Comparison of Estimated Late Toxicities between IMPT and IMRT Based on Multivariable NTCP Models for High-Risk Prostate Cancers Treated with Pelvic Nodal Radiation.

Purpose: To compare the late gastrointestinal (GI) and genitourinary toxicities (GU) estimated using multivariable normal tissue complication probability (NTCP) models, between pencil-beam scanning proton beam therapy (PBT) and helical tomotherapy (HT) in patients of high-risk prostate cancers requiring pelvic nodal irradiation (PNI) using moderately hypofractionated regimen. Materials and Methods: Twelve consecutive patients treated with PBT at our center were replanned with HT using the same planning goals. Six late GI and GU toxicity domains (stool frequency, rectal bleeding, fecal incontinence, dysuria, urinary incontinence, and hematuria) were estimated based on the published multivariable NTCP models. The ΔNTCP (difference in absolute NTCP between HT and PBT plans) for each of the toxicity domains was calculated. A one-sample Kolmogorov-Smirnov test was used to analyze distribution of data, and either a paired t test or a Wilcoxon matched-pair signed rank test was used to test statistical significance. Results: Proton beam therapy and HT plans achieved adequate target coverage. Proton beam therapy plans led to significantly better sparing of bladder, rectum, and bowel bag especially in the intermediate range of 15 to 40 Gy, whereas doses to penile bulb and femoral heads were higher with PBT plans. The average ΔNTCP for grade (G)2 rectal bleeding, fecal incontinence, stool frequency, dysuria, urinary incontinence, and G1 hematuria was 12.17%, 1.67%, 2%, 5.83%, 2.42%, and 3.91%, respectively, favoring PBT plans. The average cumulative ΔNTCP for GI and GU toxicities (ΣΔNTCP) was 16.58% and 11.41%, respectively, favoring PBT. Using a model-based selection threshold of any G2 ΔNTCP >10%, 67% (8 patients) would be eligible for PBT. Conclusion: Proton beam therapy plans led to superior sparing of organs at risk compared with HT, which translated to lower NTCP for late moderate GI and GU toxicities in patients of prostate cancer treated with PNI. For two-thirds of our patients, the difference in estimated absolute NTCP values between PBT and HT crossed the accepted threshold for minimal clinically important difference.

Impact of spot positional errors in robustly optimized intensity-modulated proton therapy plan of craniospinal irradiation.

We investigated the influence of random spot positioning errors (SPEs) on dosimetric outcomes of robustly optimized intensity-modulated proton therapy (RB-IMPT) plans in craniospinal irradiation (CSI). Six patients with CSI treated using the RB-IMPT technique were selected. An in-house MATLAB code was used to simulate a random SPE of 1 mm in positive, negative, and both directions for 25%, 50%, and 75% of the total spot positions in the nominal plan. The percentage dose variation (ΔD%) in the six nominal and 54 error-introduced plans was evaluated using standard dose-volume indices, line dose difference, and 3D gamma analysis method. The introduction of a random SPE of 1 mm resulted in a reduction in D99%, D98%, and D95% of both CTVs and PTVs by < 2% compared with the corresponding nominal plans. However, this leads to an increase in D1% of the lens by up to 16.9%. The line dose in the junction region showed ΔD% < 2% for the brain and upper spine and < 4% for the upper and lower spine. The 3D gamma values for 3% at 3 mm and 2% at 2 mm were above 99% and 95%, respectively, in all 54 error-introduced plans. The worst decrease in gamma values was observed for 1% at 1 mm, with values ranging from 64 to 78% for all types of SPE. The RB-IMPT plan for CSI investigated in this study is robust enough for target coverage, even if there are random SPEs of 1 mm. However, this leads to an increase in the dose to the critical organ located close to the target.

Dosimetric impact of random spot positioning errors in intensity modulated proton therapy plans of small and large volume tumors.

OBJECTIVE: To study dosimetric impact of random spot positioning errors on the clinical pencil beam scanning proton therapy plans. METHODS AND MATERIALS: IMPT plans of 10 patients who underwent proton therapy for tumors in brain or pelvic regions representing small and large volumes, respectively, were included in the study. Spot positioning errors of 1 mm, -1 mm or ±1 mm were introduced in these clinical plans by modifying the geometrical co-ordinates of proton spots using a script in the MATLAB programming environment. Positioning errors were simulated to certain numbers of (20%, 40%, 60%, 80%) randomly chosen spots in each layer of these treatment plans. Treatment plans with simulated errors were then imported back to the Raystation (Version 7) treatment planning system and the resultant dose distribution was calculated using Monte-Carlo dose calculation algorithm.Dosimetric plan evaluation parameters for target and critical organs of nominal treatment plans delivered for clinical treatments were compared with that of positioning error simulated treatment plans. For targets, D95% and D2% were used for the analysis. Dose received by optic nerve, chiasm, brainstem, rectum, sigmoid, and bowel were analyzed using relevant plan evaluation parameters depending on the critical structure. In case of intracranial lesions, the dose received by 0.03 cm3 volume (D0.03 cm3) was analyzed for optic nerve, chiasm and brainstem. In rectum, the volume of it receiving a dose of 65 Gy(RBE) (V65) and 40 Gy(RBE) (V40) were compared between the nominal and error introduced plans. Similarly, V65 and V63 were analyzed for Sigmoid and V50 and V15 were analyzed for bowel. RESULTS: The maximum dose variation in PTV D95% (1.88 %) was observed in a brain plan in which the target volume was the smallest (2.7 cm3) among all 10 plans included in the study. This variation in D95% drops down to 0.3% for a sacral chordoma plan in which the PTV volume is significantly higher at 672 cm3. The maximum difference in OARs in terms of absolute dose (D0.03 cm3) was found in left optic nerve (9.81%) and the minimum difference was observed in brainstem (2.48%). Overall, the magnitude of dose errors in chordoma plans were less significant in comparison to brain plans. CONCLUSION: The dosimetric impact of different error scenarios in spot positioning becomes more prominent for treatment plans involving smaller target volume compared to plans involving larger target volumes. ADVANCES IN KNOWLEDGE: Provides information on the dosimetric impact of various possible spot positioning errors and its dependence on the tumor volume in intensity modulated proton therapy.

A novel hybrid 3D dose reconstruction approach for pre-treatment verification of intensity modulated proton therapy plans.

AIM: A novel hybrid three-dimensional (3D) dose reconstruction method, based on planar dose measured at a single shallower depth, was developed for use as patient-specific quality assurance (PSQA) of intensity modulated proton therapy (IMPT) plans. The accuracy, robustness and sensitivity of the presented method were validated for multiple IMPT plans of varying complexities. METHODS AND MATERIALS: An in-house MATLAB program was developed to reconstruct 3D dose distribution from the planar dose (GyRBE) measured at 3 g cm-2 depth in water or solid phantom using a MatriXX PT ion chamber array. The presented method was validated extensively for 11 single-field optimization (SFO) and multi-field optimization (MFO) plans on Proteus Plus. A total of 47 reconstructed planar doses at different depths were compared against the corresponding RayStation treatment planning system (TPS) and MatriXX PT measurement using a gamma passing rate (γ%) evaluated for 3%/3 mm. The robustness of the reconstruction method with respect to depth, energy layers, field dimensions and complexities in the spot intensity map (SIM) were analysed and compared against the standard PSQA. The sensitivity of the reconstruction method was tested for plans with intentional errors. RESULTS: The presented reconstruction method showed excellent agreement (mean γ% > 98%) and robustness with both TPS-calculated and measured dose planes at all depths (2.97-30 g cm-2), energy layers (82.1-225.5 MeV), field dimensions, target volume (17.7-1000 cm3) and SIMs from both SFO and MFO plans. In comparison to the overall mean ± SD γ% from standard PSQA, the reconstruction method showed reductions in mean γ% within 1% for both standard cubes and clinical plans. The reconstruction method was sensitive enough to detect intentional spot positional errors in a selected energy layer of a plan. CONCLUSION: The presented hybrid reconstruction method is sufficiently accurate, robust and sensitive to estimate planar dose at any user-defined depth. It simplifies the measurement setup and eliminates multiple depth measurements.

Dynamics of the COVID -19 Related Publications

BackgroundThis study aims to analyze the dynamics of the published articles and preprints of Covid-19 related literature from different scientific databases and sharing platforms. MethodsThe PubMed, Elsevier, and Research Gate (RG) databases were under consideration in this study over a specific time. Analyses were carried out on the number of publications as (a) function of time (day), (b) journals and (c) authors. Doubling time of the number of publications was analyzed for PubMed "all articles" and Elsevier published articles. Analyzed databases were (1A) PubMed "all articles" (01/12/2019-12/06/2020) (1B) PubMed Review articles (01/12/2019-2/5/2020) and (1C) PubMed Clinical Trials (01/01/2020-30/06/2020) (2) Elsevier all publications (01/12/2019-25/05/2020) (3) RG (Article, Pre Print, Technical Report) (15/04/2020-30/4/2020). FindingsTotal publications in the observation period for PubMed, Elsevier, and RG were 23000, 5898 and 5393 respectively. The average number of publications/day for PubMed, Elsevier and RG were 70.0 {+/-}128.6, 77.6{+/-}125.3 and 255.6{+/-}205.8 respectively. PubMed shows an avalanche in the number of publication around May 10, number of publications jumped from 6.0{+/-}8.4/day to 282.5{+/-}110.3/day. The average doubling time for PubMed, Elsevier, and RG was 10.3{+/-}4 days, 20.6 days, and 2.3{+/-}2.0 days respectively. In PubMed average articles/journal was 5.2{+/-}10.3 and top 20 authors representing 935 articles are of Chinese descent. The average number of publications per author for PubMed, Elsevier, and RG was 1.2{+/-}1.4, 1.3{+/-}0.9, and 1.1{+/-}0.4 respectively. Subgroup analysis, PubMed review articles mean and median review time for each article were <0|17{+/-}17|77> and 13.9 days respectively; and reducing at a rate of-0.21 days (count)/day. InterpretationAlthough the disease has been known for around 6 months, the number of publications related to the Covid-19 until now is huge and growing very fast with time. It is essential to rationalize the publications scientifically by the researchers, authors, reviewers, and publishing houses. FundingNone

Electronic Portal Imaging Device-Based Three-Dimensional Volumetric Dosimetry for Intensity-modulated Radiotherapy Pretreatment Quality Assurance.

AIM: This study aimed at evaluating the efficacy of treatment planning system (TPS)-based heterogeneity correction for two- and three-dimensional (2D and 3D) electronic portal imaging device (EPID)-based pretreatment dose verification. An experiment was conducted on the EPID back-projection technique and intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Treatment plans were delivered in EPID without a patient to obtain the fluence pattern (FEPID). A heterogeneity correction plane (Fhet) for an open beam of 30 cm × 30 cm was extracted from the TPS. The heterogeneity-corrected measured fluence is developed by matrix element multiplication (FResultant = FEPID × Fhet). Further planes were summed to develop a 3D dose distribution and exported to the TPS. Dose verifications for 2D and 3D were carried out with the corresponding TPS values using 2D gamma analysis (É£) and dose volume histogram (DVH) comparison, respectively. Totally, 33 patients (17 head-neck and 16 thorax cases) were evaluated in this study. RESULTS: The head-neck and thorax plans show a 3-mm-distance to agreement (DTA) 3% DD gamma passing of 96.3% ± 2.0% and 95.4% ± 1.8% points, respectively, between FTPS and FResultant. The comparison of the uncorrected measured fluence (FEPID) with FTPS reveals a gamma passing of 82.2% ± 7.3% and 80.4% ± 8.6% for head-neck and thorax cases, respectively. A total of 87 out of the 102 head-neck and thorax beams exhibit a planner gamma passing of 97.6% ± 2.1%. In the 3D-DVH comparison of thorax and head-neck cases, D5% for planning target volume were -0.5% ± 2.2% and -2.1% ± 3.5%, respectively; D95% varies as 1.0% ± 2.7% and 1.4% ± 1.1% between TPS calculated and heterogeneity-corrected-EPID-based dose reconstruction. CONCLUSION: The novel TPS-based heterogeneity correction can improve the 2D and 3D EPID-based back projection technique. Structures with large heterogeneities can also be handled using the proposed technique.

Ambient neutron and photon dose equivalent H*(10) around a pencil beam scanning proton therapy facility.

OBJECTIVES: To measure leakage ambient dose equivalent H*(10) from stray secondary neutron and photon radiation around proton therapy (PT) facility and evaluate adequacy of shielding design. METHODS AND MATERIALS: H*(10) measurement were carried out at 149 locations around cyclotron vault (CV), beam transport system (BTS) and first treatment room (GTR3) of a multiroom PT facility using WENDI-II and SmartIon survey meter. Measurement were performed under extreme case scenarios wherein maximum secondary neutrons and photons were produced around CV, BTS and GTR3 by stopping 230MeV proton of 300nA on beam degrader, end of BTS and isocenter of GTR3. Weekly time average dose rate (TADR) were calculated from H*(10) value measured at selective hot spots by irradiating actual treatment plans of mix clinical sites. RESULTS: The maximum total H*(10) were within 2 µSv/hr around CV, 5 µSv/hr around outer wall of BTS which increases up to 62 µSv/hr at the end of inside BTS corridor. Maximum H*(10) of 20.8 µSv/hr in treatment control console (P125), 23.4 µSv/hr behind the common wall between GTR3 and GTR2 (P132) and 25.7 µSv/hr above isocenter (P99) were observed around GTR3. Reduction of beam current from 6 to 3 nA and 1 nA at nozzle exit lead to decrease in total H*(10) at P125 from 20.8 to 11.35 and 4.62 µSv/hr. In comparison to extreme case scenario, H*(10) value at P125, P132 and P99 from clinically relevant irradiation parameters were reduce by a factor ranging from 8.6 for high range cube to 46.4 for brain clinical plan. The maximum weekly TADR per fraction was highest for large volume, sacral chordoma patient at 8.5 µSv/hr compare to 0.3 µSv/hr for brain patient. The calculated weekly TADR for 30 mix clinical cases and 15 fractions of 1 L cube resulted total weekly TADR of 83-84 µSv/hr at P125, P132 and P99. The maximum annual dose level at these hot spots were estimated at 4.37 mSv/Yr. CONCLUSION: We have carried out an extensive measurement of H*(10) under different conditions. The shielding thickness of our PT facility is adequate to limit the dose to occupational worker and general public within the permissible stipulated limit. The data reported here can bridge the knowledge gap in ambient dose around PT facility and can also be used as a reference for any new and existing proton facility for intercomparison and validation. ADVANCES IN KNOWLEDGE: First extensive investigation of neutron and photon H*(10) around PT facility and can bridge the knowledge gap on ambient dose.

A Homogeneous Water-Equivalent Anthropomorphic Phantom for Dosimetric Verification of Radiotherapy Plans.

Water is treated as radiological equivalent to human tissue. While this seems justified, there is neither mathematical proof nor sufficient experimental evidence that a water phantom can be treated as equivalent to human tissue. The aim of this work is to simulate and validate a water phantom that is tissue equivalent in terms of the dosimetric characteristics of both water and human tissue Dynamic, intensity-modulated radiotherapy plans for two head and neck, one brain, one pelvis, and three lung/mediastinum cases were chosen for this study. Using a treatment planning system (TPS) (Eclipse, Varian Medical System, Polo Alto, CA, USA) and Anisotropic Analytic Algorithm in a grid resolution of 5 mm × 5 mm, a patient-equivalent water phantom was calculated from all rays in the isocentric plane as an array of water equivalent depths (dWE). These rays were plotted versus isocentric separation and ray-tracing direction. Planar doses were compared between the isocentric plane in the patient computed tomography and the water equivalent phantom using gamma criteria of 2%-2 mm and 3%-3 mm. Except in one lung case, >95% gamma agreement was seen when using 3%-3 mm and >90% pass rate was seen when using 2%-2 mm. For head and neck cases, gamma-fail was restricted to the periphery. For mediastinum cases, gamma-fail was restricted to the lungs. This study demonstrates that a heterogeneous patient can be converted to a water phantom with comparable dosimetric characteristics and disagreements restricted to the lung area for both modulated and open beams. Potential sources of error include the dWE calculation and TPS dose computation.