Metabolic Activity Via 18 F-FDG PET/CT is Predictive of Microsatellite Instability Status In Colorectal Cancer

Purpose: Identification of microsatellite instability high (MSI-H) colorectal cancer (CRC) is crucial for screening patients most likely to benefit from immunotherapy. We aim to investigate whether the metabolic characteristics is related to MSI status and can be used to predict the MSI-H CRC. Methods: A retrospective analysis was conducted on 420 CRC patients who were identified via [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography(CT) prior to therapy. Maximum standardised uptake (SUVmax), mean standardised uptake (SUVmean), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the primary tumour were calculated and compared between MSI-H and microsatellite stability (MSS). Predictive factors of MSI status were selected from metabolic parameters and clinicopathological profiles via a multivariate analysis.Results: Of 420 colorectal cancers, 44 exhibited a high incidence of MSI. Both MTV and TLG were significantly higher in MSI-H group compared with the MSS group (P=0.004 and P=0.010, respectively). Logistic regression analysis indicated that CRC with MSI-H were related to younger age (P=0.013), primary lesion located at right hemi-colon (P<0.001) and larger MTV on PET/CT imaging (P=0.019). MTV more than 32.19 cm3 of colorectal cancer was linked to the presence of MSI (P=0.019). Conclusion: Tumor metabolic burden were higher in MSI-H CRC which may be useful for predicting the MSI status of CRC patient and thus aid in determination of immunotherapy for patients with CRC.

Metabolic Tumor Volume for Patients with Lymphomas

Visual analysis of positron emission tomography/computed tomography (PET/CT) scans and semiquantitative parameter of glucose’s standardized uptake value are used in PET/CT with 18F-fluorodeoxyglucose (18F-FDG). Recently some volumetric parameters, which can evaluate metabolic tumor volume for patients with lymphomas and total lesion glycolysis in the tumor sites are established. In our study this problem was analyzed for different types of lymphomas considering clinical importance of these rates and their bond to known factors of international prognostic index.

Metabolic Tumor Volume and Total Lesion Glycolysis Can Predict Response to Very Low Dose Radiotherapy (4 Gy) in Indolent B-Cell Lymphomas

Numerous studies have established the role of very low dose radiotherapy (VLDRT), only 4 Gy in 2 fractions, in the management of indolent non-Hodgkin's lymphoma (NHL). While objective response rates to VLDRT are excellent, there are no widely accepted biomarkers of the depth and the durability of response after VLDRT. Radiosensitivity to VLDRT is not clearly linked to clinical features, such as tumor grade, histology, prior treatments or [18F]-FDG-PET standardized uptake values (SUV). Our group has recently demonstrated that pre-treatment tumor size greater than 6 cm may predict suboptimal response to VLDRT; however, this remains an imperfect predictor, and the majority of patients selected for VLDRT have lesions smaller than 6 cm. [18F]-FDG-PET metrics like baseline metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are shown to stratify patient response to chemotherapy for some NHLs, but neither has been shown to predict radiotherapy response to VLDRT. Therefore, we aimed to determine if these features could predict response to VLDRT in indolent B-cell NHLs. Between 2005 and 2018, 250 patients with follicular or marginal zone lymphoma were locally irradiated to 299 sites using 2 Gy x2. Response was assessed within 1.5-6 months of VLDRT (n=231), and local failure (LF) was assessed over a median follow-up of 29 months. Out of the 299 treated sites, 254 (85%) had a corresponding [18F]-FDG-PET/CT scan performed prior to radiotherapy. PET scans were imported into MIM, a radiotherapy contouring and planning software program, and pre-radiotherapy disease was manually defined. A uniform expansion of 0.5 cm was performed to define a larger region of interest containing the contoured lesion but accounting for technical variability in defining the tumor edges. Of the 254 lesions, 207 (81%) had a maximum SUV (SUVmax) greater than 2.5 and were considered for further analysis. PET parameters were obtained using an SUV of 2.5 as a cutoff for MTV (MTV2.5) and TLG (TLG2.5), which capture lesion bulk, and using 41% of the SUVmax as a cutoff for MTV (MTV41%) and TLG (TLG41%), which capture the most metabolically active parts of a lesion. Maximum lesion size was analyzed using 4 cm and 6 cm as predetermined cutoffs. Lesion response was analyzed using multivariate logistic LASSO regression to account for predictor multicollinearity, and receiver operating characteristic curve analysis to obtain estimates of the area under the curve (AUC). To analyze time to LF, we performed Cox proportional hazards multivariate regression using stepwise selection. PET parameters were divided in quartiles to aid in interpretability. Estimates are shown with 95% confidence intervals. A complete response (CR) was seen in 156 (68%) lesions and LF was seen in 81 (27%) lesions after VLDRT. Using size alone had similar predictive value for response (AUC: 0.57(0.49-0.65) compared to MTV2.5 (AUC:0.66 (0.57-0.74)), MTV41% (AUC:0.64 (0.56-0.73)), TLG2.5 (AUC:0.64 (0.54-0.74)), and TLG41% (AUC:0.64 (0.54,0.75)). Through LASSO logistic regression, we determined that only MTV41% &gt; 75 th percentile was associated with lower odds of CR (odds ratio (OR):0.21 (0.08-0.53)) versus size ≥4 (OR: 0.94 (0.32, 2.73) ) with no interaction noted. Likewise, in a multivariate model of LF, TLG2.5&gt; 75 th percentile was shown to be a better predictor of worse LF (HR: 2.44 (1.32, 4.52)) than size when considering lesions &lt; 6 cm. In stratifying response and local control for patients receiving VLDRT for indolent lymphomas, MTV and TLG may aid in patient selection, especially for lesions smaller than 6 cm. As PET-based radiotherapy planning is routinely performed in the treatment of indolent lymphomas, these parameters are easily attained after contouring and may have immediate clinical utility. These findings may also be applicable to radiotherapy response with higher doses, and the incorporation of [18F]-FDG-PET metrics into treatment decisions is an area of active research. It remains to be seen in ongoing work whether higher-order PET radiomic features (which for instance capture heterogeneity of tumor glucose metabolism) can further improve the accuracy of [18F]-FDG-PET-based radiotherapy outcome prediction. Disclosures Mayerhoefer: Siemens: Other: Speaker Honoraria; General Electric: Other: Speaker Honoraria; Bristol Myers Squibb: Other: Speaker Honoraria.

Het gebruik van 18F-FDG PET/CT ter evaluatie van multipel myeloom

The use of 18F-FDG PET/CT to evaluate patients with multiple myeloma. Detection of bone lesions are important to diagnose multiple myeloma. In this study we investigate the role of an 18F-FDG PET/CT exam. Fifteen newly diagnosed multiple myeloma patients were included in this retrospective study. A 18F-FDG PET/CT was performed at diagnosis and after induction therapy. The response of a treatment is examined by semi-quantitative parameters (standardised 18F-FDG uptake values) and volumetric parameters (metabolic tumor volume and total lesion glycolysis). The aim of this study is to evaluate the use of these parameters for response evaluation and risk assessment in multiple myeloma. The prognostic value of an increased metabolic activity of the spleen is also examined. All semi-quantitative and volumetric parameters in this study are useful for response evaluation. Lower values of maximum or mean standardized uptake values (SUVmax, SUVmean) and total lesion glycolysis at diagnosis are prognostic favourable. We could not prove prognostic relevance for a spleen to liver ratio. Due to the small study population, all these results have to be confirmed in a larger patient cohort. 18F-FDG PET/CT is a reliable technique for response evaluation and risk stratification in multiple myeloma. In the future semi-quantitative and volumetric parameters will probably be incorporated in the risk classification systems of multiple myeloma patients.

The utility of the standardized uptake value, metabolic tumor volume and total lesion glycolysis as predictive markers of recurrent breast cancer

Background Breast cancer is the second leading cancer killer of women globally. An early measure utilizing a noninvasive molecular marker for predicting cancer aggressiveness is important to better manage the patient and to avert early disease progression. We aimed to determine whether metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are able to predict risk in high TNM tumor staging and the need for the appropriate treatment in breast cancer patients. This is a retrospective study of confirmed breast cancer patients who underwent neoadjuvant, local and adjuvant treatment and follow-up. The 18F-FDG PET/CT study for initial staging was performed, and metabolic parameters (MTV, TLG, SUVmax mean) were analyzed. Spearman correlation was used to assess correlations between metabolic parameters and clinicopathological factors with TNM staging and treatment intention. SUVmean, wbMTV and wbTLG were analyzed to predict the dichotomization of patient endpoint for low (stage I and II) and high (stage III and IV) TNM stage. Results Twenty-six patients (4 low stage, 22 high stage) with a mean age of 51.8 ± 11.8 years with confirmed breast cancer underwent 18FFDG PET/CT. The MTV and TLG parameters in the tumor (T) were significantly correlated with the TNM stage (P < 0.050); the SUVmax mean (4.18 ± 1.68 g/dl), wbMTV mean (404.68 ± 558.02 cm3) and wbTLG (1756.55 ± 2432.11 g) differed significantly in the high versus low TNM staging with the best predictive cut-off value of SUVmax mean (3.55 g/ml, p < 0.05), wbMTV (20 cm3, p < 0.05) and wbTLG (130 g, p < 0.05) when these values were exceeded. Only wbTLG (130 g, p < 0.05) showed significance difference in treatment intention. Conclusions In this study, the metabolic parameters SUVmax mean, MTV and TLG showed potential good relationships with TNM staging. TLG was the only marker that influenced the treatment intention in predicting breast cancer aggressiveness.

Total Lesion Glycolysis Improves Tumor Burden Evaluation and Risk Assessment at Diagnosis in Hodgkin Lymphoma

Hodgkin lymphoma (HL) is a hematological malignancy with an excellent prognosis. However, we still need to identify those patients that could experience failed standard frontline chemotherapy. Tumor burden evaluation and standard decisions are based on Ann Arbor (AA) staging, but this approach may be insufficient in predicting outcomes. We aim to study new ways to assess tumor burden through volume-based PET parameters to improve the risk assessment of HL patients. We retrospectively analyzed 101 patients with HL from two hospitals in the Balearic Islands between 2011 and 2018. Higher metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were significantly associated with a higher incidence of III-IV AA stages, B-symptoms, hypoalbuminemia, lymphopenia, and higher IPS. Standardized uptake value (SUVmax) was significantly related to AA stage and hypoalbuminemia. We found that TLG or the combination of SUVmax, TLG, and MTV significantly improved the risk assessment when compared to AA staging. We conclude that TLG is the best single PET/CT-related tumor-load parameter that significantly improves HL risk assessment when compared to AA staging. If confirmed in a larger and validated sample, this information could be used to modify standard frontline therapy and justifies the inclusion of TLG inside an HL prognostic score.

The metabolic parameters based on volume in PET/CT are associated with clinicopathological N stage of colorectal cancer and can predict prognosis

Background A combination of positron emission tomography and computed tomography (PET/CT) is an important modality for the diagnosis of carcinoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been reported as metabolic parameters in PET/CT since the late 1990s, and they are expected to be useful in diagnosing diverse cancers and as prognostic biomarkers. We evaluated the potential of these parameters in the prognosis of colorectal cancer (CRC) by comparing them with conventional parameters, including the maximum standardized uptake value (SUVmax). We enrolled 84 patients who underwent surgery for CRC without distal metastasis between April 2015 and April 2019. SUVmax, MTV, and TLG were measured by 18F-fluorodeoxyglucose (FDG)-PET/CT. To find an optimal threshold value related to prognosis, the volume of interest in the primary carcinoma was measured at fixed relative and absolute thresholds based on SUVmax (30%, 40%, and 50%; 2.5, 3.0, and 3.5, respectively), tumor-to-liver standardized uptake ratios, TLR (1.0, 1.5, and 2.0), and SUV normalized to lean body mass, SUL (2.0, 2.5, and 3.0). After classifying the patients into two groups according to pathological N stage, the optimal threshold values of all metabolic parameters were compared between groups using a non-parametric comparison test. Result The most suitable thresholds for MTV were a SUVmax of 3.5 and a TLR 2.0. TLG with a SUVmax value of 40% showed the most significant difference. The MTV standard uptake ratio of 2.0 was significantly associated with pathological N stage. Conclusion Our results suggest that an MTV TLR 2.0 on PET/CT reflects pathological N stage in local patients with CRC.

Total metabolic tumor volume as a survival predictor for patients with diffuse large B-cell lymphoma in the GOYA study

This retrospective analysis of the phase III GOYA study investigated the prognostic value of baseline metabolic tumor volume parameters and maximum standardized uptake values for overall and progression-free survival in treatment-naïve diffuse large B-cell lymphoma. Baseline total metabolic tumor volume (determined for tumors >1 mL using a threshold of 1.5 times the mean liver standardized uptake value +2 standard deviations), total lesion glycolysis, and maximum standardized uptake value positron emission tomography data were dichotomized based on receiver operating characteristic analysis and divided into quartiles by baseline population distribution. Of 1,418 enrolled patients, 1,305 had a baseline positron emission tomography scan with detectable lesions. Optimal cut-offs were 366 cm3 for total metabolic tumor volume and 3,004g for total lesion glycolysis. High total metabolic tumor volume and total lesion glycolysis predicted poorer progression-free survival, with associations retained after adjustment for baseline and disease characteristics (high total metabolic tumor volume hazard ratio: 1.71 [95% CI, 1.35–2.18]; total lesion glycolysis hazard ratio: 1.46 [95% CI, 1.15–1.86]). Total metabolic tumor volume was prognostic for progression-free survival in subgroups with International Prognostic Index scores 0–2 and 3–5, and those with different cell-of-origin subtypes. Maximum standardized uptake value had no prognostic value in this setting. High total metabolic tumor volume associated with high International Prognostic Index or non-germinal center B-cell classification identified the highest-risk cohort for unfavorable prognosis. In conclusion, baseline total metabolic tumor volume and total lesion glycolysis are independent predictors of progression-free survival in patients with diffuse large B-cell lymphoma after first-line immunochemotherapy.

18 F-FDG-PET/MRI in patients with Graves’ orbitopathy.

Purpose Currently, therapeutic management of patients with Graves’ orbitopathy (GO) relies on clinical assessments and MRI. However, monitoring of inflammation remains difficult since external inflammatory signs do not necessarily represent the orbital disease activity. Therefore, we aimed to evaluate the diagnostic value of 18F-FDG-PET/MRI to assess the inflammation of GO patients. Methods Enrolled patients with new onset of GO underwent ophthalmological examinations to evaluate the activity (CAS) and severity of GO (NOSPECS), as well as an 18F-FDG-PET/MRI (Siemens Biograph mMR) with dual time point imaging (immediately post-injection and 60 min p.i.). A subset of PET parameters including maximum standardized uptake value (SUVmax), metabolic target volume (MTV), and total lesion glycolysis (TLG) were obtained separately per eye and per extraocular eye muscle (EOM). EOM thickness was measured on the co-registered MRI. Results Of 14 enrolled patients, three showed mild, seven moderate-to-severe, and four sight-threatening GO. Patients with severe GO showed statistically significant higher TLG than patients with mild GO (p = 0.02) and higher MTV than patients with mild (p = 0.03) and moderate (p = 0.04) GO. Correlation between NOSPECS on one hand and MTV and TLG on the other was significant (R2 = 0.49–0.61). Conclusion TLG and MTV derived from FDG-PET appear to be good discriminators for severe vs. mild-to-moderate GO and show a significant correlation with NOSPECS. As expected, PET parameters of individual eye muscles were not correlated with associated eye motility, since fibrosis, and not inflammation, is mainly responsible for restricted motility. In conclusion, 18F-FDG-PET/MRI can be used for assessment of GO inflammation.