bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal effect of initial TNM stage on follow-up intensity for rectal cancer patients
Authors: Ode K. , Virgo K. S. , Longo W. E. , Audisio R. A. , Johnson F. E. 
Published: March 2020

14508 Background: For rectal cancer patients, the risk of recurrence after curative-intent treatment is directly related to initial tumor stage. It is often assumed that more intensive follow-up is worthwhile in patients with high TNM stage lesions, while less intensive follow- up is sufficient for those with low TNM stage cancers. We carried out a survey of members of the American Society of Colon and Rectal Surgeons (ASCRS) to determine the surveillance strategies they use after primary curative-intent treatment for their own patients. This report describes the variation in surveillance intensity ascribable to initial TNM stage. Methods: We created a series of 4 vignettes succinctly describing generally healthy patients with rectal carcinoma (stage I treated with local excision, stage I treated with radical surgery, stage II treated with radical surgery, and stage III treated with radical surgery ± adjuvant therapy). We mailed a questionnaire based on the vignettes to all 1,795 members of ASCRS. Evaluable replies were entered into a computer database. The effect of TNM stage on follow-up intensity was analyzed using repeated-measures ANOVA. Results: There were 566 responses (32%), among which 347 (61%) were evaluable. The most frequent surveillance modality was office visit. In post-operative year 1 for patients with stage I lesions treated with local therapy, 3.8 ± 1.4 office visits (mean ± SD) were recommended, decreasing to 1.5 ± 0.8 in year 5. For patients with stage III lesions treated with radical surgery ± adjuvant therapy, 4.0 ± 2.8 office visits were recommended in year 1, decreasing to 1.7 ± 1.2 in year 5. Similar results were generated for all commonly used modalities on the questionnaire (3 blood tests, 2 endoscopic procedures, 8 imaging studies). Conclusions: The intensity of post-operative surveillance following curative-intent treatment for rectal cancer varies minimally by TNM stage. Because of this, a randomized trial of alternate follow-up strategies may be feasible without stratification according to stage. We will present the schema of such a trial at the meeting. No significant financial relationships to disclose.
High serum YKL-40, but not plasma VEGF and serum HER2, as a prognostic biomarker of short survival in patients with metastatic colorectal cancer
Authors: Nicolaisen N. , Johansen J. S. , Pfeiffer P. , Christensen I. J. , Qvortrup C. , Nielsen S. E. , Glimelius B. , Keldsen N. , Fokstuen T. , Jensen B. V. 
Published: March 2020

14517 Purpose: To evaluate the prognostic value of plasma VEGF, serum YKL-40 and HER2 before, during and after chemotherapy in patients with their first manifestation of metastatic colorectal cancer (mCRC). Patients and Methods: Prospective, longitudinal study of 105 patients (60 men and 45 women, median age 65, range 36–79 years, PS 0–2) from 7 centers referred with their first manifestation of mCRC. The patients were treated with Oxaliplatin 130 mg/m2 day 1 and Capecitabine 2000 mg/m2 days 1–14 every 3 weeks. Median follow-up was 1.8 years. 92 patients had progression and 62 died. The biomarkers were determined by ELISAs. Results: Pretreatment plasma VEGF (median 90 ng/l, range 3–2622, 37% had high level >137 ng/l) and serum YKL-40 (102 μg/l, 28–692, 40% had higher level than the age-corrected 95th percentile in healthy individuals) were significantly (p<0.001) elevated in the patients compared to normal levels. Serum HER2 was not elevated (7.90 μg/l, 3.6–92, 6% had high level >15 μg/l). Pretreatment serum YKL-40 was higher in patients who died compared to those alive (115 vs. 75 μg/l, p=0.004). No differences in plasma VEGF (97 vs. 85 ng/l, p=0.27) and serum HER2 (8.0 vs. 7.4 μg/l, p=0.16) were found. Univariate Cox analysis showed that plasma VEGF and serum HER2 before treatment or during follow-up could not predict progression-free and overall survival. Pretreatment serum YKL-40 (log transformed, scored as a continuous variable) was in a univariate analysis a prognostic biomarker of overall survival (HR=1.8, 95% CI: 1.3–2.6, p=0.0006), but not of progression- free survival (p=0.81). Multivariate Cox analysis (age, sex, number of organs with metastasis, pretreatment serum YKL-40 (continuous variable)) showed that serum YKL-40 (HR=1.8, 95% CI: 1.3–2.6, p=0.001) and possible the number of organs with metastasis (p=0.06) were independent predictors of overall survival. During follow-up, a high serum YKL-40 (log transformed continuous variable and landmark time) predicted shorter time to progression (HR=1.5, 95% CI 1.1–2.1, p=0.01) and overall survival (HR=1.7, 95% CI 1.2–2.4, p=0.005). Conclusion: Serum YKL-40 is a prognostic biomarker of overall survival and during follow-up also of progression-free survival in patients with mCRC. No significant financial relationships to disclose.
Heparanase and Survivin—potential markers of aggressiveness of colon cancers
Authors: Hoffmann A. C. , Hoffmann C. , Danenberg K. D. , Lenz H. J. , Danenberg P. V. 
Published: March 2020

14524 Background: Survivin is an inhibitor of apoptosis and specifically expressed in several human cancers. Heparanase seems to play an important role in cancer metastasis, angiogenesis and regulation of COX-2 expression. The purpose of this pilot study was to evaluate whether there is a difference in the level of survivin and heparanase expression in paraffin-embedded tissue from patients with colon cancer with and without metastasis. Methods: Paraffin-embedded tissue samples were obtained from 32 patients with primary colon tumors with (n = 15) and without liver metastases (n = 17) at the time of diagnosis. After laser capture microdissection direct quantitative real-time reverse transcriptase PCR (RT-PCR, TaqMan™) assays were performed in triplicates to determine survivin and heparanase gene expression levels. Gene expression was normalized with beta-Actin. Decision tree analysis was used to assess whether higher levels of these genes are associated with the existence of metastasis. Results: Neither survivin nor heparanase gene expression alone showed a significant relationship with the pM-Stage, although the detection levels of heparanase showed a tendency towards significant correlation with the existence of liver metastasis (p = 0.06). Decision tree analysis was used to split patients into two groups based on cut-off values of gene expression most closely associated with the pM-stage. The groupings determined by this analysis were significantly differently correlated with metastasis by Spearman’s test (p=0.03). Conclusions: Our results show that high expression levels of both survivin and heparanase in paraffin- embedded tissue are significantly correlated with the pM-Stage in this patient cohort. In conclusion, using intratumoral survivin and heparanase gene expression levels might be useful to identify patients at risk for liver metastasis. Prospective and larger clinical studies are warranted to validate our preliminary findings. No significant financial relationships to disclose.
Postgraduate medical education homogenizes follow-up strategies after primary therapy for rectal cancer patients
Authors: Patel U. , Ode K. , Virgo K. S. , Audisio R. A. , Longo W. E. , Johnson F. E. 
Published: March 2020

14533 Background: The pedagogical literature suggests that continuing medical education (CME) is valuable, but objective evidence of its value has proved difficult to obtain. We investigated how self-reported surgeon age affects self-reported surveillance strategies utilized by expert surgeons following their own patients with rectal carcinoma after curative-intent treatment. We reasoned that, if there were no significant differences in strategies among surgeons of various ages, the homogenization would be ascribable to CME. Methods: We surveyed the 1,795 members of the American Society of Colon and Rectal Surgeons (ASCRS) using a questionnaire based on 4 succinct vignettes describing idealized patients treated with curative intent for TNM stages I-III rectal carcinoma. The surgeons were asked how often they use 14 specific surveillance modalities (office visit, 3 blood tests, 2 endoscopic procedures, 8 imaging studies) during years 1–5 after surgery. The motivation underlying their surveillance practices was analyzed using a menu of 12 possible factors and a Likert scale of 1 (lowest effect on motivation) to 10 (highest effect). We assessed the effect of surgeon age on follow-up intensity, controlling for TNM stage and year post- treatment, using repeated-measures ANOVA. One-way ANOVA was used to analyze the effect of surgeon age on motivation. Results: Of the 566 responses, 347 were considered evaluable. There were no significant differences among age strata (30–39, 40–49, 50–59, and = 60) in surveillance practices for any of the 4 vignettes. Only one motivating factor differed significantly among age strata: psychosocial support for the patient; surgeons = 60 were motivated more strongly (Likert score 6.9; p < .05) by this factor than younger surgeons (Likert score 5.8). Conclusions: CME contributes to homogenization of this important aspect of clinical management among ASCRS surgeons. No significant financial relationships to disclose.
Phase I/II study of S-1 combined with triweekly irinotecan for advanced or recurrent colorectal cancer
Authors: Kakeji Y. , Oki E. , Yoshida R. , Ikeda K. , Ohta M. , Honboh T. , Egashira A. , Sadanaga N. , Morita M. , Maehara Y. 
Published: March 2020

14541 Background: A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced or recurrent colorectal cancer. Methods: The subjects were untreated patients with inoperable advanced or recurrent colorectal cancer aged 20–75 years. S-1 was administered orally at 80 mg m-2 day-1 from day 1 to 14 of a 21-day cycle and CPT-11 was given intravenously on day 1 at an initial dose of 80 mg m-2 day-1, stepping up to 150 mg m-2. The treatment was repeated every 3 weeks, unless disease progression was observed. Results: In the phase I portion, only one of six patients at level 1 (80 mg m-2 of CPT-11) developed DLT, grade 3 diarrhea. No other serious adverse reactions occurred (either hematological or non- hematological), and all patients at levels 2 (100 mg m-2) to 5 (150 mg m-2) could receive therapy safely on an outpatient basis. The final RD was determined to be 150 mg m-2. In the phase II portion, fourteen patients including three patients in the final RD phase I portion were evaluated. The median treatment course was six (range: 2–17). The incidences of severe (grade 3–4) haematological and nonhaematological toxicities were 41.7 and 8.3%, respectively, but all were manageable. The RR was 50% (7 of 14, 95%CI: 23.0–77.0%), and Disease Control Rate (PR + SD) was seen in 71.4%. MST is not reached. Conclusions: Our phase I/II trial showed that S-1 combined with CPT-11 achieved a high response rate and could be given safely on an outpatient basis. These findings suggest that the therapy has potential as first- line treatment for inoperable advanced recurrent colorectal cancer. The updated analysis will be presented at the meeting. No significant financial relationships to disclose.
Phase I trial of neoadjuvant concurrent chemoradiotherapy with S-1 and weekly irinotecan in locally advanced rectal cancer
Authors: Ahn J. , Choi H. , Cheon S. , Shin S. , Keum K. , Min B. , Baik S. , Kim N. , Jeung H. , Roh J. , Chung H. 
Published: March 2020

14543 Background: S-1 is a novel, orally administered 5-FU analogue and is known of radiosensitizer. The aim of this study was to establish the feasibility and efficacy of S-1 in combination with weekly irionotecan with concurrent pelvic radiotherapy (RT) in patients with locally advanced rectal cancer. Methods: Clinical stage T3–4 or N+(on MRI) rectal adenocarcinoma patients received weekly irinotecan 40mg/m2(day1,8,15,22,29) and S-1 at dose levels of 40, 50, 60 and 70mg/m2 (5days a week from day 1 to 38) according to phase I methodology. Concurrently conventional RT was given at daily fractions of 1.8 Gy on 5 days a week for a total dose of 50.4 (45 + 5.4)Gy. Surgery was performed 4–8 weeks following completion of chemoradiation. Results: A total 16 patients (10M/7F, median age 46 years, ECOG PS0–1) were enrolled between August 2005 and July 2006. One pt withdrew the consent during CCRT. Dose-limiting toxicity (DLT) occurred at 50mg/m2 of S-1 in one of six pts (G4 cerebral infarction). At dose of 60, 70mg/m2 of S-1, no DLT occurred. G3/4 toxicties were rare. Fifthteen pts underwent surgery and R0 resection was achieved in 13 pts. Four pts (25.0%) had a pathological complete response. Conclusions: The recommended dose (RD) for further study is S-1 70mg/m2 with irinotecan and radiotherapy. Neoadjuvant S-1/irinotecan/RT is feasible and well tolerated. Phase II trial is being conducted. No significant financial relationships to disclose.
Assessment of influence of hepatitis B or C virus (HBV or HCV) infection on occurence of colorectal liver metastasis (CLM)
Authors: Takahashi S. , Kinoshita T. , Saito N. , Sugitoh M. , Ochiai A. 
Published: March 2020

14559 Background: Rare occurrence of CLM was reported in patients (pts) with HBV or HCV infection, or liver cirrhosis (LC). However, it is obscure whether HBV or HCV infection itself influence occurrence of CLM irrespective of liver cirrhosis (LC). The aim of this retrospective study was to evaluate correlation between HBV or HCV infection and occurrence of CLM. Methods: Subjects of this study were colorectal carcinomas treated by curative resection at our institution between Nov ’92 and Dec ’01 and fulfilled the following criteria; TNM Stage I-III, histologically confirmed colorectal adenocarcinoma, having definitive results of preoperative tests for HB surface antigen (HBsAg) and HCV antibody, and no LC. Results: A total of 1040 pts met the recruitment criteria. Eleven and 60 pts were positive for HBsAg and HCV antibody respectively. Both HBsAg and HCV antibody were negative in the remaining 969 pts. Comparing characteristics between the infection group and the non-infection group, stage (I/II/III: 19/31/21, 305/306/358), lymph node metastasis (present/absent: 51/20, 607/362), histological type (well, mod/por, others: 62/9, 895/74) depth of tumor (T1,T2/T3,T4: 21/50, 358/611), and preoperative CEA level (ng/ml: 6.5±7.5, 9.2±24.6) did not differ between two groups significantly by the chi-square test (stage, lymph node metastasis, histological type, and depth of tumor) and Mann-Whitney’s U test (CEA). Hepatic function of the infection group was slightly worse than those of the non-infection group by student t-test; alb (g/dl: 3.8±0.5, 4.0±0.4, p<0.01), t-bil (mg/dl: 0.8±0.4, 0.7±0.3, p<0.01). When correlations between hepatic recurrence-free survival and clinicopathological factors were examined, depth of tumor (T3.T4), lymph node metastasis, and alb < 3.8g/dl were the independent poor prognostic factors by the Cox regression model. HBV or HCV infection did not correlate with hepatic recurrence-free survival, recurrence- free survival, or overall survival. Conclusions: HBV or HCV infection does not influence on occurrence of CLM. No significant financial relationships to disclose.
Serum p53 antibodies is a postoperative predictive biomarker after curative resection in colorectal cancer patients
Authors: Takeda A. 
Published: March 2020

14567 Background: Because alternations of the p53 tumor suppressor gene are the most commonly observed and can occur early in the carcinogenic process, the accumulation of mutant p53 often leads to the production of p53 antibodies in the sera. The aim of this study is to evaluate the clinical usefullness as early detection marker and as a predictive biomarker of serum p53 antibodies in primary colorectal cancer. Methods: Serum samples are obtained before treatment and from time to time postoperatively and stored - 800C until assay. We employed the newly produced quantitative p53 antibodies ELISA Kit (MESACUP anti-p53 Test, MBL, Japan) to determine the presence of p53 antibodies in 311 patients with colorectal adenocarcinoma compared with the conventional two markers of CEA and CA19–9. Post operative clinical course and the long time survival were evaluated in sero-positive patients after resection. Results: The sensitivities of serum p53 antibodies, CEA and CA19–9 were 32.9%, 36.0% and 23.1%, almost equivalent to CEA and significantly higher than CA19–9. No obvious correlations were evident between the status of serum p53 antibodies and values of two markers, resulting in independent of the other markers. The sensitivity rate of CEA turned up as promotion of pathological stage, but the presence of serum p53 antibodies was more significantly associated with stage 0,I,II. One hundred-nine patients who showed preoperatively sero-positive patients were monitored for at least one year after resection. There was a significant correlation between operative curability and postoperative absence of serum p53 antibodies. Most of repeatedly positive patients treated as curative resection developed recurrence within one year in stageIIandIII. Repeatedly detected patients for serum p53 antibodies have a significantly poor prognosis compared with changed negative patients after curative resection in stageIIandIII. Conclusions: Serum p53 antibodies is easy and convenient, non- invasive, detectable many times and not necessary for surgical specimens for assay. Surveillance of p53 antibodies is rapid and readily facilitated test, which appears to be useful as a new tool for early diagnosis and as a postoperative predictive marker for colorectal cancer patients. No significant financial relationships to disclose.
Cetuximab and irinotecan (CPT11) salvage treatment for colorectal cancer (CRC) in progression after two or more chemotherapy (CT) lines: The POLONORD Group experience
Authors: Fagnani D. , Bertolini A. , Menatti E. , Duro M. , Luchena G. , Ardizzoia A. , Zavallone L. , Filipazzi V. 
Published: March 2020

14575 Background: Cetuximab is a monoclonal antibody blocking the Epidermal Growth Factor Receptor (EGFR), that showed activity in advanced CRC. His safety and therapeutic profile in clinical practice is still carefully evaluating. Methods: 7 Italian Oncology Units (PoloNord Group) treated, from December 2004 to December 2006, 72 patients (pts) affected by metastatic (mts) CRC, in progression after two or more previous CT lines, with Cetuximab + CPT11 ± Fluorouracil (5FU). Cetuximab initial dose was 400 mg/m2, followed by 250 mg/m2 as weekly infusion; dose adjustments based on cutaneous toxicity. Median courses: 12 (range 2–59). CPT11 and 5FU was administered according centres favourite schedules. We evaluated pts for safety, objective response (RO), progression free survival (PFS) and overall survival (OS) Results: Pts characteristics: M/F 48/25; median age 64 years (range 39–74); previous chemotherapy lines: 2–6 (Oxaliplatin and CPT11± 5FU); EGFR positive: 72. Mts sites: liver 56%, lung 21%, peritoneum 10%; 13% of pts had two or more mts sites. Safety: 8/72 (11%) pts showed G3–4 toxicity (WHO): cutaneous 5 pts; vomiting 1 pts, and neutropenia 3 pts . No allergic reactions. 4/72 pts stopped therapy to unacceptable toxicity, while 53/72 pts to disease progression. RO in 68/72 pts were: 9 RP (13%), 14 SD (21%) and 45 PD (66%). 6/14 SD pts showed tumor markers (CEA/Ca19.9) reduction. No pts had surgery option after treatment. Median PFS from start of therapy in 58/72 pts was 4 months (range 1–15). Median OS from diagnosis of mts disease in 67/72 pts was 28 months (range 7–81). Conclusions: According to safety and control disease reporting by international trials, our experiences showed that, also in clinical practice, Cetuximab + CPT11 is a valid option for the treatment of advanced, pretreated CRC. No significant financial relationships to disclose.
Coagulation abnormalities in patients with metastatic colon cancer on bevacizumab therapy
Authors: Fradkina P. , Locker G. , Du H. 
Published: March 2020

14578 Background: Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF) that functions as an anti-angiogenic agent. VEGF is a glycoprotein, important for regulation of angiogenesis in normal and pathologic cells and is required for the maintenance of immature blood vessels, found in tumors. In addition to direct antiangiogenic effects, bevacizumab improves chemotherapy delivery by altering tumor vasculature as well as decreasing the size and number of liver tumors in mouse xenograft model of human colon cancer metastases. This study aimed to look for predictors of the development of major toxicities such as bleeding and clotting that would increase the incidence of such events in patients with metastatic colorectal carcinoma on Bevacizumab therapy. Methods: The study was a retrospective analysis over the past 2 years, reviewing the charts of 59 successive patients receiving bevacizumab in our institution. Particular emphasis was placed on age, gender, tumor type and location, location of metastases, chemotherapy regiment/number of cycles, past medical history, hemoglobin/hematocrit values, PT/INR values, liver function tests and albumin values at the time of the diagnosis and event. Utilizing univariant and multivariant analysis the goal was to determine contributing risk factors for increased incidence of bleeding and clotting. Results: 20.3% of the patients were found to have a major complication, such as clotting or bleeding. Once analyzed, there were four statistically significant indicators (p < 0.05) that predicted for the incidence of either one of the events. They included older patient age, low albumin values at the time of the event (as defined by the institution value of less than 3.6), location of the tumor (cecum, ascending colon and sigmoid colon were predominant), and the site of the metastasis (liver and lung). Conclusions: Clotting and bleeding complications in patients on Bevacizumab are not uncommon. It is clear that age, low albumin values, metastatic site and tumor location contribute to an increased incidence of such events in patients with metastatic colon cancer on Bevacizumab therapy. [Table: see text]