Treatment decision based on molecular profiling in metastatic colorectal cancer with a focus on RAS pathway mutations

2022 ◽  
Author(s):  
Johannes Schöche ◽  
Dora Niedersüß-Beke
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Treatment Decision ◽  
Molecular Profiling ◽  
Ras Pathway

Treatment decision-making preferences in older patients with metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8519-8519 ◽  
Author(s):  
E. B. Elkin ◽  
S. Lee ◽  
E. S. Casper ◽  
D. Kissane ◽  
N. E. Kemeny ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Decision Making ◽  
Metastatic Colorectal Cancer ◽  
Functional Status ◽  
Patient Preference ◽  
Older Patients ◽  
Treatment Decision ◽  
Demographic Characteristics ◽  
Treatment Decision Making ◽  
Decision Control

8519 Background: Shared decision-making is a tenet of contemporary oncology practice. However, it is uncertain how involved elderly patients want to be in making treatment decisions and how physicians perceive patient preferences for involvement in decision-making. Methods: In structured interviews about multiple facets of chemotherapy treatment decision-making, we asked patients age 70 and older seen at our specialty cancer center with a recent diagnosis of metastatic colorectal cancer (CRC) about their preferences for making treatment decisions. We used Degner’s control preference scale to measure patient preference for decision control. Treating oncologists described their perception of each patient’s preference for decision control using the same scale. Control preference was assessed in relation to socio-demographic characteristics and functional status. Results: Of 52 patients interviewed, the mean age was 76 years (range 70–89), 52% were male, 60% were educated beyond high school and 25% required some help with activities of daily living (ADL). Preferences for involvement in treatment decision-making demonstrated marked variation (Table). Compared with female patients, males expressed a stronger preference for decision control (p<0.05). Preference for decision control was somewhat greater in patients under age 80, those with more education, and those with no ADL impairment, but these associations were not statistically significant. In 26% of cases, the treating physician’s perception and the patient’s expressed preference for decision control were concordant. Conclusions: In older patients with advanced CRC, preference for control in treatment decision-making shows marked heterogeneity and some correlation with socio-demographic characteristics and functional status. Physicians’ perceptions of patient preference for decision control are often inconsistent with patients’ actual preferences. [Table: see text] No significant financial relationships to disclose.

scholarly journals Deep learning for the prediction of early on-treatment response in metastatic colorectal cancer from serial medical imaging

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lin Lu ◽  
Laurent Dercle ◽  
Binsheng Zhao ◽  
Lawrence H. Schwartz
Keyword(s):  
Colorectal Cancer ◽  
Deep Learning ◽  
Metastatic Colorectal Cancer ◽  
Treatment Response ◽  
Morphological Change ◽  
Tumor Size ◽  
Tumor Response ◽  
Treatment Decision ◽  
Response Assessment ◽  
Size Change

AbstractIn current clinical practice, tumor response assessment is usually based on tumor size change on serial computerized tomography (CT) scan images. However, evaluation of tumor response to anti-vascular endothelial growth factor therapies in metastatic colorectal cancer (mCRC) is limited because morphological change in tumor may occur earlier than tumor size change. Here we present an analysis utilizing a deep learning (DL) network to characterize tumor morphological change for response assessment in mCRC patients. We retrospectively analyzed 1,028 mCRC patients who were prospectively included in the VELOUR trial (NCT00561470). We found that DL network was able to predict early on-treatment response in mCRC and showed better performance than its size-based counterpart with C-Index: 0.649 (95% CI: 0.619,0.679) vs. 0.627 (95% CI: 0.567,0.638), p = 0.009, z-test. The integration of DL network with size-based methodology could further improve the prediction performance to C-Index: 0.694 (95% CI: 0.661,0.720), which was superior to size/DL-based-only models (all p < 0.001, z-test). Our study suggests that DL network could provide a noninvasive mean for quantitative and comprehensive characterization of tumor morphological change, which may potentially benefit personalized early on-treatment decision making.

scholarly journals Predictive Biomarkers in Metastatic Colorectal Cancer: A Systematic Review

2019 ◽  
pp. 1-17
Author(s):  
Juan Ruiz-Bañobre ◽  
Raju Kandimalla ◽  
Ajay Goel
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Metastatic Colorectal Cancer ◽  
Retrospective Studies ◽  
Predictive Biomarkers ◽  
Treatment Decision ◽  
Final Analysis ◽  
Predictive Biomarker ◽  
Relevant Information ◽  
Mutational Status

PURPOSE The development and use of predictive biomarkers to guide treatment decisions are paramount not only for improving survival in patients with metastatic colorectal cancer (mCRC), but also for sparing them from unnecessary toxicity and reducing the economic burden of expensive treatments. We conducted a systematic review of published studies and evaluated the predictive biomarker landscape in the mCRC setting from a molecular and clinical viewpoint. METHODS Studies analyzing predictive biomarkers for approved therapies in patients with mCRC were identified systematically using electronic databases. Preclinical studies and those providing no relevant information were excluded. RESULTS A total of 173 studies comprising 148 biomarkers were selected for final analysis. Of all the biomarkers analyzed, 1.4% (two of 148) were explored in a prospective manner, whereas 98.6% (146 of 148) were evaluated in retrospective studies. Of the latter group, 78.8% (115 of 146) were not tested in subsequent phases, 9.6% (14 of 146) were tested in other retrospective cohorts, 8.9% (13 of 146) were retrospectively tested in at least one or more randomized cohorts, and only 2.7% (four of 146) were prospectively tested in a clinical trial. Finally, only 1.4% (two of 148) were validated sufficiently and are recognized as biomarkers for guiding treatment decision making in patients with mCRC. These markers were RAS mutational status for anti-EGFR antibodies and microsatellite instability status for anti–programmed cell death-1 drugs. CONCLUSION Despite notable efforts to identify predictive biomarkers for various therapies used in the mCRC setting, because of a lack of data beyond retrospective studies and successful biomarker-driven approaches, only two molecular biomarkers have thus far found their translation into the clinic, highlighting the imperative need for implementing novel strategies and additional research in this clinically important field.

scholarly journals Molecular Profiling in Metastatic Colorectal Cancer

ONCOLOGY ◽  
2020 ◽  
pp. 352-355
Author(s):  
Benjamin Weinberg ◽  
Rita Malley ◽  
Samantha Armstrong
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Molecular Profiling

Utility of circulating tumor DNA in the clinical management of patients with BRAFV600E metastatic colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 119-119
Author(s):  
Van K. Morris ◽  
Kanwal Pratap Singh Raghav ◽  
Arvind Dasari ◽  
Michael J. Overman ◽  
Bryan K. Kee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Targeted Therapies ◽  
Clinical Management ◽  
Tumor Tissue ◽  
Tumor Biology ◽  
Molecular Profiling ◽  
Circulating Tumor Dna ◽  
Md Anderson ◽  
Tumor Dna

119 Background: Molecular profiling is critical for oncologists in personalizing treatment decisions for patients (pts) with metastatic colorectal cancer (mCRC). In contrast to archival tumor tissue specimens classically used profiling, sequencing of circulating tumor DNA (ctDNA) is more sensitive at quantifying low mutation allele frequencies and characterize “real time” tumor biology. We assessed the relationship between detection of BRAFV600E mutations in ctDNA and the clinical management of pts with mCRC. Methods: We retrospectively analyzed mCRC patients evaluated at MD Anderson Cancer Center with BRAFV600E mutations on ctDNA. ctDNA was isolated and sequenced for somatic mutations using a 70-gene next-generation sequencing assay (MD Anderson/GuardantHealth LB70 panel). Variant allele frequency (VAF) was characterized as the ratio of mutant reads: total reads for a given gene. BRAFV600E mutations were classified as “clonal” if the relative VAF (rVAF) exceeded 50% of the maximum VAF. “Major” and “minor” subclonal mutations were called for a rVAF of 10-50% and < 10%, respectively. Associations between BRAFV600E clonality and treatment decision were performed using a Fisher’s exact test. Survival outcomes were estimated using the Kaplan-Meier method. Results: 64 patients with mCRC had a BRAFV600E mutation detected in ctDNA. Concordance between tissue and ctDNA for BRAFV600E mutation was occurred in 44/55 (80%) patients with evaluable tumor specimen. There were 9 patients with BRAFV600E mutations identified in the absence of evaluable tumor tissue. Median VAF for BRAFV600E in the ctDNA was 3.6% (interquartile range, 0.50 – 17%). The majority of patients had a clonal BRAFV600E mutation (50/64, 78%). There were 3 (5%) and 11 (17%) patients with major subclonal and minor subclonal BRAFV600E mutations, respectively. Among patients with minor subclonal BRAFV600E mutations, 91% (10/11) had developed resistance to anti-EGFR therapies for management of RASwild-type mCRC. Discordance between tissue and ctDNA BRAFV600E status was associated with minor subclones (odds ratio (OR) 56, p < .0001). Clonal BRAFV600E mutations in the ctDNA were associated with a higher likelihood for treatment with BRAF targeted therapies (OR 5.8, p = .008). Median progression-free survival among 37 evaluable patients was 6.4 months. Conclusions: Reported VAF in the ctDNA served to stratify BRAFV600E according to relative clonality. Lower VAF was linked to acquired resistance to anti-EGFR therapies, whereas higher VAF was associated with receipt of matched targeted therapies for BRAFV600E mCRC. ctDNA technologies for identifying BRAFV600E mutations are feasible and informative for conducting relevant molecular profiling for patients with mCRC.

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.

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