Molecular profiling to predict outcomes following Y90 radioembolization for metastatic colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 686-686
Author(s):  
Petra Prins ◽  
Alexandra Gradzka ◽  
Alexander Y. Kim ◽  
John Marshall ◽  
Keith Robert Unger
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Retrospective Chart Review ◽  
Molecular Profiling ◽  
Inclusion Criteria ◽  
Kras Mutations ◽  
Response Data ◽  
Y90 Radioembolization ◽  
Colorectal Cancer Patients ◽  
Generation Sequencing

686 Background: Radioembolizaton with yttrium-90 (Y90) has been shown to decrease progression within the liver in patients with unresectable metastatic colorectal cancer (CRC). Molecular profiling (MP) plays an important role in providing precision based therapy for our patients. The purpose of this study was to evaluate predictive associations between genetic mutations in Y90 treated CRC pts and treatment outcomes. Methods: A retrospective chart review of patients at GUMH was conducted for patients who underwent Y90 radioembolization for metastatic CRC between 2010 and 2017. Inclusion criteria were: Liver metastasis, Y90 treatment and MP. Y90 response of the treated liver lesions was evaluated according to RECIST criteria within 4 months of treatment; non-responders were classified as those with progressive disease (PD) and all others were considered responders. Statistical analysis was performed to reveal any significant associations. Results: Out of 285 CRC records with MP screened, 32 pts adhered to our inclusion criteria. Of these 47% were male and 53% female. The average age at diagnosis was 50.4 yrs. For22 pts (69%) Y90 treatment was combined with chemotherapy. Y90 response data showed response in 50% (n = 16) and PD in 31% (n = 10) of the pts. Six pts did not have Y90 response data. Median OS between groups was not significant but longer for those responders (33 vs 26 m). Next Generation Sequencing revealed pathogenic mutations for APC in 20 pts (63%), KRAS in 12 (38%) and TP53 in 13 pts (41%) none of them showing any significant association with Y90 response data (p > 0.05). OS from date of Y90 was significantly improved in patients with TP53 mutations and KRAS WT. There was no association between differences in MP and OS from date of diagnosis. Conclusions: TP53 and KRAS mutations were predictive of survival but not response following Y90 for metastatic colorectal cancer patients. This hypothesis generating study demonstrates the MP may be helpful in stratifying CRC patients who benefit from radiation therapy. Further study is necessary.

scholarly journals KRAS and NRAS mutational gene profile of metastatic colorectal cancer patients in Jordan: Molecular spectrum, frequency and distribution pattern

2019 ◽  
Author(s):  
Muhammad Awidi ◽  
Nidaa Ababneh ◽  
Maha Shomaf ◽  
Feras Al Fararjeh ◽  
Laila Owaidi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Distribution Pattern ◽  
Cancer Patients ◽  
Molecular Spectrum ◽  
Kras Mutations ◽  
Exon 2 ◽  
Ras Mutations ◽  
Colorectal Cancer Patients ◽  
Kras Exon

Abstract Background A constitutively active RAS protein in the absence of stimulation of the epidermal growth factor receptor (EGFR) is the result of mutations in KRAS and NRAS genes. Mutations in the KRAS exon 2 and outside exon 2 have been found to predict the resistance to anti-EGFR monoclonal therapy. A substantial proportion of metastatic colorectal cancer cases (mCRC) exhibit RAS mutations outside KRAS exon 2, particularly in KRAS exon 3 and 4 and NRAS exons 2, 3. No data about RAS mutations outside KRAS exon 2 are available for Jordanian patients with mCRC. We aim to study the molecular spectrum, frequency, and distribution pattern of KRAS and NRAS mutations in Jordanian patients with mCRC. Methods A cohort of 190 Jordanian metastatic colorectal cancer patients were enrolled in the trial. We detected mutations in exon 2 of the KRAS and NRAS gene as well as mutations outside of exon 2 using the StripAssay technique. The KRAS StripAssay covered 29 mutations and 22 NRAS mutations. Results Mutations were observed in 92 (48.42%) cases, and KRAS exon 2 accounted for 76 cases (83.69%). KRAS G12D was the most common mutation, occurring in 18 cases, followed by KRAS G12A in 16 cases, and G12T in 13 cases. Mutations outside of KRAS exon 2 represented 16.3% of the mutated cases. Among those, 6 cases (6.48%) carried mutations in NRAS exon 2, 3 and 10 cases (10.87%) in KRAS exon 3 and 4. Conclusion The frequency of NRAS and KRAS mutations outside of exon 2 appears to be higher in Jordanian patients in comparison with patients from western countries. KRAS mutations outside of exon 2 should be tested routinely to identify patients who should not be treated with anti-EGFR antibodies.

scholarly journals Prevalence and coexistence of KRAS, BRAF, PIK3CA, NRAS, TP53, and APC mutations in Indian colorectal cancer patients: Next-generation sequencing–based cohort study

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769226 ◽  
Author(s):  
Mayank Jauhri ◽  
Akanksha Bhatnagar ◽  
Satish Gupta ◽  
Manasa BP ◽  
Sachin Minhas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Cancer Patients ◽  
Gene Mutations ◽  
Next Generation ◽  
Kras Mutations ◽  
Pik3ca Mutations ◽  
Potential Biomarker ◽  
Colorectal Cancer Patients ◽  
Generation Sequencing

Colorectal cancer incidences are on a rise in India. In this study, we have analyzed the mutation frequencies of six potential biomarkers, their coexistence, association with clinicopathological characteristics, and tumor location in Indian colorectal cancer patients. Next-generation sequencing was performed to identify mutations in the six potential biomarker genes using formalin-fixed paraffin-embedded tissue blocks of 112 colorectal cancer patients. The mutation frequency observed in KRAS, BRAF, PIK3CA, NRAS, TP53, and APC was 35.7%, 7.1%, 16.1%, 6.3%, 39.3%, and 29.5%, respectively. The significant associations of mutations were KRAS with age less than 60 years (p = 0.041), PIK3CA with males (p = 0.032), tumor stage I–II (p = 0.013), lack of metastasis in lymph nodes (p = 0.040), NRAS with rectum (p = 0.002), and APC with T2 stage of tumor growth (p = 0.013). No single patient harbored mutations in these six genes or any five genes simultaneously. Significance was noted in coexistence of KRAS with APC (p = 0.024) and mutual exclusion of KRAS with BRAF (p = 0.029). PIK3CA exon 9 was observed to be more frequently associated with KRAS mutations than PIK3CA exon 20 (p = 0.072). NRAS mutations were mutually exclusive with BRAF and PIK3CA mutations. As per our knowledge, this is the first next-generation sequencing–based biomarker study in Indian colorectal cancer patients. Frequent coexistence of gene mutations in pairs and triplets suggests that synergistic effect of overlapping mutations might further trigger the disease. In addition, infrequent coexistence of multiple gene mutations hints toward different signaling pathways for colorectal cancer tumorigenesis.

scholarly journals KRAS mutations: variable incidences in a Brazilian cohort of 8,234 metastatic colorectal cancer patients

2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Carlos Gil Ferreira ◽  
Veronica Aran ◽  
Ilana Zalcberg-Renault ◽  
Ana Paula Victorino ◽  
Jonas H Salem ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Kras Mutations ◽  
Colorectal Cancer Patients ◽  
Brazilian Cohort

scholarly journals A comparison of four methods for detecting KRAS mutations in formalin-fixed specimens from metastatic colorectal cancer patients

2016 ◽  
Vol 12 (1) ◽  
pp. 150-156 ◽  
Author(s):  
MOTOTSUGU MATSUNAGA ◽  
TOSHIKADO KANETA ◽  
KEISUKE MIWA ◽  
WATARU ICHIKAWA ◽  
KEN-ICHI FUJITA ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Kras Mutations ◽  
Colorectal Cancer Patients ◽  
Formalin Fixed
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