ĐÁNH GIÁ SHUNT GAN-PHỔI Ở BỆNH NHÂN UNG THƯ BIỂU MÔ TẾ BÀO GAN TRƯỚC XẠ TRỊ TRONG CHỌN LỌC BẰNG HẠT VI CẦU PHÓNG XẠ 90Y

Mục tiêu: Nhận xét một số yếu tố liên quan tới giá trị shunt gan-phổi khi ghi hình bằng 99mTc-MAA ở các bệnh nhân ung thư biểu mô tế bào gan (UTBMTBG) trước xạ trị trong chọn lọc bằng hạt vi cầu phóng xạ 90Y. Phương pháp nghiên cứu: Nghiên cứu tiến hành trên 44 bệnh nhân được chẩn đoán UTBMTBG và điều trị tại trung tâm Y học hạt nhân & Ung bướu, bệnh viện Bạch Mai từ năm 2019 đến 2021. Các bệnh nhân được ghi hình bằng máy SPECT với 99mTc-macroaggregted albumin (MAA) trước khi điều trị phương pháp xạ trị trong chọn lọc (Selective Internal Radiotherapy – SIRT) bằng hạt vi cầu phóng xạ 90Y. Giá trị shunt gan-phổi được tính toán và đánh giá mức độ liên quan với một số yếu tố lâm sàng, cận lâm sàng. Ngoài ra, theo dõi các bệnh nhân theo thời gian để kiểm tra có hay không mối tương quan giữa giá trị shunt gan-phổi với đáp ứng điều trị bằng SIRT. Kết quả: Giá trị shunt gan-phổi trung bình 5,3±3,7%, nhỏ nhất 1,2%, lớn nhất 19% (sau đó không điều trị bằng SIRT). Khi ghi hình bằng máy SPECT có 03 bệnh nhân có sự tập trung 99mTc-MAA ngoài gan (vị trí túi mật và dạ dày). Khảo sát cho thấy rằng có thể có mối liên hệ có ý nghĩa thống kê giữa đặc điểm giới của bệnh nhân, mức độ xơ gan, kích thước khối u, mức độ tăng sinh mạch của khối u với giá trị shunt gan-phổi. Ban đầu thấy rằng giá trị shunt gan-phổi không phải là một yếu tố tiên lượng sự đáp ứng với điều trị SIRT của bệnh nhân UTBMTBG, nhưng có thể thấy rằng giá trị shunt liên quan có ý nghĩa thống kê tới nguy cơ di căn phổi của khối u gan ác tính. Kết luận: Ghi hình với 99mTc-MAA tính shunt gan-phổi trước điều trị SIRT là cần thiết vì nó giúp giảm thiểu nguy cơ tai biến xảy ra do xạ trị, tăng cường tính an toàn và hiệu quả điều trị. Giá trị shunt gan-phổi hứa hẹn còn mang lại nhiều thông tin hữu ích không chỉ cho riêng SIRT mà kể cả các bệnh nhân điều trị phương án khác.

The Role of Ablative Radiotherapy to Liver Oligometastases from Colorectal Cancer

Purpose of Review This review describes recent data supporting locoregional ablative radiation in the treatment of oligometastatic colorectal cancer liver metastases. Recent Findings Stereotactic body radiotherapy (SBRT) demonstrates high rates of local control in colorectal cancer liver metastases when a biologically equivalent dose of > 100 Gy is delivered. Future innovations to improve the efficacy of SBRT include MRI-guided radiotherapy (MRgRT) to enhance target accuracy, systemic immune activation to treat extrahepatic disease, and genomic customization. Selective internal radiotherapy (SIRT) with y-90 is an intra-arterial therapy that delivers high doses to liver metastases internally which has shown to increase liver disease control in phase 3 trials. Advancements in transarterial radioembolization (TARE) dosimetry could improve local control and decrease toxicity. Summary SBRT and SIRT are both promising options in treating unresectable metastatic colorectal cancer liver metastases. Identification of oligometastatic patients who receive long-term disease control from either therapy is essential. Future advancements focusing on improving radiation design and customization could further improve efficacy and toxicity.

Clinical Impact of 99mTc-MAA SPECT/CT-based Personalized Predictive Dosimetry in Selective Internal Radiotherapy: a Retrospective, Single-center Study for Unresectable HCC Patients

BackgroundRecent data indicates that personalized dosimetry-based selective internal radiotherapy (SIRT) may be associated with better outcome for unresectable hepatocellular carcinoma (HCC).AimWe aim to evaluate the contribution of personalized predictive dosimetry (performed with Simplicity90® software) in HCC patients by comparing them to our historical cohort whose activity was determined by standard dosimetry. MethodsThis is a retrospective, single-center study conducted between February 2016 and December 2020 that included patients with HCC who received SIRT after simulation based on either standard dosimetry (group A) or, as of December 2017, on personalized dosimetry (group B). Primary objectives were best overall response (BOR) and objective response rate (ORR) evaluated by mRECIST at 3 months. Safety and toxicity profiles were evaluated at day 1, 1- and 3-months post-treatment. For group A we studied the dose-response relationship at 3 months and compared the activity to be administered determined a posteriori using Simplicit90Y® and the activity actually administered determined by the standard approach.ResultsBetween February 2016 and December 2020, 66 patients received 69 simulations leading to 40 treatments. The median follow-up time was equal for both groups, 21 months (range 3-55) in group A and 21 months (range 4-39) in group B. The per patient analysis revealed a significant benefit of personalized predictive dosimetry in terms of better overall response at 3 months (80% vs. 33.3%, p= 0.007) and at 6 months (77.8% vs. 22.2%, p= 0.06). This trend was found in the analysis by nodule with a response rate according to mRECIST of 87.5% for personalized dosimetry versus 68.4% for standard dosimetry at 3 months, p= 0.24. Only one grade 3 biological toxicity (hyperbilirubinemia) was noted in group A. The comparison between the administered activity and the recommended activity recalculated a posteriori using Simplicit90Y® showed that the vast majority of patients who progressed (83.33%) received less activity than that recommended by the personalized approach or an inadequate distribution of the administered activity. ConclusionsOur study confirms that the use of personalized dosimetry allows a better selection of HCC patients who can benefit from SIRT, and consequently, improves the effectiveness of this treatment.

Development of A Decahedral Nanoenzyme Capable of Overcoming Hypoxia to Facilitate the Iodine-125 Radiosensitization of Esophageal Cancer

Radioisotopes have long been leveraged for internal radiotherapy-mediated cancer treatment. However, such therapeutic approaches are associated with serious side effects, and their efficacy is limited by intratumoral hypoxia. Herein, we prepared a folic acid-decorated palladium decahedral platform capable of enhancing the radiotherapeutic efficacy of iodine-125 (125I) seed treatment. This decahedral nanoenzyme was able to target tumor regions and catalyze the conversion of intracellular H2O2 to O2, thereby alleviating hypoxia within the tumor microenvironment. In addition, palladium was hypoxia can be alleviated, on the other hand, palladium was able to enhance the radiotherapeutic energy deposition within tumor tissues. The results of this analysis indicated that synthesized decahedral constructs can efficiently target and modify the hypoxic tumor microenvironment while simultaneously enhancing radiation energy deposition therein. Relative to palladium nanodots, the prolonged in vivo circulation of these decahedral constructs better enabled them to facilitate sustained radiosensitization. Overall, the results of this study highlight a novel approach to improving the therapeutic utility of 125I seed interstitial implantation, thus underscoring an important direction for future clinical research.

Tissue dose estimation after extravasation of 177Lu-DOTATATE

Background Extravasation of radiopharmaceuticals used for vectorized internal radiotherapy can lead to severe tissue damage (van der Pol et al., Eur J Nucl Med Mol Imaging 44:1234–1243, 2017). Clinical management of these extravasations requires the preliminary estimation of the dose distribution in the extravasation area. Data are scarce regarding the dose estimation in the literature. This work presents a methodology for estimating the dose distribution after an extravasation occurred in September 2017, in the arm of a patient during a 7.4-GBq infusion of Lutathera ® (AAA). Methods A local quantification procedure initially developed for renal dosimetry was used. A calibration factor was determined and verified by phantom study. Extravasation volume of interest and its variation in time were determined using 4 whole body (WB) planar acquisitions performed at 2 h (T2h), 5 h (T5h), 20 h (T20h), and 26 h (T26h) after the beginning of the infusion and three SPECT/CT thoracic acquisitions at T5h, T20h, and T26h. For better estimation of initial extravasation volume, 3 volumes were defined on SPECT images using a 3D activity threshold. Cumulated activities and associated absorbed doses (D1, D2, D3) were calculated in the 3 volumes using the MIRD formalism. Results Volumes estimated using 3D threshold were V1 = 1000 mL, V2 =400 mL, and V3 =180 mL. Cumulated activities were evaluated using a monoexponential fit on activities calculated on SPECT images. Estimated local absorbed doses in V1, V2, and V3 were D1 = 2.3 Gy, D2 = 4.1 Gy, and D3 = 6.8 Gy. Evolution in time of local activity in the extravasation area was consistent with an effective local half-life (Teff) of 2.3 h. Conclusions Rapid local dose estimation was permitted thanks to knowledge of the calibration factor determined previous to accidental extravasation. Lutathera® lymphatic drainage was quick in the arm (Teff = 2.3h). Estimated doses were in the lower range of deterministic effects and far under soft tissue necrosis threshold. Thus, no surgical rinse was proposed. The patient did not show any clinical consequence of the extravasation.

Cost-Effectiveness Analysis of Selective Internal Radiotherapy With Yttrium-90 Versus Sorafenib in Locally Advanced Hepatocellular Carcinoma

PURPOSE: The recent sorafenib versus radioembolization in advanced hepatocellular carcinoma (SARAH) and selective internal radiation therapy versus sorafenib in locally advanced hepatocellular carcinoma (SIRveNIB) trials showed no statistically significant difference in overall survival for randomization to selective internal radiotherapy (SIRT) versus sorafenib for locally advanced hepatocellular carcinoma, although SIRT was better tolerated. Given the high cost of both treatments, we investigated their comparative cost-effectiveness from a US healthcare sector perspective. PATIENTS AND METHODS: We constructed a state-transition microsimulation model to simulate patients allocated to SIRT versus sorafenib according to an intention-to-treat principle. Hazard rates of disease progression and death were based on pooled individual patient data generated from the SARAH and SIRveNIB trials’ Kaplan-Meier curves. Inputs for adverse events, treatment adherence, and quality of life utility weights were derived from trial data as well. Costs were based on Medicare reimbursement rates and literature. We performed probabilistic sensitivity analysis and estimated costs and quality-adjusted life years (QALYs) over a 5-year time horizon. We evaluated sensitivity to uncertainty of key model parameters. RESULTS: Costs were $78,859 v $58,397 (difference $20,462; 95% uncertainty interval $14,444 to 27,205) and QALYs were 0.88 v 0.87 (difference 0.02, −0.02 to 0.05) for sorafenib versus SIRT, respectively. The incremental cost-effectiveness ratio (ICER) of sorafenib was $1,280,224/QALY. The likelihood that sorafenib would be cost effective did not exceed 1%, assuming cost-effectiveness thresholds up to $200k/QALY. If the monthly price of sorafenib decreased from $16,390 to below $7,000, the ICER of sorafenib fell below $200k/QALY, and an ICER < $100k/QALY was reached if the monthly price fell below $6,600. CONCLUSION: Sorafenib is unlikely to provide a gain in quality-adjusted survival compared with SIRT at an acceptable cost for the US healthcare sector. Only if the current price decreased by more than 50% would sorafenib be considered economically attractive.