Fractionated SRT using VMAT and Gamma Knife for brain metastases and gliomas--a planning study.

Stereotactic radiosurgery using Gamma Knife (GK) or linear accelerators has been used for decades to treat brain tumors in one fraction. A new positioning system, Extend™, was introduced by Elekta AB for fractionated stereotactic radiotherapy (SRT) with GK. Another option for fractionated SRT is advanced planning and delivery using linacs and volumetric modulated arc therapy (VMAT). This project aims to assess the performance of GK Extend™ for delivering fractionated SRT by comparing GK treatments plans for brain targets performed using Leksell GammaPlan (LGP) with VMAT treatment plans. Several targets were considered for the planning: simulated metastasis- and glioma-like targets surrounding an organ at risk (OAR), as well as three clinical cases of metastases. Physical parameters such as conformity, gradient index, dose to OARs, and brain volume receiving doses above the threshold associated with risk of damaging healthy tissue, were determined and compared for the treatment plans. The results showed that GK produced better dose distributions for target volumes below 15 cm3, while VMAT results in better dose conformity to the target and lower doses to the OARs in case of fractionated treatments for large or irregular volumes. The volume receiving doses above a threshold associated with increased risk of damage to normal brain tissue was also smaller for VMAT. The GK consistently performed better than VMAT in producing a lower dose-bath to the brain. The above is subjected only to margin-dependent fractionated radiotherapy (CTV/PTV). The results of this study could lead to clinically significant decisions regarding the choice of the radiotherapy technique for brain targets.

Promising outcome of patients with recurrent glioblastoma after Gamma Knife-based hypofractionated radiotherapy.

BACKGROUND: The role of Gamma Knife radiosurgery (GKRS) in recurrent glioblastoma remains unclear. The purpose of this study is to evaluate the effects of GKRS in a group of patients with recurrent glioblastoma, focusing on survival and safety. METHODS: Patients undergoing GKRS for recurrent glioblastoma between September 2014 and April 2019 were included in this study. Relevant clinical and radiosurgical data, including GKRS-related complications, were recorded and analyzed. Overall survival (OS), local progression free survival (LPFS) and prognostic factors for outcome were thoroughly evaluated. RESULTS: Fifty-three patients were analyzed (24 female, 29 male). The median age was 50 years (range, 19-78 years). The median GKRS treatment volume was 35.01 cm3 (range, 2.38-115.57 cm3). Twenty patients (38%) were treated with single fraction GKRS, while 33 (62%) were treated with GKRS-based hypofractionated stereotactic radiotherapy (HSRT). The median prescription dose for single fraction GKRS, 3-fractions HSRT and 5-fractions HSRT were 16 Gy (range, 10-20 Gy), 27 Gy (range, 18-33 Gy) and 25 Gy (range, 25-30 Gy), respectively. The median LPFS and OS times were 8.1 months and 11.4 months after GKRS, respectively. HSRT and Bevacizumab were associated with improved LPFS, while HSRT alone was associated with longer OS. CONCLUSION: Our findings suggested that HRST would likely improve LPFS and OS in definite settings; the addition of Bevacizumab to GKRS was associated with increased rates of local control. No major complications were reported. Further prospective studies are warranted to confirm our findings.

Gamma Knife Radiosurgery Modulates micro-RNA Levels in Patients with Brain Metastasis.

BACKGROUND: The relation between micro-RNA (miRNA) modulation and immune cell activity in high-dose radiation settings is not clearly understood. OBJECTIVE: To investigate the role of stereotactic radiosurgery (SRS) in (i) the regulation of tumorsuppressor and oncogenic miRNAs as well as (ii) its effect on specific immune cell subsets in patients with metastatic brain tumors (MBT). METHODS: 9 MBT patients who underwent gamma knife-based stereotactic radiosurgery (GKRS) and 8 healthy individuals were included. Serum samples were isolated at three-time intervals (before GKRS, 1 hour, and 1-month post-GKRS). Expressions of tumor-suppressor (miR-124) and oncogenic (miR-21, miR-181a, miR-23a, miR-125b, and miR-17) miRNAs were quantified by qPCR. The lymphocytic frequency (CD3+, CD4+, CD8+, CD56+, CD19+, and CD16+) was investigated by means of flow cytometry. RESULTS: The median age was 64 years (range: 50-73 years). The median prescription dose was 20Gy (range: 16Gy-24Gy), all delivered in a single fraction. The median overall survival and progression- free survival were 7.8 months (range: 1.7-14.9 months) and 6.7 months (range: 1.1-11.5 months), respectively. Compared to healthy controls, baseline levels of oncogenic miRNAs were significantly higher, while tumor-suppressing miRNA levels remained markedly lower in MBT patients prior to GKRS. Following GKRS, there was a reduction in the expression of miR-21, miR-17, and miR-181a; simultaneously, increased expression increased of miR-124 was observed. No significant difference in immune cell subsets was noted post GKRSIn a similar fashion. We noted no correlation between patient characteristics, radiosurgery data, miRNA expression, and immune cell frequency. CONCLUSION: For this specific population with MBT disease, our data suggest that stereotactic radiosurgery may modulate the expression of circulating tumor-suppressor and oncogenic miRNAs, ultimately enhancing key anti-tumoral responses. Further evaluation with larger cohorts is warranted.

Thirteen-year long-term follow-up in a rare case of anaplastic astroblastoma: What makes the difference?

Background: Astroblastomas are uncommon neuroepithelial tumors of the central nervous system with a distinct, yet, controversial radiological, histological, and molecular profile. Debatable differences between low- and high-grade astroblastoma have been reported in the medical literature; indeed, despite the increasing relevance of molecular genetic profiling in the realm of astroblastoma, its application is still in its early stages. As a result, the diagnostic criteria for astroblastoma remain undecided with yet no real consensus on the most ideal management. Case Description: This report describes a case of astroblastoma diagnosed 13 years ago in a young woman who despite six episodes of recurrence, transformation, and progression was able to retain a perfomace status of 0 by World Health Organization standard, throughout. Conclusion: This report discusses the clinical, radiological, histological features, and management of this rare tumor with an extraordinarily long survival, with an aim to strengthen the literature on management options. To the best of our knowledge, this is the longest surviving case of anaplastic astroblastoma reported in the available medical literature.

Improving on whole-brain radiotherapy in patients with large brain metastases: A planning study to support the AROMA clinical trial.

PURPOSE: To develop a novel dose-escalated volumetric modulated arc therapy (VMAT) strategy for patients with single or multiple large brain metastases which can deliver a higher dose to individual lesions for better local control (LC), and to compare dosimetry between whole brain radiotherapy (WBRT), hippocampal-sparing whole brain radiotherapy (HS-WBRT) and different VMAT-based focal radiotherapy approaches. METHODS AND MATERIALS: We identified 20 patients with one to ten brain metastases and at least one lesion larger than 15 cm3 who had received WBRT as part of routine care. For each patient, we designed and evaluated five radiotherapy treatment plans, including WBRT, HS-WBRT and three VMAT dosing models. A dose of 20 Gy in 5 fractions was prescribed to the whole brain or target volumes depending on the plan, with higher doses to smaller lesions and dose-escalated inner planning target volumes (DE-iPTV) in VMAT plans, respectively. Treatment plans were evaluated using the efficiency index, mean dose and D0.1 cc to the target volumes and organs at risk. RESULTS: Compared with WBRT, VMAT plans achieved a significantly more efficient dose distribution in brain lesions, especially with our DE-iPTV model, while minimising the dose to the normal brain and other organs at risks (OARs) (p < 0.05). CONCLUSIONS: VMAT plans obtained higher doses to brain metastases and minimised doses to OARs. Dose-escalated VMAT for larger lesions allows higher radiotherapy doses to be delivered to larger lesions while maintaining safe doses to OARs.

Adenoid cystic carcinoma and chronic lymphocytic leukaemia: synchronous presentations in the lung.

A 59-year-old male active smoker presented with a 6-month history of cough and breathlessness and was found to have a right upper lobe mass. Histology revealed this to be an adenoid cystic carcinoma (ACC) of the lung, while local lymph node dissection revealed a synchronous diagnosis of chronic lymphocytic leukaemia (CLL). The connection between CLL and solid organ malignancy is well documented, but the reporting of ACC in this context is novel. Mechanisms linking the two processes are revealed with the possibility of causality, and heightened vigilance for the development of primary lung tumours in CLL, and their management, is recommended.

Malignant intracerebral nerve sheath tumor in a patient with Noonan syndrome: illustrative case.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) within the neuroaxis are rare, usually arising from peripheral and cranial nerves. Even more scarce are cranial subclassifications of MPNSTs termed "malignant intracerebral nerve sheath tumors" (MINSTs). These tumors are aggressive, with a strong tendency for metastasis. With this presentation, alongside resistance to adjunctive therapy, complete excision is the mainstay of treatment, although it is often insufficient, resulting in a high rate of mortality. OBSERVATIONS: The authors report the case of an adult patient with a history of Noonan syndrome (NS) presenting with slowly progressive right-sided hemiparesis and right-sided focal motor seizures. Despite initial imaging and histology suggesting a left frontal lobe high-grade intrinsic tumor typical of a glioblastoma, subsequent molecular analysis confirmed a diagnosis of MINST. The patient's neurological condition improved after gross-total resection and adjuvant chemo-radiation; he remains on follow-up. LESSONS: MINSTs are rare neoplasms with a poor prognosis; management options are limited, with surgery being the cornerstone of treatment. Reports on rare tumors such as this will increase awareness of this particular pathology and disclose clinical experience. In this case, the authors were unable to establish a definite cause-and-effect relation between NS and MINST. Nevertheless, it remains the first reported case in the literature.

An integrated disease-specific graded prognostic assessment scale for melanoma: contributions of KPS, CITV, number of metastases, and BRAF mutation status.

BACKGROUND: Stereotactic radiosurgery (SRS) remains a mainstay therapy in the treatment of melanoma brain metastases (BM). While prognostic scales have been developed for melanoma patients who underwent SRS treatment for BM, the pertinence of these scales in the context of molecularly targeted therapies remains unclear. METHODS: Through a multi-institutional collaboration, we collated the survival patterns of 331 melanoma BM patients with known BRAF mutation status treated with SRS. We established a prognostic scale that was validated in an independent cohort of 174 patients. All patients with BRAF mutations in this series were treated with BRAF inhibitors. Prognostic utility was assessed using Net Reclassification Index (NRI > 0) and integrated discrimination improvement (IDI) metrics. RESULTS: In a multivariate Cox proportional hazards model, BRAF mutation status, KPS, number of metastases, and cumulative intracranial tumor volume (CITV) independently contributed to survival prognostication for melanoma patients with SRS-treated BM (P < .05 for all variables). These variables were incorporated into a prognostic scale using the disease-specific graded prognostic assessment (ds-GPA) framework. This integrated melanoma ds-GPA scale was validated in 2 independent cohorts collated through a multi-institutional collaboration. In terms of order of prognostic importance, BRAF mutation status exerted the greatest influence on survival, while KPS, the number of metastases, and CITV exhibited comparable, lesser impacts. CONCLUSIONS: Optimal survival prognostication for SRS-treated patients with melanoma BM requires an integrated assessment of patient characteristics (KPS), tumor characteristics (CITV and number of metastases), and the mutational profile of the melanoma (BRAF mutation status).

Considerations for future novel human-infecting coronavirus outbreaks.

Up until, June 13, 2020, >7,500,000 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and >400,000 deaths, across 216 countries, have been confirmed by the World Health Organization (WHO). With reference to the two previous beta-CoV outbreaks (SARS-CoV and middle east respiratory syndrome [MERS]), this paper examines the pathophysiological and clinical similarities seen across all three CoVs, with a special interest in the neuroinvasive capability and subsequent consequences for patients with primary or metastatic brain tumors. More widely, we examine the lessons learned from the management of such large-scale crises in the past, specifically looking at the South Korean experience of MERS and the subsequent shift in disaster management response to SARS-CoV-2, based on prior knowledge gained. We assess the strategies with which infection prevention and control can, or perhaps should, be implemented to best contain the spread of such viruses in the event of a further likely outbreak in the future.

Rare case of clear cell renal cell carcinoma presenting as a unilateral tonsil lesion.

A 70-year-old man presented with gradually worsening throat discomfort. He had no prior diagnosis of cancer and no travel history of note. Examination revealed a right-sided painless neck lump. He underwent an MRI of the neck, revealing a gadolinium-enhancing tonsillar mass and two brain lesions. Biopsy of the tonsil lesion was in keeping with an epithelial neoplasm, suggesting metastatic renal cell carcinoma. This was confirmed following a staging CT, which revealed a left renal mass and lung metastases. Due to his brain metastases, the patient has been started on the tyrosine kinase inhibitor cabozantinib. A brief discussion on the diagnostic evaluation of a tonsil mass as a rare presentation of renal cell cancer follows this report.

Integrating navigated transcranial magnetic stimulation motor mapping in hypofractionated and single-dose gamma knife radiosurgery: A two-patient case series and a review of literature.

BACKGROUND: The aim of the study was to demonstrate the feasibility of integrating navigated transcranial magnetic stimulation (nTMS) in preoperative gamma knife radiosurgery (GKRS) planning of motor eloquent brain tumors. CASE DESCRIPTION: The first case was a 53-year-old female patient with metastatic breast cancer who developed focal epileptic seizures and weakness of the left hand. The magnetic resonance imaging (MRI) scan demonstrated a 30 mm metastasis neighboring the right precentral gyrus and central sulcus. The lesion was treated with adaptive hypofractionated GKRS following preoperative nTMS-based motor mapping. Subsequent follow-up imaging (up to 12 months) revealed next to complete tumor ablation without toxicity. The second case involved a previously healthy 73-year-old male who similarly developed new left-handed weakness. A subsequent MRI demonstrated a 26 mm metastatic lesion, located in the right postcentral gyrus and 5 mm from the hand motor area. The extracranial screening revealed a likely primary lung adenocarcinoma. The patient underwent preoperative nTMS motor mapping prior to treatment. Perilesional edema was noted 6 months postradiosurgery; nevertheless, long- term tumor control was demonstrated. Both patients experienced motor function normalization shortly after treatment, continuing to final follow-up. CONCLUSION: Integrating preoperative nTMS motor mapping in treatment planning allowed us to reduce dose distributions to perilesional motor fibers while achieving salvage of motor function, lasting seizure freedom, and tumor control. These initial data along with our review of the available literature suggest that nTMS can be of significant assistance in brain radiosurgery. Prospective studies including larger number of patients are still warranted.

Adaptive radiosurgery based on two simultaneous dose prescriptions in the management of large renal cell carcinoma brain metastases in critical areas: Towards customization.

BACKGROUND: The long-term benefits of local therapy in metastatic renal cell carcinoma (mRCC) have been widely documented. In this context, single fraction gamma knife radiosurgery (SF-GKRS) is routinely used in the management of brain metastases. However, SF-GKRS is not always feasible due to volumetric and regional constraints. We intend to illustrate how a dose-volume adaptive hypofractionated GKRS technique based on two concurrent dose prescriptions termed rapid rescue radiosurgery (RRR) can be utilized in this particular scenario. CASE DESCRIPTION: A 56-year-old man presented with left-sided hemiparesis; the imaging showed a 13.1 cc brain metastasis in the right central sulcus (Met 1). Further investigation confirmed the histology to be a metastatic clear cell RCC. Met 1 was treated with upfront RRR. Follow-up magnetic resonance imaging (MRI) at 10 months showed further volume regression of Met 1; however, concurrently, a new 17.3 cc lesion was reported in the boundaries of the left frontotemporal region (Met 2) as well as a small metastasis (<1 cc) in the left temporal lobe (Met 3). Met 2 and Met 3 underwent RRR and SF-GKRS, respectively. RESULTS: Gradual and sustained tumor ablation of Met 1 and Met 2 was demonstrated on a 20 months long follow- up. The patient succumbed to extracranial disease 21 months after the treatment of Met 1 without evidence of neurological impairment post-RRR. CONCLUSION: Despite poor prognosis and precluding clinical factors (failing systemic treatment, eloquent location, and radioresistant histology), RRR provided optimal tumor ablation and salvage of neurofunction with limited toxicity throughout follow-up.

Adaptive hypofractionated gamma knife radiosurgery in the acute management of brainstem metastases.

BACKGROUND: Intrinsic brainstem metastases are life-threatening neoplasms requiring rapid, effective intervention. Microsurgery is considered not feasible in most cases and systemic treatment seldom provides a successful outcome. In this context, radiation therapy remains the best option but adverse radiation effects (ARE) remain a major concern. A dose-adaptive gamma knife procedure coined as Rapid Rescue Radiosurgery (3R) offers the possibility to treat these lesions whilst reducing the risk of ARE evolvement. We report the results of 3R applied to a group of patients with brainstem metastases. METHODS: Eight patients with nine brainstem metastases, having undergone three separate, dose-adapted gamma knife radiosurgery (GKRS) procedures over 7 days, were retrospectively analyzed in terms of tumor volume reduction, local control rates, and ARE-development under the period of treatment and at least 6 months after treatment completion. RESULTS: Mean peripheral doses at GKRS 1, GKRS 2, and GKRS 3 were 7.4, 7.7, and 8.2 Gy (range 6-9 Gy) set at the 35-50% isodose lines. Mean tumor volume reduction between GKRS 1 and GKRS 3 was -15% and -56% at first follow-up. Four patients developed radiologic signs of ARE but remained clinically asymptomatic. One patient developed a local recurrence at 34 months. Mean survival from GKRS 1 was 13 months. Two patients were still alive at the time of paper submission (10 and 23 months from GKRS 1). CONCLUSIONS: In this study, 3R proved effective in terms of tumor volume reduction, rescue/preservation of neurological function, and limited ARE evolvement.

A challenging case of concurrent multiple sclerosis and anaplastic astrocytoma.

BACKGROUND: Cases of gliomas coexisting with multiple sclerosis (MS) have been described over the past few decades. However, due to the complex clinical and radiological traits inherent to both entities, this concurrent phenomenon remains difficult to diagnose. Much has been debated about whether this coexistence is incidental or mirrors a poorly understood neoplastic phenomenon engaging glial cells in the regions of demyelination. CASE DESCRIPTION: We present the case of a 41-year-old patient diagnosed with a left-sided frontal contrast enhancing lesion initially assessed as a tumefactive MS. Despite systemic treatment, the patient gradually developed signs of mass effect, which led to decompressive surgery. The initial microscopic evaluation demonstrated the presence of MS and oligodendroglioma; the postoperative evolution proved complex due to a series of MS-relapses and tumor recurrence. An ulterior revaluation of the samples for the purpose of this report showed an MS-concurrent anaplastic astrocytoma. We describe all relevant clinical aspects of this case and review the medical literature for possible causal mechanisms. CONCLUSION: Although cases of concurrent glioma and MS remain rare, we present a case illustrating this phenomenon and explore a number of theories behind a potential causal relationship.

Pituitary carcinomas: Rare and challenging.

BACKGROUND: Pituitary carcinomas (PCs) are defined as adenohypophyseal tumors with metastatic activity within and outside the boundaries of the central nervous system (CNS). The condition is rare and therefore seldom reported; most lesions are hormone producing and have a tendency for complex evolution. As such, the management of PCs remains difficult. We present an illustrative case of PC with a brief review of the recent medical literature. CASE DESCRIPTION: A 58-year-old patient was diagnosed with prolactinoma in 2005. The ensuing biochemical and radiological evolution proved contentious; local tumor control was never fully achieved despite multimodal management including pharmacological treatment, repeated resections, and radiotherapy. In late 2017, the patient developed metastatic lesions within the confinements of the CNS requiring further surgical interventions, high-dose radiation, and systemic treatment. CONCLUSION: As it was the case in our patient, PCs require tailored, multimodal treatments according to the degree of infiltration, site of invasion, and hormone status. Further studies are necessary to understand the mechanisms promoting "extra-sellar" activity, particularly at distant sites; the identification of biomarkers exposing the risk of PC remains a crucial aspect of diagnostics, prevention and future customized therapies.

The concept of rapid rescue radiosurgery in the acute management of critically located brain metastases: A retrospective short-term outcome analysis.

BACKGROUND: Adaptive hypofractionated gamma knife radiosurgery has been used to treat brain metastases in the eloquent regions while limiting the risk of adverse radiation effect (ARE). Ablative responses might be achieved within days to weeks with the goal to preserve the neurological function. The application of this treatment modality in selected acute/subacute settings has been termed Rapid Rescue Radiosurgery (RRR) in our department. We report the expeditious effects of RRR during treatment and 4 weeks after treatment completion. METHODS: In all, 34 patients with 40 brain metastases, each treated over a period of 7 days in three separate gamma knife radiosurgery sessions (GKRS 1-3) between November 2013 and August 2017, were retrospectively analyzed in terms of tumor volume reduction, salvage of organs at risk (OAR), and radiation induced toxicity under the period of treatment (GKRS 1-3 = one week) and at first follow-up magnetic resonance imaging (MRI) (4 weeks after GKRS 3). RESULTS: Mean tumor volume at GKRS 1 was 12.8 cm3. Mean peripheral doses at GKRS 1, GKRS 2, and GKRS 3 were 7.7 Gy, 8.1 Gy, and 8.4 Gy (range: 6.0-9.5 Gy) at the 35% to 50% isodose lines. In the surviving group at first follow-up (n = 28), mean tumor volume reduction was - 10% at GKRS 3 (1 week) and - 48% four weeks after GKRS 3. There was no further clinical deterioration between GKRS 3 and first follow-up in 21 patients. Six patients died prior to first follow-up due to extracranial disease. No ARE was noticed/reported. CONCLUSIONS: In this study, RRR proved effective in terms of rapid tumor volume reduction, debulking, and preservation/rescue of neurological function.

Gamma knife radiosurgery in the management of endolymphatic sac tumors.

BACKGROUND: Although widely regarded as rare epithelial tumors with a low grade of malignancy, endolymphatic sac tumors (ELST) often lead to disabling petrous bone destruction and significantly impairing symptoms at the time of primary diagnosis and/or recurrence. ELST is not uncommon in von Hippel Lindau (VHL) patients. Although open surgery is regarded as the best treatment option, recurrence remains a challenge, particularly when gross tumor resection (GTR) is deemed unachievable due to topographic conditions. Tumor recurrence successfully treated with fractionated radiotherapy and radiosurgery have been reported in selected cases. We present the case of a patient with recurrent ELST treated with salvage gamma knife radiosurgery (GKRS) adding a review of current literature. CASE DESCRIPTION: A 65-year-old patient underwent GKRS of an unresectable, recurrent ELST. Tumor volumetric analysis showed almost 15% increase in tumor volume in the 4 months between the pre-GKRS magnetic resonance imaging (MRI) and the stereotactic MRI (s-MRI) at treatment. Follow-up MRI at 12 and 20 months showed significant decrease in local tumor volume, decreased contrast enhancement and no perifocal edema. The patient's general and neurological status remains stable to the present day. CONCLUSION: In the present case, GKRS was effective in the management of a recurrent ELST over the course of 20 months. Because of ELSTs recurrence potential, long-term follow up is required. The present case as well as previous reports might suggest a possible salvage/adjunctive role of radiosurgery in the management of ELST. Further studies are deemed necessary.

Correction: Identification of neoepitopes recognized by tumor-infiltrating lymphocytes (TILs) from patients with glioma.

[This corrects the article DOI: 10.18632/oncotarget.24955.].

Identification of neoepitopes recognized by tumor-infiltrating lymphocytes (TILs) from patients with glioma.

Neoepitope-specific T-cell responses have been shown to induce durable clinical responses in patients with advanced cancers. We explored the recognition patterns of tumor-infiltrating T lymphocytes (TILs) from patients with glioblastoma multiforme (GBM), the most fatal form of tumors of the central nervous system. Whole-genome sequencing was used for generating DNA sequences representing the entire spectrum of 'private' somatic mutations in GBM tumors from five patients, followed by 15-mer peptide prediction and subsequent peptide synthesis. For each mutated peptide sequence, the wildtype sequence was also synthesized and individually co-cultured with autologous GBM TILs, which had been expanded in vitro with a combination of interleukin (IL)-2, IL-15 and IL-21. After seven days of culture, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) and/or IL-17A production was measured by ELISA in culture supernatants, and used as an epitope-specific immune response readout. Mutated peptides that induced a strong cytokine response were considered to contain legitimate neoepitopes. TILs from 5/5 patients with GBM exhibited specific immune reactivity profiles to the nominal target peptides, defined by IFN-γ and/or TNF-α production, as well as IL-17A. Neoepitopes, defined by mutated peptides inducing IFN-γ and/or TNF-α production without or only minimal reactivity to the wildtype sequences, were found for each individual patient. CD8+ TILs dominated the patients' responses to private neoepitopes. The present study shows that neoepitope-specific TIL reactivity constitutes an important arm of anti-tumor immune responses in patients with GBM, and thus a powerful tool for developing next-generation personalized immunotherapies.