rano 2.0 Background of standard development
Different response evaluation criteria such as RANO-HGG, mRano and Irano may be used in different clinical trials of glioma, and inconsistent efficacy evaluation results may occur. A multicenter study of glioblastoma found no statistically significant difference between different evaluation criteria for PFS or the association between PFS and OS. In addition, in 2021, the World Health Organization (WHO) formulated a new standard for the classification of tumors in the CNS, and the traditional method of distinguishing between high and low tumors based on whether they are intensified or not is no longer applicable. In view of this, RANO integrated the RANO-HGG and RANO-LGG criteria to form a unified efficacy evaluation standard for glioma**RANO20。
rano 2.0 is suitable for glioblastoma, all grades of IDH mutant glioma and other glioma types, and is suitable for all kinds of special ** modalities.
rano 2.0 of the evaluation method
1.2D measurement vs 3D volume measurement
There is currently no evidence that volumetric analysis has a clear advantage over 2D measurements. rano 2.0 Two-dimensional tumor measurement is still recommended as the primary measurement method, and volume measurement methods can also be used if conditions allow. It is important to note that for any particular trial, a two-dimensional measurement or a three-dimensional volume measurement should be pre-specified for all patients undergoing ** to ensure consistency. In 3D volumetric measurements, partial response (PR) is defined as a 65% reduction in volume, which corresponds to a 50% reduction in area in the current standard; Disease progression (PD) is defined as a 40% increase in volume, which corresponds to a 25% increase in area.
Table. The correspondence between the bilateral product and the change in volume during the evaluation of efficacy.
2.Measurable and non-measurable lesions
1) Measurable lesions: defined as enhancing or non-enhancing lesions that appear on MRI as well-defined, with two vertical diameters of 10 mm on a single level and visible on two or more layers, with a layer thickness of 4 mm and a layer spacing of 0 mm. For two-dimensional measurements, the maximum plane of the lesion extent (axial, coronal, or sagittal view) should be selected.
In three-dimensional volume measurement, lesions can be measured as enhanced or non-enhancing lesions with at least 1 cm in all three orthogonal directions.
Thick layers on MRI scans are not recommended, but in this case, the two vertical diameters of the baseline measurable lesion should be at least twice the layer thickness and layer spacing (i.e., if the layer thickness is 5 mm, the layer spacing should be 1.).5 mm, the tumor is at least 13 mm on both vertical diameters).
Measurement of cystic or perioperative tumors remains challenging. This lesion should generally be considered unmeasurable unless there is a nodular component of 10 to 10 mm in diameter. The cyst cavity or surgical cavity should not be measured when determining the ** response.
2) Non-measurable lesions: defined as lesions that are only one-dimensional measurable or have unclear boundaries or a maximum vertical diameter of <10mm. If the patient is completely resected, the best imaging efficacy in the follow-up ** is evaluated as stable disease (SD) until a new lesion appears. Therefore, only patients with measurable lesions should be included in the overall response rate assessment, while patients without measurable lesions could be included in the assessment of other outcomes, such as time to endpoint events (e.g., progression-free survival or overall survival) and clinical functioning.
3.Target lesions
When there are multiple measurable lesions, for studies that only evaluate enhancement lesions or non-enhancement lesions, at least 2 but no more than 3 lesions should be measured as target lesions; For studies that required both enhancing and non-enhancing lesions to be measured, the target lesions that needed to be measured included up to 2 enhancing lesions and up to 2 non-enhancing lesions. Enhancing lesions can occur in non-enhancing lesions. The sum of the vertical diameter products of these lesions should be determined.
Selection of target lesions: In general, the largest enlarged lesions should be selected, and the lesions should also be reproducibly measurable. Sometimes, the largest lesion may not be reproducible, and the next largest lesion that can be reproducibly measured should be selected. For patients with multiple lesions, the growing lesion should be selected as the target lesion, regardless of its relative size.
The process of identifying target lesions is as follows:
4.Baseline MRI
rano 2.0 It is recommended to use an MRI scan about 4 weeks (21-35 days) after the end of radiotherapy as a baseline scan for the evaluation of the efficacy of newly diagnosed glioma. Patients who have had severe deterioration before baseline MRI scans after radiotherapy can withdraw from clinical studies due to clinical progression. For newly diagnosed glioma patients who did not receive radiation**, MRI scans prior to adjuvant ** were used as baseline scans after surgical resection. For patients with glioma, the MRI scan before is used as the baseline scan.
In general, baseline MRI scans should be as close to ** as possible, with a maximum interval of no more than 14 days, especially for patients with glioblastoma. Although immediate postoperative MRI is no longer used as a baseline scan for response evaluation, immediate postoperative scanning is still important for detecting surgical complications and determining the degree of surgical resection.
5.** Access criteria for clinical trials in progressive disease
rano 2.0 It is recommended that in the case of a stable or increased dose of corticosteroids, an increase in the product of the maximum vertical diameter of the lesion is greater than 25%, or the volume increases by more than 40%, or a new measurable lesion appears, it can be included in the clinical trial of ** disease. Clinical deterioration alone or corticosteroid dose escalation alone is not sufficient to diagnose disease progression.
Given the challenge of determining imaging progression, RANO 20 recommends that neuroimaging for at least 3 months be routinely performed for ** glioblastoma and WHO grade 4 IDH-mutant astrocytoma. Patients with WHO grade 2 and 3 IDH-mutant gliomas and other gliomas routinely undergo neuroimaging for at least 12 months before disease progression can be determined to be included in the appropriate clinical studies.
Because of the high incidence of pseudoprogression in the first 12 weeks after chemoradiotherapy for glioblastoma (30% to 40%), and because of the poor correlation between radiographic changes and disease progression (PD) and survival during this period, RANO20 recommends that within 12 weeks after concurrent chemoradiotherapy, if imaging suggests progression (25% increase in area or 40% increase in volume compared to previous scan), but the patient is clinically stable, MRI scans should be repeated every 4 to 8 weeks to confirm progression before the patient needs to withdraw from the study. If subsequent imaging supports true tumor progression, the date of progression should be retroactive to the time of the scan when the progression was first measured. Patients who have progressed within the first 12 weeks after the end of radiotherapy should be excluded from clinical trials for ** disease, unless progression is significantly beyond the radiation range or histopathologically confirmed progression.
Currently, pathology has limited reliability in differentiating progression from pseudoprogression, and the RANO Working Group is addressing this issue. Advanced imaging techniques such as diffusion MRI, perfusion MRI, amino acid PET, etc., may help distinguish progression from pseudoprogression, but are not included in RANO20 requires further validation.
For IDH-mutant gliomas and other gliomas, the time frame for pseudoprogression may be well beyond 3 months. For these tumors, rano20 It is recommended to reconfirm progression at 3 months after the completion of radiotherapy and to scan again at the last time point before entering the ** tumor trial.
6.Definition of radiographic response and progression
For newly diagnosed patients with glioma who are undergoing radiation**, the imaging response must be determined by comparison with tumor measurements obtained at baseline before ** or at the first scan after radiotherapy. Partial response (PR) is defined as a 50% reduction in the sum of the vertical diameter products of all measurable target lesions, or a 65% reduction in volume, compared to baseline, for at least 4 weeks with a stable or reduced corticosteroid dose.
Disease progression (PD) is defined as a 25% increase in the sum of the vertical diameters of all measurable target lesions, or a 40% increase in volume, compared to the minimum tumor measurements before baseline or after the start of the disease. The emergence of new measurable lesions is also considered progression, unless confirmed progression is required according to the study protocol, in which case it should be added to the sum of existing target lesions, and progression will only occur if there is a 25% increase in area or a 40% increase in volume on repeat imaging. Steroid dosage must also be considered.
Occasionally, there may be definite progression of non-measurable lesions (lesions increase by at least 5 5 mm and become measurable, i.e., 10 10 mm) or non-target lesions (25% increase in area or 40% increase in volume). These lesions should be added to the sum of existing target lesions, and if there is a 25% increase in total area or a 40% increase in volume, even if the target lesion is SD or PR, it is still considered progressive and needs to be stopped**.
Enhancing lesions should be measured for IDH wild-type glioblastoma, and T2 flair should be measured for non-enhancing lesions with IDH mutations and rare non-enhancing glioblastoma. For tumors with a mix of enhancing and non-enhancing components, enhancing and non-enhancing lesions can be measured, however, if the lesions determine the progression required for enrollment in the study, it is also acceptable to measure only enhancing lesions.
The following table summarizes the specific reaction criteria.
Criteria for determining the response of enhanced lesions.
Response criteria for non-enhancing lesions.
Tumor response evaluation criteria with both enhancing and non-enhancing components.
Not related to peritumoral edema).
Reference: Patrick Y wen; et al. rano 2.0: update to the response assessment in neuro-oncology criteria for high- and low-grade gliomas in adults. j clin oncol 2023 sep, doi.org/10.1200/jco.23.01059
Please note that this article is for the purpose of learning and reference of relevant professionals, and all information in this article is not used as a basis for diagnosing and ** diseases. If you experience any of the symptoms described in this article, seek medical attention promptly. In addition, this article is only an excerpt of the original text, and the content may be incomplete or deviate from the original text, please refer to the original text for more complete information.
Written by: Zhang Jiapeng.
Reviewer: Gai Jingjing, Zhang Junping.
Typesetting: Zhang Jingjing.