bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial disparities in colon cancer: Retrospective analysis of VACCR database.
Authors: Didwaniya N. , Gonsalves W. , Silberstein P. T. , Subbiah S. 
Published: February 2017

528 Background: A racial/ethnic difference in colon cancer survival has been described in literature. However the reasons for this are unclear and access to health care is one of the factors that have been implicated. We plan to examine the clinicopathologic factors of Caucasians (CA) and African Americans (AA) in an equal to access health care system. Methods: 21,992 patients from 1995 to 2009 were identified from the VA Central Cancer Registry database. Age, race, stage, histology, lymph node status, and type of treatment received data were collected. Results: Out of 21,992 patients, 17,924 were CA and 4,068 were AA. 98.07% of CA and 97.83% of all AA were males. Pathological T stages were as follows: T1 = 15.58% vs. 16.13%, T2 = 18.81% vs. 17.56%, T3 = 55.48% vs. 56.03%, T4 = 10.13% vs. 10.28% for CA and AA respectively. Stage-specific incidence, histological grades, and lymph nodal involvement rates were similar in both groups. 77.16% of CA and 77.03% of all AA received chemotherapy. 82.07% of CA and 78.78% of all AA underwent surgery. Median overall survival in CA was 30.73 months and in AA it was 27 months (p < 0.0001). Stage-specific survival (in months) was significantly better for CA in early-stage disease (p < 0.0001) but is similar for both races in metastatic disease (see Table). Median survival in male and female sex irrespective of race was 29.867 months and 35.667 months respectively. Conclusions: Overall survival is better in CA when compared to AA in an equal to access health care system. This survival difference was present only in early-stage disease while in metastatic disease the survival was uniformly poor. Incidence as per stage, lymph node status,and grade were not significantly different among AA and CA. Tumor biology and post-treatment surveillance are potential factors and this needs to be investigated further. [Table: see text] No significant financial relationships to disclose.
Coagulo-fibrinolytic activity as a predictor of efficacy in bevacizumab-combined chemotherapy in metastatic colorectal cancer patients.
Authors: Suenaga M. , Matsusaka S. , Watanabe T. , Takagi K. , Kuboki Y. , Ozaka M. , Shinozaki E. , Chin K. , Mizunuma N. , Hatake K. 
Published: February 2017

533 Background: The combination of bevacizumab (BV) and chemotherapy in the first-line and second-line treatment of metastatic colorectal cancer (mCRC) has been shown to improve survival. Bevacizumab is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor. However, the relationship between coagulo-fibrinolytic activity factors and treatment efficacy remains to be clarified. The aim of this study was to determine potential coagulo-fibrinolytic activity markers impacting survival. Methods: Among 119 consecutive patients included in the study, 85 received first-line FOLFOX4 plus BV 5 mg/kg and 34 received second-line FOLFIRI plus BV 5 mg/kg until progression of disease or unmanageable toxicity occurred. Coagulo-fibrinolytic activity factors, including D-dimer, thrombin antithrombin complex (TAT) and carbohydrate antigen 125 (CA125) encoded by the MUC16 mucin gene were evaluated as candidate predictors of outcome. Results: In first-line treatment, overall response, median progression-free survival (PFS) and two-year survival rate were 61.9%, 518 days and 67.3%, respectively. In second-line treatment, overall response, median PFS and median overall survival (OS) were 23.5%, 248 days and 651 days, respectively. The outcomes of the univariate analysis were as follows: normal D-dimer and CA125 levels at baseline were associated with better PFS and OS in first-line treatment; normal TAT and CA125 levels at baseline were associated with better PFS and OS in second-line treatment. According to the results of the multivariate analysis, normal D-dimer level was associated with longer PFS in first-line treatment, and only CA125 level at baseline was an independent predictor of both PFS and OS in second-line treatment. Conclusions: The results suggest that coagulo-fibrinolytic activity factors such as TAT, D-dimer or CA125 may be useful predictors of outcome in mCRC patients receiving BV in combination with chemotherapy. No significant financial relationships to disclose.
Phase II study of preoperative helical tomotherapy with a simultaneous integrated boost for rectal cancer.
Authors: Engels B. , Tournel K. , Everaert H. , Sermeus A. , Storme G. , Verellen D. , De Ridder M. 
Published: February 2017

537 Background: The addition of concomitant chemotherapy to preoperative radiotherapy is standard of care for patients with T3-4 rectal cancer. The combined treatment modality increases the complete response rate and local control, but has no impact on survival or the incidence of distant metastases. Besides, it is associated with considerable toxicity. As an alternative strategy, we explored prospectively preoperative helical tomotherapy with a simultaneous integrated boost (SIB). Methods: 106 patients were treated with intensity-modulated and image-guided radiotherapy using the Tomotherapy Hi-Art II system. A dose of 46 Gy, in daily fractions of 2 Gy, was delivered to the mesorectum and draining lymph nodes, without concomitant chemotherapy. In patients with a circumferential resection margin (CRM) less than 2 mm on magnetic resonance imaging, a SIB was delivered to the tumor up to a total dose of 55.2 Gy. Acute and late side effects were scored using the NCI-CTC AE v. 3.0. Stage III patients received standard adjuvant chemotherapy. Results: 100 patients (94%) presented with a T3-4 tumor, of which 52 patients entered the boost group (CRM < 2 mm). 54 patients entered the no-boost group. One patient in the no-boost group developed a radiohypersensitivity reaction, resulting in a complete tumor remission, a grade 3 acute and grade 5 late enteritis. No other grade 3+ acute toxicities occurred. With a median follow-up of 32 months (range, 6-58), grade 3+ late gastrointestinal and urinary toxicity was observed in 7 patients (6%) and 4 patients (4%), respectively. Until yet, 2 locoregional relapses were observed. The actuarial 3-year local control, progression-free survival, and overall survival were 97%, 74% and 83%, respectively. Conclusions: Preoperative helical tomotherapy displays a favourable toxicity profile in patients with T3-4 rectal cancer. A SIB can be safely administered in patients with a narrow CRM and results in a promising local control. No significant financial relationships to disclose.
Phase I dose escalation and pharmacokinetics study of intravenous aflibercept plus irinotecan, 5-fluorouracil, and folinic acid (FOLFIRI) in patients with metastatic colorectal cancer.
Authors: Yamazaki K. , Yoshino T. , Yamaguchi K. , Boku N. , Machida N. , Onozawa Y. , Asayama M. , Doi T. , Ohtsu A. , Aoyama T. 
Published: February 2017

538 Background: Aflibercept (AF), a recombinant fusion protein, is a potent inhibitor of vascular endothelial growth factor. This study assessed the safety, dose limiting toxicities (DLTs), recommended dose (RD), and the pharmacokinetics (PK) of AF in combination with FOLFIRI. Methods: This was an open-label, sequential-cohort, dose-escalation study of intravenous AF administered every 2 weeks, in combination with FOLFIRI (fixed doses) in patients (pts) with metastatic colorectal cancer (MCRC). Two dose levels (DL) of AF (2 and 4 mg/kg) were set, and 3-6 pts were to be recruited in each DL. DLTs were to be evaluated in the first 2 cycles. RD was defined as the highest AF dose at which <33% of all evaluable pts experienced DLTs. After establishment of RD, 10 additional pts were treated at RD. PK of AF, irinotecan, SN38, and 5-FU were studied in cycle 1. Results: 16 pts (3 at 2 mg/kg and 13 at 4 mg/kg) with MCRC were treated (M/F, 10/6; median age, 57.0 [47-69]; and ECOG PS 0/1, 9/7), and all had received prior chemotherapies. A total of 131 cycles of AF + FOLFIRI were administered at the two DLs of AF (2 and 4 mg/kg). No DLT was observed. The most common all-causality grade 3/4 adverse events were neutropenia (75.0 %) including one febrile neutropenia after DLT evaluation period and hypertension (25.0%). There was no major safety issue at the RD. Response rate and progression free survival at RD (N=13 pts) was 7.8% and 7.6 month, respectively. Conclusions: RD was determined as 4 mg/kg in this first clinical study of AF in Japanese pts with MCRC. The combination of AF (4 mg/kg) and FOLFIRI was well tolerated in line with results of prior overseas studies. The PK results in Japanese patients showed similar tendency to those reported in patients from other regions of the world. [Table: see text]
Single-institution experience comparing double-barreled wet colostomy to ileal conduit for urinary and fecal diversion.
Authors: Chokshi R. J. , Kuhrt M. P. , Arrese D. , Parks L. , Johnson M. , Martin E. W. 
Published: February 2017

542 Background: Patients with advanced primary or recurrent colorectal cancers that undergo total pelvic exenteration for cure or palliation require proximal urinary and fecal diversion. The most commonly used diversion technique is use of an ileal conduit (IC) and end colostomy. At our institute, the double-barreled wet colostomy (DBWC) has been shown to be have similar outcomes and technically feasible. Methods: Between 2004 and 2010, 37 patients underwent total pelvic exenteration for advanced primary or recurrent colorectal cancer. Two groups were identified based on the technique used for their urinary diversion, either by way of an IC (n = 4) or DBWC (n = 33). Demographics, periprocedural events, and outcomes were compared between the two groups. Results: The two groups were similar in the terms of age, gender, and comorbidities. Thirty-three patients (89%) underwent a DBWC and four patients (11%) underwent an IC. All of these patients underwent a total pelvic exenteration for advanced primary (27%) or recurrent colorectal cancer (73%) either for cure or for palliation. Twenty patients underwent R0 resection (54%), and 17 patients had non-R0 resection (46%). Complications, length of stay, and operative times between both groups were similar. Median survival for both groups showed no statistical difference. Conclusions: DBWC is a safe and feasible alternative to the traditional ileal conduit for urinary diversion. It provides a single stoma to care for, and an intact contralateral abdominal muscle to use as a vertical rectus abdominus musculocutaneous flap for reconstruction. This technique is easy to learn and is not associated with higher operative times, length of stay, morbidity, or mortality. [Table: see text] No significant financial relationships to disclose.
Preclinical antitumor activity and mechanisms of action of apricoxib, a clinical COX-2 inhibitor.
Authors: Burrows F. 
Published: February 2017

543 Background: Apricoxib, a selective COX-2 inhibitor, is currently in phase II trials, but its anticancer mechanisms of action could be better defined. Apricoxib inhibits COX-2 enzymatic activity and suppresses production of PGE2 and VEGF at low nanomolar concentrations but also directly inhibits tumor cell proliferation and survival with 10-20μM potency. In this study we characterized the in vivo activity of apricoxib in xenograft models of lung, breast and colorectal carcinoma. Also, we examined the relationship between the PK, PD and antitumor activity and the effect of the drug on both tumor cell-autonomous functions and aspects of the tumor-host relationship in the HT29 model. Methods: Human tumor xenografts were grown in nude mice and apricoxib was given daily PO. Drug levels were quantified by LC-MS and VEGF levels by ELISA. Vessel density, apoptosis, proliferation and EMT were assessed by immunohistochemistry. Results: Apricoxib significantly retarded tumor growth in NSCLC models and also enhanced the efficacy of SOC drugs in breast and lung tumors. In the HT29 model, the drug was active at both doses tested. Drug concentrations in plasma and tumors peaked at 2-10 μM within an hour and decreased rapidly to submicromolar levels but concentrations persisted above the active concentration for inhibition of PGE2 production for >24h. This strongly indicates that apricoxib exerts its in vivo activity via blockade of COX-2-dependent PGE2 production. Plasma VEGF levels decreased to zero for 6h post-dose, but returned to baseline by 24h. CD31 and Endomucin staining revealed no drug effect on microvessel density, although the percentage of immature vessels was reduced, as determined by pericyte coverage/NG2 expression. Apoptosis was significantly increased by TUNEL in apricoxib-treated tumors. PCNA analysis revealed a decrease in proliferating cells. ECAD expression was significantly increased in treated animals, whereas ZEB1 expression was lower, suggesting that COX-2 activity also plays an important role in EMT. Conclusions: Apricoxib possesses antitumor activity as a single agent and in combination. In the HT29 model, apricoxib inhibits tumor proliferation and survival, normalizes tumor vasculature and reverses EMT. [Table: see text]
SUNCAP, a phase II study with sunitinib and capecitabine in patients with metastatic colorectal cancer (MCRC) refractory to previous treatment with 5FU/irinotecan/oxaliplatin.
Authors: Samson B. , Latreille J. , Nguyen N. T. , Sperlich C. , Berbiche D. , Tournigand C. 
Published: February 2017

545 Background: Patients (pts) with MCRC refractory/resistant to Irinotecan and Oxaliplatin have a poor prognosis. Sunitinib is an oral TKI that selectively inhibits the VEGFR 1, 2, 3, PDGFR and FLT3, CSF-1R, RET. Phase II studies with single agent sunitinib in patients with MCRC did not demonstrate a meaningful ORR but showed acceptable safety profile and warranted further study. Methods: We conducted a phase II escalating dose of sunitinib (S) and capecitabine (C) to assess the efficacy of this oral treatment given on a 2 wks every 3 wks schedule, (level 0, S: 37,5 mg, C: 2,000mg/m2, level +1, S: 50 mg, C: 2,000 mg/m2, level +2, S: 50 mg, C: 2,500 mg/m2 and level -1:S: 25 mg, C: 1,500 mg/m2. Treatment was initiated at level 0 and increased at level +1 and +2 at cycle 3 and 5 if no grade 2/3 toxicity was observed. Between 02.2009 and 06.2010, 15 pts previously exposed to oxaliplatin/irinotecan/bevazizumab were enrolled, all of them had progressive disease at the time of study entry. Primary objective was ORR. Treatment was given until PD or unacceptable toxicity. Results: Pts characteristics were: sex: 12M/3F, median age: 65 years [41-75], primary tumors: colon: 13, rectum: 2, ECOG PS 0/1: 8/7, median nb of metastatic sites: 3, KRAS status: WT/MT/Unknown: 1/9/5. Escalating to level +1:53%, level +2: 7%. Median nb of cycles received/pt: 5. All pts were evaluable for toxicity (tox): SAEs: 40%, any tox. grade 1/2/3(%): 93/60/ 40. Neutropenia gr. 1/2/3(%): 13/13/7, thrombocytopenia gr.1/2/3(%): 13/20/7. Fatigue gr.1/2/3(%): 27/20/7. Nausea gr.1: 27%. Diarrhea gr.1: 13%. Hand foot syndrome gr. 1/2/3 (%): 13/13/27. Mucositis gr. 1/2/3(%): 7/20/7. Hypertension gr.2: 13%. Thyroïd gr.1: 27%. ORR (CR+PR): 0%, confirmed SD: 7/15: 47%, PD: 8/15: 53%. Median PFS: 137 days [95%CI: 112-162], median OS: 291 days [95%CI: 99-482]. Conclusions: In this heavily pretreated patients, sunitinib in combination with capecitabine appears feasible, with acceptable toxicity. 47% of patients had a confirmed stable disease. Although no objective response was observed, the high level of stable disease may suggest a role of this combination for maintenance therapy. [Table: see text]
Preoperative chemoradiotherapy with capecitabine and oxaliplatin in patients with locally advanced rectal cancer.
Authors: Marrodan I. , Azkona E. , Carrera S. , Aresti U. , Calvo B. , Buque A. , Sancho A. , Ruiz de Lobera A. , Munoz Llarena A. , Lopez-Vivanco G. 
Published: February 2017

548 Background: Locally advanced rectal carcinoma is associated with high rate of abdomino-perineal amputation. We analyzed a cohort of patients (pts) diagnosed of locally advanced rectal cancer, treated with neoadjuvant chemoradiotherapy (QT-RT) with capecitabine and oxaliplatin (XELOX) followed by four cycles of adjuvant XELOX after surgery. Methods: Patients with locally advanced rectal cancer (T3-T4 and/or N+) were treated with oxaliplatin (50mg/m2 day 1, 8, 22 and 29) and capecitabine (1,650mg/m2 on days 1 to 14 and 22 to 35) combined with pelvic radiotherapy (180 cGy/day; 45Gy in 25 fractions). Surgery was scheduled 4 to 6 weeks after completion QT-RT. Four cycles of adjuvant XELOX were administered (capecitabine 2,000mg/m2 on days 1 to 14 and oxaliplatin 130mg/m2 on day 1) every 3 weeks. Main end points assessed were: rate of sphincter preservation, pathologic complete response (pCR) rate and the feasibility of postoperative chemotherapy. Results: From March 2007 to April 2010, 98 pts with locally advanced rectal cancer were included. M/F: 66/32; ECOG 0/1: 19/79; median age: 64 (38-81); upper/mid/distal rectum: 13/50/35; clinical stage: cT3/N- 9, cT2-T3/N+ 72, cT4/N- 4, cT4/N+ 13. Full dose of preoperative QT-RT was administered in 93 pts (95%). Main toxicities were grade 1/2 neurotoxicity (56/4) and grade 2/3 diarrhea (23/10). After treatment 96 pts underwent surgery. Sphincter preservation, R0 resections and pCR were achieved in 57, 93 pts and 17 (18%) patients, respectively, and 65 pts (66%) received all 4 cycles of adjuvant XELOX. Grade 3/4 toxicities included diarrhea 3/0, vomiting 2/0, neurotoxicity 5/0, hand-foot syndrome 1/0, neutropenia 4/0 and thrombopenia 0/4. 3-year progression-free and overall survival were 66% and 72%, respectively. No toxic deaths were reported. Downstaging in T/N stage was achieved in 53/71 pts (55/74%) respectively. Conclusions: Combination preoperative QT-RT with capecitabine and oxaliplatin is a well tolerated regimen and achieves encouraging rates of pCR, R0 resection, sphincter preservation and tumor downstaging in patients with locally advanced rectal cancer. No significant financial relationships to disclose.
A phase Ib, open-label, dose-escalation study of tivozanib and FOLFOX6 in patients (pts) with advanced gastrointestinal (GI) tumors.
Authors: Eskens F. , Oldenhuis C. N. , Bhargava P. , Loos W. , Esteves B. , van Doorn L. , Cotreau M. M. , Dhillon R. , Gietema J. A. , De Vries E. 
Published: February 2017

549 Background: Tivozanib (AV-951), a highly potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3, has shown additive antitumor activity with fluorouracil (5-FU) in preclinical studies. An open-label phase Ib study was conducted to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics (PK), and antitumor activity of escalating doses of tivozanib combined with standard-dose FOLFOX6 (i.e., oxaliplatin, leucovorin, and 5-FU) in pts with advanced GI tumors. Methods: Tivozanib was administered orally once daily in 4-week cycles (3 weeks on, 1 week off), with FOLFOX6 administered on days 1 and 15 of each cycle. Pts were allowed to continue tivozanib following discontinuation of FOLFOX6. Results: 22 pts (14 male/8 female; median age of 58 years [range, 40-75]) received 0.5 mg (n = 9), 1.0 mg (n = 3), or 1.5 mg (n = 10) tivozanib plus FOLFOX6. Pts received a median of 8.1 weeks (range, 0.1 - 43.1) of treatment. DLTs were observed in 2 pts receiving 0.5 mg tivozanib (reversible grade 3 diarrhea and grade 3 and 4 transaminase elevations, respectively) and in 2 pts receiving 1.5 mg tivozanib (reversible grade 3 seizures and grade 3 vertigo, respectively). Other grade 3/4 drug-related adverse events (AEs) included neutropenia, fatigue, and hypertension (n = 2 each); and pyrexia, pulmonary embolism, and thrombosis (n = 1 each). There was no indication that drug-related AEs in this study were more frequent or severe than those observed with tivozanib or FOLFOX6 alone. The MTD was 1.5 mg tivozanib with full dose FOLFOX6. The PK profiles of tivozanib, oxaliplatin, and 5-FU will be presented. Several durable partial responses were observed. Additional safety and efficacy data are being obtained in 8 pts currently being treated at the 1.5-mg dose level. Conclusions: The combination of tivozanib and FOLFOX6 is tolerable and safe, with tivozanib given at its recommended dose of 1.5 mg. Observed clinical activity merits further exploration in several GI tumors, and these studies are being planned. [Table: see text]
Delays in adjuvant chemotherapy following AP resection for low rectal cancer: Audit results and implications for clinical practice.
Authors: Nimalasena S. S. , Gaya A. M. 
Published: February 2017

562 Background: Abdominoperineal resection (APR) remains the surgical procedure of choice for low rectal cancer. Historically, it has been associated with high rates of postoperative haemorrhage, infection, and wound dehiscence. The perineal wound is particularly at risk, with rates of 16-41% reported. This may delay adjuvant chemotherapy and adversely affect survival. Methods: Patients who underwent APR in our cancer network between March 2009 and June 2010 were identified. Records were reviewed with respect to complications and any impact on adjuvant chemotherapy. Results: 28 patients underwent APR. The majority had Duke's C (68%) and Duke's B (14%) tumors. All received neoadjuvant chemoradiotherapy (CRT) to 45-54Gy with capecitabine 825 mg/m2 BD. Adjuvant chemotherapy (CAPOX, FOLFOX or capecitabine) was planned in 25/28 (89%) patients. 2 declined, and of the remaining 23, 12 patients (52%) could not receive chemotherapy (Table). Of patients who received adjuvant chemotherapy, the average delay in starting was 2 weeks. At the time of reporting, 25/28 (86%) patients are alive without disease recurrence. One patient who did not receive adjuvant chemotherapy due to wound dehiscence, has recurrent pelvic disease, and is receiving best supportive care. Two patients died of metastatic disease; one could not receive adjuvant chemotherapy due to wound infection. Conclusions: Our audit has highlighted that a significant proportion of patients undergoing APR do not receive adjuvant chemotherapy on time due to wound complications. Often the time taken for wound healing exceeds 3 months, by which time the benefit of chemotherapy is negligible. Phase II studies of neoadjuvant chemotherapy prior to CRT for locally advanced rectal cancer have shown impressive progression-free and overall survival rates, with good compliance rates and favorable toxicity profiles. Further studies are needed. Patients with low rectal tumours who require APR, should be considered for a neoadjuvant chemotherapy approach. [Table: see text] No significant financial relationships to disclose.