bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colorectal cancer patient utilization of an internet based clinical trials matching system
Authors: Bui C. , Hampshire M. , Vachani C. , Metz J. 
Published: March 2020

3624 Background: Colorectal cancer patients are increasingly looking to the Internet for information on clinical trials; however, services offering clinical trials recruitment have not been well defined. This study describes one of the first web-based cancer clinical trials matching resources and the demographics of the colorectal cancer patient user base. Methods: Oncolink ( http://www.oncolink.org ) is the web-based educational resource at the University of Pennsylvania and serves between 1.5–2 million pages per month to over 385,000 unique IP addresses. Oncolink, in conjunction with EmergingMed (New York, NY), launched one of the first clinical trials matching resources on the Internet. Patients input demographic and tumor-specific information via secure Internet-only registration or via the Internet with assistance from a call center, to match to trials. As of 12/2005, there were 112 total colorectal trials in the database. Results: Between 12/2000 and 9/2005 a total of 41,970 individual profiles were created, with 3289 (7.8%) by colorectal cancer patients. Other GI tumors accounted for 15% of profiles. Of the 3289 patients, 54% were male and 46% were female, and the median age was 55 (range 19–96). Most patients reported their disease as having spread to another organ (62%) or to lymph nodes (15.4%). Most patients were previously treated with surgery (81%), radiation (26%), chemotherapy (74%), and/or biological therapies (21%) (bevacizumab, cetuximab, interferon or interleukin). Patients who used the call center with the Internet were more likely to apply for enrollment in a clinical trial after review of the matches (77% vs. 10%, p<0.001). The median number of trial matches in the system was 7 per patient. Of the 3289 colorectal patients, 681 patients (21%) went on to apply for enrollment to trials based on their matches. Conclusions: This report demonstrates that a significant percentage of colorectal cancer patients are willing to use the Internet to match to clinical trials. Contact with a call center greatly increases the likelihood of application to trials. Internet based clinical trials resources should maintain options for personal communication to increase the likelihood of enrollment to clinical trials. No significant financial relationships to disclose.
Intergroup RTOG 98–11: A phase III randomized study of 5-fluorouracil (5-FU), mitomycin, and radiotherapy versus 5-fluorouracil, cisplatin and radiotherapy in carcinoma of the anal canal
Authors: Ajani J. A. , Winter K. A. , Gunderson L. L. , Pedersen J. , Benson A. B. , Thomas C. , Mayer R. J. , Haddock M. G. , Willett C. , Willett C. , Rich T. A. 
Published: March 2020

4009 Background: An ∼65% 5-year disease-free-survival (DFS) rate from 5-FU/mitomycin/radiation for anal carcinoma needs improvement. Methods: A phase III randomized trial compared 5-FU (1,000mg/m2 days 1–4 and 29–32) plus mitomycin (10mg/m2 days 1 and 29) and radiation (45 to 59 Gy) (Arm A) to 5-FU (1,000mg/m2 days 1–4, 29–32, 57–60 and 85–88) plus cisplatin (75mg/m2 on days 1, 29, 57 and 85) and radiation (45 to 59 Gy; start day=57) (Arm B) in anal carcinoma patients. Stratification included gender, clinical N status and tumor diameter. Primary endpoint was DFS. Statistical power was 80% with two-sided test to detect 10% DFS increase for Arm B. Results: Of 682 patients accrued, 598 were analyzable. Most unanalyzed patients’ data are early. Patient characteristics were balanced. Median age was 55 years, women predominated (69%), 27.5% had >5 cm tumor diameter and 26% had clinically N+ cancer. Preliminary 5-year estimated DFS was 56% for Arm A and 48% for Arm B (p=0.28) and 5-year estimated overall survival was 69% for both arms (p=0.24). Men(p=0.04), clinically N+ cancer (p<0.0001) and tumor diameter >5 cm (p=0.005) independently prognosticated DFS in a multivariate analysis. 5-year colostomy rate was 10% for Arm A and 20% for arm B(p=0.12). Grade 3/4 toxicity rates: non-hematologic=76% for Arm A and 75% for Arm B but hematologic=67% for Arm A and 47% for Arm B(p=0.0004). Conclusions: In Intergroup-98–11, induction 5-FU/cisplatin followed by 5-FU/cisplatin/radiation failed to improve DFS compared to the standard treatment, 5-FU/mitomycin/radiation. Supported by RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115. No significant financial relationships to disclose.
Final results of a multicenter phase II study of irinotecan (CPT), cisplatin (CIS), and bevacizumab (BEV) in patients with metastatic gastric or gastroesophageal (GEJ) adenocarcinoma (NCI #6447)
Authors: Shah M. A. , Ramanathan R. K. , Ilson D. , Randazzo J. , Schwartz G. K. , Tse A. , D’Adamo D. , Levner A. , Capanu M. , Kelsen D. P. 
Published: March 2020

4020 Background: BEV improves survival in several solid tumors when combined with chemotherapy. CPT/CIS is active in gastric and GEJ cancers with a median time to progression(TTP) of 4.2 months, response rate(RR) of 30%, and median survival of ∼7 months (Pozzo Ann Onc 2004). Anti-angiogenic therapy for upper GI cancers is of concern due to a potential increased risk of perforation or GI bleed. We evaluated the efficacy and safety of the combination of CPT, CIS, and BEV in the treatment of gastric and GEJ cancers. Methods: 47 patients with previously untreated metastatic gastric or GEJ adenocarcinomas were treated with BEV 15mg/kg day 1, CPT 65mg/m2 and CIS 30mg/m2 days 1 and 8, every 21 days. The primary endpoint was TTP, with 90% power to demonstrate a 50% improvement in TTP (eg. from 5 to 7.5 months) over historical control. Safety, response, and survival were secondary endpoints. Results: Patient characteristics: median age 59 (range 25–75), KPS 90% (70%-100%), Male 34, Gastric/GEJ 27:20. With a median follow up of 9.0 months, median TTP is 9.9 months (95%CI: 6.5–11.8 months). In 33 patients with measurable disease, the RR (partial + complete) is 66.7% (95%CI: 51–83%). Median survival is 12.6 months (95%CI: 10.1–17.1 months). We observed no change in expected CPT/CIS related toxicity: eg. grade 3/4 neutropenia (29%), nausea/vomiting (10%), and diarrhea (13%). Possible BEV related toxicity includes 2 gastric perforations, 1 grade 3 peri-rectal fistula, 2 cardiac events(1 ischemia, 1 reduced ejection fraction), and 10 patients with grade 3/4 hypertension. Although the primary tumor was unresected in 35 patients, we observed only 1 patient with an upper GI bleed. Grade 3/4 thromboembolic events occurred in 25%. Conclusions: The combination of CPT/CIS/BEV is active in gastric and GEJ cancers. The toxicity profile is acceptable. The primary endpoint of improving TTP was exceeded by 100% with median TTP 9.9 months. Despite the majority of patients having their primary tumor unresected, GI bleeding was not significant. The thromboembolic and perforation rates with CPT/CIS are similar with or without BEV (Shah et al JCO 2005). Further development of BEV in gastric and GEJ cancers is clearly warranted. [Table: see text]
Interim results of preoperative gemcitabine (gem) plus cisplatin followed by rapid fractionation chemoradiation for resectable pancreatic adenocarcinoma
Authors: Varadhachary G. R. , Evans D. B. , Crane C. , Xiong H. Q. , Lee J. E. , Pisters P. W. , Abdalla E. K. , Lee J. H. , Tamm E. P. , Wolff R. A. 
Published: March 2020

4037 Background: Over 80% of pts who undergo potentially curative pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma develop local or distant recurrence. Chemotherapy and external-beam radiation therapy (EBRT) prior to surgery maximizes the number of pts who receive multimodality therapy and undergo a complete (R0) resection. Methods: Pts with biopsy proven, stage I/II adenocarcinoma of the pancreatic head or uncinate process received systemic therapy with 4 infusions of gem (750 mg/m2) + cisplatin (30 mg/m2) every 2 wks followed by 30 Gy of EBRT (3 Gy/Fx, M-F over 2 wks) and 4 weekly doses of gem (400 mg/m2). Pts underwent complete restaging 4–6 wks after the last dose of gem. Those without disease progression and with acceptable PS underwent surgery. Results: This study has currently enrolled 87 pts over 4 years. Median age is 65 yrs (38–80), most pts (96%) had ECOG-PS (0–1) at study entry. Median CA19–9 is 170. Six pts were excluded from analysis and 4 are currently on treatment. Of the 77 pts who finished chemoradiation, 72 completed restaging (3 await restaging, 2 drop outs). Of these 72 pts, 10 had disease progression, 1 had a decline in PS, and 61 (79 %) went to surgery. 49 of 61 pts (64 %) underwent a successful PD and metastatic or locally advanced disease was found in 12 (15 %). 44 (90 %) of 49 pts underwent R0 resection. Pathologic PR rate (>50 % tumor kill) was 61 %. The predominant toxicity prompting hospitalization during preoperative therapy was biliary stent occlusion (44 %). Gastrointestinal toxicity ≤ grade 3 was common but controllable. Grade 3 and 4 neutropenia was seen in 19 (25 %) and 3 pts (4 %) respectively. Grade 3–4 thrombocytopenia was rare. Median survival for resected pts was ∼ 21 months. Conclusions: This study, builds on our previous gem-based preop chemoradiation program ( ASCO 2002, Abs # 516) producing good local treatment effect and a high R0 resection rate. However, interim analysis suggests that the addition of systemic chemotherapy delivered prior to preoperative chemoradiation does not appear to improve survival. Optimal treatment sequencing of chemoradiation, systemic therapy and surgery needs further refinement. Supported in part by Eli Lilly and Co. [Table: see text]
A phase II study of temozolomide and bevacizumab in patients with advanced neuroendocrine tumors
Authors: Kulke M. H. , Stuart K. , Earle C. C. , Bhargava P. , Clark J. W. , Enzinger P. C. , Meyerhardt J. , Attawia M. , Lawrence C. , Fuchs C. S. 
Published: March 2020

4044 Background: Inhibitors of the VEGF pathway have been shown to have activity in neuroendocrine tumors (NETs). Temozolomide (TMZ), an oral analog of dacarbazine is also active in this setting. We performed a prospective, phase II study to assess the safety and efficacy of TMZ, administered in combination with bevacizuamb, in patients (pts) with advanced NETs. Methods: Pts received TMZ, 150 mg/m2/day po for 7 days every other week, and bevacizumab, 5 mg/kg IV every other week. Due to anticipated lymphopenia, pts received prophylaxis with trimethoprim/sulfamethoxazole (1 DS tablet q MWF) and acyclovir (400 mg po TID). Pts were followed for toxicity, response, and survival. Results: Enrolled patients (n=34) had the following characteristics: M:F = 19:15; median age 61 (range 37–75); ECOG PS 0/1/2 = 12/20/2; carcinoid/pancreatic NET = 16/18. Prior treatments included chemoembolization (n=7) chemotherapy (n=12); and octreotide (n=17); pts on octreotide remained on octreotide at stable doses for the duration of the study. Pts had either well-differentiated tumors (n=27) or moderately/poorly-differentiated NETs (n=7); pts with small cell carcinoma were not eligible for the study. Pts have received treatment for a median of 22 weeks. Grade 3–4 toxicities included: lymphopenia (n=21, 62%), leukopenia (n=2, 6%), thrombocytopenia (n=7, 21%), neutropenia (n=2, 6%), hyponatremia (n=1, 3%), vomiting (n=3, 9%), nausea (n=2, 6%), dehydration (n=1, 3%), fatigue (n=2, 6%), constipation (n=1, 3%), and hypertension (n=1, 3%). 20 pts had elevated CGA levels (>36.4 ng/ml) at baseline; 0/9 (0%) carcinoid and 4/11 (36%) pancreatic NET experienced CGA decreases of >50% from baseline on two consecutive assessments. 29 pts are currently evaluable for radiologic response ( Table ). Conclusions: The combination of TMZ and bevacizumab can be safely administered and shows promising activity in pts with advanced pancreatic NETs. Additional studies with this combination are warranted. [Table: see text] [Table: see text]
Impact of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) on outcomes of postoperative patients with gastric cancer
Authors: Matsubara J. , Yamada Y. , Shimoda T. , Eguchi T. , Hamaguchi T. , Shimada Y. , Okayama Y. , Sugimoto Y. , Oka T. , Shirao K. 
Published: March 2020

4053 Background: The clinical significance of biomarkers in resected gastric cancer (GC) remains unclear. Detailed exploratory evaluations are required to better understand the clinical implications of biomarkers. Methods: The study group comprised 87 patients who received chemotherapy for recurrent or residual GC after resection of their primary tumors at National Cancer Center Hospital. The patients received 1 to 5 regimens of chemotherapy (median: 2). Total RNA was isolated from laser-captured tumor cells of the resected cancer specimens, and the gene expressions of TS, DPD, DHFR, ERCC1, MRP1, and 22 other biomarkers related to anticancer drug sensitivity were quantitatively evaluated by a real-time RT-PCR assay. Results: The gene expressions of TS, DHFR, MTHFD, RRM1, and ERCC1 were significantly related to survival ( Table ). Multivariate analysis revealed that high DHFR (p < 0.001, RR = 1.70 [95% CI, 1.28–2.29]) and high TS (p = 0.004, RR = 1.53 [1.15–2.06]) gene expressions were independently related to poor survival. As compared with intestinal type tumors, diffuse type tumors had higher DPD (p < 0.001) and lower Her2 (p < 0.001) gene expressions. As for first line chemotherapy, an analysis of 29 patients treated with S-1, an oral DPD inhibitory fluoropyrimidine, showed that patients with diffuse type tumors tended to respond better (p = 0.13) than those with intestinal type tumors. An analysis of 29 patients treated with cisplatin plus irinotecan as first line therapy showed that low ERCC1 gene expression was slightly but not significantly related to a better response (p = 0.087). Analyses of patients treated with other first line regimens revealed no significant correlation of any biomarker with response. Conclusions: Increased gene expressions of DHFR and TS in surgical specimens are significantly predictors of poor outcomes in postoperative patients with GC. [Table: see text] [Table: see text]
Neoadjuvant combined modality therapy with weekly docetaxel (D) and cisplatin (P), 5-fluorouracil (5FU) continuous infusion (c.i.) and concurrent radiotherapy (RT) provides high pathological response rate in esophageal cancers (EC): A phase II study
Authors: Pasini F. , De Manzoni G. , Grandinetti A. , Pedrazzani C. , Griso C. , Sava T. , Minicozzi A. , Durante E. , Bonetti A. , Maluta S. , Cetto G. 
Published: March 2020

4057 Background: The achievement of pathological complete response (pCR) is deemed essential to improve survival in EC. In a phase I study (Pasini et al, Ann Oncol 16; 1123, 2005) we demonstrated the feasibility of a novel protocol of neoadjuvant chemoradiation based on weekly D and P, c.i. of 5-FU and concurrent RT. Based on the promising results of the study, we then performed a phase II study aimed at evaluating pathological response rate and toxicity. Methods: 50 pts with stage II-III EC (26 adenocarcinomas) were enrolled (Simon test: P0=0.2, P1=0.6, alpha 0.05 beta 0.1; 54 pts); median age was 59 yrs (42–73). Treatment consisted of D 35 mg/m2 and P 25 mg/m2 d 1,8,15,29,36,43,50,57 plus 5-FU 180 mg/m2 c.i. d 1–21 and 150 mg/m2 c.i. d 29–64; concurrent RT (50 Gy) started on d 29. Surgery was performed 6 to 8 weeks after completion of RT. Results: 49/50 pts (98%) completed the planned chemo-radiation. Median follow-up is 22 mo (7–39). During chemo-radiation, grade 3–4 hematological toxicity occurred in 9 pts (18%)(4 pts grade 4) requiring GCSF support and postponement of CT of one week in 4. One HCV+ pt discontinued CT and continued with RT alone. In the last 2 weeks 12 pts (24%) experienced grade 3 non-hematological toxicities (asthenia, esophagitis, nausea) without need of treatment discontinuation. There was a fatal pulmonary embolism in a non neutropenic pt after completion of the therapy. 45 pts underwent surgery, while 5 did not (2 refusal). Pathological findings: pT0 pN0 (pCR): 25 (50%); pTrm pN0: 6 (12%)[residual microfoci]; pT2 pN0: 1 (2%); pT0–4 pN+: 9 (18% ); R+:4 ( 8%). Response rate was similar between adeno and squamous cell carcinoma. With a median follow-up of 24 mo, only 2 of 25 pCRs (8%) died (1 relapse, 1 postoperative death). Conclusions: i) a substantial pCR rate (50%) was achieved; ii) the weekly schedule allowed concomitant chemo-radiation at cumulative doses otherwise impossible with standard three weeks protocols; iii) because of the acceptable, but not negligible toxicity, this protocol requires to be managed in dedicated institutions. No significant financial relationships to disclose.
Inter-criteria reproducibility of RECIST, WHO, Japanese response criteria for gastric cancer or esophageal cancer: From the response dataset of Japan Clinical Oncology Group (JCOG) phase III trials
Authors: Kurokawa Y. , Yoshimura K. , Yamamoto S. , Sato A. , Saito I. , Fukuda H. 
Published: March 2020

4065 Background: For assessments of tumor response in upper gastrointestinal cancers, Japanese criteria (JPN), which needs X-ray or endoscopic findings for primary lesion, has been generally used in Japan instead of international RECIST or WHO criteria. To compare the inter-criteria reproducibility of these radiological assessments, we analyzed the datasets of tumor responses from two phase III trials. Methods: A total of 115 gastric cancer patients in two treatment arms of JCOG9205, 5-FU and 5-FU plus cisplatin, and 103 esophageal cancer patients in a neoadjuvant 5-FU plus cisplatin arm of JCOG9907 were eligible for this analysis. Overall response rates (ORR) were calculated according to each of three criteria. The tumor responses, furthermore, were divided into four categories (CR, PR, SD, PD), following estimation of kappa statistics between two criteria as agreement measure. Results: As shown in the Table , ORR according to RECIST and WHO were very similar in both cancers. JPN tended to estimate higher ORR comparing to RECIST or WHO, particularly in esophageal cancer. In gastric cancer, kappa for concordance to RECIST were 0.92 for WHO and 0.86 for JPN. While in esophageal cancer, kappa were 0.72 for WHO and 0.40 for JPN. Conclusions: In these trials for gastric cancer and esophageal cancer, there was fairly consistent reproducibility between unidimensional RECIST and bidimensional WHO criteria. JPN criteria, depending on assessment of primary lesion, may give higher ORR particularly in esophageal cancer, and cautious interpretation may be necessary when evaluating ORR from Japanese trials using JPN criteria (Table). Overall response rates of respective treatment arms calculated according to RECIST, WHO and JPN criteria. [Table: see text] No significant financial relationships to disclose.
Preliminary results of a randomized phase III trial comparing streptozotocin plus fluorouracil versus interferon for metastatic carcinoid tumors (FNCLCC - FFCD 9710)
Authors: Seitz J. F. , Dahan L. , Rougier P. , Raoul J. L. , Gamelin E. , Etienne P. L. , Cadiot G. , Smith D. , Ricard F. , Bonnetain F. 
Published: March 2020

4090 Background: Streptozotocin and 5 FU in combination is widely used for the treatment of advanced carcinoids tumors. Interferon is an effective treatment of the malignant carcinoids tumors. This randomized multicenter phase III trial compared those treatments in patients with metastatic carcinoïd tumors. Methods: Patients with metastatic carcinoid tumors, clinical or biological progression, WHO status 0–2 (PS) and age ≤ 75 years were randomized 1:1 between interferon alpha 2a recombinant (3MU × 3 per weeks) and 5FU (400 mg/m2/day day1 to day5) plus streptozotocin (500 mg/m2/day day1 to day5) every 6 weeks. Stratification was done according to center, PS and anterior treatment. Primary endpoint was progression free-survival (PFS). It was required to include 120 pts and to observe 38 progressions to detect an expected improvement in 1year PFS from 55% to 80% (bilateral α = 5 % and β = 20 %). Secondary endpoints included 1-year and 2-year overall survival (OS). Intent to treat analyses were performed. Results: From February 1998 to june 2004, in 23 centers, 63 patients has been included, 32 in 5FU-STZ arm and 32 in interferon arm: median age (59 years [37–77] vs 63 [39–75]), male/female ratio (1.2 vs 1), PS 0–1 (91% vs 97%), anterior chemotherapy (13% vs 16%), surgery (69% vs 59%), radiotherapy (6% vs 0%) are well balanced between arms. The median number of 5FU-STZ and Interferon cycles was respectively 5 and 4. After a median follow-up of 26 months, the median OS for interferon was 44.3 months versus 37.7 months for chemotherapy: HR = 0.90 [0.43–1.90]; 1- year and 2-year survival rates were 89% and 72% for interferon versus 84% and 73% for chemotherapy. Conclusions: Interferon alpha 2a does not prolong OS in advanced metastatic carcinoid tumors as compared to the combination of 5FU-streptozotocin. After checking clinical and biological progression, PFS analyses will be presented at the meeting. No significant financial relationships to disclose.
Neuroendocrine tumors (NET) of the gastrointestinal tract: A decade of experience at the Princess Margaret Hospital
Authors: Rothenstein J. , Cleary S. , Pond G. R. , Dale D. , Gallinger S. , Siu L. L. 
Published: March 2020

4093 Background: NET are uncommon malignancies with variable natural history and often indolent biological behavior. Over the past decade novel treatment approaches have been developed. There have been few recent descriptions of large institutional experiences with multi-modality therapy for this disease. Methods: The Princess Margaret Hospital cancer registry identified 207 patients (pts) with NET of the gastrointestinal tract or unknown primary who had their initial visits between 1992 and 2002. A retrospective chart review was performed. Results: The median follow-up duration was 25 months for pts who have died and 54 months for those alive at last follow-up. Demographics of the entire cohort of 207 pts were as follows: M:F = 53%:47%; mean age = 55 years; age-adjusted Charlson score 0 = 71%. Anatomical distribution of the primary location revealed that 33% were from the foregut, 37% from midgut, 13% from hindgut and 17% from unknown origin. Pathological distribution demonstrated that 73% were NET/carcinoids, 21% were islet cell tumors and 6% were small cell carcinomas. One-third of the cohort had biochemically and/or clinically functional tumors, 24% were non-functional, and 43% were not biochemically tested and were clinically non-functional. At presentation, 61% of pts had distant metastases and 39% had locoregional disease. Curative surgery was performed in 38% of the cohort, whereas radiotherapy and chemotherapy of any intent were delivered to 15% and 34% respectively. Octreotide LAR was part of the therapeutic regime in 13% of pts. Two-year survival analysis was evaluated among 114 pts, with the remaining cohort being excluded due to either insufficient follow-up or because pts were seen for second-opinion only. Factors that were significantly related to decreased survival in univariate analyses were the presence of distant metastases and small cell histology. All pts who underwent curative surgery in this subgroup were alive at 2 years, and 88% were alive at 5 years. Conclusions: Pts with NET who are offered curative surgery have a good outcome. Distant metastases are commonly found at presentation and portend a worse prognosis. These patients should be evaluated by a multidisciplinary team regarding new approaches to surgery and other therapies. No significant financial relationships to disclose.