Radiotherapy and radiosurgery for Cushing's disease

Abstract

Patients with residual or recurrent Cushing's disease receive external beam radiotherapy (RT) with the aim of achieving long-term tumour control and normalization of elevated hormone levels. Treatment is given either as conventional radiotherapy using conformal techniques or as stereotactic radiotherapy, which is either used as fractionated treatment (SCRT) or as single fraction radiosurgery (SRS). We describe the technical aspects of treatment and report a systematic review of the published literature on the efficacy and toxicity of conventional RT, SCRT and SRS. There are no studies directly comparing the different radiation techniques and the reported results are inevitably of selected patients by investigators with interest in the treatment tested. Nevertheless the review of the published literature suggests better hormone and tumour control rates after fractionated irradiation compared to single fraction radiosurgery. Hypopituitarism represents the most commonly reported late complication of radiotherapy seen after all treatments. Although the incidence of other late effects is low, the risk of radiation injury to normal neural structures is higher with single fraction compared to fractionated treatment. Stereotactic techniques offer more localized irradiation compared with conventional radiotherapy, however longer follow-up is necessary to confirm the potential reduction of long-term radiation toxicity of fractionated SCRT compared to conventional RT. On the basis of the available literature, fractionated conventional and stereotactic radiotherapy offer effective treatment for Cushing's disease not controlled with surgery alone. The lower efficacy and higher toxicity of single fraction treatment suggest that SRS is not the appropriate therapy for the majority of patients with Cushing's disease. RESUMORadioterapia e Radiocirurgia para a Doença de Cushing. Pacientes com doença de Cushing residual ou recorrente recebem radioterapia externa em feixe (RT) com o objetivo de alcançar um controle tumoral prolongado e a normalização dos níveis hormonais elevados. O tratamento é realizado tanto com RT convencional, usando técnicas conformacionais, ou com RT estereotáxica, que é usada tanto como tratamento fracionado (RTF) ou como radiocirurgia em procedimento único (RCU). Descreveremos os aspectos técnicos do tratamento e mostraremos uma revisão sistemática da literatura sobre a eficácia e toxicidade da RT convencional, da RTF e da RCU. Não existem estudos comparando diretamente as diferentes técnicas de radiação, e os resultados reportados são inevitavelmente os de pacientes selecionados pelos investigadores com interesse no tratamento testado. De qualquer maneira, a revisão dos dados publicados sugere que há melhores taxas de controle hormonal e tumoral após RTF em comparação com RCU. O hipopituitarismo representa a complicação tardia mais comumente relatada da RT, vista após todos os tipos de tratamento. Embora a incidência de outros efeitos tardios seja baixa, o risco de a radiação comprometer estrutura...

The Treatment of Cushing's Disease

“…However, no study has definitely demonstrated a clear correlation between these conditions and a worse outcome of SRT. No correlation between change in tumor volume and hormone response to GK has been described (282,351). The absence of hormone-suppressive medication at the start of GK seems to be associated with a higher likelihood of and earlier remission (328,334,342,343,346).…”

“…a. Hypopituitarism. The main hormonal consequence of pituitary radiotherapy is hypopituitarism (one or more hormone deficiencies), which seems to be mediated by hypothalamic-pituitary damage in the case of CRT, and by direct damage to the pituitary gland and/or pituitary stalk in the case of SRT (282,351,354,355). Actually, the incidence of hypopituitarism attributable to pituitary radiotherapy is difficult to ascertain because persistent hypercortisolism, pituitary mass effects, and prior pituitary surgery beyond radiation therapy may lead to a deficiency of pituitary function (1, 2, 7, 84 -88, 264 -270, 279 -290).…”

Cushing’s disease: current trends in treatment

“…Another option involves stereotactic radiosurgery ('g-knife') as a single dose delivered through multiple portals [22]. The dose used in g-knife surgery is 18-24 Gy.…”

“…Several studies analyzing the outcomes of conventional RT report tumor control in 93-100% of patients at a median follow-up of 8 years (3.5-12.4 years) and normalization of cortisol levels in 46-84% of patients in the same follow-up time [22,[24][25][26]. Data related to the results of radiosurgery are claimed to show significantly shorter median follow-up time of 45 months with comparable tumor control in 94% of patients and hormonal normalization achieved in 48% in 6-36 months' time [27][28][29], but no head-to-head comparison of conventional versus radiosurgical RT has been performed.…”

Pituitary Adenoma

“…Nelson syndrome was originally reported in 1960 when Nelson et al 107 described hyperpigmentation after bilateral adrena- 108 These adenomas tend to be more aggressive in nature, are often associated with extrasellar extension, and thus are more difficult to cure. 56 There have been few studies investigating the role of RT in the treatment of Nelson syndrome, as surgery is often complex given the typical brisk growth of these adenomas.…”