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.

Development of severe intrapulmonary shunting in a patient with carcinoid heart disease after closure of a persistent foramen ovale: a case report

Background Neuroendocrine tumors (NETs) can affect the cardiopulmonary system causing carcinoid heart disease and valve destruction. Persistent foramen ovale (PFO) occlusion is indicated in patients with carcinoid heart disease and shunt-related left-heart valve involvement. Case Summary We report the case of a 54-year-old female patient with metastatic NET originating from the small bowel. The patient was on medication with octreotide and telotristat. One year after diagnosis, cardiac involvement of carcinoid developed with regurgitation of right-sided and, due to PFO, left-sided heart valves. Closure of PFO was performed (Occlutech 16/18 mm). One year later she presented with recurrent severe dyspnoea. The PFO-occluder was in situ without residual shunt. Valvular heart disease, including left-sided disease, and metastatic spread of NET were stable. Blood gas analysis revealed arterial hypoxemia (pO2 = 44 mmHg/5.87 kPa), which was related to extensive intrapulmonary shunting (31% shunt fraction) confirmed using contrast-enhanced echocardiography. The patient was prescribed long-term oxygen supplementation as symptomatic therapy and anti-tumoral therapy was intensified with selective internal radiotherapy of the liver metastases in order to improve biochemical control of the carcinoid syndrome. Discussion An echocardiographic assessment of the presence of a PFO is recommended in patients with NET as PFO closure minimizes the risk of left-sided carcinoid valve disease. Deterioration of symptomatic status in metastasized NET might also be due to a hepatopulmonary-like physiology with intrapulmonary shunting and arterial desaturation thought to be caused by vasoactive substances secreted by the tumor. This is a rare case describing the development of this syndrome after PFO closure.

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.

Selective Internal Radiation Combined with Chemotherapy Maintains the Quality of Life in Intrahepatic Cholangiocarcinomas

Background: In the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) single-arm phase 2 trial, concomitant chemotherapy and selective internal radiotherapy (SIRT) showed antitumor activity as a first-line treatment of unresectable intrahepatic cholangiocarcinomas (ICCs). In this sub-analysis, we aimed to evaluate one of the secondary endpoints, the health-related quality of life (QoL), evaluated with an EORTC QLQ-C30 instrument at the baseline and during treatment. Methods: The MISPHEC trial included treatment-naïve patients with an unresectable ICC between November 2013 and June 2016. Patients received concomitant first-line chemotherapy with cisplatin and gemcitabine for 8 cycles; SIRT was administered during cycle 1 (for patients with unilobar disease) or cycles 1 and 3 (for patients with bilobar disease) using glass Yttrium-90 microspheres. We evaluated the QoL—measured by the QLQ-C30 questionnaire—at the baseline, every 8 weeks during chemotherapy and follow-up, between 12 and 15 weeks after embolization and every 12 weeks after a liver resection if applicable. Results: A total of 41 patients were included, of which 34 completed questionnaires at the baseline. No clinically significant changes in the global health score or the sub-scales of the QLQ-C30 were observed during follow-up. The physical, social and role function mean score worsened during treatment and fatigue, nausea and pain scores increased although the differences were not clinically significant. In patients undergoing subsequent surgery, the QoL was not impaired. Conclusions: A combination of SIRT and chemotherapy with gemcitabine and cisplatin as the first-line treatment of unresectable ICCs was found to maintain the QoL.

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.