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Multi-institutional study of ‘Sandwich treatment’ for motor area large brain metastases (LBM) with diameter over 3 cm

Zheng Wang
Zheng Wang
, 
Haining Chen
Haining Chen
, 
Qun Chen
Qun Chen
, 
Yucun Zhu
Yucun Zhu
, 
Min Li
Min Li
 and 
Jia Zhou
Jia Zhou
   | Jan 06, 2024
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Article Category: Research Article
Published Online: Jan 06, 2024
Page range: 145 - 152
Received: Jul 03, 2023
Accepted: Sep 23, 2023
DOI: https://doi.org/10.2478/raon-2024-0002
Keywords
© 2024 Zheng Wang et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

FIGURE 1.

The mean tumor and peri-tumor edema volume changes. (A) The mean tumor volume decreased dramatically from 20.1 cm3 (range: 17.2–29.7 cm3) at the time of ‘Sandwich treatment’ to 12.3 cm3 (range: 7.7–22.4 cm3) 3 months later (P < 0.001); (B) The mean peri-tumor edema volume at first-stage SRS and second-stage SRS of ‘Sandwich treatment’ was 12.6 cm3 (range: 4.9–19.6 cm3) and 5.2 cm3 (range: 1.2–13.2 cm3) (P < 0.001).2-SSRS = two-staged stereotactic radiosurgery
The mean tumor and peri-tumor edema volume changes. (A) The mean tumor volume decreased dramatically from 20.1 cm3 (range: 17.2–29.7 cm3) at the time of ‘Sandwich treatment’ to 12.3 cm3 (range: 7.7–22.4 cm3) 3 months later (P < 0.001); (B) The mean peri-tumor edema volume at first-stage SRS and second-stage SRS of ‘Sandwich treatment’ was 12.6 cm3 (range: 4.9–19.6 cm3) and 5.2 cm3 (range: 1.2–13.2 cm3) (P < 0.001).2-SSRS = two-staged stereotactic radiosurgery

FIGURE 2.

A typical case with LBM located in motor area that received ‘Sandwich treatment’. (A) The lesion had severe peri-tumor edema and invading towards the frontal lobe; (B) 3 months after ‘Sandwich treatment’, peri-tumor edema and tumor volume significantly reduced.
A typical case with LBM located in motor area that received ‘Sandwich treatment’. (A) The lesion had severe peri-tumor edema and invading towards the frontal lobe; (B) 3 months after ‘Sandwich treatment’, peri-tumor edema and tumor volume significantly reduced.

FIGURE 3.

Patients’ median MMT and BI score. (A) MMT score at the beginning and the end of ‘Sandwich treatment’ (P < 0.001); (B) BI score before ‘Sandwich treatment’ and at 3 months later (P < 0.001).BI score = Barthel Index score; MMT score = manual muscle testing score; 2-SSRS = two-staged stereotactic radiosurgery
Patients’ median MMT and BI score. (A) MMT score at the beginning and the end of ‘Sandwich treatment’ (P < 0.001); (B) BI score before ‘Sandwich treatment’ and at 3 months later (P < 0.001).BI score = Barthel Index score; MMT score = manual muscle testing score; 2-SSRS = two-staged stereotactic radiosurgery

FIGURE 4.

Kaplan - Meier curve of the patient’s (A) Overall survival (OS) and (B) tumor local control (TLC) rate.
Kaplan - Meier curve of the patient’s (A) Overall survival (OS) and (B) tumor local control (TLC) rate.

Risk factors of TLC for LBM in motor area after ‘Sandwich treatment’

Univariate analysis Multivariate analysis
HR ratio 95%CI P-value HR ratio 95%CI P-value
Age 0.978 (0.598–1.686) 0.697
  >=62
  <62
Sex 1.678 (0.913–2.174) 0.781
  Male
  Female
Primary tumor
  Lung/Breast 0.459 (0.359–0.898) < 0.01 0.539 (0.339–0.812) 0.007
  Lung/GL tract 0.913 (0.478–1.316) < 0.01 0.784 (0.498–0.987) 0.006
  Breast/Gl tract 1.987 (0.878–1.974) 0.411
KPS score 2.113 (1.159–6.733) 0.139
  >= 60
  <60
Total tumor volume 0.719 (0.419–1.598) 0.211
  >=20.1cm3
  <20.1cm3
Peri-tumor edema volume 1.589 (0.973–2.894) 0.566
  >=12.6cm3
  <12.6cm3
Dose at first-stage SRS 1.325 (0.53–1.734) 0.989
  >= 13.0 Gy
  < 13.0 Gy
Dose at second-stage SRS 0.845 (0.356–1.250) 0.593
  >= 12.5 Gy
  < 12.5 Gy

Comparison between ‘Sandwich treatment’ and other reports of 2-SSRS strategy for BM

Author Year Case number Median diameter/volume of BM Total dose 2-SSRS interval 6 Months OS/median OS 6 Months TLC/median TLC Radiation necrosis
Yomo et al.9 2012 27 17.8 cm3 27 Gy 3−4 weeks 8.8 months 89.8% 11.1%
Yomo and Hayashi29 2014 58 16.4 cm3 28 Gy 3−4 weeks 63% 85.0% 8.6%
Angelov et al.10 2018 54 Diameter>=2cm 30 Gy 34 days 65% 88.0% 11.0%
Dohm et al.8 2018 33 LBM 29 Gy 30 days 65% 96.8% 6.06%
Hori et al.31 2020 181 4 cm3 N/A N/A 14.6 months 91.0% N/A
Ito et al.32 2020 178 10 cm3 26 Gy 7−38 days 6.6 months 93.2% 6.20%
Damron et al.30 2022 24 8.1 cm3 30 Gy 32 days 9.1months 80% N/A
Cho et al.33 2022 142 Median 7.4 cm3 27−28 Gy 32 days 14 months 88−90% 17%
Present study 2023 51 20.1 cm3 25.5 Gy 7 days 91.8%, 14 months 93.4% 13.11%

Patient characteristics

Characteristic Value Range
Age(median, years) 62 34–81
Sex
  Female 36
  Male 25
Primary tumor
  Lung 39
  Breast 13
  Gastric-intestinal tract 9
KPS (median) 60 50 –80
Dose at first-stage SRS (median, Gy) 13.0 11–15
Dose at second-stage SRS (median, Gy) 12.5 11–14
Total tumor volume (mean, cm3) 20.1 17.2–29.7
Peri-tumor edema volume (mean, cm3) 12.6 4.9–19.6
Follow-up time (median, months) 18.3 6.3–47.9
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