bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival with cetuximab/FOLFOX or cetuximab/FOLFIRI of patients with nonresectable colorectal liver metastases in the CELIM study.
Authors: Folprecht Gunnar , Gruenberger Thomas , Bechstein Wolf , Lordick Florian , Lang Hauke , Weitz Jürgen , Suedhoff Thomas , Hartmann Joerg Thomas , Liersch Torsten , Kohne Claus-Henning 
Published: February 2017

540 Background: Non-resectable liver metastases (mets) can be resected if they responded to systemic treatment. Cetuximab increases response rates in patients with k-ras wild type (wt) tumours. Methods: Patients (pts) with non-resectable liver mets (defined as technically non-resectable or ≥ 5 liver mets) were randomized to cetuximab/FOLFOX (arm A) or cetuximab/FOLFIRI (arm B). Resectability was re-evaluated after four and then every 2 months. Resection was offered to pts who became resectable during treatment. (Folprecht et al, Lancet Oncol 2010) Progression free survival (PFS) and overall survival (OS) were analysed in June 2011. Results: One hundred nine pts were randomized to cetuximab/FOLFOX or cetuximab/FOLFIRI, 106 evaluable for response. The median OS in all pts was 33.1 months [95% CI: 25.8-40.4], 35.7 [29.9-41.6] mo. in arm A and 29.0 [18.1-39.8] mo. in arm B (HR 1.09 [0.69-1.72]). The 4-year OS was 28% in all pts. The PFS was 11.2 [7.2-15.3] and 10.5 [8.9-12.2] mo. in arm A and B, respectively (HR 1.15 [0.77-1.70]). According to the k-ras mutational status, the OS and PFS was 36.1 [24.4-47.8] and 11.9 [8.25-15.6] in k-ras wt, 27.4 [15.7-39.1] and 9.9 [4.5-15.2] in k-ras mutant pts. In the k-ras wt subset, the OS was 35.8 [30.2-41.4] and 41.6 [24.8-58.5] mo. in arm A and B (HR 1.01 [0.55-1.86]), the PFS 12.1 [5.2-19.1] and 11.5 [8.8-14.1] mo. in arm A and B (HR 1.09 [0.66-1.79]). Pts with R0 resection had a significantly longer OS (median 46.7 [30.7-62.7] mo.) than pts without (median OS: 27.3 [21.2-33.3] mo, p=0.002). In R0 resected pts, the 3- and 4 year OS was 64% and 49%. The median disease free survival (DFS) was 9.9 mo after R0 resection, the 2 year DFS 19%. According to a review of CT/MRI scans which was performed by surgeons blinded to all clinical data, there was no survival difference between “resectable” pts and pts not categorized as “resectable” at baseline (HR 0.81 [0.44-1.50]), but a significantly better OS was observed for pts regarded as “resectable” after treatment vs. other categories (HR 0.47 [0.27-0.83], p=0.007). Conclusions: Pts had a favourable overall survival which was longer in R0 resected pts. Resectability after treatment seems to be important for the pts outcome.
Quality of life (QoL) assessment in patients (pts) with K-RAS wild-type (WT) chemotherapy refractory metastatic colorectal cancer (mCRC) treated with cetuximab (CET) plus brivanib alaninate (BRIV) or placebo: Results of the NCIC Clinical Trials Group and AGITG CO.20 trial.
Authors: Ringash Jolie , Au Heather-Jane , Siu Lillian L. , Shapiro Jeremy D. , Jonker Derek J. , Zalcberg John Raymond , Moore Malcolm J. , Strickland Andrew H. , Kotb Rami , Jeffery Mark , Alcindor Thierry , Ng Siobhan , Salim Muhammad , Sabesan Sabe S. , Easaw Jacob C. , Shannon Jennifer Anne , El-Tahche Fabyolla , Walters Ian B. , Tu Dongsheng , O'Callaghan Christopher J. ,   the NCIC-CTG and the AGITG
Published: February 2017

542 Background: The CO.20 trial randomized pts with K-RAS WT chemotherapy refractory mCRC to receive CET + BRIV (Arm A) or CET + placebo (Arm B). Although overall survival (primary endpoint) was not significantly improved (HR=0.88, p=0.12) in this heavily pre-treated population, progression free survival (PFS) favoured Arm A (HR=0.72 p<0.0001). Methods: Patients with K-RAS WT mCRC previously treated with or with contraindications to a fluoropyrimidine, irinotecan, and oxaliplatin were randomized to a loading dose of IV CET followed by weekly IV CET + BRIV 800 mg PO daily or CET + placebo daily. QoL, a secondary endpoint, was assessed using the EORTC QLQ-C30 at baseline and at 2, 4, 6, 8, 12, 16 and 24 weeks until progression or clinical deterioration. Co-primary QoL endpoints were defined a priori as definitive deterioration (first worsening from baseline of ≥10 points) on the physical function (PF) and Global scales. Time to QoL deterioration (DET) was measured from randomization using the Hochberg procedure to adjust for multiple testing. Results: 721 (358 Arm A) of 750 randomized pts were assessable for QoL. QoL compliance did not differ by arm and declined in follow-up from 87% to 47% over time. Baseline Global and PF scores did not differ by arm. Median time to QoL DET was 1.6 vs 1.1 mo for Global (p=0.02) and 5.6 vs 1.7 mo. for PF (p<0.0001) in Arm B vs A, respectively. Secondary QoL response evaluation showed a greater proportion of patients on Arm A to have worsening on the PF (31 vs 17% at 6 wks) and cognitive functioning scales, and on the fatigue, nausea, appetite and diarrhea symptom scales. Clinical adverse events ≥ Grade 3 were more common on Arm A than B including fatigue (25 vs 10%), hypertension, rash, diarrhea, abdominal pain, dehydration and anorexia. Conclusions: Despite a PFS benefit, the combination of CET + BRIV worsened time to QoL DET on the PF and Global scales of EORTC QLQ-C30 in pts with chemotherapy refractory K-RAS WT mCRC. This result may be due to higher rates of fatigue and gastrointestinal adverse events observed with the combination.
Exploratory analysis of adjuvant chemotherapy effects after preoperative chemoradiotherapy and radical resection for rectal cancer.
Authors: Park In Ja , Eng Cathy , You Y. Nancy , Kopetz Scott , Rodriguez-Bigas Miguel A. , Overman Michael J. , Skibber John Michael , Chang George J. 
Published: February 2017

557 Background: Evidence regarding adjuvant chemotherapy (CTx) for patients with rectal cancer after preoperative chemoradiotherapy (CXRT) is limited. The aim of study was to explore the relationship between CXRT response and adjuvant CTx for patients with rectal cancer treated by CXRT and radical resection. Methods: We performed a retrospective consecutive cohort study of patients with locally advanced (cStage II-III by EUS, CT, or MRI) rectal carcinoma treated with preoperative CXRT and radical resection, 1993 to 2008. To explore the late effects, we performed a landmark analysis of patients alive without recurrence at 24 months. The duration free from recurrence (FFR) was compared among patients with complete (CR, ypT0N0), intermediate (IR, ypT1-2N0), or poor (PR, ypT3-4 or N+) response according to adjuvant CTx use and type using multivariate Cox regression. Results: A total of 725 patients met criteria and were evaluated. Median follow-up was 69 months (IQR: 39-104 months). 611 patients received adjuvant CTx: 447 with fluoropyrimidine only (FP), and 139 also received oxaliplatin (Ox). Although receipt of adjuvant chemotherapy was not associated with 5-year FFR overall, (HR: 0.91, 95% CI: 0.58-1.43), adjuvant therapy did appear to suggest a benefit in the IR group (HR, 0.49; 95%CI, 0.21-1.19). Adjusted landmark analysis showed that adjuvant CTx was associated with a significant improvement in FFR among the IR patients only (HR, 0.28; 95% CI, 0.08-1.00, P=.04). Among PR patients FP alone did not improve FFR (HR, 1.22; 95% CI, 0.7-2.12) but the addition of Ox was associated with a non-significant reversal in the direction of the effect (HR, 0.53; 95% CI, 0.16-1.79). Conclusions: In this exploratory analysis, the addition of adjuvant FP CTx appeared to favorably affect the duration FFR only for patients with rectal cancer and intermediate response to CXRT followed by radical resection. These data support the investigation of the role for adjuvant fluoropyrimidine therapy among patients with CR or IR and oxaliplatin for PR patients.
Do patients with metastatic colorectal cancer (mCRC) with late relapse after curative surgery have a better survival?
Authors: Price Timothy Jay , Beeke Carol , Woodman Richard , Karapetis Christos Stelios , Kim Susan , Maddern Guy , Broadbridge Vy , Hakendorf Paul , Padbury Rob 
Published: February 2017

558 Background: Patients who relapse after potentially curative surgery for CRC tend to relapse within 5 years, with the greatest risk said to be in the first 2 to 3 years post surgery. There is however a group of patients who relapse beyond 5 years post resection. This late relapsing group may have a different behaviour and prognosis. Methods: A retrospective cohort study was perfomed to compare the characteristics and survival of relapsed patients with metachronous (m) mCRC. Patients were categorised into relapse at < 2yrs, 2-5 yrs and > 5yrs following their initial surgery. Univariate log-rank tests and and multivariate Cox regression was performed to determine whether time to relapse (TTR) and other factors were associated with overall survival (OS). Results: Of 750 mmCRC, 56% percent relapsed at < 2yrs, 32.4% at 2-5yrs, and 11.6% at > 5yrs. Patient characteristics are summarised in the table. Median OS, from the time of diagnosis of the recurrence, was 17 mths, 24.8 mths, and 26.5 mths respectively. Age (HR = 1.01, 95% CI=1.005-1.02, p=0.003) and liver resection (HR = 0.2, 95% CI=0.1-0.3, p < 0.001) were significant independent predictors of OS. TTR was also significantly associated with OS (HR = 0.75, 95 % CI = 0.60-0.93 and HR = 0.73, 95% CI = 0.53-1.01 respectively for 2-5 yrs and > 5 yrs versus < 2yrs, p < 0.05). There was no significant difference in survival between patients that relapsed at 5 yrs or later compared to those who relapsed between 2 and 5 yrs (HR = 0.98, 95% CI = 0.69-1.38, p = 0.90). Conclusions: TTR predicted shorter survival for mmCRC patients whose relapse occurred within 2 yrs. However, when comparing TTR 2-5 yrs and TTR > 5 yrs, there is no evidence that mmCRC patients with later relapse have a better prognosis. [Table: see text]
Use of detailed pathologic characteristics of the primary colorectal tumor to predict outcome after hepatectomy for metastases.
Authors: Cardona Kenneth , D'Amico Francesco , Shia Jinru , Gönen Mithat , Weiser Martin R. , Paty Philip , Kingham T. Peter , Allen Peter J , DeMatteo Ronald P. , Fong Yuman , Jarnagin William R. , D'Angelica Michael Ian 
Published: February 2017

559 Background: Outcome after hepatic resection for colorectal liver metastases (CRLM) is heterogeneous and accurate predictors of survival are lacking. The aim of our study was to analyze the prognostic relevance of pathologic details of the colorectal primary tumor in patients undergoing hepatic resection of CRLM. Methods: Retrospective review of a prospective database identified patients who underwent potentially curative hepatic resection of CRLM. Clinicopathological variables were investigated and their association with outcome was analyzed. Results: From 1997-2007, 1004 patients underwent hepatic resection for CRLM. The median follow-up for survivors was 59 months with a 5-year predicted survival of 47%. Ninety-two percent of patients received perioperative chemotherapy and 34% received adjuvant hepatic artery infusion chemotherapy. Univariate analysis identified 10 factors associated with poor survival. Three of these related to the pathology of the primary tumor: lymphovascular invasion (LVI, p<0.0001), perineural invasion (p=0.005), and degree of regional lymph node involvement (N0 vs N1 vs N2, p<0.0001). Multivariate analysis identified 7 factors associated with poor survival. Two of these related to the pathology of the primary tumor: LVI (HR 1.3, 95% CI 1.06-1.64, p=0.01) and degree of regional lymph node involvement where an increase in the number of metastatic regional lymph nodes from N1 (HR 1.3, 95% CI 1.04-1.69, p=0.02) to N2 (HR 1.7, 95% CI 1.27-2.21, p <0.0005) was associated with a reduced survival. LVI positive patients had a median survival of 48 months compared to 69 months for LVI negative patients (p<0.0001); moreover, patients who were LVI positive with N2 nodal disease had a reduced survival to 40 months compared to 74 months for patients who were LVI negative with no nodal disease (p<0.0001). Conclusions: Resection of CLRM is associated with long-term survival. Pathologic details of the primary colorectal tumor, particularly LVI and the degree of lymph node involvement, are strong predictors of survival. Future biomarker studies should consider utilizing factors related to the primary colorectal tumor.
Meta-analysis of anti-VEGF class adverse events from three double-blind (Db) placebo (Pbo)-controlled phase III trials with IV aflibercept (Afl).
Authors: Allegra Carmen Joseph , Tabernero Josep , Rougier Philippe , Scagliotti Giorgio , Philip Philip Agop , Lakomy Radek , Ramlau Rodryg , Assadourian Sylvie , Chevalier Soazig , Van Cutsem Eric 
Published: February 2017

561 Background: Three Db Pbo controlled studies were conducted with IV Afl in metastatic cancer patients [colorectal (CRC) Afl+FOLFIRI (WCGC 2011 abstract O-0024), lung (LC) Afl+docetaxel (WCLC 2011, abstract 511) and pancreatic (PC) Afl+gemcitabine (WCGC 2009 abstract O-0006)]. Each study used the same weekly Afl dose intensity (4 mg/kg q2w for CRC and PC; 6mg/kg q3w for LC). A safety meta-analysis of anti-VEGF class adverse events (AE) was performed on data from these studies. Methods: A fixed-effect logistic regression model was used, including study, treatment and study-by-treatment interaction factors as covariates to test the consistency of treatment effect across studies for each of the considered AE. When no evidence of heterogeneity of treatment effects was found across studies, relative risks (RR) and 95% confidence intervals (CI) were estimated. Summary incidences (% of patients [pts]) and RR are presented for NCI grade 3-4 events. Results: Safety data from total of 2,662 pts (Afl: 1,333; Pbo: 1,329) were included for analysis (Table). Among pts treated with Afl, 0.4 and 0.5% experienced grade 4 hypertension and nephrotic syndrome, respectively. Conclusions: The addition of Afl to concurrent chemotherapies did not increase the risk of VTE. The risk of grade 3-4 anti-VEGF class AEs was increased when adding Afl to concurrent chemotherapies. This increased risk was statistically significant (**) only for hypertension, proteinuria and hemorrhage. Further analyses, when more data are available, should improve the precision of these results. Studies were sponsored by Sanofi NCT00561470 , NCT00532155 , and NCT00574275 . [Table: see text]
FOCUS 3: A study to determine the feasibility of molecular selection of therapy using K-RAS, B-RAF, and topo-1 in patients with advanced colorectal cancer (ACRC).
Authors: Maughan Tim , Wilson Richard H. , Williams Geraint T , Seymour Matthew T. , Richman Susan D. , Quirke Philip , Pope Janet , Pope Malcolm , Parmar Mahesh , Nelson Annmarie , Meade Angela M. , Nichols Laura L , Jasani Bharat , Hodgkinson Elizabeth , Fisher David , Butler Rachel , Bridgewater John A. , Adams Richard A. , Kaplan Richard S. 
Published: February 2017

563 Background: Molecular characteristics of cancer vary between individuals. In future increasing numbers of trials will require assessment of biomarkers in order to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The FOCUS 3 trial is a feasibility study to assess whether tumour samples could be collected from referring hospitals’ pathology departments, sent to designated reference laboratories for biomarker evaluation, and results provided to oncologists within 10 working days. Methods: Patients with ACRC, fit for chemotherapy, were registered from 24 centres between 02.10 and 04.11. Following consent, paraffin embedded tumour samples were sent to Cardiff or Leeds for analysis of topoisomerase 1 (topo-1) by immunohistochemistry and of KRAS and BRAF mutation status, and results were forwarded to the MRC CTU. Patients were classified into 1 of 4 molecular strata, which determined the set of 2 hypothesis driven experimental therapies they could be randomised to in addition to control chemotherapy (irinotecan + 5FU). At this stage eligibility was reconfirmed and consent for randomisation obtained. Results: 332 patients were registered to participate in FOCUS 3. Biomarker results were provided to oncologists within 10 working days (wd) in 71%, within 15 wd in 91% and within 20 wd in 99% patients. A 4 stage suite of patient information sheets (PIS) was designed and implemented to avoid patient overload; separate information sheets were provided to patients at stages during the consent process and patient understanding was assessed. 93% of eligible patients gave consent to randomisation. KRAS mutation was detected in 88 (36%), BRAF in 15 (6%), 2 patients had both mutations and 133 were double wildtype. 77% of patients were high (2-3), 19% low (0-1) and 4% inconclusive for topo-1. Tumour response and toxicity results for the 244 randomised patients will be presented. Conclusions: Patient samples can be collected and analysed at designated reference laboratories within acceptable timeframes. Multi-arm designs can be made acceptable to patients through good PIS, ensured by patient and carer input into their design.
TJ-107 for the prevention of oxaliplatin-induced peripheral neuropathy: Results of a phase II randomized placebo-controlled clinical trial.
Authors: Kono Toru , Hata Taishi , Munemoto Yoshinori , Matsui Takanori , Kojima Hiroshi , Takemoto Hiroyoshi , Fukunaga Mutsumi , Shimada Mitsuo , Nagata Naoki , Morita Satoshi , Sakamoto Junichi , Mishima Hideyuki 
Published: February 2017

567 Background: Oxaliplatin-induced peripheral neuropathy (OPN) continues to be a substantial problem for many cancer patients. In light of the promising data on TJ-107 from a previous pilot study (ASCO-GI, 2009), the present clinical trial was conducted to evaluate its efficacy for the prevention of OPN. To determine whether TJ-107 given as an adjuvant therapy effectively prevents oxaliplatin-induced peripheral neuropathy Methods: A phase II, randomized, double-blind, placebo-controlled trial was conducted in colorectal cancer patients undergoing therapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX). TJ-107 (7.5g) or matching placebo was orally administered three times daily. The primary endpoint was the incidence of grade 2 or greater OPN according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) criteria after 8 cycles of chemotherapy. Patient-reported neurotoxicity symptoms were also assessed using the neurotoxicity subscale of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx, version 4). Secondary endpoints included the incidence of all grades of OPN after each cycle and chemotherapy response rates. Results: A total of 93 patients were enrolled from May 1, 2009 to March 31, 2010 at 37 participating GONE trial institutions in Japan. Eighty-nine evaluable patients were randomized to either the TJ-107 group (n = 44) or the placebo group (n = 45). Placebo patients showed a significantly higher rate of neurotoxicity than that of TJ-107 patients (p < 0.001), with the median difference in NTX-12 score of 3 and 3.5 at the 8th week and 26th week, respectively. There were no significant between-group differences in response to chemotherapy (55.5% in TJ-107, 39.1% in placebo). In addition, TJ-107 treatment was well tolerated overall. Conclusions: TJ-107 shows promise in reducing the incidence of OPN. Further investigation in a larger phase III trial is necessary before any conclusions can be drawn. [Table: see text]
Systemic chemotherapy in the setting of unresectable appendiceal epithelial neoplasms (AEN).
Authors: Eng Cathy , Blackham Aaron Udell , Overman Michael J. , Fournier Keith F. , Royal Richard E. , Gajula Prianka , Levine Edward Allen , Wolff Robert A. , Mansfield Paul F. 
Published: February 2017

568 Background: AEN is a malignancy including both indolent well-differentiated and highly aggressive signet ring carcinoma. Optimal therapy is believed to be cytoreductive surgery (CRS) followed by heated intraperitoneal chemotherapy (HIPEC). Yet, some patients (pts) will recur, are suboptimal for surgery, and are considered for systemic chemotherapy (SC). The purpose of this study is to compare SC regimens in treatment-naïve surgically unresectable AEN pts. Currently, no standard exists. Methods: A retrospective review of AEN pts who were registered in our tumor registries between Jan. 2005 to Dec. 2009 was completed. Electronic medical records were reviewed for CRS, HIPEC, histology, stage, SC received, CEA, CA-125, and/or CA 19-9, response (R), and progression-free survival (PFS). All patients were required to be restaged at their respective institution with R defined as clinical or radiographic benefit. K-M method, Log-Rank, and Cox proportional hazard regression models were used for statistical analysis. Results: Of 659 pts with AEN diagnosis, 134 pts were evaluable for PFS and R. Forty-eight (36%) pts were poorly-differentiated; 29 (22%) signet ring; and 22 (16%) had both features. Thirty-four (25%) were well-differentiated. After a median follow-up of 35M, adjusting PFS for prior CRS, HIPEC, histology, ascites, and biologic therapy, pts who received 5-FU alone fared worse vs. FOLFOX [HR: 2.39; 95% CI: 1.2-4.6; p-value = 0.01]. FOLFIRI trended in favor of improved PFS, but was underpowered. No statistical difference in R was noted (Table). Conclusions: In the treatment of surgically unresectable AEN, combination chemotherapy resulted in improved PFS vs. single agent 5-FU. Quality of life analysis will be reported at a later date. Randomized prospective analysis should be considered. [Table: see text]
Use of MRI-defined tumor distance from the anal verge to predict tumor response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.
Authors: Yu Stanley Ka Tung , Brown Gina , Tait Diana M. 
Published: February 2017

573 Background: Neoadjuvant Chemoradiotherapy (CRT) and surgical resection is the current standard management for patients with locally advanced rectal cancer (i.e. T3 or 4 N0/1 M0) (LARC). Tumour predictive factors for response to CRT in rectal cancer remain controversial. Staging investigations are not standardised and MRI has not been used consistently to approach this. The aim of this study is to investigate whether tumour distance from anal verge, as measured on MRI, is a predictive factor for response to CRT in LARC. Methods: This is a retrospective study. Patients with LARC or low T2 N0/1 M0 rectal cancer (i.e. ≤ 5cm from anal verge measured by MRI) treated with preoperative CRT in 2003- 2009 were included. Pelvic MRIs acquired before CRT and no less than 4 weeks post CRT were reviewed. Patients with ypT0-2 in the resected specimen were classified as responders because ypT0-2 has been shown with significant OS and DFS benefit (Valentini V et al. Int J Radiat Oncol Biol Phys. 2002; 53(3): 664-74). Downstage of mrT2 low rectal cancer was defined as ypT0-1 post CRT. Univariate binary logistic regression (UBLR) was used to analyse the predictor associated between responders and non-responders to CRT treated in the same period of time. Results: 281 patients with LARC who underwent CRT were included in the study. 96% patients in this study had T3/T4 LARC and 4% had T2 low rectal cancer. 114 (41%) were responders as defined above, 167 (59%) were non-responders to CRT. The mean MRI defined tumour distance from anal verge was significantly less in responders (6.4cm [Confidence Intervals (CI) = 5.7 -7.1]) when compared with non-responders (7.9cm [CI =7.3 – 8.6]) (P<0.05). Conclusions: The UBLR analysis from our study indicated that an MRI measured tumour distance of ≤ 5cm from the anal verge independently predicted higher tumour downstaging rate (p < 0.001) to CRT in LARC. Further investigation is recommended regarding tumour downstaging and sphincter preserving surgical resection rate in low rectal cancer post neoadjuvant CRT. [Table: see text]