Robotic Stereotactic Body Radiation Therapy Research Articles

Robotic Stereotactic Body Radiation Therapy for Oligometastatic Liver Metastases: A Systematic Review of the Literature and Evidence Quality Assessment.

The role of stereotactic body radiation therapy (SBRT) as a locally effective therapeutic approach for liver oligometastases from tumors of various origin is well established. We investigated the role of robotic SBRT (rSBRT) treatment on oligometastatic patients with liver lesions. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The PubMed and Scopus databases were accessed by two independent investigators concerning robotic rSBRT for liver metastases, up to 3 October 2023. In total, 15 studies, including 646 patients with 847 lesions that underwent rSBRT, were included in our systematic review. Complete response (CR) after rSBRT was achieved in 40.5% (95% CI, 36.66-44.46%), partial response (PR) in 19.01% (95% CI, 16.07-22.33%), whereas stable disease (SD) was recorded in 14.38% (95% CI, 11.8-17.41%) and progressive disease (PD) in 13.22% (95% CI, 10.74-16.17%) of patients. Progression-free survival (PFS) rates at 12 and 24 months were estimated at 61.49% (95% CI, 57.01-65.78%) and 32.55% (95% CI, 28.47-36.92%), respectively, while the overall survival (OS) rates at 12 and 24 months were estimated at 58.59% (95% CI, 53.67-63.33%) and 44.19% (95% CI, 39.38-49.12%), respectively. Grade 1 toxicity was reported in 13.81% (95% CI, 11.01-17.18%), Grade 2 toxicity in 5.57% (95% CI, 3.82-8.01%), and Grade 3 toxicity in 2.27% (955 CI, 1.22-4.07%) of included patients. rSBRT represents a promising method achieving local control with minimal toxicity in a significant proportion of patients. Further studies are needed to evaluate the role of rSBRT in the management of metastatic liver lesions.

Stereotactic body radiotherapy takes on Lung Oligometastases: Latest breakthroughs

AbstractLung oligometastases represent an intermediate state of cancer dissemination between localized and widespread metastases. Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment option, with an efficacy comparable to that of surgical resection. This review aimed to provide a comprehensive summary of the latest advancements and controversial issues regarding SBRT for lung oligometastases. It focuses on four crucial perspectives: efficacy of SBRT, optimal patient selection criteria, technological innovations, and synergistic effects of SBRT combined with systemic therapy. Relevant clinical trials investigating SBRT for lung oligometastases have been conducted, with median 1‐ and 5‐year local control rates of 90% and 79%, respectively. The origin of the primary tumor, size and number of lesions, and biomarker profiles were highlighted as pivotal considerations in patient selection. The precise dose delivery was enhanced using robotic SBRT and optimized dose fractionation schemes. Evidence suggests that dose escalation above 100 Gy biologically effective dose may improve tumor control. Combined immunotherapy and SBRT have demonstrated synergistic effects in prolonging progression‐free survival and overall survival. This review provides valuable insights into the precise treatment of oligometastatic lung diseases using SBRT. Further multicenter randomized trials are warranted to develop definitive patient selection criteria and optimize the integration with systemic therapies.

Feasibility of patient-specific quality assurance (PSQA) for real-time robotic stereotactic body radiotherapy (SBRT) based on tumor motion traces.

To design a patient specific quality assurance (PSQA) process for the CyberKnife Synchrony system and quantify its dosimetric accuracy using a motion platform driven by patient tumor traces with rotation. The CyberKnife Synchrony system was evaluated using a motion platform (MODUSQA) and a SRS MapCHECK phantom. The platform was programed to move in the superior-inferior (SI) direction based on tumor traces. The detector array housed by the StereoPhan was placed on the platform. Extra rotational angles in pitch (head down, 4.0°±0.15° or 1.2°±0.1°) were added to the moving phantom to examine robot capability of angle correction during delivery. A total of 15 Synchrony patients were performed SBRT PSQA on the moving phantom. All the results were benchmarked by the PSQA results based on static phantom. For smaller pitch angles, the mean gamma passing rates were 99.75%±0.87%, 98.63%±2.05%, and 93.11%±5.52%, for 3%/1mm, 2%/1mm, and 1%/1mm, respectively. Large discrepancy in the passing rates was observed for different pitch angles due to limited angle correction by the robot. For larger pitch angles, the corresponding mean passing rates were dropped to 93.00%±10.91%, 88.05%±14.93%, and 80.38%±17.40%. When comparing with the static phantom, no significant statistic difference was observed for smaller pitch angles (p=0.1 for 3%/1mm), whereas a larger statistic difference was observed for larger pitch angles (p<0.02 for all criteria). All the gamma passing rates were improved, if applying shift and rotation correction. The significance of this work is that it is the first study to benchmark PSQA for the CyberKnife Synchrony system using realistically moving phantoms with rotation. With reasonable delivery time, we found it may be feasible to perform PSQA for Synchrony patients with a realistic breathing pattern.

Bothersome Hot Flashes Following Neoadjuvant Androgen Deprivation Therapy and Stereotactic Body Radiotherapy for Localized Prostate Cancer.

Androgen deprivation therapy (ADT) improves local cancer control in unfavorable localized prostate cancer treated with radiotherapy. ADT is known to cause hormonally related symptoms that resolve with testosterone recovery. Hot flashes are particularly burdensome. This study sought to evaluate the timeline of hot flashes following short-course ADT and stereotactic body radiotherapy (SBRT) as well as its relationship with testosterone recovery. Institutional IRB approval was obtained for this retrospective review of prospectively collected data (IRB#: 2009-510). ADT was initiated three months prior to the start of SBRT. Hot flashes were self-reported via question 13a of the Expanded Prostate Index Composite (EPIC)-26 prior to ADT initiation, the first day of robotic SBRT, and at each follow-up (one, three, six, nine, 12, 18, 24, and 36 months). The responses were grouped into three relevant categories (no problem, very small-small problem, and moderate-big problem). Scores were transformed to a 0-100 scale with higher scores reflecting less bother. Testosterone levels were measured at each follow-up. From 2007 to 2010, 122 localized prostate cancer patients (nine low-, 64 intermediate-, and 49 high-risk according to the D'Amico classification) at a median age of 72 years (range 54.5-88.3) were treated with short course ADT (three to six months) and SBRT (35-36.25 Gy) at Georgetown University Hospital. Thirty-two percent were Black and 27% were obese. Seventy-seven percent of patients received three months of ADT. At baseline, 2% of men experienced hot flashes that were a "moderate to big problem" and that proportion peaked at the start of SBRT (45%) before returning to baseline (2%) nine months post-SBRT with a cumulative incidence of 52.4%. The median baseline EPIC-26 hot flash score of 94 declined to 50 at the start of SBRT but this returned to baseline (92) by six months post SBRT. These changes were both statistically and clinically significant (MID = 9.5083, p<0.01). Testosterone recovery (> 230 ng/dL) occurred in approximately 70% of patients by 12 months post SBRT. Resolution of hot flashes correlated with testosterone recovery. Bothersome hot flashes occur in greater than 50% of men treated with neoadjuvant ADT. Resolution of hot flashes occurs in the majority of patients within one year after treatment. Reassurance of the temporary nature of hot flashes may assist in reducing patient anxiety. Measuring testosterone levels at follow-up visits may allow for anticipatory counseling that may limit the associated bother.

Robotic Stereotactic Body Radiotherapy for Spine Metastasis Pain Relief

Spinal metastasis may occur in 40–70% of patients with cancer. Symptoms can vary from pain to spinal cord compression (SCC) and can affect their quality of life (QoL). Stereotactic body radiotherapy (SBRT) allows dose escalation of spinal tumor metastases, minimizing doses to organs at risk and improving pain control. The aim of this study is to retrospectively describe our institution’s experience with robotic SBRT (CyberKnife®, Accuray Incorporated, Sunnyvale, CA, USA) for spinal metastases, in terms of feasibility, oncological results, toxicities, and pain relief observed. In total, 25 patients with 43 lesions were assessed, most of them with dorsal metastases (48.8%). The median total dose was 27 Gy (16–35 Gy), the median number of fractions administered was 3 (1–5), and the median dose per fraction was 9 Gy. Pain was evaluated using the visual analogue scale at baseline and at the end of treatment. The statistically significant reduction in pain (p &lt; 0.01) was associated with the total dose of radiotherapy delivered (p &lt; 0.01). Only one patient developed grade 3 dermatitis. Female gender, adenocarcinoma tumors, and lack of previous surgery were associated with better response to SBRT (p &lt; 0.05). Robotic spine SBRT is feasible, well-tolerated, and improves patients’ QoL through a statistically significant reduction in pain, so it should be offered to patients at an early stage in their process.

High-risk prostate cancer treated with a stereotactic body radiation therapy boost following pelvic nodal irradiation.

Modern literature has demonstrated improvements in long-term biochemical outcomes with the use of prophylactic pelvic nodal irradiation followed by a brachytherapy boost in the management of high-risk prostate cancer. However, this comes at the cost of increased treatment-related toxicity. In this study, we explore the outcomes of the largest cohort to date, which uses a stereotactic body radiation therapy (SBRT) boost following pelvic nodal radiation for exclusively high-risk prostate cancer. A large institutional database was interrogated to identify all patients with high-risk clinical node-negative prostate cancer treated with conventionally fractionated radiotherapy to the pelvis followed by a robotic SBRT boost to the prostate and seminal vesicles. The boost was uniformly delivered over three fractions. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Oncologic outcomes were assessed using the Kaplan-Meier method. Cox proportional hazard models were created to evaluate associations between pretreatment characteristics and clinical outcomes. A total of 440 patients with a median age of 71 years were treated, the majority of whom were diagnosed with a grade group 4 or 5 disease. Pelvic nodal irradiation was delivered at a total dose of 4,500 cGy in 25 fractions, followed by a three-fraction SBRT boost. With an early median follow-up of 2.5 years, the crude incidence of grade 2+ genitourinary (GU) and gastrointestinal (GI) toxicity was 13% and 11%, respectively. Multivariate analysis revealed grade 2+ GU toxicity was associated with older age and a higher American Joint Committee on Cancer (AJCC) stage. Multivariate analysis revealed overall survival was associated with patient age and posttreatment prostate-specific antigen (PSA) nadir. Utilization of an SBRT boost following pelvic nodal irradiation in the treatment of high-risk prostate cancer is oncologically effective with early follow-up and yields minimal high-grade toxicity. We demonstrate a 5-year freedom from biochemical recurrence (FFBCR) of over 83% with correspondingly limited grade 3+ GU and GI toxicity measured at 3.6% and 1.6%, respectively. Long-term follow-up is required to evaluate oncologic outcomes and late toxicity.

Retrospective study on the toxicity induced by stereotactic body radiotherapy: overview of the reunion experience on prostate cancer in elderly patients.

Prostate cancer is the fourth most commonly diagnosed cancer among men worldwide. Various tools are used to manage disease such as conventional radiotherapy. However, it has been demonstrated that large prostate volumes were often associated with higher rates of genitourinary and gastrointestinal toxicities. Currently, the improvements in radiotherapy technology have led to the development of stereotactic body radiotherapy, which delivers higher and much more accurate radiation doses. In order to complete literature data about short-term outcome and short-term toxic effects of stereotactic body radiotherapy, we aimed to share our experience about gastrointestinal and genitourinary toxicities associated with stereotactic body radiotherapy in prostate cancer in patients over 70 years old. We retrospectively reviewed the medical records of elderly patients with prostate cancer treated between 2021 and 2022. The elderly patients were treated with a non-coplanar robotic stereotactic body radiotherapy platform using real-time tracking of implanted fiducials. The prostate, with or without part of the seminal vesicles, was treated with a total dose of 36.25 Gy delivered in five fractions, each fraction being administered every other day. We analyzed a total of 80 elderly patients, comprising 38 low-, 37 intermediate- and 5 high-risk patients. The median follow-up duration was 12 months. We did not observe biochemical/clinical recurrence, distant metastasis, or death. Grade 2 acute genitourinary toxicity was observed in 9 patients (11.25%) and Grade 2 acute gastrointestinal toxicity in 4 patients (5.0%). We did not observe any grade 3 or more acute or late toxicities. Over the follow-up period, we noted a low frequency of gastrointestinal and genitourinary toxicities induced by stereotactic body radiotherapy in the context of prostate cancer in elderly patients. Therefore, stereotactic body radiotherapy seems to represent a promising treatment option for elderly patients, with acceptable acute toxicity.

Intensity modulated radiation therapy with stereotactic body radiation therapy boost for unfavorable prostate cancer: five-year outcomes

PurposeIntensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.Materials and methodsBetween 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45–50.4 Gy) according to an institutional protocol. For the first year, the patient’s PSA level was monitored every 3 months, biannually for 2 years, and annually thereafter. Failure was defined as nadir + 2 ng/mL or a rising PSA with imaging suggestive of recurrence. Detection of recurrence also included digital rectal examination and imaging studies, such as MRI, CT, PET/CT, and/or bone scans. PFS and PCSS were calculated using the Kaplan–Meier method.ResultsThe median follow-up period was 71 months. According to the NCCN risk classification, 5% (13/255) of the patients had favorable intermediate-risk disease, 23% (57/255) had unfavorable intermediate-risk disease, 40% (102/255) had high-risk disease, and 32% (83/255) had very high-risk disease. Androgen deprivation therapy was administered to 80% (204/255) of the patients. Elective pelvic lymph node IMRT was performed in 28 (10%) patients. The PFS for all patients at 5 years was 81% (favorable intermediate risk, 91%; unfavorable intermediate risk, 89%; high-risk, 78%; and very-high risk, 72%). The PCSS for all patients at 5 years was 97% (favorable intermediate risk, 100%; unfavorable intermediate risk, 100%; high risk, 100%; and very high risk, 89%).ConclusionThe incidence of failure following IMRT plus SBRT for unfavorable prostate cancer remains low at 5 years.

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old-Updated Results.

Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports updated outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. Between April 2006 and December 2022, 6,130 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator. Information was available for 4,143 patients. 3568 (86.12%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 575 (13.88%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 1,035 (24.98%) of these cases. The mean age was 67.4 years old. 48 patients were younger than 50 years old (mean age 46.6). 4,095 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 43.75%, 50.00%, 6.25% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 23.88%, 57.05%, 19.07% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 47.92%, 7 in 47.92%, and 8-10 in 4.16%. 44 younger patients were treated with SBRT alone. 4 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.42%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 29.84%, 7 in 54.14%, and 8-10 in 16.02%. 3522 were treated with SBRT alone. 573 patients also received supplemental external beam radiation (median dose 4500cGY) and 1030 patients (25.15%) received Androgen Deprivation Therapy (ADT) as part of their treatment. At 75 months the 6-year biochemical relapse free survival was 95.83% in younger patients compared to 98.41% in older patients using the Phoenix definition of biochemical failure. The 6-year median post treatment PSA was 0.3 in younger patients and 0.2 in the older patients. There were no significant differences in the risk stratification between the 2 groups. This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With updated 6-year follow up, SBRT remains an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

Risk Factors Predicting Relapse 10 Years Following Extreme Dose-Escalated SBRT for Intermediate-Risk Prostate Cancer: Is De-Intensification Feasible in Unfavorable Subgroups?

Adding short-term androgen-deprivation therapy (ADT) to radiotherapy is recommended in unfavorable intermediate-risk (UIR) prostate cancer (PCa). Data supporting the addition of ADT to stereotactic body radiotherapy (SBRT) in intermediate-risk (IR) patients are limited. Given ADT has well-documented toxicities, we sought to identify the UIR prognostic factors that predict for relapse following SBRT without ADT. We combined results from two mature multicenter trials to determine if extreme dose-escalated SBRT yielded UIR subgroups in which the omission of ADT may be considered. Between 2008 and 2011, two prospective national trials enlisted 39 centers to enroll 285 patients with IR PCa: 182 had Memorial Sloan Kettering (MSK) favorable intermediate-risk (FIR) and 103 had MSK UIF PCa. All were treated with a non-coplanar robotic SBRT platform using real-time tracking of implanted fiducials. Two dose regimens were used: 40Gy in 5 fractions of 8Gy, and 38Gy in 4 fractions of 9.5Gy. ADT was not allowed. Univariate and multivariate analyses using a Cox proportional hazards model was performed for relapse free survival (RFS): relapse included pathologic or radiographic failure, initiation of salvage or systemic therapy, or biochemical relapse by the nadir + 2 definition. Insufficient events prevented similar analyses for local control, metastasis-free and PCa-specific survival. Examined risk factors included dose regimen, clinical T-stage, Gleason score, pre-treatment PSA, % positive biopsy cores, and number of unfavorable risk factors (URFs). All reported rates are actuarial, using Kaplan-Meier method. Median follow-up was 8.1 years. 71 patients were followed 10 years. There were no statistically significant differences in rates of toxicity, local failure, RFS, overall nor metastasis-free survival between the two dose regimens. For the entire group, 10-year overall survival was 82.9%, RFS was 83.2%, and the local failure rate was 3.6%. On univariate analysis, primary Gleason pattern 4 (PGP4) and >2 URFs predicted for RFS. On multivariate analysis, only PGP4 (hazard ratio: 3.71, p = 0.0053) was statistically significant. Examining the UIR subgroup, the only predictor for RFS was PGP4 (HR: 3.64, p = 0.0253). 10-year RFS was 88.4% for FIR and 89.1% for UIR without PGP4; this fell to 58.5% in patients with a PGP4. Following dose-escalated SBRT monotherapy, 10-year RFS rates were favorable in UIR patients without PGP4. Extreme dose escalation appeared to effectively address UIR factors correlating with tumor bulk (i.e., CS T2b, >50% cores+, PSA 10-20), but was less effective with biologically aggressive pathology (PGP4). A randomized trial, ideally including genomic classification, would be necessary to determine if dose-escalated SBRT allows de-intensification (omission of ADT) in such biologically less aggressive UIR subgroups. The high relapse rate observed in UIR patients with PGP4 affirms the need for adjuvant ADT in this subgroup.

Low Incidence of Late Lymphopenia Following Stereotactic Body Radiotherapy for Localized Prostate Cancer.

Stereotactic body radiotherapy (SBRT) is increasing in use for the treatment of localized prostate cancer. The utilization of highly conformal photon therapy such as SBRT may increase the whole-body integral dose. Lymphocytes are very radiation sensitive. This dose increase could lead to unintended consequences such as lymphopenia. Prior studies have shown that lymphopenia following radiation therapy may negatively impact long-term outcomes. This study sought to evaluate the incidence and timeline of chronic lymphopenia following prostate SBRT. Institutional IRB (IRB#: 2012-1175) approval was obtained. The absolute lymphocyte count was measured 1-2 hours prior to robotic SBRT (35-36.25 Gy in 5 fractions) and at each follow-up (3, 6, 12, 18 and 24 months). Lymphopenia was graded using the CTCAEv.4: Grade 1 (1.0-0.8 k/μl), Grade 2 (0.8-0.5 k/μl), Grade 3 (0.5-0.2 k/μl) and Grade 4 (<0.2 k/μl). Late lymphopenia was defined as lymphopenia occurring 3 or more months post-SBRT. From 2019 to 2022, 198 localized prostate cancer patients (23 low-, 148 intermediate-, and 27 high-risk according to the D'Amico classification) at a median age of 73.5 years were treated with SBRT (35-36.25 Gy) at Georgetown University Hospital on a prospective clinical trial. Baseline lymphopenia was uncommon: Grade 1 (3.5%), Grade 2 (1.5%) and Grade 3 (0%). The baseline ALC of 1.9 k/μl decreased to 1.5 k/μl at 3 months post-SBRT and then remained stable for the remainder of the two-year follow-up. Overall, 14.6% of men experienced lymphopenia in the two years following SBRT: Grade 1 (7.6%), Grade 2 (6.6%) and Grade 3 (0.5%). No patient experienced Grade 4 lymphopenia. Prostate SBRT leads to a low rate of late lymphopenia with the vast majority of toxicities being low grade. The peak incidence occurred at 3 months post-SBRT. Resolution of lymphopenia occurs in most patients within two years after SBRT. Future studies should explore the possible impact on quality of life and cancer control outcomes.

Planning Target Volume Margin Quantification of Retroperitoneal Tumors Using Robotic Stereotactic Body Radiotherapy with Spine Tracking

Stereotactic body radiotherapy treatment (SBRT) is an effective modality for treating primary and oligometastatic malignant lesions. Appropriate planning target volume (PTV) margins are essential when delivering SBRT to maximize target prescription coverage while minimizing dose to surrounding organs-at-risk. Spine tracking uses boney spinal anatomy as a surrogate for tumor localization during treatment delivery on robotic linear accelerator platforms that employ intrafraction kV x-ray imaging. The aim of this study was to quantify the PTV margin needed when spine tracking was used for tumor localization when treating retroperitoneal metastatic lesions with robotic SBRT. A single institution chart review was performed and identified 16 patients with retroperitoneal tumors treated stereotactically over 19 courses in 103 fractions. Daily cone-beam computed tomography (CBCT) images that were registered based on tumor position at the time of treatment were analyzed. Rigid registrations were re-performed aligning the position of the spine on the CBCT relative to its position on the planning CT. Shifts from the treatment position were recorded and per-patient mean shifts and standard deviations were calculated. Van Herk's margin recipe was used to determine the additional PTV margin required if spine tracking was used instead of soft tissue alignment. Patient tumors were stratified and compared based on proximity to the vertebral column (≤1 cm vs >1 cm) and location within the retroperitoneum (superior vs inferior to the renal artery). Student's t-test was used to compare statistical differences of shifts based on location. The additional margins calculated by van Herk's margin recipe to adequately cover the target volumes within the 95% isodose surface for 90% of the entire patient cohort in the vertical, longitudinal, and lateral directions were 2.7, 2.8, and 2.8 mm, respectively. When tumors were stratified by proximity to the vertebral column, average longitudinal (p<0.001) and total shifts (p<0.001) were statistically significant. Isometric PTV expansions of 3, 4, and 5 mm would have encompassed 55%, 76%, and 86% of the maximum total shifts for lesions >1 cm from the vertebral column versus 94%, 100%, and 100% for lesions ≤1 cm. When stratified by location within the retroperitoneum, isometric PTV expansions of 3, 4, and 5 mm would have encompassed 82%, 94%, and 100% of the maximum total shifts for lesions superior to the renal artery versus 78%, 94%, and 98% for lesions inferior to the renal artery. When treating retroperitoneal tumors with robotic SBRT, a minimum isometric margin expansion between 3 to 5 mm when creating the PTV is recommended if spine tracking is used for intrafraction tumor localization. Target volumes adjacent to the vertebral column may have PTV margins decreased to ≤4 mm without compromising target coverage.

Bothersome Hot Flashes Following Neoadjuvant Androgen Deprivation Therapy and Stereotactic Body Radiotherapy for Localized Prostate Cancer

Androgen deprivation therapy (ADT) may improve cancer control in unfavorable localized prostate cancer treated with stereotactic body radiotherapy (SBRT). ADT is known to cause hormonally related symptoms that resolve with testosterone recovery. Hot flashes are particularly burdensome. This study sought to evaluate the timeline of hot flashes following short-course ADT and SBRT as well as its relationship with testosterone recovery. Institutional IRB approval was obtained for this retrospective review of prospectively collected data (IRB#: 2009-510). ADT was initiated three months prior to the start of SBRT. Hot flashes were self-reported via question 13a a healthcare software prior to ADT initiation, the first day of robotic SBRT, and at each follow-up (1, 3, 6, 9, 12, 18, 24 and 36 months). The responses were grouped into three relevant categories (no problem, very small-small problem and moderate-big problem). Scores were transformed to a 0-100 scale with higher scores reflecting less bother. Testosterone levels were measured at each follow-up. From 2007 to 2010, 122 localized prostate cancer patients (9 low-, 64 intermediate-, and 49 high-risk according to the D'Amico classification) at a median age of 72 years (range 54.5-88.3) were treated with short course ADT (3-6 months) and SBRT (35-36.25 Gy) at Georgetown University Hospital. Thirty-two percent were black and 27% were obese. 77% of patient received three months of ADT. At baseline, 2% of men experienced hot flashes that were a "moderate to big problem" and that proportion peaked at the start of SBRT (45%) before returning to baseline 9 months post-SBRT with a cumulative incidence of 52.4%. The median baseline healthcare software hot flash score of 94 declined to 50 at the start of SBRT but this returned to baseline by six months post SBRT. These changes were both statistically and clinically significant (MID = 9.5083). Testosterone recovery (> 230 ng/dL) occurred in approximately 70% of patients by 12 months post SBRT. Resolution of hot flashes correlated with testosterone recovery. Bothersome hot flashes occur in greater than 50% of men treated with neoadjuvant ADT. Resolution of hot flashes occurs in the majority of patients within one year after treatment. Reassurance of the temporary nature of hot flashes may assist in reducing patient anxiety. Measuring testosterone levels at follow-up visits may allow for anticipatory counseling that may limit the associated bother.

Bothersome Gynecomastia Following Neoadjuvant GnRH Agonists and Stereotactic Body Radiotherapy for Localized Prostate Cancer

Androgen deprivation therapy (ADT) is increasingly utilized in combination with stereotactic body radiotherapy (SBRT) for unfavorable prostate cancer. ADT such as gonadotropin releasing hormone (GnRH) agonists are known to cause hormonal-related side effects such as gynecomastia. The incidence of bothersome breast tenderness and/or enlargement following short course GnRH agonists and SBRT is unknown. This study sought to evaluate the timeline of gynecomastia as well as its relationship with testosterone recovery. Gynecomastia was self-reported via question 13b of a healthcare software prior to ADT initiation, the first day of robotic SBRT, and at each follow-up (1, 3, 6, 9, 12, 18, 24 and 36 months). The responses were grouped into three relevant categories (no problem, very small-small problem, and moderate-big problem). Scores were transformed to a 0-100 scale with higher scores reflecting less bother. Testosterone levels were measured at each follow-up. From 2007 to 2010, 122 localized prostate cancer patients (9 low-, 64 intermediate-, and 49 high-risk according to the D'Amico classification) at a median age of 72 years (range 54.5-88.3) were treated with short course ADT (3-6 months) and SBRT (35-36.25 Gy) at Georgetown University Hospital. Of the participants, 48% percent were non-white and 48% were overweight. 77% of patients received three months of ADT. At baseline, 2% of men experienced gynecomastia that was a "moderate to big problem" and that proportion peaked at 3 and 12 months post-SBRT (7%) before returning to less than baseline (0%) 24 months post-SBRT with a cumulative incidence of 14.75%. The median baseline healthcare software hot flash score of 98 declined to 90 at 3 months post-SBRT but this returned to baseline by 24 months post SBRT. These changes were both statistically and clinically significant (MID = 6.5). Testosterone recovery (> 230 ng/dL) occurred in approximately 70% of patients by 12 months post SBRT. The development and resolution of gynecomastia fluctuated at various timepoints and did not directly correlate with testosterone recovery. Bothersome gynecomastia occurs in less than 15% of men treated with neoadjuvant ADT. Resolution of gynecomastia occurs in most patients within two years after treatment. Reassurance of the temporary nature of gynecomastia may assist in reducing patient anxiety. Institutional IRB (IRB#: 2009-510) approval was obtained for retrospective review of prospectively collected data.

CyberKnife® stereotactic radiation therapy for stage I lung cancer and pulmonary oligometastases: is fiducial implantation still relevant?-a cohort study.

Few studies have investigated whether there is a difference in local control or overall survival rates following treatment with robotic stereotactic body radiation therapy (SBRT) with or without prior fiducial marker implantation. Our study aimed to investigate this in patients with primary or secondary lung tumors. A retrospective study was conducted at the Institut de Cancérologie de Lorraine of patients treated for primary lung cancer or pulmonary oligometastases with SBRT from January 2013 to July 2016. We included patients at least 18 years old who had stage I non-small cell lung cancer (NSCLC) or lung metastases and a follow-up of at least 1 month. A total of 294 patients were included. Tumors included 122 lung metastases, 89 stage I NSCLC, and 83 non-histologically confirmed lung lesions. The tracking methods were Synchrony® in 191 cases (119 gold seeds and 72 coils) and Xsight® Spine with 4D computed tomography in 103 cases. Median follow-up was 31.6 months [interquartile range (IQR), 18.1-50.2 months]. The two- and five-year probability of local control were respectively 92.22% [95% confidence interval (CI): 0.89-0.95] and 85.35% (95% CI: 0.79-0.99). The two- and five-year probability of overall survival were respectively 87.46% and 72.77% (P=0.586). Local control rates did not significantly differ between techniques at 2 and 5 years (P=0.685) (gold seeds, coils or Xsight® Spine) within tumors grouped by location, gross tumor volume (GTV) (respectively P=0.9, P=0.7, and P=0.4), planning target volume (PTV) (respectively P=0.4, P=0.9, and P=0.7), or PTV/GTV ratio (respectively P=0.6, P=0.6, and P=0.5). Metastasis-free survival and Overall survival rates did not significantly differ between techniques at 2 and 5 years (P=0.664 and P=0.586, respectively). There were no grade 4 or 5 toxicities and only one grade 3 pneumonitis and one grade 3 pneumothorax. Fiducial-less SBRT using Xsight® Spine is a safe alternative to Synchrony® using gold seeds or coils, with comparable local control and overall survival rates and a similar toxicity profile.

Testosterone as a Biomarker for Quality of Life (QOL) Following Androgen Deprivation Therapy (ADT) and Stereotactic Body Radiotherapy (SBRT).

Androgen deprivation therapy (ADT) causes fatigue and sexual dysfunction. The time to testosterone recovery depends on patient and treatment-specific characteristics. The kinetics of testosterone recovery in men treated with neoadjuvant ADT and stereotactic body radiotherapy (SBRT) is not well established. This study seeks to characterize testosterone recovery and evaluate its relationship with the improvement in patient-reported hormonal and sexual function. Institutional review board (IRB) approval was obtained for retrospective review of prospectively collected data. All patients with localized prostate cancer treated with short-course ADT (3-6 months of Leuprolide) and robotic SBRT (35-36.25 Gy in five fractions) at a single institution were included in this analysis.Testosterone levels were measured at the start of radiation, every 3 months for the first year, and every 6 months thereafter. Total testosterone recovery was defined as a serum level of >230 ng/dL. Sexual and hormonal function was recorded using the Expanded Prostate Index Composite (EPIC)-26 prior to ADT initiation, the first day of SBRT, and at each follow-up. The EPIC-26 subdomain scores were transformed to a 0-100 scale with higher scores reflecting less bother. Between January 2009 and May 2018, 122 men with a median age of 72 years (range: 55-89 years) received ADT followed by SBRT. Thirty-two percent(N=39) were black and 27% [N=39 were obese (BMI > 30)]. The median pre-SBRT testosterone level was 15 ng/dL (range: 3-89 ng/dL). Around 77% (N=94) of patients received 3 months of ADT. The median pre-ADT EPIC-26 Hormone and Sexual Domain Scores were 94 and 41, respectively. At 12 months, 71% (N=87) of patients recovered to a eugonadal state with a mean recovery time of 4 months post-SBRT. Hormonal and sexual subdomain scores declined significantly following ADT but recovered to within the minimally important difference (MID) for sexual and hormonal domain scores by 12 months post-SBRT. Testosterone recovery following short-course ADTwith leuprolide and SBRT occurs rapidly in the majority of patients within one year after treatment. Quality of life domain improvements followed the testosterone recovery trend closely. Testosterone testing at follow-up appointments would allow for anticipatory counseling that may limit the bother associated with temporary quality of life decrements.

Efficacy and Toxicity of Robotic Stereotactic Body Radiotherapy of Lung Metastases in Patients With Oligometastatic Disease.

Stereotactic body radiotherapy is a locally effective treatment for lung metastases in patients with oligometastatic disease, a modern variant of which is robotic (rSBRT). Since it is unclear which factors determine the success of rSBRT, we investigated a cohort of patients with lung metastases treated with rSBRT. In our retrospective single-center analysis, we included patients with oligometastatic disease of different cancer types who underwent SBRT of lung metastases using an Accuray Cyberknife® device between 2012 and 2019. We evaluated local control rate (LC), progression-free (PFS) and overall (OS) survival, and toxicity. Multivariate analysis was performed to identify independent factors associated with the efficacy and toxicity of rSBRT. A total of 70 lung metastases of 54 patients were evaluated. The 4-year Kaplan-Meier estimate for LC, PFS and OS were 72.0%, 12.4% and 49.7%, respectively. Cox regression showed that LC of metastases of colorectal carcinoma and metastases treated with a biological effective dose at an α/β-ratio of 10 (BED10) of <100 Gy was significantly worse than for other metastases. Patients suffered from grade I-II pneumonitis in 21.4% of cases treated with rSBRT (grade I: 20.0%; grade II: 1.4%). rSBRT is an effective and safe therapy for lung metastases. A BED10 of >100 Gy should be aimed for, especially for potentially radioresistant histologies such as colorectal carcinoma.

PSMA PET-based stereotactic body radiotherapy for locally recurrent prostate cancer after definitive first-line therapy.

Advances in prostate-specific membrane antigen (PSMA) PET-computed tomography (CT) and magnetic resonance imaging (MRI) allow the detection and localization of exclusively local prostate-cancer-recurrences after definitive first-line therapy. PSMA-based early detection of circumscribed local recurrences followed by hypofractionated high-precision stereotactic body radiotherapy (SBRT) might yield long-term disease control at moderate rates of adverse effects. Retrospective analysis of 35 patients treated for locally recurrent prostate cancer between November 2012 and December 2021 with PSMA PET- and MRI-based robotic SBRT. Thirty-five patients treated with local prostate cancer recurrence post surgery, post surgery, and adjuvant/salvage radiotherapy (RT) and after definitive RT. All but one patients had fractionated SBRT in 3-5 fractions. Median progression-free survival (PFS) was 52.2 months for all patients and 52.2 months in the radical prostatectomy (RPE) group, 31.2 months in the RPE + RT group and not reached in the RT group. The most common event was increased urinary frequency grade 1-2. 54.3% of all patients had no acute and 79.4% no late toxicity during follow-up. Our PFS of 52.2 months (RPE), 31.2 months (RPE + RT) and not reached (RT) compares favorably with published data. This method constitutes a valid alternative to morbidity-prone invasive approaches or palliative systemic therapy.

Towards fast adaptive replanning by constrained reoptimization for intra-fractional non-periodic motion during robotic SBRT.

Periodic and slow target motion is tracked by synchronous motion of the treatment beams in robotic stereotactic body radiation therapy (SBRT). However, spontaneous, non-periodic displacement or drift of the target may completely change the treatment geometry. Simple motion compensation is not sufficient to guarantee the best possible treatment, since relative motion between the target and organs at risk (OARs) can cause substantial deviations of dose in the OARs. This is especially evident when considering the temporally heterogeneous dose delivery by many focused beams which is typical for robotic SBRT. Instead, a reoptimization of the remaining treatment plan after a large target motion during the treatment could potentially reduce the actually delivered dose to OARs and improve target coverage. This reoptimization task, however, is challenging due to time constraints and limited humansupervision. To study the detrimental effect of spontaneous target motion relative to surrounding OARs on the delivered dose distribution and to analyze how intra-fractional constrained replanning could improve motion compensated robotic SBRT of the prostate. We solve the inverse planning problem by optimizing a linear program. When considering intra-fractional target motion resulting in a change of geometry, we adapt the linear program to account for the changed dose coefficients and delivered dose. We reduce the problem size by only reweighting beams from the reference treatment plan without motion. For evaluation we simulate target motion and compare our approach for intra-fractional replanning to the conventional compensation by synchronous beam motion. Results are generated retrospectively on data of 50patients. Our results show that reoptimization can on average retain or improve coverage in case of target motion compared to the reference plan without motion. Compared to the conventional compensation, coverage is improved from 87.83 % to 94.81 % for large target motion. Our approach for reoptimization ensures fixed upper constraints on the dose even after motion, enabling safer intra-fraction adaption, compared to conventional motion compensation where overdosage in OARs can lead to 21.79 % higher maximum dose than planned. With an average reoptimization time of 6 s for 200 reoptimized beams our approach shows promising performance for intra-fractional application. We show that intra-fractional constrained reoptimization for adaption to target motion can improve coverage compared to the conventional approach of beam translation while ensuring that upper dose constraints on VOIs are notviolated.

Treatment planning comparison of high-dose-rate brachytherapy vs. robotic and conventional stereotactic body radiotherapy for ultrahypofractionated treatment of prostate cancer.

Ultrahypofractionated radiation therapy is increasingly used in the treatment of prostate cancer. High-dose-rate brachytherapy (HDR-BT) and stereotactic body radiotherapy (SBRT) are representative methods of ultrahypofractionation. This study was performed to compare clinically applied treatment plans for patients who had been treated using HDR-BT vs. conventional or robotic SBRT. Calculated dose-volume indices between HDR-BT without a perirectal spacer (n=20), robotic SBRT without a spacer (n=40), and conventional (non-robotic) SBRT with a spacer (n=40) were compared. Percentages against the prescription dose regarding the planning target volume (PTV), bladder, rectum, and urethra were statistically compared. The D50% of the PTV with HDR-BT (140.5%±4.9%) was significantly higher than that with robotic or conventional SBRT (116.2%±1.6%, 101.0%±0.4%, p<0.01). The D2cm3 of the bladder with HDR-BT (65.6%±6.4%) was significantly lower than those with SBRT (105.3%±2.9%, 98.0%±1.3%, p<0.01). The D2cm3 of the rectum with HDR-BT (60.6%±6.2%) was also significantly lower than those with SBRT (85.1%±8.8%, 70.4%±9.6%, p<0.01). By contrast, the D0.1cm3 of the urethra with HDR-BT (117.1%±3.6%) was significantly higher than those with SBRT (100.2%±0.7%, 104.5%±0.6%, p<0.01). HDR-BT could administer a higher dose to the PTV and a lower dose to the bladder and rectum, at the cost of a slightly higher dose to the urethra compared with SBRT.