Robotic Stereotactic Radiotherapy Research Articles

Large institutional experience of early outcomes and dosimetric findings with postoperative stereotactic partial breast irradiation in breast cancer

PurposeTo analyze the dosimetric and toxicity outcomes of patients treated with postoperative stereotactic partial breast irradiation (S-PBI). MethodsWe identified 799 women who underwent S-PBI at our institution between January 2016 and December 2022. The most commonly used dose-fraction and technique were 30 Gy in 5 fractions (91.7 %) and a robotic stereotactic radiation system with real-time tracking (83.7 %). The primary endpoints were dosimetric parameters and radiation-related toxicities. For comparison, a control group undergoing ultra-hypofractionated whole breast irradiation (UF-WBI, n = 468) at the same institution was selected. ResultsA total of 815 breasts from 799 patients, with a median planning target volume (PTV) volume of 89.6 cm3, were treated with S-PBI. Treatment plans showed that the mean and maximum doses received by the PTV were 96.2 % and 104.8 % of the prescription dose, respectively. The volume of the ipsilateral breast that received 50 % of the prescription dose was 32.3 ± 8.9 %. The mean doses for the ipsilateral lung and heart were 2.5 ± 0.9 Gy and 0.65 ± 0.39 Gy, respectively. Acute toxicity occurred in 175 patients (21.5 %), predominantly of grade 1. Overall rate of late toxicity was 4 % with a median follow-up of 31.6 months. Compared to the UF-WBI group, the S-PBI group had comparably low acute toxicity (21.5 % vs. 25.2 %, p = 0.12) but significantly lower dosimetric parameters for all organs-at-risks (all p < 0.05). ConclusionIn this large cohort, S-PBI demonstrated favorable dosimetric and toxicity profiles. Considering the reduced radiation exposure to surrounding tissues, external beam PBI with advanced techniques should at least be considered over traditional WBI-based approaches for PBI candidates.

Predictors of local control after robotic stereotactic radiotherapy for brain metastases: 10-years-experience after Cyberknife installation.

To evaluate the factors influencing brain metastases (BM) local control (LC) after stereotactic radiotherapy (SRT). Between 2010 and 2020, a cohort of 145 patients (246 BM) treated consecutively with robotic radiosurgery was analysed. Median age was 61 years (range, 29-90 years). Median radiological follow-up of the lesions was 21.7 months (range, 3-115 months). The mean overall survival and LC were 33.0 and 82.7 months, respectively. On univariate analysis, sex, primary cancer site, histological type, use of systemic steroids, maximum diameter, volume, early MRI response, isodose line, number of fractions, BED10 value, and BED10 value proportional to volume and maximum diameter were significant factors for LC. On multivariate analysis, female sex (hazard ratio [HR]: 2.10 P: 0.035), adenocarcinoma histology (HR: 6.54 P: 0.001), no steroid use (HR: 3.60 P: 0.001), maximum diameter (≤1 cm) (HR: 2.64 P: 0.018), complete response of lesion at first follow-up MRI compared to stable or progressive disease (HR: 4.20, P = 0.024; HR: 19.15, P < 0.001), isodose line (≥90%) (HR: 2.00 P: 0.036), and tumour volume (PTV ≤2 cc) (HR: 5.19 P: 0.001) were independent factors improving LC. SRT is an effective treatment for patients with a limited number of BM with a high LC rate. There are many factors related to the patient, tumour, and radiotherapy plan that have an impact on LC after SRT in brain metastases. These results warrant further investigation in a prospective setting.

Robotic Stereotactic Radiotherapy for Intracranial Meningiomas-An Opportunity for Radiation Dose De-Escalation.

To evaluate the possibility of dose de-escalation, with consideration of the efficacy and safety of robotic stereotactic CyberKnife radiotherapy in patients diagnosed with intracranial meningiomas. The study group consisted of 172 patients (42 men and 130 women) treated in III Radiotherapy and Chemotherapy Clinic of Maria Sklodowska-Curie National Research Institute of Oncology in Gliwice between January 2011 and July 2018. The qualification for dose de-escalation was based on MRI (magnetic resonance imaging) features: largest tumor diameter less than 5 cm, well-defined tumor margins, no edema, and no brain infiltration. The age of patients was 21-79 years (median 59 years) at diagnosis and 24-80 years (median 62 years) at radiotherapy. Sixty-seven patients (Group A) were irradiated after initial surgery. Histopathological findings were meningioma grade WHO 1 in 51 and WHO 2 in 16 cases. Group B (105 patients) had no prior surgery and the diagnosis was based on the typical features of meningioma on MRI. All patients qualified for the robotic stereotactic CyberKnife radiotherapy, and the total dose received was 18 Gy in three fractions to reference isodose 78-92%. Follow-up period was 18 to 124 months (median 67.5 months). Five- and eight-year progression free survival was 90.3% and 89.4%, respectively. Two patients died during the follow-up period. Progression of tumor after radiotherapy was registered in 16 cases. Four patients required surgery due to progressive disease, and three of them were progression free during further follow-up. Twelve patients received a second course of robotic radiotherapy, 11 of them had stable disease, and one patient showed further tumor growth but died of heart failure. Crude progression free survival after both primary and secondary treatment was 98.8%. Radiotherapy was well-tolerated: acute toxicity grade 1/2 (EORTC-RTOG scale) was seen in 10.5% of patients. We did not observe any late effects of radiotherapy. Stereotactic CyberKnife radiotherapy with total dose of 18 Gy delivered in three fractions showed comparable efficacy to treatment schedules with higher doses. This could support the idea of dose de-escalation in the treatment of intracranial meningiomas.

Comparison of Early Outcomes of Stereotactic Accelerated Partial Breast Irradiation vs. Volumetric Modulated Arc Therapy-Based FAST-FORWARD Whole Breast Irradiation for Breast Cancer

Despite evidence supporting APBI from 8 published prospective randomized trials enrolling over 10,000 women, the uptake of APBI in clinical practice is surprisingly low. This is being exacerbated by a new, convenient, and safe shortened WBI schedule. Here, we report the dosimetric and early outcome analyses of the first >1000 patients treated at our institution since the first adoption of stereotactic APBI and the ultra-hypofractionated WBI regimen. From 2016 to 2022, 801 women with breast cancers in the suitable or cautionary categories according to the ASTRO APBI consensus panel guidelines, received 30 Gy in 5 fractions (92%) either using a robotic stereotactic radiation system (83%) or stereotactic volumetric-based arc therapy (VMAT, 17%). Between 2020 and 2022, 468 women, who were not candidates for APBI and not undergoing any regional irradiation received 26 Gy in 5 fractions using VMAT to the whole breast with the addition of cardiac sparing technique in left-sided breast cancer patients. Tumor bed boosts were delivered in 99% of FF-WBI patients. We evaluated dose-volume histogram parameters for target volumes and organs-at-risk and radiation-related toxicities during RT or within 6 months after the end of RT. Target volume coverage was acceptable in both groups, with mean 96% of the target volumes receiving 95% of the prescribed doses and 0 cm3 within target volumes exceeding 105% of the prescribed doses. S-APBI resulted in small, but statistically significant, reductions in the radiation dose delivered to the ipsilateral breast, contralateral breast, lungs, heart, and coronary artery compared with FF-WBI. Comparing WBI to APBI, the mean contralateral breast dose, ipsilateral lung V20 Gy, mean contralateral lung dose, and mean heart dose, were reduced by 89%, 78%, 73%, and 29%, respectively. With median follow-up periods of 32 months for s-APBI and 19 months for FF-WBI, acute toxicity was assessable in all patients. The risks of any grade acute toxicity were 21% for s-APBI and 25% for FF-WBI (p = .117). Among them, grade 2 rates were 1.3% in both groups and no severe toxicity has been reported. We found s-APBI and VMAT-based FF WBI were associated with favorable dosimetric and acute toxicity profiles. However, considering significantly less irradiated volume in the breast, lungs, and heart, APBI with advanced available technique options should be considered over any WBI-based approach for patients at low risk for local recurrence.

Effectiveness of Robotic Stereotactic Radiotherapy in Patients Undergoing Re-irradiation: A Review.

Stereotactic ablative radiotherapy (SABR) is a possible treatment option for patients who develop recurrence within or at the edge of a previously irradiated volume.Robotic stereotactic radiotherapy is the result of technological advances in robotic precision, real-time imaging, non-invasive, highly customizable treatment plan, and delivery with sub-millimeter accuracy. This article reviews the radiobiologic, technical, and clinical aspects of robotic-based SABR re-irradiation for various anatomical sites. An extensive literature search was performed to identify articles on the utilization of robotic stereotactic radiotherapy for patients undergoing re-irradiation.The reported prescription dose and fractionation data along with outcomes such as overall survival, local control rates, and toxicities were qualitatively reviewed. The findings consistently indicate that re-irradiation using robotic SABR provides encouraging survival rates with minimal toxicity in the clinical setting of various anatomical sites delivered using locally non-invasive means where other treatment options are scarce.

PO-1111 Robotic stereotactic radiotherapy for ≥ 10 brain metastases treated with single treatment planning.

PO-1111 Robotic stereotactic radiotherapy for ≥ 10 brain metastases treated with single treatment planning.

Evaluation of Early Cosmetic Outcome and Toxicity after 5-Fraction Stereotactic Partial Breast Irradiation in Early-Stage Breast Cancer: A Prospective Cohort Study

<h3>Purpose/Objective(s)</h3> Partial breast irradiation (PBI) is a promising approach to minimize the patient burden by reducing irradiated volumes with accelerated schedules. Stereotactic-PBI (S-PBI) using a robotic stereotactic radiation system is a less invasive modality. However, prospective data are limited regarding the course of breast fibrosis and cosmesis as objective measures. We prospectively evaluated early toxicity and cosmetic outcome in women undergoing 5-fraction S-PBI. <h3>Materials/Methods</h3> Women undergoing S-PBI for invasive carcinoma and/or carcinoma in situ were prospectively enrolled. S-PBI was delivered with a robotic radiosurgery system with a dose of 30 Gy in 5 fractions. Simultaneously, women who were not a candidate for PBI, but were undergoing whole breast irradiation (WBI) were also enrolled for comparison. Patient-reported and physician-assessed adverse events were noted. Breast fibrosis was measured with a tissue compliance meter. Cosmesis was assessed with automatic computer-based software, BCCT.core. <h3>Results</h3> In total, 204 patients (n = 103, S-PBI; n = 101, WBI) were included, of whom 197 (97%) and 133 (65%) completed a 12-month and 24-month evaluation, respectively. The amount of fibrosis in uninvolved quadrants decreased over time following S-PBI for 12 months. In contrast, this finding peaked at 6 months and further decreased at 12 months in the WBI group. The amount of fibrosis of uninvolved quadrants at 6 months was significantly lower in the S-PBI group than in the WBI group (<i>P = 0.002</i>), while that of involved quadrants or scar sites was not significantly different between groups. In the S-PBI group, patient-reported grade 3–4 events were 3% at 6 months and 0% at 12 months. Physician-assessed grade 3–4 events were 2% at 6 months and 0% at 12 months. Moreover, in the S-PBI group, most cosmetic outcomes were excellent or good (82%) at 24 months, and there was no significant cosmetic detriment from baseline (<i>P = 0.353</i>). <h3>Conclusion</h3> Patients who underwent S-PBI presented with less fibrosis affecting their uninvolved breast quadrants than those who underwent WBI. Patients showed minimal toxicity with no detrimental effect on cosmesis after S-PBI. Longer-term follow-up is ongoing and necessary.

PO-1740 Commissioning of a new treatment planning system for CyberKnife robotic stereotactic radiotherapy

PO-1740 Commissioning of a new treatment planning system for CyberKnife robotic stereotactic radiotherapy

Applications of Frameless Image-Guided Robotic Stereotactic Radiotherapy and Radiosurgery in Pediatric Neuro-Oncology: A Systematic Review

Simple SummaryRadiotherapy plays a vital role in the multimodal treatment of pediatric central nervous system (CNS) tumors. In cases of small-to-medium-sized, well-demarcated lesions, high-precision treatment modalities such as stereotactic radiosurgery (SRS) are well-established in adult patients. SRS and, more specifically, robotic radiosurgery (RRS) and robotic stereotactic radiotherapy (RSRT) have only limited evidence in the field of pediatric neuro-oncology. This systematic review aims to report and assess the available RRS and RSRT data and studies. Results demonstrate that both treatment modalities are infrequently applied and primarily used in specific situations, including postoperative, palliative, and salvage treatments. Treatment outcomes are encouraging, but high-quality studies are lacking. Prospective studies are necessary to determine the actual utility of RRS and RSRT in pediatric neuro-oncology. Nevertheless, RRS and RSRT may be applied for selected patients.Background: CyberKnife-based robotic radiosurgery (RRS) is a widely used treatment modality for various benign and malignant tumors of the central nervous system (CNS) in adults due to its high precision, favorable safety profile, and efficacy. Although RRS is emerging in pediatric neuro-oncology, scientific evidence for treatment indications, treatment parameters, and patient outcomes is scarce. This systematic review summarizes the current experience and evidence for RRS and robotic stereotactic radiotherapy (RSRT) in pediatric neuro-oncology. Methods: We performed a systematic review based on the databases Ovid Medline, Embase, Cochrane Library, and PubMed to identify studies and published articles reporting on RRS and RSRT treatments in pediatric neuro-oncology. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied herein. Articles were included if they described the application of RRS and RSRT in pediatric neuro-oncological patients. The quality of the articles was assessed based on their evidence level and their risk for bias using the original as well as an adapted version of the Newcastle Ottawa Quality Assessment Scale (NOS). Only articles published until 1 August 2021, were included. Results: A total of 23 articles were included after final review and removal of duplicates. Articles reported on a broad variety of CNS entities with various treatment indications. A majority of publications lacked substantial sample sizes and a prospective study design. Several reports included adult patients, thereby limiting the possibility of data extraction and analysis of pediatric patients. RRS and RSRT were mostly used in the setting of adjuvant, palliative, and salvage treatments with decent local control rates and acceptable short-to-intermediate-term toxicity. However, follow-up durations were limited. The evidence level was IV for all studies; the NOS score ranged between four and six, while the overall risk of bias was moderate to low. Conclusion: Publications on RRS and RSRT and their application in pediatric neuro-oncology are rare and lack high-quality evidence with respect to entity-related treatment standards and long-term outcomes. The limited data suggest that RRS and RSRT could be efficient treatment modalities, especially for children who are unsuitable for surgical interventions, suffer from tumor recurrences, or require palliative treatments. Nevertheless, the potential short-term and long-term adverse events must be kept in mind when choosing such a treatment. Prospective studies are necessary to determine the actual utility of RRS and RSRT in pediatric neuro-oncology.

Iodine-125 brachytherapy and robotic stereotactic radiotherapy — treatment options for patients with localized prostate cancer

Introduction. Modern radiological treatment options for patients with localized prostate cancer (PCa) have several advantages and allow achieving high rates of biochemical control.Purpose of the study. To compare immediate, proximate, and long-term results of low-dose Iodine-125 brachytherapy (I-125 BT) and robotic stereotactic radiotherapy (SBRT) in patients with localized low- and intermediate-risk PCa.Materials and methods. The study included 296 patients with localized low- and intermediate-risk PCa. I-125 BT and SBRT were performed in 208 and 88 patients, respectively. All patients with an intermediate-risk PCa were prescribed neoadjuvant androgen-deprivation therapy (NADT) with luteinizing hormone-releasing hormone analogues (LHRH) for 4-6 months. Only radiation treatment was used for low-risk PCa. As a result, two groups and four subgroups of patients were formed depending on the treatment method. The immediate, proximate, and long-term results of radiation treatment methods were studied in groups and subgroups.Results. No complications were recorded during brachytherapy I-125. Radiation cystitis grade 1 and radiation rectitis grade 1 were diagnosed after SBRT in 16.6% and 4.0% of cases, respectively. In the only I-125 BT subgroup, the PSA level during the year decreased from 8.3 to 1.1 ng/ml, in the SBRT subgroup — from 7.5 to 0.8 ng/ml. In the case of combined treatment, PSA decreased from 1.2 to 0.93 ng/ml and from 4.5 to 0.5 ng/ml, respectively. Changes in prostate volume, residual volume, and urinary quality (I-PSS) were comparable in all subgroups. Five-year cancer-specific survival and overall survival in the group of patients after SBRT was 100%, after I-125 BT — more than 90%.Conclusion. Radiation treatment options for patients with localized PCa are safe. Conducting NADT does not significantly reduce the prostate volume and does not affect the indicators of urodynamics. High rates of cancer-specific five-year survival rate testify to the effectiveness of the evaluated treatment options.

Preliminary Results of Multi-Institutional Phase 1 Dose Escalation Trial Using Single-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer

We report on our early experience of our prospective multicenter phase 1 dose- escalation study of single-fraction stereotactic partial breast irradiation (S-PBI) for early stage breast cancer after partial mastectomy using a robotic stereotactic radiation system. Thirty women with in situ or invasive breast cancer stage 0, I, or II with tumor size <3 cm treated with lumpectomy were enrolled in this phase 1 single-fraction S-PBI dose-escalation trial. Women received either 22.5, 26.5, or 30 Gy in a single fraction using a robotic stereotactic radiation system. The primary outcome was to reach tumoricidal dose of 30 Gy in a single fraction to the lumpectomy cavity without exceeding the maximum tolerated dose. Secondary outcomes were to determine dose-limiting toxicity and cosmesis. Tertiary goals were ipsilateral breast recurrence rate, distant disease-free interval, recurrence-free survival, and overall survival. From June 2016 to January 2021, 11, 8, and 10 patients were treated to doses of 22.5, 26.5, or 30 Gy in a single fraction, respectively, with median follow-up being 47.9, 25.1, and 16.2 months. No patients experienced acute (<90 days) grade 3 or higher treatment-related toxicity, and maximum tolerated dose was not reached. There were 2 delayed grade 3 toxicities. Four patients (13.8%) developed fat necrosis across all 3 cohorts, which compares favorably with results from other PBI trials. No dose cohort had a statistically significant cosmetic detriment from baseline to 12 months or 24 months follow-up by patient- or physician-reported global cosmetic scores. There were no reports of disease recurrence. This phase 1 trial demonstrates that S-PBI can be used to safely escalate dose to 30 Gy in a single fraction with low toxicity and without detriment in cosmesis relative to baseline.

Early Follow-Up of Multi-Institutional Trial of Phase I Dose Escalation Using Single Fraction Stereotactic Partial Breast Irradiation (S-PBI) for Early-Stage Breast Cancer

We report on our early experience of a phase I dose escalation study of single fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer after partial mastectomy using a robotic stereotactic radiation system.Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior to simulation, 3-4 gold fiducials were placed around the lumpectomy cavity to be used for real-time tracking during treatments. Dose limiting toxicity (DLT) was defined as grade ≥ 3 toxicity by CTCAE (version 4) deemed definitely related to treatment for: skin, ribs/bone (fracture), pulmonary (radiation pneumonitis), or neurological (intercostal or brachial plexus nerves) or any grade 4 or 5 toxicity definitely attributed to therapy. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires using a 4-point scale ranging from excellent, good, fair, or poor. Cohort 1 was 22.5 Gy, cohort 2 26.5 Gy, and cohort 3 30 Gy all delivered in a single fraction. Dose escalation was permitted provided that one or fewer of the first seven, or two or fewer of nine patients experienced a DLT within 90 days of treatment within each dose group. If more patients had DLT in a given dose cohort, the maximum tolerable dose (MTD) would have been exceeded.From 4/2016 to 1/2021, 11, 9, and 10 patients were treated on cohorts 1, 2 and 3 respectively. Of these, data from 18 evaluable patients from cohorts 1 and 2 and 6 patients from cohort 3, with at least 12 months of follow up are reported. Median f/u for cohort 1 was 36 m (r 24-48m), cohort 2 was 18 m (r 18-24m), and cohort 3 12 m (r 1-18m). Average age was 66.8 (r 47-84). Histology included 11 DCIS, and 19 invasive carcinomas. Of 11 DCIS, 9 were ER+, and 2 were ER-. All 19 invasive tumors were ER+. 23/29 patients received endocrine therapy, and no patient received chemotherapy. No patients experienced grade 3 or higher treatment related toxicity in the acute period (≤ 90 days), and MTD was not reached. There were two delayed grade 3 toxicities, (dose cohort 1 and 2, one patient had breast pain, and another had mastitis at 12 months and 9 months). No patients experienced grade 4 or 5 toxic events. Five patients developed fat necrosis in all three cohorts. Physicians scored cosmesis excellent or good at last follow-up in (10/11) 90%, (7/8) 87.5%, and (6/6)100%, in cohort 1,2, and 3 respectively, while patients scored excellent or good in (11/11) 100%, 8/8 (100%), and 5/6 (83%) patients. There has been no report of disease recurrences.Dose was escalated to 30 Gy in single fraction, and the majority of patients maintained good or excellent cosmetic outcome, without grade 3 or 4 toxicity. Continued analysis of all cohorts are in progress.

A new prognostic score for predicting survival in patients treated with robotic stereotactic radiotherapy for brain metastases

The study aimed to analyze potential prognostic factors in patients treated with robotic radiosurgery for brain metastases irrespective of primary tumor location and create a simple prognostic score that can be used without a full diagnostic workup. A retrospective analysis of 142 patients with 1–9 brain metastases treated with stereotactic radiosurgery (1–4 fractions) was performed. Volumes of all lesions were calculated using linear dimensions of the tumors (CC, LR, AP) and 4/3*π*(CC/2)*(LR/2)*(AP/2) formula. Kaplan–Meier method and log-rank test were used to analyze survival. Variables significantly associated with overall survival in univariate analysis were included in Cox multivariate analysis. The validity of the model was tested with the bootstrap method. Variables from the final model were used to construct a new prognostic index by assigning points according to the impact of a specific variable on overall survival. In the multivariate analysis, four factors: Karnofsky Performance Status (p = 0.000068), number of brain metastases (p = 0.019), volume of the largest lesion (p = 0.0037), and presence of extracerebral metastases (p = 0.0017), were independent predictors of survival. Total scores ranged from 0 to 12 points, and patients were divided into four groups based on median survival of each subgroup: 0–1 points—18.8 months, 2–3 points—16.9 months, 4–5 points—5.6 months, and ≥ 6 points—4.9 months (p < 0.001). The new prognostic index is simple to calculate. It has a strong prognostic value in a heterogeneous population of patients with a various number of brain metastases, but its value requires confirmation in another cohort.

Synthetic digital reconstructed radiographs for MR-only robotic stereotactic radiation therapy: A proof of concept

PurposeTo create synthetic CTs and digital reconstructed radiographs (DRRs) from MR images that allow for fiducial visualization and accurate dose calculation for MR-only radiosurgery. MethodsWe developed a machine learning model to create synthetic CTs from pelvic MRs for prostate treatments. This model has been previously proven to generate synthetic CTs with accuracy on par or better than alternate methods, such as atlas-based registration. Our dataset consisted of 11 paired CT and conventional MR (T2) images used for previous CyberKnife (Accuray, Inc) radiotherapy treatments. The MR images were pre-processed to mimic the appearance of fiducial-enhancing images. Two models were trained for each parameter case, using a sub-set of the available image pairs, with the remaining images set aside for testing and validation of the model to identify the optimal patch size and number of image pairs used for training. Four models were then trained using the identified parameters and used to generate synthetic CTs, which in turn were used to generate DRRs at angles 45° and 315°, as would be used for a CyberKnife treatment. The synthetic CTs and DRRs were compared visually and using the mean squared error and peak signal-to-noise ratio against the ground-truth images to evaluate their similarity. ResultsThe synthetic CTs, as well as the DRRs generated from them, gave similar visualization of the fiducial markers in the prostate as the true counterparts. There was no significant difference found for the fiducial localization for the CTs and DRRs. Across the 8 DRRs analyzed, the mean MSE between the normalized true and synthetic DRRs was 0.66 ± 0.42% and the mean PSNR for this region was 22.9 ± 3.7 dB. For the full CTs, the mean MAE was 72.9 ± 88.1 HU and the mean PSNR was 31.2 ± 2.2 dB. ConclusionsOur machine learning-based method provides a proof of concept of a way to generate synthetic CTs and DRRs for accurate dose calculation and fiducial localization for use in radiation treatment of the prostate.

Dosimetric comparison and secondary malignancy risk estimation for linac-based and robotic stereotactic radiotherapy in uveal melanoma

It was aimed to investigate the dosimetric differences among linac-based and robotic stereotactic radiotherapy (SRT) techniques for the treatment of uveal melanoma and to evaluate secondary malignancy risks for these different SRT techniques. Ten patients who received robotic SRT with CyberKnife were retrospectively included in this study. A total dose of 54 Gy in three fractions was prescribed to the planning target volume (PTV). For each patient, non-coplanar micro-multileaf collimator based dynamic conformal arc (DCA), intensity-modulated radiotherapy (IMRT) and circular cone based DCA (cDCA) plans were generated. During the analysis dose-volume histogram (DVH) parameters, homogeneity index, new conformity index, the volume received more than or equal to 30% and 50% of the prescribed dose were compared. Additionally, secondary malignancy risk for each technique was estimated using the risk factors recommended by The International Commission on Radiological Protection. Robotic SRT plans provided a high degree of conformity within the PTV and better normal tissue sparing compared to linac-based treatment plans. However, dose distribution was more heterogeneous in robotic SRT plans than that in linac-based techniques. Estimated secondary malignancy risk was also found as 3.4%, 1.4%, 1.4% and 1.6% for robotic SRT and linac-based IMRT, DCA, cDCA plans, respectively. Treatment parameters of uveal melanoma patients planned with robotic SRT had superior conformity and organ-at-risk (OAR) sparing compared with those planned with the linac-based system. However, estimated secondary malignancy risk was almost two-times higher in robotic SRT than that in linac-based techniques.

Multi-Institutional Trial of Phase I Dose Escalation Using Single Fraction Stereotactic Partial Breast Irradiation (S-PBI) for Early Stage Breast Cancer

We report on our early experience of a phase I dose escalation study of single fraction stereotactic partial breast irradiation (S-PBI) for early stage breast cancer after partial mastectomy using a robotic stereotactic radiation system. Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior to simulation, 3-4 gold fiducials were placed around the lumpectomy cavity to be used for real-time tracking during treatments. Dose limiting toxicity (DLT) was defined as grade ≥ 3 toxicity by CTCAE (version 4) deemed definitely related to treatment for: skin, ribs/bone (fracture), pulmonary (radiation pneumonitis), or neurological (intercostal or brachial plexus nerves) or any grade 4 or 5 toxicity definitely attributed to therapy. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires using a 4-point scale ranging from excellent, good, fair, or poor. Initial dose cohort was 22.5 Gy delivered in single fraction, and dose cohorts 2 and 3 (26.5 Gy and 30 Gy in single fraction, respectively). Dose escalation was permitted provided that one or fewer of the first seven, or two or fewer of nine patients experienced a DLT within 90 days of treatment within each dose group. If more patients had DLT in a given dose cohort, the maximum tolerable dose (MTD) would have been exceeded. From 4/2016 to 1/2020, 11, 8, and 8 patients were treated on cohorts 1, 2 and 3 respectively. Of these, data from 19 evaluable patients from cohorts 1 and 2 with at least 12 months of follow up are reported. Median f/u for cohort 1 was 27.3 m (r 24-36m), and cohort 2 was 15 m (r 12-18m). Average age was 65 (r 47-84). Histology included 9 DCIS, and 10 invasive carcinomas. Of 9 DCIS, 8 were ER+, and 1 was ER-. All 10 invasive tumors were ER+. 17/19 patients received endocrine therapy, and no patient received chemotherapy. In cohorts 1 and 2, no patients experienced grade 3 or higher treatment related toxicity in the acute period (≤ 90 days), and MTD was not reached. There were two delayed grade 3 toxicities, one in each cohort (one patient had breast pain, and another had mastitis, at 12 months and 9 months). No patients experienced grade 4 or 5 toxic events. Four patients developed fat necrosis diagnosed at 10 and 12 mo. in cohort 1, and 9 and 10 months after radiation treatments (with only 1 being painful and others asymptomatic). Physicians scored cosmesis excellent or good in 100%, 100%, 100%, and 100%, respectively, at baseline, 3, 6, and 12 months post S-PBI, while patients scored the same periods 89.5%, 95%, 100%, and 90.9%. There has been no report of disease recurrences. Dose was escalated to 30 Gy in single fraction without a DLT, and the majority of patients maintained good or excellent cosmetic outcome. Continued analysis of all cohorts is in progress.

Effect Of Robotic Stereotactic Radiotherapy For Parasellar Tumors On The Eye Structure And Function

To evaluate radiation-induced effect on the anterior and posterior segment of the eye in patients undergoing robotic stereotactic radiotherapy for parasellar tumors A prospective analysis was performed on 34 patients (68 eyes) undergoing CK radiotherapy for parasellar tumors from 2010 to 2015. A total of 10 patients were diagnosed with cavernous sinus meningioma, 9 with pituitary adenoma, 5 with meningioma in the region close to optic chiasm, 5 with meningioma of the anterior and middle cranial fossa, 3 with craniopharyngioma, and 2 with meningioma of the orbit. All treatment plans were designed to fulfill Timmermann criteria for the optic pathway. Doses delivered to eye structures were in the range of 1-2227 cGy. Radiation-induced impact on the eye was evaluated based on the changes in the condition of the eye surface, central corneal thickness (CCT), endothelial cell density (ECD), lens densitometry, central macular thickness (CMT), retinal nerve fiber layer (RNFL) in the proximal eye (on the side of the tumor) and in the distal eye (on the opposite side). Best-corrected visual acuity (BCVA), intraocular pressure (IOP), and visual evoked potentials (VEP) were analyzed as functional features. All ophthalmological examinations were performed before radiotherapy and at 6, 12, 18 and 24 months after radiotherapy. There were no statistically significant changes in the BCVA, IOP, condition of the eye surface, CCT, lens densitometry and CMT during the 24-month follow-up period. We observed significant decrease of ECD for all observation intervals when compared to EDC before radiotherapy. The decrease in ECD was greater than approximated age-related physiological loss (0.3% vs 1.9% ±0.5% per year). However, no significant correlation was found between the radiation dose delivered to the cornea and the change in ECD. We observed statistically significant decrease of RNFL in all observation time points. In 6 eyes in (5 patients) the decrease of RNFL was greater than 10%. There was also no correlation between dose delivered to optic pathway and decrease of RNFL. Moreover, doses delivered to individual parts of the optic pathway did not differ significantly for the eyes with 10% drop of RNFL more compared to doses delivered for other eyes. Changes of RNFL were not significant enough to affect visual function. We did not observe significant changes for VEP latency but a significant decrease in VEP amplitude was observed. Robotic RT is a precise and advanced treatment modality with a high safety profile and a low risk for radiation-induced complications in the anterior and posterior segment of the eye. Detailed ophthalmological examination showed significant changes in corneal structure (decrease of ECD) and optic nerve structure (decrease of RNFL) after radiotherapy. Structural changes did not result in alteration of visual function.

Reducing the Risk of Secondary Lung Cancer in Treatment Planning of Accelerated Partial Breast Irradiation.

Purpose: Adjuvant accelerated partial breast irradiation (APBI) results in low local recurrence risks. However, the survival benefit of adjuvant radiotherapy APBI for low-risk breast cancer might partially be offset by the risk of radiation-induced lung cancer. Reducing the lung dose mitigates this risk, but this could result in higher doses to the ipsilateral breast. Different external beam APBI techniques are equally conformal and homogenous, but the intermediate to low dose distribution differs. Thus, the risk of toxicity is different. The purpose of this study is to quantify the trade-off between secondary lung cancer risk and breast dose in treatment planning and to compare an optimal coplanar and non-coplanar technique.Methods: A total of 440 APBI treatment plans were generated using automated treatment planning for a coplanar VMAT beam-setup and a non-coplanar robotic stereotactic radiotherapy beam-setup. This enabled an unbiased comparison of two times 11 Pareto-optimal plans for 20 patients, gradually shifting priority from maximum lung sparing to maximum ipsilateral breast sparing. The excess absolute risks of developing lung cancer and breast fibrosis were calculated using the Schneider model for lung cancer and the Avanzo model for breast fibrosis.Results: Prioritizing lung sparing reduced the mean lung dose from 2.2 Gy to as low as 0.3 Gy for the non-coplanar technique and from 1.9 Gy to 0.4 Gy for the coplanar technique, corresponding to a 7- and 4-fold median reduction of secondary lung cancer risk, respectively, compared to prioritizing breast sparing. The increase in breast dose resulted in a negligible 0.4% increase in fibrosis risk. The use of non-coplanar beams resulted in lower secondary cancer and fibrosis risks (p < 0.001). Lung sparing also reduced the mean heart dose for both techniques.Conclusions: The risk of secondary lung cancer of external beam APBI can be dramatically reduced by prioritizing lung sparing during treatment planning. The associated increase in breast dose did not lead to a relevant increase in fibrosis risk. The use of non-coplanar beams systematically resulted in the lowest risks of secondary lung cancer and fibrosis. Prioritizing lung sparing during treatment planning could increase the overall survival of early-stage breast cancer patients by reducing mortality due to secondary lung cancer and cardiovascular toxicity.

Assessment of Spinal Tumor Treatment Using Implanted 3D-Printed Vertebral Bodies with Robotic Stereotactic Radiotherapy

SummaryTo investigate the feasibility and early efficacy of 3D-printed vertebral body implantation combined with robotic radiosurgery in the treatment of spinal tumors. This study included 14 patients with spinal tumors from December 2017 to June 2018. Before surgery, all patients were subjected to CT scan and 3D data of the corresponding vertebral segments were collected. Titanium alloy formed 3D-printed vertebral body implantation and robotic stereotactic radiotherapy were performed because of the risk of postoperative residual, high risk of recovery, or recurrence after surgery. The main outcomes included the remission of symptoms, vertebral body stability, robotic stereotactic surgical precision, and local tumor control. All patients received complete and successful combination therapy, and all healed primarily without complications. The error of the coverage accuracy for robotic radiosurgery was less than 0.5 mm, and the error of the rotation angle was less than 0.5°. The therapeutic toxicity was limited (mainly in grades 1–2), and adverse events were uncommon. The evaluation of vertebral body stability and histocompatibility for all patients met the postoperative clinical requirements. For patients with post spinal injury, the pain symptoms were reduced or disappeared (93%), and nerve function was improved or even recovered after treatment (100%). During our follow-up period, most tumors were locally well controlled (93%). 3D- printed vertebral body implantation combined with robotic radiosurgery may offer a new treatment of spinal tumors.Chinese clinical trial registry: ChiCTR-ONN-17013946.

Robotic stereotactic ablative radiotherapy for renal cell carcinoma in patients with impaired renal function

BackgroundRobotic stereotactic ablative radiotherapy (SABR) is currently under investigation as a noninvasive treatment option for patients with renal cell carcinoma (RCC). For radiation therapy of RCC, tumor motion and the need for high ablative doses while preserving the remaining renal parenchyma is a challenge. We aimed to analyze the safety and efficacy of robotic radiosurgery in RCC in a specific difficult subgroup of patients with impaired renal function.MethodsWe retrospectively identified all patients with RCC, treated with robotic SABR and motion compensation in our institution between 2012 and 2017. Either single fraction SABR of 24 or 25 Gy or 3 fractions of 12 Gy prescribed to the 70% isodose line was applied. Local control, overall survival, radiation side effects were evaluated together with renal function and tumor motion.ResultsWe analyzed data of 13 lesions treated in 10 patients with clear cell RCC and a mean age of 70.5 ± 13.6 years (range: 48–87). Prior to SABR, 8 patients underwent previous complete and/or partial nephrectomy, 7 patients presented with chronic kidney disease ≥ stage 3. The median of minimum, mean and maximum planning target volume doses were 23.2, 29.5 and 35.0 Gy for single fraction and 24.4, 42.5 and 51.4 Gy for the three fractions regime. Persistent local control by robotic SABR was achieved in 9 out of 10 patients (92.3% of all lesions) within a median follow-up period of 27 month (range: 15–54). One patient underwent nephrectomy due to progressive disease and sufficient renal function of the contralateral kidney. Renal function remained stable with a mean estimated glomerular filtration rate (eGFR) of 51.3 ± 19.7 ml/min at baseline and 51.6 ± 25.8 ml/min at follow-up. The largest respiratory-induced tumor motion was seen in superior-inferior direction, compensated by the CyberKnife with mean targeting errors of maximal 2.2 mm.ConclusionsRobotic SABR is technically feasible for the treatment of RCC in preexisting kidney disease with good local tumor control at about 2 years follow-up. Robotic SABR with motion tracking offers a valid treatment option for patients, who are at increased risk for progression to end-stage renal disease due to partial nephrectomy or ablative techniques.