Proton beam therapy versus stereotactic body radiotherapy for hepatocellular carcinoma: practice patterns, outcomes, and the effect of biologically effective dose escalation

Hasan, Shaakir; Abel, Stephen; Verma, Vivek; Webster, Patrick; Arscott, W. Tristram; Wegner, Rodney E.; Kirichenko, Alexander; Simone, Charles B.

doi:10.21037/jgo.2019.08.03

Cited by 37 publications

(26 citation statements)

References 29 publications

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“…We assumed that all medications were taken by the patients as prescribed until tumor progression; therefore, the sorafenib dosage may be overestimated 25 . Second, although modern radiotherapy such as stereotactic body radiation therapy (SBRT) and proton therapy provide better tumor coverage and sparing of normal tissues, our database did not provide enough information regarding these techniques 27 . However, the effect of these modern radiotherapy on survival might be greater than that observed in our analysis.…”

Section: Discussionmentioning

confidence: 99%

Effect of radiotherapy on survival in advanced hepatocellular carcinoma patients treated with sorafenib: a nationwide cancer-registry-based study

Chu

Kuo

Liu

et al. 2021

Sci Rep

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Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) patients. This study aims to determine whether combining radiotherapy with sorafenib administration increases its efficacy. The study cohort included 4763 patients with diagnosed advanced HCC who received sorafenib between January 2012 and December 2015, as reported in medical records in the Taiwan Cancer Registry database. The effect of sorafenib with or without radiotherapy on survival was calculated using the Kaplan–Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Patients receiving sorafenib plus radiotherapy had greater 1-year survival than did those receiving sorafenib alone (P < 0.001). Uni- and multivariate analyses also showed that radiotherapy increased survival after adjusting for confounders (adjusted HR 0.57; 95% CI 0.51–0.63). Further stratified analysis according to the timing of radiotherapy relative to sorafenib treatment revealed that patients who underwent radiotherapy after sorafenib had greater 1-year survival than did those undergoing radiotherapy within sorafenib use or sorafenib alone (adjusted HR 0.39; 95% CI 0.27–0.54). Combined treatment with sorafenib and radiotherapy results in greater HCC patient survival and should be considered an option for treating this challenging disease.

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Section: Discussionmentioning

confidence: 99%

Effect of radiotherapy on survival in advanced hepatocellular carcinoma patients treated with sorafenib: a nationwide cancer-registry-based study

Chu

Kuo

Liu

et al. 2021

Sci Rep

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“…25,26 The use of SBPT for HCC is intriguing, as proton therapy was an independent predictor of better OS in an National Cancer Database (NCDB) analysis comparing proton therapy to photon SBRT. 27 The current study is limited by its retrospective nature. Patient selection, both in terms of tumor burden and liver function, is particularly important when reporting toxicity and outcomes of HCC treatment.…”

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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“…Due to this, heavier ions, like carbon ions, which have less lateral scattering but still deposit energy at the tumor, are increasingly part of the discussion of treatment options for different types of cancers [26]. [27][28][29] [ [30][31][32] Head and Neck Proton Trial study unknown…”

Section: Proton Therapymentioning

confidence: 99%

Immunomodulatory Effects of Radiotherapy

Kumari

Mukherjee

Sinha

et al. 2020

IJMS

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Radiation therapy (RT), an integral component of curative treatment for many malignancies, can be administered via an increasing array of techniques. In this review, we summarize the properties and application of different types of RT, specifically, conventional therapy with x-rays, stereotactic body RT, and proton and carbon particle therapies. We highlight how low-linear energy transfer (LET) radiation induces simple DNA lesions that are efficiently repaired by cells, whereas high-LET radiation causes complex DNA lesions that are difficult to repair and that ultimately enhance cancer cell killing. Additionally, we discuss the immunogenicity of radiation-induced tumor death, elucidate the molecular mechanisms by which radiation mounts innate and adaptive immune responses and explore strategies by which we can increase the efficacy of these mechanisms. Understanding the mechanisms by which RT modulates immune signaling and the key players involved in modulating the RT-mediated immune response will help to improve therapeutic efficacy and to identify novel immunomodulatory drugs that will benefit cancer patients undergoing targeted RT.

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Proton beam therapy versus stereotactic body radiotherapy for hepatocellular carcinoma: practice patterns, outcomes, and the effect of biologically effective dose escalation

Cited by 37 publications

References 29 publications

Effect of radiotherapy on survival in advanced hepatocellular carcinoma patients treated with sorafenib: a nationwide cancer-registry-based study

Effect of radiotherapy on survival in advanced hepatocellular carcinoma patients treated with sorafenib: a nationwide cancer-registry-based study

Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience

Immunomodulatory Effects of Radiotherapy

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