bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic analysis to identify markers for response to treatment in esophageal cancer.
Authors: Zlotnik Oran , Goshen-Lago Tal , Brenner Baruch , Kundel Yulia , Menasherov Nikolai , Kashtan Hanoch , Ben-Aharon Irit 
Published: January 2019

61 Background: Neoadjuvant chemoradiotherapy (NCRT) followed by surgery represents a key therapeutic strategy for locally advanced esophageal cancer (LAEC). Former studies addressed the clinicopathological patterns of patients who demonstrated good response to NCRT compared with inferior response. Nevertheless, there is paucity of data regarding potentially involved cellular pathways that account for tumor response to NCRT. We performed a comprehensive proteomic analysis to identify the key differences in protein function and pathway activation between patients with a poor response and those with a favourable response to treatment. Methods: Patients diagnosed with LAEC who were treated with NCRT and operated at our institution were included in the study. Patients were defined as good responders (GR) upon the tumor regression grade (TRG) in the pathological specimen: GR defined as TRG 0/1 and no evidence of recurrence at 1-year post surgery. Bad responders (BR) were defined as TRG 2/3 and recurrence < 1year. Tumor was isolated from the surgical specimen and proteins were extracted and processed for mass spectrometry-based analysis. Clinical data of demographics, response to treatment, and survival was retrieved from electronic medical records. Difference in protein expression between GR and BR were analysed using validated gene expression pathways tools and correlated to clinical data. Results: Forty-four patients were included in the cohort. Mean age was 66.7 years, male predominance (33/44). Thirty-five patients had adenocarcinoma – 17 GR and 18 BR. Nine patients had squamous cell carcinoma – 6 GR and 3 BR. Protein expression patterns significantly differed between GR and BR regardless of histology, mainly in cellular pathways account for nucleic acid metabolism (p < 10-9), whereas BR had overexpression of these genes. Conclusions: Our study indicate that lack of response to NCRT may derive from overexpression of unique cellular pathways. Former studies imply these cellular pathways may play a role in resistance to cisplatin. Larger transcriptomic studies are warranted for future analysis to extend these observations.
The effect of adjuvant chemotherapy for stage III colon cancer in elderly patients.
Authors: Hayashi Naomi 
Published: January 2019

611 Background: Adjuvant chemotherapy (ACT) has been recommended for stage III colon cancer patients in NCCN guidelines. However, the benefit of ACT is still controversial in elderly patients. Methods: We retrospectively included stage III colon cancer patients with aged over 70 that were operated between 2008 and 2015 in Tosei general hospital from Japan. We calculated 3 years recurrence rate and performed a multivariate analysis to estimate the risk of recurrence. The model was adjusted by including the following 7 confounders: Age, ECOG-PS (0-1 or ≥ 2), tumor site (right or left), T stage (T1-3 or T4 ), N stage (N1 or N2), pathological type (por-sig or other), and complete ACT (yes or no). No complete ACT was defined as discontinuation ACT and surgery alone. Results: 182 patients were identified (87 patients aged < 70 and 95 patients aged ≥ 70). ACT was performed in 58 patients (61.1%) and complete rate was 67.2% in elderly patients. The median follow up was 36.0 months. 29 patients (30.0%) had relapse. 3 years recurrence rate was 24.3% and 37.8% with complete ACT or no complete ACT (p = 0.29). In multivariate analysis, N2 was only the risk of recurrence (HR 6.95, p < 0.01). In further analysis, addition of oxaliplatin was significant risk factor of recurrence in elderly patients (HR 10.4, p < 0.01). On the other hand, in young patients, no complete ACT was only risk of recurrence (p = 0.01). 3 years survival rate was 89.1% and 81.0% with complete ACT or no complete ACT (p = 0.27). Conclusions: The multivariate analysis showed that ACT did not reduce the risk of recurrence in elderly patients. Moreover, addition of oxaliplatin suggested not only futile but harmful in those patients. These results support the previous reports (MOSAIC study and PETACC-8 trial) that microsatellite instability and RAS status may affect the effect of oxaliplatin.
What is the role of the anti-angiogenic therapy in BRAF (V600E) mutant metastatic colorectal cancer patients in a real-world setting?
Authors: Martinez Lago Nieves , Covela Rúa Marta , Brozos Vazquez Elena , Fernandez Montes Ana Fernandez , De La Camara Gomez Juan Cruz , Méndez Méndez Carlos , Jorge Fernández Mónica , Cousillas Castiñeira Antia , Suárez Begoña Graña , Quintero Aldana Guillermo Alfonso , Candamio Folgar Sonia , Salgado Fernandez Mercedes , Pellon Augusto Maria Luz , Gonzalez Villarroel Paula , Gallardo Martin Elena , Carmona Campos Marta , Vazquez Rivera Francisca , Grande Ventura Carlos , Carral Maseda Alberto , Reboredo Lopez Margarita 
Published: January 2019

620 Background: Activating B-type Raf kinase (BRAF) mutations, mostly missense V600E, occur in approximately 8% to 12% of patients with metastatic colorectal cancer (mCRC). BRAF (V600E)mt is a strong predictor of a poor prognosis, with distinct clinical and pathological features. However, it is unknown whether this mutation is predictive of any treatment benefit in a real world setting. Methods: We conducted an observational, retrospective, multicentric study of patients with BRAF V600E-mt mCRC treated at nine university Spanish hospitals in NW Spain, belonging to GITuD (Galician Research Group on Digestive Tumors). Demographic, clinic and pathological characteristics, overall survival (OS) and first-line progression free survival (PFS) were retrospectively collected and analyzed. Results: Data from 65 patients treated between November 2010 to June 2018 were recorded in this study. Median age was 62.8 years (range 30-83 years), 55.4 % female, 75.4% ECOG PS0-1, 49.2% right-sided, 35.2% high grade, 69.2% synchronous presentation, 66.2% primary tumor resection and median metastatic locations was 2 (range 1-5). With a median follow up of 64.6 months, median OS was 12.9 months (95% CI, 9.8-16.0 months) and first line PFS was 4.1 months (95% CI, 2.7-5.5 months). First line PFS according treatment: Bev+Triplet-CT/Bev+Doublet-CT/antiEGFR+Doublet-CT/Doublet-CT: 6.2 vs 4.8 vs 2.9 vs 2.1 months (p = 0.020). Bevacizumab based chemotherapy was associated with a prolonged first line PFS (median 5.0 vs. 2.1 months, HR, 0.406; 95% CI, 0.20-0.81; p = 0.005). Nevertheless, no statistical differences between bevacizumab based regimes, (Triplet-CT vs Doublet-CT (HR 0.830; 95% CI 0.4-1.9; p = 0.666)) or between Doublet-CT with or without a antiEGFR were found (HR 0.511; 95% CI 0.2-1.6; p = 0.223). Conclusions: Our study confirms the negative prognostic impact of BRAF V600Emt in mCRC and encourage the use of anti-angiogenic based chemotherapy in this subgroup of patients.
“Should we be generous in peritonectomy?”: First prospective comparative analysis of total versus involved field parietal peritonectomy in CRS-HIPEC for peritoneal surface malignancies from COLO-rectal cancer—ISPSM collaboration study.
Authors: Somashekhar S.P. , C Rohit Kumar , Zaveri Shabber , Rajgopal Ashwin K , Rauthan Amit , Ahuja Vijay , Yethadka Ramya 
Published: January 2019

633 Background: Peritonectomy is the important components in management of peritoneal surface malignancies (PSM). Immunofluoresecne study done after involved field peritonectomy (IFP) has showed diease in areas not suspected on gross examination stressing the need for total parietal peritonectomy (TPP) for complete cytoreduction. The aim of this study was to assess the morbidity & mortality, recurrence pattern & oncological outcomes of extent of parietal peritonectomy with CRS & HIPEC for colorectal carcinoma. Methods: Patients with PSM from CRC underwent TPP or IFP with CRS- HIPEC. Pre & intraoperative data were analyzed with main focus on postoperative morbidity, mortality, recurrence pattern and oncological outcomes. Results: 40 cases of CRC of which four upfront, 17 interval and 19 recurrent cases. 19 & 21 patients underwent TPP & IFP respectively. Base line characteristics were comparable except median PCI (17 versus 12). TPP group had longer duration of surgery (11 vs 9), more blood loss (1300 vs 700 ml) increased diaphragmatic resections ( 46.2% vs 14.2%), multivisceral resection ( 46.2% vs 28.5%). Number of bowel resections, anastomosis and stoma were comparable. Overall TPP group had more G3-G5 morbidity (46.1% vs 35.7%) & surgical morbidity (30.7% vs 21.5%) . TPP group had increased pleural & intra-abdominal collections which needed intervention. With a median follow up of 30 months, DFS was significantly higher in TPP group (12months vs 8months, p < 0.01) and median overall survival was 21 months in IFP group (yet to be achieved in TPP group). TPP group had most of the recurrences in visceral liver & lung (50.0%) followed by peritoneal (37.5%) & nodal (12.5%) whereas in IFP it was peritoneum (42.8%), visceral ( 38.4%) & nodal (15.3%). Conclusions: It is the first prospective comparative study done on total parietal peritonectomy in PSM of colorectal cancer origin. TPP group had significantly higher DFS, with comparable postoperative morbidity. However, longer follow up and a prospective multi-institutional randomized study needs to be designed for more evidence of the same.
Nivolumab (NIVO) + low-dose ipilimumab (IPI) in previously treated patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Long-term follow-up.
Authors: Overman Michael J. , Lonardi Sara , Wong Ka Yeung Mark , Lenz Heinz-Josef , Gelsomino Fabio , Aglietta Massimo , Morse Michael , Van Cutsem Eric , McDermott Raymond S. , Hill Andrew G , Sawyer Michael B. , Hendlisz Alain , Neyns Bart , Svrcek Magali , Atasoy Ajlan , Zhao Huanyu , Lei Ming , Kopetz Scott , Andre Thierry 
Published: January 2019

635 Background: In the phase II CheckMate-142 trial, NIVO + low-dose IPI (1 mg/kg) provided meaningful clinical benefit in previously treated MSI-H/dMMR mCRC pts after a median follow-up of 13.4 mo. Here, we present long-term follow-up (median 25.4 mo) of these pts. Methods: Pts received NIVO 3 mg/kg + low-dose IPI Q3W (4 doses) followed by NIVO 3 mg/kg Q2W until disease progression. Primary endpoint was investigator (INV)-assessed objective response rate (ORR; RECIST v1.1). Results: Of 119 treated pts, 76% had ≥ 2 prior lines of therapy. ORR and disease control rates (DCR) were 58 and 81%, respectively (Table). Complete response (CR) rate increased with long-term follow-up from 3 (13.4 mo) to 6% (25.4 mo). Median duration of response (DOR) was not reached, with 68% of responses ongoing at data cutoff. At 24 mo, progression-free survival (PFS) and overall survival (OS) rates were 60 and 74%, respectively; OS rates were 96, 56, and 29% in pts with CR or partial response (PR), stable disease (SD), and progressive disease (PD), respectively. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 31% of pts; 10% (grade 3–4) and 13% (any grade) of pts had TRAEs leading to discontinuation. Conclusions: Long-term follow-up with NIVO + low-dose IPI provides durable clinical benefit with deepening of response and a manageable safety profile with no new safety signals, demonstrating long-term benefit of NIVO + low-dose IPI for previously treated pts with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188. [Table: see text]
Multicenter phase Ib/II study of biweekly trifluridine/tipiracil with bevacizumab combination for patients with metastatic colorectal cancer refractory to standard therapies (BiTS study).
Authors: Kotaka Masahito , Satake Hironaga , Oba Koji , Kagawa Yoshinori , Yasui Hisateru , Nakamura Masato , Watanabe Takanori , Matsumoto Toshihiko , Kii Takayuki , Terazawa Tetsuji , Makiyama Akitaka , Takano Nao , Yokota Mitsuru , Okita Yoshihiro , Matoba Koreatsu , Hasegawa Hiroko , Tsuji Akihito , Nagata Naoki , Sakamoto Junichi , Kato Takeshi 
Published: January 2019

647 Background: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (Bmab) combination therapy has shown a promising activity with manageable safety profile in patients (pts) with heavily pretreated metastatic colorectal cancer (mCRC). The aim of this multicenter, phase Ib/II study was to assess the activity and safety of biweekly FTD/TPI with Bmab combination for pts with mCRC who were refractory or intolerant to standard therapies. Methods: Inclusion criteria were ≥ 20 years; histologically confirmed unresectable mCRC; refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumors with wild-type RAS); ECOG PS 0 or 1; evaluable lesion according to the RECIST version 1.1. Phase Ib part is designed to determine the recommended phase II dose (RP2D), and pts received the RP2D in phase Ib part were included in efficacy and safety populations. The primary endpoint in phase II part was an investigator assessed progression-free survival rate at 16 weeks (16w-PFS) with a hypothesis of 15% considered unacceptable and 38.7% deemed promising. Given a one-sided α of 0.025 and statistical power of 90%, a minimum of 40 pts were required for phase II part. Results: From October 2017 to January 2018, totally 46 pts were enrolled (6 pts in phase Ib and 40 pts in phase II). The RP2D was determined to be 5 mg/kg for Bmab and 30 mg/m2 for FTD/TPI in phase Ib. Of the 44 eligible pts (median age, 69; male, 55%; PS 0, 57%; right-sided primary, 29.5%), 16w-PFS rate was 40.9 % (95% CI: 26.3 to 56.8 %) and the null hypothesis of 16w-PFS rate ≤ 15% was rejected (p < 0.0001). Response rate and disease control rate were 0 % (95 %CI: 0 to 6.6 %) and 59.1 % (95%CI: 43.3 to 73.7 %), respectively. With a median follow up of 5.86 months (range, 1.53-9.79), median PFS was 4.25 months (95% CI: 2.54 to 5.57). Grade 3 or higher adverse events were hypertension (40.9%), neutropenia (11.4 %), leucopenia (11.4 %), anemia (9.1 %), anorexia (9.1 %), nausea (6.8 %), hyperbilirubinemia (6.8 %) and proteinuria (6.8 %). Conclusions: Bi-weekly FTD/TPI plus Bmab showed promising anti-tumor effect with acceptable toxicities. Clinical trial information: UMIN000029198.
National trends in intensity modulated radiation therapy (IMRT) use for rectal cancer.
Authors: Horne Zachary D. , Abel Stephen , Hasan Shaakir , Kirichenko Alexander V. , Wegner Rodney E 
Published: January 2019

648 Background: Neoadjuvant chemoradiation represents the current standard of care for locally advanced rectal cancer prior to surgical resection. Traditionally, 3D conformal radiation therapy (3D CRT) was used in this setting. With advancing technology, intensity modulated radiation therapy (IMRT) was developed with the goal of delivering a more conformal radiation dose, with the potential for reduced toxicity providing a potential advantage across many disease sites. We sought to use the national cancer database (NCDB) to examine trends and predictors for IMRT use in rectal cancer. Methods: We queried the NCDB from 2004-2015 for patients with rectal adenocarcinoma treated with neoadjuvant concurrent chemoradiation to a standard doses (50.4-54Gy) followed by surgical resection. Odds ratios were used to determine predictors of IMRT use. Univariable and multivariable cox regressions were used to determine potential predictors of overall survival (OS). Propensity matching was used to account for any indication bias. Results: We identified 21,490 patients satisfying eligibility criteria, of which 3,131 were treated with IMRT. IMRT use increased from 1% in 2004 to 22% in 2014. Predictors for IMRT use included increased N stage, more recent treatment year, treatment at an academic facility, increased income, and higher educational level. On multivariable analysis including propensity score male gender, increased distance to facility, higher comorbidity score, IMRT technique, government insurance, African American race, and non-metro location were predictive of worse OS. Of note, the complete response rate at time of surgery was 28% with non-IMRT and 21% with IMRT. Conclusions: IMRT use has steadily increased in the treatment of rectal cancer, but still remains only a fraction of overall treatment technique. IMRT use correlated with worse survival likely due to utilization in higher stages and patients with worse disease features.
Systematic review of three decades of clinical trials in metastatic colorectal cancer: Making lemonade out of lemons?
Authors: Tannenbaum Daniel , Raghav Kanwal Pratap Singh , Horn Robert Asa , Overman Michael J. , Eng Cathy , Kopetz Scott , Johnson Benny , Morris Van K. , Parseghian Christine Megerdichian , Chang George J. , Rogers Jane Elizabeth , Parker Susan , Lopez-Olivo Maria de los Angeles , Dasari Arvind 
Published: January 2019

656 Background: Despite multiple trials of new agents in metastatic colorectal cancer (mCRC), long term outcomes remain poor. This study explores the changing trends in the design, interpretation and outcomes of phase III randomized controlled trials (RCT) in mCRC over time. Methods: Phase III RCTs of systemic therapy for mCRC with enrollment between 1986 and 2016 were identified through 4 electronic databases and grouped into 3 time periods (1986-1996 – T1; 1997-2006 – T2 & 2007-2016 – T3). Study selection, quality appraisal and data collection were performed by 2 independent investigators. Study characteristics, primary and secondary endpoints, and authors’ interpretation of results and conclusions were analyzed. Improvement in overall survival (OS) was the difference between experimental and control arms. A study was deemed positive if it met its end point, was recommended for further study or for adoption for clinical use (p ≤ 0.05 significant for all analyses). Results: One hundred fifty trials (T1=36, T2=62, T3=52) with 77494 patients (T1=12406, T2=39158, T3=25930) were included. Although 1st line therapy trials continued to be the most common across all T, the percentage (%) of trials evaluating 3rd line and beyond (T1=0, T2=3, T3=27) have increased significantly over time as have trials with targeted agents (T1=11, T2=34, T3=79). Although OS remains the most common primary end point, more trials in T2 & T3 have used progression-free survival instead (14 vs 47 & 44). The % of trials with negative results but interpreted as positive increased over time (T1=18; T2=42; T3=35). Across all T, the median improvement in OS (months, m) of these trials was significantly lower compared to the trials that met primary end point across all T (T1 = 0 vs 1.8 m, T2 = -0.1 vs 3.25, T3 = -0.25 vs 2.55). Conclusions: A significant shift has occurred over the past three decades in the design and interpretation of phase III trials in advanced CRC. Any interpretations of potential survival benefits from trials that have not met primary end point must be made with significant caution.
Clinicopathological features, efficacy of anti-EGFR therapy, and survival outcomes in patients with BRAF non-V600 mutated metastatic colorectal cancer.
Authors: Kotani Daisuke , Mondaca Sebastián , Parikh Aparna , Bando Hideaki , Van Seventer Emily , Taniguchi Hiroya , Yoshino Takayuki , Corcoran Ryan Bruce , Yaeger Rona , Ebi Hiromichi 
Published: January 2019

659 Background: BRAF non-V600 mutations occur in 2-3% of colorectal cancer. These mutants can be classified as RAS independent (class 2) or RAS dependent (class 3). We reported BRAF non-V600 mutations could be a negative predictive factor for anti-EGFR therapy in patients (pts) with pretreated metastatic colorectal cancer (mCRC), while mCRC pts with class 3 BRAF mutations could respond to anti-EGFR therapy because of its dependency on receptors and RAS. Methods: This study evaluates the efficacy to anti-EGFR therapy in a large cohort of pts with BRAF non-V600 mutated mCRC. Pts with mCRC referred to the participating centers from 2010 to 2017 were included. Clinicopathological features, efficacy of anti-EGFR therapy, and survival outcomes were stratified by BRAF mutational class. Results: One hundred seventeen pts with BRAF non-V600 mutated mCRC were identified. Median age was 58 years (range, 27-83), 68 pts (58%) were male, and 38 pts (33%) had right-sided tumors. Mucinous histology was seen in 11 cases (9%); concurrent RAS mutations occurred in 31 cases (27%), and 3 cases (3%) were MSI-H. Also, TP53 mutations were detected in 74 pts among 90 analyzed cases (82%). Regarding BRAF mutation subtype, 25/63/29 pts were classified as class 2/3/not reported (NR), respectively. Median OS in RAS wild-type/mutant were 44.8/34.6 months, respectively (p=0.082). The median OS in RAS wild-type pts with BRAF non-V600 mutations for class 2, 3, and NR were 25.7, 44.2, and 79.1 months, respectively (class 2 vs. 3, p=0.219). Among 40 pts treated with anti-EGFR therapy, response rates were 14%, 44%, and 40% for class 2, 3, and NR, respectively. Median PFS was 4.4, 8.3, 4.0 months for class 2, 3, and NR, respectively. Moreover, in 25 pts receiving anti-EGFR therapy as third or later line, response rate was 0%, 27%, and 50% in class 2, 3, and NR, and median PFS was 2.8, 3.7, and 4.0 months (p=0.762), respectively. Conclusions: Pts with class 2 BRAF mutations tend to have a poor prognosis compared to those with class 3 mutations. While almost half of pts with class 3 BRAF mutations responded to anti-EGFR therapy, response was rare for pts with class 2 BRAF mutations, and none achieved objective response in the third or later line.
Ambulatory 5FU infusion pumps: Patient perceptions and quality of life.
Authors: Al-Kadhimi Munaf , Hill Marisa E. , Fine Elita , Adess Matthew Eric , Polish Ari , Wiebe Lauren Allison , Whalen Margaret , Van Pelt Eileen , Callahan Teresa , Gustafson Cory , Collins Kathleen , Marsh Robert de Wilton 
Published: January 2019

663 Background: Infusional-5-fluorouracil (inf-5FU), administered over 48 hours every 2 weeks, is frequently prescribed for the treatment of gastrointestinal cancers. A portable infusion device (ID) may be used for this purpose to enable treatment at home. At our institution, patients are educated by an oncology nurse as to what to expect, and how to function once they leave the infusion center. However, there is no formal process in place to report their experience and to record and analyze the results. The intended goal of this study was to accomplish this, such that the data could improve the education and experience of future patients. Methods: After verbal consent, a sequential cohort of patients, who had received 2 or more treatments with inf-5FU for gastrointestinal cancer, was invited to complete a de-identified paper questionnaire concerning their experience. Eleven specific questions suggested by the GI group were included, with an opportunity to add comments. The surveys were then collated and reviewed. Results: See table. Conclusions: While most patients felt well prepared by their medical team as to what to expect from the ID (93.1%), ≥ 25% had issues with bathing (73.6%), sleep (37.5%), exercising (30.6%), intimacy (26.4%), social interactions (25%) and anxiety (25%). These insights will be used to improve the education of future patients and a second assessment will follow. 72/72 patients approached over 6 months completed the survey with results below: [Table: see text]