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Background Since IDH-mutant (mIDH) low-grade gliomas (LGGs) progress slowly and have a relatively long survival, there is a significant need for earlier measurements of clinical benefit. Guidance using the LGG RANO criteria recommends serial bidirectional (2D) measurements on a single slice; however, questions remain as to whether volumetric (3D) measurements are better, since they would allow for more accurate measurements in irregular shaped lesions and allow readers to better assess areas of subtle change. Methods Twenty-one (out of 24) non-enhancing, recurrent mIDH1 LGGs were enrolled in a phase I, multicenter, open-label study of oral ivosidenib (NCT02073994), and with imaging pre- and post-treatment as part of this exploratory ad hoc analysis. 2D and 3D measurements on T2-weighted FLAIR images were centrally evaluated at an imaging contract research organization using a paired read and forced adjudication paradigm. The effects of 2D vs 3D measurements on progression-free survival (PFS), growth rate measurement variability, and reader concordance and adjudication rates were quantified. Results 3D volumetric measurements showed significantly longer estimated PFS (P = .0181), more stable (P = .0063) and considerably slower measures of tumor growth rate (P = .0037), the highest inter-reader agreement (weighted kappa = 0.7057), and significantly lower reader discordance rates (P = .0002) with 2D LGG RANO. Conclusion 3D volumetric measurements are better for determining response assessment in LGGs due to more stable measures of tumor growth rates (ie, less “yo-yo-ing” of measurements over time), highest inter-reader agreement, and lowest reader discordance rates. Continued evaluation in future studies is warranted to determine whether these measurements reflect clinical benefit.

BACKGROUND Accurate response criteria are crucial for determining treatment efficacy. The response assessment in neuro-oncology (RANO) criteria was developed to standardize response assessment in neuro-oncology. Modified RANO (m-RANO) criteria were recently proposed to address some limitations of the initial criteria including the use of a post-radiation baseline and an additional scan to confirm progression. We sought to identify differences in the association of progression-free survival (PFS) and overall survival (OS) using RANO and m-RANO criteria. METHODS We conducted a retrospective review of newly diagnosed glioblastoma (GBM) patients treated at Dana-Farber Cancer Institute from January 2013 until December 2019. Patients with available clinical and imaging data obtained before initiation of treatment, after radiation completion and at intervals of 1 to 3 months were included. MRIs were evaluated by two independent readers, and PD dates determined using RANO and m-RANO criteria. RESULTS 552 patients were included. 97.1% of the tumors were IDH wild-type. MGMT promoter was unmethylated in 51.4%, methylated in 35.1% and undetermined in 8.5%. Median OS among patients was 18.1 months. 72 patients (13%) did not have PD at the end of the study. 83 patients had treatment change while being clinically stable and without a confirmation scan and were excluded from the final analysis. PFS was 8.2 months with RANO and 8.4 months with mRANO. Difference in PD dates between RANO and m-RANO was detected in 76 patients (14%), where PFS was 3.5 months with RANO and 5.1 months with m-RANO. These patients had a worse median OS than those with identical RANO and m-RANO PD dates (15.2 vs. 22.4 months, p< 0.0001). CONCLUSION RANO and m-RANO criteria resulted in identical PFS for most patients. 14% of patients had discordant PD dates and a worse prognosis. These patients progressed early, and their PD was identified sooner with RANO criteria.

Antiangiogenic agents can induce a distinct MRI pattern in glioblastoma, characterized by a decrease in the contrast enhancement on T1‐weighted images and a simultaneous hyperintensity on T2‐weighted or fluid‐attenuated inversion recovery images.

Purpose Although we have shown the clinical benefit of bevacizumab (BEV) in the treatment of unresectable newly diagnosed glioblastomas (nd-GBM), the relationship between early radiographic response and survival outcome remains unclear. We performed a volumetric study of early radiographic responses in nd-GBM treated with BEV. Methods Twenty-two patients with unresectable nd-GBM treated with BEV during concurrent temozolomide radiotherapy were analyzed. An experienced neuroradiologist interpreted early responses on fluid-attenuated inversion recovery (FLAIR) and gadolinium-enhanced T1-weighted images (GdT1WI). Volumetric changes were evaluated using diffusion-weighted imaging (DWI) and GdT1WI according to the Response Assessment in Neuro-Oncology (RANO) criteria. The results were categorized into improved (complete response [CR] or partial response [PR]) or non-improved (stable disease [SD] or progressive disease [PD]) groups; outcomes were compared using Kaplan–Meier analysis. Results The volumetric GdT1WI improvement was a significant predictive factor for overall survival (OS) prolongation (p = 0.0093, median OS: 24.7 vs. 13.6 months); however, FLAIR and DWI images were not predictive. The threshold for the neuroradiologist’s interpretation of improvement in GdT1WI was nearly 20% of volume reduction, which was lesser than 50%, the definition of PR applied in the RANO criteria. However, even less stringent neuroradiologist interpretation could successfully predict OS prolongation (improved vs. non-improved: p = 0.0067, median OS: 17.6 vs. 8.3 months). Significant impact of OS on the early response in volumetric GdT1WI was observed within the cut-off range of 20–50% (20%, p = 0.0315; 30%, p = 0.087; 40%, p = 0.0456). Conclusions Early response during BEV-containing chemoradiation can be a predictive indicator of patient outcome in unresectable nd-GBM.

ObjectivesReal-time assessment of treatment response in glioblastoma (GBM) patients on immune checkpoint blockade (ICB) remains challenging because inflammatory effects of therapy may mimic progressive disease, and the temporal evolution of these inflammatory findings is poorly understood. We compare GBM patient response during ICB as assessed with the Immunotherapy Response Assessment in Neuro-Oncology (iRANO) and the standard Response Assessment in Neuro-Oncology (RANO) radiological criteria.Methods49 GBM patients (seven newly diagnosed and 42 recurrent) treated with ICBs at a single institution were identified. Tumor burden was quantified on serial MR scans according to RANO criteria during ICB. Radiographic response assessment by iRANO and RANO were compared.Results82% (40/49) of patients received anti–PD-1, 16% (8/49) received anti-PD-L1, and 2% (1/49) received anti-PD-1 and anti-CTLA4 treatment. Change in tumor burden and best overall response ranged from −100 to +557% (median: +48%). 12% (6/49) of patients were classified as concordant non-progressors by both RANO and iRANO (best response: one CR, one PR, and four SD). Another12% (6/49) had discordant assessments: 15% (6/41) of RANO grade progressive disease (PD) patients had iRANO grade of progressive disease unconfirmed (PDU). The final classification of these discordant patients was pseudoprogression (PsP) in three of six, PD in two of six, and PDU in one of six who went off study before the iRANO assessment of PDU. iRANO delayed diagnosis of PD by 42 and 93 days in the two PD patients. 76% (37/49) patients were classified as concordant PD by both RANO and iRANO. 12% (6/49) of all patients were classified as PsP, starting at a median of 12 weeks (range, 4–30 weeks) after ICB initiation.ConclusionsStandard RANO and iRANO have high concordance for assessing PD in patients within 6 months of ICB initiation. iRANO was beneficial in 6% (3/49) cases later proven to be PsP, but delayed confirmation of PD by

INTRODUCTION Gliomas are one of the most common central nervous system tumors in adults. The Response Assessment Criteria in Neuro-Oncology (RANO) was developed to standardize the radiographic parameters used to assess therapeutic outcomes in glioma patients. A previous study has shown an association between therapeutic response based on RANO criteria and overall survival in glioma patients. However, the feasibility of applying RANO criteria in settings with limited resources has never been reported. This study aims to assess the feasibility of applying RANO criteria in clinical settings in Indonesia. This study also wants to see the role of the RANO criteria as a prognostic factor for gliomas in Indonesia. METHOD Data of glioma patients were retrospectively collected from Dharmais Cancer Hospital in Jakarta, Indonesia. Dharmais Cancer Hospital is the highest referral hospital for brain tumors in the country. Clinical and demographic data were collected from the medical record. RESULTS From 138 identified glioma patients from 2017 to May 2020, only 34 patients can be assessed using RANO criteria. The majority of the patients do not have post-surgical MRI that can be used as a baseline. Among 34 included patients, 38.2% were categorized as responsive, 23.5% as stable disease and 38.2% were categorized as progressive. Kaplan-Meier analysis showed that the median overall survival in the progressive group is significantly shorter than the median survival of responsive/stable group (21.2 vs. 57.5 months respectively, p=0.001). Multivariate cox regression analysis was performed to see the association of RANO criteria and other confounding variables (sex, age, glioma grade, glioma location, and therapy) with overall survival. The result showed that RANO progression was significantly associated with decreased survival (HR 18.38, p=0.045). CONCLUSION This retrospective analysis demonstrates the feasibility of applying RANO criteria in Indonesia and its association with overall survival.

Fotemustine (FTM) is a treatment option in recurrent malignant gliomas (MGs) after first-line Stupp treatment. The efficacy and the safety of fractionated FTM schedule proposed by Addeo et al was analysed in the present study in recurrent MGs patients. A retrospective analysis on 40 recurrent MGs patients and second-line fractionated FTM chemotherapy was performed. Response evaluation was assessed using RANO criteria and safety was assessed using CTCAE v.4.03. Subgroup analyses based on MGMT methylation, resurgery and reirradiation were performed. A review of the literature was also performed. The results revealed 5 partial responses (13%) and 19 stable diseases (47%) with a disease-control rate of 60%. Median progression-free survival (PFS) was 4 months, with a PFS of 33% at 6 months and 13% at 1 year. The median overall survival (OS) was 9 months and OS at 6 months was of 55% and at 1 year of 30%. Methylated patients experienced longer mPFS (6 vs. 3 months; p=0.004) and mOS (10 vs. 4 months; p

Background and purpose To evaluate the patterns of failure following clinical introduction of amino-acid O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET)-PET-guided target definition for radiotherapy (RT) of glioblastoma patients. Materials and methods The first 66 consecutive patients with confirmed histology, scanned using FET-PET/CT and MRI were selected for evaluation. Chemo-radiotherapy was delivered to a volume based on both MRI and FET-PET (PET vol ). The volume of recurrence (RV) was defined on MRI data collected at the time of progression according to RANO criteria. Results Fifty patients were evaluable, with median follow-up of 45months. Central, in-field, marginal and distant recurrences were observed for 82%, 10%, 2%, and 6% of the patients, respectively. We found a volumetric overlap of 26%, 31% and 39% of the RV with the contrast-enhancing MR volume, PET vol and the composite MRPET vol , respectively. MGMT-methylation ( p =0.03), larger PET vol ( p p vol overlap. Conclusion The combined MRPET vol had a stronger association with the recurrence volume than either of the modalities alone. Larger overlap of PET vol and RV was observed for patients with MGMT-methylation, less extensive surgery, and large PET vol on the RT-planning scans.

The Response Assessment in Neuro-Oncology (RANO) Working Group is an international multidisciplinary group whose goal is to improve response criteria and define endpoints for neuro-oncology trials. The RANO criteria for high-grade gliomas attempt to address the issues of pseudoprogression, pseudoresponse, and nonenhancing tumor progression. Incorporation of advanced MR imaging may eventually help improve the ability of these criteria to define enhancing and nonenhancing disease better. The RANO group has also developed criteria for neurologic response and evaluation of patients receiving immunologic therapies. RANO criteria have been developed for brain metastases and are in progress for meningiomas, leptomeningeal disease, spinal tumors, and pediatric tumors.

INTRODUCTION Magnetic resonance imaging (MRI) is a fundamental component of longitudinal neuro-oncology evaluation and decision-making. The Response Assessment in Neuro-Oncology criteria for low-grade gliomas (RANOLGG) was designed as an outcome measure for clinical trials. Thus, this project intends to study the reliability of RANOLGG in the clinic setting. METHODS 21 pairs of brain MRIs, that averaged three years apart, were selected from 21 patients with tissue diagnosis of WHO grade 2 gliomas. Two neuro-oncologists and two neuro-radiologists reviewed and independently scored the MRI pairs according to RANOLGG categories of progressive disease, stable disease, minor response, partial response, and complete response. Kappa-Fleiss (KF) was used to evaluate agreement among reviewers. RESULTS Reviewers awarded identical scores in only 33% of MRI pairs and there was a complete disagreement in one MRI pair. Overall reliability of the criteria in the clinical setting is moderate (KF = 0.44). Agreement between neuroradiologists (KF = 0.51) and between neuro-oncologists (KF = 0.48) were similar. Interpretation of post-contrast T1-weighted images had a better agreement (KF = 0.31) than T2/FLAIR-weighted images which had a poor agreement (KF = -0.02). Classification of progression versus non-progression had only a moderate agreement (KF= 0.49). History of radiation therapy or chemotherapy did not influence the criteria reliability (fisher exact text, p = 0.58, p =0.27, respectively). CONCLUSION RANOLGG reliability in the clinical setting is moderate, therefore it should be used cautiously for clinical decision-making. Other tools that can support the neuro-oncologist in the follow-up of patients with low-grade glioma are additional MRI sequences other than T2/FLAIR and contrast – weighted images, computer-aided diagnosis such as volumetrics, spectroscopy, positron emission tomography, and multidisciplinary tumor boards. Likewise, when image criteria for low-grade gliomas are designed, T2/FLAIR should be used guardedly, due to low interpretation agreement.

INTRODUCTION: The purpose of this study was to evaluate the implementation of the radiological aspects of HERBY trial, and the practicality and feasibility of including multimodal imaging (MMI) to the response assessment in neuro-oncology (RANO) criteria in a pediatric high grade glioma cohort. METHODS: We analyzed MMI compliance rates and scan quality for participating sites, adjudication rates and reading times for the central review process, the influence of the different RANO criteria in the final response, and the benefit of incorporating MMI to the decision process. RESULTS: MMI compliance rates were: diffusion 82%, perfusion 60% and spectroscopy 48%. Of the received data 2% of the structural scans and 23% of the MMI scans were not of sufficient quality. Adjudication rates due to differing neuroradiologist responses were 50%, which resulted in a total average reading time per patient of ~3 hours. Increase in diameters of the target enhancing lesion was a reason for progression in 8/86 cases (9.3%) but never the only radiological or clinical reason. EFS was predicted earlier in 5/86 (5.8%) patients by MMI (diffusion, n=4; perfusion, n=1). CONCLUSION: The addition of MMI to the response criteria was difficult to assess due to low return rates and data quality, but MMI helped to determine progression prediction than structural imaging alone. Increase of target lesion diameter measurement, which accounts for a large proportion of reading time, was never the only reason to stablish disease progression.

The value of magnetic resonance (MR) imaging for the clinical management of brain tumour patients has greatly increased in recent years through the introduction of functional MR sequences. Previously, MR imaging for brain tumours relied for the most part on contrast-enhanced T1-weighted MR sequences but today with the help of advanced functional MR sequences, the pathophysiological aspects of tumour growth can be directly visualised and investigated. This article will present the pathophysiological background of the MR sequences relevant to neuro-oncological imaging as well as potential clinical applications. Ultimately, we take a look at possible future developments for ultra-high-field MR imaging.

Background. Diagnosis of pseudoprogression in patients with glioblastoma multiforme (GBM) is limited by Response Assessment in Neuro-Oncology (RANO) criteria to 3 months after chemoradiotherapy (CRT). Frequency of pseudoprogression occurring beyond this time limit was determined. Survival comparison was made between pseudoprogression and true progression patients as determined by using perfusion magnetic resonance imaging with ferumoxytol (p-MRI-Fe). Methods. Fifty-six patients with GBM who demonstrated conventional findings concerning for progression of disease post CRT were enrolled in institutional review board-approved MRI protocols. Dynamic susceptibility-weighted contrast-enhanced p-MRI-Fe was used to distinguish true progression from pseudoprogression using relative cerebral blood volume (rCBV) values. rCBV of 1.75 was assigned as the cutoff value. Participants were followed up using RANO criteria, and survival data were analyzed. Results. Twenty-seven participants (48.2%) experienced pseudoprogression. Pseudoprogression occurred later than 3 months post CRT in 8 (29.6%) of these 27 participants (ie, 8 [14.3%] of the 56 patients meeting the inclusion criteria). Overall survival was significantly longer in participants with pseudoprogression (35.2 months) compared with those who never experienced pseudoprogression (14.3 months; P , .001). Conclusions. Pseudoprogression presented after 3 months post CRT in a considerable portion of patients with GBM, which raises doubts about the value of the 3-month time limit of the RANO criteria. Accurate rCBV measurement (eg, p-MRI-Fe) is suggested when there are radiographical concerns about progression of disease in GBM patients, regardless of any time limit. Pseudoprogression correlates with significantly better survival outcomes.

Recently, the Neuro-oncology Working Group, Response assessment in neuro-oncology (RANO) introduced new response criteria for gliomas and its clinical implication. Establishing this working-progress platform and its first report, represent an important step forward in the accurate assessment of response to therapy in patients with malignant gliomas, not only in clinical trials but also in daily practice. Anti-angiogenic therapy and other new treatment modalities have increased the incidence and our awareness of novel imaging phenomena, such as pseudoprogression and pseudoresponse not only within clinical trials, but also in clinical practice. The new RANO criteria include imaging findings and also clinical parameters, such as steroid medication and neurological symptoms into account. Neuroradiologists, oncologists and neuro-oncologists must know the criteria, apply them to standardized findings communication and gain experience in order to correctly use these information. Further research is needed to allow the inclusion of new imaging techniques, such as perfusion, diffusion-weighted imaging, spectroscopy, and volumetric measurements, which will be probably incorporated in the near future.

The Macdonald criteria and the Response Assessment in Neuro-Oncology (RANO) criteria define radiologic parameters to classify therapeutic outcome among patients with malignant glioma and specify that clinical status must be incorporated and prioritized for overall assessment. But neither provides specific parameters to do so. We hypothesized that a standardized metric to measure neurologic function will permit more effective overall response assessment in neuro-oncology.An international group of physicians including neurologists, medical oncologists, radiation oncologists, and neurosurgeons with expertise in neuro-oncology drafted the Neurologic Assessment in Neuro-Oncology (NANO) scale as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. The scale was subsequently tested in a multicenter study to determine its overall reliability, inter-observer variability, and feasibility.The NANO scale is a quantifiable evaluation of 9 relevant neurologic domains based on direct observation and testing conducted during routine office visits. The score defines overall response criteria. A prospective, multinational study noted a90% inter-observer agreement rate with kappa statistic ranging from 0.35 to 0.83 (fair to almost perfect agreement), and a median assessment time of 4 minutes (interquartile range, 3-5).The NANO scale provides an objective clinician-reported outcome of neurologic function with high inter-observer agreement. It is designed to combine with radiographic assessment to provide an overall assessment of outcome for neuro-oncology patients in clinical trials and in daily practice. Furthermore, it complements existing patient-reported outcomes and cognition testing to combine for a global clinical outcome assessment of well-being among brain tumor patients.

In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of "omics in radiology"-radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

Purpose: Response assessment in brain tumors is currently done with the 2D Response Assessment in Neuro-Oncology (RANO) criteria. However, bevacizumab-treated patients may show pseudoresponse on contrast enhanced T1w- (T1w+C), and more infiltrative growth on T2w/FLAIR images at recurrence. We assessed whether in recurrent glioblastoma volumetric methods improve assessment of progressive disease (PD) over the RANO criteria, by correlating PD with overall survival (OS), the golden endpoint in oncology studies.

In der Behandlung hohergradiger hirneigener Tumoren muss man verlasslich beurteilen konnen, wie die Tumoren auf die Therapie ansprechen. Dies gilt fur den klinischen Alltag und klinische Studien gleichermasen. Die klassische Beurteilung des Therapieansprechens anhand der Macdonald-Kriterien wird den komplexer werdenden neuroonkologischen Therapien mit oft antiangiogen wirkenden Substanzen jedoch haufig nicht gerecht. Beispielsweise blieben fur die korrekte radiologische Beurteilung wichtige Phanomene wie Pseudoprogression und T2-Progress bislang unberucksichtigt. Die Arbeitsgruppe „Response Assessment in Neuro-Oncology (RANO)“ hat daher neue Kriterien (RANO-Kriterien) erarbeitet, die sowohl radiologische Besonderheiten neuer Therapieregime berucksichtigen als auch eine Standardisierung der Auswertung klinischer Studien ermoglichen soll. Im folgenden Artikel wird ein Uberblick uber die wichtigsten Neuerungen gegeben, welche fur den Radiologen bei der Befundung unmittelbar eine Rolle spielen.

Antiangiogenic treatment using bevacizumab may cause difficulties in distinguishing between antivascular and true antitumor effects when using MRI response criteria based on changes of contrast enhancement (i.e., Macdonald criteria). Furthermore, more precise tumor response assessment criteria (i.e., RANO criteria), which incorporate nonenhancing T2/FLAIR sequences into Macdonald criteria, may be influenced by other causes of T2/FLAIR hyperintensity (e.g., radiation-induced gliosis). The authors present discrepant MR and [18F]fluoroethyl-L-tyrosine PET imaging findings in a patient with bevacizumab treatment failure.

BACKGROUND: Accurate tumor measurement and response to therapy continue to be a challenge due to tumor heterogeneity, variation of imaging techniques and contrast administration and inter-observer variability. Structural imaging (T1 with enhancement, T2, FLAIR) plus multimodal imaging (diffusion, perfusion, 1H-spectroscopy, PET) combined with clinical information and guidelines from the RANO and RAPNO working groups are very helpful. However, for unresectable, non-radiated low grade asstrocytomas with ill-defined borders accurate measurement is critical to assess response to therapy. METHODS: We selected three patients with low-grade, mid-brain astrocytoma following biopsy or incomplete resection who received only chemotherapy. Three Pediatric Neuroradiologists measured the tumors at three time points in the longitudinal and two orthogonal short axes; RANO, linear measurements, and calculated tumor volume were recorded. Two experienced 3D-technologists used tumor segmentation software (IntelliSpace Portal, Philips, Cleveland, OH) to determine tumor volume. RESULTS: Percent change in tumor measurements over the three time points: Patient 1: RANO 0.41%, calculated volume 23.1%, segmented volume 48%. Patient 2: RANO 11.5%, calculated volume 14.6%, segmented volume 1.9%. Patient 3: RANO 1%, calculated volume 4.4%, segmented volume 8%. CONCLUSION: For our selected patients 3D measurements differed significantly and were incongruous with RANO measurements, indicating both minimal change and marked interval tumor growth in the same patient over time. Larger studies are required to confirm accuracy and feasibility of 3D volumetric analysis as a method to measure response to therapy in future low grade astrocytoma clinical trials.

One of the most vexing problems in neuro-oncology is the accurate determination of disease progression, which is often confounded by phenomena such as pseudoprogression. The advent of antiangiogenic agents has further obfuscated an already difficult problem by producing a new imaging artifact, namely pseudoresponse. With the increasing number of novel agents and delivery techniques being explored in clinical trials there is a strong need for robust and adaptable criteria to monitor response assessment and thus define endpoints. The Response Assessment in Neuro-Oncology (RANO) working group was created to address these and other problems as they relate to outcome assessments in neuro-oncology. This chapter provides a review of the work as of this writing performed by RANO to update response assessment criteria and endpoint definition as part of the fundamentals of clinical trial design across the spectrum of neuro-oncology.

BACKGROUND: The assessment of Bevacizumab efficacy in high-grade gliomas (HGG) depends on the response criteria used, with discrepancies between T1 Gadolinium-enhanced sequences, T2 sequences and neurological outcome. The aim was to compare McDonald's, RANO and RECIST 1.1 criteria to the clinical outcome in a consecutive series of HGG patients. METHODS: HGG patients treated at the Montpellier Cancer Institute were retrospectively selected. Patients with a Performance Status (PS) 20% of the product of perpendicular diameters. CONCLUSIONS: The high correlation between McDonald's and RANO criteria demonstrates the importance of accurately assessing changes in steroids and neurological state, as well as imaging response, in order to avoid concluding to a false efficacy on imaging only, when using the McDonald's criteria. These results raise the question of the value of the FLAIR assessment when McDonald's criteria are rigorously applied.

BACKGROUND: CNS progression results in frequent treatment failure for ALK+ NSCLC patients receiving the ALK inhibitor crizotinib. CNS efficacy is important in assessing new ALK inhibitors and accurate assessment of response/progression is vital in determining treatment efficacy. Data from two phase II studies in pre-treated ALK+ NSCLC were pooled to examine the CNS efficacy of the highly selective ALK inhibitor alectinib, using both Response Evaluation Criteria in Solid Tumors (RECIST) and Response Assessment in Neuro-Oncology (RANO) criteria to evaluate brain metastases. METHODS: The phase II, single-arm, multicenter studies both enrolled ALK+ NSCLC patients aged ≥18 years who had previously received crizotinib. NP28761 was conducted in North America only (NCT01871805); NP28673 was a global study (NCT01801111). All patients in both studies received 600mg oral alectinib twice daily. Patients underwent imaging at baseline to assess CNS metastases and CNS response was determined by an independent review committee (IRC) according to RECIST v1.1 or RANO criteria. RESULTS: Fifty-one patients had baseline measurable CNS disease by IRC according to RECIST v1.1, and 43 according to RANO criteria. The CNS objective response rate (ORR) was 60.8% by RECIST (95% CI 46.1–74.2; 9 CNS complete responses [CRs]; CNS disease control rate [DCR] 90.2%) and 51.2% by RANO (95% CI 35.5–66.7; 5 CNS CRs; CNS DCR 83.7%). Responses by RECIST included both confirmed and unconfirmed responses; those by RANO had to be confirmed. Median duration of CNS response was 9.1 months with RECIST (95% CI 5.8–NE; 39% of responders with event) and 9.1 months with RANO (95% CI 7.4–NE; 36% of responders with event). CONCLUSION: Alectinib demonstrated promising and durable efficacy in the CNS for ALK+ NSCLC patients previously treated with crizotinib, regardless of the assessment criteria used. Updated results from a later cut-off, plus correlative data and additional analyses, will be presented.

INTRODUCTION: Response assessment for Glioblastoma (GBM) is often assessed using the RANO criteria based on linear measurements. However linear measurements may be an inaccurate reflection of volume for tumours with cystic necrotic elements or complex geometric shapes. Automated computer-assisted volumetric analysis may offer a more accurate assessment in such situations. This study explores the differences between linear and volumetric tumour measurements. METHOD: 10 patients with heterogeneously enhancing GBM on 3D post contrast T1 volumetric MRI sequence were selected for this study. Spherical volume of GBM was estimated from 2D measurements (linear) by taking the average of two perpendicular diameters. Volumetric analysis was performed by manually contouring gadolinium enhanced sections of tumour on Agfa PACS. RESULTS: Mean tumour volume was 13.19 cm3 and 10.06 cm3 using linear and volumetric techniques respectively. The nonparametric Wilcoxon signed-rank test (p = 0.092) informs that distributions of 2D Volume and Volumetry are different at the 10% significance level. The one-sided nonparametric sign test (p = 0.05) informs that the 2D Volume is greater than Volumetry for 8 out of 10 observations. CONCLUSION: Linear measurements can over estimate the volume of tumour compared to volumetric analysis. Measuring the change in volume of GBM may provide a more accurate assessment of response than conventional linear measurements used for existing RANO criteria, particularly for necrotic tumours. The benefit of volumetric analysis to assess response in GBM requires prospective validation. Integration of this technique into a prospective study will be discussed.