Recurrent Intracranial Tumors Research Articles

Early Experience and Perioperative Risk of GammaTile® for Upfront Brain Metastases: Report from a Prospective Multicenter Study

Abstract Background GammaTile (GT), a form of brachytherapy utilizing cesium-131 seeds in a bioresorbable collagen tile, has gained popularity for treatment of recurrent intracranial tumors and more recently for newly diagnosed metastases. This study reports early experience utilizing GT in upfront brain metastases with a focus on clinical applications and perioperative safety. Methods The STaRT Registry (NCT04427384) was queried for all patients receiving GT for upfront metastases from August 2021 to August 2023. Data regarding patient demographics, procedure details, and adverse events (AEs) were extracted and analyzed. Results Twenty-eight patients, median age 65 years (range 28-81), with 30 treated metastases were reported from 6 institutions. Patients had 2.8 metastases on average (range 1-15) at time of surgery; however, most patients had a single metastasis (60.7%). Mean diameter of treated metastases was 3.4 cm (range 1.5-4.7). A median of 4.0 tiles (range 1-10) were used per tumor. The median follow-up was 3.0 months (range 1.0-11.2) with 6 attributed AEs (21.4%), including one Grade ≥3 (infection). In the immediate postoperative period (<14 days), two patients reported pain or headache, and one reported facial edema. One patient developed seizures on postoperative day 8 requiring medication. At one-month follow-up, there was one superficial wound infection, in a previously colonized patient, requiring surgical intervention without explantation of tiles. At three-month follow-up, one patient reported facial pain not requiring treatment. There were no symptomatic hematomas. Conclusions GammaTile demonstrates a favorable safety profile in upfront brain metastases with a 3.6% rate of serious AEs (Grade ≥3) within 90 days of the procedure.

Conventionally fully fractionated Gamma Knife Icon re-irradiation of primary recurrent intracranial tumors: the first report indicating feasibility and safety.

With the incorporation of real-time image guidance on the Gamma Knife system allowing for mask-based immobilization (Gamma Knife Icon [GKI]), conventionally fully fractionated (1.8-3.0 Gy/day) GKI radiation can now be delivered to take advantage of an inherently minimal margin for delivery uncertainty, sharp dose falloff, and inhomogeneous dose distribution. This case series details the authors' preliminary experience in re-irradiating 7 complex primary intracranial tumors, which were considered to have been previously maximally radiated and situated adjacent to critical organs at risk. The authors retrospectively reviewed all patients who received fractionated re-irradiation using GKI at the Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada, between 2016 and 2021. Patients with brain metastases, and those who received radiotherapy courses in 5 or fewer fractions, were excluded. All radiotherapy doses were converted to the equivalent total dose in 2-Gy fractions (EQD2), with the assumption of an α/β ratio of 2 for late normal tissue toxicity and 10 for the tumor. A total of 7 patients were included in this case series. Three patients had recurrent meningiomas, as well as 1 patient each with ependymoma, intracranial sarcoma, pituitary macroadenoma, and papillary pineal tumor. Six patients had undergone prior linear accelerator-based conventional fractionated radiotherapy and 1 patient had undergone prior proton therapy. Patients were re-irradiated with a median (range) total dose of 50.4 (30-63.4) Gy delivered in a median (range) of 28 (10-38) fractions with GKI. The median (range) target volume was 6.58 (0.2-46.3) cm3. The median (range) cumulative mean EQD2 administered to the tumor was 121.1 (107.9-181.3) Gy, and the median (range) maximum point EQD2 administered to the brainstem, optic nerves, and optic chiasm were 91.6 (74.0-111.5) Gy, 58.9 (6.3-102.9) Gy, and 59.9 (36.7-127.3) Gy, respectively. At a median (range) follow-up of 15 (6-42) months, 6 of 7 patients were alive with 4 having locally controlled disease. Only 3 patients experienced treatment-related toxicities, which were self-limited. Fractionated radiotherapy using GKI may be a safe and effective method for the re-irradiation of complex progressive primary intracranial tumors, where the aim is to minimize the potential for serious late effects.

Resection of Recurrent Intracranial Tumors for Molecular Diagnostics in the Age of Precision Oncology: A Risk-Benefit Analysis

Resection of Recurrent Intracranial Tumors for Molecular Diagnostics in the Age of Precision Oncology: A Risk-Benefit Analysis

Repeat laser interstitial thermal therapy for recurrent primary and metastatic intracranial tumors.

Background: Repeat craniotomy in patients with primary and metastatic brain tumors carries significant morbidity and can delay adjuvant treatments. Repeat laser interstitial thermal therapy (LITT) for recurrent disease has been described and could benefit patients with limited cytoreductive options. We aim to describe the indications, safety, and efficacy of repeat LITT for recurrent primary and metastatic intracranial tumors.Methods: Patients undergoing repeat ablations for the same lesion were included in the study. We retrospectively analyzed 13 patients treated with 29 total LITT ablations.Results: Eleven patients were treated for glioblastoma (GBM), while two had brain metastases. Eleven patients had LITT performed only 2 times, while three patients underwent three total iterations of LITT for disease recurrence. Median length of stay after the 1st ablation was 2 days, while the median length of stay after the 2nd ablation was 1 day. The median time to resuming adjuvant treatments after the 1st LITT was 11 days. The median time to resuming adjuvant treatments after the 2nd LITT was 28 days. Four patients after the 1st and 2nd LITT sustained deficits persisting through 30-day follow-up. The median progression-free survival among the GBM patients from the first ablation was 6.0 months, 3.2 months from the 2nd ablation, and 2.1 months from the 3rd ablation.Conclusion: Recurrent tumors, especially GBM, can be safely treated using repeat LITT when surgery cannot be effectively performed. Our results indicate that patients tolerate the procedure well and have a meaningful survival given the salvage nature of the procedure.

CTNI-59. A MULTICENTER OBSERVATIONAL STUDY OF CS-131 SEEDS EMBEDDED IN A COLLAGEN CARRIER TILE FOR NEWLY DIAGNOSED AND RECURRENT OPERABLE INTRACRANIAL NEOPLASMS – TRIAL IN PROGRESS

Abstract BACKGROUND For patients with operable intracranial neoplasms, there are opportunities to augment local control beyond traditional methods, such as external beam radiation therapy. Brachytherapy, the implantation of radioactive sources into the resection cavity, can be useful in this setting by providing immediate initiation of radiation and limiting the exposure of surrounding normal tissue to radiation. Traditional intracranial brachytherapy has been limited by uneven dose distributions, complicated workflows, extended procedural times, cost of dedicated equipment, and frequent adverse events. To address these issues, a permanently implanted device with Cs-131 radiation seeds embedded in a bioresorbable collagen carrier tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. Described as surgically targeted radiation therapy (STaRT), it is FDA-cleared for use in newly-diagnosed malignant intracranial neoplasms and recurrent intracranial tumors, and has demonstrated excellent safety and efficacy in early commercial use. The primary objectives of this multicenter, prospective, observational (phase IV) registry study are to evaluate “real-world” clinical outcomes and patient-reported outcomes that measure the safety and efficacy of STaRT using the GammaTile. METHODS Patients undergoing resection (R) of brain tumors with intra-operative GammaTile placement are eligible for enrollment. Planned sample size is 600 at up to 50 enrolling sites. First subject was enrolled 10/14/2020. Tumor pathology, overall survival, radiation- and surgery-related adverse events, patient- and provider-reported quality of life, serial MRIs, and timing of surgical bed and/or distant recurrence are collected. Powered primary endpoints for recurrent brain metastases, recurrent glioblastoma, and recurrent meningioma (surgical bed-progression free survival (PFS), overall survival, and PFS, respectively), compare STaRT to standard-of-care benchmarks. Results will be used to improve awareness and access to this treatment, benchmark clinical outcomes in the real-world setting, allow for comparisons to existing treatments, facilitate the design of future clinical trials, and contribute to the optimal sequencing of treatments for intracranial neoplasms.

INNV-32. ACCESS TO SPECIALTY RADIATION CARE FOR PATIENTS WITH RESECTABLE BRAIN TUMORS

Abstract INTRODUCTION Many patients with brain tumors face challenges with access to care. For rural patients, prolonged travel times may limit access to appropriate radiotherapy. Radiation centers (RCs) offering specialized brain radiotherapy, e.g., stereotactic radiosurgery (SRS), are geographically limited. Brain brachytherapy at the time of resection offers an option for such patients, but technical challenges have limited the adoption. To address the limitations of traditional brachytherapy, a device with Cs-131 seeds embedded in a bioresorbable collagen tile (GammaTile (GT), GT Medical Technologies, Tempe, AZ) was developed. The device is FDA-cleared for permanent implantation at the time of resection for all recurrent intracranial tumors and newly diagnosed malignant intracranial neoplasms. To investigate if wider availability of this treatment could possibly lower the geographic barrier to access to care, we mapped the US population against existing RCs with brain tumor expertise and neurosurgery centers (NSCs) performing craniotomies. METHODS We analyzed 2018 CMS claims data using CPT codes for single- and multi-fraction SRS to identify RCs with brain tumor treatment expertise and mapped these against the population. Using similar methodology, using CPT codes for craniotomies, we identified NSCs, as any facility performing craniotomies is potentially eligible to implant the device. RESULTS 135 RCs used CPT codes for SRS. 193-, 119-, 82-, and 52-million Americans lived >30-, >60-, >90-, and >120-minutes from one of these centers, respectively. 530 NSCs preform craniotomies, including ≥ 1 in every state, a 4-fold increase over the number of RCs offering SRS. CONCLUSIONS For many patients, substantial travel distances limit access to RCs with brain tumor treatment expertise. In contrast, the 530 craniotomy-performing NSCs have far greater geographic dispersion. The option of undergoing brain radiation with GT implantation at the time of brain tumor craniotomy brings treatment closer to millions, ensures compliance, and reduces additional travel for follow-up radiation treatment.

Definitive Reirradiation of Intracranial Neoplasms With Intensity-Modulated Proton Therapy: Early Outcomes and Toxicities

Management of recurrent or new primary intracranial tumors in a previously irradiated area presents a significant challenge. For inoperable patients, reirradiation (re-RT) may provide the best chance for prolonged disease control. However, given concerns for excessive morbidity, re-RT with definitive doses (≥ 45 Gy) is not commonly prescribed. Given its dosimetric advantages over photon-based techniques, we hypothesize that intensity-modulated proton therapy (IMPT) may permit safer dose escalation in the re-RT setting. This study examined feasibility of definitive brain re-RT in a cohort of patients treated with IMPT.The electronic medical record of a pencil beam scanning-only proton center was queried for adult patients who developed in-field recurrence or new primary tumor for which they subsequently received definitive-dose (≥ 45 Gy) re-RT. Dosimetric and clinical characteristics were collected. Survival was examined using the Kaplan-Meier method. Toxicities were assessed using the Common Terminology Criteria for Adverse Events v.5.0.Between August 2019 and February 2021, 62 consecutive patients received intracranial re-RT with IMPT. Twelve (18%) were treated to ≥ 45 Gy and were included for analysis. Median age at the time of re-RT was 51.5 years, and 83% of patients had an Eastern Cooperative Oncology Group score of 0. The most common histologies were oligodendroglioma (n = 4), astrocytoma (n = 3), and meningioma (n = 3). Median time from prior radiation course to IMPT was 9.4 years (range, 3.6 - 42.0 years). IMPT was delivered with conventional fractionation in 92% and hypofractionation in 8% of cases. Median equivalent dose in 2 Gy fractions (EQD2) for initial course was 53.1 Gy. Median EQD2 for the re-RT course was 54.0 Gy. The entire re-RT course was completed as planned by 83% of patients. Patients received concurrent temozolomide (66%) or temozolomide plus bevacizumab plus nivolumab (8%). Dosimetric data from the initial course were available for 58% of patients. The median cumulative (initial radiation and re-RT combined) maximum EQD2 doses were 116.8 Gy to brain, 66.2 Gy to brainstem, 67.7 Gy to chiasm, 72.0 Gy to ipsilateral optic nerve, and 54.5 Gy to contralateral optic nerve. At a median follow-up of 5.4 months, 58.3% (n = 7) of patients developed grade 2 toxicities including fatigue (n = 6) and alopecia (n = 5). No grade ≥3 neurotoxicities were documented. Median progression free survival was 7 months; median overall survival was not reached.Early results of our single-institution experience suggest a potential for safe intracranial re-RT with definitive-dose IMPT for select patients. Based on these findings, we are activating a prospective study to identify subsets of patients who are best fit for IMPT re-RT and formulate optimal dose regimens and normal tissue composite dose constraints.L. Maillie: None. S. Sharma: None. J.T. Yang: None. N. Ohri: Consultant; Merck, AstraZeneca. I.J. Choi: Employee; New York Proton Center. Travel Expenses; Varian; National Association of Proton Therapy, Proton Collaborative Group. Oversee and provide guidance for new and existing research protocols, ensure best practices for organization research endeavors.; Proton Collaborative Group. B.K. Yeh: None. R.H. Press: None. A. Chhabra: None. M.K. Garg: None. Y. Yamada: Consultant; University of Wollongong. Speaker's Bureau; Varian Medical Systems, BrainLab. Medical advisor; Chordoma Foundation. C.B. Simone: Employee; New York Proton Center. Honoraria; Varian Medical System, Novocure. Travel Expenses; Varian Medical System; Proton Collaborative Group (PCG), Annals of Palliative Medicine, American Society for Radiation Oncology. S. Lazarev: None.

TRLS-05. A multicenter observational study of Cs-131 seeds embedded in a collagen carrier tile for newly diagnosed and recurrent operable intracranial neoplasms –Trial in progress

Abstract Background For patients with operable intracranial neoplasms, there are opportunities to augment local control beyond traditional methods, such as external beam radiation therapy (EBRT),. Brachytherapy, the implantation of radioactive sources into the resection cavity, can be useful in this setting by providing immediate initiation of radiation and limiting the exposure of surrounding normal tissue to radiation. Traditional intracranial brachytherapy methods have been limited by uneven dose distributions, complicated workflows, extended procedural times, the cost of dedicated equipment, and frequent adverse events. To address these issues, a permanently implanted device with Cs-131 radiation seeds embedded in a bioresorbable collagen carrier tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. Described as surgically targeted radiation therapy (STaRT), it is FDA-cleared for use in newly-diagnosed malignant intracranial neoplasms and recurrent intracranial tumors, including brain metastases, and has demonstrated excellent safety and local control in early commercial use. The primary objectives of this multicenter, prospective, observational (phase IV) registry study [NCT04427384] are to evaluate “real-world” clinical outcomes and patient-reported outcomes that measure the safety and efficacy of STaRT using the device. Methods Subjects (N=600) at up to 50 enrolling sites undergoing resection of brain tumors of any pathology with intra-operative GammaTile placement are eligible for enrollment. We project 40% of enrollees to have brain metastasis. Tumor pathology, overall survival, radiation- and surgery-related adverse events, quality of life, serial MRIs, and timing of surgical bed recurrence and/or distant recurrence will be collected. The powered primary endpoint for recurrent brain metastases, surgical bed-progression free survival, will compare STaRT to standard-of-care benchmarks. This study will be the first observational study of resection plus GammaTile. Results will be used to benchmark clinical outcomes in the real-world setting, allow for comparisons to existing treatments, and facilitate the design of future clinical trials.

A multicenter observational study of cs-131 seeds embedded in a collagen carrier tile in intracranial brain neoplasms: Trial in progress.

TPS2073 Background: Brachytherapy is an efficacious means for radiation delivery in the treatment of a spectrum of central nervous system tumors. Traditional brachytherapy methods have been limited by uneven dose distribution, complicated workflow, extended procedural times, the cost of dedicated equipment, and frequent adverse events. To address these issues, a permanently implanted device with Cs-131 radiation seeds embedded in a bioresorbable collagen carrier tile (GammaTile [GT], GT Medical Technologies, Tempe, AZ USA) was developed. Described as surgically targeted radiation therapy (STaRT) to distinguish it from external beam radiation therapy, the device is FDA-cleared for use in newly diagnosed malignant intracranial neoplasms and recurrent intracranial tumors, and has demonstrated excellent safety and local control outcomes in early commercial use. Methods: The overarching primary objectives of this multicenter, prospective, observational (phase IV) registry study are to evaluate “real-world” clinical outcomes and patient reported outcomes that measure the safety and efficacy of STaRT using the GT device. The registry is planned for 600 prospectively enrolled subjects at up to 50 enrolling sites. All adult patients undergoing surgical resection of brain tumors of any pathology with intra-operative GT placement are eligible for enrollment, upon consent. Information on patient demographics, tumor pathology, overall survival, adverse events related to radiation or surgery, and quality of life (FACT-Br and LASA) will be collected. Serial MRIs will be collected, and timing of surgical bed recurrence and/or distant recurrence will be collected. Data will be collected at 1-, 3-, 6-, 9-, 12-, 18-, and 24-months, then every 6 months through 5 years. Results will be used to benchmark clinical outcomes of GT therapy, allow for comparisons to other existing treatments, and facilitate the design of future clinical trials. Enrollment opened on November 15, 2020, and seven subjects have been enrolled to date at three centers. This study will be the first observational study of resection plus STaRT, delivered by Cs-131 sources in permanently implanted bioresorbable collagen tile carriers, and will allow for evaluation of this treatment approach in a real world setting, as well as provide an information platform for cross-comparison of results obtained from ongoing GT clinical trials. Clinical trial information: NCT04427384.

Access to radiation oncology centers with brain tumor treatment expertise for patients with resectable brain tumors.

e18509 Background: Many patients with brain tumors face challenges with access to care. For rural patients, prolonged travel times may limit access to appropriate radiotherapy. Radiation centers (RCs) offering specialized brain radiotherapy, e.g., stereotactic radiosurgery (SRS), are geographically limited. Utilization of brain brachytherapy at the time of resection offers an option for such patients, but technical challenges have limited the adoption. To address the limitations of traditional brachytherapy, a device with Cs-131 seeds embedded in a bioresorbable collagen tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. GammaTile (GT) is FDA-cleared for permanent implantation at the time of resection for all recurrent intracranial tumors and for newly diagnosed malignant intracranial neoplasms. To investigate if wider availability of this treatment could possibly lower the geographic barrier to access to care, we mapped the US population against existing RCs with brain tumor expertise and neurosurgery centers (NSCs) performing craniotomies. Methods: We analyzed 2018 CMS claims data using CPT codes for single- and multi-fraction SRS to identify RCs with brain tumor treatment expertise and mapped these against the population. Using similar methodology, using CPT codes for craniotomies, we identified NSCs, as any facility performing craniotomies is potentially eligible to implant GT. Results: 135 RCs used CPT codes for SRS. 193-, 119-, 82-, and 52-million Americans lived >30-, >60-, >90-, and >120-minutes from one of these centers, respectively. 530 NSCs preform craniotomies, including ≥1 in every state, a 4-fold increase over the number of RCs offering SRS. Conclusions: For many patients, substantial travel distances limit their access to RCs with brain tumor treatment expertise. In contrast, the 530 craniotomy-performing NSCs have far greater geographic dispersion. The option of undergoing brain radiation with GT implantation at the time of brain tumor craniotomy brings treatment closer to millions, ensures compliance, and reduces additional travel for follow-up radiation treatment.[Table: see text]

CovidNeuroOnc: A UK multicenter, prospective cohort study of the impact of the COVID-19 pandemic on the neuro-oncology service.

BackgroundThe COVID-19 pandemic has profoundly affected cancer services. Our objective was to determine the effect of the COVID-19 pandemic on decision making and the resulting outcomes for patients with newly diagnosed or recurrent intracranial tumors.MethodsWe performed a multicenter prospective study of all adult patients discussed in weekly neuro-oncology and skull base multidisciplinary team meetings who had a newly diagnosed or recurrent intracranial (excluding pituitary) tumor between 01 April and 31 May 2020. All patients had at least 30-day follow-up data. Descriptive statistical reporting was used.ResultsThere were 1357 referrals for newly diagnosed or recurrent intracranial tumors across 15 neuro-oncology centers. Of centers with all intracranial tumors, a change in initial management was reported in 8.6% of cases (n = 104/1210). Decisions to change the management plan reduced over time from a peak of 19% referrals at the start of the study to 0% by the end of the study period. Changes in management were reported in 16% (n = 75/466) of cases previously recommended for surgery and 28% of cases previously recommended for chemotherapy (n = 20/72). The reported SARS-CoV-2 infection rate was similar in surgical and non-surgical patients (2.6% vs. 2.4%, P > .9).ConclusionsDisruption to neuro-oncology services in the UK caused by the COVID-19 pandemic was most marked in the first month, affecting all diagnoses. Patients considered for chemotherapy were most affected. In those recommended surgical treatment this was successfully completed. Longer-term outcome data will evaluate oncological treatments received by these patients and overall survival.

COVD-15. COVIDNEUROONC: A UK MULTI-CENTRE, PROSPECTIVE COHORT STUDY OF THE IMPACT OF THE COVID-19 PANDEMIC ON THE NEURO-ONCOLOGY SERVICE

BACKGROUNDThe COVID-19 pandemic has profoundly affected cancer services. Our objective was to determine the effect of the COVID-19 pandemic on decision making and the resulting outcomes for patients with newly diagnosed or recurrent intracranial tumors.METHODSWe performed a multi-centre prospective study of all adult patients discussed in weekly neuro-oncology and skull base MDTs who had a newly diagnosed or recurrent intracranial (excluding pituitary) tumor between 01 April and 31 May 2020. All patients had follow-up data at least 30-days after the index MDT date. Descriptive statistical reporting was used.RESULTSThere were 1357 referrals for newly diagnosed or recurrent intracranial tumors across fifteen neuro-oncology centres. Of centres with all intracranial tumors, a change in initial MDT management was reported in 8.6% of cases (n=104/1210). Decisions to change the MDT management plan reduced over time from a peak of 19% referrals at the start of the study to 0% by the end of the study period. Changes in management were reported in 16% (n=75/466) of cases previously recommended for surgery and 28% of cases previously recommended for chemotherapy (n=20/72). The reported SARS-CoV-2 infection rate was similar in surgical and non-surgical patients (2.6% vs. 2.4%, p >0.9).CONCLUSIONSDisruption to neuro-oncology services in the UK caused by the COVID-19 pandemic was most marked in the first month, affecting all diagnoses. Patients considered for chemotherapy were most affected. In those recommended surgical treatment this was successfully completed. Longer-term outcome data will evaluate oncological treatments received by these patients and overall survival.

Reduced-Dose Whole Brain Radiation Therapy Combined With Stereotactic Irradiation For Solitary Or Oligo Brain Metastases Aiming At Minimizing Deterioration Of Neurocognitive Function Without Compromising Intracranial Tumor Control: Preliminary Results

To minimize cognitive decline without increasing the intracranial tumor recurrence rate by optimizing whole brain dose fractionation pattern when WBRT is combined with stereotactic irradiation (STI) in patients with no more than 4 brain metastases. JROSG 13-1 was a single-arm multi-institutional phase II study of RD-WBRT. At multiple institutions in Japan, eligible patients; no more than 4 brain metastases and Karnofsky Performance Status ≥ 60; received RD-WBRT of 25Gy in 10 fractions and STI. Contrast-enhanced MRI was taken at baseline and 4, 6, 9, and 12 months and every 6 months thereafter. Neurocognitive function tests including Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association and Trail Making Tests, and health-related quality of life questionnaires were performed at baseline and 4, 8, and 12 months and every 6 months thereafter. The primary endpoint was the free from incidence of new intracranial metastases at 6 months and that analyzed by Kaplan-Meier method. The free from incidence of new intracranial metastases at 6 months in the WBRT+SRS group of JROSG99-1 was 81% (95%CI: 67.4-93.6%), so this study allowed a 10% difference, up to 71%. Twenty analyzable patients were required to ensure 80% statistical power with α = 0.05. If the survival rate at six months is calculated as 60%, the minimum required number of cases was 33, but the final required number of cases was set to 40, assuming some cases of dropout. Secondary endpoints were the neurocognitive function, the intracranial local control rate, the adverse events and overall survival. Regarding neurocognitive function, early cognitive failure was defined as reliable change index decline on one or more tests at 4 months. We enrolled 40 patients with no more than 4 brain metastases at multiple institution in Japan from April 2013 to October 2018. Since the observation period ended in November 2019, the data has not yet been fixed. This presentation is preliminary results up to 6 months. The mean age was 68.3 years, 60% of primary cancers were non-small cell lung cancer, and 20 patients had solitary brain metastasis. The primary endpoint, the free-from incidence of new intracranial metastases at 6 months, was 73.8% (95%CI: 60.4-90.2%). The frequency of early cognitive failure was 65.7% (95%CI: 50.6-80.8%). RD-WBRT may not compromise free-from intracranial tumor control. However, the effect of minimizing early cognitive deterioration at 4 months was modest. The analysis of the status of neurocognitive function at 8 months or later is now underway.

The value of intraoperative MRI in recurrent intracranial tumor surgery

OBJECTIVE Identifying tumor remnants in previously operated tumor lesions remains a challenge. Intraoperative MRI (ioMRI) helps the neurosurgeon to reorient and update image guidance during surgery. The purpose of this study was to analyze whether ioMRI is more efficient in detecting tumor remnants in the surgery of recurrent lesions compared with primary surgery. METHODS All consecutive patients undergoing elective intracranial tumor surgery between 2013 and 2018 at the authors’ institution were included in this retrospective cohort study. The cohort was divided into two groups: re-craniotomy and primary craniotomy. In contrast-enhancing tumors, tumor suspicion in ioMRI was defined as contrast enhancement in T1-weighted imaging. In non–contrast-enhancing tumors, tumor suspicion was defined as hypointensity in T1-weighted imaging and hyperintensity in T2-weighted imaging and FLAIR. In cases in which the ioMRI tumor suspicion was a false positive and not confirmed during in situ inspection by the neurosurgeon, the signal was defined as a tumor-imitating ioMRI signal (TIM). Descriptive statistics were performed. RESULTS A total of 214 tumor surgeries met the inclusion criteria. The re-craniotomy group included 89 surgeries, and the primary craniotomy group included 123 surgeries. Initial complete resection after ioMRI was less frequent in the re-craniotomy group than in the primary craniotomy group, but this was not a statistically significant difference. Radiological suspicion of tumor remnants in ioMRI was present in 78% of re-craniotomy surgeries and 69% of primary craniotomy surgeries. The incidence of false-positive TIMs was significantly higher in the re-craniotomy group (n = 11, 12%) compared with the primary craniotomy group (n = 5, 4%; p = 0.015), and in contrast-enhancing tumors was related to hemorrhages in situ (n = 9). CONCLUSIONS A history of previous surgery in contrast-enhancing tumors made correct identification of tumor remnants in ioMRI more difficult, with a higher rate of false-positive ioMRI signals in the re-craniotomy group. The majority of TIMs were associated with the inability to distinguish contrast enhancement from hyperacute hemorrhage. The addition of a specific sequence in ioMRI to further differentiate both should be investigated in future studies.

Re-Irradiation Using Brachytherapy for Recurrent Intracranial Tumors: A Systematic Review and Meta-Analysis of the Literature.

IntroductionWe aim to compare the efficacy and toxicity of re-irradiation using brachytherapy for patients with locally recurrent brain tumors after previous radiation therapy. MethodsWe performed a systematic review of the major biomedical databases from 2005 to 2020 for eligible studies where patients were treated with re-irradiation for recurrent same site tumors using brachytherapy. Tumor types included high-grade gliomas (HGG) (World Health Organization (WHO) Grades 3 and 4), meningiomas, and metastases. The outcomes of interest were median overall survival (OS) and progression-free survival (PFS) after re-irradiation, the incidence of radiation necrosis (RN), and other relevant radiation-related adverse events (AE). We used a fixed-effect meta-analysis regression moderation model to compared results of interstitial versus intracavitary therapy, treatment with low-dose-rate (LDR) versus high-dose-rate (HDR) techniques, and outcomes by tumor type.ResultsThe search resulted in a total of 194 articles. A total of 16 articles with 695 patients fulfilled the inclusion criteria and were selected for analysis. For high-grade glioma, meningioma, and brain metastasis the pooled meta-analysis showed mean symptomatic RN rates of 3.3% (standard error (SE) = 0.8%), 17.3% (SE = 5.0%), and 22.4% (SE = 7.0%), respectively, and mean rates of RN requiring surgical intervention of 3.0% (SE = 1.0%), 11.9% (SE = 5.3%), and 10.0% (SE = 7.3%), respectively.The mean symptomatic RN rates in the meta-analysis comparing interstitial versus intracavitary therapy were 3.4% and 4.9%, respectively (p = 0.36), and for the comparison of LDR versus HDR, the rates were 2.6% and 5.7%, respectively (p = 0.046). In comparing the symptomatic RN rates in comparison to HGG versus meningioma, the means were 3.3% and 17.3%, respectively (p = 0.006), and in HGG versus metastatic tumors, the means were 3.3% and 22.4%, respectively (p = 0.007). There was no significant difference in rates of RN requiring surgery in any of these groups. Due to the small number of studies and inconsistent recording of OS and PFS, statistical analysis of these parameters could not be performed.ConclusionPublished literature on the same site re-irradiation using brachytherapy for recurrent brain tumors is highly limited, with inconsistent reporting of safety and efficacy outcomes. To overcome these shortcomings, we utilized a structured meta-analysis approach to show that re-irradiation with modern brachytherapy is generally safe in terms of the risks of symptomatic RN. We also found that symptomatic RN rates for brachytherapy are significantly lower in recurrent HGG compared to recurrent meningiomas (p = 0.006) and metastatic tumors (p = 0.007). Re-irradiation with brachytherapy is a feasible option for appropriately selected patients. The availability of Cesium-131 (Cs-131) shows promise in reducing toxicity while achieving excellent local control due to its physical properties, and the recent introduction of a novel surgically targeted radiation therapy device, that makes brachytherapy less technically demanding, may allow for more widespread adoption. Prospective trials with consistent reporting of endpoints are needed to explore whether these advances improve safety and efficacy in patients with recurrent, previously irradiated tumors.

Effects of anterolateral thigh free flap with fascia lata in repairing dura mater defect after resection of head squamous cell carcinoma

Objective: To evaluate the clinical effects of anterolateral thigh free flap with fascia lata in the repair of dura mater defect after resection of head squamous cell carcinoma. Methods: From June 2016 to June 2018, Xijing Hospital of Air Force Medical University applied the free transplantation of anterolateral thigh flap with fascia lata to repair the dura mater defect of 12 patients with head squamous cell carcinoma, including 9 males and 3 females, aged from 35 to 74 years. The size of scalp soft tissue defects in patients after carcinoma resection ranged from 12 cm×10 cm to 24 cm×21 cm, and the size of dura mater defect of patients ranged from 7 cm×6 cm to 16 cm×14 cm. The size of flap of patients ranged from 14 cm×12 cm to 27 cm×24 cm, and the size of fascia lata ranged from 8 cm×7 cm to 17 cm×15 cm. The superficial temporal artery and middle temporal vein were connected by end to end anastomosis with the first musculocutaneous perforating branch of the descending branch of lateral femoral artery and its accompanying vein. The flap donor area was transplanted with autologous split-thickness skin graft from trunk and fixed with packing. Postoperative survival of flaps and skin grafts was observed. The patients were followed up regularly. The cranial magnetic resonance imaging was performed to observe the recurrence of intracranial tumors and dural integrity, shape of the flap and whether the donor site region was left with significant dysfunction were observed. Results: All the flaps and skin grafts survived well in 12 patients after surgery. Ten patients had primary healing at the edge of the flap suture; 2 patients had local sinus tract formation at the suture site of flap, with a small amount of cerebrospinal fluid leakage, and were recovered after outpatient dressing change. The patients were followed up for 10 to 36 months, and 3 patients with tumors involving in the dura mater sagittal sinus region had postoperative intracranial tumor recurrence. The tumor was resected again. All the patients had good dural integrity. The flaps of all patients were in good shape, and no obvious dysfunction remained in the flap donor site. Conclusions: Free transplantation of anterolateral thigh flap with fascia lata is an effective and reliable method to repair the dura mater defect following head squamous cell carcinoma resection. It can repair the scalp and dura mater defects caused by the invasion of squamous cell carcinoma and provide possibilities for skull reconstruction.

Fluoroethyltyrosine in Detecting Tumors in Participants With Recurrent Intracranial Tumors

Fluoroethyltyrosine in Detecting Tumors in Participants With Recurrent Intracranial Tumors

Treatment-Plan Comparison of Three Advanced Radiation Treatment Modalities for Fractionated Stereotactic Radiotherapy to the Head and Neck

Purpose: Fractionated stereotactic radiosurgery (FSRS) can be given with at least three modalities: Gamma Knife, with the noninvasive frameless extend system (GKE); linear accelerator-based volumetric modulated arc therapy (VMAT); and intensity-modulated proton therapy (IMPT). We extracted treatment plans for patients who had received FSRS with GKE for recurrent skull base or intracranial tumors, created corresponding plans for VMAT and IMPT, and compared the quality of the three sets of plans. Methods and materials: Plans were extracted for 9 patients with recurrent malignant skull-base tumors (n = 6) or large intracranial tumors (n = 3) who had received FSRS with GKE (median dose 24 Gy in 3 fractions) in 2013 through 2015. Plans for VMAT were generated with a TrueBeam STx LINAC machine using 6-MV photons, and plans for IMPT were generated with multi-field optimization. The optimized VMAT and IMPT plans were normalized to achieve the best possible target coverage while meeting the same dose-volume constraints on organs at risk (OARs) as the GKE plans. Plans were evaluated on the basis of target coverage, conformity index, homogeneity index, gradient index, and treatment efficiency. Results: The median target volume was 10.2 cm3 (range 1.9 - 33.8 cm3). The VMAT and IMPT plans met all OAR constraints, and target coverage and conformity were comparable among all plans. VMAT and IMPT plans showed significantly better target uniformity and treatment delivery efficiency (P P

Repeated craniotomies for intracranial tumors: is the risk increased? Pooled analysis of two prospective, institutional registries of complications and outcomes

PurposeDeciding whether to re-operate patients with intracranial tumor recurrence or remnant is challenging, as the data on safety of repeated procedures is limited. This study set out to evaluate the risks for morbidity, mortality, and complications after repeated operations, and to compare those to primary operations.MethodsRetrospective observational two-center study on consecutive patients undergoing microsurgical tumor resection. The data derived from independent, prospective institutional registries. The primary endpoint was morbidity at 3 months (M3), defined as significant decrease on the Karnofsky Performance Scale (KPS). Secondary endpoints were mortality, rate and severity of complications according to the Clavien–Dindo Grade (CDG).Results463/2403 (19.3%) were repeated procedures. Morbidity at M3 occurred in n = 290 patients (12.1%). In univariable analysis, patients undergoing repeated surgery were 98% as likely as patients undergoing primary surgery to experience morbidity (OR 0.98, 95% CI 0.72–1.34, p = 0.889). In multivariable analysis adjusted for age, sex, tumor size, histology and posterior fossa location, the relationship remained stable (aOR 1.25, 95% CI 0.90–1.73, p = 0.186). Mortality was n = 10 (0.4%) at discharge and n = 95 (4.0%) at M3, without group differences. At least one complication occurred in n = 855, and the rate (35.5% vs. 35.9%, p = 0.892) and severity (CDG; p = 0.520) was similar after primary and repeated procedures. Results were reproduced in subgroup analyses for meningiomas, gliomas and cerebral metastases.ConclusionsRepeated surgery for intracranial tumors does not increase the risk of morbidity. Mortality, and both the rate and severity of complications are comparable to primary operations. This information is of value for patient counseling and the informed consent process.

Utility of Magnetic Resonance Perfusion Imaging in Quantifying Active Tumor Fraction and Radiation Necrosis in Recurrent Intracranial Tumors

Ancillary criteria to identify tumor recurrence such as the McDonald criteria or Response Assessment in Neuro-Oncology criteria can provide false diagnoses. Magnetic resonance perfusion (MRP) imaging has been proposed to differentiate post-treatment changes from recurrence. We investigated the utility of MRP to quantify the histological fraction of active tumor (AT), treatment-related changes, and radiation necrosis in recurrent post-treatment intracranial tumors. We conducted an exploratory single-blind study of patients with intracranial glioblastoma or metastases with previous radiation therapy and MRP before surgery. Biopsy specimens (n= 19) were analyzed for the percentage of AT, radiation necrosis, and treatment effect. Nonparametric Spearman's rho analysis and multivariable analysis of covariance were performed to assess the correlation between quantitative MRP and AT histological fraction. The mean patient age was 58 ± 11.5 years. The mean relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were 1.33 ± 0.71 and 1.34 ± 0.73, respectively. On analysis of covariance, significant associations were identified between increased rCBF (P=0.0004) and increased rCBV (P= 0.007) and percentage of AT. A significant interaction was identified between rCBF and rCBV and tumor histological features (glioblastoma vs. metastases; P= 0.003 and P= 0.03, respectively). An rCBF >1 predicted a mean AT fraction of ≥53% for all intracranial tumors and 74% for glioblastoma. MRP can help quantitatively predict tumor recurrence and/or progression for glioblastomas. The AT histological fraction correlated with quantitative radiologic measurements, including rCBV and rCBF. For metastases, MRP might not be as useful in predicting the AT fraction. Clinicians must be judicious with their use of MRP in predicting tumor recurrence and radiation necrosis.