bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose escalation of capecitabine in combination with biweekly cetuximab and hepatic arterial infusion (HAI) of oxaliplatin in patients with liver metastases of colorectal cancer: Preliminary clinical results
Authors: Viudez A. , Zárate R. , Garrido M. , Rodríguez J. , Chopitea A. , Fernández-Troconiz I. , Pardo F. , García-Foncillas J. 
Published: August 2020

e15080 Background: To determine the maximum-tolerated dose (MTD) and the doses-limiting-toxicities (DLT) of concurrent capecitabine and cetuximab plus HAI of oxaliplatin (LOHP) in patients with hepatic metastases from colorectal cancer (CCR). Methods: Successive cohorts of 3–6 patients (pts) were treated with HAI LOHP (100 mg/m2), biweekly cetuximab (500 mg/m2) and escalation doses of capecitabine (825 mg/m2 BID d1–7:DL1; 1000 mg/m2 BID d1- 7:DL2; 1250 mg/m2 BID d1–7:DL3; 1500 mg/m2 BID d1–7:DL4) recycled every 14 days. Dose-limiting-toxicities (DLT) were defined as any grade 3–4 events, excepting grade 3–4 skin rash. LOHP and cetuximab PK/PD data were prospectively collected. Results: 19 patients (median age: 60; range: 34–74; 52.9% men, 47.1% females) and ECOG performance status of 1 (range 0–2) were treated at 4 DLs (dose level) as follows: DL: 3 pts, DL2: 6 pts, DL 3: 7 pts and DL 4: 3 pts. All pts were evaluable for toxicity. With a median of follow-up of 21.23 months, ORR was 78.9%, all of them partial response, with 4 pts SD (21.1%). Initially, only 4 pts were considered potentially resectable. Among the remaining 15 pts, 4 (20.6%) could be resected after treatment. Disease progression occurred in 15 pts (78.9%; 3 pts in liver only; 4 pts with extrahepatic metastases; 8 cases with both, hepatic and extrahepatic disease). The TTP was 9.6 months. OS has not been reached. 4 pts have died during the follow-up. Grade ¾ toxicities including Hand-foot Syndrome in 3 pts (1 pt at DL1, other at DL3 and other at DL4), diarrhoea in 3 pts ( one at DL3 and 2 at DL4), anaemia in 2 pts (DL2 and DL4), asthenia in 2 pts (DL2 and DL4) and mucositis in 1 pts (DL3). DLT and MTD were established in DL4 (two pts with diarrhoea grade IV with one of them with grade III HFS) Conclusions: Combination therapy with HAI LOHP plus concurrent capecitabine and cetuximab, can be safely administered to patients with liver metastases from CCR. The MTD and DLT was established in 1500 mg/m2 BID d1 to d7 of capecitabine. The Doses-recommended (DR) has not been obtained yet. oxaliplatin PK/PD is best defined through a bicompartimental model. Mature results of PK/PD analysis will be presented at 2009 ASCO Symposium. No significant financial relationships to disclose.
Variation in enrollment of colorectal cancer patients in clinical trials
Authors: Joubert R. , Raeth U. , Moehler T. 
Published: August 2020

e15094 Background: Correct estimation of patient enrollment is an important success factor for planning clinical studies including studies for metastatic colorectal cancer (CRC). Methods: We reviewed all CRC studies published in the Journal of Clinical Oncology and Annals of Oncology between 01/2007 and 10/01/2008. 43 studies were found and the following data were collected from 39 studies: indication, phase, number of sites, number of patients enrolled, mean patient age, recruitment time, sponsor (Industry, NIH, Organization, University), region, line of treatment and type of drug (6 categories). 4 studies were omitted from analysis as recruitment data were largely missing. Our analysis is based on a literature review as information from unpublished trials is unavailable. This implies some limitations regarding the data interpretation. Results: An average enrollment of 0.92 Patient/Site/Month (range 0.10–7.38) was observed for these trials. The highest recruitment efficacy with a median of 4.11 Pt/S/M (range 1.81–7.38) was found in 5 single institution phase II trials. For multi-center phase II and III studies the median enrollment was 1.82 and 0.32 Pt/S/M respectively, with significant higher recruitment in phase II studies. The highest enrollment rate was observed for studies located in Europe or in USA (0.77 and 2.21 Pt/S/M respectively, p=0.03). No correlation was seen with the mechanism of action (targeted drug vs. chemotherapy), sponsor (NIH vs. Industry vs. IIT), line of treatment (first line vs. 2nd and subsequent line). For phase I recruitment analysis we retrieved 2 studies that investigated novel agents in solid tumor patients including advanced or metastatic colorectal cancer patients with a median recruitment of 0.46 Pt/S/M. For phase Ib and I/II recruitment analysis 5 studies were found with a median recruitment of 0.78 Pt/S/M. Conclusions: Single institution phase II clinical trials on novel agents with high potential to change future treatment standard demonstrate almost a tenfold higher than average recruitment rate for multi-center trials (0.45 Pt/S/M). Despite some limitations in the interpretation of results our analysis provides important information to support estimation of patient recruitment in future clinical trials for colorectal cancer. No significant financial relationships to disclose.
Chemotherapy-free interval following initial chemotherapy in patients with stage IV colorectal cancer
Authors: Melmed G. , Becerra C. , Saracino G. , Bowman E. , McCollum A. D. 
Published: August 2020

e15096 Background: Patients with metastatic colorectal cancer (mCRC) have improved survival due to recent advances in systemic therapy. It remains unclear whether patients responding to initial chemotherapy can be offered a chemotherapy free interval (CFI) without compromising survival. An initial CFI is potentially beneficial from a quality of life and health care economics standpoint. Methods: We studied patients with mCRC treated at Baylor University Medical Center (Dallas, TX) who had a CFI after first-line chemotherapy. Eligible patients had unresectable mCRC and had stable or responding disease after initial chemotherapy. Records were analyzed to record patient characteristics, chemotherapy details, initial response, duration of CFI, progression free survival (PFS), and overall survival (OS). Results: We identified 29 eligible patients treated between 11/02 and 11/08. Analyses are based on data from 8/08. Patient characteristics included: median age 63 (range 34–81), M/F 16/13, ECOG PS 0 (9) or 1 (20), and median number of sites of disease 2 (range 1–7). Initial chemotherapy regimens included mFOLFOX6 with or without bevacizumab (10), FOLFIRI/bevacizumab (12), XELOX/bevacizumab (2), 5-fluorouracil/leucovorin/bevacizumab (3), and capecitabine with or without bevacizumab (2). With a median follow-up of 31.1 months, the median duration of CFI was 8.0 months (95% CI: 4.3–9.6). In addition, the median OS was 33.7 months (95% CI: 27.8 -56.3) and PFS was 15.0 months (95% CI: 9.4–21.4). Conclusions: In this selected group of patients with mCRC, we found a CFI of 8 months. The OS nearing 34 months and PFS of 15 months compares favorably with other studies of patients treated for mCRC. An initial CFI may reduce the medical and financial burden of therapy for patients with mCRC without compromising outcomes and warrants further study. [Table: see text]
Oxaliplatin-based neoadjuvant chemoradiation for locally advanced rectal cancer
Authors: Kazmi S. S. , Azfar M. , Syed A. A. , Yusuf M. A. 
Published: August 2020

e15102 Background: Preoperative chemoradiation improves local recurrence in patients with locally advanced rectal cancer1. The survival benefit of 5-FU based chemotherapy with radiation has been questioned2. Oxaliplatin based protocols have shown promise but the optimal regime remains to be defined3,4. We report our experience with addition of Oxaliplatin to neoadjuvant chemoradiation for rectal cancer. Methods: For this retrospective study, thirty-six consecutive patients referred for neoadjuvant chemoradiation for rectal cancer between May 2007 and March 2008 were identified. All patients had histologically proven adenocarcinoma, and were clinical stage T3/T4 or N+, except for one who was T2N0. Outcomes of interest were R0 resection rate and pathological complete response rate(pCR). Neoadjuvant treatment consisted of upto 4 cycles of CapOx(oxaliplatin 130 mg/m2, IV, D1, capecitabine (2,000 mg/m2/day, D1–14, q3 weeks), followed by capecitabine(1650mg/m2/day) with concurrent pelvic radiation(50.4Gy/28 fractions). Restaging to assess resectability was done at 4–6 weeks and definitive TME surgery was undertaken 6–8 weeks after end of chemoradiation Results: Thirty patients(oxaliplatin group) received at least 1 cycle of CapOx(range 1–8). Radical radiotherapy to 50.4Gy/28# was completed in 29/36 patients(81%). Surgical resection was undertaken in 24/36 patients(67%). Resection rate, R0 resection rate, pCR and local recurrence rate were 63%(19/30), 95%(18/19), 32%(6/19), and 5%(1/19) in the oxaliplatin group. In patients with low rectal cancer (0–5cm from anal verge), 16/26(62%) underwent resection. Sphincter sparing surgery was carried out in 7 patients, all of whom had received oxaliplatin, giving a sphincter sparing surgery rate of 64%(7/11) in the oxaliplatin group. Conclusions: Addition of oxaliplatin to neoadjuvant chemoradiation results in a significant number of patients achieving R0 resection, pCR and sphincter sparing surgery, compared to historical controls. No significant financial relationships to disclose.
Prognostic factors for colorectal cancer patients with pulmonary metastases
Authors: Li W. , Zhang W. , Cai S. , Yin J. , Li J. 
Published: August 2020

e15107 Background: Pulmonary is the second common metastastic site of CRC with a good survival after metastasectomy, however the general situation of pulmonary metastases from CRC has received little attention, especially for unresectable ones. The aim of this study was to determine factors that may influence survival and disease free interval from primary radical surgery to pulmonary metastases (DFI). Methods: From 01/2000 to 11/2008, a total of 206 pts with pulmonary metastases (colon72, rectal ca131, 3 unknown) were collected retrospectively and the clinical data were analyzed using Kaplan-Meier survival curves, univariate and multivariate analysis. Results: 128 pts (62.1%) had lung disease as the first metastatic site and 33 pts (26.7%) had synchronous liver involvement. Only 17 patients (8.3%) followed pulmonary metastatic resection, and others underwent palliative medical treatment including the chemotherapy and intervention. Median survival was 16.0 months (range 12.240–19.760) with a 18% 5-year survival. Of the totally 160 patients who had synchronous pulmonary metastases after radical primary tumor surgery, the mDFI was 20 months (range 16.738–23.262) months. Rectal cancer had a high chance (65%) for lung recurrence with longer DFI (21 vs 14 mo, P=0.02), but no difference of survival was shown compared to colon cancer. Factors that significantly predicted a poor prognosis on univariate analysis included vessel invasion (P=0.022) and high T stage (P=0.009), but neither of them was the independent prognostic factors after multivariate analysis. The factors influencing the DFI of metachronous pulmonary metastases included primary tumor site, pathological morphology, tumor infiltration stage and regional lymph node stage (P<0.05). There was a trend of better survival of patients receiving resection surgery after pulmonary metastases than receiving chemotherapy alone though no statistical significant was reached (mOS:34 vs 16 mo, P=0.125). But to patients who receiving metastatic site resection, chemotherapy after surgery improved the survival (P=0.042). Conclusions: No independent prognostic factors of survival had been found. The invasive tumor with high stage may have a shorter disease free interval of pulmonary metastases after primary surgery. No significant financial relationships to disclose.
Downregulation of RIZ1 protein expression in left-sided versus right-sided primary colorectal carcinomas and their distant metastases and the association with NF-B activation
Authors: Torlakovic E. , Marginean E. C. , Torlakovic G. , Geyer R. , Neufeld H. , Decoteau J. 
Published: August 2020

e15112 Background: Activation of NF- B leads to enhanced proliferation and the expression of anti-apoptotic proteins, which are cancer phenotypes. RIZ1 inactivation through various molecular events was linked to increased proliferation, migration induction and apoptosis inhibition in human cancer. RIZ1 frameshift mutations were recently reported to be confined to MSI-H colorectal tumors and proximal tumor origin, while its hypermethylation was not limited to MSI-H tumors. However, RIZ1 protein expression has not been evaluated in colorectal carcinoma. Methods: TMAs included 28 left-sided and 12 right-sided primary colorectal adenocarcinomas, their matched normal mucosa and their respective distant metastases. Left-sided tumors were compared to right-sided tumors for expression of RIZ1 protein and NF- B activation. RIZ1 immunostaining was scored semiquantitatively (0–3+). NF- B activation was determined by IHC detecting nuclear translocation of its p65 subunit in more than 30% tumor nuclei. Discrepant results were defined as score difference of 2. Results: RIZ1 was less expressed in tumors than in benign mucosa (p<0.0001, r=- 0.377, Chi-Square). The difference between primary vs. metastatic carcinoma was not significant. Low RIZ1 was associated with NF- B activation (p<0.0001, Linear-by-Linear). Left-sided primary tumors showed less RIZ1 protein expression than right-sided (p=0.03, Chi-Square). NF- B activation was more frequent in left-sided primary tumors and their respective metastases (35% in right vs. 67% in left; p=0.002, Chi-Square Test). RIZ1 expression and NF- B activation were almost identical in primary and their respective metastatic tumors with only 3 discrepant results for NF- B status and 2 discrepant results in RIZ1 expression. Conclusions: While RIZ1 downregulation in colorectal adenocarcinoma due to RIZ1 mutations appears to be associated with MSI-H and proximal origin, its protein expression appears to be downregulated more often in distal tumors. NF- B activation is strongly associated with lower RIZ1 protein expression in colorectal adenocarcinoma. No significant financial relationships to disclose.
Phase II study of bevacizumab (B), camptosar (I), high-dose 24-hour continuous intravenous infusion of floxuridine (F) and leucovorin (L) in patients with previously untreated metastatic colon cancer. (B-IFL)
Authors: Ardalan B. , Feagans M. , Mezentsev D. , Jones C. , Subbarayan P. R. , Walker G. , Sapp M. , Stephenson K. , Ness J. , Franceschi D. , Livingstone A. 
Published: August 2020

e15114 Background: In a previous study, IFL was used in patients (pt) with untreated metastatic colon cancer and a median overall survival (MOS) of 31 months (m). In the current study we added B to IFL to determine toxicity profiles (TP) and the response rate (RR) to the B-IFL regimen. The primary end-point is MOS Methods: Each cycle involved 6 weeks (wks) of treatment. The treatment cycle consisted of a 90 minute infusion of I (110 mg/m2), followed by a 24 hour infusion of F (120mg/kg) and L (500 mg/m2) on wks 1, 2, 4, 5. Pt received B (7.5mg/kg) over 90 minutes on wks 1 and 4 prior to IFL. No therapy was given on wks 3 and 6. Eligible pt received 2 cycles of B-IFL followed by CT scan. Quality of life data and thymidylate synthase expression in peripheral blood mononuclear cells was monitored Results: 22 pt with a median age of 57 (38–82), 11 males and 11 females were enrolled. Median KPS was 90% (50–100). 8 pt (36%) had bilobar liver disease and involvement of 1 other organ, 6 pt (27%) had bilobar liver disease with involvement of ≥ 2 other organs; 5 pt (23.5%) had bilobar liver disease; 2 pt (9%) had abdominal carcinomatosis; 1 pt (4.5 %) had involvement in one liver lobe. Grade (Gr) 4 toxicity: pulmonary embolus 1 pt (5%) incidental CT finding. Gr 3 occurred in 11 pt (50%); DVT, diarrhea (Drh) 3 pt (14%); fatigue (Ftg), infection, port site thrombosis (Pst), small bowel obstruction 2 pt (9%); wound dehiscence 1pt (5%); Gr 2 and 1: constipation; Drh; Ftg; nausea; neutropenia; Pst; alopecia; anorexia; mucositis. 17 pt remain alive with median follow up of 15 m (2–28). 5 pt have died due to progression of disease. The estimated median time to progression was 13 m with corresponding lower 95% confidence bound of 8.4 m. Kaplan-Meier estimate at 2 yr survival is 61% (95% CI 27–83%). RR in 21 pt was 67% (95% CI: 43–85%). Conclusions: B-IFL regimen has a manageable TP. RR and progression free interval were promising. Pt accrual is ongoing. Supported by Pfizer. No significant financial relationships to disclose.
The relationship and optimal cutoff value between dual phase corrected whole body uptake ratio (CUR) and serum CEA level in recurrent/metastatic colorectal carcinoma: Dual phase whole body protocol using time of flight (TOF) imaging
Authors: Oh S. , Kim S. , Jun Suk K. 
Published: August 2020

e15116 Background: We evaluate whether the corrected SUR has a lineal relationship with a serum CEA level, and to determine the cutoff level of SUV and CEA level in metastatic focus of recurrent colorectal carcinoma. Tumor to background contrast in whole body PET/CT at 1 hour and 2 hour The relationship and optimal cutoff value between change max SUV and serum CEA level in metastatic colorectal carcinoma: ROC analysis. Methods: 48 patients (M: F=32:16, mean age 56.1) who were previously operated for primary colorectal carcinoma enrolled for evaluating metastasis / recurrence from April 2007 to Feb 2008. An one hour and two hour whole body PET/CT (brain to foot) (Gemini TF PET/CT, Philips Medical Systems) was performed after injection of 370–555 MBq of F18 FDG. The serum CEA level (CEA) measured. The time interval between the PET/CT and the CEA 6.8 ± 3.1 days. Background (BG) correct uptake ratio (CUR)[CUR/BG]= maximum SUV of the ROI/ background value (mean SUV of the liver) calculated and then change of the CUR at 1 hour and CUR at 2 hour were calculated. Results: Among the 48 patients, recurrence was confirmed in 41patients, and the remaining 9 patients were disease free. A significant lineal correlation between change of the CUR at 1 hour and CUR at 2 hour and CEA was founded using ROC analysis (P<0.05). The optimal cutoff value of the change of the CUR at 1 hour and CUR at 2 hour and CEA were 71 % (sensitivity86.7, specificity 83.3, AUC 0.8780.047) and 9.44ng/ml (sensitivity 73.3, specificity 87.5, AUC 0.857±0.051) respectively. The difference of AUC between the change of the CUR at 1 hour and CUR at 2 hour and CEA was not significantly different (0.022±0.065, P = 0.739). Conclusions: The change of CUR of 70 % and the CEA level of 9.44 ng/ml was best cutoff value in detecting the recurrent/metastatic focus in colorectal carcinoma. No significant financial relationships to disclose.
Effect of AbGn-7, a glycotope-specific monoclonal antibody, on apoptosis in colon cancer cells and tumor growth in xenograft models
Authors: Lin S. , Chiang E. , Tsai Y. , Lee S. , Kuo B. , Lin R. 
Published: August 2020

e15118 Background: While clinical benefit against colorectal cancer has been observed with therapeutic monoclonal antibodies such as bevacizumab, cetuximab and panituzumab, the death rate of advanced colorectal cancer remains high that warrants further development of more potent therapeutics. Methods: A cell-based immunization approach was used to generate monoclonal antibodies against targets expressed on human colorectal cancer cells. A chimeric monoclonal antibody, AbGn-7, was selected and evaluated for the potential clinical use to treat colorectal cancer. Results: Expression of AbGn-7 antigen: Carbohydrate competition assay demonstrated that AbGn-7 recognizes a Lewis-A-like carbohydrate antigen (AbGn-7 antigen). Immunohistochemical studies showed that AbGn-7 antigen is expressed in colorectal cancer tissue. No significant binding could be detected in non-tumor tissues except in the epithelia of GI track. Effector function of AbGn-7: AbGn-7 triggered dose-dependent apoptosis in COLO 205 colon cancer cell. In addition, AbGn-7 elicited potent complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) in a dose-dependent manner. Molecular mechanism of apoptosis induced by AbGn-7: Tunel assay, PARP cleavage assay as well as caspase inhibitor studies demonstrated that AbGn-7 induced apoptosis in COLO 205 colon cancer cells via a caspase-independent pathway. Xenograft study: AbGn-7 alone, or in combination with 5FU-Leucovorin, effectively inhibited the growth of COLO 205 xenograft in SCID mice and prolonged their survival. Conclusions: The results of the present study suggest that AbGn-7 is a potential candidate for effective treatment of colorectal cancer. [Table: see text]
The clinical pathogensis significance associated with mutation of APC MCR in colorectal neoplasms
Authors: Lai R. , Feng L. , Liu L. , Xie L. , Wu X. , Zhang S. , Tang X. , Geng J. , Chen T. 
Published: August 2020

e15119 Background: To explore the clinical pathogensis evalution of codon 1493,1367 and 1328 mutations in MCR (mutation cluster region) of exon 15 of APC (Adenomatous polyposis coli) gene in cases of colorectal neoplasm and the family history. Methods: The specimens from 21 colorectal adenoma specimens groups,16 colorectal carcinoma groups, 20 healthy germline groups with positive familial history and 8 healthy germline groups without familial history. MCR of APC gene were extracted and specificly amplified, then sequenced by sequencer, the codon mutations were analyzed between the 4 groups and various genotypes tested with Chi-square. Results: The codon mutations were three variations: 1493(ACG > ACA), 63/69(91.3%); 1367(CAG > TAG), 1/69(1.4%) and 1328(CAG>TAG), 5/69(7.2%). The allele mutations were checked out four genotypes such as 4478(G→A), 41/69(59.4%); 4478(G/A), 22/69(31.9%); 4096(C/T), 1/69 (1.4%) and 3979(C/T), 5/69(7.2%); but the significant groups status (P<0.05) were shown between the adenoma and nonfamily history group on the analysis of 4478(G→A) and (G/A), also the significant differences were tested between the with and without family history on the analysis of 4478(G→A). The significant differences (P<0.05) in pathogensis mutant phenotypes were involved between 4478(G→A) with 4478(G/A), 4096(C/T) and 3979(C/T), respectively; also showed between 4478(G/A) with 4096(C/T) and 3979(C/T); but not between 4096(C/T) and 3979(C/T) (P>0.05). Conclusions: In our data, the highest mutant frequency 4478(G→A) of 1493(ACG>ACA) presented to the significant phenotype of positive history and adenoma, but 4478 (G/A) were associated with colorectal adenocancer, which was discovered in the different effect to candidators despite the same synonymous mutation. In researches, APC MCR codon 1367 and 1328 genotyping were significantly presented in the colorectal cancergenetic phenotypes in somatic cells only. No significant financial relationships to disclose.