Abstract Background and purpose To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and ...between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. Materials and methods A retrospective multi-institutional ( n = 22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. Results After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose–response relationship was observed in the primary NSCLC and metastatic cohort but dose–response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151–223) and 160 Gy (123–237) (n.s.), respectively. The dose–response relationship was not influenced by the primary cancer site within the metastatic cohort. Conclusions Dose–response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases.
Purpose
External-beam radiotherapy (EBRT) is the predominant method for localized brain radiotherapy (LBRT) after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50-kV ...x‑rays is an alternative way to focally irradiate the resection cavity after BM surgery, with the option of shortening the overall treatment time and limiting normal tissue irradiation.
Methods
We retrospectively analyzed the outcomes of all patients who underwent neurosurgical resection of BM and 50-kV x‑ray IORT between 2013 and 2020 at Augsburg University Medical Center.
Results
We identified 40 patients with 44 resected BM treated with 50-kV x‑ray IORT. Median diameter of the resected metastases was 2.8 cm (range 1.5–5.9 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including 3‑monthly MRI of the brain. Mean FU was 14.4 months, with a median MRI FU for alive patients of 12.2 months. Median overall survival (OS) of all treated patients was 26.4 months (estimated 1‑year OS 61.6%). The observed local control (LC) rate of the resection cavity was 88.6% (estimated 1‑year LC 84.3%). Distant brain control (DC) was 47.5% (estimated 1‑year DC 33.5%). Only 25% of all patients needed WBI in the further course of disease. The observed radionecrosis rate was 2.5%.
Conclusion
IORT with 50-kV x‑rays is a safe and appealing way to apply LBRT after neurosurgical resection of BM, with low toxicity and excellent LC. Close MRI FU is paramount to detect distant brain failure (DBF) early.
Many technological and methodical advances have made stereotactic body radiotherapy (SBRT) more accurate and more efficient during the last years. This study aims to investigate whether experience in ...SBRT and technological innovations also translated into improved local control (LC) and overall survival (OS).
A database of 700 patients treated with SBRT for lung metastases in 20 German centers between 1997 and 2014 was used for analysis. It was the aim of this study to investigate the impact of fluorodeoxyglucose positron-emission tomography (FDG-PET) staging, biopsy confirmation, image guidance, immobilization, and dose calculation algorithm, as well as the influence of SBRT experience, on LC and OS.
Median follow-up time was 14.3 months (range, 0-131.9 months), with 2-year LC and OS of 81.2% (95% confidence interval CI 75.8%-85.7%) and 54.4% (95% CI 50.2%-59.0%), respectively. In multivariate analysis, all treatment technologies except FDG-PET staging did not significantly influence outcome. Patients who received pre-SBRT FDG-PET staging showed superior 1- and 2-year OS of 82.7% (95% CI 77.4%-88.6%) and 64.8% (95% CI 57.5%-73.3%), compared with patients without FDG-PET staging resulting in 1- and 2-year OS rates of 72.8% (95% CI 67.4%-78.8%) and 52.6% (95% CI 46.0%-60.4%), respectively (P=.012). Experience with SBRT was identified as the main prognostic factor for LC: institutions with higher SBRT experience (patients treated with SBRT within the last 2 years of the inclusion period) showed superior LC compared with less-experienced centers (P≤.001). Experience with SBRT within the last 2 years was independent from known prognostic factors for LC.
Investigated technological and methodical advancements other than FDG-PET staging before SBRT did not significantly improve outcome in SBRT for pulmonary metastases. In contrast, LC was superior with increasing SBRT experience of the individual center.
Highlights • SBRT for inoperable pulmonary metastases achieved excellent LC and promising OS. • LC was mainly influenced by BED at both isocenter and periphery. • Important prognostic factors were ...identified for selecting patients for SBRT treatment. • Important prognostic factors for OS were performance status, metastasis diameter and tumor histology. • OS was further significantly affected by number of metastases and time interval between primary tumor diagnosis and SBRT treatment.
Background and objective
The ideal delivery of radiation to the surgical cavity of brain metastases (BMs) remains the subject of debate. Risks of local failure (LF) and radiation necrosis (RN) have ...prompted a reappraisal of the timing and/or modality of this critical component of BM management. IORT delivered at the time of resection for BMs requiring surgery offers the potential for improved local control (LC) afforded by the elimination of delay in time to initiation of radiation following surgery, decreased uncertainty in target delineation, and the possibility of dose escalation beyond that seen in stereotactic radiosurgery (SRS). This study provides a retrospective analysis with identification of potential predictors of outcomes.
Methods
Retrospective data was collected on patients treated with IORT immediately following surgical resection of BMs at three institutions according to the approval of individual IRBs. All patients were treated with 50kV portable linear accelerator using spherical applicators ranging from 1.5 to 4.0 cm. Statistical analyses were performed using IBM SPSS with endpoints of LC, DBC, incidence of RN, and overall survival (OS) and p < 0.05 considered significant.
Results
54 patients were treated with IORT with a median age of 64 years. The most common primary diagnosis was non-small cell lung cancer (40%) with the most common location in the frontal lobe (38%). Median follow-up was 7.2 months and 1-year LC, DBC, and OS were 88%, 58%, and 73%, respectively. LMD was identified in 2 patients (3%) and RN present in 4 patients (7%). The only predictor of LC was extent of resection with 1-year LC of 94% for GTR versus 62% for STR (p = 0.049).
Conclusions
IORT is a safe and effective means of delivering adjuvant radiation to the BM resection cavities with high rates of LC and low incidence of RN. Further studies are warranted directly comparing LC outcomes to SRS.
Most radiobiological models for prediction of tumor control probability (TCP) do not account for the fact that many events could remain unobserved because of censoring. We therefore evaluated a set ...of TCP models that take into account this censoring.
We applied 2 fundamental Bayesian cure rate models to a sample of 770 pulmonary metastasis treated with stereotactic body radiation therapy at German, Austrian, and Swiss institutions: (1) the model developed by Chen, Ibrahim and Sinha (the CIS99 model); and (2) a mixture model similar to the classic model of Berkson and Gage (the BG model). In the CIS99 model the number of clonogens surviving the radiation treatment follows a Poisson distribution, whereas in the BG model only 1 dominant recurrence-competent tissue mass may remain. The dose delivered to the isocenter, tumor size and location, sex, age, and pretreatment chemotherapy were used as covariates for regression.
Mean follow-up time was 15.5 months (range: 0.1-125). Tumor recurrence occurred in 11.6% of the metastases. Delivered dose, female sex, peripheral tumor location and having received no chemotherapy before RT were associated with higher TCP in all models. Parameter estimates of the CIS99 were consistent with the classical Cox proportional hazards model. The dose required to achieve 90% tumor control after 15.5 months was 146 (range: 114-188) Gy10 in the CIS99 and 133 (range: 101-164) Gy10 in the BG model; however, the BG model predicted lower tumor control at long (≳20 months) follow-up times and gave a suboptimal fit to the data compared to the CIS99 model.
Biologically motivated cure rate models allow adding the time component into TCP modeling without being restricted to the follow-up period which is the case for the Cox model. In practice, application of such models to the clinical setting could allow for adaption of treatment doses depending on whether local control should be achieved in the short or longer term.
We read with great interest the recent review, entitled "Current status and recent advances in resection cavity irradiation of brain metastases". It is a comprehensive summary of currently available ...techniques for treatment of post-resection cavity in patients with this diagnosis. We would like to complement this manuscript by including intraoperative techniques as other viable approaches in the management of these patients.
To report outcome (freedom from local progression FFLP, overall survival OS and toxicity) after stereotactic, palliative or highly conformal fractionated (>12) radiotherapy (SBRT, Pall‐RT, ...3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (≤12 fractions, biologically effective dose BED10 ≥ 50 Gy), 3DCRT/IMRT (>12 fractions, BED10 ≥ 50 Gy) or Pall‐RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan‐Meier/log‐rank), we calculated the competing‐risk‐adjusted local recurrence rate (CRA‐LRR). Three hundred twenty‐six patients with 366 metastases were included by 21 centers (median follow‐up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT and Pall‐RT in 260, 27 and 79 cases, respectively. Most frequent primary tumors were non‐small‐cell lung cancer (NSCLC; 52.5%), SCLC (16.3%) and melanoma (6.7%). Unadjusted FFLP was higher after SBRT vs Pall‐RT (P = .026) while numerical differences in CRA‐LRR between groups did not reach statistical significance (1‐year CRA‐LRR: 13.8%, 17.4% and 27.7%). OS was longer after SBRT vs other groups (P < .05) and increased in patients with locally controlled metastases in a landmark analysis (P < .0001). Toxicity was mostly mild; notably, four cases of adrenal insufficiency occurred, two of which were likely caused by immunotherapy or tumor progression. Radiotherapy for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1‐year CRA‐LRR after SBRT or 3DCRT/IMRT. One‐year FFLP was associated with longer OS. Dose‐response analyses for the dataset are underway.
What's new?
When added to systemic therapy, does local treatment reduce recurrence or overall survival (OS) for patients with limited metastases? In this study, the authors found that, in patients with adrenal metastases, both stereotactic body radiotherapy (SBRT) and highly conformal, intensity‐modulated radiotherapy (3DCRT/IMRT) were associated with a decreased local recurrence rate and a mild toxicity profile. Local control at 12 months was, in turn, associated with increased OS.
•PRIDE trial aims to improve survival of MGMT-non methylated glioblastoma patients.•FET-PET supported dose escalation up to 75 Gy is planned.•This paper analyzes the results of the dummy run of the ...study centers.•DICE and Hausdorff analyses show differences, the manual was subsequently improved.•QA is a central aspect in the planning and conduct of radiation oncology studies.
The PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06; NCT05871021) is designed to determine whether a dose escalation with 75.0 Gy in 30 fractions can enhance the median overall survival (OS) in patients with methylguanine methyltransferase (MGMT) promotor unmethylated glioblastoma compared to historical median OS rates, while being isotoxic to historical cohorts through the addition of concurrent bevacizumab (BEV). To ensure protocol-compliant irradiation planning with all study centers, a dummy run was planned and the plan quality was evaluated.
A suitable patient case was selected and the computed tomography (CT), magnetic resonance imaging (MRI) and O-(2-18Ffluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) contours were made available. Participants at the various intended study sites performed radiation planning according to the PRIDE clinical trial protocol. The treatment plans and dose grids were uploaded as Digital Imaging and Communications in Medicine (DICOM) files to a cloud-based platform. Plan quality and protocol adherence were analyzed using a standardized checklist, scorecards and indices such as Dice Score (DSC) and Hausdorff Distance (HD).
Median DSC was 0.89, 0.90, 0.88 for PTV60, PTV60ex (planning target volume receiving 60.0 Gy for the standard and the experimental plan, respectively) and PTV75 (PTV receiving 75.0 Gy in the experimental plan), respectively. Median HD values were 17.0 mm, 13.9 mm and 12.1 mm, respectively. These differences were also evident in the volumes: The PTV60 had a volume range of 219.1–391.3 cc (median: 261.9 cc) for the standard plans, while the PTV75 volumes for the experimental plans ranged from 71.5–142.7 cc (median: 92.3 cc). The structures with the largest deviations in Dice score were the pituitary gland (median 0.37, range 0.00–0.69) and the right lacrimal gland (median 0.59, range 0.42–0.78).
The deviations revealed the necessity of systematic trainings with appropriate feedback before the start of clinical trials in radiation oncology and the constant monitoring of protocol compliance throw-out the study.
NCT05871021
Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose‐volume cut‐points associated with decreased local recurrence rates ...(LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 ≥50 Gy, ≤12 fractions) was analyzed. Details on dose‐volume parameters were required (planning target volume: PTV‐D98%, PTV‐D50%, PTV‐D2%; gross tumor volume: GTV‐D50%, GTV‐mean). Cut‐points for LRR were optimized using the R maxstat package. One hundred and ninety‐six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n = 101). Cut‐point optimization resulted in significant cut‐points for PTV‐D50% (BED10: 73.2 Gy; P = .003), GTV‐D50% (BED10: 74.2 Gy; P = .006), GTV‐mean (BED10: 73.0 Gy; P = .007), and PTV‐D2% (BED10: 78.0 Gy; P = .02) but not for the PTV‐D98% (P = .06). Differences in LRR were clinically relevant (LRR ≥ doubled for cut‐points that were not achieved). Further dose‐escalation was not associated with further improved LRR. PTV‐D50%, GTV‐D50%, and GTV‐mean cut‐points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut‐point for the PTV‐D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (<2% difference). Associations of cut‐points with overall survival (OS) and progression‐free survival were not significant but durable freedom from local recurrence was associated with OS in a landmark model (P < .001). To achieve a significant improvement of LRR for adrenal SBRT, a moderate escalation of PTV‐D50% BED10 >73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered.
What's new?
Stereotactic body radiation therapy (SBRT), a method of precisely targeting tumors with radiation, has been successful in treating adrenal metastases. However, the optimal dose has not yet been established. Here, the authors retrospectively analyzed 218 lesions in 196 patients who had been treated with SBRT and for whom dose‐volume parameters were available. They identified dose‐volume cut points above which higher doses did not provide additional benefit. Moderate escalation to 73.2 Gy for the PTV‐D50% achieved a clinically relevant improvement in recurrence rate.
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