Let's make size not matter: tumor control and toxicity outcomes of hypofractionated Gamma Knife radiosurgery for large brain metastases.

PURPOSE: Management of patients with large brain metastases poses a clinical challenge, with poor local control and high risk of adverse radiation events when treated with single-fraction stereotactic radiosurgery (SF-SRS). Hypofractionated SRS (HF-SRS) may be considered, but clinical data remains limited, particularly with Gamma Knife (GK) radiosurgery. We report our experience with GK to deliver mask-based HF-SRS to brain metastases greater than 10 cc in volume and present our control and toxicity outcomes. METHODS: Patients who received hypofractionated GK radiosurgery (HF-GKRS) for the treatment of brain metastases greater than 10 cc between January 2017 and June 2022 were retrospectively identified. Local failure (LF) and adverse radiation events of CTCAE grade 2 or higher (ARE) were identified. Clinical, treatment, and radiological information was collected to identify parameters associated with clinical outcomes. RESULTS: Ninety lesions (in 78 patients) greater than 10 cc were identified. The median gross tumor volume was 16.0 cc (range 10.1-56.0 cc). Prior surgical resection was performed on 49 lesions (54.4%). Six- and 12-month LF rates were 7.3% and 17.6%; comparable ARE rates were 1.9% and 6.5%. In multivariate analysis, tumor volume larger than 33.5 cc (p = 0.029) and radioresistant histology (p = 0.047) were associated with increased risk of LF (p = 0.018). Target volume was not associated with increased risk of ARE (p = 0.511). CONCLUSIONS: We present our institutional experience treating large brain metastases using mask-based HF-GKRS, representing one of the largest studies implementing this platform and technique. Our LF and ARE compare favorably with the literature, suggesting that target volumes less than 33.5 cc demonstrate excellent control rates with low ARE. Further investigation is needed to optimize treatment technique for larger tumors.

Does Size Matter? On the Role of Stereotactic Radiosurgery for Large Vestibular Schwannomas as Seen in an Institutional Experience of Gamma Knife Radiosurgery for High-Grade Tumors.

OBJECTIVE: Management of large vestibular schwannoma (VS) is controversial. Surgery has historically been the treatment of choice, but emerging literature suggests that definitive stereotactic radiosurgery is feasible. We report our institutional experience of control and morbidity outcomes treating Koos grade 3-4 VS with Gamma Knife radiosurgery (GKRS). METHODS: An institutional review board-approved database compiled outcomes of Koos grade 3-4 VS treated by GKRS from March 2014 to January 2021 with >6 months' follow-up. Baseline symptoms per Common Terminology Criteria for Adverse Events definitions were recorded. Control rates, toxicities, and post-treatment volumetric changes were analyzed. Aggregate impairment scores (AIs) were defined by the sum of relevant Common Terminology Criteria for Adverse Events grades to categorize symptomatic burdens. Baseline and post-treatment AIs were tested for association with definitive versus adjuvant strategies. RESULTS: In total, 34 patients with Koos grade 3-4 VS were identified, 19 treated with definitive GKRS (GKRS-D) and 15 with adjuvant GKRS (GKRS-A). Median follow-up was 34.2 months for GKRS-D and 48.8 months for GKRS-A. Patients who received GKRS-A had greater AIs at presentation (3.73 vs. 2.11, P = 0.017). Irrespective of treatment approach, tumor control rates were 100% without instances of brainstem necrosis or shunt placement. Six of 19 patients who received GKRS-D had improved post-treatment AI, and 63% of patients who received GKRS-D and 66% of patients who received GKRS-A had tumor shrinkage >20%. CONCLUSIONS: In well-selected patients with Koos grade 3-4 VS, definitive stereotactic radiosurgery may be an appropriate strategy with excellent control and minimal toxicity. Our data suggest that the need for surgical decompression should be considered based on pretreatment symptom burden rather than tumor size.

Direct dosimetric comparison of linear accelerator vs. Gamma Knife fractionated stereotactic radiotherapy (fSRT) of large brain tumors.

The purpose of this study was to directly compare the plan quality of Gamma Knife (GK) (Elekta, Stockholm, Sweden)- vs linear accelerator (LINAC)-based delivery techniques for fractionated stereotactic radiotherapy (fSRT) of large brain metastases. Eighteen patients with clinical target volumes (CTVs) larger than 9.5 cc were selected to generate comparative plans for the prescription dose of 9 Gy × 3 fractions, utilizing the Eclipse (Varian, Palo Alto, US) vs Leksell GammaPlan (LGP) (Elekta, Stockholm, Sweden) treatment planning systems (TPS). Each GK plan was first developed using LGP's automatic planning, followed by manual adjustments/refinements. The same MRI and structures, including CTVs and organs at risk, were then DICOM-transferred to the Eclipse TPS. Volumetric Modulated Arc Therapy (VMAT) and Dynamic Conformal Arc (DCA) plans for a Truebeam, with high-definition multi-leaf collimators (MLCs), were developed on these MR images and structures using a single isocenter and 3 non-coplanar arcs. No planning target volume (PTV) margins were added, and no heterogeneity correction was used for either TPS. GK plans were prescribed to the 50% isodose line, and Eclipse VMAT and DCA plans allowed a maximum dose up to 170% and ∼125%, respectively. Gradient index (GI), Paddick Conformity Index (PCI), V20GyRind, and V4GyRind of all 3 techniques were calculated and compared. One-way analysis of variance (ANOVA) was performed to determine the statistical significance of the differences of these planning indices for the 3 planning techniques. A total of eighteen treatment targets were analyzed. Median CTV volume was 14.4 cc (range 9.5 cc - 55.9 cc). Mean ± standard deviation of PCI were 0.85 ± 0.03, 0.90 ± 0.03, and 0.72 ± 0.11 for GK, VMAT and DCA plans, respectively. They were respectively 2.64 ± 0.17, 2.46 ± 0.18, and 2.83 ± 0.48 for GI; 15.33 ± 8.45 cc, 10.47 ± 4.32 cc and 23.51 ± 16 cc for V20GyRind; and 316.28 ± 138.35 cc, 317.81 ± 108.21 cc, and 394.85 ± 142.16 cc for V4GyRind. The differences were statistically significant with p < 0.01 for all indices, except for V4GyRind (p > 0.129). In conclusion, a direct dosimetric comparison using the same MRI scan and contours was performed to evaluate the plan quality of various fSRT delivery techniques for CTV > 9.5 cc. LINAC VMAT plans provided the best dosimetric outcome in regard to PCI, GI, and V20GyRind. GK outcomes were similar to LINAC VMAT plans while LINAC DCA outcomes were significantly worse. Even though GK has a smaller physical penumbra, LINAC VMAT outperformed GK in this study due to enhanced penumbra sharpening and better beam optimization.

Retrospective Analysis of Treatment Workflow in Frame-Based and Frameless Gamma Knife Radiosurgery.

Objective To improve the efficiency of frame-based and frameless Gamma Knife® Icon™ (GKI) treatments by analyzing the workflows of both treatment approaches and identifying steps that lead to prolonged patient in-clinic or treatment time. Methods The treatment processes of 57 GKI patients, 16 frame-based and 41 frameless cases were recorded and analyzed. For frame-based treatments, time points were recorded for various steps in the process, including check-in, magnetic resonance imaging (MRI) completion, plan approval, and treatment start/end times. The time required for completing each step was calculated and investigated. For frameless treatments, the actual and planned treatment times were compared to evaluate the patient tolerance of the treatment. In addition, the time spent on room cleaning and preparation between treatments was also recorded and analyzed. Results For frame-based cases, the average in-clinic time was 6.3 hours (ranging from 4 to 8.7 hours). The average time from patient check-in to plan approval was 4.2 hours (ranging from 2.8 to 5.5 hours), during which the frame was placed, stereotactic reference MRI images were taken, target volumes were contoured, and the treatment plan was developed and second-checked. For patients immobilized with a mask, treatment pauses triggered by the intra-fractional motion monitoring system resulted in a significantly longer actual treatment time than the planned time. In 50 (or 55%) of the 91 frameless treatments, the patient on-table time was longer than the planned treatment time by more than 10 minutes, and in 19 (or 21%) of the treatments the time difference was larger than 20 minutes. Major treatment interruptions, defined as pauses leading to a longer than 10-minute delay, were more commonly encountered in patients with a planned treatment time longer than 40 minutes, which accounted for 64% of the recorded major interruptions. Conclusion For frame-based cases, the multiple pretreatment steps (from patient check-in to plan approval) in the workflow were time-consuming and resulted in prolonged patient in-clinic time. These pretreatment steps may be shortened by performing some of these steps before the treatment day, e.g., pre-planning the treatment using diagnostic MRI scans acquired a few days earlier. For frameless patients, we found that a longer planned treatment time is associated with a higher chance of treatment interruption. For patients with a long treatment time, a planned break or consideration of fractionated treatments (i.e., 3 to 5 fractionated stereotactic radiosurgery) may optimize the workflow and improve patient satisfaction.

Assessing initial plan check efficacy using TG 275 failure modes and incident reporting.

Plan checks are important components of a robust quality assurance (QA) program. Recently, the American Association of Physicists in Medicine (AAPM) published two reports concerning plan and chart checking, Task Group (TG) 275 and Medical Physics Practice Guideline (MPPG) 11.A. The purpose of the current study was to crosswalk initial plan check failure modes revealed in TG 275 against our institutional QA program and local incident reporting data. Ten physicists reviewed 46 high-risk failure modes reported in Table S1.A.i of the TG 275 report. The committee identified steps in our planning process which sufficiently checked each failure mode. Failure modes that were not covered were noted for follow-up. A multidisciplinary committee reviewed the narratives of 1599 locally-reported incidents in our Radiation Oncology Incident Learning System (ROILS) database and categorized each into the high-risk TG 275 failure modes. We found that over half of the 46 high-risk failure modes, six of which were top-ten failure modes, were covered in part by daily contouring peer-review rounds, upstream of the traditional initial plan check. Five failure modes were not adequately covered, three of which concerned pregnancy, pacemakers, and prior dose. Of the 1599 incidents analyzed, 710 were germane to the initial plan check, 23.4% of which concerned missing pregnancy attestations. Most, however, were caught prior to CT simulation (98.8%). Physics review and initial plan check were the least efficacious checks, with error detection rates of 31.8% and 31.3%, respectively, for some failure modes. Our QA process that includes daily contouring rounds resulted in increased upstream error detection. This work has led to several initiatives in the department, including increased automation and enhancement of several policies and procedures. With TG 275 and MPPG 11.A as a guide, we strongly recommend that departments consider an internal chart checking policy and procedure review.

A novel and effective method for validation and measurement of output factors for Leksell Gamma Knife® Icon™ using TRS 483 protocol.

The objective of this work was to identify the exact location of the effective point of measurement (EPM) of four different active detectors to compare the relative collimator output factors (ROF) of Leksell Gamma Knife (LGK) according to IAEA TRS-483 recommendations. ROF was measured at the center of the spherical LGK-Solid Water (LGK-SW) Phantom for three (4-, 8-, and 16-mm in diameter) collimators using four (PTW-TN60008, PTW-TN60016, PTW-TN60017, and PTW-60019 diode/diamond) detectors. Since diode detectors have a much smaller sensitive volume than the PTW-31010 ion chamber used for reference dosimetry, its EPM might not be at the center of the phantom, or (100, 100, 100) of the Leksell Coordinate System, particularly in the z-direction. Hence for each diode detector, a CBCT image was acquired after it was inserted into the phantom, from which the z-Leksell coordinate of EPM was determined. Relative collimator output factors was then measured by focusing GK beams on the determined EPM of each diode. Measured ROFs were compared with the vendor-provided values in GK treatment planning system. For validation, a plan was generated to measure the output of 4-mm collimator for PTW-TN60017 at various couch locations along the z-axis. For PTW-TN60008, the percentage variations were 0.6 ± 0.4%, and -0.8 ± 0.2% for 4 and 8-mm collimators, respectively. For PTW-TN60016, the percentage variations were 0.8 ± 0.0%, and 0.2 ± 0.1%, respectively. The percentage variations were -3.3 ± 0.0% and -0.9 ± 0.1%, respectively, for PTW-TN60017, and -0.5 ± 0.0% and -0.8 ± 0.2%, respectively, for PTW-TN60019. Center of the measured profile for PTW-TN60017 was only 0.1 mm different from that identified using the CBCT. In conclusion, we have developed a simple and effective method to determine the EPMs of diode detectors when inserted into the existing LGK-SW phantom. With the acquired positional information and using TRS-483 protocol, good agreements were obtained between the measured ROFs and manufacturer recommended values.

Is there a role for postimplant dosimetry after real-time dynamic permanent prostate brachytherapy?

PURPOSE: To evaluate the correlation of real-time dynamic prostate brachytherapy (RTDPB) dosimetry and traditional postimplant dosimetry for permanent prostate brachytherapy. METHODS AND MATERIALS: A total of 164 patients underwent RTDPB for clinically confined prostate cancer. Of these 164 patients, 45 were implanted with 103Pd and 119 with 125I. Additionally, 44 patients underwent combined external beam radiotherapy and brachytherapy and 120 patients underwent brachytherapy alone. The postimplant dosimetry with computed tomography was performed at 4 weeks and compared with the RTDPB dose plan using the intraclass correlation coefficient. The millicurie/gram of the prostate volume and the percentage of the minimal dose to 90% of the prostate relative to the prescribed implant dose (D90%) of the RTDPB patients was compared with 400 patients treated with a free-seed technique. RESULTS: The mean D90% achieved in the operating room and on the 3-week dose plan was 109% (range, 93-139%) and 105% (range, 88-140), respectively. The mean percentage of prostate volume receiving 100% of the prescribed minimal peripheral dose (V100) achieved in the operating room and on the 3-week dose plan was 93% (range, 78-98%) and 91% (range, 64-98%), respectively. The intraclass correlation coefficient for each calculated relationship was 0.586 for D90 (p<0.001), 1.19 for V100 (p=0.135), 0.692 for the urethral D90 (p<0.001), 0.602 for the maximal rectal dose (p<0.001), 0.546 for D90 with 125I (p<0.001), and 0.565 for D90 with 103Pd (p<0.001). A 12% decrease was noted in the millicurie/gram of the isotope, with a 2.5% increase in the D90 comparing RTDPB and the free-seed technique. CONCLUSION: The results of this study demonstrated a correlation between the dose assessment obtained intraoperatively and postoperatively at 3 weeks. With reliable dose data available in the operating room, our results question the need for routine postimplant dose studies. Furthermore, patients treated with RTDPB received less radioactivity per gram of the prostate with a corresponding small increase in the D90. Future analyses will assess variations in the inverse dose planning rules and the clinical correlation of patients undergoing RTDPB vs. older techniques for toxicity and biochemical outcomes.

Importance of implant dosimetry for patients undergoing prostate brachytherapy.

OBJECTIVES: To evaluate the disease and treatment-related factors for predicting biochemical freedom from recurrence (BFR) in patients with clinically localized prostate cancer undergoing permanent prostate brachytherapy. METHODS: Between November 1992 and June 1998, 883 consecutive patients with T1-T2 prostate cancer underwent permanent prostate brachytherapy. Computed tomography-based dosimetry was performed, and the minimal dose to 90% of the prostate volume relative to the prescribed dose (D(90)) was calculated. BFR was defined as three prostate-specific antigen (PSA) rises from nadir, with patients having one or two PSA rises censored early. Follow-up was calculated by censored events. Kaplan-Meier actuarial outcome was determined, and multivariate Cox regression analysis was performed to assess the significance of the D(90), initial PSA value, Gleason score, addition of external beam radiotherapy, addition of hormonal therapy, and isotope selection. RESULTS: The mean follow-up was 55 months (range 3 to 125). The 10-year BFR rate was 79.1%. Cox proportional analysis identified D(90) as a predictor of BFR (P <0.0001), along with Gleason score, initial PSA level, and clinical stage (P = 0.001, P = 0.001, and P = 0.011, respectively). The addition of external beam radiotherapy, hormonal therapy, and isotope selection did not have an impact on BFR (P = 0.128, P = 0.399, and P = 0.224, respectively). CONCLUSIONS: The quality of permanent prostate brachytherapy as measured by the D(90) was the most significant predictor for BFR in this study cohort at 10 years. Furthermore, adding external beam radiotherapy and/or hormonal therapy as adjuvant therapies did not independently predict for BFR. Overall, the reported 10-year BFR rates in this study were favorable. Strategies for ensuring the best quality implant should be used and, when reporting brachytherapy outcomes, the implant quality should be noted.