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Objective: To determine the long-term normal tissue complication probability with stereotactic body radiation therapy (SBRT) treatments for targets that move with respiration and its relation with the type of respiratory motion management (tracking vs. compression or gating). Methods: A PubMed search was performed for identifying literature regarding dose, volume, fractionation, and toxicity (grade 3 or higher) for SBRT treatments for tumors which move with respiration. From the identified papers logistic or probit dose-response models were fitted to the data using the maximum-likelihood technique and confidence intervals were based on the profile-likelihood method in the dose-volume histogram (DVH) Evaluator. Results: Pooled logistic and probit models for grade 3 or higher toxicity for aorta, chest wall, duodenum, and small bowel suggest a significant difference when live motion tracking was used for targeting tumors with move with respiration which was on the average 10 times lower, in the high dose range. Conclusion: Live respiratory motion management appears to have a better toxicity outcome when treating targets which move with respiration with very steep peripheral dose gradients. This analysis is however limited by sparsity of rigorous data due to poor reporting in the literature. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To report the local control, survival, and low toxicity observed at the Cooper University Hospital CyberKnife Center post stereotactic body radiation therapy (SBRT) in the treatment of lung tumors near the mediastinum. Methods and Materials: Twenty-four medically inoperable lung cancer patients with tumors near the mediastinum were treated using the Accuray CyberKnife system (Accuray, Sunnyvale, CA) with Monte Carlo dose calculations and heterogeneity corrections from July 2008 to May 2010. The prescription dose ranged from 28.5 Gy to 60 Gy in 3-5 fractions. For conventional fractionation schemes, Emami et al1 organized the dose tolerance limits into a unified format for clinical utility and partitioned them into 2 risk levels (5% and 50%) with preset volumes for most critical structures throughout the body. In contrast, statistical SBRT dose tolerance limits for mediastinal structures have not been established yet. We have sufficient experience at least to begin organizing a unified format with low-risk and high-risk partitions and preset volumes for 1-5 fractions exposing mediastinal structures. With the help of the (dose-volume histogram) DVH Evaluator, a software tool developed by our senior author, each treatment plan was assessed for safety and feasibility prior to treatment. The DVH Evaluator was also used to analyze the follow-up data and to create graphs of risk, called DVH Risk Maps, superimposing clinical data onto the unified SBRT dose tolerance limits. Results: It was not feasible to prescribe the doses of peripheral lung lesions for all tumors near the mediastinum because of known toxicity. The crude local tumor control rate achieved in our series was 92%. Median survival was 26.8 months for the primary lung cases and 9.6 months for the metastatic cases. No patients experienced grade 3 or higher toxicities. Conclusions: We affirm that SBRT is feasible in the treatment of centrally located lung cancers when the dose tolerance limits of critical structures are diligently respected. The low adverse event rates that we have experienced, combined with a good local tumor control rate, are encouraging. [Copyright &y& Elsevier]

Purpose: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS).Methods and Materials: Eligible studies provided NTCPs for the endpoints of radionecrosis, edema, or symptoms after cranial SRS/fSRS and quantitative dose-volume metrics. Studies of patients with only glioma, meningioma, vestibular schwannoma, or brainstem targets were excluded. The data summary and analyses focused on arteriovenous malformations (AVM) and brain metastases.Results: Data from 51 reports are summarized. There was wide variability in reported rates of radionecrosis. Available data for SRS/fSRS for brain metastases were more amenable to NTCP modeling than AVM data. In the setting of brain metastases, SRS/fSRS-associated radionecrosis can be difficult to differentiate from tumor progression. For single-fraction SRS to brain metastases, tissue volumes (including target volumes) receiving 12 Gy (V12) of 5 cm3, 10 cm3, or >15 cm3 were associated with risks of symptomatic radionecrosis of approximately 10%, 15%, and 20%, respectively. SRS for AVM was associated with modestly lower rates of symptomatic radionecrosis for equivalent V12. For brain metastases, brain plus target volume V20 (3-fractions) or V24 (5-fractions) <20 cm3 was associated with <10% risk of any necrosis or edema, and <4% risk of radionecrosis requiring resection.Conclusions: The risk of radionecrosis after SRS and fSRS can be modeled as a function of dose and volume treated. The use of fSRS appears to reduce risks of radionecrosis for larger treatment volumes relative to SRS. More standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses that can refine predictive models of brain toxicity risks. [ABSTRACT FROM AUTHOR]

Purpose: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature.Methods and Materials: PubMed-indexed studies published between January 1995 and September 2017 were used to evaluate dosimetric and clinical predictors of TCP after SRS or fSRS for brain metastases. Eligible studies had ≥10 patients and included detailed dose-fractionation data with corresponding ≥1-year local control (LC) data, typically evaluated as a >20% increase in diameter of the targeted lesion using the pre-SRS diameter as a reference.Results: Of 2951 potentially eligible manuscripts, 56 included sufficient dose-volume data for analyses. Accepting that necrosis and pseudoprogression can complicate the assessment of LC, for tumors ≤20 mm, single-fraction doses of 18 and 24 Gy corresponded with >85% and 95% 1-year LC rates, respectively. For tumors 21 to 30 mm, an 18 Gy single-fraction dose was associated with 75% LC. For tumors 31 to 40 mm, a 15 Gy single-fraction dose yielded ∼69% LC. For 3- to 5-fraction fSRS using doses in the range of 27 to 35 Gy, 80% 1-year LC has been achieved for tumors of 21 to 40 mm in diameter.Conclusions: TCP for SRS and fSRS are presented. For small lesions ≤20 mm, single doses of ≈18 Gy appear generally associated with excellent rates of LC; for melanoma, higher doses seem warranted. For larger lesions >20 mm, local control rates appear to be ≈ 70% to 75% with usual doses of 15 to 18 Gy, and in this setting, fSRS regimens should be considered. Greater consistency in reporting of dosimetric and LC data is needed to facilitate future pooled analyses. As systemic and biologic therapies evolve, updated analyses will be needed to further assess the necessity, efficacy, and toxicity of SRS and fSRS. [ABSTRACT FROM AUTHOR]

Purpose: Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation.Methods and Materials: Eligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION).Results: Thirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P = .66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in <1% RION risks include 12 Gy in 1 fraction (which is greater than our recommendation of 10 Gy in 1 fraction), 20 Gy in 3 fractions, and 25 Gy in 5 fractions. Omitting multi-fraction data (and thereby eliminating uncertainties associated with dose conversions), a single-fraction dose of 10 Gy was associated with a 1% RION risk. Insufficient details precluded modeling of NTCP risks after prior radiation therapy.Conclusions: Optic apparatus NTCP and tolerance doses after single- and multi-fraction stereotactic radiosurgery are presented. Additional standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses and better define RION NTCP after SRS/fSRS. [ABSTRACT FROM AUTHOR]