High-Dose Rate Brachytherapy Combined with PD-1 Blockade as a Treatment for Metastatic Adrenocortical Carcinoma - A Single Center Case Series.

The response rate of advanced adrenocortical carcinoma (ACC) to standard chemotherapy with mitotane and etoposide/doxorubicin/cisplatin (EDP-M) is unsatisfactory, and benefit is frequently short lived. Immune checkpoint inhibitors (CPI) have been examined in patient's refractory to EDP-M, but objective response rates are only approximately 15%. High-dose rate brachytherapy (HDR-BT) is a catheter-based internal radiotherapy and expected to favorably combine with immunotherapies. Here we describe three cases of patients with advanced ACC who were treated with HDR-BT and the CPI pembrolizumab. None of the tumors were positive for established response markers to CPI. All patients were female, had progressed on EDP-M and received external beam radiation therapy for metastatic ACC. Pembrolizumab was initiated 7 or 23 months after brachytherapy in two cases and prior to brachytherapy in one case. Best response of lesions treated with brachytherapy was complete (n=2) or partial response (n=1) that was ongoing at last follow up after 23, 45 and 4 months, respectively. Considering all sites of tumor, response was complete and partial remission in the two patients with brachytherapy prior to pembrolizumab. The third patient developed progressive disease with severe Cushing's syndrome and died due to COVID-19. Immune-related adverse events of colitis (grade 3), gastroduodenitis (grade 3), pneumonitis (grade 2) and thyroiditis (grade 1) occurred in the two patients with systemic response. HDR-BT controlled metastases locally. Sequential combination with CPI therapy may enhance an abscopal antitumoral effect in non-irradiated metastases in ACC. Systematic studies are required to confirm this preliminary experience and to understand underlying mechanisms.

Efficacy and safety of adjuvant radiation therapy in localized adrenocortical carcinoma.

Context: Adrenocortical carcinoma (ACC) is rare and have high rates of recurrence and mortality. The role of adjuvant radiation therapy (RT) in localized ACC was controversial. Methods: We conducted a retrospective study in our center between 2015 and 2021 to evaluate the efficacy and safety of adjuvant RT in localized ACC. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to estimate the independent risk factors. Adverse events associated with RT were documented according to the toxicity criteria of the radiation therapy oncology group (RTOG) and the common terminology criteria for adverse events (CTCAE v5.0). Results: Of 105 patients with localized ACC, 46 (43.8%) received adjuvant RT after surgery. The median radiation dose was 45.0Gy (range:30.0-50.4) and median follow up time was 36.5 (IQR: 19.7-51.8) months. In comparison to the no adjuvant RT group, patients with adjuvant RT had better 3-year OS (87.9% vs 79.5%, P=0.039), especially for patients with ENSAT I/II stage (P=0.004). Adjuvant RT also improved the median DFS time from 16.5months (95%CI, 12.0-20.9) to 34.6months (95%CI, 16.1-53.0). Toxicity of RT was generally mild and moderate with six grade 3 events. Conclusions: Postoperative adjuvant RT significantly improved OS and DFS compared with the use of surgery alone in resected ACC patients. Although this retrospective study on RT in localized ACC indicates that RT is effective in ACC, its findings need to be prospectively confirmed.

Impact of postoperative radiotherapy on the outcomes of resected adrenocortical carcinoma-a real-world, population-based study.

OBJECTIVE: To assess the impact of postoperative radiotherapy on the outcomes of resected adrenocortical carcinoma in a real-world setting. METHODS: The Surveillance, Epidemiology, and End Results Research Plus database was accessed, and patients with resected non-metastatic adrenocortical carcinoma diagnosed 2010-2015 were reviewed. Kaplan-Meier estimates and log-rank testing were used to examine the impact of postoperative radiotherapy on overall and cancer-specific survival. Multivariable Cox regression analysis was used to explore factors associated with overall and cancer-specific survival. RESULTS: A total of 294 patients were included in the final analysis, including 60 patients (20.4%) who received postoperative radiotherapy. Using Kaplan-Meier estimates, individuals who received postoperative radiotherapy have better overall survival (P = 0.002). Multivariable cox regression analysis showed that the following factors were associated with worse overall survival: older age (HR: 1.01; 95% CI: 1.00-1.03), male sex (HR for female sex versus male sex: 0.61; 95% CI: 0.43-0.85), and non-receipt of postoperative radiation therapy (HR: 2.29; 95% CI: 1.38-3.77). Systemic therapy was not associated with differences in overall survival (HR: 0.77; 95% CI: 0.54-1.10). Likewise, the following factors were associated with worse cancer-specific survival: male sex (HR for female sex versus male sex: 0.60; 95% CI: 0.41-0.88), non-receipt of postoperative radiation therapy (HR: 2.17; 95% CI: 1.27-3.70), and receipt of perioperative systemic therapy (HR: 0.67; 95% CI: 0.45-0.99). CONCLUSION: Postoperative radiotherapy following resection of adrenocortical carcinoma is associated with better overall and cancer-specific survival.

Benefit of Postoperative Radiotherapy for Patients With Nonmetastatic Adrenocortical Carcinoma: A Population-Based Analysis.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive cancer with high recurrence rates and poor prognosis, even after radical surgery. The survival benefit of adjuvant radiotherapy (RT) in patients with ACC has not been well explored. The aim of this study was to evaluate the effect of adjuvant RT on the survival outcome of patients with ACC. PATIENTS AND METHODS: All patients with nonmetastatic ACC who underwent complete resection were identified from the SEER database (2004-2016). Overall survival (OS) was estimated using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to identify prognostic factors associated with survival. RESULTS: Of 365 patients with nonmetastatic ACC, 55 (15.1%) received adjuvant RT and the remainder underwent surgery alone. Patient characteristics were similar between the 2 groups, but those with a higher disease stage were more likely to receive adjuvant RT. Overall, patients receiving RT seemed to have better survival compared with the non-RT group (3-year OS rate, 63.1% vs 52.8%; P<.062). After adjustment for confounding factors, adjuvant RT was indeed associated with a 48% decreased risk of death (hazard ratio, 0.52; 95% CI, 0.29-0.91; P=.023) for all patients. In addition, adjuvant RT may confer a survival benefit only in patients with a high risk of recurrence (3-year OS rate, 55.1% vs 40.0%; P=.048) rather than in those with low/moderate-risk ACC (P=.559). CONCLUSIONS: Our findings suggest that adjuvant RT may be associated with improved survival in patients with nonmetastatic ACC who underwent radical surgery, especially those with high risk of recurrence.

Stage Presentation, Care Patterns, Treatment Outcomes, and Impact of Radiotherapy on Overall Survival for Adrenocortical Carcinoma.

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare cancer with few well-powered studies regarding epidemiology or outcomes and even fewer studies to guide an evidence-based management approach. The effect of radiation therapy (RT) is particularly understudied and remains unclear, outside of general oncologic principles. We sought to describe current care patterns in the management of ACC and how these practices affect survival outcomes using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients with ACC who could be staged by the American Joint Committee on Cancer (AJCC) system diagnosed between 1988 and 2015 were included. A classification and regression tree analysis identified subgroups of patients who may have benefitted from RT. Multivariable Cox regression analysis was used to compare overall survival (OS). Propensity score adjustment was used to compare OS for a subset of node-negative, nonmetastatic patients who received adjuvant RT following radical surgery. RESULTS: Among 865 eligible patients included in the analysis, only 10.5% received RT. In stage III node-negative patients, adjuvant RT following radical surgery was associated with a significantly improved OS compared with surgery alone. CONCLUSION: Medically fit persons with stage III, node-negative ACC should receive adjuvant RT after surgical resection.

Oligometastatic adrenocortical carcinoma: the role of image-guided thermal ablation.

OBJECTIVES: To evaluate the impact of image-guided ablation of liver and lung metastases from adrenocortical carcinoma (ACC). METHODS: Patients with oligometastatic ACC (liver and lung metastases) who underwent image-guided ablation were retrospectively included in the study. Complete ablation (CA) at the first contrast-enhanced CT control, local tumor progression (LTP), local tumor progression-free survival (LTPFS), liver disease-free survival (LDFS), and overall survival (OS) were evaluated. Correlation between outcomes and other prognostic factors (including Ki67, hormonal secretion, and progression-free survival after primary tumor resection (PR-PFS)) was also analyzed. Kaplan-Meier methods, log-rank tests, and Spearman correlation models were applied. RESULTS: Thirty-two ACC metastases (4 lung and 28 liver) from 16 patients (10 females; mean age 41 years) were treated with RFA or MWA. A single major adverse event was observed (intrahepatic hematoma with subsequent right hemothorax). One patient (2 lesions) was lost to follow-up. CA was obtained in 97% (29/30). During follow-up, LTP was registered in 7/29 cases (24.1%), with a median LTPFS of 21 months (± 12.6). Metastasis size was significantly higher in case of LTP (20 mm vs. 34.5 mm; p = 0.009) and was an independent predictive factor of local tumor control with an AUC of 0.934 (p = 0.0009). Hepatic progression was observed in 66% of the cases, with a median LDFS of 25 months. Median OS was 48.6 months. PR-PFS and hormonal secretion were independent predictors of OS (p < 0.001 and p = 0.045, respectively). CONCLUSIONS: Image-guided ablation achieves adequate local tumor control of ACC liver and lung metastases, providing a safe and effective treatment option in the multidisciplinary management of the oligometastatic ACC. KEY POINTS: • Image-guided ablation allows adequate local tumor control in the oligometastatic adrenocortical carcinoma setting. • After percutaneous thermal ablation, complete ablation was achieved in 29 out of 30 lesions (97%). • Lesion size together with primary resection disease-free survival and hormonal secretion play a significant role in determining outcomes.

Efficacy of adjuvant radiotherapy for treatment of adrenocortical carcinoma: a retrospective study and an updated meta-analysis.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy. Surgical resection is the standard treatment for localized ACC, but the local recurrence remains high. Adjuvant radiation (ART) has been proposed as a means to reduce recurrence rates in ACC after surgery with conflicting results from nonrandomized studies. We performed a retrospective study and a meta-analysis to determine the impact of ART on survival outcomes. METHODS: A retrospective study of the adrenocortical cancer database in Peking Union Medical College was conducted. We selected postoperative ACC patients with or without ART. A meta-analysis is also performed to compare the outcomes between ART and only surgical resection in ACC patients. The obtained data were analyzed using SPSS 23.0 and Stata 15.0 statistical software. Differences between two groups were compared using the log-rank test for retrospective analysis and estimated by calculating the odds ratio (OR) and 95% confidence interval (CI) for meta-analysis. RESULTS: Of a total of 75 patients available in the database, 12 patients underwent postoperative ART and were matched one to one to patients with only surgical resection. There was no significant difference on overall survival between ART group and control group (log-rank P = 0.149). Locoregional recurrence was diagnosed in 2 of the ART group, and in 4 of the control group (P = 0.64). A total of 238 participants were selected for the meta-analysis, of which 111 and 127 patients underwent ART after surgical resection and only surgical resection, respectively. Overall survival is significantly higher in ART group, with an odds ratio (OR) of 2.41 (95% CI of 1.33, 4.38; P = 0.004). Besides, meta-analysis significantly favored ART for locoregional recurrence-free survival and disease-free survival, with an OR of 4.08 and 2.27, respectively. CONCLUSIONS: Our results show that compared to only surgical resection, ART is an effective postoperative treatment for ACC.

Treatment With 90Y/177Lu-DOTATOC in Patients With Metastatic Adrenocortical Carcinoma Expressing Somatostatin Receptors.

CONTEXT: We investigated the role of Gallium 68 dodecanetetraacetic acid Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/computed tomography (PET/CT) in detecting somatostatin receptors (SSTRs) in 19 patients with metastatic adrenocortical carcinoma (ACC) and explored the activity of yttrium-90/lutetium-177 (90Y/177Lu-DOTATOC) peptide receptor radionuclide therapy (PRRT). CASE DESCRIPTION AND METHODS: 68Ga uptake in metastatic sites was scored in terms of intensity and anatomical uptake distribution of standard uptake value (SUV). Tissue expression of SSTR2A and SSTR5 was also evaluated by immunohistochemistry (IHC) on primary tumors. Eight (42%) patients displayed radiometabolic uptake of any-grade intensity with focal and limited distribution. Two (11%) patients displayed strong uptake in multiple lesions and were treated with PRRT. Both obtained an overall disease control lasting 4 and 12 months, respectively. CONCLUSIONS: ACC can express SSTRs as detected by IHC and 68Ga-DOTATOC PET. SSTRs-based PRRT may represent a potential treatment opportunity for a minority of patients with advanced ACC. This treatment modality deserves further investigation.

Evaluating the effectiveness of computed tomography-guided 125I seed interstitial implantation in patients with secondary adrenal carcinoma.

AIM: This study aimed to evaluate the feasibility, safety, and clinical efficacy of computed tomography (CT)-guided 125 I seed interstitial implantation in patients with secondary adrenal carcinoma. MATERIALS AND METHODS: Twenty patients with secondary adrenal carcinoma received CT-guided 125 I seed interstitial implantation. A three-dimensional treatment planning system was used to calculate the dose distribution before 125 I seed interstitial implantation. CT scans were performed every 2 months after the treatment to evaluate local therapeutic efficacy according to the Response Evaluation Criteria in Solid Tumors. RESULTS: The mean follow-up time was 23.65 months (5-102 months). The mean maximum tumor diameter was 34.16 ± 18.94 mm at the beginning of follow-up and 14.42 ± 24.07 mm at the end of follow-up. Eleven patients had complete response (CR), seven had partial response (PR), one had stable disease, and one had progressive disease. Local control rate (CR + PR) was 90% (18/20). The median survival time was 19 months (5-71 months). The 1-, 2-, 3-, and 5-year overall survival rates were 83.70%, 46.8%, 20.80%, and 20.80%, respectively. CONCLUSION: CT-guided 125 I radioactive seed interstitial implantation may be a feasible, safe, effective, and minimally invasive treatment for secondary adrenal carcinoma.

Adjuvant Radiation Improves Recurrence-Free Survival and Overall Survival in Adrenocortical Carcinoma.

CONTEXT: Adrenocortical carcinoma (ACC) is a rare malignancy with high rates of recurrence and poor prognosis. The role of radiotherapy (RT) in localized ACC has been controversial, and RT is not routinely offered. OBJECTIVE: To evaluate the benefit of adjuvant RT on outcomes in ACC. DESIGN: This is a retrospective propensity-matched analysis. SETTING: All patients were seen through the University of Michigan's Endocrine Oncology program, and all those who underwent RT were treated at the University of Michigan. PARTICIPANTS: Of 424 patients with ACC, 78 were selected; 39 patients underwent adjuvant radiation. INTERVENTION: Adjuvant RT to the tumor bed and adjacent lymph nodes. MAIN OUTCOMES MEASURES: Time to local failure, distant failure, or death. RESULTS: Median follow-up time was 4.21 years (95% CI, 2.79 to 4.94). The median radiation dose was 55 Gy (range, 45 to 60). The 3-year overall survival estimate for patients improved from 48.6% for patients without RT (95% CI, 29.7 to 65.2) to 77.7% (95% CI, 56.3 to 89.5) with RT, with a hazard ratio (HR) of 3.59 (95% CI, 1.60 to 8.09; P = 0.002). RT improved local recurrence-free survival (RFS) from 34.2% (95% CI, 18.8 to 50.3) to 59.5% (95% CI, 39.0 to 75.0), with an HR of 2.67 (95% CI, 1.38 to 5.19; P = 0.0035). RT improved all RFS from 18.3% (95% CI, 6.7 to 34.3) to 46.7% (95% CI, 26.9 to 64.3), with an HR 2.59 (95% CI, 1.40 to 4.79; P = 0.0024). CONCLUSIONS: In the largest single institution study to date, adjuvant RT after gross resection of ACC improved local RFS, all RFS, and overall survival in this propensity-matched analysis. Adjuvant RT should be considered a part of multidisciplinary management for patients with ACC.

Adjuvant Radiation is Associated with Improved Survival for Select Patients with Non-metastatic Adrenocortical Carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy for which surgery is the mainstay of treatment and for which adjuvant radiation is infrequently employed; however, small, single-institution series suggest adjuvant radiation may improve outcomes. METHODS: All patients with non-metastatic ACC treated with either surgery alone or surgery followed by adjuvant radiation were identified in the 2004-2013 National Cancer Database. Factors associated with receipt of radiation and the impact of adjuvant radiation on survival were determined by multivariable analysis. RESULTS: Of 1184 patients, 171 (14.4%) received adjuvant radiation. Patient demographics were similar between the two groups, but those receiving radiation were more likely to have had positive margins following surgery (37.4 vs. 14.6%; p < 0.001), evidence of vascular invasion (14.0 vs. 5.1%; p = 0.05), and receive concurrent chemotherapy (57.3 vs. 28.8%; p < 0.001). After adjustment for tumor and other treatment factors, only positive margins following surgery was associated with an increased likelihood of receiving adjuvant radiation (odds ratio 3.84, 95% confidence interval [CI] 1.95-7.56). Radiation therapy did not confer a difference in median overall survival in the general cohort. However, for patients with positive margins, adjuvant radiation was associated with a 40% decreased yearly risk of death after adjustment for concurrent chemotherapy (hazard ratio 0.60, 95% CI 0.40-0.92; p = 0.02). This survival advantage was not evident for other traditional high-risk features. CONCLUSION: Adjuvant radiation appears to decrease the risk of death in ACC patients with positive margins following surgical resection, but only a small percentage are currently receiving radiation. Multidisciplinary treatment with surgery and radiation should be considered for these patients.

Adjuvant radiotherapy for the primary treatment of adrenocortical carcinoma: Are we offering the best?

PURPOSE: To evaluate the role of ARDT after surgical resection of ACC. MATERIALS AND METHODS: Records of patients from our institutional ACC database were retrospectively assessed. A paired comparison analysis was used to evaluate the oncological outcomes between patients treated with surgery followed by ARDT or surgery only (control). The endpoints were LRFS, RFS, and OS. A systematic review of the literature and meta-analysis was also performed to evaluate local recurrence of ACC when ARDT was used. RESULTS: Ten patients were included in each Group. The median follow-up times were 32 months and 35 months for the ARDT and control Groups, respectively. The results for LRFS (p=0.11), RFS (p=0.92), and OS (p=0.47) were similar among subsets. The mean time to present with local recurrence was significantly longer in the ARDT group compared with the control Group (419±206 days vs. 181±86 days, respectively; p=0.03). ARDT was well tolerated by the patients; there were no reports of late toxicity. The meta-analysis, which included four retrospective series, revealed that ARDT had a protective effect on LRFS (HR=0.4; CI=0.17-0.94). CONCLUSIONS: ARDT may reduce the chance and prolong the time to ACC local recurrence. However, there were no benefits for disease recurrence control or overall survival for patients who underwent this complementary therapy.

The efficacy of radiation therapy in adrenocortical carcinoma: A propensity score analysis of a population-based study.

Adrenocortical carcinoma (ACC) is a rare and malignant tumor. The main treatment is primary surgical resection with or without mitotane therapy. The role of radiation therapy is still controversial. We aim to investigate the survival efficacy of radiotherapy in a large population-based cohort.We queried the Surveillance, Epidemiology, and End Results (SEER) database (1973-2013) to identify cases with ACC. Traditional multivariate Cox regression and propensity score analysis were used to evaluate the effect of radiotherapy on cancer survival. The survival outcomes included overall survival and cancer-specific survival. The treatment effect was evaluated using a hazard ratio (HR) and its 95% confidence interval (95% CI).Five hundred thirty patients diagnosed with ACC were identified. Among them, 74 patients received radiotherapy. In the multivariate Cox regression, radiotherapy did not increase the overall survival (HR 0.794, 95% CI 0.550-1.146, P = .218) or cancer-specific survival (HR 0.842, 95% CI 0.574-1.236, P = .388). In the propensity score analysis, the results consistently showed no survival benefit of radiotherapy regardless of the different propensity score analysis methods.Radiotherapy did not improve overall or cancer-specific survival in ACC patients. Further confirmation is needed from multi-institutional prospective studies in the future.

Hirsutismo y amenorrea en carcinoma adrenocortical oncocítico hormonalmente activo. Aportación de un caso y revisión de la literatura / Functioning adrenocortical oncocytic carcinoma presenting with hirsutism and amenorrhea. A rare case report and literature review

Los carcinomas de la corteza suprarrenal son tumores poco frecuentes y agresivos, con mal pronóstico. Las neoplasias oncocíticas son una variante excepcional de carcinomas de la corteza suprarrenal y raramente se encuentran en la glándula suprarrenal. Por lo general, son benignas y no funcionantes. Presentamos el caso de un carcinoma adrenocortical oncocítico, secretor de testosterona, en una mujer de 37 años de edad que presenta acné, hirsutismo y ciclos menstruales irregulares. Las investigaciones clínicas revelaron una testosterona y DHEA-S elevadas, así como una masa de 11×8cm dependiente de la glándula suprarrenal izquierda. Se decide adrenalectomía izquierda. La histología mostró la presencia de una tumoración compuesta de células oncocíticas con citoplasma granular y eosinófilo, características compatibles con un carcinoma oncocítico. Durante el seguimiento se lleva a cabo una nueva TAC, a los 2 meses de la intervención, que revela la presencia de metástasis pulmonares. En estos casos la cirugía está asociada con un aumento de la supervivencia, incluso en la enfermedad metastásica. Por ello, debe ser considerada, en pacientes adecuadamente seleccionados, como parte de un tratamiento multimodal. La quimioterapia citotóxica y el uso de mitotane se han utilizado con un grado de beneficio variable, con escasas respuestas a largo plazo. Posteriormente, llevamos a cabo una revisión de la literatura, con la intención de resaltar y resumir los aspectos más significativos de su epidemiología, clínica, diagnóstico, pronóstico y tratamiento (AU)

Adrenocortical carcinoma is a rare and aggressive cancer and its prognosis is frequently unsatisfactory. Oncocytic neoplasms are an exceptional variant of adrenocortical carcinoma and most rarely found in the adrenal gland. They are usually benign and non-functioning. We present a case of a testosterone-secreting oncocytic adrenocortical carcinoma in a 37-year-old female who presented with acne, hirsutism and irregular menses. Clinical investigations revealed an elevated testosterone and DHEA-S and a 11×8cm left adrenal mass. The tumour was successfully excised. Histopathological result of adrenal mass showed the tumour to be comprised of oncocytic cells with granular, eosinophilic cytoplasm, features consistent with an oncocytic carcinoma. However, follow-up computed tomography at 2 months after the left adrenalectomy revealed lung metastasis. Surgery is associated with improved survival, even in metastatic disease. Therefore, surgery should be considered for select patients as part of multimodality treatment. Cytotoxic chemotherapy and mitotane have been utilized with a variable degree of benefit and few long-term responses. Then we deal with a literature review to highlight and summarize most significant aspects of epidemiology, clinical, diagnosis, prognosis and therapy (AU)

Investigating the Chemokine Receptor 4 as Potential Theranostic Target in Adrenocortical Cancer Patients.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor with limited treatment options. Preclinical studies confirmed overexpression of the chemokine receptor 4 (CXCR4) in this cancer type. This study aimed to analyze the role of CXCR4 imaging using Ga-pentixafor for ACC staging and selection of patients for CXCR4-directed endoradiotherapy. METHODS: Thirty patients with histologically proven advanced, metastasized ACC underwent F-FDG PET/CT and Ga-pentixafor PET/CT within a time interval of 3 ± 4 days to evaluate suitability for CXCR4-directed endoradiotherapy. Scans were analyzed retrospectively for visual extent of ACC and SUVmax/mean of the tumor lesions. Ga-pentixafor PET was compared with F-FDG PET, the reference imaging standard. All patients were rated for suitability of CXCR4-directed endoradiotherapy considering patient's history, previous treatment, and CXCR4 expression of FDG-positive lesions compared with background activity within the same organ. RESULTS: All patients had lesions that were positive for both F-FDG and Ga-pentixafor PET and were rated as positive for disease. In 2 patients (7%), Ga-pentixafor PET identified more lesions compared with F-FDG PET. In 5 patients (17%) and 10 patients (33%), complementary and comparable information, respectively, was provided by dual-tracer imaging. In 13 patients (43%), more tumor lesions were identified by F-FDG PET compared with Ga-pentixafor PET. The F-FDG uptake of the malignant lesions was significantly higher (P < 0.01) than the SUVmax/mean for Ga-pentixafor. Overall, 70% of the patients were rated as suitable or potentially suitable for CXCR4-directed treatment. CONCLUSIONS: Ga-pentixafor allows in vivo imaging of CXCR4 expression in patients with advanced ACC and may serve as companion diagnostic tool in selecting patients for potential CXCR4-directed endoradiotherapy. Seventy percent of the patients with advanced, metastasized ACC may be suitable for a CXCR4-directed treatment after failure of standard treatment options.

Volumetric-modulated arc stereotactic radiotherapy for canine adrenocortical tumours with vascular invasion.

OBJECTIVES: To evaluate the feasibility and efficacy of hypofractionated stereotactic volumetric-modulated arc radiotherapy in treating canine adrenal tumours with vascular invasion. METHODS: A single-arm clinical study was performed. The dogs underwent total body computed tomography, brain and abdomen magnetic resonance imaging and endocrine assay. Adrenal masses were classified as cortisol-secreting adrenal tumour or non-secreting adrenal tumour. Radiotherapy treatments were delivered by hypofractionated stereotactic volumetric-modulated arc radiotherapy via a linear accelerator. The overall survival was estimated by the Kaplan-Meier method. The overall response and radio-toxicity effects were determined. RESULTS: Nine dogs were enrolled. Three dogs were affected by cortisol-secreting adrenal tumours and the remaining dogs had non-secreting adrenal tumours. The prescribed doses ranged from 30 to 45 Gy in three or five consecutive daily fractions. The median overall survival time was 1030 days, and the overall mean reduction of the diameter and volume were ~32 and 30% respectively. The endocrine profile normalised in two dogs with cortisol-secreting adrenal tumours. Radio-toxicities were mild and self-limiting. Seven deaths were recorded during the follow-up period and two dogs were censored. CLINICAL SIGNIFICANCE: Hypofractionated stereotactic volumetric-modulated arc radiotherapy should be considered as a feasible and effective therapeutic option for adrenal tumours with vascular invasion.

Adjuvant radiation therapy improves local control after surgical resection in patients with localized adrenocortical carcinoma.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. METHODS AND MATERIALS: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. RESULTS: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. CONCLUSIONS: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

Expression of STAT3 and IGF2 in adrenocortical carcinoma and its relationship with angiogenesis

OBJECTIVE: The aim of this study was to determine the correlation between human adrenocortical carcinoma and the proteins involved in tumor angiogenesis, and to evaluate the angiogenic status of adrenocortical carcinoma. METHODS: The expression of signal transducer and activator of transcription 3 and insulin-like growth factor 2 as well as microvessel density was measured in a series of tissue samples from 44 human sporadic adrenocortical tumors by immunohistochemistry. These specimens were classified as adenomas (n = 20) and carcinomas (n = 24) according to the histological criteria defined by Weiss. RESULTS: A total of 19 of 24 (79.17 %) malignant cases showed positive staining for signal transducer and activator of transcription 3 and 4 of 20 (20.00 %) benign cases showed positive, the difference of signal transducer and activator of transcription 3 expression between adrenocortical adenomas and adrenocortical carcinomas was statistically significant (P < 0.001). Similarly, insulin-like growth factor 2 staining was seen in 70.83 % (17/24) of the malignant cases versus 25.00 % (5/20) of the benign, the difference of insulin-like growth factor 2 expression among two groups was statistically significant (P = 0.002). Malignant cases showed higher microvessel density compared to benign tumors (84.70 ± 12.44 vs 21.05 ± 8.07, P < 0.001). Signal transducer and activator of transcription 3 and insulin-like growth factor 2 expression were positively correlated with microvessel density in all specimens (r_s = 0.832, P < 0.001; r_s = 0.703, P = 0.001). CONCLUSIONS: This study has confirmed that adrenocortical carcinoma overexpress signal transducer and activator of transcription 3 and insulin-like growth factor 2; these results suggest that angiogenesis of human adrenocortical carcinoma may be mediated by these proteins and they could represent selective targets for the molecularly targeted treatments of adrenocortical carcinoma (AU)

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