Radiosurgery Timing In Brain Cancer Patients
Metastatic brain cancer, also known as brain metastases, occurs when cancer cells from a primary tumor elsewhere in the body spread to the brain. Metastatic brain cancer represents an advanced stage of cancer, indicating that cancer cells have already spread from their original site to the brain. Dealing with cancer in multiple locations poses a greater challenge for effective treatment.
The brain is a delicate organ, and certain limitations exist in terms of treatment options. The blood-brain barrier, a protective barrier in the brain, can restrict the entry of some systemic therapies. Additionally, the potential damage to healthy brain tissue during treatments like surgery or radiation therapy must be carefully managed.
Treatment for metastatic brain cancer may include surgery, radiation therapy, chemotherapy, targeted therapy, and immunotherapy. The choice of treatment depends on factors such as the size and number of tumors, the primary cancer type, and the overall health of the patient.
Whole Brain Radiotherapy (WBRT) was traditionally regarded as the gold standard for treating metastatic brain cancer (MBC) following complete resection. It played a crucial role in providing symptom relief, enhancing local tumor control, and preventing central nervous system (CNS) recurrence. However, the use of WBRT has been associated with a significant concern – irreversible cognitive decline.
As a consequence of whole-brain radiotherapy, patients experienced cognitive impairment as a side effect. This necessitated the exploration and development of alternative radiation techniques to address this issue and improve the overall quality of life for individuals undergoing treatment for metastatic brain cancer. Among these alternatives, stereotactic radiosurgery (SRS) emerged as a notable advancement.
SRS represents a non-invasive ablative technique that deploys a three-dimensional coordinate system. This sophisticated approach significantly enhances the precision of radiation delivery while simultaneously minimizing neurotoxicity. Unlike WBRT, which exposes the entire brain to radiation, SRS precisely targets the tumor or tumors with highly focused beams of radiation. This not only contributes to more effective tumor control but also reduces the impact on surrounding healthy brain tissue, thereby lowering the risk of cognitive decline.
The Study
The study is a systematic review and meta-analysis that aims to examine the relationship between the timing of stereotactic radiosurgery (SRS) following neurosurgical resection of metastatic brain cancer (MBC). The primary objectives are to delineate any potential effects on oncologic outcomes and to delve deeper into the various clinical and pathophysiologic factors that might influence the efficacy of adjuvant treatment.
Methods
In December 2022, a systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review encompassed a database search across PubMed, Cochrane Library, Excerpta Medica DataBASE, and OVID. The search utilized terms such as (brain neoplasms OR brain tumor OR brain cancer) AND (metastasis or neoplasm metastasis) AND (radiosurgery OR gamma knife OR Linac). The inclusion criteria encompassed all human studies restricted to the English language.
Two independent authors conducted the screening and review process, examining titles, abstracts, and manuscripts. Additionally, the bibliographies of each manuscript were scrutinized for the potential inclusion of supplementary articles. This iterative process continued until completion.
The meta-analysis incorporated studies with a sample size of at least 20 patients diagnosed with histopathology-proven metastatic brain cancer. The selected studies involved patients who had undergone neurosurgical resection of at least one metastasis, followed by stereotactic radiosurgery (SRS). Exclusion criteria comprised inaccessible full-text articles, insufficient information regarding radiosurgery timing and/or survival, primary CNS histopathology, and the presence of metastases outside of the intracranial compartment.
The analysis involved extracting various data points for examination, including the study sample size, median age in years, percentage of female participants, disease severity, extent of neurosurgical resection, location of treated intracranial metastases, the proportion of single brain metastasis cases, percentage of primary breast cancer cases, total stereotactic radiosurgery (SRS) dose in Gy, postoperative timing of SRS administration in days, treatment cavity volume in mL, treatment complications (such as surgical cavity radionecrosis), the incidence of local and regional failure, and median overall survival (OS) in months.
For the purpose of the analysis, local failure was defined as metastatic recurrence at the surgical site, while regional failure referred to the recurrence of intracranial metastasis at a location untreated with surgery and SRS. To delineate disease severity, scores from the Recursive Partitioning Analysis class (RPA), Graded Prognostic Assessment (GPA), and Medical Research Council (MRC) Scale were utilized.
Results
A total of 579 studies underwent screening, and 22 articles published between 2008 and 2022 were found to meet the inclusion criteria for analysis. Studies were mainly excluded due to insufficient sample size, inclusion of inappropriate patient populations, or lack of reported timing for stereotactic radiosurgery (SRS).
A total of 1,338 patients were included in the analysis. The median age ranged from 55 to 67 years (SD=2.9). To calculate the overall sex distribution, the percentage of females in each study was multiplied by the total number of patients in that study, these values were summed, and the total was divided by the overall number of patients across all studies.
The sex distribution resulted in a female-to-male ratio of 1:0.85, with the female population varying from 38% to 76% across the studies. There was no significant correlation between the percentage of females and the prevalence of breast cancer in the series (R2=0.09, p=0.23)
In each group of patients, the percentage of those with low disease severity, classified as RPA class I, GPA 1–2, or an MRC scale of 1, varied between 16.6% and 69.0%. The portion of patients with breast cancer ranged from 3.5% to 36.0%, with an average of 16.3% (SD=7.7).
Most of the treated cases involved a single metastatic lesion, making up 68.1% of the group being analyzed. On the other hand, metastatic lesions in the lower part of the brain were less common, ranging from 8.0% to 33.0%. Complete removal of tumors (Grosstotalresection or GTR) was reportedly achieved in 68.0% to 100.0% of patients.
Final Thoughts
Postoperative stereotactic radiosurgery (SRS) stands out as a safe and effective treatment option for individuals dealing with metastatic brain cancer, commonly administered within the timeframe of two to six weeks following the surgical removal of tumors. This meta-analysis, however, revealed an intriguing finding – there was no discernible correlation between the median postoperative SRS timing and the rates of local failure or median overall survival (OS).
While these results are enlightening, it’s essential to acknowledge the limitations inherent in our conclusions. The study population exhibited significant variability, and the methodologies employed in the publications varied considerably. These factors introduce potential confounders that might impact the reliability and generalizability of our findings.
Therefore, to gain a more comprehensive understanding of the potential relationships between postoperative SRS timing and treatment outcomes, and to optimize the workflow of radiosurgery, further research is imperative. Larger-scale studies with consistent methodologies are needed to provide more robust evidence and enhance the precision of our insights. By delving deeper into these nuances, we can refine treatment strategies, improve patient outcomes, and contribute to the ongoing advancements in the management of metastatic brain cancer.
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