Dataset Information

Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235.

ABSTRACT: To determine whether higher pre-treatment metabolic tumor volume (tMTV-pre) is associated with worse overall survival (OS) in patients with inoperable NSCLC treated with definitive chemoradiation (CRT).This is a secondary analysis of the American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group 0235 trial. Pre-treatment PET scans were performed on ACRIN-qualified scanners. Computer-aided MTV measurement was performed using RT_Image. Kaplan-Meier curves and Cox proportional hazards regression models were used to assess the association between tMTV and OS.Of the 250 patients enrolled on the study, 230 were evaluable for tMTV-pre. Patients with MTV-pre >32 mL (median value) vs. ?32 mL had worse median OS (14.8 vs. 29.7 months, p?32 mL who received ?60 Gy compared with those who received 61-69 Gy or ?70 Gy (p?=?0.001).Higher tMTV-pre is associated with significantly worse OS in inoperable stage III NSCLC treated with definitive CRT. Our findings suggest that for patients with large tMTV-pre, achieving a therapeutic radiation dose may help maximize OS. Prospective studies are needed to confirm this finding.

SUBMITTER: Bazan JG

PROVIDER: S-EPMC5121029 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235.

Bazan Jose G JG Duan Fenghai F Snyder Bradley S BS Horng Dunstan D Graves Edward E EE Siegel Barry A BA Machtay Mitchell M Loo Billy W BW

European journal of nuclear medicine and molecular imaging 20160919 1

<h4>Purpose</h4>To determine whether higher pre-treatment metabolic tumor volume (tMTV-pre) is associated with worse overall survival (OS) in patients with inoperable NSCLC treated with definitive chemoradiation (CRT).<h4>Methods</h4>This is a secondary analysis of the American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group 0235 trial. Pre-treatment PET scans were performed on ACRIN-qualified scanners. Computer-aided MTV measurement was performed using RT_Imag ...[more]

PMID: 27645692

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Project description:PurposeThe American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group (RTOG) 0235 study demonstrated that standardized uptake values (SUV) on post-treatment [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET) correlated with survival in locally advanced non-small cell lung cancer (NSCLC). This secondary analysis determined whether SUV of regional lymph nodes (RLNs) on post-treatment FDG-PET correlated with patient outcomes.Methods and materialsIncluded for analysis were patients treated with concurrent chemoradiation therapy, using radiation doses ≥60 Gy, with identifiable FDG-avid RLNs (distinct from primary tumor) on pretreatment FDG-PET, and post-treatment FDG-PET data. ACRIN core laboratory SUV measurements were used. Event time was calculated from the date of post-treatment FDG-PET. Local-regional failure was defined as failure within the treated RT volume and reported by the treating institution. Statistical analyses included Wilcoxon signed rank test, Kaplan-Meier curves (log rank test), and Cox proportional hazards regression modeling.ResultsOf 234 trial-eligible patients, 139 (59%) had uptake in both primary tumor and RLNs on pretreatment FDG-PET and had SUV data from post-treatment FDG-PET. Maximum SUV was greater for primary tumor than for RLNs before treatment (P<.001) but not different post-treatment (P=.320). Post-treatment SUV of RLNs was not associated with overall survival. However, elevated post-treatment SUV of RLNs, both the absolute value and the percentage of residual activity compared to the pretreatment SUV were associated with inferior local-regional control (P<.001).ConclusionsHigh residual metabolic activity in RLNs on post-treatment FDG-PET is associated with worse local-regional control. Based on these data, future trials evaluating a radiation therapy boost should consider inclusion of both primary tumor and FDG-avid RLNs in the boost volume to maximize local-regional control.

Project description:UnlabelledIn a secondary analysis of American College of Radiology Imaging Network (ACRIN) 6668/RTOG 0235, high pretreatment metabolic tumor volume (MTV) on (18)F-FDG PET was found to be a poor prognostic factor for patients treated with chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). Here we utilize the same dataset to explore whether heterogeneity metrics based on PET textural features can provide additional prognostic information.MethodsPatients with locally advanced NSCLC underwent (18)F-FDG PET prior to treatment. A gradient-based segmentation tool was used to contour each patient's primary tumor. MTV, maximum SUV, and 43 textural features were extracted for each tumor. To address overfitting and high collinearity among PET features, the least absolute shrinkage and selection operator (LASSO) method was applied to identify features that were independent predictors of overall survival (OS) after adjusting for MTV. Recursive binary partitioning in a conditional inference framework was utilized to identify optimal thresholds. Kaplan-Meier curves and log-rank testing were used to compare outcomes among patient groups.ResultsTwo hundred one patients met inclusion criteria. The LASSO procedure identified 1 textural feature (SumMean) as an independent predictor of OS. The optimal cutpoint for MTV was 93.3 cm(3), and the optimal SumMean cutpoint for tumors above 93.3 cm(3) was 0.018. This grouped patients into three categories: low tumor MTV (n = 155; median OS, 22.6 mo), high tumor MTV and high SumMean (n = 23; median OS, 20.0 mo), and high tumor MTV and low SumMean (n = 23; median OS, 6.2 mo; log-rank P < 0.001).ConclusionWe have described an appropriate methodology to evaluate the prognostic value of textural PET features in the context of established prognostic factors. We have also identified a promising feature that may have prognostic value in locally advanced NSCLC patients with large tumors who are treated with chemoradiotherapy. Validation studies are warranted.

Project description:PurposeIn recent years, multiple studies have demonstrated the value of volumetric FDG-PET/CT parameters as independent prognostic factors in patients with non-small cell lung cancer (NSCLC). We aimed to determine the optimal cut-off points of pretreatment volumetric FDG-PET/CT parameters in predicting overall survival (OS) in patients with locally advanced NSCLC and to recommend imaging biomarkers appropriate for routine clinical applications.MethodsPatients with inoperable stage IIB/III NSCLC enrolled in ACRIN 6668/RTOG 0235 were included. Pretreatment FDG-PET scans were quantified using semiautomatic adaptive contrast-oriented thresholding and local-background partial-volume-effect-correction algorithms. For each patient, the following indices were measured: metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmax, SUVmean, partial-volume-corrected TLG (pvcTLG), and pvcSUVmean for the whole-body, primary tumor, and regional lymph nodes. The association between each index and patient outcome was assessed using Cox proportional hazards regression. Optimal cut-off points were estimated using recursive binary partitioning in a conditional inference framework and used in Kaplan-Meier curves with log-rank testing. The discriminatory ability of each index was examined using time-dependent receiver operating characteristic (ROC) curves and corresponding area under the curve (AUC(t)).ResultsThe study included 196 patients. Pretreatment whole-body and primary tumor MTV, TLG, and pvcTLG were independently prognostic of OS. Optimal cut-off points were 175.0, 270.9, and 35.5 cm3 for whole-body TLG, pvcTLG, and MTV, and were 168.2, 239.8, and 17.4 cm3 for primary tumor TLG, pvcTLG, and MTV, respectively. In time-dependent ROC analysis, AUC(t) for MTV and TLG were uniformly higher than that of SUV measures over all time points. Primary tumor and whole-body parameters demonstrated similar patterns of separation for those patients above versus below the optimal cut-off points in Kaplan-Meier curves and in time-dependent ROC analysis.ConclusionWe demonstrated that pretreatment whole-body and primary tumor volumetric FDG-PET/CT parameters, including MTV, TLG, and pvcTLG, are strongly prognostic for OS in patients with locally advanced NSCLC, and have similar discriminatory ability. Therefore, we believe that, after validation in future trials, the derived optimal cut-off points for primary tumor volumetric FDG-PET/CT parameters, or their more refined versions, could be incorporated into routine clinical practice, and may provide more accurate prognostication and staging based on tumor metabolic features.

Project description:PurposeIn this prospective National Cancer Institute-funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non-small-cell lung cancer (NSCLC).Patients and methodsPatients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models.ResultsOf 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak.ConclusionHigher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.

Project description:ObjectiveAnal cancer is an uncommon malignancy with the primary treatment for localized disease being concurrent radiation and chemotherapy. Pre-treatment PET/CT is useful for target delineation, with minimal exploration of its use in prognostication. In the post-treatment setting there is growing evidence for advanced PET metrics in assessment of treatment response, and early identification of recurrence essential for successful salvage, however this data is limited to small series.MethodsPatient with non-metastatic anal cancer from a single institution were retrospectively reviewed for receipt of pre- and post-treatment PET/CTs. PET data was co-registered with radiation therapy planning CT scans for precise longitudinal assessment of advanced PET metrics including SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), for assessment with treatment outcomes. Treatment outcomes included local recurrence (LR), progression free survival (PFS), and overall survival (OS), as defined from the completed radiation therapy to the time of the event. Cox proportional hazard modeling with inverse probability weighting (IPW) using the propensity score based on age, BMI, T-stage, and radiation therapy dose were utilized for assessment of these metrics.ResultsFrom 2008 to 2017 there were 72 patients who had pre-treatment PET/CT, 61 (85%) had a single follow up PET/CT, and 35 (49%) had two follow up PET/CTs. The median clinical follow-up time was 25 months (IQR: 13-52) with a median imaging follow up time of 16 months (IQR: 7-29). On pre-treatment PET/CT higher MTV2.5 and TLG were significantly associated with higher risk of local recurrence (HR 1.11, 95% CI: 1.06-1.16, p<0.001; and HR 1.12, 95% CI: 1.05-1.19, p<0.001), and worse PFS (HR 1.09, 95% CI: 1.04-1.13, p<0.001; and HR 1.09, 95% CI: 1.03-1.12, p = 0.003) and OS (HR 1.09, 95% CI: 1.04-1.16, p = 0.001; and HR 1.11, 95% CI: 1.04-1.20, p = 0.004). IPW-adjusted pre-treatment PET/CT showed higher MTV2.5 (HR 1.09, 95% CI: 1.02-1.17, p = 0.012) and TLG (HR 1.10, 95% CI: 1.00-1.20, p = 0.048) were significantly associated with worse PFS, and post-treatment MTV2.5 was borderline significant (HR 1.16, 95% CI: 1.00-1.35, p = 0.052).ConclusionAdvanced PET metrics, including higher MTV2.5 and TLG, in the pre-treatment and post-treatment setting are significantly associated with elevated rates of local recurrence, and worse PFS and OS. This adds to the growing body of literature that PET/CT for patient with ASCC should be considered for prognostication, and additionally is a useful tool for consideration of early salvage or clinical trial of adjuvant therapies.

Project description:Purpose To evaluate factors contributing to interreader variation (IRV) in parameters measured at dynamic contrast material-enhanced (DCE) MRI in patients with glioblastoma who were participating in a multicenter trial. Materials and Methods A total of 18 patients (mean age, 57 years ± 13 [standard deviation]; 10 men) who volunteered for the advanced imaging arm of ACRIN 6677, a substudy of the RTOG 0625 clinical trial for recurrent glioblastoma treatment, underwent analyzable DCE MRI at one of four centers. The 78 imaging studies were analyzed centrally to derive the volume transfer constant (Ktrans) for gadolinium between blood plasma and tissue extravascular extracellular space, fractional volume of the extracellular extravascular space (ve), and initial area under the gadolinium concentration curve (IAUGC). Two independently trained teams consisting of a neuroradiologist and a technologist segmented the enhancing tumor on three-dimensional spoiled gradient-recalled acquisition in the steady-state images. Mean and median parameter values in the enhancing tumor were extracted after registering segmentations to parameter maps. The effect of imaging time relative to treatment, map quality, imager magnet and sequence, average tumor volume, and reader variability in tumor volume on IRV was studied by using intraclass correlation coefficients (ICCs) and linear mixed models. Results Mean interreader variations (± standard deviation) (difference as a percentage of the mean) for mean and median IAUGC, mean and median Ktrans, and median ve were 18% ± 24, 17% ± 23, 27% ± 34, 16% ± 27, and 27% ± 34, respectively. ICCs for these metrics ranged from 0.90 to 1.0 for baseline and from 0.48 to 0.76 for posttreatment examinations. Variability in reader-derived tumor volume was significantly related to IRV for all parameters. Conclusion Differences in reader tumor segmentations are a significant source of interreader variation for all dynamic contrast-enhanced MRI parameters. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Wolf in this issue.

Dataset Information

Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235.

Publications

Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235.

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