What if: A retrospective reconstruction of resection cavity stereotactic radiosurgery to mimic neoadjuvant stereotactic radiosurgery

Abstract

Introduction: Neoadjuvant stereotactic radiosurgery (NaSRS) of brain metastases has gained importance, but it is not routinely performed. While awaiting the results of prospective studies, we aimed to analyze the changes in the volume of brain metastases irradiated pre- and postoperatively and the resulting dosimetric effects on normal brain tissue (NBT).

Methods: We identified patients treated with SRS at our institution to compare hypothetical preoperative gross tumor and planning target volumes (pre-GTV and pre-PTV) with original postoperative resection cavity volumes (post-GTV and post-PTV) as well as with a standardized-hypothetical PTV with 2.0 mm margin. We used Pearson correlation to assess the association between the GTV and PTV changes with the pre-GTV. A multiple linear regression analysis was established to predict the GTV change. Hypothetical planning for the selected cases was created to assess the volume effect on the NBT exposure. We performed a literature review on NaSRS and searched for ongoing prospective trials.

Results: We included 30 patients in the analysis. The pre-/post-GTV and pre-/post-PTV did not differ significantly. We observed a negative correlation between pre-GTV and GTV-change, which was also a predictor of volume change in the regression analysis, in terms of a larger volume change for a smaller pre-GTV. In total, 62.5% of cases with an enlargement greater than 5.0 cm³ were smaller tumors (pre-GTV < 15.0 cm³), whereas larger tumors greater than 25.0 cm³ showed only a decrease in post-GTV. Hypothetical planning for the selected cases to evaluate the volume effect resulted in a median NBT exposure of only 67.6% (range: 33.2-84.5%) relative to the dose received by the NBT in the postoperative SRS setting. Nine published studies and twenty ongoing studies are listed as an overview.

Conclusion: Patients with smaller brain metastases may have a higher risk of volume increase when irradiated postoperatively. Target volume delineation is of great importance because the PTV directly affects the exposure of NBT, but it is a challenge when contouring resection cavities. Further studies should identify patients at risk of relevant volume increase to be preferably treated with NaSRS in routine practice. Ongoing clinical trials will evaluate additional benefits of NaSRS.

Keywords: CyberKnife®; brain metastases (BM); neoadjuvant; preoperative; stereotactic radiosurgery (SRS).

Figure 1

Patients with surgically resected brain metastases who underwent postoperative stereotactic radiosurgery to the resection cavity in our department were included. One pediatric patient with neuroblastoma was excluded from the cohort. Additional exclusion criteria included: no adequate intracranial MRI before surgery, previous SRS at the index lesion or WBRT as well as a diameter of the preoperative lesion greater than 5 cm. Two patients had to be additionally excluded because their data could not be extracted from the Accuray archive. RC, resection cavity; BM, brain metastasis; SRS, stereotactic radiosurgery.

Figure 2

Flowchart for the selection process of published studies for preoperative SRS. SRS, stereotactic radiosurgery.

Figure 3

Kaplan-Meier-Curves for (A) local progression-free, (B) distant progression-free, (C) leptomeningeal disease-free survival and (D) overall survival. (A) Patients at risk were n = 30 (0 months), n = 23 (6 months), n = 15 (12 months), n = 7 (24 months), and n = 3 (36 months). (B) Patients at risk were n = 30 (0 months), n = 17 (6 months), n = 10 (12 months), n = 6 (24 months), and n = 4 (36 months). (C) Patients at risk were n = 30 (0 months), n = 25 (6 months), n = 14 (12 months), n = 7 (24 months), and n = 4 (36 months). (D) The estimated median survival of our patients was 23.4 months (95% CI: 11.3 – 35.6). Patients at risk were n = 30 (0 months), n = 19 (12 months), n = 11 (24 months), n = 7 (36 months). In total, 14 events occurred within 24 months after the radiosurgical treatment, but only 4 events in the subsequent years were reported.

Figure 4

Quantification of the preoperative (pre) and postoperative (post) (A) gross tumor volume (GTV) and (B) planning target volume (PTV) including hypothetical standardized PTV with a 2 mm margin to post-GTV (n = 30; no significant differences, Wilcoxon test), (C) shows the volume change of binarized pre-GTV volumes depending on size with a cut-off of 15 cm³ (n = 22 for pre-GTV < 15.0 cm³ and n = 8 for pre-GTV > 15.0 cm³; no significant differences, Mann-Whitney-U-test.) Boxplots represent the interquartile range, the thicker line inside the boxes the median, and the whiskers indicate the range from minimum to maximum. Representative case presentations with one deep (D) one superficial (E) and one intraventricular (F) metastasis from non-small cell lung carcinoma shown in axial MRI images with contrast demonstrating comparison of GTV in red for preoperative metastases and in green for the resection cavity. In these cases, an increase in post-GTV compared with pre-GTV can be seen, which was 227.3% in (D), 86.6% in (E), and 19.3% in (F).

Figure 5

Plot of individual patient data (n = 30) for resection cavity volume changes compared with preoperative volumes, (A) for gross tumor volume (GTV), (B) for planning target volume (PTV), and (C) for standardized PTV, shown relative to preoperative (pre) GTV. (D) shows the volume change of the resection cavity after surgical resection in relation to the days between surgery and MRI.

Figure 6

Graphical representation for the seven simulated plannings, visualizing the dose-defined dose-volume histogram (DVH) parameter ratio between simulated NaSRS and postoperative original irradiation (pre/post) against the absolute difference in GTV volume. Fractionations are color coded: Single fraction in green, 3-fractions in blue, and 5-fractions in red. GTV, gross tumor volume.