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      Systematic review of patient reported quality of life following stereotactic ablative radiotherapy for primary and metastatic liver cancer

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          Abstract

          Background

          Stereotactic ablative radiotherapy (SABR) is a safe and effective modality in patients with liver cancer who are ineligible for other local therapies. However SABR is not current standard of practice and requires further validation. Patient reported quality of life (QOL) is key to this validation, yet no systematic reviews to date have been performed to analyse QOL following liver SABR. QOL is a critical part of therapy evaluation, particularly in disease states with short life expectancy. The purpose of this study was to conduct a systematic review of QOL outcomes for liver SABR.

          Materials and methods

          MEDLINE and EMBASE databases from 1996 to October 2015 were queried to obtain English language studies analysing QOL following liver SABR. Included studies described patient-reported QOL as either a primary or secondary endpoint, and analysed QOL change over time. Studies were screened, and relevant data were abstracted and analysed.

          Results

          Of 2181 initially screened studies, 5 met all inclusion criteria. Extracted studies included a total of 392 eligible patients with hepatocellular carcinoma, liver metastases and intrahepatic cholangiocarcinoma. Four studies were prospective in design, and only one study was a conference abstract. Extracted studies were heterogeneous in dose prescription used (11–70 Gy in 3–30 fractions), in addition to reported QOL metrics (EORTC QLQ C-15 PAL,/C-30/LM-21, EuroQol 5D, FACT-Hep, FLIC) and final endpoints (range 6 weeks to 12 months). Despite this there were few statistically significant declines in QOL scores following SABR. Four studies demonstrated transient fatigue in the first 1–4 weeks, while 2 studies showed transient worsening of appetite at 1 month. In all but one instance (loss of appetite at 6 weeks), levels returned to insignificant difference baseline by the final endpoints. All studies showed no significant QOL decline in any domain at their respective endpoints. In studies with overlapping QOL tools, estimates of 3-month post SABR global QOL were similar.

          Conclusion

          Results of this systematic review demonstrate well-preserved post liver SABR QOL. These findings strengthen the argument for liver SABR, and should aim to support future comparative effectiveness trials with other local modalities including surgery, chemoembolization and radiofrequency ablation, with a focus on QOL outcomes as an important endpoint.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13014-017-0818-8) contains supplementary material, which is available to authorized users.

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          Most cited references29

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          Radiation-associated liver injury.

          The liver is a critically important organ that has numerous functions including the production of bile, metabolism of ingested nutrients, elimination of many waste products, glycogen storage, and plasma protein synthesis. The liver is often incidentally irradiated during radiation therapy (RT) for tumors in the upper- abdomen, right lower lung, distal esophagus, or during whole abdomen or whole body RT. This article describes the endpoints, time-course, and dose-volume effect of radiation on the liver. Published by Elsevier Inc.
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            Stereotactic body radiation therapy for primary and metastatic liver tumors: A single institution phase i-ii study.

            The feasibility, toxicity and tumor response of stereotactic body radiation therapy (SBRT) for treatment of primary and metastastic liver tumors was investigated. From October 2002 until June 2006, 25 patients not suitable for other local treatments were entered in the study. In total 45 lesions were treated, 34 metastases and 11 hepatocellular carcinoma (HCC). Median follow-up was 12.9 months (range 0.5-31). Median lesion size was 3.2 cm (range 0.5-7.2) and median volume 22.2 cm3 (range 1.1-322). Patients with metastases, HCC without cirrhosis, and HCC or =4 cm and cirrhosis received 5 x 5 Gy or 3 x 10 Gy. The prescription isodose was 65%. Acute toxicity was scored following the Common Toxicity Criteria and late toxicity with the SOMA/LENT classification. Local failures were observed in two HCC and two metastases. Local control rates at 1 and 2 years for the whole group were 94% and 82%. Acute toxicity grade > or =3 was seen in four patients; one HCC patient with Child B developed a liver failure together with an infection and died (grade 5), two metastases patients presented elevation of gamma glutamyl transferase (grade 3) and another asthenia (grade 3). Late toxicity was observed in one metastases patient who developed a portal hypertension syndrome with melena (grade 3). SBRT was feasible, with acceptable toxicity and encouraging local control. Optimal dose-fractionation schemes for HCC with cirrhosis have to be found. Extreme caution should be used for patients with Child B because of a high toxicity risk.
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              Phase I study of individualized stereotactic body radiotherapy of liver metastases.

              To report on the outcomes of a phase I study of stereotactic body radiotherapy (SBRT) for treatment of liver metastases. Patients with liver metastases that were inoperable or medically unsuitable for resection, and who were not candidates for standard therapies, were eligible for this phase I study of individualized SBRT. Individualized radiation doses were chosen to maintain the same nominal risk of radiation-induced liver disease (RILD) for three estimated risk levels (5%, 10%, and 20%). Additional patients were treated at the maximal study dose (MSD) in an expanded cohort. Median SBRT dose was 41.8 Gy (range, 27.7 to 60 Gy) in six fractions over 2 weeks. Sixty-eight patients with inoperable colorectal (n = 40), breast (n = 12), or other (n = 16) liver metastases were treated. Median tumor volume was 75.2 mL (range, 1.19 to 3,090 mL). The highest RILD risk level investigated was safe, with no dose-limiting toxicity. Two grade 3 liver enzyme changes occurred, but no RILD or other grade 3 to 5 liver toxicity was seen, for a low estimated risk of serious liver toxicity (95% CI, 0 to 5.3%). Six (9%) acute grade 3 toxicities (two gastritis, two nausea, lethargy, and thrombocytopenia) and one (1%) grade 4 toxicity (thrombocytopenia) were seen. The 1-year local control rate was 71% (95 CI, 58% to 85%). The median overall survival was 17.6 months (95% CI, 10.4 to 38.1 months). Individualized six-fraction liver metastases SBRT is safe, with sustained local control observed in the majority of patients.
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                Author and article information

                Contributors
                adam.mutsaers@medportal.ca
                905-387-9495 , greenspj@hhsc.ca
                905-527-4322 , walkerc@mcmaster.ca
                905-387-9495 , swaminath@hhsc.ca
                Journal
                Radiat Oncol
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central (London )
                1748-717X
                29 June 2017
                29 June 2017
                2017
                : 12
                : 110
                Affiliations
                [1 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Department of Medicine, , McMaster University, ; 1280 Main Street West, Hamilton, ON L8S 4 L8 Canada
                [2 ]ISNI 0000 0004 0408 1354, GRID grid.413615.4, , Juravinski Cancer Centre at Hamilton Health Sciences, ; Hamilton, ON Canada
                [3 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Department of Oncology, , McMaster University, Juravinski Cancer Centre, ; 699 Concession St, Hamilton, ON L8V 5C2 Canada
                [4 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Program in Evidence Based Care, , McMaster University, Juravinski Hospital, ; 60 (G) Wing, 2nd Floor, 711 Concession Street, Hamilton, ON L8V 1C3 Canada
                Author information
                http://orcid.org/0000-0002-2185-6874
                Article
                818
                10.1186/s13014-017-0818-8
                5492951
                28662680
                b3e4e948-749f-4310-b23b-59d0d87b1605
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 December 2016
                : 3 May 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100008360, Hamilton Health Sciences;
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Oncology & Radiotherapy
                sabr,sbrt,stereotactic,hepatocellular carcinoma,liver metastases,systematic review,quality of life,qol

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