Stereotactic body radiotherapy in hepatocellular carcinoma: patient selection and predictors of outcome and toxicity

Loi, Mauro; Comito, Tiziana; Franzese, Ciro; Dominici, Luca; Faro, Lorenzo Lo; Clerici, Elena; Franceschini, Davide; Mancosu, P.; Reggiori, G.; Gallo, P.; Badalamenti, Matteo; Scorsetti, Marta

doi:10.1007/s00432-020-03389-2

Cited by 11 publications

(5 citation statements)

References 32 publications

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“… No UVA or MVA; no planned therapy/TACE Yeung et al 35 2019; retrospective 31 Median size=3.3 cm (1.3–5 cm) 45 Gy/3-5# 1-year LC= 94% 1-yr OS=84% 19% worsened CP score by>2 points; 32% > Grade 3 toxicities Child-Pugh Class A or B, with small HCCs measuring ≤5 cm; On UVA, small tumour size predicted for improved overall survival (P = 0.01); no planned therapy/TACE Mathew et al 28 2020; retrospective 297; ineligible or recurrent/residual after RFA/TACE; CP A/B/C=76/20/2 Median size=2.7cm (0.5–18.1cm) 27–60 Gy/3-6# 3-yr LRR=13% 3-yr OS= 39% Worsening of CP score by ≥2 points three months after SBRT in 16%. Liver transplant after downstaging post SBRT in 25 patients, CP A liver function, AFP ≤ 10 ng/mL, and ECOG status 0 significantly improved OS; no planned TACE Kimura et al 31 2020; prospective 36 (target 60; closed early due to poor accrual) Median size=2.3 cm (1–5 cm) 40 Gy/5# 3-yr LC= 90% 3-yr OS=78% ≥Grade 3 toxicities= 11% Previously untreated solitary HCC Loi et al 32 2020; retrospective 128 (BCLC Class A/B=31%/56%) Median size= 3 cm (1.4–9.9 cm) Median BED 10 =103 Gy/3-10#; Range=30–75 Gy in 3–10 # 2-yr LC= 78% 2-yr OS=58% (whole cohort; separately NA) Acute Grade 3 Toxicity- acute liver failure and ascites in 1 pt. In BCLC stage A-B disease (n=112), LC associated with improved OS (median 30 months vs not reached, p=0.036) Park et al 36 2020; retrospective 290 (BCLC Class A=86%) Median size=1.7 cm Median 45 Gy in 3 −4# (Range 30–60 Gy/3-4 #) …”

Section: Evidence For Indications and Efficacy Of Sbrt In Early Hccmentioning

confidence: 99%

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Current Understanding of Ablative Radiation Therapy in Hepatocellular Carcinoma

Mathew¹,

Dawson²

2021

JHC

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The role of ablative stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC) has been evolving over the last few decades. SBRT has mostly been used in early stages of HCC, including few (≤ 3 in number) tumors, small tumours (< 3 cm in size), as well as larger tumours which are ineligible for other ablative modalities, mostly without vascular invasion. In early stage HCC, SBRT is used as a definitive treatment with curative intent or with intent to bridge to liver transplant. Retrospective and prospective institutional series document a high rate of local control (68–95% at 3 years) following SBRT. This coupled with a low risk of toxicity makes this non-invasive ablative treatment an attractive option for patients who are ineligible for other ablative treatments. Small randomized studies of ablative radiation have also shown non-inferiority of radiation as compared to radiofrequency ablation (RFA). Currently, SBRT is widely available as a safe and effective liver directed therapy, although there is a need for more studies providing higher level evidence. This review gives a brief overview of SBRT and the evidence for its use in HCC patients with ablative intent.

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Section: Evidence For Indications and Efficacy Of Sbrt In Early Hccmentioning

confidence: 99%

“…Recent multi-institutional series from these countries though report outcomes of patients who were treated with SBRT upfront as first line of treatment, indicating a more widespread adoption/acceptance of SBRT in treatment of early tumors. [30][31][32][33][34][35][36][37]…”

Section: Definitive Treatment Of Early Hccmentioning

confidence: 99%

Current Understanding of Ablative Radiation Therapy in Hepatocellular Carcinoma

Mathew¹,

Dawson²

2021

JHC

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“…HCC is a radiosensitive tumour, and the presence of a significant dose response effect within the range of reported SABR dosing schedules has not been consistently demonstrated. [22][23][24] Local control rates for earlystage disease are generally high, more advanced disease is likely to receive lower doses, and patients often have significant competing risks for mortality including out-offield recurrences and progression of underlying liver disease. Thus, in comparison to SABR for other indications, more conservative dosing is often applied in the setting of HCC.…”

Section: Discussionmentioning

confidence: 99%

Stereotactic ablative radiotherapy for hepatocellular carcinoma: A systematic review and meta‐analysis of local control, survival and toxicity outcomes

et al. 2021

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There is a growing body of literature supporting the use of stereotactic ablative body radiotherapy (SABR) in the management of primary hepatocellular carcinoma (HCC). This systematic review and meta-analysis of the current published evidence for SABR for HCC assessed the impact of treatment dose, fractionation and tumour size on the outcomes of local control (LC), overall survival (OS) and toxicity. A systematic search was independently performed by two authors for articles published in peer-reviewed journals between January 2005 and December 2019. A DerSimonian and Laird random effects model was used to assess pooled results. A multivariate meta-regression analysis incorporated the effect of explanatory variables (radiation dose in EQD2 [10], fractionation and tumour size) on outcomes of OS, LC and toxicity. Forty-nine cohorts involving 2846 HCC patients with 3088 lesions treated with SABR were included. Pooled 1-, 2-and 3-year LC rates were 91.1% (95% confidence interval [CI] 88.3-93.2), 86.7% (95% CI 82.7-89.8) and 84.2% (95% CI 77.9-88.9) respectively. Pooled 1-, 2-and 3-year OS rates were 78.4% (95% CI 73.4-82.6), 61.3% (55.2-66.9) and 48.3% (95% CI 39.0-57). Population-weighted median grade 3 toxicity rates were 6.5% (IQR 3.2-16) and mean grade 4/5 rates were 1.4% (IQR 0-2.1). Within EQD2 [10] ranges of 40 to 83.33 Gy corresponding to common dose-fractionation regimens of 30-50 Gy in 5 fractions, there was a multivariate association between superior LC and OS with increasing EQD2 [10] , with a proportionately smaller increase in grade 3 toxicity and no association with grade 4/5 toxicity. Stereotactic ablative body radiotherapy is a viable treatment option for HCC with high LC rates and low rates of reported grade 3/4 toxicity. Increasing EQD2 [10] was associated with improvements in LC and OS with a comparatively smaller increase in toxicity. Prospective randomised trials are warranted to define optimal patient selection and dose-fractionation regimens.

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“…It is easy to spread in the liver through the portal vein system to form intrahepatic metastasis, and it is also easy to form tumor thrombus in the portal vein and cause portal hypertension. HCC is mostly found in the middle and late stages, which leads to its generally poor prognosis (4)(5)(6)(7)(8). According to statistics, the recurrence rate of HCC after surgery is as high as about 70% (9), and the survival rate is only 15%-40% (10).…”

Section: Introductionmentioning

confidence: 99%

Ensemble learning based on efficient features combination can predict the outcome of recurrence-free survival in patients with hepatocellular carcinoma within three years after surgery

Wang

Zhu

et al. 2022

Front. Oncol.

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Preoperative prediction of recurrence outcome in hepatocellular carcinoma (HCC) facilitates physicians’ clinical decision-making. Preoperative imaging and related clinical baseline data of patients are valuable for evaluating prognosis. With the widespread application of machine learning techniques, the present study proposed the ensemble learning method based on efficient feature representations to predict recurrence outcomes within three years after surgery. Radiomics features during arterial phase (AP) and clinical data were selected for training the ensemble models. In order to improve the efficiency of the process, the lesion area was automatically segmented by 3D U-Net. It was found that the mIoU of the segmentation model was 0.8874, and the Light Gradient Boosting Machine (LightGBM) was the most superior, with an average accuracy of 0.7600, a recall of 0.7673, a F1 score of 0.7553, and an AUC of 0.8338 when inputting radiomics features during AP and clinical baseline indicators. Studies have shown that the proposed strategy can relatively accurately predict the recurrence outcome within three years, which is helpful for physicians to evaluate individual patients before surgery.

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Stereotactic body radiotherapy in hepatocellular carcinoma: patient selection and predictors of outcome and toxicity

Cited by 11 publications

References 32 publications

Current Understanding of Ablative Radiation Therapy in Hepatocellular Carcinoma

Current Understanding of Ablative Radiation Therapy in Hepatocellular Carcinoma

Stereotactic ablative radiotherapy for hepatocellular carcinoma: A systematic review and meta‐analysis of local control, survival and toxicity outcomes

Ensemble learning based on efficient features combination can predict the outcome of recurrence-free survival in patients with hepatocellular carcinoma within three years after surgery

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