Prostate Restored
Prostate Restored
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Most patients with brain metastases from extracranial primary tumors such as lung or breast cancer receive palliative treatment approaches, because the common pattern of polymetastatic spread may cause compromised performance status (PS) and eventually also limited survival, often in the range of 3–9 months [1].
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Read More »After more than a decade of partially successful attempts by our group to develop and validate models that predict short survival after treatment of brain metastases, the present study represents a rigorous effort with modified methodology. We increased the number of evaluated variables, selected a narrowly defined cohort of patients with maximum survival of 3 months, and focused primarily on a dichotomized outcome (30-day mortality yes/no), which undoubtedly represents very short survival. We hoped that an in-depth analysis of a limited number of real-world patients treated with different standard approaches might pave the way towards clinically applicable risk stratification, provided external validation of the resulting model will be successful. As demonstrated in the Results section, 30-day mortality is a highly multifactorial event. Patient-, intra- and extracranial disease-related risk factors were identified, e.g. KPS, number of brain metastases, pattern and extent of extracranial metastases, and blood test results. Interestingly, age was not associated with 30-day mortality, despite its well-known prognostic impact in analyses that looked at complete Kaplan–Meier curves [3, 4]. Given that the model did not identify or explain all instances of 30-day mortality, the real picture is probably even more complicated. This is also illustrated by the example of the 93-year-old patient included in Table 4. Reality might in fact be too complex to replace clinical judgement by partially helpful models. On the other hand, a large proportion of patients in the highest risk group (> 16 points) died within 30 days, and none survived for more than 2 months. Therefore, the model could be regarded as one of several components of decision making. As also evident from Table 4, no more than two of these 28 early deaths can be considered relatively unexpected. Causes such as accident, suicide or sudden cardiac death were not recorded. It is also important to realize that 30-day mortality rarely was caused by the brain metastases themselves, although a certain number of patients had causes of death that remained difficult to assign. Only 5 of 100 patients did not harbor active extracranial disease, while more than 50% had at least 3 sites. In this context, one should note that we did not account for the number and size of organ lesions. Both, single bone metastases and widespread involvement were grouped under the same label (bone metastases present). Maybe, a more nuanced assessment would improve the predictive model. On the other hand, there is reason to believe that the LabBM score reflects the extracranial disease burden [16]. As suggested from our regression analysis, several measures of extracranial disease activity contributed relevant information. A different group conducted a retrospective study of patients evaluated for palliative radiotherapy (different indications) from 2017 to 2019 who died within 90 days of consultation [20]. Data were collected for the TEACHH and Chow models and one point was assigned for each adverse factor. The TEACHH model included primary site of disease, PS, age, prior palliative chemotherapy courses, hospitalization within the last 3 months, and presence of hepatic metastases. The Chow model included non-breast primary, site of metastases other than bone only, and PS. A total of 505 patients with a median overall survival of 2.1 months were studied. Based on the TEACHH model, 2%, 77% and 21% were predicted to live > 1 year, > 3 months to ≤ 1 year, and ≤ 3 months, respectively. Utilizing the Chow model, 21%, 50% and 29% were expected to live 15.0, 6.5, and 2.3 months, respectively. Thus, neither model correctly predict prognosis in a patient population with a survival < 3 months.
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Learn More »External validation of our results in a larger study is necessary, given that some of the findings are surprising and based on small numbers. For example, breast cancer patients with hormone receptor-positive Her2-negative disease were at high risk, while those with triple negative disease were not. Accidental findings and overfitting of data are of concern as long as validation results are lacking. In addition, limitations include the single-institution design and the uncertainty about the cause of death in a proportion of patients. For validation studies, it would also be desirable to include intracranial tumor volume and additional surrogate markers of poor survival, e.g. hypercalcemia or cancer-related pericardial effusion or ascites. There are different ways of measuring radio- or chemotherapy utilization near the end of life, e.g. 30-day mortality calculated from start of treatment, 30-day mortality calculated from end of treatment, or treatment in the last 30 days of life. Regardless of this study’s limitations and the unique patient selection, the topic of active treatment in the terminal phase of cancer continues to be important for patients and providers alike [21,22,23,24].
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