Stereotactic Radiation and Dual Human Epidermal Growth Factor Receptor 2 Blockade with Trastuzumab and Pertuzumab in the Treatment of Breast Cancer Brain Metastases: A Single Institution Series

(1) Background: This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and pertuzumab–trastuzumab (PT) in patients with breast cancer brain metastases (BCBM). (2) Methods: Patients with HER2+ BCBM who received FSRT from 2015 to 2019 were identified. Patients were included if they were treated with fSRT within 21 days of receiving PT. All lesions were treated with LINAC-based fSRT to a total dose of 27 Gy delivered in three consecutive fractions. All patients received concurrent PT. Patients were evaluated 4–6 weeks after SRS and subsequently every 2–3 months with MRI re-imaging (3) Results: A total of 49 patients with HER2+ brain metastases were identified. Of these patients, a total of 10 patients with 32 HER2+ BCBM were treated with concurrent SRT and PT and included in the analysis. No local progression was observed. Overall response rate was 68.7%. Only one patient developed asymptomatic radionecrosis. Median time to BM occurrence was 15.6 (range: 1–40.5 months). Distant intracranial failure occurred in 4/10 patients (40.0%). Overall BCBM median survival was 33.9 months (95%CI 24.1–43.6). Mean duration of PT treatment was 27.9 months (range: 10.1–53.7 months). (4) Conclusions: In our single institution experience, fSRT and PT showed to be a safe treatment for patients with BCBM with an adequate overall response rate.

Lung Stereotactic Radiation Therapy: Intercomparison of Several Irradiation Devices in Terms of Outcome and Predictive Factors

Background: Stereotactic body radiotherapy (SBRT) is recommended for the treatment of inoperable early stage non-small-cell lung cancer and lung oligometastases. The radiation oncology department of the Lausanne University Hospital (CHUV) gathers three different radiotherapy devices able to treat pulmonary lesions in SBRT conditions: CyberKnife® (CK), Helical Tomotherapy® (HT), and volumetric modulated arc therapy (VMAT). The aim of this study is to define the patients’ outcome in terms of irradiation efficacy and toxicities after lung SBRT depending of the choice of the SBRT technique.Methods: We retrospectively analyzed the clinical, radiological, and dosimetric data of patients with primary lung tumor or pulmonary oligometastases treated with SBRT between January 2016 and February 2020. We analyzed descriptive data using the Chi-2 test for proportions and the T-test for means comparisons, survival data by the Kaplan-Meier method and comparisons between groups by the Log-rank test and Cox-regression.Results: We identified 111 patients mostly in good condition (82.9% PS 0-1) with a median age of 71.4 years. One hundred forty-two lesions were treated with a typical fractionation of 55 Gy in 5 fractions, delivered by CK (59.9%), VMAT (38.0%), or HT (2.1%). Compared to other techniques, CK technique allowed to treat comparable gross tumor volume (GTV; 2.1 vs 1.4cc, p = 0.84) with smaller planning treatment volume (PTV; 12.3 vs 21.9 cc, p = 0.013), and was associated with a lower mean lung dose (MLD; 2.6 vs 4.1 Gy, p < 0.001), a lower V5 (13.5 vs 19.9 cc, p = 0.002) and a lower V20 (2.3 vs 5.4 cc, p < 0.001). Local control rates at 2 years were not different depending on the irradiation device, respectively of 96.2% (range, 90.8-100) and 98.1% (range, 94.4-100), p = 0.68. Toxicity incidence was significantly increased with V5 value > 17.2% (56.0 vs 77.4%, p = 0.021). Conclusions: Compared to other SBRT techniques, CK treatments permitted to treat comparable GTV with reduced PTV, MLD, V20, and V5. The dosimetric benefit of CK SBRT was not associated with a clear clinical benefit, with comparable outcome in terms of control rates and toxicity. Toxicity incidence was less frequent when reducing the V5. The use of CK is particularly attractive in case of multiple courses of lung SBRT or in case of local relapse requiring lung re-irradiation.Trial registration: Registered on February 24th 2021, ID 2021-00267, with the authorization of the CER-VD ethics committee (Switzerland).

Secondary Trigeminal Neuralgia: a Case Report and Literature Review of Red Flags

Introduction: Trigeminal neuralgia (TN) is characterized by recurrent paroxysmal brief episodes of electric shock-like pain along the trigeminal nerve distribution. Based on the underlying cause, current classification systems have classified TN into idiopathic, classical, and secondary TN. This manuscript presents a case report of a patient seen in the clinic with features of trigeminal neuralgia secondary to an intracranial lesion. Case description: A 39-year-old female presented to the clinic with a 15-month history of severe, intermittent, short-lasting episodes of pain affecting the left lower teeth, jaw, nose, and temporal region. The patient reported familiar shock-like pain during the physical examination when the skin of the left ala of the nose was lightly touched. The rest of the clinical examination was non-significant. The magnetic resonance imaging of the brain showed an approximately 20 mm wide lesion at the level of the cerebellopontine angle. After subsequent tests, the lesion was diagnosed as meningioma, and the patient was treated with stereotactic radiation therapy. Practical Implications: In up to 10 % of TN cases, the underlying cause can be due to a brain tumor. Although persistent pain, sensory or motor nerve dysfunction, gait disturbances, and other neurological signs may concurrently exist, raising a red flag for intracranial pathology, patients often present with pain alone as the heralding symptom of a brain tumor. Due to this, it is imperative that all patients suspected of having TN undergo an MRI of the brain as part of the diagnostic work-up.

Malignant ossifying fibromyxoid tumor of the brain treated with post-operative fractionated stereotactic radiation therapy: A case report and literature review

Background: Ossifying fibromyxoid tumor (OFMT) is a rare musculoskeletal soft-tissue neoplasm of uncertain histogenesis most frequently occurring in the lower extremities. Conventionally, considered benign, these tumors are often managed by surgical resection followed by surveillance. However, malignant OFMTs with an increased propensity for local recurrence and distant metastasis have been recently identified, and the role of adjuvant therapy in these more aggressive cases is unclear. Case Description: We present, to the best of our knowledge, the first reported case of a primary, malignant, and intracranial OFMT. A 29-year-old female presented with recurrent headaches secondary to a large mass in her right frontal lobe. She underwent gross total resection of the brain mass with final pathology consistent with malignant OFMT demonstrating high-risk features including increased cellularity, grade, and mitotic activity. Due to these high-risk features, she received postoperative fractionated stereotactic radiation therapy (FSRT) to the resection cavity, and to the best of our knowledge, she represents the only known patient with OFMT to be treated with adjuvant FSRT. She tolerated the adjuvant treatment well with no acute or late toxicities and remains disease-free over 5 ½ years after resection. Conclusion: Adjuvant FSRT appears to be a safe and efficacious approach for managing this rare intracranial disease presentation. We review this patient’s clinical course in the context of the literature to demonstrate the difficulties associated with accurate diagnosis of this rare tumor and the controversial role of adjuvant therapy in preventing disease recurrence in this patient population.

IMMU-42. OPTIMIZING IMMUNOTHERAPY FOR GLIOMA USING CYTOKINE-ACTIVATED NATURAL KILLER CELLS

INTRODUCTION Glioblastoma multiforme (GBM) is the most common primary central nervous system malignancy associated with a 12-15 month survival after surgery and radio-chemotherapy. Utilizing adoptive cellular immunotherapy using natural killer (NK) cells has developed over the past two decades for a variety of hematologic malignancies. This approach in solid malignancies is limited by questions of cell dose versus tumor burden, insufficient tumor infiltration, and a tumor microenvironment that suppresses NK cell function. METHODS We isolated NK cells from healthy volunteers and activated them using IL-2, -15, -12, -18, then perform cytotoxic assays in the presence of glioma stem cells. We also tested the efficacy of the NK cells with intracranial delivery in a pre-clinical murine model of glioma. We tested various concentrations of IL-2 and IL-15 on the cytokine culture platform. RESULTS In this study, we demonstrate human NK cells, activated using a cytokine cocktail of interleukins-2, -15, -12, and -18, exert strong cytotoxic events against glioma cell lines. To further examine the efficacy of activated NK cells in vitro, we utilized intracranially xenografted glioma lines and demonstrated a survival benefit with tumor bed injections of these cytokine-activated NK cells (p=0.0089). We were able to confirm that NK cells cultured with low doses (200u IL2; 50ng/ml IL15) of both cytokines are just as effective as higher doses. This is important, as in vivoexhaustion of NK cells stimulated with high doses of either cytokine has been well validated. We also found that low-dose irradiation (4Gy) of glioma cells prior to co-culture with cytokine-activated NK cells promoted increased targeted glioma cell killing within 4 hours(32% cell killing). CONCLUSIONS These findings suggest that in a clinical study, injection of cytokine-activated NK cells into the glioblastoma tumor bed could be used as adjuvant treatment following either stereotactic radiation or surgical resection.

RADT-07. DETERMINATION OF THE OPTIMAL TIME INTERVAL BETWEEN POST-OPERATIVE MRI AND CT SIMULATION FOR STEREOTACTIC RADIOSURGERY PLANNING

BACKGROUND The incidence of brain metastasis is approximately 200,000 worldwide annually. Stereotactic radiation therapy of post-operative cavity reduces local recurrence. Surgical cavity size changes significantly with 96.5% demonstrating volumetric change during post-operative period. We sought to define the optimal time interval that preserved the volumetric dimensions between the post-surgical MRI and the CT simulation used for stereotactic radiosurgery planning. METHODS Seven patients with brain metastasis that underwent surgical resection and stereotactic radiation treatment at Albany Medical Center from February 2019 to April 2020 were included in the study. A total of 8 target lesions were included. Brain lab planning system was used for contouring the target volume. A postoperative MRI within 24-48 hours after surgery was obtained. 3 patients required an additional interim MRI 16-50 days after surgery. The planning CT simulation was performed 2 days prior and up to 15 days after the post-operative/interim MRI and target volumes were compared. RESULTS The average volume of the post-surgical cavity contoured by the neurosurgeons on the post-operative/interim MRI was 15.96 cc (± 7.79 cc, range of 6.54 -24.9 cc). The average volume of the post-surgical cavity contoured by the radiation oncologists on the planning CT was 15.71 (± 7.49 cc, range of 6.53 -24.31 cc). There was no noticeable change in volume size between post-operative/interim MRI and planning CT up to the period of 15 days. LIMITATION This was a retrospective pilot study with a small sample size and patients recruited from a single center. CONCLUSION There is no change in size of the cavity volume for up to 15 days between post-operative/interim MRI and planning CT. This knowledge will help understand the optimal time interval between post-operative MRI and CT simulation for the stereotactic radiation therapy planning.

Planar EPID-Based Dosimetry for SRS and SRT Patient-Specific QA

The study’s purpose was to develop and validate Electronic Portal Imaging Device (EPID)-based dosimetry for Stereotactic Radiosurgery (SRS) and Stereotactic Radiation Therapy (SRT) patient-specific Quality Assurance (QA). The co-operation between extended Source-to-Imager Distance (SID) to reduce the saturation effect and simplify the EPID-based dosimetry model was used to perform patient-specific QA in SRS and SRT plans. The four parameters were included for converting the image to dose at depth 10 cm; dose-response linearity with MU, beam profile correction, collimator scatter and water kernel. The model accuracy was validated with 10 SRS/SRT plans. The traditional diode arrays with MapCHECK were also used to perform patient-specific QA for assuring model accuracy. The 150 cm-SID was found a possibility to reduce the saturation effect. The result of model accuracy was found good agreement between our EPID-based dosimetry and TPS calculation with GPR more than 98% for gamma criteria of 3%/3 mm, more than 95% for gamma criteria of 2%/2 mm, and the results related to the measurement with MapCHECK. This study demonstrated the method to perform SRT and SRT patient-specific QA using EPID-based dosimetry in the FFF beam by co-operating between the extended SID that can reduce the saturation effect and estimate the planar dose distribution with the in-house model.