PURPOSE: To assist radiation oncology centers in implementing Lutetium-177-dotatate ( 177 Lu) radiopharmaceutical therapy for midgut neuroendocrine tumors. Here we describe our workflow and how it was revised based on our initial experience on an expanded access protocol (EAP). METHODS: A treatment team/area was identified. An IV-pump-based infusion technique was implemented. Exposure-based techniques were implemented to determine completion of administration, administered activity, and patient releasability. Acute toxicities were assessed at each fraction. A workflow failure modes and effects analysis (FMEA) was performed. RESULTS: A total of 22 patients were treated: 11 patients during EAP (36 administrations) and 11 patients after EAP (44 administrations). Mean 177 Lu infusion time was 37 min (range 26e65 min). Mean administered activity was 97% (range 90e99%). Mean patient exposures at 1 m were 1.9 mR/h (range 1.0e4.1 mR/h) post-177 Lu and 0.9 mR/h (range 0.4e1.8 mR/h) at discharge, rendering patients releasable with instructions. Treatment area was decontaminated and released same day. All patients in the EAP experienced nausea, and nearly half experienced emesis despite premedication with antiemetics. Peripheral IV-line complications occurred in six treatments (16.7%), halting administration in 2 cases (5.6%). We transitioned to peripherally inserted central catheter (PICC)-lines and revised amino acid formulary after the EAP. The second cohort of 11 patients after EAP were analyzed for PICC-line complications and acute toxicity. Nausea and emesis rates decreased (nausea G1þ 61%e27%; emesis G1þ 23%e7%), and no PICC complications were observed. FMEA revealed that a failure in amino acid preparation was the highest risk. CONCLUSION: 177 Lu-dotatate can be administered safely in an outpatient radiation oncology department.

Background Biological specimens from patients who have received radiopharmaceuticals are often collected for diagnostic testing and sent to clinical laboratories. Residual radiation has long been assumed to be minimal. However, literature is sparse and may not represent the specimen volumes or spectrum of radionuclides currently seen at National Cancer Institute (NCI)–designated cancer centers. This study examined the radiopharmaceuticals associated with patient specimens received in the hospital core laboratory and assessed the potential risk of external radiation exposure to laboratory personnel. Methods The types and amounts of radiopharmaceuticals administered in a large metropolitan hospital system were retrospectively examined over a 20-month study period. The associated biological specimens sent to the largest core laboratory in the system for testing were evaluated. In addition, manual survey meter assessment of random clinical specimens and weekly wipe tests were performed for 44 weeks, and wearable and environmental dosimeters were placed for 6 months. Results Over 11 000 specimens, collected within 5 physical half-lives of radiopharmaceutical administration, were processed by our laboratory. Manual survey meter assessment of random clinical specimens routinely identified radioactive specimens. If held in a closed palm for >2 min, many samples could potentially deliver a 0.02 mSv effective dose of radiation. Conclusions The laboratory regularly receives radioactive patient specimens without radioactive labels. Although the vast majority of these are blood specimens associated with low-dose diagnostic radiopharmaceuticals, some samples may be capable of delivering a significant amount of radiation. Recommendations for laboratories associated with NCI cancer centers are given.

The historic and ongoing evolution of the practice, technology, terminology, and implementation of programs related to quality in the medical radiological professions has given rise to the interchangeable use of the terms Quality Management (QM), Quality Assurance (QA), and Quality Control (QC) in the vernacular. This White Paper aims to provide clarification of QM, QA, and QC in medical physics context and guidance on how to use these terms appropriately in American College of Radiology (ACR) Practice Parameters and Technical Standards, generalizable to other guidance initiatives. The clarification of these nuanced terms in the radiology, radiation oncology, and nuclear medicine environments will not only boost the comprehensibility and usability of the Medical Physics Technical Standards and Practice Parameters, but also provide clarity and a foundation for ACR's clinical, physician‐led Practice Parameters, which also use these important terms for monitoring equipment performance for safety and quality. Further, this will support the ongoing development of the professional practice of clinical medical physics by providing a common framework that distinguishes the various types of responsibilities borne by medical physicists and others in the medical radiological environment. Examples are provided of how QM, QA, and QC may be applied in the context of ACR Practice Parameters and Technical Standards.

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The majority of patients with TNBC fail to derive benefit from PD-L1 blockade alone. Recent phase III trial results show that PD-L1 blockade increases survival when combined with chemotherapy, warranting exploration of more effective treatment combinations. One potential new agent is the V-domain Ig suppressor of T cell activation (VISTA), a negative checkpoint ligand that inhibits T cell activation via a mechanism that is non-redundant with PD-1. In this study, the highly metastatic 4T1 mouse model of TNBC is used to test the combination of focal tumor radiation (RT) with low dose cyclophosphamide (CYP), VISTA and anti-PD-1 therapy, and explore its impact on the microbiome (MB). Materials/Methods: Mice were inoculated with 4T1 cells (day 0) and randomly assigned to one of several treatment groups (6-10 per group). RT was 12 Gy x 2 on d13 and 14. Anti-VISTA was given 3x/wk starting d14; anti-PD-1 on d14, 17 and 20; and CYP on day 9. Mice were followed for tumor growth and survival or euthanized at day 21 or 32 to assess tumorinfiltrating lymphocytes/ T-cell responses or mets. MB samples were obtained at d8, 12, 13 and 15. Results: RT significantly delayed tumor growth (p<0.05) but did not impact mets. Anti-VISTA or anti-PD-1, alone or combined, did not reduce primary tumor growth or mets, but VISTA blockade was as effective as anti-PD-1 when combined with RT. No further improvement in met control was seen with RT+dual PD-1/VISTA blockade. Surprisingly, addition of CYP 4 days before RT led to further significant improvement in met control in RT+ dual PD-1/VISTA treated mice (30% met-free on d32 (p<0.001)), increased priming of tumor-specific CD8+ T cells, and increased tumor infiltration of CD8+ T cells (53.5% vs 14.0% in control vs 16.5% in RT+anti-VISTA vs 21.1% in RT+anti-PD1, p<0.05). Strikingly, the quadruple treatment group displayed the highest median survival (54.5d vs 34d in control vs 45.5d in RT+anti-PD1, p<0.01). The therapeutic effects of anti-VISTA were in part due to reduced intra-tumoral granulocytic MDSC. The impact of CYP and RT on the composition, diversity and abundance of the MB were analyzed for distinctive changes. Conclusion: PD-1 blockade has shown remarkable benefits in a small subset of patients, prompting investigations to identify promising combinations such as the use of RT + anti-PD-1. Here we show that RT can also synergize with anti-VISTA in inducing systemic anti-tumor responses, providing the first evidence that RT sensitizes refractory tumors to VISTA blockade. Remarkably, treatment with anti-VISTA markedly improved the therapeutic effect of RT+PD-1 blockade, but only in the presence of lowdose CYP prior to RT. We are currently investigating the mechanisms of this very promising combination, particularly on the changes in gut MB. Overall, these results suggest that a multipronged approach may be necessary to enhance response to IT in TNBC.