Whole-Brain Radiotherapy (WBRT) for Brain Metastases: Does the Interval Between Imaging and Treatment Matter?

Abstract

Background/Aim: Many patients with brain metastases receive whole-brain radiotherapy (WBRT). An important question is whether a delay between diagnosis of brain metastases and treatment impairs the patient's prognosis. Patients and Methods: This retrospective study investigated the impact of the interval between diagnosis of brain metastases and WBRT plus ten additional factors on overall survival (OS) in 573 patients. Prospective trials cannot be performed due to ethical concerns. Results: On univariate analyses, age (p<0.001), performance status (p<0.001), controlled primary tumor (p=0.047), metastases outside the brain (p<0.001) and completion of WBRT (p<0.001) were associated with OS. The interval between diagnosis and WBRT had no significant impact (p=0.84). On multivariate analysis, age (p=0.047), performance status (p<0.001), metastases outside the brain (p=0.029) and completion of WBRT (p<0.001) maintained significance. Conclusion: WBRT may be postponed for good reasons (multidisciplinary coordination of treatment, missing histology). OS was significantly associated with previously identified factors, which demonstrates consistency of the present data.Depending on the type of primary tumor, up to 30% of adult cancer patients develop brain metastases during the course of their malignant disease (1). The majority of these patients have already more than three metastases at their first presentation. This situation is often associated with a poor overall survival (OS). Therefore, whole-brain radiotherapy (WBRT) alone is the most common treatment for this patient group. For patients with a very limited number of brain metastases, WBRT may be combined with a local treatment such as neurosurgical resection or stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) (2). In patients with very few intracerebral lesions and a low risk of developing new brain metastases outside the treated lesions, SRS may be delivered without WBRT (3). However, many patients with poor performance status or significant co-morbidities and a few brain metastases receive WBRT alone because they would not tolerate neurosurgery or SRS (4). Generally, it is considered important that WBRT is started as soon as possible, because brain metastases often cause significant symptoms such as headache, nausea/vomiting and neurologic deficits (5, 6). Several issues may cause a delay of up to two or three weeks between the diagnosis of brain metastases and the start of WBRT, e.g. presentation and discussion of the case in a multidisciplinary tumor board, waiting for a definitive histology, treatment planning, and sometimes even limited capacities of linear accelerators. An important question is whether such a delay has a negative impact on the patient's prognosis. This question has not yet been evaluated. Therefore, we investigated the potential impact of the interval between diagnosis of brain metastasis and start of WBRT on OS. In order to reduce the risk of a selection bias due to the WBRT regimen, only patients assigned to l...

Seizures Prior to Whole-brain Irradiation for Metastatic Disease: Prevalence, Risk Factors and Association With Survival

“…Moreover, it investigated pre-treatment seizures to exclude a bias caused by treatment-associated effects. According to previous studies, a bias due to the interval between diagnosis of brain metastases and start of WBI appeared very unlikely (22,23).…”

Potential Impact of the Interval Between Imaging and Whole-brain Radiotherapy in Patients With Relatively Favorable Survival Prognoses

“…An important question is, whether such a delay would decrease patients' expected survival. To address this question, we performed a previously reported study of 573 patients treated with WBRT alone (4). Three intervals between imaging leading to the diagnosis of brain metastasis and the start of WBRT, i.e.…”

“…Thus, the interval between imaging and WBRT had no significant impact on survival. However, the median survival time in that study was quite short (2 months), and a potential negative impact of this delay may have been missed (4). Therefore, we also performed this study in patients who survived at least 4 months following WBRT.…”

“…If discussion of the entire treatment concept in a multidisciplinary tumor board or a definitive histology are lacking but considered mandatory, a delay of up to a very few weeks may be justified. In a previous study, we have investigated whether such a delay would result in worse survival (4). According to the findings of that previous study, which compared three intervals between diagnostic imaging identifying the brain metastases and the start of WBRT (0-7 days, 8-14 days and 15-21 days), a delay of up to 21 days had no impact on survival.…”

“…According to the findings of that previous study, which compared three intervals between diagnostic imaging identifying the brain metastases and the start of WBRT (0-7 days, 8-14 days and 15-21 days), a delay of up to 21 days had no impact on survival. However, one unanswered question was whether a possible impact of the interval between diagnostic imaging and WBRT on survival may have been missed, because the median survival time was only 2 months and possibly too short to detect a significant impact (4). Therefore, we conducted this additional analysis limited to patients who survived at least 4 months following WBRT.…”