bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensive CT scan surveillance for patients who have undergone curative intent treatment for colorectal cancer: The Medstar Washington Hospital Center experience.
Authors: Leventakos Konstantinos , Lu Stanlee Santos , Perry David John 
Published: March 2020

e14675 Background: The current ASCO guideline for surveillance after curative intent treatment of colorectal cancer is yearly CT scan of the chest, abdomen and pelvis with every 3-6 months history and physical exam and serial measurement of Carcinoembryonic antigen (CEA). The benefit of doing more intensive CT scan surveillance has not been adequately substantiated. Methods: Data of patients with resectable stage I-III colorectal cancer treated at Medstar Washington Hospital Center from January 2000-June 2012 were retrospectively reviewed. Epidemiologic, histopathologic , surveillance schedule (CT scan and CEA), and survival data were analyzed. Our institutional standard was to obtain CT scans every 3 months for the first year, every 6 months for the second year and then yearly for years 3-5. Results: Thirty-three patients with adequate documentation were included. The mean age of the patients was 59.6 years at diagnosis, 55% were female and 78% ethnically African American. 6% were in stage I, 37% were in stage II and 57% in stage III. CT scan was used in 100% of the patients done with a median interval of 7 months. At follow up, 28 (85%) patients had recurrence at a median of 21.6 months from surgery. 67% had recurrence in the liver. 96% of these recurrences were diagnosed primarily by CT scan and only 1 patient (3%) was diagnosed with MRI of the liver following an elevated CEA with a negative CT scan. Only 50% of patients with recurrence had an elevated CEA. 54% of patients with recurrence were able to undergo curative treatment (resection and/or chemotherapy). Conclusions: In this single institution, retrospective review, CT scan surveillance was utilized more frequently than specified in current ASCO guidelines. CEA screening alone would have missed 50% of patients with potentially curable recurrent cancer. Our data shows that more intensive CT scan surveillance led to earlier detection of recurrences that allowed patients to undergo curative intent treatment. A prospective study is warranted to further support this finding.
UGT1A1*28 polymorphism and vomiting in advanced colorectal cancer.
Authors: El Bastawisy Ahmed El Saied , El-Zeiny Amany , Farid Samar , Bahnasy Abeer 
Published: March 2020

e14678 Background: UGT1A1*28 polymorphism is associated with neutropenia and diarrhea in previous reports, this study tried to investigate correlation with other toxicities like vomiting. Methods: This is a prospective case control study including all eligible cases of advanced colorectal cancer. The genotypes of UGT1A1*28 was assessed in the peripheral blood and/or in tissues by PCR. Patients were divided into two groups, group1: patients with no or hetero mutation, group 2: patients with homo mutation. All patients received standard IFL regimen. Primary endpoints were: 1-comparison between the 2 groups as regard vomiting .2-assessement of the incidence of UGT1A1*28 polymorphism. Secondary endpoints were: comparison between the 2 groups as regard: neutropenia, diarrhea, progressive diseases (PD), progression free survival (PFS) and overall survival (OS). Results: 43 cases of advanced colorectal cancer aged between 19 and 68 years with a median age of 45 years were included and followed up during the period from September 2010 to January 2013 with a median follow up of 9 months. UGT1A1*28 polymorphism were present in 21 patients (42%) of them 14% are homozygous. Grade (II-III) vomiting was found in 18.9% of group 1 versus 66.7% of group2. (P=0.03).Grade (II-IV) neutropenia were found in 27% of group 1 versus 83.4% of group2. (P=0.01). Grade (II-III) diarrhea was found in 37.8% of patients of group1 and 16.7% of patients with group 2. (P=0.44).20% of group 1 showed PD versus 40% of group 2. (P=0.5).1year PFS was 19% in group 1 versus 0% in group 2. (P= 0.74) while there was a trend towards better OS in group 1 (47% versus 0%). (P= 0.0892). Conclusions: UGT1A1*28 polymorphism is present frequently (42%) in a Caucasian population and is associated with more vomiting and neutropenia.
Choice of sequential biologic therapies in metastatic colorectal cancer (mCRC): A cost comparison analysis for wild-type KRAS mCRC patient population in Brazil.
Authors: Weschenfelder Rui , Buschinelli Caio Timko 
Published: March 2020

e14679 Background: Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death in Brazil. Metastatic disease affects up to 50% of patients resulting in 5-year survival of less than 10%. Therefore, there is an increasing interest about the best treatment options, mainly regarding biologics and their sequencing across first line (1L) and second line (2L) treatment of mCRC. Modern series show that the probability of a patient receives 1L, 2L and a third line (3L) therapy is approximately 99%, 70% and 40%, respectively. In addition, in 2012, the ML 18147 study demonstrated the benefit of sequential use, 1L and 2L, of bevacizumab (bev) based combination in mCRC and considering this emerging data, it is important to understand the implications in terms of costs for the Brazilian private healthcare system. Methods: A costing tool was developed to compare the sequencing costs of 1L → 2L regimens used for treatment of wild-type KRAS mCRC patients. Dosing schedules were derived from labels, clinical trials and expert opinion. Analysis was performed from a private payer perspective and included drug-acquisition and administration costs only. Sequences in the ML18147 study (1L bev 5mg/kg+FOLFOX → 2L bev 5mg/kg+FOLFIRI and 1L bev 5mg/kg+FOLFIRI→2L bev 5mg/kg+FOLFOX) were compared to another frequently used sequence in Brazil where bev is replaced by cetuximab(cet) in 1L (1L cet 400-250mg/m2+ FOLFIRI → 2L bev 5 mg/Kg + FOLFOX). Results: Average costs per patient per month were Brz 21,285.50 for sequences with bev in 1L and 2L and Brz 24,191.68 when bev is replaced by cet in 1L. The average cost savings per patient for the entire treatment were Brz 28,767 (1L bev 5mg/kg + FOLFOX → 2L bev 5mg/kg + FOLFIRI vs 1L cet + FOLFIRI → 2L bev + FOLFOX) and Brz 29,938 (1L bev 5mg/kg + FOLFIRI → 2L bev 5mg/kg + FOLFOX vs1L cet + FOLFIRI → 2L bev + FOLFOX). Conclusions: Sequential use of bev in 1L and 2L mCRC according to the ML18147 study protocol is less costly compared to another sequence of biologics that starts with cet in 1L followed by bev in 2L. Resources savings with sequential bev have the potential to optimize 3L treatment strategy for wild-type kras mCRC patients in Brazil.
CTLs/regulatory T-cells ratio as a prediction marker of chemotherapy in metastatic colorectal cancer.
Authors: Sasatomi Teruo , Oochi Takafumi , Ogata Yutaka , Akagi Yoshito , Shirouzu Kazuo 
Published: March 2020

e14684 Background: Many multiple anti cancer drugs regimens have been established for metastaticcolorectal cancer recently. We investigated cellular immunoreaction of these patients to their cancer. Methods: 32 metastatic colorectal cancer patients have been started chemotherapies. Their PBMCs were harvested and investigated their character by Fac scan with fluorescent labeled antibodies (CD3,CD8, CD4, CD25, Foxp3) at before and after chemotherapy. Results: After chemotherapy, both CTLs(CD3, CD8 positive) and regulatory T cells (CD4, CD25, Foxp3 positive) were decreased in number among all patients. On the other hand, CTL/T reg ratio were significantly increased among tumor marker decreased patients and significantly decreased among tumor marker increased or stable patients. CEA levels among 85.7% of increased CTL/T reg ratio patients became to decrease less thanhalf. CEA levels among 66.7% of decreased CTL/T reg ratio patients became to increase or to be stable, if their regimens have not been changed. The Reactive Rate of chemotherapy of CTL/T reg ratio increased patients was significantly higher than that of ratio decreased or stable patients. (P=0.021) The Disease Control Rate of chemotherapy of CTL/T reg ratio increased patients was higher than that of ratio decreased patients. Both resectability rate of liver metastatic lesion and early tumor shrinkage rate were higher at the CTL/T reg ratio increased patients group than at the other patients group. Conclusions: We found that the CTL/T reg ratios of PBMC in metastatic colorectal cancer patients were useful for prediction of the effect of chemotherapy.
The study on functions and mechanisms of miR-106b in the metastasis of colorectal cancer.
Authors: Ni Shujuan , WANG Qifeng , Tan Cong , Du Xiang 
Published: March 2020

e14685 Background: Emerging evidence has shown that aberrantly expressed microRNAs (miRNAs) are highly associated with tumour initiation, development and progression. However, little is known about the potential role of miRNAs in colorectal cancer (CRC) metastasis. Methods: The miR-106b expression levels in CRC tissues were deteted by quantitative reverse transcription polymerase chain reaction (qRT-PCR) to investigate its relationship with clinical characteristics or survival of CRC patients. Using the CRC cell lines ectopically expressing miR-106b conducted by lentivirus transduction as experimental material, cell culture, cell growth analysis and transwell used to analyze the potential influence of miR-106b on CRC metastasis. In addition, luciferase assays and western blot were used for the target gene study. Results: In this study, we firstly investigate the role and related mechanism of miR-106b in CRC metastasis. We found that miR-106b expression was lower than in CRC compared with their corresponding non-tumorous tissues (P=0.009), and the downregulated miR-106b was negatively associated with lymph-node metastasis. Functional assays demonstrated that overexpression of miR-106b suppressed CRC cell migration and invasion in vitro. In addition, we confirmed that ATAD2 was a direct and functional target of miR-106b. Overexpression of miR-106b in CRC cells could reduce the mRNA and protein levels of ATAD2, whereas miR-106b silencing significantly increased ATAD2 expression. Luciferase assays confirmed that miR-106b could directly bind to 3′ untranslated region of ATAD2. Knockdown of ATAD2 significantly inhibited CRC cell migration and invasion. We further found that ATAD2 was involved in miR-106b-induced suppression of CRC cell migration and invasion. Conclusions: By understanding the functions and molecular mechanisms of miR-106b in CRC, we found mir-106b through targeting ATAD2 inhibited CRC cell migration and invasion. These results suggest that patients with downregulated miR-106b are prone to lymph node metastasis and tumour progression. miR-106b may have a therapeutic potential to suppress CRC metastasis.
Use of VEGF expression to predict for first-line treatment chemotherapy regimen in metastatic colorectal cancer.
Authors: Ozkan Metin , Berk Veli , Deniz Kemal , Karaca Halit , Inanc Mevlude , Bozkurt Oktay , Duran Ayse Ocak 
Published: March 2020

e14695 Background: In metastatic colorectal cancer treatment more successful results are achieved by adding anti-angiogenic therapy to the chemotherapy. Over expression of VEGF in colorectal cancer is known to be a poor prognosis factor but its effects on designating the therapy is not clear. In this study, results of the patients receiving FOLFIRI + Bevacizumab or XELOX + Bevacizumab were compared for VEGF expression. Methods: VEGF was assessed immunohistochemically in primary tumors of the 53 metastatic colorectal cancers. Severity and conformity of VEGF expression was evaluated. Results were used to assess the association with the therapy response, progression free survival (PFS) and overall survival (OS). Results: The median age of the patients was 55 (range, 32-79). In combination with bevacizumab 38 patients received FOLFIRI and 15 patients received XELOX. In 30 patients (57%) there was a strong expression of VEGF and in 23 patients (23%) the expression was weak. In the high VEGF expression group, PFS was 11 months in FOLFIRI receiving patients and 8 months in XELOX receiving ones but in low expression group PFS was 8 months in patients receiving either one of the two treatment protocols. In high expression group, PFS in FOLFIRI-bevacizumab combination receiving patients was different and this difference was statistically significant (p=0.009). Overall survival in FOLFIRI receiving patients with high VEGF expression was 26 months and with low VEGF expression it was 16 months (p=0.04). Median OS was not reached in the XELOX receiving patient group. FOLFIRI regime clinical benefit was 58% in high VEGF expression group whilst it was 34% in low expression group. This difference was not statistically significant but it was close to the significance threshold (p=0.06). There was no association between the therapy responses and VEGF expression of the 15 patients who received XELOX. Conclusions: There is no difference in efficacy between the first line chemotherapy regimens of the metastatic colorectal cancer. In this study, in metastatic colorectal patients with over expressed VEGF first line FOLFIRI-bevacizumab combination led to better response and survival rates.
Results of monoclonal antibodies against EGFR-receptors application in patients with metastatic colorectal cancer (mCRC).
Authors: Vladimirova Liubov Yu , Kit Oleg Ivanovich , Nikipelova Elena A , Abramova Natalya A 
Published: March 2020

e14701 Background: Monoclonal antibodies against the epidermal growth factor receptor(EGFR)are standard components of treatment in mCRC.This study was designed to evaluate the tolerability and efficacy of the combinations of Panitumumab(P) and Cetuximab(C) with chemotherapy in patients with wild type(WT) KRAS tumors mCRC. Methods: Mutation analysis of KRAS(codons12,13) was done on samples at diagnosis. Key elegibility criteria included measurable mCRC stage IV, ECOG ≤2, adequate liver,kidney and bone marrow function, no brain metastases. P was administered 6mg/ kg 1 day q2w. C was administered 400mg/m² 1day and 250mg/m² q1w. Combination with FOLFOX-6 or FOLFIRI pegimens was allowed. Endpoints include response rate, OS, PFS and safety. Results: Of 38 testable samples there were 21(55.3%) WT KRAS tumors. All of these 21 (13male and 8female) pts were recruited. Mean age was 58.1±12.3. Synchronous metastases had 33.3%(7pts). Majority of pts benefited from anti-EGFR combined with cytotoxic chemotherapy 80.9% (17), mostly FOLFIRI – 57,1%(12).There were23.8%(5) in the 1st line CT, 76.1%(16) in the 2nd line CT. 6 mos of the treatment were analyzed. Overall RR was76.1 %(16) including 6PR(28.5%) and 10SD(47.6%). Med OS= 9.1mo, Med PFS= 4.3mo. 8 pts(38.1%) are alive till the abstract submission. Most common toxicities were:skin rash 2/3Gd.-90.5%(19), xeroderma 2Gd.-42.9%(9),skin itch 1/3Gd.-42.9%(9), paronychia 2Gd. -14.2%(3), purulent psorophthalmia 2Gd.-14.2%(3). All kinds of toxicities were controlled by symptomatic medication if necessary and did not lead to anti-EGFR agents dalay. Besides,diarrhea 1/2Gd.- 66.7%(14), 3Gd.-14.3%(3), neutropenia 1/2Gd.-28.6%(6), 3/4Gd.-9.5%(2), nausea 3/4Gd.- 14.3%(3), vomiting 1/2Gd.- 42.9%(9), fatigue 1/2Gd.-47.6%(10). Conclusions: These results consider significant efficacy of anti-EGFR agents combined with CT in pts with mCRC. Controlled toxicity of the therapy allows to use it widely.
Pathologic response, KRAS status, and bevacizumab: The Bermuda triangle for outcome prediction after hepatic colorectal cancer metastases (HCRM) resection.
Authors: Fanetti Giuseppe , Biondani Pamela , Tessari Anna , Melotti Flavia , Milione Massimo , De Braud Filippo G. , Perrone Federica , Miceli Rosalba , Mariani Luigi , Gevorgyan Arpine , Di Bartolomeo Maria , Pietrantonio Filippo 
Published: March 2020

e14716 Background: Clinicopathologic factors are insufficient to stratify prognosis after HCRM resection. The identification of prognostic biomarkers is an unmet clinical need. Even if the prognostic role of KRAS mutations in the metastatic setting is controversial, recent data hypothesized a correlation to worse outcome after HCRM resections. This analysis evaluated the correlation between KRAS mutation, pathological response and outcome. Methods: Fifty-eight pts with HCRM were resected at National Cancer Institute of Milan from 2007 to 2012 following bevacizumab (Bev) (n=30) or cetuximab (Cmab) (n=28) based neoadjuvant regimens. Tumor regression grade (TRG) was classified from TRG 1 for pathological complete response (pCR), to TRG5 for no response; TRG 1-3 for response; TRG 4-5 for scarce/no response. KRAS exons 2 to 4 were sequenced by direct PCR. Results: KRAS missing in 3 pts (1 Bev/2 Cmab), mutated in 23 (42%) vs wild-type in 32 (58%), mutated in 18 (62%) of Bev group vs 5 (19%) of Cmab. Mean TRG: 2.9 (2.2-4) in Bev vs 3.8 (3-5) in Cmab group (p=0.04 at Kruskal-Wallis test). Pathological response higher for Bev vs Cmab (70% vs 39%; p=0.037 at Chi-square test). Bev also increased pCRs (20% vs 0%, p=0.024 at Fisher’s test). Pathological response higher for KRAS mutant vs wild-type (70% vs 41%; p=0.003 at Chi-square test). At log-rank test, DFS significantly shorter for KRAS mutated vs wild-type (7.6 vs 14.6 months; p=0.05), and for TRG4-5 vs TRG1-3 (8.1 vs 15.3 months; p=0.02), while no difference observed according to treatment. OS data are not mature. Multivariable Cox model for DFS shown in the Table. Conclusions: After Bev-based neoadjuvant treatment, patients with KRAS mutated HCRM and without good pathological response may have the worst outcome after curative resection. [Table: see text]
Iiteglinα4 (ITGα4) rs7562325 polymorphism was associated with better survivals in Austrian but not in Japanese patients with gastric cancer.
Authors: Iqbal Syma , Wakatsuki Takeru , Bohanes Pierre Oliver , Zhang Wu , Gerger Armin , Azuma Mizutomo , Stotz Michael , Yang Dongyun , Ning Yan , Volz Nico Benjamin , Stintzing Sebastian , El-Khoueiry Rita Elie , Labonte Melissa Janae , Li Joseph Ethan , Maus Martin K. H. , Koizumi Wasaburo , Watanabe Masahiko , Barzi Afsaneh , Lenz Heinz-Josef , El-Khoueiry Anthony B. 
Published: March 2020

e15009 Background: Integrins mediate cell-extracellular matrix and cell-cell interactions. It has been demonstrated that integrins may play a crucial role in carcinogenesis, progression, and metastasis.Recently, we demonstrated that ITGα4 rs7562325 C/T, ITGβ1 rs2298141, and ITGβ3 rs4642 were associated with outcomes in stage II and III adjuvant colorectal cancer in the US cohort. To apply these results in gastric cancer, we tested whether ITGpolymorphisms could predict outcome in two ethnically and epidemiologically different GC cohorts from Japan and Austria. Methods: Sixty-three (stage Ib-III) Austrian patients and one-hundred and sixty-nine Japanese (stage Ib-IV) with histopathologically-confirmed localized GC (AJCC-6th) were enrolled from 2001 to 2010. Both cohorts were treated with D2 lymphadenectomy based surgery. Results: The median DFS and OS in the Austrian cohort were 4.0 and 4.8 years, while median DFS and OS in the Japanese cohort were 4.8 and 5.8 years, respectively. Adjuvant chemotherapy was conducted 109 (64%) patients in the Japanese cohort, while 14 (22%) patients in the Austrian cohort. Only ITGα4rs7562325 C/T were associated with survivals in the Austrian cohort; patients homozygous T/T (n=10) showed a median DFS of 20.1+ years vs. 2.8 years in patients harboring at least one-C allele (n=53) (HR: 9.18 [95%CI: 1.25-67.5] p=0.029). Similar finding was also seen for OS; patients homozygous T/T showed a median OS of 20.1+ years vs. 4.3 years in patients harboring at least one-C allele (HR: 9.33 [95%CI: 1.27-68.6] p=0.028). In multivariate analysis stratified by stage and gender, this result was conserved in DFS (HR: 9.40 [95%CI: 1.26-69.9] p=0.029), but not in OS (HR: 1.77 [95%CI: 0.87-3.62] p=0.112). These results were consistent with previous our results of adjuvant CRC in the US cohort; however, we could not validate these findings in patients with GC in the Japanese cohort. Conclusions: ITGα4 rs7562325 polymorphism was associated with longer DFS in Austrian patients with GC, not in Japanese patients. Ethnic difference and different implementation rates of adjuvant chemotherapy between Austria and Japan may influence these results.
Impact of virologic factors on recurrence-free survival in HBV-related hepatocellular carcinoma after surgical resection: Post hoc analysis from a prospective study with long-term follow-up.
Authors: Chiang Nai-Jung , Chen Miin-Fu , Hsiao Chin-Fu , Lee Po-Huang , Chen Pei-Jer , Chen Li-Tzong ,   Taiwan Cooperative Oncology Group (TCOG)
Published: March 2020

e15032 Background: To investigate the impact of virologic factors on recurrence of post-operative hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in a prospective study population with long-term follow-up. Methods: 183 patients who had participated an adjuvant trial with detectable HBV DNA and of genotype B and/or C and negative for anti-hepatitis C antibody were included. All analyses were censored upon Dec 30st, 2010. Results: The genotype distribution was B in 99 (54.1%), and C or mixed B+C (C/B+C) in 84 (45.9%). Genotype C/B+C infected patients had significantly higher incidence of HBeAg-seropositivity, high baseline HBV viral load, elevated serum ALT level, and underlying cirrhosis than patients with genotype B infection. The median time-to-recurrence (TTR) was 94.9 months and 33 months for genotype B and C/B+C infected patients, respectively (p=0.0495), and that for viral titer <104 and ≥104 copies/mL was 129.8 and 39.9 months, respectively (p=0.059). Tumor size >5 cm (p=0.008), presence of venous invasion (p=0.007) and moderately or poorly differentiation (p=0.039) were adverse prognostic factors for TTR in multivariate Cox’s regression analysis, but neither HBV DNA titer nor genotype. Of patients with tumor size ≤5 cm, HBV genotype C/B+C and baseline HBV viral load ≥104 copies/mL are significant adverse prognostic factors for TTR. On the other hand, microvascular invasion but not viral factor was prognostically significant for tumor size >5 cm subpopulation. Compared with patients with neither genotype C/B+C infection nor baseline viral load ≥104 copies/mL, the relative risk for TTR of patients with either and both of the virological risk factors was 2.581 (p=0.068) and 3.384 (p=0.019), respectively, for the entire study cohort. Conclusions: HBV genotype and baseline viral load are associated with risk of recurrence in post-operative HCC, especially in patients with tumor ≤5 cm. Adjuvant anti-viral therapy may be more likely benefit to curatively resected small HBV-related HCC patients, which is currently tested in TCOG1206 trial.