The Prognostic Value of &lt;sup&gt;18&lt;/sup&gt;F-FDG PET/CT and KRAS Mutation in Colorectal Cancers

Arslan, Esra; Aksoy, Tamer; Gürsu, Rıza Umar; Dursun, Nevra; Çakar, Ekrem; Çermik, Tevfik Fikret

doi:10.4274/mirt.galenos.2019.33866

Cited by 17 publications

(20 citation statements)

References 23 publications

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“…The phantom was scanned on the same PET scanner where all patients were scanned with two bed positions for 15 min each to reduce image noise. Spherical VOIs with diameters matching those of the inner diameter of the phantom spheres (10,13,17,22,28, and 37 mm) were centered in the CT images of the phantom spheres and then copied to the same location in the registered PET images using the Hermes software. Then, the mean, peak and maximum SUV for each sphere were recorded to calculate the respective recovery coefficients as described below.…”

Section: Pet Image Analysismentioning

confidence: 99%

“…However, others found that EGFR mutations correlate with NSCLC PET image features whereas KRAS mutations do not [22]. Similarly for CRC, one investigation of the effect of KRAS mutations on 2-[18F]FDG uptake of CRC lesions found no correlation [23], while others found statistically significant correlations for primary tumors [13,[24][25][26].…”

Section: Introductionmentioning

confidence: 99%

“…For CRC metastases, SUV MAX was significantly associated with KRAS mutations when considering only tumors larger than 10 mm in diameter in order to minimize bias due to the partial-volume effect (PVE) [30]. Primary tumor SUV MAX was found to be significantly higher in CRC subjects with KRAS mutation compared to wild type [13].…”

Section: Introductionmentioning

confidence: 99%

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KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver

Popović

Talarico

Hoff

et al. 2020

Preprint

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Background: Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regards to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM). Methods : 2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: 1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter; and 2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak, and maximum SUV were investigated using Student ’ s t-test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SUR_mean, SUR_peak, and SUR_max , respectively. Results: Fifteen patients harbored KRAS missense mutations ( KRAS+ ) while another 3 harbored KRAS gene amplification. For 31 lesions the mutational status was derived from the PET/CT-guided biopsy. The Student ’ s-t p-values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SUR MAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve (AUC) = 0.77 and 0.75 for the two different segmentations respectively with a mean specificity of 0.69 and sensitivity of 0.85. Conclusions: The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.

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Section: Pet Image Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver

Popović

Talarico

Hoff

et al. 2020

Preprint

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“…KRAS mutation has been associated with relatively higher rates of local failure or positive resection margins after thermal ablation or resection of CLM [11,12]. Recently, others have found that the coexistence of KRAS mutation with increased 2-[18F]FDG uptake is a negative prognostic factor in primary CRC [13]. KRAS mutation status has a predictive value also for image-guided ablation for lung adenocarcinoma [14].…”

mentioning

confidence: 99%

“…Therefore, KRAS mutant lesions may be distinguishable using images of metabolic activity. The manifestation of KRAS mutations in PET images has been studied for non-small cell lung cancer (NSCLC) patients [21,22] as well as for CRC [13,[23][24][25][26][27][28][29][30]. For NSCLC, one study showed that a multivariate model, including 2-[18F]FDG SUV MEAN , may be used as a predictive marker for KRAS mutations [21].…”

mentioning

confidence: 99%

KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver

et al. 2020

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Background Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regard to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM). Methods 2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: (1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter and (2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak and maximum SUV were investigated using Student’s t test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SURMEAN, SURPEAK and SURMAX, respectively. Results Fifteen patients harbored KRAS missense mutations (KRAS+), while another 3 harbored KRAS gene amplification. For 31 lesions, the mutational status was derived from the PET/CT-guided biopsy. The Student’s t test p values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SURMAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve = 0.77 and 0.75 for the two different segmentations, respectively, with a mean specificity of 0.69 and sensitivity of 0.85. Conclusion The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.

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Metabolism in tumor microenvironment: Implications for cancer immunotherapy

Shi

Tang

Miao

2020

MedComm

125

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Tumor microenvironment is a special environment for tumor survival, which is characterized by hypoxia, acidity, nutrient deficiency, and immunosuppression. The environment consists of the vasculature, immune cells, extracellular matrix, and proteins or metabolic molecules. A large number of recent studies have shown that not only tumor cells but also the immune cells in the tumor microenvironment have undergone metabolic reprogramming, which is closely related to tumor drug resistance and malignant progression. Tumor immunotherapy based on T cells gives patients new hope, but faces the dilemma of low response rate. New strategies sensitizing cancer immunotherapy are urgently needed. Metabolic reprogramming can directly affect the biological activity of tumor cells and also regulate the differentiation and activation of immune cells. The authors aim to review the characteristics of tumor microenvironment, the metabolic changes of tumor‐associated immune cells, and the regulatory role of metabolic reprogramming in cancer immunotherapy.

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The Prognostic Value of <sup>18</sup>F-FDG PET/CT and KRAS Mutation in Colorectal Cancers

Cited by 17 publications

References 23 publications

KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver

KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver

KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver

Metabolism in tumor microenvironment: Implications for cancer immunotherapy

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