Stereotactic Body Radiation Therapy Patients Research Articles

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.

Repeat stereotactic body radiotherapy for oligometastatic disease

BackgroundPatients with oligometastatic disease (OMD) treated with metastasis-directed definitive local therapy such as stereotactic body radiotherapy (SBRT) are at risk of developing new metastases. Here, we compare characteristics and outcomes of patients treated with a single course and repeat SBRT. Materials/MethodsOMD patients treated with SBRT to 1–5 metastases were included in this retrospective study, and classified as single course or repeat SBRT. Progression-free survival (PFS), widespread failure-free survival (WFFS), overall survival (OS), systemic therapy-free survival (STFS) and cumulative incidence of different first failures were analyzed. Patient and treatment characteristics predicting the use of repeat SBRT were investigated using univariable and multivariable logistic regression. ResultsAmong the 385 patients included, 129 and 256 received repeat or single course SBRT, respectively. The most common primary tumor and OMD state in both groups were lung cancer and metachronous oligorecurrence. Patients treated with repeat SBRT had shorter PFS (p < 0.0001), while WFFS (p = 0.47) and STFS (p = 0.22) were comparable. Distant failure, particularly with a single metastasis, was more frequently observed in repeat SBRT patients. Repeat SBRT patients had longer median OS (p = 0.01). On multivariable logistic regression, low distant metastases velocity and more previous lines of systemic therapy significantly predicted the use of repeat SBRT. ConclusionDespite shorter PFS and comparable WFFS and STFS, repeat SBRT patients had longer OS. The role of repeat SBRT for OMD patients warrants further prospective investigation, focussing on predictive factors to select patients that might derive a benefit.

Reproducibility of surface-based deep inspiration breath-hold technique for lung stereotactic body radiotherapy on a closed-bore gantry linac.

Tumor motion and delivery efficiency are two main challenges of lung stereotactic body radiotherapy (SBRT). The present work implemented the deep inspiration breath hold technique (DIBH) with surface guided radiation therapy (SGRT) on closed-bore linacs and investigated the correlation between SGRT data and internal target position. Thirteen lung SBRT patients treated in DIBH using a closed-bore gantry linac and a ring-mounted SGRT system were retrospectively analysed. Visual coaching was used to achieve DIBH with a±1mm threshold window in the anterior-posterior direction. Three kV-CBCTs were added to the treatment workflow and examined offline to verify intra-fraction tumor position. Surface-based DIBH was analysed using SGRT treatment reports and an in-house python script. Data from 73 treatment sessions and 175kV-CBCTs were studied. Correlations between target and surface positions were studied with Linear Mixed Models. Median intra-fraction tumor motion was 0.8mm (range: 0.7-1.3 mm) in the anterior-posterior direction, 1.2mm (range: 1-1.7 mm) in the superior-inferior direction, and 1mm (range: 0.7-1.1 mm) in the left-right direction, with rotations of <1° (range: 0.6°-1.1°) degree in all three directions. Planned target volumes and healthy lung volumes receiving 12.5Gy and 13.5Gy were reduced on average by 67% and 54%, respectively. Lung SBRT in DIBH with the ring-mounted SGRT system proved reproducible. The surface monitoring provided by SGRT was found to be a reliable surrogate for internal target motion. Moreover, the implementation of DIBH technique helped reduce target volumes and lung doses.

Clinical Outcome of Stereotactic Body Radiotherapy in Patients with Early-Stage Lung Cancer with Ground-Glass Opacity Predominant Lesions: A Single Institution Experience.

The detection rate of early-stage lung cancer with ground-glass opacity (GGO) has increased, and stereotactic body radiotherapy (SBRT) has been suggested as an alternative to surgery in inoperable patients. However, reports on treatment results are limited. Therefore, we performed a retrospective study to investigate the clinical outcome after SBRT in patients with early-stage lung cancer with GGO-predominant tumor lesions at a single institution. This study included 89 patients with 99 lesions who were treated with SBRT for lung cancer with GGO-predominant lesions that had a consolidation-to-tumor ratio of ≤0.5 at Asan Medical Center between July 2016 and July 2021. A median total dose of 56.0 Gy (range, 48.0-60.0) was delivered using 10.0-15.0 Gy per fraction. The overall follow-up period for the study was median 33.0 months (range, 9.9 to 65.9 months). There was 100% local control with no recurrences in any of the 99 treated lesions. Three patients had regional recurrences outside of the radiation field, and three had distant metastasis. The 1-year, 3-year, and 5-year overall survival rates were 100.0%, 91.6%, and 82.8%, respectively. Univariate analysis revealed that advanced age and a low level of diffusing capacity of the lungs for carbon monoxide were significantly associated with overall survival. There were no patients with grade ≥3 toxicity. SBRT is a safe and effective treatment for patients with GGO-predominant lung cancer lesions and is likely to be considered as an alternative to surgery.

Impact of Postoperative Stereotactic Body Radiation Therapy on Survival of Patients with Spinal Metastases in the Context of Additional Systemic Adjuvant Therapy

Stereotactic body radiotherapy (SBRT) has been established as a safe and effective treatment modality for control of long-term pain and tumor growth. However, few studies have investigated the efficacy of postoperative SBRT versus conventional external beam radiation therapy (EBRT) in extending survival within the context of systemic therapy. A retrospective chart review of patients who underwent surgery for spinal metastasis at our institution was conducted. Demographic, treatment and outcome data were collected. SBRT was compared with EBRT and non-SBRT, and analyses were stratified by whether or not patients received systemic therapy. Survival analysis was conducted using propensity score matching. Bivariate analysis in the non-systemic therapy group revealed longer survival with SBRT compared to EBRT and non-SBRT. Further analysis also showed that primary cancer type and preoperative mRS significantly affected survival. Within patients who received systemic therapy, overall median survival for SBRT patients was 22.7 months (95% CI: 12.1 - 52.3) versus 16.1 months (95% CI: 12.7 - 44.0; p = 0.28) for EBRT patients and 16.1 months (95% CI: 12.2 - 21.9; p = 0.07) for non-SBRT patients. Within patients who did not receive systemic therapy, overall median survival for SBRT patients was 62.1 months (95% CI: 18.1 - unknown) versus 5.3 months (95% CI: 2.8 - unknown; p = 0.08) for EBRT patients and 6.9 months (95% CI: 5.0 - 45.6; p = 0.02) for non-SBRT patients. In patients who do not receive systemic therapy, treatment with postoperative SBRT may increase survival time compared to patients not receiving SBRT.