We read the Letter to the Editor titled “Does early adjuvant brain metastasis SRS increase mortality?” and we are grateful for the thoughtful analysis by Dr. Moss on this intriguing topic. We agree with the author that more robust data will be necessary for driving meaningful changes to management algorithms; however, our manuscript1 in conjunction with Bander et al.’s manuscript,2 and others open the door for discussion to whether there is indeed an optimal adjuvant radiation window in the setting of brain metastasis.
Our discussion addresses some possible mechanisms associated with early postoperative brain radiation complications, such as “Increased time from surgery allows for more contraction (of the resection cavity), which leads to a decrease in the volume of normal tissue being irradiated, and therefore reduced risk of symptomatic radiation necrosis.” 3 Additionally, “Another study observed a significant volume reduction for larger tumors during the intermediate phase of 22–42 days postoperatively.4 The authors cautioned not to treat any cavities in intervals earlier than 21 days after surgery due to the risk of irradiating more normal tissue.” 4 Another mechanistic hypothesis states hypoxia and edema of the surgical bed from recent resection may diminish the radiosensitivity of the targeted tumor bed.5
We acknowledge the limitation in our dataset incurred by including patients spanning a 9-year period starting in 2009. This is, however, a limitation in neuro-oncology research as treatments continue to rapidly improve and likely will continue to rapidly improve with increasing overall survival. While difficult to completely control for this confounder, this heterogeneity over the long inclusion period is equally distributed across the dataset. The long inclusion period was necessary to obtain a large enough sample size for study.
We agree with the author that association does not equal causation, and a retrospective study will likely never be adequate to answer this question, however, our work adds to mounting evidence that there is an optimal radiation window, and some amount of time delay postoperatively is beneficial prior to initiating radiation.
The observations that intracranial disease is no longer the most common cause of death in patients with metastatic malignancies are noteworthy and a reflection of the advances gained in local CNS therapies including surgical adjuncts and radiotherapies. Thus, it is crucial our community continue to question and refine radiation delivery methods. In this vain, we watch with great interest what roles neoadjuvant, reradiation, and hippocampal sparing modalities will take in our toolbox.
There still remains a gap in evidence needed to make treatment decisions regarding the timing of adjuvant therapies following surgical resection in the setting of brain metastasis. We believe despite limitations, our work contributes to beginning the discussion “when is too soon to initiate radiation,” and helps establish a potential guide for radiation timing to maximize treatment effects while minimizing complications.
We thank the author once again for the thoughtful letter and interest in our work. We look forward to continuing to work together in the field to further evaluate this critical question, and obtain a higher level of evidence to support definitive treatment recommendations.
Contributor Information
Nasser K Yaghi, Department of Neurological Surgery, Oregon Health and Science University, Portland, Oregon, USA.
Seunggu Jude Han, Department of Neurological Surgery, Stanford Medicine, Palo Alto, CA, USA.
Conflict of interest statement
None declared.
References
- 1. Yaghi NK, Radu S, Nugent JG, et al. Optimal timing of radiotherapy following brain metastases surgery. Neurooncol Pract. 2022;9(2):133–141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Bander ED, Yuan M, Reiner AS, et al. Durable 5-year local control for resected brain metastases with early adjuvant SRS: the effect of timing on intended-field control. Neurooncol Pract. 2021;8(3):278–289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Atalar B, Choi CY, Harsh GR, et al. Cavity volume dynamics after resection of brain metastases and timing of postresection cavity stereotactic radiosurgery. Neurosurgery. 2013;72(2):180–185; discussion 185. [DOI] [PubMed] [Google Scholar]
- 4. Alghamdi M, Hasan Y, Ruschin M, et al. Stereotactic radiosurgery for resected brain metastasis: cavity dynamics and factors affecting its evolution. J Radiosurg SBRT. 2018;5(3):191–200. [PMC free article] [PubMed] [Google Scholar]
- 5. Blumenthal DT, Won M, Mehta MP, et al. Short delay in initiation of radiotherapy may not affect outcome of patients with glioblastoma: a secondary analysis from the radiation therapy oncology group database. J Clin Oncol. 2009;27(5):733–739. [DOI] [PMC free article] [PubMed] [Google Scholar]