High dose proton and photon-based radiation therapy for 213 liver lesions: a multi-institutional dosimetric comparison with a clinical perspective

Abstract

Background: Stereotactic radiotherapy (SRT) and Proton therapy (PT) are both options in the management of liver lesions. Limited clinical-dosimetric comparison are available. Moreover, dose-constraint routinely used in liver PT and SRT considers only the liver spared, while optimization strategies to limit the liver damaged are poorly reported.

Methods: Primary endpoint was to assess and compare liver sparing of four contemporary RT techniques. Secondary endpoints were freedom from local recurrence (FFLR), overall survival (OS), acute and late toxicity. We hypothesize that Focal Liver Reaction (FLR) is determined by a similar biologic dose. FLR was delineated on follow-up MRI. Mean C.I. was computed for all the schedules used. A so-called Fall-off Volume (FOV) was defined as the area of healthy liver (liver-PTV) receiving more than the isotoxic dose. Fall-off Volume Ratio (FOVR) was defined as ratio between FOV and PTV.

Results: 213 lesions were identified. Mean best fitting isodose (isotoxic doses) for FLR were 18Gy, 21.5 Gy and 28.5 Gy for 3, 5 and 15 fractions. Among photons, an advantage in terms of healthy liver sparing was found for Vmat FFF with 5mm jaws (p = 0.013) and Cyberknife (p = 0.03). FOV and FOVR resulted lower for PT (p < 0.001). Three years FFLR resulted 83%. Classic Radiation induced liver disease (RILD, any grade) affected 2 patients.

Conclusions: Cyberknife and V-MAT FFF with 5mm jaws spare more liver than V-MAT FF with 10 mm jaws. PT spare more liver compared to photons. FOV and FOVR allows a quantitative analysis of healthy tissue sparing performance showing also the quality of plan in terms of dose fall-off.

Keywords: Cholangiocarcinoma; HCC; Liver metastasis; Proton therapy; SBRT; SRT.

Fig. 1

Representation of the isodose extraction process. In brief, coregistration of planning CT and 3 months follow-up MRI (hepatobiliary phase, fat-suppressed T1 weighted images), delineation on the FLR on MRI, coregistration of dose deliverd and CI extraction. Such process has been performed for all patients respecting study inclusion criteria

Fig. 2

Pictorial representation of FOV computing. FOV is obtained by subtraction of whole liver volume-PTV—(rVx) for 3, 5 and 15 fractions). Where “rVx” is the liver volume receiving less than the isotoxic dose (Gy). Such volume represents the area of liver damage after SRT

Fig. 3

Pictorial representation of FOVR computing and interpretation of results. FOVR is obtained dividing fall-off Volume (FOV) / PTV. Such ratio represents a way to show the quantity of liver damaged in relationship to the treated PTV