bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifactorial prospective study of tumoral factors related to disease-free survival (DFS) in colorectal cancer patients
Authors: Milano G. , Francoual M. , Bourgeon A. , Benchimol D. , Chazal M. , Laurent-Puig P. , André T. , Letoublon C. , Gilly F. N. , Etienne-Grimaldi M. C. 
Published: March 2020

3604 Background: There is still a need to identify faithful biological prognostic factors in colorectal cancer, particularly in stage 2, so as to decide upon adjuvant treatment. We thus conducted a prospective multicentric multifactorial study to this end. Methods: Primary colorectal tumors (30 stage 1, 119 stage 2, 107 stage 3) were prospectively collected in 256 patients undergoing total tumor resection (152 men, 104 women ; mean age 69, extremes 29–90). Adjuvant 5FU-based chemotherapy was administered in 92 patients. Median follow-up was 54 months (53 patients developed metastasis or recurrence). Tumors were analyzed for thymidylate synthase (TS), thymidine phosphorylase and dihydropyrimidine dehydrogenase expression (RT-PCR), TS activity (radioenzymatic assay), EGFR level (ligand-binding assay), VEGF (Elisa), DNA content and cell cycle (flow cytometry), p53 mutations (exon 4 to 8), microsatellite instability (bat 25, bat 26), EGFR genotype (CA repeats in intron 1 and -216G>T), TS genotype in 3’ (6 bp deletion) and 5’ (28 bp repeats including the G>C mutation), and methylenetetrahydrofolate reductase genotype (677C>T and 1298A>C). Results: With the exception of tumor TS expression (p = 0.034, the higher the expression, the better the DFS), none of the analyzed parameters were linked to DFS. In multivariate Cox analysis, tumor staging (p = 0.001) and TS expression (p = 0.062) were the sole factors associated to DFS. Focus on tumoral EGFR revealed large inter-patient variability (from 1 to 510 fmol/mg prot) with a significant influence of tumor localisation (p = 0.009, higher in proximal colon) and differentiation status (p = 0.01, higher in poorly differentiated tumors). EGFR within the tumors was 30 % lower than in adjacent normal mucosa (p<0.001). The longer the intron 1 CA repeats, the higher the tumor EGFR (p = 0.044). EGFR -216G>T polymorphism was linked to intron 1 polymorphism, although -216G>T did not influence EGFR levels. Conclusions: The present results underline the major impact of TS expression as a prognostic factor and provide new insights in the knowledge of EGFR in colorectal cancer. No significant financial relationships to disclose.
Potential role of ERBB-2 and cyclooxygenase-2 expression in human colon carcinomas
Authors: Antonacopoulou A. , Tsamandas A. , Skopa C. , Bonikos D. , Kalofonos H. 
Published: March 2020

3608 Background: ERBB2 receptor tyrosine kinase and cyclooxygenase-2 (COX-2) represent promising molecular targets for cancer therapy and/or prevention. This study investigates the relation between ERBB2 and COX-2 expression in human colon carcinomas. Methods: Immunohistochemistry to detect membranous ERBB2 and cytoplasmic COX-2 expression was performed on 124 archived human primary colon carcinomas and matched normal tissues. Results were expressed as % positive cells. In addition, the mRNA levels of ERBB2 and COX-2 were evaluated in a subset of the colonic tissue samples (46 tumor, 7 normal) using real time RT-PCR (expression relative to a calibrator) Results: The results are displayed in the table . ERBB2 and COX-2 expression was higher in well-differentiated tumors (p<0.001 and p<0.05, respectively). However, both ERBB2 and COX-2 protein levels increased in a statistically significant way towards more advanced stages. Linear regression revealed a strong positive correlation between ERBB2 and COX-2 expression in neoplastic populations (r=0.83, p=0.000082 for protein; r=0.411, p=0.00404 for mRNA). Thus, ERBB2 and COX-2 may transcriptionally regulate each other in colon carcinomas. Conclusions: Overexpression of ERBB2 and COX-2 may represent an early dysfunctional event in human colon carcinogenesis regarding tumor differentiation. However, their expression is increased in advanced stages. These markers may constitute important targets for chemoprevention or adjunct therapy of well-differentiated colon carcinomas. [Table: see text] No significant financial relationships to disclose.
Do racial differences predict survival amongst VA patients with colon cancer?
Authors: Safa M. , Atiq M. , Komrokji R. , Nahleh Z. , Pancoast J. , Muhleman A. , Jazieh A. R. 
Published: March 2020

3628 Background: Several reports suggested that African-American patients with colon cancer have poor survival. The outcome of colon cancer in patients treated within the VA system is not well studied. Patients treated in the VA usually share common features and socioeconomic class that will allow studying any potential effect of racial difference on outcome. Methods: We used the VA Central Cancer Registry (VACCR) to analyze VA patients with colon cancer diagnosed between 1995–2005. The reference date for data collection and reporting is January 1, 1995. Data are entered by tumor registrars at the VA medical centers. This site aggregates the data collected by the medical centers’ cancer registries. Data was analyzed using bio-statistical software SPSS. Results: There were a total of 14,816 cases with invasive adenocarcinoma.Majority of patients (98%) were males. Median age was 69 years among caucasian patients as compared to 67 years among African- American (p-value <0.005). There was no difference between the two groups with regards to sex, histological grade, histological subtype, use of chemotherapy or radiation therapy. However, African-Americans had less definitive surgery (84% vs. 86%) (p-value 0.003).The staging information was missing or unknown in 59% of the patients. In patients with known stage, no difference was observed.Median survival for caucasians was greater than African-Ameircans (42 months vs. 39 months)(p-value 0.009). Median survival for stage IV patients was not statistically significant between the two groups (8.8 months vs. 8.6 months);(p-value 0.53). Race was not statistically significant independent variable in Cox multiple regression analysis. Conclusions: In the VA system, African-American patients with colon cancer seem to have a trend towards inferior survival. However, race was not an independent prognostic variable. This slight difference could be due to other variables like definitive surgery. No significant financial relationships to disclose.
Patterns of use and outcomes with irinotecan and oxaliplatin in the treatment of 5-fluorouracil (5-FU) refractory metastatic colorectal cancer: An Australian population based analysis
Authors: Damianovich D. , Adena M. , Tebbutt N. 
Published: March 2020

3630 Background: Randomised clinical trials have established an important role for oxaliplatin (O) and irinotecan (I) in the management of advanced colorectal cancer (CRC). However, patients (pts) enrolled in clinical studies represent a restricted population and little is known about the use of O and I in the general population and the subsequent outcomes outside clinical studies. We used the Australian Health Insurance Commission (HIC) database to describe prescribing patterns of O and I and their impact on survival in all patients with 5-FU refractory CRC in Australia in 2002 and 2003. Methods: The Australian HIC database was searched to identify all patients with 5-FU refractory CRC who received initial treatment with either O or I in 2002 and 2003. Survival of patients was determined based on subsequent receipt of any other prescriptions for other medication identified in the HIC database. Results: 2999 patients received initial treatment with O or I in Australia in 2002 and 2003. 62% of pts were male and 23% and 2% were aged ≥70 years and ≥80 years respectively. There was a marked increase in initial treatment with O rather than I; 48% of pts received O first in 2002 versus 66% in 2003 (p<0.001). Overall 40–45% of pts received both O and I, however younger pts were more likely to receive both drugs (p<0.001). After 5-FU failure and treatment with O or I, estimated 6-month and 12-month survival was 0.67 (95% CI 0.66–0.69) and 0.42 (95% CI 0.40–0.44) respectively. Six and twelve month survival was superior for pts who received both O and I, however the sequence of O and I had no impact on survival. Survival of older pts (≥70 years) was inferior to younger pts no matter whether O or I was used as initial treatment. Conclusions: Analysis of the Australian HIC database provides a valuable means of assessing patterns of use and outcomes of new therapies. This type of analysis could also be used to evaluate other new agents. [Table: see text]
A multicentre analysis of the long-term outcomes of patients with localized rectal cancer treated with chemotherapy and/or radiotherapy alone due to medical inoperability or patient refusal
Authors: Lim L. , Chao M. , Shapiro J. , Millar J. , Kipp D. , Rezo A. , Fong A. , Jones I. , McLaughlin S. , Gibbs P. 
Published: March 2020

3633 Background: The outcome for patients with localized rectal cancer treated with chemoradiotherapy (CMT) or radiotherapy alone (RT) and no planned subsequent surgery is unknown. Insights can be provided by study of patients that do not undergo surgery due to excessive operative risk (medically inoperable) as a result of advanced age and/or co-morbidities, or patient refusal. Methods: A retrospective analysis at 6 Australian centers. Patients with recurrent rectal cancer, metastatic disease or primary tumors that were considered unresectable were excluded from the study. Results: We identified 48 patients treated between August 1998 and June 2005 meeting our criteria. There were 13 females and 35 males with a median age of 76 years (range 49 - 94). 24 patients (50%) were deemed medically inoperable and 24 patients refused surgery (the most common reasons were the desire to avoid a stoma or fear of surgery). Treatment was with standard long course radiation plus 5-FU (either bolus or continuous infusion) in 36 patients (75%) and 12 (25%) received RT alone. A complete clinical response was documented in 23 patients (48%) and a partial clinical response was documented in 14 patients (30%). At a median follow-up of 49 months, 18 patients (37.5%) have documented disease progression including 10 of 24 in the medically inoperable group and 8 of 24 in the refused surgery group. The median progression-free survival for all patients was 30+ months. 7 had local progression only, 7 had distant progression only and 4 patients had both local and distant progression. Of the 23 deceased patients, 16 (70%) died from progressive disease and 7 (30%) from non-cancer causes, including 4 from the refused surgery group. The median survival for all patients was 35 + months. Conclusions: In patients who are not suitable candidates for surgical resection due to advanced age and/or comorbidity CRT or RT alone is a safe alternative that results in significant progression-free and overall survival times, with many patients succumbing to co-morbidities rather than progressive disease. Many of these patients refusing surgery will have long periods of disease control after treatment with CRT or RT. No significant financial relationships to disclose.
In vivo platform for translational drug development and biomarker discovery in pancreatic cancer
Authors: Hidalgo M. , Rubio-Viqueira B. , Weekes C. , Song D. , Shah P. , Messersmith W. , Messersmith W. , Altiok S. , Kulesza P. , Maitra A. , Jimeno A. 
Published: March 2020

4000 While there are many new agents entering clinical development, there is very little data to prioritize which agents should be explored in pancreas cancer. Furthermore, often there is no information on biomarkers that may predict the activity of these drugs in pancreas cancer. In this project, we have generated a cohort of 30 pancreatic cancer xenografts by implanting in nude mice tumor materials from surgical specimens. Molecular studies show that a) these tumors maintain the genetic features of the originator cancer such as KRAS, p53 and DPC4 gene status; b) tumors represent the heterogeneity of pancreatic cancer well (there is not selection of any genotype in the xenograft ) and c) features do not changed over time. We have used this platform to explore the activity of a battery with a total of 10 new anticancer agents including inhibitors of MAPK, EGFR, mTOR, src kinase, Ras oncogene, mitosis regulators, angiogenesis, heat shock protein and hedgehog pathway inhibitors using a methodology similar to a two stage phase II clinical trial. All agents are tested against 10 xenografts. Those inactive are not explored anymore. Active agents are tested against the full set of tumors. Thus far we have shown that inhibitors of mTOR and MAPK have substantial activity in this model while Ras interacting agents and EGFR targeted drugs have no single agent activity. For active agents, we have characterized the tumors for potential strategies and biormarkers that may predict activity using both a target-focus approach as well as general profiling approach. Signaling inhibitors are more active in tumors with evidence of activation of the targeted pathway. In addition, ex vivo assays indicate that the ability to inhibit the targeted pathway is associated with agent activity. This information may help to prioritize agents for clinical development in pancreatic cancer. [Table: see text]
RTOG 9704 a phase III study of adjuvant pre and post chemoradiation (CRT) 5-FU vs. gemcitabine (G) for resected pancreatic adenocarcinoma
Authors: Regine W. F. , Winter K. W. , Abrams R. , Safran H. , Hoffman J. P. , Konski A. , Benson A. B. , MacDonald J. S. , Willett C. G. , Rich T. A. 
Published: March 2020

4007 Background: RTOG 9704 was designed to determine if the addition of G to postoperative adjuvant 5-FU CRT improved survival for patients(pts) with resected pancreatic adenocarcinoma. Methods: In this Intergroup trial involving RTOG, ECOG and SWOG, pts post gross total resection of pancreatic adenocarcinoma (path stage T1 - 4, N0 - 1, M0) were randomized to receive pre and post CRT 5-FU vs pre and post CRT G. 5-FU = continuous (CI) at 250 mg/m2/day. G = 1000 mg/m2 IV weekly. Both were given over 3 weeks pre and 12 weeks post - CRT. CRT = 50.4 Gy 1.8 Gy/fx/day with CI 5-FU, 250 mg/m2/day during RT for all pts. Pts were stratified by nodal status (uninvolved vs involved), primary tumor diameter ( < 3 cm vs ≥ 3 cm) and surgical margins (negative vs positive vs unknown). Survival was the primary endpoint with an original targeted accrual of 330 pts. Rapid enrollment allowed study amendment for increased targeted accrual to add survival among pts with lesions of the pancreatic head as a primary, prospective endpoint. Results: From 7/98 - 7/02, 538 pts were entered; 442 were eligible and analyzable. Major reasons for patient ineligibility were serum not sent for CA-19–9 analysis (n=22) and treatment starting > 8 weeks post surgery (n=19). Treatment arms were well balanced except for T-stage (T3/4 > for G, p=0.013). Pts with pancreatic head tumors(n=380) experienced significantly improved survival, with median and 3-year survival of 18.8 months and 31% respectively for the G arm vs. 16.7 months and 21% for the 5-FU arm (p=0.047; HR=0.79, CI=0.63–0.99). When analysis was inclusive of pts with body/tail tumors(n=442) no significant difference in survival was found (p=0.20). No significant difference in non-hematologic grade ≥ 3 toxicity was seen. The grade 4 hematologic toxicity rate was 14% in the G arm and 2% in the 5-FU arm (p<0.0001) without difference in febrile neutropenia/infection. The ability to complete chemotherapy (86%, 5-FU vs. 90%, G) and RT (85%, 5-FU vs. 88%, G) as per study was similar. Conclusions: The addition of G to postoperative adjuvant 5-FU CRT significantly improves survival in pts with pancreatic head adenocarcinoma. No significant financial relationships to disclose.
Does endoscopy accurately predict response to chemoradiation in patients undergoing esophagectomy?
Authors: Sarkaria I. S. , Rizk N. , Bains M. , Flores R. , Park B. , Ison D. H. , Minsky B. D. , Rusch V. W. 
Published: March 2020

4024 Background: Endoscopic biopsy after chemoradiation therapy (CRT) for esophageal cancer has been used to determine response to treatment. To test the validity of this methodology, we conducted a study to determine if endoscopic biopsy can accurately establish evidence of local pathologic complete response (pCR), defined as no residual local disease in the esophagus, in patients undergoing esophagectomy after CRT. Methods: We retrospectively queried a prospectively maintained database for patients seen at Memorial Sloan-Kettering Cancer Center from 1996 to the present who underwent, 1) CRT for esophageal cancer with the intent to proceed to esophagectomy post-treatment, and 2) post-CRT endoscopic biopsy. Data points included the pathology of the post-CRT endoscopy and resected surgical specimens, tumor histology, mean time from end of CRT to endoscopic biopsy, and mean time from endoscopic biopsy to surgery. Correlations were analyzed by the chi-square test and one way analysis of variance. Results: One-hundred thirty seven patients meeting our search criteria were identified. Ninety-percent of patients received cisplatin based chemotherapy and 5040 cGy of radiation. One-hundred four patients had a negative pathology on endoscopic biopsy. A negative pathology at endoscopic biopsy was a poor predictor of pCR (Positive Predictive Value = 37.5%), with 65% of these patients having residual local disease at esophagectomy. This result was not influenced by mean time from completion of CRT to endoscopy (p=0.5), or by mean time from endoscopy to surgery (p=0.47). A positive pathology at endoscopic biopsy was highly predictive of residual disease (p<0.001). When analyzed by histology, a negative endoscopic biopsy better predicted response for squamous cell carcinomas versus adenocarcinomas (p<0.001). Conclusions: Although improved for squamous cell cancers versus adenocarcinomas, a disease free endoscopic biopsy does not appear to be a useful predictor of a complete pathologic response after CRT. Neither the time to endoscopy after CRT, nor the time to surgery after endoscopy, influence this finding. No significant financial relationships to disclose.
Phase III preliminary results of preoperative fluorouracil (F) and cisplatin (P) versus surgery alone in adenocarcinoma of stomach and lower esophagus (ASLE): FNLCC 94012-FFCD 9703 trial
Authors: Ychou M. , Pignon J. P. , Lasser P. , Conroy T. , Bouché O. , Boige V. , Segol P. , Bedenne L. , Saint-Aubert B. , Rougier P. 
Published: March 2020

4026 Background: The combination of 5FU in continuous infusion and cisplatin (FP) is one of the more active regimen in advanced ASLE. The trial was designed to evaluate the impact on survival of 2–3 cycles of preoperative FP in resectable ASLE. Methods: Patients (pts) with resectable adenocarcima of the stomach (S) without cardia involvement, cardia (C) or lower esophagus (LE), age ≤ 75 yrs, WHO performance status (PS) < 2 were eligible. Pts were centrally randomized between surgery alone (arm 1) and preoperative FP (arm 2). Chemotherapy (CT) included 2–3, cycles of P (100 mg/m2) and F (800 mg/m2 d1-d5 continuous infusion) every 28 days. Post-operative FP was recommended in arm 2 in case of response to FP preoperative or stable disease with pN+. The main endpoint was overall survival. Sample size was 250 (20 % vs 35 % 5-year rates, two-sided logrank test, α = 5 %, β = 20 %). Results: Between 1995 and 2003, 224 pts (arm 1 = 111 pts, arm 2 = 113 pts) were randomized from 28 centers with early stopping because of low accrual. Initial pts characteristics were equally balanced for age (61 yrs), gender (83 % male), PS (75 % WHO 0), tumor site (S = 25 %,C = 64 %, LE = 11 %). In arm 2, FP was given before surgery in 109 pts (98 pts > 2 cycles) and after surgery in 54 pts. Preoperative FP toxicity : 41 pts with at least one grade 3–4 toxicity (polynuclear, 22 pts, vomiting 10 pts), 9 treatment interruption, 1 toxic death. The number of patients with no surgery / no tumor resection / macroscopic incomplete resection (R2)/ microscopic incomplete resection (R1) by arm were 1/10/12/6 in arm 1 and 4/7/2/4 in arm 2. The number of postoperative deaths were 5 in each arm. Complete resection (R0) rate were 73 % in arm 1 versus 84 % in arm 2 (p=0.04). Among eligible RO, R1 patients (85 & 98 pts in arm 1 & 2): the numbers of pts with T0–2/N0/M+ were 27/17/6 and 41/32/1 en arm 1 & 2, the corresponding p-value were 0.16, 0.05 and 0.05 respectively; 3 pts with complete response in arm 2. For DFS, 160 events are observed so far with a median follow-up of 5 years. Conclusions: Preoperative chemotherapy was well tolerated and led to an increase in R0 resection rate, and a decrease in N+/M+ tumors. Disease-free survival will be presented at the meeting. No significant financial relationships to disclose.
A phase II study of gemcitabine (GEM) given at fixed-dose rate (FDR) infusion, low-dose cisplatin (CDDP), and bevacizumab in metastatic pancreatic cancer (PanCa)
Authors: Ko A. H. , Dito E. , Schillinger B. , Hajnal R. , Venook A. P. , Bergsland E. K. , Allen J. , Rajpal S. , Tempero M. A. 
Published: March 2020

4041 Background: The objectives of this study are to determine safety and efficacy in pts with metastatic PanCa treated with a novel combination consisting of FDR GEM, low-dose CDDP, and BEV. We present here interim results of the first 35 pts. Methods: Chemotherapy-naive pts with histologically confirmed PanCa and documented extrapancreatic metastases received the following: GEM 1000 mg/m2 at FDR infusion (10 mg/m2/min), CDDP 20 mg/m2, and BEV 10 mg/kg, all administered on dd 1 and 15 of a 28-dd cycle. Pts were monitored by CT scans every 2 cycles and monthly serum CA19–9 measurements. Results: 35 pts (15M,20F; median age 60 y.o. [range 39–85]; ECOG PS 0–1) have been enrolled betw 6/2004 and 1/2006 (med f/u, 288 dd; range, 50–542). 18 pts remain alive, with 7 still undergoing study rx. Pts received a median of 4 cycles of rx (range, 0.5–12). Reasons for study discontinuation: 15 pts had progressive dz (med # of cycles, 6; range, 0.5–10); 2 pts completed max # of allowable rx cycles (twelve); 2 pts came off rx 2 o to cumulative asthenia after plateau in response with 8 and 10 cycles of rx. Other major events inc. 2 bowel perforations, one associated with placement of a duodenal stent; 3 major GI bleeds; 1 malignant HTN; and 1 stroke-like sx. 3 pts d/c’ed rx 2o to prolonged rx delays (two persistent bowel obstruction, one grade 3 renal/liver function abnls). Addn grade 3/4 toxicities inc. 7 pts with LFT abnls (20%), 4 with HTN (11.4%), and 3 with thromboembolic events (8.6%). Hematologic toxicities were rare (grade 3/4 neutropenia 5.7%, plts 2.9%). 7 pts (20%) required dose reduction of GEM and 2 required d/c of CDDP. No rx-associated deaths were observed. 7 of 33 evaluable pts (21.2%) have had an unconfirmed response (1 CR, 6 PR) and 15 pts (45.5%) have had stable dz for > 2 cycles, inc. 2 with minor response, for an overall dz control rate of 66.7%. 13 of 21 pts (61.9%) with elev. baseline CA19–9 levels (≥2X ULN) have had ≥50% biomarker decline during rx. Updated efficacy data will be presented at the meeting. Conclusions: The toxicity profile observed in this trial is similar to that previously reported with other BEV-containing regimens. Rates of disease control and CA 19–9 response are encouraging, suggesting this combination is deserving of further study. [Table: see text]