Application of Novel Response/Progression Measures for Surgically Delivered Therapies for Gliomas: Response Assessment in Neuro-Oncology (RANO) Working Group
ABSTRACT The Response Assessment in Neuro-Oncology (RANO) Working Group is an international, multidisciplinary effort to develop new standardized response criteria for clinical trials in brain tumors. The RANO group identified knowledge gaps relating to the definitions of tumor response and progression after the use of surgical or surgically based treatments.
To outline a proposal for new response and progression criteria for the assessment of the effects of surgery and surgically delivered therapies for patients with gliomas.
The Surgery Working Group of RANO identified surgically related end-point evaluation problems that were not addressed in the original Macdonald criteria, performed an extensive literature review, and used a consensus-building process to develop recommendations for how to address these issues in the setting of clinical trials.
Recommendations were formulated for surgically related issues, including imaging changes associated with surgical resection or surgically mediated adjuvant local therapies, the determination of progression in the setting where all enhancing tumor has been removed, and how new enhancement should be interpreted in the setting where local therapies that are known to produce nonspecific enhancement have been used. Additionally, the terminology used to describe the completeness of surgical resections has been recognized to be inconsistently applied to enhancing vs nonenhancing tumors, and a new set of descriptors is proposed.
The RANO process is intended to produce end-point criteria for clinical trials that take into account the effects of prior and ongoing therapies. The RANO criteria will continue to evolve as new therapies and technologies are introduced into clinical trial and/or practice.
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ABSTRACT: The aim of this prospective longitudinal study was to identify static and dynamic O-(2-[(18)F]fluoroethyl)-l-tyrosine PET ((18)FET-PET)-derived imaging biomarkers in patients with glioblastoma (GBM). Seventy-nine patients with newly diagnosed GBM were included; 42 patients underwent stereotactic biopsy (unresectable tumors) and 37 patients microsurgical tumor resection. All patients were scheduled to receive radiotherapy plus concomitant and adjuvant temozolomide (RCx/TMZ). (18)FET-PET evaluation using static and dynamic analysis was done before biopsy/resection, after resection, 4 to 6 weeks following RCx, and after 3 cycles of TMZ. Endpoints were survival and progression-free-survival. Prognostic factors were obtained from proportional hazards models. Biological tumor volume before RCx (BTVpreRCx) was the most important (18)FET-PET-derived imaging biomarker and was independent of MGMT promoter methylation and clinical prognostic factors: patients with smaller BTVpreRCx had significantly longer progression-free and overall survival (OS). (18)FET time-activity curves (TACs) before treatment and their changes after RCx were also related to outcome; patients with initially increasing TACs experienced longer OS. BTVpreRCx and TAC represent important (18)FET-PET-derived imaging biomarkers in GBM. Increasing TACs are associated with prolonged OS. The BTVpreRCx is a strong prognostic factor for progression-free survival and OS independent of the mode of surgery. Our data furthermore suggest that patients harboring resectable GBM might benefit from maximal PET-guided tumor resection. © 2015 American Academy of Neurology.Neurology 01/2015; 84(7). DOI:10.1212/WNL.0000000000001262 · 8.30 Impact Factor
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ABSTRACT: Due to the various intensities of 5-aminolevulinic acid (5-ALA) fluorescence, neurosurgeons tend to be uncertain about which tissues to resect. This study aimed to reveal the shortcomings of the human visual perception of fluorescence, particularly the factors guiding the tissue removal and the correlation of fluorescence with contrast enhancement (CE) on magnetic resonance imaging (MRI). Various colour features [CIE L*a*b* colour space, colour difference described by DE and contrast ratio (CR)] of total 206 noticed fluorescent areas and their surroundings were measured from the video recordings of 21 primary high grade glioma (HGG) surgeries. The position of a fluorescent region was related to the corecorded navigational image. Following early postoperative MRI, 17 additional regions of corresponding to CE remnants were identified, their colour features were compared to the resected CEs. The targeted video post-processing method was designed, based on the results. There were no complications attributed to 5-ALA use and the median survival was \10 months. 82.5 % of recognised fluorescent areas were removed. Colour spaces of the resected regions and their backgrounds did not overlap. Opposite to the separate colour components (p[0.05), the distant background colour (p\0.05) and higher CR and DE (p\0.01) determined the resection of a fluorescent region. Noneloquent location and CR both independently increased the resection rate in logistic regression. However, greater area under the receiver operating characteristic curve (AUC) in case of CR (AUC = 0.78; 95 % CI 0.71–0.83) determined its dominant role in neurosurgeon’s fluorescence perception. CE regions presented with a significantly more saturated shade of violet (consistently higher a* and b*) than other tumour parts (p\0.05). Regions corresponding to tumour remnants had a significantly lower a* component value (p = 0.02) as well as a lower DE than the matched background (AUC = 0.73; 95 % CI 0.65–0.80). In order to increase the resection rate, DE[60 was needed. These results directed essential improvements in the 5-ALA fluorescence visualisation toward enhanced resection rate. The conventional filtering, unadjusted to the 5-ALA colour space converted some background shades to colours resembling relevant fluorescence. This is one of the first studies to demonstrate that perceived colours, their contrasting and CR are of significance in the decision-making during HGG 5-ALA fluorescence-guided surgery. Irrespective of the shortcomings of conventional video filtering, further development of a tailored post-processed contrast stretching will allow to achieve safe and radical tumour resection.Journal of Neuro-Oncology 02/2015; DOI:10.1007/s11060-015-1750-0 · 2.79 Impact Factor
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ABSTRACT: Object Resection of glioblastoma adjacent to motor cortex or subcortical motor pathways carries a high risk of both incomplete resection and postoperative motor deficits. Although the strategy of maximum safe resection is widely accepted, the rates of complete resection of enhancing tumor (CRET) and the exact causes for motor deficits (mechanical vs vascular) are not always known. The authors report the results of their concept of combining monopolar mapping and 5-aminolevulinic acid (5-ALA)-guided surgery in patients with glioblastoma adjacent to eloquent tissue. Methods The authors prospectively studied 72 consecutive patients who underwent 5-ALA-guided surgery for a glioblastoma adjacent to the corticospinal tract (CST; < 10 mm) with continuous dynamic monopolar motor mapping (short-train interstimulus interval 4.0 msec, pulse duration 500 μsec) coupled to an acoustic motor evoked potential (MEP) alarm. The extent of resection was determined based on early (< 48 hours) postoperative MRI findings. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. Results Five patients were excluded because of nonadherence to protocol; thus, 67 patients were evaluated. The lowest motor threshold reached during individual surgery was as follows (motor threshold, number of patients): > 20 mA, n = 8; 11-20 mA, n = 13; 6-10 mA, n = 10; 4-5 mA, n = 13; and 1-3 mA, n = 23. Motor deterioration at postsurgical Day 1 and at discharge occurred in 30% (n = 20) and 10% (n = 7) of patients, respectively. At 3 months, 3 patients (4%) had a persisting postoperative motor deficit, 2 caused by vascular injury and 1 by mechanical injury. The rates of intra- and postoperative seizures were 1% and 0%, respectively. Complete resection of enhancing tumor was achieved in 73% of patients (49/67) despite proximity to the CST. Conclusions A rather high rate of CRET can be achieved in glioblastomas in motor eloquent areas via a combination of 5-ALA for tumor identification and intraoperative mapping for distinguishing between presumed and actual motor eloquent tissues. Continuous dynamic mapping was found to be a very ergonomic technique that localizes the motor tissue early and reliably.Neurosurgical FOCUS 12/2014; 37(6):E16. DOI:10.3171/2014.10.FOCUS14524 · 2.14 Impact Factor