Dose coverage impacts local control in ultra-central lung oligometastases treated with stereotactic radiotherapy.

INTRODUCTION: The use of Stereotactic Body Radiotherapy (SBRT) is controversial in Ultra-Central lung tumors, a subset of central lung tumors characterized by proximity to critical mediastinal structures. This is of interest in oligometastatic (≤3 metastases) patients, who can yield survival benefit from local treatments. The aim of our study is to assess the determinants of efficacy and toxicity in this setting. MATERIALS AND METHODS: Clinical and dosimetric parameters were reviewed in a cohort of oligometastatic patients treated with SBRT for ultra-central tumors. Local control rate (LC) and toxicity were assessed. Statistical Analysis was carried out to assess the impact of those predictors on local recurrence and adverse events. RESULTS: One-hundred-nine consecutive patients were included. A median Biologic Effective Dose (BED) of 105 (75-132) Gy10 was prescribed. At a median follow-up of 17 (range 3-78) months, 2-year LC was 87%. Improved LC was correlated to Planning Treatment Volume (PTV) covered by 95% of the prescription dose (V95% PTV) > 85% (HR 0.15, 95%CI 0.05-0.49, p = 0.0017) and to Gross Tumor Volume (GTV) < 90 cm3 (HR 0.2, 95%CI 0.07-0.56, p = 0.0021). Overall and grade ≥ 3 toxicity incidence was 20% and 5%, respectively. Patients experiencing acute and late toxicities received significantly higher dose to 1 cm3 (D1cm3) of esophagus and lung volume receiving ≥5 Gy (V5Gy) (p = 0.016 and p = 0.013), and higher dose to 0.1 cm3 (D0.1cm3) of heart (p = 0.036), respectively. CONCLUSION: V95% PTV > 85% and GTV < 90 cm3 are independent predictors of LC. Dose to esophagus, lung and heart should be carefully assessed to minimize treatment-related toxicities.

Machine learning and lean six sigma for targeted patient-specific quality assurance of volumetric modulated arc therapy plans.

Background and purpose: Radiotherapy plans with excessive complexity exhibit higher uncertainties and worse patient-specific quality assurance (PSQA) results, while the workload of measurement-based PSQA can impact the efficiency of the radiotherapy workflow. Machine Learning (ML) and Lean Six Sigma, a process optimization method, were implemented to adopt a targeted PSQA approach, aiming to reduce workload, risk of failures, and monitor complexity. Materials and methods: Lean Six Sigma was applied using DMAIC (define, measure, analyze, improve, and control) steps. Ten complexity metrics were computed for 69,811 volumetric modulated arc therapy (VMAT) arcs from 28,612 plans delivered in our Institute (2013-2021). Outlier complexities were defined as >95th-percentile of the historical distributions, stratified by treatment. An ML model was trained to predict the gamma passing rate (GPR-3 %/1mm) of an arc given its complexity. A decision support system was developed to monitor the complexity and expected GPR. Plans at risk of PSQA failure, either extremely complex or with average GPR <90 %, were identified. The tool's impact was assessed after nine months of clinical use. Results: Among 1722 VMAT plans monitored prospectively, 29 (1.7 %) were found at risk of failure. Planners reacted by performing PSQA measurement and re-optimizing the plan. Occurrences of outlier complexities remained stable within 5 %. The expected GPR increased from a median of 97.4 % to 98.2 % (Mann-Whitney p < 0.05) due to plan re-optimization. Conclusions: ML and Lean Six Sigma have been implemented in clinical practice enabling a targeted measurement-based PSQA approach for plans at risk of failure to improve overall quality and patient safety.

Twenty Years of Advancements in a Radiotherapy Facility: Clinical Protocols, Technology, and Management.

BACKGROUND: Hypo-fractionation can be an effective strategy to lower costs and save time, increasing patient access to advanced radiation therapy. To demonstrate this potential in practice within the context of temporal evolution, a twenty-year analysis of a representative radiation therapy facility from 2003 to 2022 was conducted. This analysis utilized comprehensive data to quantitatively evaluate the connections between advanced clinical protocols and technological improvements. The findings provide valuable insights to the management team, helping them ensure the delivery of high-quality treatments in a sustainable manner. METHODS: Several parameters related to treatment technique, patient positioning, dose prescription, fractionation, equipment technology content, machine workload and throughput, therapy times and patients access counts were extracted from departmental database and analyzed on a yearly basis by means of linear regression. RESULTS: Patients increased by 121 ± 6 new per year (NPY). Since 2010, the incidence of hypo-fractionation protocols grew thanks to increasing Linac technology. In seven years, both the average number of fractions and daily machine workload decreased by -0.84 ± 0.12 fractions/year and -1.61 ± 0.35 patients/year, respectively. The implementation of advanced dose delivery techniques, image guidance and high dose rate beams for high fraction doses, currently systematically used, has increased the complexity and reduced daily treatment throughput since 2010 from 40 to 32 patients per 8 h work shift (WS8). Thanks to hypo-fractionation, such an efficiency drop did not affect NPY, estimating 693 ± 28 NPY/WS8, regardless of the evaluation time. Each newly installed machine was shown to add 540 NPY, while absorbing 0.78 ± 0.04 WS8. The COVID-19 pandemic brought an overall reduction of 3.7% of patients and a reduction of 0.8 fractions/patient, to mitigate patient crowding in the department. CONCLUSIONS: The evolution of therapy protocols towards hypo-fractionation was supported by the use of proper technology. The characteristics of this process were quantified considering time progression and organizational aspects. This strategy optimized resources while enabling broader access to advanced radiation therapy. To truly value the benefit of hypo-fractionation, a reimbursement policy should focus on the patient rather than individual treatment fractionation.

Universal evaluation of MLC models in treatment planning systems based on a common set of dynamic tests.

PURPOSE: To demonstrate the feasibility of characterising MLCs and MLC models implemented in TPSs using a common set of dynamic beams. MATERIALS AND METHODS: A set of tests containing synchronous (SG) and asynchronous sweeping gaps (aSG) was distributed among twenty-five participating centres. Doses were measured with a Farmer-type ion chamber and computed in TPSs, which provided a dosimetric characterisation of the leaf tip, tongue-and-groove, and MLC transmission of each MLC, as well as an assessment of the MLC model in each TPS. Five MLC types and four TPSs were evaluated, covering the most frequent combinations used in radiotherapy departments. RESULTS: Measured differences within each MLC type were minimal, while large differences were found between MLC models implemented in clinical TPSs. This resulted in some concerning discrepancies, especially for the HD120 and Agility MLCs, for which differences between measured and calculated doses for some MLC-TPS combinations exceeded 10%. These large differences were particularly evident for small gap sizes (5 and 10 mm), as well as for larger gaps in the presence of tongue-and-groove effects. A much better agreement was found for the Millennium120 and Halcyon MLCs, differences being within ± 5% and ± 2.5%, respectively. CONCLUSIONS: The feasibility of using a common set of tests to assess MLC models in TPSs was demonstrated. Measurements within MLC types were very similar, but TPS dose calculations showed large variations. Standardisation of the MLC configuration in TPSs is necessary. The proposed procedure can be readily applied in radiotherapy departments and can be a valuable tool in IMRT and credentialing audits.

Knowledge-based DVH estimation and optimization for breast VMAT plans with and without avoidance sectors.

BACKGROUND: To analyze RapidPlan knowledge-based models for DVH estimation of organs at risk from breast cancer VMAT plans presenting arc sectors en-face to the breast with zero dose rate, feature imposed during the optimization phase (avoidance sectors AS). METHODS: CT datasets of twenty left breast patients in deep-inspiration breath-hold were selected. Two VMAT plans, PartArc and AvoidArc, were manually generated with double arcs from ~ 300 to ~ 160°, with the second having an AS en-face to the breast to avoid contralateral breast and lung direct irradiation. Two RapidPlan models were generated from the two plan sets. The two models were evaluated in a closed loop to assess the model performance on plans where the AS were selected or not in the optimization. RESULTS: The PartArc plans model estimated DVHs comparable with the original plans. The AvoidArc plans model estimated a DVH pattern with two steps for the contralateral structures when the plan does not contain the AS selected in the optimization phase. This feature produced mean doses of the contralateral breast, averaged over all patients, of 0.4 ± 0.1 Gy, 0.6 ± 0.2 Gy, and 1.1 ± 0.2 Gy for the AvoidArc plan, AvoidArc model estimation, RapidPlan generated plan, respectively. The same figures for the contralateral lung were 0.3 ± 0.1 Gy, 1.6 ± 0.6 Gy, and 1.2 ± 0.5 Gy. The reason was found in the possible incorrect information extracted from the model training plans due to the lack of knowledge about the AS. Conversely, in the case of plans with AS set in the optimization generated with the same AvoidArc model, the estimated and resulting DVHs were comparable. Whenever the AvoidArc model was used to generate DVH estimation for a plan with AS, while the optimization was made on the plan without the AS, the optimizer evidentiated the limitation of a minimum dose rate of 0.2 MU/°, resulting in an increased dose to the contralateral structures respect to the estimation. CONCLUSIONS: The RapidPlan models for breast planning with VMAT can properly estimate organ at risk DVH. Attention has to be paid to the plan selection and usage for model training in the presence of avoidance sectors.

Locally Advanced Non-Small Cell Lung Cancer: Clinical Outcome, Toxicity and Predictive Factors in Patients Treated with Hypofractionated Sequential or Exclusive Radiotherapy.

BACKGROUND: This study evaluated the outcome, toxicity and predictive factors in patients unfit for concurrent chemo-radiotherapy (CT-RT) treated with hypofractionated sequential CT-RT or exclusive radiotherapy (RT) for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: We included patients affected by LA-NSCLC (stage IIA-IVA) treated with a total dose of 50-60 Gy in 20 fractions. The primary outcomes were local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS). Univariate analysis was used to correlate outcomes with prognostic factors. RESULTS: Between 2011 and 2019, 210 patients were treated, 113 (53.8%) with sequential CT-RT and 97 (46.2%) with exclusive RT. After a median follow-up of 15.3 months, 74 patients (35.2%) had a local progression and 133 (63.3%) had a distant progression. The one-, two- and five-year LC were 73.6%, 55.3% and 47.9%, respectively. At the time of analysis, 167 patients (79.5%) died. The one-, two- and five-year OS were 64.7%, 36% and 20%, respectively. PTV volume correlated with PFS (p = 0.001) and LC (p = 0.005). Acute and late toxicity occurred in 82% and 26% of patients. CONCLUSIONS: Albeit with the known limitations of a retrospective and heterogeneous study, our work shows that hypofractionated sequential CT-RT or exclusive RT offer a good local control and toxicity profile and a promising survival rate in LA-NSCLC patients unfit for the concurrent CT-RT scheme.

Critical Re-Evaluation of a Failure Mode Effect Analysis in a Radiation Therapy Department After 10 Years.

PURPOSE: Failure mode effect analysis (FMEA) is a proactive methodology that allows one to analyze a process, regardless of whether an adverse event occurs. In our radiation therapy (RT) department, a first FMEA was performed in 2009. In this paper we critically re-evaluate the RT process after 10 years and present it in terms of a lesson learned. METHODS AND MATERIALS: A working group (WG), led by a qualified clinical risk engineer, which included radiation oncologists, physicists, a radiation therapist, and a nurse, evaluated the possible failure modes (FMs) of the RT process. For each FM, the estimated frequency of occurrence (O, range 1-4), the expected severity of the damage (S, range 1-5), and the detectability lack (D, range 1-4) were scored. A risk priority number (RPN) was obtained as RPN = OxSxD. The data were compared with the 2009 edition. RESULTS: In the 2020 analysis, 67 FMs were identified (27 in the 2009 series). The absolute risk values of the previous 3 highest FMs were generally reduced. The patient identification risk (highest value in the 2009 analysis) was reduced from 48.0 to 6.9, becoming the 51st RPN score, thanks to a patient barcode recognition within the bunker. The 2020 highest risk values regarded: (i-2020) the patient's inadequate recollection and reporting of his/her medical history (ie, anamnesis) during the first medical examination and (ii-2020) the incorrect interpretation of tumor and normal tissue in computed tomography images. The WG proposed corrective actions. CONCLUSIONS: In this single institution experience, the 10-year FMEA analysis showed a reduction in the previous higher RPN values thanks to the corrective actions taken. The new FMs and subsequent RPNs reveal the need for a continuous iterative improvement process.

MLC parameters from static fields to VMAT plans: an evaluation in a RT-dedicated MC environment (PRIMO).

BACKGROUND: PRIMO is a graphical environment based on PENELOPE Monte Carlo (MC) simulation of radiotherapy beams able to compute dose distribution in patients, from plans with different techniques. The dosimetric characteristics of an HD-120 MLC (Varian), simulated using PRIMO, were here compared with measurements, and also with Acuros calculations (in the Eclipse treatment planning system, Varian). MATERIALS AND METHODS: A 10 MV FFF beam from a Varian EDGE linac equipped with the HD-120 MLC was used for this work. Initially, the linac head was simulated inside PRIMO, and validated against measurements in a water phantom. Then, a series of different MLC patterns were established to assess the MLC dosimetric characteristics. Those tests included: i) static fields: output factors from MLC shaped fields (2 × 2 to 10 × 10 cm2), alternate open and closed leaf pattern, MLC transmitted dose; ii) dynamic fields: dosimetric leaf gap (DLG) evaluated with sweeping gaps, tongue and groove (TG) effect assessed with profiles across alternate open and closed leaves moving across the field. The doses in the different tests were simulated in PRIMO and then compared with EBT3 film measurements in solid water phantom, as well as with Acuros calculations. Finally, MC in PRIMO and Acuros were compared in some clinical cases, summarizing the clinical complexity in view of a possible use of PRIMO as an independent dose calculation check. RESULTS: Static output factor MLC tests showed an agreement between MC calculated and measured OF of 0.5%. The dynamic tests presented DLG values of 0.033 ± 0.003 cm and 0.032 ± 0.006 cm for MC and measurements, respectively. Regarding the TG tests, a general agreement between the dose distributions of 1-2% was achieved, except for the extreme patterns (very small gaps/field sizes and high TG effect) were the agreement was about 4-5%. The analysis of the clinical cases, the Gamma agreement between MC in PRIMO and Acuros dose calculation in Eclipse was of 99.5 ± 0.2% for 3%/2 mm criteria of dose difference/distance to agreement. CONCLUSIONS: MC simulations in the PRIMO environment were in agreement with measurements for the HD-120 MLC in a 10 MV FFF beam from a Varian EDGE linac. This result allowed to consistently compare clinical cases, showing the possible use of PRIMO as an independent dose calculation check tool.

Is the PTW 60019 microDiamond a suitable candidate for small field reference dosimetry?

A systematic study of the PTW microDiamond (MD) output factors (OF) is reported, aimed at clarifying its response in small fields and investigating its suitability for small field reference dosimetry. Ten MDs were calibrated under 60Co irradiation. OF measurements were performed in 6 MV photon beams by a CyberKnife M6, a Varian DHX and an Elekta Synergy linacs. Two PTW silicon diodes E (Si-D) were used for comparison. The results obtained by the MDs were evaluated in terms of absorbed dose to water determination in reference conditions and OF measurements, and compared to the results reported in the recent literature. To this purpose, the Monte Carlo (MC) beam-quality correction factor, [Formula: see text], was calculated for the MD, and the small field output correction factors, [Formula: see text], were calculated for both the MD and the Si-D by two different research groups. An empirical function was also derived, providing output correction factors within 0.5% from the MC values calculated for all of the three linacs. A high reproducibility of the dosimetric properties was observed among the ten MDs. The experimental [Formula: see text] values are in agreement within 1% with the MC calculated ones. Output correction factors within +0.7% and -1.4% were obtained down to field sizes as narrow as 5 mm. The resulting MD and Si-D field factors are in agreement within 0.2% in the case of CyberKnife measurements and 1.6% in the other cases. This latter higher spread of the data was demonstrated to be due to a lower reproducibility of small beam sizes defined by jaws or multi leaf collimators. The results of the present study demonstrate the reproducibility of the MD response and provide a validation of the MC modelling of this device. In principle, accurate reference dosimetry is thus feasible by using the microDiamond dosimeter for field sizes down to 5 mm.

Are pitch and roll compensations required in all pathologies? A data analysis of 2945 fractions.

OBJECTIVE: New linear accelerators can be equipped with a 6D robotic couch, providing two additional rotational motion axes: pitch and roll. These shifts in kilo voltage-cone beam CT (kV-CBCT) image-guided radiotherapy (IGRT) were evaluated over the first 6 months of usage of a 6D robotic couch-top, ranking the treatment sites for which the two compensations are larger for patient set-up. METHODS: The couch compensations of 2945 fractions for 376 consecutive patients treated on the PerfectPitch™ 6D couch (Varian(®) Medical Systems, Palo Alto, CA) were analysed. Among these patients, 169 were treated for brain, 111 for lung, 54 for liver, 26 for pancreas and 16 for prostate tumours. During the set-up, patient anatomy from planning CT was aligned to kV-CBCT, and 6D movements were executed. Information related to pitch and roll were extracted by proper querying of the Microsoft(®) SQL server (Microsoft Corporation, Redmond, WA) ARIA database (Varian Medical Systems). Mean values and standard deviations were calculated for all sites. Kolmogorov-Smirnov (KS) test was performed. RESULTS: Considering all the data, mean pitch and roll adjustments were -0.10° ± 0.92° and 0.12° ± 0.96°, respectively; mean absolute values for both adjustments were 0.58° ± 0.69° and 0.69° ± 0.72°, respectively. Brain treatments showed the highest mean absolute values for pitch and roll rotations (0.73° ± 0.69° and 0.80° ± 0.78°, respectively); the lowest values of 0.36° ± 0.47° and 0.49° ± 0.58° were found for pancreas. KS test was significant for brain vs liver, pancreas and prostate. Collective corrections (pitch + roll) >0.5°, >1.0° and >2.0° were observed in, respectively, 79.8%, 61.0% and 29.1% for brain and 56.7%, 39.4% and 6.7% for pancreas. CONCLUSION: Adjustments in all six dimensions, including unconventional pitch and roll rotations, improve the patient set-up in all treatment sites. The greatest improvement was observed for patients with brain tumours. ADVANCES IN KNOWLEDGE: To our knowledge, this is the first systematic evaluation of the clinical efficacy of a 6D Robotic couch-top in CBCT IGRT over different tumour regions.

In-vivo dosimetry with Gafchromic films for multi-isocentric VMAT irradiation of total marrow lymph-nodes: a feasibility study.

BACKGROUND: Total marrow (lymph-nodes) irradiation (TMI-TMLI) by volumetric modulated arc therapy (VMAT) was shown to be feasible by dosimetric feasibility studies. It was demonstrated that several partially overlapping arcs with different isocenters are required to achieve the desired coverage of the hematopoietic or lymphoid tissues targets and to spare the neighbouring healthy tissues. The effect of isocenter shifts was investigated with the treatment planning system but an in- vivo verification of the procedure was not carried out. The objective of this study was the in-vivo verification of the consistency between the delivered and planned doses using bi-dimensional GafChromic EBT3 films. METHODS: In a first phase a phantom study was carried out to quantify the uncertainties under controlled conditions. In a second phase three patients treated with TMLI were enrolled for in-vivo dosimetry. The dose prescription was 2Gy in single fraction. Ten arcs paired on 4-6 isocenters were used to cover the target. Cone Beam Computed Tomography (CBCT) was used to verify the patient positioning at each isocenter. GafChromic EBT3 films were placed below the patient on the top of a dedicated immobilization system specifically designed. The dose maps measured with the EBT3 films were compared with the corresponding calculations along the patient support couch. Gamma Agreement Index (GAI) with dose difference of 5% and distance to agreement of 5 mm was computed. RESULTS: In the phantom study, optimal target coverage and healthy tissue sparing was observed. GAI(5%,5 mm) was 99.4%. For the patient-specific measurements, GAI(5%,5 mm) was greater than 95% and GAI (5%,3 mm) > 90% for all patients. CONCLUSIONS: In vivo measurements demonstrated the delivered dose to be in good agreement with the planned one for the TMI-TMLI protocol where partially overlapping arcs with different isocenters are required.