Central Nervous System

PV QA 2 - Poster Viewing Q&A 2

MO_3_2520 - Phase II Prospective Trial to Assess the Feasibility and Efficacy of Dynamic 24Gy Single Dose Ablative Stereotactic Radiation Therapy in Oligometastatic Human Cancer

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Phase II Prospective Trial to Assess the Feasibility and Efficacy of Dynamic 24Gy Single Dose Ablative Stereotactic Radiation Therapy in Oligometastatic Human Cancer
C. Greco1, O. Pares1, N. Pimentel1, M. Possanzini1, V. Louro1, J. Morales1, B. Nunes1, J. Castanhera1, C. Oliveira1, A. Silva1, S. Vaz1, D. Costa1, R. Kolesnick2, and Z. Fuks1,2; 1Champalimaud Centre for the Unknown, Lisbon, Portugal, 2Memorial Sloan Kettering Cancer Center, New York, NY

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.

Author Disclosure: C. Greco: None. N. Pimentel: None. M. Possanzini: None. J. Morales: None. S. Vaz: None. R. Kolesnick: None. Z. Fuks: None.

Send Email for Carlo Greco


Assets

MO_3_2520 - Phase II Prospective Trial to Assess the Feasibility and Efficacy of Dynamic 24Gy Single Dose Ablative Stereotactic Radiation Therapy in Oligometastatic Human Cancer



Attendees who have favorited this

Please enter your access key

The asset you are trying to access is locked. Please enter your access key to unlock.

Send Email for Phase II Prospective Trial to Assess the Feasibility and Efficacy of Dynamic 24Gy Single Dose Ablative Stereotactic Radiation Therapy in Oligometastatic Human Cancer