bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inmunohistochemical expression of thymidilate synthase, ERCC1, pKDR, and LDH5 as predcitive markers of efficacy in patients with advanced colon cancer treated with XELOX or FOLFOX with or without bevacizumab.
Authors: Garde Javier , Evgenyeva Elena , Mireia Gil raga , Bernet Laia , Juarez Asuncion , Laforga Juan , Gassent Juan Manuel , Demarchi Martin , Camps Carlos , Llombart Antonio 
Published: March 2020

e14671 Background: Low Thymidilate Synthase (TS) and ERCC1 expression have been related with efficacy of Fluoropirimidines and Platinum compounds respectively. High expression of angiogenic related proteins pKDR and LDH5 have been related with worse prognosis. The aim of our study is to analyze the inmunohistochemical expression of these proteins and their role as predictive markers of efficacy in advanced colorectal carcinoma. Methods: Retrospective study of patients with advanced colorectal cancer treated in first line with FOLFOX or XELOX +/- Bevacizumab between 2007 and 2011. Inmunoreactivity has been scored for staining intensity and proportion of positive cells. Staining was semiquantitative evaluated: intensity scored as none (0), to Strong (3), and percentage was categorized into five groups 0 = 0%, 1 (1-25%), 2 (26-50%), 3 (51-75%), 4 (76-100%). Staining and percentage scores were multiplied to obtain final T score (range 0-12), low expression was defined as T score <7, and high expression as T score ≥ 7. Results: 112 patients met inclusion criteria. Median age 68 years, 66 male (58.9%), 87 ECOG 0-1 (77.7%) and 58 (51,7%) with primary tumor removed before chemotherapy treatment. Seventy-five patients received bevacizumab (66.9%). Overall response rate was 56,3%, disease control rate 76.8%, and 18.8% of patients underwent surgery after treatment. Median PFS was 12 months and median OS 23 months. Preliminary results of TS expression showed 33.3% of patients with high vs 66.7% with low expression. There were not differences in response rate (60.7 vs 57.6%, p= 0.49), PFS (12 vs 13 m, p=0.48) or OS (22 vs 20 m, p= 0.6) between patients with low and high TS expression. Inmunohistochemical expression of ERCC1, LDH5 and pKDR is currently ongoing. Conclusions: Low inmunohistochemical expression of Thymidilate Synthase is not associated in our study with better outcomes in patients with advanced colon cancer treated with XELOX/FOLFOX +/- bevacizumab. Predictive value of ERCC1, LDH5 and pKDR expression is been evaluated, pending final results.
Capecitabine plus bevacizumab (Cape-Bev) as a maintenance treatment after induction treatment with FOLFIRI plus bevacizumab (FOLFIRI-Bev) in metastatic colorectal cancer (mCRC).
Authors: Tatli Ali Murat , Coskun Hasan Senol , Uysal Mukremin , Goksu Sema Sezgin , Arslan Deniz , Gunduz Seyda , Ozdogan Mustafa , Bozcuk Hakan Sat , Savas Burhan 
Published: March 2020

e14683 Background: Bevacizumab is human monoclonal antibody that inhibits vascular endothelial growth factor and has been shown improvement progression-free survival and overall survival when combined with chemotherapy for treatment of mCRC in the first and second-line settings. The purpose of this study is to show the effectiveness of maintenance therapy with Cape-Bev in patients with mCRC who benefit of first-line (induction) chemotherapy with FOLFIRI-Bev. Methods: The study included patients with mCRC who received FOLFIRI-Bev as first-line chemotherapy. Maintenance therapy with Cape-Bev (Cape 1000 mg/m2 bid d1-14, Bev 7,5 mg/kg d1 q3w) was given until disease progression to patients who had achieved an objective response after 6-months FOLFIRI-Bev regimen. The time to disease progression, survival and toxic effects were analyzed from the beginning of bevacizumab-based chemotherapy. Results: We enrolled 30 patients, 16 men and 14 women. The mean age of the patients was 62 years. The patients who administered maintenance treatment received a median number of 11 cycles. The median progression-free and overall survivals were 22±4 months and 39±4 months, respectively. Significantly higher PFS and OS were seen among patients who complete or near-complete response to induction therapy with FOLFIRI-Bev (Table). Acceptable hand-foot syndrome was observed 14 patients (%51) treated with the Cape-Bev. No patient experienced severe toxicity. Conclusions: Cape-Bev regimen may be an effective maintenance treatment after response to first-line (induction) FOLFIRI plus bevacizumab treatment in selected mCRC with favorable safety profile. Further studies will be needed to demonstrate conclusively that. [Table: see text]
Sporadic rectal cancers in young adults: Experience from a tertiary cancer center in India.
Authors: Malik Monica , Adavikolanu Kesava Ramgopal , Jilla Swapna , Andra Vindhya Vasini , Lella Yugandhar , Naidu K. V. Jagannath Rao , Pamidighantam Suresh , Sunkavalli Venkata Ratnam 
Published: March 2020

e14694 Background: Recent years have witnessed a trend towards an increase in incidence of rectal cancers in young adults both in western and asian populations. It has been noted that these cancers are more aggressive and associated with poorer outcomes. Methods: We conducted a retrospective analysis of young adults (age ≤ 40 years) with rectal cancers treated at our institute from 2007 to 2012. Information regarding stage, histology, treatment and outcomes were collected from patient records. Patients/family members were contacted for information regarding demographic, socioeconomic, dietary habits and occupational parameters. Disease free and overall survival was analyzed by Kaplan Meier estimates using the SPSS version 20. Results: A of total of 153 cases of rectal cancer were treated between 2007 to 2012 of which 48 patients (31%) were ≤ 40 years of age. Median age at presentation for the younger patients (≤40 years) was 30 years. There were 29 males and 19 females. None of these patients had a positive family history and no synchronous cancers were detected. Six patients were agricultural laborers and four worked in coal or cement factories. 23% of patients hailed from the coastal agricultural belt. At presentation, 41 patients had locally advanced disease and 7 had distant metastases. 25 patients received neoadjuvant chemoradiation, 17 underwent surgery and adjuvant chemoradiation and 6 were treated with palliative intent. Four patients progressed during treatment and eight had recurrent disease during follow up. Median overall survival (OS) was 21 months. 5-year OS was 37.5%. On multivariate analysis, poorly differentiated/mucinous tumors were associated with worse survival (p=0.01). Conclusions: 2-10% of colorectal cancers are reported to occur in young adults with many showing a familial association. In our series we had a higher proportion of young adults with sporadic cancers. Various occupational and environmental factors may be associated with these cancers. They are often detected in late stages and are associated with an aggressive course and unfavorable outcomes; hence early detection is of vital importance. Towards this end, identification of risk factors and screening programs need to be carried out.
Restoration of pro-death function of BAX MSI mutation for selective chemotherapy in colorectal cancer cells.
Authors: Zhang Honghong , Haferkamp Bonnie , Xiang Jialing , Wang Xin 
Published: March 2020

e14707 Background: Microsatellite instability (MSI) is a common cause for a frameshift mutation in Bax the exon 3 microsatellite region leading to Bax-negative phenotype. However, we found that a unique Bax isoform (BaxΔ2) can be generated in combination of the deletion mutation (from G8 to G7) and alternative splicing. BaxΔ2 is a potent cell death inducer and specific to MSI tumors. Methods: The cell death assay, immunoblotting and immunohistochemisty are used for conducting the experiments. Results: The colon cancer cells with Bax G7, not G8, are selectively sensitive to certain chemotherapeutic drugs, such as 5-FU and Adriamycin. Unlike the parental Baxα, BaxΔ2 does not directly target to mitochondria, rather activates the caspase 8-dependent apoptotic pathway. Conclusions: Our data may provide an explanation that some colon cancer patients with “Bax negative” MSI tumor having a better prognosis and suggest that MSI colon cancer with Bax G7 mutation may potentially have a better response to selective chemotherapeutic drugs.
Clinical impact of first response evaluation (FRE) in metastatic colorectal cancer (mCRC) patients (pts) treated with a cetuximab-based regimen (C-R): Results of a mono-institutional experience.
Authors: Rojas Llimpe Fabiola Lorena , Di Fabio Francesca , Giaquinta Stefania , Pini Sara , Adua Daniela , Pinto Carmine 
Published: March 2020

e14717 Background: Some reports suggest positive impact from early tumor shrinkage in progression-free survival (PFS) and overall survival (OS) in mCRC pts receiving C-R. The aim was to evaluate the clinical impact of FRE in mCRC pts treated with a C-R in first-line (1st-L) or after 1st-L. Methods: Between May 2004 and Dec. 2012, 73 pts referred to our institution. The FRE was assessed 8-10 wks after the start of treatment by a CT-scan according to RECIST criteria 1.0. At the time of FRE, pts who achieved CR/PR were considered as responders (resp), and SD/PD as non-responders (non-resp). Were included KRAS wild-type (KRAS-wt) and KRAS undefined tumors (KRAS-ud). PFS and OS are reported in months. Results: Pt characteristics: 51M (70%) and 22F (30%); median age 62(27-80) yrs; 59 colon (80.8%) and 14 rectum (19.2%); median number of metastatic sites 2 (1-5); synchronous mts 47 (64.4%), metachronous mts 26 (35.6%); 46 (63%) KRAS-wt, 27 (37%) KRAS-ud. Twenty-nine (39.7%) pts were treated with C-R in 1st-L (all KRAS-wt), and 44 (60.3%) after 1st-L (17 KRAS-wt, 27 KRAS-ud). C was combined with FOLFIRI in 36 (49.3%) pts, irinotecan in 36 (49.3%), and was alone 1 (1.4%). At the time of FRE 26(35.6%) pts were resp: 13 1st-L and 13 after 1st-L; 47 (64.4%) were non-resp: 16 (34%) 1st-L and 31 (66%) in after 1st-L. In pts treated as 1st-L, the PFS in resp vs non-resp was: 13 (95% CI 6-20) vs 5 (95% CI 4-5) (p=0.03); the OS was: 23 (95% CI 11-34) vs 11 (95% CI 9-13) (p=0.11). In pts treated after 1st-L the PFS in resp vs non-resp was: 13 (95% CI 8-18) vs 5 (95% CI 0.4-9) (p< 0.0001); the OS was: 17 (95% CI 12-21) vs 12 (95% CI 6-19) (p 0.67). In the KRAS-wt pts the PFS in resp vs non-resp was: 13 (95% CI 11-15) vs 5 (95% CI 4-6) (p 0.00); the OS was 23 (95% CI 16-30) vs 11 (95% CI 8-14) (p 0.02). In the KRAS-ud pts the PFS, in resp vs non-resp was: 9 (95% CI 0-20) vs 3 (95% CI 0-8) (p 0.00), the OS was: 18 (95% CI 1-36) vs 13 (95% CI 10-15) (p 0.03). A Cox regression model, including: sex, age, KRAS, line of therapy, FRE, skin rash grade, shows that the FRE was the main predictor of PFS (p<0.0001) and OS (p=0.011). Conclusions: The FRE seems to predict the clinical outcome in pts receiving C-R as 1st-L or after 1st-L.
Phase I/II trial of carbon-ion radiotherapy with concurrent gemcitabine for patients with locally advanced pancreatic cancer.
Authors: Shinoto Makoto , Yamada Shigeru , Yasuda Shigeo , Imada Hiroshi , Shioyama Yoshiyuki , Honda Hiroshi , Kamada Tadashi , Tsujii Hirohiko , Saisho Hiromitsu 
Published: March 2020

e15008 Background: Carbon-ion radiotherapy (CIRT) offers the potential advantage of improved dose localization and enhanced biologic effect. The purpose of this trial was to establish the recommended dose of gemcitabine and CIRT, evaluating the tolerance and efficacy of gemcitabine combined with CIRT for the treatment of the patients with locally advanced pancreatic cancer. Methods: Patients with histopathologically proven, locally advanced pancreatic adenocarcinoma, which involved the celiac trunk or superior mesenteric artery without distant metastasis, were eligible for this trial. The radiation fractions were fixed at 12 fractions in 3 weeks, and the dose of gemcitabine and radiation were gradually increased. First, the dose was fixed at 43.2GyE/8 fractions and the gemcitabine dose was increased from 400, to 700 to 1000mg/m2. Subsequently, the gemcitabine dose was fixed at 1000mg/m2 and the radiation dose was increased from 43.2GyE to 55.2GyE by 5% increments. Gemcitabine was administered for 3 consecutive weeks, once a week. Results: Seventy-five patients were registered from April 2007 through February 2012. Of these patients, 71 were clinically eligible for the study. The most common Grade 3 acute toxicities were hematological toxicity (51%) and anorexia (8%). Dose limiting toxicity developed in three patients: Grade 3 gastric ulcer in 1 and Grade 4 leukopenia in 2. No other serious side effects were found. The two-year local control rate and two-year overall survival rate were 40% and 40% in all patients. The median survival time was 21 months. In the high dose group (n=47), in which patients were irradiated with at least 45.6 GyE, the two-year survival rate was 62%. Conclusions: CIRT was well tolerable even when concomitantly administered with the highest dose of gemcitabine (1000mg/m2).
What are NCI-designated cancer centers using for gastric and esophageal cancer HER2 testing?
Authors: Trosman Julia R. , Weldon Christine B. , Tsongalis Gregory J. , Schink Julian C. , Benson Al Bowen 
Published: March 2020

e15010 Background: HER2 testing in gastric and esophageal cancers (GEC) is a new area with evolving research on which testing methods are best. Based on the ToGA trial, guidelines recommend IHC/reflex to FISH, but studies show effectiveness of other protocols as well (e.g. Yan et al, J Clin Pathol 2011). Our study provides a benchmark on practices for GEC HER2 testing at NCI Cancer Centers. Methods: We conducted an IRB approved web survey of 58 NCI cancer centers (pathologists and oncologists) providing adult GEC care. The survey included 14 questions on HER2 testing methods, reflex and retest practices and awareness of institutional lab accreditation. Results: The study achieved a response rate of 93% (54/58 sites). In this cohort, 41% (22/54) of sites conduct HER2 GEC tests using concurrent FISH and IHC methods. An IHC testing method with reflex to FISH is used at 39% (21/54) of sites, of which all 21 sites reflex IHC 2+ results, and 9 of 21 automatically reflex IHC beyond 2+ (see table, results are not mutually exclusive). FISH only testing is done at 15% (8/54); concurrent FISH and CISH testing at 2% (1/54); concurrent SISH and IHC testing at 2% (1/54), and SISH only testing at 2% (1/54) of sites. The survey separately asked about HER2 testing methods for breast cancer (BC), which were compared by site to GEC HER2 practices: 65% (35/54) of sites conduct HER2 testing in a similar manner - analogous methods in similar order (p= 0.0471); 19% (10/54) of sites use primary IHC in GEC but primary FISH in BC, and 17% (9/54) of sites conduct primary or concurrent FISH testing in GEC but primary IHC in BC. Lab CAP certification for their sites was known by 89% (56/63) of GEC pathologists vs 34% (19/56) of GEC oncologists (p < .0001). 67% (42/63) of GEC pathologists were aware of whether their lab underwent a HER2 IHC and/or FISH proficiency test, vs 4% (2/56) of GEC oncologists (p<.0001). Conclusions: For gastric and esophageal HER2 testing, concurrent FISH and IHC and expanded reflex testing, beyond IHC 2+ results, are the common practice at the NCI cancer centers. [Table: see text]
A phase I/II study of biweekly docetaxel (D) in combination with fixed-dose cisplatin plus fluorouracil (CF) in patients (pts) with advanced esophageal cancer (AEC) (JCOG0807).
Authors: Hironaka Shuichi , Tsubosa Yasuhiro , Mizusawa Junki , Kii Takayuki , Kato Ken , Tsushima Takahiro , Chin Keisho , Tomori Akihisa , Okuno Tatsuya , Taniki Toshikatsu , Ura Takashi , Matsushita Hisayuki , Kojima Takashi , Doki Yuichiro , Fujitani Kazumasa , Taira Koichi , Seki Shiko , Nakamura Tsutomu , Kitagawa Yuko ,   Japan Esophageal Oncology Group
Published: March 2020

e15016 Background: Thougha triplet chemotherapy with D plus CF (DCF) has shown promising activity, high incidence of adverse events (AEs) especially in febrile neutropenia (FN) was observed in previous studies for head and neck cancer (TAX323, 324) and gastric cancer (TAX325). To reduce its AEs with keeping activity, we conducted a multicenter open-label phase I/II study of biweekly D plus CF for AEC. Methods: Eligibility criteria included histologically proven AEC with measurable disease, age 20 to 75, non-resectable or recurrent disease, performance status (PS) 0 to 1. Pts received escalating doses of D (dose level (DL) 1: 30 mg/m2, DL 2: 40 mg/m2, on days 1, 15) in combination with fixed dose of CF (cisplatin 80 mg/m2 on day 1, fluorouracil 800 mg/m2on days 1-5) repeated every 4 weeks with 3+3 design in phase I part (P-I). The primary endpoint of P-I was dose limiting toxicity (DLT) and that of phase II part (P-II) was response rate (RR) defined by central peer review. Based on a SWOG two stage design (p0=35%, p1=50%; one-sided a=0.1, β =0.2) at least 22 responders among 50 eligible pts should be observed to satisfy the primary endpoint. Results: Between Feb 2009 and Mar 2010, 62 pts were enrolled for P-I and P-II. In P-I, 10 pts were enrolled with DLT of 0/3 in DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended dose for P-II was determined as DL1. Thus, 3 (P-I) and additional 52 pts (P-II) were analyzed: 53 for efficacy (excluded 2 ineligible pts) and 55 for safety. Pts characteristics were as follows: male/female 49/6, age median 61 (range 44 to 75), PS 0/1 39/16. The RR was 62% (95% confidence interval, 48-75%, p<0.0001) by central peer review. Median OS and PFS were 11.1 and 5.8 months. Grade 3/4 toxicity was observed in neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%) and nausea (11%). No grade 3/4 FN was observed. Treatment related death occurred in one patient due to pneumonitis. Conclusions: Biweekly D (30mg/m2) combined with CF showed promising activity and tolerability. A phase III study comparing CF with DCF is warranted. Clinical trial information: UMIN000001737.
Efficacy of platinum chemotherapy agents in the adjuvant setting for adenosquamous carcinoma of the pancreas.
Authors: Wild Aaron Tyler , Dholakia Avani Satish , Fan Katherine Y. , Kumar Rachit , Laheru Dan , Diaz Luis A. , Zheng Lei , Le Dung T. , De Jesus-Acosta Ana , Ellsworth Susannah G. , Hacker-Prietz Amy , Voong K Ranh , Weiss Matthew , Hruban Ralph H. , Tran Phuoc T. , Cameron John L. , Pawlik Timothy M. , Wolfgang Christopher Lee , Herman Joseph M. 
Published: March 2020

e15028 Background: Pancreatic adenosquamous carcinoma (PASC) is a rare morphological subtype of pancreatic adenocarcinoma. PASC accounts for only 1-4% of exocrine pancreatic cancers and carries a particularly poor prognosis. Due to the rarity of PASC, studies of therapies specifically targeting this histopathologic entity are exceedingly limited. Based on efficacy exhibited by platinum agents against squamous carcinoma of other body sites, addition of these agents to adjuvant regimens may benefit patients with PASC. This retrospective study was performed among the largest series of patients with PASC identified to date in order to determine whether addition of platinum agents improves survival. Methods: Records of all patients who underwent pancreatic resection at our institution from 1986-2012 were reviewed to identify those with PASC. Demographic, surgical, pathologic, adjuvant therapy, and survival data were collected. Patients were divided into non-platinum (NPG) and platinum (PG) groups based on whether or not they received a platinum agent as part of adjuvant therapy. Results: In total, 62 patients with PASC were identified among 5,627 cases (1.1%). Fourteen patients received a platinum agent in the adjuvant setting (PG), while 48 did not (NPG). These two groups were comparable in regard to median age (65 vs. 69 yrs, p=0.34), gender (36 vs. 46% female, p=0.50), performance status (78 vs. 79% ECOG 0, p=0.98), histologic grade (86 vs. 77% grade 3, p=0.49), positive resection margins (14 vs. 29%, p=0.26), lymph node involvement (71 vs. 79%, p=0.54), median tumor diameter (4.0 vs. 4.3 cm, p=0.64), and proportion receiving radiotherapy (57 vs. 42%, p=0.31). PG patients received a median of 5.5 cycles (IQR, 3.3-6.0) of platinum chemotherapy, with 10 patients (71%) receiving cisplatin-based regimens and 4 (29%) receiving oxaliplatin-based regimens. PG patients experienced significantly longer median survival (19.1 months, 95% CI 12.8-25.4) compared to NPG patients (9.8 months, 95% CI 7.3-12.4) (p=0.024). Conclusions: Addition of a platinum agent to adjuvant regimens for resected PASC may improve survival among these high risk patients, though collaborative prospective investigation is needed.
From functional genomics to precision medicine: The therapeutic potential of targeting ROCK signaling in pancreatic cancer.
Authors: Chin Venessa T. , Nagrial Adnan , Chantrill Lorraine A. , Chang David K. , Chou Angela , Humprhis Jeremy , Cowley Mark , Wu Jiamin , DiPetro Renee , Watson Clare , Spielman Calan , Steinmann Angela , Pinese Mark , Pettitt Jessica , Johns Amber , Waddell Nicola , Grimmond Sean , Timpson Paul , Biankin Andrew Victor , Pajic Marina ,   Australian Pancreatic Cancer Genome Initiative
Published: March 2020

e15029 Background: Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options for metastatic disease. PC is a genetically highly heterogeneous disease that lends itself to a personalised approach to translational research (Biankin et al. Nature. 2012 Nov 15;491(7424):399-405.). Genomic sequence data from the Australian Pancreatic Genome Initiative (APGI) has identified a subset of patients with ROCK-1 amplification. ROCK-1 is a downstream target of Rho, a small GTPase, which is involved in cell adhesion and motility and has been shown to play a role in cancer cell growth and invasiveness (S. Boeck, P. Stieber, et al. Oncology 2006; 70:255., Lane J, Martin T et al. Int J Onc 2008; 33:585-593.). Our aim is to identify biologically and clinically relevant, targetable phenotypes for PC by examining therapeutic efficacy of two ROCK-1 inhibitors, Y-27632 and fasudil in model systems with aberrant Rho/ROCK signaling. Methods: Using extensively characterised model systems of PC, including unique primary patient derived xenografts (PDX) and patient derived cell lines (PDCL) established in the laboratory, we are examining the efficacy of individualized rationally designed combination therapies based on targeting Rho/ROCK signaling. Using innovative techniques, including organotypic assays, we are examining the effect of the targeted approach on cell proliferation, migration, invasion and metastasis in relevant models of PC. Results: Here we demonstrate significant differential sensitivity of pancreatic PDXs and PDCLs with aberrant Rho/ROCK signaling to ROCK combination therapy when compared with standard therapy, gemcitabine. Finally, these compounds impair invasiveness of human pancreatic tumour cells, suggesting that ROCK-1 is a targetable phenotype for the treatment of PC. Conclusions: By carefully defining the key cancer subtypes and expanding our knowledge about the interplay of the key regulators and activators of the Rho/ROCK pathway, the promise of ROCK inhibitors for PC therapy may be realized. As fasudil is already in clinical use for the treatment of cerebral vasospasm, this work may be quickly translated to the clinic.