Glioblastoma (GBM) is the most common primary brain tumor. Due to high resistance to treatment, local invasion, and a high risk of recurrence, GBM patient prognoses are often dismal, with median survival around 15 months. The current standard of care is threefold: surgery, radiation therapy, and chemotherapy with temozolomide (TMZ). However, patient survival has only marginally improved. Radioimmunotherapy (RIT) is a fourth modality under clinical trials and aims at combining immunotherapeutic agents with radiotherapy. Here, we develop in vitro assays for the rapid evaluation of RIT strategies. Using a standard cell irradiator and an Electric Cell Impedance Sensor, we quantify cell migration following the combination of radiotherapy and chemotherapy with TMZ and RIT with durvalumab, a PD-L1 immune checkpoint inhibitor. We measure cell survival using a cloud-based clonogenic assay. Irradiated T98G and U87 GBM cells migrate significantly (p < 0.05) more than untreated cells in the first 20–40 h post-treatment. Addition of TMZ increases migration rates for T98G at 20 Gy (p < 0.01). Neither TMZ nor durvalumab significantly change cell survival in 21 days post-treatment. Interestingly, durvalumab abolishes the enhanced migration effect, indicating possible potency against local invasion. These results provide parameters for the rapid supplementary evaluation of RIT against brain tumors.

Unlike plants that have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm the known effects of simulated microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 h of exposure to simulated microgravity via a NASA-developed rotary cell culture system. Through fluorescence-guided morphometry, we found that microgravity abolished a significant reduction (p < 0.01) in the nuclear-to-cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on the impact of microgravity on cellular drug response, in light of the growing need for space medicine, as space exploration grows.

Purpose: Linear accelerator‐based stereotactic radiosurgery (SRS) has become a mainstay for simultaneous management of multiple intracranial targets. Recent improvements in treatment planning systems (TPS) have enabled treatment of multiple brain metastases using dynamic conformal arcs (DCA) and a single treatment isocenter. However, as the volume of healthy tissue receiving at least 12 Gy (V12) is linked to the probability of developing radionecrosis, balancing target coverage while minimizing V12 is a critical factor affecting SRS plan quality. Current TPS allow users to adjust various parameters influencing plan optimization. The purpose of this work is to quantify the effect of negative margins on V12 for cranial SRS plans managing multiple brain metastases.Methods: Using the Brainlab Elements v3.0 TPS (Brainlab, Munich, Germany), we calculated V10, V12, V15, monitor units, and conformity index for seventeen SRS plans treating 2–10 metastases on our Elekta Versa HD (Elekta, Stockholm, Sweden) linear accelerator. We compared plans optimized using 70%‐90% prescription isodose lines (IDL) in 5% increments.Results: Irrespective of the number of treated metastases, optimization at a lower prescription IDL reduced V10, V12, and V15 and increased MU compared to the 90% IDL (p < 0.01). However, comparing the 70% and 75% IDL optimizations, there was little difference in tissue sparing. The conformity index showed no consistent trends at different IDLs due to a significant spread in case data.Conclusion: For our plans treating up to 10 metastases, diminishing returns for tissue sparing at IDLs below 80% paired with increasing treatment MU and dosimetric hot spot made optimization at lower IDLs less favorable. In our clinic, after consulting with a physician, it was determined that optimization at the 80% IDL achieved the best balance of V12, treatment MU, and maximum dose. Clinics implementing LINAC‐based SRS programs may consider using similar evaluations to develop their own clinical protocols.

Stereotactic ablative radiotherapy (SABR) has become a key technique in management of spine metastases. With improved control over treatment plan dosimetry, there is a greater need for accurate patient positioning to guarantee agreement between the treatment plan and delivered dose. With serious potential complications such as fracture and myelopathy, the margins of error in SABR of the spine are minimal. In this study, we assessed the performance of two patient immobilization setups in SABR for spinal metastases. First, a Type‐S head and shoulders mask (CQ Medical, Avondale, PA), and second, the BPL1 setup, which includes a wing board, vacuum bag, and the Respiratory Belt for the Body Pro‐Lok ONE (CQ Medical, Avondale, PA). Immobilization was assessed using image‐guided intrafraction repositioning shifts. Required planning target volume (PTV) margins were calculated based on repositioning data for 172 treated fractions using 2 standard deviation (2SD) and analytic approaches. Overall, 91.7% and 74.1% of fractions treated had total 3D repositioning shifts ≤3.0 mm using the Type‐S and BPL1 setups, respectively. In the thoracic spine, 43.2% and 46.5% of fractions had shifts ≤1.5 mm for the respective setups. Suggested margins were under 3.5 mm in all directions and use cases. In the posterior‐anterior direction, the BPL1 setup had a 0.6 mm smaller suggested margin for the thoracic spine compared to the Type‐S setup, at 1.4 mm, calculated using the analytic approach. Both the Type‐S and BPL1 setups are effective for immobilization in spine SABR. The Type‐S demonstrated superior immobilization in the upper spine and remains the clinical standard for cervical and upper thoracic spine positioning. The BPL1 setup showed effective immobilization in use cases treating the mid‐to lower thoracic spine and lumbar spine and remains our clinical standard for those use cases. Results additionally demonstrate feasibility of potential PTV margin reduction.

Motion management presents a significant challenge in thoracic stereotactic ablative radiotherapy (SABR). Currently, a 5.0 mm standard planning target volume (PTV) margin is widely used to ensure adequate dose to the tumor. Considering recent advancements in tumor localization and motion management, there is merit to reassessing the necessary PTV margins for modern techniques. This work presents a large-scale analysis of intrafraction repositioning for lung SABR under forced shallow breathing to determine the margin requirements for modern delivery techniques. Treatment data for 124 lung SABR patients treated in 607 fractions on a linear accelerator were retrospectively collected for analysis. All patients were treated using pneumatic abdominal compression and intrafraction 4D cone beam computed tomography (4D CBCT)-guided repositioning halfway through treatment. Executed repositioning shifts were collected and used to calculate margin requirements using the 2-standard deviation (2SD) method and an analytic model which accounts for systematic and random errors in treatment. 85.7% of treated fractions had 3D repositioning shifts under 5.0 mm. 53 fractions (8.7%) had shifts ≥5.0 mm in at least one direction. Margins in the right-left, inferior-superior, and posterior-anterior directions were 3.62 mm, 4.34 mm, and 3.50 mm, respectively, calculated using the 2SD method. The analytic approach estimated 4.01 mm, 4.37 mm, and 3.95 mm margins were appropriate for our workflow. Executing intrafraction repositioning reduced margin requirements by 0.73 ± 0.07 mm. Clinical data suggests that the uniform 5.0 mm margin is conservative for our workflow. Utilizing modern techniques such as 4D CT, 4D CBCT, and effective motion management can significantly reduce required margins, and therefore necessary healthy tissue dose. However, the limitations of margin calculation models must be considered, and margin reduction must be approached with caution. Users should conduct a formal risk assessment prior to adopting new standard PTV margins.

Unlike plants which have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm known effects of microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 hours of exposure to microgravity via a NASA-developed rotary cell culture system. Fluorescence-guided morphometry revealed microgravity-induced loss of the significant reduction (p < 0.0l) to the nuclear to cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on impact of microgravity on cellular drug-response, in view of the growing need for space medicine, as space exploration grows.