NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022.

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.

Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.

Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study.

BACKGROUND: The leading cause of mortality for patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the development of malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma. In the setting of NF1, this cancer type frequently arises from within its common and benign precursor, plexiform neurofibroma (PN). Transformation from PN to MPNST is challenging to diagnose due to difficulties in distinguishing cross-sectional imaging results and intralesional heterogeneity resulting in biopsy sampling errors. METHODS AND FINDINGS: This multi-institutional study from the National Cancer Institute and Washington University in St. Louis used fragment size analysis and ultra-low-pass whole genome sequencing (ULP-WGS) of plasma cell-free DNA (cfDNA) to distinguish between MPNST and PN in patients with NF1. Following in silico enrichment for short cfDNA fragments and copy number analysis to estimate the fraction of plasma cfDNA originating from tumor (tumor fraction), we developed a noninvasive classifier that differentiates MPNST from PN with 86% pretreatment accuracy (91% specificity, 75% sensitivity) and 89% accuracy on serial analysis (91% specificity, 83% sensitivity). Healthy controls without NF1 (participants = 16, plasma samples = 16), PN (participants = 23, plasma samples = 23), and MPNST (participants = 14, plasma samples = 46) cohorts showed significant differences in tumor fraction in plasma (P = 0.001) as well as cfDNA fragment length (P < 0.001) with MPNST samples harboring shorter fragments and being enriched for tumor-derived cfDNA relative to PN and healthy controls. No other covariates were significant on multivariate logistic regression. Mutational analysis demonstrated focal NF1 copy number loss in PN and MPNST patient plasma but not in healthy controls. Greater genomic instability including alterations associated with malignant transformation (focal copy number gains in chromosome arms 1q, 7p, 8q, 9q, and 17q; focal copy number losses in SUZ12, SMARCA2, CDKN2A/B, and chromosome arms 6p and 9p) was more prominently observed in MPNST plasma. Furthermore, the sum of longest tumor diameters (SLD) visualized by cross-sectional imaging correlated significantly with paired tumor fractions in plasma from MPNST patients (r = 0.39, P = 0.024). On serial analysis, tumor fraction levels in plasma dynamically correlated with treatment response to therapy and minimal residual disease (MRD) detection before relapse. Study limitations include a modest MPNST sample size despite accrual from 2 major referral centers for this rare malignancy, and lack of uniform treatment and imaging protocols representing a real-world cohort. CONCLUSIONS: Tumor fraction levels derived from cfDNA fragment size and copy number alteration analysis of plasma cfDNA using ULP-WGS significantly correlated with MPNST tumor burden, accurately distinguished MPNST from its benign PN precursor, and dynamically correlated with treatment response. In the future, our findings could form the basis for improved early cancer detection and monitoring in high-risk cancer-predisposed populations.

Socio-economic factors do not affect overall survival in soft tissue sarcoma when patients treated at a single high-volume center.

BACKGROUND: Treatments for soft tissue sarcoma (STS) include extensive surgical resection, radiation and chemotherapy, and can necessitate specialized care and excellent social support. Studies have demonstrated that socioeconomic factors, such as income, marital status, urban/rural residence, and educational attainment as well as treatment at high-volume institution may be associated with overall survival (OS) in STS. METHODS: In order to explore the effect of socio-economic factors on OS in patients treated at a high-volume center, we performed a retrospective analysis of STS patients treated at a single institution. RESULTS: Overall, 435 patients were included. Thirty-seven percent had grade 3 tumors and 44% had disease larger than 5 cm. Patients were most commonly privately insured (38%), married (67%) and retired or unemployed (43%). Median distance from the treatment center was 42 miles and median area deprivation index (ADI) was 5 (10 representing most deprived communities). The majority of patients (52%) were treated with neoadjuvant therapy followed by resection. As expected, higher tumor grade (HR 3.1), tumor size > 5 cm (HR 1.3), and involved lymph nodes (HR 3.2) were significantly associated with OS on multivariate analysis. Demographic and socioeconomic factors, including sex, age at diagnosis, marital status, employment status, urban vs. rural location, income, education, distance to the treatment center, and ADI were not associated with OS. CONCLUSIONS: In contrast to prior studies, we did not identify a significant association between socioeconomic factors and OS of patients with STS when patients were treated at a single high-volume center. Treatment at a high volume institution may mitigate the importance of socio-economic factors in the OS of STS.

NCCN Guidelines Insights: Soft Tissue Sarcoma, Version 1.2021.

The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.

T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas.

BACKGROUND: Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited. METHODS: The authors identified patients with the common STS subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), well-differentiated/dedifferentiated liposarcoma, and myxoid/round cell liposarcoma. Gene expression, immunohistochemistry for programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), and T-cell receptor Vß gene sequencing were performed on formalin-fixed, paraffin-embedded tumors from 81 patients. Differences in liposarcoma subsets also were evaluated. RESULTS: UPS and leiomyosarcoma had high expression levels of genes related to antigen presentation and T-cell infiltration. UPS were found to have higher levels of PD-L1 (P≤.001) and PD-1 (P≤.05) on immunohistochemistry and had the highest T-cell infiltration based on T-cell receptor sequencing, significantly more than SS, which had the lowest (P≤.05). T-cell infiltrates in UPS also were more oligoclonal compared with SS and liposarcoma (P≤.05). A model adjusted for STS histologic subtype found that for all sarcomas, T-cell infiltration and clonality were highly correlated with PD-1 and PD-L1 expression levels (P≤.01). CONCLUSIONS: In the current study, the authors provide the most detailed overview of the immune microenvironment in sarcoma subtypes to date. UPS, which is a more highly mutated STS subtype, provokes a substantial immune response, suggesting that it may be well suited to treatment with immune checkpoint inhibitors. The SS and liposarcoma subsets are less mutated but do express immunogenic self-antigens, and therefore strategies to improve antigen presentation and T-cell infiltration may allow for successful immunotherapy in patients with these diagnoses. Cancer 2017;123:3291-304. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

A patient safety education program in a medical physics residency.

Education in patient safety and quality of care is a requirement for radiation oncology residency programs according to accrediting agencies. However, recent surveys indicate that most programs lack a formal program to support this learning. The aim of this report was to address this gap and share experiences with a structured educational program on quality and safety designed specifically for medical physics therapy residencies. Five key topic areas were identified, drawn from published recommendations on safety and quality. A didactic component was developed, which includes an extensive reading list supported by a series of lectures. This was coupled with practice-based learning which includes one project, for example, failure modes and effect analysis exercise, and also continued participation in the departmental incident learning system including a root-cause analysis exercise. Performance was evaluated through quizzes, presentations, and reports. Over the period of 2014-2016, five medical physics residents successfully completed the program. Evaluations indicated that the residents had a positive experience. In addition to educating physics residents this program may be adapted for medical physics graduate programs or certificate programs, radiation oncology residencies, or as a self-directed educational project for practicing physicists. Future directions might include a system that coordinates between medical training centers such as a resident exchange program.

The impact of individual-level income predicted from the BRFSS on the association between insurance status and overall survival among adults with cancer from the SEER program.

INTRODUCTION: Among patients with cancer in the United States, Medicaid insurance is associated with worse outcomes than private insurance and with similar outcomes as being uninsured. However, prior studies have not addressed the impact of individual-level socioeconomic status, which determines Medicaid eligibility, on the associations of Medicaid status and cancer outcomes. Our objective was to determine whether differences in cancer outcomes by insurance status persist after accounting for individual-level income. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for 18-64 year-old individuals with cancer from 2014-2016. Individual-level income was imputed using a model trained on Behavioral Risk Factors Surveillance Survey participants including covariates also present in SEER. The association of 1-year overall survival and insurance status was estimated with and without adjustment for estimated individual-level income and other covariates. RESULTS: A total of 416,784 cases in SEER were analyzed. The 1-yr OS for patients with private insurance, Medicaid insurance, and no insurance was 88.7%, 76.1%, and 73.7%, respectively. After adjusting for all covariates except individual-level income, 1-year OS differences were worse with Medicaid (-6.0%, 95% CI = -6.3 to -5.6) and no insurance (-6.7%, 95% CI = -7.3 to -6.0) versus private insurance. After also adjusting for estimated individual-level income, the survival difference for Medicaid patients was similar to privately insured (-0.4%, 95% CI = -1.9 to 1.1) and better than uninsured individuals (2.1%, 95% CI = 0.7 to 3.4). CONCLUSIONS: Income, rather than Medicaid status, may drive poor cancer outcomes in the low-income and Medicaid-insured population. Medicaid insurance coverage may improve cancer outcomes for low-income individuals.

Script-based implementation of automatic grid placement for lattice stereotactic body radiation therapy.

Background and purpose: Spatially fractionated radiation therapy (SFRT) has demonstrated promising clinical response in treating large tumors with heterogeneous dose distributions. Lattice stereotactic body radiation therapy (SBRT) is an SFRT technique that leverages inverse optimization to precisely localize regions of high and lose dose within disease. The aim of this study was to evaluate an automated heuristic approach to sphere placement in lattice SBRT treatment planning. Materials and methods: A script-based algorithm for sphere placement in lattice SBRT based on rules described by protocol was implemented within a treatment planning system. The script was applied to 22 treated cases and sphere distributions were compared with manually placed spheres in terms of number of spheres, number of protocol violations, and time required to place spheres. All cases were re-planned using script-generated spheres and plan quality was compared with clinical plans. Results: The mean number of spheres placed excluding those that violate rules was greater using the script (13.8) than that obtained by either dosimetrist (10.8 and 12.0, p < 0.001 and p = 0.003) or physicist (12.7, p = 0.061). The mean time required to generate spheres was significantly less using the script (2.5 min) compared to manual placement by dosimetrists (25.0 and 29.9 min) and physicist (19.3 min). Plan quality indices were similar in all cases with no significant differences, and OAR constraints remained met on all plans except two. Conclusion: A script placed spheres for lattice SBRT according to institutional protocol rules. The script-produced placement was superior to that of manually-specified spheres, as characterized by sphere number and rule violations.

Overview and Recommendations for Prospective Multi-institutional Spatially Fractionated Radiation Therapy Clinical Trials.

PURPOSE: The highly heterogeneous dose delivery of spatially fractionated radiation therapy (SFRT) is a profound departure from standard radiation planning and reporting approaches. Early SFRT studies have shown excellent clinical outcomes. However, prospective multi-institutional clinical trials of SFRT are still lacking. This NRG Oncology/American Association of Physicists in Medicine working group consensus aimed to develop recommendations on dosimetric planning, delivery, and SFRT dose reporting to address this current obstacle toward the design of SFRT clinical trials. METHODS AND MATERIALS: Working groups consisting of radiation oncologists, radiobiologists, and medical physicists with expertise in SFRT were formed in NRG Oncology and the American Association of Physicists in Medicine to investigate the needs and barriers in SFRT clinical trials. RESULTS: Upon reviewing the SFRT technologies and methods, this group identified challenges in several areas, including the availability of SFRT, the lack of treatment planning system support for SFRT, the lack of guidance in the physics and dosimetry of SFRT, the approximated radiobiological modeling of SFRT, and the prescription and combination of SFRT with conventional radiation therapy. CONCLUSIONS: Recognizing these challenges, the group further recommended several areas of improvement for the application of SFRT in cancer treatment, including the creation of clinical practice guidance documents, the improvement of treatment planning system support, the generation of treatment planning and dosimetric index reporting templates, and the development of better radiobiological models through preclinical studies and through conducting multi-institution clinical trials.

Simulation-Free Radiation Therapy: An Emerging Form of Treatment Planning to Expedite Plan Generation for Patients Receiving Palliative Radiation Therapy.

Purpose: Herein we report the clinical and dosimetric experience for patients with metastases treated with palliative simulation-free radiation therapy (SFRT) at a single institution. Methods and Materials: SFRT was performed at a single institution. Multiple fractionation regimens were used. Diagnostic imaging was used for treatment planning. Patient characteristics as well as planning and treatment time points were collected. A matched cohort of patients with conventional computed tomography simulation radiation therapy (CTRT) was acquired to evaluate for differences in planning and treatment time. SFRT dosimetry was evaluated to determine the fidelity of SFRT. Descriptive statistics were calculated on all variables and statistical significance was evaluated using the Wilcoxon signed rank test and t test methods. Results: Thirty sessions of SFRT were performed and matched with 30 sessions of CTRT. Seventy percent of SFRT and 63% of CTRT treatments were single fraction. The median time to plan generation was 0.88 days (0.19-1.47) for SFRT and 1.90 days (0.39-5.23) for CTRT (P = .02). The total treatment time was 41 minutes (28-64) for SFRT and 30 minutes (21-45) for CTRT (P = .02). In the SFRT courses, the maximum and mean deviations in the actual delivered dose from the approved plans for the maximum dose were 4.1% and 0.07%, respectively. All deliveries were within a 5% threshold and deemed clinically acceptable. Conclusions: Palliative SFRT is an emerging technique that allowed for a statistically significant lower time to plan generation and was dosimetrically acceptable. This benefit must be weighed against increased total treatment time for patients receiving SFRT compared with CTRT, and appropriate patient selection is critical.

Nearest Neighbor-Based Strategy to Optimize Multi-View Triplet Network for Classification of Small-Sample Medical Imaging Data.

Multi-view classification with limited sample size and data augmentation is a very common machine learning (ML) problem in medicine. With limited data, a triplet network approach for two-stage representation learning has been proposed. However, effective training and verifying the features from the representation network for their suitability in subsequent classifiers are still unsolved problems. Although typical distance-based metrics for the training capture the overall class separability of the features, the performance according to these metrics does not always lead to an optimal classification. Consequently, an exhaustive tuning with all feature-classifier combinations is required to search for the best end result. To overcome this challenge, we developed a novel nearest-neighbor (NN) validation strategy based on the triplet metric. This strategy is supported by a theoretical foundation to provide the best selection of the features with a lower bound of the highest end performance. The proposed strategy is a transparent approach to identify whether to improve the features or the classifier. This avoids the need for repeated tuning. Our evaluations on real-world medical imaging tasks (i.e., radiation therapy delivery error prediction and sarcoma survival prediction) show that our strategy is superior to other common deep representation learning baselines [i.e., autoencoder (AE) and softmax]. The strategy addresses the issue of feature's interpretability which enables more holistic feature creation such that the medical experts can focus on specifying relevant data as opposed to tedious feature engineering.

A pilot study of same-day MRI-only simulation and treatment with MR-guided adaptive palliative radiotherapy (MAP-RT).

We conducted a prospective pilot study evaluating the feasibility of same day MRI-only simulation and treatment with MRI-guided adaptive palliative radiotherapy (MAP-RT) for urgent palliative indications (NCT#03824366). All (16/16) patients were able to complete 99% of their first on-table attempted fractions, and no grades 3-5 toxicities occurred.

First treatments for Lattice stereotactic body radiation therapy using magnetic resonance image guided radiation therapy.

Two abdominal patients were treated with Lattice stereotactic body radiation therapy (SBRT) using magnetic resonance guided radiation therapy (MRgRT). This is one of the first reported treatments of Lattice SBRT with the use of MRgRT. A description of the treatment approach and planning considerations were incorporated into this report. MRgRT Lattice SBRT delivered similar planning quality metrics to established dosimetric parameters for Lattice SBRT. Increased signal intensity were seen in the MRI treatments for one of the patients during the course of treatment.

Considerations for Optimal Implementation of Radiation Therapy Into Multidisciplinary Care for Patients With Sarcoma.

Radiation therapy (RT) plays an important role in reducing the risk of local recurrence associated with localized soft-tissue sarcoma (STS) treated with resection alone. The use of image guidance and intensity modulated RT has allowed for excellent local control after wide resection, even with positive margins, with an improved toxicity profile compared with historical strategies used in the literature. However, optimal implementation of RT into multidisciplinary care remains a challenge. Tumors can arise anywhere in the body and exhibit a wide range of behavior, so individualized use of RT is difficult. Data regarding RT for STS are also limited, so making evidence-based decisions is difficult. The American Society for Radiation Oncology recently commissioned a multidisciplinary task force, led by radiation oncologist chair and cochair Drs Kilian Salerno and Ashleigh Guadagnolo. Through 5 key questions (KQs), the recommendations address the most important topics for consideration when discussing RT use with a multidisciplinary treatment team. For patients with localized extremity sarcoma, the authors generally recommend delivering RT for patients at a high risk of recurrence (ie, patients with large, high-grade tumors, especially those expected to have positive margins after surgery). KQ2 and KQ3 recommend that most patients undergo preoperative intensity modulated RT using small clinical target volumes that have been associated with excellent local control in prospective studies. The final KQ discusses the role of preoperative RT in the management of patients with retroperitoneal sarcoma, which is controversial. Overall, the guidelines offer evidence-based expert consensus recommendations that can be used today as a starting point for a multidisciplinary recommendations about RT for patients at your clinic. I look forward to future versions of this guideline, which will consider the results of ongoing work aimed at further improving the value of RT for patients with STS.

Remote Symptom Monitoring of Patients With Cancer Undergoing Radiation Therapy.

The goal of the study was to develop and test an automated short message service (SMS) and web service platform using CareSignal for remote symptom monitoring in a diverse population of patients with cancer. Twenty-eight patients with cancer undergoing radiotherapy were recruited at the start of their treatment regimen. Patients received a weekly SMS symptom survey to assess the severity of the side effects they experienced from treatment. An assessment of patient perceptions of the system in terms of patient-provider communication, feasibility, and overall satisfaction was conducted, finding overall good compliance in a sick patient population and patient willingness to engage with the software in the future.

Treatment of Stage I Lung Cancer Detected by Computed Tomography Screening.

Introduction: Reducing lung cancer deaths through early detection by computed tomography (CT) screening requires delivery of effective treatment. We performed this retrospective study to determine the types of treatment used for screen-detected stage I lung cancer at our academic center and to compare the demographic and clinical characteristics of patients by type of treatment. Methods: All persons screened in the lung cancer screening program at our institution through June 16, 2021, were included. Those with screening CT findings needing follow-up were managed through a thoracic surgery clinic. Demographic and clinical characteristics of patients diagnosed with having stage I lung cancer through June 16, 2021, were compared by type of treatment, with follow-up through December 31, 2021. Results: Stage I NSCLC was diagnosed in 54 of 2203 persons screened (2.5%), on the basis of biopsy in 37 and on imaging findings in 17 patients in whom a tissue diagnosis could not be obtained. Treatment was by lobectomy in 18, sublobar resection in 14, and stereotactic body radiation therapy (SBRT) in 22. Patients treated with SBRT had lower forced expiratory volume in 1 second (p < 0.001) and diffusing capacity of the lung for carbon monoxide (p < 0.001) and more comorbidities (p = 0.003) than those treated with surgery. New or recurrent cancer developed in nine patients (three lobectomy, three sublobar resection, three SBRT). Conclusions: Many patients with screen-detected stage I lung cancer are medically unfit for lobectomy, and a variety of treatments are being used. Assessment of treatment-based outcomes will be critical for ensuring an optimal balance of the risks and benefits of CT screening in a medically diverse population.

LITE SABR M1: Planning design and dosimetric endpoints for a phase I trial of lattice SBRT.

PURPOSE: Lattice stereotactic body radiation therapy (SBRT) is a form of spatially fractionated radiation therapy (SFRT) using SBRT methods. This study reports clinical dosimetric endpoints achieved for Lattice SBRT plans delivering 20 Gy in 5 fractions to the periphery of a tumor with a simultaneous integrated boost (SIB) of 66.7 Gy, as part of a prospective Phase I clinical trial (NCT04133415). Additionally, it updates previously reported planning and delivery techniques based on extended experience with a broader patient population. METHODS: Patients were enrolled on a single-arm phase I trial conducted between November 2019 and August 2020. Eligibility was restricted to tumors >4.5 cm in the largest dimension. Characteristic SFRT dose gradients were achieved using a lattice of 1.5 cm diameter spheres spaced within the GTV in a regular pattern, with peak-to-valley dose varying from 66.7 Gy to 20 Gy within 1.5 cm. Organ-at-risk (OAR) sparing followed AAPM TG101 recommendations for 5-fraction SBRT. RESULTS: Twenty patients (22 plans) were enrolled on study, with one additional plan treated off study. All OAR and target coverage planning objectives were achieved, with the exception of a single small bronchus. Conformity of the 20 Gy isodose line significantly improved over the course of the study. The majority (85.2%) of treatment fractions were delivered in a 30 minutes timeslot, with 4 (3.5%) exceeding a total treatment time of 40 minutes. CONCLUSION: Lattice SBRT planning techniques produce consistent and efficient treatment plans. Refined techniques described here further improve the quality of the planning technique.

LITE SABR M1: A phase I trial of Lattice stereotactic body radiotherapy for large tumors.

PURPOSE: Stereotactic body radiotherapy (SBRT) is an attractive treatment option for patients with metastatic and/or unresectable tumors, however its use is limited to smaller tumors. Lattice is a form of spatially fractionated radiotherapy that may allow safe delivery of ablative doses to bulky tumors. We previously described Lattice SBRT, which delivers 20 Gy in 5 fractions with a simultaneous integrated boost to 66.7 Gy in a defined geometric arrangement (Lattice boost). The goal of this study was to prospectively evaluate the acute toxicity and quality of life (QoL) of patients with large tumors (>5 cm) treated with Lattice SBRT. METHODS: This was a single-arm phase I trial conducted between October 2019 and August 2020. Patients with tumors > 4.5 cm were eligible. Lattice SBRT was delivered every other day. The primary outcome was the rate of 90-day treatment-associated (probably or definitely attributable) grade 3 + acute toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Other outcomes included changes in patient reported toxicity and QoL inventories, GTV, and peripheral blood cytokines. RESULTS: Twenty patients (22 tumors) were enrolled. Median GTV was 579.2 cc (range: 54.2-3713.5 cc) in volume and 11.1 cm (range: 5.6-21.4 cm) in greatest axial diameter. Fifty percent of tumors were in the thorax, 45% abdomen/pelvis, and 5% extremity. There was no likely treatment-associated grade 3 + toxicity in the 90-day period (acute and sub-acute). There was one case of grade 4 toxicity possibly associated with Lattice SBRT. CONCLUSIONS: This phase I study met its primary endpoint of physician reported short-term safety. An ongoing phase II clinical trial of Lattice SBRT will evaluate late safety and efficacy of this novel technique.