bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploratory analysis of adjuvant chemotherapy benefits after preoperative chemoradiotherapy and radical resection for rectal cancer.
Authors: Chang George J. , Park In Ja , Eng Cathy , You Y. Nancy , Kopetz Scott , Overman Michael J. , Rodriguez-Bigas Miguel A. , Skibber John Michael 
Published: March 2020

3556 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). 2-year 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=0.04). 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 the addition of oxaliplatin for PR patients.
Prognostic significance of lymph node retrieval in localized rectal cancer (RC): A registry analysis of 8,964 patients (pts).
Authors: Gill Amandeep , Brunson Ann , Lara Primo , Olson Kristin , Monjazeb Arta , Khatri Vijay P. , Semrad Thomas John 
Published: March 2020

3566 Background: In contrast to colon cancer, the prognostic implications of reduced lymph node retrieval in RC are unclear. We investigated the association between the total number of lymph nodes examined in early stage RC and disease specific survival (DSS) in two cohorts: 1) pts who underwent surgery and adjuvant (ADJ) chemoradiation (chemoXRT), and 2) those who received neoadjuvant (NEO) chemoXRT. Methods: Using the California Cancer Registry, we identified 8,946 pts with stage I – III RC diagnosed from 2000 to 2007. Of these, 4,790 underwent tri-modality therapy: 2,946 patients (61.5%) had NEO chemoXRT and 1,844 patients (38.5%) had ADJ chemoXRT. Multivariate Cox proportional hazards models were constructed for DSS, adjusting for age, sex, race, socioeconomic status, T-stage and lymph node number. DSS was compared between NEO and ADJ cohorts within separate subgroups of pathologic node positive and node negative RC. Results: Although there was no difference in overall DSS between the NEO and ADJ cohorts, the median number of lymph nodes examined was reduced in patients who had undergone NEO chemoXRT (8 vs. 11, p<0.0001). For all pts treated with tri-modality therapy, advancing age and higher T-stage were associated with significantly reduced DSS. Positive lymph nodes were associated with worse DSS regardless of the timing of therapy, although the effect was stronger for residual lymph nodes in the NEO cohort (HR 2.8 vs. 1.8 in ADJ cohort, p<0.001). For node negative pts in the ADJ cohort, increased lymph node retrieval was associated with improved DSS (HR per node 0.952, p=0.017); however, no association between lymph nodes examined and DSS was seen in the NEO cohort (p=0.282). Conclusions: Residual positive lymph nodes in pts treated with NEO chemoXRT are more strongly associated with poorer DSS than in pts treated with surgery and ADJ chemoXRT. NEO chemoXRT dissociates the connection between lymph node retrieval and survival in RC. This finding highlights a key difference between colon and RC and underscores the need for a different interpretation of the pathologic findings after NEO therapy.
The role of TP, TS, and DPD as potential predictors of outcome following capecitabine plus oxaliplatin (XELOX) versus bolus 5-fluorouracil/leucovorin (5-FU/LV) as adjuvant therapy for stage III colon cancer: Biomarker findings from study NO16968 (XELOXA).
Authors: Schmoll Hans-Joachim , Tabernero Josep , Maroun Jean Alfred , De Braud Filippo G. , Price Timothy Jay , Van Cutsem Eric , Hill Mark , Hoersch Silke , Rittweger Karen , Chen David , Haller Daniel G. 
Published: March 2020

3578 Background: In NO16968, XELOX was superior in terms of disease-free survival (DFS) and overall survival (OS) to bolus 5-FU/LV as adjuvant therapy for stage III colon cancer (Schmoll et al. ASCO GI 2012). Three key enzymes appear to have the potential to predict efficacy and/or safety of fluoropyrimidine-based treatment: thymidine phosphorylase (TP), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD). We evaluated the association between baseline TP, TS and DPD and outcome (DFS and OS). Methods: Pts with stage III colon cancer received either XELOX (8 cycles, 24w) or bolus 5-FU/LV (Mayo Clinic, 6 cycles, 24w; Roswell Park, 4 cycles, 32w). The primary study endpoint was DFS; secondary endpoints included OS. TP, TS and DPD expression levels were determined in formalin-fixed, paraffin-embedded tissues by RT-PCR, and the median used as a cut-off point: high (above median) vs. low (below median). Results: The biomarker population included 498 (26%) of 1886 pts entered (XELOX, n=242; 5-FU/LV, n=256). Baseline demographics, tumor characteristics, cancer history and efficacy (DFS and OS) were similar to those in the main study population. Cox regression analysis for DFS (Table). In the XELOX group pts with low DPD and TP levels and a high TP/DPD ratio appeared to have significantly better DFS; this effect was not observed with 5-FU/LV. Subgroup analysis shows that the difference between XELOX and 5-FU/LV was also higher in pts with low DPD levels. Conclusions: These exploratory findings suggest that tumor DPD and TP RNA levels could be used to predict outcomes of adjuvant treatment with fluoropyrimidine/oxaliplatin combinations, and should be validated prospectively. Analysis of the current dataset is ongoing and further details on potential biomarkers will be available. [Table: see text]
Association of genetic variants in obesity-related genes with tumor recurrence in stage II/III colon cancer.
Authors: Ladner Robert D. , Gerger Armin , Zhang Wu , Labonte Melissa Janae , Yang Dongyun , Lenz Felicitas , Lenz Cosima , Bohanes Pierre Oliver , Ning Yan , Winder Thomas , Wilson Peter M.D. , Benhaim Leonor , El-Khoueiry Rita , El-Khoueiry Anthony B. , Iqbal Syma , Lenz Heinz-Josef 
Published: March 2020

3584 Background: High body mass index (BMI) is an established risk factor for colorectal cancer incidence and death. Recent studies found obesity before the diagnosis of colon cancer was associated with worse survival compared with normal weight. Single nucleotide polymorphisms (SNPs) of obesity-related gene have been related with different cancer risk including colorectal cancer. Here we tested the hypothesis whether SNPs in obesity-related genes (PPAR, LEP, NFKB, CD36, DRG1, NGAL, REGIA and DSCR1) may predict tumor recurrence in adjuvant colon cancer. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 years (range 22–78 years)) with stage II (105 patients) or III (129 patients) colon cancer at the University of Southern California/Norris Comprehensive Cancer Center. The median follow-up was 4.4 years. SNPs in obesity-related genes were determined by PCR-RFLP or PCR-based direct sequence. The primary endpoint of the study was time to tumor recurrence (TTR). Results: in univariable analysis, PPAR rs1801282 and DSCR1 rs6517239 were independently associated with time to tumor recurrence (TTR). Patients with PPAR CC genotype had longer median TTR 9.4 months (95% C.I: 5.6, 12.4+) compared to those with CG genotype, had median TTR 3.4 months (95% C.I: 1.7, 16.8+)(p=0.04, log-rank test). Patients with DSCR1 AA genotype had shorter median TTR 6.6 months (95% C.I: 4.0, 16.8+) compared to those with AG and GG genotypes, which had longer median TTR 9.4 months (95% C.I: 5.7, 10.7+)(p=0.027, log-rank test). The multivariate analysis adjusting for stage and type of adjuvant therapy showed a trend in the association between PPAR rs1801282 and DSCR1 rs6517239 and time to recurrence (Wald test p=0.08 and 0.058, respectively). Conclusions: Our preliminary results demonstrated polymorphisms in obesity-related gene might be potential molecular markers to predict TTR in adjuvant colon cancer. Further large and biomarker embedded trial needed to confirm our findings.
Cost-effectiveness analysis per life-year gained based on predictors of response for first-line metastatic colorectal cancer therapy in Spain.
Authors: Belda-Iniesta Cristobal , Moreno Victor , Martinez-Amores Brezo , Barriuso Jorge , Mezquita Laura , Ibañez de Cáceres Inmaculada , Ayuso Sacido Angel , Peña Jose Maria , Perona Rosario 
Published: March 2020

3601 Background: Economic crisis, increasing prevalence and cost of mCRC management endanger availability of biological therapies for public health systems due to budget limitations. We performed a cost-effectiveness analysis based on markers of response/resistance including biological therapies available in Spain for mCRC. Methods: We aimed to calculate incremental cost-effectiveness ratio (ICER) per life-year gained (LYG) and progression-free year gained based on predictive markers for mCRC. Efficacy data include randomized trials (RT) that guided on-label uses of bevacizumab and cetuximab. Control arms from these trials were used as reference to calculate ICERs. Markers of clinical benefit (biological and radiological) were included in this model. Toxicity as predictor of efficacy was excluded for any therapy. Prices for drugs in Spain were assumed to represent the best-value for each drug including all possibilities to reduce pharmacy costs. For 1st line, median duration of therapy reported by RT was used to calculate the final budget. 70kg and 1.7 m were used as reference for patients dose calculations. If accessible, HR for PFS and OS were used instead of medians. Results: K-Ras status and early response measured by CT at 8 weeks were used as predictors of resistance and increased efficacy for cetuximab-based combinations. We have not identified any predictor marker for other drugs from RT. In this regard, FOLFIRI+cetuximab combination obtained an ICER below the widely-proposed Spanish threshold of 30,000 € per LYG if patients harbored wt K-Ras tumors and evidenced an objective response at 8 weeks. Other ICERs for different schedules were too distant from this limit, they will be presented at the meeting. Multivariate analysis confirmed the robustness of results. Conclusions: 1st line FOLFIRI+cetuximab therapy for wt K-Ras patients that get an objective response measured by CT at 8 weeks is the only cost-effective therapy option for mCRC below usual health-economic thresholds for Spain. Our results are critical to design cost-effectiveness based clinical guidelines for mCRC that will contribute to financial sustainability of public health system in Spain.
Prognostic significance of intermediate mucinous carcinoma in patients with microsatellite stable stage II or III colon cancer.
Authors: Kim Gun Min , Ahn Joong Bae , Han Jung Woo , Kim Han Sang , Shin Sang Joon , Kwon Woo Sun , Park Chan Hee , Kim Tae Soo , An Sungwhan , Shin Im-Hee , Yang Woo Ick , Kim Nam Kyu , Chung Hyun Cheol 
Published: March 2020

3606 Background: Mucinous adenocarcinoma (MC) is a histological subtype of colorectal cancer with ≥50% of mucinous component of tumor volume. According to WHO classification, tumor less than 50% of the lesion composed of mucin was considered as non-mucinous carcinoma (NMC).Mucinous histology has been shown to be an independent adverse prognostic factor in some studies, but not in others. However, prognostic implication of intermediate mucinous carcinoma (IMC) which had focal mucinous component <50% of tumor volume has not been studied yet. The aim of this study is to explore prognostic impact of IMC in patients with resected stage II or III colon cancer. Methods: This study involved 917 patients who underwent curative resection for stage II or III colon cancer in Severance Hospital, from 2003 to 2009. The proportion of mucinous component was reviewed and re-classified correctly by pathologists. MC was defined tumor having >50% mucinous component. Tumor with mucinous component but less than 50% regarded as IMC and less than 10% mucin as NMC. Results: Among 917 patients, 63 (6.9%) and 60 (6.5%) were MC and IMC, respectively. Median follow-up duration was 50.2 months (0.9~109.7) and Stage 3 was 48.1% (441/917). The similarities between MC and IMC were found as right colon dominant (MC: IMC: NMC = 60%: 67%: 34%, p<.001) and higher incidence of MSI-high compared to NMC (MC: IMC: NMC = 27%: 30%: 11%, p<.001). In stage III, the disease-free survival (DFS) rate at 5 years was 44% for MC, 56% for IMC, and 74% for NMC (p<.001). Subgroup analysis according to MSI status showed that DFS had significant inverse correlation with proportions of mucinous components in MSI-low or MSS group, but patients with MSI-high tumor showed higher five-year DFS rate (>85%) regardless of mucinous component. For stage II colon cancer patients, both mucinous histology and MSI had little clinical significance. Conclusions: In patients with curative resection for stage II or III colon cancer, IMC had similar characteristics to MC, which were right colon dominant and high incidence of MSI-high tumor. The prognostic impact of IMC was intermediate risk between MC and NMC in stage III patients with MSI-low or MSS tumor, but not in MSI-high group.
Colorectal cancer characteristics and outcomes in patients less than age 50: A comparison of an urban university hospital with the NCI SEER database.
Authors: Mitchell Edith P. , Topham Allan , Anne Pramila R. , Goldstein Scott , Isenberg Gerald , Guiles Fran , Palazzo Juan 
Published: March 2020

3621 Background: Cancer of the colon and rectum is the third most commonly occurring cancer, as well as the third leading cause of cancer deaths in American men and women. Colorectal cancer in younger patients is believed to have worse pathological features and prognosis than in older patients. The objective of this study was to assess pathological features and outcomes of CRC in patients less than age 50 using an institutional sample and comparing to the Surveillance, Epidemiology and End Results (SEER) database. Methods: Included in the study were a total of 4595 cases from the Tumor Registry at Thomas Jefferson University Hospital (TJUH) over a twenty year period from 1988 through 2007 and 290,338 cases from the Surveillance, Epidemiology and End Results (SEER) database from 1988 through 2004. Patients less than age 50 were compared to those age 50 and older. Results: Patients under age 50 with CRC presented with more advanced stage tumors in both data sets (<0.0001) , and had more poorly differentiated tumors than older patients (PTJUH=0.02754; PSEER<0.0001). Patients under 50 also had more mucinous/signet ring cell tumors with 12 percent to 8.1 percent in the TJUH data (p=0.002916) and 13.2 percent to 10.3 percent in the SEER data (p<0.0001), with younger males having the highest prevalence in both data sets. Younger patients had fewer proximal tumors than patients 50 and over, and a higher proportion of rectal tumors (p<0.001). Patients under age 50 were more likely to have positive nodes at all stages (PSEER <0.0001) relative to 50 and over, as well as more likely to develop peritoneal metastases (PTJUH=0.3507),, but less likely to have lung metastases PTJUH=0.05249) than older pts. Despite their poor pathologic features, patients under age 50 had better than or equal survival to those 50 and older. Conclusions: Colorectal cancer patients under age 50 presented with worse histological characteristics and metastasized much sooner, yet the younger patients had better than or equal survival to those ages 50 and older. Ongoing studies will assess differences in treatment and molecular features between younger and older colorectal cancer patients.
Methylations of NEUROG1, p16, and MLH1 and recurrence following adjuvant FOLFOX in colorectal cancer.
Authors: Lee Hyun-Jung , Han Sae-Won , Bae Jeong Mo , Cho Nam-Yun , Lee Kyung-Hun , Oh Do-Youn , Im Seock-Ah , Bang Yung-Jue , Jeong Seung-Yong , Park Kyu Joo , Park Jae-Gahb , Kang Gyeong Hoon , Kim Tae-You 
Published: March 2020

3624 Background: CpG island methylator phenotype (CIMP) is characterized by concurrent methylation of multiple CpG islands in tumor DNA, which can inactivate tumor suppressor genes or promote carcinogenesis. The prognostic impact of CIMP on treatment outcome of colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) is unclear. We investigated CIMP markers in colorectal cancer patients treated with adjuvant FOLFOX. Methods: Sporadic colorectal cancer patients treated with curative resection followed by adjuvant FOLFOX were included. DNA was extracted from formalin-fixed paraffin-embedded surgical specimen. 8 CpG island loci (CACNA1G, CRABP1, IGF2, MLH1, NEUROG1, P16, RUNX3 and SOCS1) were examined using MethyLight analysis. Disease-free survival (DFS) was evaluated according to each methylation loci. Results: A total of 322 patients were included. Methylation at 1 or more loci was observed in 150 patients (46.6%) and 6 or more loci in 15 (4.7%). During a median follow-up duration of 39.7 months, 55 recurrences were observed. Three year DFS in the patient cohort was 84%. CRABP1 (23.9%) was the most frequently methylated loci, followed by p16 (22.7%) and NEUROG1 (20.8%). Patients having methylation at NEUROG1 (3 year DFS 78% in (+) vs. 86% in (-), p = 0.014) and p16 (3 year DFS 78% in (+) vs. 86% in (-), p = 0.12) had worse DFS, whereas methylation at MLH1 had better DFS (3 year DFS 100% in (+) vs. 86% in (-), p = 0.19). In a combined analysis, patients with MLH1(-)/NEUROG1(+)/p16(+) had worst treatment outcome compared to MLH1(-)/NEUROG1(+) or p16(+), MLH1(-)/ NEUROG1(-) /p16(-), and MLH1(+) (3 year DFS 62%, 82%, 87%, and 100%, respectively; p = 0.002). In multivariate analysis, NEUROG1(+)/p16(+) was associated with significantly higher recurrence compared with other patients (adjusted hazard ratio (HR) 2.15 (95% confidence interval (CI) 1.08 - 4.27, p = 0.029). Conclusions: Methylation status of NEUROG1, p16, and MLH1 is associated with recurrence following adjuvant FOLFOX in stage II/III colorectal cancer. Further validation and translational studies to improve treatment outcome in the subset of patients are warranted in the future.
Evaluation of MET pathway biomarkers in a phase II study of rilotumumab (R, AMG 102) or placebo (P) in combination with epirubicin, cisplatin, and capecitabine (ECX) in patients (pts) with locally advanced or metastatic gastric (G) or esophagogastric junction (EGJ) cancer.
Authors: Oliner Kelly S. , Tang Rui , Anderson Abraham , Lan Yun , Iveson Timothy , Donehower Ross C. , Jiang Yizhou , Dubey Sarita , Loh Elwyn 
Published: March 2020

4005 Background: R is an investigational, fully human, monoclonal antibody to HGF/SF, the ligand of the MET receptor. A double-blind, P-controlled, phase 2 study randomized 121 G/EGJ cancer pts 1:1:1 to 15 mg/kg R + ECX (Arm A, n = 40), 7.5 mg/kg R + ECX (Arm B, n = 42), or P + ECX (Arm C, n = 39). OS and PFS improved with the addition of R to ECX (Iveson et al, European Multidisciplinary Cancer Congress 2011; abstr 6.504). High tumor MET levels have been associated with poor prognosis in G cancer (Nakajima et al, Cancer 1999;85:1894-1902). We explored MET pathway biomarkers to identify pts who may benefit from R. Methods: MET protein levels and gene copy numbers were measured in archival tumor samples by immunohistochemistry (IHC) and fluorescence in situ hybridization, respectively. High and low MET subgroups were defined by several predefined strategies. Total HGF and soluble MET (sMET) protein in plasma were measured by ELISA and MSD assays, respectively. Treatment and biomarker effects on OS and PFS were analyzed by Cox proportional hazard models and Kaplan-Meier estimates. Results: Tumor samples were evaluable for MET protein from 62 pts in Arms A + B and 28 pts in Arm C. Pts with METHigh tumors (> 50% tumor cells positive) in Arms A + B had improved median OS than those in Arm C (11.1 mo [80% CI: 9.2-13.3] vs 5.7 mo [80% CI: 4.5-10.4]; HR = 0.29, 95% CI: 0.11-0.76, p = 0.012). Conversely, pts with METLow tumors (≤ 50% positive) in Arms A + B had a trend toward unfavorable OS compared with those in Arm C (HR = 1.84, 95% CI: 0.78-4.34). In the chemotherapy only arm (Arm C), pts with METHigh tumors had poorer OS (HR = 3.22, 95% CI: 1.08-9.63) than pts with METLow tumors. Similar trends were seen with PFS. Predefined dichotomization schemes for tumor MET gene copy number and baseline plasma levels of total HGF or sMET did not correlate with OS or PFS. Conclusions: High MET expression by IHC may predict clinical benefit to R + ECX in G/EGJ cancer pts. High MET expression may also be associated with poor prognosis for ECX-treated pts. Further investigation is needed to confirm these findings.