Comparative Efficacy of Treatments for Improving Progression-Free Survival Among Low Grade Glioma: A Systematic Review and Survival Network Meta-Analysis

Faizul Hasan; Jiun-Lin Yan; Hsiao–Yean Chiu; Kuan-Hao Fu; Lia Taurussia Yuliana; Pin‐Yuan Chen

doi:10.12688/f1000research.179142.1

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Systematic Review

Comparative Efficacy of Treatments for Improving Progression-Free Survival Among Low Grade Glioma: A Systematic Review and Survival Network Meta-Analysis

[version 1; peer review: awaiting peer review]

Faizul Hasan ¹, Jiun-Lin Yan^2,3, Hsiao–Yean Chiu^4-7, Kuan-Hao Fu², Lia Taurussia Yuliana⁴, Pin‐Yuan Chen^2,8

Faizul Hasan ¹, Jiun-Lin Yan^2,3, [...] Hsiao–Yean Chiu^4-7, Kuan-Hao Fu², Lia Taurussia Yuliana⁴, Pin‐Yuan Chen^2,8

PUBLISHED 18 Apr 2026

Author details Author details

¹ Faculty of Nursing, Chulalongkorn University, Bangkok, Bangkok, Thailand
² Department of neurosurgery, Keelung Chang Gung Memorial Hospital of the CGMF, Keelung, Taiwan Province, Taiwan
³ School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Taoyuan, Taoyuan City, Taiwan
⁴ School of Nursing, Taipei Medical University, Taipei City, Taipei City, Taiwan
⁵ Research Center of Sleep Medicine, Taipei Medical University College of Medicine, Taipei City, Taipei City, Taiwan
⁶ Department of Nursing, Taipei Medical University Hospital, Taipei City, Taipei City, Taiwan
⁷ Department of Psychiatry and Sleep Center, Taipei Medical University Hospital, Taipei City, Taipei City, Taiwan
⁸ School of Medicine, Chang Gung University College of Medicine, Taoyuan, Taoyuan City, Taiwan

Faizul Hasan
Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Jiun-Lin Yan
Roles: Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing

Hsiao–Yean Chiu
Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Kuan-Hao Fu
Roles: Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing

Lia Taurussia Yuliana
Roles: Data Curation, Investigation, Project Administration, Resources, Validation, Writing – Original Draft Preparation, Writing – Review & Editing

Pin‐Yuan Chen
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS AWAITING PEER REVIEW

Abstract

Background

Low-grade gliomas (LGGs) are slow-growing primary brain tumors for which the optimal treatment to prolong progression-free survival (PFS) in adults remains debated. This network meta-analysis compares the efficacy of various treatment modalities for improving PFS in adult patients with LGG.

Methods

We systematically searched PubMed, Embase, and the Cochrane Library from inception to September 22, 2025 for studies evaluating PFS outcomes in adult LGG. Included studies were analyzed following PRISMA guidelines using a frequentist framework random-effects network meta-analysis with survival modeling.

Results

Seventeen trials involving 3,588 patients were included. Compared with biopsy alone, gross total resection with radiation (GTRR; HR = 0.47), subtotal resection with radiation and chemotherapy (STRRC; HR = 0.49), gross total resection alone (GTR; HR = 0.59), subtotal resection with chemotherapy (STRC; HR = 0.66), and subtotal resection with radiation (STRR; HR = 0.67) all significantly reduced progression risk (all p < 0.05). GTRR, STRRC, GTR, and STRC also outperformed subtotal resection alone (STR; HR = 0.57, 0.59, 0.70, and 0.79 respectively; all p < 0.05). SUCRA analysis ranked GTRR (84.7%) and STRRC (82.2%) as the most effective regimens.

Conclusions

These results demonstrate that combination therapies—particularly gross total resection with radiation or subtotal resection with radiation and chemotherapy—significantly improve PFS in adult LGG patients.

PROSPERO registration number: CRD42023470802.

Keywords

Low grade glioma, gross total resection, radiation, chemotherapy, network meta-analysis

Corresponding authors: Faizul Hasan, Pin‐Yuan Chen

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2026 Hasan F et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Hasan F, Yan JL, Chiu H et al. Comparative Efficacy of Treatments for Improving Progression-Free Survival Among Low Grade Glioma: A Systematic Review and Survival Network Meta-Analysis [version 1; peer review: awaiting peer review]. F1000Research 2026, 15:558 (https://doi.org/10.12688/f1000research.179142.1) First published: 18 Apr 2026, 15:558 (https://doi.org/10.12688/f1000research.179142.1) Latest published: 18 Apr 2026, 15:558 (https://doi.org/10.12688/f1000research.179142.1)

1. Introduction

Low-grade gliomas (LGGs), classified as World Health Organization (WHO) Grades I and II, represent a common category of primary brain tumors.¹ In the United States, LGGs account for approximately 17% of all primary brain tumor cases.^2,3 These tumors demonstrate diverse pathological characteristics and clinical manifestations. Patients with LGGs face significantly reduced survival rates when early recurrence occurs.⁴ Consequently, multidisciplinary teams comprising neurosurgeons, medical oncologists, and radiation oncologists collaborate to improve progression-free survival (PFS).

Gross total resection (GTR) significantly improves PFS in LGG patients. Current evidence demonstrates that GTR is associated with prolonged PFS, particularly in molecularly defined subtypes such as IDH-mutant tumors.⁵ Cohort studies reveal a marked difference in outcomes, with GTR patients achieving a median PFS of 46 months compared to just 29 months for those undergoing subtotal resection.⁶ The evolution of surgical techniques over recent decades has further enhanced GTR’s survival benefits.⁷ As a cornerstone of LGG management, GTR plays a pivotal role in maximizing PFS, underscoring the critical importance of surgical approach in therapeutic decision-making.

Recent systematic reviews and meta-analyses examining LGG management^4,8–13 have demonstrated that various therapeutic interventions - including surgical resection,^4,8,10–13 radiation therapy,^9,12 and chemotherapy¹² - can effectively prolong PFS. However, current evidence has not yet established any single treatment approach as the optimal strategy for maximizing PFS outcomes.

Network meta-analysis (NMA) represents an advanced methodological approach that facilitates comprehensive comparisons of multiple interventions through both direct and indirect evidence. This technique is particularly valuable for evaluating treatment options that may not have been directly compared in randomized controlled trials (RCTs).¹⁴ In the present study, we employed NMA to systematically assess all available evidence regarding LGG treatments and their effects on PFS in adult patients. This analytical approach enabled us to identify the most efficacious therapeutic strategies for this patient population.

2. Methods

2.1 Search strategy

We conducted a systematic search of three major electronic databases (PubMed, Embase, and Cochrane Library) from their inception through September 22, 2025. Additionally, we performed an exhaustive review of 10 relevant pairwise meta-analyses and their reference lists. The search strategy employed multiple keyword combinations related to LGG treatment. No restrictions were applied regarding publication language or date. Complete details of the search methodology are provided in Table 1.

Table 1. Search strategy.

Databases	Keywords
PubMed	(((“gross total resection”[All Fields] OR “subtotal resection”[All Fields] OR (“resect”[All Fields] OR “resectability”[All Fields] OR “resectable”[All Fields] OR “resectates”[All Fields] OR “resected”[All Fields] OR “resecting”[All Fields] OR “resection”[All Fields] OR “resectional”[All Fields] OR “resectioned”[All Fields] OR “resectioning”[All Fields] OR “resections”[All Fields] OR “resective”[All Fields] OR “resects”[All Fields]) OR (“chemotherapy s”[All Fields] OR “drug therapy”[MeSH Terms] OR (“drug”[All Fields] AND “therapy”[All Fields]) OR “drug therapy”[All Fields] OR “chemotherapies”[All Fields] OR “drug therapy”[MeSH Subheading] OR “chemotherapy”[All Fields]) OR (“radiate”[All Fields] OR “radiated”[All Fields] OR “radiates”[All Fields] OR “radiating”[All Fields] OR “radiation”[MeSH Terms] OR “radiation”[All Fields] OR “electromagnetic radiation”[MeSH Terms] OR (“electromagnetic”[All Fields] AND “radiation”[All Fields]) OR “electromagnetic radiation”[All Fields] OR “radiations”[All Fields] OR “radiation s”[All Fields] OR “radiator”[All Fields] OR “radiators”[All Fields]) OR (“radiotherapy”[MeSH Terms] OR “radiotherapy”[All Fields] OR “radiotherapies”[All Fields] OR “radiotherapy”[MeSH Subheading] OR “radiotherapy s”[All Fields])) AND “low-grade glioma”[All Fields]) OR (“astrocytoma”[MeSH Terms] OR “astrocytoma”[All Fields] OR “astrocytomas”[All Fields]) OR (“oligodendroglioma”[MeSH Terms] OR “oligodendroglioma”[All Fields] OR “oligodendrogliomas”[All Fields])) AND ((clinicaltrial [Filter] OR randomizedcontrolledtrial [Filter]) AND (alladult [Filter]))
Embase	(‘gross total resection’ OR ‘subtotal resection’ OR resection OR chemotherapy OR radiation OR radiotherapy) AND ‘low-grade glioma’ OR astrocytoma OR oligodendroglioma #3 AND (‘clinical article’/de OR ‘clinical study’/de OR ‘clinical trial’/de OR ‘clinical trial topic’/de OR ‘controlled clinical trial’/de OR ‘controlled study’/de OR ‘major clinical study’/de OR ‘phase 1 clinical trial’/de OR ‘phase 2 clinical trial’/de OR ‘phase 2 clinical trial topic’/de OR ‘phase 3 clinical trial topic’/de OR ‘pilot study’/de OR ‘randomized controlled trial’/de OR ‘randomized controlled trial topic’/de) AND ([adult]/lim OR [aged]/lim) AND (‘article’/it OR ‘article in press’/it)
Cochrane Library	“gross total resection” OR “subtotal resection” OR resection OR chemotherapy OR radiation OR radiotherapy AND “low-grade glioma” OR astrocytoma OR oligodendroglioma in All Text - in Trials (Word variations have been searched) Source: CINAHL

2.2 Study inclusion and selection

This systematic review and NMA were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.¹⁵ The study protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42023470802).

We considered RCTs that satisfied the subsequent criteria: (1) patients diagnosed with LGG; (2) diverse therapeutic strategies aimed at enhancing PFS; (3) a control group receiving any treatment or biopsy; and (4) PFS documented as a study endpoint. The definition of therapies is outlined in Table 2. Thresholds for GTR (>80%) and STR (<80%) were based on NCCN Guidelines.^16–18

Table 2. Description of each intervention.

Treatment	Abbreviation	Description
Biopsy	B	Extraction of a small tissue sample to check for malignancy.
Gross total resection (GTR)	GTR	Surgical removal of >80% of abnormal tissue/cancer.
Subtotal resection (STR)	STR	Surgical removal of <80% of abnormal tissue/cancer.
GTR + Radiation	GTRR	GTR followed by radiation therapy.
STR + Radiation	STRR	STR followed by radiation therapy.
STR + Chemotherapy	STRC	STR followed by chemotherapy.
STR + Radiation + Chemotherapy	STRRC	STR followed by radiation therapy and chemotherapy.
Biopsy + Radiation	BR	Biopsy followed by radiation therapy.

Two researchers, designated as F.H. and L.T.Y., performed independent assessments and analyses of the titles and abstracts of eligible papers. Subsequently, the entirety of the remaining research was meticulously analyzed. In instances of disagreement, discussions were held with a third reviewer to attain consensus.

2.3 Study outcome

The primary outcome was PFS. The PFS was given as a Hazards ratio (HR).

2.4 Data extraction and risk-of-bias assessment

Two investigators (F.H. and L.T.Y.) autonomously gathered data from every study that was included. Information pertaining to the study, patients, interventions, additional treatments, and results were compiled. Correspondence with the original authors via email was initiated to acquire any missing or essential data. Any discrepancies were settled through deliberation.

A trio of researchers (H.Y.C., F.H., and L.T.Y.) independently assessed the potential for bias in each study that was included utilizing the Cochrane risk-of-bias tool¹⁹ and the Joanna Brigg Institute for cohort study.²⁰ Consensus was reached to resolve any conflicts that arose.

2.5 Statistical analysis

We performed all NMA using the network command in Stata version 15 (StataCorp, TX, USA). Treatment effects on PFS were expressed as HR with 95% confidence intervals (CIs), calculated by exponentiating Cox regression coefficients (HR = e^β). These multiplicative measures interpret HR > 1 as increased risk and HR < 1 as decreased risk relative to the reference group. Our frequentist approach incorporated random-effects modeling to account for between-study variability. We assessed heterogeneity using the Cochrane Q test (P < 0.01 threshold) and I² statistics (I² > 50% indicating substantial heterogeneity). Consistency between direct and indirect evidence was evaluated through loop-specific, side-splitting, and design-by-treatment interaction models.^14,21 Treatment hierarchies were established using Surface Under the Cumulative Ranking (SUCRA) values and relative efficacy measures,²² while publication bias was examined via Egger’s test.²² Final forest plots comparing treatments against standard care were generated using R version 4.2.2 (R Foundation) with the netmeta package.²³

3. Results

3.1 Study selection and characteristics

Figure 1 depicts the procedure for conducting a literature search. In our initial search, we found 11,141 articles. After removing duplicates and irrelevant articles, there were 27 left for full-text screening. 1 of them were withdrawn for the reason mentioned in Table 3. We found three more RCTs through prior reviews and one through investigating other sources. As a result, we considered 17 RCTs in our study.^24–40

Figure 1. PRISMA 2020 flow diagram for new systematic reviews which included searches of databases, registers and other sources.

Table 3. Number of studies exclude after a full-text review.

Author, year	Reasons of exclusion
Reijneveld, et al 2016	Insufficient data for analysis

Table 4 summarizes the patient and study characteristics of the 17 RCTs that met the inclusion criteria. The total sample size was 3,588 people. The majority of the research was conducted in the United States of America. Tables 5 contain further information and study characteristics.

Table 4. The participant’s characteristics.

Author, year	Country	Participant	Age	AE
Baumert et al 2016²⁴	Netherland	Adult LGG patients	aged ≥18 years	Overall, 22 (9%) of 235 patients in the safety population who received temozolomide had grade 3–4 haematological damage, compared to one (1% of 228 patients in the radiation group). Two (1%) patients had grade 3 or worse infections during radiation, and eight (3%) patients had Pneumocystis jirovecii pneumonia (one in each treatment group). The most common non-haematological adverse effects were neurological (sensory deficits, mood changes, ischaemia, seizures, and neurocognitive problems), which occurred in both groups and were most likely due to the underlying brain disease. Moderate to severe fatigue was noted in eight (4%) radiotherapy patients (grade 2) and 16 (7%) temozolomide patients (one classified as grade 4). Three (1%) individuals experienced thromboembolic events (two in the radiation group and one in the temozolomide group). Two patients in the radiotherapy group died of progressive disease 8 days after the last dose of treatment, and two patients in the temozolomide group died of progressive disease 5 days after the last dose of treatment, and one for unknown reasons 2 days after the last dose of treatment.
Bell et al 2020²⁵	USA	Adult LGG patients	≤29, 30–39, 40–49, ≥50	NR
Buckner et al 2016²⁶	USA	Adult LGG patients	Median 40/41	The most common symptomatic toxic effects were fatigue, anorexia, nausea, and vomiting, all of which were grade 1 or 2. Three patients required red cell transfusions, and one required platelet transfusions. There was one case of neutropenic fever. All of these events occurred in patients who received radiation therapy in addition to chemotherapy.
Gousias et al 2014²⁷	Germany	Adult LGG patients	Median 38 (18.0–74.1)	NR
Ius et al 2012²⁸	Italy	Adult LGG patients	<40, 40–60, >60	NR
Jung et al 2011²⁹	South Korea	Adult LGG patients	<18, 18–60, >60	NR
Karim et al 1996³⁰	Netherland	Adult LGG patients	(age 16–65 years)	Acute minor complications of short duration were observed in both arms of the trial, as is common during and after radiation treatment (e.g., skin reactions, vomiting, headache, otitis).
Rezvan et al 2009³¹	Germany	Adult LGG patients	Median 36.9 (18–70)	NR
Schomas et al 2009³²	USA	Adult LGG patients	Median 36 (18–74)	NR
Shaw et al 2008³³	USA	Adult LGG patients	Median 30 (18–39)	NR
Shaw et al 2012³⁴	USA	Adult LGG patients	Median 40 (22–79)/41 (18–82)	The incidence of grade 3 and 4 hematologic toxicity with RT alone was 8% and 3%, respectively, compared to 51% and 15% with RT+ PCV. Late grade 3 RT toxicity occurred in 1% to 2% of patients. There were no reports of late grades 4 to 5 RT or chemotherapy toxicities.
Sunyach et al 2007a³⁵	France	Adult LGG patients	Median 45 (21–72)	NR
Sunyach et al 2007b³⁵	France	Adult LGG patients	≤45, >55	NR
Youland et al 2013³⁶	USA	Adult LGG patients	Mean 39.5 (18.6–76.0)	NR
Smith et al 2008³⁷	USA	Adult LGG patients	Median 38 (19–72)	NR
McGirt et al 2008³⁸	USA	Adult LGG patients	STR 35 ± 14 NTR 36 ± 16 GTR 32 ± 15	NR
Nitta et al 2015³⁹	Japan	Adult LGG patients	NR	NR
Yeh et al 2005⁴⁰	Taiwan	Adult LGG patients	<40, ≥40	During the follow-up period, 23 patients had somnolence.

Table 5. The study characteristic.

Author, year	Country	Intervention	Control
Baumert et al 2016²⁴	Netherland	STRR	STRC
Bell et al 2020²⁵	USA	STRR	STRRC
Buckner et al 2016²⁶	USA	STRRC	STRR
Gousias et al 2014²⁷	Germany	GTR STR	Biopsy
Ius et al 2012²⁸	Italy	GTR STR	Biopsy
Jung et al 2011²⁹	South Korea	STR	Biopsy
Karim et al 1996³⁰	Netherland	GTRR STRR	BR
Rezvan et al 2009³¹	Germany	GTRR	STRR
Schomas et al 2009³²	USA	GTRR	STRR
Shaw et al 2008³³	USA	GTR	STR
Shaw et al 2012³⁴	USA	STRR	STRRC
Sunyach et al 2007a³⁵	France	STRR	STR
Sunyach et al 2007b³⁵	France	STRC	STR
Youland et al 2013³⁶	USA	GTRR	STRR
Smith et al 2008³⁷	USA	GTR	STR
McGirt et al 2008³⁸	USA	GTR	STR
Nitta et al 2015³⁹	Japan	GTR	STR
Yeh et al 2005⁴⁰	Taiwan	STRR	STR

3.2 Network plots

Figure 2 depicts a PFS network plot. The plot comprises 8 nodes (treatments), 17 trials, 10 head-to-head comparisons, and 3 closed loops. Subtotal resection was the most common comparative intervention, followed by subtotal resection combined with radiation therapy.

Figure 2. Network geometry for progression-free survival parameters in network meta-analysis.

The sizes of each node correspond to the population size associated with each treatment. The line’s thickness corresponds with the quantity of trials linked to the network.

3.3. Effects of treatment on progression-free survival

The overall effects are depicted in Figure 3. Figure 4 compares the impact of several treatments with biopsy. The SUCRA analysis findings are shown in Figure 5.

Figure 3. Forest plots for effects of treatment on progression-free survival.

Figure 4. Forest plots for effects of treatments compared with biopsy.

Figure 5. Cumulative ranking probabilities of treatment.

Compared with biopsy, GTRR, STRRC, GTR, STRC, and STRR significantly decreased the hazard of progression (HRs = 0.47 [CIs 0.27 to 0.84], 0.49 [0.27 to 0.89], 0.59 [0.52 to 0.68], 0.66 [0.49 to 0.90], and 0.67 [0.47 to 0.96], all P < 0.05, respectively, see Table 2). GTRR, STRRC, GTR, and STRC (0.57 [0.34 to 0.92], 0.59 [0.35 to 0.99], 0.70 [0.55 to 0.91], and 0.79 [0.69 to 0.90]) achieved superior results compared with STR (P < 0.05, Table 6). The SUCRA analysis indicated that GTRR was ranked first (84.7%) and followed by STRRC (82.2%). Additionally, the dose of radiation was presented in Table 7.

Table 6. League table of treatment comparative efficacy for progression-free survival.

Treatment	B (Ref )	GTR	STR	GTRR	STRR	STRRC	STRC	BR
B	1	0.59 (0.52–0.68)	0.83 (0.64–1.09)	0.47 (0.27–0.84)	0.67 (0.47–0.96)	0.49 (0.27–0.89)	0.66 (0.49–0.90)	0.68 (0.30–1.52)
GTR	1.68 (1.48–1.92)	1	1.42 (1.09–1.82)	0.79 (0.46–1.39)	1.13 (0.79–1.60)	1.12 (0.84–1.48)	1.14 (0.51–2.56)	-
STR	1.20 (0.91–1.58)	0.70 (0.55–0.91)	1	0.57 (0.34–0.92)	0.79 (0.62–1.01)	0.59 (0.35–0.99)	0.79 (0.69–0.90)	0.81 (0.38–1.73)
GTRR	2.12 (1.20–3.71)	1.26 (0.72–2.18)	1.77 (1.08–2.92)	1	1.40 (0.91–2.18)	1.39 (0.84–2.32)	1.43 (0.70–2.89)	-
STRR	1.49 (1.04–2.13)	0.89 (0.63–1.26)	1.26 (0.99–1.60)	0.71 (0.46–1.09)	1	0.99 (0.76–1.27)	1.01 (0.49–2.08)	-
STRRC	2.03 (1.13–3.67)	1.21 (0.67–2.23)	1.70 (1.01–2.88)	0.96 (0.51–1.91)	1.36 (0.85–2.17)	1	1.38 (0.79–2.29)	0.73 (0.31–1.72)
STRC	1.51 (1.12–2.03)	0.90 (0.68–1.20)	1.27 (1.12–1.45)	0.72 (0.43–1.19)	1.01 (0.79–1.31)	0.74 (0.44–1.27)	1	0.97 (0.46–2.06)
BR	1.48 (0.66–3.28)	0.88 (0.39–1.96)	1.23 (0.58–2.64)	0.70 (0.35–1.42)	0.99 (0.48–2.03)	0.73 (0.31–1.72)	0.97 (0.45–2.10)	1

Table 7. Radiation dose of GTRR studies.

Author, year	Country	Radiation dose
Karim et al 1996³⁰	Netherland	45 or 54 Gy −59.4 Gy
Rezvan et al 2009³¹	Germany	Did not provide detail dose
Schomas et al 2009³²	USA	28.5–70.2 Gy (median dose 54 Gy)
Youland et al 2013³⁶	USA	45–72 Gy (median dose 54 Gy)

3.4 Inconsistency and publication bias testing

We employed the loop-specific methodology and node-splitting approach to detect local inconsistencies. We employed the design-by-treatment method to detect global discrepancies. There were no loop inconsistencies (P = 0.93), design-by-treatment inconsistencies (P = 0.93), or side-splitting inconsistencies (all P > 0.05; Table 8). Egger’s test found no evidence of publication bias among the studies examined (P = 0.55).

Table 8. Side-splitting inconsistency.

Side	Direct		Indirect		Difference			Tau
Side	Coefficient	SE	Coefficient	SE	Coefficient	SE	P > I z I	Tau
Biopsy-GTR	−0.51	0.07	−0.67	0.28	0.16	0.29	0.58	3.69e-10
Biopsy-STR	−0.28	0.24	−0.12	0.17	−0.16	0.29	0.57	2.25e-07
GTR-STR	0.39	0.15	0.23	0.25	0.16	0.29	0.58	2.47e-10
STR-STRR	−0.25	0.14	−0.17	0.24	−0.08	0.28	0.78	4.66e-0.9
STR-STRC	−0.23	0.07	−0.31	0.27	0.08	0.28	0.78	4.35e-08
GTRR-STRR	0.37	0.23	0.13	0.69	0.24	0.73	0.75	1.59e-10
GTRR-BR	0.27	0.46	0.5	0.57	−0.24	0.74	0.75	1.40e-10
STRR-STRC	−0.06	0.23	0.01	0.16	−0.08	0.28	0.78	1.20e-08
STRR-BR	0.13	0.52	−0.1	0.52	0.24	0.74	0.75	3.04e-10

3.5 Risk of bias

The results of the risk of bias for RCT studies were presented in Table 9. Meanwhile, the quality assessment of cohort studies was tabulated in Table 10. Overall, most of the included studies had a low risk of bias.

Table 9. Risk of bias of randomized control trials.

Author, year	Random sequence generation	Allocation concealment	Performance bias	Detection bias	Attrition bias	Reporting bias
Baumert et al 2016²⁴	L	L	H	L	L	L
Buckner et al 2016²⁶	U	U	U	U	L	L
Karim et al 1996³⁰	L	L	L	L	L	L
Shaw et al 2012³⁴	L	U	U	L	L	L

Table 10. Risk of bias of retrospective analysis.

Author, year	1	2	3	4	5	6	7	8	9	10	11
Bell et al 2020²⁵	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Gousias et al 2014²⁷	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Ius et al 2012²⁸	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Jung et al 2011²⁹	Y	Y	Y	Y	Y	Y	Y	Y	Y	UC	Y
Rezvan et al 2009³¹	Y	Y	Y	Y	Y	Y	Y	Y	Y	UC	Y
Schomas et al 2009³²	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Shaw et al 2008³³	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Sunyach et al 2007a³⁵	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Sunyach et al 2007b³⁵	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Youland et al 2013³⁶	Y	Y	Y	Y	Y	Y	Y	Y	Y	UC	Y
Smith et al 2008³⁷	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
McGirt et al 2008³⁸	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Nitta et al 2015³⁹	Y	Y	Y	Y	Y	Y	Y	Y	Y	UC	Y
Yeh et al 2005⁴⁰	Y	Y	Y	Y	Y	Y	Y	Y	Y	UC	Y

4. Discussion

To the best of our knowledge, this is the first novel systematic review and network meta-analysis of survival studies investigating the effect of multiple treatments on PFS among LGG patients. Our results suggest that GTRR is the most effective treatment, ranking number one compared to other treatments, for prolonging PFS in this population. Because we used relatively recent study methods and rigorous methodology, our results should be considered valid.

In line with previous findings, the implementation of GTR may enhance PFS in non-conventional meta-analyses.^8,12 Similarly, LGG patients engaged in radiation therapy were found to have a prolonged survival rate.¹² However, both individual studies failed to identify the best treatment or combination. Interestingly, our novel findings are able to suggest that GTRR may enhance PFS among LGG patients. Hence, we recommend the implementation of GTRR to prolong PFS among LGG patients.

The enhanced PFS results linked to GTRR might be ascribed to its capacity to attain maximal tumor burden reduction while limiting residual malignant cells that may lead to disease recurrence. Complete tumor excision via GTR diminishes the probability of residual tumor growth, while the supplementary application of radiation efficiently eliminates microscopic tumor cells that may remain after surgery.^30–32,36 This integrated strategy improves local tumor management and postpones disease advancement, hence enhancing long-term survival rates. Moreover, prior research indicates that individuals who get gross complete resection followed by radiotherapy experience markedly reduced recurrence rates in comparison to those undergoing subtotal resection or radiotherapy alone.^30–32,36 These data indicate that adopting GTRR as a routine treatment approach may enhance PFS, offering significant clinical direction for neurosurgeons and oncologists in therapeutic decision-making.

The radiation dose in the GTRR studies ranged from 28.5 to 70.2 Gy, with a median dose of 54 Gy ( Table 3), provided in fractions of 1.8–2.0 Gy over a duration of 5–6 weeks.^30–32,36 This dosage is frequently employed for its efficacy in controlling residual disease while minimizing harm. Certain research³⁰ suggest that increased dosages may not provide further advantages and could exacerbate neurotoxicity; yet, a definitive agreement on dose escalation is lacking. Further investigation is necessary to evaluate the possible advantages of customizing radiation doses based on patient or tumor attributes on treatment results.

The National Comprehensive Cancer Network (NCCN) guidelines¹⁶ suggest that the treatment of a patient with LGG should involve a GTR. However, if a GTR is not possible due to diffuseness, the application of STR with combination therapy, such as radiation or chemotherapy, might be the preferable choice.¹⁶ Similarly, the findings of this NMA support the NCCN guidelines. Compared to biopsy, both GTR, either alone (GTR) or in combination (GTRR), and STR with combination therapy (including STRRC, STRC, and STRR), have been shown to prolong PFS among adults with LGG. It’s worth noting that from a clinical perspective, ideally, the neurosurgeon will pursue GTR as the initial step. However, if the tumor is diffusely spread or if the tumor is located within the eloquent cortex or deeply seated, they may only achieve STR and will then need to consider radiation or chemotherapy.

We found the alternative approaches such as STRRC also present advantages over biopsy alone. In line with the guideline from the oncologist association, the resection¹⁰ combined with additional therapy such as radiation and chemotherapy may improve the life expectancy among cancer patients.⁴¹ Numerous evidences also prove the efficacy of treatment combination between resection and radiation or chemotherapy on patient survival.⁴¹ This finding offers valid clinical evidence for researchers and neurosurgeons, particularly for better LGG management in clinical settings.

Molecular markers, particularly IDH mutation status and 1p/19q codeletion, have become essential for prognosis, treatment selection, and outcome prediction in modern neuro-oncology. Current evidence demonstrates that IDH-mutant tumors show significantly better response to temozolomide compared to radiation therapy.²⁴ Furthermore, 1p/19q codeletion has been established as both a prognostic marker and predictor of enhanced chemosensitivity to procarbazine, lomustine, and vincristine chemotherapy when combined with radiation.²⁵ Molecular stratification by IDH status and 1p/19q codeletion reliably identifies patients who benefit most from adjuvant therapies, confirming these markers’ dual prognostic and predictive value.²⁶

Despite the WHO’s incorporation of molecular classification, our analysis revealed that only 3 of 17 included studies reported IDH or 1p/19q status,^42–44 severely limiting opportunities for molecular subgroup analysis. This striking gap underscores the critical need to integrate molecular profiling into routine clinical practice to enable truly personalized treatment approaches. Future prospective studies must prioritize comprehensive molecular characterization to address this knowledge gap and optimize therapeutic decision-making for LGG patients.

The investigation brings to light several limitations, aside from its strengths. To begin with, the study’s internal validity suffered from discrepancies in participant characteristics and study factors (e.g., disease features, treatment duration, sample size), potentially undermining result reliability. Furthermore, the study’s inability to evaluate the impact of varying treatment dosages on the correlation between different treatments and PFS restricts the practicality of our discoveries in clinical settings. The absence of molecular stratification (e.g., by IDH mutation or 1p/19q status) in most included studies limits the clinical applicability of our conclusions. Given the known prognostic and predictive roles of these markers, the benefits of GTR or adjuvant therapies may vary significantly across molecular subtypes. Future prospective studies should prioritize molecular stratification to refine treatment recommendations. Lastly, it is worth mentioning that our NMA did not uncover any discrepancies. Nevertheless, it is crucial to recognize that the statistical power to detect inconsistencies was limited due to the inclusion of a minimal number of studies compared to the number of treatment comparisons, particularly those related to STRRC.

5. Conclusion

In conclusion, GTRR becomes the best treatment to prolong the PFS among adult with LGG. Nevertheless, in the case of a tumor that has spread extensively, the attainment of gross total resection may not be feasible, and alternative treatment options such as radiation therapy or chemotherapy should be considered. This NMA provides evidence supporting the effectiveness of a combination therapy such as GTR with radiation therapy and STR with radiation and chemotherapy for improving PFS in adult with LGG.

Availability of data, code and other materials

No data are associated with this article. Supplementary materials are available in the supplementary data.

Extended data

Zenodo: Supplementary data: https://doi.org/10.5281/zenodo.19332616.⁴⁵

This project contains the following extended data:

• PRISMA NMA Checklist.docx.

Data are available under the terms of the Creative Commons Attribution 4.0 International.

Acknowledgments

None.

References

1. Louis DN, Perry A, Reifenberger G, et al.: The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016; 131: 803–820. PubMed Abstract | Publisher Full Text
2. Forst DA, Nahed BV, Loeffler JS, et al.: Low-grade gliomas. Oncologist. 2014; 19(4): 403–413. PubMed Abstract | Publisher Full Text | Free Full Text
3. Ostrom QT, Cote DJ, Ascha M, et al.: Adult glioma incidence and survival by race or ethnicity in the United States from 2000 to 2014. JAMA Oncol. 2018; 4(9): 1254–1262. PubMed Abstract | Publisher Full Text | Free Full Text
4. Jiang C, Wang J: Post-traumatic stress disorders in patients with low-grade glioma and its association with survival. J. Neuro-Oncol. 2019; 142: 385–392. PubMed Abstract | Publisher Full Text
5. Tom MC, et al.: Risk factors for progression among low-grade gliomas after gross total resection and initial observation in the molecular era. Int. J. Radiat. Oncol. Biol. Phys. 2019; 104(5): 1099–1105.
6. Rossi M, Gay L, Ambrogi F, et al.: Association of supratotal resection with progression-free survival, malignant transformation, and overall survival in lower-grade gliomas. Neuro-Oncology. 2021; 23(5): 812–826. PubMed Abstract | Publisher Full Text | Free Full Text
7. Jin M, et al.: TRENDS IN LOW GRADE GLIOMA PROGNOSIS AND THE EVOLVING IMPACT OF GROSS TOTAL RESECTION ACROSS FIFTY YEARS: A MULTICOHORT ANALYSIS. NEURO-ONCOLOGY. CARY, NC 27513 USA: OXFORD UNIV PRESS INC JOURNALS DEPT, 2001 EVANS RD; 2024.
8. Brown TJ, et al.: Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol. 2016; 2(11): 1460–1469.
9. Ryken TC, Parney I, Buatti J, et al.: The role of radiotherapy in the management of patients with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J. Neuro-Oncol. 2015; 125: 551–583. PubMed Abstract | Publisher Full Text
10. Aghi MK, et al.: The role of surgery in the management of patients with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J. Neuro-Oncol. 2015; 125: 503–530.
11. Jiang B, et al.: Biopsy versus resection for the management of low-grade gliomas. Cochrane Database Syst. Rev. 2017; 4.
12. Brown TJ, Bota DA, van den Bent MJ, et al.: Management of low-grade glioma: a systematic review and meta-analysis. Neuro-oncology practice. 2019; 6(4): 249–258. PubMed Abstract | Publisher Full Text | Free Full Text
13. Brown TJ, et al.: Association of aggressive resection with survival and progression-free survival in adult low-grade glioma: A systematic review and meta-analysis with numbers needed to treat. American Society of Clinical Oncology; 2017.
14. Lu G, Ades A: Combination of direct and indirect evidence in mixed treatment comparisons. Stat. Med. 2004; 23(20): 3105–3124.
15. Hutton B, Salanti G, Caldwell DM, et al.: The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann. Intern. Med. 2015; 162(11): 777–784. Publisher Full Text
16. Nabors LB, Portnow J, Ahluwalia M, et al.: Central nervous system cancers, version 3.2020, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Cancer Netw. 2020; 18(11): 1537–1570. Publisher Full Text
17. Karschnia P, Vogelbaum MA, van den Bent M, et al.: Evidence-based recommendations on categories for extent of resection in diffuse glioma. Eur. J. Cancer. 2021; 149: 23–33. PubMed Abstract | Publisher Full Text
18. Chammas M, Saadeh FS, Maaliki M, et al.: Therapeutic interventions in adult low-grade gliomas.2019.
19. Jpt H: Cochrane handbook for systematic reviews of interventions.Reference Source2008.
20. Moola S, et al.: Systematic reviews of etiology and risk. Joanna Briggs Institute reviewer’s manual; 2017; vol. 5. : 217–269.
21. White IR: Multivariate random-effects meta-regression: updates to mvmeta. Stata J. 2011; 11(2): 255–270. Publisher Full Text
22. Chaimani A, Higgins JPT, Mavridis D, et al.: Graphical tools for network meta-analysis in STATA. PloS one. 2013; 8(10): e76654. PubMed Abstract | Publisher Full Text | Free Full Text
23. Balduzzi S, Rücker G, Nikolakopoulou A, et al.: netmeta: an R package for network meta-analysis using frequentist methods. J. Stat. Softw. 2023; 106: 1–40. Publisher Full Text
24. Baumert BG, Hegi ME, van den Bent MJ, et al.: Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016; 17(11): 1521–1532. Publisher Full Text
25. Bell EH, Zhang P, Shaw EG, et al.: Comprehensive genomic analysis in NRG oncology/RTOG 9802: a phase III trial of radiation versus radiation plus procarbazine, lomustine (CCNU), and vincristine in high-risk low-grade glioma. J. Clin. Oncol. 2020; 38(29): 3407–3417. PubMed Abstract | Publisher Full Text | Free Full Text
26. Buckner JC, Shaw EG, Pugh SL, et al.: Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N. Engl. J. Med. 2016; 374(14): 1344–1355. PubMed Abstract | Publisher Full Text | Free Full Text
27. Gousias K, Schramm J, Simon M: Extent of resection and survival in supratentorial infiltrative low-grade gliomas: analysis of and adjustment for treatment bias. Acta Neurochir. 2014; 156: 327–337. PubMed Abstract | Publisher Full Text
28. Ius T, Isola M, Budai R, et al.: Low-grade glioma surgery in eloquent areas: volumetric analysis of extent of resection and its impact on overall survival. A single-institution experience in 190 patients. J. Neurosurg. 2012; 117(6): 1039–1052. Publisher Full Text
29. Jung T-Y, Jung S, Moon JH, et al.: Early prognostic factors related to progression and malignant transformation of low-grade gliomas. Clin. Neurol. Neurosurg. 2011; 113(9): 752–757. PubMed Abstract | Publisher Full Text
30. Karim AB, et al.: A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844. Int. J. Radiat. Oncol. Biol. Phys. 1996; 36(3): 549–556.
31. Rezvan A, Christine D, Christian H, et al.: Long-term outcome and survival of surgically treated supratentorial low-grade glioma in adult patients. Acta Neurochir. 2009; 151: 1359–1365. Publisher Full Text
32. Schomas DA, Laack NNI, Rao RD, et al.: Intracranial low-grade gliomas in adults: 30-year experience with long-term follow-up at Mayo Clinic. Neuro-Oncology. 2009; 11(4): 437–445. PubMed Abstract | Publisher Full Text | Free Full Text
33. Shaw EG, Berkey B, Coons SW, et al.: Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial. J. Neurosurg. 2008; 109(5): 835–841. PubMed Abstract | Publisher Full Text | Free Full Text
34. Shaw EG, Wang M, Coons SW, et al.: Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J. Clin. Oncol. 2012; 30(25): 3065–3070. PubMed Abstract | Publisher Full Text | Free Full Text
35. Sunyach MP, Jouvet A, Perol D, et al.: Role of exclusive chemotherapy as first line treatment in oligodendroglioma. J. Neuro-Oncol. 2007; 85: 319–328. PubMed Abstract | Publisher Full Text
36. Youland RS, Brown PD, Giannini C, et al.: Adult low-grade glioma: 19-year experience at a single institution. Am. J. Clin. Oncol. 2013; 36(6): 612–619. PubMed Abstract | Publisher Full Text | Free Full Text
37. Smith JS, Chang EF, Lamborn KR, et al.: Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J. Clin. Oncol. 2008; 26(8): 1338–1345. PubMed Abstract | Publisher Full Text
38. McGirt MJ, Chaichana KL, Attenello FJ, et al.: Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery. 2008; 63(4): 700–708. Publisher Full Text
39. Nitta M, Muragaki Y, Maruyama T, et al.: Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection. Neurosurg. Focus. 2015; 38(1): E7. PubMed Abstract | Publisher Full Text
40. Yeh SA, Ho JT, Lui CC, et al.: Treatment outcomes and prognostic factors in patients with supratentorial low-grade gliomas. Br. J. Radiol. 2005; 78(927): 230–235. Publisher Full Text
41. Soffietti R, Baumert BG, Bello L, et al.: Guidelines on management of low-grade gliomas: report of an EFNS–EANO* Task Force. Eur. J. Neurol. 2010; 17(9): 1124–1133. Publisher Full Text
42. Horbinski C, et al.: Central Nervous System Cancers, Version 2.2022 Featured Updates to the NCCN Guidelines. J. Natl. Compr. Cancer Netw. 2023; 21(1): 12–20.
43. Delfanti RL, Piccioni DE, Handwerker J, et al.: Imaging correlates for the 2016 update on WHO classification of grade II/III gliomas: implications for IDH, 1p/19q and ATRX status. J. Neuro-Oncol. 2017; 135: 601–609. PubMed Abstract | Publisher Full Text | Free Full Text
44. Bhandari AP, Liong R, Koppen J, et al.: Noninvasive determination of IDH and 1p19q status of lower-grade gliomas using MRI radiomics: a systematic review. Am. J. Neuroradiol. 2021; 42(1): 94–101. PubMed Abstract | Publisher Full Text | Free Full Text
45. Hasan F: Prisma Checklist NMA. Zenodo. 2026.

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Author details Author details

¹ Faculty of Nursing, Chulalongkorn University, Bangkok, Bangkok, Thailand
² Department of neurosurgery, Keelung Chang Gung Memorial Hospital of the CGMF, Keelung, Taiwan Province, Taiwan
³ School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Taoyuan, Taoyuan City, Taiwan
⁴ School of Nursing, Taipei Medical University, Taipei City, Taipei City, Taiwan
⁵ Research Center of Sleep Medicine, Taipei Medical University College of Medicine, Taipei City, Taipei City, Taiwan
⁶ Department of Nursing, Taipei Medical University Hospital, Taipei City, Taipei City, Taiwan
⁷ Department of Psychiatry and Sleep Center, Taipei Medical University Hospital, Taipei City, Taipei City, Taiwan
⁸ School of Medicine, Chang Gung University College of Medicine, Taoyuan, Taoyuan City, Taiwan

Faizul Hasan
Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Jiun-Lin Yan
Roles: Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing

Hsiao–Yean Chiu
Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Kuan-Hao Fu
Roles: Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing

Lia Taurussia Yuliana
Roles: Data Curation, Investigation, Project Administration, Resources, Validation, Writing – Original Draft Preparation, Writing – Review & Editing

Pin‐Yuan Chen
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

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Hasan F, Yan JL, Chiu H et al. Comparative Efficacy of Treatments for Improving Progression-Free Survival Among Low Grade Glioma: A Systematic Review and Survival Network Meta-Analysis [version 1; peer review: awaiting peer review]. F1000Research 2026, 15:558 (https://doi.org/10.12688/f1000research.179142.1)

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[1] 1. Louis DN, Perry A, Reifenberger G, et al.: The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016; 131: 803–820. PubMed Abstract | Publisher Full Text

[2] 2. Forst DA, Nahed BV, Loeffler JS, et al.: Low-grade gliomas. Oncologist. 2014; 19(4): 403–413. PubMed Abstract | Publisher Full Text | Free Full Text

[3] 3. Ostrom QT, Cote DJ, Ascha M, et al.: Adult glioma incidence and survival by race or ethnicity in the United States from 2000 to 2014. JAMA Oncol. 2018; 4(9): 1254–1262. PubMed Abstract | Publisher Full Text | Free Full Text

[4] 4. Jiang C, Wang J: Post-traumatic stress disorders in patients with low-grade glioma and its association with survival. J. Neuro-Oncol. 2019; 142: 385–392. PubMed Abstract | Publisher Full Text

[5] 5. Tom MC, et al.: Risk factors for progression among low-grade gliomas after gross total resection and initial observation in the molecular era. Int. J. Radiat. Oncol. Biol. Phys. 2019; 104(5): 1099–1105.

[6] 6. Rossi M, Gay L, Ambrogi F, et al.: Association of supratotal resection with progression-free survival, malignant transformation, and overall survival in lower-grade gliomas. Neuro-Oncology. 2021; 23(5): 812–826. PubMed Abstract | Publisher Full Text | Free Full Text

[7] 7. Jin M, et al.: TRENDS IN LOW GRADE GLIOMA PROGNOSIS AND THE EVOLVING IMPACT OF GROSS TOTAL RESECTION ACROSS FIFTY YEARS: A MULTICOHORT ANALYSIS. NEURO-ONCOLOGY. CARY, NC 27513 USA: OXFORD UNIV PRESS INC JOURNALS DEPT, 2001 EVANS RD; 2024.

[8] 8. Brown TJ, et al.: Association of the extent of resection with survival in glioblastoma: a systematic review and meta-analysis. JAMA Oncol. 2016; 2(11): 1460–1469.

[9] 9. Ryken TC, Parney I, Buatti J, et al.: The role of radiotherapy in the management of patients with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J. Neuro-Oncol. 2015; 125: 551–583. PubMed Abstract | Publisher Full Text

[10] 10. Aghi MK, et al.: The role of surgery in the management of patients with diffuse low grade glioma: a systematic review and evidence-based clinical practice guideline. J. Neuro-Oncol. 2015; 125: 503–530.

[11] 11. Jiang B, et al.: Biopsy versus resection for the management of low-grade gliomas. Cochrane Database Syst. Rev. 2017; 4.

[12] 12. Brown TJ, Bota DA, van den Bent MJ, et al.: Management of low-grade glioma: a systematic review and meta-analysis. Neuro-oncology practice. 2019; 6(4): 249–258. PubMed Abstract | Publisher Full Text | Free Full Text

[13] 13. Brown TJ, et al.: Association of aggressive resection with survival and progression-free survival in adult low-grade glioma: A systematic review and meta-analysis with numbers needed to treat. American Society of Clinical Oncology; 2017.

[14] 14. Lu G, Ades A: Combination of direct and indirect evidence in mixed treatment comparisons. Stat. Med. 2004; 23(20): 3105–3124.

[15] 15. Hutton B, Salanti G, Caldwell DM, et al.: The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann. Intern. Med. 2015; 162(11): 777–784. Publisher Full Text

[16] 16. Nabors LB, Portnow J, Ahluwalia M, et al.: Central nervous system cancers, version 3.2020, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Cancer Netw. 2020; 18(11): 1537–1570. Publisher Full Text

[17] 17. Karschnia P, Vogelbaum MA, van den Bent M, et al.: Evidence-based recommendations on categories for extent of resection in diffuse glioma. Eur. J. Cancer. 2021; 149: 23–33. PubMed Abstract | Publisher Full Text

[18] 18. Chammas M, Saadeh FS, Maaliki M, et al.: Therapeutic interventions in adult low-grade gliomas.2019.

[19] 19. Jpt H: Cochrane handbook for systematic reviews of interventions.Reference Source2008.

[20] 20. Moola S, et al.: Systematic reviews of etiology and risk. Joanna Briggs Institute reviewer’s manual; 2017; vol. 5. : 217–269.

[21] 21. White IR: Multivariate random-effects meta-regression: updates to mvmeta. Stata J. 2011; 11(2): 255–270. Publisher Full Text

[22] 22. Chaimani A, Higgins JPT, Mavridis D, et al.: Graphical tools for network meta-analysis in STATA. PloS one. 2013; 8(10): e76654. PubMed Abstract | Publisher Full Text | Free Full Text

[23] 23. Balduzzi S, Rücker G, Nikolakopoulou A, et al.: netmeta: an R package for network meta-analysis using frequentist methods. J. Stat. Softw. 2023; 106: 1–40. Publisher Full Text

[24] 24. Baumert BG, Hegi ME, van den Bent MJ, et al.: Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016; 17(11): 1521–1532. Publisher Full Text

[25] 25. Bell EH, Zhang P, Shaw EG, et al.: Comprehensive genomic analysis in NRG oncology/RTOG 9802: a phase III trial of radiation versus radiation plus procarbazine, lomustine (CCNU), and vincristine in high-risk low-grade glioma. J. Clin. Oncol. 2020; 38(29): 3407–3417. PubMed Abstract | Publisher Full Text | Free Full Text

[26] 26. Buckner JC, Shaw EG, Pugh SL, et al.: Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N. Engl. J. Med. 2016; 374(14): 1344–1355. PubMed Abstract | Publisher Full Text | Free Full Text

[27] 27. Gousias K, Schramm J, Simon M: Extent of resection and survival in supratentorial infiltrative low-grade gliomas: analysis of and adjustment for treatment bias. Acta Neurochir. 2014; 156: 327–337. PubMed Abstract | Publisher Full Text

[28] 28. Ius T, Isola M, Budai R, et al.: Low-grade glioma surgery in eloquent areas: volumetric analysis of extent of resection and its impact on overall survival. A single-institution experience in 190 patients. J. Neurosurg. 2012; 117(6): 1039–1052. Publisher Full Text

[29] 29. Jung T-Y, Jung S, Moon JH, et al.: Early prognostic factors related to progression and malignant transformation of low-grade gliomas. Clin. Neurol. Neurosurg. 2011; 113(9): 752–757. PubMed Abstract | Publisher Full Text

[30] 30. Karim AB, et al.: A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) Study 22844. Int. J. Radiat. Oncol. Biol. Phys. 1996; 36(3): 549–556.

[31] 31. Rezvan A, Christine D, Christian H, et al.: Long-term outcome and survival of surgically treated supratentorial low-grade glioma in adult patients. Acta Neurochir. 2009; 151: 1359–1365. Publisher Full Text

[32] 32. Schomas DA, Laack NNI, Rao RD, et al.: Intracranial low-grade gliomas in adults: 30-year experience with long-term follow-up at Mayo Clinic. Neuro-Oncology. 2009; 11(4): 437–445. PubMed Abstract | Publisher Full Text | Free Full Text

[33] 33. Shaw EG, Berkey B, Coons SW, et al.: Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial. J. Neurosurg. 2008; 109(5): 835–841. PubMed Abstract | Publisher Full Text | Free Full Text

[34] 34. Shaw EG, Wang M, Coons SW, et al.: Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J. Clin. Oncol. 2012; 30(25): 3065–3070. PubMed Abstract | Publisher Full Text | Free Full Text

[35] 35. Sunyach MP, Jouvet A, Perol D, et al.: Role of exclusive chemotherapy as first line treatment in oligodendroglioma. J. Neuro-Oncol. 2007; 85: 319–328. PubMed Abstract | Publisher Full Text

[36] 36. Youland RS, Brown PD, Giannini C, et al.: Adult low-grade glioma: 19-year experience at a single institution. Am. J. Clin. Oncol. 2013; 36(6): 612–619. PubMed Abstract | Publisher Full Text | Free Full Text

[37] 37. Smith JS, Chang EF, Lamborn KR, et al.: Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J. Clin. Oncol. 2008; 26(8): 1338–1345. PubMed Abstract | Publisher Full Text

[38] 38. McGirt MJ, Chaichana KL, Attenello FJ, et al.: Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery. 2008; 63(4): 700–708. Publisher Full Text

[39] 39. Nitta M, Muragaki Y, Maruyama T, et al.: Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection. Neurosurg. Focus. 2015; 38(1): E7. PubMed Abstract | Publisher Full Text

[40] 40. Yeh SA, Ho JT, Lui CC, et al.: Treatment outcomes and prognostic factors in patients with supratentorial low-grade gliomas. Br. J. Radiol. 2005; 78(927): 230–235. Publisher Full Text

[41] 41. Soffietti R, Baumert BG, Bello L, et al.: Guidelines on management of low-grade gliomas: report of an EFNS–EANO* Task Force. Eur. J. Neurol. 2010; 17(9): 1124–1133. Publisher Full Text

[42] 42. Horbinski C, et al.: Central Nervous System Cancers, Version 2.2022 Featured Updates to the NCCN Guidelines. J. Natl. Compr. Cancer Netw. 2023; 21(1): 12–20.

[43] 43. Delfanti RL, Piccioni DE, Handwerker J, et al.: Imaging correlates for the 2016 update on WHO classification of grade II/III gliomas: implications for IDH, 1p/19q and ATRX status. J. Neuro-Oncol. 2017; 135: 601–609. PubMed Abstract | Publisher Full Text | Free Full Text

[44] 44. Bhandari AP, Liong R, Koppen J, et al.: Noninvasive determination of IDH and 1p19q status of lower-grade gliomas using MRI radiomics: a systematic review. Am. J. Neuroradiol. 2021; 42(1): 94–101. PubMed Abstract | Publisher Full Text | Free Full Text

[45] 45. Hasan F: Prisma Checklist NMA. Zenodo. 2026.

Comparative Efficacy of Treatments for Improving Progression-Free Survival Among Low Grade Glioma: A Systematic Review and Survival Network Meta-Analysis

Abstract

Background

Methods

Results

Conclusions

Keywords

1. Introduction

2. Methods

2.1 Search strategy

Table 1. Search strategy.

2.2 Study inclusion and selection

Table 2. Description of each intervention.

2.3 Study outcome

2.4 Data extraction and risk-of-bias assessment

2.5 Statistical analysis

3. Results

3.1 Study selection and characteristics

Figure 1. PRISMA 2020 flow diagram for new systematic reviews which included searches of databases, registers and other sources.

Table 3. Number of studies exclude after a full-text review.

Table 4. The participant’s characteristics.

Table 5. The study characteristic.

3.2 Network plots

Figure 2. Network geometry for progression-free survival parameters in network meta-analysis.

3.3. Effects of treatment on progression-free survival

Figure 3. Forest plots for effects of treatment on progression-free survival.

Figure 4. Forest plots for effects of treatments compared with biopsy.

Figure 5. Cumulative ranking probabilities of treatment.

Table 6. League table of treatment comparative efficacy for progression-free survival.

Table 7. Radiation dose of GTRR studies.

3.4 Inconsistency and publication bias testing

Table 8. Side-splitting inconsistency.

3.5 Risk of bias

Table 9. Risk of bias of randomized control trials.

Table 10. Risk of bias of retrospective analysis.

4. Discussion

5. Conclusion

Availability of data, code and other materials

Extended data

Acknowledgments

References

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