bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant therapy for pancreatic cancer in patients older than age 75.
Authors: Miura John Thomas , Krepline Ashley N , Duelge Kaleb D , George Ben , Ritch Paul S. , Erickson Beth , Thomas James P. , Mahmoud Anna , Quebbeman Edward J , Turaga Kiran , Johnston Fabian McCartney , Christians Kathleen K. , Gamblin T. Clark , Evans Douglas B. , Tsai Susan 
Published: February 2017

287 Background: Multiple treatments in series may be difficult for older patients (pt) to tolerate. We sought to examine the outcomes associated with neoadjuvant therapy in older pt with resectable (R) or borderline resectable (BLR) pancreatic cancer (PC). Methods: Pt ≥75 years (O) with those <75 (Y) with R or BLR PC receiving neoadjuvant therapy from 2008-2012 were identified. Clinicopathologic and treatment data were abstracted. Completion of all therapy was defined as the receipt of neoadjuvant therapy followed by surgical resection. Results: We identified 77 (42.5%) R and 104 (57.5%) BLR pt; 29 (16%) were ≥ 75 years. Higher Charlson Comorbidity Index (CCI) (median CCI 4 vs. 2, p<0.01) and more hospitalizations during neoadjuvant therapy (50% vs. 28%, p=0.04) were associated with O vs. Y pt. Older pt were less likely to complete all therapy as compared to Y pt (72.4 vs. 89.5%, p<0.01). Poor performance status was the most common reason for failure to complete all therapy in O vs. Y pt (17.2% vs. 0.7%; p<0.01). Higher CCI (OR 0.25; 95% CI: 0.08-0.74, p=0.01) and higher clinical stage (OR 0.17; 95%CI: 0.06-0.48, p<0.01) were associated with failure to complete all therapy. Of the 138 pt that completed all therapy, no significant differences in complication rates (15 vs. 15.3%, p=0.33), median length of hospital stay (10 vs. 9 days, p=0.29), 30 day readmission rates (10 vs. 11.9%, p=0.81), or median overall survival (24.3 mo vs. 36.7 mo, p=0.20) were observed between O vs. Y pt. Conclusions: After neoadjuvant therapy, 25% of pt ≥ 75 years of age will not undergo surgical resection. The most common reason for not completing all therapy is a decline in performance status. Whether neoadjuvant therapy improves the selection of older pts who should not undergo an operation or prevents successful resection of pt who may have tolerated an operation is unclear. With evolving paradigms of treatment sequencing, the management of PC pt with advanced age will require further assessment.
Efficacy and safety of FOLFIRINOX in patients with metastatic pancreatic cancer.
Authors: Metges Jean Philippe , Ramée Jean François , Douillard Jean-Yves , Boucher Eveline , Faroux Roger , Guerin-Meyer Veronique , Cumin Isabelle , Miglianico Laurent , Le Roux Catherine , Dupuis Olivier , Porneuf Marc , Lam You Heng , Achour Nacredine , Etienne Pierre-Luc , Cojocarasu Oana , Corbinais Stephane , Deguiral Philippe , Geslin Guillaume , Campion Loic , Grude Francoise 
Published: February 2017

305 Background: FOLFIRINOX, one of the gold standard in metastatic pancreatic cancer as first-line therapy for patients under 76 years with PS 0-1, good haematological and renal function and a subnormal bilirubin level (Prodige 4 criteria), was analysed in Brittany (B) and Pays de la Loire (PL) in routine clinical practice. Methods: Our aim is to evaluate the use of Folfirinox between July 2010 and December 2012 in B/PL. Results: Data of 340 patients have been studied (198 men, median age 63 years [29-81]). 208 patients were metastatic at diagnosis (liver 67%). 62 primary tumors were resected and 51 patients had received previous adjuvant chemotherapy (gemcitabine, n=48). The median progression free survival PFS and overall survival OS were respectively 6.80 months IC95% [6.18-7.43] and 10.97 months IC 95% [9.56-11.83]. Patients could be divided into 4 groups : Group 1 composed of patients treated according to Prodige 4 trial (n=242), Group 2 1st line metastatic patients with at least one Prodige 4 non-eligibility criterion (n=25), Group 3 locally advanced patients (n=59) and Group 4 by Folfirinox in 2ndline (n=14). The median number of cycles was 9 [1-27] in Group 1 and 6 [1-12] in Group 2. Clinical benefit was 65% (group 1) vs 56% (group 2). During treatment, 81% of patients had a dose adjustment (Group 1) vs 72% (Group 2) and 32% vs 40% presented grade III/IV toxicity (mostly neuro- or haematotoxicity). Median PFS were respectively in Group 1 vs Group 2 : 6.54 months IC95% [5.98-7.29] vs 4.14 [1.68-6.21] (p=0.0107) and median OS :10.91 months IC 95% [8.94-12.02] vs 7.0 IC95% [4.01-11.20] (p=0.0166). For Group 3 and 4, median OS were respectively 11.24 months [10.0-15.01] vs 11.50 [4.83-14.09]. Others results will be shown at the meeting. For Group 1, stopping treatment before progression induced significatively better median PFS and OS than going on treatment until progression : PFS : 8.25 IC95[7.52-8.74] vs 3.48. IC95 [3.09-4.44] (p<0.0001) and OS : 12.78 months IC95 [11.60-15.54] vs 7.62 IC95 [6.44-9.49] (p<0.0001). Conclusions: Our results for Group 1 are relatively consistent with those of Prodige 4: objective response rate (39% vs 32%), PFS (6.5 vs 6.4 months) and OS (10.9 vs 11.1 months). Non eligibity for Prodige 4’s criteria decreases PFS and OS significantly.
A randomized phase I/II study of everolimus, irinotecan, and cetuximab versus capecitabine and oxaliplatin in gemcitabine-resistant patients with pancreatic cancer.
Authors: Bjerregaard Jon Kroll , Ladekarl Morten , Farr Katherina Podlekareva , Vestermark Lene Weber , Jensen Helle Anita , Pfeiffer Per 
Published: February 2017

337 Background: Little evidence exists on 2nd line therapy for gemcitabine resistant patients. The combination of oxaliplatin (Ox) and 5-FU has shown efficacy in small trials. We wanted to establish a tolerable dose of the combination of irinotecan, cetuximab and everolimus(ICE), and test it vs. the combination of capecitabine (Cap) and Ox in a randomized phase I/II setting. Methods: Patients were initially recruited in a 3+3 dose finding design with an expanded MDT cohort. After establishing MDT; patients were randomized between ICE (at MDT-1) and CapOx (Cap: 1250 mg/m2 BID and Ox: 70 mg/m2q14d). Patients that progressed could cross-over to the other arm. (NCT01042028). Results: Between January 2010 and November 2012, 40 patients were recruited. Due to DLT toxicity (mainly mucositis) at dose level 1 of the phase I trial, the protocol was amended and patients were treated at dose level -1. Ten patients were safely treated at this dose. The final dose for everolimus was 2.5 mg q1d, for irinotecan 180 mg/m2 q14d and 500 mg/m2q14d for cetuximab. At this dose level patients were randomized to either ICE or CapOx. Planned accrual was 90 patients, but due to the emergence of FOLFIRINOX and slow accrual, the study was terminated after randomization of 26 patients. One patient died before randomization. Median PFS for the ICE regime was 3.8 months (2.5-7.8), CapOx 3.5 (1.7-5.3) p=0.72. Median OS for ICE was 7.7 (4.5-11.8) and for CapOx 4.5 (2.2-7.4) p=0.04. Six patients crossed from CapOx to ICE, and 3 patients from ICE to CapOx upon progression. RR for ICE was 25% (5-57), CapOx 29% (8-58). Toxicity grade 3+ in the ICE regime was acne-like-rash (20%), fatigue (16%), infection (16%) and emboli (12%). CapOx was associated with grade 3+ neuropathy (21%), emboli (14%), pain (21%) and PPE (14%). Conclusions: The triple combination of ICE displayed similar PFS but significantly increased OS compared to CapOx. Both regimes displayed cancer activity with acceptable response rates. Toxicity was manageable. Due to early termination no solid conclusions can be drawn. Selected patients may benefit from dual-targeted therapy. Clinical trial information: NCT01042028.
The relationship between systemic inflammation-based prognostic scores and body composition analysis in colorectal cancer patients.
Authors: Douglas Euan , Richards Colin H. , Roxburgh Campbell S. D. , Horgan Paul G. , Mcmillan Donald C. 
Published: February 2017

407 Background: Weight loss in cancer is increasingly recognised as part of syndrome associated with chronic activation of the systemic inflammatory response (McMillan DC, 2009). The aim of the present study was to examine the relationship between systemic inflammation based prognostic scores (SIBPS) and CT measured parameters of body composition in patients with primary operable colorectal cancer (CRC). Methods: 303 patients with primary operable CRC who underwent resection with curative intent (2003-2012) were studied. Image analysis of CT scans was used to measure total fat index (cm2/m2), subcutaneous fat index (cm2/m2), visceral fat index (cm2/m2) and skeletal muscle index (cm2/m2). SIBPS included the Glasgow Prognostic Score (mGPS), Neutrophil: Lymphocyte ratio (NLR), Platelet: Lymphocyte Ratio (PLR), Prognostic Index (PI), and Prognostic Nutritional Index (PNI). Results: In all patients there was a significant association between lower BMI and skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p=0.028 and p<0.001), NLR (p=0.004 and p=0.002), and PNI (p=0.001 and p=0.022). In male patients there was a significant association between lower BMI, total fat mass and skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p= 0.027, p=0.048 and p=0.001), NLR (p=0.002, p=0.034 and p=0.003), and PNI (p=0.003, p<0.001 and p0.048). In female patients total body fat was associated with the PLR (p=0.001) and PNI (p=0.009) but only the mGPS (p=0.007) and the PI (p=0.013) were associated with reduced skeletal muscle. Conclusions: The present study highlights a consistent association between lower BMI and skeletal muscle mass and the presence of a systemic inflammatory response. These results are consistent with the hypothesis that chronic activation of the systemic inflammatory response results in the loss of lean tissue and that ultimately compromises survival in patients with CRC. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12:223-6.
Association between ColDx assay result and recurrence-free interval in stage II colon cancer patients on CALGB (Alliance) 9581.
Authors: Niedzwiecki Donna , Frankel Wendy , Venook Alan Paul , Ye Xing , Friedman Paula N. , Goldberg Richard M. , Mayer Robert J. , Colacchio Thomas Anthony , Kennedy Richard D. , Davison Timothy , O'Brien Eamonn J. , Mulligan Jude , Johnston Patrick G. , Harkin D. Paul , Schilsky Richard L. , Bertagnolli Monica M. , Innocenti Federico 
Published: February 2017

455 Background: Only 15-25% of pts with stage II colon cancer (CC) experience recurrence and conventional staging methods neither allow accurate identification of low (L) and high-risk (H) subgroups nor predict benefit of adjuvant chemotherapy. The ColDx assay (Almac Diagnostics) is a 634-probeset gene expression signature shown to be independently prognostic for recurrence-free interval (RFI). The objective of this study was to assess the ability of ColDx to classify stage II CC pts at L- and H-risk of relapse. Methods: This validation study was conducted using formalin fixed paraffin embedded biospecimens and clinical data from CALGB 9581, a phase III trial of edrecolomab v. observation in pts with normal risk, stage II CC. 1,454 CALGB 9,581 pts met eligibility criteria. A case-cohort sampling design was used to randomly select (RS) 514 pts from 901 eligible pts with available tissue; supplemented by 49 non-RS recurrent pts (total 563). Risk status for each pt was based on a positive or negative ColDx score using a pre-specified cutpoint, 0.4377. The Self Prentice method was used to test the association between ColDx categories and RFI (distant recurrence or death due to primary disease). Results: Initial results in 563 pts were erroneous due to a quality failure in a batch of reagent. 524 samples were re-labeled, re-ordered, and re-assayed using reagents that passed quality control (36 samples had insufficient material; 95 failed ColDx QC). Final analysis comprised 393 pts, 360 RS (58 events; 16%); 33 non-RS events. 216 pts (55%) were predicted H (62 events); 177 (45%) pts were predicted L (29 events). H pts exhibited significantly worse RFI (univariable hazard ratio (HR), 2.0; 95% CI, 1.3-3.3; p < 0.01). ColDx remained significant after adjustment for prognostic factors; HR, 2.1 (95% CI, 1.3-3.4; p < 0.01). Conclusions: The ColDx assay result is associated with RFI in the CALGB 9,581 sub-sample and is independent from other prognostic factors, including MSI. Further investigation is needed to establish the role of this classifier in guiding treatment decisions in this patient population.
Molecular subtyping of colorectal cancer to identify a mesenchymal tumor type that might benefit from TGF-beta pathway inhibition.
Authors: Salazar Ramon , Roepman Paul , Willems Stefan M. , Brunen Diede , Kellner Udo , Midgley Rachel A , Bernards Rene , Simon Iris M. 
Published: February 2017

456 Background: Currently, most colorectal cancer (CRC) patients receive chemotherapy treatment, even though many patients do not benefit. Therefore, a better understanding of the biology is required to identify those patients who will benefit from chemotherapy and to find a more tailored therapy plan for all other patients. Methods: A molecular subtype classification was developed using full genome expression data of 188 stage I-IV CRC patients and validated in 543 stage II and III patients. Subtypes were correlated to clinical factors, prognosis and treatment benefit (stage III). To determine whether TGF-β signaling is elevated in the tumors, 78 patient biopsies were analyzed for p-SMAD2/3 expression using immunohistochemistry. To analyze the effect of TGF-β activation, we studied the effects of MED12 suppression in SKCO-1 CRC cells under treatment with Cisplatin, Oxaliplatin or 5-FU. Results: We developed a diagnostic test that allows the classification of colorectal cancer tumors into different intrinsic molecular subtypes (A-, B-, C-type). The heterogeneity of these subtypes is largely based on 3 biological hallmarks of the tumor: an epithelial-to-mesenchymal transition, deficiency in mismatch repair genes resulting in a high mutation frequency associated with MSI, and cellular proliferation. Especially the C-type (~15% of CRC tumors) is of clinical interest, as C-type patients have the worst outcome, a mesenchymal phenotype and show no benefit from chemotherapy treatment in our patient set or a public dataset. The C-type subgroup has elevated TGF-β signaling, as shown by TGF-beta and TGF-beta receptor over-expression (TGFB1, p=0.0012; TGFBR1, p=0.0005) and increased phopho-SMAD2/3 staining in the tumor cells (1.9-fold, p=0.0002). In cell line experiments, we show that up-regulation of TGF-β signaling by MED12 knockdown resulted in resistance against chemotherapy by preventing apoptosis. Conclusions: The molecular subtypes differ largely in prognosis and response to chemotherapy. A treatment strategy combining standard drugs with agents suppressing TGF-β signaling might benefit C-type patients.
Comparison of ColoPrint risk classification with clinical risk in the prospective PARSC trial.
Authors: Salazar Ramon , Capdevila Jaume , Rosenberg Robert , de Waard Jan Willem , Glimelius Bengt , Bibeau Frederic , Klaase Joost , Van der Hoeven Jacobus JM , Midgley Rachel A , Chang George J. , Bachleitner-Hofmann Thomas , Asano Michio , Ziebermayr Reinhard , Levine Edward Allen , Deck Kenneth B. , Sington Jamie , Law Wai Lun , Shbeeb Imad , Stork Lisette , Marshall John 
Published: February 2017

465 Background: The 18-gene expression profile, ColoPrint, has been developed and validated for identifying risk of recurrence in patients with early-stage colon cancer (CC). In a pooled stage II validation study ColoPrint identified 63% of patients as Low Risk with a 3-yr recurrence-free survival (RFS) of 93% while High Risk patients had a 3-yr RFS of 82% with a HR of 2.7 (p=0.001). PARSC is a prospective study for the assessment of recurrence risk in stage II CC patients using ColoPrint. ColoPrint classification is compared to NCCN risk classification. Methods: The study enrolled 468 patients with histologically proven stage II CC from 31 institutes in Europe, the United States, and Asia between October 2008 and May 2013. Synchronous tumors were excluded. ColoPrint results were not disclosed to the physician and patient. Treatment was at the discretion of the physician, adhering to NCCN approved regimens or a recognized alternative. A McNemars test is performed to compare ColoPrint with NCCN risk classification. A p value ≤ 0.05 indicates the two tests differ significantly. Results: ColoPrint classified 320 (68%) patients as Low Risk and 148 (32%) as High Risk. 89 patients (19%) received adjuvant chemotherapy. In the ColoPrint Low Risk group, 57 (18%) patients received adjuvant chemotherapy while 32 (22%) of ColoPrint High Risk patients received chemotherapy. According to NCCN high risk factors (T4, high grade (exclusive of MSI-H), lymphovascular/perineural invasion, perforation/obstruction, <12 nodes examined, positive margins) 234 (50%) patients were NCCN Low Risk and 234 were NCCN High Risk. 72 (31%) of the NCCN Low Risk patients are ColoPrint High Risk. 158 (68%) of the NCCN High Risk patients are ColoPrint Low Risk. MSI-status was assessed in 86 (18%) patients of which 29 were MSI high and 57 were MSS. All MSI high were classified as ColoPrint Low Risk. Conclusions: The PARSC study is the first prospective study to compare genomic and clinical risk assessment and we observed marked differences between NCCN risk classification and ColoPrint. The clinical validity of these methods will be based on the outcomes at 3 and 5 years. Clinical trial information: NCT00903565. [Table: see text]
The relationship between tumor cell density in the pretreatment biopsy and survival after chemotherapy in OE02 trial esophageal cancer patients.
Authors: Hale Matthew D. , Nankivell Matthew Guy , Mueller Wolfram , West Nicholas P. , Stenning Sally Patricia , Wright Alexander I. , Treanor Darren , Langley Ruth E. , Ward Lindsay C. , Allum William H. , Cunningham David , Hayden Jeremy D. , Grabsch Heike I. 
Published: February 2017

49 Background: Neoadjuvant chemotherapy (chemo) followed by surgery is the standard treatment for UK patients with resectable oesophageal cancer [OeC] since the OE02 trial (Allum et al. J. Clin. Oncol, 2009), yet some patients receive no benefit from chemo. We investigated whether tumour cell density (TCD) in the pre-chemo biopsy can predict patient benefit from chemo among OE02 patients. Methods: Hematoxylin and eosin stained diagnostic biopsy slides from 281 OE02 trial OeC patients reflective of the whole trial population based on patient characteristics and survival (70% adenocarcinoma, surgery alone: n=141; chemo followed by surgery: n=140) were digitized. TCD (percentage of epithelial tumor cells/viable tumor mass) was quantified by point counting and cut offs for overall survival analyses were identified. The relationship between TCD and clinicopathological data and its predictive value (heterogeneity of treatment effect) were assessed. Results: TCD ranged between 16-99% with 85% of cases in the 25-75% range. TCD was initially divided into tertiles. The treatment hazard ratio (HR) was examined within each tertile showing evidence of heterogeneity with clear benefit from chemo seen only in the middle tertile. Cut offs were refined through examination of treatment HR within TCD quintiles. Treatment HRs were 1.25 (95%confidence interval 0.66, 2.35), 1.94 (1.39, 2.71) and 0.65 (0.36, 1.18), respectively, for TCD <40% (n=46), 40-70% (n=183) and >70% (n=52), suggesting that only patients with 40-70% TCD benefit from neoadjuvant chemo (HR>1 favours chemo, heterogeneity p=0.006). Low Mandard tumor regression grade (1-3 versus 4-5) was related to a lower biopsy TCD (median: 47% versus 56%, p=0.0402). Conclusions: TCD appears to be able to predict survival benefit from neoadjuvant chemo in OeC patients and is associated with tumour regression. Our result requires validation in an independent dataset to confirm its potential clinical utility. If validated, TCD measurement in the diagnostic biopsy could be used to determine which OeC patients would benefit from neoadjuvant chemo versus those who would benefit most from management with surgery alone.
The effect of postoperative morbidity on survival after resection for gastric adenocarcinoma: Results from the U.S. Gastric Cancer Collaborative.
Authors: Jin Linda X. , Moses Lindsey E. , Yan Yan , Squires Malcolm Hart , Weber Sharon M. , Bloomston Mark , Poultsides George A. , Votanopoulos Konstantinos I. , Pawlik Timothy M. , Hawkins William G. , Linehan David , Strasberg Steven M. , Archer Alexandra W. , Ejaz Aslam , Kooby David A. , Schmidt Carl Richard , Swords Doug S. , Worhunsky David J. , Maithel Shishir Kumar , Fields Ryan C. ,   US Gastric Cancer Collaborative
Published: February 2017

5 Background: The negative impact of postoperative complications (POCs) on survival is well documented for many cancer types, but has not been well described in gastric cancer. Here, we evaluated the effect of POCs on survival after surgery for gastric cancer in a cohort of patients from a multi-institutional database. Methods: Patients who underwent surgery with curative intent for gastric adenocarcinoma between 2000-2012 from participating institutions of the U.S. Gastric Cancer Collaborative were analyzed. Patients who died within 30 days of surgery were excluded. Ninety-day postoperative complication data were collected. Survival probabilities were estimated by Kaplan-Meier analysis and compared using the log-rank test. Results: A total of 853 patients from seven institutions met inclusion criteria. Median follow-up was 32 months. The overall complication rate was 40% (n=344). The most frequent complications were: infectious (25%, including surgical site infection [8%]), and anastomotic leak (6%). 7% of patients underwent reoperation during the same hospitalization. Five-year overall survival (OS) for patients without perioperative complications was 54%, compared with 39% for patients with POCs (p=0.001). Disease free survival (DFS) at five years was 61% for patients without POCs compared to 49% in patients with POCs (p=0.002). Patients without POCs were significantly more likely to receive adjuvant therapy (55% vs 42%; p<0.001). Conclusions: In a large, multi-institutional cohort, POCs were associated with decreased survival in patients undergoing surgery for gastric adenocarcinoma. This may be due, in part, to the negative impact of complications on the receipt of adjuvant therapy. Efforts aimed at reducing perioperative morbidity are important not only for short-term surgical outcomes, but also for enhancing long-term oncologic outcomes in patients with gastric cancer. [Table: see text]