Predictors of Radiation-Induced Liver Disease in Eastern and Western Patients With Hepatocellular Carcinoma Undergoing Proton Beam Therapy

Hsieh, Cheng‐En; Venkatesulu, Bhanu Prasad; Lee, Ching-Hsin; Hung, Sheng-Ping; Wong, Pei Fong; Aithala, Sathvik Panambur; Kim, Byung Kyu; Rao, Arvind; Chang, Joseph Tung-Chieh; Tsang, Ngan‐Ming; Wang, Chun‐Chieh; Lee, Chung-Chi; Lin, Chen‐Chun; Tseng, Jeng‐Hwei; Chou, Wen‐Chi; Wang, Yuchao; Krishnan, Sunil; Hong, Ji-Hong

doi:10.1016/j.ijrobp.2019.02.032

Cited by 40 publications

(20 citation statements)

References 52 publications

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“…20 More recently, a multiinstitutional dosimetric analysis of patients undergoing proton therapy identified unirradiated liver volume (liver receiving <1Gy [RBE]) as an independent predictor of CP increase by 2 points. 21 The importance of minimizing radiation-related liver injury is supported by 2 separate clinical comparisons of proton and photon therapy for HCC. In a multicenter study, patients who received proton therapy had significantly improved OS compared with those who received photon therapy and also had a significantly decreased risk of developing a CP increase by 2 points.…”

Section: Discussionmentioning

confidence: 99%

Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience

Bhangoo

Mullikin

Ashman

et al. 2021

Advances in Radiation Oncology

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Our purpose was to assess the safety and efficacy of intensity modulated proton therapy (IMPT) for the treatment of hepatocellular carcinoma (HCC). Methods and Materials: A retrospective review was conducted on all patients who were treated with IMPT for HCC with curative intent from June 2015 to December 2018. All patients had fiducials placed before treatment. Inverse treatment planning used robust optimization with 2 to 3 beams. The majority of patients were treated in 15 fractions (n Z 30, 81%, 52.5-67.5 Gy, relative biological effectiveness), whereas the remainder were treated in 5 fractions (n Z 7, 19%, 37.5-50 Gy, relative biological effectiveness). Daily image guidance consisted of orthogonal kilovoltage x-rays and use of a 6 of freedom robotic couch. Outcomes (local control, progression free survival, and overall survival) were determined using Kaplan-Meier methods. Results: Thirty-seven patients were included. The median follow-up for living patients was 21 months (Q1-Q3, 17-30 months). Pretreatment Child-Pugh score was A5-6 in 70% of patients and B7-9 in 30% of patients. Nineteen patients had prior liver directed therapy for HCC before IMPT. Eight patients (22%) required a replan during treatment, most commonly due to inadequate clinical target volume coverage. One patient (3%) experienced a grade 3 acute toxicity (pain) with no recorded grade 4 or 5 toxicities. An increase in Child-Pugh score by ! 2 within 3 months of treatment was observed in 6 patients (16%). At 1 year, local control was 94%, intrahepatic control was 54%, progression free survival was 35%, and overall survival was 78%.Sources of support: This work had no specific funding. Disclosures: S.K. reports grants from NIH, DoD, CPRIT, Celgene, and Elekta outside the submitted work. In addition, S.K. has issued patents on gold nanoparticles and radiation minibeams. W.L. reports grants from Arizona Biomedical Research Commissioning, grants from the National Cancer Institute (NCI) Career Developmental Award K25CA168984, grants from the Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, and grants from the Kemper Marley Foundation outside the submitted work. In addition, W.L. has a patent, "An Accurate and Efficient Hybrid Method Based on Ray Casting to Calculate Physical Dose and Linear Energy Transfer (LET) Distribution for Intensity Modulated Proton Therapy" with royalties paid to.Decimal LLC. T.T.S. provides strategic and scientific recommendations as a member of the advisory board and a speaker for Novocure, Inc.All data generated and analyzed during this study are included in this published article. Research data are stored in an institutional repository and will be shared upon request to the corresponding author.

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Section: Discussionmentioning

confidence: 99%

Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience

Bhangoo

Mullikin

Ashman

et al. 2021

Advances in Radiation Oncology

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“…Most published liver dosage tolerances are based on whole liver irradiation data (13,14) and available data relating liver tolerance to PBT are scarce. It is thought that liver function or irradiation volume affects radiation-induced liver dysfunction (15,16); however, no definite consensus has been reached because of sparse data and reports. We therefore defined our own dose constraint as an unirradiated liver volume of > 500 cm 3 based on our previous studies and clinical experience (15).…”

Section: Discussionmentioning

confidence: 99%

Three cases of hepatocellular carcinoma treated 4�times with proton beams

Murakami

Fukumitsu²,

Okumura

et al. 2019

mol clin onc

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HCC may recur following surgery or radiofrequency ablation. Proton beam therapy (PBT) is a type of radiotherapy that achieves excellent local control of HCC without severe toxicity. The present study reported the long-term outcome of 3 HCC patients who each received 4 repeat courses of PBT. All patients had a hepatitis B or C viral infection. A total of 14 lesions were treated using a curative PBT protocol and irradiated liver volumes in each treatment were 7–50% of the total liver volume. Liver function in all cases was considerably preserved until the last follow-up and patient survival was 51–107 months from the first PBT with no local recurrence observed in the 14 lesions. The presented cases indicated that repeated PBT is an effective treatment option for recurrent HCC due to reduced liver damage and superior local treatment compared with other treatment options such as transarterial chemoembolization.

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“…Furthermore, Sanford et al [ 70 ] reported that the overall survival (OS) benefit of proton-RT over photon-RT might be due to decreasing the incidence of RILD. Hsieh et al [ 71 ] further identified the predictors of RILD in HCC patients treated with PBT beyond the conventional concept of minimizing the mean liver dose. A "volume-response" relationship between unirradiated liver volume (ULV)/standard liver volume (SLV) and RILD was found: For Child-Pugh A patients, it was < 50%; for Child-Pugh B patients, it was < 30%[ 71 ].…”

Section: The Role Of Rt In Hccmentioning

confidence: 99%

Role of modern radiotherapy in managing patients with hepatocellular carcinoma

Lin¹,

Hung²,

Chiou³

et al. 2021

WJG

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Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Several treatment options are available for managing HCC patients, classified roughly as local, local-regional, and systemic therapies. The high post-monotherapy recurrence rate of HCC urges the need for the use of combined modalities to increase tumor control and patient survival. Different international guidelines offer treatment recommendations based on different points of view and classification systems. Radiotherapy (RT) is a well-known local-regional treatment modality for managing many types of cancers, including HCC. However, only some of these treatment guidelines include RT, and the role of combined modalities is rarely mentioned. Hence, the present study reviewed clinical evidence for the use of different combined modalities in managing HCC, focusing on modern RT's role. Modern RT has an increased utility in managing HCC patients, mainly due to two driving forces. First, technological advancement ( e.g. , stereotactic body radiotherapy and advanced proton-beam therapy) enables precise delivery of radiation to increase tumor control and reduce side effects in the surrounding normal tissue. Second, the boom in developing target therapies and checkpoint-blockade immunotherapy prolongs overall survival in HCC patients, re-emphasizing the importance of local tumor control. Remarkably, RT combines with systemic therapies to generate the systemic therapy augmented by radiotherapy effect, a benefit now being actively investigated.

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Predictors of Radiation-Induced Liver Disease in Eastern and Western Patients With Hepatocellular Carcinoma Undergoing Proton Beam Therapy

Abstract: Bing-Shen Huang for his pertinent comments on unirradiated liver volume to standard liver volume ratio calculation.

Cited by 40 publications

References 52 publications

Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience

Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience

Three cases of hepatocellular carcinoma treated 4�times with proton beams

Role of modern radiotherapy in managing patients with hepatocellular carcinoma

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