Are hypothalamic- pituitary (HP) axis deficiencies after whole brain radiotherapy (WBRT) of relevance for adult cancer patients? – a systematic review of the literature

Abstract

BackgroundCranial radiotherapy (cRT) can induce hormonal deficiencies as a consequence of significant doses to the hypothalamic-pituitary (HP) axis. In contrast to profound endocrinological follow-up data from survivors of childhood cancer treated with cRT, little knowledge exists for adult cancer patients.MethodsA systematic search of the literature was conducted using the PubMed database and the Cochrane library offering the basis for our debate of the relevance of HP axis impairment after cRT in adult cancer patients. Against the background of potential relevance for patients receiving whole brain radiotherapy (WBRT), a particular focus was set on the temporal onset of hypopituitarism and the radiation dose to the HP axis.ResultsTwenty-eight original papers with a total of 1728 patients met the inclusion criteria. Radiation doses to the HP area ranged from 4 to 97 Gray (Gy). Hypopituitarism incidences ranged from 20 to 93% for adult patients with nasopharyngeal cancer or non-pituitary brain tumors. No study focused particularly on hypopituitarism after WBRT. The onset of hypopituitarism occurred as early as within the first year following cRT (range: 3 months to 25.6 years). However, since most studies started follow-up evaluation only several years after cRT, early onset of hypopituitarism might have gone unnoticed.ConclusionHypopituitarism occurs frequently after cRT in adult cancer patients. Despite the general conception that it develops only after several years, onset of endocrine sequelae can occur within the first year after cRT without a clear threshold. This finding is worth debating particularly in respect of treatment options for patients with brain metastases and favorable survival prognoses.

Sparing the hippocampus and the hypothalamic- pituitary region during whole brain radiotherapy: a volumetric modulated arc therapy planning study

“…Functional endocrine deficiencies after brain radiotherapy are common [23]. Long term follow-up studies indicate that radiation induced HT-P dysfunction may occur in up to 80% of patients and is often associated with an adverse impact on growth, body image, skeletal health, fertility, sexual function and physical and psychological health [24].…”

“…Until now, most data of radiation induced endocrine sequelae in adults originate from patients being treated for head and neck cancer and non-pituitary brain tumors. Endocrine follow-up data on hormonal changes after WBRT are scarce [23].…”

The Study of Cerebral Blood Flow Variations Following Radiation Dose Gradients for Brain Metastasis Patients During Radiotherapy

“…For decades,whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) to control neurologic symptoms and intracranial tumor growth has become a standard treatment procedure for BMs patients [8,9]. However, WBRT is usually accompanied by potential toxicity while SRS alone treatment of BMs causes a higher recurrence rate [10][11][12]. Therefore, the lack of accurate assessment methods for RT response and radiation-induced brain injury limits local control.…”

Whole-brain irradiation differentially modifies neurotransmitters levels and receptors in the hypothalamus and the prefrontal cortex.

“…Many of these symptoms are closely related to alterations of the hypothalamic function. Moreover, it has been observed that endocrine disruption of the hypothalamic-pituitary-adrenal (HPA) axis can frequently appear after WBI [12]. The hypothalamus is a region that controls many critical homeostatic functions, including those that are perturbed after whole-brain radiotherapy [12,13].…”