Mid-Ventilation (Mid-V) Approach Combined with 4D Cone Beam CT (CBCT) Guidance in Stereotactic Body Radiotherapy of Hepatocellular Carcinoma (HCC): A Clinical Evaluation

Abstract

Purpose/Objective(s) Tumor motion typically leads to large treatment volumes with internal-target-volume (ITV) based approach among abdominal tumors. Mid-ventilation (Mid-V) based planning target volume (PTV) margins often lead to smaller treatment volumes, yet clinical experience is limited in hepatocellular carcinoma (HCC). This study aimed at evaluating the Mid-V approach on clinical outcome of stereotactic body radiotherapy (SBRT) among HCC patients. Materials/Methods 149 patients with 158 tumors treated during 2011-2016 were analyzed from a prospectively collected database. Each patient was planned on the Mid-V scan from the 4D-CT using volumetric modulated arc radiotherapy (VMAT). Tumor amplitudes were determined separately in left–right (LR), cranio–caudal (CC) and anterior–posterior (AP) directions, to derive the individualized PTV margins by means of the van herk formula. On-line 4D-CBCT was performed to verify the treatment position by lipiodol retention if present and liver or diaphragm otherwise. Primary end point was local control (LC). Secondary end points were overall survival (OS) and objective response rate (ORR) by RECIST 1.1 criteria. Results The median tumor size was 8.4 cm (range: 1.1 – 20.5 cm) and GTV volume was 322.9 mL (range: 2.9–3990.7 mL). The median total equivalent dose in 2Gy/fr (EQD2, a/b = 10) was 37.5 Gy (range: 28–85.5 Gy). The median LR, CC and AP tumor amplitudes were 1 mm (0.1–5.7 mm), 6.1 mm (0.3–17.5 mm) and 1.7 mm (0.1–15 mm), respectively, yielding a median CTV-to-PTV margin of 11.5 mm (8.4—20.0 mm). While an ITV + 5 mm based PTV margin would have been bigger in 44.3% of the patients, the LC and OS differences of our mid-V generated PTV margins of <10mm and ≥10mm were insignificant (p = 0.587, p = 0.622 respectively). It has yielded overall 1-year and 2-year LC rates of 88.9% (95% CI 86.3—91.5%) and 82.1% (95% CI 78.4—85.8%) respectively, of which tumors <5cm achieved an excellent 1-year LC rate of 96.9% with a trend towards better LC as compared to those ≥5cm (p = 0.062). The overall 1-year and 2-year OS rates of 57.4% (95% CI 53.5—61.3%) and 35.9% (95% CI 32.1—39.7%) respectively. ORR was 57% while clinical benefit rate was up to 94% (complete response: 6.0%, partial response: 51.0%, stable disease: 37.0%, progressive disease: 6.0%). Conclusion This first report of SBRT with Mid-V planning, 4D CBCT and individualized PTV margin generation by Van herk formula among HCC patients has achieved promising local control results. It supports that such image-guidance strategy is a safe approach and warrants further studies. Table 1. Comparison of local control and overall survival rates of different tumor sizes.