Real-World Implementation of Simulation-Free Radiation Therapy (SFRT-1000): A Propensity Score-Matched Analysis of 1000 Consecutive Palliative Courses Delivered in Routine Care.

PURPOSE: The feasibility of simulation-free radiation therapy (SFRT) has been demonstrated but information regarding its routine care impact and scalability is lacking. METHODS AND MATERIALS: In this single-institution, retrospective cohort study, all patients receiving palliative radiation therapy at an Australian tertiary cancer center were eligible for consideration of SFRT unless mask immobilization, a stereotactic technique, or a definitive dose was indicated. Coprimary endpoints were SFRT utilization, impact on consultation-to-RT time, and on-couch treatment duration. Timing metrics were compared with a contemporary local cohort that received simulation-based palliative radiation therapy using unadjusted Wilcoxon rank-sum tests and a propensity score-matched regression. Electronic patient-reported outcomes captured 2-week toxicity and pain response. RESULTS: Between April 2018 and February 2024, 2849 palliative radiation courses were delivered, of which 1904 were eligible. Of the 1904 courses, 1000 (52.5% SFRT utilization) received SFRT, including 668 using intensity-modulated radiation therapy/volumetric-modulated arc therapy. A total of 788 individual patients received SFRT and the median age was 71 years (IQR, 61-80) with 59% being male and 42% being Eastern Collaborative Oncology Group 2-4. SFRT utilization increased from 41% to 54% between years 2018-2019 and 2022-2024. SFRT reduced median consultation-to-RT time from 7.0 to 5.1 days (P < .0001) corresponding to an adjusted average treatment effect in the treated of -2.1 days (95% CI, -2.8 to -1.3). SFRT increased median on-couch treatment duration from 17.8 to 20.5 minutes (P < .0001; adjusted average treatment effect in the treated 2.6 minutes, 95% CI, 1.3-3.9). Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events grade 3 acute toxicity was 9% and at 4 weeks after RT, patients with moderate/severe pain at baseline (≥5/10) had a mean pain reduction of 3.5 points (7.1-3.6; P < .0001). CONCLUSIONS: Using widely available technologies, the SFRT-1000 cohort demonstrates routine care scalability with patient-centered and workflow benefits. SFRT is an attractive new paradigm implementable in most settings following adaptation to local requirements. Thus, SFRT opens new avenues to potentially improve access to palliative RT, which remains a global area of need.

CD11c+ and IRF8+ cell densities in rectal cancer biopsies predict outcomes of neoadjuvant chemoradiotherapy.

Approximately 20% of locally advanced rectal cancer (LARC) patients treated preoperatively with chemoradiotherapy (CRT) achieve pathologically confirmed complete regression. However, there are no clinically implemented biomarkers measurable in biopsies that are predictive of tumor regression. Here, we conducted multiplexed immunophenotyping of rectal cancer diagnostic biopsies from 16 LARC patients treated preoperatively with CRT. We identified that patients with greater tumor regression had higher tumor infiltration of pan-T cells and IRF8+HLA-DR+ cells prior to CRT. High IRF8+HLA-DR+ cell density was further associated with prolonged disease-specific survival with 83% survival at 5 y compared to 28% in patients with low infiltration. Contrastingly, low CD11c+ myeloid cell infiltration prior to CRT was a putative biomarker associated with longer 3- and 5-y disease-free survival. The results demonstrate the potential use of rectal cancer diagnostic biopsies to measure IRF8+ HLA-DR+ cells as predictors of CRT-induced tumor regression and CD11c+ myeloid cells as predictors of LARC patient survival.

Evaluation of the clinical feasibility of cone-beam computed tomography guided online adaption for simulation-free palliative radiotherapy.

Background and purpose: Simulation-free radiotherapy, where diagnostic imaging is used for treatment planning, improves accessibility of radiotherapy for eligible palliative patients. Combining this pathway with online adaptive radiotherapy (oART) may improve accuracy of treatment, expanding the number of eligible patients. This study evaluated the adaptive process duration, plan dose volume histogram (DVH) metrics and geometric accuracy of a commercial cone-beam computed tomography (CBCT)-guided oART system for simulation-free, palliative radiotherapy. Materials and methods: Ten previously treated palliative cases were used to compare system-generated contours against clinician contours in a test environment with Dice Similarity Coefficient (DSC). Twenty simulation-free palliative patients were treated clinically using CBCT-guided oART. Analysis of oART clinical treatment data included; evaluation of the geometric accuracy of system-generated synthetic CT relative to session CBCT anatomy using a Likert scale, comparison of adaptive plan dose distributions to unadapted, using DVH metrics and recording the duration of key steps in the oART workflow. Results: Auto-generated contours achieved a DSC of higher than 0.85, excluding the stomach which was attributed to CBCT image quality issues. Synthetic CT was locally aligned to CBCT anatomy for approximately 80% of fractions, with the remaining suboptimal yet clinically acceptable. Adaptive plans achieved a median CTV V95% of 99.5%, compared to 95.6% for unadapted. The median overall oART process duration was found to be 13.2 mins, with contour editing being the most time-intensive adaptive step. Conclusions: The CBCT-guided oART system utilising a simulation-free planning approach was found to be sufficiently accurate for clinical implementation, this may further streamline and improve care for palliative patients.

Interim Results of a Prospective Prostate-Specific Membrane Antigen-Directed Focal Stereotactic Reirradiation Trial for Locally Recurrent Prostate Cancer.

PURPOSE: To report the feasibility, toxicity, and preliminary outcomes (metabolic and biochemical) of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-directed focal prostate reirradiation using linear accelerator (LINAC)-based stereotactic body radiation treatment (SBRT). METHODS AND MATERIALS: From March 2016 to March 2019, 25 patients were enrolled in a prospective single institution trial (ACTRN12617000035325). Eligibility criteria included patients with biopsy proven isolated prostate recurrence after definitive irradiation, with concordant multiparametric MRI and 68Ga-PSMA PET/CT findings, and a prostate-specific antigen of less than 15 ng/mL at the time of recurrence. The study included a sequential dose escalation component with the first 18 patients receiving 36 Gy in 6 fractions on alternate days with subsequent patients receiving 38 Gy in 6 fractions assuming acceptable toxicity. RESULTS: Median age was 72 years (range, 62-83) with a median time between first radiation treatment and salvage SBRT of 8.3 years (range, 4.5- 13.6). Median prostate-specific antigen at reirradiation was 4.1 (range, 1.1-16.6). The median follow-up was 25 months (range, 13-46). Acute grade 1 and 2 genitourinary (GU) toxicity occurred in 6 (24%) and 1 (4%) men, respectively. Acute grade 1 gastrointestinal (GI) toxicity occurred in 8% with one acute grade 3 GI toxicity (4%) due to a rectal ulcer overlying the hydrogel. Late grade 1 and 2 GU toxicity occurred in 28% and 4%. Late grade 1 GI toxicity occurred in 8% with no grade 2 or greater toxicity. Twenty-four patients have undergone per-protocol 12-month 68Ga-PSMA PET/CT, of which 23 (92%) demonstrated a complete metabolic response. Biochemical freedom from failure was 80% at 2 years with 3 out of 4 of the biochemical failures exhibiting recurrent local disease. CONCLUSIONS: PSMA-directed salvage focal reirradiation to the prostate using linear accelerator-based SBRT is feasible and safe. Toxicity was low, with very favorable short term local and biochemical control in a carefully selected cohort of patients.

Prophylactic procedure tract radiotherapy for malignant pleural mesothelioma: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive cancer with a propensity for seeding procedure tracts, leading to symptomatic metastases. There is conflicting evidence on the value of prophylactic procedure tract radiotherapy in reducing tract metastases. We performed a systematic review and meta-analysis to estimate the benefit of radiotherapy in this setting. MATERIALS AND METHODS: Electronic databases were searched to January 1, 2018 for prospective randomized control trials with prophylactic procedure tract radiotherapy as the intervention arm. Pooled odds ratios and 95% confidence intervals were calculated using a random effects model. Study heterogeneity was assessed using the I2 statistic, and publication bias was evaluated by funnel plot and Egger's regression model. RESULTS: Five studies were included for meta-analysis. Prophylactic radiotherapy did not have a statistically significant reduction on the risk of procedure site recurrence, with a pooled relative risk of 0.69 (95% CI 0.33-1.43). There was moderate heterogeneity between trials. All trials were assessed as moderate or high risk of bias overall. CONCLUSION: This systematic review has confirmed that there is no role for prophylactic procedure tract radiotherapy in MPM. In the absence of effective prophylactic procedures, patients need to be monitored closely, and palliative interventions delivered in a timely manner to reduce morbidity associated with procedure tract metastases.