Carbon ion radiotherapy with pencil beam scanning for hepatocellular carcinoma: Long‐term outcomes from a phase I trial

Abstract

This study evaluates the feasibility of the pencil beam scanning technique of carbon ion radiotherapy (CIRT) in the setting of hepatocellular carcinoma (HCC) and establishes the maximum tolerated dose (MTD) calculated by the Local Effect Model version I (LEM‐I) with a dose escalation plan. The escalated relative biological effectiveness‐weighted dose levels included 55, 60, 65, and 70 Gy in 10 fractions. Active motion management techniques were employed, and several measures were applied to mitigate the interplay effect induced by a moving target. CIRT was planned with the LEM‐I‐based treatment planning system and delivered by raster scanning. Offline PET/CT imaging was used to verify the beam range. Offline adaptive replanning was performed whenever required. Twenty‐three patients with a median tumor size of 4.3 cm (range, 1.7–8.5 cm) were enrolled in the present study. The median follow‐up time was 56.1 months (range, 5.7–74.4 months). No dose limiting toxicity was observed until 70 Gy, and MTD had not been reached. No patients experienced radiation‐induced liver disease within 6 months after the completion of CIRT. The overall survival rates at 1, 3, and 5 years were 91.3%, 81.9%, and 67.1% after CIRT, respectively. The local progression‐free survival and progression‐free survival rates at 1, 3 and 5 years were 100%, 94.4%, and 94.4% and 73.6%, 59.2%, and 37.0%, respectively. The raster scanning technique could be used to treat HCC. However, caution should be exercised to mitigate the interplay effect. CIRT up to 70 Gy in 10 fractions over 2 weeks was safe and effective for HCC.

Current perspectives on radiotherapy in hepatocellular carcinoma management: a comprehensive review

“…The trial achieved a 5-year OS and local control rates of 67.1% and 94.4%, respectively. 49 Limited retrospective studies exist comparing CIRT with other treatment modalities for HCC. According to Shiba et al, 117 CIRT was compared with TACE for a single HCC lesion.…”

“…[38][39][40][41][42][43][44][45][46] Furthermore, proton beam therapy (PBT) and carbon ion RT (CIRT) have been proven through various studies to provide outstanding disease control and acceptable toxicity. 19,22,25,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64] Recent research has shifted focus toward the combined therapy of EBRT with other modalities or the potential of EBRT as an alternative to conventional local treatments in specific liver locations or depending on the patient's condition and liver function. [65][66][67][68] Numerous comparative studies are being reported in this area.…”

“…With the advancement of RT techniques, there has been a significant increase in reported studies on meaningful particle therapy in HCC (Table 3). 19,22,25,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] PBT is characterized by its exceptional dose concentration, enabling the safe delivery of high doses directly to tumors. This is particularly advantageous in treating large lesions, which are often challenging to manage with SBRT.…”

Carbon Ion Radiotherapy in the Treatment of Hepatocellular Carcinoma

“…Dose levels ranged from 55 to 70 Gy (RBE) in 10 fractions, and no dose-limiting toxicity was observed. The 5-year local control rate was 94.4% [ 17 ].…”

“…The efficacy and feasibility of CIRT for HCC have been investigated in several prospective phase I and II studies ( [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] The first prospective phase I trial was reported from the National Institute of Radiological Sciences in 2004 exploring dose escalation from 49.5 Gy (RBE) in 15 fractions to 79.5 Gy (RBE) in 15 fractions. 21 No severe adverse effects or treatment-related deaths were reported.…”