ML-4 A case of primary CNS lymphoma diagnosed 5 years after stereotactic radiosurgery

Central nervous system primary malignant lymphoma (PCNSL) is rarely diagnosed as multiple metastatic brain tumors. Almost tumors recure early after receiving stereotactic radiosurgery (SRS). Regardless of the fact, the following case report displays PCNSL, diagnosed five years after the initial treatment with SRS as brain metastases of unknown primary origin. This extraordinal case suggests long-term follow-up regarding PCNCL. The case was a 55-year-old woman with a history of a total hysterectomy for cervical cancer. She developed left paralysis. Brain MRI confirmed a 27 mm contrast-enhanced lesion in the right frontal lobe and three other lesions. SRS was performed as a diagnosis of multiple brain metastases for urgent symptom relief. No extra-cranial cancerous lesions were found. Unknown primary cancer was a probable diagnosis at that time. Two years after SRS, local regrowth of tumor of the right frontal primary motor area was discovered. Re-irradiation was performed. Cerebral edema, contrast enhancement, and left paralysis progressed following five months, taking an oral corticosteroid. Craniotomy and debulk. The pathological diagnosis was brain radiation necrosis due to no viable tumor cells. New lesions in the left temporal lobe and basal ganglia appeared three years after surgery. Awake craniotomy was performed for the left temporal lobe lesion. Histopathology showed diffuse growth of tumor cells with a high nucleo-cytoplasmic ratio and irregular nuclear shape. Immunohistochemistry revealed positive CD10, CD20, CD45 (LCA), MUM1, and negative CD3, CD5. The Ki- 67 labeling rate was as high as almost 100% to diagnose diffuse large B-cell lymphoma, PCNSL. Multidrug chemotherapy consisting of rituximab, high-dose methotrexate, procarbazine, and vincristine were performed. Complete remission was obtained without any serious adverse events. Considering the residual radiation necrosis, whole-brain irradiation was avoided. Moreover, consolidation therapy was performed only with high-dose cytarabine therapy.

RT-4 Treatment outcome of proton beam therapy for glioblastoma

Introduction: Proton beam therapy enables high dose irradiation for tumors while reducing the dose to surrounding normal tissue due to the sharp energy peak called the Bragg peak. We retrospectively analyzed the efficacy of the high dose radiotherapeutic strategy using proton beam for glioblastoma (GBM) in our institution. Methods: Twenty-nine patients with newly diagnosed GBM who underwent high dose proton beam therapy concomitant with temozolomide were investigated. All patients received hyperfractionated concomitant radiotherapy consisting of X-ray radiotherapy (50.4Gy in 28 fractions) and proton beam therapy (46.2Gy [RBE] in 28 fractions). The survival outcome and adverse events were analyzed. Results: The median overall survival time and progression free survival time for all 29 patients were 31.0 months (95%CI, 25.9–36.1) and 11.0 months (95%CI, 7.8–14.2), respectively. No significant survival difference according to the MGMT methylation status was shown. Failure patterns after proton beam therapy included 17 cases of local recurrence, 3 cases of distant recurrence, and 5 cases of dissemination. Although there was no significant difference in time to recurrence according to the failure pattern, there was a tendency of longer survival in the local recurrence group. Regarding adverse events, radiation necrosis was observed in 8 cases (including 2 asymptomatic cases). The median time to onset of necrosis after radiation was 18.2 months (95%CI, 10.3–26.2). There were 5 cases of long survivor over 5 years out of 29 cases (17.2%). Of these, 4 cases developed radiation necrosis. Conclusions: Our results indicate that high dose proton beam therapy of 96.6Gy (RBE) prolonged survival in selected GBM patients. Particularly in long survivors, special attention and effective treatment to radiation necrosis is a remaining problem.

Negative 18F-FET PET/CT in brain metastasis recurrence: a teaching case report

Positron emission tomography (PET) using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET has been shown to be a useful tool for differentiating radiation therapy outcomes, such as brain metastasis recurrence or radiation necrosis. We present the case of a female patient with brain metastases from pulmonary mucinous adenocarcinoma with suspicion of tumor recurrence on follow-up magnetic resonance imaging (MRI) after radiosurgery. 18F-FET PET/computed tomography (CT) was indicative of radiation necrosis. Due to the patient's medical history and the discrepancy between the brain MRI and PET/CT results, surgical biopsies were decided, which were positive for brain metastasis recurrence. The diagnosis of metastasis recurrence may also be challenging on 18F-FET PET/CT. In case of discrepancies between MRI and PET/CT results, false-negative 18F-FET PET/CT remains a possibility and requires careful follow-up or biopsy.

RADT-06. RADIOTHERAPY FOR BRAIN METASTASES FROM THYROID CANCER: A RETROSPECTIVE COHORT STUDY

PURPOSE/OBJECTIVE(S) Brain metastases from thyroid carcinoma are rare. Although stereotactic radiosurgery (SRS) is a standard of care for patients with brain metastases across many histologies, the current NCCN guidelines do not support a universal role for this modality in thyroid cancer. MATERIALS AND METHODS Thyroid cancer patients with brain metastases treated with radiotherapy at our institution from 2002-2020 were studied. Cumulative risk of local failure, distant intracranial failure and radiation necrosis were calculated using a competing risk of death analysis and censored at the last imaging follow-up. Overall survival was analyzed using Kaplan-Meier method. Stratified cox regression was used to study per-lesion outcomes. RESULTS We identified 34 patients with 203 treated brain metastases. 179 (88.2%) lesions were of differentiated histology; the remainder were anaplastic histology. Four patients received whole brain radiotherapy (WBRT) while 30 patients received SRS (SFED 22, interquartile (IQ) range 20-22). Of the patients receiving WBRT, one (25%) had anaplastic histology, and the median number of lesions was 15 (as compared to 2 for SRS). Median follow up among survivors was 32.3 months and median survival was 10.8 months. There were no observed failures (local or distant intracranial) observed at 1 year in the 24 metastases with anaplastic histology, although competing risk of death was high (91.7%). The 1 year cumulative incidences of local failure and distant intracranial failures were 9.8% (95CI 5.7%-13.9%) and 35.0% (95CI 29.0%-41.0%), respectively, in differentiated tumors. 6 (10.2%) of the distant intracranial failures were new cases of leptomeningeal disease. The 1 year risk of radiation necrosis was 15.5%. Of these cases, most were Grade 2 (57.1%); 3 (42.9%) were Grade 4 (there were no Grade 1 or 3 events). CONCLUSION In the largest known cohort of thyroid cancer brain metastasis patients, radiotherapy and SRS appear to be safe and effective treatment modalities.

RADT-21. DUAL FET PET-GUIDED SIB IN RADIOTHERAPY OF NEWLY DIAGNOSED GLIOBLASTOMA - A PILOT STUDY

BACKGROUND PET using FET is a valuable tool to determine the actual glioblastoma infiltration.The FET-PET examination can be performed using the dual-time point acquisition of FET . Infiltration defined in dual FET PET corresponds to the location and shape of the recurrence. The aim of this study was to evaluate safety and efficacy of simultaneous integrated boost based on dual FET PET combined with temozolomide TMZ for the postoperative treatment of GBM. METHODS AND MATERIALS In a prospective pilot study, 17 patients were enrolled. All patient presented an active tumor in postoperative PET imaging. The radiotherapy was performed as an FET-PET-based integrated-boost IMRT. The prescribed dose was 78 and 60 Gy (single dose 2.6 and 2.0 Gy, respectively). The progression-free survival (PFS) and overall survival (OS), toxicities and radiation necrosis rate were evaluated. RESULTS The median follow up was 37 months.Two patients were found to have uncontrolled seizures during radiation treatment and were not able to received treatment per protocol. Patients treated per protocol presented new or increased neurological deficits in 7/15 cases in a month after irradiation. In 4 patients radiation necrosis was confirmed in pathological report after re-surgery. Three patients were still alive after 26,28 and 38 months of follow up without progression and any signs of treatment related late toxicity. The 2-year survival rate was 43% in all patients treated per protocol. Median overall survival (OS) and disease-free survival (DFS) were 20 and 12 months, respectively. In a subgroup of MGMT methylated and unmethylated the median survival was 25 and 12 months. CONCLUSIONS Our dose escalation concept with a total dose of 78 Gy, based on FET-PET, have lead to promising survival results even within MGMT unmethylated subgroup. However rate of early toxicity and radiation necrosis is high.

NIMG-03. TUMOR HABITAT ANALYSIS BY MAGNETIC RESONANCE IMAGING DISTINGUISHES TUMOR PROGRESSION FROM RADIATION NECROSIS IN BRAIN METASTASES AFTER STEREOTACTIC RADIOSURGERY

OBJECTIVES Identification of viable tumor after stereotactic radiosurgery (SRS) is important for future targeted therapy. This study aimed to determine whether tumor habitat on structural and physiologic MRI can distinguish viable tumor from radiation necrosis of brain metastases after SRS. METHOD Multiparametric contrast-enhanced T1-and T2-weighted imaging, apparent diffusion coefficient (ADC), and cerebral blood volume (CBV) were obtained from 52 patients with 69 metastases, showing enlarging enhancing masses after SRS. Voxel-wise clustering identified three structural MRI habitats (enhancing, solid low-enhancing, and nonviable) and three physiologic MRI habitats (hypervascular cellular, hypovascular cellular, and nonviable). Habitat-based predictors for viable tumor or radiation necrosis were identified by logistic regression. Performance was validated using the area under the curve (AUC) of the receiver-operating-characteristics curve in an independent dataset with 24 patients. RESULTS None of the physiologic MRI habitats were indicative of viable tumor. Viable tumor was predicted by a high-volume fraction of solid low-enhancing habitat (low T2-weighted and low CE-T1-weighted values; odds ratio [OR] 1.74, P< .001) and a low-volume fraction of nonviable tissue habitat (high T2-weighted and low CE-T1-weighted values; OR, 0.55, P< .001). Combined structural MRI habitats yielded good discriminatory ability in both development (AUC 0.85, 95% confidence interval [CI]: 0.77–0.94) and validation sets (AUC 0.86, 95% CI:0.70–0.99), outperforming single ADC (AUC 0.64) and CBV (AUC 0.58) values. The site of progression matched with the solid low-enhancing habitat (72%, 8/11). CONCLUSION Solid low-enhancing and nonviable tissue habitats on structural MRI can help to localize viable tumor in patients with brain metastases after SRS.