Tecnología de imagenología intraoperatoria para maximizar el grado de resección del glioma
Referencias
Referencias de los estudios incluidos en esta revisión
Referencias de los estudios excluidos de esta revisión
Referencias de los estudios en curso
Referencias adicionales
Referencias de otras versiones publicadas de esta revisión
Characteristics of studies
Characteristics of included studies [ordered by study ID]
| Study characteristics | ||
| Methods | Randomised controlled trial. Randomisation: Participants were randomised and allocated to either conventional neurosurgery or iMRI. Randomisation was performed by the first author using specific software for randomisation in clinical trials. No randomisation blocks were used. Sample size: "To reduce the chance for type I errors (false positive) we used an alpha value of 0.05. To reduce the chance for type II errors (false negative) we used a beta value of 0.2 leading to a power of 0.8. We considered a 10% additional resection of the preoperative tumor volume as the minimal clinically relevant difference, with an estimated standard deviation of approximately 12%. This led to 23 patients in each treatment group. To compensate for loss to follow‐up we intended to include a total of 54 patients for the complete study." Blinding: "The neurosurgeon could not be blinded for the procedure. We did not intend to blind the physicians on the ward, nor the patients. Volumetric assessment of pre‐ and postoperative tumor volume was performed by a single blinded researcher." | |
| Participants | Inclusion criteria: Supratentorial brain tumour suspected to be glioblastoma on contrast‐enhanced diagnostic MRI, indication for gross total resection of the tumour, age 18 years or older, WHO Performance Scale 2 or better, ASA class 3 or better, adequate knowledge of the Dutch or French language, and informed consent. Exclusion criteria: Recurrent brain tumour, multiple brain tumour localisations, earlier skull radiotherapy, earlier chemotherapy for glioblastoma, chronic kidney disease or other renal function disorder, and a known magnetic resonance‐contrast allergy. | |
| Interventions | Intervention: Low field intraoperative MRI (Medtronic PoleStar N20 0.15 Tesla moveable magnet and the StarShield tent). Control: Neuronavigation guided tumour resection. | |
| Outcomes | Residual tumour volume; complications; quality of life (EORTC QLQ‐C30); overall survival | |
| Notes | Sponsored by Medtronic: "This study is part of the PhD thesis of the first author, and has been financially supported by Medtronic Navigation. Medtronic Navigation was not involved in writing the protocol, had no access to the data, was not involved in writing the manuscript, and had no veto right for submission." Definitions: Residual tumour volume (RTV) percentage is used as the primary endpoint to assess extent of tumour resection. Pre‐ and postoperative tumour volume was calculated by segmenting the hyperintense area on contrast‐enhanced T1 MRI (including enclosed central necrosis) and subtracting the hyperintense area on native T1 MRI to compensate for blood in the resection cavity. Measurements were performed using OsiriX software (Pixmeo SARL, Bernex, Switzerland) on Mac OS X using a Wacom Bamboo pen mouse for contour drawing. Postoperative tumour volume was divided by preoperative tumour volume to calculate the fraction of RTV. Multiplying the fraction with 100% provided the RTV. In formula: RTV = (postoperative contrast enhancement/preoperative contrast enhancement) × 100% | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation was performed by the first author using TEN‐ALEA software for randomisation in clinical trials. |
| Allocation concealment (selection bias) | Unclear risk | Not stated |
| Blinding of participants and personnel (performance bias) | High risk | "The neurosurgeon could not be blinded for the procedure. We did not intend to blind the physicians on the ward, nor the patients. Volumetric assessment of pre‐ and postoperative tumor volume was performed by a single blinded researcher." |
| Blinding of outcome assessment (detection bias) | Low risk | "The neurosurgeon could not be blinded for the procedure. We did not intend to blind the physicians on the ward, nor the patients. Volumetric assessment of pre‐ and postoperative tumor volume was performed by a single blinded researcher." |
| Incomplete outcome data (attrition bias) | Low risk | All participants are accounted for and included in the analysis. |
| Selective reporting (reporting bias) | High risk | Quality of life data not reported: "After consultation of a health‐technology assessment expert we decided to refrain from any further statistical analyses due to the small sample size." |
| Other bias | High risk | 1. Interim analysis/abbreviated study. Stopped on the basis of the interim analysis, although this was not specified a priori. Reasons for stopping included slow recruitment, technical issues with the equipment, prolonged duration of surgery, and concerns over effect size ("the main reason was that we estimated that our minimally required difference of 10% would not be consistent with the actual results"). 2. Industry sponsorship: "This study is part of the PhD thesis of the first author, and has been financially supported by Medtronic Navigation. Medtronic Navigation was not involved in writing the protocol, had no access to the data, was not involved in writing the manuscript, and had no veto right for submission." |
| Study characteristics | ||
| Methods | Randomised controlled trial. Randomisation of participants was done in blocks of 4 on a 1‐to‐1 ratio using BiAS for Windows 9.01 by an assistant who had no clinical involvement in the trial. Sample size: The sample size calculation was done to detect a difference of 25% between groups for the primary endpoint with a power of 80%. Blinding: Investigators who assessed eligibility of participants and scheduled surgeries were masked to treatment group assignment by use of a sealed envelope design. Surgeons and participants were not masked to the treatment group assignment, but the neuroradiologist who analysed MRI data was masked. | |
| Participants | Inclusion criteria: Adults ( ≥ 18 years) with known or suspected gliomas showing distinct contrast enhancement on T1‐ weighted MRI amenable to radiologically complete resection were eligible. Exclusion criteria: Presence of cardiopulmonary or hepatorenal comorbidities; tumours that crossed the midline or were located in the basal ganglia, cerebellum, brain stem, or otherwise in close proximity to eloquent brain structures prohibiting or questioning complete resectability; contraindications to MRI examination (e.g. pacemaker); and inability to give consent due to neuropsychological deficits or a language barrier. | |
| Interventions | Intervention: Mobile intraoperative ultralow field (0.15 Tesla) MRI system (PoleStar N‐20, Odin Medical Technologies, Yokneam, Israel and Medtronic, Louisville, CO, USA). Control: "Conventional micro neurosurgical resection" including Cavitron Ultrasonic Aspirator (CUSA) and neuronavigation. The use of intraoperative ultrasound or fluorescence‐guided surgery with 5‐aminolevulinic acid was not allowed in either group. | |
| Outcomes | Primary: Extent of resection. Secondary: "Volume of residual tumour on postoperative MRI and progression‐free survival (PFS) at 6 months. We also compared the duration of surgery and treatment‐related morbidity." | |
| Notes | Definitions: All participants underwent high‐field MRI at 1.5 T or 3.0 T with and without contrast agent within 7 days before surgery and within 72 h after surgery. 1 masked, independent, and experienced neuroradiologist (AB) assessed MRIs to establish the extent of resection and undertake volumetric analyses of the tumours and tumour residues. Residual tumour was defined as detectable contrast enhancement on T1‐weighted imaging with a volume of more than 0.175 cm3 on postoperative MRI as done previously. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation of participants was done in blocks of 4 on a 1‐to‐1 ratio using BiAS for Windows 9.01 by an assistant who had no clinical involvement in the trial. |
| Allocation concealment (selection bias) | High risk | Sealed envelope design |
| Blinding of participants and personnel (performance bias) | High risk | Surgeons and participants were not blinded. |
| Blinding of outcome assessment (detection bias) | Low risk | Only the neuroradiologist analysing the MRI data was blinded, which is important for assessing extent of resection. Assessors of clinical outcomes were not masked, which would have affected PFS and treatment‐related morbidity. |
| Incomplete outcome data (attrition bias) | High risk | 49 of 58 participants analysed (4 excluded in each arm due to diagnosis of a metastasis, and 1 in the iMRI arm withdrew consent). |
| Selective reporting (reporting bias) | Low risk | All prespecified outcomes reported (extent of resection, residual tumour volume, PFS, and treatment‐related morbidity). |
| Other bias | High risk | 1. Interim analysis/abbreviated trial. Stopped early due to an interim analysis resulting in a reduced sample size from 80 to 58. Due to the possible effect of this adjustment on the alpha error and to avoid over‐interpretation of the data, a P value of less than 0.04 was considered significant for the primary endpoint. 2. Industry sponsorship. No external funding source for the study declared, but one of the authors received an honorarium from Medtronic, which manufactures the scanner used. |
| Study characteristics | ||
| Methods | Randomised controlled trial. Randomisation was done by use of a dynamic allocation algorithm at a separate research unit, in which participants were allocated to minimise the imbalance between treatment groups. No permuted block randomisation was applied. Treatment allocation was communicated to local investigators first by telephone and additionally by fax. Sample size: Initial power calculations estimated 350 participants were required for an 80% power, but to allow premature study termination an interim analysis was scheduled after 270 participants whereby a 20\5 difference in PFS could be identified with a power of 80%. | |
| Participants | Inclusion criteria: People aged 18 to 72 years with suspected (as assessed by study surgeon) newly diagnosed and untreated malignant glioma. Tumours were to have a distinct ring‐like pattern of contrast enhancement with thick irregular walls on MRI and a core area of reduced signal suggestive of tumour necrosis. Exclusion criteria: Tumours in the midline, basal ganglia, cerebellum, or brain stem; more than 1 contrast‐enhancing lesion; substantial, non‐contrast‐enhancing tumour with areas suggesting low‐grade glioma with malignant transformation; medical reasons precluding MRI; inability to give consent; a tumour location that did not enable complete resection; KPS of 60 or less; renal or liver insufficiency; and a history of previous systemic malignancy. | |
| Interventions | Intervention: 5‐aminolevulinic acid (20 mg/kg body weight; medac, Wedel, Germany) in freshly prepared solutions orally 3 h (range 2 to 4) preoperatively. Solutions were prepared by dissolving the contents of a vial (1.5 g) in 50 mL of drinking water. Surgery was done by use of a modified neurosurgical microscope (OPMI Neuro/NC4 system with fluorescence kit, Carl Zeiss Surgical GmbH, Oberkochen, Germany), which enabled switching from conventional white xenon illumination to violet–blue excitation light. Control: Conventional microsurgery with white light. There was no placebo. For participants assigned white light, the tumour was resected by use of conventional illumination. | |
| Outcomes | Primary endpoints: complete tumour resection on MRI (< 72 hours post‐operation and > 1.5 T) and PFS. Secondary endpoints: residual tumour volume, overall survival, type and severity of neurological deficits after surgery, and toxic effects. Follow‐up was at 6 weeks then 3 months and subsequently at 3 monthly intervals until 18 months. | |
| Notes | Residual tumour was defined as contrast enhancement with a volume more than 0.175 cm3. Progression was defined as the occurrence of a new tumour lesion with a volume greater than 0.175 cm3, or an increase in residual tumour volume of more than 25%. Progression‐free survival was defined radiologically in the initial trial and by combined measures in the follow‐up paper (radiological criteria as above plus any new tumour or neurological worsening as defined by an NIHSS score increase over 1). Adverse events were classified according to the US National Cancer Institute common toxicity criteria (version 1.0). The NIHSS was used to measure postoperative deficits at 2 and 7 days after surgery, radiological progression at 6 weeks, then at 3, 6, 9, 12, 15, and 18 months' postsurgery. Intercentre consistency was not presented. The manufacturer of 5‐aminolevulinic acid (medac GmbH) was involved in the trial, and authors received assistance from the sponsor. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Performed independently with a dynamic allocation algorithm |
| Allocation concealment (selection bias) | Low risk | Treatment allocation was communicated by telephone and fax. |
| Blinding of participants and personnel (performance bias) | High risk | There was no blinding of surgeons, participants, or those involved with treatment. |
| Blinding of outcome assessment (detection bias) | Low risk | Neuropathology and neuroradiological assessments were blinded, which is important for assessing extent of resection. Clinical outcome assessment was not blinded, which would have affected PFS and adverse events. |
| Incomplete outcome data (attrition bias) | High risk | 13 participants were excluded for major violations of MRI inclusion criteria. 34 participants were excluded for histological criteria. In total, out of 322 randomly assigned participants, 270 were analysed intention to treat and 251 per protocol. |
| Selective reporting (reporting bias) | High risk | Full outcome data were not presented for survival, PFS, and adverse events (particularly in the earlier article and less so in the follow‐up paper). For example, Kaplan‐Meier plots with hazard ratio, 95% confidence interval and log‐rank analyses for the full cohort were not present for survival, PFS (no hazard ratio with 95% confidence interval), or time to deteriorate in the NIHSS (subgroup only of those with complete resection). Timing and severity of all adverse events were not fully documented (e.g. there were no data on wound infections or related complications and medical complications such as pulmonary thromboembolism). |
| Other bias | High risk | 1. Industry involvement. The sponsor was involved in the study. It was emphasised that there was no direct link with data interpretation. In addition, selected authors received remuneration from the sponsor. |
| Study characteristics | ||
| Methods | Randomised controlled trial. Participants were stratified by age (< 45 or ≥ 45) and KPS (≤ 70 or > 70), and they were evenly randomised to SS (without neuronavigation) or SN (with neuronavigation) using a computer‐generated list with allocation codes in random order, balanced for each stratum using blocks of 4. Sample size: Based on the results of a power analysis (details not specified in the paper), the authors planned to include 182 participants in the study, but the trial was stopped at 45 participants after an early pilot analysis. There was no blinding. | |
| Participants | Inclusion criteria: Solitary intracerebral space‐occupying lesion with (partial) contrast enhancement eligible for surgical debulking with the intention of gross total resection. Exclusion criteria: Previous neurosurgical treatment or any other known primary tumour elsewhere in the body. | |
| Interventions | Intervention: Neuronavigation was performed with bone fiducial markers. Preoperative magnetic resonance images were obtained using a 0.5‐Tesla system with contrast‐enhanced T1 weighted images. Volumetric measurements were performed to assess total lesion volume. Functional grading was recorded according to the MD Anderson scheme (Sawaya 1998). Planning involved localisation using fiducial markers, trajectory planning, and segmentation of the tumour boundary. Tools included an infrared pointer or mechanically tracked operating microscope. | |
| Outcomes | The primary outcome was extent of resection and survival. Other outcomes were procedure duration, usefulness of neuronavigation, extent of resection, quality of life, and postoperative course (including neurological status and adverse events). | |
| Notes | There were 3 early deaths in the navigation arm from systemic causes, which with the low numbers in each arm skewed the results. Interim analysis/abbreviated study. Definitions: Postoperative magnetic resonance images were obtained within 72 hours and subject to volumetric analysis. Clinical assessment was performed postoperatively within 3 days, 1 week, 6 weeks, and 3 months to assess adverse events and neurological status (using KPS and BI scores). A quality of life questionnaire (EORTC QLQ‐C30 and BR‐20) was filled out preoperatively and approximately 3 months after surgery. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | The participants were randomised to SS (without neuronavigation) or SN (with neuronavigation) using a computer‐generated list with allocation codes in random order, balanced for each stratum using blocks of 4. However, groups were not evenly distributed at baseline, with more eloquently located tumours in the standard surgery arm and histology with more metastasis in the navigation arm (although the latter was a variable not able to be determined preoperatively). |
| Allocation concealment (selection bias) | Unclear risk | Unclear risk |
| Blinding of participants and personnel (performance bias) | High risk | Not blinded |
| Blinding of outcome assessment (detection bias) | High risk | Not blinded |
| Incomplete outcome data (attrition bias) | High risk | 1 participant was excluded due to an alternative diagnosis (meningioma). Postoperative imaging was only assessed in 34/45 participants for tumour volume and 40/45 for contrast‐enhancing volume. Data for quality of life at 3 months were only reported on 64.5% of the total eligible population. |
| Selective reporting (reporting bias) | High risk | All outcome measures were reported to a degree. However, full data with suitable presentation and analysis were not available for survival (no Kaplan‐Meier plots), quality of life (no statistical analysis), and adverse events (no presentation of numbers of events). |
| Other bias | High risk | The trial was significantly underpowered and was terminated prematurely. Out of 280 potentially eligible participants, only 46 participants were included, with a planned target of 182. |
ASA: American Society of Anesthesiologists
EORTC QLQ‐C30: European Organisation for Research and Treatment of Cancer quality of life assessment
KPS: Karnofsky performance score
iMRI: intraoperative magnetic resonance imaging
MRI: magnetic resonance imaging
NIHSS: National Institutes of Health Stroke Scale
PFS: progression‐free survival
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
| Only abstract available (report is of published conference proceedings). Contacted authors but no reply. Insufficient information available to fully assess trial for either qualitative or quantitative inclusion. | |
| Only abstract available (report is of published conference proceedings). Contacted authors but no reply. Insufficient information available to fully assess trial for either qualitative or quantitative inclusion. | |
| Not a randomised controlled trial | |
| The addition of repetitive photodynamic therapy essentially precludes analysis of this trial as a test of intraoperative imaging alone. | |
| Prospective study; participants were not randomised. | |
| This trial assessed specificity and sensitivity of intraoperative 3D ultrasound as diagnostic test rather than treatment option. | |
| Only abstract available (report is of published conference proceedings). Contacted authors but no reply. Insufficient information available to fully assess trial for either qualitative or quantitative inclusion. | |
| Further report of Stummer 2006 trial; only new data are on spectroscopy and photodynamic therapy. | |
| A randomised controlled trial on the diagnostic effects of different doses of 5‐aminolevulinic acid (clinical, spectrophotometric, pathological). | |
| Author stated that this was not a randomised controlled trial. | |
| Author stated that this was not a randomised controlled trial. | |
| Author stated that this was not a randomised controlled trial. | |
| Not a randomised controlled trial; "patient selection was based on economic status and the availability of iMRI'" |
iMRI: intraoperative magnetic resonance imaging
Characteristics of ongoing studies [ordered by study ID]
| Study name | Imaging procedure using ALA in finding residual tumor in grade IV malignant astrocytoma |
| Methods | "Randomised" ‐ possibly diagnostic only trial design |
| Participants | Newly diagnosed and recurrent grade IV glioma |
| Interventions | 2 doses of 5‐ALA |
| Outcomes |
|
| Starting date | August 2008 |
| Contact information | Andrew Sloan |
| Notes | Case Medical Center, Cleveland, Ohio, USA |
| Study name | Comparison of neuronavigational systems for resection‐control of brain tumors |
| Methods | Randomised trial |
| Participants | Neuroradiological evidence of a brain lesion |
| Interventions | Intraoperative magnetic resonance (PoleStar N‐20) versus intraoperative ultrasound (SonoWand) |
| Outcomes |
|
| Starting date | 2009 |
| Contact information | Andrew Kanner |
| Notes | Tel Aviv, Israel |
| Study name | Fluorescence‐guided surgery for low‐ and high‐grade gliomas |
| Methods | Randomised. Single‐blind |
| Participants | Newly diagnosed glioma (high and low grade) |
| Interventions | 5‐ALA (Gliolan) versus placebo (ascorbic acid) |
| Outcomes |
|
| Starting date | November 2010 |
| Contact information | Nader Sanai (principal investigator), Norissa Honea (overall contact) |
| Notes | Barrow, Phoenix, Arizona, USA |
| Study name | Intraoperative MRI and 5‐ALA Guidance to Improve the Extent of Resection in Brain Tumor Surgery (IMAGER) |
| Methods | Randomised |
| Participants | Newly diagnosed supratentorial intra‐axial brain tumour suspicious for malignant glioma. Deemed resectable |
| Interventions | Intervention: 5‐ALA and intraoperative MRI Control: 5‐ALA |
| Outcomes |
|
| Starting date | February 2013 |
| Contact information | Christian Senft |
| Notes | Johann Wolfgang Goethe University Hospitals, Germany |
| Study name | |
| Methods | Randomised controlled trial. Randomisation was done by 2 clinical research associates (QY Wu and Ye Wang) at the clinical research institute, Huashan Hospital, using software specially designed for this trial according to a dynamic allocation algorithm. This software ensured that no one could predict the randomisation result. This dynamic allocation algorithm ensured the minimum imbalance between groups after recruiting each participant within 6 covariates with different weights, including tumour grade · 3 (HGG versus LGG), age · 2 (18 to 44, 45 to 64, or 65 to 70 years), KPS · 2 (70 to 90 versus 100), the vicinity of tumour to eloquent brain regions · 1 (non‐eloquent versus eloquent), tumour site · 1 (frontal, parietal, temporal, insular, or occipital lobe), and hemisphere mainly involved by tumour · 1 (non‐dominant versus dominant). Sample size: The estimated sample size was 320 participants to detect a difference of 15% between the study arms for the primary endpoint in the full analysis set, given 90% complete power (e.g. probability of rejecting all false null hypotheses) with an experiment‐wise type I error of 0.05. |
| Participants | Inclusion criteria: 18 to 70 years of age with newly diagnosed (diagnosed presurgically by board‐certified radiologists and neurosurgeons), untreated malignant cerebral glioma (WHO grade II‐IV); with supratentorial lesion involving the frontal, temporal, parietal, occipital, and/or insular lobe; with or without the lesion in an eloquent area; with preoperative assessment of attainable radiologically gross total tumour resection (by board‐certified anaesthesiologists and neurosurgeons); and with presurgical KPS score 70. Exclusion criteria: Recurrent glioma after initial surgical intervention (except needle biopsy); primary glioma with prior radiotherapy or chemotherapy; lesions of the midline, basal ganglia, cerebellum, or brainstem; renal insufficiency or hepatic insufficiency; history of malignancy at the body site; other critical tumour location or physical status that did not enable complete resection of the tumour or restricted life expectancy; and contraindications precluding iMRI acquisition. |
| Interventions | Intervention: All resections were completed as safely as possible by the consultant surgeons in the same 3‐Tesla iMRI integrated neurosurgical suite by IMRIS Neuro (IMRIS, Inc). Control: No further surgery. |
| Outcomes | Primary: Extent of resection (EOR). Secondary: Progression‐free survival; overall survival; and surgery‐related morbidity. |
| Starting date | September 2011 |
| Contact information | Jinsong Wu |
| Notes | Interim analysis ‐ awaiting full results. Definitions: Gross total resection (GTR) was defined as the complete disappearance of all enhancing lesions (T1‐weighted) for HGG and the complete disappearance of all non‐enhancing (T2‐weighted fluid‐attenuated inversion recovery) lesions for LGG. The EORs were assessed quantitatively in volumetric analyses and stratified as follows: GTR, 100% resection; subtotal resection, 90% resection; partial resection, 70% resection; and biopsy. |
5‐ALA: 5‐aminolevulinic acid
HGG: high‐grade glioma
iMRI: intraoperative magnetic resonance imaging
LGG: low‐grade glioma
MRI: magnetic resonance imaging
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
| iMRI image‐guided surgery compared to standard surgery for high‐grade glioma | ||||||
| Patient or population: high‐grade glioma | ||||||
| Outcomes | Illustrative comparative risk* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | |||||
| Control | Image‐guided surgery | |||||
| Extent of resection: complete resection | 321 per 100 | 4 per 100 | RR 0.13 (0.02 to 0.96) | 49 participants | ⊕⊝⊝⊝1,2,3 | Small trial of highly selected participants with potential bias in allocation and performance. One other trial reported this outcome but did not contribute towards the analysis. |
| Adverse events | Inadequately and inconsistently reported in the trial | ⊕⊝⊝⊝4 | Adverse events were reported in an inconsistent manner and not according to the manner prespecified in our protocol. Additionally, we were mainly interested in identifying serious adverse events, which were inadequately reported | |||
| Overall survival | Not estimable | ⊕⊝⊝⊝4 | Not reported by trial authors so graded as very low quality evidence | |||
| Progression‐free survival | Not estimable | ⊕⊝⊝⊝4 | Progression‐free survival or time to progression was not adequately reported in the trial | |||
| Quality of life | Not estimable | ⊕⊝⊝⊝4 | Quality of life was not reported in the trial | |||
| *The basis for the assumed risk is only based on individual trials as only single trial reports were available. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Expressed in terms of risk of incomplete resection (bad outcome). | ||||||
| 5‐ALA image‐guided surgery compared to standard surgery for high‐grade glioma | ||||||
| Patient or population: high‐grade glioma | ||||||
| Outcomes | Illustrative comparative risk* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | |||||
| Control | Image‐guided surgery | |||||
| Extent of resection: complete resection | 641 per 100 | 35 per 100 | RR 0.55 (0.42 to 0.71) | 270 participants (1 study) | ⊕⊕⊝⊝2 | Highly selected participants with potential bias in allocation and performance |
| Adverse events | Inadequately and inconsistently reported in the trial | ⊕⊝⊝⊝3 | Adverse events were reported in an inconsistent manner and not according to the manner prespecified in our protocol. Additionally, we were mainly interested in identifying serious adverse events, which were inadequately reported | |||
| Overall survival | Not estimable due to reporting of HR and since just a single trial reported on this outcome we did not arbitrarily choose a snap shot in time in which to use as basis to calculate the assumed and corresponding risks as this may be misleading. | HR 0.82 (0.62 to 1.07) | 270 participants (1 study) | ⊕⊕⊝⊝2 | The overall quality of this outcome was low in this trial and was downgraded for highly selected participants with potential bias in allocation and performance | |
| Progression‐free survival | Not adequately reported in the trials | ⊕⊝⊝⊝3 | Progression‐free survival or time to progression was not adequately reported in the trial | |||
| Quality of life | Inadequately reported or not assessed at all in the included trials | ⊕⊝⊝⊝3 | Quality of life was not reported in the trial | |||
| *The basis for the assumed risk is only based on individual trials as only single trial reports were available. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Expressed in terms of risk of incomplete resection (bad outcome). | ||||||
| Neuronavigation image‐guided surgery compared to standard surgery for high‐grade glioma | ||||||
| Patient or population: high‐grade glioma | ||||||
| Outcomes | Illustrative comparative risk* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | |||||
| Control | Image‐guided surgery | |||||
| Extent of resection: complete resection | Not estimable | Not estimable | Not reported | 45 participants | ⊕⊝⊝⊝1,2,4 | Small study of highly selected participants at very high risk of allocation bias.Complete resection was achieved in three participants in the control group and five participants in the neuronavigation group. However, there was significant attrition, with not all participants completing imaging, and the denominators for these figures were not stated, precluding formal analysis |
| Adverse events | Inadequately and inconsistently reported in the trial | ⊕⊝⊝⊝2 | Adverse events were reported in an inconsistent manner and not according to the manner prespecified in our protocol. Additionally, we were mainly interested in identifying serious adverse events, which were inadequately reported | |||
| Overall survival | Not estimable | ⊕⊝⊝⊝3 | Not reported by trial authors so graded as very low quality evidence | |||
| Progression‐free survival | Not estimable | ⊕⊝⊝⊝2 | Progression‐free survival or time to progression was not reported in the trial | |||
| Quality of life | Inadequately reported or not assessed at all in the included trials | ⊕⊝⊝⊝3 | Quality of life was reported in the trial but only 19 participants (8 in the neuronavigation arm and 11 in the standard surgery arm) completed questionnaires postoperatively at 3 months', constituting only 64.5% of all eligible participants, and no statistical analysis was presented | |||
| *The basis for the assumed risk is only based on individual trials as only single trial reports were available. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Small trial so quality of the evidence downgraded by one level. | ||||||
| Score | Definition |
|---|---|
| 100 | Normal, no complaints, no evidence of disease |
| 90 | Able to carry on normal activity: minor symptoms of disease |
| 80 | Normal activity with effort: some symptoms of disease |
| 70 | Cares for self: unable to carry on normal activity or active work |
| 60 | Requires occasional assistance but is able to care for needs |
| 50 | Requires considerable assistance and frequent medical care |
| 40 | Disabled: requires special care and assistance |
| 30 | Severely disabled: hospitalisation is indicated, death is not imminent |
| 20 | Very sick, hospitalisation is necessary: active treatment is necessary |
| 10 | Moribund, fatal processes are progressing rapidly |
| 0 | Dead |
| Grade | Definition |
|---|---|
| 0 | Fully active, able to carry on all pre‐disease performance without restriction |
| 1 | Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. |
| 2 | Ambulatory and capable of all self care, but unable to carry out any work activities. Up and about more than 50% of |
| 3 | Capable of only limited self care, confined to bed or chair more than 50% of waking hours |
| 4 | Completely disabled. Cannot carry out any self care. Totally confined to bed or chair |
| 5 | Dead |
