Analysis of Retrospective Versus Prospective Peer Review in a Multisite Academic Radiation Department.

Purpose: Our multisite academic radiation department reviewed our experience with transitioning from weekly primarily retrospective to daily primarily prospective peer review to improve plan quality and decrease the rate of plan revisions after treatment start. Methods and Materials: This study was an institutional review board-approved prospective comparison of radiation treatment plan review outcomes of plans reviewed weekly (majority within 1 week after treatment start) versus plans reviewed daily (majority before treatment start, except brachytherapy, frame-based radiosurgery, and some emergent plans). Deviations were based on peer comments and considered major if plan revisions were recommended before the next fraction and minor if modifications were suggested but not required. Categorical variables were compared using χ2 distribution tests of independence; means were compared using independent t tests. Results: In all, 798 patients with 1124 plans were reviewed: 611 plans weekly and 513 plans daily. Overall, 76 deviations (6.8%) were noted. Rates of any deviation were increased in the daily era (8.6% vs 5.2%; P = .026), with higher rates of major deviations in the daily era (4.1% vs 1.6%; P = .012). Median working days between initial simulation and treatment was the same across eras (8 days). Deviations led to a plan revision at a higher rate in the daily era (84.1% vs 31.3%; P < .001). Conclusions: Daily prospective peer review is feasible in a multisite academic setting. Daily peer review with emphasis on prospective plan evaluation increased constructive plan feedback, plan revisions, and plan revisions being implemented before treatment start.

Variability of Low-Z Inhomogeneity Correction in IMRT/SBRT: A Multi-Institutional Collaborative Study.

Dose-calculation algorithms are critical for radiation treatment outcomes that vary among treatment planning systems (TPS). Modern algorithms use sophisticated radiation transport calculation with detailed three-dimensional beam modeling to provide accurate doses, especially in heterogeneous medium and small fields used in IMRT/SBRT. While the dosimetric accuracy in heterogeneous mediums (lung) is qualitatively known, the accuracy is unknown. The aim of this work is to analyze the calculated dose in lung patients and compare the validity of dose-calculation algorithms by measurements in a low-Z phantom for two main classes of algorithms: type A (pencil beam) and type B (collapse cone). The CT scans with volumes (target and organs at risk, OARs) of a lung patient and a phantom build to replicate the human lung data were sent to nine institutions for planning. Doses at different depths and field sizes were measured in the phantom with and without inhomogeneity correction across multiple institutions to understand the impact of clinically used dose algorithms. Wide dosimetric variations were observed in target and OAR coverage in patient plans. The correction factor for collapsed cone algorithms was less than pencil beam algorithms in the small fields used in SBRT. The pencil beam showed ≈70% variations between measured and calculated correction factors for various field sizes and depths. For large field sizes the trends of both types of algorithms were similar. The differences in measured versus calculated dose for type-B algorithms were within ±10%. Significant variations in the target and OARs were observed among various TPS. The results suggest that the pencil beam algorithm does not provide an accurate dose and should not be considered with small fields (IMRT/SBRT). Type-B collapsed-cone algorithms provide better agreement with measurements, but still vary among various systems.

Age and Sex Divergence in Hematopoietic Radiosensitivity in Aged Mouse Models of the Hematopoietic Acute Radiation Syndrome.

The hematopoietic system is highly sensitive to stress from both aging and radiation exposure, and the hematopoietic acute radiation syndrome (H-ARS) should be modeled in the geriatric context separately from young for development of age-appropriate medical countermeasures (MCMs). Here we developed aging murine H-ARS models, defining radiation dose response relationships (DRRs) in 12-month-old middle-aged and 24-month-old geriatric male and female C57BL/6J mice, and characterized diverse factors affecting geriatric MCM testing. Groups of approximately 20 mice were exposed to ∼10 different doses of radiation to establish radiation DRRs for estimation of the LD50/30. Radioresistance increased with age and diverged dramatically between sexes. The LD50/30 in young adult mice averaged 853 cGy and was similar between sexes, but increased in middle age to 1,005 cGy in males and 920 cGy in females, with further sex divergence in geriatric mice to 1,008 cGy in males but 842 cGy in females. Correspondingly, neutrophils, platelets, and functional hematopoietic progenitor cells were all increased with age and rebounded faster after irradiation. These effects were higher in aged males, and neutrophil dysfunction was observed in aged females. Upstream of blood production, hematopoietic stem cell (HSC) markers associated with age and myeloid bias (CD61 and CD150) were higher in geriatric males vs. females, and sex-divergent gene signatures were found in HSCs relating to cholesterol metabolism, interferon signaling, and GIMAP family members. Fluid intake per gram body weight decreased with age in males, and decreased after irradiation in all mice. Geriatric mice of substrain C57BL/6JN sourced from the National Institute on Aging were significantly more radiosensitive than C57BL/6J mice from Jackson Labs aged at our institution, indicating mouse source and substrain should be considered in geriatric radiation studies. This work highlights the importance of sex, vendor, and other considerations in studies relating to hematopoiesis and aging, identifies novel sex-specific functional and molecular changes in aging hematopoietic cells at steady state and after irradiation, and presents well-characterized aging mouse models poised for MCM efficacy testing for treatment of acute radiation effects in the elderly.

Dosimetric evaluation of high-Z inhomogeneity used for hip prosthesis: A multi-institutional collaborative study.

PURPOSE: A multi-institutional investigation for dosimetric evaluation of high-Z hip prosthetic device in photon beam. METHODS: A bilateral hip prosthetic case was chosen. An in-house phantom was built to replicate the human pelvis with two different prostheses. Dosimetric parameters: dose to the target and organs at risk (OARs) were compared for the clinical case generated by various treatment planning system (TPS) with varied algorithms. Single beam plans with different TPS for phantom using 6 MV and 15 MV photon beams with and without density correction were compared with measurement. RESULTS: Wide variations in target and OAR dosimetry were recorded for different TPS. For clinical case ideal PTV coverage was noted for plans generated with Corvus and Prowess TPS only. However, none of the TPS were able to meet plan objective for the bladder. Good correlation was noticed for the measured and the Pinnacle TPS for corrected dose calculation at the interfaces as well as the dose ratio in elsewhere. On comparing measured and calculated dose, the difference across the TPS varied from -20% to 60% for 6 MV and 3% to 50% for the 15 MV, respectively. CONCLUSION: Most TPS do not provide accurate dosimetry with high-Z prosthesis. It is important to check the TPS under extreme conditions of beams passing through the high-Z region. Metal artifact reduction algorithms may reduce the difference between the measured and calculated dose but still significant differences exist. Further studies are required to validate the calculational accuracy.

Analysis of Virtual Versus In-Person Prospective Peer Review Workflow in a Multisite Academic Radiation Oncology Department.

PURPOSE: In radiation oncology, peer review is a process where subjective treatment planning decisions are assessed by those independent of the prescribing physician. Before March 2020, all peer review sessions occurred in person; however due to the COVID-19 pandemic, the peer-review workflow was transitioned from in-person to virtual. We sought to assess any differences between virtual versus in-person prospective peer review. METHODS AND MATERIALS: Patients scheduled to receive nonemergent nonprocedural radiation therapy (RT) were presented daily at prospective peer-review before the start of RT administration. Planning software was used, with critical evaluation of several variables including treatment intent, contour definition, treatment target coverage, and risk to critical structures. A deviation was defined as any suggested plan revision. RESULTS: In the study, 274 treatment plans evaluated in-person in 2017 to 2018 were compared with 195 plans evaluated virtually in 2021. There were significant differences in palliative intent (36% vs 22%; P = .002), but not in total time between simulation and the start of treatment (9.2 vs 10.0 days; P = .10). Overall deviations (8.0% in-person vs 2.6% virtual; P = .015) were significantly reduced in virtual peer review. CONCLUSIONS: Prospective daily peer review of radiation oncology treatment plans can be performed virtually with similar timeliness of patient care compared with in-person peer review. A decrease in deviation rate in the virtual peer review setting will need to be further investigated to determine whether virtual workflow can be considered a standard of care.

A dosimetric comparison of whole-lung treatment techniques in the pediatric population.

To demonstrate the dosimetric advantages and disadvantages of standard anteroposterior-posteroanterior (S-AP/PAAAA), inverse-planned AP/PA (IP-AP/PA) and volumetry-modulated arc (VMAT) radiotherapies in the treatment of children undergoing whole-lung irradiation. Each technique was evaluated by means of target coverage and normal tissue sparing, including data regarding low doses. A historical approach with and without tissue heterogeneity corrections is also demonstrated. Computed tomography (CT) scans of 10 children scanned from the neck to the reproductive organs were used. For each scan, 6 plans were created: (1) S-AP/PAAAA using the anisotropic analytical algorithm (AAA), (2) IP-AP/PA, (3) VMAT, (4) S-AP/PANONE without heterogeneity corrections, (5) S-AP/PAPB using the Pencil-Beam algorithm and enforcing monitor units from technique 4, and (6) S-AP/PAAAA[FM] using AAA and forcing fixed monitor units. The first 3 plans compare modern methods and were evaluated based on target coverage and normal tissue sparing. Body maximum and lower body doses (50% and 30%) were also analyzed. Plans 4 to 6 provide a historic view on the progression of heterogeneity algorithms and elucidate what was actually delivered in the past. Averages of each comparison parameter were calculated for all techniques. The S-AP/PAAAA technique resulted in superior target coverage but had the highest maximum dose to every normal tissue structure. The IP-AP/PA technique provided the lowest dose to the esophagus, stomach, and lower body doses. VMAT excelled at body maximum dose and maximum doses to the heart, spine, and spleen, but resulted in the highest dose in the 30% body range. It was, however, superior to the S-AP/PAAAA approach in the 50% range. Each approach has strengths and weaknesses thus associated. Techniques may be selected on a case-by-case basis and by physician preference of target coverage vs normal tissue sparing.

Correlation between target volume and electron transport effects affecting heterogeneity corrections in stereotactic body radiotherapy for lung cancer.

Recently, stereotactic body radiotherapy (SBRT) for lung cancer is conducted with heterogeneity-corrected treatment plans, as the correction greatly affects the dose delivery to the lung tumor. In this study, the correlation between the planning target volume (PTV) and the dose delivery is investigated by separation of the heterogeneity correction effects into photon attenuation and electron transport. Under Institutional Review Board exemption status, 74 patients with lung cancer who were treated with SBRT were retrospectively evaluated. All treatment plans were generated using an anisotropic analytical algorithm (AAA) of an Eclipse (Varian Medical Systems, Palo Alto, CA) treatment planning system. Two additional plans were created using the same treatment parameters (monitor units, beam angles and energy): a plan with no heterogeneity correction (NC), and a plan calculated with a pencil beam convolution algorithm (PBC). Compared with NC, AAA and PBC isocenter doses were on average 13.4% and 21.8% higher, respectively. The differences in the isocenter dose and the dose coverage for 95% of the PTV (D95%) between PBC and AAA were correlated logarithmically (ρ = 0.78 and ρ = 0.46, respectively) with PTV. Although D95% calculated with AAA was in general 2.9% larger than that for NC, patients with a small PTV showed a negative ΔD95% for AAA due to the significant effect of electron transport. The PTV volume shows logarithmic correlation with the effects of the lateral electron transport. These findings indicate that the dosimetric metrics and prescription, especially in clinical trials, should be clearly evaluated in the context of target volume characteristics and with proper heterogeneity correction.

Evaluation of rotational errors in treatment setup of stereotactic body radiation therapy of liver cancer.

PURPOSE: To evaluate the dosimetric impact of rotational setup errors in stereotactic body radiotherapy (SBRT) treatment of liver tumors and to investigate whether translational shifts can compensate for rotation. METHODS AND MATERIALS: The positioning accuracy in 20 patients with liver malignancies treated with SBRT was reevaluated offline by matching the patients' cone-beam computed tomography (CT) scans (n=75) to the planning CT scans and adjusting the 3 rotational angles (pitch, roll, and yaw). Systematic and random setup errors were calculated. The dosimetric changes caused by rotational setup errors were quantified for both simulated and observed patient rotations. Dose distributions recalculated on the rotated CT scans were compared with the original planned doses. Translational corrections were simulated based on manual translational registration of the rotated images to the original CT scans. The correction efficacy was evaluated by comparing the recalculated plans with the original plans. RESULTS: The systematic rotational setup errors were -0.06° ± 0.68°, -0.29° ± 0.62°, and -0.24° ± 0.61°; the random setup errors were 0.80°, 1.05°, and 0.61° for pitch, roll, and yaw, respectively. Analysis of CBCT images showed that 56.0%, 14.7%, and 1.3% of treated fractions had rotational errors of >1°, >2°, and >3°, respectively, in any one of the rotational axes. Rotational simulations demonstrated that the reduction of gross tumor volume (GTV) coverage was <2% when rotation was <3°. Recalculated plans using actual patient roll motions showed similar reduction (<2%) in GTV coverage. Translational corrections improved the GTV coverage to within 3% of the original values. For organs at risk (OAR), the dosimetric impact varied case by case. CONCLUSION: Actual rotational setup errors in SBRT for liver tumors are relatively small in magnitude and are unlikely to affect GTV coverage significantly. Translational corrections can be optimized to compensate for rotational setup errors. However, caution regarding possible dose increases to OAR needs to be exercised.

A simple method for dose fusion from multimodality treatment of prostate cancer: brachytherapy to external beam therapy.

PURPOSE: Suboptimal dosage evaluated from postimplant dosimetry of prostate brachytherapy creates conundrum that needs resolution. This pilot study was undertaken to explore the feasibility of summing and visualizing radiation dosage from multimodality treatment. METHODS AND MATERIALS: Four weeks after (125)I permanent prostate seed implant, CT scans were performed on the whole pelvis of patients using our standard protocol for prostate planning. The acquired CT data sets were reconstructed using different sizes of field of view (FOV). The images with limited FOV focusing on prostate were imported into Variseed (Varian Medical Systems, Inc., Palo Alto, CA) for postimplant evaluation, whereas images with full FOV were imported to Eclipse (Varian Medical Systems, Inc., Palo Alto, CA) treatment planning system (TPS) for future managements, that is, for external beam salvage. RESULTS: The dose matrix resulted from the postimplant dosimetry was exported from Variseed in standard DICOM format and imported into Eclipse TPS. The brachytherapy dose matrix was registered with the patient images with full FOV in Eclipse TPS. Targets for dose boost were defined based on the isodose curves generated from brachytherapy. An external photon beam plan was successfully generated to deliver dose for selected underdose regions. CONCLUSION: Accurate external beam radiation treatment planning can be accomplished using our planning protocols when inadequate brachytherapy dose delivery occurs. The proposed technique can be used to safely deliver additional external radiation dose using intensity-modulated radiation therapy technique after suboptimal brachytherapy procedure.

Development of a porcine delayed wound-healing model and its use in testing a novel cell-based therapy.

PURPOSE: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. METHODS AND MATERIALS: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm(2) wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. RESULTS: The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. CONCLUSIONS: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.

Treatment delays using an automated afterloading low-dose-rate brachytherapy system.

PURPOSE: Low-dose-rate (LDR) brachytherapy is an integral treatment modality in radiation oncology. Clinical efficacy is based on experience with manual source loading and continuous dose delivery. With remote afterloading technology, sources may be loaded and unloaded during the treatment course to prevent radiation exposure to nursing staff members and visitors. The aim of this study was to investigate treatment interruptions in terms of frequency and duration as well as extension of the overall treatment time period. The potential clinical impact of treatment interruptions was also considered. MATERIALS AND METHODS: The treatment records of 20 patients who underwent brachytherapy in the Indiana University Department of Radiation Oncology administered with a Selectron LDR remote afterloader were reviewed. Results were tabulated and analysis performed with respect to 1) the number of interruptions, 2) delay time, 3) delay time (T(d)) as a function of total implant time (T), 4) the time of day that each interruption occurred, and 5) the time in minutes of each individual interruption. RESULTS: The mean number of interruptions was 44.9 per patient, (range, 24-76), with a mean prescription implantation duration of 45.7 hours and a mean actual treatment time of 51.2 hours resulting in a mean interruption time of 6.4 minutes per treatment hour. The number of interruptions was standardized and divided by the number of prescribed dose in grays, translating to 1.2 to 3.7 interruptions per gray delivered, with a mean of 1.6, resulting in an average T(d) of 11.21% (range, 7.35%-17.12%). CONCLUSION: Significant interruptions are frequent using remote afterloading LDR techniques, reducing the effective dose rate. Careful monitoring of such interruptions is warranted.

The role of Gamma Knife Radiosurgery in the management of unresectable gross disease or gross residual disease after surgery in ependymoma.

PURPOSE/OBJECTIVE: To evaluate the efficacy and the toxicity of Gamma Knife (GK)-based stereotactic radiosurgery (SRS) in the management of gross disease in ependymoma. MATERIALS AND METHODS: Eight patients with 13 ependymomas were treated with GK-based SRS in our institution for gross disease. Five patients were treated for recurrent disease that developed after surgery and external beam radiotherapy (EBRT), two received SRS to the gross disease after surgery and EBRT, and one received SRS alone (in a 1.3 year old child). Median EBRT dose was 54.4 Gy (range 50-55.8 Gy). Median SRS dose was 14 Gy (range 12-20 Gy). Seven of eight (87.5%) patients had SRS to a single lesion and one of eight (12.5%) patients had treatment to six tumors in three different sessions. RESULTS: The median follow up was 30.2 months (range 8-65.4 months). Out of the eight patients treated with SRS, six (75%) were alive, four (50%) were alive with no recurrence, two (25%) were alive with recurrence, and two (25%) died of recurrent disease. Both patients treated with SRS as a boost were alive and without recurrence. Out of the five patients who received SRS as salvage treatment, three (60%) were alive, two (40%) were alive without recurrence, two (40%) developed distant failure, and three (60%) had in-field control. Two patients who received SRS to their brainstem lesions developed symptoms related to radionecrosis and were successfully treated with steroid with good control of symptoms. CONCLUSIONS: GK-based SRS appears to be a feasible and safe treatment modality for patients with ependymoma with unresectable gross disease or gross residual disease after surgery. SRS provides reasonable local control but out-of-field tumor progression remains an issue. For patients who receive SRS as a boost, the local control appears to be excellent.

Lung cancer radiation therapy: Monte Carlo investigation of "under dose" by high energy photons.

Loss of electronic equilibrium in lung tissue causes a build-up region in the tumor. Increasing the photon energy increases the depth at which electronic equilibrium is reestablished within the lung tumor. This study uses the Monte Carlo code PENELOPE for simulations of radiation treatment of tumor surrounded by lung. Six MV photons were compared to 15 MV photons using four beam arrangements in both homogeneous and heterogeneous media. The experimental results demonstrate that for every beam arrangement in heterogeneous media 15 MV photons delivered 5% to 10% lower dose to the tumor periphery than 6 MV photons. The simulations also show that in axial coplanar treatment plans, the loss of electronic equilibrium was greatest in the coronal plane. In conclusion there is a tumor sparing effect at the tumor-lung interface that is a function of beam energy. As an alternative to increasing beam energy, the addition of multiple beam angles with lower energy photons improved target coverage. If higher energy beams are required for patients with large separation, then adding multiple beam angles does offer some improved target coverage. The non-coplanar technique with the lower energy photons covered the tumor with a greatest isodose at the tumor periphery without tangential sparing in the coronal plane.