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Background: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience., Methods: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival., Discussion: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone., Trial Registration: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023., (© 2024. The Author(s).)

Background: A recent randomized phase II trial evaluated stereotactic ablative radiotherapy (SABR) in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with a significant improvement in progression-free survival and a trend to an overall survival benefit, supporting progression to phase III randomized trials., Methods: Two hundred and ninety-seven patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care [SOC] palliative-intent treatments), and the SABR arm (consisting of SOC treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (prostate, breast, or renal vs. all others), and disease-free interval (defined as time from diagnosis of primary tumor until first detection of the metastases being treated on this trial; divided as ≤2 vs. > 2 years). The primary endpoint is overall survival, and secondary endpoints include progression-free survival, cost effectiveness, time to development of new metastatic lesions, quality of life (QoL), and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival., Discussion: This study will provide an assessment of the impact of SABR on survival, QoL, and cost effectiveness to determine if long-term survival can be achieved for selected patients with 1-3 oligometastatic lesions., Trial Registration: Clinicaltrials.gov identifier: NCT03862911. Date of registration: March 5, 2019.

Background: Bone metastases in the lower spine and pelvis are effectively palliated with radiotherapy (RT), though this can come with side effects such as radiation induced nausea and vomiting (RINV). We hypothesize that high rates of RINV occur in part because of the widespread use of inexpensive simple unplanned palliative radiotherapy (SUPR), over more complex and resource intensive 3D conformal RT, such as volumetric modulated arc therapy (VMAT)., Methods: This is a randomized, multi-centre phase III trial of SUPR versus VMAT. We will accrue 250 patients to assess the difference in patient-reported RINV. This study is powered to detect a difference in quality of life between patients treated with VMAT vs. SUPR., Discussion: This trial will determine if VMAT reduces early toxicity compared to SUPR and may provide justification for this more resource-intensive and costly form of RT., Trial Registration: Clinicaltrials.gov identifier: NCT03694015 . Date of registration: October 3, 2018.

Background: Oligometastases refer to a state of disease where cancer has spread beyond the primary site, but is not yet widely metastatic, often defined as 1-3 or 1-5 metastases in number. Stereotactic ablative radiotherapy (SABR) is an emerging radiotherapy technique to treat oligometastases that require further prospective population-based toxicity estimates., Methods: This is a non-randomized phase II trial where all participants will receive experimental SABR treatment to all sites of newly diagnosed or progressing oligometastatic disease. We will accrue 200 patients to assess toxicity associated with this experimental treatment. The study was powered to give a 95% confidence on the risk of late grade 4 toxicity, anticipating a < 5% rate of grade 4 toxicity., Discussion: SABR treatment of oligometastases is occurring off-trial at a high rate, without sufficient evidence of its efficacy or toxicity. This trial will provide necessary toxicity data in a population-based cohort, using standardized doses and organ at risk constraints, while we await data on efficacy from randomized phase III trials., Trial Registration: Registered through clinicaltrials.gov NCT02933242 on October 14, 2016 prospectively before patient accrual.

Background: The purpose of this study is to evaluate the clinical impact of using deformable registration in tumor volume definition between separately acquired PET/CT and planning CT images., Methods: Ten lung and 10 head and neck cancer patients were retrospectively selected. PET/CT images were registered with planning CT scans using commercially available software. Radiation oncologists defined two sets of gross tumor volumes based on either rigidly or deformably registered PET/CT images, and properties of these volumes were then compared., Results: The average displacement between rigid and deformable gross tumor volumes was 1.8 mm (0.7 mm) with a standard deviation of 1.0 mm (0.6 mm) for the head and neck (lung) cancer subjects. The Dice similarity coefficients ranged from 0.76-0.92 and 0.76-0.97 for the head and neck and lung subjects, respectively, indicating conformity. All gross tumor volumes received at least 95% of the prescribed dose to 99% of their volume. Differences in the mean radiation dose delivered to the gross tumor volumes were at most 2%. Differences in the fraction of the tumor volumes receiving 100% of the radiation dose were at most 5%., Conclusions: The study revealed limitations in the commercial software used to perform deformable registration. Unless significant anatomical differences between PET/CT and planning CT images are present, deformable registration was shown to be of marginal value when delineating gross tumor volumes.

Background: Three-dimensional ultrasound (3DUS) at simulation compared to 3DUS at treatment is an image guidance option for partial breast irradiation (PBI). This study assessed if user dependence in acquiring and contouring 3DUS (operator variability) contributed to variation in seroma shifts calculated for breast IGRT., Methods: Eligible patients met breast criteria for current randomized PBI studies. 5 Operators participated in this study. For each patient, 3 operators were involved in scan acquisitions and 5 were involved in contouring. At CT simulation (CT1), a 3DUS (US1) was performed by a single radiation therapist (RT). 7 to 14 days after CT1 a second CT (CT2) and 3 sequential 3DUS scans (US2a,b,c) were acquired by each of 3 RTs. Seroma shifts, between US1 and US2 scans were calculated by comparing geometric centers of the seromas (centroids). Operator contouring variability was determined by comparing 5 RT's contours for a single image set. Scanning variability was assessed by comparing shifts between multiple scans acquired at the same time point (US1-US2a,b,c). Shifts in seromas contoured on CT (CT1-CT2) were compared to US data., Results: From an initial 28 patients, 15 had CT visible seromas, met PBI dosimetric constraints, had complete US data, and were analyzed. Operator variability contributed more to the overall variability in seroma localization than the variability associated with multiple scan acquisitions (95% confidence mean uncertainty of 6.2 mm vs. 1.1 mm). The mean standard deviation in seroma shift was user dependent and ranged from 1.7 to 2.9 mm. Mean seroma shifts from simulation to treatment were comparable to CT., Conclusions: Variability in shifts due to different users acquiring and contouring 3DUS for PBI guidance were comparable to CT shifts. Substantial inter-observer effect needs to be considered during clinical implementation of 3DUS IGRT.

Background: This paper compares the calculated dose to target and normal tissues when using pencil beam (PBC), superposition/convolution (AAA) and Monte Carlo (MC) algorithms for whole breast (WBI) and accelerated partial breast irradiation (APBI) treatment plans., Methods: Plans for 10 patients who met all dosimetry constraints on a prospective APBI protocol when using PBC calculations were recomputed with AAA and MC, keeping the monitor units and beam angles fixed. Similar calculations were performed for WBI plans on the same patients. Doses to target and normal tissue volumes were tested for significance using the paired Student's t-test., Results: For WBI plans the average dose to target volumes when using PBC calculations was not significantly different than AAA calculations, the average PBC dose to the ipsilateral breast was 10.5% higher than the AAA calculations and the average MC dose to the ipsilateral breast was 11.8% lower than the PBC calculations. For ABPI plans there were no differences in dose to the planning target volume, ipsilateral breast, heart, ipsilateral lung, or contra-lateral lung. Although not significant, the maximum PBC dose to the contra-lateral breast was 1.9% higher than AAA and the PBC dose to the clinical target volume was 2.1% higher than AAA. When WBI technique is switched to APBI, there was significant reduction in dose to the ipsilateral breast when using PBC, a significant reduction in dose to the ipsilateral lung when using AAA, and a significant reduction in dose to the ipsilateral breast and lung and contra-lateral lung when using MC., Conclusions: There is very good agreement between PBC, AAA and MC for all target and most normal tissues when treating with APBI and WBI and most of the differences in doses to target and normal tissues are not clinically significant. However, a commonly used dosimetry constraint, as recommended by the ASTRO consensus document for APBI, that no point in the contra-lateral breast volume should receive >3% of the prescribed dose needs to be relaxed to >5%.