Real-World Evaluation of the Management, Treatment Pathways and Outcome of Melanoma Patients with Target Therapies in Italy.

INTRODUCTION: In recent years, an increasing trend in the incidence of melanoma has been observed in Europe. Although early diagnosis and prompt intervention with local resection often results in positive outcomes, conversely, metastatic disease is still clinically challenging with a poor prognosis and a 5-year survival of around 30%. The growing awareness of melanoma biology and of antitumor immune responses has allowed the development of novel therapies targeted at specific molecular alterations occurring at advanced stages. This real-world analysis examined patients with melanoma in Italy, focusing on treatment patterns, outcome, time to discontinuation (TTD), and resource consumption. METHODS: Two retrospective observational analyses were conducted for BRAF+ patients with metastatic melanoma and those with a positive sentinel lymph node biopsy in an adjuvant setting, retrieving data from the administrative databases covering 13.3 million residents. The cohort melanoma BRAF+ in metastatic setting comprised 729 patients with targeted therapy (TT) (n = 671 with TT as first line and 79 as second line). RESULTS: Median TTD was 10.6 months in first line and 8.1 months in second line. Median overall survival from the start of first TT line was 27 months and was 11.8 months for patients with brain metastasis. In the dabrafenib plus trametinib patients, main healthcare resource consumption tended to increase in the presence of brain metastasis. The cohort with a positive sentinel lymph node biopsy under adjuvant therapy (n = 289) included 8% patients treated with dabrafenib plus trametinib or tested BRAF+, 5% BRAF wild-type, and 10% under immunotherapy. CONCLUSION: Our findings provided an overview on TT utilization on metastatic melanoma patients in real clinical practice and highlighted an increased burden in brain metastatic patients.

The role of Geriatric screening tool (G8) in predicting side effect in older patients during therapy with aromatase inhibitor.

BACKGROUND: Endocrine therapy is the main treatment in hormonosensitive breast cancer; the most frequent side effects are arthralgia, osteoporosis, depression, dyslipidemia and hypertension. G8 is a simple test developed to identify older patients who could benefit from a comprehensive geriatric assessment (CGA). The aim of this study is to evaluate the possible role of G8 in predicting side effects from treatment with aromatase inhibitor in women ≥65 years old. MATHERIAL AND METHOD: Women ≥65 years old affected by breast cancer about to start a therapy with an aromatase inhibitor, in the adjuvant setting, were evaluated with the G8 tool. Patients were classified as "fit" with G8 score > 14 or "vulnerable" with G8 score ≤ 14; they then started treatment and clinical-instrumentalfollow-up. RESULTS: From April 2016 to February 2018, 50 consecutive patients were screened. Median age was 75.1 (range 65-86). G8 identified 30 patients (60%) as "fit" (score > 14) and 20 (40%) as "vulnerable" (score ≤ 14). The grade of concordance between G8 score and the appearance/absence of adverse events were statistically significant (41/50 patients, 82%, p = 0.0002); sensitivity resulted in 78% and specificity was 81%; positive predictive value was 70% and negative predictive value was 87%. The most frequent adverse event was arthromyalgia. CONCLUSION: The G8 screening tool has a potential role in predicting side effects during a treatment with aromatase inhibitor. G8 could be very useful in everyday clinical practice for this population.

Long-Lasting Exceptional Radiological Complete Response after Treatment with Eribulin in a Patient with Triple-Negative Breast Cancer with Liver Involvement.

We report the case of a 50-year-old woman with a triple-negative Ki67 80% breast cancer with liver metastases, who obtained a radiological long-lasting complete response after treatment with eribulin. The patient initially experienced progressive disease after a standard anthracycline/taxane-based adjuvant chemotherapy, a first-line treatment for metastatic disease with paclitaxel-bevacizumab, and a second-line maintenance treatment with bevacizumab and capecitabine. Eribulin was administered according to a 1.23 mg/m2 scheme on days 1 and 8 every 3 weeks, and the treatment was always well tolerated. After 45 cycles of therapy, we still detected radiological evidence of complete response on liver sites of disease. This case report underlines the great efficacy of eribulin as third-line treatment for metastatic disease in a very aggressive form of breast cancer.

Metformin Use Is Associated With Longer Progression-Free Survival of Patients With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or Somatostatin Analogues.

BACKGROUND & AIMS: Metformin seems to have anticancer effects. However, it is not clear whether use of glycemia and metformin affect outcomes of patients with advanced pancreatic neuroendocrine tumors (pNETs). We investigated the association between glycemia and progression-free survival (PFS) of patients with pNETs treated with everolimus and/or somatostatin analogues, as well as the association between metformin use and PFS time. METHODS: We performed a retrospective analysis of 445 patients with advanced pNET treated at 24 medical centers in Italy from 1999 through 2015. Data on levels of glycemia were collected at time of diagnosis of pNET, before treatment initiation, and during treatment with everolimus (with or without somatostatin analogues), octreotide, or lanreotide. Diabetes was defined as prior or current use of glycemia control medication and/or fasting plasma glucose level ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5% (48 mmol/L), or a random sample of plasma glucose ≥ 200 mg/dL (11.1 mmol/L), with reported classic symptoms of hyperglycemia or hyperglycemic crisis. Patients were assigned to groups based on diagnosis of diabetes before or during antitumor therapy. PFS was compared between patients with vs without diabetes. Among patients with diabetes, the association between metformin use and PFS was assessed. We performed sensitivity and landmark analyses to exclude patients who developed diabetes while receiving cancer treatment and to exclude a potential immortal time bias related to metformin intake. RESULTS: PFS was significantly longer in patients with diabetes (median, 32.0 months) than without diabetes (median, 15.1 months) (hazard ratio for patients with vs without diabetes, 0.63; 95% confidence interval, 0.50-0.80; P = .0002). PFS of patients treated with metformin was significantly longer (median PFS, 44.2 months) than for patients without diabetes (hazard ratio for survival of patients with diabetes receiving metformin vs without diabetes, 0.45; 95% confidence interval, 0.32-0.62; P < .00001) and longer than for patients with diabetes receiving other treatments (median PFS, 20.8 months; hazard ratio, 0.49; 95% confidence interval, 0.34-0.69; P < .0001). In multivariable analysis, adjusted for other factors associated with outcomes, metformin was associated with longer PFS but level of glycemia was not. Metformin was associated with increased PFS of patients receiving somatostatin analogues and in those receiving everolimus, with or without somatostatin analogues. Sensitivity and landmark analyses produced similar results. CONCLUSIONS: In a retrospective study of patients with pNETs, we found a significant association between metformin use and longer PFS.

A classification prognostic score to predict OS in stage IV well-differentiated neuroendocrine tumors.

No validated prognostic tool is available for predicting overall survival (OS) of patients with well-differentiated neuroendocrine tumors (WDNETs). This study, conducted in three independent cohorts of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy; n = 515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (n = 457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (n = 415). The score was developed using data from patients included in cohort (i) (training set); external validation was performed by applying the score to the data of the two independent cohorts (ii) and (iii) evaluating both calibration and discriminative ability (Harrell C statistic). We used data on age, primary tumor site, metastasis (synchronous vs metachronous), Ki-67, functional status and primary surgery to build the score, which was developed for classifying patients into three groups with differential 10-year OS: (I) favorable risk group: 10-year OS ≥70%; (II) intermediate risk group: 30% ≤ 10-year OS < 70%; (III) poor risk group: 10-year OS <30%. The Harrell C statistic was 0.661 in the training set, and 0.626 and 0.601 in the RARECAREnet and Italian multicentric validation sets, respectively. In conclusion, based on the analysis of three 'field-practice' cohorts collected in different settings, we defined and validated a prognostic score to classify patients into three groups with different long-term prognoses.

Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: A real-world study.

INTRODUCTION: Besides data reported in a Phase-III trial, data on sunitinib in pancreatic Neuroendocrine Tumors (panNETs) are scanty. AIM: To evaluate sunitinib efficacy and tolerability in panNETs patients treated in a real-world setting. PATIENTS AND METHODS: Retrospective analysis of progressive panNETs treated with sunitinib. Efficacy was assessed by evaluating progression-free survival, overall survival, and disease control (DC) rate (stable disease (SD) + partial response + complete response). Data are reported as median (25th-75th IQR). RESULTS: Eighty patients were included. Overall, 71.1% had NET G2, 26.3% had NET G1, and 2.6% had NET G3 neoplasms. A total of 53 patients (66.3%) had received three or more therapeutic regimens before sunitinib, with 24 patients (30%) having been treated with four previous treatments. Median PFS was 10 months. Similar risk of progression was observed between NET G1 and NET G2 tumors (median PFS 11 months and 8 months, respectively), and between patients who had received ≥ 3 vs ≤ 2 therapeutic approaches before sunitinib (median PFS 9 months and 10 months, respectively). DC rate was 71.3% and SD was the most frequent observed response, occurring in 43 pts (53.8%). Overall, 59 pts (73.8%) experienced AEs, which were grade 1-2 in 43 of them (72.9%), grade 3 in 15 pts (25.4%), and grade 4 in one patient (1.7%). Six pts (7.5%) stopped treatment due to toxicity. CONCLUSIONS: The present real-world experience shows that sunitinib is a safe and effective treatment for panNETs, even in the clinical setting of heavily pre-treated, progressive diseases.

Everolimus in Combination with Octreotide Long-Acting Repeatable in a First-Line Setting for Patients with Neuroendocrine Tumors: A 5-Year Update.

BACKGROUND: We previously presented data of this multicentric, phase II study showing that everolimus plus octreotide long-acting repeatable (LAR) for advanced neuroendocrine neoplasms (NENs), in the first line setting, is an active and safe treatment. We now present updated data at 5 years. METHODS: Patients with advanced well-differentiated, previously untreated neuroendocrine tumors of the gastroenteropancreatic tract and of the lung received octreotide LAR 30 mg plus everolimus 10 mg/day. The primary endpoint was the objective response rate (ORR). We performed an analysis of "long responder" patients and of time to progression (TTP) and overall survival (OS) at 5 years. RESULTS: Fifty patients were enrolled; the primary tumor site was: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum/duodenum (2 patients), and unknown (14 patients). Seventeen (34%) of these patients have received treatment for more than 2 years. The median exposure to study drugs was 519.5 days (range 48-2,024). Currently 3 patients are still in treatment. The ORR (partial response + complete response) was 18% (95% confidence interval [CI] 7.4-28.6): complete response 1 patient (2%), partial response 8 patients (16%), stable disease 37 patients (74%). The median TTP was 33.6 months (95% CI 18.7-41.2) and the median OS was 61.0 months (95% CI 49.8-not reached). CONCLUSION: In this update of clinical outcome at 5-year follow-up, everolimus plus octreotide has been shown to be active in advanced NENs. The current analysis showed a further prolongation of TTP and a long exposure to the study drug without major side effects in the long term.

Activity of a three-drug combination including cisplatin (CLOVER regimen) for poorly differentiated neuroendocrine carcinoma.

BACKGROUND/AIM: No standard treatment has been established for poorly-differentiated neuroendocrine carcinomas (PDNEC). The aim of this study is to evaluate the response to the combination of three drugs. MATERIAL AND METHODS: We reviewed 21 PDNEC patients treated from 2008 to 2013 in two Institutions. Five patients were initially treated with epirubicin, fluorouracil and temozolomide. Because of toxicity, the regimen was modified into cisplatin, capecitabine and dacarbazine (scheme B-CLOVER regimen). RESULTS: Primary tumor site was: pancreas 7 (33%), lung 5 (24%), colon-rectum 5 (24%), unknown 3 (14%) and stomach 1 (5%). The response rate was 24% (0 complete response, 24% partial responses, 38% stable disease, 9% progression and 19% unassessable). The global overall survival (OS) is 13 months (range=1-29) and progression-free survival (PFS) was 6 months (range=1-11). CONCLUSION: The combination chemotherapy of cisplatinum, capecitabine and dacarbazine is feasible and should be considered as an option for PDNEC.

Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: an ITMO group study.

BACKGROUND: Preclinical and clinical studies suggest synergistic activity between somatostatin analogues and mammalian target of rapamycin inhibitors. The activity and safety of everolimus was assessed in combination with octreotide long-acting repeatable (LAR) in patients with neuroendocrine tumors (NETs) of gastroenteropancreatic and lung origin. METHODS: This was a phase 2, multicenter trial using a Simon's 2-stage minimax design. Treatment-naive patients with advanced well-differentiated NETs of gastroenteropancreatic tract and lung origin received everolimus 10 mg daily, in combination with octreotide LAR 30 mg every 28 days. The primary endpoint was objective response rate (ORR). RESULTS: A total of 50 patients (median age, 60.5 years) were enrolled. Primary tumor sites were: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum and duodenum (2 patients), and unknown (14 patients). Thirteen patients (26%) had carcinoid syndrome. Treatment-related adverse events (AEs) were mostly grade 1 or 2; the only grade 4 AE was mucositis in 1 patient, whereas grade 3 AEs included skin rash in 1 case (2%), stomatitis in 4 cases (8%), and diarrhea in 11 cases (22%). The ORR was 18%; 2% of patients had a complete response (CR), 16% a partial response (PR) and 74% achieved stable disease (SD). All CRs and all PRs as well as 92% of SDs had a duration ≥ 6 months. The clinical benefit (CR+PR+SD) was 92%. At a median follow-up of 277 days, median time to progression and overall survival were not reached. CONCLUSIONS: The everolimus-octreotide LAR combination was active and well tolerated in these previously treated patients with advanced NETs, suggesting a possible role as first-line treatment in patients with NET.

New perspectives in the treatment of neuroendocrine tumours.

The treatment of neuroendocrine tumours (NETs) is mainly based on their biological characteristics of aggressiveness and functional features. Radical surgery is the sole effective approach. In other types of well-differentiated tumours, hormonal therapy is the treatment of choice, as well as chemotherapy is the treatment of choice for aggressive diseases. Recent advances in the field of targeted therapies have expanded options for NETs, particularly of pancreatic neuroendocrine tumours. The radiotherapy option in NETs is based on radiopharmaceuticals targeting receptors over-expressed by these diseases and acting on the cell metabolism.

Neuroendocrine tumors of unknown primary site: gold dust or misdiagnosed neoplasms?

AIMS AND BACKGROUND: Neuroendocrine tumors of an unknown primary site are rarer than other neuroendocrine tumors (0.6-2% of all neuroendocrine tumors) and have a poor prognosis. The aim of the study was to review the cases of unknown primary site neuroendocrine tumors encountered at the Istituto Nazionale Tumori of Milan between 1984 and 2008 in order to verify their incidence and evaluate their characteristics and prognosis. METHODS AND STUDY DESIGN: During the study period, 750 neuroendocrine tumor patients attended our Institute, 82 of whom (10.9%) were diagnosed as having neuroendocrine tumors of an unknown primary site. The data from their medical records were analyzed descriptively, and survival probabilities were calculated using the Kaplan-Meier method and the logrank test, considering patient, tumor and treatment-related characteristics. RESULTS: The 82 patients with neuroendocrine tumors of an unknown primary site (34 males) had a median age of 60 years; 57 (69.5%) had histologically well-differentiated tumors, 3 (3.7%) poorly differentiated tumors, and 22 (26.8%) had tumors that could not be classified. Of the 52 patients (62.2%) who underwent Octreoscan® (Bykgulden Italia SpA), 40 (78.4%) showed a pathological uptake and 11 (21.6%) were negative. Thirty-one patients (37.8%) underwent metastatic site surgery, which was radical in 11 cases (35.4%). Forty-eight patients (58.5%) received somatostatin analogues, and 41 (50.0%) underwent chemotherapy. At the end of the study period, 59 patients (72.0%) had died, 31 (53.0%) because of disease progression, and 23 (28.0%) were still alive. CONCLUSIONS: Neuroendocrine tumors of an unknown primary site are difficult to identify but their incidence is higher than previously reported, and the prognosis remains unfavorable.

Mammalian target of rapamycin expression in poorly differentiated endocrine carcinoma: clinical and therapeutic future challenges.

While the mammalian target of rapamycin (mTOR) signaling pathway is a promising target for well-differentiated endocrine carcinoma therapy with the mTOR inhibitor everolimus (RAD001), poorly differentiated endocrine carcinomas (PDECs) are usually excluded from clinical trials due to their aggressiveness. So far, mTOR activity in PDECs has only been tested in cell lines. This study reviewed 36 mono-institutional PDECs to determine mTOR expression. Slides of normal kidney as positive control were used to optimize mTOR staining. To ensure antibody specificity, consecutive sections were incubated in the absence of primary antibody. Immunoreactivity was evaluated on a semi-quantitative scale scoring the extent and intensity of staining. The product of these two scores was used to obtain a total immunostaining score. The main primary site of disease was the pancreas, and 83% of patients had stage IV disease. In 80% of samples, mTOR expression was maintained at similar levels, with no relationship to tumor origin or proliferation rate determined by MIB-1. This study seems to demonstrate that mTOR is expressed in human PDECs regardless of tumor site. Its role in relation to the activity of everolimus in this subset of patients needs to be confirmed.

Common Diagnostic Challenges in the Histopathologic Diagnosis of Neuroendocrine Lung Tumors: A Case Report.

Bronchopulmonary neuroendocrine tumors are an uncommon group of neoplasms, accounting for about 20% of all lung carcinomas, arising from stem cells of the bronchial epithelium known as Kulchitsky cells. In the past, these tumors were grouped among benign or less aggressive malignant pulmonary tumors. Currently, according to the 2004 World Health Organization categorization, these tumors are separated into 4 subtypes characterized by increasing biologic aggressiveness: low-grade (typical carcinoid; TC), intermediate-grade (atypical carcinoid; AC) and high-grade (large-cell neuroendocrine carcinoma, LCNEC, and small-cell lung carcinoma, SCLC). They differ by morphologic, immunohistochemical and structural features. At histopathologic analysis, these tumors share progressive increase in a number of mitotic figures per 10 high-power fields and in the extent of necrosis, with TC having the lowest values and SCLC having the highest. TCs and ACs make up approximately 1-2% of all primary lung tumors. Differentiating ACs from TCs or LCNEC and SCLC is clinically important because the treatment modalities and prognoses for these types of tumors are different. We report a case of misdiagnosis of bronchopulmonary neuroendocrine tumor in a young woman which has heavily influenced her clinical history.

Pitfalls in the diagnosis of neuroendocrine tumors: atypical clinical and radiological findings as cause of medical mistakes.

AIMS AND BACKGROUND: Carcinoids are infrequent neoplasms arising from neuroendocrine cells. Due to blurred symptoms and the presence of equivocal diagnostic findings, these tumors are sometimes misdiagnosed. Therefore, increased rates of false neuroendocrine tumors represent an emerging problem in clinical practice. Our aim is to alert clinicians on this matter by supplying them with useful warnings. METHODS: In the specialized neuroendocrine tumor study Center Centro di Riferimento per lo Studio e la Cura dei Carcinoidi e dei Tumori Neuroendocrini (Ce.Ri.Ca), some patients highly suspected to have a neuroendocrine tumor have been recognized as having false neuroendocrine tumors. The related clinical and instrumental findings leading to a previous wrong neuroendocrine tumor diagnosis are reported. RESULTS: From July 2006 to December 2008, 88 consecutive cases of neuroendocrine tumors (Nets) were referred at Ce.Ri.Ca. In the former group, 8 cases of false Nets were discovered while in the remaining 80 cases a correct Net diagnosis was carried out. Watchful differential diagnoses and skill appraisal of laboratory investigations resulted in: chronic atrophic gastritis with enterochromaffin-like cell hyperplasia (4 cases), estrogen-deprivation syndrome (1), hypochondriac disorder (1), metabolic syndrome (1), and sarcoidosis (1). CONCLUSIONS: Neuroendocrine tumors are still relatively known clinical entities. To discriminate false neuroendocrine tumors from neuroendocrine tumors requires a good expertise and a large daily practice with the disease. Good knowledge and skillfulness in identifying biochemical alterations and false radiological positive results could avoid both patient inconvenience and very expensive workup. The importance of a multidisciplinary approach in specialized centers is emphasized.

The impact of antithrombotic prophylaxis on infectious complications in cancer patients with central venous catheters: an observational study.

Infections in cancer patients after implantation of a central venous device (CVD) are not infrequent and are potentially serious. The possibility of limiting this complication with antithrombotic drugs is still debated. For this observational study, we recorded the routine management of CVD in cancer patients in 18 oncology centers in Lombardy (northern Italy), assessing the effect of antithrombotic prophylaxis on catheter-related infections. Out of 1410 patients enrolled, 451 received antithrombotic prophylaxis continuously after implantation of the central line. During a median follow-up of 30 months, 57 catheter-related infections were reported in the 1390 patients seen at least once at follow-up visits (4.1% of the whole series), giving an overall incidence of 0.10 infections per 1000 catheter days. This complication was significantly more frequent among patients with an indwelling central venous catheter, or peripherally inserted catheter, than among those with a port device, and the group not given antithrombotic prophylaxis had 0.14 infective complications/1000 CVD days compared with 0.05/1000 CVD days (odds ratio 2.4; 95% confidence interval 1.7-5.0) for those treated. Antithrombotic prophylaxis protected against infections at the catheter exit site and track but not against systemic infections. Confirming earlier evidence, this study found a reduction in catheter-related infections in patients given antithrombotic prophylaxis. However, this reduction, reflecting local infections, seems unlikely to be one of the mechanisms explaining the lower mortality among our patients treated with anticoagulants.

Merkel cell carcinoma after liver transplantation: a case report.

BACKGROUND: Merkel cell carcinoma is a rare and aggressive neuroendocrine skin cancer with a very low incidence in the general population. MCC seems to be common in transplant recipients and 52 cases have been reported in the literature. METHODS AND RESULTS: This report describes a Merkel cell carcinoma which developed in a liver transplant recipient. To our knowledge, this is the second such case reported, as Merkel cell carcinoma most commonly occurs after kidney and heart transplants. The treatment approach is described and the literature on the subject is reviewed. CONCLUSION: There is currently no consensus regarding the optimal therapeutic approach to Merkel cell carcinoma. In transplant recipients, such tumors are more common and more aggressive but their treatment does not differ from the treatment of Merkel cell carcinomas in the general population.

Renal cell cancer and sorafenib: skin toxicity and treatment outcome.

We describe the case of a young man with refractory renal cell carcinoma who achieved an objective response in a metastatic lesion after biotherapy with the multikinase inhibitor sorafenib and also developed a severe skin reaction. The patient had been previously treated with various combinations of immunochemotherapy without any clinical benefit. We performed a brief review of the literature where similar cases were documented with the use of various anti-EGFR agents. The hypothesis of the correlation of skin toxicity with disease response is not new, but in the absence of any strong evidence remains controversial.

Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours?

PURPOSE: The aim of this trial was to evaluate the safety and efficacy of oxaliplatin and capecitabine (XELOX) in neuroendocrine tumours' (NETs) treatment. METHODS: Forty patients (pts) with advanced NETs were treated. Of these, 13 had untreated poorly differentiated NETs, 27 had well-differentiated NETs in progression after somatostatin analogues. Patients received oxaliplatin e.v. 130 mg/mq i.v. and capecitabine 2,000 mg/mq/die. The primary sites of the disease were: lung (10 pts), pancreas (15 pts), small bowel (8 pts), unknown (1 pt), others (6 pts). RESULTS: In 13 pts with poorly differentiated NETs objective responses (OR) were: 3 PR (23%), 1 SD (7%), 9 PD (70%). Biochemical responses were 11%. In 27 patients with well-differentiated NETs the OR were: 8 PR (30%), 13 SD (48%) and 6 PD (22%). Biochemical and symptomatic responses were 20 and 50%, respectively. CONCLUSIONS: The XELOX regimen is effective and tolerated in well-differentiated NETs after progression following somatostatin analogues.

Pulmonary carcinoid tumours: indolent but not benign.

BACKGROUND: The aim of this retrospective study was to analyse the malignant behaviour of low-grade pulmonary neuroendocrine tumours (NETs) treated at our institution. PATIENTS AND METHODS: We reviewed 48 consecutive patients with pulmonary NETs referred to our Medical Oncology Unit between 1998 and 2006, including 33 subjects with typical carcinoids (TCs) and 15 with atypical carcinoids (ACs). RESULTS: At diagnosis, there were 37 metastatic and 11 non-metastatic patients. Medical treatments used were somatostatin analogues, combined chemotherapy, within study protocols, 5-fluorouracil/dacarbazine/epiadriamycin (FDE), and oxaliplatin plus capecitabine (XELOX). Median disease-free survival was 72 months for the TC patients and 38 months for the AC patients. Actuarial 5-year survival was 93% for those with TCs and 73% for those with ACs. The mean overall survival was 68 months for the non-metastatic patients (78 months for TC patients and 58 months for AC patients) and 36 months for patients with advanced disease (42 and 32 months, respectively). CONCLUSION: Cell type is the strongest determinant of prognosis, and the degree of malignancy increases from TCs to ACs. Moreover, the prognosis of metastatic pulmonary carcinoids is not as good as expected. Our analysis suggests that patients with advanced disease should receive first-line therapy with a somatostatin analogue, with chemotherapy regimens (FDE, XELOX) used in progressing cases.