E Borsò

Optimal Detection of Sentinel Lymph Node Metastases by Intraoperative Radioactive Threshold and Molecular Analysis in Patients with Melanoma

The aim of this study was to optimize a protocol for radioguided biopsy of the sentinel lymph node (SLN) in patients with melanoma. The protocol was based on a combination of ex vivo counting of the nodes detected intraoperatively and analysis of the harvested nodes by hematoxylin and eosin staining plus immunohistochemistry (conventional histopathology [PATH]) and by molecular biology (reverse-transcriptase polymerase chain reaction [RT-PCR]). Methods: A total of 124 patients with primary clinical stage I–II (according to the American Joint Committee on Cancer) cutaneous melanoma underwent successful radioguided SLN biopsy. SLNs harvested for analysis included any additional nodes whose ex vivo counting rate exceeded 20% of the hottest node. All removed SLNs were examined by conventional PATH and with RT-PCR analysis for the expression of messenger RNA for tyrosinase and the melanoma antigens recognized by T cells. Complete lymph node dissection (CLND) was performed only in the case of SLN metastasis detected by PATH. Different combinations of the intraoperative parameters (only the hottest node and all nodes harvested) and of analysis (PATH and RT-PCR) were tested as predictors of clinical outcome on the basis of long-term follow-up (12–81 mo; median, 55 mo). Results: A total of 197 SLNs were harvested, 41 of which harbored metastasis as detected by RT-PCR analysis; PATH detected metastasis in only 24 of 41 metastatic SLNs. In 5 of 41 instances, metastasis was not in the hottest SLN. The main factor determining correct classification of the SLN status was RT-PCR, which significantly improved detection of metastasis, even if applied only to the hottest node (P < 0.0001 vs. PATH analysis of either the hottest SLN or all nodes above the 20% threshold). Metastatic disease recurred locally in 5 patients who had not undergone CLND; RT-PCR analysis showed metastasis in 4 of these patients. The false-negative rate of SLN biopsy progressively decreased when applying PATH only to the hottest node (32.1%), additional RT-PCR to the hottest node (21.4%), PATH to all nodes (17.9%), and RT-PCR to all nodes (3.6%, P = 0.015 vs. PATH analysis of only the hottest SLN). Conclusion: On the basis of long-term follow-up (the gold standard for final clinical outcome of SLN biopsy), both 20% threshold and RT-PCR analysis should be applied for optimal detection of nodal metastases in patients with melanoma.

Thyroid and Parathyroid Tumors

Thyroid cancer occurred in approximately 45,000 patients, in the USA in 2010. There is a 3:1 ratio of women to men. Histologic types are divided into categories of differentiated thyroid cancer (DTC): papillary, mixed papillary and follicular, and follicular—including Hurthle cell variant, undifferentiated (anaplastic), and medullary cancer (arising from parafollicular C-cells). Other rare thyroid carcinoma accounts non-epithelial tumors, lymphoma and carcinomas characterized by the presence of mucin-producing cells and keratin. Differentiated thyroid cancer usually presents as a thyroid nodule. Thyroid ultrasonography is useful to detect and characterize thyroid nodules, as well as guide fine needle aspiration (FNA) biopsy. Radioiodide or 99mTc-pertechnetate thyroid scan has a low diagnostic specificity and sensitivity for characterizing thyroid nodules. X-ray of the neck is useful to disclose a deviation of the trachea or lumen restriction, in large nodules and in multinodular goiter. CT or MRI are generally reserved for mediastinal thyroid masses, or the identification of regional or distant metastasis. The most widely used staging system for thyroid carcinoma is the TNM classification system defined jointly by the UICC and by AJCC. 131I-iodide thyroid remnant ablation is indicated in differentiated thyroid cancer patients with a moderate to high likelihood of recurrence. 131I-iodide therapy is usually administered in the amount of 1.85 to 3.7 GBq for ablation. Patients are prepared with rhTSH and low iodine diet. Whole body scan (preferably with SPECT/CT of the neck) is performed 4–7 days after radioiodine therapy to detect lymph node involvement or unexpected metastases. The major diagnostic modalities employed to follow patients with differentiated thyroid cancer treated with remnant ablation is measurement of serum Tg, 131I-WBS, and neck US examination. Neck US examination is an integral component of follow-up evaluation in all DTC patients. If a lymph node metastasis is suspected, an FNA should be performed. Serum Tg levels that become detectable upon TSH stimulation indicate the need for further evaluation, possibly with additional radioiodine therapy. Although CT and MRI can in principle localize very small lesions in the neck, chest, and bones, the features of such lesions are rarely specific for recurrent/metastatic DTC. Patients with recurrent thyroid cancer may develop lesions which cannot concentrate radioiodide. [18F]FDG PET/CT is useful in these patients to determine the sites and extent of these metastases. The anaplastic thyroid carcinoma (ATC) is a rare tumor (<3% of all thyroid cancers) with poor prognosis derived from follicular cells. The most clinical presentation of an ATC is a new, large, firm thyroid nodule, often associated with signs/symptoms of local compression/invasion. Multimodality treatment of ATC includes surgery, EBRT, and combination chemotherapy. Therapy with 131I-iodide is not useful, since these tumors rarely concentrate radioiodide. Preoperative imaging with US, CT, MRI play an important role, and [18F]FDG PET is useful. Medullary thyroid carcinoma (MTC) is a well-differentiated thyroid tumor arising from the parafollicular, calcitonin-producing C cells. Its prevalence is 5–10% in all thyroid malignancies. Sporadic and familial forms are recognized. Elevated baseline serum levels of calcitonin (above 10 ng/mL) are diagnostic for MTC. Following surgery, MTC patients are monitored with serum calcitonin and CEA levels, and serial neck US examinations are performed. Calcitonin doubling time in serum is the most sensitive biomarker for MTC progression. Scintigraphy with 123I-MIBG has very high sensitivity for staging patients with MEN II and familial MTC. However, it has a low sensitivity in patients with increased serum calcitonin but no clinical site of disease. [18F]FDG PET is accurate in detecting lymph node involvement. Radionuclide therapy with the radiolabeled somatostatin analog 90Y-DOTA-Tyr3-octreotide (90Y-DOTA-TOC) has been tested in metastatic MTC. Parathyroid carcinoma is a very rare endocrine malignancy that occurs in <1% of primary HPTH. The initial clinical manifestations of parathyroid carcinoma are primarily linked to the effects of markedly elevated serum PTH levels. At initial presentation, very few patients have metastasis at regional lymph nodes or at distant sites. Parathyroid carcinoma tends to infiltrate adjacent structures in the neck. US, CT, and MRI have been used to localize parathyroid carcinomas and to detect mediastinal and thoracic recurrences or distant metastases. 99mTc-Sestamibi scintigraphy can be successful for preoperative localization of the neoplasia and can identify metastases in lymph nodes and at distant sites. PET with [18F]FDG can also detect metastatic parathyroid cancers. Parathyroid carcinoma recurs in more than 50% of the cases and imaging studies should be performed in all patients before reoperation.

Radium 223 dichloride: a multidisciplinary approach to metastatic castration-resistant prostate cancer

The role of nuclear medicine physicians in the multidisciplinary team for the management of patients with prostate cancer has been restricted because of a lack of available tools. The only drugs approved to relieve pain related to bone metastases were β-emitting radiopharmaceuticals. These drugs did not prove to prolong survival when used as single agent and resulted associated with important adverse events. This situation has changed with the introduction of radium 223 because of evidence of improved survival in patients, the good safety profile and the opportunity to avoid clonal selection of tumor cells. Cooperation among physicians involved in cancer management will lead to improvements in the treatment of bone metastases due to prostate cancer and is thought to extend to other tumor types.

Safety and antitumor efficacy of 153Sm-EDTMP and docetaxel administered sequentially to patients with metastatic castration-resistant prostate cancer

BackgroundBone metastases are responsible for most of the morbidity associated with metastatic castration-resistant prostate cancer (mCRPC). Bone-seeking radiopharmaceuticals have been approved for palliation of painful skeletal metastases, but their clinical use is limited by concerns of toxicities both when administered alone and especially when combined with chemotherapy agents. ObjectiveWe investigated whether docetaxel administered to mCRPC patients after treatment with samarium-153-labeled ethylene-diamine-tetra-methylene-phosphonic acid (153Sm-EDTMP) has increased toxicity and/or reduced antitumor efficacy. Materials and methodsThirty mCRPC patients with skeletal metastases were enrolled. Patients received standard therapy with docetaxel (75 mg/m2 intravenously every 21 days for at least six cycles) on average 6 weeks after 153Sm-EDTMP (37 MBq/kg). Patients were monitored for the presence of toxicities, and antitumor efficacy was assessed by changes in serum prostate-specific antigen levels. Besides standard descriptive statistical analysis, progression-free survival and overall survival were defined using the Kaplan–Meier method. ResultsOver 80% of the patients showed favorable biochemical responses. Median time to progression was 9.1 months (mean 9.8, 95% confidence interval 7.8–9.9), and median overall survival was 19.9 months (mean 24.5, 95% confidence interval 16.9–22.8); five patients were still alive over 5 years after enrollment. No additional hematological toxicities were observed when docetaxel was administered after 153Sm-EDTMP other than those expected when administering the agent alone. ConclusionPrior administration of 153Sm-EDTMP does not cause additional toxicities for subsequent treatment with docetaxel and does not reduce the antitumor efficacy of the latter. This work justifies further investigations on the possible synergistic effects of combined strategies with the two agents.

Tecniche diagnostiche per lo studio dei tumori neuroendocrini

Il sistema neuroendocrino e costituito da un insieme eterogeneo di cellule accomunate dalla capacita di secernere neuro-ormoni. Secondo le piu recenti evidenze anatomiche, si distingue un Sistema Neuroendocrino Difuso (DNES, comprendente cellule nervose ed endocrine “disperse” in vari organi e tessuti) e un Sistema Neuroendocrino Confinato (CNES, comprendente i tessuti ghiandolari neuroendocrini collocati in strutture anatomicamente definibili).

Disseminated bone metastases from occult thyroid cancer effectively treated with debulking surgery and a single dosimetry-guided administration of radioiodine

In this paper we report on a successful management of multiple bone metastases from differentiated thyroid cancer. In 2007, a 75-year-old female patient, previously referred for thyroidectomy for multinodular goiter, underwent surgical removal of a lumbar mass with histological findings of metastasis from well differentiated thyroid cancer. After surgery, serum thyroglobulin (sTg) was 204.4 ng/mL. A diagnostic/dosimetric (123)I WBS was performed, following stimulation by rTSH. Serial WBSs were acquired, along with SPECT/CT and bone scan for localization of lesions. sTg raised to 3.810 ng/mL, and (123)I WBS showed thyroid remnants and numerous areas with high iodine-uptake corresponding to skeletal sites, the two largest loading on the skull, with osteolytic pattern. Calculated radiation absorbed dose for skull lesions, determined by mean of MIRD methodology, was 63.5 mGy/MBq. The patient underwent surgical removal of the two major skull lesions. Successively, 100 mCi (131)I was administered after stimulation by rTSH, with stimulated sTg 297 ng/mL. After 8 months, diagnostic WBS was negative both for remnants and metastases and rTSH-stimulated Tg was 0.6 ng/mL. To date, the patient has maintained sTg values <1 ng/mL during L-T4 suppressive therapy and after rTSH stimulations. In this unusual case of extensive bone cancerous involvement with high iodine avidity, a multidisciplinary approach based on surgery and dosimetry-guided radiometabolic therapy allowed to accurately assess the patient, execute a small number of treatments and achieve a complete remission of the disease in a very short time, with no additive morbidity.