scholarly journals Plasma metanephrines and prospective prediction of tumor location, size and mutation type in patients with pheochromocytoma and paraganglioma

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Graeme Eisenhofer ◽  
Timo Deutschbein ◽  
Georgiana Constantinescu ◽  
Katharina Langton ◽  
Christina Pamporaki ◽  
...  
Keyword(s):  
Tumor Size ◽  
Clinical Decision Making ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Tumor Location ◽  
Other Information ◽  
Catecholamine Metabolites ◽  
Plasma Metanephrines ◽  
Plasma Free Metanephrines ◽  
Mutation Type

AbstractObjectivesPlasma free metanephrines are commonly used for diagnosis of pheochromocytoma and paraganglioma (PPGLs), but can also provide other information. This multicenter study prospectively examined whether tumor size, location, and mutations could be predicted by these metabolites.MethodsPredictions of tumor location, size, and mutation type, based on measurements of plasma normetanephrine, metanephrine, and methoxytyramine were made without knowledge of disease in 267 patients subsequently determined to have PPGLs.ResultsPredictions of adrenal vs. extra-adrenal locations according to increased plasma concentrations of metanephrine and methoxytyramine were correct in 93 and 97% of the respective 136 and 33 patients in who these predictions were possible. Predicted mean tumor diameters correlated positively (p<0.0001) with measured diameters; predictions agreed well for pheochromocytomas but were overestimated for paragangliomas. Considering only patients with mutations, 51 of the 54 (94%) patients with NF1 or RET mutations were correctly predicted with those mutations according to increased plasma metanephrine, whereas no or minimal increase in metanephrine correctly predicted all 71 patients with either VHL or SDHx mutations; furthermore, among the latter group increases in methoxytyramine correctly predicted SDHx mutations in 93% of the 29 cases for this specific prediction.ConclusionsExtents and patterns of increased plasma O-methylated catecholamine metabolites among patients with PPGLs allow predictions of tumor size, adrenal vs. extra-adrenal locations and general types of mutations. Predictions of tumor location are, however, only possible for patients with clearly increased plasma methoxytyramine or metanephrine. Where possible or clinically relevant the predictions are potentially useful for subsequent clinical decision-making.

scholarly journals Pheochromocytoma Catecholamine Phenotypes and Prediction of Tumor Size and Location by Use of Plasma Free Metanephrines

2005 ◽  
Vol 51 (4) ◽  
pp. 735-744 ◽  
Author(s):  
Graeme Eisenhofer ◽  
Jacques WM Lenders ◽  
David S Goldstein ◽  
Massimo Mannelli ◽  
Gyorgy Csako ◽  
...  
Keyword(s):  
Tumor Size ◽  
Clinical Decision Making ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
High Plasma ◽  
Adrenal Tumors ◽  
Tumor Diameter ◽  
Urinary Catecholamines ◽  
Additional Information ◽  
Plasma Free Metanephrines

Abstract Background: Measurements of plasma free metanephrines (normetanephrine and metanephrine) provide a useful test for diagnosis of pheochromocytoma and may provide other information about the nature of these tumors. Methods: We examined relationships of tumor size, location, and catecholamine content with plasma and urinary metanephrines or catecholamines in 275 patients with pheochromocytoma. We then prospectively examined whether measurements of plasma free metanephrines could predict tumor size and location in an additional 16 patients. Results: Relative proportions of epinephrine and norepinephrine in tumor tissue were closely matched by relative increases of plasma or urinary metanephrine and normetanephrine, but not by epinephrine and norepinephrine. Tumor diameter showed strong positive relationships with summed plasma concentrations or urinary outputs of metanephrine and normetanephrine (r = 0.81 and 0.77; P &lt;0.001), whereas relationships with plasma or urinary catecholamines were weaker (r = 0.41 and 0.44). All tumors in which increases in plasma metanephrine were &gt;15% of the combined increases of normetanephrine and metanephrine either had adrenal locations or appeared to be recurrences of previously resected adrenal tumors. Measurements of plasma free metanephrines predicted tumor diameter to within a mean of 30% of actual diameter, and high plasma concentrations of free metanephrine relative to normetanephrine accurately predicted adrenal locations. Conclusions: Measurements of plasma free metanephrines not only provide information about the likely presence or absence of a pheochromocytoma, but when a tumor is present, can also help predict tumor size and location. This additional information may be useful for clinical decision-making during tumor localization procedures.

Single-dose pharmacokinetics of orally administered terbinafine in bearded dragons (Pogona vitticeps) and the antifungal susceptibility patterns of Nannizziopsis guarroi

2021 ◽  
pp. 1-8
Author(s):  
Michael S. McEntire ◽  
Jennifer M. Reinhart ◽  
Sherry K. Cox ◽  
Krista A. Keller
Keyword(s):  
Single Dose ◽  
High Performance ◽  
Clinical Decision Making ◽  
Peak Plasma ◽  
Antifungal Susceptibility ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Oral Solution ◽  
Susceptibility Data ◽  
Pogona Vitticeps

Abstract OBJECTIVE To identify the antifungal susceptibility of Nanniziopsis guarroi isolates and to evaluate the single-dose pharmacokinetics of orally administered terbinafine in bearded dragons. ANIMALS 8 healthy adult bearded dragons. PROCEDURES 4 isolates of N guarroi were tested for antifungal susceptibility. A compounded oral solution of terbinafine (25 mg/mL [20 mg/kg]) was given before blood (0.2 mL) was drawn from the ventral tail vein at 0, 4, 8, 12, 24, 48, 72, and 96 hours after administration. Plasma terbinafine concentrations were measured with high-performance liquid chromatography. RESULTS The antifungal minimum inhibitory concentrations against N guarroi isolates ranged from 4,000 to > 64,000 ng/mL for fluconazole, 125 to 2,000 ng/mL for itraconazole, 125 to 2,000 ng/mL for ketoconazole, 125 to 1,000 ng/mL for posaconazole, 60 to 250 ng/mL for voriconazole, and 15 to 30 ng/mL for terbinafine. The mean ± SD peak plasma terbinafine concentration in bearded dragons was 435 ± 338 ng/mL at 13 ± 4.66 hours after administration. Plasma concentrations remained > 30 ng/mL for > 24 hours in all bearded dragons and for > 48 hours in 6 of 8 bearded dragons. Mean ± SD terminal half-life following oral administration was 21.2 ± 12.40 hours. CLINICAL RELEVANCE Antifungal susceptibility data are available for use in clinical decision making. Results indicated that administration of terbinafine (20 mg/kg, PO, q 24 to 48 h) in bearded dragons may be appropriate for the treatment of dermatomycoses caused by N guarroi. Clinical studies are needed to determine the efficacy of such treatment.

Serial plasma and CSF cell-free tumor DNA (cf-tDNA) tracking in diffuse midline glioma patients undergoing treatment with ONC201.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2012-2012
Author(s):  
Evan Cantor ◽  
Kyle Wierzbicki ◽  
Rohinton Tarapore ◽  
Chase Thomas ◽  
Rodrigo Cartaxo ◽  
...  
Keyword(s):  
Tumor Size ◽  
Clinical Decision Making ◽  
Phase 1 ◽  
Complete Response ◽  
Clinical Decision ◽  
Experimental Therapy ◽  
Plasma Samples ◽  
Mri Scans ◽  
Tumor Dna ◽  
Diffuse Midline Glioma

2012 Background: Diffuse midline glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis. There are few available means of monitoring the disease beyond serial MRI scans, making clinical decision making slow, difficult, and often reactive. Methods: We conducted a multi-site phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma (NCT03416530). Patients enrolled on Arm D of the trial (n=24) underwent serial lumbar puncture (baseline, 2 and 6 months) for cell-free tumor DNA (cf-tDNA) analysis at time of MRI. Additionally, patients on all arms of the trial at the University of Michigan underwent serial plasma collection. CSF collection was feasible in this cohort, with no procedural complications. We collected a total of 96 plasma samples and 53 CSF samples from 29 patients, including those with H3F3A (H3.3) (n=13), HIST13HB (H3.1) (n= 4), and unknown H3 status/not biopsied (n=12) [range of 0-8 CSF samples and 0-10 plasma samples]. We performed digital droplet polymerase chain reaction (ddPCR) analysis and/or amplicon-based electronic sequencing (Oxford Nanopore) of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal 2D tumor area on MRI). Results: Preliminary analysis of samples (n=58) demonstrates a correlation between changes in tumor size and H3K27M cf-tDNA VAF, when removing samples with concurrent bevacizumab. Analysis of remaining CSF and plasma samples is ongoing, including analysis of novel biomarkers of response. In multiple cases, early reduction in CSF cf-tDNA predicts long-term clinical response (>1 year) to ONC201 and does not increase in cases of later-defined pseudo-progression (radiation necrosis). For example, a now 9-year old patient with thalamic H3K27M-mutant DMG underwent treatment with ONC201 after initial radiation and developed an increase in tumor size at 4 months post-radiation (124% baseline) of unclear etiology at the time. Meanwhile, her ddPCR declined from baseline 6.76% VAF to <1%, which has persisted, with now near complete response (85% tumor reduction) at 30 months on treatment from diagnosis. Conclusions: In summary, we present the feasibility and utility of serial CSF/plasma monitoring of a promising experimental therapy for DMG.

Therapeutic Drug Monitoring of Imatinib and Impact on Clinical Decision Making.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4820-4820 ◽  
Author(s):  
Carolyn Blasdel ◽  
Yanfeng Wang ◽  
Theodore Lagattuta ◽  
Brian Druker ◽  
Laurie Letvak ◽  
...  
Keyword(s):  
Decision Making ◽  
Drug Monitoring ◽  
Dose Adjustment ◽  
Clinical Decision Making ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Therapeutic Drug ◽  
Dose Increase ◽  
Qrt Pcr ◽  
Drug Concentrations

Abstract OBJECTIVES: Imatinib (IM) has demonstrated durable clinical efficacy in the majority of chronic myeloid leukemia (CML) patients. Optimal response may be influenced by multiple innate and external factors, some of which may be controlled by monitoring plasma concentrations of the drug. This abstract reports 6 cases where analyzing plasma IM trough concentrations (Cmin) in patients treated with three commonly used IM doses (400, 600, and 800 mg daily) influenced clinical decision making. METHODS: IM trough blood samples were collected at a time before that day’s IM dosing. Plasma concentrations of IM were determined by a validated LC/MS/MS method. RESULTS: In large population studies of CML patients enrolled in Phase I, II, and III clinical trials, the mean Cmin levels of IM at 400 mg qd, 600 mg qd, and 400 mg bid doses were: 981 (±543, 55%, n=394), 1572 (±1032, 66%, n=14), and 3479 (±1264, 36%, n=14) ng/mL, respectively. Large inter-patient variability was shown at all three doses. Of the 6 cases detailed in the table below, 4 (ID 1, 3, 4, and 5) had dose reduction due to tolerability concerns with subsequent improvement of symptoms following dose adjustment. One patient (ID 2) had a dose increase because of a poor qRT-PCR response. Another (ID 6) had a dose increase due to low plasma IM exposure resulting from drug-drug interaction with phenytoin, a known inducer of CYP3A4 (the major metabolizing isozyme for IM). After dose adjustment, all six patients showed good clinical response to IM treatment. The new mean Cmin value in these patients was 2000 (±471) ng/mL, representing a 24% coefficient of variability. CONCLUSIONS: Although the data is limited, IM drug monitoring proved useful in managing tolerability, lack of efficacy, adherence or potential drug interactions that modulate imatinib drug concentrations. More prospective studies are needed to demonstrate the value of IM drug monitoring in routine clinical practice. Patient ID Age, Sex CML Stage IM Daily Dose 1st Cmin (ng/mL) Reason for Dose Change New Dosing Regimen New Cmin (ng/mL) CP, chronic phase1 1 54, f CP 200 mg bid, Jan 03 3048, Sep 05 transfusion-dependent, anemia, Sep 05 300 mg, Oct 05 2130, Jan 06 2 9, f CP 300 mg, Jan 05 not done qRT-PCR 0.016, Jan 06 400 mg, Jan 06 2341, Jul 06 3 13, f CP 300 mg bid, May 05; 700 mg, Aug 05; 600 mg, Sep 05 1966, Feb 06 nausea, fatigue, arthralgias, myalgia, ongoing 400 mg, Mar 06 1222, May 06 4 67, f CP 400 mg, Feb 05 not done myelosuppression, Mar 05 200 mg, Mar 05 1928, May 06 5 53, f CP 400 mg, Apr 03; 600 mg, May 03; 800 mg, Jul 04 not done inflammatory pulmonary reaction with shortness of breath; dose held, Mar 05 400 mg, Oct 05 2378, May 06 6 73, m CP 350 mg, on phenytoin, Apr 99 35, Jun 99 stopped phenytoin, Jul 99 500 mg, Jul 99 not done; qRT-PCR negative, Jul 06

scholarly journals Prolactin ≤1 ng/mL predicts macroprolactinoma reduction after cabergoline therapy

2020 ◽  
Vol 182 (2) ◽  
pp. 177-183
Author(s):  
Daham Kim ◽  
Cheol Ryong Ku ◽  
Kyungwon Kim ◽  
Hyein Jung ◽  
Eun Jig Lee
Keyword(s):  
Tumor Size ◽  
Prolactin Level ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Post Treatment ◽  
Size Reduction ◽  
Multivariable Logistic Regression Analysis ◽  
High Dose ◽  
Pituitary Hormone ◽  
Level 1

Objective The association between prolactin level variation and prolactinoma size reduction remains unclear. This study aimed to determine the prolactin level cut-off predictive of a tumor size reduction. Design Retrospective cohort study. Methods We reviewed medical records of patients with prolactinoma who received primary cabergoline therapy and for whom complete data on pituitary hormone assays and sellar MRI at baseline and 3 months post treatment were available. We tested whether the certain prolactin level after 3 months post treatment predicted better response. Results Prolactin levels normalized in 109 (88.6%) of 123 included macroprolactinoma patients. The mean tumor size reduction was 22.9%, and patients in the lowest prolactin tertile (≤0.7) had the highest frequency of tumor size reductions of ≥20% (73.7 vs 52.9% and 45.9% in tertiles 2 (>0.7 to 2.6) and 3 (>2.6 to 20), P = 0.015). Patients with prolactin levels ≤1 ng/mL exhibited larger tumor size reductions vs those with prolactin levels of 1–20 (27.2 ± 18.3% vs 19.5 ± 13.9%, P = 0.014), 1–10 (19.3 ± 13.7%, P = 0.017) and 1–5 ng/mL (19.2 ± 14.3%, P = 0.039). A multivariable logistic regression analysis revealed that a prolactin level ≤1 ng/mL at 3 months and high-dose cabergoline therapy were significantly associated with tumor size reductions of ≥20% (odds ratio (OR): 2.8, 95% confidence interval (CI): 1.2–6.7, P = 0.017; OR: 2.0, 95% CI: 1.0–3.9, P = 0.043). Conclusions A prolactin level ≤1 ng/mL at 3 months after cabergoline treatment was correlated with a significant tumor size reduction in patients with macroprolactinoma. This finding may help clinical decision making when treating macroprolactinoma patients.

The impact of tumor size on survival in T3 non-small cell lung-cancer with direct extension.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20033-e20033
Author(s):  
Clara H. Kim ◽  
Michelle C. Salazar ◽  
Jessica R. Hoag ◽  
Joshua E. Rosen ◽  
Brian N. Arnold ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Tumor Size ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Adjuvant Chemoradiation ◽  
Direct Extension ◽  
Cox Proportional Hazard Models ◽  
N Stage ◽  
The Impact

e20033 Background: Tumor size is an important prognostic variable that affects clinical decision-making in NSCLC including the use of adjuvant therapy. However, the association between tumor size and survival in a subset of patients who have T3 NSCLC with direct extension into nearby structures (T3dx) has not been explicitly characterized. We hypothesize that tumor size impacts survival and prognosis within this cohort. Methods: Patients with T3dxin 2006-2013 who underwent lobectomy or pneumonectomy were identified in the National Cancer Database. Patients who received neoadjuvant therapy or had positive margins were excluded. Tumor size was categorized based on cutoffs used by current staging guidelines and patients were stratified by pathologic N stage (see table). Cox proportional hazard models were used to measure the independent impact of tumor size on survival. Results: Overall, 0.1-3cm tumors exhibit superior 5-year survival compared to 3.1-5cm and >5cm tumors. Tumor size is significantly associated with survival in N0 patients but not in N1 and N2 patients. Use of adjuvant chemotherapy is associated with improved survival in the overall cohort and all subgroups; however, use of adjuvant chemoradiation may be associated with inferior survival in the overall cohort. Conclusions: Larger tumor size is associated with inferior survival in T3dx in the absence of nodal disease. T3dx requires a more tailored approach to adjuvant therapy than other T3 subgroups. Adjuvant chemotherapy appears to benefit all patients with T3dx; however, the role of adjuvant chemoradiation is less clear. [Table: see text]

scholarly journals An Accidental Repetitive 10-Fold Overdose of Sildenafil in a Young Infant with Pulmonary Hypertension

Neonatology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Laura E.J. Peeters ◽  
Suzan C.M. Cochius-den Otter ◽  
Bregje C.M. Witjes ◽  
Saskia J. Gischler ◽  
Robert B. Flint
Keyword(s):  
Pulmonary Hypertension ◽  
Clinical Decision Making ◽  
Young Infant ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Therapeutic Drug ◽  
Serious Adverse Events ◽  
High Exposure ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Phosphodiesterase Type

Sildenafil is a selective phosphodiesterase type-5 inhibitor that is increasingly used to treat pulmonary hypertension (PH) in neonates. Only little is known about the relation between the dose of sildenafil, plasma concentrations, and the degree of toxicity. Here, we present a young infant with congenital diaphragmatic hernia and PH who received an unintentional 10-fold overdose of oral sildenafil for 6 consecutive days. This overdose, compared to the therapeutic dose, resulted in increased plasma concentrations of sildenafil from 42 to 521 mcg/L and desmethylsildenafil from 81 to 393 mcg/L. However, the high exposure only led to diarrhea, without any other serious adverse events. This case describes the mild symptoms upon an overdose with the role of therapeutic drug monitoring to monitor exposure in relation to symptoms and therewith support clinical decision-making.

Plasma Measurement of D-Dimer as Diagnostic Aid in Suspected Venous Thromboembolism: An Overview

1994 ◽  
Vol 71 (01) ◽  
pp. 001-006 ◽  
Author(s):  
H Bounameaux ◽  
P de Moerloose ◽  
A Perrier ◽  
G Reber
Keyword(s):  
Venous Thromboembolism ◽  
Clinical Decision Making ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Elisa Test ◽  
Diagnostic Approach ◽  
Plasma Measurement ◽  
Patients At Risk ◽  
Elisa Technique ◽  
D Dimer

SummaryThis paper reviews the published experience with plasma measurement of D-dimer (DD), a specific degradation product of crosslinked fibrin, in the diagnostic approach of venous thromboembolism (VTE). Pooling 11 studies (with weighting of the figures according to sample size) with a total of 1337 patients clinically suspected of deep venous thrombosis (DVT) (prevalence of DVT 35%) disclosed an average weighted sensitivity of 96.8% (95% CI: 95.2–98.4) and specificity of 35.2% (95% Cl: 32.0–38.4) for the presence of DVT when the ELISA technique was used. In 908 patients suspected of pulmonary embolism (PE) from 9 trials (prevalence of PE 38%), the ELISA technique was associated with a weighted sensitivity of 96.8% (95% Cl: 95.0–98.6) and specificity of 45.1% (95% Cl: 40.8–49.4) for the disease. Figures obtained with latex assays were definitely lower, precluding their use in the diagnostic approach of VTE.These results show that a low concentration of plasma DD measured by the ELISA technique (usually less than 500 μg/1) might be used to rule out VTE in clinically suspected patients. Increased plasma concentrations are of no utility because of the low specificity of this test result.The clinical usefulness of the DD ELISA test should now be assessed in management trials under routine conditions, in the frame of clinical decision-making diagnostic processes. Lastly, the promising data obtained in a small number of asymptomatic, postoperative patients at risk of VTE deserve confirmation before the test can be recommended for initial screening in thrombo-prophylactic trials.

scholarly journals First Identification of Circulating Prepro–A-Type Natriuretic Peptide (PreproANP) Signal Peptide Fragments in Humans: Initial Assessment as Cardiovascular Biomarkers

2012 ◽  
Vol 58 (4) ◽  
pp. 757-767 ◽  
Author(s):  
Chris J Pemberton ◽  
Maithri Siriwardena ◽  
Torsten Kleffmann ◽  
Peter Ruygrok ◽  
Suetonia C Palmer ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Signal Peptide ◽  
Cardiac Tissue ◽  
Clinical Decision Making ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Heart Tissue ◽  
Initial Assessment ◽  
Arterial Blood ◽  
Creatine Kinase Mb

Abstract BACKGROUND New biomarkers are needed to assist clinical decision making in cardiovascular disease. We have recently shown that signal peptides may represent a novel biomarker target in cardiovascular diseases. METHODS We developed a novel immunoassay for the signal peptide of preproANP (ANPsp) and used it to document cardiac tissue levels of ANPsp in explant human hearts (n = 9), circulating venous concentrations of ANPsp in healthy volunteers (n = 65), temporal ANPsp concentrations in patients with ST-elevation myocardial infarction (STEMI) &lt;4 h after chest pain onset (n = 23), and regional plasma ANPsp concentrations in patients undergoing clinically indicated catheterization (n = 10). We analyzed the structure and sequence of circulating ANPsp by tandem mass spectrometry (MS/MS). RESULTS ANPsp levels in human heart tissue were 50–1000 times lower than those of ANP/NT-proANP. ANPsp was detectable in control human plasma at concentrations comparable with ANP itself (approximately 20 ng/L). In STEMI patients, plasma concentrations of ANPsp rose to peak values at 5 h after symptom onset, significantly earlier than myoglobin, creatine kinase-MB, and troponin (P &lt; 0.001). There were significant arteriovenous increases in ANPsp concentrations (P &lt; 0.05) across the heart and kidney; arterial and coronary sinus concentrations of ANPsp both negatively correlated with systolic and mean arterial blood pressures (both P &lt; 0.01). MS/MS verified circulating ANPsp to be preproANP(16–25) and preproANP(18–25). CONCLUSIONS ANPsp is a novel circulating natriuretic peptide with potential to act as a cardiovascular biomarker. The rapid increase of plasma ANPsp in STEMI and its significant relationship with blood pressure encourage further study of its potential clinical utility.

scholarly journals Recent developments in the treatment of metastatic colorectal cancer

2017 ◽  
Vol 9 (8) ◽  
pp. 551-564 ◽  
Author(s):  
Jonathan M. Loree ◽  
Scott Kopetz
Keyword(s):  
Colorectal Cancer ◽  
Decision Making ◽  
Clinical Decision Making ◽  
Growth Factor Receptor ◽  
Low Frequency ◽  
Clinical Decision ◽  
Tumor Location ◽  
Targeted Agents ◽  
Braf Mutations ◽  
Exon 2

Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS/tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease. Even with few new targeted agents receiving approval in CRC, the incorporation of next-generation sequencing into clinical decision making represents an important step forward. Biomarkers such as BRAF mutations, microsatellite instability, and HER2 amplification represent promising molecular aberrations with therapies in various stages of development, and highlight the importance of companion diagnostics in supporting targeted agents. In this review, we will discuss the importance of incorporating biomarkers into clinical decision making and regimen selection in CRC. We will particularly focus on the recent evidence suggesting an important role for tumor location in selecting first-line therapy, the importance of recent advances in biomarker development and molecular subtyping, as well as recently approved agents (regorafenib and TAS-102) and promising targeted agents that have the potential to change the standard of care.

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