Stereotactic Body Radiation Therapy Regimen Research Articles

Stereotactic Body Radiotherapy for Centrally Located Inoperable Early-Stage NSCLC: EORTC 22113–08113 LungTech Phase II Trial Results

IntroductionThe international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC. MethodsPatients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT. ResultsThe trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range 1.2–5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [CI]: 62.7%–91.4%) and 61.1% (90% CI: 44.1%–74.4%), respectively. Cumulative incidence rates of local, regional, and distant progression at three years were 6.7% (90% CI: 1.6%–17.1%), 3.3% (90% CI: 0.4%–12.4%), and 29.8% (90% CI: 16.8%–44.1%), respectively. SBRT-related acute adverse events and late adverse events ≥ G3 were reported in 6.5% (n = 2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4% (n = 6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively. ConclusionsThe LungTech trial suggests that SBRT with 8 × 7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after a thorough risk–benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial.

Early Experience With Two-Fraction Spine Stereotactic Body Radiation Therapy in Treating Spinal Metastases.

Spinal metastases are common in metastatic cancer, affecting around 40% of patients. The primary treatment involves radiation therapy, transitioning from conventional external beam radiation therapy (EBRT) to stereotactic body radiation therapy (SBRT) for its superior, durable response. While spine SBRT has gained popularity in the United States, Level I evidence supporting it over EBRT is limited to a Canadian trial using a 2-fraction SBRT regimen. We present our findings from one of the earliest US experiences of 2-fraction spine SBRT for spinal metastases. A retrospective analysis of patients with metastatic spine cancer receiving 2-fraction spine SBRT at a single center was conducted. Patients received treatment based on Level 1 evidence (24Gy in 2 fractions). Follow-up records were assessed for local control outcomes and toxicity. Twenty patients since August 2022 have been treated with 2-fraction spine SBRT. Most patients were treated at 1 (45%) or 2 (40%) spinal levels, with the thoracic (55%) and lumbar (50%) spine being the most common locations. Common primary sites included the lung (30%), breast (20%), esophagus (15%), and prostate (10%). The rate of local control was 100%, while the rate of vertebral compression fracture was 15%. No esophageal or bowel toxicity occurred, and no fractures required intervention. These findings suggest that 2-fraction spine SBRT is safe and effective, consistent with existing Level I evidence. Our local control rate exceeding 95% aligns with the literature, indicating the feasibility and achievability of implementing this approach in the United States over a short period of time.

Time to next systemic therapy after stereotactic body radiation therapy for oligoprogressive metastatic castrate-resistant prostate cancer.

62 Background: Patients with castrate-resistant prostate cancer (CRPC) with progressive disease are generally require a change/escalation in systemic therapy. For patients with limited ( ≤3) sites of progressive disease (oligoprogression), metastasis-directed therapy with stereotactic body radiation therapy (SBRT) may allow a longer interval before next line systemic therapy, but there is limited data describing this approach. Methods: This is a retrospective study of patients with oligoprogressive metastatic CRPC (omCRPC) treated with SBRT at a single center between 2011-2022. The primary endpoint was time to next systemic therapy (TTNST) after SBRT. Secondary endpoints included overall survival (OS) after SBRT and TTNST stratified by presence of untreated non-progressing metastases. Results: Thirty-two patients with omCRPC received SBRT to 38 metastases. Patients had a median age of 72.5 years (range 50.6-84.3) and median PSA 6.85 ng/mL (range 0.39-922.0) at time of SBRT. The majority had an ECOG of 1-2 (29 patients, 90.6%) and metastases detected on conventional CT and/or bone scans (26 patients, 81.3%). The most commonly utilized SBRT regimen was 3000 cGy in 5 fractions (18 metastases, 47.4%) (Table). Sixteen patients were treated to all known sites of disease, whereas 16 patients received SBRT to oligoprogressive metastases but had at least one untreated non-progressing metastasis at the time of SBRT. Of 32 patients, 23 (65.7%) received SBRT to bone only, 3 (9.4%) to lymph node (LN) only, and 6 (18.8%) to other sites (pelvic tumor, n=2; pelvic tumor + LN, n =1; LN + bone, n=1; dura + bone, n=1; liver, n=1). Patients had received a median of 1.0 prior line of androgen receptor signaling inhibitors and were predominantly (26 patients, 81.3%) chemotherapy naïve. Following SBRT, the median TTNST was 10.1 months and median OS was 41.3 months. For patients with 0 versus ≥1 untreated non-progressing metastasis, TTNST was 11.3 versus 8.7 months, respectively (HR 0.67, 95% CI 0.33-1.36, logrank p=0.24). There were no grade ≥3 toxicities due to SBRT. Conclusions: In this cohort, patients with omCRPC treated with SBRT delayed the next line of systemic therapy for a median of 10.1 months. SBRT in patients with omCRPC may delay initiation of next line systemic therapy in well selected patients, including those with ≥1 untreated non-progressing metastases. [Table: see text]

Five Fractions versus Seven Fractions SBRT for Intermediate- and High-Risk Prostate Cancer: A Propensity Score Matched Pair Analysis.

To compare two stereotactic body radiotherapy (SBRT) regimens in patients with intermediate- or high-risk prostate cancer with regards toxicity and efficacy. We retrospectively collected data from 198 patients treated with SBRT for prostate cancer at two different institutions. Patients received either 35-36.25 Gy in five fractions (group A) using Cyberknife robotic platform or 42.7 Gy in seven fractions (group B) using a C-arm LINAC (image-guided). Propensity score matching was done (2:1 nearest neighbor matching without replacement), resulting in 120 patients (80 patients for group A, 40 patients for group B). Toxicity, PSA nadir, biochemical failure and disease-free survival (DFS) were analyzed. Median follow up of all patients was 13 months (range 1-91 months). Overall, 23.3% of patients had ≥G2 acute GU toxicity (21.1% group A versus 30% group B (p = 0.222)) and 6.6% of patients ≥G2 GI toxicity (2.5% versus 15% (p = 0.010)). There was one acute G3 GU toxicity in arm A and one acute G4 rectal bleeding in group B (anticoagulated patient). Regarding late toxicity, 14.1% of patients had ≥G2 late GU toxicity (17.4% versus 6.6% (p = 0.159)) and 5.0% of patients had ≥G2 late GI toxicity (1.4% versus 13.3% (p = 0.013)). There was one G3 late GU toxicity in arm B and two G3 late GI toxicities, one in each arm. Relative median PSA reduction was 92.4% (-53.9-99.9%) from baseline PSA (93.7% (-53.9-99.9%) in group A versus 87.7% (39.8-99.9%) in group B (p = 0.043). In total, 4.2% of patients had biochemical relapse, 5.0% in group A and 2.5% in group B (p = 0.518). One-year DFS in the overall cohort was 97.3%, 98.8% in group A and 94.3% in group B (p = 0.318). Both SBRT regimens have acceptable acute and late toxicity and good efficacy. There are significantly more GI toxicities in the seven-fraction regimen. Longer follow-up is warranted for better comparison of long-term efficacy.

Dosimetric Analysis of Proximal Bronchial Tree Subsegments to Assess The Risk of Severe Toxicity After Stereotactic Body Radiation Therapy of Ultra-central Lung Tumors

Background and purposeStereotactic body radiotherapy (SBRT) of ultra-central lung tumors (UCLT) is associated with an increased risk of severe toxicity. The aim of this study was to perform a detailed dosimetric analysis of the proximal bronchial tree (PBT) anatomical sub-segments to evaluate the safety of risk-adapted SBRT and to evaluate potential differences in radiation tolerance between PBT sub-segments. Material and methodsFifty-seven patients treated with SBRT for UCLT between 2014 and 2021 were included. UCLT were defined as tumor abutting or overlapping with the trachea, PBT, or esophagus. This study analyzed overall survival, local control, progression-free survival, and grade ≥3 toxicity events. Bayesian inference was used to build a dose-response model with upper limits for toxicity. ResultsTwenty-seven (47.4%) of the irradiated lesions were primary or locoregionally recurrent NSCLC and 30 (52.6%) oligometastases. All patients were treated with risk-adapted SBRT of median 45.0 Gy (range: 30.0-60.0 Gy) in 8 or 10 fractions. Grade ≥3 radiation pneumonitis was observed in two patients (3.5%), while no bronchial stenosis, hemorrhage or fistula were observed. The dose-response model predicted a grade ≥3 toxicity (stenosis, hemorrhage or fistula) limited to 4.9% (0 - 11.4%) when delivering EQD2_3 = 100 Gy to any location of the PBT (D0.2cc). Detailed dosimetric analysis of PBT substructures showed no variation in the dose-response model between the anatomical PBT sub-segments. ConclusionRisk-adapted SBRT regimens delivered in 8 or 10 fractions for ultra-central lung tumors resulted in high rates of local tumor control with low toxicity rates, without differences in radiation tolerance between the anatomical PBT sub-segments.

Differential Use of Radiotherapy Fractionation Regimens in Prostate Cancer

Technical advances in treatment of prostate cancer and a better understanding of prostate cancer biology have allowed for hypofractionated treatment courses using a higher dose per fraction. Use of ultrahypofractionated stereotactic body radiotherapy (SBRT) has also been characterized. To characterize US national trends of different RT fractionation schemes across risk groups of prostate cancer. This retrospective cohort study used data collected by the National Cancer Database (NCDB) to characterize the fractionation regimens used for 302 035 patients diagnosed as having prostate cancer from January 1, 2004, to December 31, 2020, who underwent definitive RT. The analysis was performed between February 1 and April 30, 2023. Stereotactic body RT or ultrahypofractionation, defined as 5 or fewer fractions of external beam RT (EBRT), moderate hypofractionation, defined as 20 to 28 fractions of EBRT, or conventional fractionation, defined as all remaining EBRT fractionation schemes. Temporal trends and clinical and sociodemographic factors associated with SBRT, moderate hypofractionation, and conventional fractionation use. A total of 302 035 men receiving EBRT for localized prostate cancer between 2004 and 2020 were identified (40.1% aged 60-69 years). Black patients comprised 17.6% of this cohort; White patients, 77.9%; and other races and ethnicities, 4.5%. Patients with low-risk disease comprised 17.5% of the cohort; favorable intermediate-risk disease, 23.5%; unfavorable intermediate-risk disease, 23.9%; and high-risk disease, 35.1%. Treatment consisted of conventional fractionation for 81.2%, moderate hypofractionation for 12.9%, and SBRT for 6.0%. The rate of increase over time in patients receiving SBRT compared with conventional fractionation was higher (adjusted odds ratio [AOR] for 2005 vs 2004, 3.18 [95% CI, 2.04-4.94; P < .001]; AOR for 2020 vs 2004, 264.69 [95% CI, 179.33-390.68; P < .001]) than the rate of increase in patients receiving moderate hypofractionation compared with conventional fractionation (AOR for 2005 vs 2004, 1.05 [95% CI, 0.98-1.12; P = .19]; AOR for 2020 vs 2004, 4.41 [95% CI, 4.15-4.69; P < .001]). Compared with White patients, Black patients were less likely to receive SBRT compared with conventional fractionation or moderate hypofractionation (AOR for conventional fractionation, 0.84 [95% CI, 0.80-0.89; P < .001]; AOR for moderate hypofractionation, 0.77 [95% CI, 0.72-0.81; P < .001]). Compared with 2019, patients treated with all fractionation regimens declined in 2020 by 24.4%. In this hospital-based cohort study of patients with prostate cancer treated with definitive EBRT, use of moderate hypofractionation and SBRT regimens for definitive prostate cancer treatment has increased from 2004 to 2020. Despite this increasing trend, findings suggest potential health care disparities for Black patients receiving EBRT for localized prostate cancer. The number of patients treated with EBRT in the year 2020 decreased, coinciding with official onset of the COVID-19 pandemic in March 2020.

Utilization of the Triangle Volume in Patients with Localized PDAC Undergoing Pre-Operative SBRT: Report of Early Outcomes

In patients with borderline resectable or locally advanced pancreatic adenocarcinoma (BRPC/LAPC), advances in neoadjuvant therapy have led to an increased proportion of patients undergoing margin negative resection. Nevertheless, locoregional recurrence rates remain high. We have previously reported that the location of locoregional recurrences in this setting map to the "Triangle Volume (TV)," the anatomical space between the celiac artery, superior mesenteric artery, common hepatic artery, and portal vein, which is enriched in extrapancreatic perineural tracts at risk for microscopic residual disease after resection. At the beginning of 2021, we systematically changed our target volume to include the TV, in addition to gross disease and involved vasculature. Herein, we report early locoregional failure outcomes after resection in the setting of BRPC or LAPC treated with pre-operative stereotactic body radiation therapy (SBRT) to the TV, as compared to historical rates. Patients who received a diagnosis of BRPC or LAPC and who were treated at our institution with neoadjuvant chemotherapy (CTX) and SBRT between 2016 and 2022 were retrospectively reviewed. Between 2016 and 2020, the SBRT clinical tumor volume (CTV) included gross disease and full circumference of involved vasculature at the level of involvement. From 2021 onward, the CTV also included the TV. Survival was estimated using the Kaplan-Meier method. Statistical analyses were performed using scientific 2-D graphing and statistics software. From January 2016 to December 2022, 204 patients with localized PDAC underwent neoadjuvant CTX followed by SBRT. After completion of SBRT, all patients proceeded with surgical exploration. Of these patients, 111 (54%) had LAPC and 92 (45%) had BRPC disease. All patients were treated with induction CTX, mostly commonly with FOLFIRINOX (N = 166, 81%). Following CTX, the most frequently used SBRT regimen was 33 Gy in 5 fractions (N = 191, 94%). 155 (67%) patients were treated between 2016 and 2020 to the traditional CTV, while 49 (24%) patients were treated after 2020 to a CTV that included the TV. The 2-year local progression free survival rate of patients treated with SBRT using the TV was 77.6% as compared to 47.5% in patients treated with the traditional CTV. Over a median follow up of 15.7 months (range: 1 to 78.2 months), 47% (N = 73 out of 155) of patients who underwent SBRT with the traditional CTV developed locoregional recurrence, but only 12% (N = 6 out of 49) treated with SBRT to the TV have thus far developed locoregional recurrence (p<0.0001). In patients with localized PDAC who undergo pre-operative SBRT for BRPC/LAPC, targeting the TV may help reduce locoregional recurrence. More data and longer follow-up are needed to verify these findings and inform whether the TV may serve as a new standard for target volume delineation in this setting.

Interim Analysis of DD3: A Phase IB/II Trial of Dose-Deescalated 3-Fraction SBRT for Centrally Located Lung Cancer

Prior studies suggested excessive toxicity for central lung tumors treated with 3-fraction stereotactic body radiation therapy (SBRT). This may be related to the high biologically equivalent dose assuming alpha/beta of 10 (BED) of 54 Gy in 3 fractions (BED = 151.2), as 50-60 Gy in 5 fractions (BED = 100.0-132.0) was well-tolerated in RTOG 0813. We initiated a prospective phase IB/II trial to test the hypothesis that a dose-deescalated regimen of 45 Gy in 3 fractions (BED 112.5) would be safe and efficacious in central lung tumors. We enrolled patients with primary or secondary lung tumors ≤5cm in a central but not ultra-central tumor location defined as within 2 cm of (but not abutting) tracheobronchial tree, esophagus, or heart. Patients were either medically inoperable or refused surgical intervention. Co-primary endpoints were safety and efficacy, defined as local control (LC). Secondary endpoints included lobar control, regional control (LRC), distant control (DC), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Organ-at-risk dose constraints were consistent with those of RTOG 0236. The Bayesian predictive probability approach was utilized for continuous monitoring after 10 patients were treated and have mature assessment of toxicity, after which interim analysis was planned. We recommended terminating the trial for safety if there was sufficient evidence that the rate of grade ≥3 was greater than 0.25 (predictive probability >0.80). As of the data cut-off date of 1/26/23, the trial was open for 34 months (including a nearly-immediate suspension due to the COVID-19 pandemic). A total of 17 patients have been treated on protocol with a median follow-up of 12 months. No grade ≥3 adverse events attributable to SBRT have occurred to date, though one patient died of unrelated cardiac arrhythmias 1 month after SBRT completion (Table 1). Maximum CTCAE grade 2 adverse events attributable to SBRT occurred in 17.6% of patients. The predictive probability of concluding unacceptably high toxicity rate by the end of the trial based on toxicity data in the current stage is 0.62%. To date, there have been 0 local recurrences, 1 regional recurrence without local recurrence (8 months after SBRT completion, successfully salvaged with definitive chemoradiotherapy without additional toxicities), and 1 distant recurrence without local recurrence (6 months after SBRT in a patient with lung metastasis from colon adenocarcinoma). Interim analysis of the DD3 trial suggests that for patients with central but not ultra-central lung tumors, an SBRT regimen of 45 Gy in 3 fractions warrants continued trial accrual and follow-up given no grade ≥3 toxicities or local recurrences in the early follow-up period among the first 17 patients enrolled.

Association of neutrophil-lymphocyte ratio with survival in peripheral early-stage non–small-cell lung cancer after stereotactic body radiation therapy.

e20547 Background: Prior studies have demonstrated that neutrophil-lymphocyte ratio (NLR) can predict overall survival in patients undergoing stereotactic body radiation therapy (SBRT) for multiple types of cancer. The role of neutrophil-lymphocyte ratio (NLR) as a predictor for survival in single fraction SBRT-treated non-small cell lung cancer (NSCLC) patients remains unclear. Methods: A single-institution database of peripheral early-stage NSCLC patients treated with SBRT from February 2007 to May 2022 was queried. Consecutive patients with peripheral early-stage NSCLC (T1-2N0M0) and a complete blood count within six months of the start of SBRT treatment were included. Patients treated with SBRT regimens of more than 3 fractions were excluded as these regimens were reserved for patients with centrally located lesions with higher risk of toxicity which could affect survival. Optimal threshold of neutrophil-lymphocyte ratio (NLR) was defined based on maximally selected rank statistics. Cox multivariable analysis (MVA), Kaplan-Meier, and propensity score matching were performed to evaluate outcomes. Results: A total of 286 patients (164 female [57.3%]; median [IQR] age 76 [69-81] years) were included for analysis with median follow up of 19.7 months. The median NLR was 3.06 ([IQR] 2.21-4.33). There were 15 local failures, 27 nodal failures, and 50 distant failures. On Cox multivariate analysis, as a continuous variable, NLR was shown to be an independent predictor of OS (adjusted hazards ratio [aHR] 1.06, 95% CI 1.02-1.10, p = 0.005; Figure 1) and PFS (aHR 1.05, 95% CI 1.01-1.09, p = 0.013; Figure 1). In addition, NLR was associated with DF (aHR 1.11, 95% CI 1.05-1.18, p &lt; 0.001; Figure 1). Maximally selected rank statistics determined 3.28 as the cutoff point of high NLR versus low NLR. These findings were confirmed upon propensity matching. Conclusions: Pretreatment NLR is an independent predictor for survival outcomes of peripheral early-stage NSCLC patients after SBRT. High NLR is associated with worse overall survival, progression-free survival, and distant metastasis. Pretreatment NLR levels should be tracked on trials for early-stage NSCLC patients.

Toxicity and Patient-Reported Quality-of-Life Outcomes After Prostate Stereotactic Body Radiation Therapy With Focal Boost to Magnetic Resonance Imaging-Identified Prostate Cancer Lesions: Results of a Phase 2 Trial

In this prospective phase 2 trial, we investigated the toxicity and patient-reported quality-of-life outcomes in patients treated with stereotactic body radiation therapy (SBRT) to the prostate gland and a simultaneous focal boost to magnetic resonance imaging (MRI)-identified intraprostatic lesions while also de-escalating dose to the adjacent organs at risk. Eligible patients included low- or intermediate-risk prostate cancer (Gleason score ≤7, prostate specific antigen ≤20, T stage ≤2b). SBRT was prescribed to 40 Gy in 5 fractions delivered every other day to the prostate, with any areas of high disease burden (MRI-identified prostate imaging reporting and data system 4 or 5 lesions) simultaneously escalated to 42.5 to 45 Gy and areas overlapping organs at risk (within 2 mm of urethra, rectum, and bladder) constrained to 36.25 Gy (n=100). Patients without a pretreatment MRI or without MRI-identified lesions were treated to dose of 37.5 Gy with no focal boost (n=14). From 2015 to 2022, a total of 114 patients were enrolled with a median follow-up of 42 months. No acute or late grade 3+ gastrointestinal (GI) toxicity was observed. One patient developed late grade 3 genitourinary (GU) toxicity at 16 months. In patients treated with focal boost (n=100), acute grade 2 GU and GI toxicity was seen in 38% and 4% of patients, respectively. Cumulative late grade 2+ GU and GI toxicities at 24 months were 13% and 5% respectively. Patient-reported outcomes showed no significant long-term change from baseline in urinary, bowel, hormonal, or sexual quality-of-life scores after treatment. SBRT to a dose of 40 Gy to the prostate gland with a simultaneous focal boost up to 45 Gy is well tolerated with similar rates of acute and late grade 2+ GI and GU toxicity as seen in other SBRT regimens without intraprostatic boost. Moreover, no significant long-term changes were seen in patient-reported urinary, bowel, or sexual outcomes from pretreatment baseline.

Genitourinary Quality-of-Life Comparison Between Urethral Sparing Prostate Stereotactic Body Radiation Therapy Monotherapy and Virtual High-Dose-Rate Brachytherapy Boost

Although radiation dose escalation improves prostate cancer disease control, it can cause increased toxicity. Genitourinary (GU) symptoms after prostate radiation therapy affect patient health-related quality of life (QoL). We compared patient-reported GU QoL outcomes following 2 alternative urethral sparing stereotactic body radiation therapy regimens. Expanded Prostate Cancer Index Composite (EPIC)-26 GU scores were compared between 2 urethral sparing stereotactic body radiation therapy trials. The SPARK trial prescribed a "Monotherapy" dose of 36.25 Gy in 5 fractions to the prostate. The PROMETHEUS trial prescribed 2 phases: a 19- to 21-Gy in 2 fractions "Boost" to the prostate, followed by 46 Gy in 23 fractions or 36 Gy in 12 fractions. The biological effective dose (BED) for urethral toxicity was 123.9 Gy for Monotherapy and 155.8 to 171.2 Gy for Boost. Mixed effects logistic regression models were utilized to estimate the difference in the odds of a minimal clinically important change from baseline EPIC-26 GU score between regimens at each follow-up. 46 Monotherapy and 149 Boost patients completed baseline EPIC-26 scoring. Mean EPIC-26 GU scores revealed statistically superior urinary incontinence outcomes for Monotherapy at 12 months (mean difference, 6.9; 95% confidence interval [CI], 1.6-12.1; P=.01) and 36 months (mean difference, 9.6; 95% CI, 4.1-15.1; P < .01). Monotherapy also revealed superior mean urinary irritative/obstructive outcomes at 12 months (mean difference, 6.9; 95% CI, 2.0-12.9; P < .01) and 36 months (mean difference, 6.3; 95% CI, 1.9-10.8; P < .01). For both domains and at all time points, the absolute differences were <10%. There were no significant differences in the odds of reporting a minimal clinically important change between regimens at any time point. Even in the presence of urethral sparing, the higher BED delivered in the Boost schedule may have a small adverse effect on GU QoL compared with Monotherapy. However, this did not translate to statistically significant differences in minimal clinically important changes. Whether the higher BED of the boost arm offers an efficacy advantage is being investigated in the Trans Tasman Radiation Oncology Group 18.01 NINJA randomized trial.

Estimating Carbon Dioxide Emissions and Direct Power Consumption of Linear Accelerator–Based External Beam Radiation Therapy

Climate change is one of the direst health threats that humanity faces. We aim to estimate the carbon dioxide (CO2) emissions associated with the energy usage from linear accelerator (LINAC)-based external beam radiation therapy (EBRT) for the most common cancer diagnoses. We identified patients with the 4 most common cancer types treated with curative-intent EBRT. Beam-on time for each fraction was extracted from the treatment planning system and averaged over each site and treatment modality. The power was multiplied by the beam-on time in hours to yield kilowatt hours (kWh). Using the US Environmental Protection Agency Greenhouse Gas Equivalencies calculator, we converted the kWh into estimates of CO2-equivalent emissions for the average US power grid. Idle time of the LINAC was estimated via Varian Medical Systems. A total of 10 patients were included for each of the following modalities: conventionally fractionated for prostate cancer (28 fractions [fx]), prostate stereotactic body radiation therapy (SBRT) (5 fx), 15- and 5-fx regimens for early-stage breast cancer, 3- and 5-fx SBRT regimens for early-stage lung cancer, conventional EBRT (30 fx) for locally advanced lung cancer, and short- (5 fx) and long-course (25-28 fx) for rectal cancer. The modality with the lowest and highest carbon emissions per course, on average, was prostate SBRT (2.18 kg CO2; interquartile range, 1.92-2.30) and conventional treatment for prostate cancer (17.34 kg CO2; interquartile range, 10.26-23.79), respectively. This corresponds to CO2-equivalent emissions of driving an average of 5.4 miles and 41.2 miles in a standard vehicle, respectively. "Standby" mode for a LINAC TrueBeam and Clinac IX uses 112 kWh and 64.8 kWh per day, respectively. We have estimated CO2 emissions arising from direct energy usage of a LINAC for 4 common cancers treated with EBRT. "Standby" mode of a LINAC uses the most energy per day. Comprehensive studies are warranted to minimize the environmental effects of health and cancer care.

Sequential monoscopic image-guided motion compensation in tomotherapy stereotactic body radiotherapy (SBRT) for prostate cancer.

To manage intra-fractional motions, recent developments in tomotherapy enable a unique capability of adjusting MLC/jaw to track the moving target based on the intra-fractional motions detected by sequential monoscopic imaging. In this study, we evaluated the effectiveness of motion compensation with a realistic imaging rate for prostate stereotactic body radiotherapy (SBRT). The obtained results will guide optimizing treatment parameters and image-guided radiation therapy (IGRT) in tomotherapy using this approach. Ten retrospective prostate cases with actual prostate motion curves previously recorded through the Calypso system were used in this study. Based on the recorded peak-to-peak motion, these cases represented either large(>5mm) or median (≤ 5mm) intra-fractional prostate motions. All the cases were re-planned on tomotherapy using 35Gy/5 fractions SBRT regimen and three different jaw settings of 1cm static, 2.5cm static, and 2.5cm dynamic jaw. Two motion compensation methods were evaluated: a complete compensation that adjusted the jaw and MLC every 0.1 s (the same rate as the Calypso motion trace), and a realistic compensation that adjusted the jaw and MLC at an average imaging interval of 6 s from sequential monoscopic images. An in-house 4D dose calculation software was then applied to calculate the dosimetric outcomes from the original motion-free plan, the motion-contaminated plan, and the two abovementioned motion-compensated plans. During the process, various imaging rates were also simulated in one case with unusually large motions to quantify the impact of the KV-imaging rate on the effectiveness of motion compensation. The effectiveness of motion compensation was evaluated based on the PTV coverage and OAR sparing. Without any motion-compensation, the PTV coverage (PTV V100%) of patients with large prostate motions decreased remarkably to 55%-82% when planning with the 1cm jaw but to a less level of 67-94% with the 2.5cm jaw. In contrast, motion compensation improved the PTV coverage(>92%) when combined with the 2.5cm jaw, but less effective, around 75%-94%, with the 1cm jaw. For OAR sparing, the bladder D1cc, bladder D10cc, and rectum D1cc all increased in the motion-contaminated plans. Motion compensation improved OAR sparing to the equivalent level of the original motion-free plans. For patients with median prostate motion, motion-induced degradation in PTV coverage was only observed when planning with the 1cm jaw. After motion compensation, the PTV coverage improved to better than 94% for all three jaw settings. Additionally, the effectiveness of motion compensation depends on the imaging rate. Motion compensation with a typical rate of two KV images per gantry rotation effectively reduces motion-induced dosimetric uncertainties. However, a higher imaging rate is recommended when planning with a 1cm jaw for patients with large motions. Our results demonstrated that the performance of sequential monoscopic imaging-guided motion compensation on tomotherapy depends on the amplitude of intra-fractional prostate motion, the plan parameter settings, especially jaw setting, gantry rotation, and the imaging rate for motion compensation. Creating a patient-specific imaging guidance protocol is essential to balance the effectiveness of motion compensation and achievable imaging rate for intra-fractional motion tracking.

Protocol of the integrated boost to the dominant intraprostatic nodule in stereotactic body radiation therapy for localized prostate cancer.

Aim: To explore the safety and efficacy of the integrated boost to the dominant intraprostatic nodule (DIN) based on 68Ga prostate-specific membrane antigen PET/MRI in stereotactic body radiation therapy (SBRT) for patients with localized prostate cancer. Methods: SBRT regimen is employed - namely, sequential integrated boost (SIB) to the DIN based on 68Gaprostate-specific membrane antigen PET/MRI. SIB prescription dose of 36.25 Gy in five fractions to fixed prophylactic tumoricidal region is delivered, followed by 7.25 Gy in one fraction added to the DIN every other day. The primary end point of the study will be toxicity assessed by the Common Terminology Criteria for Adverse Events 5.0 grading scale. Secondary end points include biochemical progression-free survival, local progression-free survival, distant metastasis-free survival and overall survival. Discussion: This trial is to prove the safety and efficacy of sequential integrated boost to the DIN in SBRT. Clinical Trial Registration: NCT04599699 (ClinicalTrials.gov).

Systemic Therapy Postponement after Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer

<h3>Purpose/Objective(s)</h3> To evaluate the oncological outcome after stereotactic body radiation therapy (SBRT) for oligometastatic (OM) prostate cancer (PC) patients. <h3>Materials/Methods</h3> In this retrospective observational multi-institutional study (Health-data-hub N°F20210402112942), patients with OM (≤ 5) PC underwent SBRT. While patients were enrolled irrespective of PC initial treatment, castration sensitive (CS)/resistant (CR) and synchronous (SM)/metachronous (MM) metastatic disease status were taken into account. Primary endpoint was systemic therapy postponement (STP) after SBRT. Oncological outcome was assessed by post-SBRT biochemical response, local (LR; in SBRT field), metastatic (MR), prostatic (PR) and isolated biochemical (iBR) relapses. PSA kinetic (PSAdt; velocity) and prognostic factors for STP were investigated. Toxicity was reported (CTCAE v5). <h3>Results</h3> From 01/07 to 09/19, 169 pts (median age 71.4 y [48.7 – 100.1]) underwent SBRT. At the time of SBRT, 151 pts (89.3%) and 18 pts (10.7%) were MM and SM respectively and 119 pts (70.4%) and 50 pts (29.6%) were CS and CR respectively. Median PSA, PSAdt and velocity were 2.4 ng/ml [0.01 – 277], 5.2 months [0.9 – 45.2] and 2.3 ng/ml/an [0.1 – 25.9] respectively. Median time between initial PC/metastatic disease (TPCMD) and metastatic disease/SBRT were 68.9 months [1.9 – 273.4] and 3.1 months [0.1 – 97.9]. Metastatic anatomic sites were pelvic (PLN) and extra-pelvic lymph nodes (EPLN), bone and brain for 58 pts (34.4%), 15 pts (8.9%), 92 pts (54.4%) and 4 pts (2.4%) respectively. SBRT regimens were 27 Gy/3f (29%), 35 Gy/5f (24.3%), 36 Gy/6f (18.3%) and other (28.4%). With a MFU of 27.5 months [1 – 100.5], median time between SBRT/1^st PSA control was 2 months [0.5 – 29]. PSA decreased in 67.4%, was stable in 9.4% and increased in 23.2%. Eighty-eight pts (52.1%) underwent post-SBRT systemic therapy after a median STP of 15.4 months [2.6 – 86.9]. One hundred and thirty events (LR, MR, PR, iBR) were observed in 106 pts (62.7%), among whom 13 (12.3%) relapsed in the irradiated area (local control rate: 92.3%). MR, PR, iBR were observed in 82 pts (77.4%), 33 pts (31.1 %) and 2 pts (1.9 %) respectively. Prognostic factors for STP after SBRT were: hormonal status (CS vs CR: 20.9 vs 10.8 months; p < 0.001), post-SBRT biochemical response ([declined + stable] PSA vs increased PSA: 21 vs 11 months; p = 0.004) and TPCMD (< 42 vs ≥ 42 months; p < 0.001). G≥3 toxicity occurred in 4 pts: 2 pts with G3 post-SBRT fracture (1 surgery), 1 pt with G3 radiation pneumonitis and 1 pt with G4 intracranial hypertension (emergency surgery). <h3>Conclusion</h3> SBRT for oligometastatic prostate cancer is an option to postpone systemic therapy, mainly for CS and MM patients with an acceptable toxicity profile. Patient selection criteria remain a crucial goal in order to refine SBRT indications, while the impact of combination with systemic therapy remains under investigation.

National Trends in Definitive Radiation for Large Unresected cT3N0 Non-Small Cell Lung Cancer Tumors

<h3>Purpose/Objective(s)</h3> The ideal approach to radiation regimens for patients with unresected cT3N0 non-small cell lung cancer (NSCLC) tumors >5cm is undefined. We queried the National Cancer Database to investigate patterns of care and outcomes for this unique subset of patients treated with definitive radiation. <h3>Materials/Methods</h3> Patients with cT3N0M0 NSCLC diagnosed between 2004-2018 and a documented tumor diameter >5cm were included. Patients who underwent surgery were excluded. Conventional fractionation (CF) was defined as 59.40-70.20Gy in 30-39 fractions, hypofractionation (HF) as 45-70Gy in 8-15 fractions, and stereotactic body radiation therapy (SBRT) as 40-60Gy in 3-5 fractions. Patient characteristics and clinical factors were evaluated. Chi-Square test was used to compare frequency distributions between categorical variables. Kaplan-Meier with log-rank test was used to assess overall survival (OS) and multivariable Cox regression was performed to assess the impact of covariates on OS. <h3>Results</h3> A total of 4,047 patients met study criteria. Median age was 72 years and median tumor size was 6.5cm. Of these patients, 3172 (78%) were treated with CF, 290 (7.2%) with HF, and 585 (14.6%) with SBRT. Patients treated with SBRT were more likely to be younger (p<0.001), white (p<0.001), live farther away from the treatment center (p=0.049), have Medicare insurance (p<0.001), receive treatment in an academic center (p<0.001) located in a metropolitan region (p<0.037), have a higher Charlson-Deyo Comorbidity (CDC) score (p<0.001), and have a lower lobe primary tumor (p<0.001). With a median follow up of 18.89 months, median OS was 20.78 months (IQR: 10.41-42.91) for patients treated with CF, 20.36 months (IQR: 10.55-32.10) for HF, and 23.86 months (IQR: 11.43-42.78) for SBRT, which was significantly different on Kaplan-Meier analysis (p<0.025). However, there was no difference in OS among fractionation regimens on multivariate analysis. Female gender, African American race, and treatment center distance between 9.5-23.2 miles were associated with improved OS, with greatest impact observed for academic centers (HR 0.863, 95% CI 0.792-0.939; p < 0.001) and other non-white race (HR 0.742, 95% CI 0.566-0.974; p = 0.31). Factors associated with worse OS were age >77 years (HR 1.332, 95% CI 1.166-1.521; p < 0.001) and any CDC score (score of ≥3: HR 1.431, 95% CI 1.215-1.684; p < 0.001). <h3>Conclusion</h3> Conventional fractionation was utilized most frequently to treat large (>5cm) cT3N0 NSCLC tumors not undergoing surgical management. There was no difference in overall survival among conventional, hypofractionated, and SBRT regimens.

Stereotactic Body Radiation Therapy for Sarcoma Pulmonary Metastases: Outcomes and Fractionation Schedules

<h3>Purpose/Objective(s)</h3> Lung metastases are the most common site for distant metastases in sarcoma. Mastectomy is associated with improved survival in select patients; however, alternatives such as stereotactic body radiation therapy (SBRT) can be considered for inoperable patients or those who prefer non-surgical management. However, data regarding local control and optimal fractionation are limited. We present outcomes of 3 SBRT regimens, describe patterns of failure and chemotherapy free survival rates after SBRT for sarcoma lung metastases. <h3>Materials/Methods</h3> 50 sarcoma patients were treated with SBRT for 109 lung metastases between 2005 and 2021 with dose regimens including 30-34Gy/1fx (BED₁₀ 120-149.6 Gy), 48Gy-50Gy/4-5fx (BED₁₀ 100-106), and 60Gy/5fx (BED₁₀ 132). At least 6 month follow up was required. Overall survival (OS), local control (LC), chemotherapy free survival, patterns of failure and toxicity were evaluated. <h3>Results</h3> 10 patients received 30-34Gy/1fx, 24 patients received 48-50Gy/4-5fx and 16 patients received 60Gy/5fx. The most common histology for bone sarcomas was osteosarcoma (<i>n</i>=10), and for soft tissue sarcoma was leiomyosarcoma(<i>n</i>=9). At SBRT, median age was 64 years old and 76% of patients had a KPS ≥80. Median tumor size was 1.9 cm (range: 0.3-6.3). With a median follow-up time from SBRT of 19.5 months, 1- and 3-year LC rates were 96% and 88%, with 1- and 3-year OS of 77% and 50%, respectively. There was no statistically significant difference between the 3 regimens in terms of LC, OS or toxicity. No differences in LC or OS were noted based on primary histology; however, a size 4 cm or larger was predictor of worse LC (p=0.031) and worse OS (p= 0.039) on univariate analysis. The primary pattern of failure was new distant metastases occurring in (64%) of patients of which the majority were in the contralateral lung (52%); 4% had lobar failure, 4% had local only failure, and 4% had both local and distant failure. 1-year chemotherapy free survival was 85%. Overall, 76% of patients did not require chemotherapy initiation or change of chemotherapy regimen after lung SBRT (3 remained on same chemotherapy while receiving SBRT). Toxicity was reported in 16% of patients overall, including 25%, 20% and 14 % in the 30-34Gy/1fx, 48-50Gy/4-5fx and 60Gy/5fx cohorts, respectively. Chest wall toxicity was reported in 5 patients overall (1 patient with Grade II in 30-34Gy/1fx cohort, 3 patients, 1 Grade I, II and III in 48-50Gy/4-5fx cohort, and 1 Grade I in 60Gy/5fx cohort), pneumonitis in 3 patients (1 patient with Grade I in 30-34Gy/1fx cohort, 1 patient with Grade II in 48-50Gy/4-5fx cohort, and 1 patient with Grade II in the 60Gy/5fx cohort). <h3>Conclusion</h3> This series of SBRT for sarcoma pulmonary metastases demonstrates that SBRT is effective with comparable outcomes between dose/fractionation regimens. In addition, lung SBRT is associated with an excellent chemotherapy free survival, and can be a potential alternative to surgical resection.

Toxicity and Patient Reported Quality of Life Outcomes Following Prostate SBRT with Focal Boost to MRI Identified Prostate Cancer Lesions: Results of a Phase II Trial

<h3>Purpose/Objective(s)</h3> A focused boost to MRI identified prostate cancer lesions treated with radiotherapy has been shown to improve biochemical disease control without increased toxicity in standard fractionated radiation treatment. Prostate cancer is known to be sensitive to higher radiation doses per fraction and thus stereotactic body radiotherapy (SBRT) has become an increasingly popular treatment method. In this prospective phase II trial, we investigated the toxicity and patient reported quality of life outcomes in patients treated with SBRT to the prostate gland and a simultaneous focal boost to MRI identified intraprostatic lesions while also de-escalating dose to the adjacent organs at risk. <h3>Materials/Methods</h3> Eligible patients included low- or intermediate- risk prostate cancer (Gleason score ≤ 7, PSA ≤20, T stage ≤2b). SBRT was prescribed to 40 Gy in 5 fractions delivered every other day to the prostate, with areas of high disease burden (MRI-identified PI-RADS 4 or 5 lesions) escalated to 42.5-45 Gy and areas overlapping organs at risk (within 2 mm of urethra, anterior rectal wall, and bladder base) constrained to 36.25 Gy (n=98). Patients without a pre-treatment MRI were treated to dose of 37.5 Gy with no focal boost (n=14). Acute and late toxicity were graded using RTOG modified toxicity scales. Patient-reported outcome and quality of life was assessed using the AUA-IPSS lower urinary tract symptom score, IIEF-5 erectile function, and EPIC-26 surveys. Statistical testing was performed in statistical software. <h3>Results</h3> From 2015 to 2022, a total of 112 patients were enrolled with a median follow-up of 36 months. No acute or late grade 3+ GI or GU toxicity was observed. Within the focal boost arm, acute grade 2 GU toxicity during treatment or at 6-week follow-up was seen in 26% of patients. Acute grade 2 GI toxicity was seen in 1 patient. Cumulative late grade 2 GU toxicity was 8%. Rate of alpha blocker medication use following treatment was 26%. Cumulative late grade 2 GI toxicity was 2.3%. Patient reported outcomes showed no significant changes from baseline IPSS lower urinary tract, IIEF erectile function, or EPIC-26 urinary incontinence, urinary irritative, gastrointestinal, or sexual domain quality of life scores following treatment (p >0.05 for all tests via RANOVA). Two patients have had a biochemical recurrence to date, at 42 months and 60 months post treatment. <h3>Conclusion</h3> SBRT to a dose of 40 Gy to the prostate gland with a focal boost up to 45 Gy is well tolerated with no observed grade 3 toxicity and similar rates of acute and late grade 2 GI and GU toxicity as seen in other SBRT regimens without intraprostatic dose boost. Moreover, no significant changes were seen in patient reported urinary, bowel, or sexual outcomes from pre-treatment baseline at any follow-up date. Biochemical control data continue to mature but few treatment failures have been observed to date.

Evaluation of Psychiatric Diagnoses as a Source of Bias in Prognostication and Decision-Making for Palliative Radiotherapy

<h3>Purpose/Objective(s)</h3> Up to half of patients with advanced cancer may meet diagnostic criteria for a psychiatric disorder. Yet, the impact of psychiatric diagnosis and/or medication prescription (psych Dx/Rx) on decision-making and outcomes for radiotherapy (RT) are not well-characterized. Statistical models and decision tools can be skewed when built from source data that has been influenced by implicit and explicit biases in medical diagnoses and treatment. We investigate the impact of psych Dx/Rx on palliative RT outcomes and decisions to ascertain whether this may serve as a source of bias in prognostication and decision-making in this patient population. <h3>Materials/Methods</h3> Retrospective review identified patients treated with conventional external beam (cEBRT) or stereotactic body RT (SBRT) for bone metastases at 3 radiation oncology facilities from 5/2013-12/2019. Prevalence of psych Dx/Rx was collected, along with 27 other patient, disease, and treatment characteristics that were identified as collectively predictive of survival using the validated Bone Metastases Ensemble Trees for Survival (BMETS) machine-learning model and decision support platform. RT details were documented. Overall survival from consultation to death or last follow up was estimated using the Kaplan-Meier method. Uni- and multivariable regressions evaluated associations between psych Dx/Rx, survival, and RT fractionation and modality. Reported statistics are p<.05. <h3>Results</h3> 346 treated patients were evaluated, including 178 patients with cEBRT and 168 patients with SBRT (median 10 vs. 3 fractions). Psych Dx/Rx was more prevalent among patients treated with cEBRT vs. SBRT (40% vs. 28.6%). On univariate analysis, odds of psych Dx/Rx was significantly higher for patients requiring opiate analgesics, females, white (vs. black) race, and breast (vs. prostate) cancer (OR 2.0, 3.7, 4.3, 5.6). Psych Dx/Rx was associated with use of fewer fractions for cEBRT (β coefficient -1.0) but not SBRT. On multivariable analyses for the cEBRT cohort controlling for other univariable associations, use of fewer fractions remained significantly associated with psych Dx/Rx (β coefficient -1.1). While overall survival was significantly longer for patients treated with SBRT (median 3.3 vs. 0.8 years for cEBRT), psych Dx/Rx was not associated with survival or strongly linked to other predictors of advanced disease for either RT cohort. <h3>Conclusion</h3> Psych Dx/Rx does not appear to impact survival for patients undergoing palliative bone RT, arguing against its direct role as a source of bias in survival models like BMETS. However, given that psych Dx/Rx is associated with lower use of SBRT and foreshortened cEBRT regimens, this variable may serve a source of bias in treatment selection, albeit perhaps concordant with the patient's best interest. This highlights the importance of enhanced shared decision-making in this potentially vulnerable patient population.

GRECO-1: Phase 1/2 Study of Stereotactic Body Radiation Therapy (SBRT) with or without Rucosopasem (GC4711) for Early Stage, Peripheral or Centrally Located Non-Small Cell Lung Cancer (NSCLC)

<h3>Purpose/Objective(s)</h3> The number of patients diagnosed with early-stage non-small cell lung cancer (NSCLC) has been increasing with screening programs and more frequent thoracic imaging. SBRT is an alternative for patients who are not candidates for surgery. SBRT for larger and/or centrally located tumors may have reduced efficacy and lead to higher-grade toxicity (Timmerman 2006; Dunlap 2010). Rucosopasem (GC4711) is one of a class of investigational selective dismutase mimetics that rapidly and specifically produces hydrogen peroxide from superoxide (Riley 2006). In preclinical models including NSCLC, the addition of a dismutase mimetic to SBRT regimens demonstrated mechanism-related anticancer synergy with SBRT while protecting normal tissues from radiation damage (Sishc 2021). The purpose of this trial is to test the hypothesis that rucosopasem may improve tumor control without increasing pulmonary toxicity after SBRT. <h3>Materials/Methods</h3> This phase 1/2 trial is designed to test the safety of rucosopasem and its potential to improve tumor control and reduce lung injury due to SBRT for cT1c-3N0M0 peripheral or centrally located (within 2 cm of the proximal bronchial tree) NSCLC. An open-label, phase 1 run-in cohort of 5 patients received rucosopasem 100 mg as a 15-minute IV infusion within a 180-minute window prior to each of 5 SBRT fractions of 10–12 Gy delivered on sequential weekdays. A placebo-controlled phase 2 cohort of approximately 66 patients randomized to either rucosopasem or placebo concurrent with SBRT follows and is ongoing. The primary endpoint for phase 1 is dose-limiting toxicities during treatment or within 30 days post-SBRT, and for phase 2, in-field tumor response. Reduction from baseline in diffusion capacity of lung for carbon monoxide (DLCO) at 6 months (Stone 2015) is a secondary endpoint for phase 2. Progression-free and overall survival, locoregional control, and distant metastasis rate will be followed over 24 months. Additional secondary endpoints include clinical (CTCAE 5.0) and radiological pneumonitis, measured at the same timepoints as quarterly lung function tests, and other adverse events. Trial-in-progress NCT04476797 is currently enrolling. This study is funded by Galera Therapeutics, Inc. <h3>Results</h3> TBD <h3>Conclusion</h3> TBD