scholarly journals THER-10. IMPACT OF BRAF MUTATIONAL STATUS ON THE EFFICACY OF IMMUNOTHERAPY FOR MELANOMA BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i12-i13
Author(s):  
Adam Lauko ◽  
Soumya Sagar ◽  
Addison Barnett ◽  
Wei Wei ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tertiary Care ◽  
Rank Test ◽  
P Value ◽  
Wild Type ◽  
Braf Mutations ◽  
Mutational Status ◽  
Melanoma Brain Metastases ◽  
Melanoma Patients ◽  
Braf Mutant

Abstract BACKGROUND: BRAF mutations occur in 50% of melanoma patients. Targeted agents – BRAF and MEK inhibitors and immunotherapy improve survival of melanoma patients with BRAF mutations. These agents have intracranial efficacy as shown in clinical trials. However, the efficacy of immunotherapies (immune checkpoint blockade) in melanoma brain metastases and the correlation with BRAF status is not as well characterized. METHODS: We reviewed 351 patients with melanoma brain metastases treated at our tertiary care center between 2000 and 2018, 75 of which received immunotherapy with known BRAF mutational status. Two-year, 5-year, and median overall survival (OS) was calculated from the start of immunotherapy to compare the efficacy of immunotherapy in BRAF mutant and BRAF wild type patients using the log-rank test. RESULTS: At the time of diagnosis of brain metastasis, the median age was 61 (23–87) years, median KPS was 80 (50–100), number of intracranial lesions was 2 (1–15), and 79% had extra-cranial metastases. Sixty-three patients were treated with stereotactic radiosurgery (SRS), 27 underwent whole brain radiation (WBRT) and 21 underwent surgery. When treated with immunotherapy, BRAF mutant and BRAF wild type median survival was 15.7 months (95% CI=9.4 – 42.4) and 6.9 (95% CI=4.1– 26.7) months (p-value=0.205), respectively. Two-year BRAF mutant and BRAF wild type survival was 35% (95% CI=21 – 58) and 28% (95% CI=16 – 51), and 5-year survival was 22% (95% CI=10 – 46) and 23% (95% CI=11 – 47), respectively. CONCLUSIONS: Twenty percent of patients with BRAF mutant and BRAF wild-type patients treated with immunotherapy derive a long-term benefit from immunotherapy and multimodality treatment and are alive 5 years from diagnosis of brain metastases. This was rarely seen in the pre-immunotherapy era in melanoma brain metastases. There was no difference in outcome based on the BRAF mutational status with use of immunotherapy in melanoma brain metastases.

scholarly journals CMET-36. IMMUNOTHERAPY VERSUS STANDARD OF CARE IN MELANOMA BRAIN METASTASES WITH KNOWN BRAF STATUS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi59-vi59
Author(s):  
Addison Barnett ◽  
Soumya Sagar ◽  
Adam Lauko ◽  
Wei (Auston) Wei ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Median Survival ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Tertiary Care ◽  
Local Therapy ◽  
Rank Test ◽  
Wild Type ◽  
Melanoma Patients ◽  
The Impact ◽  
Braf Mutant

Abstract INTRO/OBJECTIVE A mutation of the BRAF protein is seen in approximately 50% of melanoma patients. Immune checkpoint inhibitors (ICI) are standard therapy in melanoma patients independent of a patient’s BRAF status. The primary objective of this study is to investigate the impact of BRAF status in patients treated with ICI compared to non-ICI systemic therapy on overall survival (OS) in patients with melanoma brain metastasis (MBM). METHODS We reviewed 351 patients with MBM treated at our tertiary care center between 2000 and 2018. Of these, 144 had known BRAF status, 71 of which were BRAF mutant and 73 were BRAF wild-type. OS was calculated from the date of diagnosis of MBM to compare the efficacy of ICI to other systemic therapies. Many of these patients received multiple lines of treatment including targeted therapies at some point during their care. The log-rank test and Cox proportional hazard model was utilized to determine differences in OS. RESULTS Eighty-four percent of patients received local therapy that included either surgery, stereotactic radiosurgery, or whole brain radiation therapy. In BRAF wild-type patients, 40 received ICI and 33 underwent non-ICI systemic therapy with a median survival (5.6 vs 7.1 months) and 2-year survival (28% vs 32%), respectively (p=0.64). Of the BRAF mutant patients, 33 received ICI and 38 did not with a median survival (17.1 vs 9.0 months) and 2-year survival (36% and 19%), respectively (p=0.014). When controlling for age, KPS, ECM, and number of lesions, BRAF mutant MBM patients treated with ICI compared to non-ICI had an OS hazard ratio, HR=0.4 (95% CI=0.21 – 0.78, p=0.0069). CONCLUSION ICI therapy in BRAF mutant MBM patients results in improved OS compared to those with non-ICI systemic therapy. No such difference was observed in the BRAF wild-type cohort.

scholarly journals THER-13. IMMUNOTHERAPY VERSUS STANDARD OF CARE IN MELANOMA BRAIN METASTASES WITH KNOWN BRAF STATUS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i13-i13
Author(s):  
Addison Barnett ◽  
Soumya Sagar ◽  
Adam Lauko ◽  
Wei Wei ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Median Survival ◽  
Systemic Therapy ◽  
Tertiary Care ◽  
Local Therapy ◽  
Rank Test ◽  
Wild Type ◽  
Melanoma Patients ◽  
The Impact ◽  
Braf Mutant

Abstract BACKGROUND: A mutation of the BRAF protein is seen in approximately 50% of melanoma patients. Immune checkpoint inhibitors (ICI) are standard therapy in melanoma patients independent of a patient’s BRAF status. The primary objective of this study is to investigate the impact of BRAF status in patients treated with ICI compared to non-ICI systemic therapy on overall survival (OS) in patients with melanoma brain metastasis (MBM). METHODS: We reviewed 351 patients with MBM treated at our tertiary care center between 2000 and 2018. Of these, 144 had known BRAF status, 71 of which were BRAF mutant and 73 were BRAF wild-type. OS was calculated from the date of diagnosis of brain metastasis to compare the efficacy of ICI to other systemic therapies. Many of these patients received multiple lines of treatment including targeted therapies at some point during their care. The log-rank test and Cox proportional hazard model was utilized to determine differences in OS. RESULTS: Eighty-four percent of patients received local therapy that included either surgery, stereotactic radiosurgery or whole brain radiation therapy. In BRAF wild-type patients, 40 received ICI and 33 underwent non-ICI systemic therapy with a median survival (5.6 vs 7.1 months) and 2-year survival (28% vs 32%), respectively (p=0.64). Of the BRAF mutant patients, 33 received ICI and 38 did not with a median survival (17.1 vs 9.0 months) and 2-year survival (36% and 19%), respectively (p=0.014). When controlling for age, KPS, ECM, and number of lesions, BRAF mutant MBM patients treated with ICI compared to non-ICI had an OS hazard ratio, HR=0.4 (95% CI=0.21 – 0.78, p=0.0069). CONCLUSIONS: ICI therapy in BRAF mutant MBM patients results in improved OS compared to those with non-ICI systemic therapy. No such difference was observed in the BRAF wild-type cohort.

scholarly journals CMET-18. IMPACT OF KRAS MUTATION STATUS ON THE EFFICACY OF IMMUNOTHERAPY IN LUNG CANCER BRAIN METASTASES

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi55-vi55
Author(s):  
Adam Lauko ◽  
Assad Ali ◽  
Soumya Sagar ◽  
Addison Barnett ◽  
Hong Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Care Center ◽  
Tertiary Care ◽  
Wild Type ◽  
Chi Square ◽  
Kras Mutations ◽  
Mutational Status

Abstract BACKGROUND Immunotherapy is increasingly used in patients with non-small cell lung cancer brain metastases (NSCLCBM). KRAS mutations are associated with worse prognosis and there is no FDA approved targeted therapy. KRAS mutations are associated with increased expression of PD-L1. We evaluated the outcomes of NSCLCBM with KRAS mutations treated with immune checkpoint inhibitors (ICI). METHODS We reviewed 800 patients with NSCLCBM treated at our tertiary care center. 226 had known KRAS mutational status, 121 of which received immunotherapy. Overall survival (OS) was calculated from either the start of immunotherapy (when both groups received immunotherapy) or from the date of diagnosis of brain metastasis. Kaplan-Meier method and Cox Proportional hazard model were utilized to determine differences in OS and the Chi-square test was utilized to determine differences in PD-L1 expression. RESULTS In 109 patients where both KRAS and PD-L1 status were known, KRAS mutations had greater PD-L1 expression (80.1% vs 61.9% positive, p=0.04). There was no difference in OS between KRAS mutant vs KRAS wild-type patients treated with immunotherapy. Median survival from the start of immunotherapy was 15.6 vs 15.5 months respectively (p=0.7), after adjusting for age, KPS, lesion number and extra-cranial metastasis (HR = .91, p=.7). Patients with KRAS mutations treated with immunotherapy versus those who received chemotherapy had a 1-year OS from the diagnosis of brain metastasis of 60.9% vs 38.7% respectively (trending towards significance, p=0.05). KRAS wild-type patients treated with immunotherapy versus those who did not receive immunotherapy had a 1-year OS from the diagnosis of brain metastasis of 61.9% vs 62.5% (p=0.85), respectively. DISCUSSION KRAS mutations are associated with increased PD-L1 expression. Use of immunotherapy negates the poor outcomes seen traditionally in patients with NSCLCBM and KRAS mutations and it improves survival compared to use of chemotherapy. Our experience supports the use of immunotherapy in these patients.

scholarly journals THER-09. IMPACT OF KRAS MUTATION STATUS ON THE EFFICACY OF IMMUNOTHERAPY IN LUNG CANCER BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i12-i12
Author(s):  
Adam Lauko ◽  
Assad Ali ◽  
Soumya Sagar ◽  
Addison Barnett ◽  
Hong Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Care Center ◽  
Tertiary Care ◽  
Wild Type ◽  
Chi Square ◽  
Kras Mutations ◽  
Mutational Status

Abstract BACKGROUND: Immunotherapy is increasingly used in patients with non-small cell lung cancer brain metastases (NSCLCBM). KRAS mutations are associated with worse prognosis and there is no FDA approved targeted therapy. KRAS mutations are associated with increased expression of PD-L1. We evaluated the outcomes of NSCLCBM with KRAS mutations treated with immune checkpoint inhibitors (ICI). METHODS: We reviewed 800 patients with NSCLCBM treated at our tertiary care center. 226 had known KRAS mutational status, 121 of which received immunotherapy. Overall survival (OS) was calculated from either the start of immunotherapy (when both groups received immunotherapy) or from the date of diagnosis of brain metastasis. Kaplan-Meier method and Cox Proportional hazard model were utilized to determine differences in OS and the Chi-square test was utilized to determine differences in PD-L1 expression. RESULTS: In 109 patients where both KRAS and PD-L1 status were known, KRAS mutations had greater PD-L1 expression (80.1% vs 61.9% positive, p=0.04). There was no difference in OS between KRAS mutant vs KRAS wild-type patients treated with immunotherapy. Median survival from the start of immunotherapy was 15.6 vs 15.5 months respectively (p=0.7), after adjusting for age, KPS, lesion number and extra-cranial metastasis (HR = .91, p=.7). Patients with KRAS mutations treated with immunotherapy versus those who received chemotherapy had a 1-year OS from the diagnosis of brain metastasis of 60.9% vs 38.7% respectively (trending towards significance, p=0.05). KRAS wild-type patients treated with immunotherapy versus those who did not receive immunotherapy had a 1-year OS from the diagnosis of brain metastasis of 61.9% vs 62.5% (p=0.85), respectively. DISCUSSION: KRAS mutations are associated with increased PD-L1 expression. Use of immunotherapy negates the poor outcomes seen traditionally in patients with NSCLCBM and KRAS mutations and it improves survival compared to use of chemotherapy. Our experience supports the use of immunotherapy in these patients.

scholarly journals Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam Lauko ◽  
Rupesh Kotecha ◽  
Addison Barnett ◽  
Hong Li ◽  
Vineeth Tatineni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Tertiary Care ◽  
Local Treatment ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Mutational Status ◽  
One Year ◽  
The Impact

AbstractImmune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p < 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials.

scholarly journals Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

2021 ◽  
Vol 22 (14) ◽  
pp. 7717
Author(s):  
Guido Giordano ◽  
Pietro Parcesepe ◽  
Giuseppina Bruno ◽  
Annamaria Piscazzi ◽  
Vincenzo Lizzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Braf Mutations ◽  
Mutational Status ◽  
First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

scholarly journals Rapid BRAF mutation detection in melanoma patients by immunohistochemistry

2017 ◽  
Vol 4 (1) ◽  
pp. 1-5
Author(s):  
László Fülöp ◽  
Katalin Götzer ◽  
Erzsébet Csernák ◽  
Danyil Szergejevics Kuznyecov ◽  
Erika Tóth
Keyword(s):  
Braf Inhibitor ◽  
Pcr Amplification ◽  
Diagnostic Algorithm ◽  
Braf V600e ◽  
Wild Type ◽  
Braf Gene ◽  
Braf Mutations ◽  
Activating Mutation ◽  
Melanoma Patients ◽  
Braf V600 Mutation

The V600E mutation is the most common (~90%) activating mutation of the BRAF gene. BRAF mutations have been frequently investigated in melanoma, colorectal cancer and papillary thyroid carcinoma. The importance of the detection of BRAF mutations has been rising by the routine use of Braf inhibitor therapy. We evaluated the usefulness of the BRAF V600E mutation-specific monoclonal antibody (VE1) in metastatic melanoma patients. To confirm the results of immunohistochemistry (IHC), we used COBAS 4800 BRAF V600 mutation test and PCR amplification followed by Sanger sequencing.36 of 105 patients have wild-type BRAF gene, 64 have V600E mutation and 5 of 105 have V600K mutation. Predicting the mutation only by IHC using VE1 antibody, all 58 positively scored specimen were V600E mutant. The V600K, the wild-type patients and 7 patients from the V600E mutant group scored as negative. Thus the specificity is 100% and the positive predictive value is 1 of the IHC method. After processing our data we could establish a cheaper diagnostic algorithm for rapid detection ofBRAF mutation.

NIMG-04. PREDICTING THE BRAF MUTATIONAL STATUS IN PATIENTS WITH MELANOMA BRAIN METASTASES USING RADIOMICS - A BICENTRIC STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi127-vi128
Author(s):  
Anna-Katharina Meissner ◽  
Robin Gutsche ◽  
Norbert Galldiks ◽  
Martin Kocher ◽  
Stephanie T Juenger ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Test Data ◽  
Targeted Therapies ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Support Vector ◽  
Mutational Status ◽  
Melanoma Brain Metastases ◽  
Group 2 ◽  
Group 1

Abstract BACKGROUND The BRAF V600E mutation is present in approximately 50% of patients with melanoma and is an important prerequisite for a response to targeted therapies such as BRAF inhibitors. In the majority of patients, the BRAF mutational status is based on the analysis of tissue samples from the extracranial primary tumor only. Since the extracranial and intracranial BRAF mutational status may be discrepant, the additional information on the BRAF mutational status of melanoma brain metastases would be of clinical value, e.g., for the prediction of response to targeted therapies. Here, we evaluated the potential of MRI radiomics for the determination of the intracranial BRAF mutational status in patients with melanoma brain metastases. PATIENTS AND METHODS Fifty-nine patients with melanoma brain metastases from two university hospitals (group 1, 45 patients; group 2, 14 patients) were operated with subsequent genetic analysis of the intracranial BRAF mutational status. All patients underwent structural MRI preoperatively. Areas of contrast enhancement were manually segmented and analyzed. Group 1 was used for model training and validation, group 2 for model testing. After image preprocessing and radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. Finally, the best performing radiomics model was applied to the test data. Diagnostic performances were evaluated using receiver operating characteristic (ROC) analyses. RESULTS Twenty-two patients (49%) in group 1, and 6 patients (43%) in group 2 had an intrametastatic BRAF V600E mutation. Using the best performing six parameter radiomics signature, a linear support vector machine classifier yielded an area under the ROC curve (AUC) of 0.92 (sensitivity, 83%; specificity, 88%) in the test data. CONCLUSION The developed radiomics classifier allows a non-invasive prediction of the intracranial BRAF V600E mutational status in patients with melanoma brain metastases and may be of value for treatment decisions.

scholarly journals 7 Assessing melanoma BRAF status through ddPCR of cfDNA

2019 ◽  
Vol 95 (1130) ◽  
pp. 686.4-687
Author(s):  
Lauren Passy ◽  
Shobha Silva ◽  
Ian Brock ◽  
Greg Wells ◽  
Angela Cox ◽  
...  
Keyword(s):  
Braf Mutation ◽  
Limit Of Detection ◽  
Wild Type ◽  
Braf Mutations ◽  
Mutation Status ◽  
Gapdh Gene ◽  
Fractional Abundance ◽  
Significant Difference ◽  
Tissue Specimens ◽  
Braf Mutant

IntroductionTreatment of recurrent and metastatic melanoma has been revolutionised by targeted therapy. Inhibitors of mutant BRAF are a systemic treatment offered for patients with stage III/IV melanoma who are known to carry a mutation in BRAF. Currently patients’ BRAF mutation status is assessed through molecular analysis of tissue specimens.Cell-free DNA (cfDNA) released from tumours can be used to non-invasively detect active disease and predict survival in melanoma. cfDNA also provides a method for detecting BRAF mutations. This project aimed to ascertain BRAF mutation status in cfDNA through digital droplet PCR (ddPCR) of plasma samples from patients with melanoma. We aimed to assess the relationship between cfDNA BRAF positivity and disease relapse and progression.MethodsPlasma from 100 patients with active or recently resected melanoma was obtained during previous work. 85 samples had cfDNA extracted. Tissue BRAF status was known for 57 samples. cfDNA was extracted from 1–2 ml plasma with the QIAamp circulating nucleic acid kit (QIAGEN®) following manufacturer protocol, eluting cfDNA into 100µL. cfDNA was quantified with SYBR green quantitative real-time PCR (Life Technologies), based on an 87bp GAPDH gene amplicon. ddPCR™ was performed using the Bio-Rad QX200 Droplet Generator™ and Droplet Reader as per manufacturer protocol. Analysis was performed with Bio-Rad QuantaSoft Version 1.7.4.ResultsMedian yield of cfDNA extracted from 85 samples was 1.97 ng/ml when eluted into 100µL. This was well-correlated with previous cfDNA extraction yields from this sample set (Pearson’s r=0.6687, p<0.0005), where a 200µL elution volume was used. 74 samples yielded >10,000 droplets and were included for analysis. 12 samples contained BRAF mutant positive droplets. A 74% concordance rate between tissue BRAF mutation status and the presence/absence of cfDNA BRAF mutant positive droplets was found. 7/18 tissue BRAF mutant samples contained BRAF mutant droplets, in comparison to 2/32 tissue BRAF wild-type samples. The presence of BRAF mutant positive droplets was significantly different between the tissue BRAF mutant and tissue BRAF wild-type groups (χ2 8.3145, p=0.004).Fractional abundance of BRAF mutant droplets in the samples containing mutant droplets ranged from 0.07–0.74%. When comparing BRAF mutant droplet-containing samples and samples without BRAF mutant droplets, there was no significant difference in rate of relapse (χ2 0.0948, p=0.758), nor mortality rate (χ2 3.3959, p=0.654).Conclusion cfDNA provides a non-invasive snapshot of the tumour genome and any potential therapeutic targets held within. This work demonstrates that a very low volume of cfDNA can be used to detect BRAF mutations in patients with melanoma through ddPCR.Previous work assessing BRAF status in cfDNA has used larger volumes of cfDNA. Though our concordance rates are comparable with other studies, it is possible that using a smaller amount of cfDNA in our ddPCR has resulted in some samples being below the limit of detection for ddPCR.Longitudinal study is warranted to monitor cfDNA BRAF status and mutant fractional abundance, and whether this better correlates with relapse of disease and disease progression.

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