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      A Multi-Institutional Experience of MR-Guided Liver Stereotactic Body Radiation Therapy

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          Abstract

          Purpose

          Daily magnetic resonance (MR)–guided radiation has the potential to improve stereotactic body radiation therapy (SBRT) for tumors of the liver. Magnetic resonance imaging (MRI) introduces unique variables that are untested clinically: electron return effect, MRI geometric distortion, MRI to radiation therapy isocenter uncertainty, multileaf collimator position error, and uncertainties with voxel size and tracking. All could lead to increased toxicity and/or local recurrences with SBRT. In this multi-institutional study, we hypothesized that direct visualization provided by MR guidance could allow the use of small treatment volumes to spare normal tissues while maintaining clinical outcomes despite the aforementioned uncertainties in MR-guided treatment.

          Methods and materials

          Patients with primary liver tumors or metastatic lesions treated with MR-guided liver SBRT were reviewed at 3 institutions. Toxicity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4. Freedom from local progression (FFLP) and overall survival were analyzed with the Kaplan-Meier method and χ 2 test.

          Results

          The study population consisted of 26 patients: 6 hepatocellular carcinomas, 2 cholangiocarcinomas, and 18 metastatic liver lesions (44% colorectal metastasis). The median follow-up was 21.2 months. The median dose delivered was 50 Gy at 10 Gy/fraction. No grade 4 or greater gastrointestinal toxicities were observed after treatment. The 1-year and 2-year overall survival in this cohort is 69% and 60%, respectively. At the median follow-up, FFLP for this cohort was 80.4%. FFLP for patients with hepatocellular carcinomas, colorectal metastasis, and all other lesions were 100%, 75%, and 83%, respectively.

          Conclusions

          This study describes the first clinical outcomes of MR-guided liver SBRT. Treatment was well tolerated by patients with excellent local control. This study lays the foundation for future dose escalation and adaptive treatment for liver-based primary malignancies and/or metastatic disease.

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          Most cited references33

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          Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases.

          Y. Fong, J. Fortner, R Sun … (1999)
          There is a need for clearly defined and widely applicable clinical criteria for the selection of patients who may benefit from hepatic resection for metastatic colorectal cancer. Such criteria would also be useful for stratification of patients in clinical trials for this disease. Clinical, pathologic, and outcome data for 1001 consecutive patients undergoing liver resection for metastatic colorectal cancer between July 1985 and October 1998 were examined. These resections included 237 trisegmentectomies, 394 lobectomies, and 370 resections encompassing less than a lobe. The surgical mortality rate was 2.8%. The 5-year survival rate was 37%, and the 10-year survival rate was 22%. Seven factors were found to be significant and independent predictors of poor long-term outcome by multivariate analysis: positive margin (p = 0.004), extrahepatic disease (p = 0.003), node-positive primary (p = 0.02), disease-free interval from primary to metastases 1 (p = 0.0004), largest hepatic tumor >5 cm (p = 0.01), and carcinoembryonic antigen level >200 ng/ml (p = 0.01). When the last five of these criteria were used in a preoperative scoring system, assigning one point for each criterion, the total score was highly predictive of outcome (p < 0.0001). No patient with a score of 5 was a long-term survivor. Resection of hepatic colorectal metastases may produce long-term survival and cure. Long-term outcome can be predicted from five criteria that are readily available for all patients considered for resection. Patients with up to two criteria can have a favorable outcome. Patients with three, four, or five criteria should be considered for experimental adjuvant trials. Studies of preoperative staging techniques or of adjuvant therapies should consider using such a score for stratification of patients.
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            Oligometastases revisited.

            Ralph Weichselbaum, Samuel Hellman (2011)
            We previously proposed a clinical state of metastasis termed 'oligometastases' that refers to restricted tumor metastatic capacity. The implication of this concept is that local cancer treatments are curative in a proportion of patients with metastases. Here we review clinical and laboratory data that support the hypothesis that oligometastasis is a distinct clinical entity. Investigations of the prevalence, mechanism of occurrence, and position in the metastatic cascade, as well as the determination of molecular markers to distinguish oligometastatic from polymetastatic disease, are ongoing.
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              Actual 10-year survival after resection of colorectal liver metastases defines cure.

              James S Tomlinson, William Jarnagin, Ronald P Dematteo … (2007)
              Resection of colorectal liver metastases (CLM) in selected patients has evolved as the standard of care during the last 20 years. In the absence of prospective randomized clinical trials, a survival benefit has been deduced relative to historical controls based on actuarial data. There is now sufficient follow-up on a significant number of patients to address the curative intent of resecting CLM. Retrospective review of a prospectively maintained database was performed on patients who underwent resection of CLM from 1985 to 1994. Postoperative deaths were excluded. Disease-specific survival (DSS) was calculated from the time of hepatectomy using the Kaplan-Meier method. There were 612 consecutive patients identified with 10-year follow-up. Median DSS was 44 months. There were 102 actual 10-year survivors. Ninety-nine (97%) of the 102 were disease free at last follow-up. Only one patient experienced a disease-specific death after 10 years of survival. In contrast, 34% of the 5-year survivors suffered a cancer-related death. Previously identified poor prognostic factors found among the 102 actual 10-year survivors included 7% synchronous disease, 36% disease-free interval less than 12 months, 25% bilobar metastases, 50% node-positive primary, 39% more than one metastasis, and 35% tumor size more than 5 cm. Patients who survive 10 years appear to be cured of their disease, whereas approximately one third of actual 5-year survivors succumb to a cancer-related death. In well-selected patients, there is at least a one in six chance of cure after hepatectomy for CLM. The presence of poor prognostic factors does not preclude the possibility of long-term survival and cure.
              Article 0 comments Cited 279 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Michael Bassetti
                Journal
                Journal ID (nlm-ta): Adv Radiat Oncol
                Journal ID (iso-abbrev): Adv Radiat Oncol
                Title: Advances in Radiation Oncology
                Publisher: Elsevier
                ISSN (Electronic): 2452-1094
                Publication date PMC-release: 23 August 2018
                Publication date Collection: Jan-Mar 2019
                Publication date (Electronic): 23 August 2018
                Volume: 4
                Issue: 1
                Pages: 142-149
                Affiliations
                [a ]Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
                [b ]Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
                [c ]Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
                [d ]Department of Radiation Oncology, University of Los Angeles School of Medicine, Los Angeles, California
                [e ]Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
                [f ]Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
                [g ]Department of Radiation Oncology, University of Colorado School of Medicine, Denver, Colorado
                Author notes
                [∗ ]Corresponding author. 600 Highland Ave., Madison, WI 53792. bassetti@ 123456humonc.wisc.edu
                Article
                Publisher ID: S2452-1094(18)30137-4
                DOI: 10.1016/j.adro.2018.08.005
                PMC ID: 6349638
                PubMed ID: 30706022
                SO-VID: d806e3b4-ef81-4a9f-a314-8ec2c712d438
                Copyright © © 2018 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 1 June 2017
                Date revision received : 5 August 2018
                Date accepted : 7 August 2018
                Categories
                Subject: Physics Contribution

                Data availability:

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