A Comparison of 2 Disease Burden Assessment Methods (3D Volume Versus the Number of Lesions) for Prognostication of Survival in Metastatic Melanoma: Implications for the Characterization of Oligometastatic Disease.

PURPOSE: Oligometastatic disease (OMD), generally defined by the presence of ≤5 metastatic lesions, represents an intermediate state between localized and widespread metastatic disease. This study aimed to question the conventional definition of OMD and assess the significance of the total volume and loci of metastases in characterizing OMD using an unselected metastatic melanoma cohort. METHODS AND MATERIALS: We identified 86 consecutive patients with metastatic melanoma who received pembrolizumab monotherapy from 2015 to 2020. We retrospectively contoured the gross tumor volumes of all metastatic lesions on baseline and follow-up imaging. The number, total volume, and loci information of metastases was collected. The primary endpoint was overall survival. A density histogram plot was used for tumor characteristic descriptions, and classification analysis using the decision tree and random forest methods was performed to determine the optimal combination of prognostic factors in the clinical setting. RESULTS: A total of 2728 gross tumor volumes were delineated. On baseline imaging, the median number and total volume of metastases was 7 (interquartile range, 3-17) and 28.4 cc (interquartile range, 8.4-88.78), respectively. The lymph node was the most common metastatic site (n = 46, 54%), followed by the lungs (n = 32, 37%), liver (n = 23, 27%), and bones (n = 21, 24%). Two-year overall survival rates of patients with 1 to 5, 6 to 10, 11 to 20, and >20 metastases were 58%, 47%, 31%, and 14%, respectively, and with ≤10, 11 to 30, 31 to 130, and >130 cc of metastatic volume were 64%, 43%, 33%, and 25%, respectively. K-adaptive partitioning revealed that the optimal cutoff was 20 and 37.9 cc. Decision tree and random forest analyses revealed that volume and loci (brain and liver metastases) were the most important factors (Harrell's C-index, 0.78). CONCLUSIONS: The OMD state could represent a continuous spectrum of disease burden instead of a binary phenomenon. We propose integrating the volumetric and spatial information of metastases into the characterization of OMD and the stratification tool of clinical trials in the metastatic setting, although external validation studies are needed.

Is SABR Cost-Effective in Oligometastatic Cancer? An Economic Analysis of the SABR-COMET Randomized Trial.

PURPOSE: The phase 2 randomized study SABR-COMET demonstrated that in patients with controlled primary tumors and 1 to 5 oligometastatic lesions, SABR was associated with improved progression-free survival (PFS) compared with standard of care (SoC), but with higher costs and treatment-related toxicities. The aim of this study was to assess the cost-effectiveness of SABR versus SoC in this setting. METHODS AND MATERIALS: A Markov model was constructed to perform a cost-utility analysis from the Canadian health care system perspective. Utility values and transition probabilities were derived from individual-level data from the SABR-COMET trial. One-way, 2-way, and probabilistic sensitivity analyses were performed. Costs were expressed in 2018 CAD. A separate analysis based on US payer's perspective was performed. An incremental cost-effectiveness ratio (ICER) at a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) was used. RESULTS: In the base case scenario, SABR was cost-effective at an ICER of $37,157 per QALY gained. This finding was most sensitive to the number of metastatic lesions treated with SABR (ICER: $28,066 per QALY for 2, increasing to $64,429 per QALY for 5), difference in chemotherapy use (ICER: $27,173-$53,738 per QALY), and PFS hazard ratio (HR) between strategies (ICER: $31,548-$53,273 per QALY). Probabilistic sensitivity analysis revealed that SABR was cost-effective in 97% of all iterations. Two-way sensitivity analysis demonstrated a nonlinear relationship between the number of lesions and the PFS HR. To maintain cost-effectiveness for each additional metastasis, the HR must decrease by approximately 0.047. The US cost analysis yielded similar results, with an ICER of $54,564 (2018 USD per QALY) for SABR. CONCLUSIONS: SABR is cost-effective for patients with 1 to 5 oligometastatic lesions compared with SoC.

Template-based Intensity-Modulated Radiation Therapy: A Cost-effective Intensity-Modulated Radiation Therapy Planning Procedure for Prostate Cancer.

INTRODUCTION: Intensity-modulated radiation therapy (IMRT) has been widely accepted for the treatment of prostate cancer. In comparison with traditional three-dimensional conformal radiation therapy (3D-CRT), it improves local control while minimizing side effects. However, IMRT comes at a significantly higher cost. In this report, we describe the development of template-based IMRT (TB-IMRT) planning for prostate cancer that does not require additional resources above 3D-CRT. METHODS: Twenty patients previously treated using 3D-CRT were retrospectively planned using the TB-IMRT planning technique. Planning target volume coverage, dose to organs at risk, and resource usage were compared between 3D-CRT and TB-IMRT techniques. RESULTS: All 3D-CRT and TB-IMRT plans met the planning guidelines. TB-IMRT compared better than 3D-CRT in terms of the homogeneity index (0.039 ± 0.007 vs. 0.052 ± 0.008) and conformity index (0.866 ± 0.024 vs. 0.752 ± 0.054). TB-IMRT also provided better sparing of organs at risk. Planning times were significantly less for TB-IMRT (average 13.43 ± 2.18 minutes) compared with conventional plans (45.4 ± 17.0 minutes). Times required for patient-specific quality assurance were similar between TB-IMRT and 3D-CRT. CONCLUSIONS: The TB-IMRT technique for prostate allows for all the potential benefits of IMRT without any additional resources above conventional 3D-CRT.

PTV margin for dose escalated radiation therapy of prostate cancer with daily on-line realignment using internal fiducial markers: Monte Carlo approach and dose population histogram (DPH) analysis.

Using internal fiducial markers and electronic portal imaging (EPID) to realign patients has been shown to significantly reduce positioning uncertainties in prostate radiation treatment. This creates the possibility of decreasing the planning target volume (PTV) margin added on the clinical target volume (CTV), which in turn may allow for dose escalation. We compared the outcome of two plans: 70Gy/35fx, 10 mm PTV margin without patient realignment (Reference Plan) vs. 78Gy/39fx, 5 mm PTV margin with patient realignment (Escalated Plan). Four-field-oblique (gantry angles 35 degrees, 90 degrees, 270 degrees, 176 degrees, 325 degrees) beam arrangement was used. Monte Carlo code was used to simulate the daily organ motion. Dose to each organ was calculated. Tumour control probability (TCP) and the effective dose to critical organ (Deff) were calculated using the biologically normalized dose-volume histograms. By comparing the biological factors, we found that the prescription dose can be escalated to 78Gy/39fx with a 5 mm PTV margin when using internal fiducial markers and EPID. Based on the available dose-response data for intermediate risk prostate patients, this will result in a 20% increase of local control and significantly reduced rectal complications provided that less serial dose-volume behaviour of rectum is proven.