bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locally advanced rectal cancer: The value of magnetic resonance imaging as a predictive tool.
Authors: Connell Louise Catherine , Stuart Charlotte , Daly Norma , Mehigan Brian , Kennedy M. John 
Published: March 2020

e14666 Background: Magnetic Resonance Imaging (MRI) of pelvis stratifies patients (pts) with rectal cancer (ca) according to locally advanced disease (dx) & risk of local recurrence. By determining the extent of lymph node (LN) positivity, it enables the appropriate selection of pts for neoadjuvant therapy (NAT) prior to curative surgical resection (Sx). We assessed our institution’s experience of NAT versus upfront Sx in stage I-III rectal ca to ascertain the utility of MRI as a predictive tool in LN status evaluation. Methods: We retrospectively reviewed a prospectively maintained database for all pts with a diagnosis of stage I-III rectal ca from January 2006 to September 2012 in a specialist colorectal cancer centre. We analysed data with respect to preoperative MRI staging & definitive histopathological confirmation of LN stage. Results: A total of 210 pts were identified that had Sx for rectal ca with curative intent. Of these, 112 pts received NAT while 98 had upfront Sx. Of those who proceeded directly to Sx, there were 41 females & 57 males. Average age in this group was 73.4 years (range 33 -90). LN staging by MRI was accurate in 45.9% (n=45). LN status could not be evaluated (Nx) in 17.3% (n=17). In 19.4% (n=19) more advanced LN staging was apparent on histology while in 17.3% (n=17) LN stage was deemed more aggressive by MRI. Of those who had NAT, there were 75 males & 37 females. Average age was 62.3 years (range 26-82). In this cohort, 81.3% (n=91) had both a preoperative MRI & pathology report available for comparison. MRI in this group matched histology in 61.5% (n=56). Nx was recorded in 3.3 % (n=3). In 17.6% (n=16) more aggressive LN involvement was evident at histology while 17.6% (n= 16) had less advanced dx at tissue sampling. Overall in this study, MRI accurately predicted LN status in 53.4% (n=101). Conclusions: While MRI is a valuable tool in determining those pts with rectal ca that would benefit from NAT, its predictive value has limitations. With further analysis of the dataset at our institution, we aim to identify other factors involved & create a predictive nomogram for the rectal ca pt with locally advanced dx. We plan to validate this work by including data from other Irish cancer centres.
The role of AP-1 in colon cancer stem cells.
Authors: Chatziioannou Marina , Apostolou Panagiotis , Toloudi Maria , Ioannou Eleni , Kopic Asir , Komiotis Dimitrios , Papasotiriou Ioannis 
Published: March 2020

e14699 Background: The AP-1 transcription factor is a heterodimeric protein, which regulates gene expression in response to a variety of stimuli. The above factor also regulates cellular processes including differentiation, proliferation and apoptosis. The AP-1 heterodimeric protein is consisted of the combination of c-Jun and c-Fos proteins. The c-Jun is activated through phosphorylation, but it has also phosphorylation independent function. The c-FOS is a cellular proto-oncogene, which is up-regulated in response to many extracellular signals. The present study aim to find out the effect of c-FOS gene in Colon CSCs according to stemness. Methods: In all experiments there have been used established human colon cancer stem cells (CelProgen). Experiments for suppression of c-FOS expression, by using specific siRNA were performed and the transfection was evaluated with qPCR assays. The stemness transcription factors Nanog, Oct3/4 and Sox2 were tested with gene expression assays, and a relative quantification was performed according to Livak method. The CD44 and CD26 genes were used as positive markers in colon cancer in all procedures. Results: The results indicated that the c-FOS proto-oncogene affects the gene expression of transcription factors, which are essential for the maintenance of stemness. However the results were different, depending on the rate of suppression. The suppression of c-FOS by 65% led to increase in gene expression of stemness transcription factors, with higher rates for Nanog, smaller for Sox2 and minimum for Oct3/4. Unlike results were observed when the expression was suppressed by 85%. In this case there was observed higher decrease in Oct3/4 and less in the other markers. Conclusions: Up to now studies have demonstrated the significant role of c-JUN in stem cells, but little is known about the other half of AP-1 complex, the c-FOS gene. In the first part of the study it was confirmed the effect of c-FOS in stemness, as it was observed change in gene expression of stemness’s significant transcription factors. However it is indicated that there is a cross-talk between JNK pathway and stemness. Further studies in more samples are needed to demonstrate all the above, so that it can be used at clinical level.
On-chip drug testing of an aggressive intra-abdominal variant of inflammatory myofibroblastic tumor by kinase activity profiling.
Authors: Ruijtenbeek Rob , van den Berg Adrienne , Hilhorst Riet , Kueffer Stefan , Gaiter Timo , Kievits Tim , Ebert Matthias 
Published: March 2020

e14702 Background: A patient presented with an expansivetumor of the liver, which infiltrated diaphragm, duodenum, gastric wall, pancreas and gall bladder. Pathological examination revealed a tumor dominated by infiltrating sheets of epithelioid-to-round cells with a prominent inflammatory infiltrate. Immunohistochemistry showed a positive reaction for vimentin but stained negative for S100, HMB45, Aktin, Desmin, CD117, DOG1, WT1, CDK4, mdm2 and ALK. Diagnosis of an ALK negative aggressive intra-abdominal variant of Inflammatory Myofibroblastic Tumor (IMT) was established. While it is know that approximately 50% of IMTs contain clonal rearrangements involving the ALK gene (Am. J. Surg. Pathol. 2011 135-144), little is known about the ALK-negative variant. The aim of the current study was to gain insights in potential aberrant signaling pathways in this rare tumor and potentially identify alternative druggable pathways. Methods: Kinase activity profiles of the tumor lysate were generated on PamChip peptide microarrays in the presence and absence of a concentration series of the protein kinase inhibitors (PKIs) erlotinib, imatinib, sorafenib, masitinib, crenolanib and tivozanib. Inhibitor effects on this IMT tumor lysate were compared to those on lysates from other tumor types, followed by bioinformatic analysis. Results: Comparing the different kinase inhibition profiles, erlotinib was the least effective inhibitor, while sorafenib and imatinib inhibited phosphorylation of a set of peptides that are known to be substrates for their kinase targets c-KIT, PDGFRα and PDGFRβ. The degree of inhibition in the IMT sample was higher than in tumor samples where these drugs are approved like CML and RCC (as well as in non-approved indications like CRC and AML). In the closely related sarcoma GIST, these kinases are successful targets. Additional prove of their involvement in this IMT variant was found in the positive inhibition profiles using crenolanib and masitinib. Conclusions: c-Kit and PDGFR and corresponding kinase inhibitors would be a pathway/drug combination of choice for drug development in this variant of IMT.
Long-course targeted therapy with bevacizumab to predict better survival in patients with advanced colorectal cancer.
Authors: Deng Yanhong , Tang Yuting , Xiao Jian , Ling Jiayu , Cai Yue , Hu Huabin , Zhang Yan , Lin Yiheng , Chen Dianke 
Published: March 2020

e14704 Background: Bevacizumab has been the standard treatment in first-line treatment of advanced colorectal cancer. This study explored whether the short-course and long-course use of bevacizumab could influence overall survival (OS). Methods: A total of 74 patients with advanced colorectal cancer who had received at least one cycle of bevacizumab-based regimens were included. The primary endpoint was OS defined as from the date of first diagnosis of advanced colorectal cancer to death. Results: The P value among the median OS of initiating bevacizumab in first-line group (n = 47), in the second-line group (n = 18), and the third-or more-line group (n = 9) was not reached statistically significance(P = 0.349). In the first-line initiating bevacizumab group, the irinotecan arm showed a trend of better activity than the oxaliplatin arm, but the significance was not reached(P = 0.128). For patients in the first-line initiating bevacizumab group who had received at least four courses of bevacizumab (n = 36), the median PFS and OS was 11 m and 29m respectively and for those receiving less than four courses of bevacizumab (n = 10), it was 3.9 m (P = 0.005) and 13m (P=0.003) respectively. Conclusions: The delayed use of bevacizumab has no negative effect on the OS of patients with advanced colorectal cancer. Long-Course targeted therapy with bevacizumab favors better survival in patients with advanced colorectal cancer.
The efficacy and safety of first-line and salvage therapies with bevacizumab combination chemotherapy regimens in metastatic colorectal cancer: A retrospective ASMO experience.
Authors: Yildiz Ramazan , Buyukberber Suleyman , Koca Dogan , Koral Lokman , Ciltas Aydin , Unal Olcun Umit , Gumus Mahmut , Ozdemir Nuriye , Dane Faysal , Berk Veli , Kaplan Mehmet Ali , Elkiran Tamer , Boruban Melih Cem , Coskun Ugur , Aydin Dincer , Uncu Dogan , Ozkan Metin , Isikdogan Abdurrahman , Benekli Mustafa ,   Anatolian Society of Medical Oncology (ASMO)
Published: March 2020

e14705 Background: The addition of bevacizumab to chemotherapy significantly shows survival advantage in metastatic colorectal cancer (mCRC), but with limited data about irinotecan combination in salvage therapy. Efficacy and toxicity of bevacizumab combination regimens were assessed in first-line and salvage therapies. Methods: Total of 1011 (659 in first-line and 352 in salvage) patients were retrospectively evaluated. Results: In first-line therapy, the ORR was 36.4%. Median PFS was 7 months for FOLFIRI, 6 months for IFL and 6 months for other chemotherapy regimens with a median overall PFS of 7 months. Median survival was 29 months for FOLFIRI, 28 months for IFL and 21 months for others with a median overall survival of 28 months. In salvage therapy, the ORR was 25.2%. Median PFS was 7 months for FOLFIRI, 7 months for IFL and 6 months for others with a median overall PFS of 7 months. Median survival was 19 months for FOLFIRI, 13 months for IFL and 21 months for others with a median overall survival of 19 months. The main toxicities in first-line and salvage therapy were neutropenia, febrile neutropenia, nausea and vomiting, diarrhea, mucositis, bleeding, hypertension, thromboembolism, fistulization and bowel perforation. Conclusions: Bevacizumab combination chemotherapy regimens are effective with a tolerable safety profile in mCRC patients in first-line and salvage therapy.
Chemoradiotherapy for squamous cell carcinoma of the anal canal: Comparison of one versus two cycles mitomycin-C.
Authors: White Evan Carl , Erickson Kelly , Aleshin Alex , Lien Winston Wei , Rao Aroor R. 
Published: March 2020

e15001 Background: Concurrent chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and mitomycin-C (MMC) is standard treatment for squamous cell carcinoma of the anal canal. Randomized clinical trials in Europe have used 1 cycle MMC, while American studies use 2 cycles. This study sought to determine any difference in treatment outcomes between patients treated with either 1 or 2 cycles of concurrent MMC. Methods: 217 consecutive patients were treated definitively with CRT from 2003 to 2012 in an integrated health system. All patients received radiotherapy at a single regional facility. Concurrent chemotherapy regimen depended on the referring provider’s practice, and consisted of 2 cycles 5-FU (1,000mg/m2/day on days 1-4 and 29-32), along with MMC (10mg/m2), given on either day 1 alone (n=154), or days 1 and 29 (n=63). Outcomes were progression-free (PFS), cancer-specific (CSS), overall (OS), and colostomy-free survival (CFS), as well as acute toxicity criteria. Toxicity scored using CTCAE version 4. Survival analysis was via Kaplan-Meier method, and multivariate Cox proportional hazards modeling was performed. Results: Median age: 60 years. 70% female. T3-T4: 52%. 40% node-positive (N1: 7%, N2: 17%, N3: 16%). Median follow-up: 26 months. At last follow-up, PFS was 79%, CSS was 87%, OS was 81%, and CFS was 88% for the entire cohort. There were no differences in clinical/treatment factors between patients who received 1 cycle MMC (MMC1) vs 2 cycles (MMC2). There was no difference in PFS (HR 0.92, 95% CI 0.41-2.08), CSS (HR 0.36, 95% CI 0.08-1.62), OS (HR 0.73, 95% CI 0.27-2), or CFS (HR 0.91, 95% CI 0.31-2.67) between the MMC1 and MMC2 groups. On multivariate analysis, stage and male gender were predictive of worse PFS, CSS, OS, and CFS. Acute grade ≥2 toxicities for the MMC2 vs MMC1 group were: Skin: 97% vs 84% (p=0.006); Heme: 89% vs 73% (p=0.01); Leukopenia: 86% vs 68% (p=0.01); Neutropenia: 71% vs 53% (p=0.02). There were 3 treatment related deaths, all in the MMC2 group. Conclusions: This study provides evidence that MMC1 results in similar outcomes to MMC2 in patients with anal cancer treated with definitive CRT, with less acute treatment-related toxicity. Randomized trials comparing these 2 regimens could be considered.
Activity and survival benefit of second-line chemotherapy (2L-Ctx) in advanced pancreatic adenocarcinoma (APC): Pooled analysis of the literature.
Authors: Teo MinYuen , McDermott Raymond S. 
Published: March 2020

e15019 Background: Many clinicians adopt a nihilistic approach to the management of APC. Delivery of 2L-Ctx is relatively uncommon and no recognized standard exists. We sought to examine the published activity of chemotherapy in the 2nd line setting, and the rate of 2L-Ctx delivery and its influence on reported overall survival in 1st line trials. Methods: 1st and 2L-Ctx randomized trials published between 2000 and 2012 were identified from Pubmed, and manuscripts were obtained for data extraction. Pooled weighted objective response rates (ORR) and disease control rates (DCR) were calculated. For 1st line studies, the percentage of patients who received 2L-Ctx were extracted and plotted against reported median overall survival (OS) and post-progression survival (PPS), defined as arithmetic difference between median OS and progression-free survival. Spearman correlation and linear regression were performed. Results: Sixty nine 2L Ctx studies (77 arms, n=2859) were identified. Majority received prior gemcitabine-based chemotherapy. Pooled ORR was 6.6% (95% CI 5.6 – 7.6%) and DCR was 36.7% (34.5 – 38.0%). When only prospective studies were evaluated (42 studies, 48 arms, n=1546), ORR was 5.0% (3.8 – 6.2%) and DCR was 33.9% (31.0 – 36.9%). Exploratory analysis suggested that intensification of gemcitabine-based therapy (ORR: 10.0%; DCR: 54.7%) might be marginally more active than fluoropyrimidine (7.6%; 32.2%) or taxane based 2L-Ctx (5.2%; 33.6%). 28/52 identified 1st line studies (54%) reported the percentage of patients treated with second-line chemotherapy (11 phase II, 28 arms, n=1450; 17 phase III, 33 arms, n=5051). Percentage of 2L-Ctx delivery ranged from 14 – 68% and correlated with OS (r=.49 [.26 – .67], p<.01) and PPS (r=.57 [.36 – .72], p<.01). When phase II studies were excluded, correlation was improved for OS (r=.63 [.35 – .81], p<.01) and PPS (r=.79 [.59 – .89], p<.01). Percentage of locally advanced disease did not correlate with OS/PPS nor affect prior analysis. Conclusions: Whilst awaiting further advancement in the 1st line setting, increased delivery of 2L-Ctx to patients with APC and maintained performance status may offer a survival benefit.
Changes in the tumor glucose-uptake measured by 18F-FDG PET with two weeks of single-agent cetuximab in localized squamous cell carcinoma of the esophagus.
Authors: Philipp-Abbrederis Kathrin , Herrmann Ken , Beer Ambros , Hapfelmeier Alexander , Peschel Christian , Lordick Florian 
Published: March 2020

e15042 Background: Cetuximab (CET), an antibody directed against epidermal growth factor receptor (EGFR) has proved efficacy in squamous cell cancer (SCC) of the head and neck in vitro and in vivo by enhancing the activity of chemo- and radiotherapy. The aim was to investigate the early metabolic response in esophageal SCC induced by single agent CET. Methods: Patients with cT3 Nx esophageal SCC received single agent CET for two weeks (400mg/m2 i. v. d -15 followed by 250mg/m2 d -8) before entering a neoadjuvant dose escalation protocol of weekly cetuximab plus weekly oxaliplatin (starting dose level 45mg/m²; d1,8,15,22,29), plus 5-FU cont. i.v. (starting dose level 180mg/m²/d; d1-5, 8-12, 15-19, 22-26, 29-33) and radiotherapy (45Gy cumulative dose; 1.8Gy/d). Surgery was scheduled 4-6 weeks after chemoradiation (CRT). Tumor FDG uptake was assessed by PET at baseline, two weeks after start of CET and two weeks after start of CRT. Standard uptake values (SUV) of the two response PETs were compared with SUVs measured at baseline and correlated with the histopathological response data. Results: 11 patients are assessable for metabolic and histopathological response. Decreases in the SUVs two weeks after the start of CET compared with baseline SUV ranged from -16% to -70% (median -24%) and from 0% to -72% (median -39%) two weeks after start of CRT. Three patients were classified as complete histopathological responders. One patient had a subtotal (<10% residual tumor) and three patients a moderate response (10-50% residual tumor). No histopathological response was seen in 4 patients. We found an association between FDG uptake decreases both after single agent CET and after two weeks of CRT and a favourable histopathological response with no statistical significance due to the low number of cases. Conclusions: This study shows that single agent CET can lead to a marked and early decrease in tumor glucose uptake. Our findings suggest that there may be an association between the early decrease in FDG uptake during CET monotherapy, indicating a growth dependency of some tumors from the EGFR signal pathway. These preliminary observations require confirmation in a larger patient cohort. Clinical trial information: 2006-001097-24.
Various clinical outcomes in patients with esophageal or gastroesophageal junction (E-GEJ) adenocarcinoma undergoing trimodality therapy: Prognostic implications.
Authors: Suzuki Akihiro , Xiao Lianchun , Taketa Takashi , Sudo Kazuki , Blum Mariela A. , Komaki Ritsuko , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Hofstetter Wayne Lewis , Swisher Stephen , Ajani Jaffer A. 
Published: March 2020

e15053 Background: Preoperative chemoradiation (trimodality therapy) has the strongest evidence in trimodality-eligible patients with esophageal or gastroesophageal junction (E-GEJ) adenocarcinoma. Pathological complete response (pathCR) and clinical complete response (clinCR) are independent prognostic factors. We hypothesized that pathCR is associated with best prognosis. Methods: Patients with E-GEJ adenocarcinoma undergoing trimodality therapy were identified from the prospectively maintained database at our institution. The Log rank test, univariate and multivariate Cox proportional hazards regression analysis were applied for the survival analysis. Variables with p value < 0.15 in the univariate analysis were included in the multivariate analysis, the backward selection procedure was used for the model selection. Variables with P value < 0.05 were considered statistically significant. Results: For 314 esophageal cancer patients, the median follow-up time was 44.0 months (95% CI; 34.2-50.9). 107 of 314 patients died at this analysis. 80 patients (25.5%) had a pathCR. 160 patients (51.0%) had a clinCR prior to surgery but did not have pathCR. The remaining 74 (23.6%) had <pathCR and <clinCR. Median OS were: not achieved in pathCR patients, 82.8 months (95% CI; 63.9, NA) in clinCR patients and 27. 6 months (95% CI; 19.4, NA) <pathCR/<clinCR (p<0.001). The median recurrence-free survival (RFS) were: 79.6 months (95% CI; 37.4, NA) in pathCR patients, 67.4 months (95% CI; 31.8, NA) in clinCR patients and 13.5 months (95% CI; 10.4, 21.4) in <pathCR/<clinCR (p<0.001). In multivariate analysis, no lymph node metastasis (p<0.001), not poorly differentiated adenocarcinoma (p=0.002) and pathCR (p=0.02), and cCR (p<0.001) were independent prognosticators of OS and RFS. Conclusions: pathCR and clinCR are associated with a better survival ourtcome compared to patients without pathCR/clinCRand may be helpful in devising new therapeutic and surveillance strategies.
Use of cardiopulmonary exercise testing (CPET) to identify patients at high risk for adverse outcome after pancreaticoduodenectomy.
Authors: Siriwardena Ajith K. , Junejo Muneer 
Published: March 2020

e15072 Background: Pancreaticoduodenectomy is the standard of care for tumours confined to the head of pancreas and can be undertaken with low operative mortality. However, the procedure has a high morbidity, particularly in older patient populations with pre-existing co-morbidities. Many of the currently available methods for assessment of pre-operative risk rely on either scoring systems or indirect measures of cardiopulmonary function. In contrast, pre-operative cardiopulmonary exercise testing (CPET) provides a direct functional assessment of integrated cardiac and respiratory performance. This study evaluates the role of pre-operative cardiopulmonary exercise testing (CPET) for prediction of post-operative morbidity and outcome after pancreaticoduodenectomy. Methods: In a prospective cohort undergoing pancreaticoduodenectomy, those aged over 65 years (or younger with co-morbidity) were categorized as high-risk and underwent preoperative assessment by CPET according to pre-defined protocol. Data were collected on functional status, postoperative complications and survival. The predictive potential of CPET-derived markers was assessed. Results: 143 patients underwent preoperative assessment of whom 50 were deemed low-risk for surgery per protocol. Of 93 high-risk patients 64 proceeded to surgery after preoperative CPET. CPET-derived ventilatory equivalent of carbon dioxide (VE/VCO2) at anaerobic threshold (AT) was a predictive marker of postoperative mortality with an AUC of 0.85 (95% CI 0.63 to 1.07, p = 0.020); a threshold of 41 was 75% sensitive and 94.6% specific (PPV 50%, NPV 98.1%). Above this threshold, raised VE/VCO2 was a predictor of poor long-term survival (HR 1.90, 95%CI: 1.02 to 3.57, p = 0.045). Conclusions: CPET is a useful adjunctive test for predicting post-operative outcome in patients being assessed for pancreaticoduodenectomy. CPET-derived VE/VCO2 above a threshold of 41 predicts early post-operative death and poor long-term survival. CPET should be considered in the pre-operative work-up prior to pancreaticoduodenectomy.