bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rectal versus left-sided colon cancers: Clinicopathological differences observed in a pooled analysis of 4,182 patients enrolled to 8 clinical trials from the ARCAD database.
Authors: Salem Mohamed E. , Yin Jun , Renfro Lindsay A. , Weinberg Benjamin Adam , Maughan Tim , Adams Richard , Van Cutsem Eric , Falcone Alfredo , Tebbutt Niall C. , Seymour Matthew T. , Diaz-Rubio Eduardo , Aranda Enrique , Bokemeyer Carsten , Heinemann Volker , De Gramont Aimery , Grothey Axel , Marshall John , Sargent Daniel J. 
Published: March 2017

675 Background: Recent retrospective analysis of CALGB/SWOG 80405 showed that left-sided colon cancers (LCC) respond differently to biological therapy compared with right-sided tumors. However, differences between rectal cancers (RC) and LCC remain undefined. Herein, we report our exploration of differences between these two groups. Methods: Individual patient data from 4182 patients (pts) with metastatic colorectal cancers, enrolled onto 8 first-line randomized trials, were pooled. Only pts with tumor locations that were clearly defined as LCC (splenic flexure to sigmoid) or RC were included in this analysis. Differences in pt characteristics and disease factors according to LCC vs. RC were identified. The prognostic effect of primary tumor location on OS and PFS was quantified via multivariable Cox proportional hazards modeling stratified by treatment arm within each study and adjusting for age, sex, performance status, and prior surgery. Results: In total, 2,479 (59%) pts with LCC and 1,703 (41%) pts with RC were identified. Pts with RC, compared with LCC, were more likely to be male (68% vs. 62%, p < 0.001), have lung metastases (mets) (56% vs. 37%, p < 0.001), and have 2 or more metastatic sites (64% vs. 60%, p < 0.02), whereas pts with LCC were more likely to have liver mets (84% vs. 76%, p < 0.001). RC had a greater frequency of KRAS mutations (41% vs. 37%, p = 0.04) than LCC but there were no differences in the frequency of BRAF mutations (5% vs. 4%, p = 0.2). In multivariable analysis, no differences in OS or PFS were observed between pts with LCC vs. RC. While risk of death did not differ by primary tumor location, across all pts with LCC or RC, those with liver mets had a 17% increased risk of death compared to those with lung mets (HR = 1.17, p = 0.03) after adjusting for effects of other variables. Forthcoming prognostic analysis of LCC vs. RC within grouped backbone treatments (e.g., FOLFOX and FOLFIRI) is underway. Conclusions: Tumors arising in the rectum may carry clinical and molecular features that are distinct from LCC. Further investigations are warranted to determine whether RC should be treated with the same chemo backbone and biological therapy as LCC.
Optimal prophylactic method of venous thromboembolism for gastrectomy in Korean patients: Prospective randomized controlled trial.
Authors: Jung Yoon Ju , Song Kyo Young , Seo Ho Seok , Park Cho Hyun 
Published: March 2017

7 Background: This study was conducted to evaluate the incidence of VTE after surgery gastric cancer patients and determined the optimal method of thromboembolic prophylaxis in Korean patients. Methods: In this trial, 682 patients were assigned to 2 groups; an intermittent pneumatic compression (IPC) with or without 40 mg of enoxaparin. The primary outcome was VTE incidence within 30 days of surgery; defined as deep vein thrombosis (DVT) or documented pulmonary thromboembolism (PTE). The duration of follow-up was 6 months. Results: The primary outcome was assessed in 666 patients. The overall incidence of VTE was 2.10%; that of IPC group was significantly higher than the IPC plus enoxaparin group. Among 14 patients with VTE; 13(92.8%) patients were diagnosed with asymptomatic DVT, 1 patient was diagnosed with PTE. The incidence of bleeding complication was significantly higher in IPC plus enoxaparin group. By month 6, no patient died. Conclusions: Although the incidence of VTE was significantly lower in IPC plus enoxaparin group, symptomatic event was extremely rare and no mortality was observed. In Korean patient with gastric cancer does not need conventional prophylaxis using heparin because of the extremely lower incidence of symptomatic VTE and relatively higher incidence of bleeding complication. Clinical trial information: NCT01448746. [Table: see text]
Patterns of care for synchronous rectal cancer with liver-only metastasis: Results from the South Australian registry of metastatic colorectal cancer.
Authors: Roy Amitesh Chandra , Karapetis Christos Stelios , Piantadosi Cynthia , Townsend Amanda Rose , Padbury Rob , Carruthers Scott , Maddern Guy , Roder David , Moore James , Price Timothy Jay 
Published: March 2017

701 Background: Management of rectal cancer with synchronous liver metastasis is not clear. Optimal timing of radiotherapy, chemotherapy, resection of primary and liver metastasis is debated. Methods: The South Australian Registry for metastatic colorectal cancer has entered all patients with mCRC since 1st February 2006. Registry data were analyzed to assess patient characteristics, therapy received and outcomes for patients with liver only metastasis and synchronous rectal or colon primary. KM analysis was used for survival outcomes. Results: 2677 patents had synchronous mCRC. 42% (n = 1125) had liver only metastasis (primary: 275 rectal/850 colon). The main differences between rectal/liver vs. colon/liver were: more males (68.7% v 57.8%, p = 0.001), younger age (65.8 v 73.3 years, p < 0.001) and less poorly differentiated histology (14.2% v 24.1%, p = 0.003). The rate of no surgery on the primary was 21.4% for rectal cancers v. 36% for colon (p ≤ 0.001). Liver surgery rates in both groups was similar (28.4% v 23.0% (p = 0.075). Out of the 275 rectal cancer patients, 100 (36.3%) had rectal surgery, 83 (30%) had chemo-RT and 47 (17%) had chemotherapy +/- targeted therapy as initial treatment, 45 (16%) patients had no treatment. Median OS of rectal cancer patients based on their initial treatment was 33.2m (Chemo-RT) vs. 22.2m (surgery) vs. 19.2m (chemotherapy +/- targeted therapy, p < 0.001). The mOS for rectal group was 22.8m v. 14.8m (p = 0.001) for colon group. For patients who had liver surgery mOS was 60.7m vs. 67.1m respectively. Survival was better if primary was rectum or left colon vs. right colon (mOS 18.3m vs 18.8m vs 10.2m respectively p < 0.001). Resection of the primary occurred first in all patients who had liver resection. Conclusions: Patients with synchronous rectal cancer with liver only metastases have better survival compared to those with colon cancer and liver only metastases. Where surgery is possible, OS is equivalent between the two groups and in our registry population surgery on the rectal primary or chemo-RT were found to be the preferred initial treatment for rectal cancer patients with synchronous liver metastases.
Cetuximab (CTX) in first-line treatment of elderly patients with metastatic colorectal cancer (mCRC), KRAS wild type: French multicentre prospective community-based registry and results.
Authors: Mineur Laurent , François Eric , Phelip Jean Marc , Guimbaud Rosine , Plassot Carine , Smith Denis Michel , Miglianico Laurent 
Published: March 2017

760 Background: Pts included in clinical trials represent the unusual population in mCRC. This study aims to provide oncologist with a better understanding of the potential benefit of CT with CTX in older patients with mCRC KRAS wild type and evaluate prognostic variables on the PFS including the age. Methods: Premium cancer study is a French multicentre prospective community-based registry. 493 pts enrolled and 487 included between September 2009 to March 2012 from 94 French centers and physicians. Pts had to provide written informed consent and protocol submitted to regulatory authorities. Predefined efficacy endpoints was PFS. CTX was administrated at 250 mg/m2 weekly (n=100; 20.3%) or 500 mg/m2 every 2 weeks (n=380;77,2%), other n=13; 2.5%) CT regimen choice was at physician’s discretion.. The main analysis is PFS as well as analysis of prognostic factors of this PFS (29 items including age (< 65 years n=229; 65-74 years n= 165.; ≥75years n=93). Univariate analysis was performed for each covariate, PFS was estimated by Kaplan-Meier curves and compared by log-rank test. univariable Cox regression analysis was used to assess the association between each variable and outcome. Multivariable stepwise Cox models were then fitted for final variable selection of prognostic factors on PFS. Results: Univariate significant prognostic factors for PFS are OMS (0-1 vs 2-3), Tobacco, Site of tumor (right vs other), Number of metastatic organ (1 vs 2-3), Resecability of metastatic disease defined before CT (definitively non resectable metastases vs possible resectable), Surgery of mCRC, folliculitis or xerosis or paronychia grade 0-1 vs 2-4. Age was unidentified as a prognostic factor in univariate analysis. Four factors were independently associated with a better PFS: xerosis [hazard ratio (HR0,651); 95% confidence interval (CI) 0,494-0,857], (WHO PS) 0–1 (HR0,519 ; 95% CI 0,371–0,726) and folliculitis (HR 0,711; 95% CI0,558–0,956) metastases surgery 0,287(CI 0,205-0,403). Conclusions: CTX in combination with standard CT is effective, age is not identified as a prognostic factor for the PFS. Both groups of pts based on age benefit from CTX.
Free and bound plasmin in esophageal tumors and surrounding tissues in men and women.
Authors: Kit Oleg Ivanovich , Frantsiyants Elena Mikhaylovna , Kozlova Larisa , Pogorelova Yulia A. , Chugunova Natalya , Kolesnikov Evgeniy N. , Averkin Michail , Sanamyants Sergey V. 
Published: March 2017

84 Background: Esophageal squamous cell carcinoma (ESCC) is 2 to 8 times more frequent in men than in women. Tumor progression is directly connected with plasmin participation in destruction of the extracellular matrix and the basement membrane surrounding tumor. The purpose of the study was a comparative analysis of plasminogen (PG), free plasmin (P) and plasmin bound in complex with α2-antiplasmin (PAP) in ESCC tissues of men (M) and women (W). Methods: ESCC tumor tissue (T) and its perifocal zone (PZ) were studied by the ELISA (19 men and 8 menopausal women aged 58-72, st II, G2, T2-3N0-1M0-1). The results were compared to the histologically unchanged tissue from the resection line (RL). PG, P and PAP were measured in 10% homogenates prepared in sterile saline, with recalculation per 1 g wet tissue). Data were processed using Statistica 10. Results: PG content in RL was 1.5 times higher in M than in W. PG in T of M was decreased by 2 times, in W by 3.3 times, in PZ of M – by 2.9 times, in W – by 2.3 times. PG in T and PZ of M was 2.5 and 1.2 times higher than in W. P content in RL of all patients was significantly lower than in other samples, but 1.4 times higher in M than in W. P in T and PZ of M was 3 and 2.5 times higher than in RL, in T and PZ of W – 3.5 and 2.8 times higher than in RL. Significant differences were observed between P levels in T (but not in PZ): 1.3 times higher in M than in W. PAP content was relatively constant in all tissues, with a slight prevalence in T and PZ of W. P/PAP ratio was elevated in all tissues compared to RL, but in T and PZ of M it was 1.4 and 1.2 times higher than in W. P/PAP in RL of M was 1.4 times higher than in W. Conclusions: The results show a higher aggressiveness of P in PZ and T of M, while P formation in T of W was less active. We reported on a higher content of PG activators in T and PZ of M, and taking into account the morbidity statistics and literature data we suppose the effect of androgens on the conditions of PG activation into P and manifestation of its biological features. P in PZ of both M and W can contribute in the expansion of a “tumor field”. P binding in PAP complex was similar in all studied tissues.
Combining pembrolizumab and palliative radiotherapy in gastroesophageal cancer to enhance anti-tumor T-cell response and augment the abscopal effect.
Authors: Chao Joseph , Chen Yi-Jen , Frankel Paul Henry , Chung Vincent M. , Lim Dean , Li Daneng , Fakih Marwan , Lee Peter P. 
Published: March 2017

TPS220 Background: Pembrolizumab has demonstrated encouraging preliminary evidence of activity in small cohorts of gastroesophageal cancer patients (pts) when selected for tumor PD-L1 overexpression. Strategies should be further developed to enhance the potency of PD-1 inhibitors, even in pts whose tumors are not considered to have detectable PD-L1 expression. The abscopal effect is a rarely observed though well annotated clinical phenomenon in cancer radiotherapy (RT), in which non-irradiated metastatic lesions are noted to regress after radiation to the primary tumor site. In preclinical models, this phenomenon has been attributed to immune-mediated effects, while RT has been observed to increase tumor PD-L1 expression. This lends credence to ongoing efforts to combine RT and immune checkpoint inhibition. We present the study design for a phase II trial combining pembrolizumab and palliative RT in metastatic gastroesophageal squamous cell and adenocarcinoma pts. Methods: A target accrual of 14 pts will be assigned to palliative RT of 30 Gy over 10 fractions for symptoms from their primary tumor or a single target metastatic site in combination with fixed dose pembrolizumab 200 mg every 3 weeks. Symptomatic brain metastases will be excluded. Pembrolizumab will be continued until disease progression, intolerable toxicity, or 35 administrations (~2 years). Pts will be required to undergo sequential biopsies of a non-target metastatic site (inclusive of malignant ascites) with timepoints occurring pre-treatment and ~21 days after completion of RT. Biomarkers of immune response and overall response rate (RECIST1.1, irRECIST) will be a composite primary endpoint; progression-free and overall survival, and toxicities will be secondary endpoints. Quantitative spatial image analyses of biopsy samples will be performed to examine changes in tumor cell-stromal interactions inclusive of CD4, CD8, Treg, and MDSC populations as well as tumor PD-L1/PD-1 expression levels. The results will assist in determining mechanisms of response and resistance to combination RT and PD-1 targeting strategies. Clinical trial information: NCT02830594.
SWOG S1505: A randomized phase II study of perioperative mFOLFIRINOX vs. gemcitabine/nab-paclitaxel as therapy for resectable pancreatic adenocarcinom.
Authors: Sohal Davendra , McDonough Shannon L , Ahmad Syed A. , Gandhi Namita , Beg Muhammad Shaalan , Wang-Gillam Andrea , Guthrie Katherine A , Lowy Andrew M. , Philip Philip Agop , Hochster Howard S. 
Published: March 2017

TPS508 Background: Clinical outcomes after curative therapy for resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. Series show that 70-85% of patients die of systemic recurrence. Improved overall survival (OS) in the metastatic setting with the use of multi-agent chemotherapy regimens (FOLFIRINOX, gemcitabine/nab-paclitaxel) holds the promise of progress in the curative setting as well. However, aggressive systemic therapy is usually not feasible after major pancreatic surgery. Therefore, early control of systemic disease by increased preoperative chemotherapy may improve outcomes. Furthermore, the perioperative platform facilitates early identification of patients with chemotherapy-resistant tumors and allows prospective biomarker studies in the future. Methods: This is a randomized phase II study intended to choose the most promising perioperative regimen to test in a larger trial. Eligibility requirements include patients with an ECOG PS of 0 or 1, a confirmed histopathologic diagnosis of PDA, and resectable disease as confirmed by central radiology review: no involvement of the celiac, common hepatic, or superior mesenteric arteries (and, if present, variants); no involvement, or < 180° interface between tumor and vessel wall, of the portal or superior mesenteric veins; patent portal vein/splenic vein confluence; no metastases. Treatment includes 12 weeks [either mFOLFIRINOX (5-fluorouracil infusion (no bolus), irinotecan, oxaliplatin), or gemcitabine/nab-paclitaxel] of preoperative chemotherapy, followed by surgical resection and 12 weeks of identical postoperative chemotherapy. Primary outcome is 2-year OS, using a “pick the winner” design with minimum activity requirements. Assuming a historical 2-year OS of 40% and a 58% alternative hypothesis, 88% power, a 1-sided α of 0.05, and 100 eligible patients, the design provides a 90% probability of selecting the better regimen. The study opened through the National Clinical Trials Network (NCT02562716), and is supported by NIH/NCI/NCTN grants CA180888, CA180819, CA180821, CA180833. Clinical trial information: NCT02562716.
Gemcitabine and cisplatin plus ramucirumab or merestinib or placebo in first-line treatment for advanced or metastatic biliary tract cancer: A double-blind, randomized phase II trial.
Authors: Sama Ashwin Reddy , Denlinger Crystal Shereen , Vogel Arndt , He Aiwu Ruth , Bousmans Nathalie , Zhang Wei , Walgren Richard A. , Valle Juan W. 
Published: March 2017

TPS509 Background: Angiogenesis and aberrant MET signaling are implicated in the pathogenesis and progression of invasive biliary tract cancers (BTC), including adenocarcinomas of the gallbladder, intra- and extra-hepatic bile ducts, and ampulla of Vater. JSBF (NCT02711553) is a phase II, multicenter, randomized, and double-blinded study, designed to evaluate the efficacy and safety of standard of care (SOC) gemcitabine and cisplatin in combination with either ramucirumab (human IgG1 VEGFR2 monoclonal antibody) or merestinib (oral type II MET kinase inhibitor) or respective placebo for the first-line treatment of advanced or metastatic BTC. Methods: Eligible patients with advanced or metastatic BTC will be randomized to oral merestinib 80 mg, oral placebo, intravenous (IV) ramucirumab 8mg/kg, or IV placebo, in a 2:1:2:1 fashion. Randomization will be stratified by primary tumor site, presence of metastases, and geographic region. In addition to the randomly assigned treatment, all patients will receive SOC first-line treatment with up to 8 cycles of IV gemcitabine 1000mg/m2 + cisplatin 25mg/m2 on days 1 and 8 of 21-day cycles. IV ramucirumab and placebo will be given on days 1 and 8 of each cycle; oral treatments will be taken daily. Investigational treatment or placebo may continue past 8 cycles until disease progression or a criterion for discontinuation is met. The primary endpoint is progression-free survival, by intention-to-treat analysis. Target enrollment is 300 patients with primary analysis at 210 events to detect potential superiority of each investigational treatment over pooled control. Secondary endpoints are overall survival, objective response, disease control rate, safety, pharmacokinetics, immunogenicity (ramucirumab), and patient reported outcomes. An exploratory endpoint is to correlate biomarkers with safety and clinical outcome; blood, plasma, serum, and tumor tissue collection is mandatory. The study began in May 2016. Clinical trial information: NCT02711553.
Utilizing total neoadjuvant therapy (TNT) in rectal cancer: NRG-GI002, a phase II clinical trial platform.
Authors: George Thomas J. , Yothers Greg , Hong Theodore S. , Russell Marcia McGory , You Y. Nancy , Parker William , Jacobs Samuel A. , Pogue-Geile Katherine L. , Wu Christina Sing-Ying , Wolmark Norman 
Published: March 2017

TPS814 Background: Improvements in outcomes for locally advanced rectal cancer (LARC) have plateaued due to an inability to consistently deliver adjuvant therapy and thus far ineffective novel therapies. Systematic testing of new chemotherapy and radiation sensitizers are needed to advance treatment outcomes. This randomized phase II modular clinical trial platform utilizes Total Neoadjuvant Therapy (TNT) with parallel experimental arms in LARC. The experimental arms are not intended for direct comparison, but to test a variety of sensitizers or hypotheses in a consistent and relatively homogenous high-risk patient (pt) population with correlative biomarkers. Success of any given experimental arm will be determined by achievement of pathologic endpoints compared to a control arm. Methods: This NCTN multi-arm randomized phase II trial serves as a modular platform to assess novel sensitizers to neoadjuvant chemotherapy and/or chemoradiotherapy (chemoRT) in LARC. Eligibility includes LARC as defined by any ONE of the following criteria: distal location (cT3-4 ≤5cm from the anal verge, any N); bulky (any cT4 or tumor within 3mm of the mesorectal fascia); high risk for metastatic disease (cN2); or not a candidate for sphincter-sparing surgical resection. After randomization, all pts receive neoadjuvant FOLFOX x 4mo → chemoRT (capecitabine with 50.4Gy) → surgical resection 8-12 wks later. Based on promising phase I results, the first experimental arm will assess the activity of veliparib added to standard chemoRT (capecitabine + RT). Primary endpoint is to demonstrate an improvement in Neoadjuvant Rectal Cancer (NAR) score for the experimental arm vs control representing a 20% relative risk reduction in DFS HR and 3-4% absolute OS improvement. Secondary endpoints include comparisons of OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, sphincter function including quality of life, and exploratory assessments of molecular and radiographic predictors of response and distant failure. Target accrual is 79 evaluable pts per arm with additional arms added through rolling protocol amendments. Support: U10 CA-180868, -180822, UG-189867; AbbVie. Clinical trial information: NCT02921256.
KEYNOTE-177: Randomized phase III study of pembrolizumab versus investigator-choice chemotherapy for mismatch repair-deficient or microsatellite instability-high metastatic colorectal carcinoma.
Authors: Diaz Luis A. , Le Dung T. , Yoshino Takayuki , Andre Thierry , Bendell Johanna C. , Koshiji Minori , Zhang Yinghua , Kang S. Peter , Lam Baohoang , Jäger Dirk 
Published: March 2017

TPS815 Background: A subset of colorectal carcinomas (CRCs) are characterized by mismatch repair (MMR) deficiency resulting in microsatellite instability (MSI). MSI-high tumors contain high levels of lymphocyte infiltrates and express the PD-1 immune checkpoint receptor and its ligand, PD-L1. In the phase 2 KEYNOTE-016 study, the anti–PD-1 antibody pembrolizumab demonstrated antitumor activity against MMR-deficient tumors in patients with treatment-refractory metastatic CRC. KEYNOTE-177 (ClinicalTrials.gov, NCT02563002) is an international, randomized, open-label, phase 3 study of pembrolizumab versus standard-of-care (SOC) chemotherapy in first-line MMR-deficient or MSI-high metastatic CRC. Methods: Key eligibility criteria include age ≥18 years, confirmed MSI-high or MMR-deficient metastatic CRC, ECOG PS 0-1, no active autoimmune disease or brain metastases, and no prior therapy for metastatic disease. ~270 patients will be randomly assigned 1:1 to receive either pembrolizumab 200 mg every 3 weeks or investigator's choice of SOC chemotherapy (mFOLFOX6 or FOLFIRI alone or in combination with bevacizumab or cetuximab, chosen before randomization). Treatment is to continue until progressive disease (PD), unacceptable toxicity, patient/investigator decision, or completion of 35 cycles (pembrolizumab only). Response is to be assessed every 9 weeks per RECIST v1.1 by central imaging vendor review and per RECIST adapted for immunotherapy response patterns. Eligible patients may continue pembrolizumab beyond initial RECIST-defined progression. Patients in the SOC arm who have PD and meet crossover criteria may be eligible to receive pembrolizumab for up to 17 treatment cycles. AEs are to be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. Patients are to be followed up for survival every 9 weeks. The primary end point is PFS per RECIST v1.1; key secondary end points include OS and ORR. Enrollment in KEYNOTE-177 is ongoing. Clinical trial information: NCT02563002.