RADT-12. USE OF FDOPA PET FOR RADIATION THERAPY TARGETING IN GRADE 2 IDH MUTANT GLIOMA

BACKGROUND Low-grade, IDH mutant (IDHmt) gliomas typically do not enhance on MRI complicating radiotherapy (RT) target delineation. Amino acid PET using 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (FDOPA) has demonstrated avidity in IDHmt gliomas and may assist in RT planning for non-enhancing tumors. This study aims to compare conventional and FDOPA-defined target volumes in grade 2 IDHmt gliomas. METHODS In a prospective pilot study, patients underwent MRI and FDOPA PET using a 3T MRI/PET system followed by standard therapy. Gross tumor volumes (GTV) included the T2/FLAIR abnormality and surgical cavity; clinical target volumes (CTV) included a 1 cm expansion constrained anatomically. Metabolic target volumes (MTVs) were generated using the FDOPA SUV > 1.5-fold normal brain isocurve. Union of GTV and MTV generated a fusion GTV (fGTV); expanding fGTV by 1 cm yielded the fusion CTV (fCTV). Target volumes were compared volumetrically with overlap (Dice coefficient) and surface metrics (Hausdorff distance). Medians are reported with ranges. RESULTS Four patients with grade 2 IDHmt glioma (3 1p/19q codeleted oligodendrogliomas, 1 non-codeleted astrocytoma) received MRI/PET before treatment. All oligodendrogliomas exhibited FDOPA avidity; the astrocytoma showed no avidity. GTV and CTV measured 16.1 cc (4.9 - 82.2 cc) and 76.7 cc (29.5 - 256.1 cc), respectively. The MTV volume outside of GTV was 0.8 cc (0.2 – 6.1 cc), but was covered in each case by the CTV. Addition of FDOPA increased fGTV and fCTV volumes by 5.4% and 17.5%, respectively. Dice coefficient and Hausdorff distances for GTV vs fGTV were 0.96 (0.95 - 0.99) and 11.2 mm (10.0 – 11.9 mm), respectively, and for CTV vs fCTV were 0.87 (0.81 – 0.95) and 10.2 mm (10.0 - 11.0), respectively. CONCLUSIONS FDOPA PET identified tracer-avid regions outside of MRI-defined GTVs in a group of IDHmt gliomas. FDOPA PET provides useful metabolic information for RT planning and warrants further investigation.

Post-Operative Accelerated-Hypofractionated Chemoradiation With Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost in Glioblastoma: A Phase I Study (ISIDE-BT-2)

BackgroundGlioblastoma Multiforme (GBM) is the most common primary brain cancer and one of the most lethal tumors. Theoretically, modern radiotherapy (RT) techniques allow dose-escalation due to the reduced irradiation of healthy tissues. This study aimed to define the adjuvant maximum tolerated dose (MTD) using volumetric modulated arc RT with simultaneous integrated boost (VMAT-SIB) plus standard dose temozolomide (TMZ) in GBM.MethodsA Phase I clinical trial was performed in operated GBM patients using VMAT-SIB technique with progressively increased total dose. RT was delivered in 25 fractions (5 weeks) to two planning target volumes (PTVs) defined by adding a 5-mm margin to the clinical target volumes (CTVs). The CTV1 was the tumor bed plus the MRI enhancing residual lesion with 10-mm margin. The CTV2 was the CTV1 plus 20-mm margin. Only PTV1 dose was escalated (planned dose levels: 72.5, 75, 77.5, 80, 82.5, 85 Gy), while PTV2 dose remained unchanged (45 Gy/1.8 Gy). Concurrent and sequential TMZ was prescribed according to the EORTC/NCIC protocol. Dose-limiting toxicities (DLTs) were defined as any G ≥ 3 non-hematological acute toxicity or any G ≥ 4 acute hematological toxicities (RTOG scale) or any G ≥ 2 late toxicities (RTOG-EORTC scale).ResultsThirty-seven patients (M/F: 21/16; median age: 59 years; median follow-up: 12 months) were enrolled and treated as follows: 6 patients (72.5 Gy), 10 patients (75 Gy), 10 patients (77.5 Gy), 9 patients (80 Gy), 2 patients (82.5 Gy), and 0 patients (85 Gy). Eleven patients (29.7%) had G1-2 acute neurological toxicity, while 3 patients (8.1%) showed G ≥ 3 acute neurological toxicities at 77.5 Gy, 80 Gy, and 82.5 Gy levels, respectively. Since two DLTs (G3 neurological: 1 patient and G5 hematological toxicity: 1 patient) were observed at 82.5 Gy level, the trial was closed and the 80 Gy dose-level was defined as the MTD. Two asymptomatic histologically proven radionecrosis were recorded.ConclusionsAccording to the results of this Phase I trial, 80 Gy in 25 fractions accelerated hypofractionated RT is the MTD using VMAT-SIB plus standard dose TMZ in resected GBM.

Automatic Segmentation of Clinical Target Volumes for Post-Modified Radical Mastectomy Radiotherapy Using Convolutional Neural Networks

BackgroundThis study aims to construct and validate a model based on convolutional neural networks (CNNs), which can fulfil the automatic segmentation of clinical target volumes (CTVs) of breast cancer for radiotherapy.MethodsIn this work, computed tomography (CT) scans of 110 patients who underwent modified radical mastectomies were collected. The CTV contours were confirmed by two experienced oncologists. A novel CNN was constructed to automatically delineate the CTV. Quantitative evaluation metrics were calculated, and a clinical evaluation was conducted to evaluate the performance of our model.ResultsThe mean Dice similarity coefficient (DSC) of the proposed model was 0.90, and the 95th percentile Hausdorff distance (95HD) was 5.65 mm. The evaluation results of the two clinicians showed that 99.3% of the chest wall CTV slices could be accepted by clinician A, and this number was 98.9% for clinician B. In addition, 9/10 of patients had all slices accepted by clinician A, while 7/10 could be accepted by clinician B. The score differences between the AI (artificial intelligence) group and the GT (ground truth) group showed no statistically significant difference for either clinician. However, the score differences in the AI group were significantly different between the two clinicians. The Kappa consistency index was 0.259. It took 3.45 s to delineate the chest wall CTV using the model.ConclusionOur model could automatically generate the CTVs for breast cancer. AI-generated structures of the proposed model showed a trend that was comparable, or was even better, than those of human-generated structures. Additional multicentre evaluations should be performed for adequate validation before the model can be completely applied in clinical practice.

Recommendation regarding the cranial upper border of level IIb in delineating clinical target volumes (CTV) for nasopharyngeal carcinoma

Purpose To recommend a cranial border for level IIb in delineating clinical target volumes (CTV) for nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy and to help reach a consensus on contouring level IIb in CTV. Methods From 2012 to 2016, 331 nonmetastatic NPC patients treated with IMRT were retrospectively enrolled. Based on the AJCC 8th staging system of NPC, there were 15 stage I, 76 stage II, 103 stage III, and 137 stage IV patients. The distribution of cervical lymph nodes in NPC was assessed based on imaging. Comparisons of the safety and parotid dose parameters between patients with and without a reduction in the size of level IIb were conducted using SPSS 25.0 and R 2.14.2 software. Results Metastasis rates in the most commonly involved lymph nodes, the lateral retropharyngeal and IIb nodes, were 82.8% and 64.0%, respectively. Among patients with level IIb involvement, the upper borders of the metastatic nodes were beyond the caudal edge of C1 in 13.7% of cases. The parotid gland D50 and V26 values were significantly reduced after modifying the upper bound of level IIb used to delineate the CTV (P = 0.000). Conclusion In principle, the upper bound of level IIb should reach the lateral skull base during delineation of the cervical CTV for NPC. To protect the parotid glands, however, individualized reduction of the upper bound of level IIb is recommended for patients who meet certain criteria.