Risk analysis of the Unity 1.5 T MR-Linac adapt-to-position workflow.

BACKGROUND AND PURPOSE: Newer technologies allow for daily treatment adaptation, providing the ability to account for setup variations and organ motion but comes at the cost of increasing the treatment workflow complexity. One such technology is the adapt-to-position (ATP) workflow on the Unity MR-Linac. Prospective risk assessment of a new workflow allows clinics to catch errors before they occur, especially for processes that include novel and unfamiliar steps. METHODS: As part of a quality management program, failure modes and effects analysis was performed on the ATP treatment workflow following the recommendations of AAPM's Task Group 100. A multidisciplinary team was formed to identify and evaluate failure modes for all the steps taken during a daily treatment workflow. Failure modes of high severity and overall score were isolated and addressed. RESULTS: Mitigations were determined for high-ranking failure modes and implemented into the clinic. High-ranking failure modes existed in all steps of the workflow. Failure modes were then rescored to evaluate the effectiveness of the mitigations. CONCLUSION: Failure modes and effects analysis on the Unity MR-Linac highlighted areas in the ATP workflow that could be prone to failures and allowed our clinic to change the process to be more robust.

Cost-utility analysis of selective internal radiation therapy with Y-90 resin microspheres in hepatocellular carcinoma.

Background: The study assessed the cost-utility of selective internal radiation therapy (SIRT) with Y-90 resin microspheres versus sorafenib in UK patients with unresectable hepatocellular carcinoma ineligible for transarterial chemoembolization. Materials & methods: A lifetime partitioned survival model was developed for patients with low tumor burden (≤25%) and good liver function (albumin-bilirubin grade 1). Efficacy, safety and quality of life data were from a European Phase III randomized controlled trial and published studies. Resource use was from registries and clinical surveys. Results: Discounted quality-adjusted life-years were 1.982 and 1.381, and discounted total costs were £29,143 and 30,927, for SIRT and sorafenib, respectively. Conclusion: SIRT has the potential to be a dominant (more efficacious/less costly) or cost-effective alternative to sorafenib in patients with unresectable hepatocellular carcinoma.

Patient preferences for advanced hepatocellular carcinoma treatment: a multicountry stated preference study.

The present study aimed to explore patient preferences for attributes of advanced hepatocellular carcinoma (HCC) treatments. A stated preference survey was completed by 150 patients with HCC living in Europe. Overall survival (OS) was the most important attribute, closely followed by risk of diarrhea and hypertension, and other adverse event (AE) risks. Patients were willing to trade OS to reduce AE risks. While less important than OS and AEs, patients also preferred shorter waiting times, and one-off administration of selective internal radiation therapy and oral tablets over intravenous infusions. Although patients placed the most value on extending OS, they were willing to forego OS to avoid risk of treatment-related AEs, to maintain their quality of life.

Lay abstract This study aimed to understand patient preferences for characteristics of advanced hepatocellular carcinoma (HCC) treatments. A total of 150 people with HCC in Europe were presented a series of questions asking them to choose between two hypothetical treatments. Overall, length of life was the most important issue for patients, followed by avoiding diarrhea and hypertension, and then other side effects and treatment risks. Patients were willing to forego some months of life to avoid side effects or risks. Patients preferred to be given their treatment via a single minimally invasive hospital procedure or oral daily tablets compared with intravenous drips. In conclusion, although patients placed the most value on overall length of life, side effects and treatment risks were also important.

SUMOylation of FOXM1B alters its transcriptional activity on regulation of MiR-200 family and JNK1 in MCF7 human breast cancer cells.

Transcription factor Forkhead Box Protein M1 (FOXM1) is a well-known master regulator in controlling cell-cycle pathways essential for DNA replication and mitosis, as well as cell proliferation. Among the three major isoforms of FOXM1, FOXM1B is highly associated with tumor growth and metastasis. The activities of FOXM1B are modulated by post-translational modifications (PTMs), such as phosphorylation, but whether it is modified by small ubiquitin-related modifier (SUMO) remains unknown. The aim of the current study was to determine whether FOXM1B is post-translationally modified by SUMO proteins and also to identify SUMOylation of FOXM1B on its target gene transcription activity. Here we report that FOXM1B is clearly defined as a SUMO target protein at the cellular levels. Moreover, a SUMOylation protease, SENP2, significantly decreased SUMOylation of FOXM1B. Notably, FOXM1B is selectively SUMOylated at lysine residue 463. While SUMOylation of FOXM1B is required for full repression of its target genes MiR-200b/c and p21, SUMOylation of FOXM1B is essential for full activation of JNK1 gene. Overall, we provide evidence that FOXM1B is post-translationally modified by SUMO and SUMOylation of FOXM1B plays a functional role in regulation of its target gene activities.

Efficacy of transarterial radioembolization using Y-90 resin microspheres versus atezolizumab-bevacizumab in unresectable hepatocellular carcinoma: A matching-adjusted indirect comparison.

INTRODUCTION: No head-to-head trials compared the efficacy of transarterial radioembolization (TARE, also known as selective internal radiation therapy) to combination immunotherapy in hepatocellular carcinoma (HCC). The analysis objective was to compare effectiveness outcomes of TARE using Y-90 resin microspheres and atezolizumab-bevacizumab (AB) in advanced unresectable HCC. METHODS: Patient-level data from SARAH randomized controlled trial for TARE and aggregate real-world data from AB-real study were used in an unanchored matching-adjusted indirect comparison. The basecase analysis used per-protocol data from SARAH; intention-to-treat data were used in sensitivity analyses. The following prognostic variables and effect modifiers were identified from literature: cause of disease, macrovascular invasion, Eastern Cooperative Oncology Group Performance Status, alpha-fetoprotein level and albumin-bilirubin score. Weights were assigned to patients from SARAH to balance baseline characteristics across studies and reflect characteristics of AB-real patients. Overall survival (OS), progression-free survival (PFS) and response rates (overall response rates [ORR]) were calculated and compared. RESULTS: The analysis of OS and PFS included 140 patients receiving TARE and 131 for the analysis of response rates, compared to 202 receiving AB. Median OS was 15.0 and 14.9 months for TARE and AB, respectively (HR=0.980; 95% confidence interval [CI]: 0.658-1.461; p-value=0.922). Median PFS was 4.4 and 6.8 months for TARE and AB, respectively (HR=0.745; 95%CI: 0.544-1.022; p-value=0.068). ORR were 19.8% and 25% with TARE and AB, respectively (OR for AB=1.386, 95%CI: 0.746-2.668; p-value=0.306). Sensitivity analyses generated similar results. CONCLUSION: In HCC patients receiving treatment, TARE using Y-90 resin microspheres may achieve comparable effectiveness outcomes compared with AB.

Selective Internal Radiation Therapy Using Y-90 Resin Microspheres for Metastatic Colorectal Cancer: An Updated Systematic Review and Network Meta-Analysis.

INTRODUCTION: This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC). METHODS: In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques. RESULTS: Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI. CONCLUSION: Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.

A Prospective Study Assessing the Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Oligometastatic Bone Metastases.

Purpose: Stereotactic body radiation therapy (SBRT) is a promising treatment for oligometastatic disease in bone because of its delivery of high dose to target tissue and minimal dose to surrounding tissue. The purpose of this study is to assess the efficacy and toxicity of this treatment in patients with previously unirradiated oligometastatic bony disease. Methods and Materials: In this prospective phase II trial, patients with oligometastatic bone disease, defined as ≤3 active sites of disease, were treated with SBRT at Brigham and Women's Hospital/Dana Farber Cancer Center and Beth Israel Deaconess Medical Center between December 2016 and May 2019. SBRT dose and fractionation regimen were not protocol mandated. Local progression-free survival, progression-free survival, prostatic specific antigen progression, and overall survival were reported. Treatment-related toxicity was also reported. Results: A total of 98 patients and 126 lesions arising from various tumor histologies were included in this study. The median age of patients enrolled was 72.8 years (80.6% male, 19.4% female). Median follow-up was 26.7 months. The most common histology was prostate cancer (68.4%, 67/98). The most common dose prescriptions were 27/30 Gy in 3 fractions (27.0%, 34/126), 30 Gy in 5 fractions (16.7%, 21/126), or 30/35 Gy in 5 fractions (16.7%, 21/126). Multiple doses per treatment regimen reflect dose painting employing the lower dose to the clinical target volume and higher dose to the gross tumor volume. Four patients (4.1%, 4/98) experienced local progression at 1 site for each patient (3.2%, 4/126). Among the entire cohort, 2-year local progression-free survival (including death without local progression) was 84.8%, 2-year progression-free survival (including deaths as well as local, distant, and prostatic specific antigen progression) was 47.5%, and 2-year overall survival was 87.3%. Twenty-six patients (26.5%, 26/98) developed treatment-related toxicities. Conclusions: Our study supports existing literature in showing that SBRT is effective and tolerable in patients with oligometastatic bone disease. Larger phase III trials are necessary and reasonable to determine long-term efficacy and toxicities.

40 Gray in 5 Fractions for Salvage Reirradiation of Spine Lesions Previously Treated With Stereotactic Body Radiotherapy.

BACKGROUND AND PURPOSE: A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed. METHODS: We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk. RESULTS: Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%. CONCLUSION: In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario.

SUMOylation of ATF3 alters its transcriptional activity on regulation of TP53 gene.

Cyclic AMP-dependent transcription factor-3 (ATF3), a stress sensor, plays an essential role in cells to maintain homeostasis and has diverse functions in cellular survival and death signal pathways. ATF3 is a novel regulator of p53 protein stability and function. The activities of ATF3 are modulated by post-translational modifications (PTMs), such as ubiquitination, but whether it is modified by small ubiquitin-related modifier (SUMO) remains unknown. The aim of this study was to investigate whether ATF3 is post-translationally modified by SUMO proteins and also to elucidate SUMOylation of ATF3 on TP53 gene activity. Here we report that ATF3 is clearly defined as a SUMO target protein both in vitro SUMOylation assay using recombinant proteins and at the cellular levels. Furthermore, ATF3 interacted with UBE2I, the only SUMO E2 enzyme found so far. In addition, PIAS3ß (a SUMO E3 ligase) enhanced and SENP2 and SENP7 (two SUMOylation proteases) decreased SUMOylation of ATF3, respectively. Finally, we found that ATF3 is selectively SUMOylated at lysine residue 42 but the SUMOylation does not alter subcellular localization of ATF3. We then characterized the functional role of ATF3 SUMOylation on TP53 gene expression. We found that SUMOylation of ATF3 is required for full repression of TP53 gene. Overall, we provide the first evidence that ATF3 is post-translationally modified by SUMO and SUMOylation of ATF3 plays a functional role in regulation of TP53 gene activity.

Advances in Delivery of Selective Internal Radiation Therapy (SIRT): Economic and Logistical Effects of Same-Stay Work-Up and Procedure in the Treatment of Unresectable Liver Tumors in England.

INTRODUCTION: Selective internal radiation therapy (SIRT) is a targeted method of treatment for unresectable liver tumors in which radiation therapy is directly delivered to the tumor(s) via the hepatic vasculature. Successful outcomes with SIRT are dependent on the specific vasculature of the liver and tumor, and the patient therefore needs to attend a "work-up" to map the hepatic vasculature prior to the SIRT procedure. Recent advances in SIRT delivery have enabled same-day or same-stay work-up and procedure, requiring only one hospital visit rather than two. We aimed to evaluate the economic, travel time, and transport-related environmental impact of a new brachytherapy device delivery program, the order-map-treat (OMT) program, in patients with unresectable hepatocellular carcinoma (HCC) in England. METHODS: A healthcare resource group (HRG)-based analysis of costs from a national payer (Department of Health and Social Care, DHSC) perspective was conducted assuming that, with OMT, patients would have to attend hospital only once for both the SIRT work-up and procedure versus twice without OMT. Patient travel time and CO2 emissions were then estimated by identifying the SIRT center closest to the centroid of each clinical commissioning group (CCG) and calculating straight-line distances with a "detour index" to capture the effect of indirect routes via road or rail. RESULTS: It was estimated that 856 patients per annum would be eligible for SIRT treatment for unresectable HCC in England. OMT would be anticipated to save GBP 2842 per patient versus performing SIRT without OMT. Furthermore, across all patients with HCC eligible for SIRT in England, OMT would avoid 74,500 km of travel, 2299 h of travel time, and 13.9 metric tons of patient transport-related CO2 emissions annually. CONCLUSION: OMT reduces the number of hospital visits required for SIRT by 50%, resulting in financial savings from the DHSC perspective, time savings from the patient perspective, and reduced CO2 emissions arising from patient transport.

Quantification of Organ Motion in Male and Female Patients Undergoing Long-Course Radiation Therapy for Rectal Cancer in the Supine Position.

Purpose: Previous studies have reported data on the internal rectal motion of patients with rectal cancer treated in the prone position. With the introduction of intensity modulated techniques, more patients are treated in the more reproducible supine position. Data informing specific margins for this treatment position are sparse, as are data comparing rectal motion characteristics and factors in male and female patients. The purpose of this retrospective study was to quantify and compare the interfractional rectal movement characteristics of male and female patients with rectal cancer treated with long-course chemoradiation therapy in the supine position. The data will aid the generation of internal target volume margins accounting for this organ's internal physiological movements. Methods and Materials: Cone beam computed tomography (CBCT) images were acquired from 19 male and 16 female patients with rectal cancer on the first 3 days of treatment and weekly thereafter. The rectum, bladder, and femoral heads were delineated on the planning CT (PCT) and 6 CBCT for each patient. Overall, 245 images were analyzed. All patients were treated with a full bladder. The rectum was divided into three 5-cm segments (upper, mid, and lower). The motion of the rectum was quantified by documenting the anteroposterior and lateral distances as measured using fixed anatomic landmarks, namely from the anterior aspect of the sacrum and mid-left femoral head, respectively. These measurements were taken at 1-cm intervals from the inferior border of L5 vertebrae. The sigmoid was excluded from these measurements. Estimations of systematic and random physiological movement error were determined and margins were calculated. Results: Two hundred forty-five image sets (19 PCT + 114 CBCT for male, 16 PCT + 96 CBCT for female) on patients who had undergone long-course radiation therapy were analyzed. Rectal tumor location was 31% in the inferior rectum, 46% in the mid rectum, and 23% in the superior rectum. Random rectal motion (mean of the per-patient standard deviation [σ]) was largest for the upper and mid rectum in the anterior direction. There were statistically significant differences in σ between male and female patients in the left lateral motion of the mid and inferior rectum as well as the anterior, posterior, and right motion of the inferior rectum (mid left: P < .0005; lower left: P < .0005; lower posterior: P = .001; lower anterior: P = .032; lower right: P = .001). Suggested internal target volume margin guidelines are therefore nonisotropic and vary per segment of rectum and sex. Conclusions: In our present study, interfractional rectal motion is shown to be significantly different between male and female patients. Our data suggest that the use of asymmetrical sex-specific margins in patients with rectal cancer treated in the supine position should be considered.

SBRT focal dose intensification using an MR-Linac adaptive planning for intermediate-risk prostate cancer: An analysis of the dosimetric impact of intra-fractional organ changes.

INTRODUCTION: Using an magnetic resonance linear accelerator (MR-Linac) may improve the precision of visible tumor boosting with ultra-hypofractionation by accounting for daily positional changes in the target and organs at risk (OAR). PATIENTS AND METHODS: Fifteen patients with prostate cancer and an MR-detected dominant lesion were treated on the MR-Linac with stereotactic body radiation (SBRT) to 40 Gy in 5 fractions, boosting the gross tumor volume (GTV) to 45 Gy with daily adaptive planning. Imaging was acquired again after initial planning (verification scan), and immediately after treatment (post-treatment scan). Prior to beam-on, additional adjustments were made on the verification scan. Contours were retrospectively adjusted on verification and post-treatment scans, and the daily plan recalculated on these scans to estimate the true dose delivered. RESULTS: The median prostate D95% for plan 1, 2 and 3 was 40.3 Gy, 40.5 Gy and 40.3 Gy and DIL D95% was 45.7 Gy, 45.2 Gy and 44.6 Gy, respectively. Bladder filling was associated with reduced GTV coverage (p = 0.03, plan 1 vs 2) and prostate coverage (p = 0.03, plan 2 vs 3). The D0.035 cc constraint was exceeded on verification and post-treatment plans in 24 % and 33 % of fractions for the urethra, 31 % and 45 % for the bladder, and 35 % and 25 % for the rectum, respectively. CONCLUSION: MR-Linac guided, daily adaptive SBRT with focal boosting of the GTV yields acceptable planned and delivered dosimetry. Adaptive planning with a MR-Linac may reliably deliver the prescribed dose to the intended tumor target.

Validation of the bladder neck as an important organ at risk in prostate seed brachytherapy based on D2cc: A single-institution, retrospective review.

Purpose: International guidelines recommend urethral dose volume constraints to minimize the risk of urinary toxicity after prostate brachytherapy. An association between dose to the bladder neck (BN) and toxicity has previously been reported, and we sought to evaluate the impact of this organ at risk on urinary toxicity, based on intra-operative contouring. Material and methods: Rates of acute and late urinary toxicity (AUT and LUT, respectively) were graded according to CTCAE version 5.0 for 209 consecutive patients who underwent low-dose-rate (LDR) brachytherapy monotherapy, with approximately equal numbers treated before and after we began routinely contouring the BN. AUT and LUT were compared in patients treated before and after we began contouring the OAR, and also for those treated after we began contouring who had a D2cc of greater than or less than 50% prescription dose. Results: AUT and LUT fell after intra-operative BN contouring was instituted. Rates of grade ≥ 2 AUT fell from 15/101 (15%) to 9/104 (8.6%), p = 0.245. Grade ≥ 2 LUT decreased from 32/100 (32%) to 18/100 (18%), p = 0.034. Grade ≥ 2 AUT was observed in 4/63 (6.3%) and 5/34 (15%) of those with a BN D2cc >/≤ 50%, respectively, of prescription dose. Corresponding rates for LUT were 11/62 (18%) and 5/32 (16%). Conclusions: There were lower urinary toxicity rates for patients treated after we commenced routine intra-operative contouring of the BN. No clear relationship was observed between dosimetry and toxicity in our population.

Cost-effectiveness of selective internal radiation therapy with Y-90 resin microspheres for intermediate- and advanced-stage hepatocellular carcinoma in Brazil.

AIMS: Hepatocellular carcinoma (HCC) is a severe condition with poor prognosis that places a significant burden on patients, caregivers, and healthcare systems. Selective internal radiation therapy (SIRT) is a treatment available to patients with HCC which addresses some of the limitations of alternative treatment options. A cost-effectiveness analysis was undertaken into the use of SIRT using Y-90 resin microspheres for the treatment of unresectable intermediate- and late-stage HCC in Brazil. MATERIALS AND METHODS: A partitioned-survival model was developed, including a tunnel state for patients downstaged to receive treatments with curative intent. Sorafenib was the selected comparator, a common systemic treatment in Brazil and for which comparative evidence exists. Clinical data were extracted from published sources of pivotal trials, and effectiveness was measured in quality-adjusted life-years (QALYs) and life-years (LYs). The analysis was conducted from the Brazilian private payer perspective and a lifetime horizon was implemented. Comprehensive sensitivity analyses were conducted. RESULTS: LYs and QALYs were higher for SIRT with Y-90 resin microspheres versus sorafenib (0.27 and 0.20 incremental LYs and QALYs, respectively) and costs were slightly higher for SIRT (R$15,864). The base case incremental cost-effectiveness ratio (ICER) was R$77,602 per QALY. The ICER was mostly influenced by parameters defining the sorafenib overall survival curve and SIRT had a 73% probability of being cost-effective at a willingness-to-pay threshold of R$135,761 per QALY (3-times the per-capita gross domestic product in Brazil). Overall, sensitivity analyses confirmed the robustness of the results indicating that SIRT with Y-90 resin microspheres is cost-effective compared with sorafenib. LIMITATIONS: A rapidly evolving treatment landscape in Brazil and worldwide, and the lack of local data for some variables were the main limitations. CONCLUSIONS: SIRT with Y-90 resin microspheres is a cost-effective option compared with sorafenib in Brazil.

Transarterial Radioembolization Versus Atezolizumab-Bevacizumab in Unresectable Hepatocellular Carcinoma: A Matching-Adjusted Indirect Comparison of Time to Deterioration in Quality of Life.

INTRODUCTION: Given the relatively short life expectancy of patients with hepatocellular carcinoma (HCC), quality of life (QOL) plays a significant role in treatment selection. This analysis aimed to compare time to deterioration (TTD) in QOL with transarterial radioembolization (TARE) and atezolizumab-bevacizumab, as well as sorafenib, in advanced and unresectable HCC. METHODS: Patient-level data from SARAH (TARE using SIR-Spheres® Y-90 resin microspheres [SIR-Spheres] versus sorafenib) and aggregate data from IMbrave150 (atezolizumab-bevacizumab versus sorafenib) randomized controlled trials were used to conduct an anchored matching-adjusted indirect comparison (MAIC). Patients with a Child-Pugh score B in SARAH were excluded to align with exclusion criteria in IMbrave150. To identify potential effect modifiers for adjustment, the literature was searched and multivariate Cox proportional hazards models were implemented using SARAH data. Patients from SARAH were then weighted to balance with baseline characteristics from IMbrave150. Median TTD in QOL and hazard ratios (HRs) were calculated. RESULTS: Four potential effect modifiers were identified and used for adjustment: cause of disease (viral/non-viral), macrovascular invasion, Eastern Cooperative Oncology Group performance score, and alpha-fetoprotein level. The MAIC included 217 patients from SARAH (TARE = 94; sorafenib = 123). Median TTD in QOL was 11.23 and 8.64 months for atezolizumab-bevacizumab and TARE, respectively (HR = 1.06; 95% confidence interval [CI] 0.75-1.50; p = 0.725). A sensitivity analysis was conducted adjusting for cause of disease defined as hepatitis B/hepatitis C/non-viral: median TTD in QOL was higher for TARE compared with atezolizumab-bevacizumab (19.88 vs 11.23 months; HR = 0.66; 95% CI 0.36-1.19; p = 0.163). Sorafenib resulted in the shortest TTD in QOL, with statistically significant differences in both base case and sensitivity analyses. CONCLUSION: TARE using SIR-Spheres may achieve similar TTD in QOL compared with atezolizumab-bevacizumab, as the analyses found no statistically significant differences between these two interventions. Both TARE using SIR-Spheres and atezolizumab-bevacizumab seem to be more efficacious than sorafenib in maintaining QOL.

For patients with hepatocellular carcinoma, as well as physicians treating hepatocellular carcinoma, the quality of life that different treatments can offer represents an increasingly important aspect to consider when choosing treatments. Transarterial radioembolization and atezolizumab­bevacizumab are two potential treatments for advanced and unresectable hepatocellular carcinoma, but no clinical trials have directly compared the outcomes of these two therapeutic options. With the data available (patient-level data from a clinical trial of transarterial radioembolization using SIR-Spheres^® Y-90 resin microspheres [SIR-Spheres] versus sorafenib and data from a trial of atezolizumab­bevacizumab versus sorafenib from the literature), this study indirectly compared the time to deterioration of quality of life (i.e., how long quality of life is maintained) after treatment with transarterial radioembolization and atezolizumab­bevacizumab. The study showed that quality of life may be preserved over a similar time period with transarterial radioembolization using SIR-Spheres and atezolizumab­bevacizumab; also, both transarterial radioembolization using SIR-Spheres and atezolizumab­bevacizumab seem to maintain patients' quality of life over a longer period of time compared with sorafenib. These results are expected to enrich the existing evidence on which patients and physicians can base their decisions, allowing them to choose the most appropriate treatment by assessing the treatments' characteristics as a whole.

Combined brachytherapy and ultra-hypofractionated radiotherapy for intermediate-risk prostate cancer: Comparison of toxicity outcomes using a high-dose-rate (HDR) versus low-dose-rate (LDR) brachytherapy boost.

PURPOSE/OBJECTIVE: To compare toxicity profiles of low-dose rate (LDR) and high-dose rate (HDR) brachytherapy boost combined with ultra-hypofractionated external beam radiation therapy (UH-EBRT). MATERIALS/METHODS: 99 patients with intermediate-risk prostate cancer underwent an HDR (n = 59) or LDR (n = 40) boost combined with UH-EBRT (5 Gy x 5) . HDR (Ir-192) was delivered a single dose (15 Gy) and LDR (Pd-103) prescription dose was 100 Gy. Median baseline IPSS was 5 for both cohorts. Median follow-up was 29.3mos. Cumulative incidences were calculated for toxicity. Fisher exact tests were used to evaluate associations. RESULTS: Overall incidence of grade 2 genitourinary toxicity for the entire cohort at 12 and 24 months was 21% and 29%, respectively. The incidence of grade 2 genitourinary toxicity at 12 and 24 months was higher for LDR cohort compared with HDR cohort (45% vs 5.1% and 55% vs 11%; p<0.001). On MVA, only treatment regimen (LDR versus HDR) was associated with grade 2+ genitourinary toxicity (p<0.001). Two patients experienced grade 2 rectal toxicity in each cohort. No grade > 3 toxicities were observed. CONCLUSIONS: Both LDR and HDR brachytherapy combined with UH-EBRT had favorable toxicity profiles, but significantly less grade 2+ genitourinary toxicity was observed in patients receiving HDR.

Changes in treatment pattern and costs in advanced hepatocellular carcinoma (HCC).

INTRODUCTION: While essential for cost-effectiveness analyses, there are no current resource use and cost data available for advanced hepatocellular carcinoma (HCC) and selective internal radiation therapy (SIRT). The study aims to assess current resource use and costs in HCC and for SIRT compared to historical survey data. AREAS COVERED: To address this data gap, resource use was elicited via surveys and interviews with medical professionals experienced with HCC and SIRT in the United Kingdom. Unit costs were from publicly available databases. Resource use and costs were estimated and compared to prior surveys. EXPERT OPINION: From eleven responses, pre-progression costs for SIRT and systemic therapy were £256.77 and £292.27/month, respectively. One-off progression and post-progression costs were £209.98 and £522.84/month. Monthly costs were 54%-79% lower than in previous surveys, due to reduction in hospitalizations and funded social care. Furthermore, substantial differences in resource use associated with SIRT between clinical practice and clinical trials were found. In conclusion, increased availability and familiarity with systemic treatments has led to important changes in HCC care and SIRT administration. The uncertainty from the use of expert opinion and the limited number of hospitals with SIRT experience can be addressed with future research using large databases, registries.

Stereotactic Magnetic Resonance-Guided Adaptive Radiation Therapy (SMART) for Abdominopelvic Oligometastases.

PURPOSE: Stereotactic body radiation therapy can be an effective treatment for oligometastases. However, safe delivery of ablative radiation is frequently limited by the proximity of mobile organs sensitive to high radiation doses. The goal of this study was to determine the feasibility, safety, and disease control outcomes of stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) in patients with abdominopelvic oligometastases. METHODS AND MATERIALS: We identified 101 patients with abdominopelvic oligometastases, including 20 patients enrolled on phase 1 protocols, who were consecutively treated with SMART on a 0.35T magnetic resonance linear accelerator (MR linac) at a single institution from October 2019 to September 2021. Local control and overall survival were analyzed using the Kaplan-Meier method. RESULTS: Overall, 114 tumors were treated. The most common histology was prostate adenocarcinoma (60 tumors [53.5%]), and 65 sites (57.0%) were centered in the pelvis. Ninety-one sites (79.8%) were treated to 8 Gy × 5, and 49 (43.0%) were treated with breath-hold respiratory gating. Online adaptation resulted in a clinically significant improvement in coverage or organ sparing in 86.6% of delivered fractions. The median time required for adaptation was 24 minutes, and the median time in the treatment room was 58 minutes. With median follow-up of 11.4 months, the 12-month local control was 93% and was higher for prostate adenocarcinoma versus other histologies (100% vs 84%; P = .009). The 12-month overall survival was 96% and was higher for prostate adenocarcinoma versus other histologies (100% vs 91%; P = .046). Three patients (3.0%) developed grade 3 toxic effects (colonic hemorrhage at 3.4 months and urinary tract obstructions at 10.1 and 18.4 months, respectively). CONCLUSIONS: In this study, SMART was feasible, safe, and effective for delivering ablative radiation therapy to abdominopelvic metastases. Adaptive planning was necessary in the large majority of cases. The advantages of SMART warrant its further investigation as a standard option for the treatment of abdominopelvic oligometastases.

Personalized Treatment Selection Leads to Low Rates of Local Salvage Therapy for Bone Metastases.

PURPOSE: Local therapy for patients with nonspine bone metastases is evolving, with data supporting the use of single-fraction treatments, and more recently, showing possible benefit from stereotactic body radiation therapy (SBRT). However, the rate of local salvage therapy (LST) after each technique has not been characterized in real-world clinic settings where patients are selected at physician discretion. We examined rates of LST in patients with nonspine bone metastases. METHODS AND MATERIALS: We reviewed records of RT for nonspine bone metastases at our institution from January 1, 2016, to December 31, 2018. We defined LST as the first occurrence of RT or surgery for oncologic progression to a bone metastasis after initial RT. Cumulative incidence functions for retreatment were generated. We conducted multivariate analysis to identify variables associated with LST. RESULTS: A total of 1754 patients were analyzed, with median follow-up of 16.2 months (range, 0-36.8 months). Of all episodes of RT, 51.5% were multifraction external beam radiation therapy (EBRT), 7.0% were single-fraction EBRT, and 41.4% were SBRT. Altogether, 88 patients (5.0%) required LST, with an incidence at 6 months of 2.5%. Incidence of LST at 6 months was 2.1% for SBRT, 5.3% for single-fraction conventional regimens, and 2.4% for multifraction conventional regimens (P = .26). Patients of younger age, who had a higher Karnofsky performance status, and/or who had lesions in the pelvis had a higher risk of retreatment. CONCLUSIONS: In this large institutional cohort, the rate of LST was low, with no difference between RT techniques. The findings indicated that SBRT for patients at high risk for treatment failure may reduce the rate of retreatment overall. When treatment modality was selected based on patient characteristics, rates of LST were lower than when treatment was randomly selected.

Evaluating the Role of Stereotactic Body Radiation Therapy With Respect to Androgen Receptor Signaling Inhibitors for Oligometastatic Prostate Cancer.

PURPOSE: Outcomes of stereotactic body radiation therapy (SBRT) with respect to androgen receptor signaling inhibitors (ARSI) have not been characterized for oligometastatic prostate cancer. We sought to characterize prostate specific antigen (PSA) response and progression-free survival (PFS) after SBRT among men who have progressed on ARSI therapy in the oligometastatic castration-resistant setting. METHODS AND MATERIALS: A single-institution retrospective analysis was performed for men with ARSI-resistant, oligometastatic, castrate-resistant prostate cancer (omCRPC). Intervention consisted of SBRT. PSA reduction greater than 50% and median PFS (PSA or radiographic progression) as determined by routine care comprised outcome measurements. Cox regression analysis was used to determine factors influencing PFS. RESULTS: Thirty-five men with ARSI-resistant omCRPC and 65 lesions treated with SBRT were followed for a median of 17.2 months. In 63% of men PSA reduction greater than 50% was achieved. Median PFS was 9.0 months. Incomplete ablation (defined as the presence of untreated lesions after SBRT or receipt of prior palliative radiation therapy doses) was associated with worse PFS (hazard ratio 4.21 [1.74-10.19]; P < .01). For a subgroup of 22 men with complete ablation of metastatic sites with SBRT, the median PFS was 13.1 months. One-year overall survival was 93.1% (95% confidence interval, 84.4-100). CONCLUSIONS: SBRT may augment the efficacy of ARSI in omCRPC, provided that all lesions receive ablative radiation doses. Future prospective study of SBRT for men receiving ARSI is warranted.