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Item A global evaluation of advanced dosimetry in transarterial radioembolization of hepatocellular carcinoma with Yttrium-90: the TARGET study(Springer, 2022) Lam, Marnix; Garin, Etienne; Maccauro, Marco; Kappadath, S. Cheenu; Sze, Daniel Y.; Turkmen, Cuneyt; Cantasdemir, Murat; Haste, Paul; Herrmann, Ken; Alsuhaibani, Hamad Saleh; Dreher, Matthew; Fowers, Kirk D.; Salem, Riad; Radiology and Imaging Sciences, School of MedicinePurpose: To investigate the relationships between tumor absorbed dose (TAD) or normal tissue absorbed dose (NTAD) and clinical outcomes in hepatocellular carcinoma (HCC) treated with yttrium-90 glass microspheres. Methods: TARGET was a retrospective investigation in 13 centers across eight countries. Key inclusion criteria: liver-dominant HCC with or without portal vein thrombosis, < 10 tumors per lobe (at least one ≥ 3 cm), Child-Pugh stage A/B7, BCLC stages A-C, and no prior intra-arterial treatment. Multi-compartment pre-treatment dosimetry was performed retrospectively. Primary endpoint was the relationship between ≥ grade 3 hyperbilirubinemia (such that > 15% of patients experienced an event) without disease progression and NTAD. Secondary endpoints included relationships between (1) objective response (OR) and TAD, (2) overall survival (OS) and TAD, and (3) alpha fetoprotein (AFP) and TAD. Results: No relationship was found between NTAD and ≥ grade 3 hyperbilirubinemia, which occurred in 4.8% of the 209 patients. The mRECIST OR rate over all lesions was 61.7%; for the target (largest) lesion, 70.8%. Responders and non-responders had geometric mean total perfused TADs of 225.5 Gy and 188.3 Gy (p = 0.048). Probability of OR was higher with increasing TAD (p = 0.044). Higher TAD was associated with longer OS (HR per 100 Gy increase = 0.83, 95% CI: 0.71-0.95; p = 0.009). Increased TAD was associated with higher probability of AFP response (p = 0.046 for baseline AFP ≥ 200 ng/mL). Conclusion: Real-world data confirmed a significant association between TAD and OR, TAD and OS, and TAD and AFP response. No association was found between ≥ grade 3 hyperbilirubinemia and NTAD.Item Clinical, dosimetric, and reporting considerations for Y-90 glass microspheres in hepatocellular carcinoma: updated 2022 recommendations from an international multidisciplinary working group(Springer, 2023) Salem, Riad; Padia, Siddharth A.; Lam, Marnix; Chiesa, Carlo; Haste, Paul; Sangro, Bruno; Toskich, Beau; Fowers, Kirk; Herman, Joseph M.; Kappadath, S. Cheenu; Leung, Thomas; Sze, Daniel Y.; Kim, Edward; Garin, Etienne; Radiology and Imaging Sciences, School of MedicinePurpose: In light of recently published clinical reports and trials, the TheraSphere Global Dosimetry Steering Committee (DSC) reconvened to review new data and to update previously published clinical and dosimetric recommendations for the treatment of hepatocellular carcinoma (HCC). Methods: The TheraSphere Global DSC is comprised of health care providers across multiple disciplines involved in the treatment of HCC with yttrium-90 (Y-90) glass microsphere-based transarterial radioembolization (TARE). Literature published between January 2019 and September 2021 was reviewed, discussed, and adjudicated by the Delphi method. Recommendations included in this updated document incorporate both the results of the literature review and the expert opinion and experience of members of the committee. Results: Committee discussion and consensus led to the expansion of recommendations to apply to five common clinical scenarios in patients with HCC to support more individualized efficacious treatment with Y-90 glass microspheres. Existing clinical scenarios were updated to reflect recent developments in dosimetry approaches and broader treatment paradigms evolving for patients presenting with HCC. Conclusion: Updated consensus recommendations are provided to guide clinical and dosimetric approaches for the use of Y-90 glass microsphere TARE in HCC, accounting for disease presentation, tumor biology, and treatment intent.Item Direct comparison and reproducibility of two segmentation methods for multicompartment dosimetry: round robin study on radioembolization treatment planning in hepatocellular carcinoma(Springer, 2023) Lam, Marnix; Garin, Etienne; Palard‑Novello, Xavier; Mahvash, Armeen; Kappadath, Cheenu; Haste, Paul; Tann, Mark; Herrmann, Ken; Barbato, Francesco; Geller, Brian; Schaefer, Niklaus; Denys, Alban; Dreher, Matthew; Fowers, Kirk D.; Gates, Vanessa; Salem, Riad; Radiology and Imaging Sciences, School of MedicinePurpose: Investigate reproducibility of two segmentation methods for multicompartment dosimetry, including normal tissue absorbed dose (NTAD) and tumour absorbed dose (TAD), in hepatocellular carcinoma patients treated with yttrium-90 (90Y) glass microspheres. Methods: TARGET was a retrospective investigation in 209 patients with < 10 tumours per lobe and at least one tumour ≥ 3 cm ± portal vein thrombosis. Dosimetry was compared using two distinct segmentation methods: anatomic (CT/MRI-based) and count threshold-based on pre-procedural 99mTc-MAA SPECT. In a round robin substudy in 20 patients with ≤ 5 unilobar tumours, the inter-observer reproducibility of eight reviewers was evaluated by computing reproducibility coefficient (RDC) of volume and absorbed dose for whole liver, whole liver normal tissue, perfused normal tissue, perfused liver, total perfused tumour, and target lesion. Intra-observer reproducibility was based on second assessments in 10 patients ≥ 2 weeks later. Results: 99mTc-MAA segmentation calculated higher absorbed doses compared to anatomic segmentation (n = 209), 43.9% higher for TAD (95% limits of agreement [LoA]: - 49.0%, 306.2%) and 21.3% for NTAD (95% LoA: - 67.6%, 354.0%). For the round robin substudy (n = 20), inter-observer reproducibility was better for anatomic (RDC range: 1.17 to 3.53) than 99mTc-MAA SPECT segmentation (1.29 to 7.00) and similar between anatomic imaging modalities (CT: 1.09 to 3.56; MRI: 1.24 to 3.50). Inter-observer reproducibility was better for larger volumes. Perfused normal tissue volume RDC was 1.95 by anatomic and 3.19 by 99mTc-MAA SPECT, with corresponding absorbed dose RDC 1.46 and 1.75. Total perfused tumour volume RDC was higher, 2.92 for anatomic and 7.0 by 99mTc-MAA SPECT with corresponding absorbed dose RDC of 1.84 and 2.78. Intra-observer variability was lower for perfused NTAD (range: 14.3 to 19.7 Gy) than total perfused TAD (range: 42.8 to 121.4 Gy). Conclusion: Anatomic segmentation-based dosimetry, versus 99mTc-MAA segmentation, results in lower absorbed doses with superior reproducibility. Higher volume compartments, such as normal tissue versus tumour, exhibit improved reproducibility.Item Post Yttrium-90 Imaging(Thieme, 2021) Rice, Mitchell; Krosin, Matthew; Haste, Paul; Radiology and Imaging Sciences, School of MedicineTransarterial radioembolization with yttrium-90 ( 90 Y) is a mainstay for the treatment of liver cancer. Imaging the distribution following delivery is a concept that dates back to the 1960s. As β particles are created during 90 Y decay, bremsstrahlung radiation is created as the particles interact with tissues, allowing for imaging with a gamma camera. Inherent qualities of bremsstrahlung radiation make its imaging difficult. SPECT and SPECT/CT can be used but suffer from limitations related to low signal-to-noise bremsstrahlung radiation. However, with optimized imaging protocols, clinically adequate images can still be obtained. A finite but detectable number of positrons are also emitted during 90 Y decay, and many studies have demonstrated the ability of commercial PET/CT and PET/MR scanners to image these positrons to understand 90 Y distribution and help quantify dose. PET imaging has been proven to be superior to SPECT for quantitative imaging, and therefore will play an important role going forward as we try and better understand dose/response and dose/toxicity relationships to optimize personalized dosimetry. The availability of PET imaging will likely remain the biggest barrier to its use in routine post- 90 Y imaging; thus, SPECT/CT imaging with optimized protocols should be sufficient for most posttherapy subjective imaging.