bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential HER2 expression in resected gastric cancer: Is there prognostic value?
Authors: Fisher Sarah B. , Fisher Kevin E. , Squires Malcolm Hart , Patel Sameer H. , Kooby David A. , Staley Charles A. , Farris Alton B. , Maithel Shishir K. 
Published: February 2017

54 Background: For advanced gastric cancer, the ToGA trial established HER2 as an important therapeutic target in the 20% of patients whose tumors exhibited HER2 overexpression or gene amplification. Others have reported that HER2-positive tumors are associated with poor survival in advanced disease. The expression profile and prognostic value of HER2 in resectable gastric cancer are unknown. Methods: 111 pts underwent curative intent resection of gastric adenocarcinoma between 1/00-6/11 and had tissue available for analysis. Immunohistochemistry (IHC) for HER2 was performed on banked tumor specimens and graded by two pathologists blinded to outcomes utilizing ToGA trial criteria. An IHC score of 0+ or 1+ was regarded as negative, 3+ as positive. Fluorescence in-situ hybridization (FISH) for HER2 was performed on equivocal (2+) IHC samples. Primary outcome was differential expression, secondary outcome was overall survival (OS). Results: Median age was 64 years, 54% were male. Median tumor size was 4 cm, 7.2% had a positive margin, 67.6% were poorly differentiated, 23.4% had perineural invasion, 35.1% had lymphovascular invasion, and 61.3% had nodal metastases. 24 patients had stage I disease (21.6%), 32 stage II (28.8%), and 55 stage III (49.6%). Mean follow-up was 28.9 months, median OS was 27.2 months. HER2 expression by IHC was negative in 61 (55%), equivocal in 37 (33.3%), and positive in 13 (11.7%). Of the 37 equivocal cases, FISH was positive in 8, for a total of 21 HER2-positive cases (18.9%) and 90 HER2-negative cases (81.1%). HER2 status did not correlate with T or N stage, tumor size or location, tumor grade, or perineural or lymphovascular invasion. HER2 status was not associated with OS (p=0.36). Conclusions: Resectable gastric cancer exhibits differential expression of HER2, similar to that of advanced disease. Despite reports suggesting HER2 positive status is associated with aggressive disease and worse outcomes in the advanced setting, HER2 status is not associated with adverse pathologic factors or survival in resectable disease. Although not prognostic, the predictive value of HER2 status for response to trastuzumab in the adjuvant setting requires further investigation.
Correlation of capecitabine associated hand-foot syndrome (HFS) and objective tumor response in patients with metastatic colorectal cancer (mCRC) treated with sorafenib and capecitabine (SorCape).
Authors: Chan Ellie , Ivey Alison Marguerite , Dang Long H. , Daily Karen Colleen , Hou Wei , Viviano Dana Lynn , Watson Scott , Granicz Renee , McEwan Margaret A. , Yan Hui , Allegra Carmen Joseph , George Thomas J. 
Published: February 2017

568 Background: Capecitabine (cape) associated hand-foot syndrome (HFS) has been previously reported to be a clinical predictor of improved survival or disease control in metastatic colorectal cancer (mCRC) and breast cancer. This study evaluates the relationship between degree of HFS and objective tumor response in patients (pts) receiving capecitabine and sorafenib (sor) for mCRC as part of an ongoing clinical trial. Methods: Pts with refractory mCRC treated on phase II prospective study with SorCape (NCT01471353) were eligible. 24 of 43 planned pts have been enrolled and all are assessable. Adverse events (AEs) related to HFS were graded by CTACE v4 during the first 3 cycles of therapy and scored as mild (graded 0 or 1), moderate (mod) (grades 2 or 3) or severe (grade 4). Independent RECIST criteria measurements of target tumor volumes were recorded with maximal volumetric regression or progression noted. The correlation between degree of HFS and objective RECIST response was analyzed. Results: Total cohort pt demographics and tumor characteristics are presented separately. 5 (21%) had mild HFS and 19 (79%) developed mod HFS. No pts had severe HFS. Baseline characteristics including age were similar in both groups. Univariate analysis showed no significant correlation between KRAS mutational status, baseline serum CEA, or LDH levels. Pts with mild HFS had a mean 25% (1-68% regression) tumor regression compared to a 20% progression (22% regression to 80% progression) with moderate HFS (p=0.046). Progression free and overall survival data are immature for analysis. Conclusions: In this exploratory analysis of an ongoing clinical trial, the degree of HFS negatively correlated with objective tumor response. The combination of overlapping HFS AEs with this specific dual therapy may impact the previously reported clinical predictor. Ongoing patient enrollment and further analysis of this clinical observation is planned. Clinical trial information: NCT01471353.
Phase II study of first-line combined chemotherapy bevacizumab with modified RPMI regimen for elderly or frail patients with unresectable or metastatic colorectal cancer (OGSG0802).
Authors: Iwamoto Shigeyoshi , Kato Takeshi , Yoshida Motoki , Miyake Yasuhiro , Nakamura Masato , Satoh Taroh , Sakai Daisuke , Matsuoka Masaki , Otsuji Toshio , Furukawa Hiroshi 
Published: February 2017

573 Background: The first-line combined chemotherapy RPMI regimen with bevacizumab (Bmab) in AVF2192g trial for elderly or frail patients (Pts) could be active to progression free survival (PFS), the secondary endpoint, although it may not prolong overall survival (OS), the primary endpoint. According to the results of efficacy and safety studies, a fluoropyrimidine (FU) + Bmab regimen is regarded as an option for 1st-line chemotherapy. We planned a phase II study of modified RPMI regimen with Bmab for elderly or frail Pts. Methods: Pts with confirmed unresectable/metastatic colorectal cancer without previous chemotherapy, and not suitable for intensive chemotherapy were enrolled. Pts received modified RPMI regimen (5-FU 600 mg/m2 and l-leucovorin 200 mg/m2 bolus day 1, 8, 15) and Bmab 5 mg/kg day 1, 15, q4w) until disease progression or study withdrawal. The primary endpoint was overall response rate (ORR), and the secondary endpoints were PFS, OS and safety. Results: 41 Pts were enrolled from 13 institutions. Pts characteristics were; median age 76 (range 56-90); male/female, 18/23; ECOG performance status 0/1/2, 21/19/1. The ORR, the rate of best response, the disease control rate (CR+PR+SD) were 36.6%, 56.1%, 85.4%, respectively. Median follow-up period was 14.4 months. 28 Pts (68%) had objective progression and a patient (2.4%) died without progression. The median PFS and OS were 9.0 months (95%CI, 7.5–19.6) and 24.0 months (95%CI, 20.1–NR). The incidences of grade 3 or 4 adverse events were: leukopenia (7%), neutropenia (24%), thrombocytopenia (2%), diarrhea (5%), anorexia (10%), fatigue (5%), stomatitis (7%) and hypertension (5%). Grade 3 febrile neutropenia and grade 4 pulmonary embolism was observed in one pt. Five pts (12%) discontinued the treatment due to severe or uncontrollable adverse event. Conclusions: The modified RPMI regimen with Bmab showed activity, and was well tolerated for elderly or frail Pts. ORR and the median PFS of this regimen were similar to historical data with FU + Bmab. This regimen may be a good option for not requiring percutaneous port placement Pts. Clinical trial information: UMIN000002182.
CEA response as a predictive marker for response according to RECIST in patients with KRAS wild-type metastatic colorectal cancer (KRAS WT mCRC) (pts) treated with panitumumab monotherapy.
Authors: van Hellemond Irene E. G. , Creemers Geert-Jan , van Warmerdam Laurence , de Jong Floris A. , Koornstra Rutger H. T. 
Published: February 2017

574 Background: Panitumumab is a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR) and is approved as treatment in KRAS WT mCRC in combination with chemotherapy and in chemotherapy-refractory pts as monotherapy. In mCRC, CEA decrease is often used as an early response predictor, but correlative studies with RECIST and formal cutoff criteria are scarcely available. Here we report on an exploratory analysis in KRAS WT mCRC pts treated with monotherapy panitumumab. Methods: A series of 29 KRAS WT mCRC pts who have been treated with panitumumab monotherapy (6 mg/kg once every 2 weeks) as second-line treatment were included (58% male; mean age 65,6 years; performance status was 0-1 in 90%). Every 12 weeks, response evaluation by CT-scan was done routinely. Responses were determined using RECIST v1.1. CEA levels were determined every 6 weeks. A CEA response was defined as two consecutive CEA decreases of ≥10% compared to the previous value. Progression was defined as two consecutive CEA increases of ≥10% compared to the previous value. Pts not meeting these criteria were defined as stable. CEA change at week 6 and CEA response at week 12 week were correlated with RECIST response at week 12 using Spearman’s correlation coefficient. Results: A 10% CEA decrease at week 6 was predictive for response according to RECIST at week 12 (r=0.71, p<0.001). Likewise, at week 12, responses determined by RECIST and CEA strongly correlated (r=0.88, p<0.001). Conclusions: Data from this small study suggest that CEA changes may have predictive potential as early time point response biomarker in pts treated with panitumumab monotherapy. More research is warranted to confirm these retrospective findings. [Table: see text]
Population-based patterns of systemic therapy use in liver-limited metastatic colorectal cancer (mCRC).
Authors: Kellock Trenton Tyler , Gresham Gillian , Cheung Winson Y. 
Published: February 2017

576 Background: Treatment of liver-limited mCRC frequently involves systemic therapy and surgery. Our aims were to 1) explore the use and choice of systemic therapy pre- and post-liver resection and 2) examine if specific patient characteristics or therapy regimens were associated with improved outcomes. Methods: Patients diagnosed with liver-limited mCRC from 2006 to 2007 in British Columbia were reviewed. Summary statistics were conducted to describe surgical and systemic treatment patterns. Kaplan-Meier methodology was used to characterize the relationship between systemic regimen and overall survival (OS). Results: Among 374 patients, 42% were aged ≥70 years, 60% were men, 29/39/32% were ECOG 0/1/2+, 80% had primary tumor surgery, and 68% received prior adjuvant chemotherapy. For liver metastases, 95 (26%) were offered hepatic resection. Compared to those who did not receive surgery, resected patients were younger (median 60 vs. 69, p<0.01), better functioning (ECOG 0/1 86% vs. 55%, p<0.01), and had smaller (median 3 vs. 4 cm, p<0.03) and fewer (median 2 vs. 4, p<0.01) lesions. They also had improved median OS (11.0 vs. 9.4 months, p<0.01). Surgical patients having a solitary lesion (p=0.03) or a largest lesion ≤3 cm (p=0.02) experienced better survival. Performance status (HR=0.54, p=0.35), age (HR=0.47, p=0.30), and sex (HR=0.68, p=0.48) did not impact outcomes. Among patients who underwent hepatic resection, 80% received some form of chemotherapy (Table). Median OS did not differ significantly based on choice of chemotherapy: FOLFOX (13.9 months), FOLFIRI (11.5 months), and capecitabine (10.9 months) (p=0.44) or receipt of bevacizumab: yes (14.5 months) vs. no (11.1 months) (p=0.57). Conclusions: In this population-based cohort of liver-limited mCRC patients, hepatic resection was associated with improved survival. Among those offered some form of peri-operative therapy, FOLFOX, FOLFIRI, and capecitabine, either alone or in combination with bevacizumab, appear to be reasonable treatment options. [Table: see text]
Treatment and outcomes of patients with metastatic colorectal cancer (mCRC) with epidermal growth factor receptor (EGFR) therapy in the third-line setting.
Authors: Ho Maria Yi , Renouf Daniel John , Cheung Winson Y. , Zhou Chen , Goktepe Ozge , Lim Howard John , Kennecke Hagen F. 
Published: February 2017

579 Background: Monoclonal antibodies targeting the EGFR improve outcomes of patients with mCRC in the first-, second-, and third-line settings. The optimal treatment setting for use of these agents is not yet defined. In British Columbia, cetuximab and panitumumab are limited to patients with KRAS wild type (wt) mCRC previously treated with 5-fluorouracil (5-FU), oxaliplatin (Ox), and irinotecan (Iri). The objective of this study was to describe the treatment and outcomes of patients with mCRC after the introduction of EGFR targeted therapy in the third-line setting. Methods: All patients with newly diagnosed mCRC and referred to 1 of 5 BC Cancer Agency clinics in 2009 were included. Prognostic and treatment information was prospectively collected while KRAS testing information was determined by chart review. Results: 443 patients with a median age of 66 were included of which 59% were men, 73% received any systemic therapy for metastatic disease of which 13% underwent hepatic resection of metastatic disease. Of 117 patients who received 5-FU, Ox and Iri, 10% were not tested for KRAS. Among those tested, 38% were KRAS mutant. In patients who were KRAS wt, 23% did not receive EGFR therapy. On chart review, poor performance status was the dominant reason for not receiving KRAS testing and anti-EGFR therapy in 67% and 50% of cases, respectively. Median survival of 321 patients who received any systemic therapy for metastatic disease was 22.3 months. Conclusions: In this study, when EGFR therapy is limited to patients with KRAS wt mCRC previously treated with 5-FU, Ox and Iri, only 15% received such therapy and poor performance status was the dominant reason for non-treatment. Earlier initiation of EGFR therapy may increase the proportion of patients treated with all active systemic agents. [Table: see text]
Clinical significance of Fas, VEGF, and EGFR expression in advanced gastric carcinoma.
Authors: Ye Sheng , Rong Jian , Fu Xiaohong , Lin Tongyu 
Published: February 2017

58 Background: Researches had proved that apoptotic signal proteins Fas-mediated cellular apoptosis influenced development of gastric carcinoma and affected survival of gastric carcinoma patients. Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) over expression had been associated with poor survival in several cancers including gastric carcinoma. Methods: Immunohisto-chemistry was performed to detect Fas, EGFR and VEGF protein expression in 60 newly diagnosed patients with gastric carcinoma in the First Affiliated Hospital of Sun Yat-sen University from November 1999 to June 2005. Clinical Data of these patients were reviewed. Time to progression (TTP) and overall survival (OS) were compared by log-rank test according to the expression status of Fas, EGFR and VEGF. Results: There were 40 males and 20 females, all patients were stage IV. All patients were treated with infused fluorouracil plus leucovorin and oxaliplatin or paclitaxel. The positive rate of Fas, EGFR and VEGF in gastric carcinoma was 73.3%, 35% and 40% respectively. TTP for patients with Fas positive was significantly superior to patients with Fas-negative (p<0.05). EGFR and VEGF were not correlated with TTP (p>0.05). Fas, EGFR and VEGF were not associated with overall survival(p>0.05). Conclusions: Fas, EGFR and VEGF are often expressed in gastric carcinoma. Fas expression is correlated with longer TTP. EGFR and VEGF expression were not associated with TTP. Fas, EGFR and VEGF were not a prognostic factor for OS.
A phase II study of oxaliplatin reintroduction in patients pretreated with oxaliplatin and irinotecan for advanced colorectal cancer (RE-OPEN study): Reports of interim analysis.
Authors: Suenaga Mitsukuni , Mizunuma Nobuyuki , Matsusaka Satoshi , Shinozaki Eiji , Ozaka Masato , Ogura Mariko , Chin Keisho , Yamaguchi Toshiharu 
Published: February 2017

580 Background: Re-introduction of oxaliplatin for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens including oxaliplatin, irinotecan and fluorouracil (5-FU) was thought to be effective approach, but has not been prospectively explored. Thus, we performed a single arm, open-label phase II study (UMIN ID: 000004884). Methods: Patients with prior chemotherapy including oxaliplatin and irinotecan, achieved tumor response or stable disease during prior oxaliplatin-based therapy, and six months or over from confirmed progression disease during previous oxaliplatin-based therapy were eligible for this study. Patients received FOLFOX regimens every two weeks. Primary endpoint was disease control rate (DCR) after 12 weeks of treatment. Tumor response was evaluated by RECIST v1.1, and DCR was defined as complete response, partial response or stable disease. This trial followed a Simon’s two-stage minimax design. Interim analysis of efficacy was planned after 12 weeks of treatment in 18 patients (Step I). If disease control were confirmed in more than five patients, 15 patients would be newly enrolled in Step II. Results: Between 01-2011 and 07-2012, 18 patients were enrolled in Step I of this study. Characteristics of patients were as follows (N=18): median age, 61 yrs (range 35-75 yrs); male/female, 11/7; ECOG PS0, 94.4%; and colon/rectum, 8/10. All patients were assigned to receive mFOLFOX6 regimen. Disease control was observed in seven patients. There was no benefit in nine patients. Two patients refused to continue treatment and one patient gave up treatment due to oxaliplatin related allergic reaction. According to the interim analysis, DCR after 12 weeks of treatment was 38.9%. There were no severe adverse events and treatment related deaths. Conclusions: In interim analysis, initial efficacy of reintroduction of oxaliplatin after 12 weeks of FOLFOX regimen was confirmed. Step II part of this study is currently ongoing. Clinical trial information: UMIN000004884.
Clinical application of electrogastrography (EGG) in stomach cancer patients with distal gastrectomy.
Authors: Kim Yong Ho , Choi Sung Il , Song Jae Wook 
Published: February 2017

59 Background: Electrogastrography (EGG) is a method of measuring action potentials of the stomach. The purposes of this study were to investigate postoperative changes in the EGG and then evaluated gastric motility and to determine the correlation between EGG and quality of life (QOL) of stomach cancer patients with distal gastrectomy. Methods: This study analyzed 20 cases of stomach cancer patients between May 2010 and Dec. 2010. All patients were measured EGG and QOL at 1, 12, and 24 weeks after the operation. The EORTC quality of life questionnaire QOL-C30 version 3.0 and QOL-STO22 were used in this study to assess QOL of gastric cancer patients. Results: Fasting and postprandial mean dominant frequency at 1 week after the operation were 2.7 and 2.6 cycles per minute (cpm), and 2.9 and 2.7 cpm at 12 weeks. Fasting and postprandial dominant power at 1 week were 36.5 and 36.4 dB, and 36.3 and 40.1 dB at 12 weeks. After postoperative week 12, the mean percentage of normal rhythm in both recordings was not changed, whereas the mean percentage of bradygastria was decreased and tachygastria was increased. Regarding QOL, global health, physical, emotional and social status were improved, but pain, insomnia, diarrhea, and financial status was worsened at 12 weeks. On the STO22, the correlation between the QOL and EGG parameters was not significant (p>0.05). Conclusions: These suggest that EGG is a simple and noninvasive method and may be applicated for evaluating motility and autonomic functions of the remnant stomach after distal gastrectomy.
Final results of a phase II multicenter study of neoadjuvant S-1 and irinotecan in patients with locally advanced gastric cancer.
Authors: Terashima Masanori , Saze Zenichiro , Hosotani Ryo , Takahashi Masahiro , Takagane Akinori , Hachiya Osamu , Koeda Keisuke , Matsui Shigeyuki , Fukushima Norimasa , Kawasaki Hitoshi , Gotoh Mitsukazu , Fukushima Masanori 
Published: February 2017

65 Background: Combination chemotherapy involving S-1 and irinotecan (IRI-S) has failed to demonstrate a survival benefit over S-1 alone in metastatic gastric cancer. However, the tumor response rate was significantly higher with I-RIS. Therefore, we evaluated the effect of I-RIS as neoadjuvant chemotherapy for locally advanced gastric cancer. Methods: Patients with locally advanced gastric adenocarcinoma, T3-4, N0-3, M0, for whom curative surgery was planned after neoadjuvant chemotherapy, PS 0-1, with adequate organ function were enrolled in this study. Patients received irinotecan 80 mg/m2 on days 1 and 15 and oral S-1 80 mg/m2/day on days 1 to 21. Treatment was repeated every 28 days for 2 courses. Patients then underwent gastrectomy with lymphadenectomy. After surgery, patients resumed treatment with S-1 alone for 1 year. Results: Of the 39 patients enrolled, 37 were eligible. Two cycles of chemotherapy were completed in 34 patients, and surgery was performed in 33 patients. Of 27 RECIST-evaluable patients, 16 (59%) had a partial response and 9 (33%) had stable disease. Major grade 3 toxicities were neutropenia in 6, anorexia in 4, nausea in 3, diarrhea in 2, and fatigue in 2. Resection was performed in 32 (86%) patients and R0 resection was possible in 20 (54%) patients. The reason for R1/R2 were cy+ in 6, M1(LYM) in 5, M1(PER) in 4, M1(HEP) in 1 and PM+ in 2. Postoperative complications were observed in 13 (39%) patients. There were no treatment-related deaths. Pathological response was observed in 13 of 32 patients (41%); 2 patients had pathological CR. Median survival time was 15.9M and median progression-free survival (PFS) was 5.9M. Overall survival and PFS were significantly better in patients underwent R0 resection (p < 0.0001). Neither objective tumor response nor pathologic response predicted the survival. Conclusions: These results show that neoadjuvant S-1 and irinotecan combination chemotherapy was active and feasible for treating locally advanced gastric cancer. R0 resection is essential to achieve long-term survival. Therefore, careful diagnosis with staging laparoscopy before surgery is mandatory to avoid non-curative operation. Clinical trial information: NCT00134095.