TERAPIA RADIORECETTORIALE CON 177Lu- DOTATATE IN PAZIENTI CON TUMORE NEUROENDOCRINO POLMONARE

Aim: Thyroid transcription factor-1 (TTF-1), a nuclear transcription protein selectively expressed in the thyroid, the diencephalon and respiratory epithelium, is expressed in more than 90% of pulmonary small cells carcinomas (SCLSs) and in almost 75% of pulmonary non-small cell carcinomas (NSCLSs) but it is absent in typical pulmonary carcinoids (TCs). Neuroendocrine tumors (NETs) overexpress somatostatin receptors (SSTR). SSTR overexpression is the basis for the use of radiolabelled somatostatin analogues in diagnosis and treatment of NETs. Peptide receptor radionuclide therapy (PRRT) with 177Lu-labelled peptides has been used in the treatment of NETs. In this study we evaluated the role of TTF-1 in predictive response and progression free survival (PFS) after 177Lu-Dotatate treatment in patients with advanced bronchopulmonary NETs. Methods: We retrospectively evaluated 36 patients with advanced bronchopulmonary NETs overexpressing SSTR and treated with 177Lu-Dotatate with a cumulative activity up to 27,7GBq. On the basis of the TTF-1, 17 patients were TTF-1 positive while 19 patients resulted TTF-1 negative. Results: After the treatment, 15 of the 19 TTF-1 negative patients showed disease control (DC, i.e. complete response + partial response + stable disease), while the other 4 patients evolved to progressive disease (PD). The effect of the treatment has been different on the 17 TTF-1 positive patients: only two of them showed DC and the other 15 patients evolved to PD. There is a direct correlation between treatment response and the expression of TTF-1 (Pearson’s chi-square <0,15). PFS index for TTF-1 negative patients is 23 months, while for TTF-1 positive patients it is only 8 months. Conclusions: These results suggest that positivity to TTF-1 causes a negative predictive response to Lu-PRRT in patients with advanced bronchopulmonary NETs. Prognosis for patients expressing TTF-1 is negative

Cardiac molecular pathways influenced by doxorubicin treatment in mice

Doxorubicin (DOX) is a potent chemotherapeutic with distinct cardiotoxic properties. Understanding the underlying cardiotoxic mechanisms on a molecular level would enable the early detection of cardiotoxicity and implementation of prophylactic treatment. Our goal was to map the patterns of different radiopharmaceuticals as surrogate markers of specific metabolic pathways induced by chemotherapy. Therefore, cardiac distribution of Tc-99m-sestamibi, Tc-99m-Annexin V, Tc-99m-glucaric acid and [F-18]FDG and cardiac expression of Bcl-2, caspase-3 and -8, TUNEL, HIF-1 alpha, and p53 were assessed in response to DOX exposure in mice. A total of 80 mice (64 treated, 16 controls) were evaluated. All radiopharmaceuticals showed significantly increased uptake compared to controls, with peak cardiac uptake after one (Tc-99m-Annexin V), two (Tc-99m-sestamibi), three ([F-18]FDG), or four (Tc-99m-glucaric acid) cycles of DOX. Strong correlations (p <0.01) were observed between Tc-99m-Annexin V, caspase 3 and 8, and TUNEL, and between [F-18]FDG and HIF-1 alpha. This suggests that the cardiac DOX response starts with apoptosis at low exposure levels, as indicated by Tc-99m-Annexin V and histological apoptosis markers. Late process membrane disintegration can possibly be detected by Tc-99m-sestamibi and Tc-99m-glucaric acid. [F-18]FDG signifies an early adaptive response to DOX, which can be further exploited clinically in the near future

The value of oro-pharyngo-esophageal scintigraphy in the management of patients with aspiration into the tracheo-bronchial tree and consequent dysphagia

Tracheo-bronchial aspiration is the most invalidating condition which can happen to patients affected by dysphagia, especially when caused by central neurologic disorders; the associated pneumonia episodes represent the most frequent cause of death in these patients. Oro-pharyngo-esophageal scintigraphy (OPES) allows both functional imaging and semiquantitative evaluation of the subsequent phases of swallowing. CASE REPORT: We evaluated by means of OPES a woman who had previously undergone high-dose external beam radiation therapy for a nasopharyngeal carcinoma, which determined tissue fibrosis and progressive dysphagia. CONCLUSION: In this patient with dysphagia, OPES was a simple, inexpensive, noninvasive, and reliable technique that allowed to show the presence of bolus aspiration and quantified tracheobronchial aspirate

Peptide receptor radionuclide therapy with 177Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and 18F-FDG PET

Purpose: Typical and atypical carcinoids (TC and AC) represent 20 â\u80\u93 25 % of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with 177Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and 18F-FDG PET as prognostic factors in patients with advanced TC or AC. Methods: A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patientâ\u80\u99s kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients. Results: The median follow-up was 29 months (range 7 â\u80\u93 69 months). The disease control rate (DCR) in patients with TC was 80 %: 6 % complete response, 27 % partial response and 47 % stable disease. The median progression-free survival (mPFS) was 20.1 months (95 % CI 11.8 â\u80\u93 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 â\u80\u93 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 % CI 12.9 â\u80\u93 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 â\u80\u93 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 % CI 14.2 â\u80\u93 48.9 months) and 15.3 months (11.7 â\u80\u93 31.1 months) in the FDG PET-positive group. Conclusion: Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of aggressive tumour and is more frequent in patients with AC than in those with TC