Hypofractionated Stereotactic Radiotherapy Research Articles

Cavity volume changes after surgery of a brain metastasis—consequences for stereotactic radiation therapy

For alarge or symptomatic brain metastasis, resection and adjuvant radiotherapy are recommended. Hypofractionated stereotactic radiotherapy (HFSRT) is increasingly applied in patients with alimited number of lesions. Exact target volume definition is critical given the small safety margins. Whilst technical advances have minimized inaccuracy due to patient positioning and radiation targeting, little is known about changes in target volume. This study sought to evaluate potential changes in the resection cavity of abrain metastasis. In all, 57patients treated with HFSRT after surgical resection of one brain metastasis between 2008 and 2015 in our institution were included in this study. Gross tumor volume (GTV) of the initial metastasis and the volume of the resection cavity in the post-operative, planning, and follow-up MRIs were measured and compared. The mean cavity size decreased after surgery with the greatest change of -23.4% (±41.5%) occurring between post-operative MRI and planning MRI (p < 0.01). During this time period, the cavity volume decreased, remained stable, and increased in 79.1, 3.5, and 17.4%, respectively. Afurther decrease of -20.7% (±58.1%) was perceived between planning MRI and first follow-up (p < 0.01). No significant difference in pattern of change could be observed depending on the volume of initial GTV, size of the post-operative resection cavity, initial or post-resection FLAIR (fluid-attenuated inversion recovery) hyper-intensity, postsurgical ischemia, or primary tumor. The resection cavities of patients with post-operative ischemia were significantly larger than resection cavities of patients without ischemia. The resection cavity seems to be very dynamic after surgery. Hence, it remains necessary to use very recent scans for treatment planning.

Evolving National Practice Patterns of Hypofractionated Stereotactic Radiation Therapy Versus Single-Fraction Radiosurgery for Brain Metastases

Single-fraction stereotactic radiosurgery (SF-SRS) has been increasingly utilized in the treatment of patients with brain metastases, but the national uptake of hypofractionated stereotactic radiotherapy (HF-SRT) is unknown. We sought to characterize the evolution of practice patterns of HF-SRT in relation to SF-SRS in the United States over the past decade. The National Cancer Database was used to identify patients with breast cancer, non-small cell lung cancer (NSCLC), colorectal cancer, melanoma, and prostate cancer diagnosed in 2004-2014 who underwent either SF-SRS or HF-SRT to the brain. SF-SRS was defined as radiotherapy dose ≥15 Gy in 1 fraction, while HF-SRT was defined as radiotherapy dose ≥21 Gy in 3 fractions, ≥24 Gy in 4 fractions, or ≥25 Gy in 5 fractions. Chi-square analyses and multivariable logistic regression were used to investigate temporal, sociodemographic, and clinicopathologic predictors of HF-SRT receipt. Our cohort included 7,068 patients, among whom 5,243 (74%) received SF-SRS and 1,825 (26%) received HF-SRT. Median age was 63 years, and 51% of patients were female. The most common histology was NSCLC (87.2%). The proportion of patients receiving HF-SRT increased steadily from 20.3% in 2004 to 30.3% in 2014 (P<.001). Patients who received surgery at a distant site from the primary were more likely to undergo HF-SRT (35.3% versus 22.5%, P<.001). On multivariable analysis, predictors of increased utilization of HF-SRT included treatment year 2010-2014 versus 2004-2009 (odds ratio [OR] 1.14), colorectal versus NSCLC histology (OR 2.13), breast versus NSCLC histology (OR 1.72), surgery versus no surgery at distant site (OR 1.93), omission versus receipt of upfront chemotherapy (OR 1.49), and non-Northeast versus Northeast location (OR 1.39) (P<.05 for each). This analysis demonstrates steadily rising utilization of HF-SRT in the treatment of brain metastases nationally over the past decade. Adoption of HF-SRT also varied widely by histology, receipt of surgery or chemotherapy, and geographic location. Given the increased utilization of HF-SRT, further study is needed to investigate the underlying explanations for these differences and their impact on local control, distant intracranial control, and toxicity outcomes.

Long-Term Follow-Up of Oligometastases Patients Treated with Hypofractionated, Stereotactic Radiation Therapy (HSRT) on a Prospective Study

To analyze the long-term follow up of patients treated with HSRT for oligometastases from non-breast malignancies. From 2001-2006, 82 non-breast cancer patients with 1-5 radiographically apparent metastatic lesions were enrolled on a prospective study of HSRT. The eligibility requirements included age ≥ 18 y, KPS ≥ 70, and metastases to 1-3 organ sites. Net GTV represents the sum of each lesion’s contoured GTV, and was grouped into five categories (<20, 20-40, 40-60, 60-80, and >100cc). A stereotactic x-ray was used. The PTV was generated with a volumetric GTV expansion of 10 mm in the craniocaudal direction and 7 mm in other directions, and was covered by the 80% isodose line. FFDM was defined from date of enrollment until death, an event (i.e. widespread distant metastasis not amenable to local therapy), or last radiographic study. Lesion local recurrence was scored as an event if pathologically confirmed or if increased by ≥20% using RECIST criteria. Prognostic variables were assessed using Cox regression analysis, and FFDM and OS rates were calculated using Kaplan-Meier survival analysis. The mean age was 61 ± 11 y with a male to female ratio of 46/36. The most common histologies were adenocarcinoma (61%), squamous cell carcinoma (9%), and sarcoma (9%). The most common metastatic sites were liver (50%), lung (48%), thoracic lymph nodes (18%), and bone (5%). 61 had 1 involved organ and 18 had 1 lesion treated. 50 Gy in 10 fractions (52/82 patients) was the preferred schedule. The mean and median net GTV were 32 and 55 ml respectively (range 0.3-422). Other analyzed variables included prior curative-intent local therapy (35%), previously had >5 metastatic lesions (20%), and systemic therapy at some point after diagnosis of metastatic disease (74%). The median follow-up was 1.7 y (and 13.4 y for 4 of 82 patients alive at last follow-up). Eleven patients lived >5 years, and 6 lived >10 years. The 5-year OS, FFDM, and LC rates were 13.4%, 13.6%, and 62.2%, and the 10-y OS, FFDM, and LC rates were 7.3%, 12.3%, and 61.0%, respectively. On both univariate (UV) and multivariate (MV) analysis, net GTV was the only variable significant for OS (MV p=0.034, HR 1.36). GTV also proved to be significant on UV and MV (p=0.039, HR 2.31) for lesion LC. Having more than one organ involved with metastasis was not significant on UV (p=0.49) but was significant on MV analysis (p=0.020) for local control. Analysis for FFDM showed that net GTV was not a significant factor. On MV analysis, systemic therapy during metastatic diagnosis was significantly associated with FFDM (p=0.046, HR 0.47). Select non-breast cancer patients with limited metastasis treated with HSRT are long-term survivors. Net GTV is a significant factor for tumor control and survival. By 5 years, only 1 in 8 patients treated remained free from distant metastasis. Further research is needed to help better select patients most likely to benefit from local therapy for metastatic disease.

Results of Hypofractionated Stereotactic Radiation Therapy (HSRT) for Large Brain Metastases and Resection Cavities

Results of Hypofractionated Stereotactic Radiation Therapy (HSRT) for Large Brain Metastases and Resection Cavities

P05.50 Hypofractionated stereotactic radiation therapy (HSRT) in skull base meningiomas

P05.50 Hypofractionated stereotactic radiation therapy (HSRT) in skull base meningiomas

Benefits of image-guided stereotactic hypofractionated radiation therapy as adjuvant treatment of craniopharyngiomas. A review.

Craniopharyngiomas account for 5.6-13% of intracranial tumors in children. Despite being histologically benign, these tumors remain a major neurosurgical challenge because of the typical tight adherence to adjacent critical structures. The optimal therapeutic approach for this disease is controversial. Large cystic size and adherence to neurovascular, neuroendocrine, and optic structures without a clear line of cleavage make complete resection problematic and often hazardous. For these reasons, partial resection and adjuvant treatment play an important role. Post-operative radiation therapy (RT) following either complete or incomplete tumor removal is associated with significantly decreased recurrence rates. The aim of this review is to analyze the potential advantage of the most modern technical advancements for RT of craniopharyngiomas. This narrative review on the topic of craniopharyngiomas was based on published data available on PUBMED/Medline. All data concerning adjuvant or upfront radiation therapy treatment of craniopharyngioma were reviewed and summarized. A more detailed analysis of fractionated frameless steretactic radiosurgery of these tumors is provided as well. We reviewed the possible improvement provided by intensity modulated beams, arc therapy, image guidance, proton radiation, and fractionated stereotactic radiosurgery. Many published findings on outcome and toxicity after RT involve the use of relatively outdated RT techniques. Technologic improvements in imaging, radiation planning, and delivery have improved the distribution of radiation doses to desired target volumes and reduced the dose to nearby critical normal tissues. Currently available techniques, providing image guidance and improved radiation doses distribution profile, have shown to maintain the efficacy of conventional techniques while significantly reducing the toxicity. Image-guided radiosurgery holds the dose distributions and precision of frame-based techniques with the remarkable advantage of multiple-session treatments that are better tolerated by sensitive peritumoral structures, such as the optic pathway and hypothalamus. This, together with the comfort of a frameless technique, candidates frameless image-guided radiosurgery to be the first option for the adjuvant post-operative treatment of craniopharyngiomas in children and young adults when total resection cannot be achieved, in particular those with hypothalamic involvement, and when the residual tumor is mostly solid.

Analysis of MRI Volumetric Changes After Hypofractionated Stereotactic Radiation Therapy for Benign Intracranial Neoplasms

PurposeTo quantitatively assess volumetric changes after hypofractionated stereotactic radiation therapy (HFSRT) in patients treated for vestibular schwannomas and meningiomas. Methods and materialsWe retrospectively reviewed records of patients treated with HFSRT at our institution from 2002 to 2014. Patients received a median dose of 25 Gy in 5 fractions. After treatment, they underwent clinical and radiologic follow-up with magnetic resonance imaging (MRI) at 3- to 12-month intervals. Gross tumor volume was outlined on each thin slice of contrast-enhanced T1 series before and on each scan after HFSRT. Volumetric changes were calculated and compared with neuroradiologist interpretations. ResultsForty-three patients underwent 182 MRI scans. Tumor types included vestibular schwannoma (n = 34) and meningioma (n = 9). Median follow-up time was 29 months. Median gross tumor volume was 3.1 cm3. Local control was 81.4% for the entire cohort at the time of last follow-up. Transient volume expansion was noted in 17 patients (50%) with vestibular schwannoma and 2 (22%) with meningioma. For all patients, transient volume expansion and subsequent regression occurred at a median time of 5.5 and 12 months, respectively. Neuroradiologist agreement with regard to tumor regression, progression, or stability occurred in 155 of 182 total reports (85%). The largest discordance identified was a stable finding on the MRI interpretation when the measured volumetric change exceeded 20% (n = 24 [13%]). ConclusionsHFSRT is associated with excellent local control and a low incidence of toxicity. With volumetric MRI measurement, transient volume expansion was a common finding and was associated with temporary adverse effects. Although the neuroradiologist’s interpretation generally agreed with the volumetric MRI measurement, the overall 15% discordance rate emphasizes the potential benefit of considering volumetric measurements, which may help clinicians correlate posttreatment symptoms with MRI findings.

Radiosurgery or hypofractionated stereotactic radiotherapy for brain metastases from radioresistant primaries (melanoma and renal cancer)

BackgroundUntil 50% of patients with renal cancer or melanoma, develop brain metastases during the course of their disease. Stereotactic radiotherapy has become a standard of care for patients with a limited number of brain metastases. Given the radioresistant nature of melanoma and renal cancer, optimization of the fractionation of stereotactic radiotherapy is needed. The purpose of this retrospective study was to elucidate if hypofractionated stereotactic radiotherapy (HFSRT) impacts local control of brain metastases from radioresistant tumors such as melanoma and renal cancer, in comparison with radiosurgery (SRS).MethodsBetween 2012 and 2016, 193 metastases, smaller than 3 cm, from patients suffering from radioresistant primaries (melanoma and renal cancer) were treated with HFSRT or SRS. The primary outcome was local progression free survival (LPFS) at 6, 12 and 18 months. Overall survival (OS) and cerebral progression free survival (CPFS) were secondary outcomes, and were evaluated per patient. Objective response rate and radionecrosis incidence were also reported. The statistical analysis included a supplementary propensity score analysis to deal with bias induced by non-randomized data.ResultsAfter a median follow-up of 7.4 months, LPFS rates at 6, 12 and 18 months for the whole population were 83, 74 and 70%, respectively. With respect to fractionation, LPFS rates at 6, 12 and 18 months were 89, 79 and 73% for the SRS group and 80, 72 and 68% for the HFSRT group. The fractionation schedule was not statistically associated with LPFS (HR = 1.39, CI95% [0.65–2.96], p = 0.38). Time from planning MRI to first irradiation session longer than 14 days was associated with a poorer local control rate. Over this time, LPFS at 12 months was reduced from 86 to 70% (p = 0.009). Radionecrosis occurred in 7.1% for HFSRT treated metastases to 9.6% to SRS treated metastases, without any difference according to fractionation (p = 0.55). The median OS was 9.6 months. Six, 12 and 18 months CPFS rates were 54, 24 and 17%, respectively.ConclusionFractionation does not decrease LPFS. Even for small radioresistant brain metastases (< 3 cm), HFSRT, with 3 or 6 fractions, leads to an excellent local control rate of 72% at 1 year with a rate of 7.1% of radionecrosis. HFSRT is a safe and efficient alternative treatment to SRS.

Clinical outcomes of perioptic tumors treated with hypofractionated stereotactic radiotherapy using CyberKnife® stereotactic radiosurgery.

Stereotactic radiation technique is widely reported as an effective treatment for various types of benign intracranial tumors. However, single fraction radiosurgery (SRS) is not recommended for tumors located close to the optic apparatus due to the restricted radiation tolerance dose of the optic pathway. Recent advances in radiotherapy include advanced frameless radiosurgery using hypofractionated stereotactic radiotherapy (HSRT), and this has become an attractive treatment option for perioptic tumors within 2-3mm of the optic pathway. Accordingly, the aim of this study was to investigate the clinical outcomes of perioptic tumors treated with HSRT using CyberKnife® (CK) robotic radiosurgery system relative to tumor control, vision preservation and toxicity. This retrospective analysis of prospectively collected data included consecutive 100 patients that were diagnosed with and treated for perioptic tumor at the Radiosurgery center, Ramathibodi Hospital during the January 2009 to December 2012 study period. The median tumor volume was 6.81cm3 (range 0.37-51.6), and the median prescribed dose was 25Gy (range 20-35) in 5 fractions (range 3-5). After the median follow-up time of 37.5months (range 21-103), two patients developed tumor progression at 6 and 34months post-HSRT. The 5-year overall survival was 97%, and the 5-year local control was 97.5%. At the last follow-up, no vision deterioration or newly developed hypopituitarism was detected in our study. Although a longer follow-up is needed, HSRT yields a high level of local control and vision preservation, and should be considered a treatment of choice for perioptic tumor located close to the optic apparatus.

Local control and possibility of tailored salvage after hypofractionated stereotactic radiotherapy of the cavity after brain metastases resection.

In patients undergoing surgical resection of brain metastases, the risk of local recurrence remains high. Adjuvant whole brain radiation therapy (WBRT) can reduce the risk of local relapse but fails to improve overall survival. At two tertiary care centers in Germany, a retrospective study was performed to evaluate the role of hypofractionated stereotactic radiotherapy (HFSRT) in patients with brain metastases after surgical resection. In particular, need for salvage treatment, for example, WBRT, surgery, or stereotactic radiosurgery (SRS), was evaluated. Both intracranial local (LF) and locoregional (LRF) failures were analyzed. A total of 181 patients were treated with HFSRT of the surgical cavity. In addition to the assessment of local control and distant intracranial control, we analyzed treatment modalities for tumor recurrence including surgical strategies and reirradiation. Imaging follow‐up for the evaluation of LF and LRF was available in 159 of 181 (88%) patients. A total of 100 of 159 (63%) patients showed intracranial progression after HFSRT. A total of 81 of 100 (81%) patients received salvage therapy. Fourteen of 81 patients underwent repeat surgery, and 78 of 81 patients received radiotherapy as a salvage treatment (53% WBRT). Patients with single or few metastases distant from the initial site or with WBRT in the past were retreated by HFSRT (14%) or SRS, 33%. Some patients developed up to four metachronous recurrences, which could be salvaged successfully. Eight (4%) patients experienced radionecrosis. No other severe side effects (CTCAE≥3) were observed. Postoperative HFSRT to the resection cavity resulted in a crude rate for local control of 80.5%. Salvage therapy for intracranial progression was commonly needed, typically at distant sites. Salvage therapy was performed with WBRT, SRS, and surgery or repeated HFSRT of the resection cavity depending on the tumor spread and underlying histology. Prospective studies are warranted to clarify whether or not the sequence of these therapies is important in terms of quality of life, risk of radiation necrosis, and likelihood of neurological cause of death.

Multicenter analysis of stereotactic radiotherapy of the resection cavity in patients with brain metastases.

Brain metastases show a recurrence rate of about 50% after surgical resection. Adjuvant radiotherapy can prevent progression; however, whole‐brain radiotherapy (WBRT) can be associated with significant side effects. Local hypofractionated stereotactic radiotherapy (HFSRT) is a good alternative to provide local control with minimal toxicity. In this multicenter analysis, we evaluated the treatment outcome of local HFSRT after resection brain metastases in 181 patients. Patient's characteristics, treatment data as well as follow‐up data were collected and analyzed with special focus on local control, locoregional control and survival. After a median follow‐up of 12.6 months (range 0.3–80.2 months), the crude rate for local control was 80.5%; 1‐ and 2‐year local recurrence‐free survival rates were 75% and 70% (median not reached). Resection cavity size was a significant predictor for local recurrence (P = 0.033). The median overall survival was 16.0 months. Both graded prognostic assessment score and recursive partitioning analysis were accurate predictors of survival. HFSRT leads to excellent local control and has a high potential to consolidate results after surgery; acute and late toxicity is low. Distant intracerebral metastases occur frequently during follow‐up, and therefore, a close patient monitoring needs to be warranted if whole‐brain radiotherapy is omitted.

EP-1195: Hypofractionated stereotactic radiotherapy (HFSRT) for 50 brain metastases: Institutional experience

EP-1195: Hypofractionated stereotactic radiotherapy (HFSRT) for 50 brain metastases: Institutional experience

Prostate Clinical Outlook Visualization System for Patients and Clinicians Considering Cyberknife Treatment—A Personalized Approach

Background: When a patient presents with localized prostate cancer, referral for radiation oncology consultation includes a discussion of likely outcomes of therapy. Among current radiation treatments for prostate cancers, hypo-fractionated stereotactic body radiation therapy (SBRT) has gained clinical acceptance based on efficacy, short duration of treatment, and the potential radiobiological advantages. The Prostate Clinical Outlook Visualization System (PCOVS) was developed to provide the patient and the clinician with a tool to visualize probable treatment outcomes using institutional, patient specific data for comparing results of treatment. Methods: We calculated the prostate cancer outcomes—for each prospective patient using the EPIC-26 quality of life parameters based on clinical outcomes data of 580 prostate cancer patients who were treated with SBRT. We applied Kaplan-Meier analysis using the ASTRO definition for biochemical recurrence (BCR) free survival and likely outcome and the PCOVS nomogram to calculate parameters for quality of life. Open-source R, RShiny, and MySQL were used to develop a modularized architecture system. Results: The PCOVS presents patient specific risk scores in a gauge chart style and risk free probability bar plots to compare the treatment data of patients treated with SBRT. The PCOVS generates reports, in PDF, which consists of a comparison charts of risk free probabilities late effects and gauge charts of risk scores. This system is now being expanded as a web-based service to patients. Conclusions: The PCOVS visualized patient specific likely outcomes were compared to treatment data from a single department, helping the patient and the clinician to visualize likely outcomes. The PCOVS approach can be expanded to other specialties of oncology with the flexible, modularized architecture, which can be customized by changing independent modules.

Hypo-fractionated stereotactic radiation therapy for lung malignancies by means of helical tomotherapy: report of feasibility by a single-center experience.

Several experiences in the literature report SBRT as an effective treatment option for medically inoperable early stage non-small cell lung cancer (NSCLC) and oligometastatic disease. The optimal fractionation schedules and total dose remain controversial. In this study, we evaluated the safety in terms of toxicity and efficacy of using of 8-10 fractions schedules with Helical Tomotherapy (HT) for primary and metastatic lung lesions. Between March 2014 and May 2016, a total of 39 patients (median age 72years, range 26-91) were treated with HT-SBRT for malignant lung lesions: 22 patients with early stage NSCLC, 17 with oligometastases. Patients received 8-10 fractions with lower daily dose for central and ultracentral lesions. Treatment-related toxicity was evaluated using CTCAE v 4.0 scale. Local control (LC), overall survival (OS) and toxicity rates were prospectively collected. Median duration of RT was 15days (range 10-26days) and no interruption occurred. With a median follow-up of 13months (range 3-29), we reported one G2 pneumonitis (2.6%) and one G2 chest pain (2.6%); no≥G2 esophagitis was registered. Actuarial local control rate was 95.5% both at 12 and 24months for early stage NSCLC and 92.9% both at 12 and 24months for metastatic patients. OS rate was 94.4 and 92.3% at 1year, and 94.4 and 83.9% at 2years in primary and metastatic group, respectively. The use of 8-10 fractions schedule HT-SBRT for lung malignancies results in high LC and OS rates with minimal toxicities reported.

Under-reported dosimetry errors due to interplay effects during VMAT dose delivery in extreme hypofractionated stereotactic radiotherapy.

Radiotherapy of extracranial metastases changed from normofractioned 3D CRT to extreme hypofractionated stereotactic treatment using VMAT beam techniques. Random interaction between tumour motion and dynamically changing beam parameters might result in underdosage of the CTV even for an appropriately dimensioned ITV (interplay effect). This study presents a clinical scenario of extreme hypofractionated stereotactic treatment and analyses the impact of interplay effects on CTV dose coverage. For a thoracic/abdominal phantom with an integrated high-resolution detector array placed on a 4D motion platform, dual-arc treatment plans with homogenous target coverage were created using a common VMAT technique and delivered in a single fraction. CTV underdosage through interplay effects was investigated by comparing dose measurements with and without tumour motion during plan delivery. Our study agrees with previous works that pointed out insignificant interplay effects on target coverage for very regular tumour motion patterns like simple sinusoidal motion. However, we identified and illustrated scenarios that are likely to result in a clinically relevant CTV underdosage. For tumour motion with abnormal variability, target coverage quantified by the CTV area receiving more than 98% of the prescribed dose decreased to 78% compared to 100% at static dose measurement. This study is further proof of considerable influence of interplay effects on VMAT dose delivery in stereotactic radiotherapy. For selected conditions of an exemplary scenario, interplay effects and related motion-induced target underdosage primarily occurred in tumour motion pattern with increased motion variability and VMAT plan delivery using complex MLC dose modulation.

Trigeminal neuropathy in vestibular schwannoma: a treatment algorithm to avoid long-term morbidity.

Trigeminal neuropathy (TGN) can occur as a presenting feature of vestibular schwannoma (VS) or as an adverse effect of radiosurgery. This study was designed to evaluate a treatment algorithm for presenting symptoms of TGN in patients with VS, and a new radiosurgery dosimetric tolerance to avoid TGN after treatment. Outcome was measured after microsurgery (MS), stereotactic radiosurgery (SRS), hypofractionated stereotactic radiotherapy (HSRT), and fractionated radiotherapy (FRT). A prospectively held VS database was retrospectively analysed from 2011 to 2016 at a tertiary university hospital. All patients who underwent MS from 2011 and all patients who underwent radiotherapy (SRS, HSRT, FRT) from 2015 were studied. Patients on surveillance and neurofibromatosis type 2 patients were not included. Patient demographic data, tumour characteristics, presenting symptoms, and post-treatment outcomes were analysed. Eighty-eight patients were included in the study (43 microsurgery, 45 radiotherapy). Twenty-seven (31%) patients presented with TGN symptoms. The median age of patients included was 56.5 (range 6-72years), with a median follow-up for MS and SRS of 38 and 20months, respectively (range 10-80months). All 27 patients with TGN were offered MS as per protocol. Three patients declined, or were not fit for surgery, and received FRT. Complete resolution of TGN symptoms was achieved in all 24 patients who underwent MS and 33% (1/3) of patients with FRT. Eleven patients experienced transient post-operative complications (pseudomeningocele (6), meningitis (3), venous sinus thrombosis, cerebellar haemorrhagic contusion, and posterior fossa haematoma). Of the 45 patients in the radiotherapy cohort, 36 were suitable for SRS, of which 30 patients who met the dose-volume constraints for trigeminal nerve underwent single-fraction SRS and 6 patients who did not meet the constraints received HSRT. Nine patients (20%) received FRT including three patients with pre-treatment TGN. None of the patients developed new TGN symptoms following SRS or HSRT. Our algorithm to select the optimal treatment modality appears to achieve comparable or better long-term outcome. Microsurgical resection in our cohort resulted in complete resolution of symptoms in all patients. None of our SRS- or HSRT-treated patients developed TGN during the follow-up period. The adherence to strict trigeminal nerve dose-volume constraints for SRS remains critical to minimise TGN post treatment. Fractionated radiotherapy is an alternative for patients who refuse surgery or those who are unfit for surgery.

Advanced Survival in Patients with Multiple Irradiations for Brain Melanoma Metastases and Associated Abscopal Effect

Brain metastases are often detected in melanoma patients. Central nervous system (CNS) involvement is usually associated with poor prognosis. We describe a case of a female patient with multiple melanoma brain metastases who survived for 49 months after detection of CNS involvement and the first radiosurgery. She underwent several courses of irradiation (five radiosurgeries, stereotactic hypofractionated radiotherapy, and whole brain radiotherapy), chemotherapy (started in 12 months after the first radiosurgery), and targeted therapy (started 30 months after the first radiosurgery). The clear abscopal effect in the form of disappearance of intradermal lesions was observed after the second radiosurgery without any systemic treatment. We believe that the application of combination of different treatment modalities can significantly prolong survival in certain patients with melanoma brain metastases, and can be recommended even in case of poor prognosis.

Automatic Intracranial Segmentation: Is the Clinician Still Needed?

Introduction:Stereotactic hypofractionated radiotherapy is an effective treatment for brain metastases in oligometastatic patients. Its planning is however time-consuming because of the number of organs at risk to be manually segmented. This study evaluates 2 automated segmentation commercial software.Methods:Patients were scanned in the treatment position. The computed tomography scan was registered on a magnetic resonance imaging and volumes were manually segmented by a clinician. Then 2 automated segmentations were performed (with iPlan and Smart Segmentation). RT STRUCT files were compared with Aquilab’s Artistruct segment comparison module. We selected common segmented volume ratio as the main judging criterion. Secondary criteria were Dice-Sørensen coefficients, overlap ratio, and additional segmented volume.Results:Twenty consecutive patients were included. Agreement between manual and automated contouring was poor. Common segmented volumes ranged from 7.71% to 82.54%, Dice-Sørensen coefficient ranged from 0.0745 to 0.8398, overlap ratio ranged from 0.0414 to 0.7275, and additional segmented volume ranged from 9.80% to 92.25%. Each software outperformed the other on some organs while performing worse on others.Conclusion:No software seemed clearly better than the other. Common segmented volumes were much too low for routine use in stereotactic hypofractionated brain radiotherapy. Manual editing is still needed.

ATIM-18. A PHASE I TRIAL OF HYPOFRACTIONATED STEREOTACTIC IRRADIATION (HFSRT) WITH PEMBROLIZUMAB AND BEVACIZUMAB IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA (NCT02313272)

There is strong pre-clinical evidence for the combination of PD-1 blockade with radiotherapy and anti-VEGF therapy. Herein, we present safety and efficacy data from a phase 1 study combining pembrolizumab, an anti-PD-1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in recurrent high grade glioma. This phase I study (3 + 3 design) explored the safety, tolerability, recommended phase II dose (RP2D), and antitumor activity of pembrolizumab administered concurrently with HFSRT and bevacizumab. Adult patients with recurrent glioblastoma or anaplastic astrocytoma (maximum diameter of target lesion ≤ 3.5 cm) were eligible. Eligible patients received HFSRT to the recurrent tumor (30 Gy in 5 fractions) combined with bevacizumab (10 mg/kg, Q2W) and pembrolizumab (100 mg or 200 mg intravenously based on dose level, Q3W). Two dose levels of pembrolizumab were explored and 20 patients were treated at RPD2. Treatment continued until disease progression or unacceptable toxicity. Twenty three patients with recurrent glioblastoma have been treated on this study (3 patients at 100 mg and 20 patients at 200 mg dose levels). Five patients had previous tumor progression on bevacizumab. Combination of HFSRT with pembrolizumab (200 mg every 3 weeks) and bevacizumab was generally well tolerated. The most common toxicities were grade 1 fatigue and grade 1 proteinuria. No treatment-related neurologic adverse events were observed. In 1 patient, study treatment was discontinued due to grade 3 elevation of liver transaminases. Durable objective responses (complete response + partial response ≥ 6 months) were observed in 53% of patients. The overall survival rate (at the time of abstract submission) at 6 and 12 months were 94% (16 out of 17 patients) and 64% (7 out of 11 patients), respectively. Combination of HFSRT with pembrolizumab (200 mg every 3 weeks) and bevacizumab is safe. Clinical activity of this combination therapy is encouraging.

Dose-Volume Predictors of Esophagitis After Thoracic Stereotactic Body Radiation Therapy

Esophageal toxicity has become a major concern as stereotactic hypofractionated radiation therapy is increasingly utilized for central pulmonary tumors. Our purpose was to define esophageal dosimetric parameters that predict potentially dose-limiting toxicities. In total, 157 patients with a planning target volume ≤5 cm from the esophagus were selected from an institutional database. Toxicity was scored with the CTCAE v4.0. Esophageal Dmax and Dv (dose D in Gy covering volume v in mL) in 0.5 mL increments were collected. Corresponding biologically effective dose (BED) was calculated for α/β=10,3 (BED10, BED3). Normal tissue complication probability was computed with conventionally fractionated radiotherapy parameters and equivalent dose in 2 Gy per fraction (EQD2). Dosimetric predictors were identified with multivariate logistic regression with a manual forward stepwise selection technique. The grade≥2 esophagitis rate was 5.7%. BED10 to 1.5 mL was the best predictor of esophagitis. BED10 to 0.5, 1.0, 2.0, 3.0, and 3.5 mL were also predictive but less strong. Results were similar when BED3 and physical dose were examined. Tumor-esophageal distance correlated with esophagitis (10.5% risk of≥grade 2 events with distance≤3.9 cm vs. 1.3% when>3.9 cm, P=0.016). BED10 to 1.5 mL correlated well with EQD2 normal tissue complication probability estimates. BED to 1.5 mL was the strongest predictor of grade≥2 esophagitis (independent of α/β ratio) with a 10.6% toxicity risk when BED10>21.1 Gy (14.3 Gy in 3 fractions, 16.0 Gy in 5). The overall rate of severe toxicity is low, suggesting that higher doses may be tolerable.