Abstract
Background/Aim: Outcomes of older persons with secondary brain lesions from carcinoma of the breast may be improved by individualized therapy. This process will likely be easier with survival scores. Patients and Methods: A retrospective study was performed in 111 older patients with carcinoma of the breast irradiated for secondary brain lesions. Dose-fractionation, age, general condition, number of brain lesions, other visceral metastases and time period from breast cancer detection until radiation therapy were investigated. Results: Post-radiation survival was significantly related to general condition (p<0.0001) and other visceral metastases (p=0.041). When using these characteristics, sum-scores of 0 (n=46), 1 (n=50) or 2 (n=15) points were gained. Six- and 12-month survival was 7% and 3% for 0 points, 43% and 19% for 1 point, and 73% and 52% for 2 points (p<0.0001). Conclusion: This survival score contributes to treatment individualisation of older patients with secondary brain lesions from carcinoma of the breast.
Carcinoma of the breast is the second most common cancer type in patients presenting with malignant secondary brain lesions (1, 2). Although these patients have better prognoses compared to other cancer types spreading to the brain, the outcomes of affected older persons are less favourable. Prognoses may be improved when therapies for secondary brain lesions are individualised. To allow for an optimal treatment individualisation, it is important to have a realistic impression of a specific patient's remaining lifespan. Patients with a very short supposed lifespan should have short, minimally stressful therapeutic approaches. When treating older patients with a high probability of relatively long-term survival, late sequelae and disease control are important. To improve the individualisation of therapies for older persons with secondary brain lesions from carcinoma of the breast, a specific scoring tool for assessment of their remaining lifetime was generated.
Patients and Methods
A retrospective study (ethics committee, University of Lübeck, 19-011A) was performed in 111 older (≥65 years) patients with carcinoma of the breast who received radiation therapy of the whole brain for secondary lesions, between 2001 and 2018. The following characteristics (Table I) were investigated for potential impact on post-radiation therapy survival: Dose-fractionation of radiation therapy (4 Gy ×5, 3 Gy ×10, 2.5 Gy ×14), age at radiation therapy (≤70 years, ≥71 years), patient's general condition [Karnofsky performance score (KPS) <70, KPS ≥70], number of secondary brain lesions (1 to 3 lesions, more than 3 lesions), other visceral metastases (absence, presence) and the time period from breast cancer detection till radiation therapy (35 months, >36 months).
For the analyses regarding post-radiation therapy survival, the Kaplan–Meier method was employed, complimented by the log-rank test. Significant characteristics, defined as p<0.05, were utilized for building the scoring tool. Each characteristic received either 0 points (lower survival rates) or 1 point (higher survival rates). For each patient, these points were added to generate a sum-score.
Results
Post-radiation therapy survival was significantly influenced by the patient's general condition (p<0.0001) and other visceral metastases (p=0.041) (Table II). The general condition received 0 points for KPS <70 and 1 point for KPS ≥70, and other visceral metastases received 0 points in case of presence and 1 point in case of absence of such metastases. By adding these, sum-scores of either 0 (n=46), 1 (n=50) or 2 (n=15) points were generated. The survival rates of the sum-scores up to 12 months post radiation therapy were significantly different (p<0.0001, Table III). The corresponding Kaplan–Meier curves are shown in Figure 1.
Patient and disease characteristics.
Discussion
The development of secondary brain lesions has been recognized as a serious situation in patients with carcinoma of the breast (1-3). When compared to other patients with secondary brain lesions, those with carcinoma of the breast are often younger (4, 5). Radiation therapy is the most commonly administered treatment modality. In case of very few lesions, radiation therapy is given as stereotactic radiosurgery alone, particularly when the risk of developing new brain lesions outside the irradiated areas is low (6, 7). This risk can be estimated with a specific tool that consists of two risk groups with 15-month rates of freedom from new secondary brain lesions of 92% and 27%, respectively (8). Using this tool, patients of the first group may receive radiosurgery alone without additional radiation therapy of the whole brain (8). Moreover, the dose of single-fraction radiosurgery should be at least 20 Gy, which was shown to be superior to lower doses regarding 1-year local control (94% versus 48%, p=0.002) (9). Many older patients with secondary brain lesions from carcinoma of the breast present with markedly reduced general condition. In our present study, 49.5% of the patients had a KPS <70. Older persons with a poor general condition may not tolerate radiosurgery and receive radiation therapy of the whole brain instead. Moreover, many breast cancer patients with secondary brain lesions have multiple intracerebral metastases and are, therefore, no candidates for radiosurgery (6). In this study, 75.7% of the patients had more than three lesions. Thus, the majority of older breast cancer patients receive radiation therapy of the whole brain alone. Post-radiation survival times can vary substantially in all age groups of patients (4, 5). This information is important when attempting to optimally individualize therapy including the dose-fractionation.
Survival data up to 12 months after radiation therapy.
Survival rates at 3, 6, 9 and 12 months after radiation therapy, related to the sum-scores 0 (n=46), 1 (n=50) and 2 (n=15) points. The difference between the sum-scores was highly significant (p<0.0001).
Survival after radiation therapy related to the sum-scores 0 (n=46), 1 (n=50) and 2 (n=15) points (Kaplan–Meier method).
We provide a tool to aid radiation oncologists in assessing the remaining lifespan of individual patients. In the 0-points group, 20% of the patients survived for 3 months and 7% survived for 6 months. The median survival was only 2 months. Therefore, these patients should be irradiated with 4 Gy ×5 over 5 working days, which was demonstrated non-inferior to a longer dose-fractionation schedule regarding cerebral progression and overall survival (10). The cohort of the 1-point group had an intermediate post-radiation survival prognosis with a median survival time of 5 months and a 6-month rate of 43%. Moreover, 19% of the patients survived for 1 year or longer. These patients appear suitable for 3 Gy ×10, the most frequently used radiation schedule for secondary brain lesions. For patients with 2-points, the median time of post-radiation survival was 13 months with 52% alive at one year. Considering this very favourable prognosis, patients of this cohort will likely benefit from radiation therapy with 2 Gy ×20, which was reported to achieve significantly increased intracerebral control and overall survival when compared to 3 Gy ×10 (11). Moreover, it has been shown for patients of any age and with various primary tumours, who survived for at least 4 months after radiation therapy, that the interval between the diagnosis of metastatic brain lesions and the start of radiation therapy did not impact the outcomes (12). This finding may be particularly important for older persons, since treatment of their co-morbidities may prolong the time between diagnosis and treatment. When using our new tool to define the most suitable dose-fractionation for radiation therapy of an older person with secondary brain lesions from carcinoma of the breast, the retrospective nature of this study should be kept in mind.
In conclusion, this survival score aids radiation oncologists to judge the remaining lifespan of older patients with secondary brain lesions from carcinoma of the breast and contributes to individualisation of therapies.
Footnotes
Authors' Contributions
D.R., T.N., S.J., M.T.K. and S.E.S, designed the study. T.N., S.J., M.T.K. and D.R. collected or provided data. Analyses of the data were performed by D.R. and S.E.S. The draft of the article was written by D.R. and S.E.S and finally reviewed and approved by all Authors.
Conflicts of Interest
On behalf of all Authors, the corresponding Author states that there are no conflicts of interest related to this study.
- Received March 5, 2020.
- Revision received March 15, 2020.
- Accepted March 16, 2020.
- Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
