This document summarizes information about adreno-cortical carcinoma (ACC), including: - ACC has an incidence rate of 0.7 to 2 per million people per year, unusually high in southern Brazil. Risk factors include genetic conditions and large tumor size. - Complete tumor removal through surgery is the most important treatment, with clear margins associated with better long-term prognosis. - Radiation therapy alone has not shown survival benefits, but can help with pain from metastases. - Drug treatments include mitotane, which can induce tumor regression in 25% of metastatic cases. Targeted therapies have shown limited effectiveness so far. - Follow up care involves repeated CT scans for at least 5 years,

1. Adreno-cortical carcinoma in
a nutshell
Dr. Shinjan Patra

2. Basics
• Incidence of 0.7 to 2 per million population per year
• Unusually high in southern brazil
• LI-fraumeni syndrome TP53 mutation
• Beckwith-wiedemann syndrome
• Increased IGF-2 expression
• Mass > 6 cm increases the chance of ACC
• < 10 HU cut-off useful
• Delayed attenuation > 35 HU & a wash out < 50%
suggests malignancy
• Ki-67 labeling index > 10% poor survival

7. Surgery
• Complete tumour removal single most important
measure
• An R0 resection (resection margins
microscopically tumor-free) utmost importance
for long-term prognosis
• Surgery for recurrent ACC should be performed in
patients with a disease-free interval of more than
12 months, in whom a complete resection is
feasible

8. Radiation therapy
• Studies failed to demonstrate a survival benefit
for patients who underwent radiation therapy
• Palliative radiotherapy in symptomatic metastatic
lesions is a well-established treatment option for
patients with ACC, in particular for bone
metastases
• Also be effective in unresectable abdominal
recurrences causing pain and vascular or
intestinal obstruction

9. Mitotane basic regimen
• Can induce significant tumor regression in up to 25% of
cases with metastatic ACC and achieve control of
hypercortisolism
• Treatment aims at mitotane concentrations between 14
and 20 mg/L
• Start with 1.5 g/day & increase to 6 g/day
• Determine mitotane blood levels after 3-4 weeks of therapy
• Continue monotherapy if conc > 8 mg/L
• Double dose GC replacement
• With blood level < 5 mg/L usually add EDP
• Continue for at least 2 years, but not longer than 5 years

10. Cytotoxic chemotherapy
• Etoposide/Doxorubicin/Cisplatin & Mitotane
(EDP-M) proved better than
Streptozotocin/Mitotane (Sz-M)
• Both as first-line & second line therapy

11. Targeted therapies
• Not satisfactory with cytotoxic chemotherapy
<50% responding to treatment
• Erlotinib + Gemcitabine exhibited limited efficacy
• Blockade of the IGF-1 has been studied
• Combination of IGF-1 receptor ab + temsirolimus
• Sunitinib shown modest activity in clinical trials
• Dovitinib showed efficacy
• Sorafenib & paclitaxel showed no efficacy
• Mitotane targeted therapies lead to CYP3A4
induction

12. Follow up
• Staging repeated every 3 months ( CT of
abdomen + chest ) for a minimum of 2 years
• Then every 3–6 months for a further 3 years
• Even after 2 years without recurrence, there
remains a high risk for relapse
• Steroid metabolomics currently investigated
for detecting tumour recurrence
• Regular surveillance for minimum 5 years

13. Additional recommendations
• Routine loco-regional lymphadenectomy
should be performed with adrenalectomy for
highly suspected or proven ACC
• Peri-operative hydrocortisone replacement in
all patients with hypercortisolism that
undergo surgery for ACC
• For advanced ACC, surveillance based on
prognostic factors

14. Thank you……………….