A biologically effective dose threshold for stereotactic body radiation therapy-can we put the issue to BED?
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ABSTRACT:
SUBMITTER: Mix M
PROVIDER: S-EPMC7729357 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
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A biologically effective dose threshold for stereotactic body radiation therapy-can we put the issue to BED?
Mix Michael M Bogart Jeffrey A JA
Annals of translational medicine 20201101 22
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Project description:BackgroundTo explore the association between biologically effective dose (BED) and survival rates in Child-Pugh A classification (CP-A) small hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT).MethodsThis retrospective study included 108 small HCC patients who were treated with SBRT between 2011 and 2014. The prescribed dose delivered to the tumor were 48Gy/8f, 49Gy/7f, 50Gy/5f and 54Gy/6f. The median biologically effective dose (BED10) of the total prescribed dose was 100Gy (76.8-102.6Gy). Factors associated with the survival rate were examined using the Cox proportion hazards model, and the factors associated with radiation-induced liver injury (RILD) were examined by logistic regression analysis.ResultsFor these patients, the median follow-up time was 42 months (6-77 months), and the 1-, 2- and 3-year overall survival (OS) rates were 96.3, 89.8 and 80.6%, respectively. The 1-, 2- and 3-year progression-free survival (PFS) rates were 85.2, 70.1 and 60.6%, respectively. The 1-, 2- and 3-year local control (LC) rates were 98.1, 96.2 and 95.1%, respectively. The 1-, 2- and 3-year distant metastasis- free survival (DMFS) rates were 86.1, 72.8 and 61.2%. The OS, PFS and DMFS were significantly higher in the BED10 ≥ 100Gy group than in the BED10 < 100Gy group (OS: p = 0.020; PFS: p = 0.017; DMFS: p = 0.012). The PLT count was a predictive factor of RILD.ConclusionsSBRT is a safe and effective option for CP-A HCC patients. A BED10 value greater than 100Gy and lower CP score are associated with improved OS and PFS. Additionally, the peripheral PLT count are predictive factors of RILD.
| S-EPMC6712687 | biostudies-literature
Project description:BackgroundThere is a lack of data on the biologically effective dose and the efficacy of stereotactic body radiotherapy in hepatocellular carcinoma patients, and this study was conducted to explore the relation between BED and efficacy.MethodsThis study is designed as a mono-center study. The participants are randomized into three group, and received the following recommended schedule: 49Gy/7f, 54Gy/6f and 55Gy/5f with BED10 in correspondence to 83.3Gy, 102.6Gy and 115.5Gy. The primary outcome measures are to calculate local control rates (LC), overall survival rates (OS) and progression-free survival rates (PFS). The secondary outcome measures are to observe radiation-induced liver injury (RILD) rates, Child-Pugh score and indocyanine green retention rate at 15 min (ICG-R15) value before and after CK-SBRT. Moreover, gastrointestinal toxicities are also observed.DiscussionThere is no uniform standard for CK-SBRT dose schedule of hepatocellular carcinoma. We propose to conduct a study determining the optimal CK-SBRT schedule of hepatocellular carcinoma patients (≤5 cm). The trial protocol has been approved by the Institutional Review Board of 302 Hospital of PLA (People's Liberation Army). The Ethics number is 2017111D.Trail registrationClinical trails number: NCT03295500. Date of registration: November, 2017.
| S-EPMC6986016 | biostudies-literature
Project description:IntroductionStereotactic body radiation therapy (SBRT) is increasingly utilized for patients with recurrent and metastatic sarcoma. SBRT affords the potential to overcome the relative radioresistance of sarcomas through delivery of a focused high biological effective dose (BED) as an alternative to invasive surgery. We report local control outcomes after metastatic sarcoma SBRT based on radiation dose and histology.MethodsFrom our IRB-approved single-institution registry, all patients treated with SBRT for metastatic sarcoma between 2014 and 2020 were identified. Kaplan-Meier analysis was used to estimate local control and overall survival at 1 and 2 years. A receiver operating characteristic (ROC) curve was generated to determine optimal BED using an α/β ratio of 3. Local control was compared by SBRT dose using the BED cut point and evaluated by histology.ResultsForty-two patients with a total of 138 lesions met inclusion criteria. Median imaging follow up was 7.73 months (range 0.5-35.0). Patients were heavily pre-treated with systemic therapy. Median SBRT prescription was 116.70 Gy BED (range 66.70-419.30). Desmoplastic small round cell tumor, Ewing sarcoma, rhabdomyosarcoma, and small round blue cell sarcomas were classified as radiosensitive (n = 63), and all other histologies were classified as radioresistant (n = 75). Local control for all lesions was 66.7% (95% CI, 56.6-78.5) at 1 year and 50.2% (95% CI, 38.2-66.1) at 2 years. Stratifying by histology, 1- and 2-year local control rates were 65.3% and 55.0%, respectively, for radiosensitive, and 68.6% and 44.5%, respectively, for radioresistant histologies (p = 0.49). The ROC cut point for BED was 95 Gy. Local control rates at 1- and 2-years were 75% and 61.6%, respectively, for lesions receiving >95 Gy BED, and 46.2% and 0%, respectively, for lesions receiving <95 Gy BED (p = 0.01). On subgroup analysis, local control by BED > 95 Gy was significant for radiosensitive histologies (p = 0.013), and trended toward significance for radioresistant histologies (p = 0.25).ConclusionThere is a significant local control benefit for sarcoma SBRT when a BED > 95 Gy is used. Further investigation into the dose-response relationship is warranted to maximize the therapeutic index.
| S-EPMC10322177 | biostudies-literature
Project description:IntroductionStereotactic Body Radiation Therapy (SBRT) is a treatment option for patients with liver metastases. This study evaluated the impact of high versus low dose image-guided SBRT of hepatic metastases.Methods and materialsThis is a single-center retrospective study of patients with liver metastases treated with SBRT. For analyses, patients were divided into two groups: ≤100 Gy and >100 Gy near-minimum Biological Effective Doses (BED98%). The main outcomes were local control (LC), toxicity and overall survival (OS). Cox regression analyses were performed to determine prognostic variables on LC and OS.ResultsNinety patients with 97 liver metastases (77% colorectal) were included. Median follow-up was 28.6 months. The two-year LC rates in the ≤100 Gy and >100 Gy BED98% group were 60% (CI: 41-80%) and 90% (CI: 80-100%), respectively (p = 0.004). Grade 3 toxicity occurred in 7% vs 2% in the ≤100 Gy and >100 Gy group (p = 0.23). Two-year OS rates in the ≤100 Gy and >100 Gy group were 48% (CI: 32-65%) and 85% (CI: 73-97%), respectively (p = 0.007). In multivariable Cox regression analyses, group dose and tumor volume were significantly correlated with LC (HR: 3.61; p = 0.017 and HR: 1.01; p = 0.005) and OS (HR: 2.38; p = 0.005 and HR: 1.01; p = <0.0001).ConclusionHigh dose SBRT provides significantly better local control and overall survival than low dose SBRT without increasing toxicity. When surgical resection is not feasible, high dose SBRT provides an effective and safe treatment for liver metastases.
| S-EPMC6906721 | biostudies-literature
Project description:Historically, the role of radiation in gynecological metastatic disease involved palliation for pain or bleeding. Stereotactic Body Radiation Therapy (SBRT) has shown survival benefits in oligometastatic disease from varying primary histologies in recent randomized trials. However, gynecologic primary oligometastases have been underrepresented in these trials. Recent studies across gynecological malignancy types have similarly shown favorable outcomes and acceptable toxicities from treating recurrent or oligometastatic gynecologic cancer (ROMGC) patients with definitive radiation therapy. The largest body of literature reported on the use of SBRT in ovarian cancer, which was found to be an effective option, especially in the setting of chemo-resistant disease. Despite the encouraging outcomes using SBRT in oligometastatic gynecologic malignancies, SBRT remains underutilized given the lack of randomized studies studying ROMGC with long term follow-up. While waiting for future prospective trials to establish the role of SBRT as the standard of care in ROMGC patients, this review focuses on reporting the advantages and drawbacks of this technique and examines the current literature to help guide patient centered treatment decisions.
| S-EPMC10340138 | biostudies-literature
Project description:PurposeUltrahypofractionationed radiation therapy for prostate cancer is increasingly studied and adopted. The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiotherapy therefore aimed to review studies examining toxicity and quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer and model its effect.Methods and materialsWe performed a systematic PubMed search of prostate SBRT studies published between 2001 and 2018. Those that analyzed factors associated with late urinary, bowel, or sexual toxicity and/or quality of life were included and reviewed. Normal tissue complication probability modelling was performed on studies that contained detailed dose/volume and outcome data.ResultsWe found 13 studies that examined urinary effects, 6 that examined bowel effects, and 4 that examined sexual effects. Most studies included patients with low-intermediate risk prostate cancer treated to 35-40 Gy. Most patients were treated with 5 fractions, with several centers using 4 fractions. Endpoints were heterogeneous and included both physician-scored toxicity and patient-reported quality of life. Most toxicities were mild-moderate (eg, grade 1-2) with a very low overall incidence of severe toxicity (eg, grade 3 or higher, usually <3%). Side effects were associated with both dosimetric and non-dosimetric factors.ConclusionsProstate SBRT appears to be overall well tolerated, with determinants of toxicity that include dosimetric factors and patient factors. Suggested dose constraints include bladder V(Rx Dose)Gy <5-10 cc, urethra Dmax <38-42 Gy, and rectum Dmax <35-38 Gy, though current data do not offer firm guidance on tolerance doses. Several areas for future research are suggested.
| S-EPMC8053668 | biostudies-literature
Project description:Background and purposeTo investigate a weighted four-dimensional (W-4D) treatment planning strategy based on the greater clinical advantage of the conformal over the intensity-modulated technique in lung stereotactic body radiotherapy (SBRT).Material and methodsTwo planning strategies (individual-phase 4D [IP-4D] and W-4D) were evaluated in eighteen lung SBRT patients. The IP-4D plan can deliver a constant fluence during whole respiratory phases. The W-4D plan's key concept was to escalate (or reduce) fluence using a 4D optimization algorithm when the tumour target was out-of-line (or in-line) with an organ-at-risk. The fluence was converted to a dynamic multi-leaf collimator leaf sequence for deliverable 4D irradiation.ResultsIn all patients, the W-4D plan enabled planning tumour volume conformity comparable to the IP-4D plan. The W-4D plan yielded a significantly lower maximum dose than the IP-4D plan for the spinal cord (-11%; p<0.01), oesophagus (-14%; p<0.01), heart (-22%; p=0.01) and stomach (-23%; p=0.07), and a lower mean dose to liver (-19%; p=0.18) while maintaining the mean dose to lung (-1%; p=0.23).ConclusionsW-4D is a robust, practical planning approach that achieves significant dose sparing relative to non-time-resolved tracking; it may be of greater clinical benefit in radiotherapy than the spatially intensity-modulated 4D approach.
| S-EPMC5201122 | biostudies-literature
Project description:A literature review of more than 200 stereotactic body radiation therapy spine articles from the past 20 years found only a single article that provided dose-volume data and outcomes for each spinal cord of a clinical dataset: the Gibbs 2007 article (Gibbs et al, 2007(1)), which essentially contains the first 100 stereotactic body radiation therapy (SBRT) spine treatments from Stanford University Medical Center. The dataset is modeled and compared in detail to the rest of the literature review, which found 59 dose tolerance limits for the spinal cord in 1-5 fractions. We partitioned these limits into a unified format of high-risk and low-risk dose tolerance limits. To estimate the corresponding risk level of each limit we used the Gibbs 2007 clinical spinal cord dose-volume data for 102 spinal metastases in 74 patients treated by spinal radiosurgery. In all, 50 of the patients were previously irradiated to a median dose of 40Gy in 2-3Gy fractions and 3 patients developed treatment-related myelopathy. These dose-volume data were digitized into the dose-volume histogram (DVH) Evaluator software tool where parameters of the probit dose-response model were fitted using the maximum likelihood approach (Jackson et al, 1995(3)). Based on this limited dataset, for de novo cases the unified low-risk dose tolerance limits yielded an estimated risk of spinal cord injury of ≤1% in 1-5 fractions, and the high-risk limits yielded an estimated risk of ≤3%. The QUANTEC Dmax limits of 13Gy in a single fraction and 20Gy in 3 fractions had less than 1% risk estimated from this dataset, so we consider these among the low-risk limits. In the previously irradiated cohort, the estimated risk levels for 10 and 14Gy maximum cord dose limits in 5 fractions are 0.4% and 0.6%, respectively. Longer follow-up and more patients are required to improve the risk estimates and provide more complete validation.
| S-EPMC4990135 | biostudies-literature
Project description:Background and purpose Recently published HyTEC report summarized lung toxicity data and proposed guidelines of mean lung dose (MLD) <8 Gy and normal lung receiving at least 20 Gy, V20Gy<10-15% to avoid lung toxicity. Support for preferred use of a particular dosimetric parameter has been limited. We performed a detailed dose-volume analysis of data on radiation pneumonitis (RP) following lung stereotactic body radiation therapy (SBRT) to search for parameters showing the strongest correlation with RP. Materials and methods Two patient cohorts (primary and metastatic lung tumor patients) from previously reported studies were analyzed. Total number of patients was 96, and incidence of grade ≥2 RP was 13.5% (13/96). Fitting to the logistic function was performed to investigate correlation between incidence of RP and reported dosimetric and volumetric parameters. Another independent cohort was used to explore correlation between dosimetric parameters. Results Among normal lung parameters (MLD and reported Vx), only MLD consistently showed significant correlation with incidence of RP. Gross tumor volume (GTV), internal target volume, planning target volume (PTV), and minimum dose covering 95% of GTV or PTV did not show statistical significance. A significant correlation between reported Vx and MLD was observed in all cohorts. Conclusions In considering tumor- and target-specific (e.g., GTV, PTV) and normal lung-specific (e.g., MLD, Vx) metrics, MLD was the only parameter that consistently correlated with incidence of RP across both cohorts. Because SBRT planning constraints allow small normal lung volumes to receive high doses, utility of MLD is not obvious. The parallel structure of lung is one possible explanation, but correlation between dosimetric parameters obscures elucidation of the preferred or mechanistically based parameter to guide radiotherapy planning.
| S-EPMC7641492 | biostudies-literature
Project description:ObjectiveTo evaluate the influence of target dose heterogeneity on normal tissue dose sparing for peripheral lung tumor stereotactic body radiation therapy (SBRT).MethodsBased on the volumetric-modulated arc therapy (VMAT) technique, three SBRT plans with homogeneous, moderate heterogeneous, and heterogeneous (HO, MHE, and HE) target doses were compared in 30 peripheral lung tumor patients. The prescription dose was 48 Gy in 4 fractions. Ten rings outside the PTV were created to limit normal tissue dosage and evaluate dose falloff.ResultsWhen MHE and HE plans were compared to HO plans, the conformity index of the PTV was increased by approximately 0.08. The median mean lung dose (MLD), V5, V10, V20 of whole lung, D2%, D1cc, D2cc of the rib, V30 of the rib, D2% and the maximum dose (Dmax) of the skin, and D2% and Dmax of most mediastinal organs at risk (OARs) and spinal cord were reduced by up to 4.51 Gy or 2.8%. Analogously, the median Dmax, D2% and mean dose of rings were reduced by 0.71 to 8.46 Gy; and the median R50% and D2cm were reduced by 2.1 to 2.3 and 7.4% to 8.0%, respectively. Between MHE and HE plans there was little to no difference in OARs dose and dose falloff beyond the target. Furthermore, the dose sparing of rib V30 and the mean dose of rings were negatively correlated with the rib and rings distance from tumor, respectively.ConclusionsFor peripheral lung tumor SBRT, target conformity, normal tissue dose, and dose falloff around the target could be improved by loosening or abandoning homogeneity. While there was negligible further dose benefit for the maximum target dose above 125% of the prescription, dose sparing of normal tissue derived from a heterogeneous target decreased as the distance from the tumor increased.
| S-EPMC8404286 | biostudies-literature