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      Whole brain radiotherapy with adjuvant or concomitant boost in brain metastasis: dosimetric comparison between helical and volumetric IMRT technique

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          Abstract

          Background

          To compare and evaluate the possible advantages related to the use of VMAT and helical IMRT and two different modalities of boost delivering, adjuvant stereotactic boost (SRS) or simultaneous integrated boost (SIB), in the treatment of brain metastasis (BM) in RPA classes I-II patients.

          Methods

          Ten patients were treated with helical IMRT, 5 of them with SRS after whole brain radiotherapy (WBRT) and 5 with SIB. MRI co-registration with planning CT was mandatory and prescribed doses were 30 Gy in 10 fractions (fr) for WBRT and 15Gy/1fr or 45Gy/10fr in SRS or SIB, respectively. For each patient, 4 “treatment plans” (VMAT SRS and SIB, helical IMRT SRS and SIB) were calculated and accepted if PTV boost was included in 95 % isodose and dose constraints of the main organs at risk were respected without major deviations. Homogeneity Index (HI), Conformal Index (CI) and Conformal Number (CN) were considered to compare the different plans. Moreover, time of treatment delivery was calculated and considered in the analysis.

          Results

          Volume of brain metastasis ranged between 1.43 and 51.01 cc (mean 12.89 ± 6.37 ml) and 3 patients had double lesions. V95% resulted over 95 % in the average for each kind of technique, but the “target coverage” was inadequate for VMAT planning with two sites. The HI resulted close to the ideal value of zero in all cases; VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS showed mean CI of 2.15, 2.10, 2.44 and 1.66, respectively (optimal range: 1.5–2.0). Helical IMRT-SRS was related to the best and reliable finding of CN (0.66). The mean of treatment time was 210 s, 467 s, 440 s, 1598 s, respectively, for VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS.

          Conclusions

          This dosimetric comparison show that helical IMRT obtain better target coverage and respect of CI and CN; VMAT could be acceptable in solitary metastasis. SIB modality can be considered as a good choice for clinical and logistic compliance; literature’s preliminary data are confirming also a radiobiological benefit for SIB. Helical IMRT-SRS seems less effective for the long time of treatment compared to other techniques.

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          Most cited references21

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          Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials.

          Promising results from new approaches such as radiosurgery or stereotactic surgery of brain metastases have recently been reported. Are these results due to the therapy alone or can the results be attributed in part to patient selection? An analysis of tumor/patient characteristics and treatment variables in previous Radiation Therapy Oncology Group (RTOG) brain metastases studies was considered necessary to fully evaluate the benefit of these new interventions. The database included 1200 patients from three consecutive RTOG trials conducted between 1979 and 1993, which tested several different dose fractionation schemes and radiation sensitizers. Using recursive partitioning analysis (RPA), a statistical methodology which creates a regression tree according to prognostic significance, eighteen pretreatment characteristics and three treatment-related variables were analyzed. According to the RPA tree the best survival (median: 7.1 months) was observed in patients or = 70, < 65 years of age with controlled primary and no extracranial metastases; Class 3: KPS < 70; Class 2- all others. Using these classes or stages, new treatment techniques can be tested on homogeneous patient groups.
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            A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database.

            The purpose of this study is to introduce a new prognostic index for patients with brain metastases and compare it with three published indices. Treatment for brain metastases varies widely. A sound prognostic index is thus important to guide both clinical decision making and outcomes research. A new index was developed because of limitations in the three existing indices and new data (Radiation Therapy Oncology Group 9508) are available since the others were developed. All four indices were compared using the Radiation Therapy Oncology Group database of 1,960 patients with brain metastases from five randomized trials. The ability of the four indices to distinguish its separate classes was determined statistically. Advantages and disadvantages of each index are discussed. Recursive partitioning analysis (RPA) and the new Graded Prognostic Assessment (GPA) had the most statistically significant differences between classes (p < 0.001 for all classes). The new index, the GPA, is as prognostic as the RPA and more prognostic than the other indices. The GPA is the least subjective, most quantitative and easiest to use of the four indices. Future clinical trials should compare the GPA with the RPA to prospectively validate these findings.
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              Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases.

              The Radiation Therapy Oncology Group (RTOG) previously developed three prognostic classes for brain metastases using recursive partitioning analysis (RPA) of a large database. These classes were based on Karnofsky performance status (KPS), primary tumor status, presence of extracranial system metastases, and age. An analysis of RTOG 91-04, a randomized study comparing two dose-fractionation schemes with a comparison to the established RTOG database, was considered important to validate the RPA classes. A total of 445 patients were randomized on RTOG 91-04, a Phase III study of accelerated hyperfractionation versus accelerated fractionation. No difference was observed between the two treatment arms with respect to survival. Four hundred thirty-two patients were included in this analysis. The majority of the patients were under age 65, had KPS 70-80, primary tumor controlled, and brain-only metastases. The initial RPA had three classes, but only patients in RPA Classes I and II were eligible for RTOG 91-04. For RPA Class I, the median survival time was 6. 2 months and 7.1 months for 91-04 and the database, respectively. The 1-year survival was 29% for 91-04 versus 32% for the database. There was no significant difference in the two survival distributions (p = 0.72). For RPA Class II, the median survival time was 3.8 months for 91-04 versus 4.2 months for the database. The 1-year survival was 12% and 16% for 91-04 and the database, respectively (p = 0.22). This analysis indicates that the RPA classes are valid and reliable for historical comparisons. Both the RTOG and other clinical trial organizers should currently utilize this RPA classification as a stratification factor for clinical trials.
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                Author and article information

                Contributors
                paolobor82@yahoo.it
                sarinape@alice.it
                luisespaces@yahoo.com
                rossella.avitabile@libero.it
                maurourpis@omeca.it
                foscarini.s@alice.it
                giulia.tesini@hotmail.it
                trevisan.francesca1@gmail.com
                paolo.ghirardelli@libero.it
                sara.pandini@virgilio.it
                triggioluca@hotmail.it
                stefano.magrini@unibs.it
                michela.buglione@unibs.it
                Journal
                Radiat Oncol
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central (London )
                1748-717X
                19 April 2016
                19 April 2016
                2016
                : 11
                : 59
                Affiliations
                [ ]Radiation Oncology Department, University and Spedali Civili Brescia, P.le Spedali Civili 1, Brescia, Italy
                [ ]Medical Physics Department, Spedali Civili Brescia, P.le Spedali Civili 1, Brescia, Italy
                Article
                634
                10.1186/s13014-016-0634-6
                4837558
                27094398
                36be7d61-344a-4855-96f1-b3c514a93d41
                © Borghetti et al. 2016

                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
                : 10 January 2016
                : 12 April 2016
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Oncology & Radiotherapy
                brain metastases,dosimetric comparison,helical imrt,stereotactic radiotherapy,vmat,homogeneity index,conformal index,conformal number

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