Pilot Feasibility Study: 18 F-DPA-714 PET/CT Macrophage Imaging in Triple-Negative Breast Cancers (EITHICS).

ABSTRACT: Tumor-associated macrophages are targets of interest in triple-negative breast cancer (TNBC). The translocator protein 18 kDa (TSPO) is a sensitive marker for macrophages and holds potential relevance in TNBC stratification. This pilot prospective study (EITHICS, NCT04320030) aimed to assess the potential of TSPO PET/CT imaging using 18 F-DPA-714 in primary TNBC, compared with immunohistochemistry, autoradiography, and TSPO polymorphism. PATIENTS AND METHODS: Thirteen TNBC patients were included. They underwent TSPO genotyping (HAB, MAB, LAB), 18 F-FDG PET/CT, and breast MRI. Semiquantitative PET parameters were computed. VOIs were defined on the tumor lesion, healthy breast tissue, and pectoral muscle to obtain SUV, tumor-to-background ratio (TBR), and time-activity curves (TACs). Additionally, immunohistochemistry, 3 H-DPA-714, and 3 H-PK-11195 autoradiography were conducted. RESULTS: The majority of TNBC tumors (11/13, 84%) had a preponderance of M2-polarized macrophages with a median proportion of 82% (range, 44%-94%). 18 F-DPA-714 PET/CT clearly identified TNBC tumors with an excellent TBR. Three distinct patterns of 18 F-DPA-714 TACs were identified, categorized as "above muscular," "equal to muscular," and "below muscular" with reference to the muscular background. For the "above muscular" group (2 HAB and 2 MAB), "equal muscular" group (3 HAB, 3 MAB, and 1 LAB), and "below muscular" group (1 LAB and 1 MAB), tumor TACs showed a 18 F-DPA-714 accumulation slope of 1.35, 0.62, and 0.22, respectively, and a median SUV mean of 4.02 (2.09-5.31), 1.66 (0.93-3.07), and 0.61 (0.43-1.02). CONCLUSIONS: This study successfully demonstrated TNBC tumor targeting by 18 F-DPA-714 with an excellent TBR, allowing to stratify 3 patterns of uptake potentially influenced by the TSPO polymorphism status. Further studies in larger populations should be performed to evaluate the prognostic value of this new biomarker.

Between Pathological Prostate Cancer Lymph Nodes and Sentinel Nodes: Which Information Is the Leader?

PURPOSE: On the basis of the concept of sentinel lymph node biopsy (SLNB), SLNs should contain decisive information for clinical outcomes. In localized prostate cancer patients, this study assessed retrospectively clinical outcome after radical laparoscopic prostatectomy associated with SLNB and extensive pelvic lymph node dissection. METHODS: A total of 231 consecutive patients of intermediate to high risk were analyzed. Recurrence-free survival (RFS) was assessed with Kaplan-Meier curves. Various pathological parameters were analyzed using univariable and multivariable analyses through Cox regression analysis. The study was approved and registered under 2007-R41. RESULTS: The median follow-up was 7.1 years (95% confidence interval, 6.6-7.5). In total, 38/231 (16.5%) patients were pN1. Of these 38 patients, 27 had only SLN involvement (SLNI), 10 patients had both SLN and non-SLNI, and 1 patient had isolated non-SLNI, indicating a false-negative (FN). If the updated Briganti nomogram threshold set at >7% for recommending extensive pelvic lymph node dissection had been applied to these patients, we would have missed 44% (12/27) of patients with SLNI and 50% (5/10) of patients with SLNI and non-SLNI, as well as the FN patient. At the time of final follow-up, 84/231 (36.5%) patients had recurrence. In multivariable analysis, and regarding node status, the most significant prognostic factor was SLN with macrometastases and/or micrometastases, respectively, P = 10-3 and P < 10-3. No more information was obtained with non-SLN status. Probabilities of RFS between negative and positive SLN patients presented a major significant difference (P < 10-15) with a risk of event 8.75 times more frequent if SLN was involved than if it was metastasis-free. CONCLUSIONS: SLNB seems to contain decisive information for the clinical outcome of patients with localized intermediate- and high-risk prostate cancer patients. The question raised is thus whether immediate additional postoperative treatment should be offered to patients with metastatic SLN.

3D Matrices for Enhanced Encapsulation and Controlled Release of Anti-Inflammatory Bioactive Compounds in Wound Healing.

Current trends in the development of wound dressings are oriented towards the use of biopolymer-based materials, due to their unique properties such as non-toxicity, hydrophilicity, biocompatibility and biodegradability, properties that have advantageous therapeutic characteristics. In this regard, the present study aims to develop hydrogels based on cellulose and dextran (CD) and to reveal their anti-inflammatory performance. This purpose is achieved by incorporating plant bioactive polyphenols (PFs) in CD hydrogels. The assessments include establishing the structural characteristics using attenuated total reflection Fourier transformed infrared (ATR-FTIR) spectroscopy, the morphology by scanning electron microscopy (SEM), the swelling degree of hydrogels, the PFs incorporation/release kinetics and the hydrogels' cytotoxicity, together with evaluation of the anti-inflammatory properties of PFs-loaded hydrogels. The results show that the presence of dextran has a positive impact on the hydrogel's structure by decreasing the pore size at the same time as increasing the uniformity and interconnectivity of the pores. In addition, there is an increased degree of swelling and of the encapsulation capacity of PFs, with the increase of the dextran content in hydrogels. The kinetics of PFs released by hydrogels was studied according to the Korsmeyer-Peppas model, and it was observed that the transport mechanisms depend on hydrogels' composition and morphology. Furthermore, CD hydrogels have been shown to promote cell proliferation without cytotoxicity, by successfully culturing fibroblasts and endothelial cells on CD hydrogels (over 80% viability). The anti-inflammatory tests performed in the presence of lipopolysaccharides demonstrate the anti-inflammatory properties of the PFs-loaded hydrogels. All these results provide conclusive evidence on the acceleration of wound healing by inhibiting the inflammation process and support the use of these hydrogels encapsulated with PFs in wound healing applications.

Radioisotope-guided Lymphadenectomy for Pelvic Lymph Node Staging in Patients With Intermediate- and High-risk Prostate Cancer (The Prospective SENTINELLE Study).

PURPOSE: Our aim was to prospectively evaluate the diagnostic accuracy of sentinel lymph node biopsy-guided lymph node dissection compared to extended pelvic lymph node dissection in patients with intermediate- or high-risk prostate cancer. MATERIALS AND METHODS: We conducted a prospective, single-arm, multicenter study at 3 tertiary centers in France between February 2012 and May 2019. Eligible patients had clinically localized intermediate- or high-risk prostate cancer. After intraprostatic injection of (99m)Tc-nanocolloid, the locations of the sentinel lymph nodes were defined by preoperative lymphoscintigraphy. Surgical excision of the sentinel lymph nodes was performed using intraoperative gamma probe guidance. After resection of the sentinel lymph nodes, extended pelvic lymph node dissection was performed in all patients. We assessed the diagnostic accuracy of the sentinel lymph node biopsy method using extended pelvic lymph node dissection as the reference standard. This trial was registered in ClinicalTrials.gov (NCT02732392). RESULTS: A total of 162 men cN0M0 (CT scan and bone scan) were enrolled: 106 (65.4%) and 56 (34.6%) patients had intermediate- and high-risk prostate cancer, respectively. The median number of nodes retrieved was 14 (mean 16, IQR 10-21) per patient. At final pathological analysis, 22 patients (13.6%) were pN+. Sensitivity, specificity, negative predictive value, and positive predictive value of sentinel lymph node biopsy method in detecting patients with at least 1 lymph node metastasis were 95.4% (95% CI, 75.1-99.7), 100% (95% CI, 96.6-100), 99.2% (95% CI, 95.5-99.9), and 100% (95% CI, 80.7-100), respectively. CONCLUSIONS: Our multicenter prospective study supports that sentinel lymph node biopsy is a very effective and sensitive method for pelvic lymph node staging in patients with intermediate- or high-risk localized prostate cancer.

Ganglioneuroma of the Bladder in Association with Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a genetic disease, with autosomal dominant transmission, related to pathogenic variant of the tumor suppressor gene NF1 (17q11.2), predisposing affected subjects to a variety of benign (neurofibromas and plexiform neurofibromas) and malignant tumors. The lack of the NF1-neurofibromin gene product can cause uncontrolled cell proliferation in the central or peripheral nervous system and multisystemic involvement, and so the disease includes a heterogeneous group of clinical manifestations. Ganglioneuromas are benign tumors developing from the neural crest cells of the autonomic nervous system, considered to be part of neuroblastic tumors. Bladder localization is extremely rare in adults, and only three such cases were reported in children so far. The aim of our study, in addition to a brief review of the literature of these pathologies, is to bring to your attention the case of a sixteen year old patient with a very rare association of NF1 and bladder ganglioneuroma, who presented at the hospital with gross hematuria. Since bladder ganglioneuroma is a rare pathological condition, the differential diagnosis is difficult and imaging investigations and pathological investigations are the ones that elucidate this disease. The clinical approach of the medical multidisciplinary team involved should help the patient in managing her medical and surgical situation.

Vaccine-Related Lymph Nodes: The Emerging Pitfalls of 18F-Fluorocholine and 68Ga-PSMA-11 PET/CT in the Era of COVID-19 Vaccination.

PURPOSE: Vaccination against coronavirus disease 2019 (COVID-19) is currently under worldwide deployment. The consequences of this vaccination can be seen in radiology and nuclear medicine explorations with visualization of axillary lymph nodes (LNs), as observed on ultrasonography, MRI, or 18F-FDG PET/CT.We aimed to evaluate on PET/CT the incidence of vaccine-related LNs and their characteristics after COVID-19 vaccination, using several radiopharmaceuticals different from 18F-FDG. PATIENTS AND METHODS: Between February and July 2021, all consecutive patients undergoing a whole-body PET/CT for any indication using a different radiopharmaceutical from 18F-FDG were eligible for inclusion if they had received at least 1 dose of the COVID-19 vaccine. The radiopharmaceutical administered and vaccine type were recorded for each patient. The incidence of positive vaccine-related axillary and supraclavicular LNs on PET/CT was our primary finding, along with the nodes characteristics. Statistical analyses were performed for patients with prostate cancer (PCa) to determine certain interaction factors that were associated with the detection of vaccine-related LNs. RESULTS: Of the 226 patients in our cohort study, 120 patients underwent an 18F-fluorocholine PET/CT, 79 a 68Ga-PSMA-11 PET/CT, 6 an 18F-FDOPA PET/CT, and 21 a 68Ga-DOTATOC PET/CT. A total of 67.3% of patients (152/226) received BNT162b2mRNA (Pfizer-BioNTech), 26.5% (60/226) ChAdOx1-S (AstraZeneca), 4.9% (11/226) mRNA-1273 (Moderna), and 1.3% (3/226) Ad26.COV2.S (Janssen). The incidence of positive vaccine-related axillary and supraclavicular LNs was 42.5% (51/120 patients) on PET/CT using 18F-fluorocholine and 12.7% (10/79 patients) with 68Ga-PSMA-11. None of our patients undergoing 18F-FDOPA or 68Ga-DOTATOC PET/CT presented any vaccine-related lymphadenopathy. Vaccine-related LNs were statistically associated with the nature of the radiopharmaceutical (P < 10-4), with the number of vaccine doses received (P = 0.041), with a short delay between vaccination and PET/CT realization (P < 10-5), and with a higher prostate-specific antigen level for patients with PCa (P = 0.032), but not with age or vaccine type. The vaccine-related nodes appeared in 85% of the cases, in the 30 days after vaccine injection, were limited in size and uptake, and were most often limited to the axilla level 1 area. CONCLUSIONS: Detecting positive LNs after COVID-19 vaccination is not an exclusive 18F-FDG PET/CT pattern but is common on 18F-fluorocholine and possible on 68Ga-PSMA-11 PET/CT. Confronting PET/CT findings with clinical data (such as date and site of injection) seems essential in the current pandemic context, just as it does for the radiopharmaceuticals used in PCa to avoid PET/CT misinterpretation and incorrect patient treatment. For 18F-FDOPA or 68Ga-DOTATOC PET/CT, this seems to have a lesser impact.

Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.

BACKGROUND: In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits. METHODS: In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization. RESULTS: Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported. CONCLUSIONS: In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).

COVID-19 vaccination may cause FDG uptake beyond axillary area.

BACKGROUND: The vaccination immune response may induce false-positive 18F-FDG PET/CT uptake. CASE PRESENTATION: An extended supraclavicular lymph nodal activation after coronavirus disease 2019 (COVID-19) vaccination revealed on 18F-FDG PET/CT mimics a Virchow nodule in a patient with medical history of well-differentiated appendicular adenocarcinoma. CONCLUSION: This case highlights a nodal activation beyond axillary area and the importance of documenting vaccination history at the time of scanning to avoid false-positive results.

A new sponge-type hydrogel based on hyaluronic acid and poly(methylvinylether-alt-maleic acid) as a 3D platform for tumor cell growth.

A new sponge-type hydrogel was obtained by cross-linking hyaluronic acid (HA) and poly(methylvinylether-alt-maleic acid) P(MVE-alt-MA) through a solvent-free thermal method. The sponge-type hydrogel was characterized and checked as a support for cell growth. The influence of concentration and weight ratio of polymers on the morphology and hydrogel stability was investigated. The total polymers concentration of 3% (w/w) and the weight ratio of 1:1 were optimal for the synthesis of a stable hydrogel (HA3P50) and to promote cell proliferation. The swelling measurements revealed a high-water absorption capacity of the hydrogel in basic medium. Diphenhydramine (DPH), lidocaine (Lid) and propranolol (Prop) were loaded within the hydrogel as a model drugs to investigate the ability of drug transport and release. In vitro studies revealed that HA3P50 hydrogel promoted the adhesion and proliferation of human hepatocellular carcinoma cell line HepG2, providing a good support for 3D cell culture to obtain surrogate tumor scaffold suitable for preclinical anti-cancer drug screening.

Predictive Value of HPV, p53, and p16 in the Post-Treatment Evolution of Malignant Tumors of the Oropharynx and Retromolar Trigone-Oropharynx Junction.

Background and objectives: Knowledge of the interactions and influences of infectious, genetic, and environmental factors on the evolution and treatment response of malignant tumors is essential for improving the management of the disease and increasing patient survival. The objective of this study was to establish the contribution of human papillomavirus (HPV), as well as p53 and p16 tumor markers, alongside associated factors (smoking and alcohol consumption), in the progression of malignancies located in the oropharynx and at the retromolar trigone-oropharyngeal junction. Materials and Methods: We performed a prospective study including 50 patients with malignant tumors of the oropharynx and retromolar trigone-oropharyngeal junction. In all patients, the presence and type of HPV were determined, as well as the status of the tumor markers p53 and p16. The associated risk factors, biopsy results, treatment method, and post-treatment evolution were all documented. Statistical analyses were performed to evaluate the correlations between the determining factors and their influence on the post-treatment evolution. An overall increased survival rate was found in HPV(+) patients. Results: Our study outlined the prevalence of different high-risk subtypes of HPV from the ones presented by other studies, suggesting a possible geographic variation. Correlations between the p53 and p16 statuses and patient survival could be established. The association of smoking and alcohol consumption strongly correlated with an unfavorable evolution. Conclusions: Awareness of the differences in the post-treatment evolution of the patients in relation to the presence of the factors determined in our study could change the future management of such cases for ensuring improved treatment outcomes.

Prognostic Impact of Pretherapeutic FDG-PET in Localized Anal Cancer.

Due to the heterogeneity of tumour mass segmentation methods and lack of consensus, our study evaluated the prognostic value of pretherapeutic positron emission tomography with fluorodeoxyglucose (FDG-PET) metabolic parameters using different segmentation methods in patients with localized anal squamous cell carcinoma (SCC). Eighty-one patients with FDG-PET before radiochemotherapy were retrospectively analyzed. Semiquantitative data were measured with three fixed thresholds (35%, 41% and 50% of Maximum Standardized Uptake Value (SUVmax)) and four segmentation methods based on iterative approaches (Black, Adaptive, Nestle and Fitting). Metabolic volumes of primary anal tumour (P-MTV) and total tumour load (T-MTV: P-MTV+ lymph node MTV) were calculated. The primary endpoint was event-free survival (EFS). Seven multivariate models were created to compare FDG-PET tumour volumes prognostic impact. For all segmentation thresholds, PET metabolic volume parameters were independent prognostic factor and T-MTV variable was consistently better associated with EFS than P-MTV. Patient's sex was an independent variable and significantly correlated with EFS. With fixed threshold segmentation methods, 35% of SUVmax threshold seemed better correlated with EFS and the best cut-off for discrimination between a low and high risk of event occurrence was 40 cm3. Determination of T-MTV by FDG-PET using fixed threshold segmentation is useful for predicting EFS for primary anal SCC. If these data are confirmed in larger studies, FDG-PET could contribute to individualized patient therapies.

Preliminary results of a 68 Ga-PSMA PET/CT prospective study in prostate cancer patients with occult recurrence: Diagnostic performance and impact on therapeutic decision-making.

BACKGROUND: In this prospective study (NCT03443609), we investigated the impact of 68Ga-PSMA-11 PET-CT on the treatment plan and therapeutic response obtained for patients with prostate cancer (PCa) presenting a recurrence with a low rising PSA. METHODS: One hundred thirty hormone-naive (PSA < 1.5 ng/mL) patients were enrolled. All patients received radical treatment. PET images were recorded 1 and 2 hours after injection of tracer and interpreted by two independent nuclear physicians. Six months after treatment ended, a PSA assay was requested to evaluate the therapeutic efficacy of the treatment based on PSMA results. RESULTS: Data analysis for the first 52 included patients has been completed. 68Ga-PSMA-11-positive lesions were detected in 38/52 (73.1%) patients. Ninety-four lesions were detected as follows, 53/94 in lymph nodes (56.4%), 25/94 in bone (26.6%), and 12/94 into the prostate bed (12.7%). Detection rates were 58%, 81%, and 82% for serum PSA levels lower than 0.25 ng/mL, between 0.25 to ≤ 0.69 ng/mL and 0.70 ng/mL, respectively. As a result of the PSMA PET-CT, therapeutic management changed in 38/52 patients (73.1%). Patients had undetectable serum PSA levels after treatment guided by 68Ga-PSMA-11 PET-CT results in 10/52 (19.2%) cases and with a PSA decrease of over 60% in 18/52 (34.6%) patients. CONCLUSION: Whilst our patient population presented a very low PSA level, preliminary results of the 68Ga-PSMA PET-CT study showed recurrence localization in more than half of the patients and this had a major clinical impact, as it resulted in treatment change in more than half of the patients and a significant decrease in PSA levels in a third of patients.

Better prediction for FGR (fetal growth restriction) with the sFlt-1/PIGF ratio: A case-control study.

The aim of this study was to check whether the sFlt-1/PIGF ratio, established as the biomarker for preeclampsia, reduces the false positive rate of late fetal growth restriction (FGR) detection by ultrasound biometry.This was a prospective case-control study, conducted at one regional maternity hospital in Romania. Study participants included singleton pregnancy women for whom the estimated fetal weight (EFW) at 28 to 35 weeks was < 10 percentiles and as controls, pregnant women with EFW >10 percentiles. All pregnancies were dated in the first trimester by crown-rump-length. We also recorded maternal characteristics, pregnancy and neonatal outcomes.The primary outcome measures were the relation between the sFlt-1/PIGF ratio and incidence of FGR. Secondary outcome was establishing a threshold for statistical significance of the marker and influence of other conditions (e.g., pre-eclampsia) on the accuracy of the marker in FGR prediction.Included in the study were 37 pregnant women and 37 controls.When we used ultrasound (US) biometry and maternal risk factors to estimate EFW <10 percentiles, the sensitivity was 44.4% with a specificity of 89% for an FPR (false positive result) of 10%. When we combined the US biometry and maternal risk factors with sFlt1/PIGF ratio, for a cut off of 38, the sensitivity was 84.21%, and the specificity was 84.31% for an FPR of 10%. The cut off value (36) did not change if we considered all cases of SGA, including those with associated preeclampsia or if we considered only FGR cases without associated preeclampsia.When associated with maternal factors and US biometry, the sFlt1/PIGF ratio enhanced the sensitivity for detecting late FGR.

68Ga-PSMA PET/CT Urachus Metastases in Recurrent Prostate Cancer With Very Low PSA Level.

Peritoneal carcinomatosis in prostate cancer is extremely rare and has been described in only few cases with high PSA level, androgen deprivation, or in symptomatic patients. To date, 2 cases of Ga-PSMA PET positive peritoneal metastases have been reported. We report a case of urachus metastases showed on Ga-PSMA PET/CT performed for biochemical recurrence with a very low PSA level at 0.50 ng/mL.

68Ga-PSMA-11 PET-CT study in prostate cancer patients with biochemical recurrence and non-contributive 18F-Choline PET-CT: Impact on therapeutic decision-making and biomarker changes.

BACKGROUND: In this retrospective study, we investigated the impact of 68 Ga-PSMA-11 PET-CT (PSMA PET-CT) upon the treatment plan and therapeutic response obtained for Prostate Cancer (PCa) patients presenting an occult biochemical recurrence. METHODS: Forty-two patients with previously negative or doubtful 18F-Choline (FCH) were enrolled. PET images were recorded 1 h after injection of tracer. Only a few months after treatment ended, a PSA assay was requested to evaluate the therapeutic efficacy of the treatment based on PSMA results. RESULTS: PSMA-positive lesions were detected in 34/42 (80.9%) patients. Detection rates were 85.7% and 89.3% for serum PSA levels lower than 2 ng/mL, and >2 ng/mL, respectively. One hundred seventy-three lesions were detected: 132/173 in lymph nodes (76.3%), 22/173 as metastatic sites (bone or lung) (12.7%), and 19/173 in the prostate bed (10.9%). As a result of the PSMA PET-CT, therapeutic management changed in 31/42 patients (73.8%). With a follow-up of 4.9 ± 2.27 months, 32/42 (76.2%) PSA assays after treatment guided by PSMA PET-CT were collected. For 37.5% (12/32) of patients, the serum PSA level was lower than 0.2 ng/mL and a PSA decrease of over 50% in 8 (25.0%) other patients were obtained. CONCLUSION: Performing a PSMA PET-CT when FCH PET-CT was doubtful or negative allows the recurrence localization in more 80% of patients and this had a major clinical impact, as it resulted in treatment change in more than 70% of patients as well as a significant decrease in PSA levels in more than 60% of them.

Recombinant Thyrotropin vs Levothyroxine Withdrawal in 131I Therapy of N1 Thyroid Cancer: A Large Matched Cohort Study (ThyrNod).

CONTEXT: Recombinant human thyrotropin (rhTSH) has been shown to be an effective stimulation method for radioactive iodine (RAI) therapy in differentiated thyroid cancer, including in those with nodal metastases (N1 DTC). OBJECTIVES: To demonstrate the noninferiority of rhTSH vs thyroid hormone withdrawal (THW) in preparation to RAI regarding disease status at the first evaluation in the real-life setting in patients with N1 DTC. DESIGN: This was a French multicenter retrospective study. Groups were matched according to age (<45/≥45 years), number of N1 nodes (≤5/>5 lymph nodes), and stage (pT1-T2/pT3). RESULTS: The cohort consisted of 404 patients pT1-T3/N1/M0 DTC treated with rhTSH (n = 205) or THW (n = 199). Pathological characteristics and initially administrated RAI activities (3.27 ± 1.00 GBq) were similar between the two groups. At first evaluation (6 to 18 months post-RAI), disease-free status was defined by thyroglobulin levels below threshold and a normal ultrasound. Disease-free rate was not inferior in the rhTSH group (75.1%) compared with the THW group (71.9%). The observed difference between the success rates was 3.3% (-6.6 to 13.0); rhTSH was therefore considered noninferior to THW because the upper limit of this interval was <15%. At the last evaluation (29.7 ± 20.7 months for rhTSH; 36.7 ± 23.8 months for THW), 83.5% (rhTSH) and 81.5% (THW) of patients achieved a complete response. This result was not influenced by any of the known prognostic factors. CONCLUSIONS: A preparation for initial RAI treatment with rhTSH was noninferior to that with THW in our series of pT1-T3/N1/M0-DTC on disease-free status outcomes at the first evaluation and after 3 years.

Advantages of systematic trunk SPECT/CT to planar bone scan (PBS) in more than 300 patients with breast or prostate cancer.

PROPOSE: The aim of our study was to evaluate the potential benefit of a systematic trunk SPECT/CT associated with a Planar Bone Scan (PBS) in breast cancer (BC) and prostate cancer (PCa) patients at initial staging or recurrence. RESULTS: In 328 patients, sensitivities and specificities were between 74.4-93% and 78.8-97.5% for PBS and 97.7-100% and 96.8-98.6% for SPECT/CT respectively. PBS was considered equivocal for 67 compared to only 6 patients for trunk SPECT/CT. Regardless of "optimistic" or "pessimistic" analysis of equivocal trunk SPECT/CT lesions, the trunk SPECT/CT was almost perfect, allowing to rely on this result for excluding metastatic disease which was corroborated by ROC curve analysis. The trunk SPECT/CT allowed downstaging for 62 patients (19%) and upstaging for 11 patients. MATERIALS AND METHODS: PBS and a trunk SPECT/CT were systematically performed in all patients. Independent review of PBS and trunk SPECT/CT was performed for each patient and an abnormality interpretative score (Sc) with 3 levels was built: Sc 1: metastatic or probably metastatic pattern, Sc 2: equivocal pattern, Sc 3: benign or probably benign pattern or no abnormality. The bone pattern status was defined by at least 1 year follow-up. The clinical impact was evaluated in terms of down and upstaging in patient analysis. CONCLUSIONS: Trunk SPECT/CT improves the performance of PBS in BC and PCa assessments and results in improvements in both the detection performance of bone metastases as well as a better characterization of equivocal lesions.

Outcome after ablation in patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up results of a randomised, phase 3, equivalence trial.

BACKGROUND: In ESTIMABL1, a randomised phase 3 trial of radioactive iodine (131I) administration after complete surgical resection in patients with low-risk thyroid cancer, 92% of patients had complete thyroid ablation at 6-10 months, defined as a recombinant human thyroid-stimulating hormone (rhTSH)-stimulated serum thyroglobulin concentration of 1 ng/mL or less and normal findings on neck ultrasonography. Equivalence was shown between low-activity (1·1 GBq) and high-activity (3·7 GBq) radioactive iodine and also between the use of rhTSH injections and thyroid hormone withdrawal. Here, we report outcomes after 5 years of follow-up. METHODS: This multicentre, randomised, open-label, equivalence trial was done at 24 centres in France. Between March 28, 2007, and Feb 25, 2010, we randomly assigned (1:1:1:1) adults with low-risk differentiated thyroid carcinoma who had undergone total thyroidectomy to one of four strategies, each combining one of two methods of thyrotropin stimulation (rhTSH or thyroid hormone withdrawal) and one of two radioactive iodine activities (1·1 GBq or 3·7 GBq). Randomisation was by computer-generated sequence, with variable block size. Follow-up consisted of a yearly serum thyroglobulin measurement on levothyroxine treatment. Measurement of rhTSH-stimulated thyroglobulin and neck ultrasonography were done at the discretion of the treating physician. No evidence of disease was defined as serum thyroglobulin of 1 ng/mL or less on levothyroxine treatment and normal results on neck ultrasonography, when performed. This study was registered with ClinicalTrials.gov, number NCT00435851. FINDINGS: 726 patients (97% of the 752 patients originally randomised) were followed up. At a median follow-up since randomisation of 5·4 years (range 0·5-9·2), 715 (98%) had no evidence of disease. The other 11 had either structural disease (n=4), raised serum thyroglobulin concentration (n=5), or indeterminate findings on neck ultrasonography (n=2). At ablation, six of these patients had received 1·1 GBq radioactive iodine (five after rhTSH and one after withdrawal) and five had received 3·7 GBq (two after rhTSH and three after withdrawal). TSH-stimulated (either after rhTSH injections or thyroid hormone withdrawal according to the treatment group) thyroglobulin concentration measured at the time of ablation was prognostic for structural disease status at ablation, ablation status at 6-10 months, and the final outcome. INTERPRETATION: Our findings suggest that disease recurrence was not related to the strategy used for ablation. These data validate the use of 1·1 GBq radioactive iodine after rhTSH for postoperative ablation in patients with low-risk thyroid cancer. FUNDING: French National Cancer Institute (INCa), French Ministry of Health, and Sanofi Genzyme.

Assessment of Lymph Nodes and Prostate Status Using Early Dynamic Curves with (18)F-Choline PET/CT in Prostate Cancer.

INTRODUCTION: Dynamic image acquisition with (18)F-Choline [fluorocholine (FCH)] PET/CT in prostate cancer is mostly used to overcome the bladder repletion, which could obstruct the loco-regional analysis. The aim of our study was to analyze early dynamic FCH acquisitions to define pelvic lymph node or prostate pathological status. MATERIAL AND METHODS: Retrospective analysis was performed on 39 patients for initial staging (n = 18), or after initial treatment (n = 21). Patients underwent 10-min dynamic acquisitions centered on the pelvis, after injection of 3-4 MBq/kg of FCH. Whole-body images were acquired about 1 h after injection using a PET/CT GE Discovery LS (GE-LS) or Siemens Biograph mCT (mCT). Maximum and mean SUV according to time were measured on nodal and prostatic lesions. SUVmean was corrected for partial volume effect (PVEC) with suitable recovery coefficients. The status of each lesion was based on histological results or patient follow-up (>6 months). A Mann-Whitney test and ANOVA were used to compare mean and receiver operating characteristic (ROC) curve analysis. RESULTS: The median PSA was 8.46 ng/mL and the median Gleason score was 3 + 4. Ninety-two lesions (43 lymph nodes and 49 prostate lesions) were analyzed, including 63 malignant lesions. In early dynamic acquisitions, the maximum and mean SUV were significantly higher, respectively, on mCT and GE-LS, in malignant versus benign lesions (p < 0.001, p < 0.001). Mean SUV without PVEC, allowed better discrimination of benign from malignant lesions, in comparison with maximum and mean SUV (with PVEC), for both early and late acquisitions. For patients acquired on mCT, area under the ROC curve showed a trend to better sensitivity and specificity for early acquisitions, compared with late acquisitions (SUVmax AUC 0.92 versus 0.85, respectively). CONCLUSION: Assessment of lymph nodes and prostate pathological status with early dynamic imaging using PET/CT FCH allowed prostate cancer detection in situations where proof of malignancy is difficult to obtain.

Clinical and Survival Impact of FDG PET in Patients with Suspicion of Recurrent Ovarian Cancer: A 6-Year Follow-Up.

BACKGROUND: The aim of this retrospective study was to evaluate the contribution of fluorine-18-fluoro-deoxyglucose (FDG) positron emission tomography (PET) to the clinical management and survival outcome of patients (pts) suspected of recurrent ovarian carcinoma, with the hypothesis that early diagnosis of recurrent ovarian cancer may improve overall survival (OS). METHODS: Fifty-three FDG PET/CT scans were retrospectively analyzed for 42 pts. CT and PET/CT findings were confirmed by imaging and clinical follow-up, and/or pathology, which were considered as the gold standard diagnosis. The treatment plan based on CT staging was compared with that based on PET/CT findings. Medical records were reviewed for pts characteristics, progression-free survival (PFS), and OS. PFS and OS were analyzed using the Cox proportional hazards regression model. RESULTS: The final diagnosis of recurrence was established pathologically (n = 16), or by a median clinical follow-up of 6.5 years (range 0.5-7.5) after the PET/CT (n = 37). PET/CT provided a higher detection sensitivity (92.2%, 47/51) than CT (60.8%, 31/51) (p < 0.001). Globally, PET/CT modified the treatment plan in 56.6% (30/53) and in 65.2% (15/23) when the CT was negative prior to PET/CT. In 30 cases, those benefited from a modified treatment plan, these changes led to the intensification of a previous treatment procedure in 83.3% (25/30), and to a reduction in the previous treatment procedure in 16.6% of cases (5/30). The Cox regression multivariate analysis showed that the number of lesions visualized by CT and presence of lung lesions detected by PET/CT were significantly associated with PFS (p = 0.002 and p = 0.035, respectively). CONCLUSION: On account of its impact on treatment planning, and especially in predicting patient outcome, FDG PET is a valuable diagnostic tool for cases of suspected ovarian cancer recurrence.