Central Nervous System
PV QA 2 - Poster Viewing Q&A 2
Purpose/Objective(s): Studies of Single Dose Radiotherapy (SDRT) of Oligometastatic (OM) lesions reported a steep dose-dependent increase of OM ablation within a narrow range of 18-24Gy, rendering >90% ablation at 24Gy, reflecting a unique biological mechanism of SDRT. The present study was designed to define the ablative efficacy and limitations of 24Gy SDRT in a group of consecutive patients with clinical presentations of OM disease. A secondary endpoint was to assess the impact of OM ablation on the timing and rate of conversion of the OM state into polymetastatic (PM) dissemination.
Materials/Methods: Between November 2011 and September 2016, 155 consecutive eligible patients with extra-cranial ≤5 OM PET/CT detectable lesions were recruited to this phase II study. The primary aim was to treat all detected lesions with SDRT at a PTV prescription dose of 24Gy. However, lesions adjacent to serial normal tissue structures, where SDRT was deemed unfeasible, were diverted to a hypofractionated regimen of 3 x 9Gy SBRT. Local relapse free survival (LRFS) and freedom from PM dissemination (PMFS) were assessed at 3, 6 and every 6 months thereafter until patient demise or inability to be assessed. Local response was exclusively assessed by metabolic PET/CT imaging according to the PERCIST criteria. Detectable lesions were characterized in terms of GTV volume, location, and metabolic parameters (SUVmax). PET/CT scans were also used to determine the timing of PM dissemination.
Results: At a median follow-up of 21 months (range, 3-60) OM lesions treated with SDRT showed an actuarial 5-year LRFS of 92.3% compared to 34.4% for SBRT (p<0.0001). Tumor size, type, OM target organ, or adjuvant systemic therapy did not significantly affect LRFS following SDRT. PM conversion, defined as-PET/CT first evidence of concomitant ≥6 OM lesions, was not affected by treatment regimen, exhibiting actuarial 4-year PMFS of 44% in the 109 patients at risk treated by SDRT alone vs. 57.2% in the 46 patients receiving SBRT (p=0.9). A univariate analysis disclosed two factors impacting PMFS, namely, the total overall tumor burden at initial referral and the intensity of its highest SUVmax 18F-FDG metabolic signal. A bivariate analysis revealed a favorable prognostic group of patients with an initial low tumor burden of <14.8cc and a low SUVmax signal of <6.5, who exhibited a 5-year actuarial PMFS of 89.4%, compared to 46.3% in a bivariate presentation of a low tumor burden of <14.8cc and a concomitant high SUVmax of ≥6.5 (p=0.0001).
Conclusion: The present study validates the efficacy of 24Gy SDRT in permanently ablating OM disease. Furthermore, the use of PET/CT in initial treatment planning and in periodic post-SDRT follow-up evaluations discloses the dynamics of PM dissemination, and enables characterization of a subgroup of OM patients that exhibit a low incidence of PM conversion and an actuarial 89% tumor-free survival at 5 years after SDRT, likely providing an opportunity to define in future studies the elusive OM phenotype.
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