Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC), but regional or distant relapses, or both, are common. Immunotherapy reduces recurrence and improves survival in people with stage III NSCLC after chemoradiotherapy, but its utility in stage I and II cases is unclear. We therefore conducted a randomised phase 2 trial of SABR alone compared with SABR with immunotherapy (I-SABR) for people with early-stage NSCLC. METHODS: We did an open-label, randomised, phase 2 trial comparing SABR to I-SABR, conducted at three different hospitals in TX, USA. People aged 18 years or older with histologically proven treatment-naive stage IA-IB (tumour size ≤4 cm, N0M0), stage IIA (tumour size ≤5 cm, N0M0), or stage IIB (tumour size >5 cm and ≤7 cm, N0M0) as per the American Joint Committee on Cancer version 8 staging system or isolated parenchymal recurrences (tumour size ≤7 cm) NSCLC (TanyNanyM0 before definitive surgery or chemoradiotherapy) were included in this trial. Participants were randomly assigned (1:1; using the Pocock & Simon method) to receive SABR with or without four cycles of nivolumab (480 mg, once every 4 weeks, with the first dose on the same day as, or within 36 h after, the first SABR fraction). This trial was unmasked. The primary endpoint was 4-year event-free survival (local, regional, or distant recurrence; second primary lung cancer; or death). Analyses were both intention to treat (ITT) and per protocol. This trial is registered with ClinicalTrials.gov (NCT03110978) and is closed to enrolment. FINDINGS: From June 30, 2017, to March 22, 2022, 156 participants were randomly assigned, and 141 participants received assigned therapy. At a median 33 months' follow-up, I-SABR significantly improved 4-year event-free survival from 53% (95% CI 42-67%) with SABR to 77% (66-91%; per-protocol population, hazard ratio [HR] 0·38; 95% CI 0·19-0·75; p=0·0056; ITT population, HR 0·42; 95% CI 0·22-0·80; p=0·0080). There were no grade 3 or higher adverse events associated with SABR. In the I-SABR group, ten participants (15%) had grade 3 immunologial adverse events related to nivolumab; none had grade 3 pneumonitis or grade 4 or higher toxicity. INTERPRETATION: Compared with SABR alone, I-SABR significantly improved event-free survival at 4 years in people with early-stage treatment-naive or lung parenchymal recurrent node-negative NSCLC, with tolerable toxicity. I-SABR could be a treatment option in these participants, but further confirmation from a number of currently accruing phase 3 trials is required. FUNDING: Bristol-Myers Squibb and MD Anderson Cancer Center Alliance, National Cancer Institute at the National Institutes of Health through Cancer Center Core Support Grant and Clinical and Translational Science Award to The University of Texas MD Anderson Cancer Center.

Adding customized electron energy beams to TrueBeam linear accelerators.

PURPOSE: To better meet clinical needs and facilitate optimal treatment planning, we added two new electron energy beams (7 and 11 MeV) to two Varian TrueBeam linacs. METHODS: We worked with the vendor to create two additional customized electron energies without hardware modifications. For each beam, we set the bending magnet current and then optimized other beam-specific parameters to achieve depths of 50% ionization (I50 ) of 2.9 cm for 7 MeV and 4.2 cm for the 11 MeV beam with the 15 × 15 cm2 cone at 100 cm source-to-surface distance (SSD) by using an ionization chamber profiler (ICP) with a double-wedge (DW) phantom. Beams were steered and balanced to optimize symmetry with the ICP. After all parameters were set, full commissioning was done including measuring beam profiles, percent depth doses (PDDs), output factors (OFs) at standard, and extended SSDs. Measured data were compared between the two linacs and against the values calculated by our RayStation treatment planning system (TPS) following Medical Physics Practice Guideline 5.a (MPPG 5.a) guidelines. RESULTS: The I50 values initially determined with the ICP/DW agreed with those from a PDD-scanned in-water phantom within 0.2 mm for the 7 and 11 MeV on both linacs. Comparison of the beam characteristics from the two linacs indicated that flatness and symmetry agreed within 0.4%, and point-by-point differences in PDD were within 0.01% ± 0.3% for the 7 MeV and 0.01% ± 0.3% for the 11 MeV. The OF ratios between the two linacs were 1.000 ± 0.007 for the 7 MeV and 1.004 ± 0.007 for the 11 MeV. Agreement between TPS-calculated outputs and measurements were -0.1% ± 1.0% for the 7 MeV and 0.2% ± 0.8% for the 11 MeV. All other parameters met the MPPG 5.a's 3%/3-mm criteria. CONCLUSION: We were able to add two new beam energies with no hardware modifications. Tuning of the new beams was facilitated by the ICP/DW system allowing us to have the procedures done in a few hours and achieve highly consistent results across two linacs. PACS numbers: 87.55.Qr, 87.56.Fc.

Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgery.

BACKGROUND: A previous pooled analysis of the STARS and ROSEL trials showed higher survival after stereotactic ablative radiotherapy (SABR) than with surgery for operable early-stage non-small-cell lung cancer (NSCLC), but that analysis had notable limitations. This study reports long-term results of the revised STARS trial, in which the SABR group was re-accrued with a larger sample size, along with a protocol-specified propensity-matched comparison with a prospectively registered, contemporary institutional cohort of patients who underwent video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND). METHODS: This single-arm prospective trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and enrolled patients aged 18 years or older with a Zubrod performance status of 0-2, newly diagnosed and histologically confirmed NSCLC with N0M0 disease (squamous cell, adenocarcinoma, large cell, or NSCLC not otherwise specified), and a tumour diameter of 3 cm or less. This trial did not include patients from the previous pooled analysis. SABR dosing was 54 Gy in three fractions (for peripheral lesions) or 50 Gy in four fractions (for central tumours; simultaneous integrated boost to gross tumour totalling 60 Gy). The primary endpoint was the 3-year overall survival. For the propensity-matching analysis, we used a surgical cohort from the MD Anderson Department of Thoracic and Cardiovascular Surgery's prospectively registered, institutional review board-approved database of all patients with clinical stage I NSCLC who underwent VATS L-MLND during the period of enrolment in this trial. Non-inferiority could be claimed if the 3-year overall survival rate after SABR was lower than that after VATS L-MLND by 12% or less and the upper bound of the 95% CI of the hazard ratio (HR) was less than 1·965. Propensity matching consisted of determining a propensity score using a multivariable logistic regression model including several covariates (age, tumour size, histology, performance status, and the interaction of age and sex); based on the propensity scores, one patient in the SABR group was randomly matched with one patient in the VATS L-MLND group using a 5:1 digit greedy match algorithm. This study is registered with ClinicalTrials.gov, NCT02357992. FINDINGS: Between Sept 1, 2015, and Jan 31, 2017, 80 patients were enrolled and included in efficacy and safety analyses. Median follow-up time was 5·1 years (IQR 3·9-5·8). Overall survival was 91% (95% CI 85-98) at 3 years and 87% (79-95) at 5 years. SABR was tolerated well, with no grade 4-5 toxicity and one (1%) case each of grade 3 dyspnoea, grade 2 pneumonitis, and grade 2 lung fibrosis. No serious adverse events were recorded. Overall survival in the propensity-matched VATS L-MLND cohort was 91% (95% CI 85-98) at 3 years and 84% (76-93) at 5 years. Non-inferiority was claimed since the 3-year overall survival after SABR was not lower than that observed in the VATS L-MLND group. There was no significant difference in overall survival between the two patient cohorts (hazard ratio 0·86 [95% CI 0·45-1·65], p=0·65) from a multivariable analysis. INTERPRETATION: Long-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended. FUNDING: Varian Medical Systems and US National Cancer Institute (National Institutes of Health).

Beam energy metrics for the acceptance and quality assurance of Halcyon linear accelerator.

PURPOSE: Establish and compare two metrics for monitoring beam energy changes in the Halcyon platform and evaluate the accuracy of these metrics across multiple Halcyon linacs. METHOD: The first energy metric is derived from the diagonal normalized flatness (FDN ), which is defined as the ratio of the average measurements at a fixed off-axis equal distance along the open profiles in two diagonals to the measurement at the central axis with an ionization chamber array (ICA). The second energy metric comes from the area ratio (AR) of the quad wedge (QW) profiles measured with the QW on the top of the ICA. Beam energy is changed by adjusting the magnetron current in a non-clinical Halcyon. With D10cm measured in water at each beam energy, the relationships between FDN or AR energy metrics to D10cm in water is established with linear regression across six energy settings. The coefficients from these regressions allow D10cm (FDN ) calculation from FDN using open profiles and D10cm (QW) calculation from AR using QW profiles. RESULTS: Five Halcyon linacs from five institutions were used to evaluate the accuracy of the D10cm (FDN ) and the D10cm (QW) energy metrics by comparing to the D10cm values computed from the treatment planning system (TPS) and D10cm measured in water. For the five linacs, the D10cm (FDN ) reported by the ICA based on FDN from open profiles agreed with that calculated by TPS within -0.29 ± 0.23% and 0.61% maximum discrepancy; the D10cm (QW) reported by the QW profiles agreed with that calculated by TPS within -0.82 ± 1.27% and -2.43% maximum discrepancy. CONCLUSION: The FDN -based energy metric D10cm (FDN ) can be used for acceptance testing of beam energy, and also for the verification of energy in periodic quality assurance (QA) processes.

Monitoring linear accelerators electron beam energy constancy with a 2D ionization chamber array and double-wedge phantom.

Validate that a two-dimensional (2D) ionization chamber array (ICA) combined with a double-wedge plate (DWP) can track changes in electron beam energy well within 2.0 mms as recommended by TG-142 for monthly quality assurance (QA). Electron beam profiles of 4-22 MeV were measured for a 25 × 25 cm2 cone using an ICA with a DWP placed on top of it along one diagonal axis. The relationship between the full width half maximum (FWHM) field size created by DWP energy degradation across the field and the depth of 50% dose in water (R50 ) is calibrated for a given ICA/DWP combination in beams of know energies (R50 values). Once this relationship is established, the ICA/DWP system will report the R50 FWHM directly. We calibrated the ICA/DWP on a linear accelerator with energies of 6, 9, 12, 16, 20, and 22 MeV. The R50 FWHM values of these beams and eight other beams with different R50 values were measured and compared with the R50 measured in water, that is, R50 Water. Resolving changes of R50 up to 0.2 cm with ICA/DWP was tested by adding solid-water to shift the energy and was verified with R50 Water measurements. To check the long-term reproducibility of ICA/DWP we measured R50 FWHM on a monthly basis for a period of 3 yr. We proposed a universal calibration procedure considering the off-axis corrections and compared calibrations and measurements on three types of linacs (Varian TrueBeam, Varian C-series, and Elekta) with different nominal energies and R50 values. For all 38 beams on same type of linac with R50 values over a range of 2-8.8 cm, the R50 FWHM reported by the ICA/DWP system agreed with that measured in water within 0.01 ± 0.03 cm (mean ± 1σ) and maximum discrepancy of 0.07 cm. Long-term reproducibility results show the ICA/DWP system to be within 0.04 cm of their baseline over 3 yr. With the universal calibration the maximum discrepancy between R50 FWHM and R50 Water for different types of linac reduced from 0.25 to 0.06 cm. Comparison of R50 FWHM values and R50 Water values and long-term reproducibility of R50 FWHM values indicates that the ICA/DWP can be used for monitoring of electron beam energy constancy well within TG-142 recommended tolerance.

Acceptance and verification of the Halcyon-Eclipse linear accelerator-treatment planning system without 3D water scanning system.

We tested whether an ionization chamber array (ICA) and a one-dimensional water scanner (1DS) could be used instead of a three-dimensional water scanning system (3DWS) for acceptance testing and commissioning verification of the Varian Halcyon-Eclipse Treatment Planning System (TPS). The Halcyon linear accelerator has a single 6-MV flattening-filter-free beam and a nonadjustable beam model for the TPS. Beam data were measured with a 1DS, ICA, ionization chambers, and electrometer. Acceptance testing and commissioning were done simultaneously by comparing the measured data with TPS-calculated percent-depth-dose (PDD) and profiles. The ICA was used to measure profiles of various field sizes (10-, 20-, and 28 cm2 ) at depths of dmax (1.3 cm), 5-, 10-, and 20 cm. The 1DS was used for output factors (OFs) and PDDs. OFs were measured with 1DS for various fields (2-28 cm2 ) at a source-to-surface distance of 90 cm. All measured data were compared with TPS-calculations. Profiles, off-axis ratios (OAR), PDDs and OFs were also measured with a 3DWS as a secondary check. Profiles between the ICA and TPS (ICA and 3DWS) at various depths across the fields indicated that the maximum discrepancies in high-dose and low-dose tail were within 2% and 3%, respectively, and the maximum distance-to-agreement in the penumbra region was <3 mm. The largest OAR differences between ICA and TPS (ICA and 3DWS) values were 0.23% (-0.25%) for a 28 × 28 cm2 field, and the largest point-by-point PDD differences between 1DS and TPS (1DS and 3DWS) were -0.41% ± 0.12% (-0.32% ± 0.17%) across the fields. Both OAR and PDD showed the beam energy is well matched to the TPS model. The average ratios of 1DS-measured OFs to the TPS (1DS to 3DWS) values were 1.000 ± 0.002 (0.999 ± 0.003). The Halcyon-Eclipse system can be accepted and commissioned without the need for a 3DWS.

Dosimetric impact and detectability of multi-leaf collimator positioning errors on Varian Halcyon.

The purpose of this study is to investigate the dosimetric impact of multi-leaf collimator (MLC) positioning errors on a Varian Halcyon for both random and systematic errors, and to evaluate the effectiveness of portal dosimetry quality assurance in catching clinically significant changes caused by these errors. Both random and systematic errors were purposely added to 11 physician-approved head and neck volumetric modulated arc therapy (VMAT) treatment plans, yielding a total of 99 unique plans. Plans were then delivered on a preclinical Varian Halcyon linear accelerator and the fluence was captured by an opposed portal dosimeter. When comparing dose-volume histogram (DVH) values of plans with introduced MLC errors to known good plans, clinically significant changes to target structures quickly emerged for plans with systematic errors, while random errors caused less change. For both error types, the magnitude of clinically significant changes increased as error size increased. Portal dosimetry was able to detect all systematic errors, while random errors of ±5 mm or less were unlikely to be detected. Best detection of clinically significant errors, while minimizing false positives, was achieved by following the recommendations of AAPM TG-218. Furthermore, high- to moderate correlation was found between dose DVH metrics for normal tissues surrounding the target and portal dosimetry pass rates. Therefore, it may be concluded that portal dosimetry on the Halcyon is robust enough to detect errors in MLC positioning before they introduce clinically significant changes to VMAT treatment plans.

Quantification of beam steering with an ionization chamber array.

Routine quality assurance for linear accelerators (linacs) usually involves verification of beam steering with a water scanning system. We established a beam steering procedure that uses a 2D ionization chamber array (ICA) and verified the equivalence of beam symmetry between the ICA and a water scanning system. The ICA calibration accuracy, reproducibility and stability were evaluated and the uncertainty in the measurement of beam symmetry due to the array calibration was examined. Forty-five photon beams and 80 electron beams across 7 Varian C-series and 4 TrueBeam linacs were steered in the radial and transverse directions using an ICA. After beam steering, profiles were re-measured using the ICA and in-water using a 3D Scanner (3DS). Beam symmetries measured with the ICA and 3DS were compared by (a) calculating the difference in point-by-point symmetry, (b) plotting the histogram distribution of the symmetry differences, and (c) comparing ICA and 3DS differences with their respective Varian symmetry protocol analysis. Array calibrations from five different occurrences (2012 to 2016) over six different beams reproduced within 0.5%. The uncertainty in beam symmetry was less than 0.5% due to the uncertainties in the array calibration. After all beams were steered using the ICA, the point-by-point symmetry differences between ICA and 3DS at the off-axis positions of 20% and 80% of field size for all beam profiles indicated that 95% of point-by-point symmetry comparisons agreed within 0.7%, and 100% agreed within 1.0%; after steering with the ICA 97.8% of photon beam profiles (88 of 90) and 97.5% of electron beam profiles (156 of 160) had symmetry within 1% when measured with the 3DS. All photon and electron beam profiles had symmetry within 1.1% and 1.2%, respectively, for profiles measured with the 3DS. Our data demonstrate that a calibrated ICA can be used to steer photon and electron beams achieving beam symmetry within 1% when re-measured with a 3D water scanning system.

Independent validation of machine performance check for the Halcyon and TrueBeam linacs for daily quality assurance.

PURPOSE: To evaluate the ability of the machine performance check (MPC) on the Halcyon to detect errors, with comparison with the TrueBeam. METHODS: MPC is an automated set of quality assurance (QA) tests that use a phantom placed on the couch and the linac's imaging system(s) to verify the beam constancy and mechanical performance of the Halcyon and TrueBeam linacs. In order to evaluate the beam constancy tests, we inserted solid water slabs between the beam source and the megavoltage imager to simulate changes in beam output, flatness, and symmetry. The MPC results were compared with measurements, using two-dimensional array under the same conditions. We then studied the accuracy of MPC geometric tests. The accuracies of the relative gantry offset and couch shift tests were evaluated by intentionally inserting phantom shifts, using a rotating or linear motion stage. The MLC offset and absolute gantry offset tests were assessed by miscalibrating these motions on a Halcyon linac. RESULTS: For the Halcyon system, the average difference in the measured beam output between the IC Profiler and MPC, after intentional changes, was 1.3 ± 0.5% (for changes ≤5%). For Halcyon, the MPC test failed (i.e., prevented treatment) when the beam symmetry change was over 1.9%. The accuracy of the MLC offset test was within 0.05 mm. The absolute gantry offset test was able to detect an offset as small as 0.02°. The accuracy of the absolute couch shift test was 0.03 mm. The accuracy of relative couch shift test of Halcyon was measured as 0.16 mm. CONCLUSION: We intentionally inserted errors to evaluate the ability of the MPC to identify errors in dosimetric and geometric parameters. These results showed that the MPC is sufficiently accurate to be effectively used for daily QA of the Halcyon and TrueBeam treatment devices.

Normal tissue doses from MV image-guided radiation therapy (IGRT) using orthogonal MV and MV-CBCT.

PURPOSE: The aim of this study was to measure and compare the mega-voltage imaging dose from the Halcyon medical linear accelerator (Varian Medical Systems) with measured imaging doses with the dose calculated by Eclipse treatment planning system. METHODS: An anthropomorphic thorax phantom was imaged using all imaging techniques available with the Halcyon linac - MV cone-beam computed tomography (MV-CBCT) and orthogonal anterior-posterior/lateral pairs (MV-MV), both with high-quality and low-dose modes. In total, 54 imaging technique, isocenter position, and field size combinations were evaluated. The imaging doses delivered to 11 points in the phantom (in-target and extra-target) were measured using an ion chamber, and compared with the imaging doses calculated using Eclipse. RESULTS: For high-quality MV-MV mode, the mean extra-target doses delivered to the heart, left lung, right lung and spine were 1.18, 1.64, 0.80, and 1.11 cGy per fraction, respectively. The corresponding mean in-target doses were 3.36, 3.72, 2.61, and 2.69 cGy per fraction, respectively. For MV-MV technique, the extra-target imaging dose had greater variation and dependency on imaging field size than did the in-target dose. Compared to MV-MV technique, the imaging dose from MV-CBCT was less sensitive to the location of the organ relative to the treatment field. For high-quality MV-CBCT mode, the mean imaging doses to the heart, left lung, right lung, and spine were 8.45, 7.16, 7.19, and 6.51 cGy per fraction, respectively. For both MV-MV and MV-CBCT techniques, the low-dose mode resulted in an imaging dose about half of that in high-quality mode. CONCLUSION: The in-target doses due to MV imaging using the Halcyon ranged from 0.59 to 9.75 cGy, depending on the choice of imaging technique. Extra-target doses from MV-MV technique ranged from 0 to 2.54 cGy. The MV imaging dose was accurately calculated by Eclipse, with maximum differences less than 0.5% of a typical treatment dose (assuming a 60 Gy prescription). Therefore, the cumulative imaging and treatment plan dose distribution can be expected to accurately reflect the actual dose.

A snapshot of medical physics practice patterns.

A large number of surveys have been sent to the medical physics community addressing many clinical topics for which the medical physicist is, or may be, responsible. Each survey provides an insight into clinical practice relevant to the medical physics community. The goal of this study was to create a summary of these surveys giving a snapshot of clinical practice patterns. Surveys used in this study were created using SurveyMonkey and distributed between February 6, 2013 and January 2, 2018 via the MEDPHYS and MEDDOS listserv groups. The format of the surveys included questions that were multiple choice and free response. Surveys were included in this analysis if they met the following criteria: more than 20 responses, relevant to radiation therapy physics practice, not single-vendor specific, and formatted as multiple-choice questions (i.e., not exclusively free-text responses). Although the results of free response questions were not explicitly reported, they were carefully reviewed, and the responses were considered in the discussion of each topic. Two-hundred and fifty-two surveys were available, of which 139 passed the inclusion criteria. The mean number of questions per survey was 4. The mean number of respondents per survey was 63. Summaries were made for the following topics: simulation, treatment planning, electron treatments, linac commissioning and quality assurance, setup and treatment verification, IMRT and VMAT treatments, SRS/SBRT, breast treatments, prostate treatments, brachytherapy, TBI, facial lesion treatments, clinical workflow, and after-hours/emergent treatments. We have provided a coherent overview of medical physics practice according to surveys conducted over the last 5 yr, which will be instructive for medical physicists.

7-year follow-up after stereotactic ablative radiotherapy for patients with stage I non-small cell lung cancer: Results of a phase 2 clinical trial.

BACKGROUND: The authors evaluated the efficacy, patterns of failure, and toxicity of stereotactic ablative radiotherapy (SABR) for patients with medically inoperable, clinical stage I non-small cell lung cancer (NSCLC) in a prospective clinical trial with 7 years of follow-up. Clinical staging was performed according to the seventh edition of the American Joint Committee on Cancer TNM staging system. METHODS: Eligible patients with histologically confirmed NSCLC of clinical stage I as determined using positron emission tomography staging were treated with SABR (50 grays in 4 fractions). The primary endpoint was progression-free survival. Patients were followed with computed tomography and/or positron emission tomography/computed tomography every 3 months for the first 2 years, every 6 months for the next 3 years, and then annually thereafter. RESULTS: A total of 65 patients were eligible for analysis. The median age of the patients was 71 years, and the median follow-up was 7.2 years. A total of 18 patients (27.7%) developed disease recurrence at a median of 14.5 months (range, 4.3-71.5 months) after SABR. Estimated incidences of local, regional, and distant disease recurrence using competing risk analysis were 8.1%, 10.9%, and 11.0%, respectively, at 5 years and 8.1%, 13.6%, and 13.8%, respectively, at 7 years. A second primary lung carcinoma developed in 12 patients (18.5%) at a median of 35 months (range, 5-67 months) after SABR. Estimated 5-year and 7-year progression-free survival rates were 49.5% and 38.2%, respectively; the corresponding overall survival rates were 55.7% and 47.5%, respectively. Three patients (4.6%) experienced grade 3 treatment-related adverse events. No patients developed grade 4 or 5 adverse events (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]). CONCLUSIONS: With long-term follow-up, the results of the current prospective study demonstrated outstanding local control and low toxicity after SABR in patients with clinical stage I NSCLC. Regional disease recurrence and distant metastases were the dominant manifestations of failure. Surveillance for second primary lung carcinoma is recommended. Cancer 2017;123:3031-39. © 2017 American Cancer Society.

Reproducibility of patient setup in the seated treatment position: A novel treatment chair design.

Radiotherapy in a seated position may be indicated for patients who are unable to lie on the treatment couch for the duration of treatment, in scenarios where a seated treatment position provides superior anatomical positioning and dose distributions, or for a low-cost system designed using a fixed treatment beam and rotating seated patient. In this study, we report a novel treatment chair that was constructed to allow for three-dimensional imaging and treatment delivery while ensuring robust immobilization, providing reproducibility equivalent to that in the traditional supine position. Five patients undergoing radiation treatment for head-and-neck cancers were enrolled and were setup in the chair, with immobilization devices created, and then imaged with orthogonal X-rays in a scenario that mimicked radiation treatments (without treatment delivery). Six subregions of the acquired images were rigidly registered to evaluate intra- and interfraction displacement and chair construction. Displacements under conditions of simulated image guidance were acquired by first registering one subregion; the residual displacement of other subregions was then measured. Additionally, we administered a patient questionnaire to gain patient feedback and assess comparison to the supine position. Average inter- and intrafraction displacements of all subregions in the seated position were less than 2 and 3 mm, respectively. When image guidance was simulated, L-R and A-P interfraction displacements were reduced by an average of 1 mm, providing setup of comparable quality to supine setups. The enrolled patients, who had no indication for a seated treatment position, reported no preference in the seated or the supine position. The novel chair design provides acceptable inter- and intrafraction displacement, with reproducibility equivalent to that reported for patients in the supine position. Patient feedback will be incorporated in the refinement of the chair, facilitating treatment of head-and-neck cancer in patients who are unable to lie for the duration of treatment or for use in an economical fixed-beam setup.

A comparison of methods for monitoring photon beam energy constancy.

In extension of a previous study, we compared several photon beam energy metrics to determine which was the most sensitive to energy change; in addition to those, we accounted for both the sensitivity of each metric and the uncertainty in determining that metric for both traditional flattening filter (FF) beams (4, 6, 8, and 10 MV) and for flattening filter-free (FFF) beams (6 and 10 MV) on a Varian TrueBeam. We examined changes in these energy metrics when photon energies were changed to ± 5% and ± 10% from their nominal energies: 1) an attenuation-based metric (the percent depth dose at 10 cm depth, PDD(10)) and, 2) profile-based metrics, including flatness (Flat) and off-axis ratios (OARs) measured on the orthogonal axes or on the diagonals (diagonal normalized flatness, FDN). Profile-based metrics were measured near dmax and also near 10 cm depth in water (using a 3D scanner) and with ioniza-tion chamber array (ICA). PDD(10) was measured only in water. Changes in PDD, OAR, and FDN were nearly linear to the changes in the bend magnet current (BMI) over the range from -10% to +10% for both FF and FFF beams: a ± 10% change in energy resulted in a ± 1.5% change in PDD(10) for both FF and FFF beams, and changes in OAR and FDN were > 3.0% for FF beams and > 2.2% for FFF beams. The uncertainty in determining PDD(10) was estimated to be 0.15% and that for OAR and FDN about 0.07%. This resulted in minimally detectable changes in energy of 2.5% for PDD(10) and 0.5% for OAR and FDN. We found that the OAR- or FDN- based metrics were the best for detecting energy changes for both FF and FFF beams. The ability of the OAR-based metrics determined with a water scanner to detect energy changes was equivalent to that using an ionization chamber array. We recommend that OAR be measured either on the orthogonal axes or the diagonals, using an ionization chamber array near the depth of maximum dose, as a sensitive and efficient way to confirm stability of photon beam energy.

Reproducibility in patient-specific IMRT QA.

The purpose of this study was to determine the reproducibility of patient-specific, intensity-modulated radiation therapy (IMRT) quality assurance (QA) results in a clinical setting. Six clinical patient plans were delivered to a variety of devices and analyses, including 1) radiographic film; 2) ion chamber; 3) 2D diode array delivered and analyzed in three different configurations (AP delivery with field-by-field analysis, AP delivery with composite analysis, and planned gantry angle delivery); 4) helical diode array; and 5) in-house-designed multiple ion chamber phantom. The six clinical plans were selected from a range of treatment sites and were of various levels of complexity. Of note, three of the plans had failed at least preliminary evaluation with our in-house IMRT QA; the other three plans had passed QA. These plans were delivered three times sequentially without changing the setup, and then delivered two more times after breaking down and rebuilding the setup between each. This allowed for an investigation of reproducibility (in terms of dose, dose difference or percent of pixels passing gamma) of both the delivery and the physical setup. This study showed that the variability introduced from the setup was generally higher than the variability from redelivering the plan. Radiographic film showed the poorest reproducibility of the dosimeters investigated. In conclusion, the various IMRT QA systems demonstrated varying abilities to reproduce QA results consistently. All dosimetric devices demonstrated a reproducibility (coefficient of variation) of less than 4% in their QA results for all plans, with an average reproducibility of less than 2%. This work provides some quantification for the variability that may be seen for IMRT QA dosimeters.

Deep learning-based automatic segmentation of cardiac substructures for lung cancers.

PURPOSE: Accurate and comprehensive segmentation of cardiac substructures is crucial for minimizing the risk of radiation-induced heart disease in lung cancer radiotherapy. We sought to develop and validate deep learning-based auto-segmentation models for cardiac substructures. MATERIALS AND METHODS: Nineteen cardiac substructures (whole heart, 4 heart chambers, 6 great vessels, 4 valves, and 4 coronary arteries) in 100 patients treated for non-small cell lung cancer were manually delineated by two radiation oncologists. The valves and coronary arteries were delineated as planning risk volumes. An nnU-Net auto-segmentation model was trained, validated, and tested on this dataset with a split ratio of 75:5:20. The auto-segmented contours were evaluated by comparing them with manually drawn contours in terms of Dice similarity coefficient (DSC) and dose metrics extracted from clinical plans. An independent dataset of 42 patients was used for subjective evaluation of the auto-segmentation model by 4 physicians. RESULTS: The average DSCs were 0.95 (+/- 0.01) for the whole heart, 0.91 (+/- 0.02) for 4 chambers, 0.86 (+/- 0.09) for 6 great vessels, 0.81 (+/- 0.09) for 4 valves, and 0.60 (+/- 0.14) for 4 coronary arteries. The average absolute errors in mean/max doses to all substructures were 1.04 (+/- 1.99) Gy and 2.20 (+/- 4.37) Gy. The subjective evaluation revealed that 94% of the auto-segmented contours were clinically acceptable. CONCLUSION: We demonstrated the effectiveness of our nnU-Net model for delineating cardiac substructures, including coronary arteries. Our results indicate that this model has promise for studies regarding radiation dose to cardiac substructures.

Quality assurance for image-guided radiation therapy utilizing CT-based technologies: a report of the AAPM TG-179.

PURPOSE: Commercial CT-based image-guided radiotherapy (IGRT) systems allow widespread management of geometric variations in patient setup and internal organ motion. This document provides consensus recommendations for quality assurance protocols that ensure patient safety and patient treatment fidelity for such systems. METHODS: The AAPM TG-179 reviews clinical implementation and quality assurance aspects for commercially available CT-based IGRT, each with their unique capabilities and underlying physics. The systems described are kilovolt and megavolt cone-beam CT, fan-beam MVCT, and CT-on-rails. A summary of the literature describing current clinical usage is also provided. RESULTS: This report proposes a generic quality assurance program for CT-based IGRT systems in an effort to provide a vendor-independent program for clinical users. Published data from long-term, repeated quality control tests form the basis of the proposed test frequencies and tolerances. CONCLUSION: A program for quality control of CT-based image-guidance systems has been produced, with focus on geometry, image quality, image dose, system operation, and safety. Agreement and clarification with respect to reports from the AAPM TG-101, TG-104, TG-142, and TG-148 has been addressed.

Proton dose perturbations caused by high-voltage leads from implanted cardioverter defibrillators.

An increasing number of patients undergoing proton radiotherapy have cardiac implantable electrical devices (CIEDs). We recently encountered a situation in which a high-voltage coil on a lead from an implanted cardiac defibrillator was located within the clinical treatment volume for a patient receiving proton radiotherapy for esophageal cancer. To study the effects of the lead on the dose delivery, we placed a high-Z CIED lead at both the center and the distal edge of a clinical spread-out Bragg peak (SOBP) in a water phantom, in both a stationary position and with the lead moving in a periodic pattern to simulate cardiorespiratory movement. We then calculated planned doses using a commercial proton treatment planning system (TPS), and compared them with the doses delivered in the phantom, measured using radiographic film. Dose profiles from TPS-calculated and measured dose distributions showed large pertubrations in the delivered proton dose in the vicinity of the CIED lead when it was not moving. The TPS predicted perturbations up to 20% and measurements revealed perturbations up to 35%. However, the perturbations were less than 3% when the lead was moving. Greater dose perturbations were seen when the lead was placed at the distal edge of the SOBP than when it was placed in the center of the SOBP. We conclude that although cardiorespiratory motion of the lead mitigates some of the perturbations, the effects of the leads should be considered and steps taken to reduce these effects during the treatment planning process.

Using Failure Mode and Effects Analysis to Evaluate Risk in the Clinical Adoption of Automated Contouring and Treatment Planning Tools.

PURPOSE: In this study, we applied the failure mode and effects analysis (FMEA) approach to an automated radiation therapy contouring and treatment planning tool to assess, and subsequently limit, the risk of deploying automated tools. METHODS AND MATERIALS: Using an FMEA, we quantified the risks associated with the Radiation Planning Assistant (RPA), an automated contouring and treatment planning tool currently under development. A multidisciplinary team identified and scored each failure mode, using a combination of RPA plan data and experience for guidance. A 1-to-10 scale for severity, occurrence, and detectability of potential errors was used, following American Association of Physicists in Medicine Task Group 100 recommendations. High-risk failure modes were further explored to determine how the workflow could be improved to reduce the associated risk. RESULTS: Of 290 possible failure modes, we identified 126 errors that were unique to the RPA workflow, with a mean risk priority number (RPN) of 56.3 and a maximum RPN of 486. The top 10 failure modes were caused by automation bias, operator error, and software error. Twenty-one failure modes were above the action threshold of RPN = 125, leading to corrective actions. The workflow was modified to simplify the user interface and better training resources were developed, which highlight the importance of thorough review of the output of automated systems. After the changes, we rescored the high-risk errors, resulting in a final mean and maximum RPN of 33.7 and 288, respectively. CONCLUSIONS: We identified 126 errors specific to the automated workflow, most of which were caused by automation bias or operator error, which emphasized the need to simplify the user interface and ensure adequate user training. As a result of changes made to the software and the enhancement of training resources, the RPNs subsequently decreased, showing that FMEA is an effective way to assess and reduce risk associated with the deployment of automated planning tools.

Body region-specific 3D age-scaling functions for scaling whole-body computed tomography anatomy for pediatric late effects studies.

Purpose.Radiation epidemiology studies of childhood cancer survivors treated in the pre-computed tomography (CT) era reconstruct the patients' treatment fields on computational phantoms. For such studies, the phantoms are commonly scaled to age at the time of radiotherapy treatment because age is the generally available anthropometric parameter. Several reference size phantoms are used in such studies, but reference size phantoms are only available at discrete ages (e.g.: newborn, 1, 5, 10, 15, and Adult). When such phantoms are used for RT dose reconstructions, the nearest discrete-aged phantom is selected to represent a survivor of a specific age. In this work, we (1) conducted a feasibility study to scale reference size phantoms at discrete ages to various other ages, and (2) evaluated the dosimetric impact of using exact age-scaled phantoms as opposed to nearest age-matched phantoms at discrete ages.Methods.We have adopted the University of Florida/National Cancer Institute (UF/NCI) computational phantom library for our studies. For the feasibility study, eight male and female reference size UF/NCI phantoms (5, 10, 15, and 35 years) were downscaled to fourteen different ages which included next nearest available lower discrete ages (1, 5, 10 and 15 years) and the median ages at the time of RT for Wilms' tumor (3.9 years), craniospinal (8.0 years), and all survivors (9.1 years old) in the Childhood Cancer Survivor Study (CCSS) expansion cohort treated with RT. The downscaling was performed using our in-house age scaling functions (ASFs). To geometrically validate the scaling, Dice similarity coefficient (DSC), mean distance to agreement (MDA), and Euclidean distance (ED) were calculated between the scaled and ground-truth discrete-aged phantom (unscaled UF/NCI) for whole-body, brain, heart, liver, pancreas, and kidneys. Additionally, heights of the scaled phantoms were compared with ground-truth phantoms' height, and the Centers for Disease Control and Prevention (CDC) reported 50th percentile height. Scaled organ masses were compared with ground-truth organ masses. For the dosimetric assessment, one reference size phantom and seventeen body-size dependent 5-year-old phantoms (9 male and 8 female) of varying body mass indices (BMI) were downscaled to 3.9-year-old dimensions for two different radiation dose studies. For the first study, we simulated a 6 MV photon right-sided flank field RT plan on a reference size 5-year-old and 3.9-year-old (both of healthy BMI), keeping the field size the same in both cases. Percent of volume receiving dose ≥15 Gy (V15) and the mean dose were calculated for the pancreas, liver, and stomach. For the second study, the same treatment plan, but with patient anatomy-dependent field sizes, was simulated on seventeen body-size dependent 5- and 3.9-year-old phantoms with varying BMIs. V15, mean dose, and minimum dose received by 1% of the volume (D1), and by 95% of the volume (D95) were calculated for pancreas, liver, stomach, left kidney (contralateral), right kidney, right and left colons, gallbladder, thoracic vertebrae, and lumbar vertebrae. A non-parametric Wilcoxon rank-sum test was performed to determine if the dose to organs of exact age-scaled and nearest age-matched phantoms were significantly different (p < 0.05).Results.In the feasibility study, the best DSCs were obtained for the brain (median: 0.86) and whole-body (median: 0.91) while kidneys (median: 0.58) and pancreas (median: 0.32) showed poorer agreement. In the case of MDA and ED, whole-body, brain, and kidneys showed tighter distribution and lower median values as compared to other organs. For height comparison, the overall agreement was within 2.8% (3.9 cm) and 3.0% (3.2 cm) of ground-truth UF/NCI and CDC reported 50th percentile heights, respectively. For mass comparison, the maximum percent and absolute differences between the scaled and ground-truth organ masses were within 31.3% (29.8 g) and 211.8 g (16.4%), respectively (across all ages). In the first dosimetric study, absolute difference up to 6% and 1.3 Gy was found for V15and mean dose, respectively. In the second dosimetric study, V15and mean dose were significantly different (p < 0.05) for all studied organs except the fully in-beam organs. D1and D95were not significantly different for most organs (p > 0.05).Conclusion.We have successfully evaluated our ASFs by scaling UF/NCI computational phantoms from one age to another age, which demonstrates the feasibility of scaling any CT-based anatomy. We have found that dose to organs of exact age-scaled and nearest aged-matched phantoms are significantly different (p < 0.05) which indicates that using the exact age-scaled phantoms for retrospective dosimetric studies is a better approach.