J Korean Neurosurg Soc.  2021 Nov;64(6):983-994. 10.3340/jkns.2021.0165.

The Tumor Control According to Radiation Dose of Gamma Knife Radiosurgery for Small and Medium-Sized Brain Metastases from Non-Small Cell Lung Cancer

• Park SJ
• Lim SH
• Kim YJ
• Moon KS
• Kim IY
• Jung S
• Kim SK
• Oh IJ
• Hong JH
• Jung TY

• KMID: 2521989
• DOI: http://doi.org/10.3340/jkns.2021.0165

Abstract

Objective
: The effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC).
Methods
: We analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1–3 and 3–5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated.
Results
: After GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0–17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150–0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5–11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment.
Conclusion
: The small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.

Keyword

Radiosurgery; Radiationy; Neoplasm metastasis; Radiation injuries; Drug therapy

Figure

• 

  Fig. 1. The progression-free survival of 230 GKR-treated metastatic lesions. A : The small-sized tumors less than 1 mL showed an improved PFS than the medium-sized tumors (p=0.003). B : The marginal radiation dose of 24 Gy showed an improved PFS than doses of 20 Gy and 18 Gy (p=0.014). C : Targeted chemotherapy showed an improved PFS compared to that with cytotoxic chemotherapy or best supportive care (p=0.004). D : There was a correlation between PFS of GKR-treated lesions and duration of targeted chemotherapy after GKR (ɣ=0.640, p=0.001). BSC : best supportive care, GKR : gamma knife radiosurgery, PFS : progression-free survival.

• 

  Fig. 2. The progression-free survival of 230 gamma knife radiosurgery-treated lesions depending on the tumor volume and radiation dose. A : For small-sized tumors less than 1 mL, progression-free survival tended to increase with an increase in the radiation dose but without a statistically significant difference (p=0.072). B : For medium-sized tumors >1 and <5 mL, there was no statistically significant difference in the outcomes with different radiation doses (p=0.783).

• 

  Fig. 3. A representative case with radiation necrosis after gamma knife radiosurgery (GKR). A : A 1.5 cm-sized heterogeneously enhancing mass in the left cingulate gyrus with perilesional edema on T1-weighted magnetic resonance imaging (MRI) with gadolinium enhancement. B : One and half months after GKR, a slightly increase in the size of the enhancing mass (1.6 cm) was observed on T1-weighted MRI with gadolinium enhancement. C : One and half months after GKR, brain T2-weighted MRI showed aggravated perilesional edema. D : Seven months after GKR, follow-up brain MRI showed a decrease in size of the enhancing mass and perilesional edema.

Reference

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