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Alfredo Berruti, Rossella Libè, Marta Laganà, Hester Ettaieb, Mohamad Anas Sukkari, Jérôme Bertherat, Richard A Feelders, Salvatore Grisanti, Jérôme Cartry, Gherardo Mazziotti, Sandra Sigala, Eric Baudin, Harm Haak, Mouhammed Amir Habra, and Massimo Terzolo

Introduction

Adrenocortical carcinoma (ACC) is a rare cancer that commonly spreads to the liver, lungs and lymph nodes. Bone metastases are infrequent.

Objective

The aim of this report was to describe the clinical characteristics, survival perspective, prognostic factors and frequency of adverse skeletal-related events (SREs) in patients with ACC who developed bone metastasis.

Methods

This is a retrospective, observational, multicenter, multinational study of patients diagnosed with bone metastases from ACC who were treated and followed up in three European countries (France, Italy and The Netherlands) and one center in the United States.

Results

Data of 156 patients were captured. The median overall survival was 11 months. SREs occurred in 47% of patients: 17% bone fractures, 17% spinal cord compression, 1% hypercalcemia, 12% developed more than one SRE. In multivariate analysis, cortisol hypersecretion was the only prognostic factor significantly associated with a higher mortality risk (hazard ratio (HR) 2.24, 95% confidence interval (CI): 1.19–4.23, P = 0.013) and with the development of a SREs (of border line significance). The administration of antiresorptive therapies (bisphosphonates and denosumab) was associated with a lower risk of death, even if not significant, and their survival benefit appeared confined in patients attaining serum mitotane levels within the therapeutic range.

Conclusion

Bone metastases in ACC patients are associated with poor prognosis and high risk of SREs. Cortisol hypersecretion was the only prognostic factor suggesting a potential benefit from antisecretory medications. The therapeutic role of bisphosphonates and denosumab to improve patient outcome deserves to be tested in a prospective clinical trial.

Free access

Eric Baudin, Mouhammed Amir Habra, Frederic Deschamps, Gilbert Cote, Frederic Dumont, Maria Cabanillas, J Arfi-Roufe, A Berdelou, Bryan Moon, Abir Al Ghuzlan, Shreyaskumar Patel, Sophie Leboulleux, and Camilo Jimenez

Metastatic pheochromocytomas and paragangliomas (MPPs) present clinicians with three major challenges: scarcity, complexity of characterization, and heterogeneous behavior and prognosis. As with the treatment for all neuroendocrine tumors, the control of hormonal symptoms and tumor growth is the main therapeutic objective in MPP patients. A significant number of MPP patients still die from uncontrolled hormone secretion. In addition, the management of MPPs remains palliative. Steps forward include proper characterization of MPP patients at large cancer referral centers with multidisciplinary teams; improved strategies to stratify patients prognostically; and implementation of trials within national and international networks. Progress in the molecular characterization and staging of MPPs constitutes the basis for significant treatment breakthroughs.

Free access

Montserrat Ayala-Ramirez, Sina Jasim, Lei Feng, Shamim Ejaz, Ferhat Deniz, Naifa Busaidy, Steven G Waguespack, Aung Naing, Kanishka Sircar, Christopher G Wood, Lance Pagliaro, Camilo Jimenez, Rena Vassilopoulou-Sellin, and Mouhammed Amir Habra

Objective

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Herein, we describe the clinical features and outcomes for a large series of ACC patients.

Design and methods

Retrospective review of ACC patients seen at The University of Texas MD Anderson Cancer Center from 1998 through 2011.

Results

A total of 330 patients with median age at diagnosis of 48.5 years; 12 (3.6%) patients were under 18 years. Hormonally functioning tumors represented 41.8% (n=138) of all cases. Surgical resection for the primary tumor was done in 275 (83.3%) patients (45 at MD Anderson (16.4%)). For those who had surgical resection, the median local-recurrence-free time was 1.04 years. Factors associated with local recurrence included positive surgical margins (P=0.007) and advanced disease stage (P=0.026). Median overall survival time for all patients was 3.21 years. Median survival times were 24.1, 6.08, 3.47, and 0.89 years for stages I, II, III, and IV respectively. In multivariable analysis, older age, functioning tumors, and higher disease stage remained significant prognostic factors associated with poor survival.

Conclusion

ACC prognosis remains poor with the use of currently available treatments. Older age, functioning tumors, and incomplete resections are clinical factors associated with poor survival. Surgical expertise is important to achieve complete resections and to improve outcome.

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Fatemeh Majidi, Samuela Martino, Mustafa Kondakci, Christina Antke, Matthias Haase, Vasileios Chortis, Wiebke Arlt, Cristina L Ronchi, Martin Fassnacht, Claire Laurent, Jean-Michel Petit, Olivier Casasnovas, Amir Mouhammed Habra, Aleem Kanji, Roberto Salvatori, An Thi Nhat Ho, Ariadni Spyroglou, Felix Beuschlein, Diego Villa, Wasithep Limvorapitak, Björn Engelbrekt Wahlin, Oliver Gimm, Martina Rudelius, Matthias Schott, Ulrich Germing, Rainer Haas, and Norbert Gattermann

Purpose:

We sought to refine the clinical picture of primary adrenal lymphoma (PAL), a rare lymphoid malignancy with predominant adrenal manifestation and risk of adrenal insufficiency.

Methods:

Ninety-seven patients from 14 centers in Europe, Canada and the United States were included in this retrospective analysis between 1994 and 2017.

Results:

Of the 81 patients with imaging data, 19 (23%) had isolated adrenal involvement (iPAL), while 62 (77%) had additional extra-adrenal involvement (PAL+). Among patients who had both CT and PET scans, 18FDG-PET revealed extra-adrenal involvement not detected by CT scan in 9/18 cases (50%). The most common clinical manifestations were B symptoms (55%), fatigue (45%), and abdominal pain (35%). Endocrinological assessment was often inadequate. With a median follow-up of 41.6 months, 3-year progression-free (PFS) and overall (OS) survival rates in the entire cohort were 35.5% and 39.4%, respectively. The hazard ratios of iPAL for PFS and OS were 40.1 (95% CI: 2.63–613.7, P = 0.008) and 2.69 (95% CI: 0.61–11.89, P = 0.191), respectively. PFS was much shorter in iPAL vs PAL+ (median 4 months vs not reached, P = 0.006), and OS also appeared to be shorter (median 16 months vs not reached), but the difference did not reach statistical significance (P = 0.16). Isolated PAL was more frequent in females (OR = 3.81; P = 0.01) and less frequently associated with B symptoms (OR = 0.159; P = 0.004).

Conclusion:

We found unexpected heterogeneity in the clinical spectrum of PAL. Further studies are needed to clarify whether clinical distinction between iPAL and PAL+ is corroborated by differences in molecular biology.