PO-1000 Vascular responses in normal brain tissue after combined immunotherapy and SRS to brain metastases (original) (raw)
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Advances in radiation oncology
To identify potentially actionable dosimetric predictors of local control (LC) for non-small cell lung cancer (NSCLC) brain metastases treated with single-fraction stereotactic radiosurgery (SRS). Patients with NSCLC brain metastases treated with single-fraction SRS were identified. Eligible patients had at least 1 follow-up magnetic resonance imaging scan and were without prior metastasectomy or SRS to the same lesion. LC and overall survival (OS) were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate (UVA) and multivariate analysis (MVA). Receiver operating characteristic (ROC) analysis was used to identify optimal cut points for dose-volume histogram metrics relative to LC. A total of 612 NSCLC brain metastasis were identified in 299 patients with single-fraction SRS between 1999 and 2014. Median follow-up was 10 months. Median OS from time of SRS was 11 months. Overall LC was 75% and 66% at 1 and 2 years, respectively. On UVA, in...
Dosimetric Comparisons of Lung SBRT with Multiple Metastases by Two Advanced Planning Systems
Purpose: To evaluate planning quality of Stereotactic body Radiotherapy (SBRT) with multiple lungmetastases generated by the Pinnacle and Tomotherapy planning systems, respectively. Methods and Materials: Nine randomly selected patients diagnosed with non-small cell lung carcinoma with multiple lesions were planned with Philips Pinnacle (version 9.2, Fitchburg, WI) and Tomotherapy (version 4.2, Madison, WI), respectively. Both coplanar and non-coplanar IMRT plans were generated on Pinnacle system. A total dose of 60 Gy was prescribed to cover 95% of Planning Target Volume (PTV) in 3 fractions based on the RTOG0236 protocol prescription [1]. All plans with single isocenter setting were used for multiple lesions planning. A set of nine static beams were used for Pinnacle plansusing Direct Machine Parameters Optimization (DMPO) algorithm of RTOT0236 dose constraints. Planning outcomes such as minimum and mean doses, V95, D 95 (95% of target volume receivesprescription dose), D 5 , and D 1 to PTV, maximum dose to heart, esophagus, cord, trachea, brachial plexus, rib, chest wall, and liver, mean dose toliver, total lung, right and left lung, volume of chest wall receives 30 Gy, volume of lungs receives 5 Gy and 20 Gy (V 5 and V 20 ), conformity index (CI) and heterogeneity index (HI) were all reported for evaluation. Results: Mean volume of PTV was 37.77 ± 23.4 cm 3 . D 95 of PTV with Tomotherapy, coplanar, non-coplanar plan was 60.2 ± 0.3 Gy, 58.6 ± 1.2 Gy, and 59.1 ± 0.7 Gy, respectively. Mean dose to PTV was lower for Tomotherapy (p < 0.0001), so were D 5 (p < 0.0001) and D 1 (p = 0.001). CI was higher with Tomotherapy plans (p < 0.0001), so was HI (p < 0.0001). Maximum dose to other critical organs were also lower exclusively with Tomotherapy plans, as expected. Treatment time was recorded only for Tomotherapy plans (73.0 ± 20.6 min) while the Intensity Modulated Radiation Therapy (IMRT) plan from Pinnacle were not registered for comparison in those cases. Conclusions: With 51 beam angles per rotation, Tomotherapy plans could generally achieve better tumor coverage Y. Zhang et al. 253 while sparing more critical structures in the multiple lung lesions study. Non-coplanar IMRT plans also have better tumor coverage with lower dose to critical organs such as lungs, liver, chest wall and cord compare to coplanar plans. Compared to the coplanar IMRT beam plans, Tomotherapy tends to have a relatively higher low dose volume in lungs such as V 5 which needs more attention for toxicity analysis.
Radiotherapy of brain metastases from lung cancer: evidences and areas of research
Journal of Cancer Metastasis and Treatment, 2020
Historically, the standard treatment for brain metastases (BM) from lung cancer involved neurosurgical resection and radiotherapy. Chemotherapy was applied, to a lesser extent, mainly for small-cell lung cancer (SCLC). However, with the ever-changing landscape of lung cancer therapy, the approach to the treatment of BM from lung cancer is also evolving. Generally, there has been a tendency to avoid wholebrain radiotherapy (WBRT) and to use more focused forms, i.e., stereotactic radiosurgery (SRS). Currently, in patients with WHO performance status 0-2 having up to 4 BM, local therapy (surgery or SRS) without WBRT is recommended [1]. The rationale for such an approach is based on evidence that the omission of WBRT minimizes neurocognitive toxicity and there is no difference in overall survival between local therapy (SRS or surgery) only and WBRT [2-4]. Nevertheless, a substantial proportion of lung cancer patients have multiple BM and for them, WBRT remains the primary treatment modality, unless their general performance status is very poor. For such patients with poor performance status, WBRT has no benefit over the use of steroids alone [5,6]. The prognosis of patients with BM from lung cancer is considered poor with a median overall survival of about 4 months with WBRT [7,8]. However, it was shown that WBRT in NSCLC patients with BM having EGFR mutations and ALK rearrangement had improved overall survival [9,10]. Novel therapies such as targeted agents for BM in lung cancer with driver mutations and immune checkpoint inhibitors have greater intracranial efficacy compared to conventional chemotherapy. In turn, this also promoted research towards combining these novel agents with SRS or WBRT. While the tumor's molecular status may have an impact on the decision to delay WBRT or SRS in subgroups of patients, there is insufficient data to make more definitive recommendations currently.
Acta Oncologica, 2014
Median survival after diagnosis of brain metastases is, depending on the Recursive Partitioning Analysis (RPA) classes, 7.1 (class I) to 2.3 months (class III). In 2011 the Dutch guideline on brain metastases was revised, advising to withhold whole brain radiotherapy (WBRT) in RPA class III. In this large retrospective study, we evaluated the guideline ' s use in daily practice. Material and methods. Data of 428 lung cancer patients undergoing WBRT for brain metastases (2004 -2012) referred from three Dutch hospitals were retrospectively analyzed. Details on Karnofsky performance score (KPS), age, control of primary tumor, extracranial metastases, histology, and survival after diagnosis of brain metastases were collected. RPA class was determined using the fi rst four items. Results. In total 327 patients had non-small cell lung cancer (NSCLC) and 101 small cell lung cancer (SCLC). 5 -1.8) months. Conclusions. Although it is advised to withhold WBRT in RPA class III patients, in daily practice 11.3 -21.3% of WBRT-treated patients were classifi ed as RPA III. The new guideline did not result in a decrease. Reasons for referral of RPA III patients despite a low KPS were not found. Despite WBRT, survival of RPA III patients remains poor and this poor outcome should be stressed in practice guidelines. Therefore, better awareness amongst physicians would prevent some patients from being treated unnecessarily.
PLoS ONE, 2012
Background: No selection criteria for helical tomotherapy (HT) based stereotactic ablative radiotherapy (SABR) to treat early stage non-small cell lung cancer (NSCLC) or solitary lung metastases has been established. In this study, we investigate the dosimetric selection criteria for HT based SABR delivering 70 Gy in 10 fractions to avoid severe toxicity in the treatment of centrally located lesions when adequate target dose coverage is desired. Materials and Methods: 78 HT-SABR plans for solitary lung lesions were created to prescribe 70 Gy in 10 fractions to the planning target volume (PTV). The PTV was set to have 9595% PTV receiving 70 Gy in each case. The cases for which dose constraints for 951 OAR could not be met without compromising the target dose coverage were compared with cases for which all target and OAR dose constraints were met. Results: There were 23 central lesions for which OAR dose constraints could not be met without compromising PTV dose coverage. Comparing to cases for which optimal HT-based SABR plans were generated, they were associated with larger tumor size (5.7261.96 cm vs. 3.7461.49 cm, p,0.0001), higher lung dose, increased number of immediately adjacent OARs (3.4561.34 vs. 1.6660.81, p,0.0001), and shorter distance to the closest OARs (GTV: 0.2660.22 cm vs. 0.8860.54 cm, p,0.0001; PTV 0.1960.18 cm vs. 0.4860.36 cm, p = 0.0001). Conclusion: Delivery of 70 Gy in 10 fractions with HT to meet all the given OAR and PTV dose constraints are most likely when the following parameters are met: lung lesions #3.78 cm (11.98 cc), #2 immediately adjacent OARs which are 0.45cmfromthegrosslesionand0.45 cm from the gross lesion and 0.45cmfromthegrosslesionand0.21 cm from the PTV.
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose: To evaluate the limitations of Hi-Art Helical Tomotherapy (Middleton, WI) stereotactic body radiotherapy (SBRT) for lung lesions, and to provide an initial report on patients treated with this method. Stereotactic body radiotherapy was shown to be an effective, well-tolerated treatment for early-stage, non-smallcell lung carcinoma (NSCLC). The Radiation Therapy Oncology Group (RTOG) 0236 protocol is currently evaluating three-dimensional conformal SBRT that delivers 60 Gy in three fractions. Methods and Materials: Inverse treatment planning for hypothetical lung gross tumor volumes (GTV) and planned treatment volume (PTV) expansions were performed. We tested the hypothesis that the maximum acceptable dose (MAD) to be delivered to the lesion by SBRT could be predicted by PTV and lung volume. Dose constraints on normal tissue were as designated by the RTOG protocol. Inverse planning was performed to find the maximum tolerated SBRT dose up to 60 Gy. Results: Regression analysis of the data obtained indicated a linear relationship between MAD, PTV, and lung volume. This generated two equations which may be useful predictive tools. Seven patients with Stage I and II NSCLC treated at the University of Virginia with this method tolerated the treatment extremely well, and suffered no greater than grade I toxicity, with no evidence of disease recurrence in follow-up from 2-20 months. Conclusions: Helical tomotherapy SBRT for lung lesions is well-tolerated. In addition, the likely MAD for patients considered for this type of treatment can be predicted by PTV and lung volume.