Stereotactic Radiotherapy Treatment Research Articles

Treatment Reproducibility in Brain Stereotactic Radiotherapy Using a Shim Mask Versus a Standard Mask.

Introduction This study aimed to evaluate the setup accuracy of the new shim mask with mouth bite compared to the standard full brain mask in stereotactic radiosurgery (SRS) and radiotherapy (SRT) treatments for brain metastases or tumors. Method A combined retrospective and prospective design was employed, involving 40 patients treated at our center. Patients previously treated using standard head masks formed the retrospective cohort, while those treated with the Shim mask and mouth bite formed the prospective cohort. Daily cone-beam computed tomography (CBCT) scans were obtained before each treatment session to ensure patient setup accuracy. Key metrics included absolute shifts in translational and rotational directions, the number of repeat CBCTs, and the time interval between CBCTs. Results The Shim mask significantly reduced the mean setup errors in the lateral translation (p=0.022) from 0.17 cm (SD=0.10) to 0.10 cm (SD=0.10), and in X-axis rotation (p=0.030) from 0.79° (SD=0.43) to 0.47° (SD=0.47). By considering cutoff points of 1 mm in translational and 1° in rotational directions, the Shim mask was significantly more accurate in the lateral direction (p=0.004). Moreover, while 70% of patients in the standard group required repeat CBCT scans, none in the Shim group did, resulting in an average time saving of 10.4 minutes per patient. Conclusion The Shim mask with mouth bite offers enhanced immobilization accuracy in SRT/SRS treatments, leading to time and potential cost savings by reducing the need for repeat CBCT scans. This underscores the importance of adopting innovative immobilization techniques to optimize patient outcomes.

Quality assurance for cancer patient safety: Clinical assessment for precise angles in linac during radiation therapy.

Quality assurance for stereotactic body radiation treatment requires that isocentric verification be ensured during gantry rotation at various angles. This study examined statistical parameters on Winston-Lutz tests to distinguish the deviation of angles from isocenter during gantry rotation using machine learning. The Varian TrueBeam linac was aligned with the marked lines on the Ruby phantom. Eight images were captured while the gantry was rotating at a 45° shift. The statistical features were derived from IsoCheck EPID software. The decision tree model was applied to these Winston-Lutz tests to cluster data into two groups: precise and error angles. At 90° and 270° angles, the gantry exhibits isocentric stability compared to other angles. In these angles, the most statistical features were inside the range. Most variations were observed at 0° and 180° angles. In most tests, the angles 45°, 135°, 225°, and 315° showed reasonable performance and with less variation. The comprehensive statistical analyses for gantry rotation of angles assists expert radiotherapists in determining the contribution of each feature that highly affects gantry movement at specific angles. Misalignment between radiation isocenter and imaging isocenter, tuning of the beam at each angle, or a slight change in the position of the Ruby phantom can further improve the inaccuracy that causes the most variations. Better precision can effectively increase patient safety and quality during cancer treatment.

2024 Guidelines for reporting radiation therapy in veterinary medicine.

Evidence-based medicine drives patient care decision-making; thus, accurate and complete reporting in scientific publications is paramount. A checklist for complete reporting of veterinary radiation therapy was proposed in 2012 using the recommendations of the International Commission of Radiation Units and Measurements (ICRU). The purpose of this study is to review the 2012 checklist and propose updates based on changes in technology. Significant technology advancements have gained traction in veterinary medicine, including intensity-modulated radiation therapy (IMRT) and stereotactic radiation therapy (SRT), both of which have related modality-specific ICRU reporting recommendations. The 2012 checklist and proposed 2024 checklist are then used to assess the completeness of reporting in veterinary radiation oncology publications between 2015 and 2022, of which one hundred and eight publications met the inclusion criteria. Prior to the publication of the 2012 checklist (2005-2010), only nine checklist items showed a good level of completeness in reporting, and from 2015 to 2022, this increased to 16 items. Encouraging and/or requiring the use of reporting checklists at the time of manuscript submission may be responsible for this improvement in reporting. Using the 2024 checklist, which is more relevant to publications discussing IMRT and SRT treatments, only 14 of the analyzed checklist items (34%) show a good level of completeness in reporting, suggesting there is a need for updated guidelines to capture the nuances of advanced techniques. This study proposes a 2024 checklist that can be used as a guideline for future reporting of radiation therapy in veterinary medicine.

Radiation-Induced DNA Damage in Uveal Melanoma Is Influenced by Dose Delivery and Chromosome 3 Status.

The purpose of this study was to analyze the extent of DNA breaks in primary uveal melanoma (UM) with regard to radiotherapy dose delivery (single-dose versus fractionated) and monosomy 3 status. A total of 54 patients with UM were included. Stereotactic radiotherapy (SRT) was performed in 23 patients, with 8 undergoing single-dose SRT (sdSRT) treatment and 15 receiving fractionated SRT (fSRT). DNA breaks in the enucleated or endoresected tumors were visualized by a TUNEL assay and quantified by measuring the TUNEL-positive area. Protein expression was analyzed by immunohistochemistry. Co-detection of chromosome 3 with proteins was performed by immuno-fluorescent in situ hybridization. The amount of DNA breaks in the total irradiated group was increased by 2.7-fold (P < 0.001) compared to non-irradiated tissue. Tumors treated with fSRT were affected more severely, showing 2.1-fold more DNA damage (P = 0.007) compared to the cases after single (high) dose irradiation (sdSRT). Monosomy 3 tumors showed less DNA breaks compared to disomy 3 samples (P = 0.004). The presence of metastases after radiotherapy correlated with monosomy 3 and less DNA breaks compared to patients with non-metastatic cancer in the combined group with fSRT and sdSRT (P < 0.05). Fractionated irradiation led to more DNA damage than single-dose treatment in primary UM. As tumors with monosomy 3 showed less DNA breaks than those with disomy 3, this may indicate that they are less radiosensitive, which may influence the efficacy of irradiation.

High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial)

IntroductionThe standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up).MethodsIn this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated.DiscussionThis is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option.Trial registrationClinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021.

Efficacy and safety of stereotactic radiotherapy on elderly patients with stage I-II central non-small cell lung cancer.

Many studies demonstrated the safety and efficacy of SBRT in the treatment of elderly patients with early-stage non-small cell lung cancer (NSCLC). However, those studies focused on patients with peripheral lung cancer. This study aimed to evaluate the clinical efficacy and toxicity of SBRT in elderly patients with stage I-II central NSCLC in single institution. From April 2009 to January 2020, a retrospective study was conducted on patients ≥ 65 years old with stage I-II NSCLC that was centrally localized and treated with SBRT at a single institution. Absolute C-reactive protein (CRP)/albumin ratio (CAR) and body mass index (BMI) recorded at pretreatment were analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), cancer-specific death, noncancer-specific death, local progression (LP) and distant progression (DP). Stereotactic body radiation treatment (SBRT) was administered to a total of 44 patients. The most common dose fractionation schedule was 60 Gy given in 5 fractions. The median PFS of the cohort was 31 months (95% CI, 19.47-42.53 months). The median OS of all patients was 69 months (95% CI, 33.8-104.2 months). The median time to noncancer-specific death was 54.5 months. The median time to cancer-specific death was 36 months. The cumulative incidences of cancer-specific death at 1 year, 5 years, and 10 years were 11.63% (95%CI, 4.2-23.23%), 42.99% (95%CI, 27.56-57.53%), and 65.94% (95%CI, 45.76-80.1%), respectively. pre-SBRT BMI of ≤ 22.77 (HR 4.60, 95% CI 1.84-11.51, P=0.001) and pre-SBRT CAR of ≤0.91 (HR 5.19, 95% CI 2.15-12.52, P<0.000) were significant predictors of higher OS on multivariable analysis. The median times to LP and DP were 10 months and 11 months, respectively. In terms of acute toxicity, grade 1 including cough (38.64%), radiation pneumonitis (29.55%), anemia (25%), and fatigue (20.45%) was often observed. There was no evidence of grade 4 or 5 acute toxicity. In terms of late toxicity, 2 patients developed grade 1 pulmonary fibrosis during follow-up. This study showed that SBRT can effectively control local tumor progression, and have acceptable toxicity for elderly patients with centrally located stage I-II NSCLC. Lower pre-SBRT BMI and lower pre-SBRT CAR were associated with a decreased risk of cancer-specific death.

Evaluation of Circulating Tumor DNA as a Liquid Biomarker in Uveal Melanoma.

Uveal melanoma (UM) has a high propensity to metastasize. Prognosis is associated with specific driver mutations and copy number variations (CNVs), but limited primary tumor tissue is available for molecular characterization due to eye-sparing irradiation treatment. This study aimed to assess the rise in circulating tumor DNA (ctDNA) levels in UM and evaluate its efficacy for CNV-profiling of patients with UM. In a pilot study, we assessed ctDNA levels in the blood of patients with UM (n = 18) at various time points, including the time of diagnosis (n = 13), during fractionated stereotactic radiotherapy (fSRT) treatment (n = 6), and upon detection of metastatic disease (n = 13). Shallow whole-genome sequencing (sWGS) combined with in silico size-selection was used to identify prognostically relevant CNVs in patients with UM (n = 26) from peripheral blood retrieved at the time of diagnosis (n = 9), during fSRT (n = 5), during post-treatment follow-up (n = 4), metastasis detection (n = 6), and metastasis follow-up (n = 4). A total of 34 patients had blood analyzed for ctDNA detection (n = 18) and/or CNV analysis (n = 26) at various time points. At the time of diagnosis, 5 of 13 patients (38%) had detectable ctDNA (median = 0 copies/mL). Upon detection of metastatic disease, ctDNA was detected in 10 of 13 patients (77%) and showed increased ctDNA levels (median = 24 copies/mL, P < 0.01). Among the six patients analyzed during fSRT, three (50%) patients had detectable ctDNA at baseline and three of six (50%) patients had undetectable levels of ctDNA. During the fSRT regimen, ctDNA levels remained unchanged (P > 0.05). The ctDNA fractions were undetectable to low in localized disease, and sWGS did not elucidate chromosome 3 status from blood samples. However, in 7 of 10 (70%) patients with metastases, the detection of chromosome 3 loss corresponded to the high metastatic-risk class. The rise in ctDNA levels observed in patients with UM harboring metastases suggests its potential utility for CNV profiling. These findings highlight the potential of using ctDNA for metastasis detection and patient inclusion in therapeutic studies targeting metastatic UM.

Stereotactic radiotherapy of intracranial tumor beds on a ring-mounted Halcyon LINAC.

This study sought to evaluate the feasibility and efficacy of the Halcyon Ring Delivery System (RDS) for delivering stereotactic radiotherapy (SRT) treatments for intracranial tumors beds. Ten previously treated brain SRT patients for 30Gy in five fractions with non-coplanar HyperArc plans on TrueBeam (6MV-FFF) were replanned on Halcyon (6MV-FFF) using the same number of arcs and Eclipse's AcurosXB dose engine. Plan quality evaluation metrics per SRT protocol included: PTV coverage, GTV dose (minimum and mean), target conformity indices (CI), heterogeneity index (HI), gradient index (GI), maximum dose 2cm away from the PTV (D2cm), and doses to organs-at-risk (OAR). Additionally, patient-specific quality assurance (QA) results and beam-on-time (BOT) were analyzed. The Halcyon RDS provided highly conformal SRT plans for intracranial tumor beds with similar dose to target. When benchmarked against clinically delivered HyperArc plans, target coverage, CI(s) and HI were statistically similar. The Halcyon plans saw no statistical difference in maximum OAR doses to the brainstem, spinal cord, and cochlea. Due to the machine's coplanar geometry, the Halcyon plans showed a decrease in optic pathway dose (0.75Gy vs. 2.08Gy, p=0.029). Overall, Halcyon's coplanar geometry resulted in a larger GI (3.33vs. 2.72, p=0.008) and a larger D2cm (39.59%vs. 29.07%, p<0.001). In this cohort, multiple cases had the PTV and the optic pathway in the same axial plane. In one such instance, the PTV was<2cm away from the optic pathway but even at this close proximity OAR, Halcyon still adequately spared the optic pathway. Additionally, the Halcyon's geometry provided slightly larger amount of normal brain dose receiving 24.4Gy (8.99 cc vs. 7.36 cc) and 28.8Gy (2.9 cc vs. 2.5 cc), although statistically insignificant. The Halcyon plans achieved similar delivery accuracy, quantified by patient-specific QA results evaluated with a 2%/2mm gamma criteria (99.42%vs. 99.70%). For both plans, independent Monte Carlo second checks calculation agreed within 1%. Average Halcyon BOT was slightly higher by 0.35min (p=0.045), however, due to the one-step patient set-up and verification overall estimated treatment times on Halcyon were lower compared to HyperArc treatments (7.61min vs. 10.26min, p<0.001). When benchmarked against clinically delivered HyperArc treatments, the Halcyon brain SRT plans provided similar plan quality and delivery accuracy but achieved faster overall treatment times. We have started treating select brain SRT patients on the Halcyon RDS for patients having tumor beds greater than 1cm in diameter with the closest OAR distance of greater than 2cm away from the target. We recommend other clinics to consider commissioning SRT treatments on their Halcyon systems-allowing including remote Halcyon-only clinics to provide exceptionally high-quality therapeutic brain SRT treatments to an otherwise underserved patient cohort.

Optimization of stereotactic radiotherapy (SRT) planning for brain metastases from lung cancer by Cyberknife system: reducing dose distribution inner ear.

Objective: Through retrospective statistical analysis of radiation distribution in inner ear avoidance for brain metastases from lung cancer by the CyberKnife (CK) system, it can provide a reference for stereotactic radiotherapy (SRT) planning and treatment optimization. Methods: Computed tomography/magnetic resonance imaging data of 44 patients with one brain metastases lesion from lung cancer were used to re-plan and analyze, who had been treated by CK system from April 2021 to April 2022. The prescribed doses of 14-30 Gy in 1-3 fractions was simultaneously delivered to the metastatic lesions. The SRT plans for the same patients were replaned under with and without inner ear avoidance setting. The plan parameters and dose distribution differences were compared between plans. Results: All plans met the dose restrictions. There were no significant differences in the coverage (Coverage), conformity index (CI), mean dose (Dmean), the maximum dose (Dmax) and minimum dose (Dmin) of planning target volume (PTV). With inner ear avoidance setting, the Dmax and Dmean of inner ear area decreased by 13.76% and 12.15% (p<0.01), respectively. The total number of machine nodes and monitor units (MU) increased by 4.63% and 1.06%. Conclusions: During the SRT plan designing for brain metastases from lung cancer, the dose distribution in inner ear area could be reduced by avoidance setting, and the patient's hearing would be well protected.

Stereotactic radiotherapy for advanced canine anal sac adenocarcinoma: an exploratory study.

For dogs with anal sac adenocarcinoma (ASAC), metastasis to intra-abdominal and pelvic lymph nodes occurs early in the disease course. Death is usually related to locoregional progression. Surgical excision is the treatment of choice, but may not be possible in advanced cases. Dogs treated with RT in the gross disease setting showed a 38%-75% overall response rate, but side effects to organs at risk in this area (especially the colon, bladder, and spinal cord) were reported. Stereotactic radiation therapy (SRT) utilizes highly conformal treatment planning with rapid dose fall-off and hypofractionation. SRT may help to reduce the risk of late side effects of radiation while also creating a larger biological effect on ASACs. A primary aim of this prospective, descriptive, exploratory study was to describe the safety and feasibility of an SRT protocol in a small sample of dogs with ASAC, using objective and subjective measures to monitor acute and late side effects. A secondary aim was to describe the anti-tumor response of the SRT protocol using CT at 3- and 6 months posttreatment. Five dogs completed the radiation protocol. Four had follow-up CT characteristics of complete response (1), partial response (2), and stable disease (1). Minimal acute side effects were observed. Despite some large tumor volumes, constraints for OAR were achieved in all but the spinal cord for one patient. Findings indicated that SRT is a safe and feasible treatment for dogs with ACAC. Future studies are warranted to compare patient outcomes for SRT versus other treatments.

A dosimetric study comparing Cyberknife and LINAC-based stereotactic radiotherapy or radiosurgery treatments

BackgroundWhile Gamma Knife and CyberKnife are commonly used for Stereotactic radiosurgery (SRS), their availability is limited. In contrast, linac-based SRS using linear accelerators (linacs) is more accessible and widely used. PurposeOur study aims to evaluate Linac-based SRS with the Varian RapidArc technique for treating brain metastases. The primary objective is to compare the quality of treatment plans between RapidArc and CyberKnife modalities. Materials & methodsTen patients with a single brain metastasis were treated using the CyberKnife machine with prescribed doses ranging from 18 to 25 Gy. Treatment plans utilized Multiplan software for CyberKnife and Eclipse for RapidArc plans. The plans were evaluated based on dose metrics for the target and critical structures, treatment time, and brain tissue volume. ResultsBoth techniques provided acceptable Gross tumor volume coverage and organs at risk sparing. CyberKnife delivered a higher integral dose to the Gross tumor volume and brain tissues compared to RapidArc (p < 0.05). The conformity index was slightly better in RapidArc (1.14 ± 0.25) compared to CyberKnife (1.22 ± 0.12), but the difference was not statistically significant (p > 0.05). However, CyberKnife exhibited a better dose gradient index (4.52 ± 0.99) compared to RapidArc (8.6 ± 7.28). The treatment time in RapidArc was significantly lower compared to CyberKnife, p < 0.05. RapidArc demonstrated lower minimum and maximum doses to some organs at risk, although some differences were not statistically significant. For normal brain tissues, V12Gy was significantly lower with RapidArc (3.27 ± 2.92) compared to CyberKnife (4.09 cc ± 3.27). ConclusionThe RapidArc technique is capable of achieving similar treatment quality as CyberKnife systems for SRS treatments. It offers improved target coverage, higher conformity, and homogeneous dose distribution within the Planning target volume if homogeneity is desirable in some intuitions or cases. In addition, it can also achieve low integral doses to organs at risk and brain tissues.

Online Adaptive MRI-Guided Stereotactic Body Radiotherapy for Pancreatic and Other Intra-Abdominal Cancers.

A 1.5T MRI combined with a linear accelerator (Unity®, Elekta; Stockholm, Sweden) is a device that shows promise in MRI-guided stereotactic body radiation treatment (SBRT). Previous studies utilized the manufacturer's pre-set MRI sequences (i.e., T2 Weighted (T2W)), which limited the visualization of pancreatic and intra-abdominal tumors and organs at risk (OAR). Here, a T1 Weighted (T1W) sequence was utilized to improve the visualization of tumors and OAR for online adapted-to-position (ATP) and adapted-to-shape (ATS) during MRI-guided SBRT. Twenty-six patients, 19 with pancreatic and 7 with intra-abdominal cancers, underwent CT and MRI simulations for SBRT planning before being treated with multi-fractionated MRI-guided SBRT. The boundary of tumors and OAR was more clearly seen on T1W image sets, resulting in fast and accurate contouring during online ATP/ATS planning. Plan quality in 26 patients was dependent on OAR proximity to the target tumor and achieved 96 ± 5% and 92 ± 9% in gross tumor volume D90% and planning target volume D90%. We utilized T1W imaging (about 120 s) to shorten imaging time by 67% compared to T2W imaging (about 360 s) and improve tumor visualization, minimizing target/OAR delineation uncertainty and the treatment margin for sparing OAR. The average time-consumption of MRI-guided SBRT for the first 21 patients was 55 ± 15 min for ATP and 79 ± 20 min for ATS.

Correlation Between Oligometastatic Tumor in Two Other Visceral Organs and Prognosis in Patients With Brain Metastases.

Background and Objective: A recent report indicated that metastases to other body organs commonly develop after stereotactic body radiation treatment for cure in patients with oligometastases (OGM) confined to one organ. This study was undertaken to determine if the presence of metastatic disease in two other visceral organs (TVO) in patients with conventionally treated brain metastases (BRM) was associated with poorer prognosis. Methods: This retrospective clinical investigation included 26 patients treated for palliation of OGM-BRM between May 1996 and February 2020. These individuals were classified according to the presence (13 patients) or absence (13 patients) of metastases in TVO. Results: With an overall mean follow-up of 16 months, 20 patients were deceased, and 6 patients were alive. The median survivals for the OGM-BRM-TVO and non-OGM-BRM-TVO subsets were 4 and 12 months, respectively; the corresponding crude survival rates at 12 months were 0% and 46% (p < 0.01). Subgroup analysis correlating prognosis to the number of BRM (single vs. multiple) and OGM-BRM categories (synchronous vs. metachronous) failed to reveal a survival advantage favoring a certain subgroup. Conclusion: Although the evidence is speculative, we believe that an aggressive disease condition is more likely present in patients with OGM-BRM-TVO. With the notion of an overall poor survival, we suggest a more tailored, less or nonharmful management approach (i.e., palliative therapy or hospice) for this particular patient cohort.

OTHER-10 EARLY CLINICAL EXPERIENCE OF SRS AND SBRT STEREOTACTIC BODY RADIOTHERAPY FOR CENTRAL NERVOUS SYSTEM (CNS) CASE SERIES AT HCG CANCER CENTRE, NAIROBI.

Abstract BACKGROUND Stereotactic Radiosurgery (SRS), Stereotactic Radiotherapy(SRT) and Stereotactic Body Radiation Therapy (SBRT) delivers fewer high-dose fractions of radiation which may be radiobiologically favorable to conventional low-dose fractions commonly used for central nervous system. We report our early experience using SBRT in central nervous tumours (CNS). METHODS / INTRODUCTION Sequential patients treated with SBRT from December 2022 to May 2023 at HCG Cancer Care Kenya for CNS tumours will be included in this retrospective review of early clinical data collected in the institutional database. SBRT treatments were delivered using VersaHD Linac with doses ranging from 36.25Gy to 30Gy delivered in 3 to 5 fractions. Local guidelines have been developed to guide stereotactic radiotherapy treatments in Kenya. The national health insurer is currently reimbursing for stereotactic treatments would further increases the uptake. Discussion The CNS cases that has been treated locally with SRS/SRT/SBRT with CNS case series shall be evaluated under clinical presentation, treatment planning process in recurrent Meningioma, Glomus tymphanicum and brain metastasis. The radiobiological advantage of SRS/SRT/SBRT over conventional radiotherapy is the short course treatment with minimal toxicity. SRS/SBRT is not oxygen dependent tumor DNA damage but related to endothelial cell damage from apoptosis. The treatment volume margins in CNS cancers are tight to a millimeter hence rigid immobilization with head fraxion frame is required. The turnaround time from diagnosis, planning to treatment delivery for the patients is 72 hours. RESULTS 30 patients underwent SBRT treatment techniques varying from CNS and other sites. The case presentations in case series met the criteria and indications for SBRT treatment. The initial patient reported the treatment to be tolerable however currently we do have data on acute and long term in terms of both outcomes and toxicity. Follow up is needed to review and report on the outcomes.

Impact of Waiting Response Evaluation to First-Line Systemic Therapy before Considering Local Ablative Therapy in Metastatic Non-Small-Cell Lung Cancer.

Stereotactic radiotherapy (SRT) is gaining increasing importance in metastatic non-small-cell lung cancer (mNSCLC) management. The optimal sequence of tumor irradiation relative to systemic treatment remains unclear. If waiting response evaluation to first-line systemic therapy (FLST) before considering local treatment may allow for the exclusion of poorer prognosis progressive tumors that may not benefit from SRT, performing irradiation near immune check point inhibitor (ICI) first administration seems to improve their synergic effect. Herein, we aimed to determine whether delaying SRT after response evaluation to FLST would result in better prognosis. We compared overall survival (OS), progression-free survival (PFS), and time to first subsequent therapy (TFST) for 50 patients locally treated before or within 90 days of initiating FLST (early SRT), with 49 patients treated at least 90 days after initiating FLST (late SRT). Patients treated with conventional chemotherapy alone exhibited significantly poorer median OS, PFS, and TFST in the early SRT arm: (in months) 16.5 [8.33-NR] vs. 58.3 [35.05-NR] (p = 0.0015); 4.69 [3.57-8.98] vs. 8.20 [6.66-12.00] (p = 0.017); and 6.26 [4.82-11.8] vs. 10.0 [7.44-21.8] (p = 0.0074), respectively. Patient receiving ICI showed no difference in OS (NR [25.2-NR] vs. 36.6 [35.1-NR], p = 0.79), PFS (7.54 [6.23-NR] vs. 4.07 [2.52-NR], p = 0.19), and TFST (13.7 [9.48-NR] vs. 10.3 [3.54-NR], p = 0.49). These results suggest that delaying SRT treatment in order to filter a rapidly growing tumor may be less necessary when ICI is administered in mNSCLC.

Pilot scale validation campaign of gel dosimetry for pre-treatment quality assurance in stereotactic radiotherapy

PurposeComplex stereotactic radiotherapy treatment plans require prior verification. A gel dosimetry system was developed and tested to serve as a high-resolution 3D dosimeter for Quality Assurance (QA) purposes. Materials and MethodsA modified version of a polyacrylamide polymer gel dosimeter based on chemical response inhibition was employed. Different sample geometries (cuvettes and phantoms) were manufactured for calibration and QA acquisitions. Irradiations were performed with a Varian Trilogy linac, and analyses of irradiated gel dosimeters were performed via MRI with a 1.5 T Philips Achieva at 1 mm3 or 2 mm3 isotropic spatial resolution. To assess reliability of polymer gel data, 54 stereotactic clinical treatment plans were delivered both on dosimetric gel phantoms and on the Delta4 dosimeter. Results from the two devices were evaluated through a global gamma index over a range of acceptance criteria and compared with each other. ResultsA quantitative and tunable control of dosimetric gel response sensitivity was achieved through chemical inhibition. An optimized MRI analysis protocol allowed to acquire high resolution phantom dose data in timeframes of ≈ 1 h. Conversion of gel dosimeter data into absorbed dose was achieved through internal calibration. Polymer gel dosimeters (2 mm3 resolution) and Delta4 presented an agreement within 4.8 % and 2.7 % at the 3 %/1 mm and 2 %/2 mm gamma criteria, respectively. ConclusionsGel dosimeters appear as promising tools for high resolution 3D QA. Added complexity of the gel dosimetry protocol may be justifiable in case of small target volumes and steep dose gradients.

Stereotactic Radiotherapy (SRT) in Combination with Aumolertinib to Treat Intracranial Oligometastatic Non-Small Cell Lung Cancer (NSCLC): An Update of a Phase II, Prospective Study

Stereotactic radiotherapy (SRT) is highly effective and less toxic for limited intracranial metastases. Aumolertinib is a tolerable third-generation epidermal growth factor receptor tyrosine kinase inhibitor that has CNS efficacy in patients with EGFR-mutant NSCLC. We aim to investigate the efficacy and safety of aumolertinib followed by SRT in patients with intracranial oligometastatic NSCLC. Intracranial oligometastatic Patients with EGFR sensitive mutations (EGFR-TKIs naive) were enrolled and received aumolertinib 110mg daily until intracranial disease progression. Then SRT (32-40 Gy total, 8 Gy/f) was given to intracranial oligo-progression disease if possible. The primary endpoint was intracranial objective response rate (iORR). Secondary endpoints included intracranial progression-free survival (iPFS), intracranial duration of response (iDOR)according to RECIST 1.1, cerebral radiation necrosis rate (CRNR) and overall survival (OS). Safety was evaluated according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). This trial is registered with ClinicalTrials.gov, NCT04519983. To February 10, 2023, a total of 38 patients were enrolled and 35 patients were assessable followed for 3 months to 18 months. All patients received 110mg aumolertinib daily and received at least one independent imaging evaluation by a radiologist. After oral administration of aumolertinib, the best response of 94% patients in intracranial and extracranial lesions was partial response (PR). Two patients had stable intracranial disease. At data cut-off, one patient developed intracranial primary lesion progression at 12 months after oral administration of aumolertinib but stable in extracranial lesions. SRT treatment was given to this patient. No grade ≥3 adverse events occurred after continued oral administration of aumolertinib. The most common adverse reactions were rash and abnormal liver enzymes, 1 patient had grade 2 CK elevation. This report showed pronounced intracranial objective response benefit in patients with intracranial oligometastatic disease followed by SRT after intracranial oligo-progression and no new safety signals. Aumolertinib has promising efficacy and good tolerability in intracranial oligometastatic EGFR mutated NSCLC. [Keywords] Non-small cell lung cancer; epidermal growth factor receptor tyrosine kinase inhibitor; Aumolertinib; Stereotactic radiotherapy.

Implementation of a Patient Specific QA Protocol for a Novel Dedicated Stereotactic Radiosurgery Linear Accelerator

To describe the patient specific QA (Quality Assurance) protocol implemented for plan integrity verification, in stereotactic radiosurgery (SRS) and radiotherapy (SRT) treatments performed on a novel dedicated frameless image guided radiosurgery system using conical collimator, and a combination of yoked gimbals to cover near2pi solid angle. Startup and commissioning results obtained for planned vs measured dose distributions with several detectors are presented. The patient specific QA protocol includes: A) Review of the approved plan based on AAPM TG 275 report recommendations B) 1D verification using small volume ionization chambers inside an anthropomorphic head phantom C) 2D dose verification of a coronal and sagittal dose plan performed with high resolution 2D Array and respective phantom apparatus D) In-house independent MU (Monitor Unit) calculation using the same formalism of the vendor TPS (Treatment Planning Systems) RayTracing dose-calculation algorithm E) Monte Carlo based secondary dose check & plan QA. A retrospective analysis of the results of the first 15 patients treated is presented, focusing on plan complexity vs QA results. The 1D results obtained for the 15 SRS plans were within ±5% for all reported cases, with a mean percent difference of -1,25%, confirming an overall good agreement and, as expected, a partial volume effect in plans with smaller collimators. For the 2D dose verifications, with a 10% dose threshold, gamma passing rates of 97,5% (coronal) and 96,78 (sagittal) with 3% 1mm criteria, 95,1% (coronal) and 94,3% (sagittal) for 2% 1 mm criteria and 90,7% (coronal) and 90,0% (sagittal) for 1% 1mm criteria were obtained. Moreover, the results showed a correlation between lesion volume or number of collimators used with gamma passing rates. All MU verification results were within ±0,3% and provides an efficient risk mitigation approach for this new delivery technique. The verification results of the first 15 treated SRS plans confirmed point dose and planar measurements in agreement with TPS calculations, with superior results for planes with smaller lesions and fewer collimators. This also represents an integral validation of the image-based alignment system and fine treatment couch movements, as treatments are intrinsically multi-isocentric.

Stereotactic radiotherapy outcomes for intraventricular brain tumours in 11 dogs.

Published radiotherapy data for canine intraventricular tumours are limited. In this retrospective, longitudinal study (9/2011-2018), 11 dogs with intraventricular masses were treated with stereotactic radiotherapy (SRT). Pathologic diagnosis was available from surgery or necropsy in 6/11 cases, revealing choroid plexus papilloma (3) or carcinoma (2), and ependymoma (1). The remainder were magnetic resonance imaging (MRI)-diagnosed as suspected choroid tumours or ependymomas. Tumours were located in the third or lateral ventricle (8), fourth ventricle (2), and cerebellopontine angle (1). Surgery was performed in three dogs prior to radiotherapy, and all showed gross residual/recurrent disease at treatment. Dogs received 8 Gray × 3 fractions (7), or 15 Gray × 1 fraction (4). Ten dogs were deceased at analysis, and one was living. The estimated median overall survival time (OS) from first SRT treatment was 16.9 months (515 days, 95% CI 33-1593 days). The survival time for two pathology-diagnosed carcinoma dogs were 24 and 133 days, respectively, and survival time for dogs with moderate to marked ventriculomegaly (4/11) ranged from 24 to 113 days. A total of 10/11 showed clinical improvement per owner or clinician, but two had short-lived benefits and were euthanized within 6 weeks of SRT. Limited conclusions on radiation-specific complications are possible due to the small dataset and limited follow-up imaging. This study provides preliminary evidence that radiotherapy outcomes are variable with intraventricular tumours, and some long-term survivors are noted.

Single fraction stereotactic radiosurgery and fractionated stereotactic radiotherapy provide equal prognosis with overall survival in patients with brain metastases at diagnosis without surgery at primary site.

Stereotactic radiosurgery (SRS) and fractionated stereotactic radiation therapy (SRT) are both treatments shown to be effective in treating brain metastases (BMs). However, it is unknown how these treatments compare in effectiveness and safety in cancer patients with BMs regardless of the primary cancer. The main objective of this study is to investigate the SRS and SRT treatments' associations with the overall survival (OS) of patients diagnosed with BMs using the National Cancer Database (NCDB). Patients in the NCDB with breast cancer, non-small cell lung cancer, small cell lung cancer, other lung cancers, melanoma, colorectal cancer, or kidney cancer who had BMs at the time of their primary cancer diagnosis and received either SRS or SRT as treatment for their BMs were included in the study. We analyzed OS with a Cox proportional hazard analysis that adjusted variables associated with improved OS during univariable analysis. Of the total 6,961 patients that fit the criteria for the study, 5,423 (77.9%) received SRS and 1,538 (22.1%) received SRT. Patients who received SRS treatment had a median survival time of 10.9 (95% CI [10.5-11.3]), and those who received SRT treatment had a median survival time of 11.3 (95% CI [10.4-12.3]) months. This difference was not found to be significant (Log-rank P=0.31). Multivariable Cox proportional hazard analysis did not yield a significant difference between the treatments' associations with OS (Hazard Ratio: 0.942, CI 95% [0.882-1.006]; P=.08) or SRS vs. SRT. In this analysis, SRS and SRT did not show a significant difference in their associations with OS. Future studies investigating the neurotoxicity risks of SRS as compared to SRT are warranted.