Purpose <p>Spatial patterns of glioblastoma (GBM) progression inform focal salvage eligibility, but interpretation across studies is limited by heterogeneous spatial definitions, high between-study heterogeneity, and incomplete reporting of non-enhancing/FLAIR-dominant progression. We synthesized reported progression-location involvement after upfront radiotherapy/temozolomide (RT/TMZ) and salvage therapy.</p> Methods <p>We systematically searched PubMed and Scopus from January 1, 2000, to February 1, 2026, and performed arm-level random-effects meta-analysis of logit-transformed proportions. Enhancing progression was harmonized as non-mutually exclusive local/in-field, marginal/field-edge, and distant/out-of-field involvement among evaluable cases, using each study’s spatial framework. The supplementary broad escape-pattern construct was defined as reported progression beyond purely local/in-field enhancing failure.</p> Results <p>We included 107 studies (122 arms; 10,529 patients). At first progression after upfront RT/TMZ ± TTF, reported local/in-field enhancing involvement among evaluable cases was 79.2% (95% CI 75.7–82.3; k = 94; <i>n</i> = 6,989; I²=84.8%), and distant/out-of-field involvement was 16.9% (95% CI 14.3–19.9; k = 89; <i>n</i> = 6,493; I²=85.2%). After salvage therapy, local/in-field involvement remained the majority pattern reported among evaluable cases (59.8%, 95% CI 52.8–66.4; k = 27; <i>n</i> = 1,572; I²=80.5%), with distant/out-of-field involvement of 17.5% (95% CI 12.9–23.3; k = 21; <i>n</i> = 1,307; I²=75.5%) and a supplementary broad escape-pattern estimate of 38.6% (95% CI 31.9–45.9; k = 27; <i>n</i> = 1,572; I²=80.1%). Non-enhancing/FLAIR-dominant progression was sparsely and likely selectively reported; only six recurrent/salvage arms contributed data, yielding an exploratory pooled estimate of 27.8% (95% CI 12.8–50.3; <i>n</i> = 216; I²=75.7%).</p> Conclusion <p>Published GBM cohorts show predominantly local/in-field enhancing progression after upfront therapy (~ 80%) and persistent majority local/in-field involvement after salvage therapy (~ 60%). Standardized reporting of enhancing, non-enhancing/FLAIR-dominant, disseminated, posterior fossa, and brainstem progression is needed.</p>

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Spatial patterns of progression in reported glioblastoma cohorts after upfront chemoradiation and salvage therapy: a systematic review and meta-analysis

  • Rafal Chojak,
  • Noah B. Drewes,
  • Katarzyna Slychan,
  • Rimas V. Lukas

摘要

Purpose

Spatial patterns of glioblastoma (GBM) progression inform focal salvage eligibility, but interpretation across studies is limited by heterogeneous spatial definitions, high between-study heterogeneity, and incomplete reporting of non-enhancing/FLAIR-dominant progression. We synthesized reported progression-location involvement after upfront radiotherapy/temozolomide (RT/TMZ) and salvage therapy.

Methods

We systematically searched PubMed and Scopus from January 1, 2000, to February 1, 2026, and performed arm-level random-effects meta-analysis of logit-transformed proportions. Enhancing progression was harmonized as non-mutually exclusive local/in-field, marginal/field-edge, and distant/out-of-field involvement among evaluable cases, using each study’s spatial framework. The supplementary broad escape-pattern construct was defined as reported progression beyond purely local/in-field enhancing failure.

Results

We included 107 studies (122 arms; 10,529 patients). At first progression after upfront RT/TMZ ± TTF, reported local/in-field enhancing involvement among evaluable cases was 79.2% (95% CI 75.7–82.3; k = 94; n = 6,989; I²=84.8%), and distant/out-of-field involvement was 16.9% (95% CI 14.3–19.9; k = 89; n = 6,493; I²=85.2%). After salvage therapy, local/in-field involvement remained the majority pattern reported among evaluable cases (59.8%, 95% CI 52.8–66.4; k = 27; n = 1,572; I²=80.5%), with distant/out-of-field involvement of 17.5% (95% CI 12.9–23.3; k = 21; n = 1,307; I²=75.5%) and a supplementary broad escape-pattern estimate of 38.6% (95% CI 31.9–45.9; k = 27; n = 1,572; I²=80.1%). Non-enhancing/FLAIR-dominant progression was sparsely and likely selectively reported; only six recurrent/salvage arms contributed data, yielding an exploratory pooled estimate of 27.8% (95% CI 12.8–50.3; n = 216; I²=75.7%).

Conclusion

Published GBM cohorts show predominantly local/in-field enhancing progression after upfront therapy (~ 80%) and persistent majority local/in-field involvement after salvage therapy (~ 60%). Standardized reporting of enhancing, non-enhancing/FLAIR-dominant, disseminated, posterior fossa, and brainstem progression is needed.