Brain irradiation as treatment option

In the radiation-oncology community, according to Prof. Corinne Faivre-Finn (The Christie NHS Foundation Trust and University of Manchester, United Kingdom), there is a falling enthusiasm for whole brain radiotherapy (WBRT). On the other hand, the benefits of stereotactic radiosurgery (SRS) are becoming evident.

Currently, more targeted treatment options for patients with driver mutations are available, which changed the role of brain radiotherapy. Additionally, the boundaries of radically treatable vs controllable systemic disease are changing. Patient selection for brain radiotherapy is an interplay between multiple factors, namely:

• extra-cranial disease: controlled or controllable tumour and prognosis;
• intra-cranial disease: number, volume, and location of metastases, including mass effect; and
• patient-related factors: performance status, comorbidities, biology of the tumour (mainly the presence or absence of driver mutations), and preference.

Discussion about QUARTZ

An important and widely discussed trial about WBRT, is the QUARTZ study [1]. In this phase 3 study, 535 NSCLC patients with brain metastases unsuitable for resection or stereotactic radiotherapy in 69 UK and 3 Australian Centres were randomized between 2007 and 2014 to either optimal supportive care (OSC) or OSC plus WBRT with 20 Gray. Study endpoints were overall survival and quality of life. The study found no difference in overall survival (HR 1.06) or quality of life in the two treatment arms [1].
“It is important to keep in mind that the study protocol was developed between 2004 and 2006”, Prof. Faivre-Finn emphasised. “Since then, a lot of things changed, particularly with respect to the use of systemic therapy in patients with driver mutations.”
QUARTZ is the only large randomised trial comparing WBRT and no WBRT for the treatment of brain metastases from NSCLC. Prof. Faivre-Finn pointed out that the OS was poor in both groups. The QALY results suggest that WBRT provides no additional clinically significant benefit for this group of patients. However, she thinks that there is a lot of misinterpretation of this trial. “Clearly, some subgroups had a better response to WBRT, for example those with a good performance status and age <60 years.” In her view, WBRT should not disappear as a treatment option.

Stereotactic radiosurgery

Stereotactic radiosurgery (SRS) is highly targeted radiotherapy, with sub-millimetre accuracy. A high dose can be delivered in a few fractions (single or during <5 visits). An advantage is that SRS spares the normal brain. “It is certainly nowadays a favoured treatment option in patients with good prognosis, in order to avoid neurocognitive decline”, said Prof. Faivre-Finn. Controversies with respect to SRS include:

• How many metastases are we able to treat with SRS?
• Do we have enough evidence that volume is more important than number? In the United Kingdom, the guidelines recommend a total volume ≤20 cc, while in clinical trials, volumes up to 30 cc have been studied.

In summary, both WBRT and SRS have reduced local recurrence following resection of brain metastases (from approximately 60-70% to 20-30% at 12 months). However, neither intervention improved OS. WBRT leads to reduced relapse elsewhere in the brain, while SRS results in better quality of life, longer functional independence, and longer time until cognitive deterioration. There is a recent change in thinking and in many institutions active surveillance is currently considered as an option. The benefit of SRS is well-established, with a declining role for WBRT. Prognosis is dictated by the control of extra-cranial disease, performance status, and the biology. Aggressive treatment of brain metastases is beneficial and justifiable in good prognostic groups. Management strategies for oncogene-addicted NSCLC are developing rapidly.

1. Mulvenna P, et al. Lancet. 2016;388:2004-2014.

Posted on 25 June 20193 April 2024