Analysis of differences between 99mTc-MAA SPECT- and 90Y-microsphere PET-based dosimetry for hepatocellular carcinoma selective internal radiation therapy

International audienceBackground: The aim of this study was to compare predictive and post-treatment dosimetry and analyze the differences, investigating factors related to activity preparation and delivery, imaging modality used, and interventional radiology.Methods: Twenty-three HCC patients treated by selective internal radiation therapy with 90Y glass microspheres were included in this study. Predictive and post-treatment dosimetry were calculated at the voxel level based on 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT respectively. Dose distribution was analyzed through mean dose, metrics extracted from dose-volume histograms, and Dice similarity coefficients applied on isodoses. Reproducibility of the radiological gesture and its influence on dose deviation was evaluated.Results: 90Y delivered activity was lower than expected in 67% (16/24) of the cases mainly due to the residual activity. A mean deviation of − 6 ± 11% was observed between the delivered activity and the 90Y PET’s FOV activity. In addition, a substantial difference of − 20 ± 8% was measured on 90Y PET images between the activity in the liver and in the whole FOV. After normalization, 99mTc-MAA SPECT dosimetry was highly correlated and concordant with 90Y-microsphere PET dosimetry for all dose metrics evaluated (ρ = 0.87, ρc = 0.86, P = 3.10−8 and ρ = 0.91, ρc = 0.90, P = 7.10−10 for tumor and normal liver mean dose respectively for example). Besides, mean tumor dose deviation was lower when the catheter position was identical than when it differed (16 Gy vs. 37 Gy, P = 0.007). Concordance between predictive and post-treatment dosimetry, evaluated with Dice similarity coefficients applied on isodoses, significantly correlated with the distance of the catheter position from artery bifurcation (P = 0.04, 0.0004, and 0.05, for 50 Gy, 100 Gy, and 150 Gy isodoses respectively).Conclusions: Discrepancies between planned activity and activity measured on 90Y PET images were observed and seemed to be mainly related to clinical hazards and equipment issues. Predictive vs. post-treatment comparison of relative dose distributions between tumor and normal liver showed a good correlation and no significant difference highlighting the predictive value of 99mTc MAA SPECT/CT-based dosimetry. Besides, the reproducibility of catheter tip position appears critical in the agreement between predictive and actual dose distribution

Large, multifocal or portal vein-invading hepatocellular carcinoma (HCC) downstaged by Y90 using personalized dosimetry: safety, pathological results and outcomes after surgery

International audienceBackground: Transarterial radioembolization (TARE) has recently been recognized as a bridging/downstaging therapy to surgery for early hepatocellular carcinomas (HCCs) with high rates of complete pathological necrosis (CPN) on liver explants. In patients with portal vein tumoral thrombus (PVTT), multifocal or large tumors, TARE has mainly a palliative role and surgery remains controversial in this poor-prognosis population. Personalized dosimetry recently proved to outperform standard dosimetry used in prior negative Y90 randomized-controlled trials.Methods: In this retrospective study, we evaluated safety, radiological and pathological response and outcomes in HCC patients with PVTT, multifocal or large tumors, who underwent surgery after downstaging using TARE with Y90-loaded glass microspheres with personalized dosimetry.Results: Between December 2015 and October 2021, 18 unresectable patients (14/18 with PVTT) had surgery (16 resections, 2 liver transplantations) 6.2 months (range, 2–14.6 months) after a single Y90 treatment. No 90-day mortality was reported. Objective modified response criteria in solid tumors (mRECIST) response were noted in all but one patient. Complete and extensive (50–99%) necrosis was observed in 36% and 45% of tumors, respectively. The post-treatment tumor-absorbed dose significantly differed depending on the extent of pathological necrosis (P=0.045). Median overall survival and progression-free survival (PFS) were respectively of 61.8 months [95% CI: 31.4 months–not reached (NR)] and 49.3 months (95% CI: 14 months–NR). PFS was longer in patients with complete imaging response [median NR (none recurred or died) vs. 21.5 months (95% CI: 10.1 months–NR), P<0.001] and in those with complete pathological response [median NR vs. 22.5 months (95% CI: 10.1 months–NR), P<0.001].Conclusions: Y90 TARE using personalized dosimetry can provide high rates of imaging and pathological response in patients with PVTT, large or multifocal HCC. Subsequent surgery is safe and leads to outcomes far exceeding expectations in an otherwise poor prognosis population with no chance for cure.Trial Registration: Clinical trial number: NCT0504557

Uni-, Bi- or Trifocal Hepatocellular Carcinoma in Western Patients: Recurrence and Survival after Percutaneous Thermal Ablation

Multifocality is usually reported as a pejorative factor after percutaneous thermal ablation (PTA) of HCC but little is known in Western series. Recurrence and survival were extracted from a prospective database of all patients who underwent PTA for ≤3 cm HCC. From January 2015 to April 2020, we analyzed 281 patients with unifocal (n = 216), bifocal (n = 46) and trifocal (n = 16) HCC. PTA of bi- and trifocal HCC resulted in a high risk of very early (&lt;6 months) distant recurrence (38.8% and 50%, respectively). Median RFS was 23.3 months (95% CI:18.6–30.4), 7.7 months (95% CI:5.1–11.43, p = 0.002) and 5.2 months (95% CI:3–12.3, p = 0.015), respectively, for uni-, bi- and trifocal HCC groups. In a multivariate analysis, both bifocal (HR = 2.46, p &lt; 0.001) and trifocal (HR = 2.70, p = 0.021) vs. unifocal HCC independently predicted shorter RFS. Median OS in trifocal HCC group was 30.3 months (95 CI:19.3-not reached). Trifocal vs. unifocal HCC independently predicted shorter OS (HR = 3.30, p = 0.008), whereas bifocal vs. unifocal HCC did not (p = 0.27). Naïve patient (HR = 0.42, p = 0.007), AFP &gt; 100 ng/mL (HR = 3.03, p = 0.008), MELD &gt; 9 (HR = 2.84, p = 0.001) and steatotic HCC (HR = 0.12, p = 0.038) were also independent predictors of OS. In conclusion, multifocal HCCs in a Western population have a dramatically increased risk of distant recurrence. OS after PTA of trifocal HCC is significantly below what was expected after a curative treatment

Transarterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin-Loaded Tandem Drug-Eluting Embolics

Objective: To describe the responses, toxicities and outcomes of HCC patients treated by transarterial chemoembolization (TACE) using idarubicin-loaded TANDEM beads. Materials and Methods: Seventy-two consecutive patients (mean age: 71 years (58–84 years)) with HCC were treated by TACE using idarubicin-loaded TANDEM in a first line, over a five-year period. Most patients (89%) had liver cirrhosis classified as Child–Pugh A (90%). BCLC B classification applied in 85% of cases. Baseline tumor burden was limited to one to three nodules in 92% of cases, unilobar in 88% cases, with a median tumor diameter of 55 mm (range: 13–150 mm). Toxicity was assessed using NCI CTC AE v4.0. Response was assessed using mRECIST criteria. Time-to-treatment failure (TTTF) and overall survival (OS) were also calculated based on Kaplan–Meier method. Result: Of 141 TACE sessions performed with bead sizes of 100 and 75 µm in 42 (29.8%) and 99 (70.2%) sessions, respectively. In 78% of all TACE sessions, the full dose of idarubicin-loaded beads was injected. Grade 3–4 AE were observed after 73 (52%) sessions, most of them being biological. Multi-organ failure was observed three days after the first TACE in a Child B patients, unfortunately leading to death. Overall, the best objective response rate (ORR) was 65%. Median follow-up lasted 14.3 months (95% CI: 11.2–18.8 months). Median TTTF and OS were 14.4 months (95% CI: 7.2–24.6 months) and 34.6 months (95% CI: 24.7—not reached) respectively. Conclusion: In this retrospective study involving well-selected HCC patients, high ORR and long TTTF and OS are observed after TACE using idarubicin-loaded TANDEM. A randomized trial is needed

Deportalization, Venous Congestion, Venous Deprivation: Serial Measurements of Volumes and Functions on Morphofunctional 99mTc-Mebrofenin SPECT-CT

International audienceThe objective was to assess the changes in regional volumes and functions under venous-impaired vascular conditions following liver preparation. Twelve patients underwent right portal vein embolization (PVE) (n = 5) or extended liver venous deprivation (eLVD, i.e., portal and right and middle hepatic veins embolization) (n = 7). Volume and function measurements of deportalized liver, venous-deprived liver and congestive liver were performed before and after PVE/eLVD at days 7, 14 and 21 using 99mTc-mebrofenin hepatobiliary scintigraphy with single-photon emission computed tomography and computed tomography (99mTc-mebrofenin SPECT-CT). Volume and function progressed independently in the deportalized liver (p = 0.47) with an early decrease in function (median -18.2% (IQR, -19.4--14.5) at day 7) followed by a decrease in volume (-19.3% (-22.6--14.4) at day 21). Volume and function progressed independently in the venous deprived liver (p = 0.80) with a marked and early decrease in function (-41.1% (-52.0--12.9) at day 7) but minimal changes in volume (-4.7% (-10.4-+3.9) at day 21). Volume and function progressed independently in the congestive liver (p = 0.21) with a gradual increase in volume (+43.2% (+38.3-+51.2) at day 21) that preceded a late and moderate increase in function at day 21 (+34.8% (-8.3-+46.6)), concomitantly to the disappearance of hypoattenuated congestive areas in segment IV (S4) on CT, initially observed in 6/7 patients after eLVD and represented 35.3% (22.2-46.4) of whole S4 volume. Liver volume and function progress independently whatever the vascular condition. Hepatic congestion from outflow obstruction drives volume increase but results in early impaired function

Hepatobiliary Scintigraphy and Glass 90Y Radioembolization with Personalized Dosimetry: Dynamic Changes in Treated and Nontreated Liver

International audienceBackground: The functional changes that occur over time in the liver following 90Y-radioembolization (RE) using personalized dosimetry (PD) remain to be investigated.Methods: November 2016–October 2019: we retrospectively included hepatocellular carcinoma (HCC) patients treated by 90Y-glass RE using PD, who underwent hepatobiliary scintigraphy (HBS) at baseline and at 15 days, 1, 2, 3, and 6 months after RE.Results: There were 16 patients with unilobar disease (100%) included, and 64 HBS were performed. Whole liver function significantly decreased over time. The loss was maximal at 2 weeks: −32% (p = 0.002) and remained below baseline at 1 (−15%; p = 0.002), 2 (−25%; p < 0.001), and 3 months (−16%; p = 0.027). No radioembolization-induced liver disease was observed. Treated liver function strongly decreased to reach −64% (p < 0.001) at 2 months. Nontreated liver function decreased at 2 weeks (−21%; p = 0.027) and remained below baseline before reaching +20% (p = 0.002) and +59% (p < 0.001) at 3 and 6 months, respectively. Volumetric and functional changes exhibited parallel evolutions in the treated livers (p = 0.01) but independent evolutions in the nontreated livers (p = 0.08).Conclusion: RE using PD induces significant regional changes in liver function over time. As early as 15 days following RE, both the treated and nontreated livers showed a decreased function. Nontreated liver function recovered after 3 months and greatly increased afterwards

Multimodal Percutaneous Thermal Ablation of Small Hepatocellular Carcinoma: Predictive Factors of Recurrence and Survival in Western Patients

International audienceBackground: To identify the predictive factors of recurrence and survival in an unselected population of Western patients who underwent multimodal percutaneous thermal ablation (PTA) for small Hepatocellular Carcinomas (HCCs).Methods: January 2015–June 2019: data on multimodal PTA for 100 ng/mL (OR = 3.027, p = 0.037) and tumor size (OR = 1.06, p = 0.001) independently predicted IDR. Multinodular HCC (HR = 2.67, p 100 ng/mL (HR = 2.767, p = 0.014) independently predicted time-to-IDR. RFS was independently predicted by multinodular HCC (HR = 2.144, p = 0.001), treatment naivety (HR = 0.546, p = 0.004) and AFP > 100 ng/mL (HR = 2.437, p = 0.013). The American Society of Anesthesiologists (ASA) score > 2 (HR = 4.273, p = 0.011), AFP (HR = 1.002, p < 0.001), multinodular HCC (HR = 3.939, p = 0.003) and steatotic HCC (HR = 1.81 × 10-16, p < 0.001) independently predicted OS.Conclusions: IDR was associated with tumor aggressiveness, suggesting a metastatic mechanism. Besides AFP association with LTP, IDR, RFS and OS, treatment-naïve patients had longer RFS, and multi-nodularity was associated with shorter RFS and OS. Steatotic HCC, identified on pre-treatment MRI, independently predicted longer OS, and needs to be further explore

Retrospective Voxel-Based Dosimetry for Assessing the Ability of the Body-Surface-Area Model to Predict Delivered Dose and Radioembolization Outcome

International audienc