Predictors of Quality of Life Decline in Patients with Oligometastases treated with Stereotactic Ablative Radiotherapy: Analysis of the Population-Based SABR-5 Phase II Trial.

AIMS: Most patients experience stable quality of life (QoL) after stereotactic ablative radiotherapy (SABR) treatment for oligometastases. However, a subset of patients experience clinically relevant declines in QoL on post-treatment follow-up. This study aimed to identify risk factors for QoL decline. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases. Prospective QoL was measured using treatment site-specific tools at pre-treatment baseline and 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. The time to persistent QoL decline was calculated as the time from SABR to the first decline in QoL score meeting minimum clinically important difference with no improvement to baseline score on subsequent assessments. Univariable and multivariable logistic regression analyses were carried out to determine factors associated with QoL decline. RESULTS: One hundred and thirty-three patients were included with a median follow-up of 32 months (interquartile range 25-43). Thirty-five patients (26%) experienced a persistent decline in QoL. The median time until persistent QoL decline was not reached. The cumulative incidence of QoL decline at 2 and 3 years were 22% (95% confidence interval 14.0-29.6) and 40% (95% confidence interval 28.0-51.2), respectively. In multivariable analysis, disease progression (odds ratio 5.23, 95% confidence interval 1.59-17.47, P = 0.007) and adrenal metastases (odds ratio 9.70, 95% confidence interval 1.41-66.93, P = 0.021) were associated with a higher risk of QoL decline. Grade 3 or higher (odds ratio 3.88, 95% confidence interval 0.92-16.31, P = 0.064) and grade 2 or higher SABR-associated toxicity (odds ratio 2.24, 95% confidence interval 0.85-5.91, P = 0.10) were associated with an increased risk of QoL decline but did not reach statistical significance. CONCLUSIONS: Disease progression and adrenal lesion site were associated with persistent QoL decline following SABR. The development of grade 3 or higher toxicities was also associated with an increased risk, albeit not statistically significant. Further studies are needed, focusing on the QoL impact of metastasis-directed therapies.

Prospective Longitudinal Assessment of Quality of Life After Stereotactic Ablative Radiotherapy for Oligometastases: Analysis of the Population-based SABR-5 Phase II Trial.

AIMS: To evaluate longitudinal patient-reported quality of life (QoL) in patients treated with stereotactic ablative radiotherapy (SABR) for oligometastases. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases, conducted in six regional cancer centres in British Columbia, Canada from 2016 to 2020. Prospective QoL was measured using treatment site-specific QoL questionnaires at pre-treatment baseline and at 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. Patients with bone metastases were assessed with the Brief Pain Inventory (BPI). Patients with liver, adrenal and abdominopelvic lymph node metastases were assessed with the Functional Assessment of Chronic Illness Therapy-Abdominal Discomfort (FACIT-AD). Patients with lung and intrathoracic lymph node metastases were assessed with the Prospective Outcomes and Support Initiative (POSI) lung questionnaire. The two one-sided test procedure was used to assess equivalence between the worst QoL score and the baseline score of individual patients. The mean QoL at all time points was used to determine the trajectory of QoL response after SABR. The proportion of patients with 'stable', 'improved' or 'worsened' QoL was determined for all time points based on standard minimal clinically important differences (MCID; BPI worst pain = 2, BPI functional interference score [FIS] = 0.5, FACIT-AD Trial Outcome Index [TOI] = 8, POSI = 3). RESULTS: All enrolled patients with baseline QoL assessment and at least one follow-up assessment were analysed (n = 133). On equivalence testing, the patients' worst QoL scores were clinically different from baseline scores and met MCID (BPI worst pain mean difference: 1.8, 90% confidence interval 1.19 to 2.42]; BPI FIS mean difference: 1.68, 90% confidence interval 1.15 to 2.21; FACIT-AD TOI mean difference: -8.76, 90% confidence interval -11.29 to -6.24; POSI mean difference: -4.61, 90% confidence interval -6.09 to -3.14). However, the mean FIS transiently worsened at 9, 18 and 21 months but eventually returned to stable levels. The mean FACIT and POSI scores also worsened at 36 months, albeit with a limited number of responses (n = 4 and 8, respectively). Most patients reported stable QoL at all time points (range: BPI worst pain 71-82%, BPI FIS 45-78%, FACIT-AD TOI 50-100%, POSI 25-73%). Clinically significant stability, worsening and improvement were seen in 70%/13%/18% of patients at 3 months, 53%/28%/19% at 18 months and 63%/25%/13% at 36 months. CONCLUSIONS: Transient decreases in QoL that met MCID were seen between patients' worst QoL scores and baseline scores. However, most patients experienced stable QoL relative to pre-treatment levels on long-term follow-up. Further studies are needed to characterise patients at greatest risk for decreased QoL.

Sci-Thur AM: Planning - 05: Lung SBRT: Dosimetric accuracy of the Analytical Anisotropic Algorithm (AAA) for 6MV FFF RapidArc planning.

PURPOSE: Stereotactic Body Radiation Therapy (SBRT) requires the delivery of a high biologically effective dose in only a few fractions. These large doses per fraction can necessitate long treatment times. The Varian Truebeam is capable of RapidArc delivery and also has the optional Flattening Filter Free (FFF) modes which greatly increase the dose rate. We have commissioned the 6MV FFF beam (1400 MU/min) for RapidArc lung SBRT, and verified heterogeneous dose calculations with Monte Carlo (MC). METHODS: The standard commissioning data was acquired for Varian's Analytical Anisotropic Algorithm (AAA) beam model. Measurements were acquired with the IBA Blue Phantom, using the CC13 and CC01 ion chambers and PTW diode. MLC-defined fields were also acquired for model verification. The Dosimetric Leaf Gap (DLG) was measured and then optimized using RapidArc lung SBRT plans, matching Eclipse with ion chamber measurements. Heterogeneous dose calculations were independently verified using MC. RESULTS: There were some discrepancies regarding leaf transmission and penumbra, but the AAA model was generally well within 2% and 2 mm. A nominal DLG value of 1.6 mm was chosen. A representative lung SBRT case utilizing FFF RapidArc was calculated with MC. For the high dose region, 99% matched Eclipse within 3% and 3 mm. The mean dose difference of the PTV was 0.7%. CONCLUSIONS: Although we have observed some minor infield discrepancies between the AAA and Monte Carlo calculations in heterogeneous media, the Eclipse AAA is reasonably accurate for complex FFF, RapidArc, SBRT lung planning.

Sci-Fri PM: Delivery - 05: A complete set of VMAT machine-specific QA tests using EPID.

During a VMAT (Volumetric Modulated Arc Therapy) radiation delivery, various machine parameters (gantry position and speed, MLC leaves position, dose rate, etc) have to be highly synchronized and coordinated. To ensure that all of the machine components are effectively operating together requires unique machine-specific quality assurance (QA) tests. The purpose of this work is to describe a complete set of VMAT machine-specific QA tests using Electronic Portal Imaging Device (EPID). To address the need for VMAT machine-specific QA tests, Varian has recommended 6 EPID-based tests for commissioning and QA of RapidArc™ capable machines. Recent studies have identified that these Varian tests do not define a complete set of tests needed for adequate commissioning and machine-specific QA of RapidArc machines. The goal of this work is twofold: a) to report and discuss the results of the original 6 Varian's EPID-based tests, and b) to extend the original set by adding 2 more EPID-based tests, which results in a more complete and comprehensive set of tests. We have demonstrated that the Varian EPID-based QA tests can be used to verify that the synchronization of Dose Rate, Gantry Speed and MLC Leaves speed is generally to within 1.5% during a RapidArc delivery. Also, the gantry rotation does not have any significant effect on MLC leaves positional accuracy during a RapidArc delivery. Finally, we have introduced a new EPID-based QA test, which can be used to verify that the angular accuracy of the gantry position during a RapidArc delivery is to within ∼1 degree.

Sci-Fri AM: YIS-06: On-line adaptive radiation therapy based on the intra-fractional digital tomosynthesis images.

PURPOSE: To investigate the feasibility of performing on-line adaptive radiation therapy (ART) based on the intra-fractional digital tomosynthesis (DTS) images. METHOD AND MATERIALS: Intra-fractional DTS images were reconstructed as the gantry rotated between treatment positions. An edge detection algorithm was used to automatically segment the DTS images as the gantry arrived at each treatment position. The original treatment plan was then re-optimized for the most recent DTS image contours and dose was delivered from each treatment position based on the newly re-optimized plan. Plan re-optimization was performed using modified direct aperture optimization (DAO). To test our system, a model representing typical prostate, bladder and rectum anatomy was generated. First, a treatment plan based on this original anatomy was created using our DAO system. To simulate prostate deformations, three clinically relevant deformations (small, medium and large) were modeled by systematically deforming the original anatomy. The ability of our approach to adapt the original treatment plan and account for the anatomy deformations was investigated. RESULTS: Based on the dose-volume constraints from the RTOG 0415 prostate protocol, the original treatment plan would have been clinically unacceptable for all three deformations. Using our approach to on-line ART, the original treatment plan was successfully adapted to arrive at a clinically acceptable plan for all three anatomy deformations. CONCLUSION: We have shown that performing on-line ART based on intra-fractional DTS images is feasible. The advantages are reduced treatment time and the ability to detect and account for patient motion during the treatment fraction.