bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and outcomes of hospitalized patients with gastrointestinal malignancies and Clostridium difficile infection: A nationwide analysis.
Authors: Gupta Arjun , Tariq Raseen , Arora Nivedita , Frank Ryan D. , Beg Muhammad S. , Pardi Darrell S. , Johnson David H. , Khanna Sahil 
Published: March 2017

704 Background: Inpatients with gastrointestinal (GI) malignancies are at a high risk for Clostridium difficile infection (CDI) but the impact of CDI on outcomes in these patients needs elucidation. We analyzed the incidence of CDI and its impact on outcomes in GI cancer patients using the National Hospital Discharge Survey (NHDS) database from 2001 - 2010. Methods: NHDS collects clinical information on patients dismissed from non-Federal short-stay United States hospitals. Demographics, diagnoses (GI malignancies, CDI and comorbidities), length of stay (LOS), and dismissal information were abstracted using ICD-9 diagnosis and procedure codes. Weighted analyses were performed using SAS version 9.4. Results: Of an estimated 317.9 million unique hospitalizations; 4.6 million had a diagnosis of a GI malignancy (1.4%); median age 68 years, 46.1% female. CDI was more common in patients with GI malignancies compared to patients with no GI malignancy (1.05% vs 0.69%, aOR 1.16, 95% CI 1.15- 1.17, p < 0.0001). There was a significant increase in CDI incidence in GI cancer patients over the 10-year study period (72.7 in 2001-2002 to 109.1 in 2009-2010, per 10,000 discharges, p < 0001). In multivariable analysis, compared to GI cancer patients without CDI, GI cancer patients with CDI had a longer mean LOS (3.94 more days, 95% CI 3.31-4.56) and dismissal to a care facility (adjusted OR, 1.75; 95% CI, 1.71-1.79), but lower all-cause in-hospital mortality (adjusted OR, 0.76; 95% CI, 0.74-0.79), all p < 0.0001 Conclusions: In this national database of hospitalized patients, an increasing incidence of CDI in patients with GI malignancies was noted over the study period. CDI prolonged hospitalization, and was associated with increased dismissal to a care-facility. Lower rates of in-hospital mortality may represent early diagnosis due to vigilance or a milder form of CDI. Despite increased attention over the last few decades, CDI remained a serious infection in GI cancer patients, and merits appropriate prevention, management and follow-up.
A phase II study of ziv-aflibercept (Z) + FOLFIRI in Japanese patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Satoh Taroh , Denda Tadamichi , Hamaguchi Tetsuya , Sugimoto Naotoshi , Ura Takashi , Yamazaki Kentaro , Fujii Hirofumi , Kajiwara Takeshi , Nakajima Takako Eguchi , Takahashi Shin , Otsu Satoshi , Komatsu Yoshito , Sasaki Toru , Sunaga Yoshinori , Yoshino Takayuki 
Published: March 2017

707 Background: VEGF promotes tumor angiogenesis and metastasis. Z blocks the activity of VEGF-A/-B, and placental growth factor and was shown in the VELOUR phase III study (NCT00561470) outside of Japan to significantly improve overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) in mCRC pts as a second-line treatment given with FOLFIRI. Goals of the current open-label, multicenter phase II study were to assess the efficacy and safety of Z + FOLFIRI in a post-oxaliplatin setting in mCRC pts in Japan. Methods: Pts received Z (4 mg/kg) + FOLFIRI (400 mg/m2 bolus 5-fluorouracil [FU]; 2400 mg/m2 continuous infusion 5-FU; 200 mg/m2 levofolinate; 180 mg/m2 irinotecan) every 2 weeks until progression, unacceptable toxicity, or study withdrawal. Primary endpoint: ORR (required 60 pts in order to obtain a 95% CI width of 16–20%, assuming an ORR of 10–20%). Secondary endpoints: PFS, OS, and safety. Tumors were assessed by independent reviewers every 6 ± 1 weeks until progression. Results: Study enrolled 62 pts; 50 pts (83.3%) had received prior bevacizumab. Of 60 pts evaluable for response, 5 had a partial response and none had a complete response, resulting in an ORR of 8.3% (95% CI: 1.3–15.3%). The median PFS was 5.42 months (95% CI: 4.140–6.702), and the median OS was 15.59 months (range 11.20–19.81). Forty-one pts (66.1%) died due to progression; none died due to study treatment. Pts underwent a median of 8 treatment cycles (range 1–31) lasting a median of 21.8 weeks (range 2–73). The median relative dose intensity was 0.99 (range 0.2–1.0) for Z, 0.87 (range 0.4–1.0) for irinotecan, and 0.96 (range 0.7–1.0) for 5-FU. All pts had ≥1 treatment emergent adverse event (TEAE; see table). Conclusions: The ORR was 8.3% (95% CI: 1.3–15.3%), and the median OS was 15.59 months. The safety profile was consistent with that reported previously. Registered as NCT01882868. Clinical trial information: NCT01882868. [Table: see text]
Preoperative chemoradiotherapy for advanced lower rectal cancer using SOX+Bev regimen.
Authors: Higashijima Jun , Shimada Mitsuo , Yoshikawa Kozo , Nishi Masaaki , Kashihara Hideya , Takasu Chie 
Published: March 2017

708 Background: We have performed preoperative CRT for advanced lower rectal cancer patients using S-1 or UFT. To improve response rate, we are performing phase 2 trial of preoperative CRT using S-1/ Oxaliplatin /Bevacizumab (SOX+Bev) regimen. In this study, we show the results of the trial and the promising predictive factor. Methods: Twenty-five patients (SOX+Bev) and 59 patients (S-1 or UFT) were included in this study. S-1(80mg/m2), UFT(300mg/m2) were administered orally every day on radiation therapy, and S-1(80mg/m2,Oxaliplatin(40-60mg/m2),Bevacizumab(5mg/kg) were administered in SOX+Bev group. Total dose of radiation was 40Gy with four field technique. As a predictive factor, we measured miR-223 with real-time PCR using pre CRT biopsy specimens. Results: Clinical response by RECIST were as follows: SOX+Bev group: CR/PR/SD/PD = 1/21/3/0, S-1/UFT group: CR/PR/SD/PD = 1/32/26/0. Clinical response rate were 88% in SOX+Bev group, higher than 56.0% in S-1/UFT group. Pathological response grade were as follows: SOX+Bev group: 1a/1b/2/3 = 5/4/10/6,S-1/UFT group :1a/1b/2/3 = 13/16/27/3. Pathological response rate was 64% in SOX+Bev group, 51% in S-1/UFT group and there was no significant difference. The pCR rate was 24% in SOX+Bev group, significantly higher than 5% in S-1/UFT group (p < 0.05)B In S-1 group, miR-223 in responder group tended to be higher than non-responder group (p = 0.06). And in SOX+Bev group, miR-223 in Grade 3 group(8.89±9.41) was significantly higher than other group (3.19±4.64) (p = 0.05). Conclusions: Preoperative CRT with SOX+Bev regimen can improve response rate and bring high pCR rate. miR-223 may be promising predictive factor and useful to perform order made therapy. Clinical trial information: 13267.
Overexpression of SETDB1 in relation to poor outcome in gastric carcinoma.
Authors: Okajima Wataru , Komatsu Shuhei , Ichikawa Daisuke , Ohashi Takuma , Imamura Taisuke , Nishibeppu Keiji , Otsuji Eigo 
Published: March 2017

71 Background: SETDB1 is a Histone H3 lysine 9-specific Methyl Transferase belonging to the SET domain. In this study, we tested whether SETDB1 acts as a cancer-promoting gene through its overexpression in gastric cancer (GC). Methods: We analyzed5 GC cell lines and 135 primary GC samples curatively resected in our hospital. Results: Overexpression of the SETDB1 protein was detected in all GC cell lines and primary GC samples (115/135 cases, 85%). Knockdown of SETDB1 using specific siRNA inhibited the proliferation, migration and invasion. Overexpression of the SETDB1 was significantly correlated with lymphatic invasion, deeper tumor depth and higher recurrence rate. Patients with SETDB1-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P = 0.0041, log-rank test) in an intensity and proportion score-dependent manner. Moreover, multivariate analysis demonstrated that SETDB1 was independently associated with worse outcome (P = 0.0178, HR 3.1 (1.20-9.83)). Conclusions: These findings suggest that SETDB1 has a crucial role in tumor cell proliferation and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.
Survival impact of CAPOX versus FOLFOX in the adjuvant treatment of stage III colon cancer.
Authors: Loree Jonathan M. , Sha Aaron , Soleimani Maryam , Ho Maria Yi , Kennecke Hagen F. , Cheung Winson Y. , Mulder Karen E. , Abadi Shirin , Spratlin Jennifer L. , Gill Sharlene 
Published: March 2017

710 Background: CAPOX and FOLFOX are used interchangeably in the adjuvant treatment of colon cancer despite the lack of comparative phase III trials.We aimed to compare toxicities, relative dose intensity (RDI), disease free (DFS) and overall survival (OS) of these regimens in the real world. Methods: We identified consecutively treated patients (pts) with stage III colon cancer at two centers who received either CAPOX or mFOLFOX6 when either option was accessible to pts. RDI was defined as total dose received divided by the total intended dose if all cycles had been delivered. Dose limiting toxicities (DLTs) were toxicities that resulted in a dose reduction of an agent. Survival was compared with the log-rank test and Cox models that adjusted for age, gender, ECOG, T-stage, and N-stage. Results: Of 394 pts, 61.7% received FOLFOX. Age, gender, ECOG, T-stage, N-stage, and time between surgery and start of therapy did not differ between groups. However, RDI and toxicity profiles differed between treatment groups (see Table). With a median follow up of 45 months, there was no difference in OS (HR 0.73, 95%CI 0.45-1.22; P= 0.24); however, CAPOX was associated with a more favorable DFS (HR 0.61, 95% CI 0.40-0.93; P= 0.022). In multivariate analysis, treatment with CAPOX showed trends towards improved OS (HR 0.61, 95% CI 0.34-1.07; P= 0.086). A significant association with improved DFS (HR 0.53, 95% CI 0.33-0.87; P= 0.012) persisted. Exploratory analysis comparing outcomes stratified by the presence of any DLT, neutropenia, thrombocytopenia, and neuropathy failed to show an association with either OS or DFS. (See table.) Conclusions: Our findings suggest that the use of adjuvant CAPOX is associated with an improved DFS despite greater toxicity and lower RDI. Patient selection, the higher starting dose of oxaliplatin in CAPOX, or the metronomic nature of capecitabine may be contributing to improved efficacy of CAPOX. [Table: see text]
Minimally invasive surgery to improve time to chemotherapy in colon cancer: Compliance to the American College of Surgeons Commission on Cancer quality metrics.
Authors: Dumitra Sinziana , Nelson Rebecca A. , Zheleva Vasilena , Raoof Mustafa , Lai Lily L. 
Published: March 2017

712 Background: One of the American College of Surgeons Commission on Cancer (ACS CoC) quality measures in colon cancer is receipt of chemotherapy (CT) in Stage III disease within 120 days of diagnosis. Minimally invasive surgery (MIS) has been associated with faster recovery times. The aim of this study is to assess whether MIS improves compliance to this metric. Methods: Stage III colon cancer patients 80 years old and younger from 2010 to 2012 were identified in the National Cancer Database. Demographic, tumor and treatment characteristics were evaluated including receipt of CT and surgical approach. Uni- and multi-variate logistic regression was used to assess factors associated with CT compliance. Results: Of the 19,963 patients identified, 14,901(74.6%) were compliant while 5,062 (25.3%) were not. Of the patients who were non-compliant, 956 (4.8%) received CT after 120 days. Surgical approach was significantly different between CT compliant and non-compliant groups (MIS 28% vs 32%,p < 0.000). Uni- and multi-variate analyses identified MIS as a significant factor associated with improved compliance to CT with an OR of 1.31 (95%CI 1.22-1.41). Other factors associated with CT compliance were nodal and tumor stage and treatment in an academic program. Non-compliance was associated with age 50-64 (OR 0.76; 95%CI 0.68-0.86), age 65-79 (OR 0.49; 95%CI 0.43-0.56) and increased co-morbidities (OR 0.60; 95%CI 0.53-0.67). Lack of insurance (OR 0.69; 95%CI 0.58-0.81) or Medicaid (OR 0.54; 95%CI 0.47-0.62) and Medicare (OR 0.69; 95%CI 0.63-0.77) as well as distance to hospital of more than 44 miles were also associated with non-compliance to CT (OR 0.86; 95%CI 0.76-0.97). Conclusions: This is the first study to demonstrate that MIS for Stage III colon cancer improves compliance to receipt of CT within the 120 days. Given the potential survival benefits as a result of adherence to ACS CoC cancer care quality metrics, MIS may benefit patients not only in faster return to recovery but also in improved cancer outcomes.
Baseline absolute neutrophil counts (ANC) and survival in second-line metastatic colorectal cancer (mCRC) patients (pts).
Authors: Grothey Axel , Tabernero Josep , Mytelka Daniel S , Li Li , Nasroulah Federico , Yoshino Takayuki 
Published: March 2017

713 Background: Exploratory analyses from RAISE (NCT01183780), FOLFIRI with ramucirumab or placebo in previously treated mCRC pts, suggested pts with treatment-emergent neutropenia may have improved overall survival (OS) compared to pts who did not experience neutropenia on study (Ciuleanu T, et al. abst. 2475, ESMO 2016). Subsequent analyses suggested an even stronger association between baseline ANC and OS, with high baseline ANC associated with shorter OS. A retrospective observational study was conducted to test this association as a pre-specified hypothesis. Methods: The IMS Oncology Database (electronic medical record data from US community practices) was used to identify pts ≥ 18 yrs with mCRC (ICD-9 code 153.x, 154.0 or 154.1) who initiated second-line fluoropyrimidine and irinotecan (+/- bevacizumab; bev) in 2007-2013, following progression during or after first-line fluoropyrimidine and oxaliplatin (+/- biologic). Eligible pts had ≥ 1 ANC in the 60 days prior to second-line therapy. Pts were stratified by second-line bev use and high/low baseline ANC ( ≥ or < 5.5x109/L) and matched by propensity scores. OS based on a validated proxy was analyzed using the Kaplan-Meier method and a Cox proportional hazards model, adjusted for age, gender, ECOG PS, stage, length of first-line treatment, and BMI. Results: 747 eligible pts were identified, of whom 617 were matched. Pts with baseline characteristic data had a median age of 59 yr, 57% were male, 67% were Caucasian, 74% had stage IV disease at diagnosis, and 63% had ECOG PS of 0/1 at start of second-line. Bev-treated pts with high baseline ANC (n = 122) had a median OS (mOS) of 7.7 mo vs 14.7 mo in pts with low baseline ANC (n = 323); adjusted HR 1.69 (95% CI, 1.35, 2.12; p < 0.0001). Pts with high baseline ANC not treated with bev (n = 59) had a mOS 5.4 mo vs 14.4 mo in pts with low baseline ANC (n = 113); adjusted HR 2.73 (95% CI, 1.89, 3.93; p < 0.0001). There was a modest interaction effect between bev treatment and baseline ANC (p = 0.012), indicating greater bev benefit in the high ANC group. Conclusions: Baseline ANC appears to be a strong prognostic factor and potentially a weak predictive factor for antiangiogenic therapy for OS in pts with previously treated mCRC.
Minimally invasive complete mesocolic excision and central vascular ligation for right colon cancer: Defining the radicality of central lymphadenectomy.
Authors: Sammour Tarik , Malakorn Songphol , Thampy Rajesh , Kaur Harmeet , Bednarski Brian , Messick Craig , Chang George J. , You Y. Nancy 
Published: March 2017

715 Background: Complete mesocolic excision (CME) with central vascular ligation (CVL) has been advocated for right colon cancer (RC), but the radicality of lymphadenectomy remains controversial. Optimal D2 lymphadenectomy removes all intermediate nodes with high ligation (HL) of feeding vessels, while D3 lymphadenectomy additionally exposes and retrieves nodes along ventral superior mesenteric vessels (SMA/V). We aim to evaluate minimally invasive CME-CVL, explicitly defining the radicality of central lymphadenectomy. Methods: Patients who underwent minimally invasive resection for RC between 2008 and 2016 were identified from a prospective institutional database. CME was standard. The radicality of central lymphadenectomy was defined as high ligation (HL, optimal D2) vs central node dissection (CND, D3) after review of operative reports and/or videos. A blinded radiologist evaluated the pre- and post-operative CT scans for radiographically abnormal nodes. Results: Among 200 patients, 169 (84.5%) underwent laparoscopic and 31 (15.5%) robotic resection. Central lymphadenectomy was performed as HL in 58 (29%) and as CND in 142 (71%) patients. Preoperative imaging identified abnormal D2 nodes in 33.0% and D3 nodes in 2.6%. CND was performed in 73% of those with abnormal D2 and 100% of those with abnormal D3 nodes. Pathologically positive nodes were identified in 41% (37.9% of the HL and 42.3% of the CND, p=0.64). The median number of nodes retrieved was 27 and 32, respectively. No patient had residual abnormal node on post-operative imaging. The 30 day mortality rate was 0%, and morbidity rate was 15% (4% grade 3, 11% grades 1-2). After a median of 22 months, one (0.5%) patient recurred locally at the anastomosis. Conclusions: Minimally invasive CME-CVL can be safely performed with excellent nodal yield with both optimal D2 as well as D3 lymphadenectomy. With imperfect clinical nodal staging, the near-zero local recurrence rate observed supports CME with optimal D2 lymphadenectomy as a minimum standard and D3 lymphadenectomy when radiographically abnormal nodes are identified.
Association of adjuvant chemotherapy with improved overall survival for patients with locally advanced rectal cancer (LARC) who achieve a pathologic complete response (pCR) to neoadjuvant chemoradiation (nCRT).
Authors: Shahab Danish , Gabriel Emmanuel M. , Attwood Kristopher , Francescutti Valerie , Ma Wen Wee , Nurkin Steven J. , Boland Patrick McKay 
Published: March 2017

716 Background: 15-20% of patients with locally advanced rectal adenocarcinoma (LARC) achieve a pathologic complete response (pCR) following neoadjuvant chemoradiation (nCRT). The role of adjuvant chemotherapy has been questioned. Methods: Patients with rectal cancer receiving nCRT in the National Cancer Data Base (NCDB) 2006-2013 data set were evaluated. The primary outcome was overall survival (OS). The association between OS and patient characteristics were examined using multivariable Cox regression models. Results: 2,903 patients were identified who achieved a pCR. The median follow up was 43.2 months. 2,102 received nCRT and 789 received nCRT + adjuvant chemotherapy. Factors significantly associated with OS included age (p<0.001), gender (p=0.011), Charlson-Deyo comorbidity score (CDI) (p<0.001), grade (p=0.029), clinical T stage (p=0.030), and CEA negativity (p=0.002), but not nodal status. The 3-year OS rate was 94% in the adjuvant therapy group as compared to 84% in the nCRT alone group (p<0.001). In considering clinical N-stage, the benefit was comparable for both N+ and N- tumors. Adjuvant chemotherapy was more likely to be given for younger patients (age < 60), lower comorbidity score, higher grade, positive CEA status, higher clinical T stage, and higher clinical N stage. When stratifying by these factors, similar benefits in OS were observed in the adjuvant cohort. Conclusions: Following nCRT and achievement of a pCR, the receipt of adjuvant chemotherapy is associated with improved OS. Patients receiving adjuvant therapy were more likely to be younger and have a low CDI, but have more advanced stage disease. Thus, a selection bias may be present. Nonetheless, in the setting of the already excellent outcome associated with pCR, the additional benefit of adjuvant chemotherapy should be weighed against toxicity.
Impact of time to surgery in locally advanced rectal cancer patients.
Authors: Naseem Madiha , Yeung Manwah , Senthilvel Suruthi , Dibajnia Pooya , Naila Doshina , Singh Brendan , De Montbrun Sandra , Burnstein Marcus J. , Baxter Nancy N. , Brezden Christine B. 
Published: March 2017

719 Background: Patients with locally advanced rectal cancer (LARC) undergo surgery at 6-8 weeks after neoadjuvant chemoradiation based on standard protocol. However, the optimal time to undergo surgery remains debatable. The goal of this study was to identify associations between time to surgery and additional variables with overall survival (OS) and recurrence rates in LARC patients. Methods: A retrospective chart review was conducted for 80 LARC patients with T3 or node positive disease, who have undergone neoadjuvant chemoradiation and surgery at St. Michael’s Hospital from January 1st 2005-December 31st 2015. Patients were divided into 4 groups based on time to surgery: 4-6 weeks (group 1), 6-8 weeks (group 2), 8-10 weeks (group 3), and > 10 weeks (group 4). Cox proportional hazards model was used to find associations with recurrence and OS. Results: Of the 80 patients, 67.5% (n = 54) were male and 32.5% (n = 26) were female. Median age at diagnosis was 59 years (range, 28-80 years). Median follow-up was 4.84 years. Recurrence occurred in 29% (n = 23) of patients. Incidence of death was 11% (n = 9). Pathologic complete response (pCR) was achieved in 15% (n = 12) of patients. Statin use during chemoradiation was prevalent in 25% (n = 20) of patients. Compared to group 1, patients in group 2 had a 14% reduction in the risk of recurrence (hazard ratio (HR): 0.86, 95% CI: 0.252.91); group 3 had a 69% reduction (HR: 0.31, 95% CI: 0.081.22) and group 4 had a 55% reduction (HR: 0.45, 95% CI: 0.073.08). There was no statistically significant difference in OS between the 4 groups. Furthermore, patients who took statins during chemoradiation had improved OS (HR: 5.42, 95% CI: 39.27.48, p < 0.019) with no difference in pCR rate. Conclusions: This study shows that surgery at 8-10 weeks after chemoradiation offers the best disease-free survival outcome. It also highlights a mortality benefit conferred by statin use during chemoradiation. This could be attributed to the radiosensitizing effects of statins, which allow tumor stem cells to undergo enhanced autophagy. Further prospective studies are warranted to investigate this therapeutic benefit.