Surgery for adrenocortical carcinoma in The Netherlands: analysis of the national cancer registry data

Kerkhofs, Thomas M.A.; Verhoeven, Rob H.A.; Bonjer, H. J.; Dijkum, E. J. Nieveen van; Vriens, Menno R.; Vries, de Erik; Eijck, Casper H. van; Bonsing, B.A.; Poll‐Franse, Lonneke V. van de; Haak, Harm R.

doi:10.1530/eje-13-0142

Cited by 61 publications

(32 citation statements)

References 28 publications

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“…Resection status is one of the most important prognostic factors. To reduce the amount of recurrences, it is recommended to perform adrenalectomies only in specialized centers performing at least 20 adrenalectomies per year (Kerkhofs et al 2013a, Ronchi et al 2014a. A recent systematic review reported that open adrenalectomy with lymph node dissection should be regarded as standard treatment for ACC (Bellantone et al 2015).…”

Section: Current Therapeutic Strategiesmentioning

confidence: 99%

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Creemers¹,

Hofland²,

Korpershoek³

et al. 2015

Endocrine-Related Cancer

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Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Discrimination between ACCs and adrenocortical adenomas (ACAs) remains challenging, with the current gold standard being the Weiss score, consisting of several histopathological characteristics. However, new markers like Ki67, a marker for proliferation, and the staining of reticulins are promising not only as it comes to identifying malignancy but also as prognostic markers in patients with ACC. Currently, surgery is still the only curative treatment for ACC. Mitotane, an adrenolytic drug, is used in the adjuvant setting and in case of metastatic or advanced disease. Patients with progressive disease are frequently treated with mitotane, alone or in combination with etoposide, doxorubicine and cisplatin. Radiotherapy is indicated in selected cases. The low response rates and high toxicity of the systemic therapies emphasize the need for markers that enable the identification of responders and non-responders. Consequently, research is focusing on predictive factors varying from the expression of DNA repair genes to clinical patient characteristics. Subgroups of ACC with different prognosis have been identified based on transcriptome characteristics. As a conclusion from large molecular studies, ACCs appear to harbor many abnormalities compared to ACAs. Altered pathways driving ACC pathogenesis include the IGF, TP53 and the Wnt signaling pathway, allowing these as new potential targets for medical therapy. However, despite efforts in preclinical and clinical studies investigating efficacy of targeting these pathways, most novel therapies appear to be effective in only a subset of patients with ACC. New treatment concepts are therefore urgently needed.

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Section: Current Therapeutic Strategiesmentioning

confidence: 99%

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Creemers¹,

Hofland²,

Korpershoek³

et al. 2015

Endocrine-Related Cancer

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“…Regarding ACC, increasing evidence suggests that establishment of (inter)national collaborative networks of expert centres has a favourable effect on survival , Lombardi et al 2012, Kerkhofs et al 2013b. The concept that rare diseases should be treated in a limited number of specialized hospitals seems intuitively logical.…”

Section: Organization and Quality Of Carementioning

confidence: 99%

“…In selected patients presenting with metastasized disease, debulking surgery might yield a survival benefit (Kerkhofs et al 2013b, Dy et al 2015. Prospective studies on this topic are not yet available, and retrospective studies inevitably hold selection bias: chances are that patients who underwent debulking surgery were in better clinical condition compared to patients who were not operated on.…”

Section: Surgery: the Primary Treatment Modalitymentioning

confidence: 99%

Developing treatment for adrenocortical carcinoma

Kerkhofs¹,

Ettaieb²,

Hermsen³

et al. 2015

Endocrine-Related Cancer

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Cancer of the adrenal cortex (ACC) is a rare endocrine malignancy with limited treatment options. Patients typically present with autonomous hormonal overproduction and/or a large abdominal mass. Hormonal assays and medical imaging can be diagnostic, but urinary steroid profiling might be a more sensitive technique to assess malignancy in adrenal tumours. The stage of the disease at diagnosis is the most important prognostic factor. The current staging system needs refinement, especially to separate aggressive from indolent disease in stage IV patients and to select patients who need adjuvant treatment after complete surgical resection. Regarding the latter, assessing the proliferation index Ki-67 seems the best tool currently available. Genomic profiling is expected to become of clinical relevance in the future. Medical therapy is centred on the adrenolytic drug mitotane, which carries considerable toxicity and is not easy to manage. Its tolerability and long plasma level build-up phase may be improved by therapeutic drug monitoring based on pharmacokinetic modelling and intensive counselling of patients. Current chemotherapy regimens can offer disease stabilization in about 50% of patients, but an objective response should be expected in !25%. Research on targeted therapy and immunotherapy is difficult in this rare disease with often heavily pre-treated patients and has not yet been successful. Quality of care should be ensured by treating patients in centres with established experience in multidisciplinary oncologic care, who adhere to prevailing guidelines and state-of-the-art in diagnostic and treatment concepts. International collaboration in fundamental research and clinical trials is the key to further elucidate the pathogenesis and to improve patient care.

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“…2–4 Unfortunately, ACC is a highly malignant tumor, with up to 70% to 85% of patients experiencing recurrence after surgical resection. 3,5–7 In turn, 5-year overall survival (OS) estimates for patients with ACC range from 15% to 84% depending on the stage of disease at presentation. 5,7–9 The results of studies 10,11 have suggested that adjuvant mitotane therapy may improve the prognosis, although prospective data have been scarce because of the low incidence of ACC.…”

mentioning

confidence: 99%

“…3,5–7 In turn, 5-year overall survival (OS) estimates for patients with ACC range from 15% to 84% depending on the stage of disease at presentation. 5,7–9 The results of studies 10,11 have suggested that adjuvant mitotane therapy may improve the prognosis, although prospective data have been scarce because of the low incidence of ACC. While several clinicopathological factors have been associated with survival and the risk of recurrence, accurate prognostication among patients with ACC remains a challenge.…”

mentioning

confidence: 99%

Nomograms to Predict Recurrence-Free and Overall Survival After Curative Resection of Adrenocortical Carcinoma

et al. 2016

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IMPORTANCE Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor, and the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. OBJECTIVES To define clinicopathological variables associated with recurrence-free survival (RFS) and overall survival (OS) after curative surgical resection of ACC and to propose nomograms for individual risk prediction. DESIGN, SETTING, AND PARTICIPANTS Nomograms to predict RFS and OS after surgical resection of ACC were proposed using a multi-institutional cohort of patients who underwent curative-intent surgery for ACC at 13 major institutions in the United States between March 17, 1994, and December 22, 2014. The dates of our study analysis were April 15, 2015, to May 12, 2015. MAIN OUTCOMES AND MEASURES The discriminative ability and calibration of the nomograms to predict RFS and OS were tested using C statistics, calibration plots, and Kaplan-Meier curves. RESULTS In total, 148 patients who underwent surgery for ACC were included in the study. The median patient age was 53 years, and 65.5% (97 of 148) of the patients were female. One-third of the patients (35.1% [52 of 148]) had a functional tumor, and the median tumor size was 11.2 cm. Most patients (77.7% [115 of 148]) underwent R0 resection, and 8.8% (13 of 148) of the patients had N1 disease. Using backward stepwise selection of clinically important variables with the Akaike information criterion, the following variables were incorporated in the prediction of RFS: tumor size of at least 12 cm (hazard ratio [HR], 3.00; 95% CI, 1.63–5.70; P < .001), positive nodal status (HR, 4.78; 95% CI, 1.47–15.50; P = .01), stage III/IV (HR, 1.80; 95% CI, 0.95–3.39; P = .07), cortisol-secreting tumor (HR, 2.38; 95% CI, 1.27–4.48; P = .01), and capsular invasion (HR, 1.96; 95% CI, 1.02–3.74; P = .04). Factors selected as predicting OS were tumor size of at least 12 cm (HR, 1.78; 95% CI, 1.00–3.17; P = .05), positive nodal status (HR, 5.89; 95% CI, 2.05–16.87; P = .001), and R1 margin (HR, 2.83; 95% CI, 1.51–5.30; P = .001). The discriminative ability and calibration of the nomograms revealed good predictive ability as indicated by the C statistics (0.74 for RFS and 0.70 for OS). CONCLUSIONS AND RELEVANCE Independent predictors of survival and recurrence risk after curative-intent surgery for ACC were selected to create nomograms predicting RFS and OS. The nomograms were able to stratify patients into prognostic groups and performed well on internal validation.

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Surgery for adrenocortical carcinoma in The Netherlands: analysis of the national cancer registry data

Cited by 61 publications

References 28 publications

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Developing treatment for adrenocortical carcinoma

Nomograms to Predict Recurrence-Free and Overall Survival After Curative Resection of Adrenocortical Carcinoma

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