Predictive value of C-X-C motif chemokine receptor 4-directed molecular imaging in patients with advanced adrenocortical carcinoma.

BACKGROUND: In patients affected with adrenocortical carcinoma (ACC), C-X-C motif chemokine receptor 4 (CXCR4) is highly expressed in sites of disease in an ex-vivo setting. We aimed to determine the predictive value of CXCR4-targeting [68Ga]Ga-PentixaFor PET/CT for outcome when compared to clinical parameters. METHODS: We identified 41 metastasized ACC patients imaged with [68Ga]Ga-PentixaFor PET/CT. Scans were assessed visually and on a quantitative level by manually segmenting the tumor burden (providing tumor volume [TV], peak/mean/maximum standardized uptake values [SUV] and tumor chemokine receptor binding on the cell surface [TRB], defined as SUVmean multiplied by tumor volume). Clinical parameters included sex, previous therapies, age, Weiss-Score, and Ki67 index. Following imaging, overall survival (OS) was recorded. RESULTS: After [68Ga]Ga-PentixaFor PET/CT, median OS was 9 months (range, 1-96 months). On univariable analysis, only higher TRB (per 10 ml, HR 1.004, 95%CI: 1.0001-1.007, P = 0.005) and presence of CXCR4-positive peritoneal metastases (PM) were associated with shorter OS (HR 2.03, 95%CI: 1.03-4.02, P = 0.04). Presence of CXCR4-positive liver metastases (LM) trended towards significance (HR 1.85, 0.9-4.1, P = 0.11), while all other parameters failed to predict survival. On multivariable analysis, only TRB was an independent predictor for OS (HR 1.0, 95%CI: 1.00-1.001, P = 0.02). On Kaplan-Meier analysis, TRB above median (13.3 months vs. below median, 6.4 months) and presence of CXCR4-positive PM (6.4 months, vs. no PM, 11.4 months) were associated with shorter survival (P < 0.05, respectively). Presence of LM, however, was also linked to less favorable outcome (8.5 months vs. no LM, 18.1 months), without reaching significance (P = 0.07). CONCLUSIONS: In advanced ACC, elevated tumor chemokine receptor binding on the tumor cell surface detected through [68Ga]Ga-PentixaFor PET/CT is an independent predictor for OS, while other imaging and clinical parameters failed to provide relevant prognostic information.

Multi-parametric whole-body MRI evaluation discerns vital from non-vital multiple myeloma lesions as validated by 18F-FDG and 11C-methionine PET/CT.

PURPOSE: We tested a novel multi-parametric (mp) whole body (WB)-MRI evaluation algorithm for medullary lesions in comparison to positron emission tomography (PET) radiotracers 18F-fluorodeoxyglucose (18F-FDG) and 11C-methionine (11C-MET). METHODS AND MATERIALS: This retrospective single-center study included 44 MM patients, who received both 18F-FDG-PET and WB-MRI within ten days. MRI classified focal lesions as vital when showing 1) significant diffusion-restriction, 2) a fat fraction (FF) less than 20 % and 3) homogenous hypointensity on T2-weighted images. On a lesion-by-lesion level the findings were compared to 18F-FDG PET by using a 5-point scoring system (analogous to the Deauville score [DS]). In 24/44 (55 %) patients additional comparison to 11C-MET PET was available. RESULTS: Among two radiologists, an excellent inter-observer reliability for mpWB-MRI in a total of 84 medullary lesions was observed (ICC = 1, k = 1, p <.01). 16/17 (94.1 %) MRI-classified vital lesions had a DS of 4 or 5 on either 18F-FDG-PET or 11C-MET-PET. MRI-rated non-vital lesions correlated with PET-based DS ≤ 3. When results of mpWB-MRI were compared to 18F-FDG, a fair inter-observer agreement was recorded (ICC = 0.52, k = 0.53, p <.01), while for 11C-MET, an excellent concordance rate was achieved (ICC = 0.81, k = 0.79, p <.01). CONCLUSION: The proposed mpWB-MRI interpretation algorithm allowed to assess tumor activity of myeloma lesions with high inter-observer reproducibility. We observed a substantial concordance between the mpWB-MRI classification of lesions and PET assessment based on a semi-automatically calculated 5-point scoring system analogous to the Deauville scores.

Adrenal wash-out CT: moderate diagnostic value in distinguishing benign from malignant adrenal masses.

OBJECTIVE: Reliable results of wash-out CT in the diagnostic workup of adrenal incidentalomas are scarce. Thus, we evaluated the diagnostic accuracy of delayed wash-out CT and determined thresholds to accurately differentiate adrenal masses. DESIGN: Retrospective, single-center cohort study including 216 patients with 252 adrenal lesions who underwent delayed wash-out CT. Definitive diagnoses based on histopathology (n = 92) or comprehensive follow-up. METHODS: Size, average attenuation values of the adrenal lesions in all CT scan phases, and absolute and relative percentage wash-out (APW/RPW) were determined by an expert radiologist blinded for clinical data. Adrenal lesions with unenhanced attenuation values >10 Hounsfield units (HU) built a subgroup (n = 142). Diagnostic accuracy was calculated. RESULTS: The study group consisted of 171 adenomas, 32 other benign tumors, 11 pheochromocytomas, 9 adrenocortical carcinomas, and 29 other malignant tumors. All (potentially) malignant and 46% of benign lesions showed unenhanced attenuation values >10 HU. In this most relevant subgroup, the established thresholds of 60% for APW and 40% for RPW misclassified 35.9 and 35.2% of the masses, respectively. When we applied optimized cutoffs (APW >83%; RPW >58%) and excluded pheochromocytomas, we missed only one malignant tumor by APW and none by RPW. However, only 11 and 15% of the benign tumors were correctly identified. CONCLUSIONS: Wash-out CT with the established thresholds for APW and RPW is insufficient to reliably diagnose adrenal masses. Using the proposed cutoff of 58% for RPW, malignant tumors will be correctly identified, but the added value is limited, namely 15% of patients with benign tumors can be prevented from additional imaging or even unnecessary surgery.

Mitotane Monotherapy in Patients With Advanced Adrenocortical Carcinoma.

Context: Although mitotane is the only approved drug for the treatment of adrenocortical carcinoma (ACC), data on monotherapy in advanced disease are still scarce. Objective: To assess the efficacy of mitotane in advanced ACC in a contemporary setting and to identify predictive factors. Design and Setting: Multicenter cohort study of three German referral centers. Patients: One hundred twenty-seven patients with advanced ACC treated with mitotane monotherapy. Outcome Measures: Response Evaluation Criteria in Solid Tumors evaluation, progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier method, and predictive factors by Cox regression. Results: Twenty-six patients (20.5%) experienced objective response, including three with complete remission. Overall, median PFS was 4.1 months (range 1.0 to 73) and median OS 18.5 months (range 1.3 to 220). Multivariate analysis indicated two main predictive factors: low tumor burden (<10 tumoral lesions), hazard ratio (HR) for progression of 0.51 (P = 0.002) and for death of 0.59 (P = 0.017); and initiation of mitotane at delayed advanced recurrence, HR 0.35(P < 0.001) and 0.34 (P < 0.001), respectively. Accordingly, 67% of patients with low tumor burden and mitotane initiation ≥360 days after primary diagnosis experienced a clinical benefit (stable disease >180 days). Patients who achieved mitotane levels >14 mg/L had significantly longer OS (HR 0.42; P = 0.003). Conclusions: At 20.5% the objective response rate was slightly lower than previously reported. However, >20% of patients experienced long-term disease control at >1 year. In general, patients with late diagnosis of advanced disease and low tumor burden might especially benefit from mitotane monotherapy, whereas patients with early advanced disease and high tumor burden are probably better candidates for combined therapy of mitotane and cytotoxic drugs.