bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical activity of MM-111, a bispecific ErbB2/ErbB3 antibody in previously treated ErbB2-positive gastric and gastroesophageal junction cancer.
Authors: Lahdenranta Johanna , Paragas Violette , Kudla Arthur J. , Overland Ryan , Moyo Victor M. , Nielsen Ulrik , McDonagh Charlotte , Onsum Matthew 
Published: February 2017

48 Background: ErbB2 (HER2) overexpression has been reported in 7-34% of gastric cancers. ErbB3 (HER3) is the preferred dimerization partner of ErbB2, and ErbB2/ErbB3 heterodimer activation is implicated in the progression and metastasis of ErbB2+ tumors. Activation of ErbB3 signaling is a postulated resistance mechanism to current ErbB2-directed therapies and select chemotherapies. In line with this research, ErbB3 levels are associated with poor prognosis in gastric cancers. MM-111 is a bi-specific antibody that docks to ErbB2 and inhibits ErbB3 signaling in cells that overexpress ErbB2. In this study, MM-111 was evaluated in ErbB2+ gastric cancer by testing the activity of MM-111 in ErbB2+ pre-clinical models of gastric cancer, and by assessing the prevalence of potentially predictive biomarkers in a panel of archived gastric and gastroesophageal junction (GEJ) tumors. Methods: MM-111 was tested in ErbB2+ gastric cancer xenografts that were either untreated or after tumors ceased to respond to trastuzumab/5-FU. Xenografts were analyzed at multiple time points for the expression of ErbB-receptor family members and their downstream signaling by Luminex -assays. Preclinical data indicate that ErbB2, ErbB3, and heregulin are predictive biomarkers for MM-111. In order to determine the prevalence of our potentially predictive biomarkers in gastric and GEJ cancers, we obtained commercially archived tumor tissue and assayed the tissue for ErbB2 and ErbB3 expression levels using quantitative IHC, and measured heregulin transcript levels by RT-PCR. Results: MM-111 synergizes with various treatment regimens in the 2nd line treatment setting in ErbB2+ gastric cancer xenografts. In our models, the combination of MM-111, trastuzumab, and paclitaxel is particularly effective after tumors progressed on trastuzumab/5-FU. MM-111 inhibits the activity of the ErbB –signaling axis in these models. In addition, 23% of GEJ tumor samples and 20% of gastric samples were positive for potentially predictive biomarkers. Conclusions: ErbB2+xenograft tumors that stop responding to trastuzumab-based therapies benefit from MM-111–based regimens.
Phase II study of sorafenib and capecitabine (SorCape) in previously treated metastatic colorectal cancer (mCRC): NCT01471353.
Authors: George Thomas J. , 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 
Published: February 2017

489 Background: Sorafenib (Sor) is an oral multi-tyrosine kinase inhibitor (TKI) affecting tumor proliferation and angiogenesis through inhibition of the Ras/Raf/MEK/ERK, VEGF and PDGF pathways. Inhibition of the MEK/ERK pathway through Raf has been shown to resensitize tumor cells resistant to chemotherapy. A similar TKI, regorafenib, has recently demonstrated efficacy as monotherapy in advanced mCRC. Demonstrating activity of this class of compounds with standard cytotoxic therapy represents a clinical unmet need for patients (pts) with mCRC. Methods: Eligible pts had progressive mCRC after prior oxaliplatin and irinotecan, at least 1 measurable target lesion by RECIST, ECOG PS 0-1, and adequate organ function. Pts received Cape (1000mg/m2PO BID D1-14) and Sor (400mg PO BID max via dose escalation per cycle). Cycles were q21d with tumor assessments q9w. Endpoints included progression-free survival (PFS), objective and biochemical response rates, overall survival (OS), toxicity, and quality of life. Sample size was based on a 50% improved median PFS from 3 (historical) to 4.5 months (m). Results: 24 of 43 planned pts have received therapy. 19 were white and 17 male. Median age 61y (37-79). 14 (58%) were KRAS-mut. Median prior lines of therapy for mCRC was 3 (1-5). All but one had liver and/or lung metastases. Most frequently observed adverse events (AEs) included fatigue (29%), HTN (38%), and HFS (91%). 18 pts (75%) had a grade 3 AE (11/18 were HFS). There were no grade 4 or 5 toxicities. Preliminary PFS is 4.1m. 5/16 (31%) evaluable pts have radiographic stable disease. Conclusions: Enrollment continues with manageable AEs, despite the overlapping toxicity of HFS. Preliminary PFS data appears promising in this refractory mCRC population. Clinical trial information: NCT01471353.
Prospective analysis of UGT1A1 promoter polymorphism for irinotecan dose escalation in metastatic colorectal cancer patients treated with bevacizumab combined with FOLFIRI as the first-line setting.
Authors: Yeh Yung-Sung , Huang Meng-Lin , Lu Chien-Yu , Wang Jaw-Yuan 
Published: February 2017

491 Background: Infusional fluorouracil/leucovorin plus irinotecan-based regimen (FOLFIRI) with bevacizumab has been widely used as first-line treatment for patients with metastatic colorectal cancer (mCRC). We prospectively analyzed the influence of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotyping for irinotecan dose escalation in mCRC patients treated with combination of FOLFIRI and bevacizumab as the first-line setting. Methods: A total of 65 mCRC patients undergoing first-line treatment with FOLFIRI combined with bevacizumab were analyzed. Genotypes were performed by analyzing the sequence of TATA box of UGT1A1 of genomic DNA from the patients. Genotype and clinical parameters were compared by univariate analysis. The irinotecan dose is escalating form 180 mg/m2 to 260 mg/m2 in UGT1A1 6/6 or 6/7, and from 120 mg/m2 to 210 mg/m2 in UGT1A17/7. Results: The response rate was observed in 44 of 60 UGT1A1 6/6 or 6/7 (73.3%) in comparison to 1 of 5 UGT1A1 7/7 (20%) patients (p=0.013). The grade III-IV adverse events (AE) was observed in 4 of 60 UGT1A1 6/6 or 6/7 (6.7%) in comparison to 3 of 5 UGT1A1 7/7 (60%) patients (p<0.001), but it was not different between age of ≥ 70 and < 70 (p=0.559). Fifteen of 60 (20%) patients with UGT1A1 6/6 or 6/7 could be performed with liver or lung metastaectomy in comparison to none of 5 patients with UGT1A1 7/7. In addition, the disease control rate was significantly higher in irinotecan dose of ≥ 210 mg/m2 than irinotecan dose of < 210 mg/m2(p=0.015). Conclusions: UGT1A1 promoter polymorphism was found to be predictive of toxicity and efficacy in mCRC patients with first-line treatment of FOLFIRI combined with bevacizumab. The higher dose of irinotecan (≥ 210 mg/m2) may achieve a better disease control rate but do not increase the incidence of GR III-IV AE in mCRC patients of age ≥ 70 years.
Differences in outcome between right- and left-sided colon cancer: A population based study.
Authors: Aarts Frits , de Hingh Ignace , de Wilt Johannes HW , Lemmens Valery E. P. , Verhoeven Rob H.A. 
Published: February 2017

493 Background: Colon cancer is the second most frequent cause of cancer death, with an increasing incidence during the last decade. Recently, there is an increased interest in possible differences in outcome after surgery between right- and left-sided colon carcinoma (RCC and LCC). Methods: A population based study was performed in the south part of the Netherlands covering a region with more than 2 million inhabitants. Patients suffering from either RCC or LCC, excluding rectal cancer, were compared with regard to epidemiological, clinical and histological parameters as well as survival data. A Cox proportional hazard model was used to estimate the impact of different parameters on survival. Results: The data of 12,731 patients with colon cancer from January first 2000 and December 31 2010 were analyzed. Of these, 42% was RCC and 55% was LCC. In the remaining 3% of patients the location was not otherwise specified. In comparison with LCC, the majority of RCC patients were female (53% vs. 46%) and older (42% vs 34% > 75 years). The majority of RCC (77%) and LCC (87%) was non-mucinous adenocarcinoma. In RCC, 18% of tumors were mucinous adenocarcinoma vs 10% in LCC, p< 0.001. Well differentiated tumors were more common in LCC, 70% vs 58% in RCC Moderately and poorly differentiated tumors were more present in RCC compared to LCC (23% vs 13%, p<0.0001). Stage I tumors were more common for LCC vs stage II-IV tumors in RCC, p<0.0001. In RCC 1-9 lymph nodes were found in 37% vs 51% in LCC. In RCC 49% >10 LN were found vs 34% in LCC. No difference was found between anatomical sites regarding tumor positive LN, nor in LN ratio. Synchronous distant metastases were present in 30% of RCC vs 25% in LCC. Median overall survival in RCC was 46 months vs 60 months in LCC, p<0.0001. Survival differed between age groups and location and was worse for RCC with age 45-59 yrs: RCC vs LCC p<0.0008, age 60-74 yrs: RCC vs LCC, p<0.0006). Also, in T4 tumors, survival was worse for RCC, p<0.007. Conclusions: Prognosis of colon carcinoma is correlated to anatomical distribution with a significantly worse prognosis for RCC patients. Since RCC is more common in people of older age and the incidence is increasing, these findings may have future implications for the planning of treatment strategies.
Intensity-modulated radiation therapy versus 3D conformal radiation therapy for squamous cell carcinoma of the anal canal.
Authors: Chuong Michael , Freilich Jessica , Hoffe Sarah , Fulp William J. , Weber Jill , Almhanna Khaldoun , Dinwoodie William R. , Meredith Kenneth , Shridhar Ravi 
Published: February 2017

494 Background: The emergence of intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer has dramatically lowered the incidence of severe toxicity while maintaining excellent long-term outcomes. We compared our institutional experience using 3D conformal radiation therapy (3DCRT) versus IMRT for anal cancer. Methods: We performed a single-institution retrospective review of all non-metastatic squamous cell carcinoma anal cancer patients treated between 2000-2011 using definitive chemoradiation with curative intent. Results: This study included 89 consecutive anal cancer patients (37 3DCRT, 52 IMRT). Median follow-up for all patients, IMRT patients alone, and CRT patients alone was 26.5 months (range, 3.5-133.6), 20 months (range, 3.5-125.5), and 61.9 months (range, 7.6-133.6), respectively. Three-year overall survival (OS), progression free survival (PFS), locoregional control (LRC), and colostomy free survival (CFS) were 91.1%, 82.3%, 90.8%, and 91.3% in the IMRT cohort and 86.1%, 72.5%, 91.9%, and 93.7% for the 3DCRT patients (all p>0.1). More patients in the 3DCRT group required a treatment break (11 vs. 4; p=0.006), although the difference in median treatment break duration was not significant (12.2 vs. 8.0 days; p=0.35). Survival outcomes did not differ based on whether a treatment break was required (all p>0.1). Acute grade ≥3 non-hematologic toxicity was significantly decreased in the IMRT cohort (21.1 vs. 59.5%; p<0.0001). Acute grade ≥3 skin toxicity was significantly worse in the 3DCRT group (p<0.0001) while an improvement in late grade ≥3 GI toxicity was observed in the IMRT patients (p=0.012). Conclusions: This is the largest retrospective review comparing 3DCRT and IMRT for definitive treatment of anal cancer. In contrast to previously published data, this study demonstrates that while long-term outcomes do not significantly differ based on RT technique, a marked decrease in adverse effects and the need for a treatment break can be achieved using IMRT.
Predicting outcomes in locally advanced rectal cancer using pretreatment FDG-PET imaging.
Authors: Fernandes Annemarie Therese , Whaley Jonathan Taylor , Teo Kevin , Plastaras John Peter , Metz James M. , Perini Rodolfo F. , Pryma Daniel A. , Apisarnthanarax Smith 
Published: February 2017

495 Background: FDG-PET/CT imaging has been shown to have clinical utility in the management of rectal cancers. The purpose of this study was to investigate multiple FDG-PET/CT parameters to predict for outcome after neoadjuvant chemoradiation (CRT) in patients (pts) with locally advanced rectal adenocarcinoma. Methods: We retrospectively evaluated pts with locally-advanced (T2-4, N0-2, M0) rectal adenocarcinoma treated with neoadjuvant CRT who received FDG-PET/CT scans for radiation therapy planning. We evaluated the impact of SUVmax and metabolic tumor volume (MTV, determined by using PET Edge MimVista), as well as dual-time point PET parameters of retention index (RI, difference in SUVmax between the two PET scans) and RI/time. Endpoints of pathologic complete response (pCR), tumor grade, margin status and pathologic downstaging were assessed using t-test, ANOVA or non-parametric analysis when appropriate. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan Meier estimates. Results: Of the 28 consecutive pts with FDG-PET/CT planning scans identified, 25 pts underwent surgical resection. All patients received a 5-FU based concurrent chemotherapy regimen with RT (median RT dose: 50.4 Gy). Median follow-up was 21 months. The median MTV was 45 cc. Compared to pts with a MTV>45 cc, pts with a MTV <45 cc had improved PFS (2-yr PFS: 86% vs. 60%, p=0.04) and improved OS (2-yr OS: 100% vs. 51%, p=0.01). The correlation between MTV and T-stage was not statistically significant (23% of pts with MTV>45 had T4 tumors vs. 0% of pts with MTV<45, p=0.17). MTV did not correlate with the other endpoints (pCR, tumor grade, margin status, pathologic downstaging). SUVmax did not correlate with any of the identified endpoints. Of the patients with dual-time point PET/CT scans (N=19), RI and RI/time did not correlate with any of the identified endpoints. Conclusions: Pretreatment MTV correlates with PFS and OS in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation. For pts with large MTVs, more aggressive treatment approaches should be considered. Dual-time point FDG-PET imaging does not appear to add clinical value in this patient population.
Phase II trial of irinotecan, S-1, and bevacizumab (IRIS/Bev) combination chemotherapy as second line for advanced colorectal cancer (NCCSG04).
Authors: Takii Yasumasa , Hurukawa Kouichi , Maruyama Satoshi , Yamazaki Toshiyuki , Nishimura Jun , Kawahara Mikako , Tomiyama Takemi , Akazawa Kohei , Hatakeyama Katsuyoshi 
Published: February 2017

496 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853-860) previously demonstrated the non-inferiority of Irinotecan plus S-1 (IRIS) to FOLFIRI for metastatic colorectal cancer (mCRC), with progression-free survival as the primary endpoint. IRIS plus bevacizumab (IRIS/Bev) was reported an active and generally well-tolerated first-line treatment for mCRC (Yuki et al. ASCO 2012 #3593). We planned a Phase II trial to evaluate the efficacy and safety of IRIS/Bev as second-line therapy for patients with mCRC. Methods: The study design was multicenter, single-arm, open-label phase II study. Eligible patients had to have mCRC with confirmed diagnosis of adenocarcinoma, history of oxaliplatin containing regimen as first-line therapy, an age from 20 to 80 years, ECOG performance status (PS) of 0-1. S-1 65 mg/m2 daily p.o. was given on days 1-14 and Irinotecan 75mg/m2 and Bevacizumab 10mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall response rate (OR), overall survival (OS), time to treatment failure (TTF) and safety. Results: From 08/12 until 11/06, 35 patients were enrolled. One patient did not start therapy. Thirty-four patients were investigated. Median age was 63 years (range, 38 to 82). Twenty-five patients were male. The mean of relative dose intensity of TS-1/Irinotecan/Bev were respectively 92.1%/87.0%/86.2%. The OR was 21.1% (7/33) and disease control rate was 84.8% (28/33). Median PFS was 9.3 months, median TTF was 8.2 month and median survival time 23.1 month. On safety analysis, the incidence of grade 3 or 4 adverse reactions were as follows: neutropenia, 14.7%; fatigue, 14.7%; white blood cell decreased, 11.8%; anorexia, 8.8%; anemia, 8.8%; diarrhea, 2.9%; proteinuria, 5.9%; thromboembolic event, 2.9%. Conclusions: IRIS/Bev is an active and well-tollarated second-line treatment for patients with mCRC. Clinical trial information: UMIN000001631.
Metastatic colorectal cancer and management in public versus private hospitals: Similarities and differences.
Authors: Field Kathryn M , Shapiro Jeremy David , McKendrick Joseph J , Wong Hui-Li , Desai Jayesh , Lipton Lara Rachel , Kosmider Suzanne , Nott Louise M. , Stefanou Gregory , Parente Phillip , Zimet Allan Solomon , Lim Lionel , Jennens Ross , Yip Desmond , Burge Matthew E. , Gibbs Peter 
Published: February 2017

497 Background: Potential differences between public and private cancer care in Australia include the degree of subspecialisation, multidisciplinary clinic review, access to clinical trials and continuity of care, all of which could impact treatment and outcomes. Here we compared demographics, tumour details, treatment and survival outcomes for patients (pts) with newly diagnosed metastatic colorectal cancer (mCRC) treated in the public versus private setting. Methods: This research was conducted using the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) mCRC clinical research database. Data collection began in June 2009 and is ongoing at 15 Australian centres. Here, data from four public and eight private hospitals are presented. Results: Of 671 pts, 253 (38%) were treated at public hospitals and 418 (62%) at private centres. For public versus private pts there was no significant difference in median age or percentage with good performance status. More private pts received first-line chemotherapy (89% vs 80%, p=0.002), but there were no significant difference in the use of bevacizumab (50% versus 43%, p=0.10). Similar proportions received combination therapy (72% private vs 68% public) but the use of single agent oral capecitabine was higher for private patients (9% vs 4%, p=0.03). More public pts were enrolled in a first-line clinical trial (17.3% vs 1.2%, p<0.0001). Preliminary analysis suggests improved overall survival for private pts (26 months versus 17 months, p<0.001). Conclusions: While public and private pts in this cohort were similar in age and performance status, significantly more private pts were given chemotherapy, but similar proportions were given bevacizumab and far less were enrolled on first-line clinical trials. This may relate to availability of first-line trials during this period. The superior survival outcomes achieved in private practice must be further explored, and might reflect a more intense approach to treatment, yet-to-be identified differences in patient characteristics, or differences in quality of care.
XELOX with bevacizumab in elderly patients age 75 or older with metastatic colorectal cancer: Results of a planned interim analysis for multicenter phase II ASCA study.
Authors: Ishibashi Keiichiro , Munemoto Yoshinori , Matsuoka Masaki , Hata Taishi , Kobayashi Michiya , Hasegawa Junichi , Fukunaga Mutsumi , Takagane Akinori , Otsuji Toshio , Miyake Yasuhiro , Nagase Michitaka , Oba Koji , Sakamoto Junichi , Mishima Hideyuki 
Published: February 2017

502 Background: Combination chemotherapy of capecitabine plus oxaliplatin (XELOX) with bevacizumab is commonly used as standard chemotherapy for metastatic colorectal cancer (mCRC). A previous meta-analysis showed that there was no difference between two age groups of <65 years and ≥65 years on overall survival (OS) after treatment with chemotherapy with bevacizumab. However, the safety and efficacy of XELOX with bevacizumab in elderly patients (pts) ≥75 years with mCRC remain unclear. Methods: This study was an open-label multicentre phase II study to evaluate the efficacy and safety of XELOX with bevacizumab in pts ≥75 years with metastatic CRC. The primary objective was to assess progression-free survival (PFS). The secondary endpoints were the safety, response rate (RR), time to treatment-failure (TTF) and OS. Results: 36 pts were enrolled. Pts characteristics were; median age 78 (range 75-86); male/female, 21/15; ECOG performance status 0/1, 30/6; colon/rectum 24/12, creatinine clearance (CCr) 60.2 ml/min (range 32.6-84.6). Median follow-up period was 220 days. RR was 55.6% and median TTF was 209 days. The median PFS and median OS are not reached. Grade 3 or 4 adverse events (AEs) were reported in 22 pts (62.8%). Common grade 3 or 4 AEs were hypertension (11.4%), leukopenia (20.0%), peripheral sensory neuropathy (14.3%), hand foot syndrome (8.6%), and fatigue (8.6%). Examining the relationship between renal function (CCr) and AEs, the incidence of Grade 3 or 4 AEs in the lower CCr group was significantly higher than that in the higher CCr group (61.6% vs. 47.8%; p=0.013); hematological toxicities (87.5% vs. 14.8%; p=0.0003) and non-hematological toxicities (61.5% vs. 11.1%; p=0.018). Conclusions: XELOX with bevacizumab is safely administered in elderly patients ≥75 years. Renal function (CCr) could be a good predictive marker for grade 3 or 4 AEs. Clinical trial information: UMIN000003500.
Risk factors for peritoneal recurrence in stage II/III gastric cancer patients who received S-1 adjuvant chemotherapy after D2 gastrectomy.
Authors: Aoyama Toru , Yoshikawa Takaki , Shirai Junya , Fujikawa Hirohito , Hayashi Tsutomu , Ogata Takashi , Cho Haruhiko , Yukawa Norio , Oshima Takashi , Rino Yasushi , Masuda Munetaka , Tsuburaya Akira 
Published: February 2017

51 Background: Peritoneum is still the most frequent site of the recurrence in stage II/III gastric cancer patients although the survival was improved by S-1 adjuvant chemotherapy. The objective of this retrospective study was to clarify the risk factors of peritoneal recurrence in patients who received S-1 adjuvant chemotherapy. Methods: Peritoneal recurrence free survival (P-RFS) was examined in 100 gastric cancer patients who underwent curative D2 surgery, were diagnosed with stage II or III pathologically, and received adjuvant S-1 between June of 2002 and March of 2011. Uni- and multi- variate analyses were performed to identify risk factors by Cox’s proportional hazard analyses. Results: P-RFS was 64.3% at 3 years and 58.8% at 5 years. A total of 18 patients were diagnosed with peritoneal recurrence. Macroscopic tumor diameter, depth of tumor invasion, and lymph node metastasis were the significant factors by univariate analysis, while tumor diameter and lymph node metastasis were the only significant independent risk factors by multivariate analysis. Conclusions: The macroscopic tumor diameter and lymph node metastasis were the most important risk factors for P-RFS. When patients had these risk factors, S-1 was not sufficient to inhibit peritoneal recurrence. When developing a novel adjuvant chemotherapy targeting peritoneal metastasis in the future, clinical trials should be limited to these patients.