Rates Of Radionecrosis Research Articles

Intraoperative radiotherapy after neurosurgical resection of brain metastases as institutional standard treatment- update of the oncological outcome form a single center cohort after 117 procedures.

Stereotactic radiotherapy (SRT) is the predominant method for the irradiation of resection cavities after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50kV x-rays is an alternative way to irradiate the resection cavity focally. We have already reported the outcome of our first 40 IORT patients treated until 2020. Since then, IORT has become the predominant cavity treatment in our center due to patients´ choice. We retrospectively analyzed the outcomes of all patients who underwent resection of BM and IORT between 2013 and August 2023 at Augsburg University Medical Center (UKA). We identified 105 patients with 117 resected BM treated with 50kV x-ray IORT. Median diameter of the resected metastases was 3.1cm (range 1.3 - 7.0cm). Median applied dose was 20Gy. All patients received standardized follow-up (FU) including three-monthly MRI of the brain. Mean FU was 14months, with a median MRI FU for patients alive of nine months. Median overall survival (OS) of all treated patients was 18.2months (estimated 1-year OS 57.7%). The observed local control (LC) rate of the resection cavity was 90.5% (estimated 1-year LC 84.2%). Distant brain control (DC) was 61.9% (estimated 1-year DC 47.9%). Only 16.2% of all patients needed WBI in the further course of disease. The observed radio necrosis rate was 2.6%. After 117 procedures IORT still appears to be a safe and appealing way to perform cavity RT after neurosurgical resection of BM with low toxicity and excellent LC.

Single versus multiple fraction stereotactic radiosurgery for medium-sized brain metastases (4-14 cc in volume): reducing or fractionating the radiosurgery dose?

Stereotactic radiosurgery (SRS) of brain metastases (BM) and resection cavities is a widely used and effective treatment modality. Based on target lesion size and anatomical location, single fraction SRS (SF-SRS) or multiple fraction SRS (MF-SRS) are applied. Current clinical recommendations conditionally recommend either reduced dose SF-SRS or MF-SRS for medium-sized BM (2-2.9 cm in diameter). Despite excellent local control rates, SRS carries the risk of radionecrosis (RN). The purpose of this study was to assess the 12-months local control (LC) rate and 12-months RN rate of this specific patient population. This single-center retrospective study included 54 patients with medium-sized intact BM (n=28) or resection cavities (n=30) treated with either SF-SRS or MF-SRS. Follow-up MRI was used to determine LC and RN using a modification of the "Brain Tumor Reporting and Data System" (BT-RADS) scoring system. The 12-month LC rate following treatment of intact BM was 66.7% for SF-SRS and 60.0% for MF-SRS (p=1.000). For resection cavities, the 12-month LC rate was 92.9%% after SF-SRS and 46.2% after MF-SRS (p=0.013). For intact BM, RN rate was 17.6% for SF-SRS and 20.0% for MF-SRS (p=1.000). For resection cavities, RN rate was 28.6% for SF-SRS and 20.0% for MF-SRS (p=1.000). Patients with intact BM showed no statistically significant differences in 12-months LC and RN rate following SF-SRS or MF-SRS. In patients with resection cavities the 12-months LC rate was significantly better following SF-SRS, with no increase in the RNFS.

Survival and Prognostic Factors in Re-irradiation for Recurrent/Progressive Malignant Gliomas: Turkish Society of Radiation Oncology Neuro-Oncology Group, TROD 007-006 Study.

To evaluate survival and prognostic factors associated with survival among patients who underwent reirradiation for recurrent/ progressive primary brain tumors. A multicenter, retrospective study (7 centers, N=236) was conducted by the Neuro-oncology Group of the Turkish Radiation Oncology Association. Median overall survival (OS) was 11 months and 1- and 2-year survival rates were 48% and 22%, respectively. Survival was negatively correlated with cumulative biologically effective dose (BED10) (r=-0.158, p=0.016) and cumulative equivalent dose in 2-Gy fractions (EQD2) (r=-0.158, p=0.016). In univariate analysis, survival was associated with performance status (p < 0.001), histopathology at diagnosis and recurrence (p < 0.001), radiotherapy (RT) method used for recurrence (p=0.025), tumor volume at recurrence (p=0.014), cumulative EQD2 ( < 110 vs. ≥110 Gy, p=0.038), and cumulative BED10 ( < 130 vs. ≥130 Gy, p=0.022). In multivariate analysis, tumor volume at recurrence (HR=1.68, 95% CI=1.06-2.64, p=0.025), Karnofsky Performance Status score (HR=5.7, 95% CI=3.26-9.98, p < 0.001), and histopathology at recurrence (glioblastoma vs. high-grade glioma: HR=0.48, 95% CI=0.26-0.88, p=0.019; glioblastoma vs. low-grade glial tumor: HR=0.16, 95% CI=0.08-0.34, p < 0.001) were found to be independent prognostic factors. Radionecrosis was detected in 25% (n=58) of the patients. Re-resection was associated with a higher rate of radionecrosis (37.7% vs. 18%, p=0.002). The prognostic factors most strongly associated with survival in glioma patients undergoing reirradiation were Karnofsky Performance Status score below 70, glioblastoma histopathology, and tumor volume greater than 4.5 cm3. In addition, survival time was negatively correlated with cumulative EQD2 and BED10. The rate of radionecrosis was higher in patients who underwent re-resection compared those who did not.

Stereotactic Radiosurgery (SRS) for Large Brain Metastases: Dosimetric and Clinical Predictors of Local Progression and Radionecrosis

Stereotactic radiosurgery (SRS) provides high rates of local control for small brain metastases with low rates of radionecrosis (RN). Larger targets are associated with increased risk of both local progression (LP) and RN. In this analysis, we hypothesized that dosimetric and clinical parameters predict for risk of LP and RN in SRS targets larger than two centimeters. We retrospectively reviewed patients with one or more targets with either an intact versus post-operative cavity larger than 2.0 cm treated with LINAC-based SRS between 2017 and 2022 at one institution. We assessed for association between patient, treatment, and disease variables with LP and RN. Variables assessed included tumor resection status, PDL1 positivity, target volume, maximum and minimum target dose, EQD2 and BED (a/b = 2 for necrosis and a/b = 10 for tumor control), as well as receipt of steroids, bevacizumab, or systemic therapy before or after SRS. Radionecrosis was determined by characteristic radiographic changes. Analyses were performed for the entire cohort and within subsets including by resection status and dose fractionation. A total of 178 lesions in 143 patients were included. Targets with volume diameters measuring at least 2 cm were used. Median follow-up was 2.3 years. Overall survival at 1 and 2 years was 56% and 32%, respectively. Most lesions (n = 119) were resected and treated with SRS post-operatively. The most common dose and fractionation schemes used were 30 Gy in 5 fractions (n = 89) and 27 Gy in 3 fractions (n = 63). For the entire cohort, the cumulative incidence of LP 1 and 2 years was 26% and 34%, respectively. The cumulative incidence of radiographic radionecrosis at 1 and 2 years was 12% and 17%, respectively. There was no difference in LP or RN between 27 Gy in 3 fractions versus 30 Gy in 5 fractions (p>0.5 for both). Median planning target volume (PTV) size was 18.5 cc for the 27 Gy in 3 fraction group compared to 21.9 cc in the 30 Gy in 5 fraction group. Minimum or maximum dose within the target was not associated with increased risk of LP or RN. Among patients receiving 27 Gy in 3 fractions, patients treated with resection followed by SRS had lower risk of LP compared to those treated with SRS alone (HR: 0.15, 95% CI: 0.03-0.64, p = 0.011). Among patients receiving 30 Gy in 5 fractions, patients who received corticosteroids prior to SRS had a lower risk of RN (HR: 0.14, 95% CI: 0.03-0.66, p = 0.013). For the entire cohort as well as within all subgroups, PD-L1≥1% was associated with increased risk of RN (p<0.001 for all). Selecting the optimal SRS dose fractionation and planning parameters to minimize both LP and RN remains a challenge for large targets. In this analysis, 27 Gy in 3 fractions appeared to provide equivalent LP and RN compared to 30 Gy in 5 fractions, and may be more convenient for patients. Patients with PD-L1≥1% with large brain targets treated with SRS may be at increased risk of RN; corticosteroid prophylaxis may be considered in this population.

Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification.

Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-yearOS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-yearprogression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

P03.05.B PRIMARY GAMMA KNIFE RADIOSURGERY FOR PINEAL REGION TUMORS, A SYSTEMATIC REVIEW AND POOLED ANALYSIS OF AVAILABLE LITERATURE WITH HISTOLOGICAL STRATIFICATION

Abstract BACKGROUND Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality following surgery or as a salvage treatment at recurrence. We aimed to gather the existing evidence on the topic and analyze single-patient level data to address the efficacy and safety of primary GKSR when only a biopsy was attempted or biochemical or neuroimaging diagnosis was available. MATERIAL AND METHODS This is a systematic review of literature (Pubmed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers in our final analysis comprising 64 patients. Additional 12 patients were included from the authors’ original series. RESULTS A total of 76 patients reached the final analysis. Presumptive diagnoses included intrinsic pineal low-grade (46%), glial low-grade (LGG, 5%), pineoblastoma (4%), germ cell tumors (GCTs, 4%), pineal tumors of intermediate differentiation (3%), other pineal tumors (3%), glial high-grade (HGG, 2%) and meningioma (1%). In 32% of cases, the diagnosis was unclear. Only 57% of cases received histological confirmation. The mean age at treatment was 38.7y and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose (50% isodose) of 14.7 ± 2.1 Gy. At a median 36mo follow-up, local control was achieved in 84% of cases. Ten patients showed progression within a mean time of 24.2mo. Progression was more common in HGG and GCTs (p=0.03) compared to intrinsic pineal tumors. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3y-OS was 100% for LGG, 90% for the intrinsic pineal, 60% for GCTs, 50% for HHG, and 82% for undetermined tumors. The 3y-PFS was 100% for LGG, 90% for the intrinsic pineal, 32% for GCTs, and 0% for HHG. Median PFS was 5mo for HHG and 34mo for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as presenting symptom strongly predicted mortality (OR 104, p=0.02), while GCTs and HHG histology well predicted PD (OR: 13, p=0.04). CONCLUSION These results support the efficacy and safety of primary GKSR treatment of pineal region tumors. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

P17.18.B RADIOTHERAPY IN GLIOBLASTOMA MULTIFORME COULD BE PLANNED WITH MARGINS LESS THAN 2 CM WITH LESS THAN 1 CM FROM THE SURGICAL BED

Abstract BACKGROUND The administration of radiotherapy (Rt) plus adjuvant temozolamide (TMZ) with IMR and VMAT techniques has become an increasingly valuable tool in the local control of glioblastoma multiforme with a survival current Rt techniques allow specific conformation with the use of better radiological images that allow us greater precision. For many years large Rt field sizes have been associated with significant adverse effects.Although we continue to give very wide margins that lead us to irradiate non-compromised organs at risk, which translates into a higher rate of radionecrosis and acute and chronic neurological toxicity.Therefore, we consider it valid to ask ourselves if we could reduce the standard margins applied in the planning of Rt. MATERIAL AND METHODS Analysis of 98 GBM patients treatedat the barros luco hospital between 2021 and 2023 with surgery followed by adjuvant therapy, radiotherapy plus concomitant chemotherapy at the Institute. Nacional de Cáncer de Santiago de Chile we reviewed the time of recurrence and the location in relation to the surgical margins vs. radiotherapy margins or other nearby areas. RESULTS After the analysis, we can see that 65% of the recurrences presented a dominant failure pattern, within the field and less than 1cm from the margin between the surgical bed and the radiotherapy margin, evaluated with perfusion brain resonance imaging and spectroscopy CONCLUSION n the local control of GBM, the application of adjuvant therapy is essential in a period of not less than 2 months after surgery, in this institutional analysis we can observe a considerable number of patients under 40 years of age with this pathology, for which reason to consider reducing the diameter of Rt margins can be considered an option, in order to limit deleterious effects in healthy organs in the times that there are advanced Rt techniques, the increasingly frequent application of brain radiosurgery (SRS) thatIt can be used as a rescue method in case of recurrences at the edge of the margin, using radiological images (MRI with perfusion and spectroscopy/C-methionine PET/CT. Figure we can see the CTV and PTV to be treated with modulated intensity technique, evidencing the large field size that receives radiation between 54 to 60 Gy.Radiation oncology must continue to develop and improve the delivery, targeting, and dose of radiation therapy in the GBM to improve its survival and treatment-associated toxicity.

Effects of Ataxia-Telangiectasia Mutated Variants on Radionecrosis and Local Control After Stereotactic Radiation Surgery for Non-Small Cell Lung Cancer Brain Metastases

Genetic variants affecting the radiation response protein ataxia-telangiectasia mutated (ATM) have been associated with increased adverse effects of radiation but also with improved local control after conventional radiation therapy. However, it is unknown whether ATM variants affect rates of radionecrosis (RN) and local intracranial progression (LIP) after stereotactic radiosurgery (SRS) for brain metastases. Patients undergoing an initial course of SRS for non-small cell lung cancer (NSCLC) brain metastases at a single institution were retrospectively identified. Kaplan-Meier estimates were calculated and Cox proportional hazards testing was performed based on ATM variant status. A total of 541 patients completed SRS for brain metastasis secondary to NSCLC, of whom 260 completed molecular profiling. Variants of ATM were identified in 36 cases (13.8%). Among patients who completed molecular profiling, RN incidence was 4.9% (95% CI, 1.6%-8.2%) at 6 months and 9.9% (95% CI, 4.8%-15.0%) at 12 months. Incidence of RN was not significantly increased among patients with ATM variants, with an RN incidence of 5.3% (95% CI, 0.0%-15.3%) at both 6 and 12 months (P=.46). For all patients who completed genomic profiling, LIP was 5.4% (95% CI, 2.4%-8.4%) at 6 months and 9.8% (5.5%-14.1%) at 12 months. A significant improvement in LIP was not detected among patients with ATM variants, with an LIP incidence of 3.1% (0.0%-9.1%) at both 6 and 12 months (P=.26). Although differences according to ATM variant type (pathologic variant or variant of unknown significance) did not reach significance, no patients with ATM pathologic variants experienced LIP. We did not detect significant associations between ATM variant status and RN or LIP after SRS for NSCLC brain metastases. The current data set allows estimation of patient cohort sizes needed to power future investigations to identify genetic variants that associate with significant differences in outcomes after SRS.

Brainstem toxicity after proton or photon therapy in children with localized intracranial ependymoma

Objectives Children's ependymomas achieve a 5-years local control rate of 50% with a standard post-operative dose of 59.4 Gy. To decrease the dose to normal tissue, proton bean therapy (PBT) is preferred when available. Recently, retrospective studies reported higher rates of radionecrosis on the brainstem after PBT than photon radiation therapy (XRT), leading several teams to decrease the dose to 54 Gy in PBT for posterior fossa ependymomas under 3 years old. The benefit-risk's balance of the dose reduction is unclear especially since the real incidence of clinically relevant brainstem's toxicity appears low.This prompt us to compare the incidence of clinical and imaging brainstem toxicity between XRT and PBT and to correlate them to the dosimetric datas in the retrospective PEPPI French cohort. Methods From 2001 to 2021, we studied the MRI brainstem's modification and clinical brainstem toxicity for patients ≤ 22 years old from 5 reference French centers treated with surgery and radiation therapy (RT) for a localized intracranial ependymoma. Pre operative, post operative and follow-up MRI during 18 months after RT were analyzed. Post-gadolinium T1, T2, FLAIR and diffusion weighted imaging were used. Results Eighty-three patients were included in the study, 42 patients were treated with PBT, 37 with XRT and 4 with both. Median follow-up was 5.6 years [95%CI: 4.8-6.2], the 5-years overall survival and progression free survival rates were respectively 86.1% [95%CI: 75.7-92.3] and 68.7% [95%CI: 56.4-78.3]. Neither clinical or MRI brainstem radionecrosis nor new or progressive brainstem symptoms were found. Four patients (whose two had received PBT) presented a punctiform brainstem enhancement with a median time of onset of 3.5 months [3.0-9.4] after RT and a median time of disappearance of 7.6 months [3.7-7.9]. Median brainstem mean dose was 47.2 Gy [45.3-53.2] for them and 48.5 Gy for the cohort. Conclusion Brainstem imaging change occurred in 4,8% of children in a large series including PBT. No radionecrosis nor symptomatic MRI change was found within the brainstem. The pursue of the study with the others French centers will strengthen our results. Children's ependymomas achieve a 5-years local control rate of 50% with a standard post-operative dose of 59.4 Gy. To decrease the dose to normal tissue, proton bean therapy (PBT) is preferred when available. Recently, retrospective studies reported higher rates of radionecrosis on the brainstem after PBT than photon radiation therapy (XRT), leading several teams to decrease the dose to 54 Gy in PBT for posterior fossa ependymomas under 3 years old. The benefit-risk's balance of the dose reduction is unclear especially since the real incidence of clinically relevant brainstem's toxicity appears low.This prompt us to compare the incidence of clinical and imaging brainstem toxicity between XRT and PBT and to correlate them to the dosimetric datas in the retrospective PEPPI French cohort. From 2001 to 2021, we studied the MRI brainstem's modification and clinical brainstem toxicity for patients ≤ 22 years old from 5 reference French centers treated with surgery and radiation therapy (RT) for a localized intracranial ependymoma. Pre operative, post operative and follow-up MRI during 18 months after RT were analyzed. Post-gadolinium T1, T2, FLAIR and diffusion weighted imaging were used. Eighty-three patients were included in the study, 42 patients were treated with PBT, 37 with XRT and 4 with both. Median follow-up was 5.6 years [95%CI: 4.8-6.2], the 5-years overall survival and progression free survival rates were respectively 86.1% [95%CI: 75.7-92.3] and 68.7% [95%CI: 56.4-78.3]. Neither clinical or MRI brainstem radionecrosis nor new or progressive brainstem symptoms were found. Four patients (whose two had received PBT) presented a punctiform brainstem enhancement with a median time of onset of 3.5 months [3.0-9.4] after RT and a median time of disappearance of 7.6 months [3.7-7.9]. Median brainstem mean dose was 47.2 Gy [45.3-53.2] for them and 48.5 Gy for the cohort. Brainstem imaging change occurred in 4,8% of children in a large series including PBT. No radionecrosis nor symptomatic MRI change was found within the brainstem. The pursue of the study with the others French centers will strengthen our results.

RADT-03. GOLDILOCKS AND THE THREE DOSES OF RADIOSURGERY FOR SMALL BRAIN METASTASES

Abstract INTRODUCTION The optimal dose for single-fraction radiosurgery (SRS) for small brain metastases (BM) (&amp;lt; 2 cm) has not been established considerable variability in dose selection. METHODS Consecutive patients diagnosed with intact BM &amp;lt; 2 cm in maximum dimension treated with SRS to prescription doses of 24, 22, or 20 Gy on the Gamma Knife® between 3/2019-1/2021 were reviewed. Institutional dosing prescriptions were: 24 Gy for &amp;lt; 10 lesions, 22 Gy for 10-20, and 20 Gy for &amp;gt;20). Endpoints included freedom-from-local-failure (FFLF) and radionecrosis on a per-lesion basis calculated from date of SRS to event. Univariable and multivariable analyses were performed using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS 133 patients with 863 BM met inclusion criteria. Prescription dose was 24 Gy for 416 (48.2%) lesions, 22 Gy for 266 (30.8%), and 20 Gy for 181 (21.0%). 20 Gy was associated (all p&amp;lt; 0.001) with younger age, presence of extracranial-disease, progressive extracranial-disease, lung primary, higher number of BM per SRS course (median 17 for 20 Gy, 14 for 22 Gy, 6 for 24 Gy), and smaller per-lesion tumor volume. With a median follow-up of 15 months, 76 (8.8%) LFs occurred. Actuarial 1-year FFLF was 91.2% (95%CI: 88.6-94.8%) for 24 Gy, 92.5% (89.1-95.9%) for 22 Gy, and 77.9% (71.2-84.6%) for 20 Gy (p&amp;lt; 0.001). On multivariable analysis, factors independently associated with adverse FFLF (all p&amp;lt; 0.05) were male sex, presence of extracranial-disease, breast or lung primary, and 20 Gy prescription dose (HR: 2.52, 95%CI: 1.34-4.76). The cumulative 1-year radionecrosis rate was 7.0% for 24 Gy, 4.0% for 22 Gy, and 3.8% for 20 Gy (p=0.035). CONCLUSION For BM &amp;lt; 2 cm, we propose a testable hypothesis that 22 Gy prescription dose may represent the “Goldilocks zone”- superior to 20 Gy regarding LF and superior to 24 Gy concerning radionecrosis.

Carotid arterial blowout after organ preserving chemoradiation therapy in hypopharyngeal cancer.

Laryngeal preserving concurrent chemoradiation has been advocated for hypopharyngeal cancers. The use of radiotherapy (RT) in the larynx could lead to increased rates of radionecrosis. In this study, we investigated a rare but disastrous complication, carotid blow-out syndrome (CBS), related with the persistent radionecrosis. Retrospective cohort study. This retrospective study enrolled hypopharyngeal cancer patients with biopsy-proven pharyngeal and laryngeal chondronecrosis (PLCRN), which was rated by the Chandler Grading System. From 2002 to 2018, a total of 346 hypopharygeal cancer patients received upfront radiation therapy, 13 PLCRN patients were identified in a rate of 3.8%. All PLRN patients received RT with a mean radiation dose of 70.81 ± 0.85 Gy. All patients had Chandler Grade IV at the time of presentation, which was a mean of 15.08 months (range: 5-109 months) from the time of cancer diagnosis to PLCRN diagnosis. In 5 of the 13 PLCRN patients developed CBS. Three of the CBS originated from superior thyroid artery, one from lingual artery and one from the carotid artery. Three (60%) of the 5 CBS patients expired due to loss of airway and hemodynamic instability. Two (40%) were rescued by emergent airway secure and emergent angiographic embolization. Persistent PLCRN could lead to disastrous vascular complications. CBSs were demonstrated to be more frequently originated from the branches of carotid artery rather than carotid artery per se. Clinical alert with early airway protection could strive for time to do interventions and prevent mortalities.

Moderately hypofractionated versus conventionally fractionated radiation therapy with temozolomide for young and fit patients with glioblastoma: an institutional experience and meta-analysis of literature

PurposeShorter hypofractionated radiation therapy (HF-RT) schedules may have radiobiological, patient convenience and healthcare resource advantages over conventionally fractionated radiation therapy (CF-RT) in glioblastoma (GBM). We report outcomes of young, fit GBM patients treated with HF-RT and CF-RT during the COVID-19 pandemic, and a meta-analysis of HF-RT literature in this patient subgroup.MethodsHospital records of patients with IDH-wildtype GBM treated with HF-RT (50 Gy/20 fractions) and CF-RT (60 Gy/30 fractions) between January 2020 and September 2021 were reviewed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariable analysis was performed using Cox regression analysis. A systematic search and meta-analysis of studies from January 2000 to January 2022 was performed.Results41 patients were treated (HF-RT:15, CF-RT:26). For both HF-RT and CF-RT groups, median age was 58 years and 80–90% were ECOG 0–1. There were more methylated tumours in the HF-RT group. All patients received concurrent/adjuvant temozolomide. At 19.2 months median follow-up, median OS was 19.8 months and not-reached for HF-RT and CF-RT (p = 0.5), and median PFS was 7.7 and 5.8 months, respectively (p = 0.8). HF-RT or CF-RT did not influence OS/PFS on univariable analysis. Grade 3 radionecrosis rate was 6.7% and 7.7%, respectively. 15 of 1135 studies screened from a systematic search were eligible for meta-analysis. For studies involving temozolomide, pooled median OS and PFS with HF-RT were 17.5 and 9.9 months (927 and 862 patients). Studies using shortened HF-RT schedules reported 0–2% Grade 3 radionecrosis rates.ConclusionHF-RT may offer equivalent outcomes and reduce treatment burden compared to CF-RT in young, fit GBM patients.

Impact of Single and Dual Immune Checkpoint Blockade on Risk of Radiation Necrosis among Patients with Brain Metastases Treated with Stereotactic Radiosurgery

<h3>Purpose/Objective(s)</h3> While stereotactic radiosurgery (SRS) is often an efficacious treatment for brain metastases, it carries a significant risk of radionecrosis (RN). Single and dual immune checkpoint inhibition (ICPI) have emerged as common treatment options for many patients, particularly those with melanoma and non-small cell lung cancer (NSCLC). Frequently, patients with brain metastases treated with SRS will also receive ICPI. While data suggest a cancer control benefit of combining SRS and ICPI, we hypothesized that concurrent receipt of dual ICPI with SRS increases the risk for RN. <h3>Materials/Methods</h3> We performed a retrospective review of serial patients with metastatic melanoma or NSCLC treated with SRS for intact brain metastases from 2014-2020 at our single institution. Patients were stratified by receipt of dual vs. single ICPI vs. SRS alone. RN was biopsy confirmed or determined radiographically, in combination with clinical assessment and steroid use. Kaplan-Meier estimates were used to compare rates of RN between cohorts. <h3>Results</h3> 673 brain lesions from 93 patients met inclusion criteria [median (Q1, Q3): 5.0 (2.0-10.0) lesions per patient]. Median follow-up of lesions was 8.1 months (95% CI: 7.3, 8.7). Median age and Karnofsky Performance Status of patients were 64.5 years and 90, respectively. Most (82.8%) lesions were supratentorial and histologies included melanoma (53.5%), adenocarcinoma NSCLC (27.3%), squamous cell NSCLC (6.1%), and NSCLC NOS (6.1%). In the entire cohort, 88 lesions from 25 patients (27%) developed RN. 77 (87%) lesions were diagnosed clinico-radiographically and 11 (13%) were biopsy-proven. ICPI use was highly enriched among lesions that developed RN (85.2%) versus those that did not (19.8%). Freedom from RN at 6 months was 80% for dual ICPI, 82% for single ICPI, and 97% for SRS alone; 12-month rates were 78% in each of the ICPI cohorts and 95% with SRS alone (P=0.0002). Rates of symptomatic RN, as measured by frequency of neurologic complications and hospitalization, were not significantly increased with the addition of ICPI to SRS. <h3>Conclusion</h3> In a large cohort of SRS-treated brain metastases, we observed an increased risk of RN among patients who received either dual or single ICPI concurrently with SRS. These results may guide clinical decision-making when performing radiographic surveillance of brain metastases following SRS. Prospective studies to validate these findings are warranted.

Mature Local Control and Radiation Necroses Outcomes Specific to Brain Metastases Treated with Salvage Stereotactic Radiosurgery for Radiosurgical Failures

<h3>Purpose/Objective(s)</h3> The management of locally recurrent brain metastases is a clinical challenge. A second course of radiosurgery may be delivered as the primary salvage treatment or as postoperative radiosurgery to the surgical cavity if the recurrence resected. We report our institutional experience of repeat radiosurgery for locally recurrent brain metastases, with a focus on local control and radionecrosis (RN) outcomes. <h3>Materials/Methods</h3> We report a single institution retrospective cohort study specific to patients with recurrent brain metastases treated with repeat radiosurgery. Clinical and dosimetric details were collected. Overall survival was estimated using the Kaplan Meier method. Local recurrence and RN rates were estimated using the Aalen-Johnson method, with death from any cause as the competing risk for both endpoints. Univariable competing risk regression using Fine and Gray's methods were performed, and subsequent multivariable (MVA) regression based on a priori variable selection generated final adjusted models. <h3>Results</h3> We identified 96 patients and 130 brain metastases re-treated with radiosurgery (either single fraction or hypofractionation between July 2010 to April 2020. The most common primary sites were lung (N = 44, 33.8%), breast, (N = 38, 29.2%), and melanoma (N = 26, 20%). More than half of the retreated lesions were postoperative cavities (N = 68, 52.3%). Re-treatment was most commonly delivered with 25 Gy in 5 fractions (N = 77, 59.2%) followed by 27.5 Gy in 5 fractions (N = 23, 17.7%). The mean BED₁₀ was 39.71 Gy (standard deviation [SD] 6.16) with a mean treatment volume of 14.94 cm³ (SD, 20.15). Nearly half (N = 64, 49.2%) of lesions were treated in the absence of systemic therapy, while 43.8% (N = 57) and 6.9% (N = 9) were treated while receiving targeted therapy/immunotherapy and chemotherapy, respectively. The median time between treatment courses was 13.7 months (IQR 10.88). With a median follow up of 34.9 months (interquartile range [IQR] 25-41.9), the 1 and 2-year overall survival rates were 59.8% (95% confidence interval [95% CI] 50.4-70.9) and 36.2% (95% CI, 27.2-48.2), respectively. The risk of local failure at 1 and 2 years was 26.2% (95%CI, 18.5-34) and 28% (95%CI, 20.1-35.9), respectively. MVA identified increasing target volume (hazard ratio [HR] 1.03; 95% CI, 1.02-1.04), and a shorter time-interval between radiosurgery courses (HR 0.29; 95% CI, 0.19-0.45) to be associated with worse local control. The crude incidence of RN was 18.5% (N = 24), of which 8 events (6.15%) were symptomatic. The 1 and 2-year rates of RN were 17.6% (95% CI, 10.9-34) and 19.3% (95%CI, 12.3-35.9), respectively. <h3>Conclusion</h3> Repeat radiosurgery for locally recurrent brain metastases results in good local control with a moderate risk of RN. Larger target volume and a shorter timeframe between radiosurgery treatments are associated with worse control.

Impact of the Neuro-Radiologist and Neuro-Surgeon in Contouring With the Neuro-Oncologist on Local Relapse Rates for Brain Metastases Treated With Stereotactic Radiosurgery

Abstract AIMS The audit evaluates the value of MDT, including neuro-radiologist and neuro-surgeon, review of contouring carried out by a clinical oncologist in stereotactic radiosurgery (SRS). METHOD Lesions were contoured first by clinical oncologist then reviewed/edited by MDT. Iinitial contour was compared with final using Jaccard conformity and geographical miss indices. Dosimetric impact of contouring change was assessed using plan metrics to both original and final contour. The impact of contouring review on local relapse, overall survival and radio necrosis rate was evaluated with at least 24 months follow up. RESULTS 113 patients and 142 lesions treated over 22 months were identified. Mean JCI was 0.92 (0.32-1.00) and 38% needed significant editing (JCI&amp;lt;0.95). Mean GMI was 0.03 (0.0-0.65) and 17% showed significant miss (GMI&amp;gt;0.05). Resection cavities showed more changes, with lower JCI and higher GMI (p&amp;lt;0.05). Dosimetric analysis indicated a strong association of conformity with PTV dose metrics. Greater association was seen in resection cavity, i.e. geographical nature of a typical contouring error gives rise to greater potential change in dose. Clinical outcomes compared well with published series. Median survival was 20 months and local relapse free rate of 0.89 (0.8-0.94) at 40 months. Radio-necrosis free rate 0.9 (0.83-0.95) at 40 months with median 17 months to developing radionecrosis for those that did. CONCLUSION MDT contour review adds significant value to SRS resulting in reduced local recurrence rates. No improvement in clinical oncologist contouring over time was shown indicating a collaborative approach is needed regardless of experience of clinical oncologist - particularly for resection cavities.

Focal cavity radiotherapy after neurosurgical resection of brain metastases: sparing neurotoxicity without compromising locoregional control

PurposeDoes focal cavity radiotherapy after resection of brain metastasis “spare” whole-brain radiotherapy, which is associated with toxicity for patients, through the complete course of their disease without compromising long-term local control of the brain?MethodsWe retrospectively analyzed outcomes of patients who underwent adjuvant focal cavity radiotherapy between 2014 and 2021 at our center.ResultsA total of 83 patients with 86 resected brain metastases were analyzed. 64% had singular, 36% two to four brain metastases. In cases with multiple metastases, omitted lesions were treated with radiosurgery. Median follow-up was 7.3 months (range 0–71.2 months), 1‑year overall survival rate was 57.8% (95% CI 44.9–68.8%). Radiotherapy was administered with a median biologically effective dose (α/β 10) surrounding the planning target volume of 48 Gy (range 23.4–60 Gy). Estimated 1‑year local control rate was 82.7% (95% CI 67.7–91.2%), estimated 1‑year distant brain control rate was 55.7% (95% CI 40.5–68.4%), estimated 1‑year leptomeningeal disease rate was 16.0% (95% CI 7.3–32.9%). Eleven distant brain recurrences could be salvaged with radiosurgery. In the further course of disease, 14 patients (17%) developed disseminated metastatic disease in the brain. Estimated 1‑year free of whole-brain radiotherapy rate was 72.3% (95% CI 57.1–82.9%). All applied treatments led to an estimated 1‑year neuro-control rate of 79.1% (95% CI 65.0–88.0%), estimated 1‑year radionecrosis rate was 23% (95% CI 12.4–40.5%).ConclusionIn our single-center study, focal cavity radiotherapy was associated with high local control. In three out of four patients, whole-brain radiotherapy could be avoided in the complete course of disease, using radiosurgery as salvage approach without compromising neuro-control.

Radiosurgery for multiple brain metastases using volumetric modulated arc therapy: a single institutional series.

BackgroundPatients with brain metastases (BM) live longer due to improved diagnosis and oncologic treatments. The association of volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with brain radiosurgery (SRS) allows complex dose distributions and faster treatment delivery to multiple lesions.Materials and methodsThis study is a retrospective analysis of SRS for brain metastasis using VMAT. The primary endpoints were local disease-free survival (LDFS) and overall survival (OS). The secondary outcomes were intracranial disease-free survival (IDFS) and meningeal disease-free survival (MDFS).ResultsThe average number of treated lesions was 5.79 (range: 2–20) per treatment in a total of 113 patients. The mean prescribed dose was 18 Gy (range: 12–24 Gy). The median LDFS was 46 months. The LDFS in 6, 12, and 24 months was for 86%, 79%, and 63%, respectively. Moreover, brain progression occurred in 50 patients. The median overall survival was 47 months. The OS in 75%, 69%, and 61% patients was 6, 12, and 24 months, respectively. IDFS was 6 and 24 months in 35% and 14% patients, respectively. The mean MDFS was 62 months; it was 6 and 24 months for 87% and 83% of patients. Acute severe toxicity was relatively rare. During follow-up, the rates of radionecrosis and neurocognitive impairment were low (10%).ConclusionThe use of VMAT–SRS for multiple BM was feasible, effective, and associated with low treatment-related toxicity rates. Thus, treatment with VMAT is a safe technique to plan to achieve local control without toxicity.

MMAP-07 IMPACT OF SINGLE AND DUAL IMMUNE CHECKPOINT BLOCKADE ON RISK OF RADIATION NECROSIS AMONG PATIENTS WITH BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY

PURPOSEWhile stereotactic radiosurgery (SRS) is often an efficacious treatment for brain metastases, it carries a significant risk of radionecrosis (RN). Single and dual immune checkpoint inhibition (ICPI) have emerged as common treatment options for many patients, particularly those with melanoma and non-small cell lung cancer (NSCLC). While data suggest a cancer control benefit of combining SRS and ICPI, we hypothesized that concurrent receipt of dual ICPI with SRS increases the risk for RN. METHODSWe performed a retrospective review of serial patients with metastatic melanoma or NSCLC treated with SRS for intact brain metastases from 2014-2020 at our single institution. Patients were stratified by receipt of dual vs. single ICPI vs. SRS alone. RN was biopsy confirmed or determined radiographically, in combination with clinical assessment and steroid use. Kaplan-Meier estimates were used to compare rates of RN between cohorts. RESULTS673 brain lesions from 93 patients met inclusion criteria [median (Q1, Q3): 5.0 (2.0-10.0) lesions per patient]. Median follow-up of lesions was 8.1 months (95% CI: 7.3, 8.7). Most (82.8%) lesions were supratentorial and histologies included melanoma (53.5%), adenocarcinoma NSCLC (27.3%), squamous cell NSCLC (6.1%), and NSCLC NOS (6.1%). In the entire cohort, 88 lesions from 25 patients (27%) developed RN. 77 (87%) lesions were diagnosed clinico-radiographically and 11 (13%) were biopsy-proven. ICPI use was highly enriched among lesions that developed RN (85.2%) versus those that did not (19.8%). Freedom from RN at 6 months was 80% for dual ICPI, 82% for single ICPI, and 97% for SRS alone; 12 month rates were 78% in each of the ICPI cohorts and 95% with SRS alone (P=0.0002). CONCLUSIONSIn a large cohort of SRS-treated brain metastases, we observed an increased risk of RN among patients who received either dual or single ICPI concurrently with SRS.

Mean Brain Dose Remains Uninfluenced by the Lesion Number for Gamma Knife Stereotactic Radiosurgery for 10+ Metastases

Gamma Knife (GK) stereotactic radiosurgery (SRS) is increasingly used as an initial treatment for patients with 10 or more brain metastases. However, the clinical and dosimetric consequences of this practice are not well established. We performed a single-institution, retrospective analysis of 30 patients who received Gamma Knife SRS for 10 or more brain metastases in 1 session. We utilized MIM Software to contour the whole brain and accumulated the doses from all treated lesions to determine the mean dose delivered to the whole brain. Patient outcomes were determined from chart review. Our cohort had a median number of 13 treated lesions (range 10-26 lesions) for a total of 427 treated lesions. The mean dose to the whole brain was determined to be 1.8±0.91Gy (range 0.70-3.8Gy). The mean dose to the whole brain did not correlate with the number of treated lesions (Pearson r= 0.23, P= 0.21), but was closely associated with tumor volume (Pearson r= 0.95, P < 0.0001). There were no significant correlations between overall survival and number of lesions or aggregate tumor volume. Fourteen patients (47%) underwent additional SRS sessions and 6 patients (20%) underwent whole-brain radiotherapy with a median of 6.6months (range 3.0-50months) after SRS. Two patients (6.6%) developed grade 2 radionecrosis following SRS beyond earlier whole-brain radiotherapy. The mean dose to the whole brain in patients treated with Gamma Knife SRS for 10 or more brain metastases remained low with an acceptable rate of radionecrosis. This strategy allowed the majority of patients to avoid subsequent whole-brain radiotherapy.

Local control and radionecrosis of brain metastases from non-small-cell lung cancer treated by hypofractionated stereotactic radiotherapy: Evaluation of predictive factors

BackgroundThe objective of our study was to report predictive factors of local control (LC) and radionecrosis (RN) of brain metastases (BM) of non-small cell lung carcinoma (NSCLC) treated by multifractionated stereotactic radiotherapy (MF-SRT) according to French recommendations. MethodFrom 2012 to 2020, 87 patients with 101 BM were retrospectively included. The median age was 63 years (37–85). GTV was defined using contrast-enhanced T1w MRI and was isotropically extended by 2 mm to form PTV. Mean maximum BM diameter was 24.5 mm (10–46). Patients were treated with dynamic arctherapy from May 2012 to February 2016 and then with VMAT. The totalprescribed dose was 23.1 Gy prescribed to the encompassing 70% isodose, in 3 fractions. ResultsLC rates at 6 months, 1 year and 2 years was 95.7%, 90.7% and 87.9% respectively. In multivariate analysis, high GTV Dmin (HR = 0.822, p = 0.012) was in favor of better LC whereas a large maximum diameter was predictive of poor LC (HR = 1.124, p = 0.02). GTV Dmin of 27.4 Gy was identified as a discriminant threshold of LC. In case of GTV Dmin ≥ 27.4 Gy, LC at 1 year was 95.3% versus 75.1% with GTV Dmin < 27.4 Gy. Cumulative incidence of RN at 6 months, 1 year and 2 years was 6.3%, 15.4% and 18.1%, respectively. In multivariate analysis, only dyslipidemia was predictive of RN (HR = 2.69, p = 0.03). No dosimetric predictive factor of RN was found in our study. ConclusionMF-SRT (3x7.7 Gy on 70% isodose line, with PTV = GTV + 2 mm; according to French recommendations) of BM from NSCLC gives high LC rates with acceptable RN rate. A GTV Dmin of at least 27.4 Gy could be proposed to optimize dosimetric objectives. No dosimetric predictive factors of RN were found in this study. However, dyslipidemia was identified as a potential predictive factor of RN.