bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma biomarker analysis of ramucirumab in Japanese patients with advanced gastric cancer: Preliminary results.
Authors: Takahari Daisuke , Wakatsuki Takeru , Mashima Tetsuo , Ichimura Takashi , Chin Keisho , Ogura Mariko , Nakayama Izuma , Matsushima Tomohiro , Osumi Hiroki , Ozaka Masato , Suenaga Mitsukuni , Shinozaki Eiji , Seimiya Hiroyuki , Fujita Naoya , Yamaguchi Kensei 
Published: March 2017

72 Background: Ramucirumab, anti-VEGFR2 receptor antibody, showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use; however, no validated biomarker has been available until today. The aim of this study is 1) to reveal the dynamics of plasma biomarkers, 2) to assess the associations between these baseline levels or dynamics and efficacy. Methods: Plasma samples were collected at three points: base line, day 8, and after disease progression. Nine kinds of plasma biomarker involved in angiogenesis were measured by means of ELISA. Progression-free survival (PFS) was estimated using Kaplan-Meier methods and compared using the log-rank test. Comparisons of plasma biomarker levels were performed using Mann-Whitney-U test. Results: Samples were collected from 35 patients. Among them, 25 patients were evaluated when analyzed and 6 patients showed disease progression at the first evaluation. In VEGF-A and PlGF, plasma biomarker levels of day 8 were dramatically elevated in all patients; Day8/ baseline ratios were 18.1 folds in VEGF-A and 19.3 folds in PlGF. On the other hand, Day8/ baseline ratio of VEGFR1 and NRP1 were 0.7 and 0.8, respectively. The others appeared to show variable change at day 8. In survival analysis, lower than median Day8/ baseline ratios of VEGF-A were significantly associated with longer PFS with 6.3 months in < median vs. 2.4 months in ≥ median (p = 0.004). In addition, patients with disease progression at the first evaluation by CT showed higher Day8/ baseline ratios of VEGF-C, Angiopoietin 1, and lower baseline NRP1 levels than those of patients with non-disease progression. Conclusions: Dramatic changes of biomarker levels at day 8 were observed among patients in each biomarker. These changes in VEGF-A, C, and Angiopoietin-1 may be candidate predictive marker of ramucirumab in Japanese patients with gastric cancer.
Examining progression-free survival in first- and second-line treatment for BRAF-mutant metastatic colorectal cancer (CRC).
Authors: Lee Belinda , Anton Angelyn , Lee Margaret , Wong Rachel , Parente Phillip , Shapiro Jeremy David , Yip Desmond , Steel Simone Anne , Nott Louise M. , Stefanou Greg , Iddawela Mahesh Y. , Gibbs Peter , Tran Ben 
Published: March 2017

728 Background: BRAF mutated (BRAFm) CRC represents ~10% of all CRC and is associated with significantly poorer prognosis. However, responses to chemotherapy do still occur. Some data suggest that the poor prognosis associated with BRAFm CRC is dominated by substantially poorer second line PFS (PFS2), whereas first line PFS (PFS1) was similar for both BRAFm and BRAF wildtype (BRAFwt) CRC. Using a large multicenter dataset, our study aimed to examine PFS1 and PFS2 in BRAFm versus BRAFwt CRC. Methods: Prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) database was interrogated. PFS was calculated and compared in patients with BRAFm versus BRAFwt CRC. Median survival was determined by the Kaplan-Meier method and compared using the log rank test. Results: TRACC identified 523 CRC patients with known BRAF mutation status, who received first-line chemotherapy: 53 (10%) were BRAFm, while 470 (90%) were BRAFwt. At the time of data analysis, only 231 (44%) CRC patients had received second-line chemotherapy, of which 21 (9%) were BRAFm and 210 (91%) were BRAFwt. PFS1 analyses demonstrated significantly poorer survival in the BRAFm population (Median 7.8mo versus 11.5mo, HR 1.72, p = 0.0026). PFS2 analyses revealed similar findings for the BRAFm population, albeit non-significant due to smaller numbers (Median 5.5mo versus 7.7mo, HR1.26, p = 0.44). Conclusions: Our study demonstrated that BRAFm CRC was associated with poorer PFS in both first- and second-line settings. Additional analyses will be performed to examine the impact of different treatment strategies and other clinicopathological features.
Cetuximab and bevacizumab in addition to chemotherapy first-line for left-side metastatic colorectal cancer: A cost-effectiveness analysis.
Authors: Zhang Yanqiao , Zheng Tongsen , Liu Maobai , Li Te , Wu Bin 
Published: March 2017

732 Background: To test the cost-effectiveness of cetuximab and bevacizumab treatment as first-line treatment for patients with left-side metastatic colorectal cancer (mCRC). Methods: A Markov model was developed to Chinese clinical practice. The model incorporated clinical and utility data from published literatures, resource utilization and unit prices based on local charge. The lifetime horizontal was used and sensitivity analyses were carried out to test the robustness of the model results. The impact of patient assistance program (PAP) was also evaluated in scenario analyses. Results: Baseline analysis showed that the addition of cetuximab gained additional 0.364 QALYs with more $39,450 relative to bevacizumab therapy, resulting in an ICER of $108,287 /QALY. When PAP was available, the incremental cost decreased to $2,464, which yielded an ICER of $6,764 /QALY, which indicated that the strategy might be very cost-effective at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China ($22,200/QALY). Sensitivity analyses found that the costs of cetuximab and bevacizumab were the most influential parameters. Conclusions: When PAP was available in Chinese context, cetuximab treatment is likely to be cost-effective versus bevacizumab therapy for patients with left-side mCRC.
Oncologic outcome and morbidity for elderly rectal cancer patients compared to younger patients after preoperative chemoradiotherapy and curative surgery: A multi-institutional and case-matched control study.
Authors: Sung Soo Yoon , Lee Jong Hoon , Kim Sung Hwan 
Published: March 2017

736 Background: To elucidate the toxicity and survival outcome of neoadjuvant chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME) in elderly rectal cancer patients compared to younger patients. Methods: A total of 1232 rectal cancer patients who received neoadjuvant CRT and curative surgery were collected from 7 tertiary institutions. After propensity-score matching, 310 patients of < 70 years for younger arm and 310 patients of ≥ 70 years for elderly arm were identified, respectively and matched with 1:1 manner. Treatment response and toxicity, surgical outcome, recurrence, and survival were assessed and compared between two arms. Results: The two younger (< 70 years) and elderly (≥ 70 years) arms were well-matched and had similar baseline characteristics. Median ages were 58 years for younger arm and 74 years for elderly arm, respectively. Pathologic complete response rates were not significantly different between younger arm and elderly arm (17.1% vs. 14.8%, P = 0.443). The 5-year recurrence-free survival (70.0% vs. 69.8%, P = 0.773) and overall survival (79.5% vs. 82.9%, P = 0.270) rates were not significantly different between two arms. Adjuvant chemotherapy after surgery was less frequently delivered to elderly arm than younger arm (69.0% vs. 83.9%, P = 0.773). Grade 3 or higher acute hematologic toxicity was observed more frequently in elderly arm than in younger arm (9.0% vs. 16.1%, P = 0.008 ), but late complication was not significantly increased in elderly arm (2.6% vs. 4.5%, P = 0.193). Conclusions: Despite an increased acute toxicity, elderly rectal cancer patients with good performance status would have equivalent tumor response and recurrence-free survival compared to younger patients.
Ziv-aflibercept (A) combined to FOLFIRI as first line treatment for metastatic colorectal cancer (mCRC): Interim safety and efficacy results of the phase II PULSAR trial.
Authors: Adenis Antoine , Ghiringhelli Francois , Raoul Jean Luc , Tresch Emmanuelle , Thirot-Bidault Anne , Vincent Julie , El Hajbi Farid , Hebbar Mohamed , Bouchahda Mohamed , Jarraya Hajer , Feutray Sylvaine , Amela Eric , Laestadius Fredrik , Le Deley Marie-Cécile , Taieb Sophie , Soncin Fabrice , Dochy Emmanuelle , Delaine Stephanie Clisant , Penel Nicolas , Lassau Nathalie 
Published: March 2017

737 Background: A is approved in combination with FOLFIRI (A-FOLFIRI) for the treatment of mCRC patients (pts) previously treated with oxaliplatin. PULSAR trial (NCT02173990) aims to measure the activity A-FOLFIRI as 1st-line mCRC treatment. Key secondary objectives are safety, as well as circulating biomarkers and dynamic contrast-enhanced ultrasound measurements as PFS prognosticators. We present here interim analysis of safety and activity. Methods: Pts received A (4 mg/kg I.V.) every 2 weeks in combination with FOLFIRI (Irinotecan: 180 mg/m2, leucovorin: 200 mg/m2, Bolus FU: 400 mg/m2, infusional FU: 2400 mg/m2 over 46hrs). The primary endpoint is 10-month [m] PFS (RECIST 1.1). The target sample size is 72 pts for the following assumptions: P0 = 0.40, P1 = 0.55, α = β = 0.1. Results: Among the first 30 recruited mCRC pts with unresectable metastases (mets), 29 received at least 1 cycle of A-FOLFIRI. 30, 23, and 28 pts were evaluable for survival (intent-to-treat), tumor response, and safety, respectively. Median age was 61.5 (45-82), 70% pts were men. ECOG PS was 0, 1, and 2, in 47%, 43%, and 10% of the pts. 6/30 pts received previous adjuvant chemotherapy. 22/30 pts presented with synchronous mets. 26/30 pts presented with liver mets. Median treatment duration was 6.3m (0.5-24.3) and pts (n = 29) received a median number of 10 cycles (1-37) of A and of 11 cycles (1-43) of FOLFIRI. Median follow-up was 7.2m (1.6-23.9). The 10-m PFS was 59.9% [95%-CI: 37.5-76.5]. Median PFS was 12.9m (95% CI: 6.1-…). 12-m OS rate was 73.7% (95% CI: 48.3-87.9). 5 pts died from PD, and 1 from treatment-related toxicity (colon perforation). 27/28 pts presented at least one severe Adverse Event (AE). Most frequent severe AE (related or not) were hypertension (43%), neutropenia (29%), diarrhea (18%), alkaline phosphatase increase (18%), fatigue (18%), GGT increase (14%), and weight loss (14%). Conclusions: A-FOLFIRI seems promising in 1st line setting mCRC, with respect to PFS. Due to high rates of severe AEs, dose modifications have to be proceeded in a coming protocol amendment. Funded by Sanofi. Clinical trial information: NCT02173990.
Treatment sequencing and outcomes in synchronous metastatic rectal cancer.
Authors: Strach Madeleine Cornelia , Lee Margaret , Lomax Anna , Ng Michael , Guerrieri Mario , Prasanna Thiru , Wong Hui-li , Lee Belinda , McKendrick Joseph James , Lim Lionel , Kosmider Suzanne , Tie Jeanne , Yip Desmond , Nott Louise M. , Johns Julie , Harold Michael , Gibbs Peter , Wong Rachel 
Published: March 2017

750 Background: Optimal sequencing of therapies in synchronous metastatic rectal cancer (SMRC) remains unknown. Aim: To compare sequencing of treatment modality and outcomes in SMRC. Methods: Retrospective audit of patients with SMRC registered on the multi-centre Treatment of Recurrent and Advanced Colorectal Cancer database between 1/1/2009 and 30/6/2015. Patients were grouped according to initial treatment mode: chemotherapy (C), chemoradiation (CRT), surgery (S) and best supportive care (BSC). Results: 247 patients were identified: median age was 62yrs, ECOG 0-1 87%, male 64%, 1-2 metastatic sites 86% (liver 56%) and treatment intent was curative in 14%. Median follow-up was 19m. Primary tumour resection occurred in 95 patients (38%). Compared to no resection, these patients had improved median OS (41 vs 16 months; p < 0.0001) and PFS (15 vs 10 months; p < 0.0001). There was no difference in outcome with varying treatment combinations and sequences of S with CRT/C (p > 0.05). For unresected patients, the most common initial treatment was C (30%). Any active treatment was associated with better OS compared to BSC (6.4m): C (16.1m, p < 0.0001), CRT (20.6m, p = 0.001) and C&CRT (21.8m, p < 0.0001). Most active treatments were associated with better PFS compared to BSC (6.4m): C (10.8m, p = 0.015) and C&CRT (10.6m, p = 0.012). There was no significant PFS difference comparing BSC to CRT (p = 0.25). There were no OS nor PFS differences between: comparisons of C, CRT and C&CRT (p > 0.05). Initial treatment strategies were compared for 129 patients receiving multimodal therapy, where 22 (17%) had initial treatment with C (60% subsequent resection) compared to 85 (66%) commencing with CRT (70% subsequent resection). Commencing with CRT was associated with a longer OS compared to C (31 vs 21 months; p = 0.014). Conclusions: For patients undergoing primary tumour resection, no difference in outcomes were demonstrated with the addition of C and/or CRT. For unresected patients, there was a survival benefit associated with active therapy, with no significant difference between C, CRT or C&CRT. This supports the current practice of using these modalities at clinicians’ discretion. Review of patient factors potentially influencing treatment choice is ongoing.
High-dose neoadjuvant intensity modulated radiotherapy/chemotherapy for distal rectal cancer followed by rectal sparing TEM.
Authors: DeNittis Albert S. , Parikh Kinjal , Zeger Erik L. , Marks Gerald J. , Marks John 
Published: March 2017

756 Background: In patients with distal rectal cancer, preoperative chemoradiotherapy remains the standard of care, however intensity modulated radiation therapy (IMRT) followed by trans-anal endoscopic microsurgery (TEM) may be able to provide more conformal and higher hoses of radiation while sparing normal tissue. It is our intent to present 11 years of experience of patients treated concurrently with chemotherapy and IMRT followed by rectal sparing TEM. We will report on local control, disease free survival (DFS), and toxicity. Methods: Forty-two patients at Lankenau Medical Center were treated for distal rectal carcinoma with IMRT and TEM from 2004 to 2016. Patients staged T1-T3 N0 M0 received 5580 cGy to the pelvis using a 9 field plan or volumetric arc therapy targeting rectal tumor and pelvic lymph nodes. The median age was 68. All patients received concurrent 5FU based chemotherapy; 54% received an infusional regimen and 46% received oral capecitabine. All patients went on to surgery with full thickness local excision via TEM. 38 underwent surgery within 7-12 weeks following neoadjuvant therapy, with median time to surgery at 11 weeks. Results: Median time to follow up time was 33 months. Complete pathologic response was achieved in 38% (n=17) of patients, good partial response in 53% (n=22), and moderate response in 6%. 4 patients had local recurrence all achieving long term control with salvage surgery. 5 patients developed distant metastasis, most commonly to the liver. Of those, 1 died from metastatic disease, occurring 11 years after initial diagnosis. 79% of patients are currently alive with no evidence of disease. Mean DFS calculated with Kaplan Meier analysis was 88 months with 95% confidence interval between 76 and 101 months. Toxicity was acceptable with only one grade 2 toxicity (diarrhea), and two patients with grade 1 neutropenia. Conclusions: Our 11 year patient experience has shown that neoadjuvant chemoradiotherapy with IMRT followed by TEM is an effective and well tolerated treatment regimen for distal rectal carcinoma. In the appropriately selected patients, local excision surgery may provide an excellent option for patients other than low anterior resection (LAR).
Outcomes in the second line treatment of metastatic colorectal cancer (mCRC): Findings from 6,462 patients (pts) in the ARCAD database.
Authors: Leal Alexis Diane , Ou Fang-Shu , De Gramont Aimery , Pederson Levi , Sobrero Alberto F. , Peeters Marc , Arnold Dirk , Pitot Henry C. , Rothenberg Mace L. , Giantonio Bruce J. , Van Cutsem Eric , Sargent Daniel J. , Grothey Axel 
Published: March 2017

757 Background: Progression free survival (PFS) and overall survival (OS) appear to differ across trials, even when pts receive the same regimen (REG). This analysis aimed to benchmark the clinical outcomes in the 2nd line treatment of metastatic colorectal cancer (mCRC). Methods: Individual patient (pt) data was available on 6,462 pts with mCRC enrolled in 7 2ndline clinical trials (8 REGs) in the ARCAD database. Regimens used in at least two trials included FOLFIRI +/- an EGFR inhibitor (EGFRi), FOLFOX +/- a VEGF inhibitor (VEGFi), and irinotecan (IRI). Descriptive statistics were used to describe pt demographics. Multivariable Cox models were used to assess differences (DIFFs) in PFS and OS, while p-value <0.05 were considered statistically significant (SS). Results: 500-1400 pts received each REG (see Table). Median OS and PFS differed by 0.2 to 4.6 months (mo) and 0.8 to 2.5 mo across trials within the same REG. These DIFFs were SS except for PFS in REGs containing FOLFIRI +/- EGFRi. After multivariable adjustment, all DIFFs in OS were attenuated and non-significant. DIFFs in PFS attenuated for most REGs but remained SS for FOLFOX and IRI. Conclusions: After multivariable adjustment, there were no SS DIFFs in outcomes across trials within the same REG, with the exception of PFS in FOLFOX and IRI. The initial observed DIFFs in outcomes could be due to confounding factors and the remaining SS DIFFs in PFS in FOLFOX and IRI may be due to variation in definition of progression across trials. Therefore, caution is warranted when using historical data to design future trials.[Table: see text]
Effect of arsenic trioxide on epithelial-mesenchymal transition via induction of SH2?containing protein tyrosine phosphatase 1.
Authors: Park Jong-Jae , Joo Moon Kyung , Yoo Hyo Soon , Lee Beom Jae , Kim Taehyun , Lee Ji ae , Sim Yu-ra , Choi Wonjae , Chun Hoon Jai , Lee Sang Woo , Bak Young-Tae 
Published: March 2017

76 Background: Arsenic trioxide (ATO) is known to inhibit epithelial-mesenchymal transition (EMT) in hepatolocellular carcinoma and breast cancer cells, however, little has been reported in gastric cancer cells. In this study, we aimed to investigate the mechanism of ATO to inhibit signal transducer and activator of transcription 3 (STAT3) activity and EMT in gastric cancer cells. Methods: We performed wound closure assay and Matrigel invasion assay for functional studies of EMT, and western blot for measurement of protein markers using AGS gastric cancer cells. Results: Compared with control, 5 and 10 μM of ATO significantly inhibited cellular migration and inhibition in a dose-dependent manner. Furthermore, ATO significantly downregulated snail expression, a mesenchymal marker, and upregulated E-cadherin expression, an epithelial marker. We could observe that ATO induced SH2-containing protein tyrosine phosphatase 1 (SHP1), a non-receptor type protein tyrosine phosphatase, and subsequently downregulated phospho-STAT3 in a dose-dependent manner. To validate the molecular link between ATO and SHP1 to inhibit EMT in gastric cancer cell, we pre-treated 50 μM of pervanadate, a phosphatase inhibitor, before treatment of 10 μM ATO, and this significantly abolished anti-invasive effect by ATO in AGS cells. In xenograft tumor model, intraperitoneal injection of ATO significantly reduced the tumor volume and upregulated SHP-1 expression by immunohistochemistry stain compared with vehicle, which were reversed by ATO with pervanadate injection. Conclusions: Our findings suggest that ATO may show anti-EMT effects via induction of SHP1 and inhibition of STAT3 activity in gastric cancer cells.
An update on rectal cancer evaluation by magnetic resonance imaging in neoadjuvant therapy decision making: Retrospective case review.
Authors: Recio Boiles Alejandro , Howell Krisha , Kalb Bobby T. , Malangone Steve , Nfonsam Valentine N. , Elquza Emad 
Published: March 2017

762 Background: During the last decade, MRI used for staging of rectal cancer has been reported to up or down stage rectal cancer by 20%. Poor staging affects guided pre-operative decision-making. Adequate staging would enable to stratify treatment, avoiding unnecessary surgical morbidity and allowing aggressive interventions according to patient risk. After novel techniques and image acquisition for MRI became available at our Cancer Center, we aimed to analyze perfusion pattern and qualitative T2 signal before and after chemoradiationtherapy (CRT) tumor response to the gold standard pathological stage. Methods: Data was retrospectively reviewed from our institution cancer registry. Patients were selected with a diagnosis of rectal cancer by biopsy, between 2011-2015. Inclusion criteria were to have documented radiological AJCC 7th edition < IV, accessible diffusion weighted MRI for apparent diffusion coefficient analyzes, completed CRT and pathology report. Results: A total of 57 patients were diagnosed with rectal cancer during this time period, of which 20 fulfilled inclusion criteria; median 61 years old, 80% males, stage IIA (6) IIIB (10) and IIIC (4), LAR 60% and APR 40%. After CRT, 90% of patients (N18) were downstaged (and 2 upstaged) on pathological review. 10 patients had a repeat pre-operative MRI. Post-treatment MRI re-stage correlated with surgical pathological stage in all 10 patients (Table). 4 patients received unnecessary APR and 2 may had benefit from further CRT or total pelvic exanteration. Conclusions: In retrospective, tumor response evaluation post CRT with high-resolution MRI correlated with pathological stage. Our analysis pointed 20% patients may avoid a morbid surgery while 10% would have required more aggressive therapy. Future clinical decisions will be complemented by repeat MRI analysis aiding surgical and clinical decision-making. [Table: see text]