bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detailed incidence and mortality trends of early-onset colorectal cancer in Canada.
Authors: O'Sullivan Dylan E. , Ruan Yibing , Sutherland Robert Liam , Cheung Winson Y. , Heitman Steven J. , Hilsden Robert , Brenner Darren 
Published: June 2021

e15539 Background: There has been a consistent increase in the incidence of early-onset colorectal cancer (eoCRC), under the age of 50, in Canada since the late 1990s. Questions remain surrounding how these trends vary by topography, histology, and stage, and related trends with CRC-specific mortality. Methods: CRC incidence data were obtained from the Canadian Cancer Registry and CRC-specific mortality data from the Canadian Vital Statistics – Death Database for the years 2000 to 2017. Age-specific average annual percent changes (AAPC) in the incidence (by topography and histology) and mortality rates of CRC were estimated using the National Cancer Institute’s Joinpoint Regression Program. To determine age-specific differences (5-year age groups) in CRC diagnosis at late stage (III and IV) for years 2011 to 2017 combined, a logistic regression model adjusting for sex with the 50-54 age group as the referent was conducted. Results: AAPCs and 95% confidence intervals in the rates of incidence (topography and histology) and mortality of eoCRC from 2000 to 2017 in Canada are presented in Table. Different trends in topography were observed across sexes with the largest increases in the distal colon (splenic flexure, descending, and sigmoid) and rectum among males and rectum only among females. Significant increases were observed for non-mucinous adenocarcinomas, while significant decreases were observed for mucinous adenocarcinomas among the 40-49 age group. Compared to the 50-54 age group, only the 45-49 group had a significantly higher odds of developing late-stage colon cancer, while men and adults 25-49 had a higher odds of developing late stage rectal cancer. Despite increases in the incidence of eoCRC there has only been a significant increase in mortality for men aged 20-39. Trends in mortality vary by site, with significant decreases observed for colon cancer-specific mortality among the 40-49 age group and increases in rectal cancer-specific mortality for adults aged 20-49. Conclusions: These results indicate that the largest increases in incidence and mortality for eoCRC have occurred in the rectum and trends have varied by sex. Further research on the etiology and treatment outcomes of eoCRC patients are warranted for this patient population.[Table: see text]
KRAS, NRAS and BRAF mutational status and first line treatment patterns in Slovenian population with metastatic colorectal carcinoma: Five year results.
Authors: Mesti Tanja , Boc Marko , Rebersek Martina , Hlebanja Zvezdana , Volk Neva , Ocvirk Janja 
Published: June 2021

e15546 Background: A phase IV non-interventional study was performed from 2013 till 2018 including 650 patients with primary aim to assess KRAS, NRAS and BRAF mutational status in Slovenian population with metastatic colorectal carcinoma (mCRC) suitable for first-line treatment. The evaluation of decisions for first-line treatment regarding the biomarkers status and assessing the possible impact of the time period of the biomarker status analysis report on the treatment decision were also incorporated in the analysis. The molecular analyses for KRAS and NRAS gene mutations were performed on exons 2, 3 and 4, and for BRAF gene mutations on exon 15. The first line systemic treatment options for RAS (KRAS/NRAS) wild type (wt) and mutated type (mt) mCRC subjects were as follows: chemotherapy - Fluoropyrimidine based systemic therapy combined with oxaliplatin and/or irinotecan with/without VEGF inhibitor bevacizumab and for RAS wt subjects, with/without EGFR inhibitors, cetuximab or panitumumab. Methods: To indicate the degree of certainty of KRAS, NRAS and BRAF status frequency as being wild type or mutant type 95% confidence interval was calculated. Results: The KRAS/NRAS/BRAF mutation rates were as follows - The distribution of subjects with KRAS mutated and wild-type tumors, was almost equal, 48.8% and 47.9% respectively. Eighty nine percent of the subjects had NRAS wild type tumours and 86.1% had BRAF wild type tumours. The most frequently used treatment regardless the biomarkers status and in accordance with the treatment guidelines was bevacizumab based combination therapy (53.1%). The EGFR inhibitor (cetuximab or panitumumab) based combination therapy was used in one third of mCRC subjects (30.9%), all with mCRC RAS wt. The time period from the initial presentation of the patient until the biomarker status analysis report was two weeks. Conclusions: With this study, we have proven that the distribution of the mutations in exons 2-4 of KRAS and NRAS genes and exon 15 in the BRAF gene in the Slovenian population with metastatic colorectal cancer matches historical data. Based on this, we conclude that the treatment decision in Slovenian population with metastatic colorectal carcinoma should be in the accordance with international treatment guidelines and on evidence based medicine. The molecular analysis performed at the Institute of Oncology Ljubljana was providing necessary biomarkers status report in an acceptable time that didn’t affect the treatment decision or delay the needed cancer treatment.
Clinicopathologic features and impact of metastasectomy in patients with BRAF-mutant metastatic colorectal cancer.
Authors: Zhang Jianwei , Shen Cailu , Li Jianxia , Wu Zehua , Hu Huabin , Cai Yue , Xie Xiaoyu , Ling Jiayu , Deng Yanhong 
Published: June 2021

e15547 Background: BRAF V600E mutation is associated with poor prognosis in patients with metastatic colorectal cancer (mCRC), while the non-V600E mutation mCRC patients showed better prognosis than that of V600E mutation. The clinicopathologic features between V600E and non-V600E mutation has not yet been fully evaluated. And the impact of metastasectomy for patients with BRAF-mutant mCRC was not well-known. Methods: A retrospective study was conducted to evaluate the clinical and pathological characteristics of patients with BRAF-mutant mCRC. Next generation sequencing (22-gene panel) was performed in some of the patients. Survival was also analyzed in the cohort of BRAF V600E and non-V600E mutation with or without metastasectomy. Results: Between December 2014 and August 2020, 116 patients with BRAF-mutant mCRC were enrolled, including 94 patients with BRAF V600E mutation and 22 patients with non-V600E mutation. Significant difference was observed in the prevalence of peritoneal metastasis (69.1% vs. 27.3%, P = 0.001) and lung metastasis (11.7% vs. 36.4%, P = 0.009) between BRAF V600E mutation and non-V600E mutations. In genomic profile, SMAD4 mutation (30.7% vs. 13.7%) showed higher prevalence in patients with BRAF V600E mutation than that of non-V600E mutations, while RAS mutation (18.2% vs. 6.4%) and FBXW7 mutation (13.7% vs 3.1%) had higher incidence in BRAF non-V600E mutations than that of V600E mutation. Patients with BRAF V600E mutation showed a poorer overall survival than those with non-V600E mutations (13.9 vs. 26.8 months, P = 0.038). Totally, 46 patients received metastasectomy after systemic treatment. The median survival for BRAF V600E patients with or without metastasectomy was not reach (42.3+ months) vs. 8.3 months, respectively ( P < 0.001), and for non-V600E patients with or without metastasectomy was not reach (64.2+ months) vs. 23.3 months, respectively (P < 0.001). In multivariate analysis, ECOG performance status (0-1 vs. 2) ( P = 0.001), Staging (IVa-b vs. IVc) ( P = 0.01) and metastasectomy ( P = 0.001) were independent prognostic factors of overall survival. Conclusions: BRAF V600E mutation defines a subgroup of mCRC with worse prognosis. Metastasectomy might improve the survival benefit in carefully selected BRAF-mutant mCRC patients after systemic treatment.
Metastasectomy in colorectal carcinoma (CRC) patients (pts) with mBRAF: Prospective database analysis.
Authors: Fedyanin Mikhail , Elsnukaeva Kheda , Demidova Irina , Stroyakovskiy Daniil , Shelygin Yuri , Tsukanov Alexey , Panina Maria V , Shubin Vitaliy , Moiseenko Fedor Vladimirovich , Karpenko Elena , Bolotina Larisa , Kudryavtseva Anna , Filipenko Maxim , Vladimirova Liubov Yu , Timoshkina Natalya N. , Kit Oleg I. , Stroganova Anna , Dranko Svetlana , Tryakin Alexey , Tjulandin Sergei 
Published: June 2021

e15549 Background: Role of metastasectomy in pts with mBRAF metastatic CRC is still controversial. We performed analysis of prospective multicentric database of pts with mBRAF mCRC to evaluate the efficacy of metastasectomy in such group of pts in the real clinical practice. Methods: We analyzed a database of pts with mCRC in 7 cancer clinics in Russia and chose pts with metastasectomy with different mutational status. The primary endpoints were disease free survival (DFS) and overall survival (OS), which were calculated from the time of metastasectomy. Analysis was performed with the SPSS v.20 software package. Results: The study included 126 pts: 26 pts with mBRAF, 57 pts with mRAS and 43 pts with wtRAS/BRAF. Pts with mBRAF more often had synchronous metastases (50%/19,3/11,6%, p<0,01), N2 status (38,5%/11%/19,6%, p=0,04). In mBRAF cohort all but 1 pt had V600 mutations; peritonectomy performed in 19,2%, liver resection – in 34,6%, lung resection, ovariectomy, metastasectomy in brain and retroperitoneal lymph nodes dissection with removal of the local relapse – over 11,5%; R0 resection was achieved in 88,5%. Median DFS was 7 months in mBRAF pts, 14 months in mRAS and not achieved in wtRAS/BRAF group treated (HR 2,1, 95%CI 1,5-3.1, p<0.01). Median OS was 26 months in mBRAF, 38 months in mRAS and not achieved in wtRAS/BRAF group (HR 1,5, 95%CI 1,0-2,4, p=0.06). Perioperative chemotherapy didn’t improve DFS in pts with mBRAF (HR 1,9, 95%CI 0,67-5,7, p=0,2). The best median DFS were in pts after ovariectomy – 10 months, the worst - after retroperitoneal lymph nodes dissection with removal of the local relapse – 2 months. Conclusions: Prognosis of pts with mBRAF after metastasectomy is worse than with other mutational phenotypes. However in selected cases metastasectomy might be considered in such aggressive mCRC.
Fruquintinib in patients with metastatic colorectal cancer failed in previously bevacizumab-based therapy: A monocentric retrospective study.
Authors: Gu Xiaoqiang 
Published: June 2021

e15555 Background: Fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, is a new targeting anti-cancer agent for refractory metastatic colorectal cancer (mCRC). Promising antitumor effect of fruquintinib monotherapy was verified in a phase III FRESCO randomized study of mCRC patients, and only 30% patients were prior bevacizumab-treated. However, comprehensive effect evaluation of fruquintinib in mCRC patients who have previously failed in bevacizumab therapy were scarce. Methods: Forty patients with metastatic CRC who had previously failed at least 2 lines of standard regimen containing bevacizumab in Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine from March 2019 to February 2020 were enrolled. These patients were administrated with fruquintinib (5mg orally, once daily) in cycles of 3 weeks on/ 1 week off. Furthermore, the primary endpoint was overall survival (OS). Secondary endpoints mainly included progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), and safety profile. Statistical analyses were performed using IBM SPSS statistics software and ‘R’ statistical software with the ‘forest plot’ package. Subsequently, the variables were screened and verified through LASSO regression with the R software “glmnet” package. Results: The mOS was 8.1months (95%CI, 5.6667-12.8667), mPFS was 4.1833 months (95% CI, 3.5333-5.0667), and DCR was 65% (26 SD in 40 patients). Particularly, gender (HR: 7.11, 95%CI:1.86-27.16,P = 0.005), age (HR:0.91, 95%CI:0.85-0.98,P = 0.012), ECOG(HR:3.75, 95%CI:1.13-12.42,P = 0.03), medication duration (HR:0.62, 95%CI:0.48-0.81,P＜0.001),and the number of metastases(HR:2.95,95%CI:1.21-7.18,P = 0.017) identified the statistically significant association with OS. Eliminating the influence of time factor, ECOG and medication cycle obtained by Lasso regression were the risk factors for OS. The most frequently reported adverse events were mainly hypertension, proteinuria, hand-foot skin reaction, fatigue and diarrhea, and any new safety signals were not observed. Conclusions: Fruquintinib showed an acceptable safety profile and promising efficacy in patients with metastatic colorectal cancer failed in previously bevacizumab-based therapy. Future studies of fruquintinib should focus on identifying the patients most likely to benefit and on minimizing toxicity.
Variation in the use of genomic testing in patients with metastatic colorectal cancer.
Authors: Markt Sarah C. , Booker Benjamin , Bensken Wyatt , Schumacher Fredrick R , Rose Johnie , Cooper Gregory S. , Koroukian Siran M. 
Published: June 2021

e15557 Background: Oncology has greatly benefited from the use of clinical genomics to aid diagnostic and treatment decisions. To inform targeted therapy, standard practice dictates molecular testing of metastatic colorectal cancer (mCRC) tumors through genomic testing (GT), including molecular biomarker, single gene, or next-generation sequencing (NGS). While persisting disparities in CRC screening, treatment, and outcomes have been well described, little is known about differences in GT for mCRC. Using all-payer electronic health record-derived de-identified data from a real-world database generated from routine clinical care across the U.S., we identified combinations of demographic and clinical characteristics, rather than individual factors, associated with GT. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. During the study period, the de-identified data originated from approximately 280 US cancer clinics (̃800 sites of care). Our study population included 26,524 patients with mCRC during the years 2013-2020. We evaluated documentation of receipt of GT (individual biomarker or NGS) measured within one year of diagnosis of metastatic disease, by demographic (age, sex, and race/ethnicity), payer type, de novo metastatic cancer (vs. progression to metastatic disease), tumor site (colon vs. rectum), Eastern Cooperative Oncology Group (ECOG) performance status, and year of diagnosis. We identified Elixhauser comorbid conditions from ICD codes, and grouped them by count (0-4, 5+). We conducted Classification and Regression Tree (CART) analysis, a machine learning approach to identify combinations of demographic and clinical characteristics associated with receipt of GT. Results: Nearly 83% had documented GT, 90% of whom did so within 6 months of diagnosis. The largest group of patients with GT at 90% consisted of individuals with colon cancer, 64 years of age or younger, 0-4 comorbidities, and an ECOG score of 0 or 1 (n = 2,004). Conversely, the lowest rates of GT ( < 60%) were observed among women 75 years of age or older, despite having 0-4 comorbidities (n = 1,314). In this group of patients, GT was higher among those with ECOG score of 1 than among those with high ECOG scores (66% and 54%, respectively). On the other hand, 71% of patients 75 years of age or older with 5+ comorbidities and high ECOG scores received GT. Conclusions: Considerable variations exist in GT across subgroups of the population. Additional analysis is warranted to characterize young and healthy patients who did not receive GT, and those who did get tested despite their older age and compromised health status. Future analyses will investigate whether documentation of receipt of GT is associated with treatment decisions and outcomes.
Identifying an immune-related gene-pair for prognosis prediction of metastatic colorectal cancer.
Authors: Zhu Qiqi , Cai Du , Wang Wei , Zhong Min-Er , Fan Dejun , Liu Xuanhui , Li Cheng-Hang , Huang Ze-Ping , Lv Min-Yi , Hu Chuling , Duan Xin , Wu Xiaojian , Gao Feng 
Published: June 2021

e15565 Background: Few robust predictive biomarkers have been applied in clinical practice due to the heterogeneity of metastatic colorectal cancer (mCRC) . Using the gene pair method, the absolute expression value of genes can be converted into the relative order of genes, which can minimize the influence of the sequencing platform difference and batch effects, and improve the robustness of the model. The main objective of this study was to establish an immune-related gene pairs signature (IRGPs) and evaluate the impact of the IRGPs in predicting the prognosis in mCRC. Methods: A total of 205 mCRC patients containing overall survival (OS) information from the training cohort ( n = 119) and validation cohort ( n = 86) were enrolled in this study. LASSO algorithm was used to select prognosis related gene pairs. Univariate and multivariate analyses were used to validate the prognostic value of the IRGPs. Gene sets enrichment analysis (GSEA) and immune infiltration analysis were used to explore the underlying biological mechanism. Results: An IRGPs signature containing 22 gene pairs was constructed, which could significantly separate patients of the training cohort ( n = 119) and validation cohort ( n = 86) into the low-risk and high-risk group with different outcomes. Multivariate analysis with clinical factors confirmed the independent prognostic value of IRGPs that higher IRGPs was associated with worse prognosis (training cohort: hazard ratio (HR) = 10.54[4.99-22.32], P < 0.001; validation cohort: HR = 3.53[1.24-10.08], P = 0.012). GSEA showed that several metastasis and immune-related pathway including angiogenesis, TGF-β-signaling, epithelial-mesenchymal transition and inflammatory response were enriched in the high-risk group. Through further analysis of the immune factors, we found that the proportions of CD4+ memory T cell, regulatory T cell, and Myeloid dendritic cell were significantly higher in the low-risk group, while the infiltrations of the Macrophage (M0) and Neutrophil were significantly higher in the high-risk group. Conclusions: The IRGPs signature could predict the prognosis of mCRC patients. Further prospective validations are needed to confirm the clinical utility of IRGPs in the treatment decision.
Predictors of lymph node metastasis in T1 colorectal cancer in young patients: Results from a national cancer registry.
Authors: Singh Jameel Kenneth , Ramai Daryl , Bhandari Peter , Kani Tarik , MD Mohamed Barakat , Tai Waqqas , Chandan Saurabh , Facciorusso Antonio 
Published: June 2021

e15590 Background: The incidence of colorectal cancer in young adults ( < 44 years) is on the rise. Identifying young patients at risk of regional lymph node metastasis (LNM) is crucial for long-term survival. Prior studies have examined rates of LMN in average risk patients. The objective of this study is to fill the knowledge gap by examining predictors of LMN in young patients using a national cancer registry. Methods: Patients diagnosed with T1 colorectal cancer were identified in the Surveillance, Epidemiology, and End Results register 2000-2017. Potential predictors of LNM and its impact on cancer-specific survival were assessed in logistic and Cox regression with and without multivariable adjustment. Results: In total, 692 patients with T1 colorectal cancer were identified. Most tumors occurred in White race (77.7%), between 40-44 years of age (49.4%), grade III tumor differentiation (59.8%), 1 to 1.9 cm in size (32.2%), and were left sided tumors (61.1%). The overall LNM rate was 22.5 % (n = 149). Using multivariate analysis, LMN was associated with tumor grade IV (undifferentiated) (odds ratio (OR) 2.94, CL: 1.06-8.12; p = 0.038), and increasing tumor size (1 cm – 1.9 cm: OR 2.92, CL: 1.71-4.97, p < 0.001; 2.0 cm – 2.9 cm: OR 2.00, CI: 1.05-3.77, p = 0.034; and ≥ 3.0 cm: OR 2.68, CI: 1.43-5.01, p = 0.002). Five-year cancer-specific survival for patients with LNM was 91% and for patients without LNM 98%. Adjusted cox proportion models showed that LMN was associated with four times higher rate of mortality (hazard ratio (HR) 4.43, CI: 1.27-15.52, p = 0.020). Conclusions: In conclusion, the overall LNM rate is approximately 22% for T1 CRC in young patients (less than 45 years). Tumor size and tumor grade are significant predictors for LNM in patients with T1 CRC cancer. Moreover, positive lymph node involvement is a significant prognostic factor for cancer specific survival. Thus, careful preoperative assessment of lymph node status is essential in clinical decision making, to achieve better long-term outcomes
“No problem” health-related quality of life (HRQoL) in patients treated with regorafenib (Reg) for relapsed metastatic colorectal cancer (mCRC).
Authors: Su Yun , Ostojic Helene , Jaeger Savina 
Published: June 2021

e15593 Background: REG has been shown to improve survival and delay time to quality of life deterioration over placebo (PBO) in two large randomized, double-blind, placebo-controlled multi-center phase III trials CORRECT and CONCUR for the treatment of relapsed mCRC. We report on findings of the five-dimensions of HRQoL in the two trials. Methods: The five key dimensions of HRQoL were captured in the CORRECT and CONCUR trials using EuroQol 5-Dimension questionnaire 3-level version (EQ-5D-3L). The 5 dimensions are mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: no problems, some problems, severe problems. We calculated the proportion of intent-to-treat (ITT) patients reporting “no problems” (NP) in each of the 5 dimensions by cycle and arm of treatment in the two trials. Results: Detailed descriptions of the trials have been reported previously. Due to space, data below focuses on CORRECT. ITT patients included 760 total in the CORRECT trial, 2:1 randomized to receive REG (N=505) and PBO (N=255). At baseline (BL), 95% of the ITT patients completed the questionnaire (Table), and patients reported the highest percentage of NP in self-care (87%) and lowest in pain/discomfort (35%). EQ-5D completion rates decline with each cycle of treatment, as are the percentages reporting NP in each dimension. The declines however appeared much more rapid for PBO than for REG. Both completion rate and percentages of NP were somewhat higher for PBO than for REG at BL, this continued until only cycle 2 and reversed completely from cycle 3 onward showing increasingly diminished proportion of those on PBO able to complete the questionnaire and reporting NP in each dimension. The differences between arms became larger with each cycle beginning cycle 3. Findings were similar for CONCUR (not shown). Conclusions: REG appeared to enable patients to maintain their mobility, self-care, usual activity, being pain-free and anxiety-free as well as their ability to complete the EQ-5D questionnaire, at much higher rates than PBO. Those whose EQ-5D were no longer available were likely poor performers that discontinued due to progression, death, toxicity or other unfavorable factors associated with their treatments. For PBO, toxicity was unlikely the reason. These findings suggest REG has a positive impact on quality of survival, as well as on length of survival. Further confirmatory analyses are needed.[Table: see text]