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Published in: Strahlentherapie und Onkologie 5/2016

01-05-2016 | Original Article

Radioablation of liver malignancies with interstitial high-dose-rate brachytherapy

Complications and risk factors

Authors: Dr. med. Konrad Mohnike, Dr. med. Steffen Wolf, Dr. med. Robert Damm, PD Dr. med. Max Seidensticker, Dr. med. Ricarda Seidensticker, Prof. Dr. med. Frank Fischbach, Nils Peters, Dr. med. Peter Hass, Prof. Dr. med. Günther Gademann, Prof. Dr. med. Maciej Pech, Prof. Dr. med. Jens Ricke

Published in: Strahlentherapie und Onkologie | Issue 5/2016

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Abstract

Background

To evaluate complications and identify risk factors for adverse events in patients undergoing high-dose-rate interstitial brachytherapy (iBT).

Material and methods

Data from 192 patients treated in 343 CT- or MRI-guided interventions from 2006–2009 at our institution were analyzed. In 41 %, the largest tumor treated was ≥ 5 cm, 6 % of the patients had tumors ≥ 10 cm. Prior to iBT, 60 % of the patients had chemotherapy, 22 % liver resection, 19 % thermoablation or transarterial chemoembolization (TACE). Safety was the primary endpoint; survival data were obtained as the secondary endpoints. During follow-up, MRI or CT imaging was performed and clinical and laboratory parameters were obtained.

Results

The rate of major complications was below 5 %. Five major bleedings (1.5 %) occurred. The frequency of severe bleeding was significantly higher in patients with advanced liver cirrhosis. One patient developed signs of a nonclassic radiation-induced liver disease. In 3 patients, symptomatic gastrointestinal (GI) ulcers were detected. A dose exposure to the GI wall above 14 Gy/ml was a reliable threshold to predict ulcer formation. A combination of C-reactive protein ≥ 165 mg/l and/or leukocyte count ≥ 12.7 Gpt/l on the second day after the intervention predicted infection (sensitivity 90.0 %; specificity 92.8 %.) Two patients (0.6 %) died within 30 days. Median overall survival after the first liver treatment was 20.1 months for all patients and the local recurrence-free surviving proportion was 89 % after 12 months.

Conclusions

Image-guided iBT yields a low rate of major complications and is effective.
Literature
1.
2.
go back to reference Pawlik TM, Assumpcao L, Vossen JA et al (2009) Trends in nontherapeutic laparotomy rates in patients undergoing surgical therapy for hepatic colorectal metastases. Ann Surg Oncol 16:371–378CrossRefPubMed Pawlik TM, Assumpcao L, Vossen JA et al (2009) Trends in nontherapeutic laparotomy rates in patients undergoing surgical therapy for hepatic colorectal metastases. Ann Surg Oncol 16:371–378CrossRefPubMed
3.
go back to reference Dhir M, Lyden ER, Smith LM, Are C (2012) Comparison of outcomes of transplantation and resection in patients with early hepatocellular carcinoma: a meta-analysis. HPB (Oxford) 14:635–645CrossRef Dhir M, Lyden ER, Smith LM, Are C (2012) Comparison of outcomes of transplantation and resection in patients with early hepatocellular carcinoma: a meta-analysis. HPB (Oxford) 14:635–645CrossRef
4.
go back to reference Jones RP, Jackson R, Dunne DF et al (2012) Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases. Br J Surg 99:477–486CrossRefPubMed Jones RP, Jackson R, Dunne DF et al (2012) Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases. Br J Surg 99:477–486CrossRefPubMed
5.
go back to reference Smith MD, McCall JL (2009) Systematic review of tumour number and outcome after radical treatment of colorectal liver metastases. Br J Surg 96:1101–1113CrossRefPubMed Smith MD, McCall JL (2009) Systematic review of tumour number and outcome after radical treatment of colorectal liver metastases. Br J Surg 96:1101–1113CrossRefPubMed
6.
go back to reference Khatri VP, Petrelli NJ, Belghiti J (2005) Extending the frontiers of surgical therapy for hepatic colorectal metastases: is there a limit? J Clin Oncol 23:8490–8499CrossRefPubMed Khatri VP, Petrelli NJ, Belghiti J (2005) Extending the frontiers of surgical therapy for hepatic colorectal metastases: is there a limit? J Clin Oncol 23:8490–8499CrossRefPubMed
7.
go back to reference Cirocchi R, Trastulli S, Boselli C et al. Radiofrequency ablation in the treatment of liver metastases from colorectal cancer. Cochrane Database Syst Rev 6:CD006317 Cirocchi R, Trastulli S, Boselli C et al. Radiofrequency ablation in the treatment of liver metastases from colorectal cancer. Cochrane Database Syst Rev 6:CD006317
8.
go back to reference Ruers T, Punt C, Van Coevorden F et al (2012) Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol 23:2619–2626CrossRefPubMedPubMedCentral Ruers T, Punt C, Van Coevorden F et al (2012) Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol 23:2619–2626CrossRefPubMedPubMedCentral
9.
go back to reference Sutherland LM, Williams JA, Padbury RT, Gotley DC, Stokes B, Maddern GJ (2006) Radiofrequency ablation of liver tumors: a systematic review. Arch Surg 141:181–190CrossRefPubMed Sutherland LM, Williams JA, Padbury RT, Gotley DC, Stokes B, Maddern GJ (2006) Radiofrequency ablation of liver tumors: a systematic review. Arch Surg 141:181–190CrossRefPubMed
10.
go back to reference Tanis E, Nordlinger B, Mauer M et al (2014) Local recurrence rates after radiofrequency ablation or resection of colorectal liver metastases. Analysis of the European Organisation for Research and Treatment of Cancer #40004 and #40983. Eur J Cancer 50:912–919CrossRefPubMed Tanis E, Nordlinger B, Mauer M et al (2014) Local recurrence rates after radiofrequency ablation or resection of colorectal liver metastases. Analysis of the European Organisation for Research and Treatment of Cancer #40004 and #40983. Eur J Cancer 50:912–919CrossRefPubMed
11.
go back to reference Herfarth KK, Debus J, Lohr F et al (2001) Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial. J Clin Oncol 19:164–170PubMed Herfarth KK, Debus J, Lohr F et al (2001) Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial. J Clin Oncol 19:164–170PubMed
12.
go back to reference Bush DA, Kayali Z, Grove R, Slater JD (2011) The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. Cancer 117:3053–3059CrossRefPubMed Bush DA, Kayali Z, Grove R, Slater JD (2011) The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. Cancer 117:3053–3059CrossRefPubMed
13.
go back to reference Kawashima M, Furuse J, Nishio T et al (2005) Phase II study of radiotherapy employing proton beam for hepatocellular carcinoma. J Clin Oncol 23:1839–1846CrossRefPubMed Kawashima M, Furuse J, Nishio T et al (2005) Phase II study of radiotherapy employing proton beam for hepatocellular carcinoma. J Clin Oncol 23:1839–1846CrossRefPubMed
14.
go back to reference Dawson LA (2011) Overview: where does radiation therapy fit in the spectrum of liver cancer local-regional therapies? Semin Radiat Oncol 21:241–246CrossRefPubMed Dawson LA (2011) Overview: where does radiation therapy fit in the spectrum of liver cancer local-regional therapies? Semin Radiat Oncol 21:241–246CrossRefPubMed
15.
go back to reference Scorsetti M, Arcangeli S, Tozzi A et al. Is stereotactic body radiation therapy an attractive option for unresectable liver metastases? A preliminary report from a phase 2 trial. Int J Radiat Oncol Biol Phys 2013;86:336–342CrossRefPubMed Scorsetti M, Arcangeli S, Tozzi A et al. Is stereotactic body radiation therapy an attractive option for unresectable liver metastases? A preliminary report from a phase 2 trial. Int J Radiat Oncol Biol Phys 2013;86:336–342CrossRefPubMed
16.
go back to reference Dawood O, Mahadevan A, Goodman KA (2009) Stereotactic body radiation therapy for liver metastases. Eur J Cancer 45:2947–2959CrossRefPubMed Dawood O, Mahadevan A, Goodman KA (2009) Stereotactic body radiation therapy for liver metastases. Eur J Cancer 45:2947–2959CrossRefPubMed
17.
go back to reference Kirkpatrick JP, Kelsey CR, Palta M et al (2014) Stereotactic body radiotherapy: a critical review for nonradiation oncologists. Cancer 120:942–954CrossRefPubMed Kirkpatrick JP, Kelsey CR, Palta M et al (2014) Stereotactic body radiotherapy: a critical review for nonradiation oncologists. Cancer 120:942–954CrossRefPubMed
18.
go back to reference Ricke J, Wust P, Wieners G et al (2004) Liver malignancies: CT-guided interstitial brachytherapy in patients with unfavorable lesions for thermal ablation. J Vasc Interv Radiol 15:1279–1286CrossRefPubMed Ricke J, Wust P, Wieners G et al (2004) Liver malignancies: CT-guided interstitial brachytherapy in patients with unfavorable lesions for thermal ablation. J Vasc Interv Radiol 15:1279–1286CrossRefPubMed
19.
go back to reference Mohnike K, Wieners G, Pech M et al (2009) Image-guided interstitial high-dose-rate brachytherapy in hepatocellular carcinoma. Dig Dis 27:170–174CrossRefPubMed Mohnike K, Wieners G, Pech M et al (2009) Image-guided interstitial high-dose-rate brachytherapy in hepatocellular carcinoma. Dig Dis 27:170–174CrossRefPubMed
20.
go back to reference Mohnike K, Wieners G, Schwartz F et al. (2010) Computed tomography-guided high-dose-rate brachytherapy in hepatocellular carcinoma: safety, efficacy, and effect on survival. Int J Radiat Oncol Biol Phys 78:172–179CrossRefPubMed Mohnike K, Wieners G, Schwartz F et al. (2010) Computed tomography-guided high-dose-rate brachytherapy in hepatocellular carcinoma: safety, efficacy, and effect on survival. Int J Radiat Oncol Biol Phys 78:172–179CrossRefPubMed
21.
go back to reference Ricke J, Mohnike K, Pech M et al. (2010) Local response and impact on survival after local ablation of liver metastases from colorectal carcinoma by computed tomography-guided high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 78:479–485CrossRefPubMed Ricke J, Mohnike K, Pech M et al. (2010) Local response and impact on survival after local ablation of liver metastases from colorectal carcinoma by computed tomography-guided high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 78:479–485CrossRefPubMed
22.
go back to reference Collettini F, Poellinger A, Schnapauff D et al (2011) CT-guided high-dose-rate brachytherapy of metachronous ovarian cancer metastasis to the liver: initial experience. Anticancer Res 31:2597–2602PubMed Collettini F, Poellinger A, Schnapauff D et al (2011) CT-guided high-dose-rate brachytherapy of metachronous ovarian cancer metastasis to the liver: initial experience. Anticancer Res 31:2597–2602PubMed
23.
go back to reference Collettini F, Schnapauff D, Poellinger A et al (2012) Hepatocellular carcinoma: computed-tomography-guided high-dose-rate brachytherapy (CT-HDRBT) ablation of large (5–7 cm) and very large (> 7 cm) tumours. Eur Radiol 22:1101–1109CrossRefPubMed Collettini F, Schnapauff D, Poellinger A et al (2012) Hepatocellular carcinoma: computed-tomography-guided high-dose-rate brachytherapy (CT-HDRBT) ablation of large (5–7 cm) and very large (> 7 cm) tumours. Eur Radiol 22:1101–1109CrossRefPubMed
24.
go back to reference Tselis N, Chatzikonstantinou G, Kolotas C, Milickovic N, Baltas D, Zamboglou N (2013) Computed tomography-guided interstitial high dose rate brachytherapy for centrally located liver tumours: a single institution study. Eur Radiol 23:2264–2270CrossRefPubMed Tselis N, Chatzikonstantinou G, Kolotas C, Milickovic N, Baltas D, Zamboglou N (2013) Computed tomography-guided interstitial high dose rate brachytherapy for centrally located liver tumours: a single institution study. Eur Radiol 23:2264–2270CrossRefPubMed
25.
go back to reference Wieners G, Mohnike K, Peters N et al (2011) Treatment of hepatic metastases of breast cancer with CT-guided interstitial brachytherapy - a phase II-study. Radiother Oncol 100:314–319CrossRefPubMed Wieners G, Mohnike K, Peters N et al (2011) Treatment of hepatic metastases of breast cancer with CT-guided interstitial brachytherapy - a phase II-study. Radiother Oncol 100:314–319CrossRefPubMed
26.
go back to reference Wieners G, Pech M, Hildebrandt B et al (2009) Phase II feasibility study on the combination of two different regional treatment approaches in patients with colorectal “liver-only” metastases: hepatic interstitial brachytherapy plus regional chemotherapy. Cardiovasc Intervent Radiol 32:937–945CrossRefPubMed Wieners G, Pech M, Hildebrandt B et al (2009) Phase II feasibility study on the combination of two different regional treatment approaches in patients with colorectal “liver-only” metastases: hepatic interstitial brachytherapy plus regional chemotherapy. Cardiovasc Intervent Radiol 32:937–945CrossRefPubMed
27.
go back to reference Trotti A, Colevas AD, Setser A et al (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13:176–181CrossRefPubMed Trotti A, Colevas AD, Setser A et al (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13:176–181CrossRefPubMed
28.
go back to reference Lawrence TS, Robertson JM, Anscher MS, Jirtle RL, Ensminger WD, Fajardo LF (1995) Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 31:1237–1248CrossRefPubMed Lawrence TS, Robertson JM, Anscher MS, Jirtle RL, Ensminger WD, Fajardo LF (1995) Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 31:1237–1248CrossRefPubMed
29.
go back to reference Bertot LC, Sato M, Tateishi R, Yoshida H, Koike K (2011) Mortality and complication rates of percutaneous ablative techniques for the treatment of liver tumors: a systematic review. Eur Radiol 21:2584–2596CrossRefPubMed Bertot LC, Sato M, Tateishi R, Yoshida H, Koike K (2011) Mortality and complication rates of percutaneous ablative techniques for the treatment of liver tumors: a systematic review. Eur Radiol 21:2584–2596CrossRefPubMed
30.
go back to reference Cheung TT, Poon RT, Yuen WK et al (2013) Long-term survival analysis of pure laparoscopic versus open hepatectomy for hepatocellular carcinoma in patients with cirrhosis: a single-center experience. Ann Surg 257:506–511CrossRefPubMed Cheung TT, Poon RT, Yuen WK et al (2013) Long-term survival analysis of pure laparoscopic versus open hepatectomy for hepatocellular carcinoma in patients with cirrhosis: a single-center experience. Ann Surg 257:506–511CrossRefPubMed
31.
go back to reference Streitparth F, Pech M, Bohmig M et al (2006) In vivo assessment of the gastric mucosal tolerance dose after single fraction, small volume irradiation of liver malignancies by computed tomography-guided, high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 65:1479–1486CrossRefPubMed Streitparth F, Pech M, Bohmig M et al (2006) In vivo assessment of the gastric mucosal tolerance dose after single fraction, small volume irradiation of liver malignancies by computed tomography-guided, high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 65:1479–1486CrossRefPubMed
32.
go back to reference Ruhl R, Seidensticker M, Peters N et al (2009) Hepatocellular carcinoma and liver cirrhosis: assessment of the liver function after Yttrium-90 radioembolization with resin microspheres or after CT-guided high-dose-rate brachytherapy. Dig Dis 27:189–199CrossRefPubMed Ruhl R, Seidensticker M, Peters N et al (2009) Hepatocellular carcinoma and liver cirrhosis: assessment of the liver function after Yttrium-90 radioembolization with resin microspheres or after CT-guided high-dose-rate brachytherapy. Dig Dis 27:189–199CrossRefPubMed
33.
go back to reference Bujold A, Massey CA, Kim JJ et al (2013) Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 31:1631–1639CrossRefPubMed Bujold A, Massey CA, Kim JJ et al (2013) Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 31:1631–1639CrossRefPubMed
34.
go back to reference Kawashima M, Kohno R, Nakachi K et al (2011) Dose-volume histogram analysis of the safety of proton beam therapy for unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 79:1479–1486CrossRefPubMed Kawashima M, Kohno R, Nakachi K et al (2011) Dose-volume histogram analysis of the safety of proton beam therapy for unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 79:1479–1486CrossRefPubMed
35.
go back to reference Seidensticker M, Seidensticker R, Mohnike K et al (2011) Quantitative in vivo assessment of radiation injury of the liver using Gd-EOB-DTPA enhanced MRI: tolerance dose of small liver volumes. Radiat Oncol 6:40CrossRefPubMedPubMedCentral Seidensticker M, Seidensticker R, Mohnike K et al (2011) Quantitative in vivo assessment of radiation injury of the liver using Gd-EOB-DTPA enhanced MRI: tolerance dose of small liver volumes. Radiat Oncol 6:40CrossRefPubMedPubMedCentral
36.
go back to reference Ricke J, Seidensticker M, Ludemann L et al (2005) In vivo assessment of the tolerance dose of small liver volumes after single-fraction HDR irradiation. Int J Radiat Oncol Biol Phys 62:776–784CrossRefPubMed Ricke J, Seidensticker M, Ludemann L et al (2005) In vivo assessment of the tolerance dose of small liver volumes after single-fraction HDR irradiation. Int J Radiat Oncol Biol Phys 62:776–784CrossRefPubMed
37.
go back to reference Ruhl R, Ludemann L, Czarnecka A et al (2010) Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases. Radiat Oncol 5:44CrossRefPubMedPubMedCentral Ruhl R, Ludemann L, Czarnecka A et al (2010) Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases. Radiat Oncol 5:44CrossRefPubMedPubMedCentral
38.
go back to reference Brinkhaus G, Lock JF, Malinowski M et al (2014) CT-guided high-dose-rate brachytherapy of liver tumours does not impair hepatic function and shows high overall safety and favourable survival rates. Ann Surg Oncol 21:4284–4292CrossRefPubMed Brinkhaus G, Lock JF, Malinowski M et al (2014) CT-guided high-dose-rate brachytherapy of liver tumours does not impair hepatic function and shows high overall safety and favourable survival rates. Ann Surg Oncol 21:4284–4292CrossRefPubMed
39.
go back to reference Sangro B, Gil-Alzugaray B, Rodriguez J et al (2008) Liver disease induced by radioembolization of liver tumors: description and possible risk factors. Cancer 112:1538–1546CrossRefPubMed Sangro B, Gil-Alzugaray B, Rodriguez J et al (2008) Liver disease induced by radioembolization of liver tumors: description and possible risk factors. Cancer 112:1538–1546CrossRefPubMed
40.
go back to reference Seidensticker M, Seidensticker R, Damm R et al (2014) Prospective randomized trial of enoxaparin, pentoxifylline and ursodeoxycholic Acid for prevention of radiation-induced liver toxicity. PLoS One 9:e112731CrossRefPubMedPubMedCentral Seidensticker M, Seidensticker R, Damm R et al (2014) Prospective randomized trial of enoxaparin, pentoxifylline and ursodeoxycholic Acid for prevention of radiation-induced liver toxicity. PLoS One 9:e112731CrossRefPubMedPubMedCentral
Metadata
Title
Radioablation of liver malignancies with interstitial high-dose-rate brachytherapy
Complications and risk factors
Authors
Dr. med. Konrad Mohnike
Dr. med. Steffen Wolf
Dr. med. Robert Damm
PD Dr. med. Max Seidensticker
Dr. med. Ricarda Seidensticker
Prof. Dr. med. Frank Fischbach
Nils Peters
Dr. med. Peter Hass
Prof. Dr. med. Günther Gademann
Prof. Dr. med. Maciej Pech
Prof. Dr. med. Jens Ricke
Publication date
01-05-2016
Publisher
Springer Berlin Heidelberg
Published in
Strahlentherapie und Onkologie / Issue 5/2016
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-016-0957-0

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