Stereotactic Body Radiation Therapy Patients Research Articles

Multicenter Retrospective Study of Stereotactic Body Radiotherapy for Patients with Previously Untreated Initial Small Hepatocellular Carcinoma.

The effectiveness of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) has been shown in many studies and its therapeutic effect is similar to radiofrequency ablation (RFA). However, many of these studies were done in combination with transcatheter chemoembolization (TACE), for recurrent HCC, or on a small scale. To better understand the specific outcomes of SBRT for HCC, we conducted a multicenter retrospective analysis of SBRT for previously untreated initial HCC at Japanese Society of Clinical Oncology (JCOG) member hospitals. Patientswho underwent SBRT for HCC at JCOG member hospitals between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤ 3 nodules, ≤ 5 cm in diameter; (3) a Child-Pugh (CP) score of A or B; and (4) unsuitability for or refusal of standard treatment, such as surgery, transplantation, RFA and TACE. We evaluated the overall survival (OS), recurrence-free survival (RFS) which was defined as the first instance of intra-hepatic recurrence after SBRT, disease-specific survival (DSS) using Kaplan-Meier analysis. Using Grey's test, patients who died of other diseases were analyzed as competing risks to estimate the cumulative incidence of local recurrence (CLR). Adverse events directly related to SBRT also analyzed using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range; 50-89 years), and the median tumor size was 23 mm (range; 6-50 mm). The median radiation dose was 40 Gy (range; 35-60 Gy) in five fractions (range; 4-8). The median follow-up period was 45 months (range; 0-103 months). There were three cases where follow-up was not possible due to unexpected events unrelated to SBRT, while the remaining 70 patients were successfully followed for at least six months. The 2 and 3year OS, RFS, DSS, and CLR rates were 84.3% (95% CI: 75.8-92.8%) and 69.9% (95% CI: 58.7-81%), 67.5% (95% CI: 56.0-79.0%) and 57.9% (95% CI: 45.2-70.5%), 95.1% (95% CI:89.7-100%)/87.6% (95% CI:78.8-96.3%), and 11.4% (95% CI: 5.3-20.0%) and 20.0% (95% CI: 11.2-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: one case of grade 3 laboratory toxicities, one case of grade 3 liver failure, one case of grade 3 portal tumor thrombosis, and one case of grade 4 duodenal ulcer. No grade 5 toxicities were observed. The results of our study demonstrate that SBRT for HCC is highly effective in achieving local control and is safe to administer. In addition, survival outcomes are favorable. SBRT is a promising treatment modality, especially for small HCCs for that is not suitable for standard treatment.

Biological Effective Dose (BED) in Evaluation of Rectal Dose in Prostate Cancer Patients with Hydrogel Spacer Who Underwent an EBRT with Different Fractionation Schemes

To evaluate rectal dose sparing in prostate cancer patients with hydrogel spacer who underwent an external beam radiotherapy (EBRT) with different fractionation schemes. In a previous study, we have reported that rectal sparing was achieved in prostate cancer patients with hydrogel spacer who underwent a combination therapy of EBRT and LDR brachytherapy (Zhang H, et al. J Appl Clin Med Phys, 2022). In this study, we focused on evaluation of spacer-related rectal sparing in patients who underwent an EBRT with conventional fractionation (81 Gy in 45 fractions), hypofractionation (70 Gy in 28 fractions), or stereotactic body radiotherapy (SBRT) for 40 Gy or 42.5 Gy in 5 fractions. In 172 patients, 119 patients were applied with injection of polyethylene-glycol hydrogel and others without the injection as control. In VMAT plans, doses to rectal wall were examined and converted to BED according to AAPM TG-137 (α/β ratio = 4 Gy). On average, an interspace of 1cm between prostate and rectum was achieved by spacer insertion. Rectal wall was defined as 0.4cm thickness inside the outer contour of rectum, and the volume ranged from 4.5 cm3 to 21.3cm3 for patients with spacer and from 8.2cm3 to 35.1cm3 for those with no spacer. In conventional scheme, an average rectal BED was 120.0 Gy, 116.9 Gy, 114.0 Gy, 108.6 Gy, 87.6 Gy and 55.6 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively, and BEDmean was 55.3 Gy in patients with no spacer. The BED decreased to 105.1 Gy, 96.3 Gy, 86.1 Gy, 75.4 Gy, 51.7 Gy and 26.9 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively (p < 0.01), and BEDmean was 46.0 Gy in patients with spacer. In hypofractionation, rectal BED was in average of 115.8 Gy, 112.3 Gy, 109.8 Gy, 103 Gy, 81.6 and 52.8 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively, and BEDmean was 48.6 Gy in patients with no spacer. Patients with spacer had significantly decreases of rectal BED, an average of 103 Gy, 91.7 Gy, 84.1 Gy, 72.8 Gy, 48.8 Gy and 26.0 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3, respectively (p < 0.01), BEDmean was 42.4 Gy. In SBRT, average rectal BED in patients with spacer decreased to 93.6 Gy, 78.4 Gy, 69 Gy, 57.5 Gy, 38.5 Gy and 21.5 Gy, in comparison of 124.1 Gy, 117,4 Gy, 110.9 Gy, 97.3 Gy, 59.7 Gy and 32.3 Gy to the volume of 0.1, 0.5, 1, 2, 5 and 10cm3 in those without spacer, respectively (p <0.01). BEDmean decreased to 32.0 Gy in patient with spacer, compared with 43.2 Gy in those with no spacer. Insertion of hydrogel spacer significantly improved rectal dose sparing, about 11.1% to 50.8% in conventional scheme, 12.4% to 51.6% in hypofractionation scheme, and 24.6% to 40.9% in SBRT patients. Furthermore, relatively more dose sparing on rectum was seen on the volume from 0.1cm3 to 2cm3 in SBRT patients.

The Feasibility of Fast, Four-Dimensional Computed Tomography-Based O-Ring Linac Plans for Stereotactic Body Radiotherapy in Patients with Poor Performance Status

As patients with poor performance status cannot endure long treatment times, it can lead to unplanned and prolonged radiation treatment or discontinuation of treatment. Moreover, prolonged radiation treatment appears to negatively affect survival for patients. We aimed to verify the feasibility of fast 4DCT-based O-ring linear accelerator (LINAC) treatment in lung 4D stereotactic body radiotherapy (SBRT). This study included data of 38 patients who received lung 4D-SBRT. Gating20-70% plans were based on 4DCT data obtained at phase values ranging from 20-70% using a C-arm LINAC. Non-GatingFB plans were retrospectively established based on 4DCT data obtained at phase values of 0-90% using an O-ring LINAC. The prescribed dose of 4,800 cGy was delivered to PTV in four fractions. The conformity index (CI), homogeneity index (HI), and gradient measurement (GM) of the PTV were analyzed to compare dosimetric data between Gating20-70% and Non-GatingFB plans. Organs at risks (OARs) were analyzed in accordance with the RTOG 0915 protocol. Treatment delivery time and total monitor units (MU) were analyzed to compare the efficiency of treatment delivery. Statistical comparisons were performed using the Wilcoxon signed-rank test (p<0.05). For the PTV, there was no significant difference in the CI or HI between Gating20-70% and Non-GatingFB plans (CI: 1.337±0.137, 1.335±0.174, HI: 0.939±0.015, 0.939±0.016, all at p>0.05). However, there was a significant difference in GM between Gating20-70% and Non-GatingFB plan (1.528±0.206 cm, 1.381±0.222 cm, p<0.001). For OARs, all plans met the criteria for dose constraint. There was a significant difference between Gating20-70% and Non-GatingFB plans except in the spinal cord. In particular, D1000cc and D1500cc values for the ipsilateral lung for Gating20-70% plans were 31.6% and 59.9% lower than those for Non-GatingFB plans (D1000cc: 50.780±132.061 cGy, 34.755±102.480 cGy, p<0.001, D1500cc: 6.641±14.598 cGy, 2.666±7.926 cGy, p<0.001). Treatment delivery time was 92% longer for Gating20-70% plans than for Non-GatingFB plans (5.0±0.4 min, 9.6±3.3 min, p = 0.043). The total MU value for Gating20-70% plans was 9.6% higher than that for Non-GatingFB plans (3665.8±230.7, 4016±236.9, p = 0.039). When compared to OARs both plans were acceptable per RTOG-0915 protocol, but significant differences were between Non-GatingFB and Gating20-70% plans. However, treatment delivery time of Non-GatingFB plans decreased by 47.9% than Gating20-70% plans. We verified the feasibility of fast 4DCT-based O-ring LINAC treatment for patients who cannot endure long treatment times due to poor performance status in lung 4D-SBRT. In further study, we will analyze dosimetric differences and treatment delivery efficiency considering tumor motion according to tumor location.

Conventionally Fractionated vs. Hypofractionated Radiotherapy for Treatment of Unresectable Pancreatic Cancer: Local Control and Survival Outcomes in a Retrospective Single-Institutional Analysis

Unresectable pancreatic cancer (UPC) is associated with dismal survival outcomes, with a reported median survival of 8-12 months. The role of radiotherapy (RT) and the choice of optimal fractionation remains unclear. Our objective was analyzing the outcomes associated with local radiotherapy as well as determine the best radiotherapeutic approach to treat these patients. From a database of 209 radiation plans of patients treated for pancreatic cancer in a single institution between August 2007 to August 2021, patients with UPC were selected for this REB approved retrospective study. From the 209 plans, 136 unique patients were identified who had RT for UPC. The mean age of the cohort was 67.6 years, 10% were >80 years and 37% were female. Median follow-up was 9.3 months. 54 patients had distant metastases at the time of RT and were analyzed separately. Outcomes where analyzed based on whether patients received Conventionally fractionated RT (CFRT) (defined as >15 fractions) (n = 23 (17%)), Hypofractionated RT (HypoRT) (defined as ≤15 fractions and EQD2<40Gy for α/β = 3) (n = 40 (29%)) and those treated with Stereotactic Body RT (SBRT) (defined as ≤5 fractions and EQD2≥40Gy for α/β = 3) (n = 19 (14%)). The mean overall survival (OS) and freedom from progression (FFP) in the SBRT cohort was 17.2 and 7.4 months respectively, in the CFRT cohort was 22.6 and 9.9 months respectively and in the HypoRT cohort was 11.4 and 4.9 months respectively. All CFRT patients received chemotherapy. Mean OS was drastically lower in SBRT and HypoRT patients who did not receive any chemotherapy (11.9 and 3.4 months respectively). Patients with metastatic disease at presentation and receiving HypoRT had mean OS of 13.4 months. The average EQD2 for the cohorts were 45.4 Gy, 49.2 Gy and 30.3 Gy for CFRT, SBRT and HypoRT respectively. Our study demonstrates that CFRT with concurrent chemotherapy offers better therapeutic outcomes in patients with UPC compared to HypoRT. The role of dose escalated SBRT needs to be explored as an equal alternative.

Using kV Triggered Imaging and Liver Dome Position to Reduce the Dosimetric Error Caused by Breath Hold Variability for Liver Stereotactic Body Radiation Therapy

In a previous study, we demonstrated that manual gating using kV triggered imaging and liver dome position can reduce targeting errors caused by breath hold variability for liver stereotactic body radiation therapy (SBRT). In this study, we quantified the dosimetric error caused by breath hold variability and investigated the effect of liver dome gating on reducing dosimetric error. Twenty-five liver SBRT patients treated with deep inspiration breath-hold were included in this IRB approved study. Volumetric modulated arc therapy was used to deliver 30-60 Gy in 1-5 fractions. To verify the breath-hold reproducibility during treatment, a KV triggered image was acquired at the beginning of each breath-hold. The liver dome position was visually compared with the expected upper/lower liver boundaries created by expanding/contracting the liver contour 5mm in the superior-inferior direction. If the liver dome position was within the boundaries, delivery continued; otherwise, beam was held manually and the patient was instructed to take another breath hold until the liver dome position was within boundaries. To calculate delivered dose, for each fraction, the treatment plan was divided into sub-beams, each corresponding to one breath hold using delivery log files. The triggered images were registered to the planning CT to determine the liver position during each breath hold. Dose delivered during each breath hold was calculated by shifting the isocenter of the sub-beam according to the liver position. Breath holds discarded by gating were excluded since no dose was delivered during these breath holds. Delivered fractional doses were compared with planned fractional doses using GTV D99 and liver Dmean. To estimate delivered dose without gating, the first "corrective" breath hold taken after the discarded breath holds was replaced with the prior discarded breath hold and dose calculation was repeated. Seven hundred eleven triggered images from 91 treatment fractions were analyzed. Without gating, in 11 of the 91 fractions from 7 of the 25 patients, delivered GTV D99 reduced > 0.50 Gy from planned value (range 0.51-1.68 Gy, 3-10% of planned fractional GTV D99). Liver dome gating was able to detect/exclude irreproducible breath holds in 8 of the 11 fractions, increasing the delivered GTV D99 by 0.70 Gy per fraction on average (range 0.21-1.63 Gy). With liver dome gating, delivered fractional GTV D99 was comparable to planned value for all fractions (12.96 +/- 5.19 Gy vs 13.04 +/- 5.18 Gy, p > 0.05). Liver mean dose was not affected by breath hold variability or gating. Fractional liver Dmean was 2.26 +/- 1.19 Gy from plan, 2.27 +/- 1.21 Gy for delivery with gating and 2.27 +/- 1.20 Gy for delivery without gating. Breath hold variability may cause tumor underdose. Liver dome gating using kV triggered imaging reduces dosimetric error and ensures tumor coverage for liver SBRT.

Fracture Risk Following Lumbosacral Spine SBRT in Patients Having Received Previous Whole Pelvis Radiation Therapy

Stereotactic body radiation therapy (SBRT) for metastatic spinal disease provides local control with palliative effects1. Previous studies have demonstrated a posttreatment fracture rate range of roughly 5.7-39%2, with 14-17% the most commonly cited fracture risk range. However, the rate of spine fracture after lumbosacral SBRT in patients having received prior pelvic radiation therapy (RT) is unclear. The purpose of this study is to investigate the incidence of fracture in patients receiving lumbosacral spine SBRT following previous whole pelvic RT. This study was a single institution retrospective chart review. All lumbar and sacral spine SBRT cases over a 5-year period (from January 2018 through September 2022) with at least three months of post-treatment follow-up were identified. Patients having previously received pelvic RT were assessed; the development of a vertebral fracture was recorded as was the time to fracture and potential intervention (if any). A total of 35 lumbosacral spine SBRT cases were identified. Of those eight (23%) previously received whole pelvic RT, ranging from 20-70 Gy/5-35 fractions. Of the lumbosacral spine SBRT patients having received prior pelvic RT, two (25%) developed a fracture post-treatment. The average time to fracture was 7.5 months. Both fractures were treated with conservative management; neither required vertebroplasty/kyphoplasty or operative stabilization. The mean dose per SBRT fraction for patients who suffered a fracture (8.5 Gy) did not significantly differ from that for patients who did not suffer a fracture (9 Gy). In the first examination of lumbosacral fracture risk following SBRT to patients having received previous pelvic RT, the fracture rate in this patient population was 25%. Noteworthy is that the SBRT dose per fraction did not differ between patients having suffered a fracture versus those without fracture. These findings indicate that patients having received previous whole pelvis RT should be counseled on the potential increased risk of fracture; however, there is no evidence that decreasing SBRT dose per fraction reduces the likelihood of fracture in this patient population. This increased fracture rate is of concern, and further investigation in larger studies to identify potential risk factors for vertebral fracture such as systemic therapy, age and gender is warranted.

Dosimetric Risk Estimation of Chest Wall Pain Following 5-Fraction Lung Stereotactic Body Radiotherapy

Development of chest wall pain (CWP) following lung stereotactic body radiotherapy (SBRT) is a known toxicity, particularly for peripheral lesions. While CW V30 has been most consistently associated with development of post-SBRT CWP, existing series included heterogeneous dose-fractionation regimens, most commonly 48-54 Gy in 3-4 fractions. The present study aims to identify clinical and dosimetric variables associated with development of CWP among patients treated with 5 fraction lung SBRT. Intradepartmental quality assurance database of SBRT patients was queried to identify lung targets treated to a minimum of 45 Gy in 5 fractions. Retrospective chart and plan reviews were performed on these cases to collect patient, tumor, and treatment-related data, selecting for patients with peripheral lesions (any histology), and recording presence or absence of CWP during or following SBRT. Patients with less than 6 months of post-SBRT clinical follow-up were excluded. The CW was defined as a 2 cm expansion of the ipsilateral lung (inclusive of intercostal musculature, ribs, and superficial soft tissue). Logistic regression analyses were performed on continuous and nominal data to determine statistically significant (p<0.05) correlations between clinical (age, gender, known osteopenia/osteoporosis, diabetes, prior thoracic radiotherapy, lesion distance to CW), treatment (interval of SBRT delivery, dose prescribed), and dosimetric (Dose to 0.1/1/5/10cc; V30, V40) factors with CWP. Between February 2011 and January 2022, 93 patients were identified for inclusion in the present analysis, treated to 100 total lesions in 99 courses of treatment. Median patient age was 75 years (range 34-90), 48 (52%) were female, and 29 (of 99 treatment courses; 29%) had received prior thoracic radiotherapy. Median SBRT dose was 50 Gy (45-60), delivered over a median of 9 days (4-18). At a median post-SBRT follow-up of 21 months, 11 patients developed CWP at a median of 9 months post-SBRT (0-32). Statistically significant correlations were identified between CWP and known pre-existing osteopenia or osteoporosis, target distance to CW, and CW D0.1cc, D1cc, D5cc, and D10cc, but not CW V30 or V40. Crude risk of CWP for selected clinically practical dose-volume thresholds are presented in Table 1: CONCLUSION: For patients treated with lung SBRT in 5 fractions, dose to CW volume thresholds appears to correlate more closely than V30 or V40 for CWP estimation. Further investigation and validation of optimal CW volume thresholds, as well as integration of pre-existing condition clinical factors in risk estimation, appears warranted.

Stereotactic Body Radiotherapy (SBRT) for Adrenal Metastases: Practice Patterns at Community-Based Radiotherapy Centers

To analyze SBRT of adrenal metastases at free-standing centers within a large network in the USA, in order to guide institutional recommendations. We interrogated records of patients treated with SBRT to adrenal metastases from January 2019 to June 2022 from a database of 13,363 patients who were treated with SBRT at 21 community-based centers clustered into five regions within a network. We reported patient characteristics, frequency, survival rate, and biologically effective dose (BED10) prescribed, respiratory motion capture according to region and treatment year. Survival was calculated by Kaplan-Meier estimates. A total of 271 patients were treated to metastatic adrenal lesions (2.0% of all SBRT patients). Median age was 69.8 years (range 32-96). Frequency of treatment increased by an average of 4.5% per year over the period. Table 1 gives the frequency of primary tumor sites, histological types, and dose fractionations. It also shows the range of BED10 used. 91% received five fractions, and 6% received 3 fractions. Median BED10 was 72 Gy (mean 68.0 Gy SD = 18.7). The most common regimen was 8 Gy x 5 (n = 75, 28%), but ranged from 5 Gy x 5 (n = 20) to 10 Gy x 5 (n = 34). BED10 varied according to geographic region ranging from 61.2 Gy to 73.0 Gy (p = 0.01). Median BED was 72 or above in 2 of 5 regions and less than 72 in 3 regions. Respiratory motion capture simulation was done in 65.1% of cases and frequency varied across the 5 locations as shown in Table1 from 93.3% in region 1 to 41.7% in region 5 (p<.0001). 4D CT simulation was used in 46.2% of cases and use was relatively stable over time: 52.8% in July to December 2020 and 40.9% from January to June 2022 with no trend over time: p = .7635 At median follow-up 6.6 months (range 0.3-48.5), 203 (74.9%) of patients were alive with a median overall survival of 24.3 months. 1-year and 2-year survival was 72.7% and 51.5% respectively. Use of respiratory motion simulation was not significantly associated with survival p = 0.47. Despite variation in BED10 and respiratory motion management, 2-year overall survival was over 50% in patients treated with SBRT for adrenal metastases in a large community network. Further study will address refinement of recommendations regarding dose and other treatment characteristics and expansion of clinical research in this setting.

Lesion Dosimetry for [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy Combined with Stereotactic Body Radiotherapy in Patients with Oligometastatic Castration-Sensitive Prostate Cancer.

A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Methods: Six patients with 9 prostate-specific membrane antigen (PSMA)-positive oligometastases received 2 cycles of [177Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [177Lu]Lu-PSMA-617 (7.46 ± 0.15 GBq), patients underwent SPECT/CT at 3.2 ± 0.5, 23.9 ± 0.4, and 87.4 ± 12.0 h. Voxel-based dosimetry was performed with calibration factors (11.7 counts per second/MBq) and recovery coefficients derived from in-house phantom experiments. Lesions were segmented on baseline PSMA PET/CT (50% SUVmax). After a second cycle of [177Lu]Lu-PSMA-617 (44 ± 3 d; 7.50 ± 0.10 GBq) and an interim PSMA PET/CT scan, SBRT (27 Gy in 3 fractions) was delivered to all PSMA-avid oligometastatic sites, followed by post-PSMA PET/CT. RPT and SBRT voxelwise dose maps were scaled (α/β = 3 Gy; repair half-time, 1.5 h) to calculate the biologically effective dose (BED). Results: All patients completed the combination therapy without complications. No grade 3+ toxicities were noted. The median of the lesion SUVmax as measured on PSMA PET was 16.8 (interquartile range [IQR], 11.6) (baseline), 6.2 (IQR, 2.7) (interim), and 2.9 (IQR, 1.4) (post). PET-derived lesion volumes were 0.4-1.7 cm3 The median lesion-absorbed dose (AD) from the first cycle of [177Lu]Lu-PSMA-617 RPT (ADRPT) was 27.7 Gy (range, 8.3-58.2 Gy; corresponding to 3.7 Gy/GBq, range, 1.1-7.7 Gy/GBq), whereas the median lesion AD from SBRT was 28.1 Gy (range, 26.7-28.8 Gy). Spearman rank correlation, ρ, was 0.90 between the baseline lesion PET SUVmax and SPECT SUVmax (P = 0.005), 0.74 (P = 0.046) between the baseline PET SUVmax and the lesion ADRPT, and -0.81 (P = 0.022) between the lesion ADRPT and the percent change in PET SUVmax (baseline to interim). The median for the lesion BED from RPT and SBRT was 159 Gy (range, 124-219 Gy). ρ between the BED from RPT and SBRT and the percent change in PET SUVmax (baseline to post) was -0.88 (P = 0.007). Two cycles of [177Lu]Lu-PSMA-617 RPT contributed approximately 40% to the maximum BED from RPT and SBRT. Conclusion: Lesional dosimetry in patients with oligometastatic castration-sensitive prostate cancer undergoing [177Lu]Lu-PSMA-617 RPT followed by SBRT is feasible. Combined RPT and SBRT may provide an efficient method to maximize the delivery of meaningful doses to oligometastatic disease while addressing potential microscopic disease reservoirs and limiting the dose exposure to normal tissues.

Overall survival in low-comorbidity patients with stage I non–small cell lung cancer who chose stereotactic body radiotherapy compared to surgery

ObjectiveTo evaluate trends in the utilization of stereotactic body radiotherapy (SBRT) and to compare overall survival (OS) of patients with early-stage non–small cell lung cancer (NSCLC) undergoing SBRT versus those undergoing surgery. MethodsThe National Cancer Database was queried for patients without documented comorbidities who underwent surgical resection (lobectomy, segmentectomy, or wedge resection) or SBRT for clinical stage I NSCLC between 2012 and 2018. Peritreatment mortality and 5-year OS were compared among propensity score–matched cohorts. ResultsA total of 30,658 patients were identified, including 24,729 (80.7%) who underwent surgery and 5929 (19.3%) treated with SBRT. Between 2012 and 2018, the proportion of patients receiving SBRT increased from 15.9% to 26.0% (P < .001). The 30-day mortality and 90-day mortality were higher among patients undergoing surgical resection versus those receiving SBRT (1.7% vs 0.3%, P < .001; 2.8% vs 1.7%, P < .001). In propensity score–matched patients, OS favored SBRT for the first several months, but this was reversed before 1 year and significantly favored surgical management in the long term (5-year OS, 71.0% vs 41.8%; P < .001). The propensity score–matched analysis was repeated to include only SBRT patients who had documented refusal of a recommended surgery, which again demonstrated superior 5-year OS with surgical management (71.4% vs 55.9%; P < .001). ConclusionsSBRT is being increasingly used to treat early-stage lung cancer in low-comorbidity patients. However, for patients who may be candidates for either treatment, the long-term OS favors surgical management.

Static couch non-coplanar arc selection optimization for lung SBRT treatment planning

Objective. Non-coplanar arc geometry optimizations that take advantage of beam’s eye view (BEV) geometric overlap information have been proven to reduce dose to healthy organs-at-risk (OARs). Recently, a metric called mean arc distance (MAD) has been developed that quantifies the arc geometry sampling of 4π space. The purpose of this research is to combine improved BEV overlap information with MAD to generate static couch lung stereotactic body radiotherapy (SBRT) treatment plans deliverable on a C-arm linear accelerator. Approach. An algorithm utilizing the Moller–Trumbore ray-triangle intersection method was employed to compute a cost surrogate for dose to overlapping OARs using distances interpolated onto a PDD. Cost was combined with MAD for 100 000 random combinations of arc trajectories. A pathfinding algorithm for arc selection was created, balancing the contributions of MAD and 4π cost for the final trajectory. This methodology was evaluated for 18 lung SBRT patients. Cases were also planned with arcs from a clinical treatment template protocol for dosimetric and plan quality comparison. Results were evaluated using dose constraints in the context of RTOG0915. Main results. Five of six OARs had maximum dose reductions when planned with the arc trajectory optimization algorithm. Significant maximum dose reductions were found for esophagus (7.41 ± 0.91 Gy, p = 0.00019), trachea (5.56 ± 1.55 Gy, p = 0.0025), spinal cord (2.87 ± 1.13 Gy, p = 0.039), large bronchus (3.47 ± 1.49 Gy, p = 0.0075), and aorta (3.13 ± 0.99 Gy, p = 0.012). Mean dose to contralateral lung was also significantly reduced (0.50 ± 0.06 Gy, p = 0.00019). There were two significant increases in OAR doses: mean dose to ipsilateral lung (0.40 ± 0.09, p = 0.00086) and V5Gy to ipsilateral lung (1.95 ± 0.70%, p = 0.011). Paddick conformity index increased by 0.03 ± 0.02 (p = 0.14), remaining below a limit of 1.2 for both techniques. Significance. Static couch non-coplanar optimization yielded maximum dose reductions to OARs while maintaining target conformity for lung SBRT.

Checkpoint Inhibitors in Combination With Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors

Although immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and PD-1 ligand 1 have improved the outcome for many cancer types, the majority of patients fails to respond to ICI monotherapy. Hypofractionated radiotherapy has the potential to improve the therapeutic ratio of ICIs. To assess the addition of radiotherapy to ICIs compared with ICI monotherapy in patients with advanced solid tumors. This open-label, multicenter, randomized phase 2 trial was conducted in 5 Belgian hospitals and enrolled participants between March 2018 and October 2020. Patients 18 years or older with locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, or non-small cell lung carcinoma were eligible. A total of 99 patients were randomly assigned to either the control arm (n = 52) or the experimental arm (n = 47). Of those, 3 patients (1 in the control arm vs 2 in the experimental arm) withdrew consent and thus were not included in the analysis. Data analyses were performed between April 2022 and March 2023. Patients were randomized (1:1) to receive anti-PD-1/PD-1 ligand 1 ICIs alone as per standard of care (control arm) or combined with stereotactic body radiotherapy 3 × 8 gray to a maximum of 3 lesions prior to the second or third ICI cycle, depending on the frequency of administration (experimental arm). Randomization was stratified according to tumor histologic findings and disease burden (3 and fewer or more than 3 cancer lesions). The primary end point was progression-free survival (PFS) as per immune Response Evaluation Criteria in Solid Tumors. Key secondary end points included overall survival (OS), objective response rate, local control rate, and toxic effects. Efficacy was assessed in the intention-to-treat population, while safety was evaluated in the as-treated population. Among 96 patients included in the analysis (mean age, 66 years; 76 [79%] female), 72 (75%) had more than 3 tumor lesions and 65 (68%) had received at least 1 previous line of systemic treatment at time of inclusion. Seven patients allocated to the experimental arm did not complete the study-prescribed radiotherapy course due to early disease progression (n = 5) or intercurrent illness (n = 2). With a median (range) follow-up of 12.5 (0.7-46.2) months, median PFS was 2.8 months in the control arm compared with 4.4 months in the experimental arm (hazard ratio, 0.95; 95% CI, 0.58-1.53; P = .82). Between the control and experimental arms, no improvement in median OS was observed (11.0 vs 14.3 months; hazard ratio, 0.82; 95% CI, 0.48-1.41; P = .47), and objective response rate was not statistically significantly different (22% vs 27%; P = .56), despite a local control rate of 75% in irradiated patients. Acute treatment-related toxic effects of any grade and grade 3 or higher occurred in 79% and 18% of patients in the control arm vs 78% and 18% in the experimental arm, respectively. No grade 5 adverse events occurred. This phase 2 randomized clinical trial demonstrated that while safe, adding subablative stereotactic radiotherapy of a limited number of metastatic lesions to ICI monotherapy failed to show improvement in PFS or OS. ClinicalTrials.gov Identifier: NCT03511391.

Local disease control after stereotactic body radiotherapy in patients with neuroendocrine neoplasms: a cohort study

Background Neuroendocrine neoplasms represent a diverse group of malignancies. Anatomic origin, histology and aggressiveness vary extensively, from low-grade tumours with an indolent prognosis to highly aggressive conditions with poor outcome. Surgery, with a curative intent, is the standard of treatment when possible. Other treatment regimens include local treatment, or systemic therapy. The role of radiotherapy in treating neuroendocrine neoplasms is not yet established, but studies indicate that a high rate of local control can be achieved by high-dose radiotherapy. Stereotactic body radiotherapy (SBRT) is high dose of radiation delivered to a small volume. We aimed to investigate the one-year local control rate of SBRT in patients with neuroendocrine neoplasms. Material and Methods Patients with neuroendocrine neoplasms treated with SBRT between 2003 and 2021 were retrospectively identified. Patient characteristics and SBRT-details were collected by review of patient records and the radiotherapy planning charts. All types except for small cell lung cancer and brain metastases were allowed. The prescribed dose was 45–67.8 Gy in three fractions. Progression, both within the target-site and in other sites, was determined based on existing imaging reports. One-year local control rate and systemic control rate was calculated. Descriptive analyses of local response duration, progression-free survival and overall survival were performed. Results Twenty-one patients were included. The one-year local control rate was 94%. Four of the patients had local progression. All patients receiving SBRT towards their primary tumour (n = 11) had a bronchopulmonary neuroendocrine neoplasm, and a one-year local control rate of 100%. In patients treated at a metastatic target, 80% developed systemic progression but the local control remained high. Conclusion Our study suggests that SBRT may offer a feasible and effective treatment of neuroendocrine neoplasms in selected cases. SBRT provides long-term local stability and may be useful in treating patients with localised disease not fit for surgery.

Association of circulating CD103+ T cells with major pathological response in a randomized phase 2 trial of neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small cell lung cancer.

8550 Background: We previously reported results of a randomized phase 2 study, demonstrating a higher rate of major pathological response to durvalumab in combination with stereotactic body radiotherapy (SBRT) compared to durvalumab alone in patients with localized (stage I-IIIA) non-small cell lung cancer (NSCLC). Biomarkers of response in NSCLC are poorly understood. To address this, we evaluated sequentially collected peripheral blood mononuclear cells (PBMCs) from study participants to identify easily accessible biomarkers associated with major pathological responses. Methods: PBMCs were obtained from study participants at defined pre-treatment, peri-operative, and post-operative timepoints. We performed 25-marker spectral flow cytometric analysis of the T cell compartment in these samples and used dimensionality reduction and clustering programs to identify populations of interest. Results: Our analysis of these samples revealed populations of both CD4+ and CD8+ T cells with hallmarks of prior antigen exposure and tissue residency (CD103+, CCR7-, CD45RA-), suggesting tumor-experienced T cells circulating into the blood. Greater pre-treatment frequency of these T cell populations was associated with major pathological responses to neoadjuvant therapy. This observation was consistent when evaluating patients with major pathological responses across both treatment arms, and within the durvalumab plus SBRT group, where we had enough patients with major pathological responses. Maturation of disease-free survival data from this trial will enable us to evaluate the association of these biomarkers with long-term survival. Conclusions: Together, these data reveal an unexpected population of T cells in the peripheral blood with features of tissue-residency, which are associated with major pathological responses, and suggest that re-circulation of tumor-experienced T cells may represent a predictive biomarker for neoadjuvant treatment of NSCLC.

Online verification of breath-hold reproducibility using kV-triggered imaging for liver stereotactic body radiation therapy.

To introduce a new technique for online breath-hold verification for liver stereotactic body radiation therapy (SBRT) based on kilovoltage-triggered imaging and liver dome positions. Twenty-five liver SBRT patients treated with deep inspiration breath-hold were included in this IRB-approved study. To verify the breath-hold reproducibility during treatment, a KV-triggered image was acquired at the beginning of each breath-hold. The liver dome position was visually compared with the expected upper/lower liver boundaries created by expanding/contracting the liver contour 5 mm in the superior-inferior direction. If the liver dome was within the boundaries, delivery continued; otherwise, beam was held manually, and the patient was instructed to take another breath-hold until the liver dome fell within boundaries. The liver dome was delineated on each triggered image. The mean distance between the delineated liver dome to the projected planning liver contour was defined as liver dome position error edome . The mean and maximum edome of each patient were compared between no breath-hold verification (all triggered images) and with online breath-hold verification (triggered images without beam-hold). Seven hundred thirteen breath-hold triggered images from 92 fractions were analyzed. For each patient, an average of 1.5 breath-holds (range 0-7 for all patients) resulted in beam-hold, accounting for 5% (0-18%) of all breath-holds; online breath-hold verification reduced the mean edome from 3.1 mm (1.3-6.1 mm) to 2.7 mm (1.2-5.2 mm) and the maximum edome from 8.6 mm (3.0-18.0 mm) to 6.7 mm (3.0-9.0 mm). The percentage of breath-holds with edome >5 mm was reduced from 15% (0-42%) without breath-hold verification to 11% (0-35%) with online breath-hold verification. online breath-hold verification eliminated breath-holds with edome >10 mm, which happened in 3% (0-17%) of all breath-holds. It is clinically feasible to monitor the reproducibility of each breath-hold during liver SBRT treatment using triggered images and liver dome. Online breath-hold verification improves the treatment accuracy for liver SBRT.

Transperineal ultrasound is a good alternative for intra-fraction motion monitoring for prostate stereotactic body radiotherapy.

To report our experience in a prospective study of implementing a transperineal ultrasound system to monitor intra-fractional prostate motion for prostate stereotactic body radiotherapy (SBRT). This IRB-approved prospective study included 23 prostate SBRT patients treated between 04/2016 and 11/2019 at our institution. The prescription doses were 36.25Gy to the Low-Dose planning target volume (LD-PTV) and 40Gy to the High-Dose PTV (HD-PTV) in five fractions with 3mm planning margins. The transperineal ultrasound system was successfully used in 110 of the 115 fractions. For intra-fraction prostate motion, the real-time prostate displacements measured by ultrasound were exported for analysis. The percentage of time prostate movement exceeded a 2mm threshold was calculated for each fraction of all patients. T-test was used for all statistical comparisons. Ultrasound image quality was adequate for prostate delineation and prostate motion tracking. The setup time for each fraction under ultrasound-guided prostate SBRT was 15.0±4.9 min and the total treatment time per fraction was 31.8±10.5 min. The presence of an ultrasound probe did not compromise the contouring of targets or critical structures. For intra-fraction motion, prostate movement exceeded 2mm tolerance in 23 of 110 fractions for 11 of 23 patients. For all fractions, the mean percentage of time when the prostate moved more than 2mm in any direction during each fraction was 7%, ranging from 0% to 62% of a fraction. Ultrasound-guided prostate SBRT is a good option for intra-fraction motion monitoring with clinically acceptable efficiency.

Safety and clinical efficacy of immune checkpoint inhibition and stereotactic body radiotherapy in patients with spine metastasis.

Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment of patients with many tumor histologies. Simultaneously, stereotactic body radiotherapy (SBRT) provides excellent local control (LC) and plays an important role in the management of spine metastasis. Promising preclinical work suggests the potential therapeutic benefit of combining SBRT with ICI therapy, but the safety profile of combined therapy is unclear. This study aimed to evaluate the toxicity profile associated with ICI in patients receiving SBRT and, secondarily, whether ICI administration sequence with respect to SBRT affects LC or overall survival (OS) outcomes. The authors retrospectively reviewed patients with spine metastasis treated with SBRT at an academic center. Patients who received ICI at any point during their disease course were compared to those with the same primary tumor types who did not receive ICI by using Cox proportional hazards analyses. Primary outcomes were long-term sequelae, including radiation-induced spinal cord myelopathy, esophageal stricture, and bowel obstruction. Secondarily, models were created to evaluate OS and LC in the cohort. Two hundred forty patients who received SBRT to 299 spine metastases were included in this study. The most common primary tumor types were non-small cell lung cancer (n = 59 [24.6%]) and renal cell carcinoma (n = 55 [22.9%]). One hundred eight patients received at least 1 dose of ICI, with the most common regimen being single-agent anti-PD-1 (n = 80 [74.1%]), followed by combination CTLA-4/PD-1 inhibitors (n = 19 [17.6%]). Three patients experienced long-term radiation-induced sequelae: 2 had esophageal stricture and 1 had bowel obstruction. No patients developed radiation-induced myelopathy. There was no association between receipt of ICI and development of any of these adverse events (p > 0.9). Similarly, ICI was not significantly associated with either LC (p = 0.3) or OS (p = 0.6). In the entire cohort, patients who received ICI prior to beginning SBRT had worse median survival, but ICI sequence with respect to SBRT was not significantly prognostic of either LC (p > 0.3) or OS (p > 0.07); instead, baseline performance status was most predictive of OS (HR 1.38, 95% CI 1.07-1.78, p = 0.012). Treatment regimens that combine ICIs before, concurrent with, and after SBRT for spine metastases are safe, with minimal risk for increased rates of long-term toxicity.

Multicenter retrospective study of stereotactic body radiotherapy for patients with previously untreated initial small hepatocellular carcinoma.

We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study. Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5cm in diameter; (3) Child-Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence-free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT. Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77years (range: 50-89years), and the median tumor size was 23mm (range: 6-50mm). The median radiation dose was 40Gy (range: 35-60Gy) in five fractions (range: 4-8). The median follow-up period was 45months (range: 0-103months). The 3-year overall survival, recurrence-free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%-81%), 57.9% (95% CI: 45.2%-70.5%), and 20.0% (95% CI: 11.2%-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed. SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment.

The use of a thin guide-wire for urethral definition in prostate SBRT treatments with Cyberknife.

To study and analyze the effect of the use of a thin guide-wire instead of a Foley catheter for urethral definition in prostate stereotactic body radiation therapy (SBRT) treatments and to compare treatment parameters in both situations. Thirty-seven prostate SBRT patients were employed in this study. A Foley catheter was employed in nine of them, and a guide-wire was employed in the other 28 patients. For each of the 28 patients in which the guide-wire was employed, a comparison between urethral positions in both situations was performed, allowing for a margin definition of the urethra when a Foley catheter was employed. Displacements of the prostate during treatment were obtained, allowing for an analysis of prostate positions in both situations. Also, different treatment parameters such as the number of treatment interruptions, couch movements performed, and x-rays needed were gathered. Large differences between urethral positions can be found in the anterior-posterior (AP) directions compared to those in the lateral (LAT) direction. Differences are also larger in areas closer to the base of the prostate, where margins applied in the case of using a Foley catheter are 16mm with a mean displacement of 6mm in the posterior direction. No differences in the treatment parameters were found during treatment in both situations. The difference found in absolute prostate pitch rotations suggests that the Foley catheter provokes a shift of the prostate position, which does not occur when employing the guide-wire. Foley catheters shift the urethral position, making them a wrong surrogate of the urethra when no catheters are present. The margins needed to assess uncertainties introduced by the use of a Foley catheter are larger than those usually applied. The use of a Foley catheter did not present any additional difficulty during treatment delivery in terms of images employed or interruptions produced.

Estimation of patient-size dependent imaging dose for stereoscopic/monoscopic real-time kV image guidance in lung and prostate SBRT

Purpose. The purpose of this work is to quantify the dependence of patient-specific imaging dose on patient-size from ExacTrac stereoscopic/monoscopic real-time tumor monitoring during lung and prostate stereotactic body radiotherapy (SBRT). Approach. Thirty lung and 30 prostate SBRT patients that were treated with volumetric modulated arc therapy (VMAT) were selected and divided into three patient size categories. Imaging doses from all SBRT fractions were calculated retrospectively assuming patients went through real-time tumor monitoring during their actual VMAT treatment times. Treatment times were divided into periods of stereoscopic and monoscopic real-time imaging depending on the imaging view with linac gantry blockage. The computed tomography (CT) images and contours of the planning target volume (PTV) and organs at risk (OARs) were exported from the treatment planning system. Based on the CT data, patient-specific 3D imaging dose distributions were calculated in a validated Monte Carlo model using DOSEXYZnrc. Vendor-recommended imaging protocols (lung: 120–140 kV, 16–25 mAs; prostate: 110–130 kV, 25 mAs) were used for each patient size category. Patient-specific imaging doses received by PTV and OARs were evaluated using dose volume histograms, dose delivered to 50% of organ volume (D50), and 2% of organ volume (D2). Results. Bone and skin received the highest imaging dose. For the lung patients, the highest D2 for bone and skin were 4.30% and 1.98% of the prescription dose respectively. For prostate patients, the highest D2 were 2.53% and 1.35% of the prescription for bone and skin. Additional imaging dose to PTV as a percentage of the prescribed dose was at most 2.42% for lung and 0.29% for prostate patients. T-test results showed statistically significant difference in D2 and D50 between at least two patient size categories for PTVs and all the OARs. Larger patients received more skin dose in both lung and prostate patients. For the internal OARs, larger patients received more dose in lung treatment while the trend was opposite in prostate treatment. Conclusion. Patient-specific imaging dose was quantified for monoscopic/stereoscopic real-time kV image guidance in lung and prostate patients with respect to patient size. Additional skin dose was 1.98% (in lung patients) and 1.35% (in prostate patients) of the prescription which is within 5% recommended value by the AAPM Task Group 180. For internal OARs, larger patients received more dose in lung patients while the trend was the opposite for prostate patients. Patient size was an important factor to determine additional imaging dose.