EPID-18. USING GERMLINE VARIANTS FOR DIFFERENTIAL DIAGNOSIS OF INDETERMINATE BRAIN LESIONS: EVALUATING THE EFFECT OF TUMOR TYPE AND RACE ON SENSITIVITY AND SPECIFICITY OF GLIOMA polygenic risk models

Abnormalities on brain MRI may be identified in ~15% of individuals aged 50-66. It can be difficult to discriminate glioma, CNS lymphoma, Inflammatory Demyelinating Disease (CNSIDD) and solitary metastasis, and misdiagnosis may expose patients to unnecessary anxiety, surgery, or radiotherapy. CNS lymphoma requires only biopsy, solitary metastasis may be resected and radiated or radiated empirically, and high-grade glioma requires maximal safe resection followed by chemoradiation. CNSIDD should only be biopsied when diagnostic uncertainty requires it, and resection and radiotherapy are unnecessary, introducing unwarranted morbidity. Polygenic risk models can identify patients at the highest risk of developing glioma; we hypothesized that these polygenic models could help with differential diagnosis of indeterminate brain lesions. We also hypothesized that race would be an important contributing factor in the models. In the initial discovery and validation European (EUR) cohorts the mean probability of glioma for IDHmut non-codeleted glioma was 0.55 and 0.52, respectively, and in healthy controls was 0.19 and 0.21, respectively. To further evaluate sensitivity, we analyzed additional genotype data from 867 gliomas (764 EUR, 54 AFR, 24 AMR, 15 EAS, 10 SAS) from The Cancer Genome Atlas (TCGA). Across 764 EUR IDHmut non-codeleted glioma, the mean probability 0.53, whereas across 54 AFR and 24 AMR the mean was 0.22 and 0.32, respectively. To evaluate specificity, we analyzed 3200 TCGA patients with primary tumor types that commonly metastasize to the brain (2676 EUR, 365 AFR, 46 AMR, 95 EAS, 18 SAS), and 236 AFR healthy controls. For patients with non-CNS primary tumors, the mean probability ranged from 0.09-0.18 for EUR and 0.04-0.07 for AFR. For AFR healthy controls, the mean was 0.05. Overall, race is a significant factor for polygenic risk models. Further work entails evaluating polygenic risk models in IDHwt glioma, CNS lymphoma and CNSIDD cohorts as well as in additional races.

Radiological Patterns of Uveal Melanoma Liver Metastases in Correlation to Genetic Status

This study reports the role played by the mutation status of Uveal Melanoma (UM) in relation to hepatic metastatic patterns as seen on imaging modalities. Radiological images were obtained from 123 patients treated at the Erasmus Medical Center Rotterdam or the Rotterdam Eye Hospital. Radiological images were derived from either computed tomography or magnetic resonance imaging. Hepatic metastatic patterns were classified by counting the number of metastases found in the liver. Miliary metastatic pattern (innumerable small metastases in the entire liver) was analyzed separately. Mutation status was determined in 85 patients. Median disease-free survival (DFS) and survival with metastases differed significantly between each of the metastatic patterns (respectively, p = 0.009, p < 0.001), both in favor of patients with less hepatic metastases. The mutation status of the primary tumor was not correlated with any hepatic tumor profiles (p = 0.296). Of the patients who had a solitary metastasis (n = 18), 11 originated from a primary BAP1-mutated tumors and one from a primary SF3B1- mutated tumor. Of the patients who had a miliary metastasis pattern (n = 24), 17 had a primary BAP1-mutated tumor and two had a primary SF3B1-mutated tumor. Chromosome 8p loss was significantly more in patients with more metastases (p = 0.045). Moreover, the primary UMs of patients with miliary metastases harbored more chromosome 8p and 1p loss, compared to patients with single solitary metastasis (p = 0.035 and p = 0.026, respectively). In conclusion, our study shows that there is an inverse correlation of the number of metastasis with the DFS and metastasized survival, indicating separate growth patterns. We also revealed that the number and type of metastases is irrelevant to the prognostic mutation status of the tumor, showing that both BAP1- and SF3B1-mutated UM can result in solitary and miliary metastases, indicating that other processes lay ground to the different metastatic patterns.

The Efficacy of Surgical Metastasectomy for Solitary Metastasis of Renal Cell Carcinoma

<b><i>Background:</i></b> Patients with solitary metastasis of renal cell carcinoma (RCC) have shown to be ideal candidates for surgical metastasectomy (SM). However, whether SM will show more benefit than systemic therapy remains unclear. <b><i>Methods:</i></b> We included 73 patients treated for solitary metastasis after nephrectomy at our institute from April 2008 to December 2018. We compared the clinical outcomes between the SM (<i>n</i> = 29) and no-SM (<i>n</i> = 44) group which were treated with only systemic therapy. <b><i>Results:</i></b> Eleven of 29 patients in the SM group received presurgical targeted therapy (PTT). Although 13 of 29 patients in the SM group showed recurrence during the study period, a Cox proportional hazards model showed that SM was significantly associated with a favorable overall survival (hazard ratio: 0.18; <i>p</i> = 0.007). Patients receiving PTT prior to SM showed a longer recurrence-free survival after SM in comparison to those who underwent SM without PTT (median: not reached vs. 27.7 months; <i>p</i> = 0.009). <b><i>Conclusions:</i></b> If resection is feasible, SM may be beneficial for patients with solitary metastasis of RCC, and we showed the possibility that PTT prior to SM may be effective for avoiding recurrence after SM. Further large-scale prospective studies are needed to clarify the ideal treatment strategy for metastatic RCC.

Delayed solitary metastasis from primary follicular thyroid carcinoma to the scapular bone, a case report, and review of the literature

Most of the bone metastasis origination from Follicular Thyroid Carcinoma (FTC) will present as non-solitary and non-isolated. We present an extremely unique case of an isolated and solitary lesion in an unusual site, scapula, originated from FTC presenting incredibly about ten years after the initial successful treatment.

Complaint of Testicular Discomfort in Patient with Esophageal Adenocarcinoma

We report a case of esophageal cancer with solitary metastasis to the testicle in a 71-year-old man. The tumor was picked up on physical exam following new onset complaints of pain and swelling. While most testicular masses in older men are due to lymphoma, this case highlights the need to consider metastatic disease as a source of new symptoms in patients with a recent cancer diagnosis.

The Potential Role of Peritumoral Apparent Diffusion Coefficient Evaluation in Differentiating Glioblastoma and Solitary Metastatic Lesions of the Brain

Objective: Differentiating glioblastoma (GBM) and solitary metastasis is not always possible using conventional magnetic resonance imaging (MRI) techniques. In conventional brain MRI, GBM and brain metastases are lesions with mostly similar imaging findings. In this study, we investigated whether apparent diffusion coefficient (ADC) ratios, ADC gradients, and minimum ADC values in the peritumoral edema tissue can be used to discriminate between these two tumors. Methods: This retrospective study was approved by the local institutional review board with a waiver of written informed consent. Prior to surgical and medical treatment, conventional brain MRI and diffusion-weighted MRI (b = 0 and b = 1000) images were taken from 43 patients (12 GBM and 31 solitary metastasis cases). Quantitative ADC measurements were performed on the peritumoral tissue from the nearest segment to the tumor (ADC1), the middle segment (ADC2), and the most distant segment (ADC3). The ratios of these three values were determined proportionally to calculate the peritumoral ADC ratios. In addition, these three values were subtracted from each other to obtain the peritumoral ADC gradients. Lastly, the minimum peritumoral and tumoral ADC values, and the quantitative ADC values from the normal appearing ipsilateral white matter, contralateral white matter and ADC values from cerebrospinal fluid (CSF) were recorded. Results: For the differentiation of GBM and solitary metastasis, ADC3 / ADC1 was the most powerful parameter with a sensitivity of 91.7% and specificity of 87.1% at the cut-off value of 1.105 (p < 0.001), followed by ADC3 / ADC2 with a cut-off value of 1.025 (p = 0.001), sensitivity of 91.7%, and specificity of 74.2%. The cut-off, sensitivity and specificity of ADC2 / ADC1 were 1.055 (p = 0.002), 83.3%, and 67.7%, respectively. For ADC3 – ADC1, the cut-off value, sensitivity and specificity were calculated as 150 (p < 0.001), 91.7% and 83.9%, respectively. ADC3 – ADC2 had a cut-off value of 55 (p = 0.001), sensitivity of 91.7%, and specificity of 77.4 whereas ADC2 – ADC1 had a cut-off value of 75 (p = 0.003), sensitivity of 91.7%, and specificity of 61.3%. Among the remaining parameters, only the ADC3 value successfully differentiated between GBM and metastasis (GBM 1802.50 ± 189.74 vs. metastasis 1634.52 ± 212.65, p = 0.022). Conclusion: The integration of the evaluation of peritumoral ADC ratio and ADC gradient into conventional MR imaging may provide valuable information for differentiating GBM from solitary metastatic lesions.