bluuebunny/crossref_metadata_2025_split huggingface dataset:
VEGF and VEGF receptor-2 (VEGFR2) gene polymorphisms predict tumor recurrence in stage II and III colon cancer
Authors: Lurje G. , Schultheis A. M. , Hendifar A. E. , Ashouri S. , Zhang W. , Gordon M. A. , Nagashima F. , Chang H. M. , Yang D. , Lenz H. J. 
Published: March 2020

4004 Background: Despite recent advances in the treatment of metastatic colorectal cancer, tailoring adjuvant treatment of stage II and III colon cancer patients remains controversial. Identifying a reliable panel of prognostic and predictive markers for tumor recurrence is critical in selecting an individualized and tailored chemotherapy. Tumor angiogenesis plays an important role in tumor development, progression and metastasis. In this retrospective study, we tested whether a specific pattern of 40 functionally significant polymorphisms in 37 genes involved in angiogenesis and tumor microenvironment will predict the risk of tumor recurrence in stage II and III colon cancer patients treated with adjuvant chemotherapy. Methods: Between 1999 and 2006 blood specimens from 140 patients (69 females and 71 males with a median age of 59 years; range=28–86) were obtained at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC). Sixty-three patients had stage II and 77 had stage III colon cancer. The median follow-up was 5.4 years (range=2.0–16.8). 51 of 140 patients (36.4%) developed tumor recurrence with a 5-year probability of 0.28 ± 0.06 for stage II and 0.40 ± 0.06 for stage III colon cancer patients. Genomic DNA was extracted from peripheral blood and genotypes were determined using PCR based RFLP. Results: Polymorphisms in VEGF (C936T; p=0.009, log-rank) and VEGFR2 (+4422 AC- repeat; p=0.04, log-rank and +1416 T/A; p=0.0009, log-rank) were associated with risk of tumor recurrence in stage III colon cancer patients (n=77). VEGFR2 AC-repeat polymorphisms were additionally associated with risk of recurrence in Stage II colon cancer patients (n=63, p=0.02, log-rank). Conclusion: VEGF C936T and VEGFR2 (+4422 AC-repeat and +1416 T/A) polymorphisms may help to identify Stage II and III colon cancer patients who are at increased risk for developing tumor recurrence. Angiogenesis seems to play a crucial role in tumor recurrence, thus targeting VEGF and VEGFR2 may be of clinical benefit for stage II and stage III colon cancer patients. Large prospective trials are needed to validate these preliminary data. No significant financial relationships to disclose.
Time-dependent patterns of failure and treatment benefit from adjuvant therapy for resectable colon cancer: Lessons from the 20,800-patient (pt) ACCENT dataset
Authors: Sargent D. J. 
Published: March 2020

4008 Background: To explore and inform 3 critical issues facing trialists and practicing oncologists testing adjuvant therapy (AT) for stage II and III colon cancer: 1) The nature and duration of AT benefit, 2) detailed information on survival and recurrence (rec) rates, including long-term event rates (> 10 years (yrs)), and 3) adequacy of statistical models for power and sample size calculations based on a disease-free survival (DFS) endpoint. Methods: The dataset assembled by the Adjuvant Colon Cancer Endpoints (ACCENT) Group, a collection of individual pt data from 18 trials and over 20,800 pts testing 5-FU based AT for pts with stage II and III colon cancer, was analyzed. Results: 1) Significant DFS benefit from AT were manifest in the first two years post randomization; after 2 years DFS rates in the AT and control groups were not significantly different. Significant Overall Survival (OS) benefit of AT was consistent over the 8 year follow-up period. 2) After 5 yrs, rec rates were <1.5%/yr, and after 8 yrs, < 0.5%/yr. 3) For DFS, a Weibull model provided superior model fit compared to the standard exponential model. In the range of Weibull values seen in trials in the dataset, however, the use of the Weibull model did not meaningfully impact power and sample size (<2% impact on power for the same sample size), assuming a constant effect of AT on DFS. Additionally, modeling a non-constant AT effect (as observed for DFS) had a similar negligible impact on statistical power compared to the standard exponential model, for the same sample size. Conclusions: AT provides significant benefit for DFS, primarily within the first 2 years, translating into long-term OS benefit. Long term follow-up for rec yields few events. Despite some increased complexity, existing methods remain appropriate for power and sample size determination for the DFS endpoint, pending further confirmation. No significant financial relationships to disclose.
Effect of alvimopan (ALV) on gastrointestinal (GI) recovery, length of hospital stay (LOS), and postoperative ileus (POI)-related morbidity in patients (PTS) undergoing bowel resection (BR) for colon or rectal cancer (CRC)
Authors: Weese J. L. , Du W. , Techner L. 
Published: March 2020

4014 Background: POI, an interruption of bowel motility, occurs universally after BR and is exacerbated by exogenous opioid analgesia. ALV, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, accelerated GI recovery after BR in multicenter, randomized phase III efficacy trials. CRC is the most common reason for BR in the US, and in the ALV trials CRC was the primary reason for BR for 723 of 1,409 (51%) PTS. This abstract examines GI recovery, LOS, POI-related morbidity, and safety in only this subset of PTS. Methods: This pooled ad hoc analysis assessed the subset of PTS in phase III ALV trials who underwent BR via laparotomy because of CRC and received ALV 12 mg or placebo (PLA) (N = 723). All PTS were scheduled for postoperative intravenous patient-controlled opioid analgesia and received oral ALV or PLA preoperatively and BID postoperatively until hospital discharge or for = 7 postoperative days. Efficacy endpoints included GI-2 recovery (first bowel movement and tolerance of solid food) and postoperative LOS (calendar day after surgery to hospital discharge order written). Treatment effect on GI-2 recovery was analyzed using Cox proportional hazards models, and magnitude of effect was expressed with Kaplan-Meier means. POI-related morbidity included nasogastric tube insertion or complications of POI resulting in prolonged hospital stay or readmission. Safety was monitored by adverse event reports. Conclusions: ALV significantly accelerated GI recovery, reduced postoperative LOS, and reduced the proportion of PTS with POI-related morbidity compared with PLA in PTS undergoing BR for CRC. ALV was well tolerated with a lower incidence of nausea and vomiting in the ALV group than in the PLA group. [Table: see text] No significant financial relationships to disclose.
The impact of dietary patterns on cancer recurrence and survival in patients with stage III colon cancer: Findings from CALGB 89803
Authors: Meyerhardt J. A. , Niedzwiecki D. , Hollis D. , Saltz L. , Willett W. , Mayer R. J. , Fuchs C. S. 
Published: March 2020

4019 Background: Dietary factors have been associated with the risk of developing colon cancer; the influence of diet on pts with established disease is unknown. Methods: We conducted a prospective observational study of 1,009 patients with stage III colon cancer enrolled in a phase III adjuvant chemotherapy trial. Patients reported on dietary intake using a food frequency questionnaire during and 6 months after adjuvant chemotherapy. We identified two major dietary patterns, prudent and Western, by factor analysis. The prudent pattern was characterized by higher intake of fruits, vegetables, poultry and fish; the Western pattern by higher intake of red meat, fat, refined grains and desserts. Since there was no difference in efficacy between the 2 treatments, data for all pts were combined and analyzed according to quintiles of each dietary pattern. Patients were followed for cancer recurrence or death. Results: A higher intake of a Western pattern diet after cancer diagnosis was associated with a significantly worsened disease-free survival (DFS). After adjustment for gender, age, T and N stage, body mass index, physical activity level, weight change, baseline performance status, and treatment arm, patients in the highest quintile of Western pattern diet intake experienced a hazard ratio for DFS of 3.15 (95% confidence interval [CI], 1.76–5.63; p trend = <0.0001), compared to those in the lowest quintile. Western pattern diet was associated with a similar detriment in recurrence-free survival (adjusted p trend = 0.001) and overall survival (adjusted p trend = 0.0002). In contrast, prudent pattern diet did not significantly influence cancer recurrence or mortality. Conclusions: Higher intake of a Western pattern diet may increase the risk of recurrence and mortality among patients with stage III colon cancer patients treated with surgery and adjuvant chemotherapy. Further studies are needed to delineate which components of such a diet are most influential. [Table: see text] No significant financial relationships to disclose.
RTOG 0315: A randomized, double-blind, placebo-controlled phase III study to determine the efficacy of octreotide acetate in preventing or reducing the severity of chemoradiation-induced diarrhea in patients with anal or rectal cancer
Authors: Zachariah B. , James J. , Gwede C. K. , Ajani J. , Chin L. , Donath D. , Kane B. L. , Rotman M. , Berk L. 
Published: March 2020

4032 Background: Diarrhea is a common side effect of chemoradiation for pelvic malignancies. Octreotide acetate has been shown to control grade 3–4 chemotherapy-induced diarrhea in >90% of patients. The primary objective of this randomized placebo-controlled phase III study was to determine the efficacy of long acting octreotide acetate in preventing the onset of grade 2–4 diarrhea. Secondary objectives were to assess the impact of diarrhea on chemoradiation delivery and medical resource utilization. Methods: Eligible patients (pts) with primary anal or rectal cancer, and scheduled to receive concurrent chemoradiation to a minimum dose of 45 Gy using pelvic field sizes greater than 10x10cm, were enrolled. Pts with history of pelvic radiotherapy, chronic bowel disease, diarrhea of grade ≥2, or colostomy were excluded from the study. Pts were stratified by RT dose (<50 Gy and ≥50 Gy), chemotherapy (bolus and continuous) and gender. Pts were randomized to receive two 30 mg intramuscular injections of octreotide acetate (Sandostatin LAR® Depot) or placebo. Injections were given between day -7 and day -4 and on day 22 (± 3 days) of RT. The primary endpoint was incidence of grade 2, 3, or 4 diarrhea (CTCAE v3.0). Assuming a 45% placebo incidence rate, a one-sided chi-square test (alpha 0.05) would require 226 pts to detect a 42% reduction in incidence due to octreotide acetate. Results: The study accrued 233 pts (215 analyzable), 106 pts in the placebo arm and 109 pts in the octreotide acetate arm. The majority of pts (80%) on each arm had rectal cancer. There was no statistically significant difference in incidence of grade 2+ diarrhea (p=0.21) with 52 (49%) and 48 (44%) in the placebo and octreotide acetate treatment arms, respectively. There was also no statistically significant difference between the treatment arms in chemoradiation delivery or medical resource utilization. Conclusions: Prophylactic use of octreotide acetate was not shown to significantly reduce the incidence of mild, moderate or severe diarrhea. No significant financial relationships to disclose.
Phase I/II study of cetuximab dose-escalation in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard dose treatment (EVEREST): Pharmacokinetic (PK), Pharmacodynamic (PD) and efficacy data
Authors: Tejpar S. , Peeters M. , Humblet Y. , Gelderblom H. , Vermorken J. , Viret F. , Glimelius B. , Ciardiello F. , Kisker O. , Van Cutsem E. 
Published: March 2020

4037 Background: Response to epidermal growth factor receptor (EGFR) inhibitor, cetuximab appears to correlate with the intensity of the associated skin reaction. This randomized study investigated cetuximab dose-escalation in patients (pts) with EGFR-expressing mCRC failing irinotecan-including therapy (I). Methods: Pts were randomized 22 days after starting cetuximab (400 mg/m2 initial dose then 250 mg/m2/week [w]) with I (180 mg/m2 q 2 w) if they had not experienced >grade (G) 1 skin reaction, any other >G 2 cetuximab-related adverse event and were tolerant to I. Randomization was to standard cetuximab dose (Arm A; 250 mg/m2/w) or dose-escalation (Arm B; cetuximab dose increased by 50 mg/m2 q 2 w, until >G 2 toxicity, tumor response or dose = 500 mg/m2). Pts not randomized (Arm C) continued on standard cetuximab dose. Primary endpoint was to compare in skin and tumor biopsies, taken before and during treatment, the effects of dose-escalation on EGFR and downstream signalling markers with those of the standard cetuximab regimen. Secondary endpoints were PK, efficacy, safety, tolerability, biomarker analyses on tumor biopsies and plasma samples. Results: 284 pts screened, 221 pts EGFR-expressing, 166 pts enrolled and randomized: 45 to Arm A; 44 to Arm B. 77 non-randomized pts were included in Arm C. M/F 106/60, median age 60 years [25–79], median KPS 90 [70–100]. 24 pts in Arm B reached 500 mg/m2/w. By the cut-off date of July 31st 2006 the preliminary response rate (RR) in Arm B was 30% vs. 13% in Arm A. RR in arm C was 22%. Preliminary progression-free survival in Arm A was 3,9 mo vs. 4,8 mo in Arm B and 3,9 mo in Arm C. In Arm B, 9% pts had G 3/4 skin reactions, 0% in Arm A (14% in Arm C). Dose related increases in Cmax and AUC were observed. T1/2 values were dose independent. Conclusions: Cetuximab dose- escalation up to 500 mg/m2/w improves RR in pts with no or slight skin reactions on standard dose treatment. Overall cetuximab PK behavior is in good agreement with previous experience. Treatment was generally well tolerated. PD and biomarker results will be presented at the meeting. No significant financial relationships to disclose.
Validation of sentinel lymph node (SLN) mapping (M) in colon cancer (Cca) over three continents: An international experience
Authors: Saha S. , Patel M. , Bilchik A. , Beutler T. , Zuber M. , Bembenek A. , Kitagawa Y. , Duben J. , Codignola C. , Cserni G. 
Published: March 2020

4047 Background: Lymph node (LN) status is the most important prognostic factor in colon cancer (Cca). In various trials, the average nodal positivity of conventional surgery in Cca is about 33%. Ultrastaging of SLNs results in higher and more accurate nodal staging of patients (pts) with Cca. However, some recent publications of SLNM in Cca have shown variable results with differing conclusions. Hence, prospective data from 3 continents were analyzed to study the international experience of SLNM in Cca. Methods: Only centers with experience of 40 or more cases of SLNM in Cca were included in the study. SLNM was performed by peri-tumoral injections of 1–3 ml of 1% lymphazurin. First 1–4 blue nodes marked as SLNs were ultrastaged by multilevel microsections for H&E and IHC. Data for calculating the success rate, accuracy, skip metastases (mets), sensitivity, negative predictive value; nodal positivity and upstaging were collected from each center. Results: Our study included a total of 1,216 Cca pts from 9 centers over 3 continents. SLNM was successful in 92.9% pts ( Table 1 ). The average number of LN/pt was 18.5 and the average number of SLN/pt was 2.7. The overall sensitivity, accuracy rate and negative predictive value were 78.3%, 89.4% and 82.8% respectively. Nodal mets were found in 52.9% pts. Of these, SLNs were the exclusive site for mets in 30.1% pts while 18.3% pts were upstaged by SLNM. Skip mets were seen in 21.7% pts (range 9.5% - 44.1%). Conclusions: SLNM is highly successful in Cca when performed by experienced surgeons worldwide. Nodal positivity was found to be much higher in pts undergoing SLNM compared to conventional surgery. Upstaged pts may benefit from adjuvant chemotherapy. Though the variation of skip mets was wide, the clinical impact of skip mets in Cca is negligible compared to that in melanoma and breast cancer, since all pts undergo standard lymphadenectomy and all node positive pts (true +ve & skip mets) are usually treated with adjuvant chemotherapy. [Table: see text] No significant financial relationships to disclose.
Systemic capecitabine and oxaliplatin administered with hepatic arterial infusion (HAI) of floxuridine (FUDR) following complete resection of colorectal metastases (M-CRC) confined to the liver
Authors: Alberts S. , Mahoney M. R. , Donohue J. H. , Roh M. S. , Green E. M. , Sargent D. J. , Wagman L. D. , Bolton J. S. 
Published: March 2020

4057 Background: The prognosis for patients with hepatic metastases from M-CRC can be poor. However, surgery followed by HAI FUDR plus systemic (SYS) 5-FU improves 5-yr survival. Dual therapy OXAL+CAPE has demonstrated activity in advanced CRC. We report final results of an analysis of SYS OXAL+CAPE, alternating with HAI FUDR. The primary endpoint is 2-yr survival (2YS), with 36 of 45 patients surviving 2 yrs as evidence of promising efficacy. Methods: Patients with M-CRC liver lesions amenable to resection ± ablation were eligible. Prior adjuvant chemotherapy for completely resected primary was allowed. HAI+SYS therapy was initiated 21–56 days post-metastasectomy. Four alternating courses of HAI consisted of 0.2 mg/m2/d FUDR and dexamethasone, d1–14 wks 1&2. SYS included 130 mg/m2 OXAL d1, with CAPE at 1,000 mg/m2 po BID, d1–14, wks 4&5. Two additional 3-wk courses of SYS were given. CAPE was reduced to 850 mg/m2/BID after interim review of toxicity. Results: 54 of 73 eligible patients initiated HAI FUDR + SYS. 52% had a solitary met and 24% presented with bilobar mets. Patients completed median of 6 cycles (range 1–6). Reasons for discontinuation included: refusal/toxicity (10), completed per protocol (32), recurrence (4), and medical/other (3). No HAI+SYS related deaths occurred. Median follow-up on the 42 survivors is 28 months (range 7–51). 6 deaths occurred within 2 yrs. 48% (26/54) have recurred; 42% (11/26) with liver involvement. Median time-to-progression is 30 months. The estimated 2YS rate is 88% (95% CI 80–98%) and median overall survival is 46 months (95% CI 41.3-NA). Conclusions: The combination of HAI FUDR and SYS therapy appears to improve outcome following resection of hepatic CRC-M. A 2YS of 88% exceeds our preplanned level of success, supporting the use of this combination in the ongoing NSABP trial C-09. Supported by NIH Grant CA25224–18, Sanofi-Synthelabo, and Roche Laboratories, Inc. No significant financial relationships to disclose.
Liver metastases of colorectal carcinoma: Prospective study on the use of transarterial chemoembolization (TACE)
Authors: Vogl T. J. , Gruber T. , Zangos S. , Balzer J. O. 
Published: March 2020

4062 Background: To evaluate the efficacy of chemoembolization (TACE) in the treatment of liver metastases in colorectal cancer patients concerning local control and survival. Methods: 207 patients with liver metastases of colorectal cancer were treated with repeated TACE in 4-week intervals. In total, 1,307 chemoembolizations were performed with a mean of 6.3 sessions per patient. At the time of first chemoembolization the average age of the patients was 68.8 years (range, 39.4–83.5 years). 158 patients were treated palliatively, 35 symptomatically and 14 patients neoadjuvantly. The chemotherapy consisted of Mitomycin C with/without Gemcitabin; embolization was performed with Lipiodol and starch microspheres for vessel occlusion. Tumor response was evaluated by magnetic resonance imaging (MRI). The change in size was calculated and the response was evaluated according to the RECIST criteria. Survival rates from the first diagnosis and from the first TACE session were both calculated according to the Kaplan-Meier method to obtain the median survival. Results: While 70% of the patients showed multiple metastases, 6% had 1 metastasis, 5.8% had 2 metastases and 18.2% had 3 to 4 metastases. Lesion size and number before, during and after treatment were assessed to deduce the morphological response. Local control results according to the RECIST criteria were as follows: partial response 12% of patients, stable disease in 51% and progressive disease in 37%. The 1-year survival rate after TACE was 62%, but the 2-year survival rate had been reduced to 38%. The median survival time from the date of diagnosis of metastases was 3.4 years (according to Kaplan-Meier), the median survival time from the start of TACE treatment was 1.34 years. The median survival time of the palliative group was 1.4 years, of the symptomatic group 0.8 years and of the neoadjuvant group 1.5 years. Conclusions: TACE is an effective minimal-invasive therapy for neoadjuvant, symptomatic or palliative treatment of liver metastases in colorectal cancer patients. No significant financial relationships to disclose.
Complete pathological response of colorectal liver metastases after neoadjuvant chemotherapy: myth or reality?
Authors: Wicherts D. A. , Haas de R. J. , Levi F. , Aloia T. , Paule B. , Bralet M. , Kunstlinger F. , Azoulay D. , Castaing D. , Adam R. 
Published: March 2020

4063 Background: A complete clinical response (CCR) of colorectal liver metastases (CLM) following chemotherapy has been shown unrelated to the real disappearance of active tumor. By contrast, a complete pathological response (PCR) could be more clinically relevant, but has not been explored. The aim of this study was to evaluate the incidence and outcome as well as predictive factors of PCR, in patients resected from CLM after neoadjuvant chemotherapy. Methods: In our institution 791 consecutive patients with CLM underwent liver resection after neoadjuvant chemotherapy. CCR was defined as the disappearance of all lesions after chemotherapy, and PCR was defined as the total necrosis of all metastases on the resection specimen. Both were selected from a prospective database. Patients with and without PCR were compared, survivals were determined and predictive factors for PCR were analyzed using a multivariate risk model. Results: There were 0.4% CCR (3/791) and 4% PCR (31/791). Among the 31 patients with PCR, the median number of CLM was 2.0 (range 1–13) with a maximum diameter = 3 cm for most cases (73%) at diagnosis. Ten patients (32%) had extrahepatic metastases. Compared to patients without PCR, patients with PCR were younger (p< 0.05) and had a smaller maximum tumor size (p=0.007). Rate of objective response was higher (81% vs. 52%; p=0.002) and last chemotherapy regimen contained more frequently oxaliplatin than irinotecan (p=0.05). Number of chemotherapy cycles and treatment lines were not different. At multivariate analysis, 4 predictive factors of PCR were identified: age = 60 yrs, maximum size at diagnosis = 3 cm, CEA = 40 ng/ml at diagnosis and achievement of an objective response. The probability of PCR ranged from 0.2% when all were absent to 33.8% when all were present. PCR strongly impacted overall survival (OS) that was 69% and 62% at 5 and 10 years with a disease-free survival (DFS) of 42% for both. Conclusions: PCR concerns overall 4% of patients receiving neoadjuvant chemotherapy allowing for surgery, but as much as one third of those aged less than 60 years, developing response on liver metastases smaller than 3 cm, with low CEA values. Uncommon high survival rates are observed in this setting. PCR more than CCR is a reality and strongly impacts patient outcome. No significant financial relationships to disclose.