Health-related quality of life and radioiodine therapy in thyroid cancer patients: a before-and-after study.

OBJECTIVE: Thyroid cancers are on the rise, but the associated vital prognosis and long-term survival rates are very good. Therefore, treated patients' quality of life and psychological well-being are important considerations. The treatment usually involves surgery and radioactive iodine (radioiodine) ablation. This study aims to investigate potential effects of radioiodine ablation therapy on health-related quality of life, anxiety and depression symptoms, and nutritional status at 6 months post-therapy. METHODS: This study included 136 patients diagnosed with thyroid cancer. Absorbed doses to the salivary glands were estimated from dosimeters worn by patients. Patient health-related quality of life, psychological status and nutritional status were assessed before and 6 months after therapy using standardized questionnaires (including SF-36, Hospital Anxiety and Depression (HAD) scale). Statistical analyses included random-effects logistic and linear regressions adjusted for potential confounders. RESULTS: While no significant association was found between radioiodine exposure and anxiety or depression symptoms, or nutritional status, a significant increase in the SF-36 role physical sub- score was observed in relation with the salivary gland dose (ß= 6.54, 95%CI 2.71;10.36 for a 1-Gy increase). CONCLUSIONS: The findings suggest an improved physical health-related quality of life, namely reduced pain and functional impairment, 6 months after radioiodine therapy in thyroid cancer patients. No significant association was found between radioiodine exposure and mental health-related quality of life, anxiety or depression scores nor nutritional status. This study does not provide any evidence that radioiodine therapy has a potentially adverse effect on patient health-related quality of life.

Feasibility of Liver Transplantation after 90 Y Radioembolization: Lessons from a Radiation Protection Incident.

ABSTRACT: Radioembolization using 90 Y is a growing procedure in nuclear medicine for treating hepatocellular carcinoma. Current guidelines suggest postponing liver transplantation or surgical resection for a period of 14 to 30 d after radioembolization to minimize surgeons' exposure to ionizing radiation. In light of a radiation protection incident, we reevaluated the minimum delay required between radioembolization and subsequent liver transplantation. A patient with a hepatocellular carcinoma underwent a liver transplantation 44 h after undergoing radioembolization using 90 Y (860 MBq SIR-Spheres). No specific radioprotection measures were followed during surgery and pathological analysis. We subsequently (1) evaluated the healthcare professionals' exposure to ionizing radiation by conducting dose rate measurements from removed liver tissue and (2) extrapolated the recommended interval to be observed between radioembolization and surgery/transplantation to ensure compliance with the radiation dose limits for worker safety. The surgeons involved in the transplantation procedure experienced the highest radiation exposure, with whole-body doses of 2.4 mSv and extremity doses of 24 mSv. The recommended delay between radioembolization and liver transplantation was 8 d when using SIR-Spheres and 15 d when injecting TheraSphere. This delay can be reduced further when considering the specific 90 Y activity administered during radioembolization. This dosimetric study suggests the feasibility of shortening the delay for liver transplantation/surgery after radioembolization from the 8th or 15th day after using SIR-Spheres or TheraSphere, respectively. This delay can be decreased further when adjusted to the administrated activity while upholding radiation protection standards for healthcare professionals.

Interim FDG-PET improves treatment failure prediction in primary central nervous system lymphoma: An LOC network prospective multicentric study.

BACKGROUND: The purpose of our study was to assess the predictive and prognostic role of 2-18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/MRI during high-dose methotrexate-based chemotherapy (HD-MBC) in de novo primary central nervous system lymphoma (PCNSL) patients aged 60 and above. METHODS: This prospective multicentric ancillary study included 65 immunocompetent patients who received induction HD-MBC as part of the BLOCAGE01 phase III trial. FDG-PET/MRI were acquired at baseline, post 2 cycles (PET/MRI2), and posttreatment (PET/MRI3). FDG-PET response was dichotomized with "positive" indicating persistent tumor uptake higher than the contralateral mirroring brain region. Performances of FDG-PET and International PCNSL Collaborative Group criteria in predicting induction response, progression-free survival (PFS), and overall survival (OS) were compared. RESULTS: Of the 48 PET2 scans performed, 9 were positive and aligned with a partial response (PR) on MRI2. Among these, 8 (89%) progressed by the end of the induction phase. In contrast, 35/39 (90%) of PET2-negative patients achieved complete response (CR). Among the 18 discordant responses at interim (PETCR/MRIPR), 83% ultimately achieved CR. Eighty-seven percent of the PET2-negative patients were disease free at 6 months versus 11% of the PET2-positive patients (P < .001). The MRI2 response did not significantly differentiate patients based on their PFS, regardless of whether they were in CR or PR. Both PET2 and MRI2 independently predicted OS in multivariate analysis, with PET2 showing a stronger association. CONCLUSIONS: Our study highlights the potential of interim FDG-PET for early management of PCNSL patients. Response-driven treatment based on PET2 may guide future clinical trials. TRIAL: LOCALYZE, NCT03582254, ancillary of phase III clinical trial BLOCAGE01, NCT02313389 (Registered July 10, 2018-retrospectively registered) https://clinicaltrials.gov/ct2/show/NCT03582254?term=LOCALYZE&draw=2&rank=1.

Enhanced therapeutic outcomes with atezolizumab-bevacizumab and SIRT combination compared to SIRT alone in unresectable HCC: A promising approach for improved survival.

BACKGROUND: Integrating immunotherapy with locoregional therapies marks a significant milestone in the realm of hepatocellular carcinoma (HCC) treatment . This study aimed to assess the impact of addition of Atezolizumab-Bevacizumab (AtezoBev) on the outcome patients treated with SIRT. METHODS: We conducted a study that included all Child-Pugh A HCC treated with SIRT since 2017. We examined the effects of the addition of 3 infusions of AtezoBev before the SIRT procedure and after SIRT on patients outcome (AtezoBev-SIRT group). Time-to-event data were analyzed using Kaplan-Meier with the log-rank test. RESULTS: Thirty five HCC patients treated with SIRT were included, of whom 23 % also received AtezoBev infusions. The two groups were similar in terms of liver function and HCC parameters. The median OS was not reached for patients who received AtezoBev in combination with SIRT and 14 months for patients only treated by SIRT. The median PFS was higher in the group treated by SIRT and AtezoBev vs SIRT alone (11.3 months vs 5.8 months). In the global cohort, 8 patients presented a downstaging (23 %), 4 underwent liver surgery (1 in the AtezoBev-SIRT group) and 4 liver transplantation (1 in the AtezoBev-SIRT group) CONCLUSIONS: The administration of AtezoBev, both before and after SIRT, is associated with enhanced OS and PFS outcomes compared to SIRT alone for unresectable HCC.

[18F]FDG PET-MRI provides survival biomarkers in primary central nervous system lymphoma in the elderly: an ancillary study from the BLOCAGE trial of the LOC network.

PURPOSE: Primary central nervous system lymphoma (PCNSL) incidence is rising among elderly patients, presenting challenges due to poor prognosis and treatment-related toxicity risks. This study explores the potential of combining [18F]fluorodeoxyglucose ([18F]FDG) PET scans and multimodal MRI for improving management in elderly patients with de novo PCNSL. METHODS: Immunocompetent patients over 60 years with de novo PCNSL were prospectively enrolled in a multicentric study between January 2016 and April 2021. Patients underwent brain [18F]FDG PET-MRI before receiving high-dose methotrexate-based chemotherapy. Relationships between extracted PET (metabolic tumor volume (MTV), sum of MTV for up to five lesions (sumMTV), metabolic imaging lymphoma aggressiveness score (MILAS)) and MRI parameters (tumor contrast-enhancement size, cerebral blood volume (CBV), cerebral blood flow (CBF), apparent diffusion coefficient (ADC)) and treatment response and outcomes were analyzed. RESULTS: Of 54 newly diagnosed diffuse large B-cell PCNSL patients, 52 had positive PET and MRI with highly [18F]FDG-avid and contrast-enhanced disease (SUVmax: 27.7 [22.8-36]). High [18F]FDG uptake and metabolic volume were significantly associated with low ADCmean values and high CBF at baseline. Among patients, 69% achieved an objective response at the end of induction therapy, while 17 were progressive. Higher cerebellar SUVmean and lower sumMTV at diagnosis were significant predictors of complete response: 6.4 [5.7-7.7] vs 5.4 [4.5-6.6] (p = 0.04) and 5.5 [2.1-13.3] vs 15.9 [4.2-19.5] (p = 0.01), respectively. Two-year overall survival (OS) was 71%, with a median progression-free survival (PFS) of 29.6 months and a median follow-up of 37 months. Larger tumor volumes on PET or enhanced T1-weighted MRI were significant predictors of poorer OS, while a high MILAS score at diagnosis was associated with early death (< 1 year). CONCLUSION: Baseline cerebellar metabolism and sumMTV may predict response to end of chemotherapy in PCNSL. Tumor volume and MILAS at baseline are strong prognostic factors.

Dysfunction of the Salivary and Lacrimal Glands After Radioiodine Therapy for Thyroid Cancer: Results of the START Study After 6-Months of Follow-Up.

Background: Understanding of changes in salivary and lacrimal gland functions after radioactive iodine therapy (131I-therapy) remains limited, and, to date, no studies have evaluated dose-response relationships between absorbed dose from 131I-therapy and dysfunctions of these glands. This study investigates salivary/lacrimal dysfunctions in differentiated thyroid cancer (DTC) patients six months after 131I-therapy, identifies 131I-therapy-related risk factors for salivary/lacrimal dysfunctions, and assesses the relationships between 131I-therapy radiation dose and these dysfunctions. Methods: A cohort study was conducted involving 136 DTC patients treated by 131I-therapy of whom 44 and 92 patients received 1.1 and 3.7 GBq, respectively. Absorbed dose to the salivary glands was estimated using a dosimetric reconstruction method based on thermoluminescent dosimeter measurements. Salivary and lacrimal functions were assessed at baseline (T0, i.e., immediately before 131I-therapy) and six months later (T6) using validated questionnaires and salivary samplings, with and without stimulation of the salivary glands. Statistical analyses included descriptive analyses and random-effects multivariate logistic and linear regressions. Results: There was no difference between T0 and T6 in the level of parotid gland pain, nor was there difference in the number of patients with hyposalivation, but there were significantly more patients with dry mouth sensation and dry eyes after therapy compared with baseline. Age, menopause, depression and anxiety symptoms, history of systemic disease, and not taking painkillers in the past three months were found to be significantly associated with salivary or lacrimal disorders. Significant associations were found between 131I-exposure and salivary disorders adjusted on the previous variables: for example, per 1-Gy increase in mean dose to the salivary glands, odds ratio = 1.43 [CI 1.02 to 2.04] for dry mouth sensation, ß = -0.08 [CI -0.12 to -0.02] mL/min for stimulated saliva flow, and ß = 1.07 [CI 0.42 to 1.71] mmol/L for salivary potassium concentration. Conclusions: This study brings new knowledge on the relationship between the absorbed dose to the salivary glands from 131I-therapy and salivary/lacrimal dysfunctions in DTC patients six months after 131I-therapy. Despite the findings of some dysfunctions, the results do not show any obvious clinical disorders after the 131I-therapy. Nevertheless, this study raises awareness of the risk factors for salivary disorders, and calls for longer follow-up. Clinical Trials Registration: Number NCT04876287 on the public website (ClinicalTrials.gov).

Salivary Dysfunctions and Consequences After Radioiodine Treatment for Thyroid Cancer: Protocol for a Self-Controlled Study (START Study).

BACKGROUND: Following radioiodine (131I) therapy of differentiated thyroid cancer, the salivary glands may become inflamed, leading to dysfunctions and decreases in patients' nutritional status and quality of life. The incidence of these dysfunctions after 131I-therapy is poorly known, and no clinical or genetic factors have been identified to date to define at-risk patients, which would allow the delivered activity to be adapted to the expected risk of salivary dysfunctions. OBJECTIVE: The aims of this study are to estimate the incidence of salivary dysfunctions, and consequences on the quality of life and nutritional status for patients after 131I-therapy; to characterize at-risk patients of developing posttreatment dysfunctions using clinical, biomolecular, and biochemical factors; and to validate a dosimetric method to calculate the dose received at the salivary gland level for analyzing the dose-response relationship between absorbed doses to salivary glands and salivary dysfunctions. METHODS: This prospective study aims to include patients for whom 131I-therapy is indicated as part of the treatment for differentiated thyroid cancer in a Paris hospital (40 and 80 patients in the 1.1 GBq and 3.7 GBq groups, respectively). The follow-up is based on three scheduled visits: at inclusion (T0, immediately before 131I-therapy), and at 6 months (T6) and 18 months (T18) posttreatment. For each visit, questionnaires on salivary dysfunctions (validated French tool), quality of life (Hospital Anxiety and Depression scale, Medical Outcomes Study 36-Item Short Form Survey), and nutritional status (visual analog scale) are administered by a trained clinical research associate. At T0 and T6, saliva samples and individual measurements of the salivary flow, without and with salivary glands stimulation, are performed. External thermoluminescent dosimeters are positioned on the skin opposite the salivary glands and at the sternal fork immediately before 131I administration and removed after 5 days. From the doses recorded by the dosimeters, an estimation of the dose received at the salivary glands will be carried out using physical and computational phantoms. Genetic and epigenetic analyses will be performed to search for potential biomarkers of the predisposition to develop salivary dysfunctions after 131I-therapy. RESULTS: A total of 139 patients (99 women, 71.2%; mean age 47.4, SD 14.3 years) were enrolled in the study between September 2020 and April 2021 (45 and 94 patients in the 1.1 GBq and 3.7G Bq groups, respectively). T6 follow-up is complete and T18 follow-up is currently underway. Statistical analyses will assess the links between salivary dysfunctions and absorbed doses to the salivary glands, accounting for associated factors. Moreover, impacts on the patients' quality of life will be analyzed. CONCLUSIONS: To our knowledge, this study is the first to investigate the risk of salivary dysfunctions (using both objective and subjective indicators) in relation to organ (salivary glands) doses, based on individual dosimeter records and dose reconstructions. The results will allow the identification of patients at risk of salivary dysfunctions and will permit clinicians to propose a more adapted follow-up and/or countermeasures to adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT04876287; https://clinicaltrials.gov/ct2/show/NCT04876287. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35565.

Radiation dose to nuclear medicine technologists when operating PET/MR compared with PET/CT.

Since 2010, positron emission tomography/magnetic resonance (PET/MR) has been increasingly used as clinical routine in nuclear medicine departments. One advantage of PET/MR over PET/computed tomography (CT) is the lower dose of ionising radiation delivered to patients. However, data on the radiation dose delivered to staff operating PET/MR compared with the new generation of PET/CT equipment are still lacking. Our aim was to compare the radiation dose to nuclear medicine technologists performing routine PET/MR and PET/CT in the same department. We retrospectively measured the daily radiation dose received by PET technologists over 13 months by collecting individual dosimetry measurements (from electronic personal dosimeters). Data were analysed taking into account the total number of studies performed with each PET modality (PET/MR with Signa 3T, General Electric Healthcare versus PET/CT with Biograph mCT flow, Siemens), the type of exploration (brain versus whole-body PET), the18F activity injected per day and per patient as well as the time spent in contact with patients after tracer injection. Our results show a significantly higher whole-body exposure to technologists for PET/MR compared with PET/CT (10.3 ± 3.5 nSv versus 4.7 ± 1.2 nSv per18F injected MBq, respectively;p< 0.05). This difference was related to prolonged contact with injected patients during patient positioning with the PET/MR device and MR coil placement, especially in whole-body studies. For an equal injected activity, radiation exposure to PET technologists for PET/MR was twice that of PET/CT. To minimise the radiation dose to staff, efforts should be made to optimise patient positioning, even in departments with extensive PET/CT experience.

Hybrid [18F]-F-DOPA PET/MRI Interpretation Criteria and Scores for Glioma Follow-up After Radiotherapy.

OBJECTIVE: 18F­fluoro-L­3,4­dihydroxyphenylalanine positron emission tomography (F­DOPA PET) is used in glioma follow-up after radiotherapy to discriminate treatment-related changes (TRC) from tumor progression (TP). We compared the performances of a combined PET and MRI analysis with F­DOPA current standard of interpretation. METHODS: We included 76 consecutive patients showing at least one gadolinium-enhanced lesion on the T1­w MRI sequence (T1G). Two nuclear medicine physicians blindly analyzed PET/MRI images. In addition to the conventional PET analysis, they looked for F­DOPA uptake(s) outside T1G-enhanced areas (T1G/PET), in the white matter (WM/PET), for T1G-enhanced lesion(s) without sufficiently concordant F­DOPA uptake (T1G+/PET), and F­DOPA uptake(s) away from hemorrhagic changes as shown with a susceptibility weighted imaging sequence (SWI/PET). We measured lesions' F­DOPA uptake ratio using healthy brain background (TBR) and striatum (T/S) as references, and lesions' perfusion with arterial spin labelling cerebral blood flow maps (rCBF). Scores were determined by logistic regression. RESULTS: 53 and 23 patients were diagnosed with TP and TRC, respectively. The accuracies were 74% for T/S, 76% for TBR, and 84% for rCBF, with best cut-off values of 1.3, 3.7 and 1.25, respectively. For hybrid variables, best accuracies were obtained with conventional analysis (82%), T1G+/PET (82%) and SWI/PET (81%). T1G+/PET, SWI/PET and rCBF ≥ 1.25 were selected to construct a 3-point score. It outperformed conventional analysis and rCBF with an AUC of 0.94 and an accuracy of 87%. CONCLUSIONS: Our scoring approach combining F­DOPA PET and MRI provided better accuracy than conventional PET analyses for distinguishing TP from TRC in our patients after radiation therapy.

Simultaneously acquired PET and ASL imaging biomarkers may be helpful in differentiating progression from pseudo-progression in treated gliomas.

OBJECTIVES: The aim of this work was investigating the methods based on coupling cerebral perfusion (ASL) and amino acid metabolism ([18F]DOPA-PET) measurements to evaluate the diagnostic performance of PET/MRI in glioma follow-up. METHODS: Images were acquired using a 3-T PET/MR system, on a prospective cohort of patients addressed for possible glioma progression. Data were preprocessed with statistical parametric mapping (SPM), including registration on T1-weighted images, spatial and intensity normalization, and tumor segmentation. As index tests, tumor isocontour maps of [18F]DOPA-PET and ASL T-maps were created and metabolic/perfusion abnormalities were evaluated with the asymmetry index z-score. SPM map analysis of significant size clusters and semi-quantitative PET and ASL map evaluation were performed and compared to the gold standard diagnosis. Lastly, ASL and PET topography of significant clusters was compared to that of the initial tumor. RESULTS: Fifty-eight patients with unilateral treated glioma were included (34 progressions and 24 pseudo-progressions). The tumor isocontour maps and T-maps showed the highest specificity (100%) and sensitivity (94.1%) for ASL and [18F]DOPA analysis, respectively. The sensitivity of qualitative SPM maps and semi-quantitative rCBF and rSUV analyses were the highest for glioblastoma. CONCLUSION: Tumor isocontour T-maps and combined analysis of CBF and [18F]DOPA-PET uptake allow achieving high diagnostic performance in differentiating between progression and pseudo-progression in treated gliomas. The sensitivity is particularly high for glioblastomas. KEY POINTS: • Applied separately, MRI and PET imaging modalities may be insufficient to characterize the brain glioma post-therapeutic profile. • Combined ASL and [18F]DOPA-PET map analysis allows differentiating between tumor progression and pseudo-progression.

Radiation dose of nuclear medicine technicians performing PET/MR.

Since october 2015, PET/MR has been used extensively for clinical routine in the nuclear medicine department of the Pitié-Salpêtrière Hospital (Paris, France) with a throughput of 11 to 15 patients each day. While many studies have been conducted to investigate dose reduction strategies to patients with hybrid PET/MR devices, no study has focused on staff radiation safety. Knowing that patient positioning within the scanner takes longer in PET/MR than in PET/CT because of the placement of several local MR receive coils, a retrospective study was carried out to measure the radiation doses to nuclear medicine technologists from the patient. The analysis was conducted during one year on 1332 clinical PET/MR studies performed with the Signa PET/MR system (General Electric Healthcare) in our department. The whole-body exposure of the technologist staff was on average for all PET/MR exams10.3 ± 4 nSv per injected MBq of 18 F. When performing brain PET/MR exams only, the whole-body exposure was on average 8.7 ± 2 nSv per injected MBq of 18 F. Brain PET/MR provides lower radiation dose than whole-body examinations for cancer screening due to a lower injected activity (2 vs. 3 MBq kg-1) and shorter patient positioning (5 vs. 15 min). When starting PET/MR in a nuclear medicine department, an important step is to optimise patient positionning within the scanner to minimise radiation dose received by the technical staff from patients.

Evaluation of quantitative criteria for glioma grading with static and dynamic 18F-FDopa PET/CT.

PURPOSE: The aim of this study was to compare various acquisition and processing protocols for noninvasive glioma grading using either static or dynamic (18)F-FDopa PET. METHODS: Dynamic studies were performed in 33 patients. Based on histopathological analysis, 18 patients had a high-grade (HG) tumor and 15 patients had a low-grade (LG) tumor. For static imaging, SUV(mean) and SUV(max) were calculated for different acquisition time ranges after injection. For dynamic imaging, the transport rate constant k1 was calculated according to a compartmental kinetic analysis using an image-derived input function. RESULTS: With the use of a 5-minute static imaging protocol starting at 38 minutes after injection, newly diagnosed HG tumors could be distinguished from LG tumors with a sensitivity of 70% and a specificity of 90% with a threshold of SUV(mean) of 2.5. In recurrent tumors, a sensitivity of 100% and a specificity of 80% for identifying HG tumors were obtained with a threshold set to 1.8. Dynamic imaging only slightly, but nonsignificantly, improved differential diagnosis. CONCLUSIONS: Static and dynamic imaging without blood sampling can discriminate between LG and HG for both newly diagnosed and recurrent gliomas. In dynamic imaging, excellent discrimination was obtained by considering the transport rate constant k1 of tumors. In static imaging, the best discrimination based on SUV was obtained for SUV(mean) calculated from a 5-minute acquisition started at 38 minutes after injection.

[Positron emission tomography in internal medicine]. / Tomographie par émission de positons en médecine interne.

FDG-PET is now an established diagnostic tool in oncology. Fluorodeoxyglucose is not a specific tracer for malignant lesions but rather for elevated glucose metabolism, present not only in cancer but also in inflammatory and infectious lesions. FDG-PET has thus been suggested for diagnosis of fevers of unknown origin, deep bone or visceral infectious foci, inflammatory vasculitis or sarcoidosis and unknown primary tumors, all frequent situation in internal medicine. The main characteristics of FDG-PET are its ability to rule out focal inflammation or infection with a high degree of certainty when the examination is negative because of its good negative predictive value and its usefulness as an early marker of therapeutic response, compared with anatomy-based or conventional scintigraphic imaging. Large-scale prospective studies are necessary, however, before FDG-PET is integrated into routine clinical use. It should be compared with different techniques already validated (biology, radiology, conventional scintigraphic imaging) and its cost-effectiveness should be evaluated.

Partial-volume effect in PET tumor imaging.

PET has the invaluable advantage of being intrinsically quantitative, enabling accurate measurements of tracer concentrations in vivo. In PET tumor imaging, indices characterizing tumor uptake, such as standardized uptake values, are becoming increasingly important, especially in the context of monitoring the response to therapy. However, when tracer uptake in small tumors is measured, large biases can be introduced by the partial-volume effect (PVE). The purposes of this article are to explain what PVE is and to describe its consequences in PET tumor imaging. The parameters on which PVE depends are reviewed. Actions that can be taken to reduce the errors attributable to PVE are described. Various PVE correction schemes are presented, and their applicability to PET tumor imaging is discussed.