Single isocenter HyperArc treatment of multiple intracranial metastases: Targeting accuracy.

PURPOSE/OBJECTIVES: (A) To examine the alignment accuracy of CBCT guidance for brain metastases with off centered isocenters, (B) to test dose delivery and targeting accuracy for single isocenter treatments with multiple brain metastases. We report the results of the end-to-end test for Truebeam stereotactic radiosurgery (SRS). MATERIALS/METHODS: An anthropomorphic CT head phantom was drilled with five MOSFET inserts and two PTW Pinpoint chamber inserts. The phantom was simulated, planned, and delivered. For the purpose of comparing the accuracy of alignment, CBCTs were acquired with the isocenter centered and offset superiorly 8 cm, inferiorly 8 cm, anteriorly 7 cm, posteriorly 7 cm, and right 5 cm. There were six degrees of freedom corrections applied to the plans, as well as intentional rotational and translational errors for dose comparisons. Dose accuracy checks were performed with MOSFET and PTW Pinpoint chamber, and targeting accuracy was assessed with GafChromic films. RESULT: (A) Compared to centered CBCT, off-centered CBCT scan showed some alignment errors, with a maximum difference of 0.6-degree pitch and 0.9 mm translation when the phantom was placed 8 cm inferior off center. (B) For the single isocenter plan, measured doses of the five MOSFET were 95%-100% of the planned dose, whereas the multiple isocenter plans were 96%-100%. With intentional setup errors of 1-degree pitch, doses were 97.1%-100.4% compared to the perfect setup. The same was found for the two pinpoint chamber readings with 1-degree rotation and 1 mm translation. (C) Targeting accuracy for targets at the isocenter is 0.67 mm, within the machine specification of 0.75 mm. Targeting accuracy for isocenters 6-12 cm away from the target is in the range 0.67-1.18 mm. CONCLUSION: (A) Single isocenter HyperArc treatments for multiple brain metastases are feasible and targeting accuracy is clinically acceptable. (B) The vertex in a cranial scan is very important for proper alignment.

A novel approach to infectious disease control and radiotherapy risk management.

BACKGROUND: Infectious disease outbreaks have always presented challenges to the operation of healthcare systems. In particular, the treatment of cancer patients within Radiation Oncology often cannot be delayed or compromised due to infection control measures. Therefore, there is a need for a strategic approach to simultaneously managing infection control and radiotherapy risks. PURPOSE: To develop a systematic risk management method that uses mathematical models to design mitigation efforts for control of an infectious disease outbreak, while ensuring safe delivery of radiotherapy. METHODS: A two-stage failure mode and effect analysis (FMEA) approach is proposed to modify radiotherapy workflow during an infectious disease outbreak. In stage 1, an Infection Control FMEA (IC-FMEA) is conducted, where risks are evaluated based on environmental parameters, clinical interactions, and modeling of infection risk. occupancy risk index (ORI) is defined as a metric for infection transmission risk level in each room, based on the degree of occupancy. ORI, in combination with ventilation rate per person (Rp ), is used to provide a broad infection risk assessment of workspaces. For detailed IC-FMEA of clinical processes, infection control failure mode (ICFM) is defined to be any instance of disease transmission within the clinic. Infection risk priority number (IRPN) has been formulated as a function of time, distance, and degree of protective measures. Infection control measures are then systematically integrated into the workflow. Since the workflow is perturbed by infection control measures, there is a possibility of introducing new radiotherapy failure modes or increased likelihood of existing failure modes. Therefore, in stage 2, a conventional radiotherapy FMEA (RT-FMEA) should be performed on the adjusted workflow. RESULTS: The COVID-19 pandemic was used to illustrate stage 1 IC-FMEA. ORI and Rp values were calculated for various workspaces within a clinic. A deep inspiration breath hold (DIBH) CT simulation was used as an example to demonstrate detailed IC-FMEA with ICFM identification and IRPN evaluation. A total of 90 ICFMs were identified in the DIBH simulation process. The calculated IRPN values were found to be progressively decreasing for workflows with minimal, moderate, and enhanced levels of protective measures. CONCLUSION: The framework developed in this work provides tools for radiotherapy clinics to systematically assess risk and adjust workflows during the evolving circumstances of any infectious disease outbreak.

The schedule of ATR inhibitor AZD6738 can potentiate or abolish antitumor immune responses to radiotherapy.

Inhibitors of the DNA damage signaling kinase ATR increase tumor cell killing by chemotherapies that target DNA replication forks but also kill rapidly proliferating immune cells including activated T cells. Nevertheless, ATR inhibitor (ATRi) and radiotherapy (RT) can be combined to generate CD8+ T cell-dependent antitumor responses in mouse models. To determine the optimal schedule of ATRi and RT, we determined the impact of short-course versus prolonged daily treatment with AZD6738 (ATRi) on responses to RT (days 1-2). Short-course ATRi (days 1-3) plus RT caused expansion of tumor antigen-specific, effector CD8+ T cells in the tumor-draining lymph node (DLN) at 1 week after RT. This was preceded by acute decreases in proliferating tumor-infiltrating and peripheral T cells and a rapid proliferative rebound after ATRi cessation, increased inflammatory signaling (IFN-ß, chemokines, particularly CXCL10) in tumors, and an accumulation of inflammatory cells in the DLN. In contrast, prolonged ATRi (days 1-9) prevented the expansion of tumor antigen-specific, effector CD8+ T cells in the DLN, and entirely abolished the therapeutic benefit of short-course ATRi with RT and anti-PD-L1. Our data argue that ATRi cessation is essential to allow CD8+ T cell responses to both RT and immune checkpoint inhibitors.

Is Halcyon feasible for single thoracic or lumbar vertebral segment SBRT?

PURPOSE: Halcyon linear accelerators employ intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) techniques. The Halcyon offers translational, but not rotational, couch correction, which only allows a 3 degrees of freedom (3-DOF) correction. In contrast, the TrueBeam (TB) linear accelerator offers full 6-DOF corrections. This study aims to evaluate the difference in treatment plan quality for single thoracic or lumbar vertebral segment SBRT between the Halcyon and TB linear accelerators. In addition, this study will also investigate the effect of patient rotational setup errors on the final plan quality. METHODS: We analyzed 20 patients with a single-level spine metastasis located between the T7 and L5 vertebrae near the spinal canal. The median planning target volume was 52.0 cm3 (17.9-138.7 cm3 ). The median tumor diameter in the axial plane was 4.6 cm (range 1.7-6.8 cm), in the sagittal plane was 3.3 cm (range 2-5 cm). The prescription doses were either 12-16 Gy in 1 fraction or 18-24 Gy in 3 fractions. All patients were treated on the TB linear accelerator with a 2.5 mm Multi-Leaf Collimator (MLC) leaf width. Treatment plans were retrospectively created for the Halcyon, which has a 5 mm effective MLC leaf width. The 20 patients had a total of 50 treatments. Analysis of the 50 cone beam computed tomography (CBCT) scans showed average rotational setup errors of 0.6°, 1.2°, and 0.8° in pitch, yaw, and roll, respectively. Rotational error in roll was not considered in this study, as the original TB plans used a coplanar volumetric modulated arc therapy (VMAT) technique, and each 1° of roll will contribute an error of 1/360. If a plan has 3 arcs, the contribution from errors in roll will be < 0.1%. To simulate different patient setup errors, for each patient, 12 CT image datasets were generated in Velocity AI with different rotational combinations at a pitch and yaw of 1°, 2°, and 3°, respectively. We recalculated both the TB and Halcyon plans on these rotated images.  The dosimetric plan quality was evaluated based on the percent tumor coverage, the Conformity Index (CI), Gradient Index (GI), Homogeneity index (HI), the maximum dose to the cord/cauda, and the volume of the cord/cauda receiving 8, 10, and 12 Gy (V8Gy, V10Gy and V12Gy). Paired t-tests were performed between the original and rotated plans with a significance level of 0.05. RESULTS: The Eclipse based VMAT plans on Halcyon achieved a similar target coverage (92.3 ± 3.0% vs. 92.4 ± 3.3%, p = 0.82) and CI (1.0 ± 0.1 vs. 1.1 ± 0.2, p = 0.12) compared to the TB plans. The Gradient index of Halcyon is higher (3.96 ±0.8) than TB (3.85 ±0.7), but not statistically significant. The maximum dose to the spinal cord/cauda was comparable (11.1 ± 2.8 Gy vs. 11.4 ± 3.6 Gy, p = 0.39), as were the V8Gy, V10Gy and V12Gy to the cord/cauda. The dosimetric influence of patient rotational setup error was statistically insignificant for rotations of up to 1° pitch/yaw (with similar target coverage, CI, max cord/cauda dose and V8Gy, V10Gy, V12Gy for cord/cauda). The total number of monitor units (MUs) for Halcyon (4998 ± 1688) was comparable to that of TB (5463 ± 2155) (p = 0.09). CONCLUSIONS: The Halcyon VMAT plans for a single thoracic or lumbar spine metastasis were dosimetrically comparable to the TB plans. Patient rotation within 1° in the pitch and yaw directions, if corrected by translation, resulted in insignificant dosimetric effects. The Halcyon linear accelerator is an acceptable alternative to TB for the treatment of single thoracic or lumbar spinal level metastasis, but users need to be cautious about the patient rotational setup error.  It is advisable to select patients appropriately, including only those with the thoracic or lumbar spine involvement and keeping at least 2 mm separation between the target and the cord/cauda. More margin is needed if the distance between the isocenter and cord/cauda is larger. It is advisable to place the planning isocenter close to the spinal canal to further mitigate the rotational error. SUMMARY: We simulated various scenarios of patient setup errors with different rotational combinations of pitch and yaw with 1°, 2°, and 3°, respectively. Rotation was corrected with translation only to mimic the Halcyon treatment scenario. Using the Halcyon for treating a tumor in a single thoracic or lumbar vertebral segment is feasible, but caution should be noted in patients requiring rotational corrections of > 1° in the absence of 6-DOF correction capabilities.