G. Bartlett

Proton Radiotherapy for Midline Central Nervous System Lesions: A Class Solution

Objective: Midline and central lesions of the brain requiring conventional radiotherapy (RT) present complex difficulties in dose avoidance to organs at risk (OAR). In either definitive or adjuvant settings, proper RT coverage of these lesions involves unnecessary treatment of large volumes of normal brain. We propose a class solution for these lesions using proton radiotherapy (PrT). Materials and Methods: The records of the Indiana University Health Proton Therapy Center were reviewed for patients presenting between January 1, 2005 and October 1, 2013 with midline central nervous system (CNS) lesions. Twenty-four patients were identified. After Institutional Review Board approval was granted, their dosimetry was reviewed for target volume doses and OAR dose avoidance. Results: For these cases, meningiomas were the most common histology (8 cases), and next most prevalent were craniopharyngiomas (6 cases). The others were various different deep midline brain tumors (10 cases). In all cases, fields formed by vertex and/or anterior/posterior superior oblique PrT beams along the midsagittal plane were used to provide coverage with minimal dose to the brain stem or to the cerebral hemispheres. The median prescribed dose to the planning target volume for treating these patients was 54.0 Gy RBE (range 48.6-62.5) with a mean dose of 53.5 Gy RBE. The average of the mean doses to the brain stems using these fields in the 24 plans was 18.4 Gy RBE (range 0.0-44.7). Similarly, the average of the mean doses to the hippocampi was 15.8 Gy RBE (range 0.0-52.6). Conclusions: We consider these patients to be optimally treated with PrT. The use of modified midsagittal PrT schemas allows for the treatment of midline CNS lesions with sparing of most of the uninvolved brain.

Steroid-induced adaptive proton planning in a pediatric patient with low grade glioma: A case report and literature review

Adaptive radiation therapy treatment planning (ARTP) is a valuable tool for modifying radiation therapy. As a feedback technique, ARTP has gained momentum with the use of image guided radiation therapy, deformable image registration software, and image fusion advances. ARTP can account for changes in target (shrinkage, growth, cystic expansion) and patient characteristics (weight changes, edema, setup errors) during fractionated radiation therapy. With highly conformal treatments and smaller planning target volumes (PTV) now common, anatomic changes that affect target and organs at risk (OAR) dosimetry mandates adaptation awareness moving forward. Yan et al1 have proposed that ARTP may supplant generic margin expansions resulting in improved OAR dosimetry while guaranteeing tumor coverage. Current indications for ARTP include cystic changes in craniopharyngioma and bulky disease regression where initial planning exceeds OAR tolerances. Though advantageous, Bragg peak properties of proton beam therapy (PBT) create dosimetric challenges secondary to OARmotion and end of range uncertainty. Less well described is the unique challenge of PBT dosimetry due to

Extended Volumetric Follow-up of Juvenile Pilocytic Astrocytomas Treated with Proton Beam Therapy

Purpose To describe volume changes following proton beam therapy (PBT) for juvenile pilocytic astrocytoma (JPA), we analyzed post-PBT magnetic resonance imaging (MRI) to clarify survivorship, response rate, and the concept of pseudoprogression. Materials and Methods Pediatric patients with a histologic diagnosis of JPA after a biopsy or subtotal resection and at least 4 post-PBT MRIs were retrospectively reviewed. After PBT, tumors were contoured on follow-up T1-contrasted MRIs, and 3-dimensional volumes were plotted against time, with thresholds for progressive disease and partial response. Patterns of response, pseudoprogression, and progression were uncovered. Post-PBT clinical course was described by the need for further intervention and survivorship. Results Fifteen patients with a median of 10 follow-up MRIs made up this report: 60% were heavily pretreated with multiple lines of chemotherapy, and 67% had undergone subtotal resection. With a median follow-up of 55.3 months after a median of 5400 centigray equivalents PBT, estimates of 5-year overall survival and intervention-free survival were 93% and 72%, respectively. The crude response rate of 73% included pseudoprogressing patients, who comprised 20% of the entire cohort; the phenomenon peaked between 3 and 8 months and resolved by 18 months. One nonresponder expired from progression. Post-PBT intervention was required in 53% of patients, with 1 patient resuming chemotherapy. There were no further resections or radiotherapy. One patient developed acute lymphoblastic leukemia, and another developed biopsy-proven radionecrosis. Conclusion The PBT for inoperable/progressive JPA provided 72% 5-year intervention-free survival in heavily pretreated patients. Although most patients responded, 20% demonstrated pseudoprogression. The need for post-PBT surveillance for progression and treatment-induced sequelae should not be underestimated in this extended survivorship cohort.

Histology, Tumor Volume, and Radiation Dose Predict Outcomes in NSCLC Patients After Stereotactic Ablative Radiotherapy

Introduction: It remains unclear if histology should be independently considered when choosing stereotactic ablative body radiotherapy dose prescriptions for NSCLC. Methods: The study population included 508 patients with 561 lesions between 2000 and 2016, of which 442 patients with 482 lesions had complete dosimetric information. Eligible patients had histologically or clinically diagnosed early‐stage NSCLC and were treated with 3 to 5 fractions. The primary endpoint was in‐field tumor control censored by either death or progression. Involved lobe control was also assessed. Results: At 6.7 years median follow‐up, 3‐year in‐field control, involved lobe control, overall survival, and progression‐free survival rates were 88.1%, 80.0%, 49.4%, and 37.2%, respectively. Gross tumor volume (GTV) (hazard ratio [HR] = 1.01 per mL, p = 0.0044) and histology (p = 0.0225) were independently associated with involved lobe failure. GTV (HR = 1.013, p = 0.001) and GTV dose (cutoff of 110 Gy, biologically effective dose with &agr;/&bgr; = 10 [BED10], HR = 2.380, p = 0.0084) were independently associated with in‐field failure. For squamous cell carcinomas, lower prescription doses were associated with worse in‐field control (12 Gy × 4 or 10 Gy × 5 versus 18 Gy or 20 Gy × 3: HR = 3.530, p = 0.0447, confirmed by propensity score matching) and was independent of GTV (HR = 1.014 per mL, 95% confidence interval: 1.005–1.022, p = 0.0012). For adenocarcinomas, there were no differences in in‐field control observed using the above dose groupings (p = 0.12 and p = 0.31, respectively). Conclusions: In the absence of level I data, GTV and histology should be considered to personalize radiation dose for stereotactic ablative body radiotherapy. We suggest lower prescription doses (i.e., 12 Gy × 4 or 10 G × 5) should be avoided for squamous cell carcinomas if normal tissue tolerances are met.

Proton Therapy for Cord Compression from Extramedullary Hematopoiesis

Abstract A patient presented with spinal cord compression due to extramedullary hematopoiesis. She was treated with decompressive surgery followed by proton beam radiation therapy to a dose of 2340 cGy relative biological effectiveness in 13 fractions. After 6 months of follow-up she has had a near complete recovery from her initial symptoms and remains free from extramedullary hematopoiesis around the spinal cord. Proton beam radiation therapy was chosen over conventional linear accelerator-based radiation therapy due to the normal-tissue sparing effects and potential decreased risk of secondary neoplasia. Proton beam radiation therapy should be considered for cases of spinal cord compression from extramedullary hematopoiesis involving young patients at risk for long-term complications.