Science Oncologia Medica 1

Firenze, Italy

Science Oncologia Medica 1

Firenze, Italy
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Pietrantonio F.,Fondazione IRCCS Instituto Nazionale dei Tumori | Miceli R.,Fondazione IRCCS Instituto Nazionale dei Tumori | Rimassa L.,Medical Oncology and Hematology Unit | Lonardi S.,Instituto Oncologico Veneto IRCCS | And 24 more authors.
Annals of Oncology | Year: 2017

Background: Regorafenib and TAS-102 have recently demonstrated statistically significant survival gains in patients with refractory metastatic colorectal cancer (mCRC). Life expectancy ≤12 weeks was an inclusion criterion in registrative trials, and the identification of proper clinical selection tools for the daily use of these drugs in heavily pre-treated patients is needed to improve the cost-benefit ratio. We aimed at building a nomogram able to predict death probability within 12 weeks from the date of assessment of refractory mCRC. Patients and methods: Four hundred eleven refractory mCRC patients with ECOG performance status (PS)≤2 receiving regorafenib, TAS-102 or other treatments were used as developing set. Putative prognostic variables were selected using a random forest model and included in a binary logistic model from which the nomogram was developed. The nomogram was externally validated and its performance was evaluated by examining calibration (how close predictions were to the actual outcome) and discriminative ability (Harrell C index) both on developing (internal validation) and validating (external validation) sets. Results: Four variables were selected and included in the nomogram: PS (P < 0.0001), primary tumor resection (P=0.027), LDH value (P=0.0001) and peritoneal involvement (P=0.081). In the developing set, the nomogram discriminative ability was high (C=0.778), and was confirmed in the validating set (C=0.778), where the overall outcome was better as a consequence of the enrichment in patients receiving regorafenib or TAS-102 (46% versus 34%; P < 0.0001). Conclusions: Our nomogram may be a useful tool to predict the probability of death within 12 weeks in patients with refractory mCRC. Based on four easy-to-collect variables, the 'Colon Life' nomogram and free app for smartphones may improve mCRC patients' selection for later-line therapies and assist researchers for the enrollment in clinical trials in this setting. © The Author 2016.


Antonuzzo L.,Science Oncologia Medica 1 | Antonuzzo L.,University of Siena | Del Re M.,Clinical Pharmacology and Pharmacogenetic Unit | Barucca V.,Misericordia General Hospital | And 6 more authors.
Cancer Treatment Reviews | Year: 2017

Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms representing less than 2% of all pancreatic malignancies. The PI3K-AKT-mTOR pathway is often deregulated in pNETs and seems to play a key role in tumorigenesis. Everolimus, an inhibitor of the mTOR pathway, has demonstrated efficacy in the treatment of pNETs. Nevertheless de novo or acquired drug resistance is responsible for disease progression and represents a major obstacle to overcome by clinicians. Blocking the PI3K/AKT/mTOR pathway may cover the supposed main mechanisms of resistance to everolimus. Therefore, BEZ-235, a potent oral dual PI3K/mTOR inhibitor was investigated in clinical trials. Globally more than 250 patients with different types of solid tumors were treated. Two studies were conducted in pNETs with BEZ-235 as single agent. The former was a phase 2 trial conducted in pNETs resistant to everolimus while the latter a randomized trial comparing everolimus and BEZ-235. Unfortunately, both the studies disappointed the expectations and were prematurely halted mainly due to severe toxicity. On this basis we reviewed m-TOR inhibitors in pNETs, focusing on their mechanisms of resistance and toxicity. © 2017 Elsevier Ltd


Ianniello A.,Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST IRCCS | Sansovini M.,Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST IRCCS | Severi S.,Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST IRCCS | Nicolini S.,Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST IRCCS | And 10 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2016

Purpose: Typical and atypical carcinoids (TC and AC) represent 20 – 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 patient’s 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 – 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 – 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 – 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 – 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 – 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 – 48.9 months) and 15.3 months (11.7 – 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. © 2015, Springer-Verlag Berlin Heidelberg.


PubMed | Nuclear Medicine, Science Oncologia Medica 1, Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST IRCCS and Italian National Cancer Institute
Type: Journal Article | Journal: European journal of nuclear medicine and molecular imaging | Year: 2016

Typical and atypical carcinoids (TC and AC) represent 20-25% 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 (177)Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and (18)F-FDG PET as prognostic factors in patients with advanced TC or AC.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 27.8GBq in four or fivecycles according to the patients 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.The median follow-up was 29months (range 7-69months). 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 20.1months (95% CI 11.8-26.8months). Stable disease was achieved in 47% of patients with AC with a mPFS of 15.7months (95% CI 10.6-25.9months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3months (95% CI 12.9-45.2months), but in patients with TTF-1-positive TC mPFS was 7.2months (4.2-14.0months; 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 26.4months (95% CI 14.2-48.9months) and 15.3months (11.7-31.1months) in the FDG PET-positive group.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.

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