Endocrine and neuroendocrine tumours
Pat Price, Karol Sikora in Treatment of Cancer, 2014
Adrenal carcinoma is a rare malignancy, accounting for 0.2%–0.5% of all cancers, with an annual incidence of 0.5–2 cases per million population, and it accounts for 0.2% of all cancer deaths.267,268,269 It affects women slightly more often than men,270 and the mean age of presentation in women may be lower than in men.271 Overall, the disease tends to afflict a younger age group than most carcinomas (median age at presentation is 37–55 years) and is also found in children less than 10 years of age. The relative incidence of functioning to non-functioning carcinomas is equal; it seems to be unaffected by the age of presentation and may not be different between the sexes, although in the MD Anderson Hospital, Houston, Texas, series more women had functioning tumours.271 Interestingly, the left adrenal has been documented as the more common site of primary disease;270,271 rarely, the disease is bilateral.
Complications of Adrenal Surgery
Kevin R. Loughlin in Complications of Urologic Surgery and Practice, 2007
Despite the best operation, most patients have a recurrence of adrenocortical carcinoma and five-year disease-specific survival is between 20% and 45% (24). For patients with a high likelihood of adrenal cortical carcinoma, open surgery may be the best option. The results of 170 patients undergoing open and laparoscopic adrenalectomy for adrenal cortical carcinoma at M.D. Anderson Cancer Center were reviewed (25). While this series contained only six patients undergoing laparoscopic surgery, an important statistically significant observation was found. The risk of peritoneal carcinomatosis as the initial failure was 83% in the laparoscopic group versus 8% for the open adrenalectomy group. The high rate of carinomatosis may be related to the standard laparoscopic technique. Direct traction on the friable adrenal cortical carcinoma during mobilization could potentially contribute to tumor fraction, capsular disruption, and peritoneal seeding. The authors concluded that open adrenalectomy remains the standard of care for lesions suspicious for adrenal cortical carcinoma.
Adrenal incidentalomas
Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner in Endocrine Surgery, 2017
The most feared diagnostic possibility for an adrenal incidentaloma is adrenal cancer, which has a mean survival of approximately 18 months and 5-year survival of approximately 16%; the clinical manifestations of this disorder are addressed in other chapters in this volume and elsewhere [52–56]. Mercifully, clinically diagnosed cases are rare; the incidence of adrenal carcinoma in general is approximately 0.5–2.0 cases per million population per year [53]. However, the relative frequency of adrenal cancer varies considerably among adrenal incidentaloma series: 4.2% in the whole National Italian Study Group (AI-SIE) series, but 25% in another study [57–59]. The reasons for the differences among adrenal incidentaloma series and between adrenal incidentaloma series and population estimates are unclear. With the increased detection of incidentalomas and their surgical removal, it might be anticipated that the adrenal cancer would be detected at an earlier stage. Although some single-site studies have suggested as much, a larger national sample found no differences across four equal time quartiles from 1973 to 2000 [60]. Adrenal cancers can be functional or nonfunctional; most are probably functional, although the steroids synthesized may have low biological activity. Adrenal cancers may also cause Cushing’s syndrome, virilizing syndromes, or a mixed Cushing–virilizing syndrome. Estrogen-secreting tumors causing feminization are rare, as are aldosterone-secreting carcinomas.
Combination immunotherapy with ipilimumab and nivolumab in patients with advanced adrenocortical carcinoma: a subgroup analysis of CA209-538
Published in OncoImmunology, 2021
Oliver Klein, Clare Senko, Matteo S Carlino, Ben Markman, Louise Jackett, Bo Gao, Caroline Lum, Damien Kee, Andreas Behren, Jodie Palmer, Jonathan Cebon
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a reported incidence of 0.5–2 cases per million population per year.1 The overall prognosis of patients with locally advanced or metastatic ACC not amendable to surgery is poor and treatment options are very limited. Expert consensus guidelines have been published to assist with the management of ACC patients.2 The current standard treatment is a polychemotherapy regimen combined with the adrenolytic agent mitotane that has demonstrated a progression free survival without an overall survival benefit and is associated with a high rate of treatment-related sided effects.3 There are no established second-line therapies and several clinical trials using different targeted agents have been unsuccessful.4
How good are the current models of adrenocortical carcinoma for novel drug discovery?
Published in Expert Opinion on Drug Discovery, 2022
Carmen Ruggiero, Mabrouka Doghman-Bouguerra, Enzo Lalli
During the last decade, significant advances have been made in the definition of the molecular mechanisms underlying the onset and progression of adrenocortical carcinoma (ACC). A better understanding of ACC tumorigenesis has come from the identification of several genetic and molecular drivers of this malignancy thanks to an extensive profiling analysis of ACC tumors. Unfortunately, the development of novel therapeutic options has been hampered by the relative lack of in vitro and in vivo preclinical models recapitulating the entire spectrum of ACC heterogeneity, molecular features, tumor microenvironment and sensitivity to the available treatments. The recent establishment and implementation of novel ACC cell lines, genetically engineered mouse models, patient-derived ACC xenografts (PDX) in mice and emerging preclinical in vivo models offer novel experimental possibilities for drug discovery.
Emerging drugs for the treatment of adrenocortical carcinoma
Published in Expert Opinion on Emerging Drugs, 2021
Vineeth Sukrithan, Marium Husain, Lawrence Kirschner, Manisha H. Shah, Bhavana Konda
There is an acute need for new therapies for the treatment of ACC. The recurrence free survival (RFS) for high-risk adrenocortical carcinoma even after radical en-bloc resection is reported to be <20% at 5 years [6]. In patients with metastatic disease, five-year survival rates range between 13% and 28% [7–9]. There have been no United States (US) Food and Drug Administration (FDA) approved medications for the treatment of ACC since mitotane was approved in 1970. The current standard of care treatment options are surgery in early stages and combination chemotherapy in patients with un-resectable disease. Adjuvant treatment with mitotane and cisplatin with etoposide are currently being studied in patients with aggressive pathologic features post-surgery. ACC therefore is a disease with a large unmet medical need that is currently lacking in effective therapeutic options.
Related Knowledge Centers
- Cancer
- Adrenal Cortex
- Steroid Hormone
- Adrenal Gland
- Paraneoplastic Syndrome
- Cushing'S Syndrome
- Primary Aldosteronism
- Virilization
- Feminization
- Metastasis