Evolution of dosimetric treatment planning for pediatric total lymphoid irradiation (TLI): a single-institution experience.

Background: Total lymphoid irradiation (TLI) is a conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) which may reduce long-term toxicities attributed to other techniques, such as total body irradiation (TBI). At our institution, TLI treatments were first planned with the three-dimensional conformal radiation therapy (3D-CRT) technique and later with volumetric modulated arc therapy (VMAT). With the recent availability of a basic helical tomotherapy (HT), the possible dosimetric gain of the latter for TLI is studied. Materials and methods: 22 pediatric patients were planned for VMAT and HT, prescribed to 8 Gy in 4 fractions. VMAT was planned with template based on a single cost function, using the Monaco treatment planning system (TPS). HT plans were planned using Accuray Precision TPS for a basic HT without the dynamic jaws feature or VOLO-Ultra algorithm. Plan quality was analyzed based on four quality indices, mean and maximum doses to planning target volume (PTV) and organs at risk (OARs), dose gradient and integral doses. Differences were analyzed with Wilcoxon signed-rank test. Results: HT plans resulted in improved conformity (CI) and homogeneity indices (HI) (p < 0.05) but less steep dose gradient (p = 0.181). VMAT plans created larger areas with high doses within the PTV, while comparable doses to OARs, except mainly for the spinal marrow, for which a reduction of 37.7% in D2% was obtained (p < 0.05). Integral dose for non-tumor tissue was 11.3% lower with the VMAT template (p < 0.05). Conclusion: HT achieves better conformity and homogeneity even without its more advanced features. Nevertheless, the VMAT template achieves dosimetric results close to those of HT, both with similar clinical outcome.

COVID-19 pneumonia treated with ultra-low doses of radiotherapy (ULTRA-COVID study): a single institution report of two cases.

INTRODUCTION: Since the outbreak of coronavirus disease 2019 (COVID-19) pandemic, healthcare systems have focused their efforts into finding a treatment to avoid the fatal outcomes of severe acute respiratory syndrome due to coronavirus­2 (SARS-CoV-2). Benefits and risks of systemic treatments remain unclear, with multiple clinical trials still ongoing. Radiotherapy could play a role in reducing the inflammatory response in the lungs and relieve life-threatening symptoms. METHODS: We designed a prospective study of Ultra-Low Doses of Therapy with Radiation Applied to COVID-19 (ULTRA-COVID) for patients who suffer pneumonia, are not candidates for invasive mechanical ventilation and show no improvement with medical therapy. RESULTS: We present the preliminary results of two patients diagnosed with COVID-19 pneumonia treated with ULTRA-COVID. After one radiotherapy session, significant clinical response and a good radiological response was observed in both cases, resulting in both patients being discharged from hospital in less than 2 weeks after radiation treatment. CONCLUSION: Preliminary clinical and radiological results suggest a potential benefit of treating COVID-19 pneumonia with ULTRA-COVID. ClinicalTrials.gov Identifier: NCT04394182.

Economic impact of immunoglobulin replacement therapy in secondary immunodeficiency to hematological cancer: a single center observational study.

This is the first report of the health economic benefits derived from preventing infections through Immunoglobulin Replacement Therapy (IgRT) in patients with secondary immunodeficiency due to hematological malignancies. We conducted a retrospective population-based cohort study using patient medical history and pharmacy data from the Hospital Clínico San Carlos for 21 patients between 2011 and 2020. The pharmacoeconomic impact of using prophylactic IgRT was assessed by comparing characteristics of the SID patients 1 year before and after initiating IgRT measured by direct medical and tangible indirect costs. Results indicate a marked reduction in hospitalization days following IgRT initiation, decreasing from an average of 13.9 to 6.1 days per patient, with the elimination of ICU admissions. While emergency department visits decreased significantly, the number of routine consultations remained unchanged. Notably, absenteeism from work dropped substantially. The financial analysis revealed significant reductions in medication use and fewer ancillary tests, resulting in considerable cost savings. Specifically, total expenditure dropped from €405,088.18 pre-IgRT to €295,804.42 post-IgRT-including the cost of IgRT itself at €156,309.60. Overall, the annual savings amounted to €109,283.84, validating the cost-effectiveness of IgRT in managing SID in patients with hematological cancers.

Measurement and correction of leaf open times in helical tomotherapy.

PURPOSE: The binary multileaf collimator (MLC) is one of the most important components in helical tomotherapy (HT), as it modulates the dose delivered to the patient. However, methods to ensure MLC quality in HT treatments are lacking. The authors obtained data on the performance of the MLC in treatments administered in their department in order to assess possible delivery errors due to the MLC. Correction methods based on their data are proposed. METHODS: Twenty sinograms from treatments delivered using both of the authors HT systems were measured and analyzed by recording the fluence collected by the imaging detector. Planned and actual sinograms were compared using distributions of leaf open time (LOT) errors, as well as differences in fluence reconstructed at each of the 51 projections into which the treatment planning system divides each rotation for optimization purposes. They proposed and applied a method based on individual leaf error correction and the increase in projection time to prevent latency effects when LOT is close to projection time. In order to analyze the dosimetric impact of the corrections, inphantom measurements were made for four corrected treatments. RESULTS: The LOTs measured were consistent with those planned. Most of the mean errors in LOT distributions were within 1 ms with standard deviations of over 4 ms. Reconstructed fluences showed good results, with over 90% of points passing the 3% criterion, except in treatments with a short mean LOT, where the percentage of passing points was as low as 66%. Individual leaf errors were as long as 4 ms in some cases. Corrected sinograms improved error distribution, with standard deviations of over 3 ms and increased percentages of points passing 3% in the fluence per angle analysis, especially in treatments with a short mean LOT and those that were more subject to latency effects. The minimum percentage of points within 3% increased to 86%. In-phantom measurements of the corrected treatments showed that, while treatments affected by latency effects were improved, those affected by individual leaf errors were not. CONCLUSIONS: Measurement of MLC performance in real treatments provides the authors with a valuable tool for ensuring the quality of HT delivery. The LOTs of MLC are very accurate in most cases. Sources of error were found and correction methods proposed and applied. The corrections decreased the amount of LOT errors. The dosimetric impact of these corrections should be evaluated more thoroughly using 3D dose distribution analysis.

Study of the uncertainty in the determination of the absorbed dose to water during external beam radiotherapy calibration.

To achieve a good clinical outcome in radiotherapy treatment, a certain accuracy in the dose delivered to the patient is required. Therefore, it is necessary to keep the uncertainty in each of the steps of the process inside some acceptable values, which implies a global uncertainty as low as possible. This work is focused on the uncertainty evaluation of absorbed dose to water in the routine calibration for clinical beams, in the range of energies used in external radiotherapy. With this aim, different uncertainty components (corrected electrometer reading, calibration factor, beam quality correction factor and reference conditions) associated to beam calibration have been considered. Results show a typical uncertainty in the determination of absorbed dose to water during beam calibration around 1.3% for photon beams and 1.5% for electron beams (k=1 in both cases) when the N(D,w) formalism is used and is theoretically calculated. These values may be different depending on the uncertainty provided by the standards laboratory for calibration factor, which is shown in the work. If the total application of the N(D,w) formalism, that is to say, specific calibrations of each chamber in the user's beam qualities, is taken into account the uncertainty in this step of the process could be placed close to 1.0%. Furthermore, the possibility of an uncertainty reduction with the absorbed dose to water formalism adoption against the air kerma one is discussed.

A general method for the definition of margin recipes depending on the treatment technique applied in helical tomotherapy prostate plans.

PURPOSE: To obtain specific margin recipes that take into account the dosimetric characteristics of the treatment plans used in a single institution. METHODS: We obtained dose-population histograms (DPHs) of 20 helical tomotherapy treatment plans for prostate cancer by simulating the effects of different systematic errors (Σ) and random errors (σ) on these plans. We obtained dosimetric margins and margin reductions due to random errors (random margins) by fitting the theoretical results of coverages for Gaussian distributions with coverages of the planned D99% obtained from the DPHs. RESULTS: The dosimetric margins obtained for helical tomotherapy prostate treatments were 3.3 mm, 3 mm, and 1 mm in the lateral (Lat), anterior-posterior (AP), and superior-inferior (SI) directions. Random margins showed parabolic dependencies, yielding expressions of 0.16σ(2), 0.13σ(2), and 0.15σ(2) for the Lat, AP, and SI directions, respectively. When focusing on values up to σ = 5 mm, random margins could be fitted considering Gaussian penumbras with standard deviations (σp) equal to 4.5 mm Lat, 6 mm AP, and 5.5 mm SI. CONCLUSIONS: Despite complex dose distributions in helical tomotherapy treatment plans, we were able to simplify the behaviour of our plans against treatment errors to single values of dosimetric and random margins for each direction. These margins allowed us to develop specific margin recipes for the respective treatment technique. The method is general and could be used for any treatment technique provided that DPHs can be obtained.

Statistical analysis of dose-volume and dose-wall histograms for rectal toxicity following 3D-CRT in prostate cancer.

The purpose of this paper is to determine the correlation between dose-volume histogram (DVH) and dose wall-histogram (DWH) in the evaluation of rectal complications for prostate cancer patients treated with three-dimensional conformal radiotherapy (3D-CRT). A retrospective analysis of DVHs and DWHs of a subset of 25 prostate cancer patients treated with 3D-CRT was performed. For every patient the rectum and the rectal wall (inner and outer surface) were contoured. Median ICRU radiation dose of 79.4 Gy was administered. Correlation between DVHs and DWHs parameters was investigated by the nonparametric Spearman test and by linear regression analysis. The results showed a statistically significant linear correlation between pairs of DVH and DWH dosimetric parameters with Spearman correlation values (S) bigger than 0.8, with p values better than 0.0005 (two-sided) when the emptied rectum is considered. The variation of S and linear fit slope values [b(1)] showed a very similar functional shape with a minimum at 91% ICRU dose [S =0.83, b(1)=0.65]. The present study confirms a high correlation (>80%) between DVH and DWH of the rectum following 3D-CRT for prostate cancer. The derived advantage is that the contouring of inner surface of rectum could be obviated in almost 90% of patients when performing predictive models for rectal complications based on dosimetric variables under the standard treatment conditions specified in this study.

Helical tomotherapy in the treatment of pediatric malignancies: a preliminary report of feasibility and acute toxicity.

BACKGROUND: Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT) provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies. METHODS: In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume. RESULTS: The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%), abdomen (17%) and thorax (6%). The most prevalent histological types were: medulloblastoma (16 patients), neuroblastoma (9 patients) and rhabdomyosarcoma (7 patients). A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72%) were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy). In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6%) of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6%) had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases) were significantly associated with severe toxicity (grade 3 or more), whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity. CONCLUSION: HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of acute toxicity that we have seen in this highly selected pediatric patient cohort with clinical features of poor prognosis and/or aggressive therapy needed. Despite of a dosimetrical advantage of HT technique, an exhaustive analysis of long-term follow-up data is needed to assess late toxicity, especially in this potentially sensitive to radiation population.