Alfredo Berruti

Brescia University, Medical and Surgical Specialities, Radiological Science and Public health, Faculty Member

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Mitotane Levels Affect the Outcome of Patients Treated Adjuvantly Following Radical Resection of Adrenocortical Cancer (ACC)

The Endocrine Society's 93rd Annual Meeting & Expo, June 4–7, 2011 - Boston, Jun 1, 2011

The prognostic role of immunohistochemical chromogranin a expression in prostate cancer patients is significantly modified by androgen-deprivation therapy

The Prostate, Jan 19, 2010

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Retrospective Evaluation of the Outcome of Open Versus Laparoscopic Adrenalectomy for Stage I and II Adrenocortical Cancer

European Urology, May 1, 2010

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Matrix metalloproteinase type 2 (MMP2) is selective expressed in adrenocortical carcinoma but not in adrenal adenoma: An immunohistochemical study

Journal of Clinical Oncology, Jun 20, 2006

14534 Background: Adrenocortical carcinoma (ACC) is a very rare disease which account for no more... more 14534 Background: Adrenocortical carcinoma (ACC) is a very rare disease which account for no more than 0.2% of all malignancies, and its differential diagnosis from adrenocortical adenomas (ACA) is based on the application of different scoring systems, which, however, lack a sensitivity and specificity of 100%. Little is known on the mechanisms leading to the malignant phenotype in adrenocortical tumors; among alternative mechanisms, metalloproteinases (MMPs) have been demonstrated in solid tumors, including endocrine ones, to be implicated in malignant progression and metastatization. Our aim was to investigate metalloproteinase 2 (MMP2) expression in adrenocortical tumors. Methods: A series of 33 ACC and 23 ACA was retrospectively collected from a large series of adrenocortical lesions, and the diagnosis was reviewed independently by three investigators (MV, EB, MP) according to the Weiss histological criteria. MMP2 was determined by immunohistochemistry and the results scored by semi-quantitative analysis, based on the intensity of the staining and the percentage of tumor cells positive. Immunohistochemical results were compared to clinico-pathological parameters, such as sex, age, hormonal secretion, and outcome. Results: MMP2 expression was detected in 1/23 ACA (4%), and in 25/33 ACC (76%) (X-square test p &amp;amp;amp;amp;amp;amp;lt; 0.001). MMP2 immunohistochemical pattern in ACC was focal to moderate to strong in 10, 12 and 3 cases, respectively. In addition, moderate to strong MMP2 expression, as compared to low or negative immunostaining, correlated with shorter disease-free survival (p = 0.012) and poor outcome (p = 0.07). No correlation were found comparing MMP2 expression and other clinico-pathological parameters. Conclusions: As reported in a variety of solid tumors, our data indicates a possible role of MMP2 in the malignant evolution of adrenocortical tumors, and its immunohistochemical localization may be a potential useful tool in the differential diagnosis of benign versus malignant adrenocortical lesions. In addition, a strong immunohistochemical MMP2 expression seems to be related to a poor prognosis in ACC. No significant financial relationships to disclose.

Plasma Concentration of o,p'DDD (Mitotane), o,p'DDA and o,p'DDE as Predictors of Tumor Response in Adrenocortical Carcinoma: Results of a Retrospective European Network for the Study of Adrenal Tumors (ENS@T) Multicentre Study

Posters II, Jun 1, 2010

Personalised Therapeutic

Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma

ESMO open, Apr 1, 2022

BACKGROUND Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognos... more BACKGROUND Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. No efficacious treatment options are currently available for patients with advanced metastatic disease with disease progression to standard etoposide, doxorubicin, cisplatin and mitotane (EDP-M) therapy. We assessed the activity and tolerability of cabazitaxel as a second/third-line approach in metastatic ACC. PATIENTS AND METHODS Patients included in this single-center, phase II study (ClinicalTrials.gov identifier NCT03257891) had disease progression to a cisplatin-containing regimen (such as EDP) plus mitotane, plus/minus a further chemotherapy line. Cabazitaxel was administered intravenously at 25 mg/m2 on day 1 of a 21-day cycle, for a maximum of six cycles. The primary endpoint was a disease control rate after 4 months. RESULTS From March 2018 to September 2019, 25 eligible patients were enrolled. A disease control rate after 4 months was obtained in six patients (24%). No patients attained a disease response according to RECIST 1.1, 9 patients (36%) had stable disease and 16 patients (64%) progressive disease. Median progression-free survival and overall survival were 1.5 months (range 0.3-7 months) and 6 months (range 1-22.2 months), respectively. Cabazitaxel therapy was well tolerated and only three (12%) patients developed grade 3 toxicity which were nausea in one patient (4%) and anemia in two patients (8%). CONCLUSIONS Cabazitaxel has a manageable toxicity profile but is poorly active as second/third-line treatment in advanced ACC patients. These results do not support further evaluation of cabazitaxel in this setting.

S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study

European journal of endocrinology, 2022

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Human ASH1 expression in prostate cancer with neuroendocrine differentiation

Modern Pathology, Jun 1, 2008

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Prolonged exposure to target mitotane concentrations is associated with better recurrence-free survival in patients with adrenocortical carcinoma on adjuvant treatment

Endocrine Abstracts, May 2, 2023

Supplementary Figure Legend from Ribonucleotide Reductase Large Subunit (<i>RRM1</i>) Gene Expression May Predict Efficacy of Adjuvant Mitotane in Adrenocortical Cancer

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New findings on presentation and outcome of patients with adrenocortical cancer: results from a national cohort study

The Journal of Clinical Endocrinology and Metabolism, Apr 6, 2023

A prospective study on adjuvant mitotane

SUN-350 Sterol-O-Acyl Transferase 1 Protein Expression Alone Is Not Sufficient to Predict Response to Mitotane Treatment in Adrenocortical Carcinoma

Journal of the Endocrine Society, Apr 1, 2019

Abstract Background: Objective response rate to mitotane in advanced ACC is only ~20% and adverse... more Abstract Background: Objective response rate to mitotane in advanced ACC is only ~20% and adverse drug effects are frequent and potentially serious. Markers of treatment response are not established. We have previously discovered that mitotane is an inhibitor of sterol-O-Acyl transferase 1 (SOAT1) which leads to depletion of cholesterol esters, endoplasmic reticulum stress and cell death in the ACC cell line NCI-H295. Data from a small cohort of patients with advanced ACC treated with mitotane monotherapy suggested longer progression-free survival in patients with high SOAT1 expression in ACC tissue. Aim: To investigate SOAT1 protein expression as a marker of treatment response to mitotane. Methods: SOAT1 protein expression was semiquantitatively determined by immunohistochemistry in full sections of 223 ACC treated with mitotane monotherapy in an adjuvant (n=151) and palliative setting (n=72) from eleven ENSAT centers. Expression was classified as high (H-score ≥2) and low (H-score <2) and correlated with recurrence-free (RFS) and progression-free survival (PFS), overall survival (OS), and mitotane levels after three and six months. Results: After multivariate adjustment for sex, ENSAT stage and Ki67 index, RFS (HR=1.3, log rank p=0.09) and OS (HR=1.6, log rank p=0.14) in adjuvantly treated ACC patients did not differ significantly between tumours with high and low SOAT1 expression. Similarly in the palliative setting, OS (HR=1.0, p=0.47) and PFS (HR=0.6, p=0.66) were not different. In line, high SOAT1 expression did not predict if patients reach the therapeutic window of mitotane. Conclusion: SOAT1 expression alone was not correlated with clinically significantly RFS, PFS, and OS in ACC patients neither in the adjuvant nor in the palliative setting.

The San Luigi hospital experience with adjuvant mitotane treatment in patients with adrenocortical cancer following radical resection

Valutazione prospettica di pazienti operati radicalmente per carcinoma corticosurrenalico in trattamento con mitotane adiuvante: correlazioni tra indici di massa corporea, livelli di mitotanemia ed efficacia

Does nephrectomy during radical adrenalectomy for stage II adrenocortical cancer affect patient outcome?

Journal of Endocrinological Investigation, Dec 22, 2015

PurposeTo evaluate if including nephrectomy in the standard surgical approach to stage II adrenoc... more PurposeTo evaluate if including nephrectomy in the standard surgical approach to stage II adrenocortical cancer (i.e., adrenalectomy) might modify oncologic outcome of patients.MethodsWe performed a retrospective analysis involving 41 patients with stage II adrenocortical cancer (ACC) who had undergone radical surgery. Patients were divided into two groups according to the surgical procedure: group A = radical adrenalectomy alone, group AN = radical adrenalectomy + radical nephrectomy. Oncologic effectiveness of the procedures was tested comparing the recurrence-free and overall survival of patients of A vs AN groups.ResultsThe group A consisted of 25 patients and group AN of 16 patients. No differences were noted between the two groups in terms of demographic data and ACC characteristics. During follow-up, 15/25 (60 %) patients of group A vs 14/16 (87.5 %) patients of group AN experienced a recurrence, after a median of 36 months in group A and 10 months in group AN (p = 0.06); a significant impairment of renal function was recorded in patients of AN group with respect to those of group A. Finally, 13/25 (52 %) patients of group A and 10/16 (62.5 %) patients of group AN died due to ACC-related causes. No differences in survival times were noted (p = 0.3).ConclusionOur study suggests that adjunctive nephrectomy does not modify the oncologic results of adrenalectomy in the treatment of stage II ACC in terms of recurrence-free and overall survival. Thus, when there are no signs of ACC local invasion, surgeon should make every effort to preserve the kidney.

Corrigendum to “Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up”

Annals of Oncology

Prognostic Factors across Poorly Differentiated Neuroendocrine Neoplasms: A Pooled Analysis

Neuroendocrinology

Introduction: Poorly differentiated neuroendocrine carcinomas (NECs) are characterized by aggress... more Introduction: Poorly differentiated neuroendocrine carcinomas (NECs) are characterized by aggressive clinical course and poor prognosis. No reliable prognostic markers have been validated to date; thus, the definition of a specific NEC prognostic algorithm represents a clinical need. This study aimed to analyze a large NEC case series to validate the specific prognostic factors identified in previous studies on gastro-entero-pancreatic and lung NECs and to assess if further prognostic parameters can be isolated. Methods: A pooled analysis of four NEC retrospective studies was performed to evaluate the prognostic role of Ki-67 cut-off, the overall survival (OS) according to primary cancer site, and further prognostic parameters using multivariable Cox proportional hazards model and machine learning random survival forest (RSF). Results: 422 NECs were analyzed. The most represented tumor site was the colorectum (n = 156, 37%), followed by the lungs (n = 111, 26%), gastroesophageal sit...