bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study to evaluate the efficacy of capecitabine combined with bevacizumab as first-line treatment in elderly patients with advanced or metastatic colorectal adenocarcinoma
Authors: Feliu J. , Safont M. , Salud A. , Losa F. , García-Girón C. , Bosch C. , Escudero P. , López R. , Madroñal C. , González-Barón M. 
Published: August 2020

4119 Background: Colorectal adenocarcinoma is the most common cancer in subjects over 70 years old. New therapies have been developed but limited data about their activity are available in elderly population. Results obtained with capecitabine have shown an appropriate safety and efficacy profile in these patients. The aim of the present study is to evaluate the overall response rate in that patient's population who presents colorectal adenocarcinoma and are treated with the combination of capecitabine+BVZ. Methods: This is a multicentric, non-controlled, open label, phase II clinical trial. Capecitabine(1250mg/m2 bid, orally)+BVZ(7.5mg/kg, intravenously) treatment was administered in 3-week length cycles until disease progression. Capecitabine dose was reduced to 1000mg/m2 when the creatinine clearance was between 30 and 50ml/min. Results: A total of 59 patients were included (57.6%, male). Mean age was 76±4.1 years. ECOG status was 0–1 in 96.5 % of the patients. Activities of daily living: moderate to severe dependence and functional incapacity in 24.5% and 5.6% of the patients by Lawton and Barthel scales, respectively. Comorbidities: hypertension (61%), venous thrombosis (5.1%), cardiac disease (5.1%) and acute cerebrovascular accident history (3.4%). Metastases were detected in liver (84.7%), lung (45.8%), local/regional (18.6%) and other locations (5.1%). Mean number of cycles of capecitabine+BVZ was 6.8±6.1. Most frequent grade 3–4 toxicities observed were hand-foot-syndrome (18.6%), diarrhea (8.5%), deep venous thrombosis (6.8%), pain (5.1%) and mucositis (3.4%). Four patients died due to toxicity (mucositis, digestive hemorrhage, hematological toxicity and sepsis, respectively). Metastasis resection was performed in 10.2% of the patients. Treatment response was: 33.3% partial response and 59.0% stable disease. Median progression-free survival was 10.8 months. Conclusions: The combination capecitabine+BVZ in elderly patients appears to have a manageable safety profile and achieves promising results in terms of response rates and progression free-survival. No significant financial relationships to disclose.
Use of tumor site as a prognosticator: Population-based analysis of rectosigmoid and rectum cancers
Authors: Raj K. P. , Ziogas A. , Barleben A. R. , Stamos M. J. , Zell J. A. 
Published: August 2020

4123 Background: The study examines the prognostic significance of tumor location exclusively in rectosigmoid and rectal cancers. Although tumor location has traditionally been regarded as a prognostic determinant, data in support of this claim are lacking. We set out to determine this using data from a large population-based California Cancer Registry (CCR). Methods: A retrospective analysis of surgically treated cancer cases involving the rectum and rectosigmoid from 1994–2006 with a follow-up until January 2008 in CCR was conducted. Sub-site tumor location of the cancers involving the rectum was either defined as rectosigmoid or mid/distal rectum. Site-specific survival analyses were conducted by Kaplan-Meier method and hazard ratio calculated using Cox proportional hazard ratios (HR). Results: A total of 33,418 rectal cancer cases were identified, including 12,407 (37.1%) rectosigmoid cancers and 21,011 (62.9%) mid/distal rectum cancers. No significant differences by tumor location were noticed for age, gender, stage, histological type, grade or socioeconomic status. Fewer rectosigmoid cancers received radiation (81.9% vs. 62.3% p=<0.0001)) compared to mid/distal rectum cancers. After adjustment for treatment and relevant clinical factors, an improved rate of CRC-specific survival was noticed in non-metastatic rectosigmoid cancers when compared to cancers involving the mid/distal rectum. A significant decrease in mortality was observed in Stage-I [HR- 0.74(0.63–0.86)], Stage-II [HR-0.76(0.69–0.85)] and Stage-III [HR- 0.90 (0.83–0.98)] rectosigmoid cancers when compared to mid/distal rectum cancers. Number of lymph nodes examined (>12 vs. <12) was an independent prognostic factor for survival in Stage-II patients [HR-0.74 (0.63–0.87)]. Conclusions: Among locoregional cases, rectosigmoid cancers were found to have an improved CRC-specific survival compared to mid/distal rectum cancers, which was independent of other relevant clinical factors. [Table: see text] No significant financial relationships to disclose.
Impact of mucinous histology on prognosis for patients with radically resected stage Dukes B2 and C colon cancer: Preliminary results
Authors: Catalano V. , Loupakis F. , Bisonni R. , Torresi U. , Santini D. , Silva R. R. , Giustini L. , Falcone A. , D’Emidio S. , Rocchi M. , Graziano F. 
Published: August 2020

4126 Background: Previous reports have suggested that mucinous colorectal adenocarcinomas have a poorer prognosis than nonmucinous colorectal adenocarcinomas. This retrospective analysis was conducted to explore whether mucinous carcinoma (MC) is associated with a worse prognosis than nonmucinous carcinoma (NMC) for patients with Dukes B2 and C radically resected colon cancer. Methods: We investigated 1,006 unselected patients who underwent curative surgery for sporadic colon cancer and followed up at six Oncology Department between 1998 and 2006. Univariate and multivariate analyses were performed to determine prognostic factors of survival. Results: MC accounted for 17.9% (n=180) of all colon carcinomas. Patient characteristics were as follows. MC: M/F 104/76; median age, 68 (range, 28–97); pT1/2/3/4, 1/4/153/22; Dukes B2/C 98/82; invasion 26 (14%); ≥12 examined lymph nodes, 115 (64%); adjuvant chemotherapy, 110 (61%). NMC: M/F 445/381; median age, 68 (range, 29–95); pT1/2/3/4, 9/51/715/51; Dukes B2/C 384/442; invasion 199 (24%); ≥12 examined lymph nodes, 499 (60%); adjuvant chemotherapy, 545 (66%). MC were more frequently located in the proximal colon (54.4% versus 34.6% for NMC; p<0.001). No difference between MC and NMC in disease-free survival (hazard ratio, HR 1.01; 95% CI, 0.76–1.36; p=0.92) and overall survival (HR 1.05; 95% CI, 0.74–1.49; p=0.78) was found. After stratification by stage of disease, MC and NMC had no statistically significant difference in 5-year disease-free survival (Dukes B2: 79.1% and 78.1%, respectively, p=0.86; Dukes C: 53.8% and 56.2%, respectively, p=0.58) and overall survival (Dukes B2: 84.2% and 85.5%, respectively, p=0.80; Dukes C: 68.0% and 67.3% p=0.52). Multivariate analysis using the Cox proportional hazards model showed that the clinically significant prognostic factors were stage at diagnosis (p<0.0001), grading (p<0.0001), and number of lymph node examined (p=0.0002) in the specimen. Conclusions: In this preliminary analysis, patients with mucinous histology who underwent surgery with curative intent for stage Dukes B2 and C colon cancer had similar prognosis compared to NMC. No significant financial relationships to disclose.
Prospective randomized study comparing fourth-week surgery versus eighth- week surgery after neoadjuvant concomitant radiotherapy and infusional 5-FU in T3–4/N0+ rectal cancer: Istanbul R-01 Study
Authors: Saglam S. , Bugra D. , Kaytan Saglam E. , Yamaner S. , Asoglu O. , Balik E. , Oral E. N. , Sakar B. , Kizir A. , Kapran Y. , Camlica H. 
Published: August 2020

4131 Background: Prospective randomized study has been designed to compare the efficacy of fourth week surgery (4WS) versus eighth week surgery (8WS) after concomitant neoadjuvant chemoradiotherapy (NeoadjCTRT) on local recurrence and overall survival (OS) in cT3–4/N0+, mid and distal localized (intraperitoneal) rectal cancers. Pathological regression grades (PRG;Dworak) were evaluated after neoadjCTRT. Methods: During Jan 2002- Nov 2007; 170 pts were randomized to the study in Istanbul University Oncology Institute and Medical Faculty. All rectal cancer pts are T3–4/N0+; distal and mid rectum and received 45 Gy conventionally fractionated RT in 25 daily fractions of 1.8 Gy combined with 225 mg/m2/day continous infusion 5-FU. Preoperative staging was performed by endorectal USG and /or MRI and abdominal CT.4cycles FUFA is standard as adjuvant treatment after surgery. Results: 17 pts have been removed (M1, frozen pelvis, refuse surgery, disease progression). Clinical T3N+ was 60.8% before surgery. 76 pts were operated at 4WS and 77 pts at 8WS. Median follow-up was 30 (2–71) months. APR was 31.4%. LAR was 68.6%. Surgical margin positiveness (SMP) and <2mm were detected in 14 pts. R0 resection rate was 90.8%. Median harvested lymph node number were 13. PRG were PRG 0 (1.3%); PRGI in (24.2%); PRGII in (40.5%); PRGIII (17%); PRGIV in (17%). There is no statistical significance between 4WS vs 8WS on pathological regression scores. Local recurrence developed in 8 pts (PRGI:3pts; PRGII:4; PRGrIV:1). There is no statistical difference 4WS v 8WS on local recurrence (5 pts/3). Local recurrence rate was 8.4% in distal rectum (7 pts) and 1.2% in mid rectum (1pts) (p=0.023). SMP and <2mm was statistically significant in local recurrence (p=0.003). 5 years OS were similar in 4WS 75.2% and 8WS 73.9%. Distant metastasis is significant (liver, lung, bone) in distal rectal tumors (p=0,007). SMP or < 2mm is significantly poor in OS (p<0.0001). Conclusions: There is no difference 4WS vs 8WS on local recurrence, OS and PRGs. Important factors for local recurrence and (OS) are having distal rectal tumor and SMP and <2mm. Distal rectal tumors have prone to distant metastases. No significant financial relationships to disclose.
The prognostic value of polymorphisms in the insulin-like growth factor receptor (IGFR) pathway in patients with locally advanced pancreatic cancer (LAPC)
Authors: Shroff R. T. , Javle M. M. , Dong X. , Kumar V. S. , Krishnan S. , Wolff R. A. , Abbruzzese J. L. , Li D. 
Published: August 2020

4500 Background: The IGFR pathway is activated in pancreatic cancer and may result in aggressive disease course. The study of single nucleotide polymorphisms (SNPs) involved in this pathway may provide prognostic information and predict response to IGFR directed agents. We investigated IGFR pathway SNPs in patients with LAPC. Methods: We evaluated 39 SNPs from 7 candidate genes in the IGFR pathway (IGF1R, IGF2R, IGF1, IGF2, IRS1, IRS2, IGFBP3) in 105 LAPC patients. DNA extraction from whole blood was performed using the Qiagen Flexigene DNA and Promega Maxwell 16 kits. Genotyping was performed using the Sequenom method. Overall survival was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype corrected for previously identified prognostic factors, including induction chemotherapy, CA 19–9, albumin, LDH, hemoglobin and Karnofsky performance status (KPS). Results: Median survival time (MST) was 15 months (95% CI 13.3–16.7). Induction chemotherapy, LDH, CA 19–9 level, hemoglobin, and KPS were not significantly associated with survival. Serum albumin and three SNPs of the IGF pathway (IGF1R IVS20–3431A>G, IRS1 G971R, and IGF2 *4352A>G) were significantly associated with prognosis ( Table ). Two of the three genotypes remained as significant predictors for survival in Cox regression analysis when adjusted for clinical factors. A significant combined genotype effect was observed wherein patients with all three deleterious alleles had significantly worse survival than those with only two or one (10 vs. 16.3 vs. 21.3 months, p< 0.0001). Conclusions: These data suggest that SNPs in the IGFR pathway genes may have prognostic value for LAPC patients. This information may identify population subgroups that could benefit from IGFR-targeted agents. [Table: see text] No significant financial relationships to disclose.
A randomized trial of gemcitabine (G) versus G plus cisplatin in chemotherapy-naive advanced pancreatic adenocarcinoma: The GIP-1 (Gruppo Italiano Pancreas— GOIM/GISCAD/GOIRC) study
Authors: Colucci G. , Labianca R. , Di Costanzo F. , Gebbia V. , Cartenì G. , Massidda B. , Frontini L. , Falconi M. , Gallo C. , Di Maio M. 
Published: August 2020

4504 Background: Single-agent gemcitabine (G) remains standard treatment for advanced pancreatic adenocarcinoma (APC). The GIP-1 randomized phase III trial (clinicaltrials.gov ID NCT00813696 ) was performed to compare the combination of cisplatin (P) and G vs. G alone as 1st-line treatment. Methods: Patients (pts) with locally advanced and/or metastatic pancreatic adenocarcinoma, age 18–75, Karnofsky Performance Status (KPS) ≥50, were randomized to receive G (arm A) or G+P (arm B). In arm A, G was administered at 1000 mg/m2 weekly for 7 consecutive wks, and, after a 2-week rest, on day 1, 8, 15 every 4 wks. In Arm B, P 25 mg/m2 weekly (with the exception of day 22) was added to G, same dose used in Arm A (Colucci et al, Cancer 2002; 94:902–10). No maximum number of cycles was planned. Primary endpoint was overall survival (OS). Clinical benefit (CB), objective response rate (ORR), progression-free survival (PFS), toxicity and quality of life were secondary endpoints. To have 80% power of detecting a 0.74 Hazard Ratio (HR) of death (corresponding to increase in median OS from 4.8 to 6.5 months, with bilateral alpha=0.05, 400 pts were planned and 355 deaths were required for final analysis. Results: From April 2002 to April 2007, 400 pts were enrolled (A:199, B; 201) in 46 Italian Institutions. Median age was 63 yrs (range 35–75), 59% were males, 84% stage IV, 83% KPS≥80. After a median follow-up of 38.2 months and 357 deaths, median OS was 8.3 vs 7.2 months in arm A and B, respectively (HR 1.10, 95% CI 0.89–1.35, p=0.38). Median PFS was 3.9 vs 3.8 months in arm A and B, respectively (HR 0.97, 95% CI 0.80–1.19, p=0.80). ORR was 10.1% in arm A and 12.9% in B (p=0.37). CB response was experienced by 23.0% and 15.1% (Arm A vs B, p=0.057). Patients assigned to combination arm experienced more anaemia (all grades: 50% vs 39%, G3: 5% vs 1%), more neutropenia (all grades: 44% vs 36%, G3&4: 25% vs 14%) and more thrombocytopenia (all grades: 57% vs 29%, G3&4: 16% vs 5%). No relevant differences were seen in non-haematological toxicity. Conclusions: Weekly combination of P and G, compared to single-agent G as 1st-line treatment of APC, failed to demonstrate any improvement in OS, PFS, ORR and clinical benefit. No significant financial relationships to disclose.
Prospective multicenter trial of sentinel node mapping for gastric cancer
Authors: Kitagawa Y. , Takeuchi H. , Takagi Y. , Natsugoe S. , Terashima M. , Murakami N. , Fujimura T. , Sakamoto J. , Aikou T. , Kitajima M. 
Published: August 2020

4518 Background: The sentinel node (SN) concept has revolutionized the approach to the surgical staging of both melanoma and breast cancer, and these techniques can yield patient benefit by avoiding various complications due to unnecessary prophylactic regional lymph node dissection in cases with negative SN for cancer metastasis. Clinical application of SN mapping for early gastric cancer had been controversial for years. However, single institutional results of SN mapping for early gastric cancer are almost acceptable results in terms of detection rate and accuracy to determine lymph node status. We hypothesized that SN mapping plays a key role to obtain individual information and allows modification of the surgical procedure for early gastric cancer. Methods: The Japan Society of Sentinel Node Navigation Surgery (JSNNS) has conducted a prospective multicenter trial of SN mapping by a dual tracer method with radioactive colloid and blue dye. Between September 2004 and March 2008, 433 patients with early gastric cancer were accrued at 12 comprehensive hospitals. Patients were enrolled under JSNNS and each institutional review board-approved protocols. Eligibility criteria were that patients had clinically T1N0M0 or T2N0M0 single tumor with diameter of primary lesion less than 4cm without any previous treatments. Technetium-99m tin colloid and isosulfan blue were utilized as dual tracers for SN mapping. Results: SN mapping has been performed for 397 patients with early gastric cancer. Detection rate of hot and/or blue node using our procedure was 97.5% (387/397). The mean number of sentinel nodes per case was 5.6. Fifty-three of 57 cases with lymph node metastasis showed positive sentinel nodes. The sensitivity to detect metastasis based on SN status was therefore 93% in our experience. Accuracy of metastatic status based on SN was 99% (383/387). In two of the four SN false-negative cases, the tumor involved to pT2, and only one case showed the metastatic lymph node beyond the SN basin. Conclusions: Our results suggest that SN concept for clinically N0 early gastric cancer could be validated, and minimized gastrectomy with individualized selective and modified lymphadenectomy for early gastric cancer with negative SN should become feasible and clinically useful as less invasive surgical procedures. No significant financial relationships to disclose.
A multicenter, randomized phase II trial of gemcitabine and oxaliplatin (GEMOX) alone or in combination with biweekly cetuximab in the first-line treatment of advanced biliary cancer: Interim analysis of the BINGO trial
Authors: Malka D. , Trarbach T. , Fartoux L. , Mendiboure J. , de la Fouchardière C. , Viret F. , Assenat E. , Boucher E. , Rosmorduc O. , Greten T. 
Published: August 2020

4520 Background: There is no standard regimen for palliative chemotherapy of advanced biliary cancers. The GEMOX regimen is an option (BJC 2008). EGFR over-expression has been observed in advanced biliary cancers suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with advanced biliary cancer, WHO performance status 0–1, and without prior palliative chemotherapy were eligible for this international, open-label, two-stage, randomized phase II trial. Patients received GEMOX (gemcitabine, 1000 mg/m2 [10 mg/m2/min] at day [D]1; oxaliplatin, 100 mg/m2 at D2) alone (arm A) or with cetuximab (500 mg/m2 at D1 or 2, arm B), every 2 weeks. Randomization was stratified according to tumor stage and location, center, and prior treatments. The primary endpoint was 4-month crude progression-free survival (PFS) rate (H0 hypothesis, < 40%; H1, ≥ 60%; planned sample size, 50 patients per arm). Secondary endpoints were response rate, PFS, overall survival, toxicity, early response assessment by PET, and blood/tumor EGFR signalling pathway member analyses. A data safety monitoring board-approved interim analysis was performed at the end of the first stage (18 patients per arm, minimal follow- up 4 months). Results: From October 2007 to October 2008, we enrolled 101 patients (median age, 62 yrs; male, 60%; metastatic, 86%; non-gallbladder, 76%). Among the 36 patients at the time of the interim analysis, the median number of treatment cycles was 6 and 8 in arms A and B, respectively. 76% (arm A) and 67% (arm B) had NCI-CTC grade 3–4 toxicity, mainly cytopenia (41%/39%), peripheral neuropathy (modified Levi's scale grade 2–3: 29%/33%), fatigue (6%/22%), gastrointestinal toxicity (12%/17%), and rash/hypersensitivity (0%/17%). The 4-month PFS rate was 44% (95% CI, 20–70) and 61% (95% CI, 36–83) in arms A and B, respectively. Conclusions: The GEMOX-cetuximab regimen seems well tolerated in patients with advanced biliary cancer. Adding cetuximab to GEMOX showed promising activity and therefore the trial was continued. Updated results on the whole population for primary and secondary endpoints will be available at the meeting. [Table: see text]
Cationic liposomal paclitaxel in combination with gemcitabine in patients with advanced pancreatic cancer: A phase II trial
Authors: Loehr M. , Bodoky G. , Fölsch U. , Märten A. , Karrasch M. , Lilla C. , Meyer I. , Osinsky D. , Szanto J. , Lutz M. 
Published: August 2020

4526 Background: EndoTAG-1 is a novel cationic liposomal formulation of paclitaxel being developed for the treatment of solid malignancies. It acts by targeting activated negatively charged endothelial cells of tumor blood vessels. We present safety and efficacy data of a randomized, controlled phase II trial in pancreatic cancer (PC). Methods: 200 patients with advanced PC were randomized to 1st line treatment with weekly gemcitabine (GEM: 1000 mg/m2) and twice weekly infusions of EndoTAG-1 (E) at 3 different dose levels (Elow: 11 mg/m2, Emed: 22 mg/m2, Ehigh: 44 mg/m2) or GEM monotherapy. Patients were treated for 7 weeks and followed up for overall survival (OS) for at least 1 year. After finishing study treatment, any anti-tumor therapy was allowed. A subgroup of patients had the option to receive repeated cycles of combination therapy in case of at least stable disease according to RECIST until disease progression. Results: Median OS was substantially higher in the GEM+Emed and GEM+ Ehigh groups than the GEM monotherapy group. Adjusted hazard ratios for OS were 0.72 (95% CI 0.46–1.13) and 0.67 (0.43–1.07). In patients receiving >1 treatment cycle, median OS was 11.5 months (GEM+Ehigh); in the GEM+Emed group 75% of patients were alive at 1 year. Treatment with EndoTAG-1 and gemcitabine was generally well tolerated. A trend for increasing adverse event frequency with EndoTAG-1 dose was observed for infusion-related reactions associated with chills and pyrexia, and thrombocytopenia. The overall frequency of serious adverse events in the GEM+E groups was low, the most frequent SAE being pyrexia in 4 (8%) patients in the GEM+Ehigh group. There was no indication for significant organ toxicity associated with EndoTAG-1, even in patients receiving multiple treatment cycles. Conclusions: This phase II trial indicates a considerable survival benefit for patients with advanced PC receiving EndoTAG-1 in combination with gemcitabine and a favourable safety profile warranting further development of EndoTAG-1 in this indication. [Table: see text]