Prediction and improvement of radioembolization outcome using personalised treatment and dosimetry

Radioembolization (also called selective internal radiation therapy, SIRT) with yttrium-90 (90Y)-loaded microspheres has been broadly adopted as a locoregional therapy for primary and metastatic liver cancers. Although radioembolization is a well-established therapy, efforts to personalise and refine the planning and administration of therapy are ongoing. The ability to accurately predict, plan and deliver optimal doses to tumour and non-tumour tissues, including final validation of dose distribution, is essential for successful radiotherapy. Determining the true dose absorbed by tissue compartments is the primary way to safely individualise therapy for maximal response while respecting normal tissue tolerances. The overarching objective of this work was to expand our knowledge of dosimetry in 90Y-resin-microsphere radioembolization, with the ultimate goal of improving the clinical outcomes in our patients. Initially we sought to identify the patient- and treatment-related variables that predict radioembolization outcome in patients with intrahepatic cholangiocarcinoma (Chapter 2). Then, as a step toward personalised radioembolization in liver metastases from colorectal cancer patients, we evaluated the relationship between radioembolization real absorbed dose, as determined by 90Y positron emission tomography, and outcome (lesion-based and patient-based) (Chapter 3). In the work described in Chapter 4, we compared predictive (simulated) and post-treatment (real) dosimetry in liver metastases from colorectal cancer patients to pursue radioembolization personalisation. Finally, based on experience accumulated in previous studies and advances reported in the literature, we generated state-of-the-art recommendations to assist practitioners in performing personalised radioembolization with 90Y-resin microspheres in patients with primary and metastatic liver tumours (Chapter 5).Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)info:eu-repo/semantics/nonPublishe

90Y-PET/CT-based dosimetry after selective internal radiation therapy predicts outcome in patients with liver metastases from colorectal cancer

Abstract Background The aim of this work was to confirm that post-selective internal radiation therapy (SIRT) 90Y-PET/CT-based dosimetry correlates with lesion metabolic response and to determine its correlation with overall survival (OS) in liver-only metastases from colorectal cancer (mCRC) patients treated with SIRT. Twenty-four mCRC patients underwent pre/post-SIRT FDG-PET/CT and post-SIRT 90Y-PET/CT. Lesions delineated on pre/post-SIRT FDG-PET/CT were classified as non-metabolic responders (total lesion glycolysis (TLG)-decrease Dmean-under-treated) and in the “under-treated” group (at least one lesion received a Dmean 39 Gy had a significantly longer OS (13 months) than patients with at least one lesion Dmean < 39 Gy (OS = 5 months) (p = 0.012;hazard-ratio, 2.6 (95% CI 0.98–7.00)). Conclusions In chemorefractory mCRC patients treated with SIRT, lesion Dmean determined on post-SIRT 90Y-PET/CT correlates with metabolic response and higher lesion Dmean is associated with prolonged OS

Combined quality and dose-volume histograms for assessing the predictive value of 99mTc-MAA SPECT/CT simulation for personalizing radioembolization treatment in liver metastatic colorectal cancer

Abstract Background The relationship between the mean absorbed dose delivered to the tumour and the outcome in liver metastases from colorectal cancer patients treated with radioembolization has already been presented in several studies. The optimization of the personalized therapeutic activity to be administered is still an open challenge. In this context, how well the 99m Tc-MAA SPECT/CT predicts the absorbed dose delivered by radioembolization is essential. This work aimed to analyse the differences between predictive 99m Tc-MAA-SPECT/CT and post-treatment 90 Y-microsphere PET/CT dosimetry at different levels. Dose heterogeneity was compared voxel-to-voxel using the quality-volume histograms, subsequently used to demonstrate how it could be used to identify potential clinical parameters that are responsible for quantitative discrepancies between predictive and post-treatment dosimetry. Results We analysed 130 lesions delineated in twenty-six patients. Dose-volume histograms were computed from predictive and post-treatment dosimetry for all volumes: individual lesion, whole tumoural liver (TL) and non-tumoural liver (NTL). For all dose-volume histograms, the following indices were extracted: D 90 ,D 70 ,D 50 ,D mean and D 20 .The results showed mostly no statistical differences between predictive and post-treatment dosimetries across all volumes and for all indices. Notably, the analysis showed no difference in terms of D mean ,confirming the results from previous studies. Quality factors representing the spread of the quality-volume histogram (QVH) curve around 0 (ideal QF = 0) were determined for lesions, TL and NTL. QVHs were classified into good (QF < 0.18), acceptable (0.18 ≤ QF < 0.3) and poor (QF ≥ 0.3) correspondence. For lesions and TL, dose- and quality-volume histograms are mostly concordant: 69% of lesions had a QF within good/acceptable categories (40% good) and 65% of TL had a QF within good/acceptable categories (23% good). For NTL, the results showed mixed results with 48% QF within the poor concordance category. Finally, it was demonstrated how QVH analysis could be used to define the parameters that predict the significant differences between predictive and post-treatment dose distributions. Conclusion It was shown that the use of the QVH is feasible in assessing the predictive value of 99m Tc-MAA SPECT/CT dosimetry and in estimating the absorbed dose delivered to liver metastases from colorectal cancer via 90 Y-microspheres. QVH analyses could be used in combination with DVH to enhance the predictive value of 99m Tc-MAA SPECT/CT dosimetry and to assist personalized activity prescription.info:eu-repo/semantics/publishe

Radiomics software comparison using digital phantom and patient data: IBSI-compliance does not guarantee concordance of feature values

Abstract Introduction. Radiomics is a promising imaging-based tool which could enhance clinical observation and identify representative features. To avoid different interpretations, the Image Biomarker Standardisation Initiative (IBSI) imposed conditions for harmonisation. This study evaluates IBSI-compliant radiomics applications against a known benchmark and clinical datasets for agreements. Materials and methods. The three radiomics platforms compared were RadiomiX Research Toolbox, LIFEx v7.0.0, and syngo.via Frontier Radiomics v1.2.5 (based on PyRadiomics v2.1). Basic assessment included comparing feature names and their formulas. The IBSI digital phantom was used for evaluation against reference values. For agreement evaluation (including same software but different versions), two clinical datasets were used: 27 contrast-enhanced computed tomography (CECT) of colorectal liver metastases and 39 magnetic resonance imaging (MRI) of breast cancer, including intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced (DCE) MRI. The intraclass correlation coefficient (ICC, lower 95% confidence interval) was used, with 0.9 as the threshold for excellent agreement. Results. The three radiomics applications share 41 (3 shape, 8 intensity, 30 texture) out of 172, 84 and 110 features for RadiomiX, LIFEx and syngo.via, respectively, as well as wavelet filtering. The naming convention is, however, different between them. Syngo.via had excellent agreement with the IBSI benchmark, while LIFEx and RadiomiX showed slightly worse agreement. Excellent reproducibility was achieved for shape features only, while intensity and texture features varied considerably with the imaging type. For intensity, excellent agreement ranged from 46% for the DCE maps to 100% for CECT, while this lowered to 44% and 73% for texture features, respectively. Wavelet features produced the greatest variation between applications, with an excellent agreement for only 3% to 11% features. Conclusion. Even with IBSI-compliance, the reproducibility of features between radiomics applications is not guaranteed. To evaluate variation, quality assurance of radiomics applications should be performed and repeated when updating to a new version or adding a new modality.info:eu-repo/semantics/publishe

Quantitative 177Lu SPECT/CT imaging for personalized dosimetry using a ring-shaped CZT-based camera

Abstract Background Dosimetry after radiopharmaceutical therapy with 177Lu (177Lu-RPT) relies on quantitative SPECT/CT imaging, for which suitable reconstruction protocols are required. In this study, we characterized for the first time the quantitative performance of a ring-shaped CZT-based camera using two different reconstruction algorithms: an ordered subset expectation maximization (OSEM) and a block sequential regularized expectation maximization (BSREM) combined with noise reduction regularization. This study lays the foundations for the definition of a reconstruction protocol enabling accurate dosimetry for patients treated with 177Lu-RPT. Methods A series of 177Lu-filled phantoms were acquired on a StarGuide™ (GE HealthCare), with energy and scatter windows centred at 208 (± 6%) keV and 185 (± 5%) keV, respectively. Images were reconstructed with the manufacturer implementations of OSEM (GE-OSEM) and BSREM (Q.Clear) algorithms, and various combinations of iterations and subsets. Additionally, the manufacturer-recommended Q.Clear-based reconstruction protocol was evaluated. Quantification accuracy, measured as the difference between the SPECT-based and the radionuclide calibrator-based activity, and noise were evaluated in a large cylinder. Recovery coefficients (RCs) and spatial resolution were assessed in a NEMA IEC phantom with sphere inserts. The reconstruction protocols considered suitable for clinical applications were tested on a cohort of patients treated with [177Lu]Lu-PSMA-I&T. Results The accuracy of the activity from the cylinder, although affected by septal penetration, was < 10% for all reconstructions. Both algorithms featured improved spatial resolution and higher RCs with increasing updates at the cost of noise build-up, but Q.Clear outperformed GE-OSEM in reducing noise accumulation. When the reconstruction parameters were carefully selected, similar values for noise (~0.15), spatial resolution (~1 cm) and RCs were found, irrespective of the reconstruction algorithm. Analogue results were found in patients. Conclusions Accurate activity quantification is possible when imaging 177Lu with StarGuide™. However, the impact of septal penetration requires further investigations. GE-OSEM is a valid alternative to the recommended Q.Clear reconstruction algorithm, featuring comparable performances assessed on phantoms and patients

Pre-trial quality assurance of diffusion-weighted MRI for radiomic analysis and the role of harmonisation

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Clinical impact of 99mTc-MAA SPECT/CT-based personalized predictive dosimetry in selective internal radiotherapy: a real-life single-center experience in unresectable HCC patients

Abstract Background Recent data demonstrated that personalized dosimetry-based selective internal radiotherapy (SIRT) is associated with better outcome for unresectable hepatocellular carcinoma (HCC). Aim We aim to evaluate the contribution of personalized predictive dosimetry (performed with Simplicity90® software) in our population of HCC patients by comparing them to our historical cohort whose activity was determined by standard dosimetry. Methods This 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 endpoints were best overall response (BOR) and objective response rate (ORR) evaluated by mRECIST at 3 months. Safety and toxicity profiles were evaluated at 1- and 3-months post-treatment. For group A we compared the activity to be administered determined a posteriori using Simplicit90Y® and the activity actually administered determined by the standard approach. Results Between 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. Conclusions Our study aligns to recent literature and 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

Clinical impact of 99mTc-MAA SPECT/ CT-based personalized predictive dosimetry in selective internal radiotherapy: a real-life single-center experience in unresectable HCC patients

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Personalised radioembolization improves outcomes in refractory intra-hepatic cholangiocarcinoma : a multicenter study

PURPOSE: Reported outcomes of patients with intra-hepatic cholangiocarcinoma (IH-CCA) treated with radioembolization are highly variable, which indicates differences in included patients' characteristics and/or procedure-related variables. This study aimed to identify patient- and treatment-related variables predictive for radioembolization outcome. METHODS: This retrospective multicenter study enrolled 58 patients with unresectable and chemorefractory IH-CCA treated with resin 90Y-microspheres. Clinicopathologic data were collected from patient records. Metabolic parameters of liver tumor(s) and presence of lymph node metastasis were measured on baseline 18F-FDG-PET/CT. 99mTc-MAA tumor to liver uptake ratio (TLR MAA) was computed for each lesion on the SPECT-CT. Activity prescription using body-surface-area (BSA) or more personalized partition-model was recorded. The study endpoint was overall survival (OS) starting from date of radioembolization. Statistical analysis was performed by the log-rank test and multivariate Cox's proportional hazards model. RESULTS: Median OS (mOS) post-radioembolization of the entire cohort was 10.3 months. Variables associated with significant differences in terms of OS were serum albumin (hazard ratio (HR) = 2.78, 95%CI:1.29-5.98, p = 0.002), total bilirubin (HR = 2.17, 95%CI:1.14-4.12, p = 0.009), aspartate aminotransferase (HR = 2.96, 95%CI:1.50-5.84, p < 0.001), alanine aminotransferase (HR = 2.02, 95%CI:1.05-3.90, p = 0.01) and γ-GT (HR = 2.61, 95%CI:1.31-5.22, p < 0.001). The presence of lymph node metastasis as well as a TLR MAA  < 1.9 were associated with shorter mOS: HR = 2.35, 95%CI:1.08-5.11, p = 0.008 and HR = 2.92, 95%CI:1.01-8.44, p = 0.009, respectively. Finally, mOS was significantly shorter in patients treated according to the BSA method compared to the partition-model: mOS of 5.5 vs 14.9 months (HR = 2.52, 95%CI:1.23-5.16, p < 0.001). Multivariate analysis indicated that the only variable that increased outcome prediction above the clinical variables was the activity prescription method with HR of 2.26 (95%CI:1.09-4.70, p = 0.03). The average mean radiation dose to tumors was significantly higher with the partition-model (86Gy) versus BSA (38Gy). CONCLUSION: Radioembolization efficacy in patients with unresectable recurrent and/or chemorefractory IH-CCA strongly depends on the tumor radiation dose. Personalized activity prescription should be performed

68Ga-PSMA PET/CT-based metastasis-directed radiotherapy for oligometastatic prostate cancer recurrence after radical prostatectomy.

The aim of this communication was to assess the efficacy of directed oligometastatic radiotherapy (RT) based on 68Ga-PSMA PET/CT in patients with prostate cancer (PCa) biochemical relapse (BCR) after primary treatment with curative intent.SCOPUS: ar.jinfo:eu-repo/semantics/publishe