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Thermal treatments can be considered as an accelerated ageing, bringing partly similar changes in properties as naturally aged wood. Thermal treatment was applied on white mulberry (Morus alba L.), a dominant species for making musical instruments from middle-East to Far-East, to investigate the effects on the vibro-mechanical and physical properties of this wood, and the results compared to previously published data on spruce (Picea abies Karst.) as a reference for the soundboard of Western string instruments. Thermal treatment (TT) at 150 °C and 0% of relative humidity was applied to five analogous groups of specimens with five different durations (2.5, 8, 24, 72, 261 hours). Humidity re-conditioning of specimens was done to explore the reversibility of TT effects. Physical and vibrational properties such as specific gravity (γ), equilibrium moisture content (EMC), CIELab colorimetric values, specific modulus of elasticity (E’/γ) and damping coefficient (tanδ) in longitudinal (L) and radial (R) directions, have been measured after stabilisation of samples in standard conditions (20 °C, 65% RH), before and after TT and then after re-conditioning. Untreated mulberry had a low EMC, very low L/R anisotropy and low E’L/γ, and relatively low tanδ. Weight loss (WL) and CIELab values evolved similarly during TT for mulberry and for previous results on spruce, however, their EMC and vibrational properties were affected differently. This could be explained in part by the low anisotropy of mulberry, and in part by its particular extractives. The parts of irreversible effects, linked to chemical modification or degradation, and of reversible effects, linked to physical configuration, were different between mulberry and spruce. The applied treatments did not bring permanent “improvements” in vibrational properties of mulberry, yet its colour appearance was enhanced.

Background: Nintedanib is a triple-angiokinase inhibitor with potential activity in patients with advanced thyroid cancers, as radioiodine refractory differentiated thyroid cancer (RAIR DTC) and medullary thyroid cancer (MTC)., Design: EORTC-1209 (NCT01788982) was a double-blind randomized (2:1 ratio) placebo-controlled phase II, multi-cohort study exploring the efficacy and safety of nintedanib in patients with progressive, locally advanced, and/or metastatic RAIR DTC and MTC. The primary endpoint was progression-free survival (PFS) in the per-protocol (PP) population for both cohorts. Secondary endpoints included response rate, duration of response, overall survival (OS), and safety., Results: RAIR DTC cohort: Seventy out of the 75 planned patients with RAIR DTC (median age, 66 years; 39 women) who had progressed after one (76%) or two lines (24%) of previous systemic therapy were randomized to receive either nintedanib (N = 45) or placebo (N = 25). Of these, 69 patients started treatment and 56 met all inclusion criteria (PP). At data cutoff, the median duration of follow-up was 26.3 months in the nintedanib arm and 19.8 months in the placebo arm. In the PP population, the median PFS was 3.7 months [80% confidence interval (CI), 1.9-6.5] in the nintedanib arm and 2.9 months (80% CI, 2.0-5.6) in the placebo arm (HR = 0.65; 80% CI, 0.42-0.99; one-sided log-rank test P = 0.0947). No objective response was observed. The median OS was 29.6 months [80% CI, 15.2-not reached (NR)] in the nintedanib arm and not reached in the placebo arm. Grade 3-4 adverse events of any attribution occurred in 50% of patients receiving nintedanib and in 36% of patients receiving placebo. MTC cohort: Thirty-one out of the 67 planned patients with MTC (median age, 57 years; eight women) who had progressed after one (68%) or two (32%) lines of previous systemic therapy were randomized to receive either nintedanib (N = 22) or placebo (N = 9). Of these, 20 patients (15 in the nintedanib arm and five in the placebo arm) started treatment and met all inclusion criteria (PP). The median PFS was 7.0 months (80% CI, 1.9-8.7) in the nintedanib arm and 3.9 months (80% CI, 3.0-5.5) in the placebo arm (HR = 0.49; 95% CI, 0.16-1.53). No objective response was reported. The median OS was 16.4 months (80% CI, 12.1-24.9) in the nintedanib arm and 12.3 months (80% CI, 7.1-NR) in the placebo arm. Grade 3-4 adverse events of any attribution during the blinded period occurred in 59.1% of patients receiving nintedanib and in 33.3% of patients receiving placebo., Conclusion: This study did not suggest a clinically significant improvement of PFS with nintedanib over placebo in patients with pretreated RAIR DTC and MTC., Competing Interests: JC: None related to nintedanib/Boehringer Ingelheim; scientific consultancy role from Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, ITM, Sirlex, Lilly, and Merck Serono. Research grants from Novartis, Pfizer, Astrazeneca, Advanced Accelerator Applications, Eisai, and Bayer. FC: None related to nintedanib/Boehringer Ingelheim; scientific consultancy role from Eisai and Bayer. YG: None related to nintedanib/Boehringer Ingelheim; scientific consultancy role from Eisai, Lilly, Sanofi, and Bayer. EK: None related to nintedanib/Boehringer Ingelheim; scientific consultancy role from Eisai, Bayer, and Genzyme; research grant from Novartis. YL: None related to nintedanib/Boehringer Ingelheim; scientific consultancy role from Eisai, Merck, MSD, and Roche. SLe: None related to nintedanib/Boehringer Ingelheim; scientific consultancy role from Eisai, Bayer, and Lilly; research grant from Novartis and Genzyme. PS: None related to nintedanib/Boehringer Ingelheim; have received institutional research support and biological material from Eisai. TL: None related to nintedanib/Boehringer Ingelheim; advisory board from EISAI, Bayer, and Genzyme-Sanofi. DLL: None related to nintedanib/Boehringer Ingelheim; advisory board from EISAI, IPSEN, MSD, Merck Serono, Bayer, Roche, Lilly, Seagen, Gilead, Novartis, Gentili SrL, and New Bridge. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Leboulleux, Kapiteijn, Litière, Schöffski, Godbert, Rodien, Jarzab, Salvatore, Zanetta, Capdevila, Bastholt, De La Fouchardiere, Lalami, Bardet, Cornélis, Dedecjus, Links, Sents, Schlumberger, Locati and Newbold.)

Purpose: To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation., Patients and Methods: A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq-150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months., Results: Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3-4 AEs in 7 patients., Conclusions: Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients., (©2023 American Association for Cancer Research.)

Given the constant pressure to increase patient throughput while respecting radiation protection, global body PET image quality (IQ) is not satisfactory in all patients. We first studied the association between IQ and other variables, in particular body habitus, on a digital PET/CT. Second, to improve and homogenize IQ, we evaluated a deep learning PET denoising solution (Subtle PET TM ) using convolutional neural networks. We analysed retrospectively in 113 patients visual IQ (by a 5-point Likert score in two readers) and semi-quantitative IQ (by the coefficient of variation in the liver, CV liv ) as well as lesion detection and quantification in native and denoised PET. In native PET, visual and semi-quantitative IQ were lower in patients with larger body habitus ( p < 0.0001 for both) and in men vs. women ( p ≤ 0.03 for CV liv ). After PET denoising, visual IQ scores increased and became more homogeneous between patients (4.8 ± 0.3 in denoised vs. 3.6 ± 0.6 in native PET; p < 0.0001). CV liv were lower in denoised PET than in native PET, 6.9 ± 0.9% vs. 12.2 ± 1.6%; p < 0.0001. The slope calculated by linear regression of CV liv according to weight was significantly lower in denoised than in native PET ( p = 0.0002), demonstrating more uniform CV liv . Lesion concordance rate between both PET series was 369/371 (99.5%), with two lesions exclusively detected in native PET. SUV max and SUV peak of up to the five most intense native PET lesions per patient were lower in denoised PET ( p < 0.001), with an average relative bias of -7.7% and -2.8%, respectively. DL-based PET denoising by Subtle PET TM allowed [ 18 F]FDG PET global image quality to be improved and homogenized, while maintaining satisfactory lesion detection and quantification. DL-based denoising may render body habitus adaptive PET protocols unnecessary, and pave the way for the improvement and homogenization of PET modalities.

Background: Prophylactic central neck dissection in clinically low-risk cT1bT2N0 papillary thyroid carcinoma is controversial, due to a large number of conflicting retrospective studies, some showing an advantage in terms of locoregional recurrence, others showing no advantage. These previous studies all show high rates of excellent response. We aim to demonstrate the non-inferiority of thyroidectomy alone as compared to total thyroidectomy with prophylactic central neck dissection in conjunction with adjuvant RAI 30 mCi with rTSH stimulation in terms of excellent response at 1 year., Trial Design and Methods: Prospective randomized open multicenter phase III trial including patients with 11-40-mm papillary thyroid carcinoma (Bethesda VI) or suspicious cytology (Bethesda V) confirmed malignant on intra-operative frozen section analysis, with no suspicious lymph nodes on a specialized preoperative ultrasound examination. Patients will be randomized 1:1 into two groups: the reference group total thyroidectomy with bilateral prophylactic central neck dissection, and the comparator group total thyroidectomy alone. All patients will receive an ablative dose of 30mCi of radioactive iodine (RAI) within 4 months of surgery. The primary outcome is to compare the rate of excellent response at 1 year after surgery between the groups, as defined by an unstimulated serum thyroglobulin (Tg) level ≤ 0.2 ng/mL with no anti-Tg antibodies, an normal neck ultrasound and no ectopic uptake on the post-RAI scintiscan. Non-inferiority will be demonstrated if the rate of patients with excellent response at 1 year after randomization does not differ by more than 5%. Setting the significance level at 0.025 (one-sided) and a power of 80% requires a sample size of 598 patients (299 per group). Secondary outcomes are to compare Tg levels at 8 +/- 2 postoperative weeks, before RAI ablation, the rate of excellent response at 3 and 5 years, the rate of other responses at 1, 3, and 5 years (biochemical incomplete, indeterminate, and structurally incomplete responses), complications, quality of life, and cost-utility., Discussion (potential Implications): If non-inferiority is demonstrated with this high-level evidence, prophylactic neck dissection will have been shown to not be necessary in clinically low-risk papillary thyroid carcinoma., Trial Registration: NCT03570021. June 26,2018., (© 2023. The Author(s).)

Background: Female thyroid cancer survivors are more likely to have a higher risk of breast cancer compared to the general population, and the underlying causes are yet to be understood. The potential role of I-131 treatment on this association remains controversial., Methods: We pooled individual data of women who were treated for differentiated thyroid cancer from 1934 to 2005 in France, Italy and Sweden. Standardized incidence ratios (SIRs) for breast cancer were estimated by comparison with age, sex and calendar-year expected values of the general population in each country. We estimated breast cancer risk in relation to I-131 treatment using time-dependent Poisson models., Results: Of 8475 women (mean age at diagnosis: 45 years, range 2-90 years), 335 were diagnosed with breast cancer [SIR = 1.52, 95% confidence interval (CI): 1.36-1.69] during a median follow-up time of 12.7 years since diagnosis. Overall, breast cancer risk did not differ between women treated or not with I-131 (relative risk=1.07, 95% CI 0.84-1.35). However, breast cancer risk increased with increasing cumulative I-131 activity, without significant departure from linearity (excess relative risk per 100 mCi=17%, 95% CI: 2% to 38%). The higher risk associated with a cumulative I-131 activity of ≥100 mCi and ≥400 mCi was translated into 4 (95% CI -4 to 13) and 42 (95% CI -8 to 93) excess breast cancer cases per 10,000 person-years, respectively., Conclusions: An elevated risk was observed for the highest cumulative administered activity (>=400 mCi), and a significant dose-dependent association was observed among thyroid cancer survivors who were treated with I-131. However, overall, I-131 treatment might only explain partly the increase in breast cancer risk among female thyroid cancer survivors., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: 18F-Fluorocholine (18FCH) PET/CT has high sensitivity for parathyroid adenoma detection and can reliably exclude malignancy in thyroid nodules with indeterminate cytology. Data regarding 18FCH uptake in chronic autoimmune thyroiditis (CAT) are scarce. We aimed to assess thyroid 18FCH uptake in CAT with biological and histological correlation., Methods: This is an ancillary study from the Chocolate trial (NCT02784223) that prospectively enrolled 107 patients planned for thyroid surgery. 18FCH PET/CT acquisitions were performed 20 and 60 min after injection. 18FCH uptake in the thyroid gland was assessed by measuring maximum (SUVmax) and mean (SUVmean) standardized uptake values. Thyrotropin, free thyroxine (FT4), thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies were collected. The intensity of thyroiditis and the degree of fibrosis were assessed on pathology., Results: CAT was evidenced in 19/107 (18%) patients. Of these, 13 (68%) displayed an increased and diffuse 18FCH thyroid uptake. This uptake pattern was not observed in patients without CAT. SUVmax and SUVmean were higher in patients with CAT than in those without (P < 0.001). At both acquisition times, SUVmax showed a monotonic relationship with the intensity of thyroiditis (Spearman ρ = 0.44 and 0.51, respectively, P < 0.001) and with the degree of fibrosis (Spearman ρ = 0.55 and 0.62, respectively, P < 0.001). SUVmax showed a linear relationship with TPOAb titers at 20 min (Pearson r = 0.54, P < 0.05; Spearman ρ = 0.59, P = 0.03)., Conclusions: More than two-thirds of the patients with CAT present high and diffuse thyroid 18FCH uptake. This uptake pattern is highly specific to CAT and is correlated with pathology and TPOAb titers.

Context: Little is known about prostate-specific membrane antigen (PSMA) expression in patients with cervical involvement of differentiated thyroid cancer (DTC)., Objective: We investigated PSMA expression in neck persistent/recurrent disease (PRD) using immunohistochemistry and the association with radioiodine (RAI) or 18-fluorodeoxyglucose (18FDG) uptake, and patient outcome., Design, Setting, and Patients: Data from 44 consecutive DTC patients who underwent neck reoperation from 2006 to 2018 in a comprehensive cancer center., Main Outcome Measure(s): Immunostaining was performed with vascular endothelial marker CD31 and PSMA. PSMA expression was quantified using the immunoreactive score (IRS). RAI and 18FDG uptake were assessed before surgery using posttherapeutic RAI scintigraphy and 18FDG positron emission tomography with computed tomography. Mean follow-up after reintervention was 6.5 ± 3.7 years., Results: Thirty patients (68%) showed at least 1 PSMA-positive lesion (IRS ≥ 2) with similar proportions in RAI-positive and RAI-negative patients (75% vs 66%). In RAI-negative patients, however, the proportion of PSMA-positive disease (79% vs 25%, P < 0.01) and the mean IRS (4.0 vs 1.0, P = 0.01) were higher in 18FDG-positive than in 18FDG-negative patients. Furthermore, mean IRS was higher in patients ≥ 55 years, large primary tumors (>40 mm) or aggressive subtypes, and was correlated with structural disease at last follow-up. Strong PSMA expression (IRS ≥ 9) was associated with shorter progression-free survival (PFS)., Conclusions: Our findings show that PSMA expression was present in two-thirds of patients with neck PRD, that it was related to poor prognostic factors and that very high expression was associated with poorer PFS. This preliminary study may offer new perspectives for the management of RAI-refractory DTC., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: With a constantly increasing number of diagnostic images performed each year, Artificial Intelligence (AI) denoising methods offer an opportunity to respond to the growing demand. However, it may affect information in the image in an unknown manner. This study quantifies the effect of AI-based denoising on FDG PET textural information in comparison to a convolution with a standard gaussian postfilter (EARL1)., Methods: The study was carried out on 113 patients who underwent a digital FDG PET/CT (VEREOS, Philips Healthcare). 101 FDG avid lesions were segmented semi-automatically by a nuclear medicine physician. VOIs in the liver and lung as reference organs were contoured. PET textural features were extracted with pyradiomics. Texture features from AI denoised and EARL1 versus original PET images were compared with a Concordance Correlation Coefficient (CCC). Features with CCC values ≥ 0.85 threshold were considered concordant. Scatter plots of variable pairs with R2 coefficients of the more relevant features were computed. A Wilcoxon signed rank test to compare the absolute values between AI denoised and original images was performed., Results: The ratio of concordant features was 90/104 (86.5%) in AI denoised versus 46/104 (44.2%) with EARL1 denoising. In the reference organs, the concordant ratio for AI and EARL1 denoised images was low, respectively 12/104 (11.5%) and 7/104 (6.7%) in the liver, 26/104 (25%) and 24/104 (23.1%) in the lung. SUVpeak was stable after the application of both algorithms in comparison to SUVmax. Scatter plots of variable pairs showed that AI filtering affected more lower versus high intensity regions unlike EARL1 gaussian post filters, affecting both in a similar way. In lesions, the majority of texture features 79/100 (79%) were significantly (p<0.05) different between AI denoised and original PET images., Conclusions: Applying an AI-based denoising on FDG PET images maintains most of the lesion's texture information in contrast to EARL1-compatible Gaussian filter. Predictive features of a trained model could be thus the same, however with an adapted threshold. Artificial intelligence based denoising in PET is a very promising approach as it adapts the denoising in function of the tissue type, preserving information where it should., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jaudet, Weyts, Lechervy, Batalla, Bardet and Corroyer-Dulmont.)

Brain metastases (BM) are frequently detected during the follow-up of patients with malignant tumors, particularly in those with advanced disease. Despite a major progress in systemic anti-cancer treatments, the average overall survival of these patients remains limited (6 months from diagnosis). Also, cognitive decline is regularly reported especially in patients treated with whole brain external beam radiotherapy (WBRT), due to the absorbed radiation dose in healthy brain tissue. New targeted therapies, for an earlier and/or more specific treatment of the tumor and its microenvironment, are needed. Radioimmunotherapy (RIT), a combination of a radionuclide to a specific antibody, appears to be a promising tool. Inflammation, which is involved in multiple steps, including the early phase, of BM development is attractive as a relevant target for RIT. This review will focus on the (1) early biomarkers of inflammation in BM pertinent for RIT, (2) state of the art studies on RIT for BM, and (3) the importance of dosimetry to RIT in BM. These two last points will be addressed in comparison to the conventional EBRT treatment, particularly with respect to the balance between tumor control and healthy tissue complications. Finally, because new diagnostic imaging techniques show a potential for the detection of BM at an early stage of the disease, we focus particularly on this therapeutic window., Competing Interests: Author NF was employed by GenesisCare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Corroyer-Dulmont, Jaudet, Frelin, Fantin, Weyts, Vallis, Falzone, Sibson, Chérel, Kraeber-Bodéré, Batalla, Bardet, Bernaudin and Valable.)

Background: The common endocrine disorder primary hyperparathyroidism (PHPT) can be cured by surgery. Preoperative localization of parathyroid adenoma (PTA) by imaging is a prerequisite for outpatient minimally invasive parathyroidectomy (MIP). Compared to inpatient bilateral cervical exploration (BCE) which is performed if imaging is inconclusive, MIP is superior in terms of cure and complication rates and less costly. The imaging procedure F18-choline (FCH) PET/CT outperforms Tc99m-sestaMIBI (MIBI) SPECT/CT for PTA localization, but it is much costlier. The aim of this study is to identify the most efficient first-line imaging modality for optimal patient care in PHPT without added cost to society., Methods: We will conduct a multicenter open diagnostic intervention randomized phase III trial comparing two diagnostic strategies in patients with PHPT: upfront FCH PET/CT versus MIBI SPECT/CT. The primary endpoint is the proportion of patients in whom the first-line imaging method results in successful MIP and cure. Follow-up including biological tests will be performed 1 and 6 months after surgery. The main secondary endpoint is the social cost of both strategies. Other secondary endpoints are as follows: FCH PET/CT and MIBI SPECT/CT diagnostic performance, performance of surgical procedure and complication rate, FCH PET/CT inter- and intra-observer variability and optimization of FCH PET/CT procedure. Fifty-eight patients will be enrolled and randomized 1:1., Discussion: FCH PET/CT is a highly efficient but expensive imaging test for preoperative PTA localization and costs three to four times more than MIBI SPECT/CT. Whether FCH PET/CT improves patient outcomes compared to the reference standard MIBI SPECT/CT is unknown. To justify its added cost, FCH PET/CT-guided parathyroid surgery should lead to improved patient management, resulting in higher cure rates and fewer BCEs and surgical complications. In the previous phase II APACH1 study, we showed that second-line FCH PET/CT led to a cure in 88% of patients with negative or inconclusive MIBI SPECT/CT. BCE could be avoided in 75% of patients and surgical complication rates were low. We therefore hypothesize that upfront FCH PET/CT would improve patient care in PHPT and that the reduction in clinical costs would offset the increase in imaging costs., Trial Registration: NCT04040946 , registered August 1, 2019.  Protocol version Version 2.1 dated from 2020/04/23.

Background: In patients with differentiated thyroid cancer (DTC), tumor burden of persistent disease (PD) is a variable that could affect therapy efficiency. Our aim was to assess its correlation with the 2015 American Thyroid Association (ATA) risk-stratification system, and its impact on response to initial therapy and outcome., Methods: This retrospective cohort study included 618 consecutive DTC patients referred for postoperative radioiodine (RAI) treatment. Patients were risk-stratified using the 2015 ATA guidelines according to postoperative data, before RAI treatment. Tumor burden of PD was classified into three categories, i.e. very small-, small- and large-volume PD. Very small-volume PD was defined by the presence of abnormal foci on post-RAI scintigraphy with SPECT/CT or 18 FDG PET/CT without identifiable lesions on anatomic imaging. Small- and large-volume PD were defined by lesions with a largest size < 10 or ≥ 10 mm respectively., Results: PD was evidenced in 107 patients (17%). Mean follow-up for patients with PD was 7 ± 3 years. The percentage of large-volume PD increased with the ATA risk (18, 56 and 89% in low-, intermediate- and high-risk patients, respectively, p < 0.0001). There was a significant trend for a decrease in excellent response rate from the very small-, small- to large-volume PD groups at 9-12 months after initial therapy (71, 20 and 7%, respectively; p = 0.01) and at last follow-up visit (75, 28 and 16%, respectively; p = 0.04). On multivariate analysis, age ≥ 45 years, distant and/or thyroid bed disease, small-volume or large-volume tumor burden and 18 FDG-positive PD were independent risk factors for indeterminate or incomplete response at last follow-up visit., Conclusions: The tumor burden of PD correlates with the ATA risk-stratification, affects the response to initial therapy and is an independent predictor of residual disease after a mean 7-yr follow-up. This variable might be taken into account in addition to the postoperative ATA risk-stratification to refine outcome prognostication after initial treatment.

Background: 18 FDG PET/CT is crucial before neck surgery for nodal recurrence localization in iodine-refractory differentiated or poorly differentiated thyroid cancer (DTC/PDTC). A dedicated head-and-neck (HN) acquisition performed with a thin matrix and point-spread-function (PSF) modelling in addition to the whole-body PET study has been shown to improve the detection of small cancer deposits. Different protocols have been reported with various acquisition times of HN PET/CT. We aimed to compare two reconstruction algorithms for disease detection and to determine the optimal acquisition time per bed position using the Siemens Biograph6 with extended field-of-view., Methods: Twenty-one consecutive and unselected patients with DTC/PDTC underwent HN PET/CT acquisition using list-mode. PET data were reconstructed, mimicking five different acquisition times per bed position from 2 to 10 min. Each PET data set was reconstructed using 3D-ordered subset expectation maximisation (3D-OSEM) or iterative reconstruction with PSF modelling with no post filtering (PSF allpass ). These reconstructions resulted in 210 anonymized datasets that were randomly reviewed to assess 18 FDG uptake in cervical lymph nodes or in the thyroid bed using a 5-point scale. Noise level, maximal standard uptake values (SUVmax), tumour/background ratios (TBRs) and dimensions of the corresponding lesion on the CT scan were recorded. In surgical patients, the largest tumoral size of each lymph node metastasis was measured by a pathologist., Results: The 120 HN PET studies of the 12 patients with at least 1 18 FDG focus scored malignant formed the study group. Noise level significantly decreased between 2 and 4 min for both 3D-OSEM and PSF allpass reconstructions (p < 0.01). TBRs were similar for all the acquisition times for both 3D-OSEM and PSF allpass reconstructions (p = 0.25 and 0.44, respectively). The detection rate of malignant foci significantly improved from 2 to 10 min for PSF allpass reconstruction (20/26 to 26/26; p = 0.01) but not for 3D-OSEM (15/26 to 19/26; p = 0.26). For each of the five acquisition times, PSF allpass detected more malignant foci than 3D-OSEM (p < 0.01). In the seven surgical patients, PSF allpass evidenced smaller malignant lymph nodes than 3D-OSEM at 8 and 10 min. At 10 min, the mean size of the lymph node metastases neither detected with PSF allpass nor 3D-OSEM was 3 ± 0.6 mm vs 5.8 ± 1.1 mm for those detected with PSF allpass only and 10.9 ± 3.3 for those detected with both reconstructions (p < 0.001)., Conclusions: PSF allpass HN PET improves lesion detectability as compared with 3D-OSEM HN PET. PSF allpass with an acquisition time between 8 and 10 min provides the best performance for tumour detection.

We tested baseline positron emission tomography (PET)/computed tomography (CT) as a measure of total tumor burden to better identify high-risk patients with early-stage Hodgkin lymphoma (HL). Patients with stage I-II HL enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and interim PET (iPET2) after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. iPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale (DS). The prognostic value of TMTV was evaluated and compared with baseline characteristics, staging classifications, and iPET2. A total of 258 patients were eligible: 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 progression-free survival (PFS) and 12 overall survival (OS) events. TMTV was a prognosticator of PFS ( P < .0001) and OS ( P = .0001), with 86% and 84% specificity, respectively. Five-year PFS and OS were 71% and 83% in the high-TMTV (>147 cm 3 ) group (n = 46), respectively, vs 92% and 98% in the low-TMTV group (≤147 cm 3 ). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared with the current staging systems proposed by the European Organization for Research and Treatment of Cancer/Groupe d'Etude des Lymphomes de l'Adulte, German Hodgkin Study Group, or National Comprehensive Cancer Network. TMTV and iPET2 were independently prognostic and, combined, identified 4 risk groups: low (TMTV≤147+DS1-3; 5-year PFS, 95%), low-intermediate (TMTV>147+DS1-3; 5-year PFS, 81.6%), high-intermediate (TMTV≤147+DS4-5; 5-year PFS, 50%), and high (TMTV>147+DS4-5; 5-year PFS, 25%). TMTV improves baseline risk stratification of patients with early-stage HL compared with current staging systems and the predictive value of early PET response as well., (© 2018 by The American Society of Hematology.)

Background: False-positive radioiodine (RAI) uptake related to chronic sinusitis and mucocele has only rarely been reported in patients with differentiated thyroid cancer (DTC) even with the recent use of single photon emission tomography with computed tomography (SPECT/CT) acquisition. No other etiology of sinus RAI uptake has been mentioned to date., Objectives: We report five cases of DTC patients with sinus RAI uptake on post-RAI scintigraphy. SPECT/CT clearly localized RAI uptake either in the sphenoid, the maxillary or the frontal sinus and highly suspected mucosal thickening in four patients and sinus aspergilloma in one patient., Conclusion: These data confirm the possibility of false-positive sinus RAI uptake, provide a new cause of such benign uptake, i.e. sinus aspergilloma, and demonstrate the clinical relevance of head and neck SPECT/CT acquisition in the diagnosis of such uptake. Nuclear medicine physicians should be aware of this pitfall when interpreting post-RAI scintigraphy.

Objectives: 18F-FDG-PET/CT is a useful tool used to evidence persistent/recurrent disease (PRD) in patients with differentiated thyroid cancer and iodine-refractory lesions. The aim of this study was to compare the diagnostic value at the cervical level of the routine whole-body (WB) acquisition and that of a complementary head and neck (HN) acquisition, performed successively during the same PET/CT study., Methods: PET/CT studies combining WB and HN acquisitions performed in 85 consecutive patients were retrospectively reviewed by two nuclear medicine physicians. 18F-FDG uptake in cervical lymph nodes (LN) or in the thyroid bed was assessed. Among the 85 patients, the PET/CT results of the 26 who subsequently underwent neck surgery were compared with surgical and pathological reports. The size of each largest nodal metastasis was assessed by a pathologist., Results: In the 85 patients, inter-observer agreement was excellent for both WB and HN PET/CT interpretation. Of the 26 patients who underwent surgery, 25 had pathology proven PRD in the neck. Of these 25 patients, 15 displayed FDG uptake on either WB or HN PET. In these 15 patients, HN PET detected more malignant lesions than WB PET did (21/27 = 78% vs. 12/27 = 44%, P = 0.006). Node/background ratios were significantly higher on HN than on WB PET (P<0.0001). Three false-negative studies (20%) on WB PET were upstaged as true-positive on HN PET. The mean size of the largest LN metastasis was 3 mm for the LN detected neither on WB nor on HN PET, 7 mm for the metastasis detected on HN but not on WB PET, and 13 mm for those detected on both acquisitions (P = 0.0004). Receiver-Operating Characteristic analysis showed that area under the curve was higher for HN PET than for WB PET (0.97 [95%CI, 0.90-0.99] vs 0.88 [95%CI, 0.78-0.95], P = 0.009)., Conclusions: HN acquisition improves the ability to detect PRD in the neck compared with WB acquisition alone. We recommend systematically adding an HN acquisition when PET/CT is performed to detect PRD in the neck., Competing Interests: The authors have declared that no competing interests exist.

Context: The impact of microscopic nodal involvement on the risk of persistent/recurrent disease (PRD) remains controversial in patients with papillary thyroid carcinoma (PTC)., Objective: The goal of the study was to assess the risk of PRD and the 4-year outcome in PTC patients according to their initial nodal status [pNx, pN0, pN1 microscopic (cN0/pN1) or pN1 macroscopic (cN1/pN1)]., Design: We conducted a retrospective cohort study., Patients: The study included 305 consecutive PTC patients referred for radioiodine ablation from 2006 to 2011., Main Outcome Measure: We evaluated the risk of structural PRD and the disease status at the last follow-up. At ablation, persistent disease was consistently assessed by using post-radioiodine ablation scintigraphy combining total body scan and neck and thorax single-photon computed tomography-computed tomography (SPECT-CT) acquisition., Results: Of 305 patients, 128 (42%) were pNx, 84 (28%) pN0, 44 (14%) pN1 microscopic, and 49 (16%) pN1 macroscopic. The 4-year cumulative risk of PRD was higher in pN1 macroscopic than in pN1 microscopic patients (49% vs 24%, P = .03), and higher in pN1 microscopic than in pN0 (12%, P = .01) or pNx patients (6%, P < .001). On multivariate analysis, tumor size of 20 mm or greater [relative risk (RR) 3.4; P = .0001], extrathyroid extension (RR 2.6; P < .003), pN1 macroscopic (RR 4.5; P < .0001), and pN1 microscopic (RR 2.5; P < .02) were independent risk factors for PRD. At the last visit, the proportion of patients with no evidence of disease decreased from pNx (98%), pN0 (93%), and pN1 microscopic (89%) to pN1 macroscopic patients (70%) (P < .0001, Cochran-Armitage trend test). Extrathyroid extension (odds ratio 9.7; P < .0001) and N1 macroscopic (OR 4.9; P < .001) independently predicted persistent disease at the last visit, but N1 microscopic did not., Conclusions: PATIENTS with microscopic lymph node involvement present an intermediate outcome between that observed in pN0-pNx patients and pN1 macroscopic patients. These data may justify modifications to the risk recurrence staging systems.

Background: The objective of this study is to investigate the feasibility and the additional interest of a parametric imaging (PI) method to monitor the early tumour metabolic response in a prospective series of oesophageal cancer patients who underwent positron emission tomography with fluoro-2-deoxy-d-glucose (FDG-PET/CT) before and during curative-intent chemo-radiotherapy., Methods: Fifty-seven patients with squamous cell carcinoma (SCC) of the oesophagus prospectively underwent FDG-PET/CT before chemo-radiotherapy (CRT) (PET1) and at 21 ± 3 days after the beginning of CRT (PET2). The outcome was assessed at 3 months and 1 year after the completion of CRT (clinical examination, CT scan or FDG-PET/CT, biopsy). For each patient, PET1 and PET2 were registered using CT images. The 2 PET image sets were subtracted, so the voxels with significant changes in FDG uptake were identified. A model-based analysis of this graph was used to identify the tumour voxels in which significant changes occurred between the two scans and yielded indices characterising these changes (green and red clusters). Quantitative parameters were compared with clinical outcome at 3 months and at 1 year., Results: The baseline tumour FDG uptake decreased significantly at PET2 (p < 0.0001). The tumour volume significantly decreased between PET1 and PET2 (p < 0.02). The initial functional volume of the lesion (TV1) was significantly lower (p < 0.02) in patients in clinical response (CR) at 3 months and 1 year. The volume of the lesion during the treatment (TV2) was significantly lower in patients identified as in CR at 3 months (p < 0.03), but did not predict the outcome at 1 year. Multivariate analyses of outcome at 3 months showed that the risk of failure/death increased with younger age (p = 0.001), larger metabolic volume on PET1 (p = 0.009) and larger volume with decreased FDG uptake (p = 0.047). As for outcome at 1 year, the risk of failure/death increased with younger age (p = 0.006), nodal involvement (p = 0.08) and larger volumes with increased uptake (p = 0.03)., Conclusion: A parametric method to assess tumour response on serial FDG-PET performed during chemo-radiotherapy was evaluated. Early metabolic changes, i.e. variations in FDG uptake, provided additional prognostic information in multivariate analyses ClinicalTrials.gov NCT 00934505., Trial Registration: Current Controlled Trials ISRCTN7824458.

Context: Treatment modalities for progressive iodine-refractory poorly differentiated thyroid carcinomas are not yet well defined. Molecular targeted therapy with multikinase inhibitors has recently shown promising results, and cytotoxic chemotherapy is generally considered of low efficacy., Objective: We report the case of a 57-yr-old woman with an advanced iodine-refractory poorly differentiated thyroid cancer who was treated sequentially between October 2006 and March 2011 with two different regimens of cytotoxic chemotherapy and three lines of multikinase inhibitors., Methods: Efficacy and adverse effects of the consecutive treatment modalities, i.e. vandetanib, doxorubicin-cisplatin combination, sorafenib, paclitaxel-carboplatin combination, and sunitinib, are reported., Results: The patient presented a complete tumor response to a doxorubicin-cisplatin combination lasting 10 months and to a paclitaxel-carboplatin regimen lasting 5 months and had no or limited response to kinase inhibitors, i.e. progression after 3 months of vandetanib, progression after 4 months of sorafenib, and stable disease for 8 months with sunitinib treatment., Conclusions: When tumor progresses with kinase inhibitors, cytotoxic chemotherapy may be an alternative in selected cases of advanced iodine-refractory poorly differentiated thyroid cancer. For those rare cases, clinical management should benefit from a multidisciplinary team approach through specialized networks.

Unlabelled: The prognosis of medullary thyroid carcinoma (MTC) varies from long- to short-term survival based on such prognostic factors as serum calcitonin and carcinoembryonic antigen (CEA) doubling times (DTs). This prospective phase II multicenter trial evaluated the efficacy and safety of anti-CEA pretargeted radioimmunotherapy (pRAIT) in rapidly progressing metastatic MTC patients and also how serum biomarker DTs correlate with clinical outcome., Methods: From June 2004 to January 2008, 42 patients were treated with anti-CEA × anti-diethylenetriaminepentaacetic acid (DTPA) bispecific antibody (hMN-14 × m734) (40 mg/m(2)), followed by (131)I-di-DTPA-indium bivalent hapten (1.8 GBq/m(2)) 4-6 d later., Results: The disease control rate (durable stabilization plus objective response) was 76.2%. Grade 3-4 hematologic toxicity was observed in 54.7% of patients and myelodysplastic syndrome in 2, including 1 heavily treated previously. After pRAIT, 21 of 37 assessed patients (56.7%) showed a significant impact on DT (≥100% increase of pre-pRAIT calcitonin or CEA DT or prolonged decrease of the biomarker concentration after pRAIT). Pre-pRAIT DT and post-pRAIT DT were significant independent predictors for overall survival (OS) from pRAIT (pre-pRAIT: hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24-0.86; P = 0.016; and post-pRAIT: HR, 5.32; 95% CI, 1.63-17.36; P = 0.006) and OS from diagnosis (pre-pRAIT: HR, 0.21; 95% CI, 0.08-0.51; P = 0.001; and post-pRAIT: HR, 6.16; 95% CI, 1.81-20.98; P = 0.004)., Conclusion: pRAIT showed antitumor activity, with manageable hematologic toxicity in progressive MTC. Increased biomarker DT after treatment correlated with increased OS.

Objectives: Sperm-associated antigen 9 (SPAG9) has been suggested as a possible biomarker in several malignancies including thyroid cancer. We investigated the expression of SPAG9 mRNA in fine needle aspiration (FNA) material from papillary thyroid carcinoma (PTC) and benign thyroid nodules., Study Design: SPAG9 expression was assessed in 36 FNA samples corresponding to 16 PTC and 20 benign nodules using the original method detecting the SPAG9 transcript containing intron 21 (NCBI X91879). The presence of the BRAF V600E point mutation was also analyzed by pyrosequencing., Results: Six of 16 (38%) PTC samples were positive for X91879 SPAG9 transcript compared to 8 of 20 (40%) benign samples (p = 0.88). Out of 12 BRAF-positive PTC, 3 (25%) also expressed the SPAG9 transcript compared to 3 out of 4 BRAF-negative PTC (75%; p = 0.12)., Conclusions: The X91879 SPAG9 transcript originally described does not appear to be overexpressed in FNA material from PTC or to be clinically relevant in the diagnosis of thyroid nodules.

Background: To assess 18-fluorodeoxyglucose (FDG) bowel uptake in patients with differentiated thyroid cancer (DTC) treated with sorafenib., Findings: Visual (5-point scale) and high maximum standard uptake value (SUVmax) semi-quantitative analyses were conducted in 63 positron emission tomography (PET) studies performed in patients on sorafenib (group 1, n = 20), in a control group (group 2, n = 28) and in patients on sunitinib or vandetanib (group 3, n = 15).Moderate or high and diffuse bowel uptake (grade 4 or 5) was observed in 90% of the PET scans of group 1 versus none in group 2. Only 20% of PET scans in group 3 were scored grade 4. SUVmax values were significantly higher for all colic segments in group 1 than in group 2 (P < 0.0001) or 3 (P < 0.0004). This uptake pattern appeared rapidly (one month) and disappeared after sorafenib withdrawal., Conclusions: FDG uptake is increased in the colon of DTC patients treated by sorafenib.

The prognostic value of interim positron emission tomography (PET) interpreted according to visual criteria is a matter of debate in diffuse large B-cell lymphoma (DLBCL). Maximal standardized uptake value reduction (ΔSUVmax) may better predict outcome. To compare the prognostic value of both methods, we analyzed PET done at baseline (PET0) and after 2 (PET2) and 4 (PET4) cycles in 85 patients with high-risk DLBCL enrolled on a prospective multicenter trial. All images were centrally reviewed and interpreted visually according to the International Harmonization Project criteria and by computing ΔSUVmax between PET0 and PET2 (ΔSUVmaxPET0-2) or PET4 (ΔSUVmaxPET0-4). Optimal cutoff to predict progression or death was 66% for ΔSUVmaxPET0-2 and 70% for ΔSUVmaxPET0-4. Outcomes did not differ significantly whether PET2 and PET4 were visually positive or negative. Inversely, ΔSUVmaxPET0-2 analysis (> 66% vs ≤ 66%) identified patients with significantly different 2-year progression-free survival (77% vs 57%; P = .0282) and overall survival (93% vs 60%; P < .0001). ΔSUVmaxPET0-4 analysis (> 70% vs ≤ 70%) seemed even more predictive for 2-year progression-free survival (83 vs 40%; P < .0001) and overall survival (94% vs 50%; P < .0001). ΔSUVmax analysis of sequential interim PET is feasible for high-risk DLBCL and better predicts outcome than visual analysis. The trial was registered at http://clinicaltrials.gov as NCT00498043.

Context: In patients with differentiated thyroid carcinoma, postablation (131)I scintigraphy aims to detect residual neck disease and distant metastases, usually found in lungs and bones. New hybrid single-photon emission computed tomography/computed tomography (SPECT-CT) cameras that permit functional and anatomical image fusion may improve its clinical relevance., Objective: Our objective was to test the added value of neck and thorax SPECT-spiral CT to whole-body scan (WBS) in postablation (131)I scintigraphy., Design and Setting: This was a single-referral-center prospective study with a median follow-up of 21 months., Patients and Methods: Postablation (131)I WBS and neck and thorax SPECT-CT were performed in 55 consecutive patients treated in 2006. WBS and SPECT-CT data were blindly reviewed, scored negative (benign), positive (malignant), or indeterminate and were correlated to the patient outcome., Results: At patient level, WBS and SPECT-CT were negative in 67 and 78% of patients, positive in 4 and 15%, and indeterminate in 29 and 7%, respectively. Overall, nine patients (16%) presented treatment failure (persistent or recurrent disease) 1-16 months after radioiodine ablation. In the 16 patients with indeterminate WBS, negative SPECT-CT ruled out suspicion of disease in nine of nine patients, and positive SPECT-CT confirmed malignant lesions in four of five patients. Positive SPECT-CT predicted treatment failure better than positive WBS (McNemar's test, P = 0.03)., Conclusions: This study demonstrates the complementary role of neck and thorax SPECT-CT to WBS in postablation (131)I scintigraphy. Because SPECT-CT allows one to confirm or to rule out residual disease in most cases where WBS remains indeterminate, we recommend its use when available.

Unlabelled: Radiation is known to be mutagenic. The present study updates a 10-y-old study regarding pregnancy outcome and the health of offspring of women previously exposed to radioiodine ((131)I) during thyroid carcinoma treatment, by doubling the number of pregnancies that occurred after exposure., Methods: Data on 2,673 pregnancies were obtained by interviewing female patients who were treated for thyroid carcinoma but had not received significant external radiation to the ovaries., Results: The incidence of miscarriages was 10% before any treatment for thyroid cancer; this percentage increased after surgery for thyroid cancer, both before (20%) and after (19%) (131)I treatment, with no variation according to the cumulative dose. In contrast to previously reported data, miscarriages were not significantly more frequent in women treated with radioiodine during the year before conception, not even in women who had received more than 370 MBq during that year. The incidences of stillbirths, preterm births, low birth weight, congenital malformations, and death during the first year of life were not significantly different before and after (131)I therapy. The incidences of thyroid and nonthyroid cancers were similar in children born either before or after the mother's exposure to radioiodine., Conclusion: There is no evidence that exposure to radioiodine affects the outcomes of subsequent pregnancies and offspring. The question as to whether the incidences of malformations and thyroid and nonthyroid cancers are related to gonadal irradiation remains to be established. The doubling dose is still being heatedly debated, and the value of 1 Gy as the doubling dose in humans should be reevaluated.

Context: Patients with progressive medullary thyroid carcinoma (MTC) undergo multiple imaging procedures for diagnosis of relapse and staging., Objective: Our objective was to assess the sensitivity and prognostic value of 18F-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT), and the imaging sensitivity of pretargeted iodine-131-radioimmunotherapy (RIT) in patients with progressive MTC., Design/setting/patients: We performed a prospective multicenter study in high-risk patients with rapidly progressing MTC enrolled in a phase-II pretargeted RIT study, as documented by short serum calcitonin (Ct) or carcinoembryonic antigen (CEA) doubling time (DT). INTERVENTIONS/MAIN OUTCOME MEASURES: Patients underwent neck-thoracic-abdominal CT, spine and pelvic magnetic resonance imaging, whole-body post-RIT immunoscintigraphy (IS) with iodine-131, and whole-body 18F-FDG-PET/CT imaging. Imaging sensitivity and the correlation between FDG uptake and biomarkers DT were evaluated., Results: A total of 33 patients with mean CEA and Ct DTs of 1.90 yr (range 0.21-8.50) and 1.52 yr (range 0.09-6.01), respectively, were evaluated. Sensitivity of FDG-PET/CT was 83% for neck, 85% for mediastinal, 75% for lung, 60% for liver, and 67% for bone metastases; overall sensitivity was 76%. Median standardized uptake value (SUVmax) was 5.23 (2.06-13.90). SUVmax correlated significantly with Ct DT (P = 0.011) and minimal DT (minimal value between CEA DT and Ct DT) (P = 0.027). Overall sensitivity of post-RIT IS, CT, and bone magnetic resonance imaging were 94, 74, and 85%, respectively., Conclusions: These results demonstrate the value of FDG-PET/CT for staging of patients with progressive MTC, especially in the neck and mediastinum, with possible prognostication by SUV quantification. Post-RIT IS was the most sensitive of the imaging modalities studied prospectively.

Sixty-one heterozygotes harboring the germline V804L mutation of the RET protooncogene were identified in five independent families. A total of 31 subjects underwent surgery. Histology identified C cell hyperplasia in 30 cases, isolated in 12 and associated with medullary thyroid carcinoma (MTC) in 18. Six patients with MTC had lymph node metastases. Among the 14 patients with basal detectable calcitonin (CT) level, 12 had MTC and 2 had isolated C cell hyperplasia. In most individuals carrying 804 RET mutation, C cell disease displayed late onset and an indolent course; a pentagastrin test was negative in the majority of heterozygotes during the first 2 decades and was positive in only half of them during the third and fourth decades of life. Interestingly, concomitant somatic M918T was detected in a 12-yr-old girl with MTC and was likely to be responsible for both the early clinical appearance and the aggressiveness of the disease. Our data show that in these gene carriers, surgery may be postponed to the fourth decade of life or until the pentagastrin stimulation test becomes positive. Indeed, our data should be confirmed on a larger series of V804L carriers, but may offer a balanced strategy to keep under control and prevent development of the full disease phenotype.

The toxicity and therapeutic efficacy of escalating doses of anti-carcinoembryonic antigen x anti-N alpha-(diethylenetriamine-N,N,N',N''-tetraacetic acid)-In bispecific monoclonal antibody (F6-734) and iodine 131-labeled bivalent hapten were determined in a Phase I/II trial. A total of 26 patients with recurrences of medullary thyroid cancer documented by imaging and a rise in serum thyrocalcitonin were enrolled. Twenty to 50 mg of F6-734 and 40-100 mCi of 131I-hapten were injected 4 days apart. Quantitative scintigraphy was performed after the second injection for dosimetry estimations in eight cases. Clinical, biological, and morphological follow-up was carried out for 1 year after treatment. The mean percentage of injected activity per gram of tumor at the time of maximum uptake was 0.08% (range, 0.003-0.26%). The tumor biological half-life ranged from 3 to 95 days, and tumor doses ranged from 2.91 to 184 cGy/mCi. The estimated tumor-to-nontumor dose ratios were 43.8 x 53.4, 29.6 x 35.3, 10.9 x 13.6, and 8.4 x 10.0 for total body, red marrow, liver, and kidney, respectively. Grade III/IV hematological toxicity was observed in seven patients, most of them with bone metastases. Among the 17 evaluable patients, 4 pain reliefs, 5 minor tumor responses, and 4 biological responses with decrease of thyrocalcitonin were observed. Nine patients developed human anti-mouse antibody. Dose-limiting toxicity was hematological, and maximum tolerated activity was 48 mCi/m2 in this group of patients, most of whom had suspected bone marrow involvement. The therapeutic responses observed in patients mainly with a small tumor burden are encouraging for the performance of a Phase II trial with minimal residual disease.

Unlabelled: The purpose of this study was to estimate the dose delivered to tumor targets and normal tissues after two-step injection of an anti-CEA/anti-DTPA-In (F6-734) bispecific antibody and a 131I-labeled di-DTPA in-TL bivalent hapten in patients with medullary thyroid carcinoma (MTC) and small-cell lung cancer (SCLC)., Methods: Five patients with persistent disease or recurrences of MTC and five patients with primary SCLC or relapse were studied. In a first step, 0.1 to 0.3 mg/kg of F6-734 bispecific antibody was injected intravenously. Four days later, 6 nmole (5.8 to 9.8 mCi) of 131I-labeled di-DTPA in-TL bivalent hapten were injected. Quantitative imaging was performed during one week after the second injection., Results: All 5 patients with MTC showed positive immunoscintigraphy (IS). In the smallest visualized and resected tumor (0.8 g), the fraction of injected activity per gram (% ID/g) was 0.1% at Day 3. IS was positive in 4 of the 5 patients with SCLC. The volume of the smallest visualized SCLC tumor was estimated at 11 +/- 2 ml, and tumor uptake was about 0.009% ID/g. Tumor dose estimates ranged from 4.2 to 174 cGy/mCi in patients with MTC and from 1.7 to 8 cGy/mCi in patients with SCLC., Conclusion: High absorbed dose values were calculated for small MTC recurrences. For SCLC recurrences the values were smaller but in the same range as those obtained by other investigators with the one-step technique in lymphoma.