Abstract
PURPOSE
18F-DOPA is sensitive/specific for identifying areas of biologically aggressive disease for glioblastoma. We report the impact of 18F-DOPA on radiation treatment planning from a ...phase II study.
METHODS
Gross target volume (GTV) was defined by the boolean of high-risk PET (tumor/normal brain SUV > 2.0) and MRI T1 contrast enhancement (MRI-CE) including surgical cavity. The clinical target volume (CTV) included the GTV with 1cm margin. Using proton beam therapy, GTV ≤ 65 cc was treated with 25 (CTV), 30 (MRI-CE), and 35 (PET) GyE over 5 fractions with a simultaneous integrated boost. GTV > 65 cc received 30 (CTV), 35 (MRI-CE), and 40 (PET) GyE over 10 fractions. Radiation field design was compared to traditional 1.5cm CTV margin on MRI-CE.
RESULTS
Between May 2019 and October 2021, 39 patients were treated. The median MRI-CE tumor diameter was 5.2cm. The median PET volume was 7.9cc (range 0–64.9cc). The median MRI-CE volume was 35.1cc (range 8.6–114cc). High-risk PET was contained within: MRI-CE 18/39 (46%), MRI-CE + T2W FLAIR 13/39 (33%), MRI-CE + T2W FLAIR + outside GTV 4/39 (10%), outside GTV 2/39 (5%) and no uptake 2/39 (5%). Utilizing this planning technique, there was a 26% volume reduction in CTV to traditional 1.5 cm margin on MRI-CE. PET imaging in treatment planning allowed inclusion of high-risk disease that would have been excluded on traditional CTV in 23% of cases (range 1.6-33.8cc). PET was more predictive HR 1.03 (95% CI 1.01, 1.05) p = 0.002 than MRI HR 1.01 (95% CI 1.00, 1.03) p = 0.02 for death with each cc increasing risk of death by 3.1%.
CONCLUSIONS
The incorporation of 18F-DOPA in treatment planning yields a more targeted approach with reductions in both normal brain treated and risk of geographic miss compared to traditional CTV margins.
Abstract
INTRODUCTION
Glioblastomas (GBMs) are highly aggressive tumors. A common clinical challenge after standard of care treatment is differentiating tumor progression from treatment-related ...changes, also known as pseudoprogression (PsP). Usually, PsP resolves or stabilizes without further treatment or a course of steroids, whereas true progression (TP) requires more aggressive management. Differentiating PsP from TP will affect the patient's outcome. This study investigated using deep learning to distinguish PsP MRI features from progressive disease.
METHOD
We included newly diagnosed GBM patients who met the inclusion criteria, including a new or increasing enhancing lesion size within the original radiation field and who had clinical, medication, and any histopathology available. The interpretation of the MR images at the image inclusion time point had to be indeterminate. We labeled those who subsequently were stable or improved on imaging and clinically as PSP and those with clinical and imaging deterioration as TP. A subset of subjects underwent a second resection. We labeled these subjects as PSP or TP based on the histological diagnosis. We performed skull stripping, coregistered contrast-enhanced T1 MRIs with T2-weighted images for each patient and used them as input to a 3-D Densenet121 model. We used several augmentation techniques and five-fold cross-validation to achieve more robust predictions.
RESULT
We included 124 patients who met the criteria, and of those, 63 were PsP and 61 were TP. We trained a deep learning model that achieved 76.4% (ranged 70%-84%, SD 5.122) mean accuracy over the 5 folds, 0.7560(ranged 0.6553-0.8535, SD 0.069) mean AUROCC, 88.72% (SD 6.86) mean sensitivity, and 62.05%(SD 9.11) mean specificity.
CONCLUSION
We report the development of a deep learning model that distinguishes PsP from TP in GBM patients treated per the Stupp protocol. Further refinement and external validation are required prior to widespread adoption in clinical practice.
Abstract
OBJECTIVES: We report radiation induced signal changes (RIC) on MRI in adult patients with brain tumors treated with pencil beam scanning proton therapy (PBS-PRT).
METHODS
All patients > 18 ...years receiving standard fractionation RT (4554 GyE) for a primary brain tumor with > 6 month follow-up were included. Post-RT MRIs were compared to the pre-RT scans. RIC was defined as new contrast enhancement (CET1W) and/or T2-FLAIR (T2W) changes MRI outside the GTV (CTCAE v4.0 grading was used). Monte Carlo, RBE (relative biologic effectiveness), and LET plan evaluation pre-RT were performed. Tumor, clinical and treatment factors were analyzed.
RESULTS
Twenty-one patients were identified. RIC developed in 17/21 (81%: 2 CET1W, 15 T2W). All RIC appeared adjacent to surgical cavity and/or GTV in areas of increased RBE. 3 patients developed symptomatic RIC: All three patients had CET1W changes within tumor. Patient 1 received 50.4 GyE for a subtotally resected skull base meningioma. T2W changes developed at 3 months and CET1W changes in the tumor appeared at 7 months. Grade 2 symptoms (headache, unsteadiness, incontinence) developed by 14 months. Symptoms and imaging improved with dexamethasone taper by 22 months. Patient 2 received 54GyE for a subtotally resected grade II oligoastrocytoma. 4 months post-RT patient developed perilesional T2W. Headaches developed at 7 months and resolved following dexamethasone taper. Patient 3 received 54GyE for a progressive tectal plate glioma. At 2 months post-RT, CET1W changes within the tumor and T2W perilesional changes developed. Grade 3 diplopia developed a month later. The CET1W and T2W changes resolved at 13 months. No relationships between factors and RIC were identified.
CONCLUSION
Asymptomatic RIC are common after RT, but symptoms are infrequent. Symptoms appear to be associated with post-PRT changes within tumor. A larger cohort including comparison to photon treatments and RBE will be evaluated in the future.
To assess acute gastrointestinal (GI) and genitourinary (GU) toxicities of intensity-modulated proton therapy (IMPT) targeting the prostate/seminal vesicles and pelvic lymph nodes for prostate ...cancer.
A prospective study (ClinicalTrials.gov: NCT02874014), evaluating moderately hypofractionated IMPT for high-risk or unfavorable intermediate-risk prostate cancer, accrued a target sample size of 56 patients. The prostate/seminal vesicles and pelvic lymph nodes were treated simultaneously with 6750 and 4500 centigray radiobiologic equivalent (cGyRBE), respectively, in 25 daily fractions. All received androgen-deprivation therapy. Acute GI and GU toxicities were prospectively assessed from 7 GI and 9 GU categories of the Common Terminology Criteria for Adverse Events (version 4), at baseline, weekly during radiotherapy, and 3-month after radiotherapy. Fisher exact tests were used for comparisons of categorical data.
Median age was 75 years. Median follow-up was 25 months. Fifty-five patients were available for acute toxicity assessment. Sixty-two percent and 2%, respectively, experienced acute grade 1 and 2 GI toxicity. Grade 2 GI toxicity was proctitis. Sixty-five percent and 35%, respectively, had acute grade 1 and 2 GU toxicity. The 3 most frequent grade 2 GU toxicities were urinary frequency, urgency, and obstructive symptoms. None had acute grade ≥ 3 GI or GU toxicity. The presence of baseline GI and GU symptoms was associated with a greater likelihood of experiencing acute GI and GU toxicity, respectively. Of 45 patients with baseline GU symptoms, 44% experienced acute grade 2 GU toxicity, compared with only 10% among 10 with no baseline GU symptoms (
= 0.07). Although acute grade 1 and 2 GI and GU toxicities were common during radiotherapy, most resolved at 3 months after radiotherapy.
A moderately hypofractionated IMPT targeting the prostate/seminal vesicles and regional pelvic lymph nodes was well tolerated with no acute grade ≥ 3 GI or GU toxicity. Patients with baseline GU symptoms had a higher rate of acute grade 2 GU toxicity.
Abstract
INTRODUCTION
Brain tumors can result in focal neurological and cognitive deficits which may impair the ability to drive. There are no evidence-based recommendations on driving restrictions ...for patients with brain metastases. Recommendations vary per practice, with extrapolation based on local driving and epilepsy laws. Occupational Therapy driving assessment (OTDA) may provide insight into limitations for this population.
OBJECTIVE
To determine whether clinical neurologic examination is sufficient to predict suitability to drive in patients with brain metastases.
METHODS
We assessed the concordance between Neurology assessment of suitability to drive (pass/fail) and OTDA in individuals with brain metastases. 40 subjects were prospectively enrolled. Neurooncology evaluation was performed as standard of care, including an interview and neurological examination. Subjects subsequently underwent OTDA during which a battery of objective measures of visual, cognitive and motor skills related to driving was administered.
RESULTS
Preliminary results from the first 29 patients included are reported. Mean age was 68 years. Lung was the primary location of the tumor in 62% cases. More patients in the group that failed OTDA had bilateral brain metastasis (77.3% vs 42.9%,p=0.0478). The sensitivity of the Neurology assessment to predict driving fitness compared to OTDA was 22.7% and the specificity 71.4%. The 22 patients who failed OTDA were more likely to fail on Vision Coach (81.8%), MOCA (68.2%) and Trail Making (50%) tests.
DISCUSSION
There was poor correlation between the assessment of suitability to drive by Neurology and the outcome of the OTDA in patients with brain metastases. Subtle deficits that may impair the ability to drive safely may not be evident on neurologic examination. The Vision Coach, MOCA and Trail Making tests were the most sensitive tests to predict driver safety. The results raise questions about the choice of assessments in making recommendations about fitness to drive in people with brain metastases.
•Whole-brain intensity modulated proton therapy capably spares hippocampal volumes.•Hippocampal avoidance whole-brain radiotherapy may benefit pediatric populations.•Intensity modulated proton ...therapy provides superior target-dose homogeneity relative to modulated x-rays.
Intensity modulated proton therapy (IMPT) allows for modulation parameterized for individual beamlets by position, intensity, and depth. This modulation capability is ideally suited for sparing organs at risk intermediate of the radiation target, such as hippocampal volumes within the whole brain. This work compared IMPT relative to volumetric modulated arc therapy (VMAT) during hippocampal avoidance whole brain radiation therapy (HA WBRT).
Ten adult and ten pediatric patients previously treated for central nervous system malignancies were identified. IMPT and VMAT treatment plans employing HA WBRT were generated for each patient, delivering 30 GyE (Gray Equivalent) in 10 fractions for adults and 36 GyE in 20 fractions for pediatrics. Dose indices, including dose volume histogram metrics and homogeneity index HI = D5% − D95%/Dmean × 100, were used to assess plan quality and describe target coverage and normal-tissue sparing.
IMPT offered significant benefits relative to VMAT for hippocampal sparing. Hippocampal mean dose was reduced from 13.7 ± 0.8 Gy with VMAT to 5.4 ± 0.3 GyE using IMPT for pediatrics, and was reduced from 11.7 ± 0.9 Gy with VMAT to 4.4 ± 0.2 GyE using IMPT for adults. IMPT similarly lowered left hippocampal mean dose. Dose to 95% of the clinical target volume was statistically equivalent for both groups; however IMPT reduced the homogeneity index by roughly half.
This manuscript demonstrates that HA IMPT can match or exceed dosimetric benefits offered with modulated X-rays. Inclusion of IMPT in future prospective studies is warranted.
Abstract
BACKGROUND
Radiation is an integral component of the multidisciplinary treatment of patients with intracranial metastasis (ICM) from melanoma. The risk of radiation necrosis (RN) ...post-treatment can range from 5–25%. We retrospectively evaluated pre- and post-radiation clinical and radiographical characteristics in patients with ICM from melanoma to identify potential risk factors for RN.
METHODS
After IRB approval, patients with ICM from melanoma who received radiation at our institution between 2013 and 2018 were retrospectively reviewed. We recorded demographics, intracranial metastasis (burden and location), systemic therapy, resection, stereotactic radiosurgery versus whole brain radiation, and outcomes. Brain MRI was evaluated using the Response Assessment in Neuro-Oncology criteria (RANO).
RESULTS
A total of 27 patients were included in the study. RN was diagnosed in 14 patients (52%) at one month to three years following radiation. Cerebellar location (n=7) was significantly associated with RN (p=0.0058). Metastasis-associated hemorrhage was present in 7 patients, 6 of which developed RN (43% vs 8%, p=0.08). Surgical resection prior to radiation was performed in 9 patients, 7 of which developed RN (50% vs 15%, p=0.1). RN appeared to be less often diagnosed when ICM were treated with higher doses of radiation (24 Gy vs 20 Gy, p=0.07). Systemic treatment was administered prior to radiation in 25 patients and we found no relationship with systemic therapy type and RN. Presumed RN was treated in 12 of 14 patients (86%). Steroids or surgical resection were the primary treatment modalities, with laser ablation used in 1 case. Following treatment, improvement was noted in 3 patients radiographically and in 1 of these clinically.
CONCLUSIONS
This series of patients with radiotherapy-treated brain metastases from melanoma reveals cerebellar involvement, hemorrhage, and prior surgical resection as potential risk factors for radiation necrosis. Neoadjuvant systemic treatment did not appear to be a risk factor in our review.
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