bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefit of fluorouracil and folinic acid adjuvant in colon cancer elderly patients
Authors: Lonardi S. , Stefani M. , Jirillo A. , Ghiotto C. , Pasetto L. M. , Falci C. , Lamberti E. , Monfardini S. 
Published: March 2020

13564 Background: Retrospective analyses on elderly people enrolled in clinical trials of adjuvant chemotherapy for colon cancer indicated the maintenance of the efficacy in that subset of patients (pts). However, data on the benefit of the routinely used adjuvant treatment in an unselected population of pts aged more than 65 years are few. Methods: All the charts of pts radically operated for colon cancer from 1996–2001 at Medical Oncology, Padua Hospital, were retrospectively analysed. 147 out of 330 pts consecutively treated with fluorouracil (FU)-based chemotherapy was aged 65 years or more at the time of diagnosis. Kaplan-Meyer progression-free-survival (PFS) and overall survival (OS) of stage II and III pts were calculated. Results: Pts characteristics were: males/females: 87/60, median age 71 (range 65–87), ECOG PS 0/1: 124/23, right/left colon primary tumor: 62/85, TNM stage: 24/63/60. 86 out of 147 pts were treated with the following regimen of adjuvant chemotherapy: FU 370 mg/mq + leucovorin (LV) 20 mg/mq day 1–5 q 28 for 6 cycles (Machover regimen, n=69), or FU 500 mg/mq + LV 250 mg/mq weekly × 6 q 56 for 4 cycles (Roswell Park regimen, n=17). Treated pts were staged as follows: TNM stage I/II/III: 1/38/47. No toxic death were observed and only nine of 86 pts (10.4%) stopped the treatment due to acute grade III gastrointestinal toxicity. At a median follow-up of 73.2 months, 19 out of 86 pts (22%) developed cancer recurrence (3-y PFS: 82.2%, 5-y PFS: 80.3%). Seventeen pts (19.7%) died, 13 (15.1%) due to tumor progression, 3 (3.4%) due to acute heart failure, and 1 (1.1%) due to chronic pulmonary disease (3-y OS: 88.8%, 5-y OS: 82.4%). No statistically significant difference in survival was observed comparing pts aged 65–70 (n=41) with pts more than 70 years old (n=45): 5-y OS 84.1% vs 77.8%, respectively (p=2.23, log rank test). A separate survival analysis on stage II pts was performed (n=63). 5 of 38 (13.1) treated pts dead, compared to 9 of 25 (36%) non treated pts; 5-y survival in the two groups were 86.6% and 60.8%, respectively (p= 0.03, log-rank test). Conclusions: The efficacy of adjuvant chemotherapy appears maintained in an unselected population of elderly pts. Surprisingly, our retrospective analysis suggest that even stage II pts may benefit of a fluorouracil-based well tolerated chemotherapy. No significant financial relationships to disclose.
DNA Image cytometry as a prognostic tool in stage II and stage III colorectal cancer
Authors: Buhmeida A. , Ålgars A. , Ristamäki R. , Collan Y. , Syrjänen K. , Pyrhönen S. 
Published: March 2020

13565 Background: We assessed the prognostic value of nuclear DNA content measured in the primary tumors of 123 patients with stage II or stage III colorectal cancer (CRC). Methods: Isolated nuclei from paraffin sections were stained with Feulgen and DNA was measured using a computer-assisted image analysis cytometry system (Ahrens ACAS). We applied 4 different approaches in analysis of DNA histograms: ABCDE approach, histogram range, peak evaluation, and DNA cut-off values. Results: Using the histogram range, narrow range was rare (3.7%) in patients who died of disease as compared with 16.4% among those alive (p=0.017). Modal peak evaluation was a significant predictor of disease free survival (DFS) (Kaplan-Meier log-rank p=0.0235). In the range evaluation, the first set (low-start gates) was a significant predictor of DFS (log-rank p=0.0121), where disease recurrence was closely associated the widest range (1.8c->10c) gates. Recurrence-free survival was markedly better among patients with narrow gate histograms than wide range histograms than among patients with wide range histograms (p<0.03). The first set also proved to be significant predictor of disease specific survival (DSS) (log-rank p=0.0045), being markedly better (78–90.0%) among the patients with the narrow-gate histograms. Grading of the histogram range into two categories (with 6.0c as cut-off for low and wide range), was a powerful predictor of both DSS (log-rank p= 0.0092) and 5-year DFS (p=0.0106) in the whole series, and separately in Stage III (but not Stage II) disease; p=0.0131 and p=0.0201, respectively. Conclusions: The DNA image cytometry with careful analysis of the histograms may provide valuable prognostic information in CRC, with potential clinical implications in patient management, particularly in predicting the patients at high risk for recurrence who should be considered as candidates for adjuvant therapy. No significant financial relationships to disclose.
Phase II trial of repeated carcinoembryonic antigen (CEA) radioimmunotherapy (RAIT) with 131I-Labetuzumab post salvage resection of colorectal metastases in the liver
Authors: Liersch T. , Meller J. , Lorf T. , Sahlmann C. , Langer C. , Ghadimi B. , Wegener W. , Becker H. , Goldenberg D. 
Published: March 2020

13572 Background: Complete resection of liver metastases (LM) remains the treatment of choice for colorectal cancer (CRC). As shown recently (Liersch et al., JCO 2005; 23:6763–70), RAIT with a single application of the humanized monoclonal anti-CEA antibody, 131I-labetuzumab, improved both the median overall survival (OS) and 5-yr survival rates significantly in patients post salvage resection of LM. The major adverse side effects (≤ grade 3 CTC) were transient myelosuppression and/or thrombocytopenia in patients receiving 40 to 60 mCi/m2 of 131I-labetuzumab. These encouraging results stimulated the current ongoing Phase-II trial to evaluate the safety of repeated RAIT at doses of 2 × 50 mCi/m2 (3 mos apart), post salvage resection of LM. Methods: At present, 13 patients (primary CRC: 8x UICC stage IV, 1× UICC stage III and 4× UICC stage II) who underwent surgery for LM of CRC (postsalvage mTMN stages: 4× mT4, 2× mT3, 6× mT2, 1× mT1) have received the first dose of 50 mCi/m2 131I-labetuzumab within 2 mos of LM surgery. Three months later, a second infusion of 50 mCi/m2 has already been given to 5 pts. In two, a dose reduction to 40 mCi/m2 was performed. At re-staging CT and PET scans) for the 2nd RAIT, in one patient pulmonary metastases were diagnosed and in another patient a re-resection of hepatic relapse was performed. Results: In the previous trial, at a median follow-up of 67 mos, the median OS from the first liver resection for 19 pts treated with single-dose RAIT was 68.0 mos and median DFS was 18.0 mos. Also, 5-year survival was achieved by 51.3% of RAIT pts independently of bilobar involvement, size and number of LM, or resection margins. In the current study with repeated RAIT, transient grade-4 myelosuppression (2 cases in combination with a myelotoxic thiamazol medication) occurred in 4/13 pts after the first dose (1× grade 4 thrombocytopenia). No cumulative toxicity was seen in 6 of 7 RAIT-re-treated patients. Complete bone marrow recovery was observed in all 6 cases within 5–12 weeks; in one pt severe neutropenia persisted to about week 16 post 2nd RAIT. As of January, 2006, patient compliance was 100%. Conclusion: RAIT re-treatment to-date appears to be safe, feasible, and well accepted. Extended follow-up data are being collected. [Table: see text]
Frequency of familiar cancer in a cohort of newly-diagnosed patients with colorectal cancer
Authors: Lastra R. , Yubero A. , Ortega M. , Lambea J. , Elena A. , Millastre E. , Ruiz M. , Escudero P. , Saenz A. , Mayordomo J. I. , Tres A. 
Published: March 2020

13588 Background: Incidence on Hereditary Non Poliposis Colorectal Cancer (HNPCC) is 3–5% of all colorectal cancers (CRC). Primary identification of patients (p) with high risk of this hereditary syndrome is the first step before genetic testing for MSH2, MLH1 or MSH6 mutations. AIMS: To determine the frequency of family history of CRC in our population Methods: We have assessed cancer history (full family pedigree, including at least 2 generations of ascendants plus all descendants) in a cohort of 100 newly-diagnosed p with CRC cancer seen as first visit at the Division of Medical Oncology of the University Hospital of Zaragoza, Spain, from 2005. We have used the revised Bethesda Guideline for HNPCC published in JNCI (Vol 96. Feb 2004) Results: Median age was 72 (range: 26 - 85). 29 females/71 males. Considering Bethesda criteria for genetic testing, percentages of families fulfilling them were: Cancer before age 50: 7 (7%), synchronous/metachronous cancer: 1 (1%), other HNPCC associated tumors before age 50: 1 (ovarian 1%), One first-degree relative with HPNCC related tumor before age 50: 4 (4%), Two or more family members with HNPCC related cancer: 5 (5%). Overall, 14 (14%) fulfilled at least 1 of these criteria. Number of cases of tumors in the family (for a total of 909 family members) was 82, 10 cases of breast cancer, 23 of colorectal, 6 of gastric, 5 of prostate, 3 gynecologic, 11 lung, and 21 others. Conclusions: Frequency of familiar CC in unselected breast cancer patients of Zaragoza, Spain, is substantially higher than that expected. Assessment of cancer familiar history in the newly-diagnosed patients with CC cancer, helps us to identify families in which a genetic study is to be considered, and this could be useful to prevent new case of cancer. No significant financial relationships to disclose.
How many colorectal cancer (CRC) patients older than 70 years may be safely treated with bevacizumab?
Authors: Pasetto L. M. , Falci C. , Sinigaglia G. , Brandes A. A. , Monfardini S. 
Published: March 2020

13589 Background: While age-associated comorbidities are not usually an obstacle to the administration of chemotherapy regimens for CRC, they could instead limit the access to an anti-angiogenic therapy. Hypertension, proteinuria, arterial thrombosis, bleeding and gastrointestinal perforation are the principal bevacizumab (Avastin®)-related events. The aim of this analysis was to estimate the percentage of patients ≥ 70 years potentially amenable with bevacizumab, taking into account age-associated cardiovascular, gastrointestinal (GI) or kidney diseases possibly interfering with its administration. Methods: From January 2004 to December 2005, 91 consecutive patients older than 70, with histologically proven CRC adenocarcinoma for whom chemotherapy had been planned (44 as an adjuvant treatment, 30 as a palliative therapy, 17 for a neoadjuvant program) and entered in our Geriatric Oncology Program, were analysed. Principal variables considered were age and the afore mentioned comorbidities. Results: Median age was 76 years (range, 70–84) and the male:female ratio, 62:28. Sixty-five patients (71.4%) had associated comorbidities. Of these, 39 had cardiovascular-, 17 had cardiovascular and GI-, 5 GI-, 2 kidney and cardiovascular-, and 2 kidney, cardiovascular and GI-associated diseases. Twenty nine out 91 (31.9%) cases presented a grade ≥ 2 either cardiovascular or GI or kidney comorbidities according to the Cumulative Illness Rating Scale-Geriatric (CIRS-G) score, 36 (39.5%) a grade 1 and 26 (28.6%) no comorbidities. Conclusions: In view of the most common bevacizumab-related adverse events, almost one third of our CRC patients with cardiovascular, GI- or kidney- associated diseases of CIRS grade ≥ 2 could have been considered at high risk for its administration. Also in about 40% of patients with CIRS grade 1 still the use of bevacizumab could have been questionable. Then less than in one third of our patients older than 70 years bevacizumab could have been safely administered. No significant financial relationships to disclose.
A phase I trial of S-1 with concurrent radiotherapy for locally advanced pancreatic cancer
Authors: Ikeda M. , Okusaka T. , Ito Y. , Ueno H. , Morizane C. , Furuse J. , Ishii H. , Kawashima M. , Kagami Y. , Ikeda H. 
Published: March 2020

14003 Background: S-1 is a novel oral fluoropyrimidine derivative, and a phase II trial of this agent has demonstrated promising results with a response rate of 37.5% and a median survival of 8.8 months with a mild toxicity profile for patients with metastatic pancreatic cancer. This study investigated the maximum tolerated dose of S-1 based on the frequency of dose-limiting toxicities (DLT) of S-1 with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Patients and Methods: Patients with locally advanced pancreatic cancer in whom adenocarcinoma had been confirmed histologically or cytologically were enrolled in this study. S-1 was administered orally in escalating doses from 50 mg/m2, which is reported to be equivalent to 200 mg/m2 intravenous 5-fluorouracil, to 80 mg/m2 bid in 10 mg/m2 increments on the day of irradiation (Monday through Friday) during radiotherapy. Radiation therapy was delivered through four fields as a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. DLT was defined as grade 4 hematological toxicity and grade 3 or 4 non-hematological toxicity during chemoradiotherapy. The maximum tolerated dose was defined when three or more patients in a cohort of six patients experienced DLT. Results: Twenty-one patients (50 mg/m2 3 patients; 60 mg/m2 5 patients; 70 mg/m2 6 patients; 80 mg/m2 7 patients) were enrolled in this trial between May 2004 and November 2005. At 70 mg/m2 S-1, two of six patients demonstrated DLT involving grade 3 nausea and vomiting and grade 3 hemorrhagic gastritis, while all patients at dose levels other than 70 mg/m2 did not demonstrate any sign of dose-limiting toxicity. Of all 21 patients enrolled, 4 (19.0%) showed a partial response. More than a 50% reduction in the serum level of carbohydrate antigen 19–9 was observed in 12 (75%) of 16 patients in whom the pretreatment level was 100 U/ml or greater. Conclusion: The recommended dose of S-1 with concurrent radiotherapy is 80 mg/m2. This regimen may offer an easy alternative to intravenous 5-fluorouracil, and may be a promising treatment for locally advanced pancreatic cancer. A multicenter phase II trial of this regimen in patients with locally advanced pancreatic cancer is now underway. No significant financial relationships to disclose.
Expression of chemokine receptor CXCR4 correlates with progression of pancreatic cancer
Authors: Schimanski C. C. , Wolfert F. , Gockel I. , Junginger T. , Galle P. R. , Moehler M. 
Published: March 2020

14018 Background: Despite many pathophysiological analyses, the process of tumor dissemination of pancreatic cancer remains vague. In diverse other tumor entities, expression of the chemokine receptor CXCR4 has been linked to tumor dissemination and poor prognosis. Therefore, we evaluated, if the expression of this chemokine receptor exerts similar effects in human pancreatic cancer. Methods: Expression of CXCR4 was evaluated in 120 patients with histologically confirmed pancreatic cancer and eight different pancreatic cancer cell lines. Expression intensities of tumor samples were correlated with both, tumor and patients characteristics. Results: Human pancreatic cancer samples and cell lines displayed variable intensities of CXCR4. CXCR4 revealed predominantly a cytoplasmatic, and in few specimens an additional weak membranous location. Strong CXCR4 expression was significantly associated with progressed disease as indicated by UICC status (P=0.031) and revealed a strong, yet not significant trend with distant tumor cell dissemination and locally progressed tumors (P=0.08; P=0.11, respectively). Conclusion: Strong expression of CXCR4 by pancreatic cancer is significantly associated with progressed tumor stages. No significant financial relationships to disclose.
Phase II study of cetuximab in mucinous peritoneal carcinomatosis
Authors: Andreopoulou E. , Muggia F. , Safa M. , Escalon J. , Downey A. , Newman E. , Hochster H. , Wojtaszek C. , Mauro D. , Lowy A. 
Published: March 2020

14020 Background: Mucinous peritoneal carcinomatosis is most commonly associated with primariy tumors of the appendix and colon. Typically, spread remains confined to the abdominal cavity. Imaging assessment of these mucinous lesions is difficult, and tumor markers (CEA and CA19.9) are often used as a surrogate for extent of disease. Patients (pts) often undergo surgical debulking, sometimes coupled with intraperitoneal (IP) drug delivery, but recurrence is common. Since mucin genes are regulated by EGFR, our two institutions initiated this study. Methods: Between Sept 2004 and Dec 2005, weekly cetuximab (loading 400 mg/m2 on first dose, followed by 250 mg/m2/week thereafter) was given to 20 pts (4 men, 16 women): 17 of appendiceal origin were entered a median 3 y (6 m-7 y) after diagnosis; 3 were unknown primaries 24, 23, and 2 m after diagnosis. Prior treatment included surgery (18), systemic (17), and intraoperative (4) or subsequent IP therapy (2). Results: Pts received a median of 12 doses (0–51) of cetuximab. No major objective responses were observed; transient > 25% decreases in CEA and CA19.9 were noted in 4/19 pts; markers were never elevated in 1. Stable disease was best response in 3 of 15 evaluable (5 too early). The most common toxicities, as expected, were skin rash, dryness, and nail fragility. Hypersensitivity reactions in 2 patients did not preclude repeated dosing with premedications. The median time to progression from the start of treatment was 3 m. Conclusions: Brisk accrual by two institutions in this rare clinical entity is noteworthy. In this heavily pretreated population, transient decrease in tumor markers and time on study with stable disease were encouraging, prompting plans for a future study of cetuximab with the addition of systemic irinotecan. [Table: see text]
Phase I trial of docetaxel, oxaliplatin and capecitabine (TEX) in patients with metastatic gastric cancer
Authors: Grothe W. , Hofheinz R. D. , Mantovani Loeffler L. , Böhme J. , Arnold D. , Radestock U. , Hochhaus A. , Schmoll H. 
Published: March 2020

14051 Background: Combination regimens of 3 active drugs have shown promising activity in treatment of metastatic gastric cancer (GC). Docetaxel (D) combined with cisplatin and 5-FU (CF) yielded superior overall survival and response rates when compared to standard CF. However, toxicity profile showed the need for development of less toxic modifications. In this phase I trial, D was combined with oxaliplatin (Ox) and capecitabine (Cape) in order to define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) in patients (pts) with metastatic GC. Methods: Pts had to have metastatic or locally advanced GC, adequate organ function, ECOG PS 0–2, no prior chemotherapy. Four dose levels were planned planned for the TEX regimen: D 35–40 mg/m2, Ox 70 mg/m2 d1 and d88, with Cape 800–1000 mg/m2 bid d1–14 q d22. Toxicity was assessed 3-weekly whereas CT scans were repeated 9-weekly. Results: 14 pts were enrolled: 9m/5f, age 64 (42–76) yrs, ECOG PS 1 [0–2]. All pts. had distant metastatis, 10 no gastrectomy. On dose level 1 (D 35 mg/m2, Ox 70 mg/m2, Cape 800 mg/m2) 3 pts were included initially. 1 pt. had grade 4 bleeding from primary tumor site after 2nd administration and therefore was excluded. For safety reasons, 6 more pts. were enrolled - without further DLT. On dose level 2 (D 40 mg/m2, Ox 70 mg/m2, Cape 800 mg/m2), diarrhea and mucositis grade 3 occurred as DLT in 2/2 patients. Level 1 was determined as MTD and 5 more pts were included to a total of 12 with toxicity displayed at the table. Out of 10 pts with measurable disease, 3 had a PR, 4 more had disease stabilization. Median PFS of all pts (5 censored) is 3.9+ (1–9.3+) mos. whereas median OS is not yet reached. Conclusion: TEX can safely be administered without higher graded toxicity in pts with GC. Preliminary efficacy results indicate promising activity that merits further testing in a phase II trial. [Table: see text] [Table: see text]
Transarterial ethanol ablation of unresectable hepatocellular carcinoma with lipiodol-ethanol mixture (LEM): A phase II study
Authors: Yu S. C. , Hui E. P. , Wong J. , Mo F. , Ho S. S. , Wong Y. Y. , Lee K. F. , Lai P. , Yeo W. , Mok T. S. 
Published: March 2020

14054 Background: Transarterial ablation with lipiodol-ethanol mixture (LEM) induced potent dual embolization of arterioles and portal venules in preclinical studies, and extensive tumor necrosis in clinical studies. It is potentially an effective treatment and a better alternative to chemoembolization for unresectable hepatocellular carcinoma (HCC). The authors aim to study the safety and efficacy of this treatment. Methods: Unresectable HCC diagnosed by histology or viral serology + AFP > 500 ug/l + typical imaging; bilirubin ≤ 30 umol/l; hypervascular tumor on CT / angiogram, no vascular invasion or extrahepatic spread. LEM with Lipiodol and ethanol mixed in ratio of 2:1 by volume was infused transarterially into tumor vasculature by superselective catheterization of tumor feeders at a subsegmental level under fluoroscopy until flow stagnation. Adverse events (AE) graded by NCI-CTC V2.0. Tumor response monitored by CT scan q3m. LEM repeated for residual enhancing lesion or intrahepatic progression on CT scan. Primary endpoint was response rate. Secondary endpoints: toxicity and survival. Results: From 7/2001 to 4/2005, 77 pts enrolled. Age 28–85 (median 64). M:F=60:17. ECOG 0=68; 1=9. Cirrhosis 92%. HBV 77%, HCV 14%, alcohol 4%. Child A 88%, B 12%. Okuda A 73%, B 27%. Histology confirmed in 78%. 39% had previous treatment. Median tumor size 4.5cm (range 1.5–15cm); Number of lesions: One (58), Two (14), Three (5). Best tumor response (WHO criteria): CR 0%, PR 43%, MR 36%, SD 17%, PD 4%. Patients received 1 to 8 LEM treatments (mean 2.2). Mean hospital stay 2.7 days (range 2 -15). Significant AEs are shown in the table. Fever in 15% for mean duration of 3.1 days. After a median follow-up of 1.65 yr, 23 pts died. One year survival 77%. 3 pts had tumor resection after downstage by LEM. Conclusions: Transarterial ablation with LEM is a well tolerated and effective local regional treatment of unresectable HCC. The high tumor response and 1-year survival rate warrants further investigation in comparative study. [Table: see text] No significant financial relationships to disclose.