivariate analysis, BL PWV was an independent determinant of the delta brachial SBP (β= -1.36 [-2.61; 0.11], p=0.034) with age (β=0.25 [0.04; 0.47], p=0.02). Conclusions: AAD induce functional alterations of large arteries, increasing arterial stiffness, independently of BP increase. In addition, pre-AAD administration arterial properties influence the hypertensive response to AAD.
Suppression of tumor progression and angiogenesis in two Lewis lung carcinoma mouse models by shRNA knockdown of fibroblast activation protein.
Authors: Xian Shuang , Peng Feng , Wang Chunting , Cai Fan , Wei Yuquan 
Published: March 2020

e13592 Background: Fibroblast activation protein (FAP), a transmembrane serine peptidase, is expressed by tumor-associated fibroblasts. As an important factor in tumor microenvironment, it has been reported that FAP plays a dual role in tumor progression, both positive and negative. In a mouse model of breast cancer, FAP increasing microvessel densities had been experimentally demonstrated. The aim of the study was to determine the effect of FAP in tumor growth and tumor microenvironment in LLC mouse models, especially in lung metastasis model. Methods: Female C57 mice received i.v injection of LLC cells into tail vein or s.c into right flank to establish lung metastasis model or subcutaneous xenograft model. 21 mice were randomly divided into 3 groups (n=7, per group) and treated with 5% GS,control-shRNA or FAP-shRNA, respectively. Xenograft tumor size and weight, numbers of pulmonary metastatic nodules and lung weight were measured. FAP expression, microvessel density and collagen fiber were evaluated. Data were analyzed using one-way analysis of variance (ANOVA), and a value of P <0.05 was considered to be statistically significant. Results: FAP-shRNA decreased significantly in the number of metastases on the lung surface and average lung weight, compared with 5%GS and control-shRNA (P<0.05).The size of metastases in treatment group was large than those of the controls (P<0.05). Moreover, FAP-shRNA showed a significant reduction of 44% in tumor volume and tumor weight, relative to other groups (P<0.05). In both models, FAP expression and microvessel density were lower in treatment group compared to the controls. And FAP-shRNA indicated an increase in the accumulation of collagen fiber. Conclusions: The study suggests that shRNA targeting FAP inhabit tumor growth in LLC mouse models, especially in lung metastasis model. We hypothesize that the anti-tumor mechanism is related to angiogenesis reduction and alteration of collage fibro accumulation, which eventually change tumor microenvironment. These findings indicate the potential of FAP as a new therapeutic strategy for lung cancer.
Uptake of adjuvant chemotherapy (AC) for colon cancer in older and younger patients (pts) in the Irish population.
Authors: Rehman Zia , Coyle Seamus , Sui Jane Sze Yin , Jordan Emmet , Lee Chalen , Deady Sandra , Comber Harry , O'Connor Miriam , Calvert Paula , Horgan Anne M. 
Published: March 2020

e14515 Background: The use of AC in older patients with colon cancer in clinical practice is uncertain. We examined uptake of AC and it’s impact on survival in older pts with stage II and III colon cancer in a national cohort. Methods: Using the National cancer Registry of Ireland, 3,486 pts with stage II and III colon cancer treated with curative resection from 2004-2009 were identified. Clinopathological features and AC use were compared between those ≥70 yrs and those < 70 yrs. Data from a single institution were reviewed to determine drivers of treatment decisions. Results: 2,026 pts with stage II disease were identified, 60% ≥ 70 yrs. AC was utilized in 10% and 40% of ≥ 70 and <70 yrs, respectively (p<0.0001). A benefit for AC over observation was seen in older [HR 0.36; p <0.0001] and younger pts [HR 0.43; p<0.0004]. Of 46 stage II pts from a single institution there were no significant differences between ≥ 70yrs (n=26) and <70yrs (n=23) in terms of ECOG PS, Charlson comorbidity scores (CCI), tumor grade, T3/T4 disease, R0/R1 resections, obstruction/perforation, lymphovascular invasion or nodal yield. However, only 12% ≥ 70yrs received AC compared to 57% of <70yrs (p=0.0002). Of 1,460 pts with stage III disease, 51% were ≥ 70 yrs. 34% of older and 83% of younger pts received AC (p<0.0001). A benefit from AC compared to observation was seen in pts ≥ 70yrs [HR 0.30; p <0.0001] and <70yrs [HR 0.22; p<0.0001]. Of 65 stage III pts from the single institution there were no differences in CCI, ECOG PS, tumor grade, R0/R1 resections between >70yrs (n=20) and <70yrs (n=45). There was a difference in those receiving AC: 75% ≥ 70yrs compared to 96% <70yrs (p=0.02). Conclusions: Adoption of AC is associated with a survival benefit in older pts (age ≥ 70 yrs), however, is still underutilized in clinical practice. Age impacts the decision to treat in our cohort.
North American (NA) subgroup results from VELOUR: Ziv-aflibercept versus placebo plus FOLFIRI in mCRC that is resistant to or has progressed after an oxaliplatin-containing regimen.
Authors: Mitchell Edith P. , Guarino Michael J. , Andria Michael L. , Bhargava Pankaj , Kirshner Jeffrey J. 
Published: March 2020

e14528 Background: Ziv-aflibercept (known outside the US as aflibercept) is a multiple angiogenic factor inhibitor that prevents VEGF-A, VEGF-B, and PlGF from binding their receptors. Ziv-aflibercept in combination with FOLFIRI was FDA approved for metastatic colorectal cancer (mCRC) patients who are resistant to or have progressed following an oxaliplatin-containing regimen. Approval was based on the multinational phase 3 VELOUR trial (N=1226) showing statistically significant improvements in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) with ziv-aflibercept/FOLFIRI. Detailed analyses of the NA subgroup are presented here. Methods: Patients were randomized 1:1 to ziv-aflibercept 4 mg/kg + FOLFIRI or placebo (pbo) + FOLFIRI q2wks. Patients had ECOG PS ≤2 and 1 prior oxaliplatin-based regimen; prior bevacizumab was allowed. Primary endpoint was OS. NA analysis was prespecified but not powered to compare within or between subgroups. Results: NA patients (n=138) were randomized to ziv-aflibercept/FOLFIRI (n=63) or pbo/FOLFIRI (n=75). Baseline characteristics were similar in both arms (ziv-aflibercept: median age 61 y; 60% male; 96% PS 0-1; 56% >1 metastatic organ; 74% prior bevacizumab) and were similar to the worldwide population. Median OS for ziv-aflibercept vs pbo was 17.94 vs 12.88 mos; median PFS was 6.01 vs 4.17 mos; ORR was 12% vs 9%. On average, patients received more cycles (median 8.5 vs 7.0), had longer duration of exposure (median 20 vs 14 wks), and more treatment modifications with ziv-aflibercept vs pbo. Most severe AEs (grade ≥3) with ziv-aflibercept were grade 3, including hypertension, venous thromboembolic events, proteinuria, diarrhea, fatigue/asthenia, infection, stomatitis/ulceration, and neutropenia; there were few grade 4 AEs. Conclusions: Ziv-aflibercept/FOLFIRI in mCRC patients previously treated with an oxaliplatin-based regimen showed improvements in OS, PFS, and ORR with an acceptable safety profile. NA results are consistent with the VELOUR worldwide population. Clinical trial information: NCT00561470.
Survival benefits of adjuvant chemotherapy in high-grade stage II and III colon cancer.
Authors: Tsang Walter , Ziogas Argyrios , Nangia Chaitali Singh , Zell Jason A. 
Published: March 2020

e14529 Background: High-grade (HG; poorly differentiated and undifferentiated) colon carcinoma has an increased risk of recurrence after surgical resection compared to low-grade tumors. However, the benefits of adjuvant chemotherapy (AC) in this patient population remain unclear. Using a large population-based database, we examined survival outcomes of HG stage II/III colon cancer patients treated with or without AC. Methods: Stage II/III adult colon cancer patients with HG tumors who have undergone resection were identified in the California Cancer Registry from 1989 to 2006, with follow-up through 2009. Estimates of Colorectal Cancer Specific Survival (CRC-SS) were generated using Kaplan-Meier methods. CRC-SS multivariate analyses were performed using Cox proportional-hazard regression models adjusted for age, gender, race/ethnicity, histology, tumor site, chemotherapy, time period of diagnosis (1989-1994, 1995-2000, 2001-2006) and socioeconomic status. Results: Significant CRC-SS improvements were observed in stage III patients treated with AC (n=3,793) versus no AC (n=2,582) in univariate (Table) and multivariate analyses (HR=0.89, 95% CI 0.82-0.96). In contrast, among stage II patients treated with AC (n=1,232) vs. no AC (n=3,470), no differences were observed in univariate analyses (Table); furthermore, an increased risk of CRC-specific mortality was observed in multivariate analyses (HR=1.23, 95% CI 1.06-1.44). Conclusions: In high-grade colon cancer, despite significant survival benefits of adjuvant chemotherapy to stage III patients, adjuvant chemotherapy was independently associated with increased mortality in stage II patients. These findings invoke new questions about the utility of adjuvant chemotherapy among patients with high-grade stage II colon cancer. [Table: see text]
Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected pulmonary metastases from colorectal cancer.
Authors: Turan Nedim , Dane Faysal , Unal Olcun Umit , Benekli Mustafa , Kara Hasan volkan , Koca Dogan , Balvan Ozlem , Eren Tulay , Tastekin Didem , Dogan Erkan , Helvaci Kaan , Demirci Umut , Berk Veli , Ozturk Selcuk Cemil , Kucukoner Mehmet , Gumus Mahmut , Oztop Ilhan , Coskun Ugur , Ozet Ahmet , Buyukberber Suleyman 
Published: March 2020

e14533 Background: To determine impact of modern chemotherapy regimens after pulmonary metastasectomy from colorectal cancer (CRC). Methods: A total of 122 consecutive patients who curatively resected for pulmonary metastases of CRC in eleven oncology centers were retrospectively analysed between January 2000 and April 2012. Results: Of 122 patients, 108 who received chemotherapy with fluoropyrimidine-based (n = 12), irinotecan-based (n = 56) and oxaliplatin-based (n = 40) combinations were analyzed. Among these, 52 patients received bevacizumab (BEV) while 56 did not (NoBEV). With a median follow-up of 14 months after metastasectomy, median recurrence-free survival (RFS) was 17 months, overall survival (OS) was not reached. Three and 5-years OS rates were 66% and 53%, respectively. There was no significant difference among cytotoxic regimens in respect to RFS and OS. Similarly, no significant difference was seen between BEV and NoBEV arms in respect to OS and RFS. In univariate analysis prior liver metastasectomy (p = 0.045), positive pulmonary margin (p = 0.028), disease-free interval < 12 months (p = 0.013), and KRAS mutation (0.009) were negative significant prognostic for RFS. Thoracic pathological lymphatic involvement (p = 0.006) and higher prethoracotomy carcinoembryonic antigen (p = 0.038) were negative significant prognostic for OS. In multivariate analysis, positive pulmonary margin was the only negative independent prognostic for RFS, while thoracic lymphatic involvement was the only negative independent prognostic for OS. Conclusions: Chemotherapy type and addition of bevacizumab have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal pulmonary metastases.
Cetuximab with irinotecan or oxaliplatin for first-line metastatic colorectal cancer: Effectiveness in the EREBUS cohort compared to pivotal trials.
Authors: Fourrier-Réglat Annie , Rouyer Magali , Noize Pernelle , Bignon Emmanuelle , Le Monies Alise , Jove Jeremy , Monnereau Alain , Sa Cunha Antonio , Francois Eric , Mitry Emmanuel , Smith Denis Michel 
Published: March 2020

e14542 Background: Cetuximab (CTX) has demonstrated improved survival outcomes in metastatic colorectal cancer (mCRC) but information from real-life use is sparse. Here, CTX survival and safety outcomes in real-life are compared to those observed in OPUS and CRYSTAL trials. Methods: EREBUS is a French multicenter cohort study that included over two years (2009-2010) patients with unresectable mCRC and wild-type KRAS initiating CTX as 1st-line therapy in 65 centres and followed for 12 months from treatment initiation. Results: We included 389 patients treated with a combination of CTX with irinotecan-based (56.0%) or CTX with oxaliplatin-based (37.8%) chemotherapy. The main characteristics, safety, response rate, and one year survival of this cohort are presented in the Table below in parallel with results obtained in pivotal trials. Conclusions: Despite differences in baseline characteristics between real-life and pivotal trials (such as ECOG status), the response rate and PFS were comparable in mCRC patients with wt KRAS treated with 1st-line CTX. The nature of adverse events was in-line with the trials but the frequency was lower probably owing to under-notification in real-life. [Table: see text]
Pooled survival analysis of series using the liver-first approach to the management of colorectal cancer with synchronous liver-limited metastases demonstrates wide variation in outcome.
Authors: Jegatheeswaran Santhalingam , Siriwardena Ajith K. 
Published: March 2020

e14547 Background: Options for the management of patients with colorectal cancer with synchronous liver-limited metastatic disease include synchronous (liver and bowel) resection or sequential surgery: either the classic bowel-first approach or the newer liver-first strategy. This latter approach is popular but has little evidence underlying it. This study undertakes a pooled analysis of protocol and outcome of all reports of the liver-first approach for synchronous metastases. Methods: PubMed, Embase, science citation index, social sciences citation index and the Derwent innovations index were searched using terms describing colorectal cancer, liver metastases and surgery. The literature search identified 417 articles of which 4 cohort study reports described the liver-first approach and reported survival data and constitute the study population. A pre-defined protocol for data extraction was utilised to retrieve data on design, distribution of primary and hepatic metastatic disease, chemotherapy, surgery, patients completing treatment algorithm, outcome and survival. Data were extracted to populate a PRIZMA quality-control chart. Results: The 4 studies comprised 121 patients starting treatment of whom 90 (74%) completed the specified treatment protocol (83 rectal primary, 33 colon primary and primary site unreported in 5). Disease progression during the protocol period occurred in 23 (19%). Ninety six (79%) of the starting cohort of 121 reached the stage of liver resection with disease progression or death during chemotherapy being the principal causes of failure. Preferred algorithm was systemic chemotherapy (median 3 to 6 cycles) followed by hepatectomy with colorectal resection as the last step. There was wide variation between the reports in terms of their survival data. Conclusions: The liver-first approach is technically feasible in patients with colorectal cancer and synchronous hepatic metastases. About 20% will fail to complete the full treatment protocol because of disease progression. To date, there are no data to suggest superiority of outcome over the classic approach or synchronous surgery.
Functional polymorphism in the microRNA-367 binding site as a prognostic factor for colonic cancer.
Authors: Chae Yee Soo , Lee Soo Jung , Kim Jong Gwang , Kang Byung Woog , Lee Yoo Jin , Park Ho Yong , Choi Gyu Seog , PARK JUN Seok 
Published: March 2020

e14549 Background: As microRNAs play important roles in cancer development and progression by regulating the expressions of oncogenes and tumor suppressor genes though interacting with the 3′ untranslated region (UTR) of target genes, we aimed to evaluate the association between genetic variants of miRNAs and their binding sites and prognosis in patients with colorectal cancer (CRC). Methods: Three miRNA variants and four variants in the miRNA binding sites were selected based on allelic frequencies and potential impact described in previous studies. DNA was extracted from fresh-frozen tissues of 344 patients with CRC who underwent curative surgery and genotyping analyses were performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: Among seven target variants, rs1044129 at the miR-367 binding site of calcium channel ryanodine receptor gene 3 (RYR3) was associated with relapse-free survival (RFS) for colon cancer patients as a recessive model in a univariate analysis. Moreover, a multivariate analysis revealed that patients carrying the GG genotype had poor RFS compared to those with the AA or AG genotype (hazard ratio, HR=2.864; p=0.005), yet there was only a marginal trend for disease-specific survival (HR=2.226; p=0.087) regardless of the patient and tumor characteristics. Conclusions: The current study suggests that the functional variant (rs1044129) in the miR-367 binding site of RYR3 may be a potential marker for prognosis in patients after curative surgery for CRC.
The efficacy and safety of XELOX plus bevacizumab with oxaliplatin stop-and-go strategy in first-line treatment for metastatic colorectal cancer: Final report of CCOG-0902 study.
Authors: Hayashi Naomi , Nakayama Goro , Ishigure Kiyoshi , Yokoyama Hiroyuki , Yaguchi Toyohisa , Kojima Hiroshi , Tsuboi Kenji , Ito Akihiro , Deguchi Tomohiro , Sekiya Masanori , Tanaka Chie , Uehara Keisuke , Ando Yuichi , Kodera Yasuhiro ,   Chubu Clinical Oncology Group
Published: March 2020

e14552 Background: XELOX plus bevacizumab (BEV) is an established first line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. The aim of this study was to evaluate efficacy and safety of XELOX plus BEV with oxaliplatin stop and go strategy. Methods: Fifty four patients with unresectable mCRC were enrolled as first line treatment. They were treated with four cycles of XELOX plus BEV, followed by maintenance therapy with capecitabine (Cape) plus BEV. Reintroduction of oxaliplatin was scheduled after eight cycles of Cape plus BEV or upon tumor progression. The primary endpoint was progression free survival (PFS). Results: Forty nine patients (90%) achieved to the maintenance therapy and thirty two patients (59%) were reintroduced oxaliplatin. After a median follow-up time of 24.2 months, median PFS was 13.4 months (95%CI: 11.7-15.1), median duration of disease control was 13.8 months (95%CI: 11.6-16.0) and median overall survival was 29.0 months (95%CI: 23.1-34.9). The response rate and disease control rate were 57.4% and 96.3% in the initial XELOX plus BEV therapy, 6.1% and 73.5% in Cape plus BEV maintenance therapy, and 0% and 72.4% in reintroduced XELOX plus BEV therapy. The incidence of neuropathy was 38% in initial therapy, 33% in maintenance therapy and 43% in reintroduced therapy. Conclusions: XELOX plus bevacizumab therapy with oxaliplatin stop-and-go strategy was feasible to maintain long disease control without increasing severe neurotoxicity in first-line treatment for mCRC. Clinical trial information: UMIN000006478.
Are XELOX and FOLFOX equivalent in colorectal cancer? Dose intensity, toxicity, and treatment duration in clinical practice.
Authors: Gao Ya Ning , Mamo Aline , Palumbo Michael Ostaric , Batist Gerald , Chaudhury Prosanto , Melnychuk David , Metrakos Peter , Panasci Lawrence , Kavan Petr ,   McGill Oncology Group
Published: March 2020

e14556 Background: Xelox and Folfox regimens have been shown to be equivalent in clinical trials for colorectal cancers. However, concerns about toxicity induced by Xelox in clinical practice have been reported, resulting in reduced dose intensity. In this retrospective analysis, we compared the dose intensity of Xelox to Folfox in relation to toxicity. Methods: 208 patients were treated in adjuvant (Xelox: n=56, median age 65 years; Folfox: n=40, median age 66 years) or metastatic (Xelox: n=65, median age 66 years; Folfox: n=47 median age 62 years) settings. 90% of patients had ECOG 0-1. Results: In the adjuvant setting, 86% of patients treated with Xelox received a lower dose of the drug up front, compared to only 10% of Folfox-treated patients. Additional dose reductions occurred in subsequent cycles in 23% of Xelox-treated patients (mean relative dose intensity (RDI) Oxaliplatin: 72%; Capecitabine: 74%) but not Folfox-treated patients (mean RDI Oxaliplatin: 85%, 5-FU: 86%). A higher percentage of Folfox-treated patients had toxicities compared to Xelox-treated patients: nausea (30% vs 18%), diarrhea (47% vs 24%), and peripheral sensory neuropathy (32% vs 3%). Treatment delays were more frequent in Folfox (40%); mean cumulative delay, 9.4 (range 2.1-52.4) weeks, compared to Xelox (20%); mean cumulative delay, 10.2 (3.1-48.1) weeks. Mean treatment duration was equal (Xelox: 22.8 (3.0-78.1); Folfox: 22.6 (2.3-64.4) weeks). In the metastatic setting, results followed a similar pattern. 75% of Xelox-treated patients received a lower dose up front compared to 33% of Folfox-treated patients. Further dose reductions occurred in 31% of Xelox-treated patients (mean RDI Oxaliplatin: 70%; Capecitabine: 67%) compared to 20% of Folfox-treated patients (mean RDI oxaliplatin: 75%; 5-FU: 69%). Treatment delays occurred in 60% of Folfox-treated patients and 43% of Xelox-treated patients becauseof toxicities. Mean treatment duration was 24.9 (3.0-65.0) and 26.1 (4.0-60.1) weeks respectively. Conclusions: The higher dose reduction of Xelox compared to Folfox appeared to enable treatment completion with less toxicities. The impact on survival and cost of treatments will be presented.