bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of a simple intervention that improves colon cancer lymph node yield and assessement
Authors: Kowalczyk L. , Shah P. , George T. , Lu L. , Sarosi G. , Beyth R. , Sultan S. 
Published: August 2020

e15058 Background: The National Quality Forum has endorsed the 12 lymph node (LN) benchmark as a quality metric. Currently, less than 40% of institutions meet this requirement. The purpose of this study was to determine whether implementation of a simple pathology template with dedicated fields for LN reporting led to an increase in the number of colon cancer resections where >12 LNs were reported. Methods: A simple pathology template, derived from the College of American Pathology, using standardized terminology and dedicated fields for LN reporting was implemented in August 2007. Using a pre and post- test design, all consecutive pathology cases were retrospectively reviewed. Inclusion criteria consisted of all stage 0-IV colon cancer patients who underwent surgical resection at a single Veterans Affairs Medical Center. The primary outcome was the percentage of cases in which >12 LNs were assessed between the pre and post-template group. Age, gender, anatomic location, and stage were also collected. Statistical comparisons were made using chi-square and Fisher's exact t-test. Results: 111 pre-template and 71 post-template cases were analyzed. The majority of patients were Caucasian (74%) males (97%). There were no significant differences between the two groups (see Table 1 ), however there was a trend towards more right-sided colon cancers in the pre-template group. 51% of all pre-template pathology reports evaluated >12 LNs compared to 68% of post-template reports (33% improvement in LN yield; p=0.03). Conclusions: Examination of >12 LNs has important therapeutic and prognostic implications in colon cancer patients. Use of a standardized pathology template with dedicated fields for LN reporting is a simple intervention that can increase yield of LN reporting. This can have a significant impact for institutions striving to reach the 12 LN quality metric. [Table: see text] No significant financial relationships to disclose.
Primary adenocarcinoma of the anus: a 22-year SEER population database analysis
Authors: Yap J. C. , Yang G. Y. , Fakih M. , Mashtare T. , Bullard Dunn K. , Kuvshinoff B. W. , Smith J. , Khushalani N. I. , Gibbs J. F. 
Published: August 2020

e15072 Background: Most anal canal cancers consist of squamous cell carcinoma (SCCA). Adenocarcinoma (AdenoCa) is rare and accounts for approximately 10% of anal cancers. A search of the SEER database (1973 to 2005) was carried out to evaluate the pattern of radiation (RT) and surgical treatment. Impact of the treatment on overall survival (OS) was evaluated. Methods: The search of the SEER database revealed 1,008 pts who had pathologically confirmed anal cancers with either SCCA or AdenoCa. All pts had single diagnosis of anal cancer with localized disease without nodal involvement. Excluded were pts with unknown use of surgery or radiation. Kaplan-Meier estimates and Cox-Mantel model were used to calculate and compare survival rates. Results: Median age of all pts was 57 years (range 29 to 99). For the SCCA group, median age was 57 years (range 29 to 99), which was younger than the AdenoCa group with median age of 74 years (range 37 to 92). Among the 1,008 pts, 954 had SCCA (94.6%), and 54 had AdenoCa (5.4%). Within the SCCA group, 14 (1.5%) had abdominoperineal resection (APR) in combination with external beam RT, and 795 (83.3%) had RT only with non-APR local surgical treatment inclusive of excision. Remaining 145 SCCA pts (15.2%) had non-APR local surgical treatment only without RT or had no treatment. Within the AdenoCa group, 10 (18.5%) had APR in combination with external beam RT, and 21 (38.9%) had RT only with non-APR local surgical treatment inclusive of excision. Remaining 23 AdenoCa pts (42.6%) had non-APR local surgical treatment only without RT. None of the adenoCa pt had no treatment. OS at 10 years was superior for pts with SCCA vs. AdenoCa (64.9% vs. 25.8%, p<0.05). Among the SCCA subset, there was no signficant difference in the 10-yr OS between the APR versus the RT pts (71% vs. 65%, p=0.78). On the other hand, among the AdenoCa subset, pts who had APR had better 10-yr OS than RT pts (53.8% vs. 0%, p=0.03) Conclusions: For localized anal SCCA, RT yielded equivalent overall survival as compared to APR. On the other hand, pts with localized anal adenoCa appeared to do worse when APR was omitted. RT only without APR might not be sufficient treatment in these patients. This database lacks information on use of chemotherapy and local disease control. Omission of APR in pts with anal canal adenoCa should be cautiously weighed. No significant financial relationships to disclose.
Phase II study of capecitabine and gemcitabine in patients with metastatic colorectal cancer (mCRC)
Authors: Iqbal S. , Yang D. , Cole S. , El-Khoueiry A. B. , Boswell W. , Agafitei R. , Lujan R. , Lenz H. J. 
Published: August 2020

e15077 Background: Failing standard chemotherapy, many mCRC patients (pts) maintain an adequate performance status necessitating therapeutic options. Preclinical data in CRC cell lines shows that 5-FU and gemcitabine have synergistic cytotoxicity by stabilization of thymidylate synthase resulting in stronger inhibition of DNA synthesis. Methods: The primary objective was to assess time to progression (TTP) in mCRC pts who had progressed on irinotecan and oxaliplatin therapy. Secondary objectives included response rate (RR), overall survival (OS), toxicity and correlates to assess genes in the 5-FU, gemcitabine pathways. This single center study was a two stage minimax design. A ≤ 30% chance of progressing within the first 6 weeks would be promising. 27 pts were enrolled in the first stage, if ≥ 13 progressed (or had unacceptable toxicity) prior to 6 weeks then the study would be terminated. The planned sample size was 53 pts. A cycle was defined as capecitabine 650 mg/m2 BID days 1–14 and gemcitabine 1,000 mg/m2 i.v. over 100 minutes days 1, 8. Results: The study met its first stage goal and continued to accrue 54 eligible pts (male 24/female 30), median age 58 years (range 31–78). Pts received a median of 2 cycles (range 1–19), with 22% of pts receiving 6 + cycles. Three pts that withdrew shortly after start were excluded from toxicity analysis. Of 51 pts, 23 had Grade 3/4 drug related toxicity, commonly 9 pts ANC/AGC; 4 pts pain. The probability of progressing at 6 weeks was .46 + .07, with 23 pts progressing or dying within that time. Median OS was 5.9 months (95% CI 4.3, 8.7), PFS was 8.1 weeks (95% CI 5.6, 11.6). Of 48 pts evaluable for response, 17 had stable disease, for these pts, the median PFS was 4.3 months (95%CI: 3.9–8.8) and OS 10 months (95%CI: 7.9–16.6); 31 had progressive disease or symptomatic deterioration. Conclusions: The combination of gemcitabine and capecitabine in refractory mCRC was well tolerated. Unfortunately, the study did not meet the primary endpoint, but there appears to be a subset of pts with stable disease who may benefit from therapy. Correlatives are pending. [Table: see text]
Evaluation of plasma total and cleaved cytokeratin 18 as predictive markers of chemotherapy in colorectal cancer
Authors: Moore M. M. , Chua W. , Zhao J. , Clarke S. J. , Horvath L. 
Published: August 2020

e15091 Background: Cytokeratin 18 (CK18) is a cytoskeletal protein present in the circulation of cancer patients. Caspase-cleaved CK18 fragments are released from apoptotic cells and may be a simple non-invasive tool for measuring response to chemotherapy. This study aims to assess the associations between levels of CK18 with clinical parameters in patients with metastatic colorectal cancer (mCRC) receiving palliative chemotherapy. Methods: Prospectively collected plasma from 23 mCRC patients were analysed for the presence of total CK18 (M65, Peviva) and cleaved CK18 (M30-Apoptosense, Peviva) using an ELISA assay. 8 patients received 2nd-line chemotherapy (irinotecan) and 15 patients received 1st-line 5FU-based chemotherapy. Levels of both total and cleaved CK18 were determined at day 0 prior to chemotherapy and +24 hours for 2nd-line patients or +72 hours for 1st-line patients post-chemotherapy. Patients were grouped as responders (CR + PR) or non-responders (SD + PD) and results were analysed by non-parametric tests (Mann- Whitney and Wilcoxon Signed Rank Tests). Results: The median age of patients was 62 (range 24–79) with 9 patients (39%) responding to chemotherapy. Pre-chemotherapy, both total and cleaved CK18 levels were significantly lower in patients that responded to chemotherapy compared to non-responders [mean total CK18 responders 447.8U/L (95%CI 286.6–609.0 U/L ) versus mean total CK18 non-responders 999.4U/L (95%CI 602.7–1396.1 U/L), p=0.033; mean cleaved CK18 responders 174.7 U/L (95% CI 26.4–323.0) versus mean cleaved CK18 non-responders 331.4 U/L (95%CI 185.3–477.6), p=0.046]. There was a statistically significant increase in the concentration of total CK18 in the post-chemotherapy samples compared to baseline (p=0.003) however there was no association with response (p=0.12). The mean ratio of cleaved: total CK18 was significantly lower after chemotherapy [baseline 0.33 (95% CI 0.28–0.38) versus post-chemotherapy 0.29 (95%CI 0.24–0.34), p=0.01]. The mean ratio of cleaved: total CK18 at baseline was unable to discriminate between responders and non responders (p=0.83). Conclusions: These data suggest that pre-chemotherapy total and cleaved CK18 plasma levels are potential predictors of chemotherapeutic response for patients with mCRC. No significant financial relationships to disclose.
AVASTERB OUEST: A prospective cohort study of unresectable metastatic colon cancer treated successively by FOLFIRI bevacizumab and cetuximab irinotecan
Authors: Metges J. , Gamelin E. , Faroux R. , Klein V. , Ganem G. , Douillard J. , Stampfli C. , Corbinais S. , Riche C. , Grude F. 
Published: August 2020

e15103 Background: Bevacizumab and cetuximab regimen are approuved since 2005 in Europe for Metastatic Colorectal Cancer Patients (MCCP). Very few studies have reported data concerning the sequence (FOLFIRI BEVA and after failure CETUXIMAB- CAMPTO) in MCCP from the real world. Methods: Since 2003, in west of France, (Bretagne-Pays de Loire),a network called OMIT(Observatoire des Médicaments et Innovations Thérapeutiques) directed by Regional Health Agencies has been created. This structure gathered prospectively data from MCCP treated with targeted therapies. Since 2006, a cohort of MCCP treated successively by FOLFIRI BEVACIZUMAB (same protocol : same dose) as first line to progression or unacceptable toxicity and CETUXIMAB- CAMPTO after the first line failure was constitued (AVASTERB cohort). Criteria for initial unresectability of metastic lesions was based on investigator's evaluations during local comitee (surgeons and oncologists). In order to have a large follow up, the 35 first patients of the cohort were studied in this abstract.Age, sex, response rate to the different regimens,secondary metastatic lesion resection, time to progression to the different regimens, follow up and overall survival are the criterias studied. Results: Median age 60 years (49–83), Males : 60%, colon 71%,rectum: 17%, colorectal jonction :12%.Response rate(OR+SD)with Folfiri Bevacizumab : 45.7%. 17% of the patients underwent hepatic surgery with curative intent (all during Folfiri bevacizumab) Time to progression with Bevacizumab : 6 months. Fifty eight percent of the patients are still alive with a median follow up of 25 months (11–29)Median overall survival was not reached.The 12 months and 24 months overall survival rates are respectively 71.4% and 45.7% (date of point: 01/01/2009). Actualisation of the data will be provided during the meeting Conclusions: The results from this prospective unselected cohort of MCCP treated with the sequence FOLFIRI BEVA and after failure CETUX-CAMPTO from the real world show promising TTP, and overall survival. The study of the Kras mutation and others biomarkers could improve these results by personalization of the treatment. This part of our study is actually ongoing. No significant financial relationships to disclose.
Preoperative concomitant chemoradiotherapy with oxaliplatin and 5-fluorouracil in locally advanced rectal carcinoma
Authors: Djellali L. , Larbaoui B. , Boukerche A. , Ghazi S. , Chaiba I. , Meziane N. , Yekrou D. , Youcef D. F. 
Published: August 2020

e15108 Background: Preoperative concomitant chemoradiotherapy has shown to improve local control and sphincter preservation with decreased acute toxicity compared with postoperative treatment in locally advanced rectal carcinoma. The primary endpoint of this phase II trial was pathologic tumor response. Secondary endpoint was sphincter preservation and toxicity Methods: Inclusion criteria: rectal adenocarcinoma <12 cms from anal verge, clinical stage T3–4, adequate renal, hematological and liver function. Planned sample for this trial was 40 patients. Treatment schedule: Pelvic radiotherapy (25 Gy/ 5 fractions: 5 Gy on day 1 to day 5) and chemotherapy: Oxaliplatin 85 mg/m2 on 2 hours, day 1 and 15, folinic acid 20 mg/m2 and 5 fluoro-uracil bolus 500 mg/m2 on day 1, 8 and 15 (cycle repeated every 4 weeks). Surgery with TME was performed after the end of the second cycle of chemotherapy. Adjuvant chemotherapy with 5FULV2 was administered after surgery Results: 15 patients have been recruited between January and October 2006: 10 males/5 females. Median age: 45 years (range 26–62). Clinical stage (determined by CT or RMI): T3: 66.6% and T4: 33.3%. Tumor location (from anal verge): < 6 cm in 10pts, >6 cm in 5pts. Surgery (performed in 14 patients) consisted of low anterior resection in 5pts and abdominal-perineal resection in 10p. Tumor down-staging was observed in 10pts (66.6%), including 5pts with complete pathological response (33.3%). Main adverse effects (NCI-CTC): diarrhea G3–4: 14.2%, sensitive peripheral neurotoxicity G1: 26.6%, nausea/vomiting G3–4: 11%, Anemia G3–4: 7.1%, neutropenia G3–4: 14.2% Conclusions: Preliminary results show that preoperative concomitant chemoradiotherapy with oxaliplatin and 5FU-folinic acid is an effective regimen with an acceptable safety profile for locally advanced rectal cancer, leading to a high probability of tumor downstaging. This interim analysis has to be confirmed by the final analysis. No significant financial relationships to disclose.
Use of anti-neuropilin 1, 2 antibodies to predict colorectal cancer prognosis
Authors: Takeda A. 
Published: August 2020

e15111 Background: Neuropilin (NRP) was initially described as non-tyrosine kinase receptors for neuron guidance factor belonging to the Semaphorin family. Two subtypes, NRP-1 and NRP-2 have been isolated. Neuropilins are widely expressed not only normal developing tissues but also several types of tumor cells. It was reported that the expression of NRP-1 is increased by VEGF, mediated through VEGFR-2, which correlates with tumor growth and invasiveness in colorectal cancer. NRP-2 knockout mice studies showed marked deficits in the development of small lymphatic vessels and its function was associated with the formation of lymphatic network, but the role of NRP-2 in colorectal cancer remains unknown. Methods: We have newly established two useful anti- Neuropilin antibodies against CUB domains of NRP-1 and cytoplasmic domains of NRP-2. In recent study, we have analyzed the expression of NRP-1 and NRP-2 in some cultured cell lines by western blot and the clinicopathological significance in colorectal cancer. Tissues samples were obtained from 72 primary colorectal adenocarcinomas (colon:39 cases, rectum:33 cases). The pathologic stage were as follows; stageI:10 patients, II:25 patients, III:26 patients and IV:11 patients. NRP-1 and NRP-2 gene expression was evaluated by RT- PCR, which was compared with immunohistochemical examination of colorectal cancer tissues. Constitutive expression of NRP-1 was detected in PC3, HT29, PC9 and PC13 cell lines and NRP-2 in HT29, PC3 and PC9. Results: There was significant correlation between NRP-1 and -2 protein expression and both of mRNA expression. The expression of NRP-1 showed apparent correlation with liver metastasis (p=0.027) and venous invasion (p=0.0025), while NRP-2 expression was correlated with lymph node metastasis (0.001) and lymphatic invasion (0.039) by immunohistochemical analysis. The post-surgical treatment observation revealed that patients with co- expression of NRP-1 and NRP-2 were significantly correlated with poorer prognosis than both NRP-1 and NRP-2 negative patients (p=0.035). Conclusions: These results suggest that NRP-1 acts as angiogenesis factor and NRP-2 acts lymphangiogenesis factor, both of them are useful predictive marker in colorectal cancer. No significant financial relationships to disclose.
Overexpression of EphA4 gene and reduced expression of EphB2 gene: Correlation with liver metastasis in colorectal cancer
Authors: Oshima T. , Yamamoto N. , Sato T. , Nagano Y. , Fujii S. , Kunisaki C. , Shiozawa M. , Akaike M. , Rino Y. , Masuda M. , Imada T. 
Published: August 2020

e15129 The Eph receptors, members of a large family of transmembrane receptor tyrosine kinases, play important roles in a variety of biologic functions. Recent studies have suggested that EphA4 and EphB2 participate in the growth and development of various carcinomas. This study examined the relations of EphA4 and EphB2 gene expression to clinicopathological factors, especially metastasis, in patients with colorectal cancer. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 205 patients with untreated colorectal cancer. The relative expression levels of EphA4 and EphB2 mRNA in the specimens were measured by quantitative real-time, reverse-transcription polymerase chain reaction. The relative expression level of EphA4 mRNA was higher in the presence than in the absence of liver metastasis, whereas the relative expression levels of EphB2 mRNA were similar. Analysis of the relations between clinicopathological features and gene expression showed that high expression of the EphA4 gene and low expression of the EphB2 gene correlated with liver metastasis. There was no correlation between EphA4 and EphB2 gene expression. Our results suggest that over-expression of the EphA4 gene and reduced expression of the EphB2 gene might promote liver metastasis in colorectal cancer. Over-expression of the EphA4 gene and reduced expression of the EphB2 gene may thus be a useful predictor of liver metastasis in patients with colorectal cancer. No significant financial relationships to disclose.
The use of panitumumab (Pan) in patients (pts) with metastatic colorectal carcinoma (CRC) whose disease has progressed through treatment (Rx) with cetuximab (Cet)
Authors: Martel C. L. , McNamara M. V. 
Published: August 2020

e15142 Background: Both Pan and Cet have activity in the Rx of metastatic CRC. As they each target the epidermal growth factor receptor, and are believed to have the same mechanism of action, pts who fail Rx with one of these agents are generally not treated with the other. Methods: A retrospective chart review was performed of pts in our practice with metastatic CRC. The response to Pan of pts whose disease had progressed despite use of a Cet containing regimen was assessed. Results: We identified three pts who received Pan after failing Rx with Cet. Pt 1 was an 81 year old female who had discontinued Rx with 5- fluorouracil (5-FU) and leucovorin (Lcv) plus bevacizumab (bev); capecitabine; and irinotecan due to intolerance. She received Cet for 6 months with initial stable disease (SD) and subsequent progressive disease (PD). She was later treated with Pan for 6 months with slight shrinkage of her metastatic disease (SD by response evaluation criteria in solid tumors) and marked improvement of her performance status (PS) before eventual PD. Pt 2 was a 43 year old female who had eventual PD after Rx with oxaliplatin and capecitabine plus bev; irinotecan plus bev; and an experimental vaccine. She was treated with Cet for 6 months with a PR, followed by PD. She received Pan for 3 months, with improvement in her PS, decreased pain and a 45% decline in her carcinoembryonic antigen level, before eventual PD (no radiologic studies were obtained during Rx with Pan). Pt 3 was a 64 year old female whose prior Rx had included oxaliplatin plus infusional 5-FU and Lcv (FOLFOX), as well as irinotecan plus infusional 5-FU and Lcv (FOLFIRI) with Cet; the latter was continued for 3.5 months, with a best response of SD. She then received 4 doses of Pan, but had PD. Conclusions: Pan led to clinical improvement with objective evidence of disease stabilization or response in 2 of 3 pts in our practice who had previously failed Cet. Pan has meaningful, although modest, activity in pts with metastatic CRC whose disease has progressed through Cet. The use of Pan should be considered in pts who have failed Cet and who do not have other viable Rx options. No significant financial relationships to disclose.
Effect of continuation of bevacizumab following disease progression in patients with metastatic colorectal cancer on survival
Authors: Samelis G. F. , Tsiakou A. , Karamanidi M. , Pelechrini M. , Zaganides A. , Ekmektzoglou K. 
Published: August 2020

e15143 Background: The management of patients with metastatic colorectal cancer (mCRC) has evolved dramatically over the last decade, with several “targeted” agents having entered the treatment arena. Multiple-line treatment is now considered as an important step towards the optimal therapeutic strategy for this patient population. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown clinical activity in patients with mCRC when used either as a first-line or second-line treatment. Currently, there is limited information in the literature on the use of bevacizumab combination chemotherapy in multiple lines with regimens including irinotecan and oxaliplatin, in mCRC patients who have progressed. Methods: We evaluated the efficacy and safety of bevacizumab in combination with standard chemotherapy (irinotecan, capecitabine, oxaliplatin, cetuximab) in 21 patients with metastatic colorectal cancer with a median age of 69 (range: 47–85) years old with PS: 0–1, included in the study. The metastatic sites were liver in 13 patients, liver and lung in 4 patients, lung in 2 patients, intra-abdominal in 1 patient and urinary-bladder in 1 patient. Bevacizumab treatment was continuously dispensed after disease progression and only other combined drugs were altered. Subgroup analysis was performed in terms of age, site of metastases, spread and co-morbidity. Results: The median age of the patients included in the analysis was 69 years (range 47–85). Progression free survival (PFS) was 17 months in first line setting (overall survival (OS) not reached yet) o, and for the age group >69 and <69 it was 23 and 16 months respectively (p=0.4565). Overall survival for the <69 years old was 36 months. Anemia (all grades) was reported in 90.6% of the patients, while hemorrhage and thrombosis were reported in 28.6% and 14.3% respectively. Conclusions: Multiple line treatment in advanced colorectal cancer, including bevacizumab combined with standard chemotherapy, may improve OS (median: 23+ months) with an acceptable toxicity profile in patients with mCRC. However, further research through well-designed randomized studies is warranted to appraise the beneficial risk- benefit ratio of such an approach. No significant financial relationships to disclose.