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Metastatic pheochromocytoma and paraganglioma (PPGL) are rare diseases with dismal prognosis and standard therapies are lacking. We herein report the first case of a germline anaplastic lymphoma kinase (ALK) mutation in a patient with chemorefractory metastatic pheochromocytoma in the absence of mutations of known PPGL-associated predisposing genes. Therapy with the ALK inhibitor (ALKi) brigatinib led to dramatic and durable disease remission, despite previous disease progression on the ALKi alectinib. This case underscores the potential clinical use of molecular profiling in rare diseases with limited treatment options and suggests that the ALK-R1192P point mutation might predict sensitivity to brigatinib., Competing Interests: Disclosure FH declares honoraria from Lilly, Pierre Fabre, and Servier; consulting or advisory role for Lilly and Servier; research funding from Paracelsus Medical University; expert testimony for Lilly; and reimbursement for travel, accommodations, expenses from Servier, BMS, Roche, Merck, PharmaMar, and Pfizer. GH declares honoraria, consulting or advisory role, and reimbursement for travel, accommodations, expenses from MSD, Roche, AstraZeneca, Pfizer, and BMS. LC declares reimbursement for travel, accommodations, expenses from Amgen, Roche, and Celgene. GR declares consulting or advisory role for Pierre Fabre, Celgene, Roche, Novartis, Pfizer, Eli Lilly, Daiichi Sankyo, and MSD; participating in speakers' bureau for Amgen, AstraZeneca, Novartis, Bristol-Myers Squibb, Roche, Pfizer, and Eli Lilly; research funding from Roche; and reimbursement for travel, accommodations, expenses from Roche, Novartis, Amgen, Pfizer, and Bristol-Myers Squibb. TM declares honoraria, consulting or advisory role, speakers' bureau, expert testimony, and reimbursement for travel, accommodations, expenses from Roche, Takeda, MSD, Novartis, Merck, and BMS. LW declares honoraria from Roche, Bristol-Myers Squibb, Lilly, Novocure, Merck Serono, Amgen, and Pierre Fabre; consulting or advisory role for Bristol-Myers Squibb, Roche, Lilly, Novocure, Merck Serono, and Takeda; and reimbursement for travel, accommodations, expenses from Ipsen, Pfizer, Merck Serono, and AstraZeneca. RG declares honoraria and consulting or advisory role for Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, and Daiichi Sankyo, and reimbursement for travel, accommodations, expenses from Roche, Amgen, Janssen, AstraZeneca, Novartis, MSD, Celgene, Gilead, BMS, and AbbVie. All other authors have declared no conflicts of interest. Data sharing The authors declare that data supporting the findings of this study are available within the paper. The complete molecular report of the NGS analysis and primer sequences are available upon request from the corresponding author. Ethics declarations Written informed consent was obtained from the patient and from the patient's daughter for publication of this case report and any accompanying images. This analysis was performed within the next-generation sequencing (NGS) Registry of the Austrian Group Medical Tumor Therapy (AGMT) (NCT 03301493). This registry has been approved by the Ethics Committee of the provincial government of Salzburg (Nr.: 415-E/2129)., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Current guidelines of the National Comprehensive Cancer Network and the European Society of Medical Oncology recommend regorafenib or trifluridine/tipiracil (TAS-102) for third-line therapy of metastatic colorectal cancer (mCRC). We evaluated the impact of regorafenib and TAS-102 treatment on skeletal muscle dynamics and sarcopenia., Patients and Methods: This retrospective analysis was based on unselected, consecutive mCRC patients treated with regorafenib and/or TAS-102 during third or later line of therapy at our tertiary-care cancer center in Salzburg, Austria. The skeletal muscle index (SMI, cm 2 /m 2 ) and sarcopenia were evaluated from cross-sectional computed tomographic images at the level of the third lumbar vertebra., Results: Between January 2013 and April 2018, a total of 45 patients had received regorafenib and/or TAS-102. At initial mCRC diagnosis and at initiation of third-line therapy, 24% and 54% of patients presented with sarcopenia. A statistically significant skeletal muscle loss was observed during regorafenib treatment (median SMI change: -2.75 cm 2 /m 2 [-6.3%]; P < .0001), which was not the case during TAS-102 therapy (-1.5 cm 2 /m 2 [-3.5%]; P = .575). Furthermore, subclassification of patients into 3 groups-normal muscle mass, stable sarcopenia, and new-onset sarcopenia-at initiation of third-line therapy permitted discrimination of overall survival, with 1-year overall survival rates of 61%, 29%, and 16%, respectively (P = .04)., Conclusion: The frequency of sarcopenia increases during the course of mCRC and negatively affects survival. In contrast to TAS-102, regorafenib is associated with increased skeletal muscle loss during mCRC treatment and should therefore be used with caution in mCRC patients with preexisting sarcopenia or a history of recent weight loss., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)