bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of HER2 overexpression with total Her2 mutation on resistance of EGFR-targeted therapy in Ras wild-type mCRC patients.
Authors: Chang Wenju , Huang Wenbai , Chen Yijiao , Ren Li , Wei Ye , Xu Jianmin 
Published: May 2019

3594 Background: Cetuximab has shown clinical benefit in patients with metastatic colorectal cancer (mCRC) harboring wild-type Ras, however, only partial patients respond to cetuximab treatment. The effect of human epidermal growth factor receptor 2 (HER2) protein overexpression and Her2 gene mutant on the efficacy of cetuximab treatment was not well elucidated in patients with Ras wild-type unresectable mCRC. Methods: From June 2008 to December 2014, we identified 216 patients with Ras wild-type unresectable liver-limited mCRC base on our previous study (ClinicalTrials: NCT01564810.), whose Her2 gene mutation was analyzed by next-generation sequencing for single nucleotide polymorphism (SNP) of Her2 gene and HER2 protein overexpression was determined by immunohistochemistry and fluorescence in situ hybridization (FISH). Results: Of these 216 patients, 103 were received cetuximab plus chemotherapy (cetuxima group) and 113 were received chemotherapy alone (chemotherapy group). The total rate of HER2 overexpression was 8.8%, including 9.7% in cetuximab group and 7.9% in chemotherapy group. HER2 overexpression caused impaired survival compared with HER2 non-overexpression patients in cetuxima group, with a median progression-free survival (PFS) of 4 months (95% CI 2.482-5.518) versus 10 months (95% CI 8.963-11.037; P< 0.0001), and a median overall survival (OS) of 15 months (95% CI 7.5-22.2) versus 36 months (95% CI 31.4-40.5) ( P< 0.0001). While, HER2 overexpression had no effect on treatment efficacy in chemotherapy group, when compared with HER2 non-overexpression paitents, with a median PFS of 5 months (95% CI 2.228-7.772) versus 5 months (95% CI 4.004-5.996; P= 0.615), and a median OS of 21 months (95% CI 6.975-35.025) versus 21 months (95% CI 17.772-24.228; P= 0.629). Meanwhile, we observed 25.5% of total Her2 mutant (24.2% in cetuximab group and 26.5% in cetuximab group), among of them 5 patients are HER2 overexpression. Total Her2 mutation has no impact on survival compared with Her2 wild-type ones in neither cetuximab group nor chemotherapy group. In further bioinformatics analysis is underdoing, and which subgroup or type of Her2 mutant potential affect cetuximab treatment need confirm. Conclusions: We show HER2 overexpression rather than total Her2 mutant contribute to resistance of cetuximab treatment in patients with mCRC harboring wild-type Ras. Next, the subgroup mutant in total Her2 mutant needs further analysis to confirm their roles in survival after cetuximab treatment.
Urban/rural disparities in stage at presentation of colorectal cancer among young adults in the United States, 2007-2015.
Authors: Nguyen Victoria , Delgado David J. , Denneny Rachel Gray , Subramoney Jay , George Brandon , Mitchell Edith P. 
Published: May 2019

3598 Background: The overall incidence rate of colorectal cancer (CRC) has declined in recent decades but is rising in young adults (YA). Disparities also exist in CRC presentation and geographical residence. We examined associations between urban/rural residence and CRC stage at presentation among YA 18-50 years old, using the Surveillance, Epidemiology, and End Results (SEER) 1973-2015 registry. Methods: Retrospective cohort study using SEER patients (pts) diagnosed with CRC between 2007-2015, aged 18-50. Urban/rural status was defined at the county level as large metro, small metro, urban non-metro, and rural. Pts were grouped by age: 18-30, 31-40, and 41-50 years old. Stage was defined as in-situ/localized and regional/distant. We used multivariable logistic regression to describe associations between urban/rural status with stage at presentation, adjusting for tumor location, histology, grade, and patient attributes (e.g. insurance status). Results: 27,198 CRC pts were analyzed: 62.2% large metro, 27.4% small metro, 9.4% urban non-metro, and 67.1% regional/distant stage. In multivariable analysis, YA in urban non-metro counties had lower odds of regional/distant stage at presentation compared to YA in large metro counties (OR = 0.87, 95% CI = 0.79-0.97). Associations between small metro and rural status with stage at presentation were not significant (OR = 0.94, 95% CI = 0.89-1.01 and OR = 0.84, 95% CI = 0.64-1.10, respectively). YA with Medicaid or no insurance had higher odds of regional/distant CRC (OR = 1.28, 95% CI = 1.17-1.39 and OR = 1.34, 95% CI = 1.20-1.51, respectively) compared to YA privately insured. Other factors in YA associated with higher odds of regional/distant CRC included signet-ring histology, poorly-, moderately-, and undifferentiated grade, and younger age (18-30 and 31-40 years old). Conclusions: YA in urban non-metro areas had lower odds of regional/distant CRC at presentation compared to YA in large metro areas. YA with Medicaid, no insurance, signet-ring histology, poorly-, moderately-, and undifferentiated grade, and younger age had higher odds of regional/distant CRC at presentation. Further research is needed to explore the etiology of these differences.
Methylated DNA markers (MDMs) in primary (pCRC) and metastatic colorectal cancers (mCRC).
Authors: Xie Hao , Mahoney Douglas W. , Peterson Molly M , Foote Patrick H. , Burger Kelli , Doering Karen A , Taylor William R. , Cao Xiaoming , McGlinch Maria , Berger Calise K. , Wu Tsung-Teh , Hubbard Joleen Marie , Ahlquist David A. , Kisiel John B. 
Published: May 2019

3599 Background: Existing tools for post-treatment CRC surveillance and monitoring are insensitive and expensive. MDMs are broadly informative for early detection of CRC but have not been extensively studied for disease monitoring. As a first step, we sought to assess the concordance of novel CRC-associated MDMs in pCRC and mCRC. Methods: A panel of 14 MDMs previously identified to be highly discriminant for pCRC was selected on the basis of high median fold-change of MDM levels relative to buffy coat (682 (IQR: 132-19347)). Surgically resected pCRC and paired mCRC were identified from institutional pathology databases. Quantitative methylation-specific PCR was used to assay MDMs. 30 paired samples per metastatic subtype were calculated to be sufficient. MDM levels were compared using two-sample and paired Wilcoxon rank sum tests. Results: 87 patients with paired pCRC and mCRC including 57 synchronous and 30 metachronous metastases were included. 41/87 (47%) had neoadjuvant and 59/87 (68%) had adjuvant chemotherapy. All synchronous metastases were to liver. Metachronous metastases were to liver in 19/30 (63%) and to lung in 11/30 (37%). The levels of 14 selected MDMs were remarkably similar between paired pCRC and mCRC (Table). Individual MDM levels and the average level of all MDMs combined were not significantly different ( p> 0.0018 by Bonferroni correction). Conclusions: MDM levels are highly concordant in pCRC and mCRC. Thus, MDMs discovered from pCRC should be further studied for non-invasive surveillance after surgical resection and monitoring of treatment response in mCRC. [Table: see text]
Differences in clinical outcomes in young-onset colorectal cancer based on ethnicity in an NCI designated comprehensive cancer center.
Authors: Fangman Benjamin David , Haff Stephen , Scielzo Shannon , Sanjeevaiah Aravind , Verma Udit N. , Cox John Vernon , Kainthla Radhika , Beg Muhammad Shaalan , Kazmi Syed Mohammad Ali 
Published: May 2019

3605 Background: Ethnic disparities can impact clinical outcomes of young-onset colorectal cancer (CRC) patients. We aimed to determine if differences in outcomes based on ethnicity exist in young–onset CRC treated at an NCI-designated comprehensive cancer center program. Methods: A retrospective chart review for stage II – IV young-onset CRC patients ≤45 years old diagnosed between 04/2011 and 11/2015. Patients had to undergo treatment at safety-net Parkland Hospital (PH) or at the Simmons Comprehensive Cancer Center (SCCC) in Dallas, TX. Demographic data, dates of surgery, adjuvant chemotherapy, recurrence or death were obtained. Results: Of 123 patients that met inclusion criteria, 15 were excluded due to incomplete information. Of the remaining 108 patients, 36 (33%) and 72 patients (67%) were treated at SCCC and PH, respectively. Sixty (55%) were non-Hispanic vs 48 (44.4%) Hispanic. There were more Stage IV patients at SCCC vs Parkland (58.3% vs 30.6%, p < 0.01) but there was no difference regarding ethnicity. Also, no significant difference was seen between non-Hispanic White (NHW), Hispanic, and Black patients in median days to colectomy (1 vs 13 vs 0; p = .402) or adjuvant chemotherapy (55.5 vs 53.0 vs 64.0 days, p = .820). Hispanic patients had significantly better overall survival (OS) than Black or NHW patients (p = 0.025). The OS benefit was driven by improved 5-year OS in stage II/III Hispanic vs NHW vs Black patients (95% vs 62% vs 60%; p = 0.06). Multivariate Cox Regression analysis showed stage II/III (p < 0.001) and Hispanic ethnicity (p < 0.001) were independently associated with improved outcomes. Conclusions: In young-onset CRC treated at an NCI-designated comprehensive cancer center, Hispanic ethnicity had better OS than other ethnicities and this was largely due to better outcomes in stage II and III CRC. The causes for these ethnic differences in young-onset CRC patients needs further exploration. [Table: see text]
The genomic landscape and its prognostic significance for stage III colorectal cancer in Japan: An ancillary study of JCOG0910 trial—JCOG1506A1.
Authors: Shida Dai , Kuchiba Aya , Shibata Tatsuhiro , Hamaguchi Tetsuya , Yamasaki Satoshi , Ito Masaaki , Kobatake Takaya , Takiguchi Nobuhiro , Masaki Tadahiko , Shiozawa Manabu , Takii Yasumasa , Uetake Hiroyuki , Okamura Shu , Ojima Hitoshi , Nishizawa Yusuke , Takeyama Hiroshi , Kanato Keisuke , Shimada Yasuhiro , Murakami Yoshinori , Kanemitsu Yukihide ,   Colorectal Cancer Study Group of Japan Clinical Oncology Group
Published: May 2019

3607 Background: To date, large-scale genomic sequencings of colorectal cancers (CRC) have been reported mainly from Western countries. However, ethnic diversities, differences by stage, and the prognostic impact of the genomic landscape in CRC remain poorly identified. Methods: The subjects were 534 patients (pts) with stage III CRC from the JCOG0910 study—a randomized phase-III trial conducted in Japan on 1564 pts to assess the efficacy of S-1 versus capecitabine as adjuvant chemotherapy. Targeted-capture sequencing of 171 potentially CRC-associated genes was performed on both normal tissue and tumor samples, and somatic single-nucleotide variants and insertion/deletions were determined. Tumors with MSIsensor scores > 7 and ultra-mutated tumors with POLE mutations were grouped as hypermutated tumors. Genes whose alterations were associated with recurrence-free survival (RFS) were evaluated using multivariable Cox regression models. Results: Of the 534 pts (right-sided: 184, left-sided: 350), 109 pts had recurrences or died during the study. Mutation frequencies were as follows: TP53, 75.3%; APC, 75.1%; KRAS, 43.6%; PIK3CA, 19.7%; FBXW7, 18.5%; SOX9, 11.8%; COL6A3, 8.2%; NOTCH3, 4.5%; NRAS, 4.1%; and RNF43, 3.7%. Thirty-one tumors were hypermutated (5.8%) (right: 14.1%, left: 1.4%). None of the 49 genes with mutation frequencies > 3% showed a significant association with RFS based on Bonferroni’s adjustment for multiple testing. The following modest associations were observed: mutant KRAS [HR, 1.66; p=0.011] and mutant RNF43 [HR, 2.17; p=0.055] had poorer RFS, whereas mutant COL6A3 [HR, 0.35; p=0.040] and mutant NOTCH3 [HR, 0.18; p=0.093] had better RFS. RFS tended to be better for hypermutated than for non-hypermutated tumors [HR, 0.53; p=0.229]. Conclusions: The overall mutation spectrum of our stage III CRC cohort was generally similar to that of the Cancer Genome Atlas (TCGA). However, the mutation frequencies of TP53, SOX9, and FBXW7 were higher, and the proportion of hypermutated tumors was lower. Multiple gene mutations seemed to impact RFS, indicating that tumor genomic profiling has a high potential to support precision medicine for pts with CRC.
Preoperative chemosensitivity testing as predictor of treatment benefit in adjuvant stage III colon cancer: Preliminary analysis of the PePiTA study.
Authors: Hendlisz Alain , Caparica Rafael , Deleporte Amélie , Van Laethem Jean-Luc , Vergauwe Philippe , Van Den Eynde Marc , Deboever Guido , Janssens Jozef , Demolin Gauthier , Holbrechts Stephane , Clausse Marylene , De Grez Thierry , Vermeij Joanna , D'Hondt Lionel A. , Geboes Karen Paula , Besse-Hammer Tatiana , Buggenhout Alexis , Paesmans Marianne , Piccart Martine , Flamen Patrick 
Published: May 2019

3610 Background: Although being the standard-of-care for stage III colon cancer, no biomarkers can identify patients (pts) who benefit from adjuvant chemotherapy. In metastatic pts, the lack of metabolic response (mR) in FDG-PET/CT after 1 chemotherapy cycle predicts the absence of treatment benefit. The PePiTA study aims to evaluate if the absence of mR after 1 cycle of pre-operative chemotherapy is predictive of recurrence in non-metastatic colon cancer pts. Herein, we report a preliminary analysis on surgical outcomes, adverse events and mR assessment after 1 cycle of pre-operative chemotherapy after completing the study accrual objective. Methods: Colon cancer pts eligible for curative resection and ECOG ≤1 received 1 cycle of mFOLFOX followed by surgery in this prospective, multicentre, non-randomized trial. FDG-PET/CT was performed at baseline and after 1 cycle of mFOLFOX. Adjuvant mFOLFOX was administered for up to 12 cycles for stage III pts, whereas for stage II pts the decision to pursue adjuvant chemotherapy was at investigator’s discretion. A decrease ≥15% in SUVmax after 1 cycle of chemotherapy was defined as mR (EORTC criteria) at central review. Results: mR was assessable on the primary tumor in 204/240 pts (85%). In 11 pts (4.6%), staging was modified by the baseline FDG-PET/CT, which detected metastatic disease or other tumors. Pre-operative mFOLFOX was administered to 218 pts, of which 14 (6%) had a grade ≥3 adverse event. Surgery was performed in 218 pts, with a median delay of 20 days (6 to 59) after chemotherapy. Surgical complications occurred in 28 (13%) pts, however no deaths occurred. The median SUVmax decrease between baseline and 2nd FDG-PET/CT was 24%. A mR was observed in 65.2% of the pts, whereas 34.8% showed no mR, including 3% who had progressive disease. Conclusions: One cycle of pre-operative mFOLFOX followed by a mR assessment has shown to be a feasible and safe strategy, raising interest on the potential of neoadjuvant chemotherapy in colon cancer. The early mR assessment identified pts that may not benefit from chemotherapy and might have a worse prognosis. The substantiation of this hypothesis is expected with the study’s long-term results. Clinical trial information: NCT00994864.
Clinical features and survival among patients with standard-onset versus early-onset colorectal cancer by age groups.
Authors: Acuna Villaorduna Ana , Shah Nishi , Goel Sanjay 
Published: May 2019

3614 Background: Colorectal cancer (CRC) incidence is increasing in patients younger than 50 years old. Currently, there are discordant recommendations regarding CRC screening: while the American Cancer Society favors to start at age 45, the National Comprehensive Cancer Network and the US Preventive Task Force suggest starting at age 50. This study is aimed to compare the incidence, clinical characteristics and survival of patients diagnosed with standard-onset CRC (SO) versus early-onset colorectal cancer by age-groups. Methods: Patients diagnosed with CRC at ages older than 35 were identified using the SEER registry and categorized into four groups based on age at diagnosis. EO1 (35-39), EO2 (40-44), EO3 (45-49) and SO (>50) years, respectively. Incidence, clinical features and survival were compared among groups. Results: 178 678 patients were identified. 9.2% were diagnosed before 50 years. Of these, 1.4%, 2.8% and 5.1% were EO1, EO2 and EO3; respectively. Patients with early-onset CRC (EO) had higher frequency of Hispanics (13.9% vs. 8.4%, p<0.01), stage IV (24.8% vs. 17.3%, p<0.01), left-sided tumors (74.1% vs. 56.9%, p<0.01) and better survival compared to SO. Among EO groups, the frequency of poor/anaplastic grade was inversely proportional to age; stage IV was similar between EO2 and EO3 and lower in EO1. Black race, grade and stage were predictors of mortality for all EO groups; laterality was a mortality predictor in EO2 and EO3. Conclusions: EO-CRC and SO-CRC have different pathological features that should be considered for CRC screening. Higher rates of stage IV disease are encountered in patients between 40-49 years old; hence early screening should be considered. Given higher rates of left-sided tumors, sigmoidoscopy might be an adequate tool for most patients with EO-CRC. [Table: see text]
APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma.
Authors: Tempero Margaret A. , Reni Michele , Riess Hanno , Pelzer Uwe , O'Reilly Eileen Mary , Winter Jordan Michael , Oh Do-Youn , Li Chung-Pin , Tortora Giampaolo , Chang Heung-Moon , Lopez Charles D. , Tabernero Josep , Van Cutsem Eric , Philip Philip Agop , Goldstein David , Berlin Jordan , Ferrara Stefano , Li Mingyu , Lu Brian D. , Biankin Andrew 
Published: May 2019

4000 Background: In metastatic pancreatic cancer (PC), nab-P/G demonstrated significantly longer overall survival (OS) vs G. APACT assessed efficacy & safety of nab-P/G vs G in surgically resected PC. Methods: Treatment (tx)-naive patients (pts) with histologically confirmed PC, macroscopic complete resection, ECOG PS 0/1, & CA19-9 < 100 U/mL were eligible. Stratification factors: resection status (R0/R1), lymph node status (LN+/−), & geographic region. Tx was initiated ≤ 12 wks postsurgery. Pts received nab-P 125 mg/m2 + G 1000 mg/m2 or G 1000 mg/m2 on days 1, 8, 15 of six 28-day cycles. Primary endpoint was disease-free survival (DFS) by independent reviewer (IR); IRs received baseline clinical data & scans. Secondary endpoints were OS & safety. ≈438 DFS events were needed for 90% power to detect an HR for disease recurrence or death of 0.73 with nab-P/G vs G at a 2-sided significance level of 0.05. Results: 866 pts were randomized. Median age was 64 y (range, 34 - 86); most pts had ECOG PS 0 (60%), LN+ (72%), & R0 (76%). 69% of pts completed 6 tx cycles ( nab-P/G, 66%; G, 71%). Median follow up for OS was 38.5 mo. Median IR-assessed DFS (439 events) was 19.4 mo ( nab-P/G) vs 18.8 mo (G) (HR, 0.88; 95% CI, 0.729 - 1.063; stratified log-rank P = 0.1824). Investigator-assessed DFS (571 events) was 16.6 mo ( nab-P/G) vs 13.7 mo (G) (HR, 0.82; 95% CI, 0.694 - 0.965; nominal P = 0.0168). Interim OS (427 events) was 40.5 mo ( nab-P/G) vs 36.2 mo (G) (HR, 0.82; 95% CI, 0.680 - 0.996; nominal P = 0.045). Grade ≥ 3 TEAEs were reported in 86% vs 68% of pts with nab-P/G vs G. The most common grade ≥ 3 hematologic & nonhematologic TEAEs with nab-P/G vs G were neutropenia (49% vs 43%) & fatigue (10% vs 3%). TEAEs led to death in 2 pts in each arm. Conclusions: IR DFS with nab-P/G was not significantly longer vs G; median DFS with G was longer than historical data. DFS by investigator (sensitivity analysis) and interim OS were improved with nab-P/G vs G (HR 0.82 for both). Adjuvant nab-P/G may be an option for pts who are ineligible for FOLFIRINOX. Additional OS follow-up may better support nab-P/G as an option in the adjuvant setting. Clinical trial information: NCT01964430.
A multicenter randomized controlled trial to evaluate the efficacy of surgery vs. radiofrequency ablation for small hepatocellular carcinoma (SURF trial).
Authors: Izumi Namiki , Hasegawa Kiyoshi , Nishioka Yujiro , Takayama Tadatoshi , Yamanaka Naoki , Kudo Masatoshi , Shimada Mitsuo , Inomata Masahumi , Kaneko Shuichi , Baba Hideo , Koike Kazuhiko , Omata Masao , Makuuchi Masatoshi , Matsuyama Yutaka , Kokudo Norihiro 
Published: May 2019

4002 Background: Surgery (SUR) and radiofrequency ablation (RFA) are both known to be effective therapy for treating patients with small oligonodular hepatocellular carcinoma (HCC), however there is only insufficient evidence about which therapy is more preferred approach. This randomized controlled trial was designed to prospectively compare the efficacy of SUR and RFA as the first approach to primary HCC. Methods: In this open-label trial undertaken at 49 hospital in Japan, we recruited patients having primary HCC with tumor foci numbering less than 3, each measuring 3 cm or less, Child-Pugh score of 7 or less, ages between 20 and 79 year. Before randomization, technical and liver functional feasibility for both treatment arms were confirmed by joint chart review by surgeons and hepatologists. Patients were then randomly assigned in a 1:1 ratio to undergo SUR or RFA, stratified by age, infection of hepatitis-C virus, number of tumors, tumor size and institution. The primary endpoint was recurrence free survival (RFS) and overall survival (OS). Results: Between April 2009 and August 2015, total 308 patients were enrolled to this trial. Because of ineligibility 15 patients were excluded, therefore 145 patients underwent SUR and 148 patients underwent RFA finally. There was no perioperative mortality. Under the median follow-up of 5 years, the 3-year RFS of patients underwent SUR and RFA was 49.8%, 47.7%, respectively (hazard ration [HR] 0.96, 95% CI 0.72-1.28; p = 0.793). OS will be analyzed and published after two years. Conclusions: SUR and RFA were both safe therapeutic approaches and provided equally RFS for early stage HCC smaller than 3 cm. Clinical trial information: UMIN000001795.