Hypofractionated Stereotactic Radiotherapy Research Articles

Dosimetric and volumetric outcomes of combining cyst puncture through an Ommaya reservoir with index-optimized hypofractionated stereotactic radiotherapy in the treatment of craniopharyngioma

Large cystic craniopharyngioma management combining cyst puncture through an Ommaya reservoir with hypofractionated stereotactic radiotherapy was evaluated. The planning optimization was focused on the gradient and selectivity. Punctured and filled cyst treatment plans were compared with a retrospective analysis of volumetric and functional outcomes.

Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma.

Objectives Hypofractionated stereotactic radiotherapy (HSRT) in two to five fractions may offer patients with large nonfunctioning pituitary adenomas (NFPAs) with chiasm involvement a safe and effective treatment over a single week. However, little has been reported regarding this novel approach. Design We compared the feasibility, outcomes, and toxicity of single-fraction stereotactic radiosurgery and HSRT. Setting This study was conducted at a tertiary academic referral center. Participants After approval by the institutional review board, we performed a retrospective cohort study of patients treated at our institution with stereotactic radiosurgery (SRS) and HSRT for NFPA. Selection for SRS or HSRT was based on clinicopathologic factors including tumor size and cavernous sinus invasion at the discretion of the treating physician. Main Outcome Measures Local control, endocrinopathy, and radiation-associated toxicity were evaluated by binary logistic regression and Cox's proportional hazards regression. Results A total of 45 patients with mean follow-up of 5 years were enrolled including 26 patients treated by HSRT with mean follow-up of 3 years and 19 patients treated by SRS with median follow-up of 6 years. Clinicopathologic characteristics were balanced between cohorts. Local failure at last follow-up was 5% in the SRS cohort and 8% in the HSRT cohort, and rates of post-SRS endocrinopathy were similar between each cohort. Late complications including radionecrosis, visual deficit, and secondary malignancy were minimal in either cohort. Conclusions HSRT is an appropriate treatment strategy for patients with NFPAs, particularly for optic pathway preservation in the setting of large tumors with chiasm involvement. Further studies are needed to optimize fractionated approaches and patient selection.

Long-term outcomes of hypofractionated stereotactic radiotherapy for refractory functional pituitary adenoma

Refractory functional pituitary adenomas are often treated with single-session stereotactic radiosurgery (SRS) or conventionally fractionated intensity-modulated radiotherapy (IMRT). While single-fraction SRS offers convenience and short time to biochemical remission, large tumors with cranial nerve or chiasmatic involvement often preclude single-fraction SRS, and toxicity may be worse following single-fraction SRS compared with IMRT. The purpose of our study was to explore the long-term outcomes of a unique hypofractionated stereotactic radiotherapy (HSRT) regimen delivered in 2–5 fractions. After approval, we studied 16 consecutive patients treated with HSRT for refractory functional pituitary adenoma. Study endpoints included local control, biochemical control, and toxicity. Descriptive statistics summarized endpoints and clinicopathologic factors. Sixteen patients with adrenocorticotropic hormone secretion (n = 9, 56%), growth hormone secretion (n = 4, 25%), and prolactin secretion (n = 3, 19%) were studied with a median follow-up time after HSRT of 10 years (IQR 2–14 years). Patients were treated with two (n = 8), three (n = 1), or five (n = 7) fractions to median dose of 20.5 Gy (range 16–32 Gy). HSRT was well-tolerated with no acute side effects greater than CTCAE grade 1. Local control was 100%, and biochemical control at last follow-up was 58%. Over 142 years patient-years, no instances of optic neuropathy, secondary malignancy, malignant transformation, radionecrosis, cavernous sinus cranial neuropathy, or cerebrovascular complications were noted. HSRT for refractory pituitary adenoma is well-tolerated with long-term local and biochemical control comparable with single-fraction SRS or IMRT. Prospective studies should evaluate whether HSRT provides non-inferior biochemical control and improved toxicity compared with single-fraction SRS.

Single-fraction radiosurgery versus fractionated stereotactic radiotherapy in patients with brain metastases: a comparative study

To compare the local control and brain radionecrosis in patients with brain metastasis primarily treated by single-fraction radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HFSRT). Between January 2012 and December 2017, 179 patients with only 1-3 brain metastases (total: 287) primarily treated by SRS (14Gy) or HFSRT (23.1Gy in 3 fractions of 7.7Gy, every other day) were retrospectively analyzed in a single center. Follow-up imaging data were available in 152 patients with 246 lesions. The corresponding Biological Effective Dose (BED) were 33.6Gy and 40.9Gy respectively for SRS and HFSRT group, assuming an α/β of 10Gy. Local control (LC) and risk of radionecrosis (RN) were calculated by the Kaplan-Meier method. The actuarial local control rates at 6 and 12months were 94% and 88.1% in SRS group, and 87.6% and 78.4%, in HFSRT group (p = 0.06), respectively. Only the total volume of edema was associated with worse LC (p = 0.01, HR 1.02, 95% CI [1.004-1.03]) in multivariate analysis. Brain radionecrosis occurred in 1 lesion in SRS group and 9 in HFSRT group. Median time to necrosis was 5.5months (range 1-9). Only the volume of GTV was associated with RN (p = 0.02, HR 1.09, 95% CI [1.01-1.18]) in multivariate analysis. Multi-fraction SRT dose of 23.31Gy in 3 fractions has similar efficacy to single-fraction SRT dose of 14Gy in patients with brain metastases. A slightly higher occurrence of radionecrosis appeared in HFSRT group.

Indications, feasibility, safety, and efficacy of CyberKnife radiotherapy for the treatment of olfactory groove meningiomas: a single institutional retrospective series

PurposeTo assess the safety and efficacy of CyberKnife® radiotherapy (CKRT) for the treatment of olfactory groove meningiomas (OGMs).MethodsA retrospective review was performed of 13 patients with OGM treated with CKRT from September 2005 to May 2018 at our institution. Nine patients were treated primarily with CKRT, 3 for residual disease following resection, and 1 for disease recurrence.ResultsFive patients were treated with stereotactic radiosurgery (SRS), 6 with hypofractionated stereotactic radiotherapy (HSRT), and 2 with fractionated stereotactic radiotherapy (FSRT). The median tumor volume was 8.12 cm3. The median prescribed dose was 14.8 Gy for SRS, 27.3 Gy for HSRT, and 50.2 Gy for FSRT. The median maximal dose delivered was 32.27 Gy. Median post treatment follow-up was 48 months. Twelve of 13 patients yielded a 100% regional control rate with a median tumor volume reduction of 31.7%. Six of the 12 patients had reduced tumor volumes while the other 6 had no changes. The thirteenth patient had significant radiation-induced edema requiring surgical decompression. Twelve patients were alive and neurologically stable at the time of the review. One patient died from pneumonia unrelated to his CKRT treatment.ConclusionsCKRT appears to be safe and effective for the treatment of OGMs.

Brain metastases treated with radiosurgery or hypofractionated stereotactic radiotherapy: outcomes and predictors of survival.

To assess treatment outcome and prognostic factors associated with prolonged survival in patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HFSRT). This study retrospectively reviewed 200 patients with 324 BM treated with one fraction (15-21Gy) or 5-10 fractions (25-40Gy) between January 2010 and August 2016. 26.5% of patients received whole brain radiotherapy (WBRT) and 25% initial surgery. Demographics, prognostic scales, systemic and local controls, patterns of relapse and rescue, toxicity, and cause of death were analyzed. A stratified analysis by primary tumor was done. Median overall survival (OS) was 8months from SRS/HFSRT. Breast cancer patients had a median OS of 17months, followed by renal (11months), lung (8months), colorectal (5months), and melanoma (4months). The univariate analysis showed improved OS in females (p 0.004), RPA I-II (p < 0.001) initial surgery (p < 0.001), absence of extracranial disease (p 0.023), and good disease control (p 0.002). There were no differences in OS or local control between SRS and HFSRT or in patients receiving WBRT. Among 44% of brain recurrences, 11% were in field. 174 patients died, 10% from confirmed intracranial progression. SRS and HSFRT are equally effective and safe for the treatment of BM, with no exceptions among different primary tumors. Disease control, surgery, age, and prognostic scales correlated with OS. However, the lack of survival benefit regarding WBRT might become logical evidence for its omission in a subset of patients.

Phase II trial of cytoreductive stereotactic hypofractionated radiotherapy with combination ipilimumab/nivolumab for metastatic kidney cancer (CYTOSHRINK).

TPS761 Background: Randomized data from the interferon era demonstrated modest survival benefits of cytoreductive nephrectomy (CN) in patients with advanced renal cell carcinoma (aRCC). Results from SURTIME and CARMENA, conducted in the VEGF-targeted therapy era, have challenged the routine use of upfront CN especially in IMDC intermediate and poor risk patients. Furthermore, the treatment landscape in aRCC now includes first-line combination immunotherapy. Data from the Checkmate-214 trial showed that intermediate/poor risk patients have improved overall survival and objective response rate with ipilimumab and nivolumab (I/N) compared to sunitinib. Stereotactic body radiation therapy (SBRT) provides a convenient method for cytoreduction of the primary kidney lesion and may induce an ‘abscopal effect’, leading to enhanced systemic anti-tumour immune response. We hypothesize that SBRT to the primary kidney mass in aRCC patients will enhance the efficacy of I/N compared to standard of care I/N alone. Methods: This phase II trial randomizes untreated aRCC patients in a 2:1 fashion to I/N plus SBRT (30-40 Gy in 5 fractions) to the primary kidney mass between cycles 1 and 2 (experimental arm, E), versus standard of care I/N alone (standard arm, S). Eligible patients have biopsy-proven aRCC (any histology), IMDC intermediate/poor risk disease, and who decline or are unsuitable for CN. Patients with a primary kidney lesion ≥ 20cm, previous abdominal radiation precluding SBRT, or who have a contraindication to I/N are excluded. The primary objective is to compare the efficacy of I/N plus SBRT versus I/N alone, as determined by the hazard ratio for progression free survival (PFS). Secondary objectives include evaluation of safety, overall survival, objective response rate, and health-related quality of life. Exploratory analyses include blood immune signatures and stool microbiome. Up to 78 patients will be enrolled under the assumption of an improved 12-month PFS from 50% (S) to 75% (E), using a two-sided α=0.1, power=80%, and accounting for loss-to-follow-up and stratification using IMDC criteria 1-2 vs 3-6. Clinical trial information: NCT04090710.

Re-Irradiation and Its Contribution to Good Prognosis in Recurrent Glioblastoma Patients.

BackgroundRadiation therapy, one of the strongest anti-cancer treatments, is already performed to treat primary glioblastoma; however, the effect of repeated radiation therapy for recurrent tumors has not been fully explored. The aim of this study was to determine the efficacy of re-irradiation in treating recurrent glioblastoma.MethodsThe study included 36 patients with recurrent glioblastoma treated with repeated radiation therapy between 2002 and 2016. Stereotactic radiosurgery (SRS) and hypo-fractionated stereotactic radiotherapy (HSRT) were performed in these patients.ResultsFourteen patients received SRS with a median dose of 25 Gy (range, 20–32 Gy) in 1–5 fractions. Twenty-two patients received HSRT with a median dose of 40 Gy (range, 31.5–52 Gy) in 6–20 fractions. There were six treatment-related grade 3 adverse events. Survival analysis showed that re-irradiation significantly prolonged overall survival (OS) and progression-free survival (PFS). The median OS and one-year OS rate after re-irradiation were 17.2 months and 60.4%, respectively. The median PFS and 6-month PFS rate after re-irradiation were 4.4 months and 41.9%, respectively. Of the 36 patients, three survived without any progression in their condition.ConclusionRe-irradiation for recurrent glioblastoma showed favorable outcomes. Radiation dose and fractionation should be carefully considered to minimize radiation necrosis.

Evidence of dose-response following hypofractionated stereotactic radiotherapy to the cavity after surgery for brain metastases.

A retrospective review of consecutive patients between January 2012 and December 2018 receiving hypofractionated stereotactic radiotherapy (HSRT) to the cavity after resection for brain metastases was performed. Treatment was delivered using an appropriately commissioned linear accelerator. The primary outcome was time to radiological or histological confirmation of local recurrence following completion of HSRT. Dose-fractionation regimens were converted to biologically 2Gy-equivalent doses assuming α/β = 10 (EQD2[10]). Multivariate Cox proportional hazards modelling was performed to determine hazard ratios (HR) with respective 95% confidence intervals (CI). The Log-rank test was used to determine p values taking statistical significance p < 0.05. There were 134 patients and 144 cavities identified. The most common primary histologies were melanoma (n = 49) and lung (n = 32). 116 patients (87%) underwent a gross total resection. Median planning target volume (PTV) was 28 cm3 (range 2.4-149.2). Median EQD2[10] was 38.4Gy (range 22.3-59.7) and 24Gy in 3 fractions was the most common regimen. 12 (9%) patients demonstrated local recurrence at median interval 215days (range 4-594). 7 (5%) patients experienced grade 3 or higher toxicities. In multivariate analysis, EQD2[10] was associated with local failure such that increased equivalent doses improved local control [HR = 0.79 and 95% CI 0.65-0.96, p = 0.0192]. There were no significant associations for primary histology, patient age, volume of residual disease, PTV volume or location. This large series demonstrates that HSFRT to the surgical resection cavity for brain metastases has improved local control with increasing dose. Rates of grade 3 or higher toxicity were low overall.

Stereotactic radiosurgery for non-functioning pituitary adenomas: meta-analysis and International Stereotactic Radiosurgery Society practice opinion.

BackgroundThis systematic review reports on outcomes and toxicities following stereotactic radiosurgery (SRS) for non-functioning pituitary adenomas (NFAs) and presents consensus opinions regarding appropriate patient management.MethodsUsing the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic review was performed from articles of ≥10 patients with NFAs published prior to May 2018 from the Medline database using the key words “radiosurgery” and “pituitary” and/or “adenoma.” Weighted random effects models were used to calculate pooled outcome estimates.ResultsOf the 678 abstracts reviewed, 35 full-text articles were included describing the outcomes of 2671 patients treated between 1971 and 2017 with either single fraction SRS or hypofractionated stereotactic radiotherapy (HSRT). All studies were retrospective (level IV evidence). SRS was used in 27 studies (median dose: 15 Gy, range: 5–35 Gy) and HSRT in 8 studies (median total dose: 21 Gy, range: 12–25 Gy, delivered in 3–5 fractions). The 5-year random effects local control estimate after SRS was 94% (95% CI: 93.0–96.0%) and 97.0% (95% CI: 93.0–98.0%) after HSRT. The 10-year local control random effects estimate after SRS was 83.0% (95% CI: 77.0–88.0%). Post-SRS hypopituitarism was the most common treatment-related toxicity observed, with a random effects estimate of 21.0% (95% CI: 15.0–27.0%), whereas visual dysfunction or other cranial nerve injuries were uncommon (range: 0–7%).ConclusionsSRS is an effective and safe treatment for patients with NFAs. Encouraging short-term data support HSRT for select patients, and mature outcomes are needed before definitive recommendations can be made. Clinical practice opinions were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Quantitative MRI Biomarkers of Stereotactic Radiotherapy Outcome in Brain Metastasis

About 20–40% of cancer patients develop brain metastases, causing significant morbidity and mortality. Stereotactic radiation treatment is an established option that delivers high dose radiation to the target while sparing the surrounding normal tissue. However, up to 20% of metastatic brain tumours progress despite stereotactic treatment, and it can take months before it is evident on follow-up imaging. An early predictor of radiation therapy outcome in terms of tumour local failure (LF) is crucial, and can facilitate treatment adjustments or allow for early salvage treatment. In this study, an MR-based radiomics framework was proposed to derive and investigate quantitative MRI (qMRI) biomarkers for the outcome of LF in brain metastasis patients treated with hypo-fractionated stereotactic radiation therapy (SRT). The qMRI biomarkers were constructed through a multi-step feature extraction/reduction/selection framework using the conventional MR imaging data acquired from 100 patients (133 lesions), and were applied in conjunction with machine learning techniques for outcome prediction and risk assessment. The results indicated that the majority of the features in the optimal qMRI biomarkers characterize the heterogeneity in the surrounding regions of tumour including edema and tumour/lesion margins. The optimal qMRI biomarker consisted of five features that predict the outcome of LF with an area under the curve (AUC) of 0.79, and a cross-validated sensitivity and specificity of 81% and 79%, respectively. The Kaplan-Meier analyses showed a statistically significant difference in local control (p-value < 0.0001) and overall survival (p = 0.01). Findings from this study are a step towards using qMRI for early prediction of local failure in brain metastasis patients treated with SRT. This may facilitate early adjustments in treatment, such as surgical resection or salvage radiation, that can potentially improve treatment outcomes. Investigations on larger cohorts of patients are, however, required for further validation of the technique.

Intrafractional 6D head movement increases with time of mask fixation during stereotactic intracranial RT-sessions

BackgroundThe present study investigates the intrafractional accuracy of a frameless thermoplastic mask used for head immobilization during stereotactic radiotherapy. Non-invasive masks cannot completely prohibit head movements. Previous studies attempted to estimate the magnitude of intrafractional inaccuracy by means of pre- and postfractional measurements only. However, this might not be sufficient to accurately map also intrafractional head movements.Materials and methodsIntrafractional deviation of mask-fixed head positions was measured in five patients during a total of 94 fractions by means of close-meshed repeated ExacTrac measurements (every 1.4 min) conducted during the entire treatment session. A median of six (range: 4 to 11) measurements were recorded per fraction, delivering a dataset of 453 measurements.ResultsRandom errors (SD) for the x, y and z axes were 0.27 mm, 0.29 mm and 0.29 mm, respectively. Median 3D deviation was 0.29 mm. Of all 3D intrafractional motions, 5.5 and 0.4% exceeded 1 mm and 2 mm, respectively. A moderate correlation between treatment duration and mean 3D displacement was determined (rs = 0.45). Mean 3D deviation increased from 0.21 mm (SD = 0.26 mm) in the first 2 min to a maximum of 0.53 mm (SD = 0.31 mm) after 10 min of treatment time.ConclusionPre- and post-treatment measurement is not sufficient to adequately determine the range of intrafractional head motion. Thermoplastic masks provide both reliable interfractional and intrafractional immobilization for image-guided stereotactic hypofractionated radiotherapy. Greater positioning accuracy may be obtained by reducing treatment duration (< 6 min) and applying intrafractional correction.Trial registrationClinicaltrials.gov, NCT03896555, Registered 01 April 2019 - retrospectively registered.

Locomotion and eating behavior changes in Yucatan minipigs after unilateral radio-induced ablation of the caudate nucleus

The functional roles of the Caudate nucleus (Cd) are well known. Selective Cd lesions can be found in neurological disorders. However, little is known about the dynamics of the behavioral changes during progressive Cd ablation. Current stereotactic radiosurgery technologies allow the progressive ablation of a brain region with limited adverse effects in surrounding normal tissues. This could be of high interest for the study of the modified behavioral functions in relation with the degree of impairment of the brain structures. Using hypofractionated stereotactic radiotherapy combined with synchrotron microbeam radiation, we investigated, during one year after irradiation, the effects of unilateral radio-ablation of the right Cd on the behavior of Yucatan minipigs. The right Cd was irradiated to a minimal dose of 35.5 Gy delivered in three fractions. MRI-based morphological brain integrity and behavioral functions, i.e. locomotion, motivation/hedonism were assessed. We detected a progressive radio-necrosis leading to a quasi-total ablation one year after irradiation, with an additional alteration of surrounding areas. Transitory changes in the motivation/hedonism were firstly detected, then on locomotion, suggesting the influence of different compensatory mechanisms depending on the functions related to Cd and possibly some surrounding areas. We concluded that early behavioral changes related to eating functions are relevant markers for the early detection of ongoing lesions occurring in Cd-related neurological disorders.

Normofractionated stereotactic radiotherapy versus CyberKnife-based hypofractionation in skull base meningioma: a German and Italian pooled cohort analysis

BackgroundThis retrospective German and Italian multicenter analysis aimed to compare the role of normofractionated stereotactic radiotherapy (nFSRT) to CyberKnife-based hypofractionated stereotactic radiotherapy (CK-hFSRT) for skull base meningiomas.MethodsOverall, 341 patients across three centers were treated with either nFSRT or CK-hFSRT for skull base meningioma. Treatment planning was based on computed tomography (CT) and magnetic resonance imaging (MRI) following institutional guidelines. Most nFSRT patients received 33 × 1.8 Gy, and most CK-hFSRT patients received 5 × 5 Gy. The median follow-up time was 36 months (range: 1–232 months).ResultsIn the CK-hFSRT group, the 1-, 3-, and 10-year local control (LC) rates were 99.4, 96.8, and 80.3%, respectively. In the nFSRT group, the 1-, 3-, and 10-year LC rates were 100, 99, and 79.1%, respectively. There were no significant differences in LC rates between the nFSRT and CK-hFSRT groups (p = 0.56, hazard ratio = 0.76, 95% confidence interval, 0.3–1.9). In the CK-hFSRT group, only one case (0.49%) of severe toxicity (CTCAE 4.0 ≥ 3) was observed. In the nFSRT group, three cases (2.1%) of grade III toxicity were observed.ConclusionThis analysis of pooled data from three centers showed excellent LC and low side effect rates for patients treated with CK-hFSRT or nFSRT. The efficacy, safety, and convenience of a shortened treatment period provide a compelling case for the use of CK-hFSRT in patients with moderate size skull base meningioma and provided that OAR constraints are met.

Image-Guided, Linac-Based, Surgical Cavity-Hypofractionated Stereotactic Radiotherapy in 5 Daily Fractions for Brain Metastases.

Cavity stereotactic radiotherapy has emerged as a standard option following resection of brain metastases. However, the optimal approach with either single-fraction or hypofractionated stereotactic radiotherapy (HSRT) remains a significant question. To report outcomes for 5-fraction HSRT to the surgical cavity, based on contouring according to a recently reported international consensus guideline. Patients treated with cavity HSRT were identified from a prospective institutional database. Local brain control (LC), distant brain failure (DBF), leptomeningeal disease (LMD), and overall survival rates were determined. Univariate and multivariable analyses were performed on potential predictive factors. One hundred thirty-seven cavities in 122 patients were treated at a median total dose of 30 Gy (range, 25-35 Gy). The median follow-up was 16 mo (range, 1-60 mo). Nonsmall cell lung cancer was the most common histology (44%), followed by breast cancer (21%). In 57% of surgical cavities, the preoperative tumor diameter was>3 cm. One-year LC, DBF, LMD, and overall survival rates were 84%, 45%, 22%, and 62%, respectively. Multivariable analyses identified colorectal (hazard ratio [HR] 4.1, P=.0066) and melanoma (HR 2.4, P=.012) metastases as predictors of local recurrence; preoperative tumor diameter>2cm (HR 8.9, P=.012) and absence of targeted therapy (HR 4.4, P=.03) as predictors of DBF; and breast cancer histology (HR 2.1, P=.05) and subtotal resection (HR 2.6, P=.009) as predictors of LMD. Symptomatic radiation necrosis was observed in 7 patients (6%). High rates of LC were observed following this 5-fraction HSRT regimen. Superiority as compared to single-fraction SRS requires a randomized trial.

408P - Whole brain radiotherapy plus simultaneous in-field boost versus whole brain radiotherapy plus fractionated stereotactic radiotherapy for multiple brain metastases of non-small cell lung cancer

BackgroundBrain metastasis (BM) is common among patients with non-small cell lung cancer (NSCLC). Whole brain radiotherapy (WBRT) plus a radiation boost is a common treatment strategy for such patients. WBRT plus simultaneous in-field boost (WBRT+SIB) and WBRT plus hypo-fractionated stereotactic radiotherapy (WBRT+FSRT) have shown promising outcomes. The current study compared the efficacy and safety of these two treatment strategies. MethodsSixty-six NSCLC patients with multiple BMs who met the inclusion criteria from January 2010 to December 2016 were enrolled. The efficacy and toxicity of WBRT+SIB and WBRT+FSRT were analyzed retrospectively. A Cox proportional hazard model was used to identify prognostic factors. ResultsThe objective response rates in the WBRT+SIB and WBRT+FSRT groups were similar (74.9% and 79.4%, respectively; p=0.5), as was the disease control rate (93.8% and 97.1%, respectively; P=0.3). The median survival time was 15.3 months in the WBRT+SIB group and 25.2 months in the WBRT+FSRT group (p=0.02). The median local progression-free survival was 13 months in the WBRT+SIB group and 17 months in the WBRT+FSRT group (p=0.04). The incidence of 1-3 grade toxicity was slightly lower in the WBRT+FSRT group than the WBRT+SIB group (31.2% vs. 38.2%). Compared to the WBRT+SIB group, the WBRT+FSRT group was associated with a lower risk of mortality (HR=0.6; 95% CI, 0.1-0.7) in the Cox multivariate model. Extracranial metastases, worse recursive partitioning analysis class, and non-surgical treatment of primary lesions were associated with a worse prognosis. ConclusionsCompared to WBRT+SIB, WBRT+FSRT treatment was associated with a better prognosis and slightly less toxicity in patients with multiple BMs from NSCLC. Further studies are warranted to better elucidate the difference and determine the optimal dose/fractionation. Legal entity responsible for the studyJinyi Lang. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

8 Stereotactic Body Radiotherapy and Precision Hypofractionated Radiotherapy Versus Surgery for Stage I Non-Small Cell Lung Cancers: An 11-Year Review of a Provincial Cancer Registry

8 Stereotactic Body Radiotherapy and Precision Hypofractionated Radiotherapy Versus Surgery for Stage I Non-Small Cell Lung Cancers: An 11-Year Review of a Provincial Cancer Registry

230 Predictors of Leptomeningeal Disease After Hypofractionated Stereotactic Radiotherapy for Intact and Resected Brain Metastases

230 Predictors of Leptomeningeal Disease After Hypofractionated Stereotactic Radiotherapy for Intact and Resected Brain Metastases

Outcomes of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy for refractory Cushing's disease.

Hypofractionated stereotactic radiotherapy (HSRT) for refractory Cushing's disease may offer a condensed treatment schedule for patients with large tumors abutting the optic chiasm unsuitable for stereotactic radiosurgery (SRS). To-date only four patients have been treated by HSRT in the published literature. We investigated the feasibility, toxicity, and efficacy of HSRT compared to SRS. After approval, we retrospectively evaluated patients treated at our institution for refractory Cushing's disease with SRS or HSRT. Study outcomes included biochemical control, time to biochemical control, local control, and late complications. Binary logistic regression and Cox proportional hazards regression evaluated predictors of outcomes. Patients treated with SRS (n = 9) and HSRT (n = 9) were enrolled with median follow-up of 3.4years. Clinicopathologic details were balanced between the cohorts. Local control was 100% in both cohorts. Time to biochemical control was 6.6. and 9.5months in the SRS and HSRT cohorts, respectively (p = 0.6258). Two patients in each cohort required salvage bilateral adrenalectomy. Late complications including secondary malignancy, radionecrosis, cranial nerve neuropathy, and optic pathway injury were minimal for either cohort. HSRT is an appropriate treatment approach for refractory Cushing's disease, particularly for patients with large tumors abutting the optic apparatus. Prospective studies are needed to validate these findings and identify factors suggesting optimal fractionation approaches.

A Phase I/II Study of Stereotactic Hypofractionated Once-weekly Radiation Therapy (SHORT) for Prostate Cancer

AimsStereotactic radiation therapy has been investigated predominantly in patients with low–intermediate-risk disease. We conducted a clinical trial of stereotactic hypofractionated radiation therapy delivered in once-weekly fractions on patients with all-risk non-metastatic disease to test feasibility, acute toxicities and patient-reported outcomes. Materials and methodsIn this phase I/II study, 30 patients with prostatic adenocarcinoma, any Gleason score, T1-4N0 and prostate-specific antigen ≤60 ng/ml were treated with volumetric intensity modulated arc radiation therapy to a dose of 35 Gy in five fractions delivered once weekly. Patients with high-risk disease also received elective nodal irradiation to a dose of 25 Gy in five fractions simultaneously. Androgen deprivation was offered to intermediate- and high-risk patients. The primary outcome was acute toxicity. Secondary outcome measures included biochemical control and late toxicity. Patient-reported outcomes were measured using the International Prostate Symptom Score and European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ). ResultsAll 30 patients completed treatment per-protocol. Most patients had T3 (60%) and Gleason 7 (50%) tumours. The median prostate-specific antigen was 17 ng/ml. High-risk disease was present in 20 patients (66.7%). There was a low incidence of acute toxicities (grade 2 + urinary 3.3%, grade 2 rectal 0%). Within the EORTC QLQ framework, only the urinary symptom score showed a clinically meaningful worsening from a mean of 20/100 at baseline to 34/100 at the end of treatment (P < 0.001), but reduced to 24/100 at 6 months (P = 0.08). With a median follow-up of 41.5 months, two patients each reported grade 2 late urinary and rectal toxicity. The 3- and 4-year biochemical control rates were 96.7 and 87.9%, respectively. ConclusionIn a cohort of mainly high-risk cancers, stereotactic once-weekly radiation therapy was easy to implement and well tolerated, with a low incidence of acute and late toxicity and excellent biochemical control.