Volumetric Tumor Measurements Research Articles

NCOG-23. ASSESSMENT OF NON-MEASURABLE DISEASE IN HIGH-GRADE GLIOMA: RANO-BASED 2D VS. 3D VOLUMETRICS

Abstract Non-measurable disease (NMD) in High grade glioma (HGG), defined as "longest perpendicular dimension of less than 10 mm”, is a limitation of RANO criteria that limits trial enrollment and biases trial populations to exclude patients with smaller tumors that eventually become measurable. Volumetric (3D) measurements may improve sensitivity and precision for measuring HGG of all sizes, however there is limited data comparing volumetric to 2D RANO measurements. AIMS: To investigate the correlation between RANO-based bidimensional 2D and 3D volumetric measurements in the postoperative setting of patients with HGG, including patients with NMD. METHODS: Contrast-enhanced (CE) postoperative and radiotherapy planning MRIs were utilized for 2D RANO measurements by neuroradiologists and volumetric (3D) measurements extracted from segmentations of CE disease. Pearson’s correlation between the 2D and 3D measurements were evaluated at each time point. The percentage of NMD based on RANO criteria and the range of tumor volumes for the NMD cases were reported. RESULTS: For 59 patients, there was lower concordance in the 2D and 3D measures at the postoperative MRI time point (Pearson =0.46) compared to the treatment planning MRI time point (Pearson=0.81). Interestingly, the postoperative time point had a higher percentage of NMD of 38% with the mean tumor volume of 13 cm3 (range: 0-21 cm3) compared to the treatment planning MRI with percentage NMD of 8% and mean tumor volume of 9 cm3 (range: 6-13cm3). CONCLUSION: In this study, higher rate of agreement was observed between RANO-based 2D and 3D volumetric tumor measurements at the time point of MR simulation when there was lower rate of NMD, suggesting NMD may contribute to the discrepancy between 2D and 3D measurements. Volumetric measurement tools may be a superior approach to improve the assessment especially of NMD in the postoperative period, improving trial enrollment for these patients.

Wait-and-scan management in sporadic Koos grade 4 vestibular schwannomas: A longitudinal volumetric study.

Volumetric natural history studies specifically on large vestibular schwannomas (VSs), commonly classified as Koos grade 4, are lacking. The aim of the current study is to present the volumetric tumor evolution in sporadic Koos grade 4 VSs and possible predictors for tumor growth. Volumetric tumor measurements and tumor evolution patterns from serial MRI studies were analyzed from selected consecutive patients with Koos grade 4 VS undergoing initial wait-and-scan management between January 2001 and July 2020. The significant volumetric threshold was defined as a change in volume of ≥10%. Among 215 tumors with a median size (IQR) of 2.7 cm3 (1.8-4.2), 147 tumors (68%) demonstrated growth and 75 tumors (35%) demonstrated shrinkage during follow-up. Growth-free survival rates (95% CI) at 1, 2, 5, and 10 years were 55% (48-61), 36% (29-42), 29% (23-36), and 28% (21-34), respectively and did not significantly differ in tumors> 20 mm (Chi-square = .40; P-value = .53). Four tumor evolution patterns (% of total) were observed: continued growth (60); initial growth then shrinkage (7); continued shrinkage (27); and stability (5). Good hearing (adjusted HR 2.21, 95% CI 1.48-3.30; P < .001) and peritumoral edema (adjusted HR 2.22, 95% CI 1.18-4.13; P = .01) at diagnosis were significantly associated with an increased likelihood of growth. Koos grade 4 VSs show a wide variety in size and growth. Due to variable growth patterns, an initial wait-and-scan strategy with short scan intervals may be an acceptable option in selected tumors, if no significant clinical symptoms of mass effect that warrant treatment are present.

The Natural History of Observed SDHx-Related Head and Neck Paragangliomas Using Three-Dimensional Volumetric Tumor Analysis.

Characterize the natural history and clinical behavior of head and neck paragangliomas (HNPGLs) in subjects with succinate dehydrogenase (SDHx) pathogenic variants using volumetric tumor measurements. Cohort study. Tertiary academic referral center. Subjects with SDHx HNPGLs under observation for at least 6 months with 2 or more magnetic resonance imaging or computed tomography scans. Diagnostic interventions include next-generation sequencing, magnetic resonance imaging, and computed tomography. Therapeutic interventions include microsurgical resection or stereotactic radiosurgery. Radiographic progression was defined as a 20% or greater increase in volume. Cranial nerve (CN) functional outcomes were assessed using clinical documentation. A total of 19 subjects with 32 tumors met the inclusion criteria. Median radiographic follow-up was 2.2 years, and the median volumetric growth rate was 0.47 cm3/yr. Kaplan-Meier estimated rates of survival free of radiographic progression for all SDHx tumors at 1, 2, and 3 years were 69, 50, and 22%, respectively. No tumors developed new CN palsies during the period of observation. Over intermediate-term follow-up, observation of treatment-naive SDHx-related HNPGLs did not result in new cranial neuropathy. Although indefinite observation is only appropriate for select cases, these data support an interval of observation to characterize growth rate in asymptomatic to minimally symptomatic patients, who are at high risk of treatment-related morbidity. Given the early age at diagnosis and high risk of bilateral multifocal phenotypes in SDHx HNPGL mutation carriers, these data may aid in optimizing patient tumor control and CN functional preservation. Further studies are necessary to determine whether pretreatment growth rate is correlated with clinical outcomes.

Comparing Linear and Volumetric Tumor Measurements During Observation of Growing Sporadic Vestibular Schwannomas.

To assess the correlation between linear and volumetric changes in vestibular schwannomas (VS). Retrospective imaging review was performed on patients diagnosed with sporadic VS from 2000 to 2019 who demonstrated linear growth on observation with serial magnetic resonance imaging (MRI). Two large tertiary care centers. Changes in diameter on serial MRI scans, measured by 1995 American Academy of Otolaryngology-Head and Neck Surgeryguidelines, were compared to changes in volume, calculated by segmentation. Ninety-two patients had VS confined to the internal auditory canal (IAC) with 236 MRIs analyzed, and 108 patients had VS involving the cerebellopontine angle (CPA) with 193 MRIs analyzed. The Spearman rank correlation coefficients between changes in diameter and volume for IAC and CPA tumors were 0.43 (p < .001) and 0.65 (p < .001), respectively. Linear diameter increases of 1 to <2 mm corresponded to a median volume change of 32% (interquartile range [IQR]: 6%-86%) for IAC tumors, compared to 23% (IQR: 13%-40%) for CPA tumors. Linear diameter increases of 2 to <3 mm (ie, the minimum linear diameter change classically considered "true growth") corresponded to a median volume change of 42% (IQR: 23%-100%) and 47% (IQR: 26%-69%) for IAC and CPA tumors, respectively. Changes in linear diameter significantly correlated with changes in volume for IAC and CPA tumors, although diameter changes that did not meet the definition of linear growth (<2 mm) had corresponding median volume changes in excess of 20% for both IAC and CPA tumors.

High-Resolution T2-Weighted Imaging for Surveillance in Postoperative Vestibular Schwannoma: Equivalence with Contrast-Enhanced T1WI for Measurement and Surveillance of Residual Tumor.

Patients with surgically resected vestibular schwannoma will undergo multiple postoperative surveillance examinations, typically including postcontrast sequences. The purpose of this study was to compare high-resolution T2WI with gadolinium T1WI in the postoperative assessment of vestibular schwannoma. This was a retrospective study of patients with a history of resected vestibular schwannoma at a single institution. High-resolution T2WI and gadolinium T1WI were independently evaluated for residual disease. In addition, 3D and 2D measurements were performed in the group of patients with residual tumor. Statistical analysis was performed to evaluate the agreement between sequences on the binary assessment (presence/absence of tumor on initial postoperative examination) and to evaluate the equivalence of measurements for the 2 sequences on 3D and 2D quantitative assessment in individuals with residual disease. One hundred forty-eight patients with retrosigmoid-approach resection of vestibular schwannomas were included in the final analysis. There was moderate-to-substantial agreement between the 2 sequences for the evaluation of the presence versus absence of tumor (Cohen κ coefficient = 0.78; 95% CI, 0.68-0.88). The 2 sequences were significantly equivalent for 2D and 3D quantitative assessments (short-axis P value = .021; long-axis P value = .015; 3D P value = .039). In this retrospective study, we demonstrate moderate-to-substantial agreement in the categoric assessment for the presence versus absence of tumor and equivalence between the 2 sequences for both 2D and volumetric tumor measurements as performed in the subset of patients with measurable residual. On the basis of these results, high-resolution T2WI alone may be sufficient for early postoperative imaging surveillance in this patient population.

Evaluation of Volumetric Lymph Node Measurements in Cutaneous T-Cell Lymphoma Patients Enrolled in the Mavoric Trial: An Interim Analysis

Lymph node assessment is an important component of staging, classification, and treatment response assessment in cutaneous T-cell lymphoma (CTCL). Although a biopsy is the only definitive way to assess nodal involvement, radiologic evaluation is commonly used in practice given its practicality. Current radiologic criteria are adapted from guidelines for lymphomas with primarily nodal involvement and have not been validated in CTCL patients. These criteria are limited by linear measurements which fail to accurately capture small and/or asymmetric nodal involvement in CTCL and may lead to flawed estimations of the overall disease burden. Furthermore, unidimensional and bidimensional measurements are subject to significant inter- and intra-observer variability. More accurate methods of lymph node evaluation are needed to improve risk stratification and treatment response assessment in CTCL. Recent advances in digital imaging techniques have made it possible to obtain volumetric tumor measurements. This technique has shown promise as a more accurate imaging biomarker than unidimensional measurements in several solid cancer types, offering improved sensitivity for changes in tumor burden during treatment. Volumetric lymph node measurements have been shown to be superior to unidimensional measurements in distinguishing between benign and malignant lymph nodes in systemic lymphoma, however volumetric measurements have never been studied in CTCL. The aim of this study was to assess the utility of volumetric lymph node measurements in CTCL using this novel imaging technique. We analyzed imaging and clinical data from the mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC) trial which included 372 CTCL patients randomized to receive either mogalizumab or vorinostat. The majority of patients randomized to vorinostat crossed over to mogalizumab due to disease progression or intolerance. As part of the trial, patients underwent computed tomography (CT) scans at baseline and regular follow-up intervals to assess for lymph node response to treatment. In our study, target lymph nodes in serial CT scans were measured by a team of radiologists using a response assessment system built on open-source software known as the Weasis imaging platform. Semi-automated segmentation algorithms were used to quantify unidimensional and bidimensional measurements as well as lymph node volumes. Our preliminary data suggests that there is a correlation between unidimensional, bidimensional, and volumetric lymph node measurements. For the first time, we validate volumetric lymph node measurement as a viable method of lymph node assessment in CTCL. This implicates lymph node volume as an alternative metric for lymph node assessment in CTCL that has the potential to improve the accuracy of current nodal assessment criteria. Additional research is underway to determine whether volumetric lymph node measurements are superior to uni- and bidimensional measurements in assessing treatment response and predicting clinical outcomes in CTCL.

Spontaneous Volumetric Tumor Regression During Wait-and-Scan Management of 952 Sporadic Vestibular Schwannomas.

Spontaneous tumor shrinkage during wait-and-scan management of sporadic vestibular schwannoma is generally considered an uncommon phenomenon. However, most data informing this understanding stem from single-slice linear tumor measurements taken in the axial imaging plane. The objective of the current work was to characterize the regression capacity of sporadic vestibular schwannomas using volumetric tumor measurements. Retrospective cohort study using slice-by-slice, three-dimensional volumetric tumor measurements. Three tertiary referral centers. Patients with sporadic vestibular schwannoma. Wait-and-scan. Regression-free survival rates with regression defined as a decrease of at least 20% of the tumor volume. Among 952 patients undergoing a total of 3,505 magnetic resonance imaging studies during observation, 123 experienced volumetric tumor regression after diagnosis at a median of 1.2 years (interquartile range, 0.6-2.9 yr). Volumetric regression-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after diagnosis were 94% (92-95%; 662), 86% (83-89%; 275), and 78% (73-82%; 132), respectively. Among 405 patients who demonstrated an initial period of tumor growth but continued wait-and-scan management, 48 experienced volumetric regression at a median of 1.2 years (interquartile range, 0.8-2.6 yr) after initial growth. Volumetric regression-free survival rates at 1, 3, and 5 years after initial growth were 94% (92-97%; 260), 84% (79-89%; 99), and 75% (67-83%; 43), respectively. Ultimately, only 82 of the 952 patients studied showed exclusively volumetric tumor regression (i.e., without any periods of tumor growth) by the time of last follow-up. Spontaneous volumetric tumor shrinkage during wait-and-scan management occurs more frequently than suggested by previous studies using linear tumor measurements and can even occur after previous episodes of documented tumor growth. These data further highlight the dynamic nature of vestibular schwannoma growth. To this end, the application of natural history data to patient management requires a nuanced approach that parallels the complex tumor behavior of vestibular schwannoma.

Long-term natural history and patterns of sporadic vestibular schwannoma growth: A multi-institutional volumetric analysis of 952 patients.

The current study aims to characterize the natural history of sporadic vestibular schwannoma volumetric tumor growth, including long-term growth patterns following initial detection of growth. Volumetric tumor measurements from 3505 serial MRI studies were analyzed from unselected consecutive patients undergoing wait-and-scan management at three tertiary referral centers between 1998 and 2018. Volumetric tumor growth was defined as a change in volume ≥20%. Among 952 patients undergoing observation, 622 experienced tumor growth with initial growth-free survival rates (95% CI) at 1, 3, and 5 years following diagnosis of 66% (63-69), 30% (27-34), and 20% (17-24). Among 405 patients who continued to be observed despite demonstrating initial growth, 210 experienced subsequent tumor growth with subsequent growth-free survival rates at 1, 3, and 5 years following initial growth of 77% (72-81), 37% (31-43), and 24% (18-31). Larger tumor volume at initial growth (HR 1.13, P = .02) and increasing tumor growth rate (HR 1.31; P < .001) were significantly associated with an increased likelihood of subsequent growth, whereas a longer duration of time between diagnosis and detection of initial growth was protective (HR 0.69; P < .001). While most vestibular schwannomas exhibit an overall propensity for volumetric growth following diagnosis, prior tumor growth does not perfectly predict future growth. Tumors can subsequently grow faster, slower, or demonstrate quiescence and stability. Larger tumor size and increasing tumor growth rate portend a higher likelihood of continued growth. These findings can inform timing of intervention: whether upfront at initial diagnosis, after detection of initial growth, or only after continued growth is observed.

Value of Latest-generation Cone-beam Computed Tomography for Post Lipiodol-embolization Imaging in Hepatic Transarterial Chemoembolization in Comparison with Multi-detector Computed Tomography

To evaluate image quality, radiation dose (phantom study) and tumor volumetry of intraprocedural cone-beam computed tomography (CBCT) compared to postprocedural multidetector computed tomography (MDCT) in patients undergoing hepatic conventional transarterial chemoembolization (cTACE). One hundred fourteen patients (64/50 female/male; mean age, 57 ± 14 years) who had undergone cTACE including intraprocedural-CBCT and postprocedural-MDCT were retrospectively enrolled. Subjective image quality (IQ) and suitability for assessing Lipiodol distribution were compared using 4-point Likert scales; additionally, lesion to liver contrast (LLC) and contrast-to-noise-ratio (CNR) were compared. Tumor volumes were measured semi-automatically and compared to magnetic resonance imaging (MRI). Effective doses were measured using an anthropomorphic phantom. The suitability of CBCT for assessing Lipiodol distribution during cTACE was comparable to MDCT (mean score, 3.2 ± 0.6) and CBCT (3.4 ± 1.0, p=0.29). Subjective overall IQ was rated with a mean score of 3.2 ± 0.7 (κ=0.66) in CBCT and 3.1 ± 0.4 (κ=0.57, p=0.15) in MDCT. Evaluation of LLC showed significant differences between CBCT and MDCT (mean scores 3.6 ± 1.2 and 2.6 ± 1.5, respectively). CNR analysis demonstrated comparable mean values for CBCT and MDCT (3.5 ± 1.3vs. 3.4 ± 1.8,p=0.31). No significant differences were found regarding tumor volumetry (mean volumes: CBCT, 27.0 ± 17.4 mm3; MDCT: 26.8 ± 16.0 mm3; p = 0.66) in comparison to T2-weighted MRI (25.9 ± 17.6 mm3). Effective doses were 3.2 ± 0.6 mSv (CBCT) and 2.5 ± 0.3 mSv (MDCT) (p < 0.001). No cTACE-related complications (bleeding, non-target embolization) were missed on intraprocedural CBCT in comparison to postprocedural MDCT. Latest-generation intraprocedural CBCT provides suitable assessment of Lipiodol distribution and similar image quality compared to MDCT while allowing for robust volumetric tumor measurements and immediate complication control by visualizing non-target embolization and hematoma. Therefore, it may improve patient safety and outcome as well as clinical workflow compared to postprocedural MDCT in hepatic cTACE in certain cases.

Predictors of recurrence and high growth rate of residual meningiomas after subtotal resection.

The extent of resection has been shown to improve outcomes in patients with meningiomas. However, resection can be complicated by constraining local anatomy, leading to subtotal resections. An understanding of the natural history of residual tumors is necessary to better guide postsurgical management and minimize recurrence. This study seeks to identify predictors of recurrence and high growth rate following subtotal resection of intracranial meningiomas. Adult patients who underwent primary surgical resection of a WHO grade I meningioma at a tertiary care institution from 2007-2017 were retrospectively reviewed. Volumetric tumor measurements were made on patients with subtotal resections. Stepwise multivariate proportional hazards regression analyses were performed to identify factors associated with time to recurrence, as well as stepwise multivariate regression analyses to assess for factors associated with high postoperative growth rate. Of the 141 patients (18%) who underwent radiographic subtotal resection of an intracranial meningioma during the reviewed period, 74 (52%) suffered a recurrence, in which the median (interquartile range, IQR) time to recurrence was 14 (IQR 6-34) months. Among those tumors subtotally resected, the median pre- and postoperative tumor volumes were 17.19 cm3 (IQR 7.47-38.43 cm3) and 2.31 cm3 (IQR 0.98-5.16 cm3), which corresponded to a percentage resection of 82% (IQR 68%-93%). Postoperatively, the median growth rate was 0.09 cm3/year (IQR 0-1.39 cm3/year). Factors associated with recurrence in multivariate analysis included preoperative tumor volume (hazard ratio [HR] 1.008,95% confidence interval [CI] 1.002-1.013, p = 0.008), falcine location (HR 2.215, 95% CI 1.179-4.161, p = 0.021), tentorial location (HR 2.410, 95% CI 1.203-4.829, p = 0.024), and African American race (HR 1.811, 95% CI 1.042-3.146, p = 0.044). Residual volume (RV) was associated with high absolute annual growth rate (odds ratio [OR] 1.175, 95% CI 1.078-1.280, p < 0.0001), with the maximum RV benefit at < 5 cm3 (OR 4.056, 95% CI 1.675-9.822, p = 0.002). By identifying predictors of recurrence and growth rate, this study helps identify potential patients with a high chance of recurrence following subtotal resection, which are those with large preoperative tumor volume, falcine location, tentorial location, and African American race. Higher RVs were associated with tumors with higher postoperative growth rates. Recurrences typically occurred 14 months after surgery.

Postural Sway Predicts Growth in Untreated Vestibular Schwannoma: A Retrospective Volumetric Study.

One in three vestibular schwannomas (VS) will grow within 3 years after diagnosis, but no reliable baseline parameter has been found to predict such growth. To determine if postural sway is associated with growth of untreated VS. Patients with newly diagnosed sporadic VS assigned to a wait-and-scan protocol were identified from a prospectively maintained database. Postural sway was measured by posturography at baseline and patients were classified as steady or unsteady. Observer-blinded volumetric tumor measurements were performed on the diagnostic MRI and a 3-year control MRI. Tumor growth quantified as relative growth (%) and volume-doubling time (VDT and VDT-1) were investigated as dependent variables against baseline parameters. Out of 204 VS patients, 53 (26%) were classified as unsteady on the platform at baseline. Median tumor volume was 0.32 cm3 (range 0.02-4.79), and 51% demonstrated significant growth within 3 years. Unsteady patients had significantly faster-growing tumors, with a mean relative growth of 172.5% compared to 79.5% in steady patients (p < 0.006). Seventy-seven percent of unsteady patients had >20% volume increase, compared to 42% in steady patients (p < 0.001). Mean VDT-1 was 0.65 doublings per year for unsteady patients, and 0.22 for steady patients (p < 0.001). Multivariate regression analysis including demographic and clinical parameters showed an OR of 5.6 (95% CI 2.6, 11.8) for growth in unsteady patients. This is the first demonstrated association between a measurable parameter and future growth in untreated VS. Our findings may help clinicians identify patients with a higher risk for tumor growth and provide closer monitoring or early treatment.

Enhanced Detection of Treatment Effects on Metastatic Colorectal Cancer with Volumetric CT Measurements for Tumor Burden Growth Rate Evaluation.

Mathematical models combined with new imaging technologies could improve clinical oncology studies. To improve detection of therapeutic effect in patients with cancer, we assessed volumetric measurement of target lesions to estimate the rates of exponential tumor growth and regression as treatment is administered. Two completed phase III trials were studied (988 patients) of aflibercept or panitumumab added to standard chemotherapy for advanced colorectal cancer. Retrospectively, radiologists performed semiautomated measurements of all metastatic lesions on CT images. Using exponential growth modeling, tumor regression (d) and growth (g) rates were estimated for each patient's unidimensional and volumetric measurements. Exponential growth modeling of volumetric measurements detected different empiric mechanisms of effect for each drug: panitumumab marginally augmented the decay rate [tumor half-life; d [IQR]: 36.5 days (56.3, 29.0)] of chemotherapy [d: 44.5 days (67.2, 32.1), two-sided Wilcoxon P = 0.016], whereas aflibercept more significantly slowed the growth rate [doubling time; g = 300.8 days (154.0, 572.3)] compared with chemotherapy alone [g = 155.9 days (82.2, 347.0), P ≤ 0.0001]. An association of g with overall survival (OS) was observed. Simulating clinical trials using volumetric or unidimensional tumor measurements, fewer patients were required to detect a treatment effect using a volumetric measurement-based strategy (32-60 patients) than for unidimensional measurement-based strategies (124-184 patients). Combined tumor volume measurement and estimation of tumor regression and growth rate has potential to enhance assessment of treatment effects in clinical studies of colorectal cancer that would not be achieved with conventional, RECIST-based unidimensional measurements.

MRI based volumetric measurements of vestibular schwannomas in patients with neurofibromatosis type 2: comparison of three different software tools

Neurofibromatosis type 2 is a neurogenetic disorder with an incidence of about 1:33.000. Hallmarks are bilateral benign vestibular schwannomas, which can lead to deafness or brainstem compression. Volumetric tumor measurements are essential to assess the efficacy of new therapies. We present a statistical and methodical comparison of three volumetric image analysis tools. We performed volumetric measurements on phantoms with predefined volumes (0.1 to 8.0 ml) and tumors seen on 32 head MRI scans from eight NF2 patients with BrainLab, ITK-Snap, or OsiriX. The software was compared with regard to accuracy and reproducibility of the measurements and time required for analysis. The mean volume estimated by all three software programs differed significantly from the true volume of the phantoms, but OsiriX and BrainLab gave estimates that were not significantly different from each other. For the actual tumors, the estimated volumes with all three software tools showed a low coefficient of variability, but the mean volume estimates differed among the tools. OsiriX showed the shortest analysis time. Volumetric assessment of MRI images is associated to an intrinsic risk of miscalculation. For precise volumes it is mandatory to use the same volumetric tools for all measurements.

The impact of quantitative CT-based tumor volumetric features on the outcomes of patients with limited stage small cell lung cancer

IntroductionLimited stage small cell lung cancer (LS-SCLC) has a poor prognosis. Additional prognostic markers are needed for risk-stratification and treatment intensification. This study compares quantitative CT-based volumetric tumor measurements versus International Association for the Study of Lung Cancer (IASLC) TNM staging to predict outcomes.Materials & methodsA cohort of 105 patients diagnosed with LS-SCLC and treated with chemoradiation (CRT) from 2000 to 2013 were analyzed retrospectively. Patients were staged by the Union for International Cancer Control (UICC) TNM Classification, 8th edition. Tumor volumes and diameters were extracted from radiation planning CT imaging. Univariable and multivariable models were used to analyze relationships between CT features and overall survival (OS), locoregional recurrence (LRR), in-field LRR, any progression, and distant metastasis (DM).ResultsMedian follow-up was 21.3 months. Two-year outcomes were as follows: 38% LRR, 31% in-field LRR, 52% DM, 62% any progression, and 47% OS (median survival 16.5 months).On univariable analysis, UICC T-stage and N-stage were not associated with any clinical outcome. UICC overall stage was only statistically associated with in-field LRR. One imaging feature (3D maximum tumor diameter) was found to be significantly associated with LRR (HR 1.10, p = 0.003), in-field LRR (HR 1.10, p = 0.007), DM (HR 1.10, p = 0.02), any progression (HR 1.10, p = 0.008), and OS (HR 1.10, p = 0.03). On multivariable analysis, this feature remained significantly associated with all outcomes.ConclusionFor LS-SCLC, quantitative CT-based volumetric tumor measurements were significantly associated with outcomes after CRT and may be better predictors of outcome than TNM stage.

Erratum. Predictors of recurrence and high growth rate of residual meningiomas after subtotal resection.

OBJECTIVE The extent of resection has been shown to improve outcomes in patients with meningiomas. However, resection can be complicated by constraining local anatomy, leading to subtotal resections. An understanding of the natural history of residual tumors is necessary to better guide postsurgical management and minimize recurrence. This study seeks to identify predictors of recurrence and high growth rate following subtotal resection of intracranial meningiomas. METHODS Adult patients who underwent primary surgical resection of a WHO grade I meningioma at a tertiary care institution from 2007-2017 were retrospectively reviewed. Volumetric tumor measurements were made on patients with subtotal resections. Stepwise multivariate proportional hazards regression analyses were performed to identify factors associated with time to recurrence, as well as stepwise multivariate regression analyses to assess for factors associated with high postoperative growth rate. RESULTS Of the 141 patients (18%) who underwent radiographic subtotal resection of an intracranial meningioma during the reviewed period, 74 (52%) suffered a recurrence, in which the median (interquartile range, IQR) time to recurrence was 14 (IQR 6-34) months. Among those tumors subtotally resected, the median pre- and postoperative tumor volumes were 17.19 cm3 (IQR 7.47-38.43 cm3) and 2.31 cm3 (IQR 0.98-5.16 cm3), which corresponded to a percentage resection of 82% (IQR 68%-93%). Postoperatively, the median growth rate was 0.09 cm3/year (IQR 0-1.39 cm3/year). Factors associated with recurrence in multivariate analysis included preoperative tumor volume (hazard ratio [HR] 1.008,95% confidence interval [CI] 1.002-1.013, p = 0.008), falcine location (HR 2.215, 95% CI 1.179-4.161, p = 0.021), tentorial location (HR 2.410, 95% CI 1.203-4.829, p = 0.024), and African American race (HR 1.811, 95% CI 1.042-3.146, p = 0.044). Residual volume (RV) was associated with high absolute annual growth rate (odds ratio [OR] 1.175, 95% CI 1.078-1.280, p < 0.0001), with the maximum RV benefit at < 5 cm3 (OR 4.056, 95% CI 1.675-9.822, p = 0.002). CONCLUSIONS By identifying predictors of recurrence and growth rate, this study helps identify potential patients with a high chance of recurrence following subtotal resection, which are those with large preoperative tumor volume, falcine location, tentorial location, and African American race. Higher RVs were associated with tumors with higher postoperative growth rates. Recurrences typically occurred 14 months after surgery.

STMO-11 CLINICAL EFFICACY OF AWAKE SURGERY: ANALYSIS OF 335 CASE ON EXTENT OF RESECTION AND SURVIVAL TIME

INTRODUCTIONAwake craniotomy (AS) with intraoperative mapping can be compatible to obtain maximal resection and preserve neurological function for glioma surgery. However, there is less evidence to improve overall survival for glioma patients. We compared the long-term outcome of glioma resection during AS and general anesthesia (GA).METHODSContinuous 335 patients with newly diagnosed glioma of WHO grade2 (G2) or higher who underwent surgery with intraoperative MRI between 2000 and 2013 were reviewed. Three-dimensional volumetric tumor measurements before and after operation were made. Multivariate analysis was used to evaluate the effect of awake surgery on overall survival (OS). RESULTSThe mean age of all cases was 46 years, male: female 199: 136, mean preoperative tumor volume (PTV) 44.5cc, mean extent of resection (EOR) 88.31%, and median survival (MST) 82.6 months. MST of G4 was significantly longer in the AS group (AS 38.9 months vs. GA group 22.0 months: p = 0.03), while multivariate analysis showed that age and KPS was a significant prognostic factor, but AS was not. There was no significant difference in the EOR of G3 (AS group 80.1% vs. general anesthesia 84.2%: p = 0.365), and MST was also not significantly different (AS group 134.8 months vs. GA group 117.9 months: p = 0.338). G2 also had no significant difference in the EOR (AS group 84.6% vs. GA group 86.7%; p = 0.92), and MST was also not significantly different (AS group 152.9 months vs. GA group 135.1 months: p = 0.235). Analysis of G2 or G3 showed no significant differences in PTV, KPS, and age at the surgery between two groups. CONCLUSIONEven if a glioma is located close to or within the eloquent area, AS can lead to EOR and OS equivalent to the removal of the non-eloquent area under GA.

CT Volumetry and Basic Texture Analysis as Surrogate Markers in Advanced Non–small-cell Lung Cancer

IntroductionWe evaluated volumetric tumor measurements and computed tomography texture analysis as prognostic indicators in patients with advanced non–small-cell lung cancer when compared with the unidimensional tumor size measurements used in Response Evaluation Criteria in Solid Tumors (RECIST). Patients and MethodsIn a retrospective review, computed tomography examinations in 77 patients with advanced non–small-cell lung cancer were evaluated before and after 2 cycles of chemotherapy. Baseline and changes in tumor diameter, volume, and texture were analyzed. Survival was analyzed with Cox regression analysis and Kaplan-Meier survival statistics. ResultsCox regression analysis demonstrated that only change in tumor volume (exp(B) = 1.006; P = .02) and the initial sum of the largest target lesion diameters predicted survival (exp(B) = 1.013; P = .02). Kaplan-Meier statistics demonstrated that patients with an initial sum of the largest target lesion diameters less than 88 mm had median survival time of 587 days (95% confidence interval [CI], 269-905 days), compared with the survival of those with larger tumor burden of 407 days (95% CI, 235-579 days). Patients in whom tumor volume decreased by more than 29% had a median survival time of 622 days (95% CI, 448-796 days), compared with 305 days for those with less decrease (95% CI, 34-240 days). ConclusionThis study demonstrates that change in lung tumor volume is a better marker of patient survival than change of unidimensional diameter measurements in our cohort. If confirmed in larger studies, this suggests that volumetry might improve clinical decision-making for individual patients and allow for faster assessment of new treatments.

Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics.

Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease. The humanized IgG1 antibody hu11B6 internalizes into prostate and prostate cancer (PCa) cells by binding to the catalytic cleft of human kallikrein 2 (hK2), a prostate specific enzyme governed by the AR-pathway. In a previous study, hu11B6 conjugated with Actinium-225 (225Ac), a high linear energy transfer (LET) radionuclide, was shown to generate an AR-upregulation driven feed-forward mechanism that is believed to enhance therapeutic efficacy. We assessed the efficacy of hu11B6 labeled with a low LET beta-emitter, Lutetium-177 (177Lu) and investigated whether similar tumor killing and AR-enhancement is produced. Moreover, single-photon emission computed tomography (SPECT) imaging of 177Lu is quantitatively accurate and can be used to perform treatment planning. [177Lu]hu11B6 therefore has significant potential as a theranostic agent.Materials and Methods: Subcutaneous PCa xenografts (LNCaP s.c.) were grown in male mice. Biokinetics at 4-336 h post injection and uptake as a function of the amount of hu11B6 injected at 72 h were studied. Over a 30 to 120-day treatment period the therapeutic efficacy of different activities of [177Lu]hu11B6 were assessed by volumetric tumor measurements, blood cell counts, molecular analysis of the tumor as well as SPECT/CT imaging. Organ specific mean absorbed doses were calculated, using a MIRD-scheme, based on biokinetic data and rodent specific S-factors from a modified MOBY phantom. Tumor tissues of treated xenografts were immunohistochemically (IHC) stained for Ki-67 (proliferation) and AR, SA-β-gal activity (senescence) and analyzed by digital autoradiography (DAR).Results: Organ-to-blood and tumor-to-blood ratios were independent of hu11B6 specific activity except for the highest amount of antibody (150 µg). Tumor accumulation of [177Lu]hu11B6 peaked at 168 h with a specific uptake of 29 ± 9.1 percent injected activity per gram (%IA/g) and low accumulation in normal organs except in the submandibular gland (15 ± 4.5 %IA/g), attributed to a cross-reaction with mice kallikreins in this organ, was seen. However, SPECT imaging with therapeutic amounts of [177Lu]hu11B6 revealed no peak in tumor accumulation at 7 d, probably due to cellular retention of 177Lu and decreasing tumor volumes. For [177Lu]hu11B6 treated mice, tumor decrements of up to 4/5 of the initial tumor volume and reversible myelotoxicity with a nadir at 12 d were observed after a single injection. Tumor volume reduction correlated with injected activity and the absorbed dose. IHC revealed retained expression of AR throughout treatment and that Ki-67 staining reached a nadir at 9-14 d which coincided with high SA- β-gal activity (14 d). Quantification of nuclei staining showed that Ki-67 expression correlated negatively with activity uptake. AR expression levels in cells surviving therapy compared to previous timepoints and to controls at 30 d were significantly increased (p = 0.017).Conclusions: This study shows that hu11B6 labeled with the low LET beta-emitting radionuclide 177Lu can deliver therapeutic absorbed doses to prostate cancer xenografts with transient hematological side-effects. The tumor response correlated with the absorbed dose both on a macro and a small scale dosimetric level. Analysis of AR staining showed that AR protein levels increased late in the study suggesting a therapeutic mechanism, a feed forward mechanism coupled to AR driven response to DNA damage or clonal lineage selection, similar to that reported in high LET alpha-particle therapy using 225Ac labeled hu11B6, however emerging at a later timepoint.

Volumetric and linear measurements of lung tumor burden from non-gated micro-CT imaging correlate with histological analysis in a genetically engineered mouse model of non-small cell lung cancer

Invivo micro-computed tomography (CT) imaging allows longitudinal studies of pulmonary neoplasms in genetically engineered mouse models. Respiratory gating increases the accuracy of lung tumor measurements but lengthens anesthesia time in animals that may be at increased risk for complications. We hypothesized that semiautomated, volumetric, and linear tumor measurements performed in micro-CT images from non-gated scans would have correlation with histological findings. Primary lung tumors were induced in eight FVB mice with two transgenes (FVB/N-Tg(tetO-Kras2)12Hev/J; FVB.Cg-Tg(Scgb1a1-rtTA)1Jaw/J). Non-gated micro-CT scans were performed and the lungs were subsequently harvested. In the acquired micro-CT scans, measurements of all identified tumors were determined using the following methods: semiautomated three-dimensional (3D) volume, ellipsoid volume, Response Evaluation Criteria in Solid Tumors (RECIST; sum of largest axial (i.e., transverse) diameter from five tumors), sum of largest axial diameters from all tumors (modified RECIST), and average axial diameter. For histological analysis, all five lung lobes were analyzed and the tumor area was summed from measurements made on five histological sections that were 300 µm apart from each other (covering a total depth of 1200 µm). All micro-CT measurement methods had very strong correlation with histological tumor burden (Pearson's correlation coefficient, 0.87 ( p = 0.0053) -0.98 ( p < 0.0001)). The only methods found to have different correlations were the semiautomated 3D method and the RECIST method (Williams' test for dependent overlapping correlations, p = 0.013). Our results suggest quantification of lung tumor burden from non-gated micro-CT imaging will reflect histological differences between mice and can therefore be used for between-group comparisons or when concerns about systemic health of research animals may limit lengthy anesthetic procedures.

Volumetric Analysis Using Low-Field Intraoperative Magnetic Resonance Imaging for 168 Newly Diagnosed Supratentorial Glioblastomas: Effects of Extent of Resection and Residual Tumor Volume on Survival and Recurrence

Extent of resection (EOR) remains controversial in therapy for glioblastoma (GBM). However, an increasing number of studies favor maximum EOR as being associated with longer patient survival. Residual tumor volume (RTV) has also recently emerged as a prognostic factor. Low-field intraoperative magnetic resonance imaging (iMRI) has contributed to improve the EOR of GBM. The purpose of this study was to analyze the relationships between EOR/RTV and overall survival (OS)/progression-free survival (PFS) in patients with newly diagnosed GBM using low-field iMRI. Adult patients who underwent surgery for newly diagnosed supratentorial GBM between 2000 and 2012 were retrospectively reviewed. Three-dimensional volumetric tumor measurements were made. Multivariate analysis was used to evaluate the relationships between EOR/RTV and OS/PFS. Of 168 patients, 126 (75%) died and 154 (91%) showed tumor recurrence. Median OS and PFS for patients with iMRI were 19.3 months (95% confidence interval, 15.4-23.7 months) and 9.5 months (95% confidence interval, 7.8-10.8 months). Median preoperative tumor volume was 37.0 cm3 (interquartile range [IQR], 19.9-59.8 cm3). Median RTV was 0 cm3 (IQR, 0-1.6 cm3). Median EOR was 100% (IQR, 96.2%-100%). In multivariate analysis, after controlling for age and Karnofsky Performance Status, EOR andRTV remained significantly associated with survival (hazard ratio, 1.56; P= 0.018) and recurrence (hazard ratio, 1.53; P= 0.013). Maximum RTV for survival was 3 cm3. This volumetric analysis for low-field iMRI showed that both EOR and RTV were significantly associated with survival and recurrence. We determined a threshold RTV of 3 cm3 as the maximum RTV associated with survival.