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Metastatic pheochromocytomas and paragangliomas (PPGLs) are frequently associated with skeletal complications. Primary objective: to describe the frequency of adverse skeletal related events (SREs) in PPGL patients with bone metastases (BMs). Secondary objectives: to 1) identify predictive and prognostic factors for SREs and 2) obtain information on the effectiveness of bone resorption inhibitors in reducing SRE risk and improving outcomes in term of survival and SREs time onset. In this retrospective multicenter, multinational study, 294 PPGL patients were enrolled. SREs occurred in 90 patients (31 %). Fifty-five patients (19 %) had bone fractures, 47 (16 %) had spinal cord compression, and 11 (4 %) had hypercalcemia. Twenty-two patients (7 %) had more than one SRE. Sixty-four patients (22 %) underwent surgery, and 136 (46 %) underwent radiotherapy. SREs occurred a median of 4.4 months after diagnosis of BM (range, 0-246.6 months). Independent factors associated with reduced risk of SREs in multivariable analysis were I-131-MIBG radionuclide therapy (hazard ratio [HR], 0.536 [95 % CI, 0.309-0.932]; P = .027) and absence of liver metastases (HR, 0.638 [95 % CI, 0.410-0.992]; P = .046). The median overall survival duration was 5.3 year. In multivariable analysis, age younger than 48 years at PPGL diagnosis (HR, 0.558 [95 % CI, 0.3877-0.806]; P = .002), absence of liver metastases (HR, 0.618 [95 % CI, 0.396-0.965]; P = .034), treatment with bisphosphonates or denosumab (HR, 0.598 [95 % CI, 0.405-0.884]; P = .010), and MIBG radionuclide therapy (HR, 0.444 [95 % CI, 0.274-0.718]; P = .001) were associated with a reduced risk of death. SREs occur frequently and early in bone-metastatic PPGL patients but do not negatively impact survival. MIBG radionuclide therapy and treatment with bone resorption inhibitors are associated with favorable outcome.
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Neoplasias de las Glándulas Suprarrenales , Neoplasias Óseas , Paraganglioma , Feocromocitoma , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Óseas/secundario , Neoplasias Óseas/complicaciones , Feocromocitoma/complicaciones , Feocromocitoma/patología , Feocromocitoma/mortalidad , Estudios Retrospectivos , Neoplasias de las Glándulas Suprarrenales/secundario , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/mortalidad , Neoplasias de las Glándulas Suprarrenales/terapia , Adulto , Anciano , Paraganglioma/complicaciones , Paraganglioma/patología , Paraganglioma/mortalidad , Adulto Joven , Compresión de la Médula Espinal/etiología , Fracturas Óseas/etiología , Adolescente , Anciano de 80 o más Años , Hipercalcemia/etiología , Factores de Riesgo , Conservadores de la Densidad Ósea/uso terapéutico , PronósticoRESUMEN
BACKGROUND: Image-guided therapies (IGTs) are commonly used in oncology, but their role in adrenocortical carcinoma (ACC) is not well defined. MATERIALS AND METHODS: 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). RESULTS: Our cohort included 26 patients (median age 56 years [range 38-76]; nâ =â 18 female) who had 51 IGT sessions to treat 86 lesions. IGTs modalities included cryoablation (nâ =â 49), microwave ablation (nâ =â 21), combined microwave and bland trans-arterial embolization (nâ =â 8), bland trans-arterial embolization alone (nâ =â 3), radio-embolization (nâ =â 3), and radiofrequency ablation (nâ =â 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. CONCLUSIONS: IGT use in properly selected patients with ACC is safe and associated with prolonged disease control and delay in the need for systemic therapy.
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BACKGROUND AND PURPOSE: Adrenal venous sampling (AVS) is used for the diagnosis of primary hyperaldosteronism. Technical difficulties with right adrenal vein (RAV) catheterization can lead to erroneous results. Our purpose was to delineate the location of the RAV on pre-procedural CT imaging in relation to the location identified during AVS and to report on the impact of successful RAV cannulation with and without the use of intra-procedural CT scanning. METHODS: Retrospective case series including patients who underwent AVS from October 2000 to September 2022. Clinical and laboratory values were abstracted from the electronic medical record. Successful cannulation of the RAV was defined as a selectivity index > 3. RESULTS: 110 patients underwent 124 AVS procedures. Pre-AVS CT imaging was available for 118 AVS procedures. The RAV was identified in 61 (51.7%) CT datasets. Biochemical confirmation of successful RAV cannulation occurred in 98 (79.0%) of 124 AVS procedures. There were 52 (85.2%) procedures in which the RAV was identified on pre-AVS CT and there was biochemical confirmation of successful RAV sampling. Among these 52 procedures, the RAV was localized during AVS at the same anatomic level or within 1 vertebral body level cranial to the level identified on pre-AVS CT in 98.1% of cases. The rate of successful RAV cannulation was higher in patients who underwent intra-procedural CT (93.8% versus 63.9%), P < 0.01. CONCLUSIONS: Pre-AVS and intra-procedural CT images provide an invaluable roadmap that resulted in a higher rate of accurate identification of the RAV and successful AVS procedures; in particular, search for the RAV orifice during AVS can be limited to 1 vertebral body cranial to the level identified on pre-AVS CT imaging and successful cannulation can be confidently verified with intra-procedural CT.
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Glándulas Suprarrenales , Hiperaldosteronismo , Tomografía Computarizada por Rayos X , Humanos , Estudios Retrospectivos , Masculino , Femenino , Tomografía Computarizada por Rayos X/métodos , Glándulas Suprarrenales/irrigación sanguínea , Glándulas Suprarrenales/diagnóstico por imagen , Persona de Mediana Edad , Hiperaldosteronismo/diagnóstico por imagen , Hiperaldosteronismo/sangre , Adulto , Anciano , Radiografía Intervencional/métodos , Cateterismo/métodosRESUMEN
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.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Tromboembolia Venosa , Humanos , Masculino , Carcinoma Corticosuprarrenal/complicaciones , Carcinoma Corticosuprarrenal/mortalidad , Carcinoma Corticosuprarrenal/patología , Femenino , Estudios Retrospectivos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/mortalidad , Tromboembolia Venosa/patología , Tromboembolia Venosa/complicaciones , Persona de Mediana Edad , Neoplasias de la Corteza Suprarrenal/complicaciones , Neoplasias de la Corteza Suprarrenal/mortalidad , Neoplasias de la Corteza Suprarrenal/patología , Anciano , Adulto , PrevalenciaRESUMEN
Malignancies may induce clinical sequelae distant from the sites of the tumor. Such paraneoplastic phenomena are known to affect many organs, including the skin. Vitiligo is a disorder of patchy depigmentation, appearing as white macules with distinct margins. Rarely, vitiligo has been reported as a paraneoplastic occurrence, in the settings of pituitary adenoma, thymoma, gastric carcinoma, and lymphoma. We now describe a man presenting with the abrupt onset of vitiligo on the hands coinciding with recurrence of adrenocortical carcinoma (ACC) in the abdomen. The vitiligo rapidly dissipated following resection of his cancer. We believe this to be the first report of paraneoplastic vitiligo associated with ACC. Endocrinologists typically manage ACC and should be aware of this link, as the de novo observation of vitiligo may signal the onset or recurrence of underlying tumor. Other practitioners that encounter patients with new vitiligo should add ACC to their differential diagnosis of potential underlying conditions.
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BACKGROUND: Metastatic phaeochromocytomas and paragangliomas (MPPGs) are orphan diseases. Up to 50% of MPPGs are associated with germline pathogenic variants of the SDHB gene. These tumours and many non-familial MPPGs exhibit a phenotype that is characterised by abnormal angiogenesis. We aimed to assess the activity and safety of cabozantinib, an antiangiogenic multi-tyrosine kinase inhibitor, in patients with MPPGs. METHODS: The Natalie Trial is a single-arm, phase 2 clinical trial being conducted at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients aged 18 years or older with histologically confirmed, progressive, and unresectable MPPGs, with an Eastern Cooperative Oncology Group performance status of 0-2, were treated with oral cabozantinib 60 mg/day. The primary endpoint was the investigator-assessed overall response rate per the Response Evaluation Criteria in Solid Tumours version 1.1 criteria. All outcomes were assessed in all evaluable participants who received any amount of study treatment. The trial is registered with ClinicalTrials.gov (NCT02302833) and is active but not recruiting. FINDINGS: From March 10, 2015, to May 11, 2021, 17 patients (13 male participants and four female participants) were enrolled. The median follow-up was 25 months (IQR 18-49). The overall response rate was 25·0% (95% CI 7·3-52·4; four of 16 patients). Seven grade 3 adverse events were reported in six patients, including single cases of hand-and-foot syndrome, hypertension, rectal fistula, QT prolongation, and asymptomatic hypomagnesaemia, and two cases of asymptomatic elevations of amylase and lipase. There were no grade 4 adverse events and no patient died on-study. INTERPRETATION: Cabozantinib shows promising activity in patients with MPPGs. FUNDING: Team NAT Foundation, Margaret Cazalot, and Clarence P Cazalot.
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Neoplasias de las Glándulas Suprarrenales , Anilidas , Paraganglioma , Feocromocitoma , Piridinas , Humanos , Piridinas/uso terapéutico , Piridinas/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Anilidas/uso terapéutico , Anilidas/efectos adversos , Feocromocitoma/tratamiento farmacológico , Feocromocitoma/patología , Feocromocitoma/genética , Paraganglioma/tratamiento farmacológico , Paraganglioma/patología , Adulto , Neoplasias de las Glándulas Suprarrenales/tratamiento farmacológico , Neoplasias de las Glándulas Suprarrenales/secundario , Anciano , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
BACKGROUND: Adrenocortical carcinoma is a rare malignancy with poor response to systemic chemotherapy. Mitotane is the only approved therapy for adrenocortical carcinoma. Cabozantinib is a multikinase inhibitor approved in multiple malignancies. This is the first prospective trial to explore the anti-tumour activity, safety, and pharmacokinetic profile of cabozantinib in patients with advanced adrenocortical carcinoma. METHODS: This investigator-initiated, single-arm, phase 2 trial in adult patients (aged ≥18 years) with advanced adrenocortical carcinoma was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible patients had histologically confirmed adrenocortical carcinoma, were not candidates for surgery with curative intent, had measurable disease, had an estimated life expectancy of at least 3 months, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with adequate organ function. Patients who had used mitotane within 6 months of study participation were required to have a serum mitotane level of less than 2 mg/L. Patients were given oral cabozantinib 60 mg daily with the option of dose reduction to manage adverse events. The primary endpoint was progression-free survival at 4 months, assessed in all patients who received at least one dose of study drug per protocol. This study is registered with ClinicalTrials.gov, NCT03370718, and is now complete. FINDINGS: Between March 1, 2018, and May 31, 2021, we enrolled 18 patients (ten males and eight females), all of whom received at least one dose of study treatment. Of the 18 patients, eight (44%) had an ECOG performance status of 0, nine (50%) patients had a performance status of 1, and one (6%) patient had a performance status of 2. Median follow-up was 36·8 months (IQR 30·2-50·3). At 4 months, 13 (72·2%; 95% CI 46·5-90·3) of 18 patients had progression-free survival and median progression-free survival was 6 months (95% CI 4·3 to not reached). One patient remains on treatment. Treatment-related adverse events of grade 3 or worse occurred in 11 (61%) of 18 patients. The most common grade 3 adverse events were lipase elevation (three [17%] of 18 patients), elevated γ-glutamyl transferase concentrations (two [11%] patients), elevated alanine aminotransferase concentrations (two [11%] patients), hypophosphatemia (two [11%] patients), and hypertension (two [11%] patients). One (6%) of 18 patients had grade 4 hypertension. No treatment related deaths occurred on study. INTERPRETATION: Cabozantinib in advanced adrenocortical carcinoma showed promising efficacy with a manageable and anticipated safety profile. Further prospective studies with cabozantinib alone and in combination with immune checkpoint therapy are ongoing. FUNDING: Exelixis.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Anilidas , Piridinas , Humanos , Anilidas/uso terapéutico , Anilidas/administración & dosificación , Anilidas/efectos adversos , Anilidas/farmacocinética , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Piridinas/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/patología , Carcinoma Corticosuprarrenal/mortalidad , Adulto , Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Neoplasias de la Corteza Suprarrenal/patología , Neoplasias de la Corteza Suprarrenal/mortalidad , Anciano , Estudios Prospectivos , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/farmacocinéticaRESUMEN
PATIENTS AND METHODS: The primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were duration of response, blood pressure control, safety, overall and progression-free survival rates, MIBG uptake, and correlations with genetic background. RESULTS: The study included 25 patients. Twenty-four patients had distant metastases, 17 (68%) had hormonally active tumors, and 13 (52%) had previously received antineoplastic treatment. In 24 evaluable patients, the ORR was 38%, including 2 patients with complete response, and the DCR was 83%; median time to response was 12.5 months (95% confidence interval, 4.6-25.1). Twelve patients had sporadic disease, among whom the ORR was 25% and DCR was 83%. Twelve patients had hereditary disease ( SDHB , VHL , RET ); among these, the ORR was 50%, and DCR was 83%. Plasma metanephrines normalized in 30% of patients and improved by greater than 50% in 46%. Sixteen patients had hormonally active tumors and hypertension; in 9 (56%) of these, blood pressure normalized, leading to discontinuation of antihypertensive therapy.The most common adverse events were grades 1-2 nausea/vomiting and transient bone marrow suppression. One patient developed premature ovarian failure. Reversible grades 3-4 myelosuppression were seen in 7 patients (28%). One patient had fatal pneumonitis. CONCLUSIONS: HSA- 131 I-MIBG is associated with a high DCR in patients with MPPGL, regardless of underlying genetic mutation.
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3-Yodobencilguanidina , Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico por imagen , Feocromocitoma/radioterapia , Feocromocitoma/tratamiento farmacológico , Femenino , Masculino , Paraganglioma/radioterapia , Paraganglioma/diagnóstico por imagen , Paraganglioma/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/radioterapia , Anciano , Adulto Joven , Resultado del Tratamiento , Adolescente , Radioisótopos de YodoRESUMEN
OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy without established association with environmental risk factors. ACC incidence is stable based on large surgical databases while referral centers data reported increasing number of cases seen. We studied ACC incidence and distribution at a county level to find potential ACC "hot spots" that could be linked to environmental exposures. METHODS: A retrospective analysis of Texas Cancer Registry that included ACC patients diagnosed between 2000 and 2018. County-level heatmaps were created and compared with breast, prostate, and lung cancer. RESULTS: We identified 448 ACC cases during the study period. Cases were registered in 110 of the 254 counties (43.3%) in Texas, representing 92.74% of the total population. The median incidence was 23 new cases/y (range 14-33). The mean population-adjusted ACC incidence rate was 0.104 per 100 000 per year (standard deviation 0.005; 95% CI, 0.092-0.116). Seven counties (6.3%) accounted for 215 (48.0%) cases, with more than 10 cases each and median standardized incidence ratio (SIR) of 0.1 (range, 0.0-0.9). One hundred three counties (93.7%) accounted for the remaining 233 cases (52%), with fewer than 10 cases per county. The highest standardized incidence ratios were found in counties with a median population of fewer than 14 000 residents and with only one reported case. CONCLUSION: Our analysis is the first report to create ACC heatmap and could not detect any geographic clustering of ACC in Texas. The incidence of ACC remained stable and consistent with data from other large databases.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Masculino , Humanos , Carcinoma Corticosuprarrenal/epidemiología , Carcinoma Corticosuprarrenal/patología , Estudios Retrospectivos , Incidencia , Sistema de Registros , Neoplasias de la Corteza Suprarrenal/epidemiología , Neoplasias de la Corteza Suprarrenal/patologíaRESUMEN
BACKGROUND: Current evidence suggests that cortisol secreting adrenocortical carcinoma has worse prognosis compared to non-secreting adrenocortical carcinoma. However, the effect of other secretory subtypes is unknown. METHODS: This multicenter study within the American-Australian-Asian Adrenal Alliance included adults with adrenocortical carcinoma (1997-2020). We compared overall survival and disease-free survival among cortisol secreting, mixed cortisol/androgen secreting, androgen secreting, and non-secreting adrenocortical carcinoma. RESULTS: Of the 807 patients (mean age 50), 719 included in the secretory subtype analysis: 24.5% were cortisol secreting, 13% androgen secreting, 28% mixed cortisol/androgen, 32.5% non-secreting, and 2% were mineralocorticoid secreting. Median overall survival and disease-free survival for the entire cohort were 60 and 9 months, respectively. Median overall survival was 36 months for cortisol, 30 for mixed, 60 for androgen secreting, and 115 for non-secreting adrenocortical carcinoma, P < .01. Median disease-free survival was 7 months for cortisol, 8 for mixed, 10 for androgen, and 12 for non-secreting adrenocortical carcinoma, P = .06. On multivariable analysis of age, sex, Ki67%, secretory subtype, stage, resection, and adjuvant therapy, predictors of worse overall survival were older age, higher Ki67%, stage IV, mixed secreting, R1, and no adjuvant therapy, P < .05. On subgroup analysis of R0 resection, predictors of worse overall survival included older age and higher Ki67%. Ki67% ≥40, stage III and cortisol secretion were associated with worse disease-free survival. CONCLUSION: Mixed cortisol/androgen secreting adrenocortical carcinoma was associated with worse overall survival, while cortisol or androgen secreting alone were not. Notably, among patients after R0 resection, secretory subtype did not affect overall survival. Cortisol secreting adrenocortical carcinoma demonstrated worse disease-free survival. Ki67% remained a strong predictor of worse overall survival and disease-free survival independent of stage.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Adulto , Humanos , Persona de Mediana Edad , Neoplasias de la Corteza Suprarrenal/cirugía , Andrógenos , Hidrocortisona , Antígeno Ki-67 , Australia , Estudios RetrospectivosRESUMEN
CONTEXT: Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors. Metastases develop in 15% to 20%. The American Joint Committee on Cancer (AJCC) established inaugural guidelines for PPGL tumor-node-metastasis (TNM) staging. OBJECTIVE: The objective of this analysis is to investigate the associations between TNM staging and overall survival (OS). METHODS: We retrospectively applied the TNM staging at the time of diagnosis of the primary tumor. The primary outcome was OS. Unadjusted survival rates were estimated by the Kaplan-Meier method. Cox proportional hazards regression models were used to evaluate the associations between OS and covariates of interest. RESULTS: The study included 458 patients. Median OS was 18.0 (95% CI, 15.6-not reached) years. At diagnosis, 126 (27.5%) tumors were stage I, 213 (46.5%) were stage II, 47 (10.3%) were stage III, and 72 (15.7%) were stage IV. The 10-year OS probabilities were 0.844 (95% CI, 0.768-0.928) for patients with stage I tumors, 0.792 (95% CI, 0.726-0.865) for stage II, 0.595 (95% CI, 0.435-0.813) for stage III, and 0.221 (95% CI, 0.127-0.384) for stage IV. Compared with stage I, the hazard ratios (HR) for death were 1.50 (0.87-2.57) for stage II, 2.85 (1.45-5.63) for stage III, and 8.88 (5.16-15.29) for stage IV (P < 0.001). Compared with patients with no germline mutations, those with RET 634/918 had better OS (HR: 0.28; 95% CI, 0.12-0.69). Other germline mutations, including SDHB, did not exhibit worse OS than patients with metastasis and sporadic disease. CONCLUSION: OS rates correlated with the recently developed AJCC TNM staging and were not worse in hereditary disease. Stage IV disease exhibited a significantly shorter OS compared with stages I-III. Future staging systems could be adjusted to better separate stages I and II.
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Neoplasias de las Glándulas Suprarrenales , Neoplasias Encefálicas , Paraganglioma , Feocromocitoma , Humanos , Estadificación de Neoplasias , Feocromocitoma/genética , Estudios Retrospectivos , PronósticoAsunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Humanos , Mitotano/uso terapéutico , Cisplatino/uso terapéutico , Etopósido/uso terapéutico , Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Neoplasias de la Corteza Suprarrenal/cirugía , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antineoplásicos Hormonales/uso terapéuticoRESUMEN
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.
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Neoplasias de las Glándulas Suprarrenales , Feocromocitoma , Humanos , Prevalencia , Tomografía Computarizada por Rayos X , Feocromocitoma/diagnóstico por imagen , Feocromocitoma/epidemiología , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/epidemiologíaRESUMEN
Background: Adrenocortical carcinoma (ACC) is a rare malignancy arising from the adrenal cortex. While ACC can be associated with adrenal hormone excess syndromes, classic paraneoplastic syndromes are rarely seen. Stauffer syndrome, a paraneoplastic phenomenon characterized by reversible cholestasis in the absence of liver metastases, has been described with renal carcinoma and other malignancies but has not been previously reported in ACC. Case Presentation: A 38-year-old man presented with emesis, painless jaundice, pruritus, and weight loss. Laboratory evaluation demonstrated elevated total bilirubin of 8.7 mg/dL (Nâ <â 1.3 mg/dL). Computed tomography revealed a 20.4-cm left adrenal mass without evidence of liver metastases. The patient's condition deteriorated rapidly with progressive renal failure and worsening hyperbilirubinemia. The patient underwent left adrenalectomy, nephrectomy, ureterolysis, and wedge liver biopsy. Histopathology showed necrotic ACC with tumor invasion into the adrenal capsule, no lymphovascular invasion, uninvolved margins, and Ki-67 of 40%. Kidney parenchyma exhibited diffuse pigment casts. The liver specimen contained diffuse bile deposits and minimal chronic inflammation in the portal tracts. He tested positive for the pathogenic variant of folliculin (FLCN) gene consistent with Birt-Hogg-Dube syndrome. Renal function recovered after surgery, and bilirubin level normalized after several weeks. Based on clinical presentation and absence of other etiologies, reversible cholestatic jaundice was attributed to Stauffer syndrome. Conclusion: This is the first report of a unique presentation of paraneoplastic-related hyperbilirubinemia in the setting of ACC. While extremely rare, Stauffer syndrome should still be considered in differential diagnosis in patients with ACC with liver dysfunction and jaundice without evidence of liver metastases.
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BACKGROUND: Oncocytic adrenocortical neoplasms (OANs) are rare endocrine tumors that present as a spectrum from benign to malignant. The outcomes after surgical resection of the oncocytic variant of adrenocortical carcinoma remain poorly understood. We sought to characterize the clinicopathologic features of OAN and compare oncocytic adrenocortical carcinoma (OAC) with conventional adrenocortical carcinoma (ACC). PATIENTS AND METHODS: Adult patients who underwent adrenalectomy for OAN or ACC between January 1990 and September 2020 were identified. Demographics, clinicopathologic factors, American Joint Committee on Cancer stage, and cancer-related outcomes were reviewed. A matched cohort analysis of disease-free survival (DFS) and overall survival (OS) was performed between patients with OACs and those with ACCs. RESULTS: Forty-one patients with OAN and 214 patients with ACC were included. The OAN cohort median age was 45.2 years [interquartile ratio (IQR) 38.5-54.0 years], and 61.0% were female. OANs were benign (n = 11), of uncertain malignant potential (UMP, n = 9), or OAC (n = 21). Disease recurrence occurred in 12 (57.1%) patients with OAC compared with 1 (11.1%) and 0 patients with UMP or benign OAN, respectively (p < 0.001). Seven (33.3%) patients with OAC died during follow-up compared with 0 patients with UMP or benign OAN (p = 0.020). Kaplan-Meier survival analysis found no difference in DFS between ACC and OAC groups before (p = 0.218) and after 2:1 matching (p = 0.417). Overall survival was shorter for patients who had ACC compared with those who had OAC (p = 0.031), but the difference was not evident with matched analysis (p = 0.200). CONCLUSIONS: OAN presents as a spectrum from benign indolent tumors to aggressive carcinomas. OACs demonstrate similar clinicopathologic behavior and recurrence-free and overall survival when matched to conventional ACCs.
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Adenocarcinoma , Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma/cirugía , Neoplasias de la Corteza Suprarrenal/patología , Adrenalectomía , Carcinoma Corticosuprarrenal/patología , Recurrencia Local de Neoplasia/cirugíaRESUMEN
Adrenocortical cancers and metastatic pheochromocytomas are the most common malignancies originating in the adrenal glands. Metastatic paragangliomas are extra-adrenal tumors that share similar genetic and molecular profiles with metastatic pheochromocytomas and, subsequently, these tumors are studied together. Adrenocortical cancers and metastatic pheochromocytomas and paragangliomas are orphan diseases with limited therapeutic options worldwide. As in any other cancers, adrenocortical cancers and metastatic pheochromocytomas and paragangliomas avoid the immune system. Hypoxia-pseudohypoxia, activation of the PD-1/PD-L1 pathway, and/or microsatellite instability suggest that immunotherapy with checkpoint inhibitors could be a therapeutic option for patients with these tumors. The results of clinical trials with checkpoint inhibitors for adrenocortical carcinoma or metastatic pheochromocytoma or paraganglioma demonstrate limited benefits; nevertheless, these results also suggest interesting mechanisms that might enhance clinical responses to checkpoint inhibitors. These mechanisms include the normalization of tumor vasculature, modification of the hormonal environment, and vaccination with specific tumor antigens. Combinations of checkpoint inhibitors with classical therapies, such as chemotherapy, tyrosine kinase inhibitors, radiopharmaceuticals, and/or novel therapies, such as vaccines, should be evaluated in clinical trials.
RESUMEN
CONTEXT: Reporting temporal trends in adrenocortical carcinoma (ACC) helps guide management strategies. OBJECTIVE: This work aimed to report the trends in disease burden and clinical outcomes over time that cannot be adequately captured from individual clinical trials. METHODS: A retrospective study was held of ACC patients seen at a referral cancer center between February 1998 and August 2019. Clinical outcomes were compared between an early cohort (February 1998-June 2007) and a late cohort (July 2007-August 2019). RESULTS: A total of 621 patients included with a median age at diagnosis of 49.3 years (range, 0.5-86.6 years). There were 285 (45.9%) patients with hormonal overproduction. More patients in the late cohort had stage IV disease compared to the early cohort (36.8% vs 23.1%; Pâ <â .0001). Resection of the primary tumor was performed in 502 patients (80.8%). Complete resection (R0) was more common in the late cohort (165 [60.2%]) than in the early cohort (100 [44.6%]; Pâ =â .0005). Of 475 patients with metastatic disease (stage IV or recurrent metastatic disease), 352 (74.1%) received mitotane, 320 (67.4%) received chemotherapy, and 53 (11.2%) received immunotherapy. In the early cohort, 70 (33%) received 2 or more lines of therapy, whereas in the late cohort, 127 (48%) received 2 or more lines of therapy. The 5-year overall survival (OS) rates were 65%, 58%, 45%, and 10% for stage I, II, III, and IV disease, respectively, whereas the 2-year OS rates in patients with stage IV disease was 24% in the early cohort and 46% in the late cohort (Pâ =â .01). CONCLUSION: ACC clinical outcomes improved over the past 2 decades as more patients had complete resection or received more lines of systemic therapy.
Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Neoplasias de la Corteza Suprarrenal/cirugía , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/cirugía , Antineoplásicos Hormonales/uso terapéutico , Humanos , Mitotano/uso terapéutico , Derivación y Consulta , Estudios RetrospectivosRESUMEN
CONTEXT: The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. OBJECTIVE: To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. DESIGN AND SETTING: We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. PATIENTS: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. INTERVENTION: Performance (or not) of cytoreductive surgery of the primary tumor. MAIN OUTCOME AND MEASURES: A propensity score match was done using age and the number of organs with metastasis (≤2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. RESULTS: Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). CONCLUSION: Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.
Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Adolescente , Neoplasias de la Corteza Suprarrenal/cirugía , Carcinoma Corticosuprarrenal/cirugía , Adulto , Australia , Estudios de Cohortes , Procedimientos Quirúrgicos de Citorreducción , Humanos , Estudios RetrospectivosRESUMEN
OBJECTIVES: Adrenal adenoma with myelolipomatous degeneration (AMD) is a rarely reported and often overlooked entity. The aim of this study is to improve understanding of these lesions by characterizing the imaging findings with pathologic and clinical correlation. METHODS: In the largest series to date, we report 11 nodules in 11 patients confirmed with a pathologic diagnosis of AMD. The available cross-sectional imaging and histopathologic features were reviewed by two radiologists and two pathologists, respectively. Clinical and laboratory data for each patient were obtained from the electronic medical records, when available. RESULTS: All 11 patients had a CT prior to resection or biopsy of the adrenal nodule, with five having received an adrenal mass protocol study. An MRI was available in three patients. The median size of the nodules on imaging was 4.5 cm (range 2.8-8.7) and all but one had macroscopic fat. The largest focus of macroscopic fat had a median size of 0.7 cm (range 0.2-1.6) and on average was 14.4% the size of the tumor, using greatest dimensions. Four (36.4%) patients had a diagnosis of Cushing syndrome prior to nodule resection. CONCLUSIONS: Not all adrenal nodules with macroscopic fat on imaging are pure myelolipomas. An AMD should be considered, especially if the foci of fat are small and other features of an adenoma are present. Some may also be associated with Cushing syndrome. ADVANCES IN KNOWLEDGE: Myelolipomatous degeneration within an adrenal adenoma has only rarely been previously reported with very few reports emphasizing the imaging features. There may be an association with cortisol hypersecretion and improved recognition of this entity could lead to changes in clinical management.