bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and prognostic factors in patents (pts) with mutant BRAF (mBRAF) metastatic colorectal cancer (mCRC) in Russia.
Authors: Fedyanin Mikhail , Elsnukaeva Kheda , Demidova Irina , Stroyakovskiy Daniil , Shelygin Yury , Tsukanov Alexey , Ponomorenko Alexey , Panina Maria V , Shubin Vitaliy , Moiseenko Fedor Vladimirovich , Bolotina Larisa , Kudryavtseva Anna , Filipenko Maxim , Voscoboev Mikhail , Vladimirova Liubov Yu , Kit Oleg Ivanovich , Stroganova Anna , Dranko Svetlana , Senderovich Anastasia , Tjulandin Sergei 
Published: May 2019

e15035 Background: m BRAF mCRC has the aggressive phenotype. The incidence of such mutation in Europe and the USA is around 8-14%, in Asian countries - 4-8%. The purpose of this population-based study was to determine the incidence and identifying prognostic factors in pts with mBRAF mCRC in Russia. Methods: A multicenter retrospective analysis of clinical data and treatment results of pts with mBRAF mCRC was performed. The main method for determining mutations was a PCR. The main efficacy endpoint was progression free survival (PFS) at the 1st line. Multivariate analysis was performed using Cox regression model. Results: 437 out of 8646 pts (5%) with a known mutational status had m BRAF (V600E). Clinical data were collected from 119/437 (27.2%): female - 65.5%, average age - 60 years (28-86), MSI-H -10%; the right-sided primary tumor – in 65%, left-sided – in 17%, rectum – in 18%; the primary tumor was removed in 76%; adjuvant chemotherapy was administered in 30%; lung metastases – in 15 %, liver - 45%, peritoneal metastases – in 38%; metastasectomy was performed in 13% pts. The first line was administered in 86 (72%) pts: FOLFIRI / XELIRI - 17 (20%), FOLFOX / XELOX - 50 (58%), FOLFOXIRI - 12 (14%), monotherapy of fluoropyrimidines – in 7 (8%). Bevacizumab was added to chemotherapy at 1st line in 25 (29%) patients, anti-EGFR – in 8 (9%) pts. PFS at the 1st line was 7 months: XELOX / FOLFOX - 7, FOLFOXIRI - 7, FOLFIRI / XELIRI - 6 and fluoropyrimidines - 2 months (HR 0.9, 95% CI 0.6-1.1, p = 0.3). None of the clinical or morphological factors except the presence of metastases in the retroperitoneal lymph nodes (HR 2.6, 95% CI 1.3-5.4, p = 0.006) did not have an independent negative prognostic value. Conclusions: In contrast to Western countries the incidence of mBRAF gene in the population of pts with mCRC in the Russia is low and we found a high incidence of localization of the primary tumor in the rectum. We didn’t reveal any prognostic factors except metastases in the retroperitoneal lymph nodes, and didn’t reveal any differences between the usual duplets and standard regimen for such mutation - FOLFOXIRI in term of 1st line PFS. This suggests we need a prospective randomized study to determine the optimal regimen of chemotherapy at 1st line for mBRAF mCRC pts.
Microsatellite instability and mutations in BRAF and KRAS in small bowel adenocarcinoma.
Authors: Michalaki Vasiliki , Polydorou Andreas , Theodosopoulos Theodosios , Frangulidis George , Dafnios Nikolaos , Frangou Plemmenou Matrona , Papadimitriou Christos 
Published: May 2019

e15037 Background: Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. Activating KRAS and/or BRAF mutations have been identified as predictors of resistance to anti-epidermal growth factor receptor (EGFR) The aim of this study was to perform a comprehensive immunohistochemical.analysis of KRAS, NRAS, V600E BRAF mutations and microsatellite instability using a cohort of surgically resected cases in our institution. Methods: A total of 17 patients (10 males and 7 females; mean age, 56.2 years old; range, 45-75 years old) received chemotherapy due to non-curative tumor resection, unresectable tumor or post-operative recurrence. Twelve patents received fluoropirimidine and oxaliplatin based first line chemotherapy. Molecular targeted agents were administered to 15 patients, for whom it was their first- or second-line therapy. Results: KRAS mutations were found in 7 cases (41%), out of which 5 (29%) were in exons 12/13. BRAFV600E mutation was observed in 1/17 pt. Microsatellite instability was identified in 3/17pt (MSI; 18%), mainly related to a loss of expression of MLH1 protein. Univariate analysis revealed a PS of 0 (P=0.0226) and treatment with platinum-based chemotherapy (P=0.0047) were significant factors for an improved prognosis. Among the 12 patients who received oxaliplatin-based chemotherapy as a first-line chemotherapy, a PS of 0 (P=0.0255) and treatment with anti-EGFR agents (P=0.0127) were significant positive prognostic factors. Toxicities due to the molecular targeted agents were not experienced. The median overall survival time was 14.3 months (range, 3-52 months), the median DFS was 14.2 months and the median OS was 32 months. Conclusions: To date, there is no standard chemotherapy regimen for advanced SBAs and little is known about their molecular characteristics. The results of the present study indicate that oxaliplatin based chemotherapy containing molecular targeted agents is a well-tolerated and effective treatment option for SBA. A better understanding of disease biology may help to identify therapeutic targets and advance precision medicine.
Efficacy of anti-EGFR-based treatment (tx) in second-line and beyond according to tumor location (TL) in RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients (pts): A mono-institutional retrospective analysis.
Authors: Vivolo Raffaella , Calegari Maria Alessandra , Basso Michele , Zurlo Ina Valeria , Di Stefano Brunella , Bensi Maria , Camarda Floriana , Martini Maurizio , Cocomazzi Alessandra , Pozzo Carmelo , Bria Emilio , Salvatore Lisa , Tortora Giampaolo 
Published: May 2019

e15038 Background: Right- (R) and left-sided (L) mCRCs exhibit different clinical and molecular features. Several retrospective analyses showed that the survival benefit of anti-EGFR-based tx is limited to RAS/BRAF wt L-sided mCRC pts, with a larger effect in the first-line setting. Few data are available concerning the anti-EGFR efficacy according to TL in 2nd and following lines. Methods: Pts affected by RAS/BRAF wt mCRC treated at our Institution with anti-EGFR-based tx in 2nd and following lines were retrospectively collected. The objective of the analysis was to compare tx activity and efficacy according to TL. Primary endpoint was overall survival (OS); secondary endpoints were progression free survival (PFS) and response rate (RR). Results: A total of 47 RAS/BRAF wt mCRC pts treated with an anti-EGFR-based tx in 2nd and following lines were identified. Of those, 32 (68%) were L-sided and 15 (32%) R-sided, respectively. Pts (age, gender, PS ECOG) and tumor (number of metastatic sites) characteristics and number of tx lines were well balanced between the two 21 pts received anti-EGFR alone, 26 pts anti-EGFR plus CT. mOS was 22.3 in L-sided and 7.3 months in R-sided group (HR 2.3, 95%CI 1.02-5.14, p = 0.04). At multivariate analysis TL and PS ECOG independently correlated with OS ( p = 0.02 and p =0.0089). mPFS was 8.4 and 3.9 months in pts with L-sided and R-sided tumor, respectively (HR 1.3; 95%CI 0.64-2.80, p =0.43). RR was higher in L-sided compared to R-sided tumor (37.5 vs 13.3) ( p= 0.09). Conclusions: Our analysis, although limited by the small sample and by its retrospective nature, indicates a better OS in L-sided compared to R-sided tumors treated with anti-EGFR-based tx in 2nd and following lines. A prospective validation is warranted.
Colorectal cancer lung metastasis: Could multidisciplinary management suggest the right strategy?
Authors: Zurlo Ina Valeria , Basso Michele , Congedo Maria Teresa , Vita Maria Letizia , Petracca Ciavarella Leonardo , Salvatore Lisa , Calegari Maria Alessandra , Pozzo Carmelo , Di Stefano Brunella , Bensi Maria , Vivolo Raffaella , Barone Carlo , Cassano Alessandra , Bria Emilio , Margaritora Stefano , Tortora Giampaolo 
Published: May 2019

e15039 Background: Unlike liver metastases surgery, the resection of colorectal cancer lung metastasis (CCLM) is not standardized and data are still poor. Therefore, we conducted a retrospective analysis to evaluate the management of CCLM at our Centre. Methods: We retrospectively analyzed patients (pts) with CCLM treated at our Institution from Jan-2007 to Jan-2017. Aim of the study was to evaluate the impact of clinical and pathological features with survival outcomes (DFS and OS). Differences were compared with the use of log-rank test and parameters considered statistically significant ( p value < 0.5) at univariate were compared at multivariate analysis. Results: 141 pts were included in the analysis. 87 pts received a preoperative chemotherapy (pCT) and 54 an adjuvant (a)CT. In the whole population median DFS (mDFS) was 24 m (20-24) and median OS (mOS) 54 m (46-82), while 21 m (20-34) and 65 m (45-108) for pts undergoing pCT and 15 m (20-28) and 53 m (38 – 76) for those receiving aCT respectively, without statistically significant differences (p=0.4). Age, gender, PS, disease-free interval (DFI) (> or <24 months), primary tumor sidedness, mucinous histology, grading, RAS status, timing of lung metastasis (metachronous vs synchronous), number of lesions (>2), metastasis location (uni vs bilateral) and liver resection were evaluated at univariate and multivariate analysis. DFS was correlated with DFI > 24m (p=0.02), timing (p=0.03), number (p<0,0001) of metastasis and metastasis location (p=0.01) whereas OS was associated to DFI (p=0.02), number (p=0.0005), metastasis location (p=0.037) and RAS status (p=0.05) at univariate. At multivariate analysis, number of lesions correlated to DFS (p=0.0006) while DFI (p=0.0034) and RAS status (p=0.05) to OS. Conclusions: Our single Centre retrospective experience suggests an important clinical impact from surgery of CCLM based on mOS of the whole population. These data strengthen the role of a multidisciplinary management to allow pts to achieve surgery whenever possible, regardless of previous liver surgery, metachronous vs synchronous metastasis, DFI and RAS status.
The impact of nodal metastasis on survival in stage IV colon cancer: Analysis of National Cancer Database 2004-2014.
Authors: Saha Sukamal , Elgamal Mohamed , Cherry Meghan , Buttar Robin , Wiese David , Kaushal Sunil , Alnounou Mustafa , Singh Trevor , Eilender David S. , Grewal Sandeep Singh , Arora Madan L. 
Published: May 2019

e15042 Background: Lymph node (LN) metastasis (mets) is the strongest prognostic factor in colon cancer (CCa), however, its significance in Stage IV disease remains controversial. We analysed National Cancer Database (NCDB) to determine the impact of nodal mets on survival in Stage IV CCa patients (pts). Methods: From 2004-2014, NCDB pts with pathologic Stage IV CCa were divided into groups based on LN status and No. of +ve LNs. Only Stage IV CCa pts who underwent surgical resection of their primary tumor with available pathologic data as well as chemotherapy data were included. Kaplan-Meier method and log rank test were used to compare 5-year overall survival. Results: A total of 33574 pts data met the criteria of the study. Adenocarcinoma represented 82.3% of the total pts. Majority of the pts (82.61%) had +ve LN status. Mean survival was 36.3 vs 24.2 months in -ve LN vs +ve LN pts respectively. Overall 5yr survival was better in LN -ve pts ( 23.4%) versus LN +ve pts ( 10.2%) Survival for all years was inversely related to the number of +ve LN ( Table). For LN +ve or LN -ve pts, receiving any form of chemotherapy was associated with significantly improved survival when compared to no chemotherapy. Conclusions: LN status and No. of +ve LNs impact the prognosis of CCa, even in stage IV. Receiving some form of chemotherapy improves the prognosis for both pts with +ve or -ve LN status. These findings suggest that separation of Stage IV LN negative versus positive patients may be warranted in staging and treatment. 5 year survival according to LN status and No. of positive LN. [Table: see text]
A phase Ib study of pembrolizumab (Pem) in combination with stereotactic body radiotherapy (SBRT) for resectable liver metastatic MSS colorectal cancer (CRC): A postoperative safety analysis.
Authors: Bassetti Michael Frederick , Turk Anita Ahmed , Lubner Sam Joseph , Uboha Nataliya Volodymyrivna , LoConte Noelle K. , Mulkerin Daniel , Kim David H. , Matkowskyj Kristina , Weber Sharon M. , Abbott Daniel , Eickhoff Jens C. , Deming Dustin A. 
Published: May 2019

e15047 Background: Adjunctive therapies are essential to enhance the effect of anti-PD1 therapies for the treatment of microsatellite stable (MSS) colorectal cancer. SBRT is utilized to treat liver metastatic CRC, causing an increase in immunogenic intra-tumoral and intra-lymphatic antigen release and a rapid influx of responding immune cells. We hypothesize that radiation enhances the immunogenicity of MSS CRC and potentiates the effectiveness of PD-1 blockade. This phase Ib study examines the safety and efficacy of the sequential combination of SBRT and Pem in patients for whom the goal is to resect all sites of known disease. Methods: Key eligibility criteria include MSS CRC with liver-confined metastatic disease with the therapeutic goal of resection of all radiographic disease with one operation. Subjects must be a candidate for SBRT to 1-3 liver metastases. Prior surgery and systemic chemotherapy are allowed. Subjects receive sequential SBRT and cycle 1 of Pem prior to operative management. Postoperatively, patients complete cycles 2-9 of Pem followed by scheduled surveillance with imaging every 12 weeks. The primary objectives are to determine the safety/tolerability of this regimen and the recurrence rate at 1 year following clearance of metastatic disease. Secondary objectives include time to recurrence, DFS, and OS. Results: 10 patients (median age 61.5 [range 39-69]) have been enrolled and completed the intended neoadjuvant therapy, operative management and at least 4 adjuvant cycles of Pem. All patients had received prior FOLFOX. SBRT median dose was 50 Gy (40-60 Gy) to a single lesion targeted in all patients. Mean gross tumor size targeted was 19.1cc (2.3-80.4). Any-grade post-operative AEs (>20%) attributable to Pem include diarrhea (30%), hyperbilirubinemia (20%%), and leukopenia (20%). Post-operative AEs included one case of biliary tract injury and biloma, not related to immunotherapy. No grade 3/4 immunotherapy AEs have occurred. Conclusions: The combination of SBRT with Pem and surgical resection is well tolerated with no signal of increased immunotherapy-related toxicity in the post-operative setting. Clinical trial information: NCT02837263.
The “effect” of T classification on colorectal liver metastasis.
Authors: Wu Lunpo , Zheng Hongjuan , Fu Jianfei , Du Jinlin , Zheng Shu , Wang Liangjing 
Published: May 2019

e15049 Background: T classification is considered as a detail and credible category of the depth of tumor invasion. Generally, with the increasing T category, the risk of metastases should be continuously rising. However, there is a group of metastatic patients with early T classification, who were supposed to have a low metastatic probability. Our study aims to present the T classification on metastatic liver colorectal cancer (CRLM) in both clinical and biological aspects, and explore preoperative predictions to develop a convenient individual assessment model for clinicians to speculate whether these patients, whose prognosis is extremely poor. Methods: Tissue samples of primary colorectal cancer were obtained at our center. Patients with CRLM during 2010 to 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier and Cox models were used to analyze the survival differences. We identified preoperative prognostic factors based on the Cox analysis and constructed a nomogram model. The predictive accuracy and discriminative ability were measured by concordance index (C-index) and calibration curve. Results: The mRNA array from our hospital showed that there is an obvious difference between the T1/2N0M1 subgroup and the T3/4N0M1 subgroup. Patients with early T classification (T1) were more often have tumors located in rectum, with well differentiation, with no lymph node metastasis and a higher CEA level. Further survival analysis indicated that early T classification (T1) was an independent prognostic factor with poorer survival. When the lymph node (N) status was taken into consideration, patients with T1 N+ had an obvious better survival than T1 N0 patients. A clinical nomogram was constructed based on preoperative factors. The calibration curves for probability of 1-, 2-, and 5-year overall survival showed a good agreement between nomogram prediction and actual observation. Conclusions: The prognosis of T1M1 is extremely poorer than T3/4M1. The prognosis of T1N+ is better than T1N0. It is time to pay more attention to the high-risk monitoring and screening of T1 in early colon cancer.
Reporting of patient (pt) characteristics (c) and use of stratification factors (SF) in phase III trials for metastatic colorectal cancer (mCRC): Urgent need for standardization.
Authors: Horn Robert Asa , Tannenbaum Daniel , Morris Van K. , Johnson Benny , Overman Michael J. , Parseghian Christine Megerdichian , Kopetz Scott , Eng Cathy , Rogers Jane E. , Raghav Kanwal Pratap Singh , Dasari Arvind 
Published: May 2019

e15055 Background: An increasing number of pt and tumor c have predictive and prognostic implications in mCRC. However, there is no consensus on their reporting in trial results. Methods: Pt c and SF from 136 phase III trials of systemic therapies (Rx) in mCRC published between 1988 and 2018 (68,326 pts) were collected. Trials were also grouped per publication date (G1: 1988-97; G2: 98 – 2007; G3: 08-18). Patterns of reporting and trends across G were evaluated. Results: Pt c consistently reported were performance status, PS (98.5%), age (92.6%) and gender (90.4%); race (20.6%) & weight/BMI/BSA were not (13.2%). Tumor c frequently reported were metastatic (met) spread (70.6%) while time intervals related to disease course (25%) and synchronous met vs not (19.1%) were omitted. Of note, primary site was largely reported as colon vs rectum (69%) and sidedness or anatomical location was discernable only in 10.3%. Prior Rx reporting focused on chemo (58.5%) with radiation and surgery and reported in 34% & 28.7%. Reporting of prognostic factors was variable and limited: histology grade CEA, alk phos, LDH (range 10.3-15.4%). Only 11.8% of trials reported genomic factors - KRAS MT was included in all with BRAF MT in 4.4%. Of 140 trials used for SF analysis, 115 had ≥ 1 (range 1-7). Common SF were PS (60%), geography /institution (55.7%). Prior Rx (27%), met spread (24.3%) were sometimes used while primary site (7.8%), genomic factors (6.1%) rarely were. Trends across G are per Table. Conclusions: There is marked inconsistency in pt c & SF reporting in mCRC trials. Consensus guidelines will aid in standardization of trial interpretation and future meta-analyses; and will need to be updated based on emerging data. [Table: see text]
Mutational burden on circulating cell-free tumor-DNA testing as a surrogate marker of mismatch repair deficiency/microsatellite instability and/or response to immunotherapy in patients with colorectal cancer.
Authors: Kamatham Saivaishnavi , Colibaseanu Dorin , Merchea Amit , Shahjehan Faisal , Starr Jason Scott , Mody Kabir , Kasi Pashtoon Murtaza 
Published: May 2019

e15066 Background: Circulating cell-free tumor-DNA (ctDNA) testing (‘liquid biopsy’) is increasingly being employed both in clinical trials as well as clinical practice. We aimed to contrast and compare the differences in the number of somatic mutations observed on ctDNA testing between mismatch repair deficient/microsatellite instability-high (dMMR/MSI-High) versus mismatch repair proficient/microsatellite stable (pMMR/MSS) colorectal cancers (CRC). Methods: We had 20 patients at Mayo Clinic Florida that were dMMR/MSI-High with testing through the commercially available platform (Guardant360) that uses a 73-gene panel. Median numbers of somatic mutations were compared between the 2 subset of CRC. Results: Patients with dMMR/MSI-High CRC had a median of 8 mutations (range: 2-15) versus a median of 4 mutations (range: 1-22) in pMMR/MSS patients, p-value of 0.001. Similarly, the mean number of somatic mutations were 7.47 (S.D. ± 4.15) versus 5.02 mutations (S.D. ± 3.83) in patients with dMMR/MSI-H and pMMR/MSS, tumors respectively. Though it is simplistic, we could still potentially identify patients who may be candidates for immunotherapy by gauging the mutational burden reported (Table). Furthermore, on serial testing, decline in mutational burden as early as few weeks into therapy was predictive of response later on imaging. Conclusions: Analysis of number of somatic mutations on ctDNA testing can be complementary to MMR/MSI-testing, especially in situations when tissue is not available or safe to obtain. This can also be of value in predicting and/or following response to immunotherapy. The utility of this may go beyond CRC in identifying patients who may benefit from immunotherapy. [Table: see text]
Patterns of metastasis and second primary malignancies (SPM) in colorectal cancer: A perspective from Peru.
Authors: Leon Jorge , Namuche Fernando , Montenegro Paola Catherine , Flores Claudio J. 
Published: May 2019

e15068 Background: The incidence of colorectal cancer (CRC) in Peru has increased in the last decades. Approximately 20% of patients with CRC already have metastases at diagnosis, and this figure has been stable over the last two decades. The lack of data makes it more difficult to manage our patients. The metastatic setting and patients with second primary malignancies are complicated scenarios. The objective of our study was to explore and describe the metastasis patterns and the second primary malignancies’ frequency in CRC patients. Methods: We retrospectively reviewed the electronic medical records of 609 patients with CRC from one specialized Peruvian cancer center between 2006 and 2016. For the evaluation of the metastasis pattern, we selected 198 patients with metastasis at debut and the patients who had relapse of the disease. Descriptive results for numeric variables were presented as means with standard deviation (SD) or medians with interquartile range (IQR), depending on their distributions; otherwise, we expressed the qualitative variables as numbers with percentages. We evaluated the metastasis pattern according to primary tumour sidedness, age, CEA, histological grade, histological type. A survival analysis was performed with Kaplan Meier method, comparing the curves with Log Rank test for metastasectomy, biological therapy and number of sites with metastatic disease. A multivariate analysis was performed using the Cox regression model with the statistically significant variables found in the univariate analysis. Results: At the time of diagnosis, stage IV disease accounted for 15.3% (93) of all CRC cases. 105 (stage I-III) pts had relapse disease. Regardless of the primary tumor site, the most common site for metastatic spread was the liver (42.9%), lung (12.6%), carcinomatosis (18.2%). Pts who underwent metastasectomy presented a better OS [HR, 0.284; 95% CI, 0.123-0.657; p < 0.05], as well as pts who received biologic therapy [HR, 0.641; 95% CI, 0.416-0.990; p < 0.05] and a greater number of sites with metastatic disease had worst OS [HR, 1.878; 95% CI, 1.181-2.985; p < 0.05] The incidence of SPM following CRC was 48/609 (7.8%), the more frequent localizations were: breast, prostate and lung with 14.6% each, then kidney 10.4%, bladder 8.3%. Conclusions: In mCRC metastasectomy, biological therapy and number of sites with metastatic disease play an important role in OS. The more frequent localizations with SPM were breast, prostate and lung.