Purpose

To develop and compare tumor-control probability (TCP) models for single-fraction stereotactic radiosurgery (SRS) for brain metastasis (BMs) with and without retreatment.

Methods and materials

We developed three different schemas to model TCP of BMs treated with linear accelerator-based SRS. Dose to 99% of each planning target volume (PTV D₉₉) and 6-month local control were fit using linear-quadratic-linear (LQ-L) models based on equivalent-dose conversions in 2 Gy (EQD2). The M1 schema had separate LQ-L TCP models for initial dose (M1-initial) and retreatment dose (M1-retreat), and the M2 schema had an LQ-L model using the sum of 50% of the initial SRS dose plus the retreatment SRS dose. The M1-initial and M1-retreat schema modeled local control after first SRS to 48 lesions (patients = 22) and second SRS to 46 lesions (patients = 21). The M0 schema included a whole data set of 349 lesions (patients = 136) receiving first SRS (no retreatment and M1-initial).

Results

LQ-L models fitted the data well (χ² = 0.059-0.525 and P = 0.999-1.000). For M0 and M1-retreat, the fitted models EQD2₅₀ and γ₅₀ parameters were similar. The LQ-L fitted EQD2₅₀ was ∼8.0 Gy for M0 and M1-retreat, ∼24 Gy for M1-initial, and ∼19 Gy for M2. The model fitted γ₅₀ was 0.1 Gy for M0, M1-retreat, and M2 and 0.5 for M1-initial. For the PTV D₉₉ of 10 and 20 Gy, the steepest to shallowest dose-response or largest change in TCP, that is, TCP_20Gy - TCP_10Gy, was observed in M1-initial (0.49) and M2 (0.17). M0 and M1-retreat showed a similar change in TCP of 0.21.

Conclusions

The model-fitted parameters predicted the recurrent BMs required a higher threshold dose and had a steeper dose-response for first SRS versus second SRS and M0. Alternatively, the recurrent BMs required ∼2 Gy higher predicted PTV D₉₉ dose for first SRS to achieve the same TCP of 0.75 compared with second SRS and M0. Further investigations on larger patient cohorts are needed for validating our findings in predictive modeling of recurrent BMs.

Purpose

To suggest PTV margins for liver SBRT with different motion management strategies based on a systematic review and meta-analysis.

Methods

In accordance with Preferred-Reporting-Items-for-Systematic-Reviews-and-Meta-Analyses (PRISMA), a systematic review in PubMed, Embase and Medline databases was performed for liver tumor position variability. From an initial 533 studies published before October 2020, 36 studies were categorized as 18 free-breathing (FB; n_patients = 401), 9 abdominal compression (AC; n_patients = 145) and 9 breath-hold (BH; n_patients = 126). A meta-analysis was performed on inter- and intra-fraction position variability to report weighted-mean with 95% confidence interval (CI₉₅) in superior-inferior (SI), left-right (LR) and anterior-posterior (AP) directions. Furthermore, weighted-mean ITV margins were computed for FB (n_studies = 15, n_patients = 373) and AC (n_studies = 6, n_patients = 97) and PTV margins were computed for FB (n_studies = 6, n_patients = 95), AC (n_studies = 7, n_patients = 106) and BH (n_studies = 8, n_patients = 133).

Results

The FB weighted-mean intra-fraction variability, ITV margins and weighted-standard-deviation in mm were SI-9.7, CI₉₅ = 9.3-10.1, 13.5 ± 4.9; LR-5.4, CI₉₅ = 5.3-5.6, 7.3 ± 7.9; and AP-4.2, CI₉₅ = 4.0-4.4, 6.3 ± 7.6. The inter-fraction-based results were SI-4.7, CI₉₅ = 4.3-5.1, 5.7 ± 1.7; LR-1.4, CI₉₅ = 1.1-1.6, 3.6 ± 2.7; and AP-2.8, CI₉₅ = 2.5-3.1, 4.8 ± 2.1. For AC intra-fraction results in mm were SI-1.8, CI₉₅ = 1.6-2.0, 2.6 ± 1.2; LR-0.7, CI₉₅ = 0.6-0.8, 1.7 ± 1.5; and AP-0.9, CI₉₅ = 0.8-1.0, 1.9 ± 1.7. The inter-fraction results were SI-2.6, CI₉₅ = 2.3-3.0, 5.2 ± 2.9; LR-1.9, CI₉₅ = 1.7-2.1, 4.0 ± 2.2; and AP-2.9, CI₉₅ = 2.5-3.2, 5.8 ± 2.7. For BH the inter-fraction variability, and the weighted-mean PTV margins and weighted-standard-deviation in mm were SI-2.4, CI₉₅ = 2.1-2.7, 5.6 ± 2.9; LR-1.8, CI₉₅ = 1.3-2.2, 5.5 ± 1.7; and AP-1.4; CI₉₅ = 1.2-1.7, 6.1 ± 2.1.

Conclusion

Our meta-analysis suggests a symmetric weighted-mean PTV margin of 6 mm might be appropriate for BH. For AC and FB, asymmetric PTV margins (weighted-mean margin of 4 mm (AP), 6 mm (SI/LR)) might be appropriate. For FB, if larger (>ITV margin) intra-fraction variability observed, the additional intra- and inter-fraction variability should be accounted in the PTV margin.

Purpose

Stereotactic body radiation therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer and is often used for recurrent lung cancer and pulmonary metastases. Radiation-induced lung toxicity (RILT), including radiation pneumonitis and pulmonary fibrosis, is a major concern for which it is important to understand dosimetric and clinical predictors.

Methods and materials

This study was undertaken through the American Association of Physicists in Medicine's Working Group on Biological Effects of Stereotactic Body Radiotherapy. Data from studies of lung SBRT published through the summer of 2016 that provided detailed information about RILT were analyzed.

Results

Ninety-seven studies were ultimately considered. Definitions of the risk organ and complication endpoints as well as dose-volume information presented varied among studies. The risk of RILT, including radiation pneumonitis and pulmonary fibrosis, was reported to be associated with the size and location of the tumor. Patients with interstitial lung disease appear to be especially susceptible to severe RILT. A variety of dosimetric parameters were reported to be associated with RILT. There was no apparent threshold "tolerance dose-volume" level. However, most studies noted safe treatment with a rate of symptomatic RILT of <10% to 15% after lung SBRT with a mean lung dose (MLD) of the combined lungs ≤8 Gy in 3 to 5 fractions and the percent of total lung volume receiving more than 20 Gy (V₂₀) <10% to 15%.

Conclusions

To allow more rigorous analysis of this complication, future studies should standardize reporting by including standardized endpoint and volume definitions and providing dose-volume information for all patients, with and without RILT.

Purpose

We sought to investigate the tumor control probability (TCP) of vestibular schwannomas after single-fraction stereotactic radiosurgery (SRS) or hypofractionated SRS over 2 to 5 fractions (fSRS).

Methods and materials

Studies (PubMed indexed from 1993-2017) were eligible for data extraction if they contained dosimetric details of SRS/fSRS correlated with local tumor control. The rate of tumor control at 5 years (or at 3 years if 5-year data were not available) were collated. Poisson modeling estimated the TCP per equivalent dose in 2 Gy per fraction (EQD2) and in 1, 3, and 5 fractions.

Results

Data were extracted from 35 publications containing a total of 5162 patients. TCP modeling was limited by the absence of analyzable data of <11 Gy in a single-fraction, variability in definition of "tumor control," and by lack of significant increase in TCP for doses >12 Gy. Using linear-quadratic-based dose conversion, the 3- to 5-year TCP was estimated at 95% at an EQD2 of 25 Gy, corresponding to 1-, 3-, and 5-fraction doses of 13.8 Gy, 19.2 Gy, and 21.5 Gy, respectively. Single-fraction doses of 10 Gy, 11 Gy, 12 Gy, and 13 Gy predicted a TCP of 85.0%, 88.4%, 91.2%, and 93.5%, respectively. For fSRS, 18 Gy in 3 fractions (EQD2 of 23.0 Gy) and 25 Gy in 5 fractions (EQD2 of 30.2 Gy) corresponded to TCP of 93.6% and 97.2%. Overall, the quality of dosimetric reporting was poor; recommended reporting guidelines are presented.

Conclusions

With current typical SRS doses of 12 Gy in 1 fraction, 18 Gy in 3 fractions, and 25 Gy in 5 fractions, 3- to 5-year TCP exceeds 91%. To improve pooled data analyses to optimize treatment outcomes for patients with vestibular schwannoma, future reports of SRS should include complete dosimetric details with well-defined tumor control and toxicity endpoints.

Background

Radiotherapy is increasingly used to treat oligometastatic patients. We sought to identify prognostic criteria in oligometastatic patients undergoing definitive hypofractionated image-guided radiotherapy (HIGRT).

Methods

Exclusively extracranial oligometastatic patients treated with HIGRT were pooled. Characteristics including age, sex, primary tumor type, interval to metastatic diagnosis, number of treated metastases and organs, metastatic site, prior systemic therapy for primary tumor treatment, prior definitive metastasis-directed therapy, and systemic therapy for metastasis associated with overall survival (OS), progression-free survival (PFS), and treated metastasis control (TMC) were assessed by the Cox proportional hazards method. Recursive partitioning analysis (RPA) identified prognostic risk strata for OS and PFS based on pretreatment factors.

Results

361 patients were included. Primary tumors included non-small cell lung (17%), colorectal (19%), and breast cancer (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate analysis, primary tumor, interval to metastases, treated metastases number, and mediastinal/hilar lymph node, liver, or adrenal metastases were associated with OS. Primary tumor site, involved organ number, liver metastasis, and prior primary disease chemotherapy were associated with PFS. OS RPA identified five classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year OS 75%, 95% CI 66-85%); class 2: patients without BKP with disease-free interval of 75+ months (3-year OS 85%, 95% CI 67-100%); class 3: patients without BKP, shorter disease-free interval, ≤ two metastases, and age < 62 (3-year OS 55%, 95% CI 48-64%); class 4: patients without BKP, shorter disease-free interval, ≥ three metastases, and age < 62 (3-year OS 38%, 95% CI 24-60%); class 5: all others (3-year OS 13%, 95% CI 5-35%). Higher biologically effective dose (BED) (p < 0.01) was associated with OS.

Conclusions

We identified clinical factors defining oligometastatic patients with favorable outcomes, who we hypothesize are most likely to benefit from metastasis-directed therapy.

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.

Background

Radiotherapy is increasingly used to treat oligometastatic patients. We sought to identify prognostic criteria in oligometastatic patients undergoing definitive hypofractionated image-guided radiotherapy (HIGRT).

Methods

Exclusively extracranial oligometastatic patients treated with HIGRT were pooled. Characteristics including age, sex, primary tumor type, interval to metastatic diagnosis, number of treated metastases and organs, metastatic site, prior systemic therapy for primary tumor treatment, prior definitive metastasis-directed therapy, and systemic therapy for metastasis associated with overall survival (OS), progression-free survival (PFS), and treated metastasis control (TMC) were assessed by the Cox proportional hazards method. Recursive partitioning analysis (RPA) identified prognostic risk strata for OS and PFS based on pretreatment factors.

Results

361 patients were included. Primary tumors included non-small cell lung (17%), colorectal (19%), and breast cancer (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate analysis, primary tumor, interval to metastases, treated metastases number, and mediastinal/hilar lymph node, liver, or adrenal metastases were associated with OS. Primary tumor site, involved organ number, liver metastasis, and prior primary disease chemotherapy were associated with PFS. OS RPA identified five classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year OS 75%, 95% CI 66-85%); class 2: patients without BKP with disease-free interval of 75+ months (3-year OS 85%, 95% CI 67-100%); class 3: patients without BKP, shorter disease-free interval, ≤ two metastases, and age < 62 (3-year OS 55%, 95% CI 48-64%); class 4: patients without BKP, shorter disease-free interval, ≥ three metastases, and age < 62 (3-year OS 38%, 95% CI 24-60%); class 5: all others (3-year OS 13%, 95% CI 5-35%). Higher biologically effective dose (BED) (p < 0.01) was associated with OS.

Conclusions

We identified clinical factors defining oligometastatic patients with favorable outcomes, who we hypothesize are most likely to benefit from metastasis-directed therapy.

PURPOSE: Current guidelines recommend surgery as standard of care for primary lung neuroendocrine tumor (LNET). Given that LNET is a rare clinical entity, there is a lack of literature regarding treatment of LNET with stereotactic body radiation therapy (SBRT). We hypothesized that SBRT could lead to effective locoregional tumor control and long-term outcomes. METHODS AND MATERIALS: We retrospectively reviewed 48 tumors in 46 patients from 11 institutions with a histologically confirmed diagnosis of LNET, treated with primary radiation therapy. Data were collected for patients treated nonoperatively with primary radiation therapy between 2006 and 2020. Patient records were reviewed for lesion characteristics and clinical risk factors. Kaplan-Meier analysis, log-rank tests, and Cox multivariate models were used to compare outcomes. RESULTS: Median age at treatment was 71 years and mean tumor size was 2 cm. Thirty-two lesions were typical carcinoid histology, 7 were atypical, and 9 were indeterminate. The most common SBRT fractionation schedule was 50 to 60 Gy in 5 daily fractions. Overall survival at 3, 6, and 9 years was 64%, 43%, and 26%, respectively. Progression-free survival at 3, 6, and 9 years was 88%, 78%, and 78%, respectively. Local control at 3, 6, and 9 years was 97%, 91%, and 91%, respectively. There was 1 regional recurrence in a paraesophageal lymph node. No grade 3 or higher toxicity was identified. CONCLUSIONS: This is the largest series evaluating outcomes in patients with LNET treated with SBRT. This treatment is well tolerated, provides excellent locoregional control, and should be offered as an alternative to surgical resection for patients with early-stage LNET, particularly those who may not be ideal surgical candidates.