Prognostic factors in a multicentre study of 247 atypical pulmonary carcinoids

Daddi, Niccolò; Schiavon, Marco; Filosso, Pier Luigi; Cardillo, Giuseppe; Ambrogi, Marcello Carlo; Palma, Angela De; Luzzi, Luca; Bandiera, Alessandro; Casali, Christian; Ruffato, Alberto; Angelis, Verena De; Andriolo, Luigi Gaetano; Guerrera, Francesco; Carleo, Francesco; Davini, Federico; Urbani, Moira; Mattioli, Sandro; Morandi, Uliano; Zannini, Piero; Gotti, Giuseppe; Loizzi, Michele; Puma, Francesco; Mussi, Alfredo; Rícci, Alberto; Oliaro, A; Rea, Federico; Capozzi, Rosanna; Tassi, Valentina; Pagliarulo, Vincenzo; Ghisalberti, Marco; Calabrese, Fiorella; Sapino, Anna; Delsedime, Luisa; Graziano, Paolo; Alì, Greta; Fontanini, Gabriella; Sidoni, Angelo; Ascani, Stefano; Trabucco, Xenia; Sina, Donatella; Arrigoni, Gianluigi; Rossi, Giulio; Agostinelli, Claudio

doi:10.1093/ejcts/ezt470

Cited by 52 publications

(49 citation statements)

References 20 publications

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“…The 5-year survival rate in this study was 83%, and RFS was at the upper end of the range of previous studies (Table 4). This finding may be explained by the R0-based selection of patients and the high rate of routine lymph node dissection [23,[25][26][27]. The majority of recurrences occurred during the first 5 years of follow-up, but the modalities of follow-up were found to be clearly suboptimal, both in terms of the time interval between control checkups and the type of examinations, suggesting the need to improve both baseline and follow-up imaging modalities.…”

Section: Discussionmentioning

confidence: 99%

“…The majority of the studies evaluated heterogeneous series of patients affected by lung NET, without investigating specific prognostic factors for each histotype [9-12, 14-20, 22, 24, 26, 27]. In the few studies that focused on AC populations, prognostic factors for overall survival rather than for recurrence-or disease-free survival have been evaluated [12,13,16,20,21,23,43]. To the best of our knowledge, only Filosso et al [25] analyzed disease-free survival in a group of exclusively AC patients, finding that the variables influencing disease-free survival in univariate analysis were male gender, age, and pT4 tumors.…”

Section: Discussionmentioning

confidence: 99%

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Natural History of Localized and Locally Advanced Atypical Lung Carcinoids after Complete Resection: A Joined French-Italian Retrospective Multicenter Study

Marciello

Mercier

Ferollà³

et al. 2017

Neuroendocrinology

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Background: The natural history and the best modality of follow-up of atypical lung carcinoids (AC) remain ill defined. The aim of this study was to analyze recurrence-free survival (RFS) after complete resection (R0) of stage I-III pulmonary AC. Secondary objectives were prognostic parameters, the location of recurrences, and the modality of follow-up. Methods: A retrospective review of 540 charts of AC patients treated between 1998 and 2008 at 10 French and Italian centers with experience in lung neuroendocrine tumor management was undertaken. The exclusion criteria were MEN1-related tumor, history of another cancer, referral after tumor relapse, and being lost to follow-up. A central pathological review was performed in each country. Results: Sixty-two patients were included. After a median follow-up time of 91 months (mean 85, range 6-165), 35% of the patients experienced recurrence: 16% were regional recurrences and 19% were distant metastases. Median RFS was not reached. The 1-, 3-, and 5-year RFS rate was 90, 79, and 68%, respectively. In univariate analysis, lymph node involvement (p = 0.0001), stage (p = 0.0001), mitotic count (p = 0.004), and type of surgery (p = 0.043) were significantly associated with RFS. In multivariate analysis, lymph node involvement was significantly associated with RFS (HR 95% CI: 0.000-0.151; p = 0.004). During follow-up, somatostatin receptor scintigraphy, fibroscopy, and abdominal examination results were available for 22, 12, and 25 patients, respectively. The median time interval for imaging follow-up was 10 months. Conclusions: After complete resection of AC, recurrences were observed mostly within the first 5 years of follow-up, within bronchi, mediastinal nodes, the liver, and bones. In R0 patients, lymph node involvement could help to stratify follow-up intervals. Suboptimal imaging is evidenced.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Natural History of Localized and Locally Advanced Atypical Lung Carcinoids after Complete Resection: A Joined French-Italian Retrospective Multicenter Study

Marciello

Mercier

Ferollà³

et al. 2017

Neuroendocrinology

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“…[9]. Retrospective analyses suggest some patients might benefit from adjuvant chemotherapy [14,36], whereas adjuvant radiotherapy has been shown to improve local control in some studies [37] but not others [14]. In one retrospective study in patients with pulmonary NET (including 36 patients with TC and 3 with AC), no local recurrences were observed after adjuvant radiation therapy in node-positive patients [37].…”

Section: Surgerymentioning

confidence: 99%

Section: Surgerymentioning

confidence: 99%

Challenges in the Diagnosis and Management of Well-Differentiated Neuroendocrine Tumors of the Lung (Typical and Atypical Carcinoid): Current Status and Future Considerations

Wolin

2015

The Oncologist

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Neuroendocrine tumors (NET) of the lung represent approximately 25% of all primary lung tumors and can be classified as low grade (typical carcinoids), intermediate grade (atypical carcinoids), or high grade (large cell neuroendocrine carcinoma or small cell lung carcinoma). Low-and intermediate-grade lung NET are increasingly recognized as biologically distinct from high-grade lung NET based on clinical behavior and underlying molecular abnormalities. This review summarizes current knowledge and challenges in the diagnosis and management of low-and intermediate-grade lung NET. Accurate histopathologic classification of lung NET is critical to determining appropriate treatment options but can be challenging even for experts. For low-and intermediate-grade lung NET, surgery remains the mainstay of treatment for localized disease.Although no standard systemic therapy has been established for the treatment of advanced, unresectable disease, a number of promising treatment options are emerging, including somatostatin analogs, temozolomide-based chemotherapy, targeted therapy with mammalian target of rapamycin or vascular endothelial growth factor inhibitors, and peptide receptor radionuclide therapy. Given the difficulty in accurately diagnosing these tumors, and the paucity of data supporting establishment of standard systemic therapy options, management of patients within the setting of a multidisciplinary team, including specialists with expertise in NET, is recommended. Ongoing and future clinical trials hopefully will provide stronger evidence to support treatment recommendations for low-and intermediate-grade lung NET. The Oncologist 2015;20:1123-1131Implications for Practice: Treatment of neuroendocrine tumors (NET), particularly those of lung origin, continues to evolve. This review seeks to educate oncologists on the most up-to-date options and supporting data regarding management of two rare lung neoplasms, typical and atypical carcinoid tumors. Although surgical resection has been the mainstay of treatment, several systemic options have been studied in the treatment of NET of various origins that may potentially play a role in treating typical carcinoid tumors and atypical carcinoid tumors.

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“…In their sporadic counterparts ACs, lymph node metastases, distant metastases, and higher proliferation rate (Ki67 labeling index or mitotic index) have been repeatedly identified as adverse prognostic factors , Daddi et al 2013. Results on the prognostic values of gender, age, and tumor size are contradictory.…”

Section: Natural History and Prognostic Factors: Pulmonary Carcinoidsmentioning

confidence: 99%

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

Pieterman¹,

Conemans²,

Dreijerink³

et al. 2014

Endocrine-Related Cancer

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Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene lead to loss of function of its protein product menin. In keeping with its tumor suppressor function in endocrine tissues, the majority of the MEN1-related neuroendocrine tumors (NETs) show loss of heterozygosity (LOH) on chromosome 11q13. In sporadic NETs, MEN1 mutations and LOH are also reported, indicating common pathways in tumor development. Prevalence of thymic NETs (thNETs) and pulmonary carcinoids in MEN1 patients is 2-8%. Pulmonary carcinoids may be underreported and research on natural history is limited, but disease-related mortality is low. thNETs have a high mortality rate. Duodenopancreatic NETs (dpNETs) are multiple, almost universally found at pathology, and associated with precursor lesions. Gastrinomas are usually located in the duodenal submucosa while other dpNETs are predominantly pancreatic. dpNETs are an important determinant of MEN1-related survival, with an estimated 10-year survival of 75%. Survival differs between subtypes and apart from tumor size there are no known prognostic factors. Natural history of nonfunctioning pancreatic NETs needs to be redefined because of increased detection of small tumors. MEN1-related gastrinomas seem to behave similar to their sporadic counterparts, while insulinomas seem to be more aggressive. Investigations into the molecular functions of menin have led to new insights into MEN1-related tumorigenesis. Menin is involved in gene transcription, both as an activator and repressor. It is part of chromatin-modifying protein complexes, indicating involvement of epigenetic pathways in MEN1-related NET development. Future basic and translational research aimed at NETs in large unbiased cohorts will clarify the role of menin in NET tumorigenesis and might lead to new therapeutic options.

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Prognostic factors in a multicentre study of 247 atypical pulmonary carcinoids

Cited by 52 publications

References 20 publications

Natural History of Localized and Locally Advanced Atypical Lung Carcinoids after Complete Resection: A Joined French-Italian Retrospective Multicenter Study

Natural History of Localized and Locally Advanced Atypical Lung Carcinoids after Complete Resection: A Joined French-Italian Retrospective Multicenter Study

Challenges in the Diagnosis and Management of Well-Differentiated Neuroendocrine Tumors of the Lung (Typical and Atypical Carcinoid): Current Status and Future Considerations

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

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