OBJECTIVE: To apply an independent GPU-accelerated Monte Carlo (MC) dose verification for CyberKnife M6 with Iris collimator and evaluate the dose calculation accuracy of RayTracing (TPS-RT) algorithm and Monte Carlo (TPS-MC) algorithm in the Precision treatment planning system (TPS).
METHODS: GPU-accelerated MC algorithm (ArcherQA-CK) was integrated into a commercial dose verification system, ArcherQA, to implement the patient-specific quality assurance in the CyberKnife M6 system. 30 clinical cases (10 cases in head, and 10 cases in chest, and 10 cases in abdomen) were collected in this study. For each case, three different dose calculation methods (TPS-MC, TPS-RT and ArcherQA-CK) were implemented based on the same treatment plan and compared with each other. For evaluation, the 3D global gamma analysis and dose parameters of the target volume and organs at risk (OARs) were analyzed comparatively.
RESULTS: For gamma pass rates at the criterion of 2%/2 mm, the results were over 98.0% for TPS-MC vs.TPS-RT, TPS-MC vs. ArcherQA-CK and TPS-RT vs. ArcherQA-CK in head cases, 84.9% for TPS-MC vs.TPS-RT, 98.0% for TPS-MC vs. ArcherQA-CK and 83.3% for TPS-RT vs. ArcherQA-CK in chest cases, 98.2% for TPS-MC vs.TPS-RT, 99.4% for TPS-MC vs. ArcherQA-CK and 94.5% for TPS-RT vs. ArcherQA-CK in abdomen cases. For dose parameters of planning target volume (PTV) in chest cases, the deviations of TPS-RT vs. TPS-MC and ArcherQA-CK vs. TPS-MC had significant difference (P < 0.01), and the deviations of TPS-RT vs. TPS-MC and TPS-RT vs. ArcherQA-CK were similar (P > 0.05). ArcherQA-CK had less calculation time compared with TPS-MC (1.66 min vs. 65.11 min).
CONCLUSIONS: Our proposed MC dose engine (ArcherQA-CK) has a high degree of consistency with the Precision TPS-MC algorithm, which can quickly identify the calculation errors of TPS-RT algorithm for some chest cases. ArcherQA-CK can provide accurate patient-specific quality assurance in clinical practice.

BACKGROUND: Radiotherapy (RT) synergizes with immune checkpoint blockade (ICB). CD1c(BDCA-1)+/CD141(BDCA-3)+ myeloid dendritic cells (myDC) in the tumor microenvironment are indispensable at initiating effector T-cell responses and response to ICB.
METHODS: In this phase II clinical trial, anti-PD-1 ICB pretreated oligometastatic patients (tumor agnostic) underwent a leukapheresis followed by isolation of CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC. Following hypofractionated stereotactic body RT (3 × 8 Gy), patients were randomized (3:1). Respectively, in arm A (immediate treatment), intratumoral (IT) ipilimumab (10 mg) and avelumab (40 mg) combined with intravenous (IV) pembrolizumab (200 mg) were administered followed by IT injection of myDC; subsequently, IV pembrolizumab and IT ipilimumab/avelumab were continued (q3W). In arm B (contemporary control arm), patients received IV pembrolizumab, with possibility to cross-over at progression. Primary endpoint was 1-year progression-free survival rate (PFS). Secondary endpoints were safety, feasibility, objective response rate, PFS, and overall survival (OS).
RESULTS: Thirteen patients (10 in arm A, eight non-small cell lung cancer, and five melanoma) were enrolled. Two patients crossed over. One-year PFS rate was 10% in arm A and 0% in arm B. Two patients in arm A obtained a partial response, and one patient obtained a stable disease as best response. In arm B, one patient obtained a SD. Median PFS and OS were 21.8 weeks (arm A) versus 24.9 (arm B), and 62.7 versus 57.9 weeks, respectively. An iatrogenic pneumothorax was the only grade 3 treatment-related adverse event.
CONCLUSIONS: SBRT and pembrolizumab with or without IT avelumab/ipilimumab and IT myDC in oligometastatic patients are safe and feasible with a clinically meaningful tumor response rate. However, the study failed to reach its primary endpoint.
BACKGROUND: Clinicaltrials.gov: NCT04571632 (09 AUG 2020).
UNASSIGNED: 2019-003668-32. Date of registration: 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022.

OBJECTIVE: To assess the diagnostic features of acromegaly, and analyse its management outcomes over a 15-year period in a tertiary care setting.
METHODS: The descriptive, cohort, retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of adult patients of either gender diagnosed with acromegaly based on biochemical and radiological evidence between January 2005 and December 2019. Data was retrieved from the medical records. Data was analysed using SPSS 19.
RESULTS: Of the 84 subjects, 54(64.3%) were males and 30(35.7%) were female. The overall mean age was 38.69±13.52 years. The patients presented 5.43±4.3 years after the onset of symptoms, with somatic growth features, such as enlarged hands and feet which was the most common complaint 81(96.4%). Of all the patients, 73(86.9%) underwent trans-sphenoidal surgery for the removal of the pituitary adenoma, while 11(13.1%) opted out of the surgical option. Further, 9(12.3%) patients showed biochemical and radiological remission 6 months post-surgery. Out of the remaining 64(87.7%) patients, 38(59.4%) received radiosurgery or radiotherapy, 15(23.4%) underwent repeat trans-sphenoidal surgery, and 11(17.2%) chose medical treatment.
CONCLUSIONS: Majority of patients failed to achieve remission after trans-sphenoidal surgery, which is the first line of treatment. Radiotherapy/repeat surgery was generally the options taken by those with persistent disease.

OBJECTIVE: This scoping review presents the preclinical and clinical data on the effects of high-dose radiation therapy (RT) on bone structure and function.
METHODS: An extensive PubMed search was performed for the relevant questions. The data were then synthesized into a comprehensive summary of the available relevant in-vitro, preclinical and clinical literature.
RESULTS: In-vitro studies of high-dose RT on cell cultures show considerable damage in the viability and functional capacity of the primary cells of the bones; the osteoclasts, the osteoblasts, and the osteocytes. In-vivo animal models show that high-dose RT induces significant morphological changes to the bone, inhibits the ability of bone to repair damage, and increases the fragility of the bone. Clinical data show that there is an increasing risk over time of damage to the bone, such as fractures, after high-dose RT.
CONCLUSIONS: These findings suggest that there may be a limit to the safe dose for single-fraction RT, and the long-term consequences of high-dose RT for the patients must be considered.

暂无摘要。

UNASSIGNED: Preoperative radiosurgery (SRS) of brain metastases (BM) aims to achieve cavity local control with a reduction in leptomeningeal relapse (LMD) and without additional radionecrosis compared to postoperative SRS. We present the final results of a prospective feasibility trial of linac-based stereotactic radiosurgery (SRS) prior to neurosurgical resection of a brain metastasis (PREOP-1).
UNASSIGNED: Eligibility criteria included a BM up to 4 cm in diameter for elective resection. The primary endpoint was the feasibility of delivering linac-based preoperative SRS in all patients prior to anticipated gross tumour resection. Secondary endpoints included rates of LMD, local control and overall survival. Exploratory endpoints were the level of expression of immunological and proliferative markers.
UNASSIGNED: Thirteen patients of median age 65 years (range 41-77) were recruited. Twelve patients (92 %) received preoperative radiosurgery and metastasectomy and one patient went directly to surgery and received postoperative SRS, thus the primary endpoint was not met. The median time between referral and preoperative SRS was 6.5 working days (1-10) and from SRS to neurosurgery was 1 day (0-5). The median prescribed dose was 16 Gy (14-19) to a median planning target volume of 12.7 cm3 (5.9-26.1). Five patients completed 12-month follow-up after preoperative SRS without local recurrence or leptomeningeal disease. The patient who received postoperative FSRT developed LMD after six months. There was one transient toxicity (grade 2 alopecia) and nine patients have died from extracranial causes. Patients reported significant improvement in motor weakness at 6 months (P = 0.04). No pattern in changes of marker expression was observed.
UNASSIGNED: In patients with large brain metastasis without raised intracranial pressure, linac-based preoperative SRS was feasible in 12/13 patients and safe in 12/12 patients without any surgical delay or intracranial complications.

Objective: To summarize our institutional prostate stereotactic body radiation therapy (SBRT) experience using auto beam hold (ABH) technique for intrafractional prostate motion and assess ABH tolerance of 10-millimeter (mm) diameter.Approach: Thirty-two patients (160 fractions) treated using ABH technique between 01/2018 and 03/2021 were analyzed. During treatment, kV images were acquired every 20-degree gantry rotation to visualize 3-4 gold fiducials within prostate to track target motion. If the fiducial center fell outside the tolerance circle (diameter = 10 mm), beam was automatically turned off for reimaging and repositioning. Number of beam holds and couch translational movement magnitudes were recorded. Dosimetric differences from intrafractional motion were calculated by shifting planned isocenter.Main Results: Couch movement magnitude (mean ± SD) in vertical, longitudinal and lateral directions were -0.7 ± 2.5, 1.4 ± 2.9 and -0.1 ± 0.9 mm, respectively. For most fractions (77.5%), no correction was necessary. Number of fractions requiring one, two, or three corrections were 15.6%, 5.6% and 1.3%, respectively. Of the 49 corrections, couch shifts greater than 3 mm were seen primarily in the vertical (31%) and longitudinal (39%) directions; corresponding couch shifts greater than 5 mm occurred in 2% and 6% of cases. Dosimetrically, 100% coverage decreased less than 2% for clinical target volume (CTV) (-1 ± 2%) and less than 10% for PTV (-10 ± 6%). Dose to bladder, bowel and urethra tended to increase (Bladder: ΔD10%:184 ± 466 cGy, ΔD40%:139 ± 241 cGy, Bowel: ΔD1 cm3:54 ± 129 cGy; ΔD5 cm3:44 ± 116 cGy, Urethra: ΔD0.03 cm3:1 ± 1%). Doses to the rectum tended to decrease (Rectum: ΔD1 cm3:-206 ± 564 cGy, ΔD10%:-97 ± 426 cGy; ΔD20%:-50 ± 251 cGy).Significance: With the transition from conventionally fractionated intensity modulated radiation therapy to SBRT for localized prostate cancer treatment, it is imperative to ensure that dose delivery is spatially accurate for appropriate coverage to target volumes and limiting dose to surrounding organs. Intrafractional motion monitoring can be achieved using triggered imaging to image fiducial markers and ABH to allow for reimaging and repositioning for excessive motion.

Randomised control trial data support the use of stereotactic radiosurgery (SRS) in up to 4 brain metastases (BMs), with non-randomised prospective data complementing this for up to 10 BMs. There is debate in the neuro-oncology community as to the appropriateness of SRS in patients with >10 BMs. We present data from a large single-centre cohort, reporting survival in those with >10 BMs and in a >20 BMs subgroup. A total of 1181 patients receiving SRS for BMs were included. Data were collected prospectively from the time of SRS referral. Kaplan-Meier graphs and logrank tests were used to compare survival between groups. Multivariate analysis was performed using the Cox proportional hazards model to account for differences in group characteristics. Median survival with 1 BM (n = 379), 2-4 BMs (n = 438), 5-10 BMs (n = 236), and >10 BMs (n = 128) was 12.49, 10.22, 10.68, and 10.09 months, respectively. Using 2-4 BMs as the reference group, survival was not significantly different in those with >10 BMs in either our univariable (p = 0.6882) or multivariable analysis (p = 0.0564). In our subgroup analyses, median survival for those with >20 BMs was comparable to those with 2-4 BMs (10.09 vs. 10.22 months, p = 0.3558). This study contributes a large dataset to the existing literature on SRS for those with multi-metastases and supports growing evidence that those with >10 BMs should be considered for SRS.

Some vestibular schwannoma (VS) show cystic morphology. It is known that these cystic VS bear different risk profiles compared to solid VS in surgical treatment. Still, there has not been a direct comparative study comparing both SRS and SURGERY effectiveness in cystic VS. This retrospective bi-center cohort study aims to analyze the management of cystic VS compared to solid VS in a dual center study with both microsurgery (SURGERY) and stereotactic radiosurgery (SRS). Cystic morphology was defined as presence of any T2-hyperintense and Gadolinium-contrast-negative cyst of any size in the pre-interventional MRI. A matched subgroup analysis was carried out by determining a subgroup of matched SURGERY-treated solid VS and SRS-treated solid VS. Functional status, and post-interventional tumor volume size was then compared. From 2005 to 2011, N = 901 patients with primary and solitary VS were treated in both study sites. Of these, 6% showed cystic morphology. The incidence of cystic VS increased with tumor size: 1.75% in Koos I, 4.07% in Koos II, 4.84% in Koos III, and the highest incidence with 15.43% in Koos IV. Shunt-Dependency was significantly more often in cystic VS compared to solid VS (p = 0.024) and patients with cystic VS presented with significantly worse Charlson Comorbidity Index (CCI) compared to solid VS (p < 0.001). The rate of GTR was 87% in cystic VS and therefore significantly lower, compared to 96% in solid VS (p = 0.037). The incidence of dynamic volume change (decrease and increase) after SRS was significantly more common in cystic VS compared to the matched solid VS (p = 0.042). The incidence of tumor progression with SRS in cystic VS was 25%. When comparing EOR in the SURGERY-treated cystic to solid VS, the rate for tumor recurrence was significantly lower in GTR with 4% compared to STR with 50% (p = 0.042). Tumor control in cystic VS is superior in SURGERY, when treated with a high extent of resection grade, compared to SRS. Therapeutic response of SRS was worse in cystic compared to solid VS. However, when cystic VS was treated surgically, the rate of GTR is lower compared to the overall, and solid VS cohort. The significantly higher number of patients with relevant post-operative facial palsy in cystic VS is accredited to the increased tumor size not its sole cystic morphology. Cystic VS should be surgically treated in specialized centers.

BACKGROUND: Both stereotactic radiosurgery (SRS) and percutaneous glycerol rhizotomy are excellent options to treat TN in patients unable to proceed with microvascular decompression. However, the influence of prior SRS on pain outcomes following rhizotomy is not well understood.
METHODS: We retrospectively reviewed all patients undergoing percutaneous rhizotomy at our institution from 2011 to 2022. Only patients undergoing percutaneous glycerol rhizotomy following SRS (SRS-rhizotomy) or those undergoing primary glycerol rhizotomy were considered. We collected basic demographic, clinical, and pain characteristics for each patient. Additionally, we characterized pain presentation and perioperative complications. Immediate failure of procedure was defined as presence of TN pain symptoms within 1-week of surgery, and short-term failure was defined as presence of TN pain symptoms within 3-months of surgery. A multivariate logistic regression model was used to evaluate the relationship of a history SRS and failure of procedure following percutaneous glycerol rhizotomy.
RESULTS: Of all patients reviewed, 30 had a history of SRS prior to glycerol rhizotomy whereas 371 underwent primary percutaneous glycerol rhizotomy. Patients with a history of SRS were more likely to endorse V3 pain symptoms, p = 0.01. Additionally, patients with a history of SRS demonstrated higher preoperative BNI pain scores, p = 0.01. Patients with a history of SRS were more likely to endorse preoperative numbness, p < 0.0001. A history of SRS was independently associated with immediate failure [OR = 5.44 (2.06-13.8), p < 0.001] and short-term failure of glycerol rhizotomy [OR = 2.41 (1.07-5.53), p = 0.03]. Additionally, increasing age was found to be associated with lower odds of short-term failure of glycerol rhizotomy [OR = 0.98 (0.97-1.00), p = 0.01] CONCLUSIONS: A history of SRS may increase the risk of immediate and short-term failure following percutaneous glycerol rhizotomy. These results may be of use to patients who are poor surgical candidates and require multiple noninvasive/minimally invasive options to effectively manage their pain.