Safety and Efficacy of Neoadjuvant SABR in Pancreatic Cancer: Effect of Magnetic Resonance Imaging-Guided Respiratory-Gated Adaptive Radiation Therapy.

Purpose: We aimed to evaluate the safety and efficacy of neoadjuvant SABR using magnetic resonance imaging-guided respiratory-gated adaptive radiation therapy (MRgRg-ART) in pancreatic cancer. Methods and Materials: We performed a single-institution retrospective review in patients with pancreatic cancer who underwent neoadjuvant SABR followed by surgical resection. After neoadjuvant chemotherapy, those considered resectable by the multidisciplinary team received SABR over 5 consecutive days using MRgRg-ART. Factors associated with severe postoperative complications (Clavien-Dindo grade ≥III) and prognostic factors for overall survival were analyzed. Results: Sixty-two patients were included in the analysis, with a median follow-up of 10.3 months. The median prescribed dose to the planning target volume was 50 Gy. Fifty-two (85.3%) patients underwent R0 resection, and 11 (18.0%) experienced severe postoperative complications. No factors were associated with the incidence of severe postoperative complications. There were 3 cases of locoregional recurrence, resulting in a 12-month local control rate of 93.1%. Elevated postoperative carbohydrate antigen 19-9 was significantly associated with poor overall survival in the multivariate analysis (P = .037). Conclusions: Neoadjuvant SABR with 50 Gy using MRgRg-ART delivered to pancreatic cancer resulted in a notable survival outcome with acceptable toxicities. Further studies are warranted to investigate the long-term effects of this method.

Combination of local radiotherapy and anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) therapy augments PD-L1 blockade-mediated anti-tumor effects in murine breast cancer model.

PURPOSE: In this study, we investigated whether local radiotherapy (RT) and an anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) agonist could increase the efficacy of PD-L1 blockade. METHODS AND MATERIALS: We analyzed a breast cancer dataset from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) to determine the role of GITR in breast cancer. We used the 4T1 murine TNBC model (primary and secondary tumors) to investigate the efficacy of PD-L1 blockade, local RT, anti-GITR agonist, and their combinations. We assessed tumor growth by tumor volume measurements, in vivo bioluminescence imaging, and metastatic lung nodule counts to evaluate the effects of these treatments. Flow cytometry and immunohistochemistry determined the proportions and phenotypes of CD8+ T-cells and regulatory T-cells (Tregs) in the tumors and spleen. Plasma cytokine levels were measured by enzyme-linked immunosorbent assay. RESULTS: In the METABRIC cohort, patients with high expression of TNFRSF18, which encodes GITR, had significantly better survival than those with low expression. Adding local RT or anti-GITR agonist to PD-L1 blockade did not significantly augment efficacy compared to PD-L1 blockade alone; however, adding both to PD-L1 blockade significantly reduced tumor growth and lung metastasis. The benefits of the triple combination were accompanied by increased CD8+ T-cells and decreased Tregs in the tumor microenvironment and spleen. CONCLUSIONS: The combination of local RT and an anti-GITR agonist significantly enhanced the anti-tumor immune responses induced by PD-L1 blockade. These results provide the preclinical rationale for the combination of therapy.

Definitive radiotherapy in patients with clinical T1N0M0 esophageal squamous cell carcinoma: A multicenter retrospective study (KROG 21-10).

PURPOSE: To assess the failure pattern and analyze the treatment scheme of definitive radiation therapy (RT) for T1N0M0 esophageal squamous cell carcinoma (ESCC). METHODS: We performed a multi-institutional retrospective analysis in T1N0M0 ESCC patients who underwent definitive RT from 2010 to 2019. Patterns of failure were demonstrated as in-, and out-field locoregional, and distant metastasis. In the analysis, freedom-from locoregional recurrence (FFLRR) and their association with clinicopathologic factors were evaluated. Propensity score matching in cT1b patients was done. RESULTS: 168 patients were included with a median follow-up of 34.0 months, and 26 cT1a, 116 cT1b disease. The rates of 3-year all and locoregional recurrence for cT1a were 30.5% and 24.1% and those for cT1b were 27.1% and 25.9%, respectively. Among 116 cT1b patients, 69 patients received elective nodal irradiation (ENI) and 47 received involved field irradiation (IFI). After propensity score matching, the 3-year FFLRR rate was 84.5%. There was no difference between ENI and IFI in FFLRR (P = 0.831) and OS (P = 0.525). The 3-year FFLRR was 83.8% (95% Confidence interval (CI), 61.8-93.8%) in IFI group and 85.3% (95% CI, 65.1-94.3%) in ENI group. In multivariate analysis, concurrent chemotherapy use was marginally associated with FFLRR (Hazard ratio, 0.16; P = 0.064). CONCLUSION: cT1a patients who cannot receive endoscopic resection showed similar failure rates as cT1b patients, questioning the staging accuracy and raised the need for thorough treatment like chemoradiotherapy. In cT1b patients, IFI with 50 to 60 Gy and concurrent chemotherapy could be reasonable.

Developing prompts from large language model for extracting clinical information from pathology and ultrasound reports in breast cancer.

PURPOSE: We aimed to evaluate the time and cost of developing prompts using large language model (LLM), tailored to extract clinical factors in breast cancer patients and their accuracy. MATERIALS AND METHODS: We collected data from reports of surgical pathology and ultrasound from breast cancer patients who underwent radiotherapy from 2020 to 2022. We extracted the information using the Generative Pre-trained Transformer (GPT) for Sheets and Docs extension plugin and termed this the "LLM" method. The time and cost of developing the prompts with LLM methods were assessed and compared with those spent on collecting information with "full manual" and "LLM-assisted manual" methods. To assess accuracy, 340 patients were randomly selected, and the extracted information by LLM method were compared with those collected by "full manual" method. RESULTS: Data from 2,931 patients were collected. We developed 12 prompts for Extract function and 12 for Format function to extract and standardize the information. The overall accuracy was 87.7%. For lymphovascular invasion, it was 98.2%. Developing and processing the prompts took 3.5 hours and 15 minutes, respectively. Utilizing the ChatGPT application programming interface cost US $65.8 and when factoring in the estimated wage, the total cost was US $95.4. In an estimated comparison, "LLM-assisted manual" and "LLM" methods were time- and cost-efficient compared to the "full manual" method. CONCLUSION: Developing and facilitating prompts for LLM to derive clinical factors was efficient to extract crucial information from huge medical records. This study demonstrated the potential of the application of natural language processing using LLM model in breast cancer patients. Prompts from the current study can be re-used for other research to collect clinical information.

Dosimetric evaluation of magnetic resonance imaging-guided adaptive radiation therapy in pancreatic cancer by extent of re-contouring of organs-at-risk.

PURPOSE: The safety of online contouring and planning for adaptive radiotherapy is unknown. This study aimed to evaluate the dosimetric difference of the organ-at-risk (OAR) according to the extent of contouring in stereotactic magnetic resonance image-guided adaptive RT (SMART) for pancreatic cancer. MATERIALS AND METHODS: We reviewed the treatment plan data used for SMART in patients with pancreatic cancer. For the online contouring and planning, OARs within 2 cm from the planning target volume (PTV) in the craniocaudal direction were re-controlled daily at the attending physician's discretion. The entire OARs were re-contoured retrospectively for data analysis. We termed the two contouring methods the Rough OAR and the Full OAR, respectively. The proportion of dose constraint violation and other dosimetric parameters was analyzed. RESULTS: Nineteen patients with 94 fractions of SMART were included in the analysis. The dose constraint was violated in 10.6% and 43.6% of the fractions in Rough OAR and Full OAR methods, respectively (p = 0.075). Patients with a large tumor, a short distance from gross tumor volume (GTV) to OAR, and a tumor in the body or tail were associated with more occult dose constraint violations-large tumor (p = 0.027), short distance from GTV to OAR (p = 0.061), tumor in body or tail (p = 0.054). No dose constraint violation occurred outside 2 cm from the PTV. CONCLUSION: More occult dose constraint violations can be found by the Full OAR method in patients with pancreatic cancer with some clinical factors in the online re-planning for SMART. Re-contouring all the OARs would be helpful to detect occult dose constraint violations in SMART planning. Since the dosimetric profile of SMART cannot be represented by a single fraction, patient selection for the Full OAR method should be weighted between the clinical usefulness and the time and workforce required.