bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaultion of CD133, VEGF, or EGFR as predictive markers of distant recurrence after preoperative chemoradiotherapy in rectal cancer
Authors: Inoue Y. , Tanaka K. , Saigusa S. , Yokoe T. , Yasuda H. , Toiyama Y. , Miki C. , Yanagi H. , Kusunoki M. 
Published: August 2020

4050 Background: CD133 has been postulated to be a colon cancer stem cells (CSCs) marker. Recent investigations suggest that CSCs might contribute to cancer recurrence and resistance to conventional therapies. This study aimed to evaluate the role of CD133 in residual cancer cells after chemoradiotherapy (CRT) for rectal cancer. Methods: Forty patients with rectal cancer underwent CRT followed by surgery. Total RNAs of rectal cancer cells before (n=30) and after (n=40) CRT were isolated. Residual cancer cells after CRT were collected from formalin-fixed paraffin-embedded (FFPE) specimens using microdissection. Intratumoral CD133, vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) were measured using real-time reverse transcription polymerase chain reaction. Immunohistochemical staining of CD133 after CRT was also investigated. Results: CD133 in residual cancer cells was higher than in stromal cells on post-CRT specimens (p<0.0001). CD133 was increased in post-CRT specimens (p=0.0184), while VEGF and EGFR were decreased during CRT (p<0.0001 and p=0.0002, respectively). There were positive correlations between CD133 and VEGF (p=0.0392) or EGFR (p<0.0001) in pre-CRT specimens. Any correlations were not found in post-CRT specimens. Patients who developed distant recurrence had a higher post-CRT CD133 compared with those patients without recurrence (p=0.0136). Elevated post-CRT CD133 was associated with poor disease free survival (p=0.0168). Immunohistochemically, cytoplasmic and apical/endoluminal membranous CD133 staining was observed in residual cancer cells after CRT. Conclusions: CD133 in residual cancer cells after CRT may indicate a treatment resistant phenotype in putative CSCs. Elevated CD133 but not VEGF or EGFR on FFPE specimens may be a predictive marker of distant recurrence and poor survival after preoperative CRT in rectal cancer. No significant financial relationships to disclose.
Comorbidity and overall survival (OS) in cetuximab-treated patients with advanced colorectal cancer (ACRC)—Results from NCIC CTG CO.17: A phase III trial of cetuximab versus best supportive care (BSC)
Authors: Powell E. D. , Asmis T. , Jonker D. , Tu D. , Karapetis C. , Jeffery M. , O’Callaghan C. 
Published: August 2020

4074 Background: The interplay between comorbidity, age and performance status (PS) as predictors of outcome in ACRC is not well described. We examined these factors as predictors of treatment toxicity and outcome in cetuximab-treated patients with ACRC. Methods: Comorbidity was independently evaluated by 2 physicians using the Charlson Comorbidity Index (CCI), a previously validated measure of comorbidity based on the presence or absence of index medical conditions weighted according to their affect on mortality. CCI score was correlated with demographic data (age, gender), PS, site of primary, time from diagnosis to randomization, body mass index, hemoglobin, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine clearance, K-ras status and OS. Results: 572 patients were included. 41% were ≥65 years and 25% had comorbidities at randomization. CCI score was 1 in 21% and ≥ 2 in 4%. In multivariate analysis (MVA) of all covariates, only older age (≥65 years) was associated with greater comorbidity (p=0.005). OS was different among 3 comorbidity groups (CCI score 0, 1, ≥ 2) in univariate analysis (median OS 4.9 vs 5.9 vs 4.8 months;, logrank p=0.04) but not in MVA. Conversely, lower PS remained associated with better OS in MVA (HR 1.96 for PS=2 vs. PS=0, p<0.0001). Age was not associated with OS (p=0.11). Other factors significantly associated with OS in MVA included time from diagnosis to randomization, LDH, ALP, hemoglobin, Kras status and cetuximab treatment. In the BSC arm, comorbidity was not associated with OS in MVA (HR 0.83 CCI 1 vs. CCI0, p=0.26 and HR 0.90 for CCI2 vs. CCI0, p=0.78) suggesting comorbidity is not prognostic in this setting. Patients with higher CCI score had a nonsignificant trend toward greater treatment effects. Patients ≥65 years had less gr≥3 vomiting (1.8 vs 7.9%, p=0.034) but more dyspnea (24.5 vs 11.2%, p=0.005). Patients with higher CCI scores had less vomiting (p=0.008) but more non-neutropenic infection (p=0.012). Conclusions: In this clinical trial, comorbidity and age were not independent predictors of survival, highlighting the difference between comorbidity and PS. [Table: see text]
mFOLFOX-bevacizumab or XELOX-bevacizumab then bevacizumab (B) alone or with erlotinib (E) in first-line treatment of patients with metastatic colorectal cancer (mCRC): Interim safety analysis of DREAM study
Authors: Tournigand C. , Samson B. , Scheithauer W. , Louvet C. , Andre T. , Lledo G. , Latreille J. , Viret F. , Chibaudel B. , de Gramont A. 
Published: August 2020

4077 Background: Anti-VEGF or EGFR inhibitors demonstrated clinical activity in combination with chemotherapy (CT) in mCRC. The DREAM trial compares, after an induction CT of 6 cy of FOLFOX-B or XELOX-B, a maintenance with B ± E. We report here a pre-planned safety analysis of induction (I) and maintenance (M) phase for the first 200 patients. Methods: Patients (pts) with untreated mCRC were randomly assigned to 2 arms (I): mFOLFOX+B (n=100), or mXELOX+B (n=100). mFOLFOX-B: LV 400 mg/m2, Oxaliplatin (ox) 100 mg/m2, B 5 mg/kg d1, 5FU ci 2.4g/m2 46h, q2w, mXELOX-B: Ox 100 mg/m2 d1, capecitabine 2.5 g/m2 d1–7, B 5mg/kg, q2w. To date, 117 pts with a disease control after 6 cy have had a 2nd randomisation (M): B alone (7.5 mg/kg q3w, n=56) or B+E 150 mg/d (n=61) until PD. Results: Pts characteristics were: sex: 124M/76F, median age: 62.4 years (26–80), primary tumors: colon 152, rectum 53, synchronous metastases: 150 pts, > 1 metastase site: 115, PS 0/1: 134/66, Alk. Ph.>UNL: 87 pts, and LDH>UNL: 88pts. For I, 92 pts in mFOLFOX-B and 93 in XELOX-B were evaluable for toxicity (tox). Tox (%) for mFOLFOX-B/XELOX-B were: any toxicity grade (gr) 3 or 4: 21/30; neutropenia gr 3 6/1, gr 4 0/2; febrile neutropenia gr 3 1/1, gr 4 0/1; thrombopenia gr 3 0/1, gr 4 0/2; anemia gr 2 8/15, gr 3 2/1; nausea gr 2 17/15, gr 3 4/6; vomiting gr 2 10/12, gr 3 2/5; mucositis gr 2 6/6, gr 3 0/4; diarrhea gr 2 8/12, gr 3 5/20, gr 4 0/1; neuropathy gr 2 23/17 gr 3 3/1; HFS gr 2 0/7, gr 3 0/2; hypertension gr 2 2/3, gr 3 1/0; proteinuria gr 2 1/5; SAEs 14/25. For M, 56 pts in B and 61 pts in B+E were evaluable. Tox (% B/B+E) were: neutropenia gr 2 0/3; thrombopenia gr 2 2/0; nausea gr 2 2/2, gr 3 2/0; vomiting gr 3 2/0; mucositis gr 2 2/3; diarrhea gr 2 0/6, gr 3 2/6; skin tox gr 1 9/31, gr 2 0/38, gr 3 0/16, gr 4 0/2; proteinuria gr 2 5/5; hypertension gr 1 9/15, gr 2 3/8, gr 3 3/0. Conclusions: This interim safety analysis demonstrated that induction with mFOLFOX-B or XELOX-B as well as maintenance with B or B + E appears to be well-tolerated, without unexpected side effects. The DREAM study is ongoing, with a prolonged induction phase of 6 months (3 mo with ox then 3 mo with fluoropyrimidines-B) before randomisation for maintenance therapy. [Table: see text]
Phase I study of the IXO regimen, irinotecan (I), capecitabine (X), oxaliplatin (O), as first-line therapy for metastatic colorectal cancer: Final survival results
Authors: Maroun J. , Jonker D. , Cripps C. , Goel R. , Asmis T. , Marginean H. , Chiritescu G. 
Published: August 2020

4082 Background: This study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and efficacy of the IXO regimen when used as first-line treatment for metastatic colorectal cancer (mCRC). Methods: Patients with ECOG PS 0–2, histologically proven, chemo-naïve, non-resectable mCRC were eligible. Phase I starting doses were as follows: I (180 mg/m2 i.v.) d1, X (850 mg/m2 bid orally) d2–15, O (85 mg/m2 i.v.) d1; q3w. Dose escalation (3+3 design) was based on toxicity observed at previous dose levels (DL) until DLT and the MTD were reached. Results: 39 pts (31 male/8 female, median age 58 years, ECOG PS 0–1 in 37, 95%) received a median of 11 cycles (range 1–34) at 8 DLs. 39 pts were evaluable for toxicity. The most common grade 3/4 hematological adverse events (AEs) were granulocytopenia (60%) and fever/febrile neutropenia (18%). The most common grade 3 non-hematological AEs were diarrhea (15%), vomiting (10%), fatigue (8%). No grade 3/4 neuropathy was reported. DLTs: 1 DLT was observed at each of the first 4 DLs, no DLTs at DL5 & 6, 1 at DL7 and 2 at DL8. MTD was reached at DL8. The recommended phase II dose (DL7) is as follows: I (160 mg/m2), X (950 mg/m2), O (100 mg/m2). Efficacy: 38 pts are evaluable for efficacy. The RR is 74% (95% CI 60–89), including 4 CRs, 25 PRs and 6 SDs. The disease control rate is 90% (95% CI 80–100). 10 (26%) pts had subsequent liver surgery with curative intent; 1 had lung resection. Median progression-free survival was 12.3 months (95% CI, 8–17). Overall median survival was 26.4 months (95% CI, 13–36). Conclusions: Diarrhea is the main DLT. Severe neutropenia was of short duration and manageable. The IXO regimen is well tolerated and highly effective as first-line treatment for mCRC. It appears to be particularly effective in downsizing of initially unresectable colorectal cancer liver metastases. A phase II study to confirm the efficacy/safety of IXO in combination with bevacizumab (Avastin) is ongoing. Supported by: Hoffmann La-Roche, Sanofi-Aventis, Pfizer Canada. [Table: see text]
Transarterial chemoembolization (TACE) of liver metastases (LM) from colorectal carcinoma (CRC) adopting drug eluting beads preloaded with irinotecan (DEBIRI): Results of a phase II study on 82 patients
Authors: Aliberti C. , Benea G. , Tilli M. , Fiorentini G. 
Published: August 2020

4092 Background: DC beads are new embolic microspheres capable to load IRI. The present phase II study investigated response and side effects after TACE adopting DEBIRI in 82 patients with LM from CRC not resectable and in progression after two lines of chemtherapy. Methods: A total of 185 TACE procedures were performed. A suspension of polyvinyl-alcohol beads (DC Bead) preloaded with Irinotecan ( 81 TACE procedures with 2ml of microspheres preloaded with 100mgr of Irinotecan and 104 with 4ml loaded with 200mgr of Irinotecan) was delivered selectively into hepatic arteries. All pts received a well defined prophylactic treatment against nausea and vomiting, infections, and upper quadrant right pain (UQRP).Tropisetron, hydration, antibiotics, morphine and intra-arterial lidocaine was delivered as reported in previous experiences ( ASCO GI abs 356,2007; IN VIVO. 21, 6, 2007). Follow-up studies were performed by contrast enhanced spiral multislice computed tomography (MsCT) 1 month after the procedures and every 3 months or when clinically required. Quality of life (QoL) was assessed by Edmonton SAS improvement scale before, after TACE and then monthly. Results: We obtained 100% technical success in TACEs performed, and no complications due to the procedure occurred. Patients developed a postembolization-syndrome with the following side effects : UQRP (G2), fever (G2), nausea (G2) and increased transaminases (G2–3) in 40%,80%,80%,70% respectively out of 185 procedures done. One pt presented acute pancreatitis. The median follow-up was 18.2 months. Within 1 month after treatment, CT scan showed significant ( 75–100%) reduction of metastatic contrast enhancement in all lesions treated. Therapeutic response (according to RECIST was observed in 78% of patients. After TACE. 75 out 82 pts (90%) declare a general improvement of QoL long lasting. Conclusions: We suggest that TACE with DEBIRI could be a palliative therapy for LM from CRC. Our promising experience need to be confirmed with further phase III studies. Mid and long-term results need to be carefully evaluated comparing them with systemic chemotherapy. No significant financial relationships to disclose.
Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from digestive or primitive origin: A multi-institutional study of 1,290 patients
Authors: Glehen O. , Elias D. , Gilly F. N. , Boutitie F. , Bereder J. M. , Quenet F. , Sideris L. , Mansvelt B. , Lorimier G. ,   Association Française de Chirurgie
Published: August 2020

4102 Background: Peritoneal carcinomatosis (PC) from non-gynecologic malignancies has long been regarded a terminal disease with a short median survival. Over the past decade, new locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved and suggest improved survival. Methods: A retrospective multicentric study was performed in French speaking centers to evaluate the toxicity and the principal prognostic factors in order to identify the best indications. All patients had cytoreductive surgery and PIC (hyperthermic intraperitoneal chemotherapy (HIPEC) and or early postoperative intraperitoneal chemotherapy (EPIC)). Results: The study included 1290 patients from 25 institutions between February 1989 and December 2007. The principal etiologies of PC were colorectal adenocarcinoma (N=523), pseudomyxoma peritonei (N=301), gastric adenocarcinoma (N=159), peritoneal mesothelioma (N=88), and appendiceal adenocarcinoma (N=50). Mortality and morbidity rates were 4.1% and 33.8%, respectively. By multivariate analysis, age, extent of the PC, and the institution's experience had a significant influence on toxicity. The overall median survival was 34 months: 30 months for colorectal PC, not reached for pseudomyxoma peritonei, 9 months for gastric PC, 41 months for peritoneal mesothelioma, and 77 months for PC from appendiceal adenocarcinoma. Independent prognostic indicators by multivariate analysis were the institution's experience, etiology, completeness of cytoreductive surgery, extent of carcinomatosis, and lymph node involvement. Conclusions: The therapeutic approach combining cytoreductive surgery with PIC may achieve long-term survival in a selected group of patients with PC from non-gynecologic origin with acceptable mortality and morbidity. This treatment should be reserved to experienced institutions involved in the management of PC. No significant financial relationships to disclose.
Impact of bevacizumab (bev) on overall survival (OS) in patients (pts) with metastatic colorectal cancer (MCRC): A population-based study
Authors: Renouf D. J. , Lim H. J. , Speers C. , Villa D. , Gill S. , Blanke C. D. , O’Reilly S. E. , Kennecke H. 
Published: August 2020

4114 Background: As of 2003, irinotecan or oxaliplatin in combination with fluorouracil was standard treatment for MCRC in British Columbia (BC). The addition of bev to chemotherapy (CT) was approved in BC in 2006. We compared OS between referred pts diagnosed with MCRC in 2003/2004 (pre-bev era) and 2006 (bev era). Methods: All pts diagnosed with MCRC in 2003/04 and 2006, and referred to the BC Cancer Agency (BCCA) were included. The BCCA is a cancer network with centers throughout BC, ≈60% of MCRC pts in BC are referred to the BCCA. Systemic therapy (ST) is centrally funded and treatment data was obtained from the pharmacy database. The primary endpoint was OS of all pts within each cohort. Secondary endpoints were OS in pts treated with ST, and in those not treated. Kaplan Meier method was used for survival analysis. Subgroup analysis based on age was performed. Results: 1417 pts were included: 969 from 2003/04, and 448 from 2006. Median age at diagnosis of MCRC was 68y in 2003/04 and 69y in 2006. Median follow up time was 47.3 and 21.4 mos respectively. Between 2003/04 and 2006 the proportion of pts treated with ST for MCRC increased from 61.1% to 67.6% (p= 0.02). Proportion of pts who received irinotecan, oxaliplatin and fluorouracil did not change (24.7% to 23.7%, p=0.68). Proportion of pts who received bev increased (5.9% to 30.6%, p<0.001). Median OS significantly improved for the entire cohort (13.8 to 17.3 mos, p<0.001). Median OS for pts who received ST for MCRC improved (18.6 to 23.6 mos, p=0.001). Median OS for pts who did not receive ST did not change (6.1 to 5.9 mos, p=0.65). Of pts who received ST, the proportion who received bev increased in pts <70 (12.7% to 58%, p<0.001) and in pts ≥70 (3.6% to 22.7%, p<0.001). Median OS for pts <70 who received ST for MCRC improved (20.3 to 26.5 mos, p = 0.002). Median OS for pts ≥70 who received ST for MCRC improved (16.5 to 19.9 mos), but this was not significant (p=0.16). Conclusions: In this population based study, median OS for MCRC significantly increased between 2003/04 and 2006. The improvement in survival appears to be limited to pts treated with ST for metastatic disease. The main difference in ST has been the addition of bev. On a population basis, the addition of bev to CT is associated with a significant improvement in OS in MCRC. No significant financial relationships to disclose.
A phase I study of pazopanib in combination with FOLFOX 6 or capeOx in subjects with colorectal cancer
Authors: Brady J. , Middleton M. , Midgley R. S. , Mallath M. K. , Corrie P. , Sirohi B. , Chau I. , Digumarti R. , Botbyl J. , Lager J. J. 
Published: August 2020

4133 Background: Pazopanib (paz) is a tyrosine kinase inhibitor of VEGFR-1, -2, -3, PDGF-α, -β, and c-kit. Inhibition of angiogenic pathways in combination with chemotherapy has been shown to benefit patients (pts) with colorectal cancer (CRC). Methods: Pts with previously untreated advanced or metastatic CRC and adequate organ function were assigned to paz with FOLFOX6 (FO) or capeOx (CO) by their physician. Doses of paz were escalated with full strength chemotherapy, starting at 400mg daily. The optimally tolerated regimen (OTR) was the combination dose at which <1/6 pts experienced dose-limiting toxicity (DLT). Results: Fifty pts were enrolled in FO (paz 400 mg, n=6; 800, 15), CO (400, 12; 800, 9) and reduced capecitabine (rc) CO (800, 8) cohorts: median age = 55.5, M/F = 37/13. Pts have remained on therapy for a median of 3 (range 0–17) months. Three pts remain on study. Safety data is available on 41. The most common AEs are summarized in the table below. The OTR was exceeded with CO in combination with 800 mg and 400 mg of pazopanib, but was not exceeded with 800 mg pazopanib when capecitabine was reduced to 850 mg/m2 twice daily or with FO with 800 mg pazopanib. Efficacy and pharmacokinetic analyses are ongoing. Conclusions: The OTRs were achieved at 800 mg paz with full-dose FO, and at 800mg paz with rcCO. [Table: see text] [Table: see text]
Gemcitabine with or without cisplatin in patients (pts) with advanced or metastatic biliary tract cancer (ABC): Results of a multicenter, randomized phase III trial (the UK ABC-02 trial)
Authors: Valle J. W. , Wasan H. S. , Palmer D. D. , Cunningham D. , Anthoney D. A. , Maraveyas A. , Hughes S. K. , Roughton M. , Bridgewater J. A. 
Published: August 2020

4503 Background: There is no established standard chemotherapy for pts with inoperable ABC. We previously reported an improvement in progression-free survival (PFS) in a randomised phase II trial of 86 pts (ABC-01) using gemcitabine/cisplatin (GemCis) vs. gemcitabine (Gem) (Valle ASCO-GI 2006, abstr. 98). This study was extended into ABC-02, a phase III trial, to recruit a further 314 pts with overall survival (OS) as the primary end-point. Methods: Consenting pts with histologically/cytologically-confirmed ABC, aged ≥18 years, ECOG performance status 0 - 2, and adequate haematological, hepatic and renal function were randomised to receive either Cis (25 mg/m2) followed by Gem (1000 mg/m2 D1, 8 q21d) for 8 cycles, or Gem alone (1000 mg/m2 on D1, 8, 15 q28d) for 6 cycles, stratified by extent of disease, site of primary tumour, ECOG score and centre. The trial had an 80% power to detect an OS hazard ratio of 0.73. Results: From May 2005 to October 2008, 324 pts were randomised to ABC- 02 from 34 UK centres. We report the pre-planned combined analysis of ABC-01 and ABC-02 based on 410 pts (GemCis=206/Gem=204). Patient characteristics: median age 64 yrs (range 23–85); male (47%); metastatic disease (75%), locally advanced (25%); gallbladder (36%), bile duct (59%), ampulla (5%); and ECOG 0–1 (87%), 2 (12%). With a median follow-up of 6.1 months and 263 deaths, the median OS was greater with GemCis than Gem, 11.7 vs. 8.2 months (log rank p=0.002), with hazard ratio 0.68 (95%-CI 0.53, 0.86). The median PFS was greater with GemCis than Gem, 8.5 vs. 6.5 months (log rank p=0.003), with hazard ratio 0.70 (95%-CI 0.56, 0.88).Toxicity was similar between the arms (by week 12, 57% had a grade 3/4 toxicity in each arm), though there was a slight excess of neutropenia using GemCis. Conclusions: This is the largest ever study in ABC and demonstrates a clear survival advantage for GemCis without added clinically significant toxicity, setting a new international standard of care. No significant financial relationships to disclose.
Neoadjuvant chemotherapy versus surgery alone for locally advanced adenocarcinoma of the stomach and cardia: Randomized EORTC phase III trial #40954
Authors: Schuhmacher C. , Schlag P. , Lordick F. , Hohenberger W. , Heise J. , Haag C. , Gretschel S. , Mauer M. E. , Lutz M. , Siewert J. R. 
Published: August 2020

4510 Background: Combined pre- and postoperative chemotherapy improves overall survival in operable gastric cancer, although postoperative treatment is not feasible in half of the patients. We conducted a randomized phase III trial with thorough attention to preoperative staging and to the extent of surgical resection to assess the value of neoadjuvant chemotherapy (CTx). Methods: Patients with locally advanced adenocarcinoma of the stomach and cardia were randomized between primary surgery or two 48-day cycles of weekly folinic acid 500 mg/m2/2h, 5-FU 2,000 mg/m2/24h plus biweekly cisplatin 50 mg/m2/1h followed by surgery. The study was designed to detect an improvement in median survival from 17 months with surgery to 24 months with CTx plus surgery (HR=0.708, power of 80%, type I error of 4% to allow for an interim analysis). It was planned to randomize 360 patients in order to observe the 262 deaths required for the final analysis. Results: From 7/99 to 2/04, 144 patients were randomized (72:72) with comparable baseline characteristics. Median follow-up is 4.4 years. Based on 67 deaths, overall survival between the two arms did not differ (HR=0.84; 95% CI: 0.52 to 1.35; p=0.466). Median survival exceeded 36 months in both arms. Due to low accrual, this trial was stopped early. The unexpected long median survival in the surgery arm would have made the primary objective difficult to reach anyway. Based on 77 events, difference in time to progression was borderline significant (HR=0.66; 95% CI, 0.42–1.03; p=0.065). Response rate to CTx was 35.2% (95% CI: 23.7%-45.7%). The R0-resection rate was 81.9 % after CTx as compared to 66.7% with surgery alone (P=0.036). There were no major differences in intra- or postoperative complications. Conclusions: This prematurely closed trial showed a significantly increased rate of R0 resections after CTx although it could not demonstrate a survival benefit. The outcome after a radical surgical procedure alone with extended lymphadenectomy was better than expected. No significant financial relationships to disclose.