bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective observational study on chemotherapy-induced nausea and vomiting (CINV) for colorectal cancer patients by the CINV study group of Japan.
Authors: Miyamoto Yuji , Baba Hideo , Tsuji Yasushi , Doi Ayako , Takeda Koji , Kobayashi Michiya , Maehara Yoshihiko , Gotoh Masahiro , Yoshida Kazuhiro , Kokudo Norihiro , Kakeji Yoshihiro , Aiba Keisuke 
Published: February 2017

652 Background: The aim of this study is to investigate the incidence of Chemotherapy Induced Nausea and Vomiting (CINV) among moderately emetogenic chemotherapy-naive patients with colorectal cancer. We also assessed whether the medical staff accurately recognized the incidence of CINV in their own practices. Methods: A prospective observational study of patients receiving the first cycle of oxaliplatin or irinotecan-based chemotherapy was performed. A 7-day diary for CINV was provided to the patients prior to chemotherapy to record daily incidence of CINV. Observed incidence rates of acute (day1) and delayed (days 2-7) CINV were compared with medical staff's predictions. Results: A total of 191 patients (110 males and 81 females) were registered during the period from April 2011 to December 2012. All patients were treated with oxaliplatin-based (n = 175) or irinotecan-based chemotherapy (n = 16). Acute vomiting was observed in 4 patients (2.1%), while delayed vomiting was observed in 19 patients (10.0%). Acute nausea occurred in 14 patients (7.3%), while 63 patients (33%) were affected by delayed nausea. Irinotecan significantly induced acute nausea more frequently than oxaliplatin did (p = 0.019). The presence of motion sickness was significantly associated with the incidence of acute nausea (p < 0.001) and vomiting (p = 0.003). Antiemetics were given along the guideline to all patients. 58 patients were administered a neurokinin-1 (NK1) receptor antagonist. Patients with NK-1 receptor antagonist showed significantly less incidence of delayed vomiting than patients without one (3% vs 13%, p = 0.048). 30 patients (15.7%) required rescue antiemetics. The staff had estimated the incidence of acute CINV in 91 patients (47.6%). However, only 14 patients (7.3%) really experienced acute CINV. Conclusions: CINV seems to be controllable with appropriate management, but delayed CINV still remains an important problem to be targeted. The presence of motion sickness should be affected by efficient antiemetic management. The extent of CINV in this patient group seems to be overestimated.
Helical tomotherapy with concurrent chemotherapy in the treatment of anal canal carcinoma: A review of clinical outcomes at a tertiary referral center.
Authors: Longo John Maclou , Siker Malika Lisa , George Ben , Kosinski Lauren , Ludwig Kirk A. , Otterson Mary F. , Thomas James P. , Wiebe Lauren Allison , Erickson Beth 
Published: February 2017

656 Background: We report the clinical outcomes of patients with anal carcinoma treated with helical tomotherapy (HT) IMRT and concurrent chemotherapy. Methods: From September 2005 to January 2013, 32 patients with squamous cell carcinoma of the anal canal received chemoradiation with HT planned in a consistent manner in parallel to the RTOG 0529 guidelines. Of the patients, 17 (53%) were T1-2, 13 (41%) were T3-T4, 15 (47%) were node positive, and 1 was M1 with para-aortic nodal metastases. There were 7 HIV positive and 3 renal transplant patients. All but 2 patients received 5-fluorouracil and mitomycin C. The median doses to the primary site, involved nodes, and uninvolved nodes were 54 Gy, 50.4 Gy, and 45 Gy, respectively. All acute and late toxicities were scored with the CTCAE v4.0. Results: Median follow-up was 31 months (range 10-97 months). Median length of treatment was 43 days. Twenty-two patients (69%) took a median of 3.5 break days. Acute grade 3-4 hematologic toxicity occurred in 27 patients (84%). There were no grade 4 gastrointestinal or dermatologic toxicities. Eight patients (25%) experienced grade 3 gastrointestinal and dermatologic toxicities. Twenty-one patients (66%) were hospitalized a total of 37 times during chemoradiation or within 90 days of therapy completion. Neutropenic fever was the most common reason for hospitalization, accounting for 30% of admissions. Thirty-one patients were followed for late toxicity with results as follows: 7 patients (23%) had grade 3 gastrointestinal toxicity, 1 patient (3%) had grade 3 dermatologic toxicity, and 3 patients (10%) had grade 3 sexual dysfunction. Nine patients (29%) developed pelvic insufficiency fractures, 5 requiring intervention. The 2-year progression-free and overall survivals were 97% and 97%, respectively. Two patients died; 1 from local progression and 1 from unrelated causes. Conclusions: HT delivering moderate radiation doses consistent with the RTOG 0529 guidelines and chemotherapy paired with aggressive, multidisciplinary management of acute and late toxicities effectively treat squamous cell carcinoma of the anal canal.
Is greater downstaging achieved if surgery is delayed beyond 8 weeks in patients with locally advanced (LA) rectal cancer?
Authors: Shrikhande Shailesh V. , Sirohi Bhawna , Gupta Alok , Sheth Vipul , Ramadvar Mukta , Goel Mahesh , Desouza Ashwin 
Published: February 2017

660 Background: Neoadjuvant Chemoradiotherapy (NACTRT) improves local recurrence rate in LA rectal cancer with no survival benefit. Pathological complete response (pCR) and better tumour regression grade (TRG) is associated with improved outcome. Debate is ongoing as to what is the best time to operate—if greater downstaging can be achieved by a longer interval to surgery and have an impact on sphincter saving surgery rates. In this study, we have correlated the pCR rate and TRG post completion of NACTRT with timing of surgery (TD). Methods: This is a retrospective study of prospective database of patients with LA adenocarcinoma of rectum treated from Jan 2012 to May 2013. 89 pts who completed NACTRT (50Gy/25 fractions with capecitabine 825 mg/m2BD) followed by surgical resection were included. For response evaluation patients were divided into two groups, group 1 (TD < 60 days, n=34) and 2 (TD > 60 days, n=55). Results: Of 89 pts (median age 48 y (22-76), 64 M/25F; 16/89 (18%) had signet ring histology) 93% pts underwent R0 resection; 7% R1 resection. Response to NACTRT was CR in 8 pts, PR in 65 (73%) pts and 15 SD, 1 not assessed. Median time from completion of NACTRT to surgery was 64 d (32-141). Median number LN resected were 11 (1-50). Overall, 25 (28%) pts achieved pCR; 6/89 (7%) pts had positive circumferential resection margin. 25 (74%) patients in group 1 compared to 28 (51%) pts in group 2 underwent sphincter preserving surgery (P=0.045). Eight (24%) pts in group 1 and 17 (31%) in group 2 achieved pCR (P=0.479). The median TRG in group 1 was 2.5 and in group 2 was 2 (P=NS). In pts who achieved pCR, median TD was 67 d compared to 63 d in pts who did not achieve pCR. Of the 16 pts with signet histology 4(25%) had pCR compared to 21(29%) in those with non-signet histology (P=NS). Conclusions: We conclude that the timing of surgery is not an important variable post completion of NACTRT and our data suggests that it's possible that earlier surgery may be better for organ conservation. There is no incremental benefit of delaying the surgery though this needs to be confirmed in a prospective randomised trial.
Observational cohort study focused on treatment continuity of patients (pts) treated with XELOX plus bevacizumab (BV) for previously untreated metastatic colorectal cancer (mCRC).
Authors: Kotaka Masahito , Ikeda Husao , Ikumoto Taro , Tsuzie Masaki , Yoshioka Shinichi , Nakamoto Yoshihiko , Ishii Takaaki , Goto Saori , Itami Atsushi , Kato Takeshi 
Published: February 2017

661 Background: Systemic chemotherapy for unresectable mCRC has remarkably progressed as a results of wide spread use of irinotecan, oxaliplatin, anti-VEGF antibody and anti-EGFR antibody. It is important to continue treatment combined with these drugs and prolong progression-free survival so as to improve overall survival. Methods: We planned and conducted the prospective observational cohort study of 40 pts treated with XELOX + BV for previously untreated mCRC to investigate the treatment continuity of XELOX + BV. Endpoints were time to treatment-failure (TTF), overall response rate, resection rate, liver resection rate, progression-free survival (PFS), overall survival (OS) and safety. Eligibility criteria were (1) histologically confirmed mCRC, (2) with lesions evaluable by imaging, (3) previously untreated (except for surgery), (4) with condition enough to receive XELOX + BV, (5) written informed consent. Forty pts were planned to be enrolled during 2 years and followed up to 2 years. Results: Between July 2010 and June 2012, 40 pts were enrolled. Baseline characteristics were the following; male/female 24/16, median age 63 yrs (range 35-84 yrs), ECOG PS 0/1/2 33/6/1, primary cite colon/rectum 24/16, primary resection prior XELOX+BV yes/no 35/5, metastatic cite liver/lung/paraaorta/peritoneal/local recurrence/others 23/16/4/7/3/4, the number of metastatic cite 1/2/3 26/9/5.The median TTF was 5.3 months (95%CI: 3.6 – 9.1 months), and the reasons for treatment discontinuation were the following; CR 4 pts, resection 10 pts, progression 12 pts, adverse events 7 pts and pts refusal 3 pts. Four pts continued their treatments.The overall response rate was 52.5% (CR 6 pts and PR 15 pts), resection rate was 25.0% (liver 6 pts, lung 2 pts and primary 2 pts), and liver resection rate was 15.0%. The median PFS was 13.3 months (95%CI: 9.8 months – NR) and the median OS was not reached. Conclusions: Although the median TTF was 5.3 months, the median PFS was prolonged to 13.6 months. This might result from chemo-free interval caused by 4 pts’ CR and 9 pts’ resections. We will further investigate 40 pts’ 2-year survival data. Clinical trial information: UMIN000003416.
Efficacy and safety of raltitrexed combinations with uracil-tegafur or Mitomycin C as salvage treatment in advanced colorectal cancer patients.
Authors: Ozkan Metin , Bozkurt Oktay , Karaca Halit , Ozaslan Ersin , Daloglu Osman Onur , Ciltas Aydin , Kaplan Mehmet Ali , Benekli Mustafa , Sevinc Alper , Demirci Umut , Eren Tulay , Kodaz Hilmi , Isikdogan Abdurrahman , Buyukberber Suleyman 
Published: February 2017

662 Background: Oxaliplatin and irinotecan in combination with 5-fluorouracil and leucovorin for metastatic colorectal cancer (mCRC) accepted as the standard treatment. There is no standard treatment approach for patients after progression with these agents. In this study aimed to evaluate the efficacy and side effects of patients with previously treated metastatic colorectal cancer a salvage combination with oral 5-fluorouracil (tegafur-uracil UFT) or Mitomycin C and Raltitrexed. Methods: In the 7 centers, data of 62 patients who received Raltitrexed 2.6 mg/m2 (max. 5 mg) (day 1) and UFT 500 mg/day (1-14. days), or Mitomycin C 6mg/m2 (day 1) every 3 weeks, with a diagnosis of metastatic colorectal cancer, between December 2008 and June 2013 has been analyzed retrospectively. Overall survival (OS), progression-free survival (PFS), and toxicity profiles were evaluated. Results: The median age of patients was 51 (min-max: 18-76 years), and 35 (56%) were male and 27 (44%) were female. Thirty nine patients (63%) had ECOG performance status 0 and 1. Four patients (10%) received a combination of UFT and Raltitrexed at the second line and 38 patients (90%) had third, fourth, and fifth lines. Otherwise Mitomycin C plus Raltitrexed protocol used at the second and third lines. Twelve patients (19%) developed grade 3/4 toxicities as diarrhea and fatigue and 13 patients (21%) needed to dose reduction. In all patients the median PFS was 3 months (%95 CI, 2,65–3,34) and the median OS was 6 months (%95 CI, 2,09–9,90). Two groups were evaluated separately; the median PFS was 3 months (%95 CI, 2,60–3,39) and median OS was 6 months (%95 CI, 2,47–9,53) in UFT arm and, the median PFS was 3 months (%95 CI, 1,64–4,35) and median OS was 12 months (%95 CI, 2,83–21,1) in Mitomycin C arm. Statistical significance could not be determined (p>0.05). Conclusions: Thecombination of Raltitrexed with UFT and Mitomycin C showed an acceptable survival time and toxicity in the treatment of patients with previously treated mCRC. It could be considered as a salvage treatment option in mCRC.
The impact of KRAS mutation on radioembolization in the treatment of unresectable liver predominant metastatic colorectal cancer.
Authors: Schacht Michael , Coldwell Douglas M. , Sharma Vivek 
Published: February 2017

664 Background: Radioembolization with either Yttrium-90 labeled resin or glass microspheres is an FDA approved treatment for hepatic metastases from primary colorectal cancer. Y-90 therapy is used almost exclusively in unresectable liver metastases. However, radioembolization is only an optional part of the treatment process along with first-line, second-line, and salvage chemotherapy. KRAS is a known proto-onco gene that has typically been studied as a negative prognostic factor in the chemotherapeutic treatment of metastatic colorectal cancer (mCRC). KRAS is a known marker for resistance to anti-EGFR antibodies and generally have a poorer prognosis. The aim of this study is to begin to shed light on the impact of KRAS status on the outcome of patients undergoing radioembolization for the treatment of unresectable liver predominant metastatic CRC, regardless of their chemotherapy regimens. Methods: This is a retrospective analysis of 18 subjects treated with radioembolization for liver predominant metastatic CRC. KRAS status and treatment outcomes were followed for each patient up to the study close date of 9/15/13. Statistical analysis was performed using the Mann-Whitney U test. Results: Of the 18 subjects included in the study, 5 were found to have KRAS mutant oncogene. The remaining 13 were found to have the KRAS wildtype. Overall, those subjects with KRAS mutant were found to have a statistically significant difference in median time to progression of intrahepatic metastatic disease burden when compared to KRAS wildtype even when liver-directed therapy was utilized (2.0 vs. 6.4 months). Differences in median time to progression of extrahepatic metastatic disease burden and overall survival were not found to be statistically significant at this time. Conclusions: KRAS mutant patients are exceedingly difficult to treat due to both intrahepatic and extrahepatic disease recurrence/progression.
Overexpression of melanoma-associated antigen D4 as an independent prognostic factor in squamous cell carcinoma of the esophagus.
Authors: Kanda Mitsuro , Oya Hisaharu , Hibino Soki , Takami Hideki , Shimizu Dai , Koike Masahiko , Nomoto Shuji , Yamada Suguru , Fujii Tsutomu , Nakayama Goro , Sugimoto Hiroyuki , Fujiwara Michitaka , Kodera Yasuhiro 
Published: February 2017

71 Background: To pursue an urgently needed treatment target for esophageal cancer (EC), we investigated the function of the recently discovered melanoma-associated antigen (MAGE)-D4 in squamous cell EC. Methods: MAGE-D4 mRNA expression was analyzed in nine EC cell lines using quantitative reverse transcription-polymerase chain reaction (RT-PCR). In 65 surgical specimens of squamous cell EC with no prior neoadjuvant therapy, MAGE-D4 mRNA expression in EC tissues and corresponding normal tissues was analyzed and compared, and evaluated in terms of clinicopathological factors. In representative cases, MAGE-D4 protein distribution was analyzed immunohistochemically. Results: The heterogeneity of MAGE-D4 mRNA expression was confirmed in EC cell lines by quantitative RT-PCR. In surgical specimens, MAGE-D4 mRNA expression was significantly higher in EC tissues than in corresponding normal tissues (P < 0.001). Patients with the highest MAGE-D4 mRNA expression in EC tissues (top quartile, n=17) had significantly shorter overall survival than patients with low expression (2-year survival: 44% and 73%, respectively, P = 0.006). Univariate analysis identified age (≥ 65 years), lymphatic involvement and high MAGE-D4 mRNA expression as significant prognostic factors; high MAGE-D4 mRNA expression was also an independent prognostic factor in multivariable analysis (hazard ratio: 2.194; P = 0.039), and was significantly associated with Brinkman index (P = 0.008) and preoperative carcinoembryonic antigen level (P = 0.002). Immunohistochemical MAGE-D4b expression was consistent with MAGE-D4mRNA profiling. Conclusions: Our results suggest that MAGE-D4 overexpression influences tumor progression and MADE-D4 can be a prognostic marker and a potential molecular target in squamous cell EC.
Expression of PI3K/p-AKT/p-mTOR in gastric carcinoma and its correlation with clinicopathologic characteristics.
Authors: Jieer Ying , Qi Xu , Bixia Liu , Xiangdong Cheng 
Published: February 2017

73 Background: The objective of this study was to explore the expression patterns of PI3K/p-AKT/p-mTOR in gastric cancer (GC) and its relationship with clinicopathological characteristics and thereby to understand the role of activated PI3K/AKT/mTOR pathway in the initiation and development of gastric cancer. Methods: Envision immunohistochemistry assay was used to examine the expression patterns of PI3K, p-AKT and p-mTOR in primary GC sites, metastatic lymph nodes and peritumoral mucosa among 50 patients who underwent radical gastrectomy for stage I-IV (M0) gastric cancer. Results: The PI3K, p-AKT and p-mTOR showed significantly higher expressions in primary tumor sites and metastatic lymph nodes as compared to that of the peritumoral mucosa. The study of the pathway components and clinicopathological characteristics revealed that p-AKT and p-mTOR expressions were selectively higher in primary tumors with less than 5 cm diameter. The PI3K, p-AKT and p-mTOR positive patients had shorter median survival time as compared to the patients negative for them (42.8 m vs. 57.0 m, 46.8 m vs. 55.9 m, 47.2 m vs. 53.0 m). However, the differences were not statistically significant. Conclusions: Activation of PI3K/AKT/mTOR pathway was associated with the development and prognosis of gastric cancer. The expression of PI3K/p-AKT/p-mTOR was correlated well with tumor specificity in gastric cancer and they might have some potential as promising targets for clinical therapy.
Role of aurora kinase A on regulating inflammation and inducing NF-κB pathway activation in gastric cancer.
Authors: Katsha Ahmed M. , Sehdev Vikas , Soutto Mohammed , Peng DunFa , Belkhiri Abbes , El-Rifai Wael 
Published: February 2017

78 Background: Aurora kinase A gene (AURKA) is frequently amplified and/or overexpressed in several malignancies. Inflammation contributes to the pathogenesis of gastric tumorigenesis. We explored the roles of AURKA in inflammation and tumorigenesis. Methods: Immunofluorescence, immunohistochemistry, Quantitative real-time PCR, immunoblot, co-immunoprecipitation, luciferase reporter, and in vitro kinase assays were used to analyze AGS and MKN28 gastric cancer cells. We also analyzed Tff1–/– mice, growth of tumor xenografts, and human tissues. Results: We showed an elevated level of AURKA in the Tff1–/– gastric tissues as compared to wild-type. We also found a positive correlation between AURKA and inflammation (coefficient r = 0.25; P = 0.0056) as well as TNF-α (coefficient r = 0.25; P = 0.0057). AURKA inhibition by MLN8237, a specific AURKA inhibitor, reduced nuclear staining of NFκB in human gastric cancer samples and mouse epithelial cells, suppressed NFκB reporter activity, and reduced the expression of NFκB target genes that regulate inflammation and cell survival. Additionally, AURKA inhibition reduced xenograft tumor size in mice and reversed the development of gastric tumors in Tff1–/– mice. Further, we found that AURKA regulate NFκB activity by directly binding and phosphorylating IκBα in vitro. Premalignant and malignant lesions from the gastric mucuosa of patients had increased levels of AURKA protein and nuclear NFκB, compared with healthy gastric tissue. Conclusions: In analyses of gastric cancer cell lines, human tissue samples, and mouse models, we found AURKA to be upregulated during chronic inflammation to promote IκBα-mediated activation of NFκB and tumorigenesis. This provides a novel role of AURKA in cancer and shows the importance of targeting it as a therapeutic approach in cancer treatment.
Effect of chemoradiotherapy, with adjuvant surgery for local control, on survival in AC and SCC of the esophagus.
Authors: Bass Gary Alan , Furlong Heidi , O'Sullivan Katie E. , Hennessy Thomas P.J. , Walsh Thomas Noel 
Published: February 2017

81 Background: Esophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials. Aims:Long-term results of 2 simultaneous RCTs comparing neo-adjuvant chemo-radiotherapy and surgery (MMT) with surgical monotherapy were examined, and the response of AC (AC) and SCC (SCC) to identical regimens compared. Methods: Between 1990 and 1997, two RCTs were undertaken on 211 patients. Patients with AC (n=113) or SCC (n=98) were separately randomised to identical protocols of MMT or surgical monotherapy. Results: 211 patients were followed to 206 months; 104 patients were randomised to MMT (58 AC and 46 SCC, respectively) and 107 to surgery. MMT provided a significant survival-advantage over surgical monotherapy for AC (P=0·004), SCC (P=0·01). There was a 54% relative risk-reduction in lymph-node metastasis following MMT, compared with surgery(64% vs 29%, P<0·001). MMT produced a pCR in 25% and 31% of AC and SCC respectively. Survival advantage accrued to MMT, pCR and node-negative patients: AC pCR vs surgical monotherapy(P=0·001); residual disease following MMT vs surgical monotherapy(P=0·008);SCC pCR vs surgical monotherapy (P=0·033). Conclusions: A survival advantage for MMT persisted long-term in AC and was replicated in SCC. MMT produced loco-regional tumor down-staging to extinction in 25-31% of patients, potentially permitting personalized treatment in this cohort that avoids the morbidity and mortality associated with resection. Node-negative patients with residual localized disease following MMT had a survival advantage over node-negative patients following surgery alone, supporting a systemic effect on micro-metastatic disease.