bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic arterial infusion (HAI) compared to systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma: A systematic review and meta-analysis of randomized controlled trials
Authors: Mocellin S. , Pilati P. , Lise M. , Nitti D. 
Published: March 2020

14519 Background: The treatment of unresectable liver confined metastatic disease from colorectal cancer is a challenging issue. Although locoregional treatments such as HAI claim the advantage of delivering higher doses of anticancer agents directly into the affected organ, the evidence for benefit in terms of overall survival (OS) is conflicting. We aimed to quantitatively summarize the results so far described in randomized trials comparing HAI to systemic chemotherapy. Methods: To date, ten randomized controlled trials (RCT) have been published, for a total of 1,277 patients enrolled. Seven RCT (n=1,098) enrolling at least 50 patients per arm (the minimum sample size required to achieve a type II error lower than 20%) were considered for OS meta-analysis, which was based on the inverse of variance method. For tumor response rates, hazard ratios (HR) and their 95% confidence intervals (CI) were obtained from raw data; for OS, HR and CI were obtained from reported Cox model survival analyses or were calculated from Kaplan-Meier survival curves according to the Parmar method. Results: HAI regimens were based on floxuridine (FUDR) in nine out of ten RCT, while in one case 5-fluorouracil (5FU) + leucovorin (LV) were used. Systemic chemotherapy consisted of FUDR, 5FU, 5FU + LV, or a miscellany of 5FU and best supportive care in three, one, four and two studies, respectively. Tumor response and median OS were better in the HAI arm in eight and three RCT, respectively. At meta-analysis, median tumor response rate was 38.84% and 17.30% for HAI and systemic chemotherapy, respectively (HR: 2.24, CI: 1.80- 2.81; P < 0.0001); on average, median OS was 16.04 and 12.64 months, respectively (HR: 0.83, CI: 0.58–1.19; P value 0.30). Conclusions: Although HAI regimens are followed by significantly higher tumor response rates, no OS advantage can be demonstrated for this locoregional treatment as compared to systemic chemotherapy. Since HAI has been so far compared to systemic chemotherapy regimens not containing modern and more effective antineoplastic agents (e.g. oxaliplatin, irinotecan), these findings do not support the clinical or investigational use of FUDR-based HAI. No significant financial relationships to disclose.
Preliminary data from a phase II study of cetuximab with irinotecan in heavily pretreated patients with epidermal growth factor (EGFR)-expressing metastatic colorectal cancer (mCRC): LABEL
Authors: Buzaid A. , de Cerqueira Mathias C. , Perazzo F. , Simon S. , Fein L. , Hidalgo J. , Murad A. M. , Esser R. , Loos A. , Lerzo G. 
Published: March 2020

14521 Background: Cetuximab (Erbitux) is a monoclonal antibody directed against EGFR that is active in combination with irinotecan in patients (pts) with mCRC, who have progressed during or after a prior irinotecan therapy. Methods: This open, single-arm phase II Latin American study investigated this combination in pts with EGFR-expressing mCRC progressing on or within 3 months of chemotherapy containing at least 6 weeks (w) of irinotecan-based therapy. The primary objective was to assess the best overall confirmed response rate (RR). Sample size calculations were based on an expected rate of 20% (±8%). Planned enrollment was 100 pts. Secondary objectives were to explore the duration of response (DOR), progression-free survival (PFS) time, the 12-week PFS rate, and overall survival time. Pts were treated with cetuximab (initial dose 400 mg/m2 then 250 mg/m2 weekly), plus irinotecan at the same dose and schedule (including dose reductions) as pre-study. Preliminary Results: Of 151 pts from 14 centers screened and in the database, 106 (70%, 3 pts missing) were EGFR-expressing and, of these, 79/106 (75%) were treated on-study. Forty (51%) were male; median age was 59 years [27–82]; 70 (89%) pts had a Karnofsky performance status = 90 and 9 (11%) pts = 80. Nineteen (24%) pts had received = 3 prior treatment regimens, 42 (53%) were previously treated with an oxaliplatin-based regimen for metastatic disease. The confirmed overall RR was 26.6% [17.3–37.7]. Median DOR was 23.9 w [17.1–30], median PFS time was 17.7 w [11.7–18.9], and the 12-week PFS rate was 58% [47–69]. Thirty-three (42%) pts were alive at data cut-off. Median survival was 9.7 months [7.9–13.1]. Treatment was well tolerated with the most common grade 3/4 adverse events including: diarrhea, 20%; neutropenia,10%; acne-like rash, 9%. No grade 3/4 infusion-related reactions were reported. Conclusions: The overall confirmed RRs observed in this heavily pretreated population fully met the expectations for the primary endpoint of this study. LABEL confirmed in a Latin American setting the activity and safety of cetuximab plus irinotecan seen in previous studies. No significant financial relationships to disclose.
Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in patients with metastatic colorectal cancer: A sensitivity marker to 5-FU-based therapy
Authors: Castillo Fernandez O. O. , Herrera L. A. , Castro C. , Calderillo G. , Herrera R. , Bauza A. 
Published: March 2020

14532 Background: 5-Fluorouracil (5FU) and Folinic Acid (FA) with either oxaliplatin or irinotecan have become the standard chemotherapy used for metastatic colorectal cancer. However, more than 50% of our patients cannot afford it. Moreover, we lack of predictive markers to 5FU/AF therapy. The methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the folate pool and its substrate 5,10-methylenetetrahydrofolate is needed for modulation of 5FU. The C677T MTHFR gene polymorphism is highly prevalent in Mexican population and is linked to altered enzyme activity and increases substrate levels. Many studies have suggested a better response rate to fluoropyrimidine based therapy related with C677T polymorphism. The aim of this study was to evaluate the presence of this polymorphism and its relation with progression free and overall survival in metastatic colon cancer treated with 5FU/FA Methods: Sections of paraffin- embedded healthy colonic mucosa of 29 patients with metastatic unresectable colorectal cancer treated with 5FU/FA as first line chemotherapy between 1998 and 2004 were collected to obtain DNA and determine the polymorphism by PCR and allele specific digestion. Results: We found a highly proportion of at least one mutated allele in our patients (8 homozygous wild type CC, 15 heterozygous CT, 6 mutated homozygous TT). C677T MTHFR gene polymorphism showed statistically significant differences in median progression free survival non polymorphic CC 3.23±0.68 month versus 4.8±0.18 month in polymorphic group CT and TT (p= 0.011 log rank test) and median overall survival in non polymorphic groups 6.7±2.63month versus 13 ±2.51 month in polymorphic group (p= 0.03 Breslow test).No other variable affected progression free or overall survival on univariate analysis. Conclusions: Our findings suggest that C677T polymorphism could play a role on survival in metastatic colorectal cancer treated with 5FU/FA. Futher studies evaluating standard chemotherapy and the analyzed polymorphism are recommended. No significant financial relationships to disclose.
The impact of metastatic sites in metastatic colorectal cancer at initial diagnosis (MCCID)
Authors: Leone B. A. , Lacava J. A. , Zwenger A. O. , Iturbe J. , Perez J. E. , Machiavelli M. R. , Romero A. O. , Vallejo C. T. , Dominguez M. E. , Rodriguez R. 
Published: March 2020

14536 Background: The role of metastatic site in MCCID is unclear. The goal of this study is to evaluate if metastatic site influence survival in this setting of patients (P). Methods: Analyses were based on individual data of 300 P with MCCID treated with biochemical modulation of 5- Fluorouracil by Methotrexate regimens in different prospective trials conducted at GOCS Institutions since May 1984 to Aug 2000. P with surgical resection of liver metastases were not included in the analyses. 38 P were excluded for incomplete data. P were grouped according to metastatic sites into group A= Liver metastases only (n=161), group B= Liver and other metastatic sites (n=61) and group C= Non liver metastases (n=40) (lung, peritoneal, others). Different prognostic variables were considered: age, sex, PS, weight loss, size of liver metastases, unilateral or bilateral liver involvement, number of liver metastases, histologic differentiation of primary tumor, location of primary tumor, lactate dehydrogenase, alkaline phosphatase, ALT, AST and hemoglobin. Overall survival (OS) was analyzed since date of diagnosis by means of Kaplan-Meier and the Log-rank test was used to assess the differences. Results: The average follow-up time was 14.4 months (0–73.4). Clinical, laboratory and tumor characteristics were similar among groups A, B and C respectively. However P in group A had bigger size of liver metastases, higher number of them and more bilateral liver involvement respect to group B (p=0.02, p=0.03, p=0.05 respectively). Median OS in group A=21.0 months, group B=13.1 months and group C=15 months (p= 0.02). Statistical difference in OS was observed between group A and group B (p= 0.015). No difference was observed between groups A plus B vs the heterogeneous group C (p= 0.83) Conclusions: P with liver only metastatic site had better prognosis respect to those with other coexisting site of metastases despite presenting higher tumor burden in the liver. No factors analysed in the study explaine this difference. The subset of P with liver only metastatic site would be considered as a distinctive group and deserve further molecular studies. No significant financial relationships to disclose.
Complications and effectiveness of combination chemotherapy in metastatic colorectal cancer (MCRC) with unresected primary (UP)
Authors: Abdal Raheem S. , Gupta B. , Tan W. , Wilding G. , Smith J. , Yang G. , Rajput A. , Bullard Dunn K. , Fakih M. G. 
Published: March 2020

14537 Background: The outcome of patients (pts) with MCRC and unresected primary (UP) has not been studied systematically in the modern era of targeted and combination chemotherapy. We conducted a single institute retrospective study to determine the rate and nature of complications in this population. Methods: MCRC-UP pts treated at Roswell Park Cancer Institute between 2002 and 2006 were identified. Demographic, toxicity, efficacy, and palliative intervention data were collected. Primary tumor related complications including obstructive symptoms, bleeding, perforation, and fistulas were assessed. Results: 24 pts with colonic UP were identified. 14/24 were treated with bevacizumab-based chemotherapy (11 FOLFOX, 3 capecitabine), 7/24 with FOLFOX, 2 with capecitabine, and 1 with FOLFIRI. No perforations, hemorrhagic events, or arterial events were noted. None of the 24 pts required palliative surgical intervention secondary to the UP. Only 2 pts developed obstructive symptoms and 1 pt developed an entero-cutaneous fistula; all 3 events were attributed to peritoneal carcinomatosis. 10 pts with rectal UP were identified. 1 pt received upfront chemoradiation followed by 5-FU/bevacizumab. 9/10 pts were treated with upfront systemic chemotherapy (6 bevacizumab-based [5 FOLFOX, 1 capecitabine], 3 FOLFOX). Of these 9 pts, 4 required subsequent palliative radiation therapy for obstructive symptoms (3 pts) or pain (1pt) while 5 continue on systemic chemotherapy (median 1st line chemotherapy duration > 7 months). No perforations, bleeding requiring transfusion, or arterial events were noted among the rectal cancer population. 1 pt required a diverting colostomy for obstruction despite palliative CRT. Median time to progression on first line chemotherapy was 7.4 months for colon cancer and 8 months for rectal cancer. The median overall survival was 13.6 months for colon cancer and has not been reached for rectal cancer (exceeded 13 months). Conclusion: Treatment of MCRC with UP is feasible and is rarely associated with complications related to the primary tumor. Rectal cancer with UP can be managed with upfront chemotherapy. Subsequent palliative RT is needed in about 50% of these pts. No significant financial relationships to disclose.
Apoptosis inducing factor is decreased in metastatic colon cancer in ex-vivo models of colon carcinogenesis by tissue microarray
Authors: Huerta S. , Amirkhan R. H. , Siddiqui A. A. , Livingston E. H. , Huerta-Yepez S. 
Published: March 2020

14539 Background: In vitro studies suggest that apoptosis inducing factor (AIF) expression is decreased in metastatic cells relative to those derived from primary tumors. This study was undertaken to determine AIF expression patterns in patients with stage I/II vs. stage III/IV colorectal cancers. Methods: Colon cancer specimens were prospectively collected (11/05–6/06) from 12 patients from 3 different sites: tumor, adjacent to tumor, and tissue 2 cm from the tumor. Paraffin-embedded specimens were examined by tissue microarray with AIF-specific antibodies. Total AIF expression as well as cytoplasmic and nuclear expression was assessed by an investigator blinded to the tissue site and patient stage. Staining was assessed as: 1=absent, 2=mild, 3=moderate, 4=high and 5=very high. The clinical characteristics and tumor stage of all patients were analyzed. Results: All patients were male. Eight patients had non-metastatic disease at the time of laparotomy, four had metastasis to: lymph nodes (n=3) and liver (n=1). Stage I/II patients (n=8) were of similar age compared to stage III/IV patients (n=4) [61.3±4.2 vs. 54.4±6.0 y.o.; p=0.6] had similar tumor size (3.81±0.7 vs. 4.08±1.4 cm; p=0.4). There was no difference in the level of expression of AIF in normal tissue collected 2-cm away from the tumor site in stage I/II vs. stage III/IV colon cancers in the cytoplasm (3.81±0.17 vs. 3.30±0.38; p=0.4), nucleus (3.19±0.43 vs. 2.49±0.46; p=0.8) or overall (4.06±0.27 vs. 3.37±0.8). A significant decrease in AIF expression was observed in stage III/IV tumors compared to stage I/II tumors in tissue collected adjacent to the tumor in the cytoplasm (3.12±0.22 vs. 4.46±0.25; p=0.03), the nucleus (2.10±0.44 vs. 3.63±0.32; p=0.03) and overall (3.12±0.22 vs. 4.46±0.25; p=0.03). There was a trend towards a decrease in AIF expression between stage III/IV vs. I/II tumors in tissue collected directly from the tumor in the cytoplasm (2.55±0.24 vs. 3.56±0.26; p=0.12), the nucleus (1.39±0.25 vs. 2.73±0.63; p=0.14) and overall (2.79±0.38 vs. 3.90±0.37; p=0.22). Conclusion: AIF expression is decreased in metastatic colon cancer. The main differences occur in the normal mucosa adjacent to the tumor. No significant financial relationships to disclose.
Nigro regimen treatment of squamous cell cancer of the anus
Authors: Kalmadi S. R. , Pelley R. J. , Kay E. , Saxton J. P. , Bukowski R. M. , Kim R. D. , Lavery I. C. , Fazio V. W. 
Published: March 2020

14545 Background: To identify prognostic factors for patients with squamous cell cancer (SCC) of the anus treated with Nigro Regimen chemo/radiation therapy. Methods: Survival data of 61 patients with SCC of the anal canal were reviewed who were treated with definitive radiochemotherapy (RCT) between 9/83 and 3/06. All patients received RCT at the Cleveland Clinic Foundation. Results: Patient characteristics were typical of other studies. Median age was 57 years (34–82), women: men (42:19), PS 0–1 (95%), smokers 52%, and clinically lymph node positive tumors 27%. T3–4 tumors were 50%, high for most series. The median follow-up time was 52 mos (7–246 mos). The median disease free survival (DFS) and overall survival (OS) have not been reached. 5-year DFS was 76% (95% C.I. 62–88%) and 5-year OS was 76% (95% C.I. 60–86%). Colostomy free survival at 5-years was 41/61 (67%). Log rank analyses showed that female sex (5-yr DFS 82 vs 55%, p=0.03), and clinical stage (5-yr DFS, stage 1 100%, stage 2 80%, stage 3a 65%, stage 3b 0%) correlated with better disease free survival. Patient age (less than 60 or greater), time of diagnosis (before 1996 or later), and smoking status did not correlate with better disease free survival. There were 14 recurrences, 7 systemic, 7 local with APR salvaging 4 patients with local relapse. There were 2 cases of treatment related hemolytic uremic syndrome, with one death. Conclusions: The Nigro regimen is successful in curing anal cancer in a significant majority of patients. We appear to have reached a therapeutic plateau and have not had any significant improvement in cure rates over the last two decades. Identification of subsets more prone to relapse is crucial, to target with more intense treatment in future trials. In the current series, male sex and advanced clinical stage correlated with poor disease free survival, when anal cancer patients were treated with the Nigro regimen RCT. Future studies should investigate whether more intensive treatment is needed in males, and patients with more advanced disease. No significant financial relationships to disclose.
Prospective control trial of cancer ultrastaging in the left colon with sentinel lymph node
Authors: Hernando R. , Serra X. , Bombardó J. , Casalots A. , Mena E. , Martín J. , Junquera F. , Pericay C. , Navarro S. 
Published: March 2020

14547 Background: The use of the sentinel node lymph (SNL) in connection with colorectal cancer is a subject in which there has been some controversy. Methods: Prospective control trial of 60 patients with left colon cancer stage II. Methylene Blue® or Nanocoll® had been used to identify the SNL. The standard pathologic examination with hematoxylin and eosin (H&E) had been compared with the study of SNL with H&E and Cytokeratine CAM 5.2. Results: Identification of the SNL: 100%, 2.4 SNL detected in each patient. Nodal disease (N+) was found in 19 patients (31.7%), and 41 patients (68.3%) were classified as node-negative (N0). Hidden micrometastasis in the SNL were found in 9.7% (4/41) patients considered as N0 by conventional histopathology. However, in 17.7% (7/41) patients considered as N0 we found large cell clusters, contatining up to 10 tumor cells, falling short of the AJCC on cancer criteria, and were considered to have high- risk disease. Having applied both the SNL study and the standard pathologic examination the number of patients N+ has increased to 38.3% (23 patients), ultrastaging: 6.6% (p= ns). If the patients with large cell clusters in the SNL had been considered as N+ the number of N+ patients would have increased to 50%(30 patients), ultrastaging 18,3%(p=0,001). Conclusions: The combined nodal study (H&E + SNL) increased 6.6% the staging in our group, and it let to identify a group of patietnts N0 with high-risk tumor progression. If the large cell clusters in the SNL were considered as micrometastases disease the ultrastaging would have been 18.3%.The implications of large cell clusters prognosis is yet, unknown. No significant financial relationships to disclose.
Dermatological toxicities of panitumumab in the treatment of patients with metastatic colorectal cancer (mCRC) from three clinical studies
Authors: Drelich D. A. , Rose L. , Ramirez M. , Jacobs M. , Mitchell E. 
Published: March 2020

14551 Introduction: Epidermal growth factor receptor (EGFr) expression in CRC is associated with metastatic potential and poor prognosis. Panitumumab, a fully human monoclonal antibody against EGFr, was approved for the treatment of patients with refractory mCRC. The main side effects of panitumumab include dermatological manifestations that have been termed “rash”. However, classification of the dermatological manifestations has not been clearly described. Methods: We summarized the dermatological manifestations of 19 patients from 3 clinical studies investigating the the safety and efficacy of panitumumab monotherapy in mCRC in a single institution. Two of these studies were open lable, phase 2 in design which enrolled patients with documented disease progression (PD) during or after adequate doses of fluoropyrimidine, irinotecan, and oxaliplatin chemotherapy. In the other panitumumab was given in combination with irinotecan or oxaliplatin with bevacuzumab, 5FU, and leucovorin. Pts received panitumumab at 6mg/kg Q2W until PD or intolerability. Skin assessments were made q2w. Results: Five patients were men (26%) and 14 (73%) women; 12 were Caucasian (63%) and 7 (36%) African American. The median age was 53 (Range 38–80). Tumor response, disease control, and skin manifestations did not correlate with tumor EGFr levels as assessed by immunohisxtochemistry (Dako EGFR pharmDxtm). No enhancement of skin toxicity was observed when panitumumab was combined with chemotherapy. The median number of cycles received was 11 (Range 3–20). All pts experienced erythema; 17 macular/papular; 13 pustular; 18 acneiform rash; 15 pruritis; 3 honey crusting; 15 dry/flaking; 11 paronychia; 9 hirsuitism; 9 trichomegaly; and all 7 African American patients had significant hyperpigmentation. Photograph illustrations of each category and severity will be presented. Conclusion: Rash associated with panitumumab is common and can be classified according to the clinical dermatological manifestations; specific treatment strategies should be developed and evaluated accordingly. This is the first report of hirsuitism in women and hyperpigmentation in African Americans. [Table: see text]
Measures of oxaliplatin-induced neutrotoxicity in 187 patients with FOLFOX4
Authors: Matsusaka S. , Mizunuma N. , Matsuda M. , Suenaga M. , Ogura M. , Ichimura T. , Shoji D. , Oya M. , Muto T. , Hatake K. 
Published: March 2020

14552 Background: Oxaliplatin-based regimen (FOLFOX regimen) for patients with colorectal cancer have improved survival. Neurotoxicity is the most frequent dose-limiting toxicity of oxaliplatin. Various strategies and pharmacologic agents are currently under investigation to prevent or treat oxaliplatin-induced neurotoxicity. One of them is Stop-and-Go strategy based on the observation of reversibility of the neurotoxic symptoms after discontinuation of oxaliplatin. Stop-and-Go concept will prolong the time of oxaliplatin-based therapy as long as antitumor efficacy is still maintained. Methods: Patients with a histologically verified advanced colorectal carcinoma were eligible for the study. From April 2005 to March 2006 at Cancer Institute Hospital, 187 patients whom treated with bimonthly oxaliplatin-based regimen (FOLFOX4) were enrolled. An oxaliplatin specific neurotoxicity scale are distinct from the National Cancer Institute common toxicity criteria classification (CTC-AE vol. 3). This study was performed to carefully assess the onset and duration to recovery of oxaliplatin neurotoxicity and resumption rate of FOLFOX4. Results: Neurotoxicity was observed in 72 patients with Grade 1, 56 patients with Grade 2 and 33 patients with Grade 3. Oxaliplatin-induced cumulative neurotoxicity develops progressively. The median cumulative doses of oxaliplatin were 170 mg/m2 with Gr. 1; 845.8 mg/m2 with Gr. 2; and 850 mg/m2 with Gr. 3. The median time to onset were 16 days with Gr. 1; 174 days with Gr. 2; and 177 days with Gr. 3. The median time to recovery after stopping the therapy and the median time to progression during the discontinuation of oxaliplatin were 56 and 59 days, respectively, in patients allocated to Gr. 2 compared with 106 and 73 days, respectively, in patients allocated to Gr. 3. The recovery time during the discontinuation showed a statistically significant reduction of the values in the Gr. 2 but not in Gr. 3 (p = 0.0024). The resumption rates of oxaliplatin were 73.7% with Gr. 2 and 46.4% with Gr. 3. Conclusions: Our results may focus to manage time course of Stop-and-Go strategy in clinical practice. No significant financial relationships to disclose.