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Journal Club

Tumor/Skull Base

Extending the multistage surgical strategy for recurrent initially low-grade gliomas: functional and oncological outcomes in 31 consecutive patients who underwent a third resection under awake mapping

Journal of Neurosurgery | 2022

Rapid review note

Journal Club is a rapid, AI-assisted appraisal layer. It highlights study design, effect estimates, and practice relevance, but it is still a briefing, not a replacement for the paper.

For education only. Not medical advice.

Paper snapshot

Rapid study overview

Open paper

DOI

10.3171/2021.3.JNS21264

PMID

N/A

PICO

Population

Thirty-one selected patients with recurrent histologically confirmed diffuse low-grade glioma who had already undergone two resections and then a third awake-mapping resection at a single French center; multicentric tumors and prior biopsy-only or outside partial resection cases were excluded.

Intervention

Third functional-based glioma resection under awake corticosubcortical direct electrical stimulation mapping.

Comparator

Group 1 had slow regrowth without enhancement and group 2 underwent third surgery after surgically accessible radiological enhancement; there was no nonsurgical control group.

Outcomes

Permanent neurological deficit, return to work, extent of resection, residual volume, malignant progression-free survival, overall survival, and timing of KPS decline and adjuvant therapy.

Design

Type

Retrospective single-center consecutive cohort

Randomized

No

Multicenter

No

Blinded

N/A

Follow-up

About 13.1 years from diagnosis and 3.1 years from third surgery

Primary endpoint

Feasibility of a third awake-mapping resection assessed through functional morbidity and oncological outcome after the third surgery.

Secondary endpoints

  • Return to work and Karnofsky Performance Scale trajectory
  • Extent of resection and residual tumor volume
  • Differences between slow-regrowth and enhancement-driven third resections

Practice impact

What this means

This paper asks whether a third awake-mapping resection is worth considering for recurrent diffuse low-grade glioma. In this selected 31-patient series, permanent morbidity was rare, most evaluable patients returned to work, and outcomes looked better when the third surgery was done before enhancement appeared on MRI. The result supports discussing another resection in highly functional patients, but the evidence is still a specialized retrospective experience rather than a definitive comparative study.

Bottom line

For selected recurrent diffuse low-grade glioma patients who remain functionally intact, a third awake-mapping resection is feasible and should be considered before radiological enhancement or functional decline when anatomy remains surgically accessible.

Strength of evidence

low

Recommendation

consider change

Why it matters

  • Permanent morbidity was low at 3.2%, and 84.6% of evaluable patients returned to work after the third surgery.
  • Earlier third surgery, before enhancement, was associated with higher extent of resection and longer malignant progression-free survival.
  • Confidence remains limited because this was a 31-patient retrospective single-surgeon series with substantial selection bias.

What would change my mind

  • A multicenter prospective cohort showing similarly low morbidity and similar return-to-work rates after third resection outside this expert center.
  • Comparative data demonstrating that third surgery before radiological enhancement improves patient-centered outcomes more than adjuvant therapy alone.

Critical appraisal

How strong is the paper?

Methods critique

Risk of bias

This was a highly selected single-center series of patients well enough to undergo a third awake resection, without any nonoperative comparison group.

Confounding

Group 2 already showed enhancement and had more pre-third-surgery radiotherapy and chemotherapy, so its worse outcomes may reflect more aggressive biology as much as timing of reoperation.

Missing data

Four prior cortical mapping pictures were unavailable for comparison, and return-to-work analyses used smaller denominators than the full cohort, but broader missing-outcome accounting was not detailed.

Multiplicity

The study reports many between-group tests and several Kaplan-Meier comparisons without a reported adjustment for multiple comparisons.

Notes

  • All third resections were performed by the same senior surgeon using awake direct electrical stimulation mapping.
  • Patient selection required preserved function and a surgically accessible pattern constrained mainly at the cortical rather than subcortical level.

Stats check

NNT

N/A

Effect sizes

  • Mean extent of resection at the third surgery was 89% in group 1 versus 70% in group 2 (p=0.003).
  • Median malignant progression-free survival was 15.3 years in group 1 versus 7.8 years in group 2 (p=0.0003).
  • Median time before KPS fell below 80 was 17.1 years in group 1 versus 14.3 years in group 2 (p=0.01).

Absolute effects

  • Only 1 of 31 patients had a permanent neurological deficit after the third resection, and 22 of 26 evaluable patients returned to work (84.6%).
  • Total or subtotal FLAIR resection was achieved in 25 of 31 patients (80.6%), with a mean residual volume of 8.8 cm3.
  • Estimated overall survival since diagnosis was 17.8 years, with 100% and 89.7% survival at 7 and 10 years, respectively.

Concerns

  • There was no comparator group of similar patients managed without a third surgery, so survival benefit cannot be isolated.
  • Selection bias is strong because every included patient had KPS 80 or higher and no neurological deficit before reoperation.
  • Follow-up after the third surgery was shorter than follow-up from diagnosis, which limits mature comparison of long-term survival by subgroup.

External validity

Who it applies to

Carefully selected adults with recurrent diffuse low-grade glioma, preserved function, and tumors amenable to another awake-mapping resection at expert centers.

Who it does not

Patients with multicentric disease, poor functional status, major neurological deficit, or tumors whose residual burden is constrained primarily by critical subcortical pathways.

Generalizability notes

  • All operations were performed at one specialized center with extensive awake-mapping experience.
  • The results are most applicable to centers already using iterative function-guided resections for low-grade glioma.
  • Because the cohort was selected for continued active life and surgical accessibility, outcomes are likely better than in an unselected recurrent glioma population.

Evidence trace

Source trace and metadata

Citations (13)

claim_id

methods_critique.risk_of_bias

locator

p. 2; p. 9

claim_id

methods_critique.confounding

locator

p. 2; p. 4 Table 1; p. 7

claim_id

methods_critique.missing_data

locator

p. 3; p. 5 Table 3

claim_id

methods_critique.multiplicity

locator

p. 3; p. 7; p. 8 Figure 4

claim_id

methods_critique.notes

locator

p. 3; p. 9

claim_id

stats_check.effect_sizes

locator

p. 5 Table 2; p. 7; p. 8 Figure 4

claim_id

stats_check.absolute_effects

locator

p. 4; p. 5 Table 2; p. 5 Table 3

claim_id

stats_check.nnt

locator

p. 5 Table 2; p. 7

claim_id

stats_check.concerns

locator

p. 7; p. 9

claim_id

practice_impact.bottom_line

locator

p. 7; p. 9

claim_id

practice_impact.strength_of_evidence

locator

p. 9

claim_id

practice_impact.recommendation

locator

p. 7; p. 9

claim_id

practice_impact.rationale

locator

p. 4; p. 5 Table 2; p. 7; p. 9

Metadata

Generated at

2026-03-08T20:55:00Z

Version

manual-pdf-repair-v1