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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      SUVmax and metabolic tumor volume: surrogate image biomarkers of KRAS mutation status in colorectal cancer

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          Abstract

          Purpose

          The objective of this study was to explore the association between KRAS mutation status and PET/CT metabolic parameters in colorectal cancer (CRC) patients.

          Materials and methods

          One hundred and sixty-four CRC patients were enrolled in this study and received PET/CT examination before operation, then KRAS mutation status was analyzed through pathologically confirmed CRC samples. The association between tumor clinical characteristics and PET/CT metabolic parameters, including maximum standardized uptake value (SUVmax), SUVmean, and metabolic tumor volume (MTV), and KRAS mutation status was analyzed using chi-squared tests, Mann–Whitney U tests, and logistic regression analysis.

          Results

          The KRAS mutation type patients exhibited high MTV and high SUVmax using a threshold of 17.8 cm 3 and 8.7 respectively and the predictive accuracy was 0.772 and 0.603 respectively. High MTV ( P=0.001; 95% CI: 1.119–1.296) and high SUVmax ( P=0.048; 95% CI: 0.564–0.985) were independent predictors for KRAS mutation status.

          Conclusion

          MTV and SUVmax were associated with KRAS mutation type in CRC patients. PET/CT metabolic parameters can be used for supplementing KRAS mutation status prediction in CRC patients.

          Most cited references29

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          The meaning and use of the area under a receiver operating characteristic (ROC) curve.

          J A Hanley, B J McNeil, Marnix van Holsbeeck (1982)
          A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.
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            Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.

            Rafael Amado, Michael Wolf, Marc Peeters … (2008)
            Panitumumab, a fully human antibody against the epidermal growth factor receptor (EGFR), has activity in a subset of patients with metastatic colorectal cancer (mCRC). Although activating mutations in KRAS, a small G-protein downstream of EGFR, correlate with poor response to anti-EGFR antibodies in mCRC, their role as a selection marker has not been established in randomized trials. KRAS mutations were detected using polymerase chain reaction on DNA from tumor sections collected in a phase III mCRC trial comparing panitumumab monotherapy to best supportive care (BSC). We tested whether the effect of panitumumab on progression-free survival (PFS) differed by KRAS status. KRAS status was ascertained in 427 (92%) of 463 patients (208 panitumumab, 219 BSC). KRAS mutations were found in 43% of patients. The treatment effect on PFS in the wild-type (WT) KRAS group (hazard ratio [HR], 0.45; 95% CI: 0.34 to 0.59) was significantly greater (P < .0001) than in the mutant group (HR, 0.99; 95% CI, 0.73 to 1.36). Median PFS in the WT KRAS group was 12.3 weeks for panitumumab and 7.3 weeks for BSC. Response rates to panitumumab were 17% and 0%, for the WT and mutant groups, respectively. WT KRAS patients had longer overall survival (HR, 0.67; 95% CI, 0.55 to 0.82; treatment arms combined). Consistent with longer exposure, more grade III treatment-related toxicities occurred in the WT KRAS group. No significant differences in toxicity were observed between the WT KRAS group and the overall population. Panitumumab monotherapy efficacy in mCRC is confined to patients with WT KRAS tumors. KRAS status should be considered in selecting patients with mCRC as candidates for panitumumab monotherapy.
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              KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab.

              Astrid Lièvre, Jean-Baptiste Bachet, Valérie Boige … (2008)
              Cetuximab is efficient in advanced colorectal cancer (CRC). We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRC patients. The aim of this study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to cetuximab and survival. Eighty-nine metastatic CRC patients treated with cetuximab after treatment failure with irinotecan-based chemotherapy were analyzed for KRAS mutation by allelic discrimination on tumor DNA. The association between KRAS mutations and tumor response, skin toxicity, progression-free survival (PFS) and overall survival (OS) was analyzed. A KRAS mutation was present in 27% of the patients and was associated with resistance to cetuximab (0% v 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P < .001) and a poorer survival (median PFS: 10.1 v 31.4 weeks in patients without mutation; P = .0001; median OS: 10.1 v 14.3 months in patients without mutation; P = .026). When we pooled these 89 patients with patients from our previous study, the multivariate analysis showed that KRAS status was an independent prognostic factor associated with OS and PFS, whereas skin toxicity was only associated with OS. In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors (severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively. These results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRC patients treated with cetuximab.
              Article 0 comments Cited 336 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): OncoTargets and Therapy
                Title: OncoTargets and therapy
                Publisher: Dove Medical Press
                ISSN (Electronic): 1178-6930
                Publication date Collection: 2019
                Publication date (Electronic): 21 March 2019
                Volume: 12
                Pages: 2115-2121
                Affiliations
                [1 ]Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong, People’s Republic of China
                [2 ]Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, People’s Republic of China
                [3 ]Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan 250117, Shandong, People’s Republic of China
                [4 ]Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong, People’s Republic of China
                [5 ]Department of Gastrointestinal Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong, People’s Republic of China, wanglei999qq@ 123456163.com
                [6 ]Department of Neurosurgery, Shandong Province Qianfoshan Hospital of Shandong University, Jinan 250014, Shandong, People’s Republic of China, dr_peterluu@ 123456163.com
                Author notes
                Correspondence: Lei Wang, Department of Gastrointestinal Surgery, Jinan Central Hospital Affiliated to Shandong University, 105 Jiefang Road, Jinan 250013, Shandong, People’s Republic of China, Email wanglei999qq@ 123456163.com
                Jie Lu, Department of Neurosurgery, Shandong Province Qianfoshan Hospital of Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, People’s Republic of China, Email dr_peterluu@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: ott-12-2115
                DOI: 10.2147/OTT.S196725
                PMC ID: 6433102
                SO-VID: 1dbff2cd-0952-4516-9643-f45fa49f4658
                Copyright © © 2019 Lv et al. This work is published and licensed by Dove Medical Press Limited
                License:

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: colorectal cancer,18f-fdg pet/ct,suvmax,suvmean,mtv,kras mutation
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: colorectal cancer, 18f-fdg pet/ct, suvmax, suvmean, mtv, kras mutation

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