Longitudinal patterns of recurrence in patients with adrenocortical carcinoma

Glenn, Jason A.; Else, Tobias; Hughes, David T.; Cohen, Mark S.; Jolly, Shruti; Giordano, Thomas J.; Worden, Francis P.; Gauger, Paul G.; Hammer, Gary D.; Miller, Barbra S.

doi:10.1016/j.surg.2018.04.068

Cited by 53 publications

(40 citation statements)

References 24 publications

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“…In ACC, even after complete surgical resection, the estimated recurrence rate of ACC is 40% to 70% [13], which is higher than other common malignancies. Thus, until prospective data become available, the use of adjuvant therapy in ACC can be justified based on biological and clinical backgrounds.…”

Section: Risk Of Recurrence Of Acc Compared With Other Cancersmentioning

confidence: 95%

“…This difference may be due to improved imaging technology that has led to earlier diagnosis in some patients before becoming symptomatic. Complete surgical resection is the mainstay of treatment of localized disease, although the recurrence rate can be as high as 70% according to some studies [13]. Adjuvant therapy to reduce the risk of ACC recurrence was reported almost five decades ago [4,14].…”

Section: Introductionmentioning

confidence: 99%

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Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions

Bedrose

Daher

Altameemi

et al. 2020

Cancers

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Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with high risk of recurrence despite macroscopically complete surgical resection. The main predictors of ACC recurrence include advanced disease stage, incomplete surgical resection, cortisol production, certain genetic alterations, and high proliferation rate (Ki-67 proliferation index). Mitotane has been the mainstay adjuvant therapy of ACC. However, the use of mitotane is based on retrospective and occasionally conflicting evidence. As mitotane levels can take a few months before reaching therapeutic levels, there is an emerging practice of combining platinum-based chemotherapy with mitotane in the adjuvant setting. Retrospective data indicate that radiotherapy is an option for select patients, particularly those with positive resection margins. There are multiple knowledge gaps in selecting patients for adjuvant therapy. It is of great importance to establish risk calculators to predict recurrence and to implement molecular profiling of ACC to guide adjuvant therapy. The role of immunotherapy in metastatic ACC is emerging and if deemed efficacious, then future studies will be needed to ascertain the role of adjuvant immunotherapy in ACC.

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Section: Risk Of Recurrence Of Acc Compared With Other Cancersmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions

Bedrose

Daher

Altameemi

et al. 2020

Cancers

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“…Therapies for metastatic ACC are primarily palliative, limited to administration of adrenolytic drug mitotane and/or cytotoxic chemotherapy (3). Patients with locoregional ACC routinely receive surgery and adjuvant mitotane, but 50% to 70% recur and develop metastases even after complete (R0) resection (4,5). Retrospective studies suggest adjuvant mitotane prolongs recurrence-free survival (6,7), but its efficacy is limited by its poor pharmacokinetic properties and dose-limiting toxicities.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, there is a substantial proportion of ACC patients who experience rapid recurrence (<12 months; refs. 4,5,9), whose aggressive disease course may preclude response to mitotane. These patients may instead benefit from more rapidly acting therapies; however, prospectively identifying this subgroup remains challenging.…”

Section: Introductionmentioning

confidence: 99%

Targeted Assessment of G0S2 Methylation Identifies a Rapidly Recurrent, Routinely Fatal Molecular Subtype of Adrenocortical Carcinoma

Mohan

Lerário

Else

et al. 2019

Clinical Cancer Research

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Purpose: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with few therapies; however, patients with locoregional disease have variable outcomes. The Cancer Genome Atlas project on ACC (ACC-TCGA) identified that cancers of patients with homogeneously rapidly recurrent or fatal disease bear a unique CpG island hypermethylation phenotype, "CIMP-high." We sought to identify a biomarker that faithfully captures this subgroup. Experimental Design: We analyzed ACC-TCGA data to characterize differentially regulated biological processes, and identify a biomarker that is methylated and silenced exclusively in CIMP-high ACC. In an independent cohort of 114 adrenocortical tumors (80 treatment-naive primary ACC, 22 adrenocortical adenomas, and 12 non-naive/ nonprimary ACC), we evaluated biomarker methylation by a restriction digest/qPCR-based approach, validated by targeted bisulfite sequencing. We evaluated expression of this biomarker and additional prognostic markers by qPCR. Results: We show that CIMP-high ACC is characterized by upregulation of cell cycle and DNA damage response programs, and identify that hypermethylation and silencing of G0S2 distinguishes this subgroup. We confirmed G0S2 hypermethylation and silencing is exclusive to 40% of ACC, and independently predicts shorter disease-free and overall survival (median 14 and 17 months, respectively). Finally, G0S2 methylation combined with validated molecular markers (BUB1B-PINK1) stratifies ACC into three groups, with uniformly favorable, intermediate, and uniformly dismal outcomes. Conclusions: G0S2 hypermethylation is a hallmark of rapidly recurrent or fatal ACC, amenable to targeted assessment using routine molecular diagnostics. Assessing G0S2 methylation is straightforward, feasible for clinical decision-making, and will enable the direction of efficacious adjuvant therapies for patients with aggressive ACC.

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“…Notwithstanding, disease control is difficult and recurrence rate is high. Abdominal recurrence was reported in up to 70-85% of cases [2][3][4] after resection of adrenal primary. Furthermore, in the setting of recurrent disease, it is known that curative redo resection offers the best therapeutic chances [1,[5][6][7][8] yet the occurrence of "surgical cure" is anecdotal.…”

Section: Introductionmentioning

confidence: 99%

Hyperthermic Intraperitoneal Chemotherapy for Primary or Recurrent Adrenocortical Carcinoma. A Single Center Study

Tiberio

Ferrari

Ballarini

et al. 2020

Cancers

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Background. This study explores the impact of Hypertermic Intra PEritoneal Chemotherapy (HIPEC) on adrenocortical carcinoma (ACC) management through a safety analysis completed by a preliminary evaluation of survival performances. Methods. Retrospective chart review of 27 patients submitted to surgical treatment completed by HIPEC for primary (SP, 13 patients) or recurrent (SR, 14 patients, 17 treatments) ACC. Safety was evaluated by means of procedural morbidity and mortality. Survival performances included multiple end points: local/peritoneal disease-free survival (l/pDFS), overall progression-free survival (OPFS), and overall survival (OS). Results. In the SP group, mortality was nil and morbidity was 46% (major 23%). At a median follow-up of 25 months, the median value for all the different survival measures had not been reached. Mortality was also nil in the SR group. However, morbidity was 77% (major 18%). Median l/pDFS and OPFS were 12 ± 4 and 8 ± 2 months, respectively. At a median follow-up of 30 months, median OS had not been reached. Conclusion. Surgery and HIPEC is an invasive procedure. Its employment in the surgery for primary setting deserves attention as it may affect oncologic outcomes positively. Its value in the management of recurrences seems less appreciable, albeit it may find its place in the multimodal management of a rare disease for which multiple therapeutic options do not yet exist.

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Longitudinal patterns of recurrence in patients with adrenocortical carcinoma

Cited by 53 publications

References 24 publications

Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions

Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions

Targeted Assessment of G0S2 Methylation Identifies a Rapidly Recurrent, Routinely Fatal Molecular Subtype of Adrenocortical Carcinoma

Hyperthermic Intraperitoneal Chemotherapy for Primary or Recurrent Adrenocortical Carcinoma. A Single Center Study

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