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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Adrenocortical carcinoma is a rare, aggressive cancer of the adrenal gland that often over-produces hormones. Surgery is the only cure, mitotane is the one drug specific to it (with real toxicity), and chemotherapy or immunotherapy help only a minority.
Adrenocortical carcinoma (ACC) arises from the adrenal cortex, with TP53 (germline in most childhood cases; R337H founder mutation in Brazil), CTNNB1, ZNRF3, and IGF2 overexpression as recurrent alterations, and molecular subgroups (CIMP-high, C1A) predicting outcome. Diagnosis relies on the Weiss score and Ki-67; staging on ENSAT (I-IV). Hormone excess is present in ~60% and complicates management.
Complete open adrenalectomy (R0) is the only curative treatment; adjuvant mitotane is recommended for high-risk resected disease (Ki-67 >10%, stage III, R1), while ADIUVO (2023) showed no benefit in low-risk patients. Advanced disease is treated with etoposide-doxorubicin-cisplatin plus mitotane (EDP-M, FIRM-ACT 2012: response ~23%, no OS gain over streptozocin-mitotane), with mitotane monotherapy for indolent disease. PD-1 blockade (pembrolizumab, ~15-23% response) and cabozantinib have phase 2 activity; no targeted therapy is approved. Cortisol excess is controlled with metyrapone, osilodrostat or mifepristone. Survival is ~80% for stage I-II and ~15% for stage IV.
| Setting | Approach | Guideline |
|---|---|---|
| Localised (ENSAT I-III) | Open en bloc adrenalectomy by an experienced surgeon with locoregional lymphadenectomy; adjuvant mitotane for high-risk (Ki-67 >10%, stage III, R1) for 2-5 years; adjuvant radiotherapy for R1. | not mapped |
| Advanced, aggressive | EDP-M (etoposide, doxorubicin, cisplatin + mitotane) ×6-8 with surgery for responders; streptozocin-mitotane second line. | NCCN Category 2A |
| Advanced, indolent | Mitotane monotherapy (target level 14-20 mg/L) with glucocorticoid replacement; local therapies (ablation, radiotherapy) for oligometastases. | not mapped |
| Progressive after chemotherapy | Pembrolizumab, cabozantinib, gemcitabine-capecitabine; control hormone excess; clinical trials. | NCCN Category 2B |