bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGFalfa, EGFR and p70S6K expression in aggressive colorectal cancer (CRC)
Authors: Tampellini M. , Longo M. , Cappia S. , Bacillo E. , Brizzi M. , Bitossi R. , Sculli C. M. , Alabiso I. , Dogliotti L. , Papotti M. 
Published: March 2020

13505 Background: Autocrine TGFa in CRC cells regulates cell adhesion via p70S6K phosphorylation in in vitro studies. The aim was to evaluate whether TGFa expression might be correlated with a higher metastatic behavior in vivo. Methods: 101 primitive CRC tumor samples with paraffin blocks available were retrospectively collected. All the specimens were immunohistochemically evaluated for EGFR clone 2–18C9 (Dako), and TGFa clone 213–4 (Calciochem) expression. A score of 0 to 3 was assigned according to staining intensity and extension. EGFR was also evaluated in randomly selected specimens with clone 111.6 (Neomarks) in 81 cases and clone 31G7 (Zymed) in 28 cases. Selected samples were stained for downstream signalling molecules STAT, p-akt, p-MAP kinase, mTor, p-mTor and p70S6K. Patients were divided into 2 groups according to tumor stage at diagnosis: group A stage II-III (51 pts); group B stage IV (50 pts). Results: EGFR clone 2–18C9 reacted in 68/101 (67.3%) cases. Positivity rates and correlation coefficients were: clone 111.6 42/81 (51.9%), r=0.54 (p<0.01); clone 31G7 20/28 (71.4%), r=0.76 (p<0.0001). TGFa was expressed in 79/101 (78.2%) cases. EGFR and TGFa diffuse staining (score 2, 3) was recorded in 14/51 (27.5%) and 18/51 (35.3%) patients in group A, and 26/50 (52.0%) and 27/50 (54.0%) in group B (p=0.01 and p=0.06). EGFR and TGFa coexpression was evident in 23/51 (45.1%) in group A and in 34/50 (68.0%) in group B (p=0.02). No difference in downstream signaling molecule expression was evident between the 2 groups. A positive correlation trend was recorded for p70S6K which was expressed in 8/20 (40%) and in 8/12 (66.7%) samples of group A and B (p=0.15). Conclusions: EGFR, TGFa and p70S6K expression was more common in patients with advanced stage at diagnosis confirming in vitro data. EGFR scores obtained with commercial antibodies from Zymed and Dako had a significant correlation. No significant financial relationships to disclose.
Prognostic value of pathological nodal status and tumor regression grade in patients with rectal cancer (RC) treated with pre-operative chemoradiotherapy
Authors: Bertolini F. , Iachetta F. , Giacobazzi P. , Depenni R. , Zironi S. , Bertoni F. , Frassoldati A. , Luppi G. , Conte P. 
Published: March 2020

13524 Background: The main objective of this study is to clarify the correlation between pathological nodal status and Dworak tumor regression grade (TRG) (Dworak et al. Int Colorectal Dis 1997, 12:19–23) after pre-operative chemoradiotherapy. Methods: From May 1998 to February 2005, 112 patients with locally advanced rectal cancer were diagnosed at Centro Oncologico Modenese and treated with pre-operative concomitant pelvic irradiation (50 Gy in 25 fractions) and chemotherapy with 5-FU in continuous infusion (225 mg/msq/daily). We considered for our analysis only pathological stage III cases. Results: Clinical positive nodal status (by CT scan or ultrasonography) was present in 71 patients on 106 (66.9%) at diagnosis. Among all radically resected patients (106), pathologic assessment of lymph nodes in surgical specimens was performed; average number of nodes examined was 11 (range: 2–22). Thirty patients (28.3%) had a positive nodal status at pathological examination: 19 (63.3%) were pN1 (≤3 lymph nodes) and 11 (36.7%) were pN2 (>3). The nodal status changed from 66.9% (clinical evaluation) to 28.3% (pathologic evaluation). Among stage III patients 5 (16.7%) had a TRG 3, 12 (40%) TRG 2, 11 (36.7%) TRG 1 and 2 (6.6%) TRG 0. At a median follow-up of 32,3 months, 20/106 patients relapsed (18.8%); of these 20, 10 (50%) had a positive pathologic nodal status. In this subset recurrence occurred in 5/10 (50%) pN1 patients (1 local and 4 with distant metastases) and 5/10 (50%) pN2 patients (2 local and 3 with distant metastases). The 3-y DFS was 63% (68% pN1 and 54% pN2) (p=0.32). The 3-y OS was 84% (94% pN1 and 68% pN2, p=0.72). The 3-y DFS in post-operative stage III patients according to tumor regression grade was 81% for TRG 2–3 and 38% TRG 0–1 (p<0.026). Conclusions: In stage III patients, TRG is confirmed as a relevant prognostic factor in locally advanced rectal cancer treated with neo-adjuvant chemo-radiotherapy. In the same subset of patients the number of positive nodes seems to impact on the prognosis, even not reaching a significant relevance. No significant financial relationships to disclose.
Clinical features of ulcerative colitis-associated colorectal cancer in Japan: an analysis of 169 cases over 20 years
Authors: Watanabe T. , Konishi T. , Muto T. , Kotake K. , Nagawa H. 
Published: March 2020

13544 Background: Development of colorectal cancer is a well-known long-term complication of ulcerative colitis (UC). However, specific clinical features of UC-associated colorectal cancer have been controversial mainly due to the small number of cases, especially in the Asian countries. This study aims to clarify the clinicopathological features of UC-associated colorectal cancer compared with non-UC-associated colorectal cancer in Japan, using a large nationwide database. Methods: All patients pathologically diagnosed as colorectal cancer from 1978 to 1998 were extracted from the nationwide database, “Multi-Institutional Registry of Large-Bowel Cancer in Japan”, which covers almost 10% of all colorectal cancers in Japan. Clinicopathological factors were compared between those associated with UC and the others. Survival analysis in each TNM stage was performed using the Kaplan-Meier method. Results: Among 108,536 cases of colorectal tumors registered from 1978 to 1998, a total of 169 cases of UC-associated colorectal cancers were identified. All cases were from the Asian population. UC-associated cases showed higher prevalence of females, younger age, higher incidence of multiple cancers, and higher incidence of mucinous adenocarcinomas. On the other hand, there were no differences in tumor sites, family history of colorectal cancer, lymph node metastasis, distant metastasis, TNM stage, and CEA level adjusted by TNM stage between the two groups. Survival analysis revealed poorer prognosis in UC-associated colorectal cancers at TNM stage 3. Conclusions: UC-associated colorectal cancer showed unique histological features compared with usual colorectal cancer. The survival of UC-associated colorectal cancer with lymph node metastasis was poorer than usual colorectal cancer, and therefore, intensive adjuvant therapy and close follow-up is needed after surgery in this patient group. No significant financial relationships to disclose.
Does serum VEGF predict prognosis in metastatic colorectal carcinoma patients treated with XELIRI?
Authors: Bozcuk H. S. , Artac M. , Akcan S. , Korgun D. K. , Ozben T. , Ozdogan M. , Samur M. , Mutlu H. , Kargi A. , Savas B. 
Published: March 2020

13548 Background: Serum vascular endothelial growth factor (sVEGF) levels have been shown to possess prognostic value in different solid tumors. However, there is no solid information on the prognostic use of sVEGF in metastatic colorectal carcinoma (MCRC) patients treated with a standard regimen. Methods: 37 consecutive MCRC patients were given XELIRI chemotherapy as the 1st line treatment (irinotecan 250 mg/m2 on day one, and Capecitabine 2000 mg/m2/day, for 14 days starting on day1, repeated in every 3 weeks). Serum VEGF levels prior to the 1st cycle of chemotherapy was measured by ELISA. Kaplan-Meier survival curves and Cox regression analyses to adjust for basic clinical features were used for the survival analysis. Binary logistic regression analysis was employed to determine correlates of objective response (CR+PR). Results: Best objective response was CR+PR in 20/33(61%) cases (3 CR; 9% + 17 PR; 52%). In 4 patients, response assessment was not possible. Median sVEGF was 650(107–1865) pg/ml. Median OAS and PFS was 16.2 and 5.9 months, respectively. Increased age turned out to be the only predictor of better OAS with borderline significance (P=0.09). After adjustment for performance status (0, 1 versus 2) and disease extent (single vs. multiple metastatic sites), age was statistically significant (P=0.042, HR=0.95(0.90–0.99)). For PFS, again age (P=0.038) was the only correlate. After controlling for performance status and disease extent, age (P=0.014, HR=0.95(0.92–0.99)) and performance status (P=0.036, HR=3.27(1.08–9.88)) were significant. No factor was associated with the likelihood of objective response. Conclusion: In this study, we failed to determine any prognostic value for sVEGF in MCRC. However, older age and good performance status appear to have a borderline positive prognostic value for MCRC patients treated with XELIRI. No significant financial relationships to disclose.
Biweekly treatment with bevacizumab (BV) as 2nd line chemotherapy in patients with metastatic colorectal cancer
Authors: Samelis G. F. , Areovimata A. , Adrachta D. , Palazi A. , Papagianni V. 
Published: March 2020

13561 Background: Bevacizumab (BV), a monoclonal antibody directed against vascular endothelial growth factor, provides a survival advantage (15.6 to 20.3 months) when added to first-line chemotherapy for metastatic colorectal cancer (metastatic CRC). Only a few trials have been conducted using BV as 2nd line chemotherapy. Methods: Sixteen patients with metastatic CRC refractory to first-line chemotherapy (oxaliplatin or irinotecan-based regimen) were enrolled. All patients, after progressing in first-line treatment, received the following regimen: BV: 5 mg/Kg* in 1000ml water for injection in 90min IV infusion plus irinotecan 125mg/m2 IV in 500ml NIS in 60min plus folinic acid 30mg/m2 and 5-fluorouracil 500mg/m2 IV bolus infusion. The schedule was repeated every 2 weeks. Fourteen men and 2 women entered the study with PS 0–1, median age of 66 years (range: 48–85). 11 patients (68.7%) had liver metastases, 3 patients (18.75%) had lung metastases and 4 patients (25%) had local tumor recurrence. All 16 patients were eligible for the study and received in total 174 (mean 10.8, range: 6–20) cycles. Six out of 16 patients (12.5%) had more than 2 metastatic sites (liver and local recurrence). Results: Six patients had partial responses (PRs) (37.5%), 4 patients had stable disease (SD) (25%) and the rest of the patients progressed (37.5%). The time to progression (TTP) was 6.4 months (range: 4–8), and the median survival was 9 (range: 5–12) months. The toxicity was mild and no toxic death was reported. Grade II toxicities were the following: epistaxis 4 patients (25%), anaemia 5 patients (31%), leukopenia 3 patients (18.7%), granulocytopenia 2 patients (12.5%) and 1 patient developed jaundice due to bile-duct obstruction. Conclusions: The bi-weekly administration of BV, irinotecan, leucovorin and 5-fluororacil is acceptable as 2nd line treatment in patients with metastatic CRC, with an overall response rate (PRs) of 37.5%, and SD of 25%. The TTP and survival were 6.4 and 9 months respectively. The study is ongoing and we expect to enrol more patients. No significant financial relationships to disclose.
Capecitabine combined with Irinotecan (CapIri) as first line treatment of advanced colorectal carcinoma (ACRC): A phase ll study
Authors: Zidan J. , Basher W. , Shnaider J. , Tmam S. , Abzah A. , Chetver L. 
Published: March 2020

13569 Background: The combination of 5-FU + LV with irinotecan as first line treatment of advanced colorectal cancer (ACRC) has shown higher response rate compared with 5-FU +LV with the same progression free survival. Capecitabine is more active than 5-FU.The aim of this study is to determine the side-effect profile, dose limiting toxicity and response rate to CapIri combination as first line treatment in ACRC, on an outpatient basis. Methods: Inclusion criteria: age >18–75 years, ECOG ≤ (0–3), measurable disease, no previous treatment for advanced disease, previous adjuvant chemo-therapy more than 6 months is allowed, signed informed consent and adequate hepatic, renal and hematological function. Exclusion criteria: Serious concurrent medical disorders, prior other malignancy, pregnancy or breast-feeding and patients with poor compliance. Capecitabine 1000mg/m2 twice daily was given for 14 days followed by 7 days rest and Irinotecan (100mg/m2) was given days 1 and 8. Treatment was repeated on day 2. Results: 28 patients (pts) were included. All patients were assessable for response and toxicity. Average age was 64 years, male/female ratio 20/8. Fourteen pts had liver metastases, 5 had lung and 9 had abdominal metastases. Median No of cycles was 4. Grade III and IV diarrhea was observed in 12 (44%) pts, vomiting in 9 (31%) pts, fatigue in 12 (44%) pts, grade IV leucopenia in 5 (17%) pts. Complete response was achieved in 3 (11%) pts, partial response in 15 (53%), stabilization of disease in 5 (18%) and tumor progression in 5 (18%) pts. Progression free survival is 8.4 months. Overall survival is not yet available. Conclusions: This regimen appears feasible with acceptable toxicity except for grade III diarrhea, on an outpatient treatment basis, with significant antitumor activity, without the requirement for indwelling catheters. It is also feasible for older patients. No significant financial relationships to disclose.
Capecitabine and oxaliplatin as first-line chemotherapy in patients with metastatic colorectal carcinoma
Authors: Gennatas C. , Michalaki V. , Gennatas S. , Kondi-Paphiti A. , Voros D. , Smyrniotis V. 
Published: March 2020

13578 Background: Capecitabine is an oral fluoropyrimidine with superior activity and safety compared with bolus 5-FU/LV in metastatic colorectal cancer (CRC). The aim of this study was to evaluate the efficacy and safety of a combination of capecitabine and oxaliplatin as first-line chemotherapy in patients with advanced CRC. Methods: Fourty-six patients (26 men and 20 women) with metastatic CRC entered this study. All patients were treated with capecitabine (1,000mg/m2 p.o.twice daily, days 1–14) and oxaliplatin (130mg/m2 on day 1). Cycles were repeated every 21 days until disease progression or unacceptable toxicity. Baseline characteristics: Median age 61 years (range 32–74), main sites of metastasis: Liver 32 patients (70%), liver and lungs 4 patients (9%), lungs 3 patients (6%), other sites 7 patients (15%). Results: 2 patients (4%) achieved complete response (CR), 17 patients (37%) achieved partial response (PR) and 7 patients (15%) attained stable disease (SD). With a median follow-up of 22 months the progression free survival was 7.5 months and overall survival was 19.0 months. All patients were assessable for toxicities. The most commonly encountered adverse events were from the gastrointestinal system (all grades 48%, grade 3, 6%). Neither toxic death nor life-threatening febrile neutropenia were reported. Conclusions: The combination of capecitabine and oxaliplatin is a convenient regimen in patients with advanced CRC that is associated with considerable efficacy and limited toxicity. No significant financial relationships to disclose.
Outpatient chemotherapy with gemcitabine and oxaliplatin in advanced biliary tract cancer; a phase II study
Authors: Harder J. , Riecken B. , Kummer O. , Lohrmann C. , Geissler M. , Otto F. , Opitz O. , Henss H. 
Published: March 2020

14006 Background: Biliary tract cancer is a heterogeneous tumor entity with a poor prognosis if unresectable. There is a need for an effective, safe and patient friendly treatment. Methods: Patients with typical histology for cholangiocarcinoma, adequate haematological, renal and liver function, measurable tumor formation, life expectancy for more than 3 months, and written informed consent were treated with Gemcitabine 1000mg/m2 (30 min infusion) day 1, 8, 15 and Oxaliplatin 100mg/m2 (2 h infusion) day 1 and 15. Chemotherapy cycles were repeated every 28 days (GEMOX-3 protocol). The data were collected according to the Simon 2-step design for a single centre phase II study (α=0.05; β=0.2). Planned sample size 29. Primary endpoint was the response rate; secondary endpoints were time to progression, median survival and safety profile. Results: Thirty-one consecutive patients were enrolled between July 2002 and April 2005. The efficacy was as follows: partial response 8 pts (26%), stable disease 14 pts (45%). Thus, the disease control rate was 71%, while 9 pts (29%) had progressive disease. Median time to progression was 6.5 months. Median overall survival after start of treatment was 10.4 months, after initial diagnosis it was 15.6 months. National Cancer Institute Common Toxicity Criteria grade 3–4 toxicities were transient thrombocytopenia in 23% of patients, peripheral sensory neuropathy 19%, leukopenia 16% and anaemia 10%. Conclusion: The GEMOX-3 protocol is active and well tolerated in patients with advanced biliary tract cancer. It can be applied in an outpatient setting with three treatments per month only. The positive results of this and other phase II trials underscore the importance of a large controlled clinical trial to verify the data. No significant financial relationships to disclose.
Phase II trial of induction GEMOX followed by a twice-weekly infusion of gemcitabine and concurrent external beam radiation for the treatment of locally advanced pancreatic cancer
Authors: Leone F. , Sperti E. , Aliberti S. , Gatti M. , Massucco P. , Magnino A. , Faggiuolo R. , Gabriele P. , Capussotti L. , Aglietta M. 
Published: March 2020

14019 Background: Combined chemo-radiation therapy may render curative resection feasible in pancreatic cancer deemed unresectable for vascular invasion. We previously demonstrated that primary radiotherapy with concurrent gemcitabine is feasible and allows clinical benefit. However, the percentage of resected patients was low. Methods: Patients with locally advanced pancreatic adenocarcinoma, received induction with 4 cycle GEMOX (gemcitabine 1000 mg/mq, day 1 and oxaliplatin 100 mg/mq, day 2) each 2-week cycle. Patients without disease progression received gemcitabine twice weekly (50 mg/mq/day) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy over 5.5 weeks) and were re-evaluated for resectability. Results: From 7/2003 to 11/2005, 20 patients entered this study, of whom 17 are evaluable for toxicity and 15 for treatment response. Twelve men and 8 women (median age 63 years; range 43–71) received a median of 3.5 cycles GEMOX (range 2–4). Fourteen patients completed the treatment with external beam radiation and received a median of 7 cycles with gemcitabine (range 3–10). In two patients chemotherapy during radiotherapy was omitted for previous toxicity, and one stopped also radiotherapy for gastrointestinal toxicity. No grade IV toxicities or deaths due to therapy were observed. Gastrointestinal grade III toxicities were observed in 3/17 patients (17.6%) after GEMOX and 6/16 patients (37.5%) during radiotherapy. Grades III hematologic toxicity and fatigue occurred in 4/16 (25%) and 2/16 (12.5%) respectively during radiotherapy. A disease control was obtained in 10/15 evaluable patients. One patient progressed after GEMOX and 4 after chemoradiotherapy. Eight patients (53%) appeared to be resectable: 1 patient is planned for surgery, 2 patients were found unresectable at lapaproscopy for peritoneal carcinomatosis or local extension; 5 patients underwent resection and in 4 of them (26%) margins were negative. Conclusions: Induction GEMOX followed by twice-weekly gemcitabine and upper abdominal radiation is feasible in patients with locally advanced pancreatic cancer and seems to induce a high resectability rate. This protocol warrants further evaluation. No significant financial relationships to disclose.
A phase I study of capecitabine (CAP), carboplatin (CARB), paclitaxel (TAX) and external beam radiation therapy (EBRT) for patients with esophageal carcinoma (EC)
Authors: Kelsey C. R. , Czito B. G. , Bendell J. C. , Willett C. G. , Morse M. A. , D’Amico T. A. , Honeycutt W. , Franklin A. , Yu D. , Hurwitz H. I. 
Published: March 2020

14044 Background: Chemoradiotherapy is used to treat esophageal cancer with curative intent or local symptom control. A phase I study of 5-FU + CARB + TAX + EBRT showed 100% RR and 50% pCR rate. CAP allows for fluoropyrimidine treatment without the inconvenience of an infusion pump. CARB allows for platinum treatment with less toxicity than cisplatin. We evaluated this combination of agents in a phase I study. Methods: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus requiring local therapy received CAP (825 mg/m2 bid on radiation days) + CARB (AUC 2 qweek) + TAX (60 mg/m2 qweek) + EBRT (1.8 Gy qd to 50.4 Gy). DLT was defined as any grade 4 heme toxicity, grade 3 heme toxicity lasting ≥ 7 days, ≥ grade 3 N/V, diarrhea, or esophagitis lasting ≥ 4 days despite optimal medical management, grade 3 other toxicity, inability to deliver 75% of scheduled CAP dose, or treatment delay > 3 days. Results: 13 pts were enrolled (10M, 3F). Median age was 62 (R- 48–78). EUS stage was uT3N0 (n=1), uT2N1 (n=1), or T3N1 (n=11). 2/3 pts had DLT at dose level 1 (both grade 4 esophagitis). Esophagectomy was performed in 2/3 patients, both pCR. Three pts were then enrolled at dose level -1 (CAP 600 mg/m2 bid + CARB AUC 1.5 + TAX 45 mg/m2). One patient developed DLT (grade 3 esophagitis) so 7 more pts were added at this dose level. Overall, 3/10 patients at dose level -1 developed DLT (two grade 3 esophagitis, one grade 3 hypotension). Esophagectomy was performed in 6/10 pts - 2/6 had pCR; 6/6 had pathologic downstaging. Conclusions: MTD for this regimen was CAP 625 mg/m2 bid + CARB AUC 1.5 + TAX 45 mg/m2 with EBRT to 50.4 Gy. However, at the MTD, this regimen is relatively toxic with no significant improvement in rate of pCR. [Table: see text]
Phase 1 study of intra-arterial hepatic (IAH) delivery of doxorubicin-transdrug (DT) for patients with advanced hepatocellular carcinoma (HCC)
Authors: Merle P. , Si Ahmed S. , Habersetzer F. , Abergel A. , Taieb J. , Bonyhay L. , Costantini D. , Dufour-Lamartinie J. , Trepo C. 
Published: March 2020

14094 Background: HCC is a highly chemoresistant due to MDR efflux pumps. DT is a newly cytotoxic chemotherapy composed of doxorubicin-loadded polyisohexylcyanoacrylate nanoparticles, allowing doxorubicin to overcome MDR pumps [Barraud, J Hepatol 2005; 42: 736]. Methods: 16 cirrhotic patients (pts) of Child-Pugh A with advanced HCC, transaminases/GGT <5N, platelets >100000/mm3, neutrophiles >1500/mm3, were enrolled in a multicentric noncontrolled study. A single IAH injection of 10, 20, 30, 35, or 40mg/m2 DT (respectively 3,3,4, and 3 pts) was performed, tolerance and efficacy being assessed 4 weeks later. Results: Grade 4 neutropenia (2pts at 40mg/m2) gave the Maximal Tolerated Dose. Grade 2–3 hypertransaminasemia (transient) occurred dose-independently. Two serious adverse events (SAE) were hypotension and acute respiratory distress syndrome. All adverse events (AE) (90% grade 1–2) occurring during injection were dose-independent, and completely and fastly recovered : cough (6pts), dyspnea (2pts), SaO2 decrease (2pts), tachycardia (2pts), bradycardia (2pts), hypotension (2pts). Anti-tumor efficacy of DT was evaluated by helicoidal CT-scan with contrast injection 4 weeks after injection : 3pts (20%) showed partial response with frank decrease of contrast enhancement at arterial perfusion, 8pts (50%) remained stable, and 5pts (30%) had progression. Conclusions: This phase 1 showed that a single IAH injection of DT was safe until 35 mg/m2 for Child-Pugh A patients with advanced HCC. This dosage will be retained for the phase 2 step comprising 3 injections at 4-week intervals which will aim at confirming the antitumour efficacy of DT for HCC. [Table: see text]