Long-Term Overall Survival After Selective Internal Radiation Therapy for Locally Advanced Hepatocellular Carcinomas: Updated Analysis of DOSISPHERE-01 Trial.

Interim analysis of the DOSISPHERE-01 study demonstrated a strong improvement in response and overall survival (OS) on using 90Y-loaded glass microspheres with personalized dosimetry compared with standard dosimetry in patients with nonoperable locally advanced hepatocellular carcinoma. This report sought to provide a long-term analysis of OS. Methods: In this phase II study (ClinicalTrials.gov identifier NCT02582034), treatment was randomly assigned (1:1) with the goal to deliver either at least 205 Gy (if possible >250-300 Gy) to the index lesion in the personalized dosimetry approach (PDA) or 120 ± 20 Gy to the treated volume in the standard dosimetry approach (SDA). The 3-mo response of the index lesion was the primary endpoint, with OS being one of the secondary endpoints. This report is a post hoc long-term analysis of OS. Results: Overall, 60 hepatocellular carcinoma patients with at least 1 lesion larger than 7 cm and more than 30% of hepatic reserve were randomized (intent-to-treat population: PDA, n = 31; SDA, n = 29), with 56 actually treated (modified intent-to-treat population: n = 28 in each arm). The median follow-up for long-term analysis was 65.8 mo (range, 2.1-73.1 mo). Median OS was 24.8 mo and 10.7 mo (hazard ratio [HR], 0.51; 95% CI, 0.29-0.9; P = 0.02) for PDA and SDA, respectively, in the modified intent-to-treat population. Median OS was 22.9 mo for patients with a tumor dose of at least 205 Gy, versus 10.3 mo for those with a tumor dose of less than 205 Gy (HR, 0.42; 95% CI, 0.22-0.81; P = 0.0095), and was 22.9 mo for patients with a perfused liver dose of 150 Gy or higher, versus 10.3 mo for those with a perfused liver dose of less than 150 Gy (HR, 0.42; 95% CI, 0.23-0.75; P = 0.0033). Lastly, median OS was not reached in patients who were secondarily resected (n = 11, 10 in the PDA group and 1 in the SDA group), versus 10.8 mo in those without secondary resection (n = 45) (HR, 0.17; 95% CI, 0.065-0.43; P = 0.0002). Only resected patients displayed favorable long-term OS rates, meaning an OS of more than 50% at 5 y. Conclusion: After longer follow-up, personalized dosimetry sustained a meaningful improvement in OS, which was dramatically improved for patients who were accurately downstaged toward resection, including most portal vein thrombosis patients.

188Re-SSS Lipiodol Radioembolization in HCC Patients: Results of a Phase 1 Trial (Lip-Re-01 Study).

BACKGROUND: Despite the wide development of 90Y-loaded microspheres, 188Re-labeled lipiodol is still being used for radioembolization of hepatocellular carcinoma (HCC). However, the use of this latter compound is limited by in vivo instability. This study sought to evaluate the safety, bio-distribution, and response to 188Re-SSS lipiodol, a new and more stable compound. METHOD: Lip-Re-01 was an activity-escalation Phase 1 study involving HCC patients progressing after sorafenib. The primary endpoint was safety based on Common Terminology Criteria for Adverse Events (AEs) of Grade ≥3 within 2 months. Secondary endpoints included bio-distribution assessed by scintigraphy quantification from 1 to 72 h, tumor to non-tumor uptake ratio (T/NT), as well as blood, urine and feces collection over 72 h, dosimetry, and response evaluation (mRECIST). RESULTS: Overall, 14 heavily pre-treated HCC patients were treated using a whole liver approach. The mean injected activity was 1.5 ± 0.4 GBq for activity Level 1 (n = 6), 3.6 ± 0.3 GBq for Level 2 (n = 6), and 5.0 ± 0.4 GBq for Level 3 (n = 2). Safety was acceptable with only 1/6 of Level 1 and 1/6 of Level 2 patients experiencing limiting toxicity (one liver failure; one lung disease). The study was prematurely discontinued unrelated to clinical outcomes. Uptake occurred in the tumor, liver, and lungs, and only sometimes in the bladder. The T/NT ratio was high with a mean of 24.9 ± 23.4. Cumulative urinary elimination and fecal eliminations at 72 h were very low, 4.8 ± 3.2% and 0.7 ± 0.8%, respectively. Partial response occurred in 21% of patients (0% in the first activity level; 37.5% in the others). CONCLUSION: The high in vivo stability of 188Re-SSS lipiodol was confirmed, resulting in encouraging responses for a Phase 1 study. As the 3.6 GBq activity proved to be safe, it will be used in a future Phase 2 study.

Prediction of left lobe hypertrophy after right lobe radioembolization of the liver using a clinical data model with external validation.

In cirrhotic patients with hepatocellular carcinoma (HCC), right-sided radioembolization (RE) with Yttrium-90-loaded microspheres is an established palliative therapy and can be considered a "curative intention" treatment when aiming for sequential tumor resection. To become surgical candidate, hypertrophy of the left liver lobe to > 40% (future liver remnant, FLR) is mandatory, which can develop after RE. The amount of radiation-induced shrinkage of the right lobe and compensatory hypertrophy of the left lobe is difficult for clinicians to predict. This study aimed to utilize machine learning to predict left lobe liver hypertrophy in patients with HCC and cirrhosis scheduled for right lobe RE, with external validation. The results revealed that machine learning can accurately predict relative and absolute volume changes of the left liver lobe after right lobe RE. This prediction algorithm could help to estimate the chances of conversion from palliative RE to curative major hepatectomy following significant FLR hypertrophy.

Trans-arterial Radioembolization Dosimetry in 2022.

Trans-arterial radioembolization is currently performed using 90Y-loaded glass or resin microspheres and also using 166Ho-loaded microspheres. The goal of this review is to present dosimetry and radiobiology concepts, the different dosimetry approaches available (simulation-based dosimetry and post-treatment dosimetry), main confounding factors as main clinical dosimetry results provided during the last decade for both hepatocellular carcinoma (HCC) and metastases of colorectal carcinoma (mCRC). Based on the different number of microspheres or different isotope used, radiobiology of the three devices is different, meaning that tumouricidal doses and maximal tolerated doses are different. Tumouricidal doses described for HCCs were 100-120 grays (Gy) with 90Y resin microspheres and 205 Gy with 90Y glass microspheres. For mCRC, it is 39-60 with 90Y resin microspheres, 139 Gy with 90Y glass microspheres and 90 Gy with 166Ho microspheres. An impact of tumoural doses with overall survival has also been reported. Personalised dosimetry has been developed and is now recommended by several international expert groups. Level-one evidence of the major impact of personalised dosimetry on response and overall survival in HCC is now available, bringing a new standard approach for TARE in clinical practice as well as for trial design.

Selective internal radiation therapy in older patients with hepatocellular carcinoma: a retrospective analysis.

BACKGROUND: Selective internal radiation therapy (SIRT) is applied to hepatocellular carcinoma (HCC), a disease with increased incidence in the elderly. However, SIRT has rarely been specifically studied in elderly population. The aim of this study was to investigate efficacy and safety of SIRT in elderly HCC patients. METHODS: We studied retrospectively data from patients treated with SIRT for HCC. Clinical and laboratory data were retrieved. We used 70-years old as threshold between younger and elderly populations, to compare outcomes. RESULTS: A total of 222 patients treated with SIRT for HCC were studied, of which 134 patients were younger and 88 older. Median overall survival (OS) was not significantly different between younger and elderly group: 15.6 months (95% CI, 11.7-19.5) and 14.8 months (95% CI, 9.4-20.3) (P = 0.86). Age was not associated with OS in multivariable analysis, with a Hazard ratio of 1.09 (95% CI, 0.82-1.45, P = 0.55). Results of progression-free survival and responses were also similar in both groups. Toxicities were similar between the two groups, including the occurrence of radioembolization-induced liver disease (11.5 vs. 11.4%, P = 0.97). CONCLUSION: SIRT appears to be a well-tolerated treatment with the same efficacy in elderly compared to younger patients in HCC. Our study is the first to study its impact with glass microspheres. This warrants confirmation in large prospective studies.

18F-FDG PET/CT-Based Prognostic Survival Model After Surgery for Head and Neck Cancer.

The aims of this multicenter study were to identify clinical and preoperative PET/CT parameters predicting overall survival (OS) and distant metastasis-free survival (DMFS) in a cohort of head and neck squamous cell carcinoma patients treated with surgery, to generate a prognostic model of OS and DMFS, and to validate this prognostic model with an independent cohort. Methods: A total of 382 consecutive patients with head and neck squamous cell carcinoma, divided into training (n = 318) and validation (n = 64) cohorts, were retrospectively included. The following PET/CT parameters were analyzed: clinical parameters, SUVmax, SUVmean, metabolic tumor volume (MTV), total lesion glycolysis, and distance parameters for the primary tumor and lymph nodes defined by 2 segmentation methods (relative SUVmax threshold and absolute SUV threshold). Cox analyses were performed for OS and DMFS in the training cohort. The concordance index (c-index) was used to identify highly prognostic parameters. These prognostic parameters were externally tested in the validation cohort. Results: In multivariable analysis, the significant parameters for OS were T stage and nodal MTV, with a c-index of 0.64 (P < 0.001). For DMFS, the significant parameters were T stage, nodal MTV, and maximal tumor-node distance, with a c-index of 0.76 (P < 0.001). These combinations of parameters were externally validated, with c-indices of 0.63 (P < 0.001) and 0.71 (P < 0.001) for OS and DMFS, respectively. Conclusion: The nodal MTV associated with the maximal tumor-node distance was significantly correlated with the risk of DMFS. Moreover, this parameter, in addition to clinical parameters, was associated with a higher risk of death. These prognostic factors may be used to tailor individualized treatment.

ALBI Score Is a Strong Predictor of Toxicity Following SIRT for Hepatocellular Carcinoma.

BACKGROUND: Selective internal radiation therapy (SIRT) is an innovative treatment of hepatocellular carcinoma (HCC). The albumin-bilirubin (ALBI) score was designed to better evaluate liver functions in HCC. METHODS: We studied, retrospectively, data from patients treated with SIRT for HCC. The primary endpoint was the occurrence of radioembolization-induced liver disease (REILD). The secondary endpoint was overall survival (OS). RESULTS: 222 patients were studied. The ALBI grade 1 patients had significantly less REILD (3.4%) after the first SIRT than ALBI grade 2 or 3 patients (16.8%, p = 0.002). Of the 207 patients with data, 77 (37.2%) had a worsening of ALBI grade after one SIRT. The baseline ALBI grade was significantly associated with OS (p = 0.001), also in the multivariable analysis. The ALBI grade after the first SIRT was significantly associated with OS (p ≤ 0.001), with median OS of 26.4 months (CI 95% 18.2-34.7) for ALBI grade 1 patients (n = 48) versus 17.3 months (CI 95% 12.9-21.8) for ALBI grade 2 patients (n = 123) and 8.1 months (CI 95% 4.1-12.1) for ALBI grade 3 patients (n = 36). CONCLUSIONS: The baseline ALBI grade is a strong predictor of REILD. The baseline ALBI score and variations of ALBI are prognostic after SIRT.

Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial.

BACKGROUND: All randomised phase 3 studies of selective internal radiation therapy for advanced hepatocellular carcinoma published to date have reported negative results. However, these studies did not use personalised dosimetry. We aimed to compare the efficacy of a personalised versus standard dosimetry approach of selective internal radiation therapy with yttrium-90-loaded glass microspheres in patients with hepatocellular carcinoma. METHODS: DOSISPHERE-01 was a randomised, multicentre, open-label phase 2 trial done at four health-care centres in France. Patients were eligible if they were aged 18 years or older and had unresectable locally advanced hepatocellular carcinoma, at least one measurable lesion 7 cm or more in size, a hepatic reserve of at least 30% after selective internal radiation therapy, no extrahepatic spread (other than to the lymph nodes of the hilum, with a lesion <2 cm in size), and no contraindications to selective internal radiation therapy, as assessed by use of a technetium-99m macro-aggregated albumin scan. Patients were randomly assigned (1:1) by use of a permutated block method, with block sizes of four and without stratification, to receive either standard dosimetry (120 ±â€ˆ20 Gy) targeted to the perfused lobe; standard dosimetry group) or personalised dosimetry (≥205 Gy targeted to the index lesion; personalised dosimetry group). Investigators, patients, and study staff were not masked to treatment. The primary endpoint was the investigator-assessed objective response rate in the index lesion, according to European Association for the Study of the Liver criteria, at 3 months after selective internal radiation therapy in the modified intention-to-treat population. Safety was assessed in all patients who received at least one selective internal radiation therapy injection, and analysed on the basis of the treatment actually received (defined by central dosimetry assessment). The trial is registered with ClinicalTrials.gov, NCT02582034, and has been completed. FINDINGS: Between Dec 5, 2015, and Jan 4, 2018, 93 patients were assessed for eligibility. Of these patients, 60 were randomly assigned: 31 to the personalised dosimetry group and 29 to the standard dosimetry group (intention-to-treat population). 56 (93%) patients (28 in each group) were treated (modified intention-to-treat population). In the modified intention-to-treat population, 20 (71% [95% CI 51-87]) of 28 patients in the personalised dosimetry group and ten (36% [19-56]) of 28 patients in the standard dosimetry group had an objective response (p=0·0074). In the safety analysis population, a least one serious adverse event was reported in seven (20%) of the 35 patients who received personalised dosimetry, and in seven (33%) of the 21 patients who received standard dosimetry. The most frequent (ie, occurring in >5% of patients) grade 3 or higher adverse events were ascites (one [3%] patient who received personalised dosimetry vs two [10%] patients who received standard dosimetry), hepatic failure (two [6%] vs none), lymphopenia (12 [34%] vs nine [43%]), increased aspartate aminotransferase concentrations (three [9%] vs two [10%]), increased alanine aminotransferase concentrations (three [9%] vs none), anaemia (two [6%] vs one [5%]), gastrointestinal haemorrhage (none vs two [10%]), and icterus (none vs two [10%]). One treatment-related death occurred in each group. INTERPRETATION: Compared with standard dosimetry, personalised dosimetry significantly improved the objective response rate in patients with locally advanced hepatocellular carcinoma. The results of this study suggest that personalised dosimetry is likely to improve outcomes in clinical practice and should be used in future trials of selective internal radiation therapy. FUNDING: Biocompatibles UK, a Boston Scientific Group company.

Personalised Dosimetry in Radioembolisation for HCC: Impact on Clinical Outcome and on Trial Design.

Selective internal radiation therapy (SIRT) of hepatocellular carcinoma (HCC) has been used for many years, usually without any specific dosimetry endpoint. Despite good clinical results in early phase studies or in cohort studies, three randomized trials in locally advanced HCC available failed to demonstrate any improvement of overall overall survival (OS) in comparison with sorafenib. In recent years, many studies have evaluated the dosimetry of SIRT using either a simulation-based dosimetry (macroaggregated albumin (MAA)-based) or a post-therapy-based one (90Y-based). The goal of this review is to present the dosimetry concept, tools available, its limitations, and main clinical results described for HCC patients treated with 90Y-loaded resin or glass microspheres. With MAA-based dosimetry, the threshold tumor doses allowing for a response were between 100 and 210 Gy for resin microspheres and between 205 and 257 Gy for glass microspheres. The significant impact of the tumor dose on OS was reported with both devices. The correlation between 90Y-based dosimetry and response was also reported. Regarding the safety, preliminary results are available for both products but with a larger range of normal liver doses values correlated with liver toxicities due to numerous confounding factors. Based on those results, international expert group recommendations for personalized dosimetry have been provided for both devices. The clinical impact of personalized dosimetry has been recently confirmed in a multicenter randomized study demonstrating a doubling of the response rate and an OS of 150% while using personalized dosimetry. Even if technical dosimetry improvements are still under investigation, the use of personalized dosimetry has to be generalized for both clinical practice and trial design.

Lymphocytes and Neutrophil-to-Lymphocyte Ratio Variations After Selective Internal Radiation Treatment for HCC: A Retrospective Cohort Study.

PURPOSE: Selective internal radiation therapy (SIRT) has been proposed for combination with immunotherapy to treat hepatocellular carcinoma (HCC). However, the toxicity of radiation toward lymphocytes is understudied after SIRT. The aim of this study was to describe variations of lymphocytes following SIRT and their potential prognostic impact. MATERIALS AND METHODS: This is a retrospective cohort study of 164 patients treated with SIRT for HCC. Lymphocyte count and neutrophil-to-lymphocyte (NLR) ratio were evaluated at baseline and at 3 months. Primary endpoint was overall survival (OS). RESULTS: Median baseline lymphocyte count was 1.32 Giga/Liter (G/L) (standard deviation (SD) 0.64) at baseline versus 0.68 G/L (SD 0.41) at 3 months. The mean decrease of lymphocyte count was - 44% (standard deviation 0.24). At 3 months, only 21% of patients had normal (1 G/L or more) lymphocyte count, and 23% had lymphocyte count < 0.5 G/L. NLR at 3 months was significantly and independently associated with OS in multivariate Cox model. Median OS was 9.9 months (95% confidence interval (CI) 6.2-13.5) for patients with NLR at 3 months higher than 7.2 compared to 19.9 months in patients with an NLR lower that the 7.2 threshold (95% CI 16.3-23.3) (p = 0.003). CONCLUSIONS: The decrease in lymphocytes was frequent and deep after SIRT for HCC. NLR increase at 3 months was associated with poor survival.

Preliminary results of the Phase 1 Lip-Re I clinical trial: biodistribution and dosimetry assessments in hepatocellular carcinoma patients treated with 188Re-SSS Lipiodol radioembolization.

PURPOSE: This study sought to provide preliminary results on the biodistribution and dosimetry following intra-arterial liver injection of 188Re-SSS Lipiodol on hepatocellular carcinoma patients included in the Phase I Lip-Re 1 study. METHODS: Results of the first six patients included are reported. Analysis of the 188Re-SSS Lipiodol biodistribution was based on planar scintigraphic and tomoscintigraphic (SPECT) studies performed at 1, 6, 24, 48, and 72 h post-administration. Quantification in blood, urine, and stool samples was performed. Determination of the tumour to non-tumour uptake ratio (T/NT) was calculated. Absorbed doses to target organs and tumours were evaluated using the MIRD formalism. RESULTS: The mean injected activity of 188Re-SSS Lipiodol was 1645 ± 361 MBq. Uptakes were seen in the liver (tumour and healthy liver) and the lungs only. All these uptakes were stable over time. A mean 1.4 ± 0.7% of 188Re-SSS Lipiodol administered was detected in serum samples at 6 h, declining rapidly thereafter. On average, 1.5 ± 1.6% of administered activity was eliminated in urine and feces over 72 h. Overall, 90.7 ± 1.6% of detected activity on SPECT studies was found in the liver (74.9 ± 1.8% in tumours and 19.1 ± 1.7% in the healthy liver) and 9.3 ± 1.6% in the lungs (5.7 ± 1.1% in right and 3.7 ± 0.5% in left lungs). Mean doses absorbed were 7.9 ± 3.7Gy to the whole liver, 42.7 ± 34.0Gy to the tumours, 10.2 ± 3.7Gy to the healthy liver, and 1.5 ± 1.2Gy to the lungs. Four patients had stable disease on CT scans at 2 months. The first patient with rapidly progressive disease died at 1 month, most probably of massive tumour progression. Due to this early death and using a conservative approach, the trial independent evaluation committee decided to consider this event as a treatment-related toxicity. CONCLUSION: 188Re-SSS Lipiodol has a favorable biodistribution profile concerning radioembolization, with the highest in-vivo stability among all radiolabeled Lipiodol compounds reported to date. These preliminary results must be further confirmed while completing this Phase I Lip Re1 study.

Yttrium-90 glass microspheres radioembolization (RE) for biliary tract cancer: a large single-center experience.

PURPOSE: Radioembolization (RE) is a promising treatment option for biliary tract cancers (BTC). We report here the largest series to date using this treatment modality. METHODS: We retrospectively studied data from 64 patients treated outside prospective clinical trial at our institution. We studied baseline characteristics as potential prognostic factors. We studied dose delivered to the tumor as predictive factors of outcomes in patients not receiving concomitant chemotherapy. RESULTS: The Progression-Free Survival and Overall Survival (OS) were 7.6 months [95% Confidence Interval (CI): 4.6-10.6] and 16.4 months [95% CI: 7.8-25.0] in the whole cohort. The factors independently associated with OS in multivariable analysis were the primary localization of ICC (HR = 0.27, 95% CI: 0.11-0.68, p = 0.005) and a PS > 0 (HR = 2.21, 95% CI: 1.11-4.38, p = 0.024). During follow-up, 12 patients (19%) underwent surgery following downstaging, with a median OS of 51.9 months. In patients not treated with concomitant chemotherapy (n = 31), OS was significantly higher in patients with a dose delivered to the tumor 260Gy or higher than in patients with a dose delivered to the tumor lower than 260Gy (median 28.2 vs 11.4 months, log-rank p = 0.019). CONCLUSION: Our results confirm that RE is a promising treatment modality in BTC. A high proportion of patients could be downstaged to surgery, with promising long-term survival. Dose delivered to the tumor correlated with clinical outcomes when chemotherapy was not used concomitantly.

A MAA-based dosimetric study in patients with intrahepatic cholangiocarcinoma treated with a combination of chemotherapy and 90Y-loaded glass microsphere selective internal radiation therapy.

PURPOSE: Selective internal radiation therapy (SIRT) appears to be an interesting treatment possibility for locally-advanced intrahepatic cholangiocarcinoma (ICC), yet the appropriate dosimetry has never been evaluated in this context. METHODS: We retrospectively studied data from 40 patients treated at our institution with 90Y-loaded glass microsphere SIRT combined with chemotherapy for inoperable ICC as first-line treatment. Macroaggregated albumin (MAA)-based single-photon emission computed tomography (SPECT)/computed tomography (CT) quantitative analysis was used to calculate the tumor dose (TD), healthy-injected liver dose (HILD), and injected liver dose (ILD). Response was evaluated at 3 months using the European Association for the Study of the Liver criteria. Factors associated with response and toxicity were analyzed using univariate analysis. RESULTS: We assessed a total of 35 patients (five excluded) receiving 55 injections. Mean TD was 322 ± 165Gy and mean HILD was 74 ± 24Gy for a mean ILD of 128 ± 28Gy. All but two lesions responded, with a minimal TD for responding lesions of 158Gy. Six Grade 3-4 permanent liver toxicities were observed. Mean HILD was not associated with liver toxicity (73.2 ± 25.8Gy for patients with liver toxicity and 77.8 ± 16.9Gy for patients without, ns). Only underlying Child-Pugh status (p = 0.0014) and underlying cirrhosis (p = 0.0021) were associated with liver toxicity. Median progression-free survival was 12.7 months and median overall survival (OS) was 28.6 months. Median OS was 52.7 months for patients with Child-Pugh A5 status. CONCLUSIONS: When combined with chemotherapy, SIRT is highly effective, with a TD > 158Gy. Tolerance was good except for the few patients with cirrhosis or Child-Pugh status ≥A6, who exhibited some liver toxicity. Prospective studies are warranted to confirm.

Dosimetric parameters predicting contralateral liver hypertrophy after unilobar radioembolization of hepatocellular carcinoma.

PURPOSE: This study aimed at identifying prior therapy dosimetric parameters using 99mTc-labeled macro-aggregates of albumin (MAA) that are associated with contralateral hepatic hypertrophy occurring after unilobar radioembolization of hepatocellular carcinoma (HCC) performed with 90Y-loaded glass microspheres. METHODS: The dosimetry data of 73 HCC patients were collected prior to the treatment with 90Y-loaded microspheres for unilateral disease. The injected liver dose (ILD), the tumor dose (TD) and healthy injected liver dose (HILD) were calculated based on MAA quantification. Following treatment, the maximal hypertrophy (MHT) of an untreated lobe was calculated. RESULTS: Mean MHT was 35.4 ± 40.4%. When using continuous variables, the MHT was not correlated with any tested variable, i.e., injected activity, ILD, HILD or TD except with a percentage of future remnant liver (FRL) following the 90Y-microspheres injection  (r = -0.56). MHT ≥ 10% was significantly more frequent for patients with HILD ≥ 88 Gy, (52% of the cases), i.e., in 92.2% versus 65.7% for HILD < 88 Gy (p = 0.032). MHT ≥ 10% was also significantly more frequent for patients with a TD ≥ 205 Gy and a tumor volume (VT) ≥ 100 cm3 in patients with initial FRL < 50%. MHT ≥10% was seen in 83.9% for patients with either an HILD ≥ 88 Gy or a TD ≥ 205 Gy for tumors larger than 100cm3 (85% of the cases), versus only 54.5% (p = 0.0265) for patients with none of those parameters. MHT ≥10% was also associated with FRL and the Child-Pugh score. Using multivariate analysis, the Child-Pugh score (p < 0.0001), FRL (p = 0.0023) and HILD (p = 0.0029) were still significantly associated with MHT ≥10%. CONCLUSION: This study demonstrates for the first time that HILD is significantly associated with liver hypertrophy. There is also an impact of high tumor doses in large lesions in one subgroup of patients. Larger prospective studies evaluating the MAA dosimetric parameters have to be conducted to confirm these promising results.

Interest of chest X-ray in tailoring the diagnostic strategy in patients with suspected pulmonary embolism.

Current diagnostic strategies for pulmonary embolism rely on the sequential use of noninvasive diagnostic tests including ventilation-perfusion (V/Q) scan and computed tomography pulmonary angiography (CTPA). V/Q scan remains criticized because of a high proportion of nondiagnostic test results, especially when the chest X-ray (CXR) is abnormal. The present study assesses whether CXR results have an impact on the conclusiveness of a noninvasive diagnostic strategy of pulmonary embolism based on the combination of pretest probability, compression ultrasonography, V/Q scan, and CTPA. Patients suspected of having pulmonary embolism were managed according to a validated diagnostic strategy. All patients underwent a CXR within 24 h of the suspicion of pulmonary embolism. CXR results were correlated to strategy conclusiveness, as assessed by the rate of required CTPA as per the diagnostic algorithm. Two hundred and twenty-three patients were retrospectively analyzed. CXRs were considered as normal in 108 (48%) patients and abnormal in 115 (52%) patients. According to the diagnostic algorithm, a CTPA was required to reach a diagnostic conclusion in 11 (10%) patients of the normal CXR group, and in 14 (12%) patients of the abnormal CXR group (P > 0.05). In this study, the presence of CXR abnormalities did not have an impact on the conclusiveness of a diagnostic strategy of pulmonary embolism based on V/Q scan. CXR abnormalities should likely not be regarded as a contraindication to the use of V/Q scan in patients with suspected pulmonary embolism.

Additional value of combining low-dose computed tomography to V/Q SPECT on a hybrid SPECT-CT camera for pulmonary embolism diagnosis.

OBJECTIVES: The aim of the study was to assess the potential interest of combining a low-dose computed tomography (ldCT) to ventilation/perfusion (V/Q) single-photon emission computed tomography (SPECT) for the diagnosis of pulmonary embolism (PE). We addressed three main questions: Could ldCT be used in substitution to ventilation SPECT? Could ldCT improve the diagnostic performance of V/Q SPECT? Could ldCT provide alternative diagnoses to PE? METHODS: A total of 393 patients previously analysed in a management outcome study that aimed at assessing the safety of V/Q SPECT for PE diagnosis were assessed. All patients underwent an ldCT under the same SPECT-computed tomography camera, which was not used at the time of initial interpretation. Three retrospective analyses were performed: Q SPECT combined with ldCT, V/Q SPECT combined with ldCT and ldCT only. RESULTS: On the basis of initial V/Q SPECT interpretation, 110 (28%) patients were positive and 283 (72%) were negative for PE.With Q SPECT-ldCT, 139 (35%) patients were positive and 254 (65%) were negative, with 55 (19%) discrepancies when compared with V/Q SPECT. Of the 283 patients with negative V/Q SPECT, 42 were positive with V/Q SPECT-ldCT, and among the 110 patients with positive V/Q SPECT 13 were negative with V/Q SPECT-ldCT. On using V/Q SPECT-ldCT, 97 (25%) patients were positive and 296 (75%) were negative, with 13 (3%) discrepancies when compared with V/Q SPECT (all had had a positive V/Q SPECT but a negative V/Q SPECT-ldCT). Finally, 67 (24%) ldCT scans showed a potential alternative diagnosis to PE. CONCLUSION: For PE diagnosis with lung SPECT, the use of ldCT in substitution to ventilation SPECT is associated with a high risk of overdiagnosis. The diagnostic value of ldCT in addition to V/Q SPECT remains unclear. Further studies are needed to determine its potential role in PE diagnosis.

Asymmetric muscle activity on (18)F-FDG PET/CT.

A 51-year-old man referred to our department to undergo an F-FDG PET/CT to detect primary tumor 7 days after diagnosis of one left brain metastasis on MRI in the aftermath of acute right-sided hemiparesis. F-FDG PET/CT was performed without sufficient fasting period. It showed abnormal uptake in the left apical lung nodule, suspicious for primary tumor. Moreover, F-FDG PET/CT showed extensive skeletal muscle accumulation which was more significant as expected but concerning only the left side of the body. So, acute right-sided hemiparesis was responsible for no muscle uptake, probably explained by denervation and altered muscle energetics.

Diagnostic performance of FDG PET/CT to detect subclinical HNSCC recurrence 6 months after the end of treatment.

PURPOSE: Posttreatment follow-up for the recurrence of head and neck squamous cell carcinoma (HNSCC) is a diagnostic challenge. Tissue distortion from radiation and surgery can obscure early detection of recurrence by conventional follow-up approaches such as physical examination or conventional imaging. Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is widely validated for the diagnosis of suspected recurrence. Moreover, we have shown in a previous prospective study the high effectiveness of FDG PET/CT in the assessment of subclinical recurrence 12 months after treatment. The aim of this prospective study was to evaluate the effectiveness of an earlier FDG PET/CT, at 6 months after the end of treatment. METHODS: All patients treated for histologically proven HNSCC from April 2009 to May 2012 at the University Hospital of Brest who did not show any findings suggestive of recurrence at 6 months of their usual follow-up underwent an FDG PET/CT examination. FDG PET/CT findings were correlated with histopathology or imaging follow-up. RESULTS: The study included 116 patients. FDG PET/CT examinations were performed within a mean period ± SD of 5.6 ± 1.8 months after treatment. FDG PET/CT examinations exhibited abnormal FDG uptake in 34 patients and found no suspected recurrence in 82 cases. Of these 82 FDG PET/CT considered as negative, only 1 had a recurrence. Among the 34 positive FDG PET/CT, 22 relapsed whereas 12 did not show evidence of recurrence. The sensitivity and specificity of FDG PET/CT in this study for the diagnosis of occult HNSCC recurrence were 96 (22/23) and 87 % (81/93), respectively. The positive predictive value was 65 % (22/34). The negative predictive value was 99 % (81/82). The overall accuracy was 89 % (103/116). Of the 116 patients, FDG PET/CT highlighted 22 (19 %) subclinical recurrences. CONCLUSION: Our study showed the high effectiveness of FDG PET/CT in the assessment of subclinical HNSCC recurrence 6 months after completion of treatment. These results confirmed that FDG PET/CT is more accurate than conventional follow-up physical examination alone in the assessment of recurrence after previous curative treatment for HNSCC, as we previously demonstrated in patients clinically asymptomatic at 12 months.

Safety of ventilation/perfusion single photon emission computed tomography for pulmonary embolism diagnosis.

PURPOSE: The aim of this management outcome study was to assess the safety of ventilation/perfusion single photon emission computed tomography (V/Q SPECT) for the diagnosis of pulmonary embolism (PE) using for interpretation the criteria proposed in the European Association of Nuclear Medicine (EANM) guidelines for V/Q scintigraphy. METHODS: A total of 393 patients with clinically suspected PE referred to the Nuclear Medicine Department of Brest University Hospital from April 2011 to March 2013, with either a high clinical probability or a low or intermediate clinical probability but positive D-dimer, were retrospectively analysed. V/Q SPECT were interpreted by the attending nuclear medicine physician using a diagnostic cut-off of one segmental or two subsegmental mismatches. The final diagnostic conclusion was established by the physician responsible for patient care, based on clinical symptoms, laboratory test, V/Q SPECT and other imaging procedures performed. Patients in whom PE was deemed absent were not treated with anticoagulants and were followed up for 3 months. RESULTS: Of the 393 patients, the prevalence of PE was 28 %. V/Q SPECT was positive for PE in 110 patients (28 %) and negative in 283 patients (72 %). Of the 110 patients with a positive V/Q SPECT, 78 (71 %) had at least one additional imaging test (computed tomography pulmonary angiography or ultrasound) and the diagnosis of PE was eventually excluded in one patient. Of the 283 patients with a negative V/Q SPECT, 74 (26 %) patients had another test. The diagnosis of PE was finally retained in one patient and excluded in 282 patients. The 3-month thromboembolic risk in the patients not treated with anticoagulants was 1/262: 0.38 % (95 % confidence interval 0.07-2.13). CONCLUSION: A diagnostic management including V/Q SPECT interpreted with a diagnostic cut-off of "one segmental or two subsegmental mismatches" appears safe to exclude PE.

Prognostic value of volumetric parameters measured by 18F-FDG PET/CT in patients with head and neck squamous cell carcinoma.

PURPOSE: The objective of this study was to investigate the value of metabolic tumour volume (MTV) assessed with (18)F-FDG PET/CT in predicting event-free survival (EFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC), and particularly to compare it with more conventional parameters such as maximum standardized uptake value (SUVmax). METHODS: Patients referred to our department for (18)F-FDG PET/CT for staging of HNSCC were prospectively included between February 2009 and March 2011. Each patient was scanned using a Philips Gemini PET/CT system at 1 h after injection. The MTV was calculated semiautomatically for the primary site using methods based on SUV with various thresholds: 3-D contour around voxels equal to or greater than 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5 and 7.0 times SUV, or more than 30%, 40% and 50% of SUVmax. ROC analysis was used to test the statistical significance of the differences among the calculated MTVs. EFS and OS were determined using the Kaplan-Meier method and compared with MTV in univariate and multivariate analyses, including the usual prognostic factors: age, sex, primary site, treatment, SCC histologic grade, AJCC stage, TNM classification, tumour SUVmax and SUVpeak. RESULTS: The study included 80 consecutive patients (70 men, 10 women; mean age 62.4 ± 9.0 years). ROC analysis revealed that pretreatment MTV using a threshold of 5.0 times SUV (MTV5.0) was the best parameter to predict recurrence and death after treatment. In univariate analysis, MTV5.0 >4.9 ml was predictive of poor EFS (p < 0.0001) and poor OS (p < 0.0001). In multivariate, MTV5.0 persisted as an independent predictive factor for EFS (p = 0.011) and OS (p = 0.010), while SUVmax became nonsignificant (p = 0.277 for EFS, p = 0.975 for OS). CONCLUSION: Our results suggest that MTV measured by (18)F-FDG PET/CT has independent prognostic value of in patients with HNSCC, stronger than SUVmax.