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The National Cancer Institute's Radiation Research Program, in collaboration with the Radiosurgery Society, hosted a workshop called Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy on August 20 and 21, 2018 to bring together experts in experimental and clinical experience in these and related fields. Critically, the overall aims were to understand the biological underpinning of these emerging techniques and the technical/physical parameters that must be further defined to drive clinical practice through innovative biologically based clinical trials.

Purpose Because children cannot reliably remain immobile during radiation therapy (RT) for cancer anatomy targeting requiring millimeter precision, daily anesthesia plays a large role in each RT session. Unfortunately, anesthesia is a source of financial burden for patients' families and is invasive and traumatic. This study attempts to assess the cost-savings benefit of audiovisual-assisted therapeutic ambiance in radiation therapy (AVATAR)-aided omission of pediatric anesthesia in RT. Methods and Materials The baseline time of anesthesia during RT was derived from documented anesthesia billing time during RT simulation at our institution and from the published literature. Current Procedural Terminology and relative value unit codes encompassing anesthesia-related charges from radiation oncology and anesthesia were analyzed in concert with this value to calculate the total cost of pediatric anesthesia per RT session. Results The mean number of RT fractions administered per patient with AVATAR-directed anesthesia omission at our institution was 19.0, similar to the 17.6 previously reported. At a mean anesthesia time exceeding 30 minutes (with mean RT duration of 4 weeks), the cost of pediatric anesthesia per RT fraction in non-AVATAR sessions was $1,904.35, yielding a total RT treatment anesthesia cost of $38,087.00 per patient (including simulation). Patients at our institution were not billed for AVATAR-assisted RT. Conclusions The ability of AVATAR to obviate the need for daily anesthesia in pediatric RT provides substantial cost-savings. These findings argue for increased utilization of AVATAR and for analyses of RT targeting the accuracy of AVATAR versus conventional anesthesia-guided treatment of pediatric malignancies.

PURPOSE The aim of this study was to report local failure (LF) outcomes and associated predictors in patients with oligometastatic colorectal cancer (CRC) treated with stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS We retrospectively reviewed patients with CRC metastases to the brain, liver, spine, or lung treated with SABR between 2001 and 2016. Time to LF was summarized using cumulative incidence of LF curves with death as a competing risk. RESULTS The analysis included a total of 130 patients and 256 lesions. Of the metastases treated, 129 (50%) were brain, 50 (20%) liver, 49 (19%) spine, and 28 (11%) lung. Median gross tumor volume was 24 mL for liver metastases, 2 mL for brain metastases, 4 mL for spine metastases, and 1 mL for lung metastases. The overall 1, 2, and 3-year cumulative incidence of LF rates were 21.6% (16.5, 27.1), 28.2% (22.3, 34.4), and 31.5% (25.2, 38.0), respectively. LF was highest among the liver metastases (1 y: 26.0%, 2 y: 38.5%), followed by spine (1 y: 25.1%, 2 y: 31.1%), brain (1 y: 20%, 2 y: 25.2%), and lung (1 y: 13.7%, 2 y: insufficient data). Metastases from right-sided primary CRC were significantly more likely to have LF (P=0.0146, HR=2.23). Biologically effective dose>70 Gy, defined using a standard linear quadratic model using α/β ratio of 10 on the individual lesion level, and pre-SABR chemotherapy were also significant predictors of LF (P= 0.0009 and 0.018, respectively). CONCLUSIONS CRC metastases treated with SABR had significantly higher rates of LF if they originated from right-sided primary CRC, compared with left-sided. Liver metastases had the highest rates of LF compared with other metastatic sites. Thus, CRC liver metastases and metastases from right-sided CRC may benefit from more aggressive radiotherapy.

Pluridirectional high-energy agile scanning electronic radiotherapy (PHASER) is next-generation medical linac technology for ultra-rapid highly conformal image-guided radiation, fast enough to "freeze" physiological motion, affording improved accuracy, precision, and potentially superior FLASH radiobiological therapeutic index. Designed for compactness, economy, and clinical efficiency, it is also intended to address barriers to global access to curative radiotherapy.

Purpose/Objective(s) Stereotactic ablative radiotherapy (SABR) is an effective treatment for lung tumors, but can result in toxicity such as chest wall pain and life-threatening damage to central lung structures. We hypothesized that while larger tumors require higher dose, small tumors up to 10cc in volume can be controlled with biologically effective dose Materials/Methods Patients in three groups were enrolled: initial diagnosis of non-small cell lung cancer (NSCLC), AJCC 7th edition stage T1-3 N0 M0 (group 1); new primary NSCLC with history of NSCLC, or multiple synchronously diagnosed NSCLCs (group 2); and lung metastases from NSCLC or another primary site (group 3). Up to four tumors could be treated with once-daily SABR. There were six dose/fractionation schedules used, depending on gross tumor volume (≤10cc, 10-30cc, > 30cc) and location (peripheral vs. central). Larger tumors received higher dose and central tumors generally received lower dose per fraction. Dose ranged from 25Gy in one fraction for 0-10cc peripheral tumors to 60Gy in 8 fractions for > 30cc central tumors. Colorectal cancer metastases were treated to higher dose, at least 50Gy in 4 fractions. The primary endpoint was per-group cumulative incidence of local recurrence at 1 year (recurrence of treated tumor within same lobe), with distant recurrence and death as competing risks. Treated tumor recurrence (recurrence with epicenter within 1cm of PTV) and toxicity were also analyzed. Results A total of 217 patients were enrolled from 2011-2018 (some patients were enrolled multiple times). Median age was 72, 59% were male, and 69% were current/former smokers. There were 240 treatment courses and 285 tumors treated (range 1-3 tumors per course). 211 tumors were peripheral and 74 were central. Tumor size distribution was: ≤10cc, 74%; 10-30cc, 19%; > 30cc, 7%. The most common dose was 25Gy in one fraction (158 tumors). Median follow-up was 30 months (range 2-95). Median overall survival was 57 months. Local recurrence data are currently being updated and will be presented at the meeting. The rate of grade 2 or higher pneumonitis was 16/217 (7%) and grade 3 or higher pneumonitis was 3/217 (1%). The rate of grade 2 or higher chest wall pain was 13/217 (6%). One patient had a grade 5 adverse event, developing pulmonary hemorrhage that was possibly related to radiotherapy, 17 months after treatment of a large central NSCLC. Conclusion Individualized SABR to lung cancers resulted in excellent local control and favorable toxicity profile.

Radiation therapy is the most effective cytotoxic therapy for localized tumors. However, normal tissue toxicity limits the radiation dose and the curative potential of radiation therapy when treating larger target volumes. In particular, the highly radiosensitive intestine limits the use of radiation for patients with intra-abdominal tumors. In metastatic ovarian cancer, total abdominal irradiation (TAI) was used as an effective postsurgical adjuvant therapy in the management of abdominal metastases. However, TAI fell out of favor due to high toxicity of the intestine. Here we utilized an innovative preclinical irradiation platform to compare the safety and efficacy of TAI ultra-high dose rate FLASH irradiation to conventional dose rate (CONV) irradiation in mice. We demonstrate that single high dose TAI-FLASH produced less mortality from gastrointestinal syndrome, spared gut function and epithelial integrity, and spared cell death in crypt base columnar cells compared to TAI-CONV irradiation. Importantly, TAI-FLASH and TAI-CONV irradiation had similar efficacy in reducing tumor burden while improving intestinal function in a preclinical model of ovarian cancer metastasis. These findings suggest that FLASH irradiation may be an effective strategy to enhance the therapeutic index of abdominal radiotherapy, with potential application to metastatic ovarian cancer.

Radiation therapy, along with surgery and chemotherapy, is one of the main treatments for cancer. While radiotherapy is highly effective in the treatment of localized tumors, its main limitation is its toxicity to normal tissue. Previous preclinical studies have reported that ultra-high dose-rate (FLASH) irradiation results in reduced toxicity to normal tissues while controlling tumor growth to a similar extent relative to conventional-dose-rate (CONV) irradiation. To our knowledge this is the first report of a dose-response study in mice comparing the effect of FLASH irradiation vs. CONV irradiation on skin toxicity. We found that FLASH irradiation results in both a lower incidence and lower severity of skin ulceration than CONV irradiation 8 weeks after single-fraction hemithoracic irradiation at high doses (30 and 40 Gy). Survival was also higher after FLASH hemithoracic irradiation (median survival >180 days at doses of 30 and 40 Gy) compared to CONV irradiation (median survival 100 and 52 days at 30 and 40 Gy, respectively). No ulceration was observed at doses 20 Gy or below in either FLASH or CONV. These results suggest a shifting of the dose-response curve for radiation-induced skin ulceration to the right for FLASH, compared to CONV irradiation, suggesting the potential for an enhanced therapeutic index for radiation therapy of cancer.

The observation of an enhanced therapeutic index for FLASH radiotherapy in mice has created interest in practical laboratory-based FLASH irradiators. To date, systems capable of 3D conformal FLASH irradiation in mice have been lacking. We are developing such a system, incorporating a high-current linear accelerator to produce a collimated X-ray beam in a stationary beamline design, rotating the mouse about a longitudinal axis to achieve conformal irradiation from multiple beam directions. The purpose of this work was to evaluate the reproducibility of mouse anatomy under rotation at speeds compatible with conformal FLASH delivery. Three short-hair mice and two hairless mice were immobilized under anesthesia in body weight-specific contoured plastic molds, and subjected to three rotational (up to 3 revolutions/s) and two non-rotational movement interventions. MicroCT images were acquired before and after each intervention. The displacements of 11 anatomic landmarks were measured on the image pairs. The displacement of the anatomical landmarks with any of the interventions was 0.5 mm or less for 92.4% of measurements, with a single measurement out of 275 (11 landmarks × 5 interventions × 5 mice) reaching 1 mm. There was no significant difference in the displacements associated with rotation compared to those associated with moving the immobilized mouse in and out of a scanner or with leaving the mouse in place for 5 min with no motion. There were no significant differences in displacements between mice with or without hair, although the analysis is limited by small numbers, or between different anatomic landmarks. These results show that anatomic reproducibility under rotation speed corresponding to FLASH irradiation times appears to be compatible with conformal/stereotactic irradiation in mice.

PURPOSE/OBJECTIVE(S) Ultra-high dose rate (FLASH) radiotherapy (RT) at ≥40 Gray per second has been shown preclinically to achieve improved normal tissue sparing while maintaining tumor control similar to that of conventional dose-rate RT. Many published FLASH-RT delivery models are inaccessible for widespread use and/or not applicable for clinical translation. We previously described a model for reversible configuration of a clinical linear accelerator (LINAC) that can deliver ∼16-18 MeV electron FLASH-RT at source-to-surface distances (SSDs) 80% of the central axis was 10.6 cm and 9.6 cm, and symmetry (defined as the maximum dose difference between any two symmetric points about the central axis in the flat portion of the beam, as a percentage of central dose) was 2.24% and 2.20%. PDD values for the cone-less set-up at Dmax, R95, R85, and R50 were, respectively, 3.1, 4.1, 5.3, and 6.8 cm. CONCLUSION We have developed a novel cone-less set-up that allows for the delivery of electron FLASH-RT utilizing a clinical LINAC at practical SSDs and verified that its beam profiles are clinically feasible. Further work will be done to characterize additional SSDs and field sizes, along with the addition of a custom skin collimator to further shape the beam. This will pave the way for practical treatment using electron FLASH-RT to a host of oncologic indications, including cutaneous malignancies and partial breast irradiation in the future.

Purpose/Objective(s) Multiple preclinical in-vivo studies of ultra-high dose rate (FLASH) radiation therapy (RT) have shown reduced normal tissue toxicity with equivalent tumor control when compared to conventional dose rate RT, with benefits seen at dose rates ≥40 Gray (Gy) per second. Leveraging these benefits for clinical translation could profoundly impact RT. Extending an institutionally established reversible configuration of a linear accelerator (LINAC) for FLASH, we explored the feasibility of LINAC-based FLASH RT for potential clinical application. Materials/Methods A standard, clinical-use treatment delivery system was used. A single decommissioned beam's program circuit board was replaced with a dedicated experimental board, holding control parameters for RF power and gun current. Dose rates at an electron beam energy of ∼16 MeV were maximized at a gun current setting of 11.8V grid voltage. Notably, this setup kept the scattering foil in the beam, maintaining the advantages of the clinical utility of a standard scattered high-energy electron beam, and its inherent achievable field sizes and depth doses. For measurements, gantry and collimator rotations were set to 0° with open primary jaws. Dose rates were measured at central axis using radiographic film, with a 3 cm buildup of solid water and 20 cm downstream. FLASH treatments were delivered in 90 pulses, with 2 independent measurements at 4 source-to-surface distance (SSD) positions, including at the machine head (59 cm SSD). Percentage depth dose (PDD) was measured with a film strip placed between two vertical 5 cm thick solid water phantoms, obtained at 70, 80, and 100 cm SSD using FLASH, and 100 cm SSD with conventional dose rate 16 MeV electrons. Results FLASH dose rates > 100 Gy/s were obtained using a standard, scattered electron beam at clinically relevant SSD's and depths with a clinical-use LINAC. Measured average dose rates at 100, 80, 70, and 59 cm SSD were 36.82, 59.52, 82.01, and 112.83 Gy/s, respectively. Average doses per pulse measured were 0.21, 0.33, 0.46, and 0.63 Gy/pulse, respectively. FLASH PDD's emulated 16-18 MeV energies, aligning closely with a conventional 16 MeV PDD. At 70, 80, and 100 cm SSD FLASH, and 100 cm SSD conventional 16 MeV, 90% fall-off measured at 5.2, 5.3, 5.5, and 5.2 cm depth, 80% at 5.9, 6.0, 6.1, and 5.7 cm and 50% at 7.0, 7.0, 7.1, and 6.8 cm depth, respectively. Conclusion Using a readily reversible configuration of a standard LINAC, FLASH dose rates > 100 Gy/s was achievable at clinically applicable SSDs and depths. Balancing clinical feasibility with FLASH, further studies characterizing the FLASH beam at 70 to 90 cm SSD are underway, including development of a cone-less electron field shaping system and solutions for energy modulation. Advantages of our setup, using a standard scattering foil with high energy electrons, bring us a step closer to clinical practicality of FLASH RT delivery using a standard LINAC.

PURPOSE/OBJECTIVE(S) We aimed to evaluate the safety of and maximum tolerated dose (MTD) for 5-fraction stereotactic ablative radiotherapy (SABR) for early-stage lung squamous cell carcinoma (SCC), for which local failure rates appears higher than that of early-stage adenocarcinomas. MATERIALS/METHODS A single institution phase I study was conducted in pathologically confirmed early-stage lung SCC. The 3+3 design involved 4 dose levels of 11, 12, 13, and 14 Gy x 5 fractions delivered every other day (dose levels DL1, DL2, DL3, and DL4, respectively). The primary objective was to determine the MTD of 5-fraction SABR, which was defined as the dose associated with a 33% rate of dose-limiting toxicities, defined as grade ≥3 respiratory/mediastinal or cardiac events (or grade ≥4 gastrointestinal or chest wall events), with toxicities reported until data lock in October 2020. Target volume delineation and organ-at-risk (OAR) constraints were based on RTOG 0813, using OAR constraints expressed in percent of prescription as fixed constraints from the 11 Gy per fraction prescription for all DL. Institutional constraints for the chest wall were used (V30 < 30cm3, up to 70 cm3 acceptable; maximum point dose 52.5 Gy). Target coverage objectives included ≥95% of the planning target volume (PTV) to be covered by 100% of the prescription dose, and 100% of the internal target volume (ITV) to receive ≥110% of the prescription dose. For technically challenging cases, it was permitted to prescribe as low as 50 Gy (BED of 100 Gy10) to a small portion of the GTV, ITV (if used) and corresponding PTV adjacent to a critical OAR (split target volume prescription). SABR was delivered using free breathing, deep inspiration breathhold, or expiratory gating. Thus, ITVs were not used for all patients. RESULTS From October 2017 to June 2020, 13 patients were enrolled: 3 in DL1, 3 in DL2, 4 in DL3, and 3 in DL4. Seven (IASLC definition) or 6 (RTOG) patients had central lesions, and the rest abutted the chest wall. All patients completed SABR per protocol without major deviations. At 18.4 months median follow-up (range, 2.4-25.6 months), no patient developed dose limiting toxicities. There were no grade 4-5 events and 1 grade 3 event (painful brachial plexopathy, which occurred in DL1 at 16 months post-SABR at the time of local progression). There were 7 instances of grade 2 toxicities. These included fatigue (n = 1, DL2), chest wall pain (n = 2, DL2 & DL4), cough (n = 1, DL3), dyspnea (n = 2, DL3 & DL4), nausea (n = 1, DL4), and wheezing (n = 1, DL4). Eight (62%) patients required utilization of "split target volume" prescriptions. The mean total dose to the GTV ranged from 60.9-62.2 Gy for DL1, 63.2-68.6 Gy for DL2, 67.3-78.8 Gy for DL3, and 75.5-82.2 Gy for DL4. The median GTV was 19.9 cc (range 5-57cc). CONCLUSION 5-fraction SABR for early-stage lung SCC up to 14 Gy x 5 fractions using a split target prescription for OAR adjacent tumor appears safe. Long term follow up will be needed to assess late toxicities and tumor control. (NCT03321747).

Peritoneal metastases are the leading cause of morbidity and mortality in ovarian cancer. Despite current surgery, chemotherapy and targeted therapies, the majority of patients diagnosed with advanced epithelial ovarian cancer develop recurrent disease and overall survival rates remain poor. It is known that ovarian cancer is a radiosensitive tumor. Historically, total abdominal irradiation (TAI) was used as an effective postsurgical adjuvant therapy in the management of chemotherapy sensitive and resistant ovarian cancer. However, TAI fell out of favor due to high toxicity, particularly of the gastrointestinal tract. We have developed a preclinical irradiation platform that allows for total abdominal ultrahigh dose rate FLASH irradiation. We demonstrate that TAI-FLASH reduces radiation-induced intestinal injury in both healthy and tumor-bearing mice compared to conventional dose rate (CONV) irradiation. Single high dose TAI-FLASH reduced mortality from gastrointestinal syndrome, spared gut function and epithelial integrity, and decreased cell death in crypt base columnar cells. Importantly, FLASH and CONV irradiation had similar efficacy in the reduction of ovarian cancer peritoneal metastases. These findings suggest that FLASH irradiation may be an effective strategy to enhance the therapeutic index of radiotherapy for the treatment of metastatic ovarian cancer in women.

Purpose: We demonstrate proof of principle that normal tissue doses can be greatly reduced in lung stereotactic body radiation therapy (SBRT) for mobile tumors, if the delivered dose is split between opposite respiratory states. Methods: Patients that underwent 5 fraction lung SBRT at our institution and had deep inspiration breath hold (DIBH) and free breathing 4D computed tomography scans were included. Volumetric modulated arc therapy plans were generated on both respiratory phases and a third composite plan was generated delivering half the dose using the DIBH plan and the other half using the expiratory phase plan for each fraction. Computed tomography scans for the composite plan were fused based on ribs adjacent to the tumor to evaluate the dose volume histogram of critical structures. Results: Four patients with 4 total tumors had requisite planning scans available. Tumor size was between 0.7 to 2.9 cm and tumor movement 1.4 to 2.9 cm. Median reduction in the chest wall (CW) V30Gy for the composite plan was 74.6% (range 33.7 to 100%), 76.9% (range 32.9 to 100%), and 89.3% (range 69.5 to 100%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Median reduction in CW maximum dose for the composite plan was 23.3% (range 0.27% to 46.4%), 23.5% (range 3.2 to 48.2%), and 23.4% (range 0.27% to 48.4%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Greater reduction in CW maximum dose was observed when patients had no overlap in planning target volumes between DIBH and expiration phases (median reduction 43.9% for no overlap vs 2.7% with overlap). Between all plans, lung V20Gy absolute differences were within 1.3%. For 2 of 4 patients, the composite plan met constraints for 3 fraction SBRT, while standard plans did not. Conclusions: We conclude that composite DIBH-expiration SBRT planning has the potential to improve organ at risk sparing.

Radiation therapy is the most effective cytotoxic cancer therapy available for the treatment of localized tumors. However, radiation-induced toxicity to normal tissues limits the radiation dose and therefore the curative potential of radiotherapy. In particular, the highly radiosensitive intestine greatly limits the use of radiation for patients with intra-abdominal tumor diseases including women with ovarian cancer. Here we sought to investigate the safety and efficacy of FLASH radiation therapy in the treatment of widespread ovarian cancer peritoneal metastases. We performed abdominal irradiation on healthy and ovarian tumor-bearing mice at conventional (CONV, (0.07 Gy/sec)) or FLASH (200 Gy/sec) dose rates and examined gut function by stool counts, DNA damage in crypt cells by γ-H2AX staining, cell death and proliferation by TUNEL/ caspase-3 staining and BrdU immunohistochemistry respectively. We report that ultrahigh dose rate FLASH irradiation causes significantly less radiation-induced intestinal injury in both healthy and tumor-bearing mice compared to CONV dose rate irradiation. Abdominal FLASH reduced the mortality from gastrointestinal syndrome, preserved gut function and epithelial integrity as reflected by their stool counts and FITC-Dextran analysis. In addition, we found decreased cell death and enhanced proliferation of crypt base columnar cells (CBCs) following FLASH irradiation in comparison to CONV irradiation. We also detected reduced number of γ-H2AX foci in crypt cells indicating less DNA damage and/or increased DNA repair after FLASH compared to CONV irradiation. Importantly, FLASH and CONV irradiation have similar efficacy in the reduction of ovarian cancer peritoneal metastases. These findings suggest that FLASH irradiation has biological advantages compared to conventional dose rate irradiation in reducing radiation-induced intestinal injury within the irradiation field and therefore may be an effective strategy to enhance the therapeutic index of radiotherapy for the treatment of abdominal and pelvic tumor disease. Citation Format: Suchitra Natarajan, Karen Levy, Jinghui Wang, Stephanie Chow, Joshua Eggold, Phoebe Loo, Rakesh Manjappa, Frederick M. Lartey, Emil Schüler, Lawrie Skinner, Marjan Rafat, Ryan Ko, Anna Kim, Duaa Al Rawi, Rie von Eyben, Oliver Dorigo, Kerriann M. Casey, Edward E. Graves, Karl Bush, Amy S. Yu, Albert C. Koong, Peter G. Maxim, Billy W. Loo, Erinn B. Rankin. FLASH irradiation enhances the therapeutic index of abdominal radiotherapy in mice [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5351.

Introduction: Ultrahigh dose-rate irradiation (FLASH RT) is rapidly emerging as new strategy to enhance the therapeutic index of radiotherapy by protecting normal tissues from radiation-induced toxicity while maintaining tumor control. In mice, FLASH has been shown to protect the lung, skin, and brain against radiation-induced toxicity. A recent study has utilized FLASH radiotherapy in preclinical models of lung cancer to demonstrate that FLASH RT radiotherapy achieves similar tumor control to conventional RT. While these findings identify an important role for FLASH RT in the protection of multiple tissues, the role of FLASH in enhancing the therapeutic index of abdominal and pelvic tumors located near the highly radiosensitive intestine is not known. For this purpose, we have developed an experimental platform using a clinical linear accelerator that enables total abdominal FLASH RT where rapid delivery of a single fraction of high-dose radiotherapy is performed in less than one second (200 Gy/sec). Methods: For the tumor model, ID8 cells were injected intraperitoneally into female mice. Radiation was delivered 10 days post-ID8 injection. Tumor burden was assessed at 28 days following tumor injection. Flow cytometry was used to profile infiltrating immune cells. Normal tissue toxicity was assessed through survival, total body weight, solid stool production, complete blood count, and histologic analysis. Results: In ID8 tumor-bearing mice, 14 Gy FLASH promotes GI function with a 2-fold increase in solid stool production at 5 days post-TAI. Both modalities extended median overall survival in the ID8 model by 5 days and reduced tumor burden by 50% relative to unirradiated controls. Irradiated cohorts also demonstrated an increase in the number of proliferating CD8+ and CD4+ T cells present in the ascites. Conclusion: We demonstrate that FLASH RT protects the gastrointestinal (GI) tract from lethal radiation-induced toxicity, improves epithelial integrity and GI function, enhances crypt survival, and provides efficient tumor control in a preclinical model of ovarian peritoneal metastasis. Here we present the first data supporting the potential for tumor control and GI protection using FLASH-TAI in a syngeneic orthotopic preclinical model of ovarian cancer. Citation Format: Karen Levy, Jinghui Wang, Joshua Eggold, Suchitra Natarajan, Peter Maxim, Bill Loo, Erinn Rankin. Ultrarapid total abdominal FLASH irradiation in a preclinical model of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A23.

Most commonly in radiation therapy, treatments are delivered in a co-planar geometry. Numerous advantages have been reported of adding non-coplanar beams to the treatment plan. The aim of this study was to compare current state-of-the-art VMAT and CyberKnife treatment plans to that of a novel linac design developed at Stanford which utilizes a static conical beam arrangement that allows the inclusion of a full ring diagnostic CT with shared isocenter with the treatment beams. Four clinical cases, prostate, lung, head/neck, and pediatric brain, were selected and treatment plans were generated with 45° or 60° (to the longitudinal axis of the patient) conical beam IMRT and compared with co-planar 90° VMAT plans. Double cone, with beams entering from both superior and inferior directions, and single cone geometries were evaluated. Plans were optimized in RayStation using an in-house developed script to minimize operator bias between the different techniques. Non-coplanar CyberKnife IMRT plans for the pediatric and prostate case were optimized separately in MultiPlan and compared to conical geometry plans. In the prostate case, increased mean dose to the rectum (2.3-3.7 Gy) and bladder (9.5-14.5 Gy) but decreased dose to the femoral heads (femurs) (7.1-10 Gy) were found with the conical arrangement compared to 90° VMAT. Only minor dosimetric differences were found in the lung case, while selective sparing of organs at risk was found with 45° or 60° conical arrangement in the pediatric brain and head/neck cases. For the prostate case, a reduction in mean doses to the bladder and rectum of 6% (2 Gy) and 18% (5.2 Gy), respectively, was found when comparing the CyberKnife to the 60° conical plan, in favor of the CyberKnife plan, but with an increase in integral dose and reduced conformity. An increase in integral dose and reduced conformity was also found for the pediatric brain case when comparing CyberKnife and 60° conical plan. Minor benefits were found with double cone compared to single cone geometry. Comparable treatment plan quality could be achieved between conical beam arrangement and 90° (coplanar) VMAT and CyberKnife (non-coplanar) IMRT, demonstrating the promise of this novel beam geometry. The use of this beam geometry allows volumetric image-guidance with full ring imaging and a common isocenter for simultaneous treatment and imaging.