Radioablation by Image-Guided (HDR) Brachytherapy and Transarterial Chemoembolization in Hepatocellular Carcinoma: A Randomized Phase II Trial

Mohnike, Konrad; Steffen, Ingo G.; Seidensticker, Max; Hass, Peter; Damm, Robert; Peters, Nils; Seidensticker, Ricarda; Schütte, Kerstin; Arend, Jörg; Bornschein, Jan; Streitparth, Tina; Wybranski, Christian; Wieners, Gero; Stübs, P.; Malfertheiner, Peter; Pech, Maciej; Ricke, Jens

doi:10.1007/s00270-018-2127-5

Cited by 34 publications

(17 citation statements)

References 30 publications

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“…In the last decade, the introduction of RE as well as advanced high conformal precision radiotherapy such as stereotactic body irradiation or CT-guided brachytherapy has boosted scientific and clinical interest in liver irradiation. A key driver has been that these techniques enable better targeting and sparing of healthy liver tissue, thus allowing delivery of substantial tumor doses despite the relatively low tolerance of liver parenchyma to radiation [ 15 , 42 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

Seidensticker

Fabritius

Beller³

et al. 2021

Cancers

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Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

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Section: Discussionmentioning

confidence: 99%

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

Seidensticker

Fabritius

Beller³

et al. 2021

Cancers

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“…Some studies suggested that high-dose-rate brachytherapy (HDR-BRT), as an ablation technique using gamma irradiation of iridium-192 ( 192 Ir) source, has successfully been used in HCC. In addition, HDR-BRT is not restricted to tumor size or tumors close to blood vessels or sensitive structures [ 22 , 23 ]. However, research on whether HDR-BRT can benefit various types of PVTT is lacking.…”

Section: Discussionmentioning

confidence: 99%

A combination of portal vein stent insertion and endovascular iodine-125 seed-strip implantation, followed by transcatheter arterial chemoembolization with sorafenib for treatment of hepatocellular carcinoma-associated portal vein tumor thrombus

Li¹,

Li²,

Li³

et al. 2021

jcb

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Purpose: This study aimed to assess efficacy of portal vein stent (PVS) insertion and endovascular iodine-125 ( 125 I) seed-strip implantation, followed by transcatheter arterial chemoembolization (TACE) with sorafenib (PVS-125 I TACE-S) in patients with hepatocellular carcinoma (HCC)-associated type II or type III portal vein tumor thrombus (PVTT).Material and methods: A retrospective study was performed on 53 consecutive patients with HCC and type II or type III PVTT, from May 2014 to July 2018. Patients were divided into 2 groups, including group A with 28 patients treated with PVS-125 I TACE-S, and group B with 25 patients treated with TACE-S. Primary end-point was overall survival (OS), while secondary endpoints were hepatic function and disease control rate (DCR). Albumin-bilirubin (ALBI) score approach was used for evaluating liver function. Cox regression analysis was applied to identify factors associated with treatment outcomes.Results: No pre-operative differences were found in ALBI scores between group A and group B (-2.57 ±0.42 vs. -2.61 ±0.38, p = 0.724), or in these scores at 1 month post-operatively (-2.62 ±0.46 vs. -2.20 ±0.59, p = 0.666). However, these scores were significantly different at 3 (-2.17 ±0.59 vs. -1.69 ±0.48, p = 0.007) and 6 (-2.28 ±1.23 vs. -1.47 ±0.31, p = 0.044) months post-operatively. In addition, group A exhibited higher DCR (71.4% vs. 44.0%, p = 0.043) after 6 months of treatment and extended OS duration (11.4 vs. 7.7 months, p = 0.007). A stratified analysis revealed that OS in patients with type II PVTT did not differ significantly (10.4 vs. 10.7 months, p = 0.689), but OS with type III varied significantly (11.5 vs. 7.5 months, p = 0.002). Multivariate analysis revealed that tumor size > 10 cm (p = 0.002) and multiple tumors (p = 0.022) were independent predictors for poor prognosis, whereas PVS-125 I TACE-S was predictor for favorable patient's prognosis (p = 0.040).Conclusions: PVS-125 I TACE-S represents a potentially viable strategy for improving hepatic functionality, DCR, and OS in HCC with type III PVTT compared with TACE-S alone.

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“…High-dose-rate (HDR) irradiation was performed in a single fraction using an Iri-dium192 source in the afterloading technique to achieve "radioablation". Ablative doses for the PTV were defined as 25 Gy for colorectal carcinoma, 20 Gy for cholangiocarcinoma, and 15 Gy for all other entities according to contemporary literature [13][14][15]. Dose constraints for organs at risk (OAR) have been published previously [11].…”

Section: Technique Of Interstitial Brachytherapymentioning

confidence: 99%

Radioablation of Upper Abdominal Malignancies by CT-Guided, Interstitial HDR Brachytherapy: A Multivariate Analysis of Catheter Placement Assisted by Ultrasound Imaging

Damm

Heinze

Surov

et al. 2021

Rofo

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Purpose To evaluate the use of ultrasound (US) during catheter placement in interstitial brachytherapy (iBT) of abdominal malignancies as an alternative to computed tomography (CT) fluoroscopy. Materials and Methods Catheter placement for CT-guided iBT was, if US visibility was sufficient, assisted by sonography in 52 consecutive patients with 82 lesions (liver N = 62; kidney N = 16; peritoneum N = 4) of various malignancies. We collected data on lesion visibility, location, depth, size, and dosimetry. Comparison of CT fluoroscopy versus US-assisted catheter placement was performed by Fisher’s exact test for frequencies and U-test for lesion visibility and dosimetric data. Factors predicting the utility of sonography were determined in a lesion-based multivariate regression analysis. A p-value < 0.05 was regarded as statistically significant. Results 150 catheters (1 to 6 per lesion; mean diameter 3.6 ± 2.4 cm) were implanted. CT fluoroscopy was used for 44 catheters, and US was used for 106 catheters. Lesion visibility assessed by 5-point Likert scale was significantly better in US (median 2 vs. 3; p = 0.011) and effective dose was significantly reduced if US guidance was applicable (median 1.75 vs. 8.19 mSv; p = 0.014). In a multivariate regression analysis, we identified increased lesion size and caudal location within the target organ to independently predict the utility of ultrasound in catheter placement for iBT. Conclusion Sonography is a helpful technique to assist CT-guided interstitial brachytherapy of upper abdominal malignancies. Especially for larger lesions localized in the lower liver segments or lower half of the kidney, superior visibility can be expected. As the effective dose of the patient is also reduced, radiation exposure of the medical staff may be indirectly lowered. Key Points: Citation Format

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Radioablation by Image-Guided (HDR) Brachytherapy and Transarterial Chemoembolization in Hepatocellular Carcinoma: A Randomized Phase II Trial

Cited by 34 publications

References 30 publications

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

A combination of portal vein stent insertion and endovascular iodine-125 seed-strip implantation, followed by transcatheter arterial chemoembolization with sorafenib for treatment of hepatocellular carcinoma-associated portal vein tumor thrombus

Radioablation of Upper Abdominal Malignancies by CT-Guided, Interstitial HDR Brachytherapy: A Multivariate Analysis of Catheter Placement Assisted by Ultrasound Imaging

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