The use of a mini-ridge filter with cyclotron-based pencil beam scanning proton therapy.

BACKGROUND: Pencil beam scanning (PBS) proton therapy allows for far superior dose conformality compared with passive scattering techniques. However, one drawback of PBS is that the beam delivery time can be long, particularly when treating superficial disease. Minimizing beam delivery time is important for patient comfort and precision of treatment delivery. Mini-ridge filters (MRF) have been shown to reduce beam delivery time for synchrotron-based PBS. Given that cyclotron systems are widely used in proton therapy it is necessary to investigate the potential clinical benefit of mini-ridge filters in such systems. PURPOSE: To demonstrate the clinical benefit of using a MRF to reduce beam delivery time for patients with large target volumes and superficial disease in cyclotron-based PBS proton therapy. METHODS: A MRF beam model was generated by simulating the effect of a MRF on our clinical beam data assuming a fixed snout position relative to the isocenter. The beam model was validated with a series of measurements. The model was used to optimize treatment plans in a water phantom and on six patient DICOM datasets to further study the effect of the MRF and for comparison with physician-approved clinical treatment plans. Beam delivery time was measured for six plans with and without the MRF to demonstrate the reduction achievable. Plans with and without MRF were reviewed to confirm clinical acceptability by a radiation oncologist. Patient-specific QA measurements were carried out with a two-dimensional ionization chamber array detector for one representative patient's plan optimized with the MRF beam model. RESULTS: Results show good agreement between the simulated beam model and measurements with mean and maximum deviations of 0.06 mm (0.45%) and 0.61 mm (4.9%). The increase in Bragg peak width (FWHM) ranged from 2.7 mm at 226 MeV to 6.1 mm at 70 MeV. The mean and maximum reduction in beam delivery time observed per field was 29.1 s (32.2%) and 79.7 s (55.3%). CONCLUSION: MRFs can be used to reduce treatment time in cyclotron-based PBS proton therapy without sacrificing plan quality. This is particularly beneficial for patients with large targets and superficial disease such as in breast cancer where treatment times are generally long, as well as patients treated with deep inspiration breath hold (DIBH).

Evaluation of the Clinical Utility of the Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP): A Case-Based Pilot Assessment.

PURPOSE: The Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP) provides patient-specific survival predictions and evidence-based recommendations to guide multidisciplinary management for symptomatic bone metastases. We assessed the clinical utility of the BMETS-DSP through a pilot prepost design in a simulated clinical environment. METHODS: Ten Radiation Oncology physicians reviewed 55 patient cases at two time points: without and then with the use of BMETS-DSP. Assessment included 12-month survival estimate, confidence in and likelihood of sharing estimates with patients, and recommendations for open surgery, systemic therapy, hospice referral, and radiotherapy (RT) regimen. Paired statistics compared pre- versus post-DSP outcomes. Reported statistical significance is P < .05. RESULTS: Pre- versus post-DSP, overestimation of true minus estimated survival time was significantly reduced (mean difference -2.1 [standard deviation 4.1] v -1 month [standard deviation 3.5]). Prediction accuracy was significantly improved at cut points of < 3 (72 v 79%), ≤ 6 (64 v 71%), and ≥ 12 months (70 v 81%). Median ratings of confidence in and likelihood of sharing prognosis significantly increased. Significantly greater concordance was seen in matching use of 1-fraction RT with the true survival < 3 months (70 v 76%) and < 10-fraction RT with the true survival < 12 months (55 v 62%) and appropriate use of open surgery (47% v 53%), without significant changes in selection of hospice referral or systemic therapy. CONCLUSION: This pilot study demonstrates that BMETS-DSP significantly improved physician survival estimation accuracy, prognostic confidence, likelihood of sharing prognosis, and use of prognosis-appropriate RT regimens in the care of symptomatic bone metastases, supporting future multi-institutional validation of the platform.

Demonstrating the benefits of corrective intraoperative feedback in improving the quality of duodenal hydrogel spacer placement.

PURPOSE: Pancreatic cancer is the fourth leading cause of cancer-related death with a 10% 5-year overall survival rate (OS). Radiation therapy (RT) in addition to dose escalation improves the outcome by significantly increasing the OS at 2 and 3 years but is hindered by the toxicity of the duodenum. Our group showed that the insertion of hydrogel spacer reduces duodenal toxicity, but the complex anatomy and the demanding procedure make the benefits highly uncertain. Here, we investigated the feasibility of augmenting the workflow with intraoperative feedback to reduce the adverse effects of the uncertainties. MATERIALS AND METHODS: We simulated three scenarios of the virtual spacer for four cadavers with two types of gross tumor volume (GTV) (small and large); first, the ideal injection; second, the nonideal injection that incorporates common spacer placement uncertainties; and third, the corrective injection that uses the simulation result from nonideal injection and is designed to compensate for the effect of uncertainties. We considered two common uncertainties: (1) "Narrowing" is defined as the injection of smaller spacer volume than planned. (2) "Missing part" is defined as failure to inject spacer in the ascending section of the duodenum. A total of 32 stereotactic body radiation therapy (SBRT) plans (33 Gy in 5 fractions) were designed, for four cadavers, two GTV sizes, and two types of uncertainties. The preinjection scenario for each case was compared with three scenarios of virtual spacer placement from the dosimetric and geometric points of view. RESULTS: We found that the overlapping PTV space with the duodenum is an informative quantity for determining the effective location of the spacer. The ideal spacer distribution reduced the duodenal V33Gy for small and large GTV to less than 0.3 and 0.1cc, from an average of 3.3cc, and 1.2cc for the preinjection scenario. However, spacer placement uncertainties reduced the efficacy of the spacer in sparing the duodenum (duodenal V33Gy: 1.3 and 0.4cc). The separation between duodenum and GTV decreased by an average of 5.3 and 4.6 mm. The corrective feedback can effectively bring back the expected benefits from the ideal location of the spacer (averaged V33Gy of 0.4 and 0.1cc). CONCLUSIONS: An informative feedback metric was introduced and used to mitigate the effect of spacer placement uncertainties and maximize the benefits of the EUS-guided procedure.

Finite Element-Based Personalized Simulation of Duodenal Hydrogel Spacer: Spacer Location Dependent Duodenal Sparing and a Decision Support System for Spacer-Enabled Pancreatic Cancer Radiation Therapy.

Purpose: Pancreatic cancer is the fourth leading cause of cancer-related death, with a very low 5-year overall survival rate (OS). Radiation therapy (RT) together with dose escalation significantly increases the OS at 2 and 3 years. However, dose escalation is very limited due to the proximity of the duodenum. Hydrogel spacers are an effective way to reduce duodenal toxicity, but the complexity of the anatomy and the procedure makes the success and effectiveness of the spacer procedure highly uncertain. To provide a preoperative simulation of hydrogel spacers, we presented a patient-specific spacer simulator algorithm and used it to create a decision support system (DSS) to provide a preoperative optimal spacer location to maximize the spacer benefits. Materials and Methods: Our study was divided into three phases. In the validation phase, we evaluated the patient-specific spacer simulator algorithm (FEMOSSA) for the duodenal spacer using the dice similarity coefficient (DSC), overlap volume histogram (OVH), and radial nearest neighbor distance (RNND). For the simulation phase, we simulated four virtual spacer scenarios based on the location of the spacer in para-duodenal space. Next, stereotactic body radiation therapy (SBRT) plans were designed and dosimetrically analyzed. Finally, in the prediction phase, using the result of the simulation phase, we created a Bayesian DSS to predict the optimal spacer location and biological effective dose (BED). Results: A realistic simulation of the spacer was achieved, reflected in a statistically significant increase in average target and duodenal DSC for the simulated spacer. Moreover, the small difference in average mean and 5th-percentile RNNDs (0.5 and 2.1 mm) and OVH thresholds (average of less than 0.75 mm) showed that the simulation attained similar separation as the real spacer. We found a spacer-location-independent decrease in duodenal V20Gy, a highly spacer-location-dependent change in V33Gy, and a strong correlation between L1cc and V33Gy. Finally, the Bayesian DSS predicted the change in BED with a root mean squared error of 3.6 Gys. Conclusions: A duodenal spacer simulator platform was developed and used to systematically study the dosimetric effect of spacer location. Further, L1cc is an informative anatomical feedback to guide the DSS to indicate the spacer efficacy, optimum location, and expected improvement.

Comparative Effectiveness of Proton Therapy versus Photon Radiotherapy in Adolescents and Young Adults for Classical Hodgkin Lymphoma.

PURPOSE: Early stage (stages I-II) classical Hodgkin lymphoma (cHL) is a highly curable disease typically diagnosed in adolescents and young adults (AYAs). Proton therapy can also reduce the late toxicity burden in this population, but data on its comparative efficacy with photon radiotherapy in this population are sparse. We assessed outcomes in AYAs with cHL in a multi-institution retrospective review. MATERIALS AND METHODS: We identified 94 patients aged 15 to 40 years with stages I and II cHL treated with radiotherapy as part of their initial treatment between 2008 and 2017. We used Kaplan-Meier analyses and log-rank testing to evaluate survival differences between groups of patients. RESULTS: A total of 91 patients were included in the analysis. The 2-year progression-free survival (PFS) rate was 89%. Of the 12 patients who experienced progression after radiotherapy, 4 occurred out-of-field, 2 occurred in-field, and 6 experienced both in- and out-of-field progression. There was no significant difference in 2-year PFS among AYA patients by radiotherapy dose received (≥ 30 Gy, 91%; < 30 Gy, 86%; P = .82). Likewise, there was no difference in 2-year PFS among patients who received either proton or photon radiotherapy (proton, 94%; photon, 83%; P = .07). CONCLUSION: Our cohort of AYA patients had comparable outcomes regardless of radiotherapy dose or modality used. For patients with significant risk of radiation-induced late effects, proton therapy is a reasonable treatment modality.

The Use of Hyperbaric Oxygen Therapy in the Management of Severe Radiation-Induced Hemorrhagic Gastritis in a Pediatric Patient.

Radiation-induced hemorrhagic gastritis is a serious and rare complication of radiation therapy. Optimal therapies in the pediatric population are not well established. We report a 2-year-old female diagnosed with rhabdomyosarcoma who developed hemorrhagic gastritis following chemotherapy and radiation therapy. The patient presented with acute onset anemia, hematemesis, and melena. Endoscopies revealed circumferential ulceration at the pylorus with spontaneous oozing that failed to respond effectively with multimodal medical and endoscopic therapies. Following hemodynamic stabilization, the patient was treated with hyperbaric oxygen therapy with excellent clinical response of the bleeding. Further research on the benefit of hyperbaric oxygen therapy is warranted to determine if this treatment can reduce the incidence of gastrointestinal complications in patients who have received radiation therapy.

Outcomes of and treatment planning considerations for a hybrid technique delivering proton pencil-beam scanning radiation to women with metal-containing tissue expanders undergoing post-mastectomy radiation.

BACKGROUND: Following mastectomy, immediate breast reconstruction often involves the use of temporary tissue expanders (TEs). TEs contain metallic ports (MPs), which complicate proton pencil-beam scanning (PBS) planning. A technique was implemented for delivering PBS post-mastectomy radiation (PMRT) to patients with TEs and MPs. METHODS: A protocol utilizing a hybrid single- and multi-field optimization (SFO, MFO) technique was developed. Plans were robustly optimized using a Monte Carlo algorithm. A CTV_eval structure including chest wall (CW) and regional nodal (RNI) targets and excluding the TE was evaluated. Organ at risk (OAR) dosimetry and acute toxicities were analyzed. RESULTS: Twenty-nine women were treated with this technique. A 2-field SFO technique was used superior and inferior to the MP, with a 3 or 4-field MFO technique used at the level of the MP. Virtual blocks were utilized so that beams did not travel through the MP. A port-to-CW distance of 1 cm was required. Patients underwent daily image-guidance to ensure the port remained within a 0.5 cm internal planning volume (ITV). Median RT dose to CTV_eval was 50.4 Gy (45.0-50.4). Median 95% CTV_eval coverage was 99.5% (95-100). Optically stimulated luminescent dosimeter (OSLD) readings were available for 8 patients and correlated to the dose measurements in the treatment planning system (TPS); median OSLD ratio was 0.99 (range, 0.93-1.02). CONCLUSIONS: Delivering PMRT with PBS for women with metal-containing TEs using a hybrid SFO/MFO technique is feasible, reproducible, and achieves excellent dose distributions. Specialized planning and image-guidance techniques are required to safely utilize this treatment in the clinic.

EUS-guided hydrogel microparticle injection in a cadaveric model.

BACKGROUND AND AIMS: A potential method to reduce gastrointestinal toxicity during radiation therapy in pancreatic head cancer is to create a physical space between the head of the pancreas (HOP) and the duodenum. To date, there have been early reports on the feasibility of endoscopic ultrasound (EUS)-guided hydrogel injection into the interface between the HOP and the duodenum to increase the peri-pancreatic space for radiotherapy. We aimed to evaluate the technical feasibility of EUS-guided hydrogel injection for the creation of space at the peri-pancreatic interface in a cadaveric model. METHODS: Baseline abdominal computerized tomography (CT) was performed on three unfixed cadaveric specimens. The hydrogel was injected transduodenally into the interface between the HOP and duodenum using linear-array EUS and a 19G needle for fine needle aspiration (FNA). This procedure was repeated along the length of the HOP. CT imaging and gross dissection were performed after the procedure to confirm the localization of the hydrogel and to measure the distance between the HOP and the duodenum. RESULTS: All cadavers underwent successful EUS-guided injection of the hydrogel. Cadavers 1, 2, and 3 were injected with 9.5, 27, and 10 cc of hydrogel, respectively; along the HOP, the formation of the peri-pancreatic space was a maximum size of 11.77, 13.20, and 12.89 mm, respectively. The hydrogel injections were clearly visualized as hyperechoic bullae during EUS and on post-procedure CT images without any artifacts in all cases. CONCLUSIONS: We demonstrated that EUS-guided delivery of hydrogel is feasible, and that it increases the peri-pancreatic space in a cadaveric model. The polyethylene glycol (PEG) hydrogel was clearly visible on EUS and CT, without significant artifacts. This may lead to new treatment approaches for pancreatic carcinomas.

Plan quality effects of maximum monitor unit constraints in pencil beam scanning proton therapy for central nervous system and skull base tumors.

PURPOSE/OBJECTIVE(S): With reports of CNS toxicity in patients treated with proton therapy at doses lower than would be expected based on photon data, it has been proposed that heavy monitor unit (MU) weighting of pencil beam scanning (PBS) proton therapy spots may potentially increase the risk of toxicity. We evaluated the impact of maximum MU weighting per spot (maxMU/spot) restrictions on PBS plan quality, prior to implementing clinic-wide maxMU/spot restrictions. MATERIALS/METHODS: PBS plans of 11 patients, of which 3 plans included boosts, for a total of 14 PBS sample cases were included. Per sample case, a single dosimetrist created 4 test plans, gradually reducing the maxMU/spot in the plan. Test Plan 1, unrestricted in maxMU/spot, was the reference for all restricted plan comparisons (comparison sets 2 vs. 1; 3 vs. 1; and 4 vs. 1). The impact of MU/spot restrictions on plan quality metrics were analyzed with Wilcoxon signed rank test analyses. Treatment delivery time was modeled for a representative case. RESULTS: A total of 14 PBS sample cases, 7 (50%) single-field optimized, 7 (50%) multi-field optimized, 9 (64%) delivering > 3500 cGy, 9 (64%) with 3 beams, and 7 (50%) without a range shifter were included. There were no differences in plan quality metrics of target coverage (V95% and V100% prescription), conformality and gradient indices, hot spot volume (V105% prescription), and dose to normal brain (V10%/30%/50%/70%/90%/100% prescription) with reductions of allowable maxMU/spot across all comparison sets (p > 0.05). Max MU/spot restrictions did not increase treatment delivery time when analyzed for a representative case. CONCLUSION: MaxMU/spot restrictions within the thresholds evaluated in this study did not degrade overall plan quality metrics. Future studies should evaluate spot weighting with linear energy transfer/relative biologic effectiveness-informed planning to determine if spot weighting manipulation impacts clinical outcomes and mitigates toxicity.

A Multi-institutional Comparative Analysis of Proton and Photon Therapy-Induced Hematologic Toxicity in Patients With Medulloblastoma.

PURPOSE: This multi-institutional retrospective study sought to examine the hematologic effects of craniospinal irradiation (CSI) in pediatric patients with medulloblastoma using proton or photon therapy. METHODS AND MATERIALS: Clinical and treatment characteristics were recorded for 97 pediatric patients with medulloblastoma who received CSI without concurrent chemotherapy or with concurrent single-agent vincristine from 2000 to 2017. Groups of 60 and 37 patients underwent treatment with proton-based and photon-based therapy, respectively. Overall survival was determined by Kaplan-Meier curves with log-rank test. Comparisons of blood counts at each timepoint were conducted using multiple t tests with Bonferroni corrections. Univariate and multivariate analyses of time to grade ≥3 hematologic toxicity were performed with Cox regression analyses. RESULTS: Median age of patients receiving proton and photon CSI was 7.5 years (range, 3.5-22.7 years) and 9.9 years (range, 3.6-19.5 years), respectively. Most patients had a diagnosis of standard risk medulloblastoma, with 86.7% and 89.2% for the proton and photon cohorts, respectively. Median total dose to involved field or whole posterior fossa was 54.0 Gy/Gy relative biological effectiveness (RBE) and median CSI dose was 23.4 Gy/Gy(RBE) (range, 18-36 Gy/Gy[RBE]) for both cohorts. Counts were significantly higher in the proton cohort compared with the photon cohort in weeks 3 to 6 of radiation therapy (RT). Although white blood cell counts did not differ between the 2 cohorts, patients receiving proton RT had significantly higher lymphocyte counts throughout the RT course. Similar results were observed when excluding patients who received vertebral body sparing proton RT or limiting to those receiving 23.4 Gy. Only photon therapy was associated with decreased time to grade ≥3 hematologic toxicity on univariate and multivariable analyses. No difference in overall survival was observed, and lymphopenia did not predict survival. CONCLUSIONS: Patients who receive CSI using proton therapy experience significantly decreased hematologic toxicity compared with those receiving photon therapy.

Evaluation of a Novel Absorbable Radiopaque Hydrogel in Patients Undergoing Image Guided Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma.

PURPOSE: We assessed the feasibility and safety of placing a radiopaque hydrogel in the pancreaticoduodenal groove via endoscopic ultrasound guidance in patients with borderline resectable/locally advanced pancreatic cancer (BR/LAPC). METHODS AND MATERIALS: Hydrogel injections were done at time of fiducial placement to form blebs in the pancreaticoduodenal groove. Patients subsequently underwent simulation computed tomography (sim-CT) followed by hypofractionated stereotactic body radiotherapy (SBRT; 33 Gy in 5 fractions). Four to 8 weeks after SBRT, patients underwent CT re-evaluation for surgical candidacy and assessment of hydrogel location and size. Hydrogel placement was considered successful if identified in the pancreaticoduodenal groove on sim-CT scan. Stability was evaluated using equivalence testing analyses, with a null hypothesis of the presence of a ≥20% mean percentage change in volume and ≥2 mm change in the median and mean interbleb surface distance with a P value <.05 required to reject the null hypothesis and conclude equivalence. For patients undergoing pancreaticoduodenectomy, hydrogel sites were histologically examined for location and local inflammatory reactions. RESULTS: Hydrogel placement was successful in 6 of the 6 evaluable patients. The average changes in median and mean interbleb distances were -0.43 mm and -0.35 mm, respectively, with P < .05. The average change in volume from sim-CT to post-SBRT CT was -1.0%, with P < .05. One patient experienced grade 3 nausea after fiducial/hydrogel placement, with no other adverse events to date. CONCLUSIONS: These data demonstrate feasibility and safety of injecting a hydrogel marker in the pancreaticoduodenal groove in patients with BR/LAPC and set the stage for a follow-up clinical trial to place hydrogel as a spacer between the pancreatic tumor and dose-limiting, radiosensitive duodenum.

Brainstem Injury in Pediatric Patients Receiving Posterior Fossa Photon Radiation.

PURPOSE: Brainstem necrosis is a rare, but dreaded complication of radiation therapy; however, data on the incidence of brainstem injury for tumors involving the posterior fossa in photon-treated patient cohorts are still needed. METHODS AND MATERIALS: Clinical characteristics and dosimetric parameters were recorded for 107 pediatric patients who received photon radiation for posterior fossa tumors without brainstem involvement from 2000 to 2016. Patients were excluded if they received a prescription dose <50.4 Gy, a brainstem maximum dose <50.4 Gy, or had fewer than 2 magnetic resonance imaging scans within 18 months after radiation. Post-radiation therapy magnetic resonance imaging findings were recorded, and brainstem toxicity was graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5. RESULTS: The most common histologies were medulloblastoma (61.7%) and ependymoma (15.9%), and median age at diagnosis was 8.3 years (range, 0.8-20.7). Sixty-seven patients (62.6%) received craniospinal irradiation (median, 23.4 Gy; range, 18.0-39.6) as a component of their radiation therapy, and 39.3% and 40.2% of patients received an additional involved field or whole posterior fossa boost, respectively. Median prescribed dose was 55.8 Gy (range, 50.4-60.0). Median clinical and imaging follow-up were 4.7 years (range, 0.1-17.5) and 4.2 years (range, 0.1-17.3), respectively. No grade ≥2 toxicities were observed. The incidence of grade 1 brainstem necrosis was 1.9% (2 of 107). These patients were by definition asymptomatic and experienced resolution of imaging abnormality after 5.3 months and 2.1 years, respectively. CONCLUSIONS: Risk of brainstem necrosis was minimal in this multi-institutional study of pediatric patients treated with photon radiation therapy for tumors involving the posterior fossa with no cases of symptomatic brainstem injury, suggesting that brainstem injury risk is minimal in patients treated with photon therapy.

Clinical practice and outcomes of palliative radiation therapy in pediatric oncology patients: An international comparison of experiences from two distinct countries and health care systems.

BACKGROUND AND PURPOSE: This study describes clinical outcomes of palliative radiation therapy (RT) for children treated in distinct health-care environments-the US where there is advanced integration of palliative resources and Brazil, a country in the process of developing provisions for pediatric palliative care. METHODS AND MATERIALS: Palliative RT cases of pediatric oncology patients aged ≤21-years from 2010 to 2016 in two Brazil-based and one US-based (Johns Hopkins Hospital, JHH) academic centers were reviewed in this study. RESULTS: Eighty-eight pediatric patients were treated to 131 lesions with palliative RT. Forty-nine patients from the JHH cohort comprised 84 cases and 39 patients from the Brazil cohort comprised 46 cases. The most common indication for palliative RT was pain (55% overall, 39% Brazil, 63% JHH). Sixty-seven percent of patients experienced a complete (CR) or partial response (PR) to palliative RT, 12% reported stable symptoms (SS), and 22% reported progressive symptoms (PS). The median survival from the end of palliative RT was 3.6 months (95% confidence interval (CI), 2.3-4.8 months). When treated with palliative RT for pain, 83% of patients experience CR/PR, facilitating reduction or discontinuation of opiates in 46% of these patients. CONCLUSION: Despite different practices, the clinical results using palliative RT for pediatric patients treated in two unique healthcare environments demonstrated it is an effective tool for pediatric oncology patients across systems.

Precision of 2 Low-dose Abdomen/Pelvis Cone Beam Computed Tomography Protocols for Alignment to Bone and Soft Tissue in Pediatric Patients Receiving Image Guided Radiation Therapy.

PURPOSE: To evaluate the precision of 2 low-dose cone (LD) beam computed tomography (CBCT) protocols to align to bone and soft tissue for pediatric patients receiving image guided radiation therapy (IGRT) to the abdomen and pelvis. METHODS AND MATERIALS: Image-quality evaluation was done for 858 CBCT scans from 46 pediatric patients treated with IGRT from January 2015 to December 2017. The evaluations guided the development of 2 significantly dose-reduced protocols, LD-CBCT1 and a further dose-reduced LD-CBCT2. Representative scans from LD-CBCT1 and LD-CBCT2 from 8 patients with at least 1 CBCT scan from both protocols were registered separately to a bone and soft-tissue landmark on the simulation computed tomography scan. Eighteen identical blinded random offsets were applied to each patient's LD-CBCT1 and LD-CBCT2 from a starting registration that was then realigned using rigid registration. The residual offset between the baseline registration and the final registration attempt was calculated and analyzed using a 1-sided, 1 sample t test to evaluate whether LD-CBCT1, delivering a higher dose, was superior to the lower-dose LD-CBCT2 for bone and soft-tissue alignment. RESULTS: In comparing 288 registrations with a bone landmark across 8 patients, no difference was found in the vector magnitude offsets using LD-CBCT 1 (mean [x¯], 0.73 mm; standard deviation [σ], 0.39 mm) and LD-CBCT2 (x¯, 0.74 mm; σ, 0.40 mm; P = .425). Comparing 216 registrations with a soft-tissue landmark across 6 patients, alignment using LD-CBCT2 (x¯, 1.55 mm; σ, 1.08 mm) resulted in larger differences in the vector magnitude of the offsets compared with LD-CBCT1 (x¯, 1.37 mm; σ, 0.74 mm; P = .049). CONCLUSIONS: Clinics treating pediatric patients should consider implementing a protocol mirroring LD-CBCT2 for abdomen and pelvis IGRT bone alignment. Further evaluation of the precision of LD-CBCTs for soft-tissue alignment is necessary.

Preoperative Intensity Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High-Grade Extremity Sarcomas in Children: Analysis of the Children's Oncology Group Study ARST0332.

PURPOSE: For pediatric patients with large, high-grade, extremity nonrhabdomyosarcoma soft-tissue sarcomas, preoperative radiation therapy (RT) provides the opportunity for smaller radiation fields and tumor shrinkage resulting in less extensive surgery. The potential disadvantage is an increased risk of wound complications after surgery compared with rates after postoperative chemoradiation. We assessed the impact of preoperative RT technique on target coverage in relationship to dose to skin and adjacent joints to determine whether acute wound complications and late musculoskeletal injury might be influenced by treatment technique. METHODS AND MATERIALS: Of 550 eligible patients <30 years of age, 200 were enrolled in arm D of ARST0332 and received neoadjuvant ifosfamide/doxorubicin, then chemoradiotherapy (45 Gy and ifosfamide) and surgery followed by postoperative RT if gross or microscopic positive surgical margins. One-hundred thirteen patients had extremity nonrhabdomyosarcoma soft-tissue sarcomas, of which 56 patients had preoperative RT plans for digital review. The doses to the target volume, skin (surface to 5 mm depth), adjacent joint, and extremity diameter were analyzed with respect to RT technique. RESULTS: Thirty-eight patients (65%) received 3-dimensional conformal RT (3D-CRT) and 18 (32%) received intensity modulated RT (IMRT). There was no difference in clinical target volume (CTV) size between groups (P = .920); however, IMRT plans had improved CTV coverage to 100% of the prescription dose compared with 3D-CRT plans (median CTV coverage, 92.7% vs 98.6%; P = .011). In patients without target overlap with the skin, IMRT use was associated with reduced percent volume of skin receiving 45 Gy or more (V45Gy) compared with 3D-CRT (median, 1.6% vs 6.3%, respectively; P = .005). IMRT was also associated with reduced V45Gy to the adjacent joint compared with 3D-CRT (median, 1.1% vs 13.2%; P = .018). CONCLUSIONS: Preoperative IMRT may improve CTV coverage and reduce the volume of skin and adjacent joint treated to high doses. Future studies should assess whether these dosimetric findings produce differences in clinical and toxicity outcomes.

A Road Map for Important Centers of Growth in the Pediatric Skeleton to Consider During Radiation Therapy and Associated Clinical Correlates of Radiation-Induced Growth Toxicity.

With the increasing use of advanced radiation techniques such as intensity modulated radiation therapy, stereotactic radiation therapy, and proton therapy, radiation oncologists now have the tools to mitigate radiation-associated toxicities. This is of utmost importance in the treatment of a pediatric patient. To best use these advanced techniques to mitigate radiation-induced growth abnormalities, the radiation oncologist should be equipped with a nuanced understanding of the anatomy of centers of growth. This article aims to enable the radiation oncologist to better understand, predict, and minimize radiation-mediated toxicities on growth. We review the process of bone development and radiation-induced growth abnormalities and provide an atlas for contouring important growth plates to guide radiation treatment planning. A more detailed recognition of important centers of growth may improve future treatment outcomes in children receiving radiation therapy.

Practice Patterns of Stereotactic Radiotherapy in Pediatrics: Results From an International Pediatric Research Consortium.

PURPOSE/OBJECTIVES: There is little consensus regarding the application of stereotactic radiotherapy (SRT) in pediatrics. We evaluated patterns of pediatric SRT practice through an international research consortium. MATERIALS AND METHODS: Eight international institutions with pediatric expertise completed a 124-item survey evaluating patterns of SRT use for patients 21 years old and younger. Frequencies of SRT use and median margins applied with and without SRT were evaluated. RESULTS: Across institutions, 75% reported utilizing SRT in pediatrics. SRT was used in 22% of brain, 18% of spine, 16% of other bone, 16% of head and neck, and <1% of abdomen/pelvis, lung, and liver cases across sites. Of the hypofractionated SRT cases, 42% were delivered with definitive intent. Median gross tumor volume to planning target volume margins for SRT versus non-SRT plans were 0.2 versus 1.4 cm for brain, 0.3 versus 1.5 cm for spine/other bone, 0.3 versus 2.0 cm for abdomen/pelvis, 0.7 versus 1.5 cm for head and neck, 0.5 versus 1.7 cm for lung, and 0.5 versus 2.0 cm for liver sites. CONCLUSIONS: SRT is commonly utilized in pediatrics across a range of treatment sites. Margins used for SRT were substantially smaller than for non-SRT planning, highlighting the utility of this approach in reducing treatment volumes.

Impact of race, ethnicity, and socioeconomic factors on receipt of radiation after breast conservation surgery: analysis of the national cancer database.

INTRODUCTION: Many eligible women with invasive breast cancer do not receive recommended adjuvant radiation (RT), despite its role in local control and overall survival. We examined trends in RT use over 10 years, and the impact of sociodemographic factors on the receipt of standard-of-care RT, using the National Cancer Database (NCDB). MATERIALS/METHODS: Women under age 70 with invasive breast cancer who underwent BCS from 2004 to 2014 were analyzed. Receipt of RT was evaluated in the whole cohort and by time period to identify temporal trends. Multiple logistic regression models were used to assess associations between factors such as race, insurance status, ethnicity, and receipt of RT. RESULTS: A total of 501,733 patients met eligibility criteria. The percentage of patients undergoing adjuvant RT increased from 86.7% in 2004 to 92.4% in 2012, and then decreased in 2013 and 2014 to 88.9%. On univariate analysis, patients of white race were significantly more likely to receive RT compared with patients of black race (90.4% vs 86.9%, p < 0.0001), as were non-Hispanic women compared to Hispanic patients (90.2% vs. 85.3%, p < 0.0001). On multivariate analysis, race, ethnicity, insurance status, education level, and age remained significantly associated with receipt of RT. On temporal analysis, gaps remained stable, with no significant improvements over time. CONCLUSIONS: This analysis suggests a recent decline in guideline-concordant receipt of RT in women under 70, and persistent disparities in the use of RT after BCS by race, ethnicity, and socioeconomic factors. These findings raise concern for a recent detrimental change in patterns of care delivery.