JLGK0901

Background

JLGK0901: Multi-institutional prospective observational study (not an RCT). 1,194 patients with 1–10 newly diagnosed brain metastases (largest tumor <10 mL, <3 cm; total cumulative volume ≤15 mL; KPS ≥70) treated with SRS alone. Enrolled Mar 2009–Feb 2012 at 23 Japanese centers. Primary endpoint: OS non-inferiority of 5-10 BM vs 2-4 BM group (non-inferiority margin: upper 95% CI for HR ≤1.30).

Interventions and follow up

Arm A: SRS alone for 5-10 brain metastases (N=208; standard SRS doses: 22 Gy for <4 mL, 20 Gy for 4-10 mL)
Primary endpoint: OS non-inferiority of 5-10 BM vs 2-4 BM
mFollow up: Study finalized Dec 31, 2012

Results

Comparator: SRS alone for 2-4 brain metastases (N=531)
OS (1 BM): Median 13.9 months
OS (2-4 BM): Median 10.8 months
OS (5-10 BM): Median 10.8 months; HR 0.97 (95% CI 0.81–1.18), P=.78, pnon-inferiority <.0001
SRS-related grade ≥3 adverse events: 2% in each group (no significant difference)

Adverse events

Main adverse events: SRS-related adverse events grade ≥3: 2% (1 BM), 2% (2-4 BM), 3% (5-10 BM) — no significant difference. Four deaths attributed to SRS complications. Total cumulative volume ≤15 mL constraint preserved brain tolerance across groups.

Conclusions

OS after SRS alone for patients with 5–10 brain metastases was non-inferior to OS after SRS for 2–4 metastases (both medians ~10.8 months), suggesting that the number of metastases alone does not preclude SRS when total tumor volume is low. This challenged the long-standing 3-metastasis cutoff for SRS eligibility.

Key Limitations

Key Limitations: Observational study — patients with 5–10 BM may have been selected to have smaller, more favorable tumors (total volume ≤15 mL constraint), introducing bias toward better prognosis. No randomized comparison with WBRT for 5-10 BM. Generalizability to Western populations or patients with higher tumor burden/volume is uncertain. Long-term neurocognitive outcomes and quality of life in the 5-10 BM group were not formally assessed in the primary publication.

Clinical Context

JLGK0901 fundamentally changed the eligibility criteria for SRS. Current guidelines (ASCO 2022, NCCN) support SRS for patients with 1–10 BM when total tumor volume is manageable, rather than using the historic ≤3 metastases cutoff. The NCCTG N107C and other post-op SRS trials extended eligibility further. SRS for up to 10 (and sometimes more) BM is now routine practice at high-volume centers.

References

References: Yamamoto M et al, Lancet Oncol 2014 (JLGK0901)