Defining the role of intensity modulation in electron conformal therapy for the treatment of head and neck cancer.

Bolus electron conformal therapy (BECT) in the treatment of cancers of the head and neck is often limited by an inability to reduce dosimetric hot spots resulting from surface irregularity or tissue heterogeneity. We examined the potential benefits of using intensity modulation for electron therapy (IM-BECT) to reduce hotspots in patients undergoing electron beam therapy for superficial cancers of the head and neck (HN). Twenty patients with HN cancer previously treated with BECT were identified. Each case included the treatment targets and a primary organ at risk (OAR) that were defined by the radiation oncologist. A target +2 cm rind structure was created for analysis of the dose deposition in areas surrounding the target volume as a measure of conformality. Each patient plan was transferred into the novel IM-BECT planning software and each case was recomputed as per the original parameters. Next, each case was replanned with the inclusion of intensity modulation, as well as a new custom conformal bolus that was redesigned for optimized range compensation when paired with an intensity modulator. The plans were then normalized to prescription dose and compared for target coverage/dose and OAR dose. For patients who had a hotspot of 125% or greater, the hotspot was on average reduced by 13.1% with IM-BECT. For IM-BECT, the average primary OAR means dose and target+2cm rind mean dose increased slightly by 10.6% and 6.4%, respectively (primary OAR mean [p = 0.0001], and Target+2cm rind mean [p = 0.0001], paired t-test). IM-BECT is an effective method of reducing hotspots in patients with superficial HN cancer. Improvements came at the expense of slight increases in dose to the underlying tissues. This retrospective planning study represents the first example of IM-BECT to actual HN patient cases. Expanding the role of IM-BECT in other disease sites could potentially compared to conventional BECT.

Targeting GPC2 on intraocular and CNS metastatic retinoblastomas with local and systemic delivery of CAR T-cells.

PURPOSE: Retinoblastoma is the most common intraocular malignancy in children. Although new chemotherapeutic approaches have improved ocular salvage rates, novel therapies are required for patients with refractory intraocular and metastatic disease. Chimeric antigen receptor (CAR) T-cells targeting glypican-2 (GPC2) are a potential new therapeutic strategy. EXPERIMENTAL DESIGN: GPC2 expression and its regulation by the E2F1 transcription factor were studied in retinoblastoma patient samples and cellular models. In vitro, we performed functional studies comparing GPC2 CAR T-cells with different co-stimulatory domains (4-1BB and CD28). In vivo, the efficacy of local and systemic administration of GPC2 CAR T-cells were evaluated in intraocular and leptomeningeal human retinoblastoma xenograft models. RESULTS: Retinoblastoma tumors, but not healthy retinal tissues, expressed cell surface GPC2 and this tumor-specific expression was driven by E2F1. GPC2-directed CARs with 4-1BB co-stimulation (GPC2.BBz) were superior to CARs with CD28 stimulatory domains (GPC2.28z), efficiently inducing retinoblastoma cell cytotoxicity and enhancing T-cell proliferation and polyfunctionality. In vivo, GPC2.BBz CARs had enhanced persistence that led to significant tumor regression compared to either control CD19 or GPC2.28z CARs. In intraocular models, GPC2.BBz CAR T-cells efficiently trafficked to tumor-bearing eyes after intravitreal or systemic infusions, significantly prolonging ocular survival. In central nervous system (CNS) retinoblastoma models, intraventricular or systemically administered GPC2.BBz CAR T-cells were activated in retinoblastoma-involved CNS tissues, resulting in robust tumor regression with substantially extended overall mouse survival. CONCLUSIONS: GPC2-directed CAR T-cells are effective against intraocular and CNS metastatic retinoblastomas.

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD. METHODS: In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions. FINDINGS: We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions. INTERPRETATION: The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD. FUNDING: The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.

Stereotactic MR-guided on-table adaptive radiation therapy (SMART) for borderline resectable and locally advanced pancreatic cancer: A multi-center, open-label phase 2 study.

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity. MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 patients (LAPC 56.6 %; BRPC 43.4 %) after ≥ 3 months of any chemotherapy without distant progression and CA19-9 ≤ 500 U/mL. SMART was delivered on a 0.35 T MR-guided system prescribed to 50 Gy in 5 fractions (biologically effective dose10 [BED10] = 100 Gy). Elective coverage was optional. Surgery and chemotherapy were permitted after SMART. RESULTS: Mean age was 65.7 years (range, 36-85), induction FOLFIRINOX was common (81.7 %), most received elective coverage (57.4 %), and 34.6 % had surgery after SMART. Median FU was 22.9 months from diagnosis and 14.2 months from SMART, respectively. 2-year OS from diagnosis and SMART were 53.6 % and 40.5 %, respectively. Late grade ≥ 3 toxicity definitely, probably, or possibly attributed to SMART were observed in 0 %, 4.6 %, and 11.5 % patients, respectively. CONCLUSIONS: Long-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted.

Advancing the Role of Proton Therapy for Spine Metastases Through Diagnostic Scan-Based Planning.

Purpose: Many patients with metastatic cancer live years beyond diagnosis, and there remains a need to improve the therapeutic ratio of metastasis-directed radiation for these patients. This study aimed to assess a process for delivering cost-effective palliative proton therapy to the spine using diagnostic scan-based planning (DSBP) and prefabricated treatment delivery devices. Materials and Methods: We designed and characterized a reusable proton aperture system that adjusts to multiple lengths for spine treatment. Next, we retrospectively identified 10 patients scan treated with thoracic proton therapy who also had a diagnostic computed tomography within 4 months of simulation. We contoured a T6-T9 target volume on both the diagnostic scans (DS) and simulation scans (SS). Using the aperture system, we generated proton plans on the DS using a posterior-anterior beam with no custom range compensator to treat T6-T9 to 8 Gy × 1. Plans were transferred to the SS to compare coverage and normal tissue doses, followed by robustness analysis. Finally, we compared normal tissue doses and costs between proton and photon plans. Results were compared using the Wilcoxon signed-rank test. Results: Median D95% on the DS plans was 101% (range, 100%-102%) of the prescription dose. Median Dmax was 107% (range, 105%-108%). When transferred to SS, coverage and hot spots remained acceptable for all cases. Heart and esophagus doses did not vary between the DS and SS proton plans (P >.2). Robustness analysis with 5 mm X/Y/Z shifts showed acceptable coverage (D95% > 98%) for all cases. Compared with the proton plans, the mean heart dose was higher for both anterior-posterior/posterior-anterior and volumetric modulated arc therapy plans (P < .01). Cost for proton DSBP was comparable to more commonly used photon regimens. Conclusion: Proton DSBP is technically feasible and robust, with superior sparing of the heart compared with photons. Eliminating simulation and custom devices increases the value of this approach in carefully selected patients.

B-cell acute lymphoblastic leukemia and juvenile xanthogranuloma in a patient with ETV6 thrombocytopenia and leukemia predisposition syndrome: novel clinical presentation and perspective.

Not available.

Evaluating Carbon Footprint of Proton Therapy Based on Power Consumption and Possible Mitigation Strategies.

PURPOSE: There is increasing concern about rising carbon dioxide (CO2) emissions and their hazardous effect on human health. This study quantifies the energy utilization of proton therapy, assesses the corresponding carbon footprint, and discusses possible offsetting strategies toward carbon-neutral health care operations. METHODS AND MATERIALS: Patients treated between July 2020 and June 2021 using the Mevion proton system were evaluated. Current measurements were converted to kilowatts of power consumption. Patients were reviewed for disease, dose, number of fractions, and duration of beam. The Environmental Protection Agency calculator was used to convert power consumption to tons of CO2 equivalent (CO2e) for scope-based carbon footprint accounting. RESULTS: There were 185 patients treated and a total of 5176 fractions delivered (average, 28). Power consumption was 55.8 kW in standby/night mode and 64.4 kW during BeamOn, for an annual total of 490 MWh. BeamOn time was 149.6 hours, and BeamOn consumption accounted for 2% of the machine total. Power consumption was 52 kWh per patient (breast, highest at 140 kWh; prostate, lowest at 28 kWh). Annual power consumption of the administrative areas was approximately 96 MWh, for a program total of 586 MWh. The carbon footprint for BeamOn time was 4.17 metric tons of CO2e, or 23 kg per patient course (breast cancer, 60 kg; prostate, 12 kg). The annual carbon footprint for the machine was 212.2 tons CO2e, and for the proton program, 253.7 tons CO2e, with an attributed footprint of 1372 kg CO2e per patient. The corresponding CO2e offset for the program could be 4192 new trees planted and grown for 10 years (23 trees per patient). CONCLUSIONS: The carbon footprint varied by disease treated. On average, the carbon footprint was 23 kg of CO2e per patient and 253.7 tons of CO2e for the proton program. There are a number of reduction, mitigation, and offset strategies possible for radiation oncologists that should be explored, such as waste minimization, less treatment commuting, efficient energy use, and renewable electricity power use.

A Multi-Institutional Phase 2 Trial of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer.

PURPOSE: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). METHODS AND MATERIALS: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART. RESULTS: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%. CONCLUSIONS: The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy.

Retrospective Cohort Analysis of the Impact of Puberty on Plexiform Neurofibroma Growth in Patients with Neurofibromatosis Type 1.

OBJECTIVE: To assess the hypothesis that plexiform neurofibroma (PN) growth rates increase during puberty. STUDY DESIGN: PN growth rates before and during puberty were compared in a retrospective cohort of children with neurofibromatosis type 1 with puberty defined by Tanner staging. Of 33 potentially eligible patients, 25 had adequate quality magnetic resonance imaging for volumetric analysis and were included in ≥1 anchor cohort. Volumetric analysis was performed for all available imaging studies within the 4 years before and after puberty, and before and after 9- and 11-year-old anchor scans. Linear regression was performed to estimate the slope of change (PN growth rate); growth rates were compared with paired t test or Wilcoxon matched-pairs signed rank test. RESULTS: There were no significant difference in rates of PN growth in milliliters per month or milliliters per kilogram per month in the prepubertal vs pubertal periods (mean, 1.33 ± 1.67 vs 1.15 ± 1.38 [P = .139] and -0.003 ± 0.015 vs -0.002 ± 0.02 [P = .568]). Percent increases of PN volumes from baseline per month were significantly higher prepubertally (1.8% vs 0.84%; P = .041) and seemed to be related inversely to advancing age. CONCLUSIONS: Puberty and its associated hormonal changes do not seem to influence PN growth rate. These findings support those previously reported, but from a typical population of children with neurofibromatosis type 1 with puberty confirmed by Tanner staging.

Adapting to the Adaptive Radiation Workflow: Incorporating Video Sign Out for Improved Safety and Efficiency as Part of Magnetic Resonance Image Guided Adaptive Radiation.

 : Magnetic resonance image guided adaptive radiation therapy (MRgART) represents a significant improvement in our ability to deliver therapeutic radiation. However, for the process of MRgART to be carried out safely and efficiently, the covering radiation oncologist must be aware of all aspects of a patient's case, because they will be required to recontour and replan the patient before each treatment. In this report, we will demonstrate our initial experience with a video sign-out process to convey the detailed level of information required for the covering physician to treat patients safely and effectively with MRgART. We then describe our optimized video sign-out process to allow for other centers to adopt a similar approach.

Morphological variations influencing the outcomes in posterior polar cataract.

Purpose: To study the intraoperative complications and postoperative clinical outcomes in different types of posterior polar cataract (PPC) following phacoemulsification, based on morphological classification. Methods: All consecutive patients with PPC who underwent phacoemulsification during the study period from 2016 to 2019 were included and sub-grouped based on the morphological characteristics according to Daljit Singh's classification. Intraoperative complications such as posterior capsular rupture (PCR), vitreous loss, nucleus drop, and Postoperative best-corrected visual acuity (BCVA) at day 1 and day 30 were documented. Results: A total of 388 eyes of 380 patients were included. Eighty nine (22.9%) eyes belonged to type 1, 135 (34.8%) belonged to type 2, 8 (2.1%) belonged to type 3, and 156 (40.2%) belonged to type 4. Thirty-five (9.3%) eyes had intraoperative PCR, with vitreous loss in 21 (60%) eyes, and nucleus/cortex drop in 5 (1.3%) eyes. Six (75%) eyes of type 3, 14 (10.04%) eyes of type 2, 12 (17.7%) eyes of type 4, and 3 (3.4%) eyes of type 1 PPC had PCR. PCR occurred more during the emulsification of the nucleus (18 cases, 51.4%). A significant correlation was seen between intraoperative PCR and type of PPC with a higher incidence in type 3 (P < 0.001). BCVA was found to be significantly worse on day 1 among patients with PCR compared to those who did not and improved well by day 30. Conclusion: PPC morphology is significantly co-related with the occurrence of PCR, emphasizing the need for careful grading of posterior polar cataracts in predicting the risk of intraoperative complications.

Proposal and Evaluation of a Physician-Free, Real-Time On-Table Adaptive Radiotherapy (PF-ROAR) Workflow for the MRIdian MR-Guided LINAC.

With the implementation of MR-LINACs, real-time adaptive radiotherapy has become a possibility within the clinic. However, the process of adapting a patient's plan is time consuming and often requires input from the entire clinical team, which translates to decreased throughput and limited patient access. In this study, the authors propose and simulate a workflow to address these inefficiencies in staffing and patient throughput. Two physicians, three radiation therapists (RTT), and a research fellow each adapted bladder and bowel contours for 20 fractions from 10 representative patient plans. Contouring ability was compared via calculation of a Dice Similarity Index (DSI). The DSI for bladder and bowel based on each potential physician-therapist pair, as well as an inter-physician comparison, exhibited good overlap amongst all comparisons (p = 0.868). Plan quality was compared through calculation of the conformity index (CI), as well as an evaluation of the plan's dose to a 'gold standard' set of structures. Overall, non-physician plans passed 91.2% of the time. Of the eight non-physician plans that failed their clinical evaluation, six also failed their evaluation against the 'gold standard'. Another two plans that passed their clinical evaluation subsequently failed in their evaluation against the 'gold standard'. Thus, the PF-ROAR process has a success rate of 97.5%, with 78/80 plans correctly adapted to the gold standard or halted at treatment. These findings suggest that a physician-free workflow can be well tolerated provided RTTs continue to develop knowledge of MR anatomy and careful attention is given to understanding the complexity of the plan prior to treatment.

Research productivity of radiation therapy physics faculty in the United States.

PURPOSE: Research productivity metrics are important for decisions regarding hiring, retention, and promotion in academic medicine, and these metrics can vary widely among different disciplines. This article examines productivity metrics for radiation therapy physicists (RTP) in the United States. METHODS AND MATERIALS: Database searches were performed for RTP faculty at US institutions that have RTP residencies accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP). Demographics, academic rank, number of publications, academic career length, Hirsch index (h-index), m-quotient, and history of National Institutes of Health (NIH) funding as a principal investigator (PI) were collected for each RTP. Logistic regression was performed to determine the probability of academic rank as a function of h-index and m-quotient. Statistical tests used included the Wilcoxon ranked sum test and the Pearson χ2 test. RESULTS: A total of 1038 faculty and staff were identified at 78 institutions with CAMPEP-accredited residencies. The average RTP academic career duration is 13.5 years, with 46.7 total publications, h-index of 10.7, and m-quotient of 0.66. Additionally, 10.5% of RTP have a history of NIH funding as a PI. Large disparities were found in academic productivity of doctoral-prepared physicists compared to those with a terminal master's degree. For differences in junior and senior faculty, statistical tests yielded significance in career duration, number of publications, h-index, and m-quotient. Gender disparities were identified in the overall distribution of RTP consistent with the membership of the American Association of Physicists in Medicine. Further gender disparities were found in the number of doctoral-prepared RTP and physicists in senior faculty roles. CONCLUSIONS: This manuscript provides objective benchmark data regarding research productivity of academic RTP. These data may be of interest to faculty preparing for promotion, and also to institutional leadership.

Impact of Radiation Oncology Alternative Payment Model on Community Cancer Centers.

PURPOSE: An episode-based payment model, the Radiation Oncology Alternative Payment Model (RO-APM), is scheduled to go into effect in January 2022. This article investigates the effects of RO-APM on hospital-based and freestanding community centers. METHODS: Historical Medicare data used to generate the RO-APM base rates were reviewed. A sensitivity analysis was performed to show how the RO-APM reimbursements compare with current reimbursements for commonly accepted treatment schedules and with current reimbursements at a large community practice. RESULTS: The RO-APM base rates represent a 2.2% decrease in overall Medicare reimbursement. Freestanding centers have historically billed at higher rates than hospital-based centers, however, and the RO-APM base rates represent a 6% decrease in global reimbursement for freestanding centers. The sensitivity analysis showed that, except for proton therapy, moderately hypofractionated treatment schedules will receive comparable reimbursement under RO-APM. Treatments using higher numbers of fractions of intensity-modulated radiation therapy or protons will see larger decreases in reimbursement. Application of the RO-APM base rates to the 2020 Medicare treatments in our health care network would result in small changes in expected reimbursement, but our sensitivity analysis indicated that Medicare reimbursement reductions could be as large as 23%. CONCLUSION: Compared with historical Medicare reimbursement, RO-APM base rates provide lower reimbursement for many common treatment scenarios, and this will have a larger effect on centers that use complex treatment techniques and longer fractionation schedules or have a large Medicare population.

Disseminated Mycobacterium chelonae infection with Hughes-Stovin syndrome.

Mycobacterium chelonae usually causes localized cutaneous infections and abscesses but has the potential to cause disseminated infections, especially in immunocompromised hosts. We report a 27-year-old man with Hughes-Stovin syndrome and catastrophic antiphospholipid syndrome who was on chronic immunosuppressant therapy and developed disseminated M. chelonae infection. To the best of our knowledge, this is the first case report of M. chelonae infection in a patient with Hughes-Stovin syndrome.

Whole brain radiotherapy with hippocampal sparing using Varian HyperArc.

The purpose of this work was to evaluate using Varian HyperArc as a planning and treatment solution for whole brain radiotherapy (WBRT) with hippocampal sparing following Radiation Therapy Oncology Group (RTOG) 0933 dosimetric criteria. Ten patients previously treated for intracranial lesions were retrospectively planned for WBRT with hippocampal sparing using HyperArc and a 2-arc coplanar VMAT technique. The whole brain and hippocampus were delineated on fused MRI and CT datasets. The planning target volume (PTV), defined as the whole brain excluding the hippocampal avoidance region, was prescribed 30 Gy in 10 fractions. Plans were evaluated using dosimetric parameters which included the volume of 105% of the prescription dose (V105%) and the maximum dose to the PTV, and the minimum dose to the hippocampus. The planning time, delivery time, and delivery quality assurance (QA) results were also evaluated. Statistical significance was performed between the HyperArc and coplanar VMAT metrics using the Wilcoxon signed-rank test with a significance level of 0.05. All plans met RTOG 0933 dosimetric criteria. HyperArc plans demonstrated significant improvements in PTV dosimetric quality which included a reduced V105% of 6 ± 7% and decreased maximum dose of 1.3 ± 0.3 Gy, compared to coplanar VMAT. Significant OAR sparing was also found for HyperArc plans that included a decreased minimum dose to the hippocampus of 0.3 ± 0.3 Gy. Coplanar VMAT plans resulted in significantly shorter planning and delivery times, compared to HyperArc, by 2.4 minutes and 1.5 minutes, respectively. No significant difference was found between the delivery QA results. This study demonstrated using Varian HyperArc as a planning and treatment solution for WBRT with hippocampal sparing following RTOG 0933 dosimetric criteria. The primary advantages of WBRT with hippocampal sparing using HyperArc, compared to coplanar VMAT, are the gains in OAR sparing and reduced high dose volumes to the PTV.

Variability in commercially available deformable image registration: A multi-institution analysis using virtual head and neck phantoms.

PURPOSE: The purpose of this study was to evaluate the performance of three common deformable image registration (DIR) packages across algorithms and institutions. METHODS AND MATERIALS: The Deformable Image Registration Evaluation Project (DIREP) provides ten virtual phantoms derived from computed tomography (CT) datasets of head-and-neck cancer patients over a single treatment course. Using the DIREP phantoms, DIR results from 35 institutions were submitted using either Velocity, MIM, or Eclipse. Submitted deformation vector fields (DVFs) were compared to ground-truth DVFs to calculate target registration error (TRE) for six regions of interest (ROIs). Statistical analysis was performed to determine the variability between each DIR software package and the variability of users within each algorithm. RESULTS: Overall mean TRE was 2.04 ± 0.35 mm for Velocity, 1.10 ± 0.29 mm for MIM, and 2.35 ± 0.15 mm for Eclipse. The MIM mean TRE was significantly different than both Velocity and Eclipse for all ROIs. Velocity and Eclipse mean TREs were not significantly different except for when evaluating the registration of the cord or mandible. Significant differences between institutions were found for the MIM and Velocity platforms. However, these differences could be explained by variations in Velocity DIR parameters and MIM software versions. CONCLUSIONS: Average TRE was shown to be <3 mm for all three software platforms. However, maximum errors could be larger than 2 cm indicating that care should be exercised when using DIR. While MIM performed statistically better than the other packages, all evaluated algorithms had an average TRE better than the largest voxel dimension. For the phantoms studied here, significant differences between algorithm users were minimal suggesting that the algorithm used may have more impact on DIR accuracy than the particular registration technique employed. A significant difference in TRE was discovered between MIM versions showing that DIR QA should be performed after software upgrades as recommended by TG-132.

Outcomes of Intravenous Chemotherapy (Chemoreduction) for Retinoblastoma Based on Patient Age in 964 Eyes of 554 Patients.

PURPOSE: To evaluate retinoblastoma control after intravenous chemotherapy (chemoreduction) by patient age at presentation. DESIGN: Retrospective case series. METHODS: This study included 964 eyes of 554 patients treated with chemoreduction at Ocular Oncology Service at Wills Eye Hospital. Patients received 6 monthly cycles of standard chemoreduction. Additional therapies for tumor control were performed as needed. RESULTS: Of 964 eyes, a comparison by age group (<6 months vs. 6-12 months vs. 13-24 months vs. >24 months) revealed more advanced age group with higher frequency of group E tumor (15% vs. 25% vs. 32% vs. 39%, P < 0.001). By treatment outcomes, complete tumor control was achieved with chemoreduction alone more often in less advanced age group (46% vs. 30% vs. 17% vs. 8%, P < 0.001). Additional treatment after chemoreduction was needed more often in more advanced age group with external beam radiotherapy (EBRT; 9% vs. 16% vs. 20% vs. 15%, P = 0.006) or enucleation (12% vs. 18% vs. 26% vs. 37%, P < 0.001). Over time (1994-1998 vs. 1999-2003 vs. 2004-2008 vs. 2009-2013 vs. 2014-2019), the paradigm for additional required treatment after chemoreduction shifted toward less EBRT (27% vs. 24% vs. 14% vs. 7% vs. 2%, P < 0.001) and more intra-arterial (0% vs. 0% vs. 1% vs. 25% vs. 48%, P < 0.001) and intravitreal (0% vs. 0% vs. 3% vs. 10% vs. 20%, P < 0.001) chemotherapy. CONCLUSIONS: Chemoreduction is a safe and effective treatment method for patients with retinoblastoma, demonstrating the best tumor control in the younger age groups.

Effect of Proposed Episode-Based Payment Models on Advanced Radiotherapy Procedures.

PURPOSE: An episode-based payment model, the Radiation Oncology Alternative Payment Model (RO-APM), has been proposed for Medicare reimbursement of radiation services provided to oncology patients. RO-APM may have significant impact on reimbursement for specific patient populations. METHODS: This investigation compares historical fee-for-service technical reimbursement estimates at a large hospital-based system to the RO-APM for advanced radiotherapy treatment of specific cancer types. These advanced techniques, stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), online-adaptive SBRT, and proton therapy, were specifically chosen because they are resource intensive and are correspondingly among the most expensive radiation oncology procedures. A total of 203 Medicare patients were analyzed. RESULTS: RO-APM base-rate reimbursements were similar for SRS and were 38%-47% higher for SBRT. The proposed rates were 1%-31% lower for online-adaptive SBRT, and 48%-71% lower for proton therapy. CONCLUSION: These data suggest that the RO-APM may have the desired effect of encouraging shorter courses of radiotherapy, such as SBRT. However, emerging technologies that require large capital and operating investments may see an overall significant reduction in proposed reimbursement.

Intrafraction motion during frameless radiosurgery using Varian HyperArcTM and BrainLab ElementsTM immobilization systems.

Commercial systems such as Varian HyperArcTM and BrainLab Elements MultiMetTM have been developed that allow radiosurgery treatment of multiple brain metastases using a single isocenter. Each software package places increased demands on frameless immobilization and requires the use of a specific immobilization system: the QFix-Encompass system for Varian and the BrainLab frameless-mask system for BrainLab. At our institution, patients receiving traditional radiosurgery (one isocenter per target lesion) were treated using both immobilization systems. Intrafraction motion was determined for each patient using multiple cone-beam CT scans and the same image-registration software during treatment. There were no statistically-significant differences in mean absolute translational shifts between the two mask systems, with a mean 3D-vector motion of approximately 0.43 mm for both systems. There were also no statistically-significant differences in the mean absolute rotational shifts between the two mask systems. Although the average residual errors were insignificant between the mask systems, special attention should be paid to individual maximum shifts with both systems. Large maximum rotational misalignments could present significant misalignment of lesions as distance increases from the isocenter. Finally, large maximum shifts highlight the need for real-time monitoring of patient movement during radiosurgery of multiple lesions using a single isocenter.