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Background and Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography/X-ray computed tomography (PET/CT) represents the mainstay diagnostic procedure for suspected ovarian cancer (OC) recurrence. PET/CT can be integrated with contrast medium and in various diagnostic settings, however, the effective benefit of this procedure is still debated. We aimed to compare the diagnostic capabilities of low-dose and contrast-enhanced PET/CT (PET/ldCT and PET/ceCT) in patients with suspected ovarian cancer relapse. Materials and Methods: 122 OC patients underwent both PET/ldCT and PET/ceCT. Two groups of nuclear medicine physicians and radiologists scored the findings as positive or negative. Clinical/radiological follow-up was used as ground truth. Sensitivity, specificity, negative/positive predictive value, and accuracy were calculated at the patient and the lesion level. Results: A total of 455 and 474 lesions were identified at PET/ldCT and PET/ceCT, respectively. At the lesion level, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were not significantly different between PET/ldCT and PET/ceCT (98%, 93.3%, 97.4%, 94.9%, and 96.9% for PET/ldCT, 99%, 95.5%, 98.3%, 97%, and 98% for PET/ceCT, p = ns). At the patient level, no significant differences in these parameters were identified (e.g., p = 0.22 and p = 0.35 for accuracy, in the peritoneum and lymph nodes, respectively). Smaller peritoneal/lymph node lesions close to physiological FDG uptake sources were found in the cases of misidentification by PET/ldCT. PET/ceCT prompted a change in clinical management in four cases (3.2%) compared to PET/ldCT. Conclusions: PET/ceCT does not perform better than PET/ldCT but can occasionally clarify doubtful peritoneal findings on PET/ldCT. To avoid unnecessary dose to the patient, PET/ceCT should be excluded in selected cases.

71 patients underwent two consecutiveHot spots in PET1 (N = 179) had a greater HU than CR (48 ± 8 vs 37 ± 9, P.01). Mean hot spots HU increased to 59 ± 12 in PET2 (P.001). New calcifications appeared at the hot spots site in 73 cases (41%). Baseline atherosclerotic plaque's (N = 375) TBR was proportional to percent HU and CS increase (P.01 for both). Aortic CS increased (P.001); the whole-aorta TBR in PET1 correlated with the CS increase between the baseline and the second PET/CT (R = .63, P.01).

The risk of relapse of differentiated thyroid carcinomas (DTC) and their indication for radioactive iodine therapy (RAI) are assessed according to ATA risk stratification system principally based on tumor-nodes-metastasis (TNM) staging. However, while establishing the indication for RAI may be a “dilemma,” performing it can improve the risk stratification. We aimed to evaluate whether (1) the stratification of risk of recurrence differs when TNM is considered with or without peri-RAI findings and (2) the assessment of the risk of disease-specific mortality is improved by adding age and gender. From our database, all DTC patients treated with thyroidectomy and RAI from 1992 to 2017 were included. Subjects with a follow-up shorter than 1 year and positive thyroid antibodies were excluded. Patients were classified into (1) a three-category ATA model based on TNM (basic model) and (2) a five-category model based on TNM plus peri-RAI findings, i.e., thyroglobulin and 131I whole-body scan (advanced model). Relapse was proven by histology and/or imaging. Differences in disease-free survival (DFS) and overall survival (OS) were assessed. We enrolled 907 patients; of these, 4.4% died and 21% suffered recurrence. According to the basic model, there were 11.8% high-risk, 32.9% intermediate-risk, and 55.3% low-risk patients. According to the advanced model, 29.9% of patients were re-classified in a higher risk category and the five categories of this model displayed significantly different risks of relapse and death. The estimate of DFS was significantly higher in the advanced model than in the basic one (ΔC-index = + 6.8%, P

Current guidelines recommend thyroid hormone withdrawal (THW) of 3–4 weeks before radioiodine remnant ablation (RRA) of differentiated thyroid carcinoma (DTC). We aimed to evaluate (1) the reliability of a shorter THW (i.e., 14 days) to achieve adequate TSH levels (i.e., 30 mU/l), (2) the association between length of THW and response to therapy, and (3) the potential association between pre-ablation TSH levels and patients’ outcome. After thyroidectomy, all patients started LT4 therapy, which was subsequently discontinued in order to perform RRA. Patients were broken down into two groups according to the length of THW: group A, 2 weeks of THW, and group B, 3–4 weeks of THW. We used clinical, biochemical, and imaging data to evaluate patients’ outcome. By means of univariate and multivariate analysis, including main DTC prognostic factors, we assessed the impact of THW length and TSH levels on patients’ outcome. We evaluated 222 patients, 85 of whom were treated with RRA after a THW period of 2 weeks (group A). All other 137 patients underwent RRA after 3–4 weeks THW (group B). At the time of RRA all patients presented TSH levels ≥30 mU/l. After a median follow-up time of 3.4 years, we found 183 patients (82%) with excellent response to treatment and 39 patients (18%) showing incomplete response. Kaplan–Meier response to therapy curves showed that ablation-Tg, tumor size, and lymph node status were significantly associated with prognosis; no associations were found between THW length, TSH levels, and prognosis. Multivariate Cox model showed that only ablation-Tg was significantly associated with treatment response. Prior to RRA, a short 2-week THW is an effective method to stimulate TSH levels. No difference in terms of incomplete response to treatment was observed between DTC patients prepared for RRA with a short THW and those with the long THW.

This study aimed to evaluate the role ofThe study prospectively enrolled high-risk DTC patients treated with thyroidectomy and radioactive iodine therapy and presenting high/increasing thyroglobulin levels under thyrotropin suppression, negative/inconclusive neck ultrasound, and negativeTwenty-five high-risk DTC patients were included; DTC relapse/persistence was confirmed in 23 patients. On PBA

Purpose To evaluate the role of 18F-flurodeoxiglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in predicting malignancy of thyroid nodules with indeterminate cytology. Patients and methods We analysed 87 patients who have been scheduled to undergo surgery for thyroid nodule with indeterminate cytology. All patients underwent 18F-FDG-PET/CT, multiparametric neck ultrasonography (MPUS), and 99mTc-methoxyisobutylisonitrile scintigraphy (99mTc-MIBI-scan). Histopathology was the standard of reference. We compared the sensitivity (SE), specificity (SP), accuracy (AC), positive (PPV) and negative predictive (NPV) values of 18F-FDG-PET/CT with those of 99mTc-MIBI-scan and MPUS in detecting cancer. Univariate and multivariate analyses evaluated the association between each diagnostic tool and histopathology. Results On histopathology, 69 out of 87 nodules were found to be benign and 18 to be malignant. The SE, SP, AC, PPV and NPV of 18F-FDG-PET/CT were 94, 58, 66, 37 and 98% respectively. The SE, AC and NPV of 18F-FDG-PET/CT were significantly higher than those of MPUS and 99mTc-MIBI-scan. The association of both positive 18F-FDG-PET/CT and MPUS (FDG+/MPUS+) showed significantly lower SE (61% vs 94%) and NPV (88% vs 98%) than 18F-FDG-PET/CT alone, but significantly higher SP (77% vs 58%). On univariate analysis, 18F-FDG-PET/CT and the combination of FDG+/MPUS+ and of FDG+/MIBI− were all significantly associated with histopathology. On multivariate analysis, only FDG+/MIBI− was significantly associated with histopathology. Conclusion The AC of 18F-FDG-PET /CT in detecting thyroid malignancy is higher than that of 99mTc-MIBI-scan and MPUS. A negative 18F-FDG-PET/CT correctly predicts benign findings on histopathology. The association of FDG+/MPS+ is significantly more specific than 18F-FDG-PET/CT alone in identifying differentiated thyroid cancer. A positive 18F-FDG-PET/CT is significantly associated with malignancy when qualitative 99mTc-MIBI-scan is rated as negative.

The aim of this study was to investigate MRI-derived diffusion weighted imaging (DWI) and arterial spin labeling (ASL) perfusion imaging in comparison with 18F–dihydroxyphenylalanine (DOPA) PET with respect to diagnostic performance in tumor grading and outcome prediction in pediatric patients with diffuse astrocytic tumors (DAT). We retrospectively analyzed 26 children with histologically proven treatment naive low and high grade DAT who underwent ASL and DWI performed within 2 weeks of 18F–DOPA PET. Relative ASL-derived cerebral blood flow max (rCBF max) and DWI-derived minimum apparent diffusion coefficient (rADC min) were compared with 18F–DOPA uptake tumor/normal tissue (T/N) and tumor/striatum (T/S) ratios, and correlated with World Health Organization (WHO) tumor grade and progression-free survival (PFS). Statistics included Pearson’s chi-square and Mann-Whitney U tests, Spearman’s rank correlation, receiver operating characteristic (ROC) analysis, discriminant function analysis (DFA), Kaplan-Meier survival curve, and Cox analysis. A significant correlation was demonstrated between rCBF max, rADC min, and 18F–DOPA PET data (p

To compare regional vascular distribution and biological determinants of visible calcium load, as assessed by computed tomography, as well as of molecular calcium deposition as assessed by (18)F-NaF positron emission tomography. Eighty oncologic patients undergoing (18)F-NaF PET/CT scan were included in the study. Cardiovascular-risk stratification was performed according to a simplified version of the Framingham model [including age, diabetes, smoking, systolic blood pressure and body mass index (BMI)]. Arterial (18)F-NaF uptake was measured by drawing regions of interest comprising the arteries on each slice of the transaxial PET/CT and normalized to blood (18)F-NaF activity to obtain the arterial target-to-background ratio (TBR). The degree of arterial calcification (AC) was measured using a software program providing Agatston-like scores. Differences in mean values and regression analysis were tested. Predictors of AC and TBR were evaluated by univariate and multivariate analysis. p value of 0.05 was considered statistically significant. No correlation was documented between regional calcium load and regional TBR in any of the studied arterial segments. Visible calcium deposition was found to be dependent upon age while it was not influenced by all the remaining determinants of cardiovascular risk. By contrast, (18)F-NaF uptake was significantly correlated with all descriptors of cardiovascular risk, with the exception of BMI. Vascular (18)F-NaF uptake displays a different regional distribution, as well as different biological predictors, when compared to macroscopic AC. The tight dependency of tracer retention upon ongoing biological determinants of vascular damage suggests that this tool might provide an unexplored window on plaque pathophysiology.

We report the finding of increased F-3,4-dihydroxyphenylalanine uptake of the brain parenchyma adjacent to developmental venous anomalies, incidentally discovered in 3 pediatric patients with diffusely infiltrating gliomas. One patient presented 3 developmental venous anomalies located distant from the tumor, whereas in the remaining 2 patients, the vascular anomalies were inside the tumoral area mimicking a focal area of increased tumor metabolism. In the setting of brain tumor imaging, focal increased F-3,4-dihydroxyphenylalanine uptake should be carefully interpreted in light of MRI findings, and nuclear medicine physicians should be aware of any incidental minor vascular abnormality for proper interpretation of PET data.

Our purpose as to evaluate the impact of adjuvant radioactive iodine therapy (RAI) on prognosis, as assessed by progression-free survival (PFS) and overall survival (OS), in patients affected by differentiated thyroid carcinoma (DTC) lymph-node relapse and previously treated with lymphadenectomy. We retrospectively evaluated DTC patients treated with lymph-node dissection for disease relapse. All patients had previously undergone total thyroidectomy and radioiodine remnant ablation (RRA). We used clinical and histological data obtained during follow-up to assess response and outcome. By means of univariate and multivariate time-to-event analyses, we assessed the impact of RAI on outcome (PFS and OS) and the prognostic role of thyroglobulin (Tg) levels under suppression with levothyroxine (Tg-on) measured 1–3 months after lymphadenectomy and of other risk factors. We evaluated 113 patients (age at diagnosis: median 41 years, interquartile range: 31–59), 64 of whom were treated with RAI. Over a median follow-up time of 5.7 years, 27 patients showed disease progression and 13 died. Kaplan-Meier PFS and OS curves showed that age on diagnosis, tumor histology, tumor size, DTC aggressive variant, and Tg-on were associated with prognosis. Patients with Tg-on ≥1 ng/ml treated with RAI showed a better PFS (Log-rank pp 0.001) and OS (p = 0.005) than untreated patients, while no effect of RAI was observed in patients with Tg-on

Purpose So far, no studies comparing 18 F-Fluoride-PET/CT and MDCT for the detection of bone metastases are available. We compared the accuracy of 18 F-Fluoride-PET/CT (MDCT: 3.75 mm thickness-image-reconstruction), whole-body Multi-Detector-CT (MDCT: 1.25 mm thickness-image-reconstruction) and 18 F-Fluoride-PET/MDCT (MDCT: 1.25 mm thickness-image-reconstruction) in identifying bone metastases in breast cancer patients. Methods We studied 39 breast cancer patients for bone metastases. Imaging was performed on an integrated PET/MDCT-system; CT images were reconstructed at 3.75 mm and 1.25 mm thickness. Two nuclear medicine physicians and one radiologist interpreted blindly 18 F-Fluoride-PET/CT, 18 F-Fluoride-PET/MDCT and MDCT. MDCT at 12 months served as the standard of reference. Results Overall, 662 bone lesions were detected in our analysis. Of these, 542 were malignant and 120 were benign according to the standard of reference. 18 F-Fluoride-PET/CT detected 491 bone metastases, 114 (23%) of which displayed no clear morphological changes on MDCT, whereas MDCT detected 416 bone metastases, 39 (9.3%) of which showed no 18 F-Fluoride-PET uptake. Overall sensitivity and specificity were: 91% and 91%, respectively, for 18 F-Fluoride-PET/CT, and 77% and 93% for MDCT. The integrated assessment of 18 F-Fluoride-PET/MDCT yielded sensitivity and specificity values of 98% and 93%, respectively. Conclusions 18 F-Fluoride-PET/MDCT has higher diagnostic accuracy than 18 F-Fluoride-PET/CT and MDCT for the evaluation of bone metastases in breast cancer.

PURPOSE: (18)F-Dopa positron emission tomography (PET)/CT has proved a valuable tool for the assessment of neuroendocrine tumours. So far no data are available on (18)F-dopa utilization in neuroblastoma (NB). Our aim was to evaluate the role of (18)F-dopa PET/CT in NB and compare its diagnostic value with that of (123)I-metaiodobenzylguanidine (MIBG) scintigraphy in patients affected by stage 3-4 NB. METHODS: We prospectively evaluated 28 paired (123)I-MIBG and (18)F-dopa PET/CT scans in 19 patients: 4 at the time of the NB diagnosis and 15 when NB relapse was suspected. For both imaging modalities we performed a scan-based and a lesion-based analysis and calculated sensitivity, specificity and accuracy. The standard of reference was based on clinical, imaging and histological data. RESULTS: NB localizations were confirmed in 17 of 19 patients. (18)F-Dopa PET/CT and (123)I-MIBG scintigraphy properly detected disease in 16 (94%) and 11 (65%), respectively. On scan-based analysis, (18)F-dopa PET/CT showed a sensitivity and accuracy of 95 and 96%, respectively, while (123)I-MIBG scanning showed a sensitivity and accuracy of 68 and 64%, respectively (p < 0.05). No significant difference in terms of specificity was found. In 9 of 28 paired scans (32%) PET/CT results influenced the patient management. We identified 156 NB localizations, 141 of which were correctly detected by (18)F-dopa PET/CT and 88 by MIBG. On lesion-based analysis, (18)F-dopa PET/CT showed a sensitivity and accuracy of 90% whereas (123)I-MIBG scintigraphy showed a sensitivity and accuracy of 56 and 57%, respectively (p < 0.001). No significant difference in terms of specificity was found. CONCLUSION: In our NB population (18)F-dopa PET/CT displayed higher overall accuracy than (123)I-MIBG scintigraphy. Consequently, we suggest (18)F-dopa PET/CT as a new opportunity for NB assessment.

Thyroid lymphoma is a rare disease which occurs mainly in elderly females. Most patients with thyroid lymphoma have Chronic Lymphocytic Thyroiditis (CLT), suggesting a role of chronic antigen stimulation in the development of the disease. We present two cases of thyroid Diffuse Large B-cell Lymphoma (DLBCL) diagnosed after surgery (subtotal thyroidectomy) by means of combined histology and immunohistochemistry (positive staining for CD-20) in two elderly female patients presenting at our institution for compressive symptoms (dysphonia in patient 1, dysphagia in patient 2) due to a gross neck mass. Fine-needle aspiration was compatible with lymphocytic thyroiditis in the first patient and was indeterminate in the second patient. The first patient had a long-lasting history of hypothyroidism due to CLT and was on L-thyroxine replacement therapy, whereas the second patient had normal thyroid function and negative thyroid autoantibodies. After surgery both patients underwent chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) plus rituximab). At one-year follow-up both patients were disease-free. Thyroid lymphoma is an uncommon tumor which requires prompt diagnosis and combined management for a high rate of cure to be achieved.

Several studies have highlighted the role of vascular (18)F-NaF uptake as a marker of ongoing calcium deposition. However, accumulation of (18)F-NaF is often inconsistent with localization of arterial plaque. Calcification activity and thus (18)F-NaF uptake might prevail in the earlier plaque stages. To test this hypothesis, we evaluated (18)F-NaF uptake in plaque of 3 different densities, using density as a marker of calcification progression. We also tested whether attenuation-weighted image reconstruction affects (18)F-NaF uptake in the different plaque stages.Sixty-four oncologic patients (14 men and 50 women; mean age, 65.3 ± 8.2 y; range, 26-81 y) underwent (18)F-NaF PET/CT. A volume of interest was drawn on each plaque within the infrarenal aorta to assess mean standardized uptake value and attenuation (in Hounsfield units [HU]). Plaque was then categorized as light (210 HU), medium (211-510 HU), or heavy (510 HU). Standardized uptake value was normalized for blood (18)F-NaF activity to obtain the plaque target-to-background ratio (TBR). During this process, several focal, noncalcified areas of (18)F-NaF were identified (hot spots). The TBR of the hot spots was computed after isocontour thresholding. The TBR of a noncalcified control region was also calculated. In 35 patients, the TBR of non-attenuation-corrected images was calculated.The average TBR was highest in light plaque (2.21 ± 0.88), significantly lower in medium plaque (1.59 ± 0.63, P0.001), and lower still in heavy plaque (1.14 ± 0.37, P0.0001 with respect to both light and medium plaque). The TBR of the control region was not significantly different from that of heavy plaque but was significantly lower than that of light and medium plaque (P0.01). Hot spots had the highest absolute TBR (3.89 ± 1.87, P0.0001 vs. light plaque). TBRs originating from non-attenuation-corrected images did not significantly differ from those originating from attenuation-corrected images.Our results support the concept that (18)F-NaF is a feasible option in imaging molecular calcium deposition in the early stages of plaque formation, when active uptake mechanisms are the main determinants of calcium presence, but that retention of (18)F-NaF progressively decreases with increasing calcium deposition in the arterial wall. Our data suggest that non-attenuation-corrected reconstruction does not significantly affect evaluation of plaque of any thickness.

Several studies highlighted the role of vascular 18F-NaF uptake as a marker of ongoing calcium deposition. However, 18F-NaF accumulation often shows inconsistent co-localization with arterial plaque. Actually, calcification activity and thus 18F-NaF uptake could prevail in the earlier plaque stages. To test this hypothesis, we evaluated18F-NaF uptake in three plaque types using plaque density as a marker of calcification progression. We also tested whether attenuation weighted image reconstruction affected 18F-NaF uptake values in the different plaque stages considered. METHODS: 64 oncologic patients (14 males, mean age 65.3±8.2 range 26-81) underwent 18F-NaF PET/CT. A volume of interest (VOI), was drawn on each plaque within the infra-renal aorta, to assess mean SUV and attenuation value (HU). Plaques were then divided in light (LP, HU 510). SUV was normalized for blood 18F-NaF activity, to obtain plaque target-to background ratio (TBR). In this process, several focal, non-calcified 18F-NaF uptake areas were identified (hot spots, HS). TBR was computed in HS, after iso-contour thresholding. TBR was also calculated in a non-calcified control region (CR). In 35 patients, TBR was furthermore calculated on non-attenuation-corrected (NAC) images. RESULTS: Among plaques, average TBR was highest in LP (2.21±0.88), while it was significantly lower in MP (1.59±0.53, p510). SUV was normalized for blood 18F-NaF activity, to obtain plaque target-to background ratio (TBR). In this process, several focal, non-calcified 18F-NaF uptake areas were identified (hot spots, HS). TBR was computed in HS, after iso-contour thresholding. TBR was also calculated in a non-calcified control region (CR). In 35 patients, TBR was furthermore calculated on non-attenuation-corrected (NAC) images. RESULTS: Among plaques, average TBR was highest in LP (2.21±0.88), while it was significantly lower in MP (1.59±0.53, p

No parameters predicting recurrence are available for high-risk differentiated thyroid cancer (DTC) patients, and 2-year-follow-up is required to modify the initial prognostic classification. High thyroglobulin (Tg) levels before ¹³¹I-remnant-ablation, during L-thyroxine-withdrawal (ablation-Tg) have undetermined predictive/prognostic significance in low-risk DTC patients. Our study aimed to assess the positive predictive value (PPV) of ablation-Tg in high-risk DTC patients and to evaluate whether high ablation-Tg levels were associated with progression-free-survival (PFS) and overall survival (OS).We selected 243 high-risk DTC patients. All patients underwent total thyroidectomy and ¹³¹I-remnant-ablation (initial therapy). Clinical data obtained during a median 5-year follow-up were used to assess the response and outcome. The association between disease persistence/recurrence after initial therapy, ablation-Tg, and other risk-factors (T, N, G, histology, and MACIS score) was evaluated through univariate and multivariate analyses, as was the association between PFS, OS ablation-Tg, and other risk factors.Ablation-Tg of 50 μg/L or greater displayed the highest PPV(97%) for disease persistence. In the univariate analysis, high levels of ablation-Tg were confirmed in patients with persistent disease after initial therapy: the higher the odds ratios, the higher the ablation-Tg levels. On multivariate analysis, ablation-Tg was the best predictive factor, especially on comparing patients with ablation-Tg levels of 50 μg/L or greater and those with ablation-Tg less than 2 μg/L (adjusted OR, 818). In a multivariate Cox model, ablation-Tg was the factor most closely associated with PFS (HR, 65.9). The prognostic value of ablation-Tg was confirmed by the overall-survival curves and adjusted risk estimates (adjusted HR=26.7).Ablation-Tg levels of 50 μg/L or greater are a valuable initial predictor of disease persistence/recurrence in high-risk DTC patients. A significant association emerged between high ablation-Tg levels of 50 μg/L or greater and both progression-free survival (PFS) and overall survival (OS).

Recombinant human TSH-stimulated thyroglobulin (Tg) levels (rhTSH-Tg) are sufficient for early follow-up of low-risk differentiated thyroid cancer (DTC) patients after thyroidectomy and radioiodine (131I) remnant ablation (RAI). Serum Tg levels at the time of remnant ablation (ablation-Tg) is thought to be related with rhTSH-Tg and may be predictive of recurrent disease. During long-term follow-up, Tg levels on levo-T4 (L-T4) suppressive treatment (suppressive-Tg) is sufficiently sensitive to avoid further evaluations in patients with undetectable rhTSH-Tg. The aim of our study was to verify whether, in a subgroup of low-risk DTC patients, the association of low ablation-Tg levels (10 microg/l) with undetectable suppressive-Tg concentrations has a sufficient negative predictive value (NPV) for recurrence of disease, leading to avoid rhTSH testing.We enrolled 169 low-risk DTC patients treated by thyroidectomy + RAI and undetectable suppressive-Tg at 12-month followup. In all patients, we retrospectively evaluated ablation-Tg and rhTSH-Tg. For all patients, 2-yr follow-up was available.Based on rhTSH-Tg2 microg/l, relapsing disease was histologically proven in 2 patients. rhTSH-Tg levels between 0.6-2.0 microg/l, with no evidence of disease, was observed in 10 patients (6%). One hundred and fifty-seven patients showed undetectable rhTSH-Tg. The NPV of undetectable suppressive- Tg was 92.8%. The ablation-Tg level was10 microg/l in 140 patients. In this group, the NPV of undetectable suppressive- Tg was 100%.Our data indicate that undetectable suppressive-Tg value, combined with ablation- Tg levels10 microg/l, may avoid a significant number of high-cost rhTSH-Tg test.

IntroductionCalcitonin measurement is advised in the diagnosis of thyroid nodules, as it is an accurate marker of medullary thyroid carcinoma (MTC). C-cell hyperplasia (CCH)-induced hypercalcitoninemia cannot be distinguished from that induced by MTC, unless surgery is performed.CaseWe report the clinical and biological features of a patient with a family history of cancer, including melanoma and pancreatic cancer, who had previously undergone surgery for melanoma. He presented the unusual association of papillary thyroid carcinoma (PTC), normocalcemic hyperparathyroidism, and hypercalcitoninemia with a pathological response to pentagastrin, which was histologically deemed secondary to CCH. Multiple endocrine neoplasia (MEN) 2A was diagnosed. RET gene analysis showed a p.V804M missense mutation in exon 14, a low- but variably penetrant defect found in both sporadic and MEN2A-associated MTC/CCH, and a p.G691S polymorphism in exon 11. Furthermore, the germline P48T mutation was found in the CDKN2A gene exon 1, which is known to be associated with melanoma and pancreatic cancer. The patient showed the uncommon coexistence of a germline mutation in two suppressor genes, RET and CDKN2A; this finding, deemed to be a mere coincidence, did not modify the phenotype expected by each single mutation. CCH associated with V804M RET mutation is a precancerous condition and surgery is recommended. In order to exclude MTC, surgery is advised in patients with a pathological calcitonin response to pentagastrin, in the absence of thyroid autoimmunity. CCH-induced hypercalcitoninemia can be associated with thyroid cancers other than MTC (e.g., PTC). Family history is important in scheduling specific genetic screening in high-risk patients and their relatives.

Purpose: To describe long-term late consequences in children who received total body irradiation (TBI) for hematopoietic stem cell transplantation 10 years earlier. Methods and Materials: A cohort of 42 children treated with TBI between 1985 and 1993, still alive at least 10 years after fractionated TBI (FTBI), was evaluated. Twenty-five patients received FTBI at 330 cGy/day for 3 days (total dose 990 cGy), whereas 17 children were administered fractions of 200 cGy twice daily for 3 days (total dose 1200 cGy). Twenty-seven patients received autologous and 16 allogeneic hematopoietic stem cell transplantation. Median age at TBI was 6.3 years, and 18.4 years at most recent follow-up. Results: Cataract was diagnosed in 78% of patients after a median of 5.7 years. Hypothyroidism was detected in 12%, whereas thyroid nodules were observed in 60% of our population after a median interval of 10.2 years. Patients treated with 990 cGy developed thyroid nodules more frequently than those treated with 1200 cGy ( p = 0.0002). Thyroid carcinoma was diagnosed in 14% of the total population. Females who received FTBI after menarche more frequently developed temporary ovarian dysfunction than those treated before menarche, but cases of persistent ovarian dysfunction did not differ between the two groups. Indirect signs of germinal testicular dysfunction were detected in 87% of males. Restrictive pulmonary disease was observed in 74% of patients. Osteochondroma was found in 29% of patients after a median interval of 9.2 years. This latter complication appeared more frequently in patients irradiated before the age of 3 years ( p Conclusions: This study shows that late effects that are likely permanent, although not fatal, are frequent in survivors 10 years after TBI. However, some of the side effects observed shortly after TBI either disappeared or remained unchanged without signs of evolution. Monitoring is recommended to pursue secondary prevention strategies and counseling on family planning.

Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still has very poor prognosis which is estimated at 25%. Metabolic radiotherapy with I(131) MIBG appears a feasible option to enhance the effects of chemotherapy. Seventeen patients having MIBG-positive residual disease received 4.1-11.1 mCi/kg of I(131) MIBG 7-10 days before initiating the high-dose chemotherapy cycle consisting of busulphan 16 mg/kg and melphalan 140 mg/m(2) followed by PBSC infusion. We compared the toxicity in these patients to that seen in 15 control subjects with neuroblastoma who underwent a PBSC transplant without MIBG therapy. We observed greater toxic involvement of the gastrointestinal system in children treated with I(131) MIBG: grade 2 or 3 mucositis developed in 13/17 patients treated with I(131) MIBG and in 9/15 treated without it. Grade 1-2 gastrointestinal toxicity occurred in 12/17 children given MIBG and in 5/15 of the controls. One child receiving I(131) MIBG developed transient interstitial pneumonia. Another child who also received I(131) MIBG after PBSC rescue developed fatal pneumonia after the third course of metabolic radiotherapy. Our experience indicates that MIBG can be included in the high-dose chemotherapy regimens followed by PBSC rescue for children with residual neuroblastoma taking up MIBG. Attention should be paid to avoiding lung complications. Prospective studies are needed to demonstrate the real efficacy of this treatment.

Incomplete response to therapy may compromise the outcome of children with advanced neuroblastoma. In an attempt to improve tumour response we incorporated 131I-metaiodobenzylguanidine (131I-MIBG) in the treatment regimens of selected stage 3 and stage 4 patients. Between 1986 and 1997, 43 neuroblastoma patients older than 1 year at diagnosis, 13 with stage 3 (group A) and 30 with stage 4 disease (group B) who had completed the first-line protocol without achieving complete response entered in this study. 131I-MIBG dose/course ranged from 2.5 to 5.5 Gbq (median, 3.7). The number of courses ranged from 1 to 5 (median 3) depending on the tumour response and toxicity. The most common acute side-effect was thrombocytopenia. Later side-effects included severe interstitial pneumonia in one patient, acute myeloid leukaemia in two, reduced thyroid reserve in 21. Complete response was documented in one stage 4 patient, partial response in 12 (two stage 3, 10 stage 4), mixed or no response in 25 (ten stage 3, 15 stage 4) and disease progression in five (one stage 3, four stage 4) Twenty-four patients (12/13 stage 3, 12/30 stage 4) are alive at 22–153 months (median, 59) from diagnosis. 131I-MIBG therapy may increase the cure rate of stage 3 and improve the response of stage 4 neuroblastoma patients with residual disease after first-line therapy. A larger number of patients should be treated to confirm these results but logistic problems hamper prospective and coordinated studies. Long-term toxicity can be severe. © 1999 Cancer Research Campaign

We report the case of a 6-year-old child with stage 4 neuroblastoma, previously treated with chemotherapy, which relapsed in the right mandibular branch, right submandibular lymph nodes, and bone marrow. These sites of recurrence were detected on diagnostic (123)I-MIBG and confirmed by (18)F-DOPA-PET/CT, which revealed the following 2 additional sites of disease: in the skull base and the left supraclavicular lymph nodes. The patient was scheduled for radioiodine therapy and received a total dose of 7400 MBq (200 mCi) of (131)I-MIBG. The whole-body scan, acquired 72 hours later, revealed all sites of disease detected by (18)F-DOPA-PET/CT, including those negative on (123)I-MIBG scan.