Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group

Postlewait, Lauren M.; Ethun, Cecilia G.; Tran, Thuy B.; Prescott, Jason D.; Pawlik, Timothy M.; Wang, Tracy; Glenn, Jason A.; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E.; Keplinger, Kara; Fields, Ryan C.; Jin, Linda X.; Weber, Sharon M.; Salem, Ahmed; Sicklick, Jason K.; Gad, Shady; Yopp, Adam C.; Mansour, John C.; Duh, Quan Yang; Seiser, Natalie; Solórzano, Carmen C.; Kiernan, Colleen M.; Votanopoulos, Konstantinos I.; Levine, Edward A.; Staley, Charles A.; Poultsides, George A.; Maithel, Shishir K.

doi:10.1016/j.jamcollsurg.2015.12.013

Cited by 74 publications

(65 citation statements)

References 42 publications

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“…Promising results with mitotane treatment were initially received with enthusiasm, 3 however, additional studies have failed to replicate these findings consistently. 4,5 Therefore, surgery remains the mainstay of treatment in patients with resectable primary ACC, with 5-year survival rates reaching 65% after margin-negative resection. 6 However, even after curative resection of ACC, recurrence of disease is relatively common and can be detected in approximately two-thirds of patients after a median time to recurrence of 19 months.…”

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confidence: 99%

Clinical Score Predicting Long-Term Survival after Repeat Resection for Recurrent Adrenocortical Carcinoma

Tran

Maithel

Pawlik

et al. 2016

Journal of the American College of Surgeons

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BACKGROUND Adrenocortical carcinoma (ACC) is an aggressive malignancy typically resistant to chemotherapy and radiation. Surgery, even in the setting of locally recurrent or metastatic disease, remains the only potentially curative option. However, the subset of patients who will benefit from repeat resection in this setting remains ill defined. The objective of this study was to propose a prognostic clinical score that facilitates selection of patients for repeat resection of recurrent ACC. STUDY DESIGN Patients who underwent curative-intent repeat resection for recurrent ACC at 1 of 13 academic medical centers participating in the US ACC Study Group were identified. End points included morbidity, mortality, and overall survival. RESULTS Fifty-six patients underwent repeat curative-intent resection for recurrent ACC (representing 21% of 265 patients who underwent resection for primary ACC) from 1997 to 2014. Median age was 52 years. Sites of resected recurrence included locoregional only (54%), lung only (14%), liver only (12%), combined locoregional and lung (4%), combined liver and lung (4%), and other distant sites (12%). Thirty-day morbidity and mortality rates were 40% and 5.4%, respectively. Cox regression analysis revealed that the presence of multifocal recurrence, disease-free interval <12 months, and extrapulmonary distant metastases were independent predictors of poor survival. A clinical score consisting of 1-point each for the 3 variables demonstrated good discrimination in predicting survival after repeat resection (5-year: 72% for 0 points, 32% for 1 point, 0% for 2 or 3 points; p = 0.0006, area under the curve = 0.78). CONCLUSIONS Long-term survival after repeat resection for recurrent ACC is feasible when 2 of the following factors are present: solitary tumor, disease-free interval >12 months, and locoregional or pulmonary recurrence.

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confidence: 99%

Clinical Score Predicting Long-Term Survival after Repeat Resection for Recurrent Adrenocortical Carcinoma

Tran

Maithel

Pawlik

et al. 2016

Journal of the American College of Surgeons

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“…Of note however, only 32/88 (36%) patients who received mitotane in this study had serum mitotane levels available, of which only 15 patients had levels between 14–20 mg/L. Thus, no definitive conclusions can be drawn from this study (19). With similar controversial results noted in small prospective studies (20, 21), there is an urgent need for large randomized prospective trials evaluating the efficacy of mitotane in the adjuvant setting.…”

Section: Current Therapies For Accmentioning

confidence: 83%

Novel targeted therapies in adrenocortical carcinoma

Konda

Kirschner²

2016

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of review Adrenocortical carcinoma is a rare cancer, but one that carries a poor prognosis due to its aggressive nature and unresponsiveness to conventional chemotherapeutic strategies. Over the past 12 years, there has been renewed interest in developing new therapies for this cancer, including identifying key signaling nodes responsible for cell proliferation. Recent findings Clinical trials of tyrosine kinase inhibitors as monotherapy have generally been disappointing, although the identification of exceptional responders may lead to the identification of targeted therapies that may produce responses in subsets of patients. Agents targeted to the Wnt signaling pathway, a known player in adrenal carcinogenesis, have been developed although have not yet been used specifically for adrenal cancer. There is current excitement about inhibitors of acetyl-coA cholesterol acetyl transferase 1 (ACAT1), an enzyme required for intracellular cholesterol handling, although trials are still underway. Tools to target other proteins such as SF1 and mTOR have been developed and are moving towards clinical application. Summary Progress is being made in the fight against adrenocortical carcinoma with the identification of new therapeutic targets and new means by which to attack them. Continued improvement in the prognosis for patients with adrenal cancer is expected as this research continues.

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“…Therefore, adjuvant mitotane therapy and local radiotherapy were initiated. Whereas, the 13 institutions study concluded that there's no association between adjuvant mitotane after resection and improvement of recurrence-free survival or overall survival (20).…”

Section: Discussionmentioning

confidence: 99%