Mouhammed Amir Habra

Adrenocortical carcinoma (ACC) is a rare malignancy with high recurrence rates. Circulating tumor DNA (ctDNA) is a minimally invasive, blood-based biomarker with multiple oncologic applications. The role of ctDNA in ACC care remains understudied. This retrospective, single-institution, study evaluated real-world use of ctDNA testing in patients with ACC and its correlation with imaging-based tumor burden. Patients with ACC (≥ 18 years) who underwent ctDNA testing via a clinically validated, personalized, tumor-informed assay (Signatera™, Natera) during their disease course were reviewed, and clinical data were obtained from the medical records. ctDNA results were tested for association with disease status and tumor burden determined by concurrent imaging and clinical evaluation. Twenty patients (55% male) were included; the median age at first ctDNA assessment was 58.3 years (range, 23.3–81.1). A total of 87 ctDNA tests were analyzed (median, 4 tests/patient; interquartile range [IQR], 1–6). The median ctDNA level was 1.27 mean tumor molecules/mL (IQR, 0.05–22.86). Detected ctDNA was strongly associated with evidence of disease (odds ratio, 74; 95% confidence interval, 9–3438). The ctDNA assay demonstrated high sensitivity (88%), specificity (91.7%), and overall accuracy (88.5%), with a positive post-test probability of 98% and a negative post-test probability of 45%. In addition, ctDNA levels were positively correlated with tumor burden (Spearman R = 0.844; p < 0.001). These findings support the potential value of ctDNA testing for disease monitoring in ACC and it may support a more personalized approach to this rare disease.

Introduction: Adrenocortical carcinoma (ACC) is a rare cancer with suboptimal response to chemotherapy. The role of immunotherapy in ACC management is evolving. Methods: An investigator-initiated, open-label, phase 2 clinical trial was performed to ascertain the activity and safety of monotherapy with pembrolizumab (a humanized monoclonal anti-programmed cell death protein 1 antibody) in patients with advanced ACC. This study was part of a basket clinical trial (ClinicalTrials.gov ID: NCT02721732). Study participants were enrolled from August 15, 2016, until December 7, 2020. Pembrolizumab (200 mg) was administered intravenously every 3 weeks. All other lines of therapy, including mitotane, were stopped before pembrolizumab initiation. The primary endpoint was the nonprogression rate (being alive without progression) at 27 weeks, which was objectively assessed by an independent radiology team based on the immune-related response evaluation criteria in solid tumors. Secondary endpoints consisted of adverse events assessed using the Common Terminology Criteria for Adverse Events (version 4.03). Results: We enrolled 23 patients with ACC (13 women [57%]) with a median age of 54 years (range, 31–78 years). Four cases were cortisol producing (17%). The median follow-up calculated by reverse Kaplan-Meier was 66.9 months. Among the 23 patients, three were not evaluable for response; two patients stopped treatment because of toxicity and did not undergo restaging scans, and one patient withdrew consent for follow-up owing to international relocation. Among 20 patients with evaluable response, six (30%) were alive without progression at 27 weeks. We saw no complete responses but did see partial responses in four patients (20%) with a mean duration of response of 17.6 months (95% CI, 9.6–25.6). The median progression-free survival time was 4.0 months (95% CI, 2.0–6.2 months), and the median overall survival time was 15.5 months (95% CI, 6.2–22.8 months). The clinical benefit rate was 30% (complete response, partial response, and stable disease at 27 weeks (after 3 radiographic evaluations). Three treatment-related adverse events were grade 3 or higher. Microsatellite instability statuses were not available. No treatment-related deaths occurred. Conclusions: Single-agent pembrolizumab in the treatment of advanced ACC has potential for durable responses and a manageable safety profile.

Context: The natural history and malignant potential of cases classified as atypical adrenal masses (AAMs) are unknown. Objective: To describe the radiological characteristics and clinical outcomes of AAMs. Design and Participants: A multicenter retrospective study. Patients ≥18 years old with AAMs [diameter of 10-39 mm on first imaging study and pre-contrast attenuation of >10 Hounsfield units (HU) on computed tomography] were studied. We excluded adrenal metastasis, pheochromocytoma, sarcoma, lymphoma, infiltrative lesions, and adrenal hemorrhage, as well as patients with genetic predisposition to adrenal neoplasms. Data are presented as percentages and median values with interquartile ranges (IQRs). Results: We included 217 patients with 224 adrenal masses (61.3% women); the median age was 58 years (IQR 49-65 years). The median size was 20.5 mm (IQR 15-27 mm), with a median precontrast attenuation of 23.5 HU (IQR 17-30 HU). The median AAM growth rate was 0.3 mm/year (IQR 0-1.8 mm/year). Seventy-one masses (31.7%) underwent pathological evaluation. Adrenal adenoma (n = 38; 17%) and adrenocortical carcinoma (ACC) (n = 25; 11.2%) were the 2 most common diagnoses. For the adenomas, the growth rate was 0.3 mm/year (IQR 0-2.3 mm/year) and for ACCs, the growth rate was 12.9 mm/year (IQR 3.5-22 mm/year). The absolute contrast washout was >60% in 5 out of 7 (71.4%) ACC cases. The best growth rate cutoff for predicting malignancy was 2.68 mm/year (area under the curve 0.939; sensitivity 87.5%, specificity 88.8%). Conclusion: AAMs carry significant malignant potential, and long-term follow-up is warranted when surgery is not pursued. Contrast washout is not reliable in predicting malignant potential of AAMs.

Image-guided therapies (IGTs) are commonly used in oncology, but their role in adrenocortical carcinoma (ACC) is not well defined. A retrospective review of patients with ACC treated with IGTs. We assessed response to therapy using RECIST v1.1, time to next line of systemic therapy, disease control rate (DCR), local tumor progression-free survival (LTPFS), and complications of IGTs (based on the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0). Our cohort included 26 patients (median age 56 years [range 38-76]; n = 18 female) who had 51 IGT sessions to treat 86 lesions. IGTs modalities included cryoablation (n = 49), microwave ablation (n = 21), combined microwave and bland trans-arterial embolization (n = 8), bland trans-arterial embolization alone (n = 3), radio-embolization (n = 3), and radiofrequency ablation (n = 2). DCR was 81.4% (70 out of 86), of which 66.3% of tumors showed complete response, 18.6% showed progressive disease, 8.1% showed partial response, and 7.0% showed stable disease. LTPFS rates were 73% and 63% at 1 and 2 years, respectively. Fourteen lesions underwent re-ablation for incomplete response on initial treatment. Sixteen patients (61.5%) received new systemic therapy following IGTs, with a median time to systemic therapy of 12.5 months (95% CI: 8.6 months upper limit not reached). There was 1 reported CTCAE grade 3 adverse event (biloma) following IGT. IGT use in properly selected patients with ACC is safe and associated with prolonged disease control and delay in the need for systemic therapy.

Background: Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Limited data exist about VTE in patients with adrenocortical carcinoma (ACC). The primary objective of this study was to identify the prevalence of VTE in a cohort of patients with ACC. Secondary objectives were to determine the impact of VTE events on overall survival (OS) and to describe the characteristics of VTE in patients with ACC. Patients and Methods: We retrospectively reviewed data from 289 patients with ACC cared for at a major referral center from February 2010 to June 2022. Results: VTE prevalence was 18.7% (54 events). Thirty patients (55.6%) had pulmonary embolism (PE); 12 patients (22.2%) had deep vein thrombosis (DVT); and 12 patients (22.2%) had both PE and DVT. VTE occurred after ACC diagnosis in 50 patients (92.6%) including 44 patients (88%) with stage 3 or 4 ACC. VTEs were CTCAE grade ≤2 in 32 cases (59.3%), grade 3 in 17 (31.5%), and grade 4 in 2 (3.7%). Thirteen patients (24%) died within 6 months after VTE diagnosis, although there was no statistically significant association between VTE and overall survival. Conclusion: Despite the potential to underestimate the prevalence of VTEs, we found a high frequency of VTE events in patients with ACC. A majority of VTEs occurred in the context of advanced ACC and we observed high short-term mortality. Further studies are needed to validate our findings and investigate mechanisms associated with VTE in ACC.

Background: The increasing use of computed tomography (CT) has identified many patients with incidental adrenal lesions. Further evaluation of these lesions is often dependent on the language used in the radiology report. Compared to the general population, patients with cancer have a higher risk for adrenal abnormalities, yet data on the prevalence and type of incidental adrenal lesions reported on radiologic reports in cancer patients is limited. In this study, we aimed to determine the prevalence and nature of adrenal abnormalities as an incidental finding reported on radiology reports of cancer patients evaluated for reasons other than suspected adrenal pathology.Methods: Radiology reports of patients who underwent abdominal CT within 30 days of presentation to a tertiary cancer center were reviewed and analyzed. We used natural language processing to perform a multi-class text classification of the adrenal reports. Patients who had CT for suspected adrenal mass including adrenal protocol CT were excluded. Three independent abstractors manually reviewed abnormal and questionable results, and we measured the interobserver agreement.Results: From June 1, 2006, to October 1, 2017, a total of 600,399 abdominal CT scans were performed including 66,478 scans obtained within 30 days of the patient’s first presentation. Of these, 58,512 were eligible after applying the exclusion criteria. Adrenal abnormalities were identified in 7,817 (13.4%) reports, with adrenal nodularity (3,401 [43.5%]), adenomas (1,733 [22.2%]), and metastases (1,337 [17.1%]) being the most reported categories. Only 10 cases (0.1%) were reported as primary adrenal carcinomas and 2 as pheochromocytoma. Interobserver agreement using 300 reports yielded a Fleiss kappa of 0.893, implying almost perfect agreement between the abstractors.Conclusions: Incidental adrenal abnormalities are commonly reported in abdominal CT reports of cancer patients. As the terminology used by radiologists to describe these findings greatly determine the subsequent management plans, further studies are needed to correlate some of these findings to the actual confirmed diagnosis based on hormonal, histological and follow-up data and ascertain the impact of such reported findings on patients’ outcomes.