Stereotactic Body Radiation Therapy Patients Research Articles

Dynamic liver volume change in predicting hepatic decompensation and long-term effects of stereotactic body radiation therapy.

This study aimed to investigate the association between liver volume change and hepatic decompensation and compare the risk of hepatic decompensation in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) who underwent stereotactic body radiation therapy (SBRT). A retrospective review of SBRT-treated HCC and compensated LC without HCC patients was conducted. Liver volume was measured using auto-segmentation software on liver dynamic computed tomography scans. The decompensation event was defined as the first occurrence of refractory ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. We evaluated the association between the rate of liver volume decrease and hepatic decompensation and compared decompensation events between the SBRT and LC cohorts using propensity score matching. A total of 138 patients from the SBRT cohort and 488 from the LC cohort were analyzed. The rate of liver volume decrease was associated with the risk of decompensation events in both cohorts. The 3-year rate of decompensation events was significantly higher in the group with a liver volume decreasing rate>7%/year compared with the group with a rate<7%/year. In the propensity score-matched cohort, the 3-year rate of decompensation events after a single session of SBRT was not significantly different from that in the LC cohort. The rate of liver volume decrease was significantly associated with the risk of hepatic decompensation in both HCC patients who received SBRT and LC patients. A single session of SBRT for HCC did not result in a higher decompensation rate compared with LC.

Assessment of stereotactic high-resolution detectors for stereotactic body radiotherapy: comparative analysis between myQA® SRS and Gafchromic EBT-XD films.

The study aimed to evaluate dosimetry systems used for stereotactic body radiotherapy (SBRT), specifically 2D array dosimetry and film dosimetry systems, for exploring their characteristics and clinical suitability. For this, high-resolution myQA SRS detectors and Gafchromic EBT-XD films were employed. Film analysis included net optical density (OD) values depending on energy, dose rate, scanner orientation, scanning side, and post-exposure growth. For myQA SRS, signal values were evaluated in terms of dose rate (400-1400 MU/min) and angular dependence (0-180° at 30° intervals) along with couch angles of 0°, 45°, and 90°. Pre-treatment verification included 32 SBRT patients for whom myQA SRS results were compared with those obtained with Gafchromic EBT-XD films. Analysis revealed less than 1% deviation in net OD for energy and dose rate dependence. Scanner orientation caused 2.5% net OD variation, with minimal differences between film front and back scan orientations (variance < 1.0%). A rapid OD rise occurred within six hours post-exposure, followed by gradual increase. The myQA SRS detector showed -3.7% dose rate dependence (400 MU/min), while the angular dependence at 90° was -26.7%. A correction factor effectively reduced these differences to < 1%. For myQA SRS, gamma passing rates were-93.6% (2%/1mm), while those for EBT-XD films were-92.8%. Improved rates were observed with 3%/1mm: for myQA SRS-97.9%, and for EBT-XD film-98.16%. In contrast, for 2%/2mm with 10% threshold, for myQA SRS-97.7% and for EBT-XD film-98.97% were obtained. It is concluded that both myQA SRS detectors and EBT-XD films are suitable for SBRT pre-treatment verification, ensuring accuracy and reliability. However, myQA SRS detectors are preferred over EBT-XD film due to the fact that they offer real-time measurements and user-friendly features.

Comparison of Treatment Outcomes Between Thoracoscopic Surgery and Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer.

Objective: To compare the risk of death, tumor recurrence, metastasis, and disease progression in early-stage non-small cell lung cancer (NSCLC) patients treated with thoracoscopic surgery and stereotactic body radiotherapy (SBRT). Methods: Patients who underwent radical surgery and SBRT for NSCLC between April 2010 and November 2021 were retrospectively analyzed. Continuous and categorical variables were compared using the Mann-Whitney U and Chi-square test, respectively. Kaplan-Meier curves were used to evaluate the survival outcomes of each patient group. Cox proportional hazard regression analyses were performed to estimate the risk of death, tumor recurrence, metastasis, and disease progression. Results: A total of 167 patients were enrolled, of whom 75 and 92 underwent SBRT and surgery, respectively. The median follow-up was 45 months (range, 4-105 months). SBRT patients were observed to be significantly older (median, 76.0 vs 67.0 years; P < .001), and associated with significantly higher mortality rate (42.7% vs 26.1%, P = .024). However, no significant difference in overall survival duration was seen between the SBRT and surgery groups (45.0 vs 41.0 months; P = .199). SBRT patients demonstrated significantly lower rates of metastasis (12.0% vs 30.4%, P = .004), and significantly longer metastasis-free survival (39.0 months vs 35.5 months, P = .020). The remaining outcomes, including tumor recurrence and disease progression rates, were similar between the groups. Compared to surgery, SBRT did not significantly associate with death, recurrence, or disease progression. Kaplan-Meier curves showed significant differences in overall, tumor recurrence-free, and disease progression-free survival between the groups (log-rank P < .05). Conclusions: SBRT demonstrated similar overall survival compared to radical surgery, and associated with significantly reduced risk of tumor metastasis. Our study thereby suggests SBRT as the best treatment option for patients with inoperable NSCLC.

Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study

Most patients with metastatic cancer eventually develop resistance to systemic therapy, with some having limited disease progression (ie, oligoprogression). We aimed to assess whether stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites could improve patient outcomes. We did a phase 2, open-label, randomised controlled trial of SBRT in patients with oligoprogressive metastatic breast cancer or non-small-cell lung cancer (NSCLC) after having received at least first-line systemic therapy, with oligoprogression defined as five or less progressive lesions on PET-CT or CT. Patients aged 18 years or older were enrolled from a tertiary cancer centre in New York, NY, USA, and six affiliated regional centres in the states of New York and New Jersey, with a 1:1 randomisation between standard of care (standard-of-care group) and SBRT plus standard of care (SBRT group). Randomisation was done with a computer-based algorithm with stratification by number of progressive sites of metastasis, receptor or driver genetic alteration status, primary site, and type of systemic therapy previously received. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, measured up to 12 months. We did a prespecified subgroup analysis of the primary endpoint by disease site. All analyses were done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03808662, and is complete. From Jan 1, 2019, to July 31, 2021, 106 patients were randomly assigned to standard of care (n=51; 23 patients with breast cancer and 28 patients with NSCLC) or SBRT plus standard of care (n=55; 24 patients with breast cancer and 31 patients with NSCLC). 16 (34%) of 47 patients with breast cancer had triple-negative disease, and 51 (86%) of 59 patients with NSCLC had no actionable driver mutation. The study was closed to accrual before reaching the targeted sample size, after the primary efficacy endpoint was met during a preplanned interim analysis. The median follow-up was 11·6 months for patients in the standard-of-care group and 12·1 months for patients in the SBRT group. The median progression-free survival was 3·2 months (95% CI 2·0-4·5) for patients in the standard-of-care group versus 7·2 months (4·5-10·0) for patients in the SBRT group (hazard ratio [HR] 0·53, 95% CI 0·35-0·81; p=0·0035). The median progression-free survival was higher for patients with NSCLC in the SBRT group than for those with NSCLC in the standard-of-care group (10·0 months [7·2-not reached] vs 2·2 months [95% CI 2·0-4·5]; HR 0·41, 95% CI 0·22-0·75; p=0·0039), but no difference was found for patients with breast cancer (4·4 months [2·5-8·7] vs 4·2 months [1·8-5·5]; 0·78, 0·43-1·43; p=0·43). Grade 2 or worse adverse events occurred in 21 (41%) patients in the standard-of-care group and 34 (62%) patients in the SBRT group. Nine (16%) patients in the SBRT group had grade 2 or worse toxicities related to SBRT, including gastrointestinal reflux disease, pain exacerbation, radiation pneumonitis, brachial plexopathy, and low blood counts. The trial showed that progression-free survival was increased in the SBRT plus standard-of-care group compared with standard of care only. Oligoprogression in patients with metastatic NSCLC could be effectively treated with SBRT plus standard of care, leading to more than a four-times increase in progression-free survival compared with standard of care only. By contrast, no benefit was observed in patients with oligoprogressive breast cancer. Further studies to validate these findings and understand the differential benefits are warranted. National Cancer Institute.

Feasibility of fast, four-dimensional computed tomography-based O-ring LINAC plans for lung stereotactic body radiotherapy in patients with poor performance status

PurposeWe aimed to retrospectively analyzed the feasibility of fast four-dimensional computed tomography (4DCT)-based O-ring LINAC treatment for patients with an average respiratory amplitude was&amp;lt; 0.5 cm and who cannot endure long treatment times due to poor performance status in lung 4D-stereotactic body radiotherapy (SBRT).MethodsThis study included data of 38 patients who received lung 4D-SBRT and had average respiratory amplitude&amp;lt; 0.5 cm in the full phase. C-arm LINAC plans were based on 4DCT data obtained at phase values ranging from 20–70% using a C-arm LINAC. O-ring LINAC plans were retrospectively established based on 4DCT data obtained at phase values of 0–90% using an O-ring LINAC. The conformity index (CI), homogeneity index (HI), and gradient measurement of the planning target volumes (PTV) were analyzed to compare dosimetric data between C-arm LINAC and O-ring LINAC plans. Organs at risk were analyzed in accordance with the Radiation Therapy Oncology Group 0915 protocol. Treatment delivery time and total monitor units were analyzed to compare the efficiency of treatment delivery. Statistical comparisons were performed using the Wilcoxon signed-rank test (P&amp;lt; 0.05).ResultsFor the PTV, there was no significant difference in the CI or HI between C-arm LINAC and O-ring LINAC plans. For organs-at-risk, all plans met the criteria for dose constraint. There was a significant difference between C-arm LINAC and O-ring LINAC plans except in the spinal cord. Treatment delivery time was 92% longer for C-arm LINAC plans than for O-ring LINAC plans. The total MU value for C-arm LINAC plans was 9.6% higher than that for O-ring LINAC plans.ConclusionWe verified the feasibility of fast 4DCT-based O-ring LINAC treatment for patients with average respiratory amplitude&amp;lt; 0.5 cm and who cannot endure long treatment times due to poor performance status in lung 4D-SBRT.

SBRT vs. Y90: HCC Treatment Outcomes and Costs.

Stereotactic Body Radiotherapy (SBRT) and Yttrium-90 (Y90) are among the ablative therapies used as treatment options for localized hepatocellular carcinoma (HCC). To date, direct comparisons of the 2 modalities' outcomes and costs are lacking. This study aimed to analyze demographic, treatment, and cost information for patients with HCC treated with SBRT and Y90. Patients with HCC treated with SBRT or Y90 radioembolization between January 2018 and January 2020 at one institution were retrospectively reviewed. Demographic and treatment data were compared utilizing χ 2 tests. Kaplan-Meier curves and log-rank tests were applied to compare overall survival and progression-free survival in different treatment groups. Cox proportional hazard models were applied to analyze the unadjusted and adjusted survival differences. Ten SBRT and 10 Y90 patients were randomly selected for Medicare cost analysis. Sixty-three patients received Y90, and 21 received SBRT. On univariable and multivariable analysis, there was no significant difference in overall survival or progression-free survival between the Y90 and SBRT cohorts. SBRT patients had higher American Joint Committee on Cancer staging ( P =0.039), greater tumor size (4.07 vs. 2.96cm, P =0.013), and greater rates of prior liver-directed therapy (71.4% SBRT vs. 12.7% Y90, P <0.001). The average cost for SBRT was $15,148, and Y90 was $41,360. SBRT and Y90 are effective therapies in the treatment of HCC, specifically having similar overall survival and progression-free survival. Y90 was found to have a significantly higher cost than SBRT. This study demonstrates the need for prospective studies to assess these modalities in treating HCC.

Long-term Outcomes from a Phase 1 Dose Escalation Study Using Stereotactic Body Radiotherapy for Patients with Low- or Intermediate-risk Prostate Cancer.

Ultrahypofractionated stereotactic body radiation therapy (SBRT) has become a standard treatment intervention for localized prostate cancer. To report final long-term tumor control outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicities from a single-center phase 1 dose escalation study using SBRT for patients with low- or intermediate-risk prostate cancer. Between 2009 and 2012, 136 patients were enrolled and treated. The initial dose level was 32.5 Gy in five fractions. Doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy in five fractions delivered every other day. The primary endpoint was late treatment-related toxicity. Secondary endpoints included prostate-specific antigen (PSA) failure. The median follow-up was 10.5 yr for the 32.5-Gy group, 9.9 yr for the 35-Gy group, 8.2 yr for the 37.5-Gy group, and 7.3 yr for the 40-Gy group. The 8-yr cumulative incidence of PSA failure was 26% for 32.5 Gy, 15% for 35 Gy, 3.4% for 37.5 Gy, and 6.6% for 40 Gy. Higher radiation dose (37.5-40 Gy) and favorable intermediate risk (vs unfavorable intermediate risk) were associated with better PSA recurrence rates (p=0.011 and 0.002, respectively). The 8-yr actuarial probability rates for survival free from late grade ≥2 toxicity were 94% for GI toxicity and 86% for GU toxicity. No grade 4 events were recorded. Higher dose levels were not associated with higher rates of late grade ≥2 GI (p=0.2) or GU (p>0.9) toxicity. SBRT doses ranging from 32.5 to 40 Gy were associated with low incidence of moderate or severe toxicities. Higher doses resulted in superior disease control outcomes 8 yr after treatment. We investigated the association between the radiotherapy dose used and the rate of control of prostate cancer. We found that higher doses resulted in more favorable outcomes without excess toxicity. This trial is registered on ClinicalTrials.gov as NCT00911118.

957P Interim report of Notable-HCC: A phase Ib study of neoadjuvant PD-1 with stereotactic body radiotherapy in patients with resectable hepatocellular carcinoma (HCC)

957P Interim report of Notable-HCC: A phase Ib study of neoadjuvant PD-1 with stereotactic body radiotherapy in patients with resectable hepatocellular carcinoma (HCC)

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.