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|LETTER TO EDITOR
|Year : 2021 | Volume
| Issue : 2 | Page : 511-512
Management of Radio Surgical Failures: New Insights and Future Prospects
Manjul Tripathi1, Aman Batish1, Sandeep Mohindra1, Amit Joshi2
1 Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Neurosurgery, Tanda Medical College, Tanda, Himanchal Pradesh, India
|Date of Submission||13-Jan-2020|
|Date of Decision||13-Jan-2020|
|Date of Acceptance||15-May-2020|
|Date of Web Publication||24-Apr-2021|
Department of Neurosurgery, Neurosurgery Office, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Tripathi M, Batish A, Mohindra S, Joshi A. Management of Radio Surgical Failures: New Insights and Future Prospects. Neurol India 2021;69:511-2
We have read with great interest the article by Misra BK, et al. We congratulate the authors for their remarkable track record of managing this traditionally difficult neurosurgical disorder with in-house multimodality management with microsurgery and gamma knife radiosurgery (GKRS). In a decade long experience, we have also encountered four cases of failed radiosurgery, which later required surgery, and echo with the findings of the authors.
GKRS failure is a known but rare possibility. With the gaining popularity of GKRS, new questions have also become evident; (i) For how long, should we wait for the late responders?; (ii) How large should Vestibular schwannoma be allowed to grow before additional intervention is undertaken, especially if repeat GKRS is an option?, and (iii) if a residual GKRS is showing a higher growth rate >2.5 mm/year, should a higher marginal dose be considered. Ironically, there is no clear consensus on the criteria to define tumor control or treatment failure after radio surgical intervention. For a very long time, the literature continued to define treatment failure if the tumor size at the end of three years remained greater than the size at the time of the GKRS. However, it has been established now that a subgroup of tumor is actually a late responder (even up to a decade) rather than a failure.
Pseudoprogression is a unique phenomenon with the radio surgical management of the VS. Pseudoprogression denotes an increase in the tumor size after radiosurgery, usually at an interval of 6 months to 1 year. It is mostly due to transient swelling in the tumor in response to radiosurgery rather than the true growth of the tumor. The majority of these patients need only radiological observation as they regress on their own in the coming years (late responders)[Figure 1]. Such a phenomenon has raised the question if any marker can predict the chances of radio surgical failure or identify tumors with phenotypically aggressive growth potential.
|Figure 1: (a) Left vestibular schwannoma at the time of gamma knife radiosurgery; (b) MRI at the end of 6 months showing an increase in the extracanalicular portion of the tumor (pseudo-progression) with subtle hypointensity inside the tumor; (c) magnetic resonance imaging at the end of 1 year showing gradual regression of the tumor volume; and, (d) 2 years follow-up MRI showing significant volumetric reduction of the tumor|
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One of the areas of the expanding insight and interest in this field is tumor immunology. Recent studies have identified tumor-associated macrophages (TAMs) as key players and potentially vital targets for novel directed immunotherapies. A higher expression of CD163+ TAMs also known as “M2 phenotype” has positively correlated with tumor aggressiveness and poor facial outcome after subtotal resection of the VS. Similarly, another potential factor is the receptor programmed cell death protein 1 (PD1) and its ligand (PD L1) as a critical immune checkpoint. With an expression of the high level of PD L1, certain tumors have demonstrated an ability to bind inactivated TAMs, resulting in decreased phagocytosis, immune cell recruitment, and, therefore more robust tumor growth.
Another area of potential interest in the management of VS with GKRS is the effect of the dose fall out rate and its correlation with progression-free survival and functional outcome. The dosimetric analysis for functional GKRS has suggested that predicted biological effective doses (BEDs) for a given prescription dose vary widely across the lifespan of radioactive cobalt-60 sources. Theoretically, a lower dose rate allows for more efficient repair of the accumulated sublethal DNA damage both within the tumor and the surrounding normal tissues. Recent studies have hypothesized that chances of progression-free survival would be nearly the same (not statistically significant) after GKRS irrespective of the dose fall; however, the treatment-related toxicities (especially cranial neuropathies) might be subtly higher in machines with recently loaded sources.,
Based on these findings, it can be concluded that radio surgical management of VS remains the standard of care as a primary treatment for small VS and adjuvant treatment for residual/recurrent tumors. It remains worthwhile and cost-effective to identify the novel markers for tumor aggressiveness to direct the targeted delivery of individualized therapies and avoid unnecessary or premature initiation of the adjuvant treatment.
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Conflicts of interest
There are no conflicts of interest.
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