bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of bone marrow micrometastases with nodal status in gastrointestinal tumors.
Authors: Nagpal Sunil , Korant Alpesh K. , Krishnamoorthy Madhumitha , Shaik Mohammed , Johnston Gregory , Dhar Vikrom K. , Arora Madan L. , Singh Trevor , Wiese David , Saha Sukamal 
Published: March 2020

e14518 Background: Presence of bone marrow (BM) micrometastases (M) is a prognostic factor for patients (pts) with solid tumors. Sentinel lymph node (SLN) mapping (M) has been found to upstage pts with gastrointestinal (GI) cancers. However, a direct correlation between the presence of BMM and nodal metastases (mets) is lacking. A retrospective study was done to determine the relationship between BMM and nodal status in GI cancers. Methods: A total of 385 consecutive pts with GI cancers were studied. Pts underwent bilateral posterior-superior-iliac-spine BM aspiration. A highly sensitive staining method was used to differentiate cytokeratin postitive cells of epithelial origin from normal hematopoetic cells. Cytospin slides were stained wtih monoclonal anti-CAM 5.2 antibody. Visualization was achieved with Ventana view-Red detection system. Slides were then counterstained with haematoxylin. Automated Cellular Imaging System was used to classify cells of interest by cellular color, size and shape. SLNM was done by peritumoral injection of 1% methylene blue in the subserosal layer. Results: A total of 385 pts were analyzed. Of these 11% were found to have BMM. The three highest sites of BMM were cholangiocarcinoma 33%, Stomach 22% and esophagus 13% (Table 1A). BMM was +ve bilaterally in 44% of pts, unilaterally in 56%. In pts who underwent SLNM, BMM were detected in 8.3% of SLN +ve vs. 12% for SLN -ve pts. For a subgroup of pts with colorectal cancer undergoing SLNM, BMM were detected in 9.6% of SLN +ve pts vs. 11% for SLN -ve pts. Conclusions: BMM did not correlate with nodal status for GI malignancies suggesting a possible different mechanism for metastases. Detection of BMM may have a significant clinical value in SLN negative pts who may benefit from adjuvant therapy. [Table: see text] [Table: see text]
The utility of PET scanning in colorectal cancer liver metastases being considered for surgery.
Authors: Ismail Jeffri R. M. , Kelly Ciara Marie , Hanrick Marian , Regan Downey Cara , McCarthy Lauragh , O'Reilly Aine , MacEneaney Peter , Bennett Michael William , O'Regan Kevin N. , Mulvihill Erica , O'Sullivan Adrian , O Suilleabhain Criostoir , McCaffrey John , O'Reilly Seamus , Power Derek Gerard 
Published: March 2020

e14519 Background: Liver resection remains the only potentially curative option for a subset of patients with colorectal cancer liver metastases (CRCLM). Preoperative imaging used to determine resectability includes computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). The objective of this study was to determine the utility of PET scanning for potentially resectable CRCLM. Methods: We retrospectively reviewed a prospectively maintained database for all patients considered for resection of CRCLM from July 2010 to July 2012 in two specialist colorectal/hepatobiliary cancer centres. We extracted and analyzed data with respect to preoperative staging imaging and definitive treatment performed on completion of staging. Results: We identified 100 patients who underwent preoperative staging investigations for potentially resectable CRCLM. The imaging techniques performed included: CT (n=99, 99%), MRI liver (n=75, 75%), PET (n= 96, 96%). In 22 (22/96, 23%) patients PET scanning added to the preoperative staging information, identifying local recurrence (n=3, 3.1%), confirming liver metastases following an inconclusive CT/MRI (n=2, 2.1%), outruling liver metastases (n=1, 1%) and identifying extrahepatic sites (EHS) suspicious for disease (n=16, 16.7%). The EHS included either lung (n=6), bone (n=2), peritoneum (n=1) or lymph nodes (n=7). There were 2 false positive results. One patient with FDG-avid mediastinal lymph nodes had no cancer on endobronchial biopsy. One patient with FDG avidity at the primary anastomosis had no evidence of disease at colonoscopy. PET definitively changed the therapeutic strategy in 16 patients (16/96, 16.6%): precluding liver resection in 10 patients (10/96, 10.4%), leading to resection of extrahepatic disease in 4 patients (4/96, 4.1%), resection of local recurrence in 1 patient (1/96, 1%) and resection of hepatic metastases in one patient (1/96, 1%). Conclusions: In this small retrospective cohort the addition of metabolic imaging altered management in 16.6% of patients with potentially resectable CRCLM. There is a need for randomized evidence to support the routine use of PET in addition to cross-sectional imaging in this setting.
Capecitabine but not 5-FU worsened hepatosplenomegaly and liver function when used with oxaliplatin and cetuximab as first-line treatment in K-ras wild-type metastatic colorectal cancer.
Authors: Lee Victor HF , Fang Weijia , Lam Ka On , Choi Cheuk Wai , Ng Sherry CY , Ho Patty PY , Ho Garrett CL , Cheng Thomas KC , Liu Rico KY , Leung To Wai , Kwong Dora Lai Wan , Zheng Shusen 
Published: March 2020

e14530 Background: MRC COIN study showed that OXA and CAP (CAPOX) have greater toxicities compared with OXA and 5-FU (FOLFOX) when cetuximab (C225) was added for mCRC. Meanwhile, OXA was associated with splenomegaly and hepatic sinusoidal injury. We investigated if CAPOX+C225 worsened hepatosplenomegaly and liver function compared with FOLFOX+C225 in K-rasWT mCRC. Methods: 97 patients with K-ras WT mCRC received either FOLFOX or CAPOX (n=57) or the same regimen+C225 (n=40) as 1st line treatment. CT scan of abdomen was performed at baseline and then after every 3-4 cycles. Liver excluding liver metastases if present, and spleen size at baseline and after treatment were contoured in Eclipse Treatment Planning System. Changes in liver and spleen size after treatment in all patients and subgroups (1) use of C225 and (2) CAPOX vs. FOLFOX +/- C225 were compared. Logistic regression was done for any predictors of hepatosplenomegaly and impaired liver function in all patients and subgroups. Results: 25, 32, 15 and 25 patients received FOLFOX, CAPOX, FOLFOX+C225 and CAPOX+C225 respectively.All patients had hepato- (p=0.014) and splenomegaly (p=0.000) after treatment. C225 did not further worsen hepato- (p=0.430) and splenomegaly (p=0.614). Cumulative dose of CAP was predictive of hepato- (p=0.003) and splenomegaly (p=0.008) even after adjusted for cumulative dose of OXA (p=0.021). For subgroup analysis, hepato- (p=0.040) and splenomegaly (p=0.041) were noted when CAPOX+C225 was compared with FOLFOX+C225, but not seen when CAPOX was compared with FOLFOX (p=0.270 and p=0.287 respectively). When comparing CAPOX+C225 with FOLFOX+C225, use of CAP was predictor of both hepato- (p=0.043) and splenomegaly (p=0.007). Dose intensity of CAP (p=0.036) and cumulative dose of OXA (p=0.044) are predictors of ≥grade 1 impaired liver function. However when comparing CAPOX with FOLFOX, no predictor was found for any complication. Conclusions: CAP further worsened hepatosplenomegaly and liver function when combined with OXA and C225 but not with OXA alone, suggesting that CAP and C225 together may add toxicity to liver and spleen.
Effect of postoperative chemotherapy (CT) on survival in patients (pts) with resected rectal cancer who received neoadjuvant therapy.
Authors: Wu Christina Sing-Ying , Wei Lai , Glass Katherine , Wilson John , Abdel-Misih Sherif , Williams Terence Marques , Martin Ludmila Katherine , Haraldsdottir Sigurdis , Harzman Alan , Husain Syed , Schmidt Carl Richard , Arnold Mark , Goldberg Richard M. , Bekaii-Saab Tanios B. 
Published: March 2020

e14535 Background: Pts with stage II/III rectal cancers are treated with neoadjuvant chemoradiation and surgical resection followed by adjuvant CT per practice guidelines. It is unclear whether adjuvant CT provides survival benefit, and the purpose of this study was to measure outcome in pts who did and did not receive adjuvant CT. Methods: We used a prospectively collected database for pts treated at The Ohio State University and analyzed overall survival (OS), time to recurrence (TTR), pt characteristics, tumor features, and treatments. Survival curves were estimated using Kaplan-Meier method and compared by the log-rank test. Age was compared using the Wilcoxon test, and other categorical variables were compared using Chi-square test or Fisher’s exact test. Results: Between August, 2005 to July, 2011, 110 pts were identified and 71 pts had received adjuvant CT. There was no significant difference in sex, race, pathologic tumor (T) stage, and pathologic complete response between the two groups. Pts receiving adjuvant CT were significantly younger (median age 54.3 vs. 62 years, p=0.01) and had more advanced pathologic nodal (N) stage (43 vs. 19% N1 or N2, p=0.02). Median OS was 72.6 months with CT vs. 36.4 months without CT (p=0.0003). Median TTR has not yet been reached. Conclusions: In this retrospective analysis, adjuvant CT was associated with a longer OS despite more advanced pathologic nodal staging. Prospective randomized studies are warranted to determine whether adjuvant CT provides a survival benefit for pts across the spectrum of stage II and III rectal cancer. [Table: see text]
Influence of KRAS mutations on outcome in patients with curatively resected stage III colon cancer treated with adjuvant chemotherapy.
Authors: Saletti Piercarlo , Nucifora Martina , De Dosso Sara , Spitale Alessandra , Sahnane Nora , Riveiro Maria Eugenia , Bertolini Valentina , Bucci Eraldo , Crippa Stefano , Ghielmini Michele E. G. , Frattini Milo 
Published: March 2020

e14536 Background: Adjuvant chemotherapy improves survival in patients with stage III colon cancer (CC) after curative resection, and oxaliplatin in combination with fluoropyrimidine-based regimens has been established as a standard treatment. KRAS mutations could predict oxaliplatin sensitivity in CC cells, as recently demonstrated. Here, we profiled KRAS and correlated it with outcome in stage III CC patients who underwent adjuvant chemotherapy. Methods: Eligible patients were those with resected stage III CC who underwent 6-months adjuvant chemotherapy, either with single-agent fluoropyrimidine (FP: modulated 5FU or capecitabine) or with oxaliplatin-based regimens (O-FP: FOLFOX or XELOX). DNA extraction was performed on formalin-fixed paraffin-embedded sections, and KRAS mutations were analyzed by direct sequencing. Disease-free survival (DFS) and overall survival (OS) analyses were computed using the Kaplan-Meier method and the Log-rank test. Results: The study population included 261 patients: 115 treated with FP, 146 O-FP. We identified KRAS mutations in 71/261 (27.4%) cases, of which 33 (46.5%) received FP, and 38 (53.5%) O-FP. In wild-type (wt) KRAS cases, DFS and OS group did not significantly differ between the two treatment modalities [in months, FP vs O-FP - median OS: 62.0 vs 49.6, HR: 1.12 (95% CI: 0.65; 1.92); median DFS: 57.1 vs 44.4, HR: 0.93 (95% CI: 0.55; 1.56)]. In patients treated with FP, a worse DFS [in months, mutant vs wt - median DFS: 46.0 vs 57.1, p=0.04; HR: 1.86 (95% CI: 1.01; 3.41)] and a trend toward a worse OS in months, mutant vs wt - median OS: 56.1 vs 62.0, p=0.08; HR: 1.71 (95% CI: 0.94; 3.10)] were observed in KRAS mutated patients. On the contrary, DFS and OS were not statistically different for mutated and wt KRAS patients treated with O-FP [in months, mutant vs wt - median DFS: 43.7 vs 44.4, p=0.62; HR: 1.17 (95% CI: 0.63; 2.18); median OS: 48.9 vs 49.6, p=0.77; HR: 1.11 (95% CI: 0.55; 2.23). Conclusions: Our results suggest that curatively resected stage III CC patients exhibiting wt KRAS status might benefit from FP alone. On the contrary, an oxaliplatin-containing regimen should be recommended in KRAS mutated patients.
Risk of tumor-related death in stage I-III colon cance based on gender and tumor location.
Authors: Ladner Robert D. , Kahn Michael , Yang Dongyun , Stintzing Sebastian , Zhang Wu , Wakatsuki Takeru , Ning Yan , Volz Nico Benjamin , Li Joseph Ethan , Labonte Melissa Janae , Wilson Peter M. D. , Kardosh Adel , Lenz Heinz-Josef 
Published: March 2020

e14538 Background: Survival of metastatic colon cancer has recently been linked to gender and location of the primary. Data on these factors in the stage I-III is still sparse. We aimed to demonstrate the influence of gender and tumor location of tumor related survival, using SEER database. Methods: 288,640 patients diagnosed with stage I-III colon cancer during 1988 through 2009 identified from SEER database were included in this study. Cox proportional hazards models were used to evaluate the effects of tumor site (left vs right-sided colon) on colorectal cancer specific survival. Age, race, T stage, N stage, histology (adenocarcinoma, mucinous tumor), grading, numbers of lymph nodes resected and type of surgery were used as covariates. Results: A total of 85,131 (stage I), 110,667 (stage II) and 92,842 (stage III) patients were identified to have data on all the factors to be looked at. In the total population female gender was statistically significant for longer TSS for all three stages (HR 0.82; HR 0.86 and HR 0.89). Furthermore, in UICC I and UICC III left side was favorable (HR 0.82 and HR 0.91) but in stage II, right sided colon cancer patients had a longer TSS (HR 1.2 for left side). This was independent of gender. Conclusions: Different prognoses of right versus left colon cancer reflect different biology. Furthermore the influence of gender points to an estrogen effect in female patients. As there is emerging knowledge about the differences in right versus left colon cancer biology, the modulating effect of SMAD4 on estrogen driven TGFß signaling might be one explanation to those differences.
Genetic variants in EGFR and its ligands to predict response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.
Authors: Sebio Ana , Páez David , Salazar Juliana , Tobena Maria , Martin-Richard Marta , Barnadas Agust , Baiget Montserrat 
Published: March 2020

e14541 Background: Epidermal growth factor receptor (EGFR) activation via ligand binding results in signaling through several pathways that fundamentally contribute to cell proliferation. Increased cell proliferation has been proposed as a radioresistance mechanism that would occur upon EGFR activation by radiation therapy. In this study we have analyzed the potential role of single nucleotide polymorphisms (SNPs) in the EGFR gene and its ligands as pharmacogentic markers of response to chemoradiation in locally advanced rectal cancer. Methods: Seventy stage II and III rectal cancer patients treated with capecitabine plus radiotherapy were analyzed. Nineteen TagSNPs in three EGFR ligands (amphiregulin, epiregulin and epidermal growth factor) were selected using HapMap database and Haploview software. One functional SNP (R521K) in the EGFR gene was also analyzed. DNA was extracted from peripheral blood and genotype was performed using the BioMarkTM System (Fluidigm). The main end point of the study was to analyze the possible association of these polymorphisms with the pathologic complete response after neoadjuvant chemoradiotherapy. Results: In the amphiregulin gene region, the rs11942466 C>A SNP was associated pathological complete response (37% in C/C vs. 21% in C/A and 0% in A/A; p=0.023). In the EGFR gene the R521K G>A SNP was associated with response in the dominant model (35 % of patients harbouring an A allele achieved complete response compared to 13 % of patients with a G/G genotype; p=0.025). In the multivariate analysis the R521K G>A polymorphism remained statistically significant with an odds ratio of 0.14 (95%CI: 0.026-0.76; p=0.023). Conclusions: EGFR and amphiregulin genetic variants might help identify patients who would benefit the most from neoadjuvant chemoradiotherapy based on capecitabine.
Association of a polymorphism in amphiregulin with worse prognosis in metastatic colorectal cancer patients treated with cetuximab.
Authors: Wilson Peter M. D. , Wakatsuki Takeru , Loupakis Fotios , Zhang Wu , Yang Dongyun , Stintzing Sebastian , Ning Yan , Volz Nico Benjamin , El-Khoueiry Rita Elie , Li Joseph Ethan , Labonte Melissa Janae , Sunakawa Yu , Maus Martin K. H. , Ladner Robert D. , Barzi Afsaneh , Iqbal Syma , El-Khoueiry Anthony B. , Lenz Heinz-Josef 
Published: March 2020

e14543 Background: Accumulating data suggests that Amphiregulin (AREG) and Epiregulin (EREG), ligands of the EGFR pathway, are potential prognostic and predictive markers in metastatic colorectal cancer (mCRC). Elevated AREG and EREG gene expression levels are predictive of improved response rates in mCRC patients treated with cetuximab and longer overall survival (OS) in patients with mCRC who did not receive cetuximab. Since polymorphisms in AREG and EREG may affect their expression or function, we tested whether AREG and EREG polymorphisms were associated with clinical outcome in mCRC patients treated with cetuximab. Methods: Seventy-three patients (n=73) with histopathologically-confirmed mCRC with Kras/Braf wild type were enrolled in Italy. These patients were treated with cetuximab monotherapy or irinotecan plus cetuximab as second or third line treatment. Genomic DNA was extracted from blood and 4 SNPs in AREG and 5 SNPs in EREG were analyzed by direct DNA-sequencing. Results: The median follow-up period was 13.3 months in this cohort. The median progression-free survival (PFS) and OS were 5.2 and 12.9 months respectively. The results indicate that the intronic AREG polymorphism rs28364983 A/C was associated with shorter PFS and OS. Patients with homozygous C/C (n=2) showed a median PFS of 2.3 months vs. 5.3 months for patients harboring at least one-A allele (n=71) (HR: 4.26 [95%CI: 0.98-18.5], p=0.05). Patients with homozygous C/C showed a median OS of 3.0 months vs. 13.1 months for patients harboring at least one-A allele (HR: 3.98 [95%CI: 0.93-16.9], p=0.062). An independent cohort of thirty-three patients was used to validate these initial findings and showed that patients with homozygous C/C (n=3) had a median PFS of 2.3 months vs. 3.8 months for patients harboring at least one-A allele (n=103) (HR: 3.79 [95%CI: 1.16-12.3], p=0.027) and a median OS of 3.0 months vs. 8.4 months (HR: 3.01 [95%CI: 0.93-9.71], p=0.065), respectively. Conclusions: AREG rs28364983 predicted worse outcome in mCRC patients treated with cetuximab; however, further analyses are necessary to understand the mechanism and further validate the prognostic and/or predictive role of this polymorphism.
Optimal treatment strategy in KRAS wild type (wt) metastatic colorectal cancer (mCRC): Cetuximab plus FOLFIRI followed by FOLFOX4 with or without cetuximab-The Capri trial from the Gruppo Oncologico Dell’Italia Meridionale (GOIM).
Authors: Ciardiello Fortunato , Maiello Evaristo , Pisconti Salvatore , Giuliani Francesco , Barone Carlo , Rizzo Mimma , Bordonaro Roberto , Montesarchio Vincenzo , Cinieri Saverio , Martinelli Erika , Troiani Teresa , Delcuratolo Sabina , Simone Gianni , Normanno Nicola , Febbraro Antonio , Tonini Giuseppe , Colucci Giuseppe 
Published: March 2020

e14565 Background: Cetuximab in combination with standard doublet chemotherapy is an effective treatment in KRAS wt mCRC patients (pts). The present study investigated a treatment strategy of cetuximab in combination with FOLFOX4 as a second line therapy for KRAS wt mCRC pts treated in first line with cetuximab plus FOLFIRI. Methods: KRAS wt m CRC pts were treated in first line with cetuximab plus FOLFIRI and at progression were randomized (1:1) to receive FOLFOX alone (Arm A) or in combination with cetuximab (Arm B). Primary endpoint for each treatment line was progression-free survival (PFS), with secondary endpoints overall survival (OS), response rate (RR), disease control rate and safety. 221 events would be required to statistically differentiate PFS between the two arms with 80% power for the second line treatment. Here we report the results of first line cetuximab plus FOLFIRI treatment. Results: From July 2009, 344 pts were enrolled: 58% males, median age 63 years (range, 20-81 years), ECOG performance status, 0 (85%); 1 (15%); synchronous metastasis (75%). For the 319 evaluable patients, median PFS was 10 months; overall response rate (ORR) was 55% with 47% partial responses (PR), 8% complete responses (CR) and 35% stable disease (SD) for a disease control rate (DCR) of 90%. The most common grade 3/4 adverse events were: skin reactions (15%), diarrhea (9%) and neutropenia (6%). As of January 31 2013, 118 pts have progressed and have been enrolled in second line treatment (58 Arm A; 60 Arm B). Conclusions: The results of first line treatment with cetuximab plus FOLFIRI confirm in a multicenter trial in prospectively selected KRAS wt mCRC pts the efficacy and tolerability of this combination. The randomized second line part of the study is currently ongoing. Multiple gene next generation sequencing to characterize a 24 genes mutation profile is currently ongoing. Clinical trial information: 2009-014041-81.
Impact of the Recurrence Score (RS) result and mismatch repair status (MMR) on agreement between oncologists (MDs) for stage II colon cancer (CC) recurrence risk (RR) assessment: A novel clinical utility endpoint for prognostic markers.
Authors: Kelley Robin Katie , Lopatin Margarita , Hwang Jimmy , Crager Michael , Brenner Adrienne A , Kuczma Jane , King Ashley , Chao Calvin , Lee Mark , Venook Alan Paul 
Published: March 2020

e14569 Background: Appropriate use of prognostic and predictive markers depends on quality of evidence for clinical utility in addition to clinical validity. In stage II CC, RR assessment is based traditionally on clinicopathologic factors (CP) with limited clinical validation and varies substantially across providers. We hypothesized that the validated Oncotype DX Colon Cancer RS and MMR tests may impact clinical decision-making by decreasing variation in RR assessment across MDs. We conducted a survey to compare the level of MD agreement on stage II CC RR assessment using CP alone vs CP+RS+MMR (CP+). Methods: A clinical trial database was randomly sampled for 100 cases of stage II CC stratified on T-stage, MMR and RS groups. Anonymous internet surveys asked each MD to assess 3-year RR for 10 cases with CP and 10 different cases with CP+. MDs were divided into panels of 5; all members of each panel reviewed the same cases. Agreement in RR among MDs was assessed using within-panel mean squared difference in RR assessments and analyzed using generalized linear models. Results: 30 community (C) and 20 university-based (U) MDs (Assoc of Northern California Oncologists or NCCN, respectively) completed evaluable surveys April-June 2012. For C vs U, median years in practice were 5 and 2; prior use of RS 13% vs 25%; and routine MMR use 21% vs 55%. The standard deviation of the differences (SDD) in RR assessments for CP alone was high overall (7%), and greater for U vs C MDs (8.2% vs 6.4%). CP+ produced higher agreement in RR assessments vs CP for both C (p<.001) and U (p=0.04) MDs, with 23% and 20% proportional reduction in SDD. ForT3 MMR-proficient (P) patients (n=70), CP+ produced higher agreement in RR for both C (p<0.001) and U (p=0.01) MDs with 37% and 29% reduction in SDD. Conclusions: Addition of RS+MMR to CP significantly increased MD agreement on RR assessment in stage II CC, including T3 MMR-P patients. Agreement was higher among C than U MDs. MD agreement on stage II CC RR assessment and Tx decision-making warrants consideration as a novel endpoint for clinical utility of RS, MMR, and other prognostic markers.