Tumor-associated edema in brain cancer patients: pathogenesis and management

Abstract

The long-term treatment of peritumoral edema remains a major challenge in clinical neuro-oncology. Steroids have been and will remain the backbone of any anti-edematous therapy because of their striking activity, convenient oral administration and also because of their cost–effectiveness. Their side effects, however, can compromise quality of life, particularly upon continuous administration. Therapeutic alternatives which may replace or – at least – help to reduce the steroid dose are limited. However, with the development of new agents such as corticorelin acetate, there is a hope that steroid-induced side effects can be delayed and reduced. The administration of anti-angiogenic agents with steroid-sparing effects, for example, bevacizumab, is limited due to their costs. Increased knowledge on boswellic acids and cyclooxygenase-2 inhibitors which are available for clinical application may help to exploit their anti-edema activity more efficiently in the future.

Keywords::

• boswellic acids
• brain tumor
• corticorelin acetate
• edema
• steroids
• VEGF

Financial & competing interests disclosure

P Roth has received honoraria for advisory board activity from Roche and MSD. M Weller has received honoraria consultancy from Magforce and Antisense Pharma, honoraria for advisory board activity from Roche, Merck Serono and MSD, and research support from Bayer, Antisense Pharma, Merck Serono and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Peritumoral edema can occur in virtually all CNS neoplasms and is most common in high-grade gliomas and metastases.

• • Several factors contribute to the development of vasogenic edema including the secretion of VEGF by tumor cells.

• • The mass effect derived from tumor-associated edema increases intracranial pressure and results in neurological symptoms, significantly contributing to morbidity.

• • Steroids are the mainstay of anti-edematous therapy. Their administration frequently leads to clinical improvement and symptom relief.

• • The mid- and long-term use of steroids is limited due to their numerous side effects such as metabolic changes, osteoporosis, myopathy, increased risk for opportunistic infections, psychiatric alterations and many more.

• • Corticorelin acetate, a synthetic analog of corticotropin releasing factor, may help to reduce steroids doses and steroid-related side effects.

• • Anti-angiogenic agents such as the VEGF inhibitor bevacizumab have pronounced anti-edema effects in many brain tumor patients.

• • Several agents with putative anti-edematous activity have only been assessed in preclinical models or small patients series including cyclooxygenase-2 and angiotensin-II inhibitors and further clinical testing is required.