Recent Advances in the Management of Typical and Atypical Lung Carcinoids

Prinzi, Natalie; Rossi, Roberta; Proto, Claudia; Leuzzi, Giovanni; Raimondi, Alessandra; Torchio, Martina; Milione, Massimo; Corti, Francesca; Colombo, Elena; Prisciandaro, Michele; Cascella, Tommaso; Spreafico, Carlo; Beninato, Teresa; Coppa, Jorgelina; Russo, Giuseppe Lo; Bartolomeo, Maria Di; Braud, Filippo de; Pusceddu, Sara

doi:10.1016/j.cllc.2020.12.004

Cited by 19 publications

(17 citation statements)

References 113 publications

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“…In addition, we also found that the proportion of AC patients with stage N2+N3 was significantly higher than that of TC patients (P<0.05). Previous studies have also proven that patients with ACs are characterized by a greater tendency to develop lymph nodal metastases and a worse prognosis (7,14,34,35). The possible reason was that ACs show more aggressive biological behaviors than TCs (11,36).…”

Section: Discussionmentioning

confidence: 99%

Prognostic nomogram for predicting long-term survival in bronchopulmonary carcinoid tumor patients receiving resection

Qiao¹,

Chen²,

Chen³

et al. 2021

Ann Transl Med

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Background: We analyzed bronchopulmonary carcinoid tumor (BPC) patients receiving resection from the Surveillance, Epidemiology, and End Results (SEER) database to identify the predictive factors of their survival. Then, we developed and validated nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in BPC patients.Methods: BPC patients registered in the SEER database were included. They were divided into a training set and an internal validation set (7:3). BPC patients from our center were included as an external validation set. Independent prognostic factors identified by a Cox regression model in the training set were used to construct nomograms to predict survival. Discrimination and calibration plots were used to evaluate the predictive accuracy of the nomograms. The nomograms were evaluated in both the internal and the external validation datasets.Results: Age, pathological type, and N stage were identified as independent prognostic factors of OS and CSS by Cox analyses (all P<0.05). Tumor size ≥2.5 cm (P=0.045) was an independent factor for unfavorable CSS. Based on these variables, nomograms were constructed. All concordance indexes of the training set, internal validation set, and external validation set indicated that the nomograms had the preferable discriminatory ability. The calibration plots for predictions of the 1-, 3-, and 5-year OS and CSS were in excellent agreement.Conclusions: Age, pathological type, N stage, and tumor size were independent predictive factors of prognosis in BPC patients receiving resection. These nomograms could serve as effective and accurate tools for the prognostic evaluation of patients with BPCs.

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Section: Discussionmentioning

confidence: 99%

Prognostic nomogram for predicting long-term survival in bronchopulmonary carcinoid tumor patients receiving resection

Qiao¹,

Chen²,

Chen³

et al. 2021

Ann Transl Med

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“…Mutations in exon 9 and 20 in 13% of TCs and 39% of ACs [10] Gene expression profiling Upregulated genes: RET, ASPM, BIRC5, BUB1, CEP55, FANCA [42] Downregulated genes: OTP, PCK1, ASB4, FOLRI1, CD44 [42,43].…”

Section: Chromosomal Instability (Cin)mentioning

confidence: 99%

“…CIN is increased in metastasized vs. non-metastasized carcinoids (gains 71% vs. 51%, losses 76% vs. 51%, cases with no chromosomal alterations 14% vs. 31%, respectively) [41] Mutations in PIK3CA Mutations in exon 9 and 20 in 13% of TCs and 39% of ACs [10] Gene expression profiling Upregulated genes: RET, ASPM, BIRC5, BUB1, CEP55, FANCA [42] Downregulated genes: OTP, PCK1, ASB4, FOLRI1, CD44 [42,43].…”

Section: Chromosomal Instability (Cin)mentioning

confidence: 99%

“…The surgical approach is dependent on the size, location, and tissue type. The treatment of choice for centrally localized TCs is conservative resection (i.e., sleeve resection, segmentectomy or wedge resection), while for ACs, especially in a peripheral location, often anatomic resection (i.e., bi/lobectomy or pneumonectomy) is required [10]. In cases of centrally located intraluminal carcinoids, bronchoscopic excision may be also a therapeutic option [11].…”

Section: Introductionmentioning

confidence: 99%

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Bronchial Carcinoids: From Molecular Background to Treatment Approach

Araujo‐Castro

Pascual‐Corrales

Molina‐Cerrillo

et al. 2022

Cancers

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A better understanding of the genetic and molecular background of bronchial carcinoids (BCs) would allow a better estimation of the risk of disease progression and the personalization of treatment in cases of advanced disease. Molecular studies confirmed that lungs neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are different entities; thus, no progression of NET to NEC is expected. In BCs, MEN1 gene mutations and deletions and decreased gene expression have been associated with a poor prognosis. ATRX mutation has also been linked to a shorter disease-specific survival. In terms of therapeutic targets, PI3K/AKT/mTOR pathway mutations have been described in 13% of typical carcinoids (TCs) and 39% of atypical carcinoids (ACs), representing a targetable mutation with kinase inhibitors. Regarding treatment, surgical resection is usually curative in localized BCs and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced BCs, although limited by a heterogeneity in the scientific evidence behind their use recommendation. These options include somatostatin analogues, everolimus, peptide receptor radionuclide therapy, chemotherapy, radiotherapy, antiangiogenic agents, and immunotherapy. In this article, we provide a comprehensive review about the molecular and genetic background of BCs, and about the treatment of local and metastatic disease, as well as the main paraneoplastic syndromes that have been associated with this tumor.

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“…[1,19,29,30] Therapeutic strategies for PC include resection of the tumour for limited disease, administration of somatostatin analogs for carcinoid syndrome or as rst-line systemic antiproliferative treatment in unresectable PCs, and systemic therapy for metastatic disease (everolimus, chemotherapy, peptide receptor radionuclide therapy (PRRT)). [1,2,4,31] In this study, we rstly wanted to study retrospectively the value of dual (SSTR/[ 18 F]FDG) PET/CT in the assessment of the tumour biology, based on the widely known " ip-op phenomenon" or the differential high uptake of TC versus a lower uptake of AC on SSTR PET/CT and vice versa for [ 18 F]FDG PET/CT. [32] Although hilar and mediastinal lymph node involvement is known as one of the most important prognostic factors in PC, no studies have been done to quantitatively assess the diagnostic performance of SSTR PET/CT in the detection of these regional lymph node metastases.…”

Section: Introductionmentioning

confidence: 99%

Value of [68Ga]Ga-Somatostatin Receptor PET/CT in the Grading of Pulmonary Neuroendocrine (Carcinoid) Tumours and the Detection of Disseminated Disease: Single Center Pathology-Based Analysis and Review of the Literature

Deleu

Laenen²,

Decaluwé

et al. 2022

Preprint

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Background Although most guidelines suggest performing a positron emission tomography/computed tomography (PET/CT) with somatostatin receptor (SSTR) ligands for staging of pulmonary carcinoid tumours (PC), only a limited number of studies have evaluated the role of this imaging tool in this specific patient population. The preoperative differentiation between typical carcinoid (TC) and atypical carcinoid (AC) and the extent of dissemination (N/M status) are crucial factors for treatment allocation and prognosis of these patients. Therefore we performed a retrospective analysis to assess the value of SSTR PET/CT in the tumour grading and the detection of lymph node involvement and distant metastases of PC with histopathology as gold standard, and compared this to [18F]FDG PET/CT in a subgroup of patients and to previous literature with group sizes of mostly 20-30 patients. Methods SSTR PET/CT scans performed between January 2007 and May 2020 in the context of PC were included. If available, [18F]FDG PET/CT images were also evaluated. The maximum standardized uptake (SUVmax) values of the primary tumour, of the pathologically examined hilar and mediastinal lymph nodes, as well as of the distant metastases, were recorded. Tumoural SUVmax values were related to the tumour type (TC versus AC) for both SSTR and [18F]FDG PET/CT in diagnosing and differentiating both tumour types. Nodal SUVmax values were compared to the pathological status (N+ versus N−) to evaluate the diagnostic accuracy of SSTR PET/CT in detecting lymph node involvement. Finally, a mixed model analysis of all pathologically proven distant metastatic lesions was performed. Results A total of 86 SSTR PET/CT scans performed in 86 patients with PC were retrospectively analyzed. [18F]FDG PET/CT was available in 46 patients. Analysis of the SUVmax values in the primary tumour showed significantly higher SSTR uptake in TC compared with AC (median SUVmax 18.4 vs 3.8; p=0.003) and significantly higher [18F]FDG uptake in AC compared to TC (median SUVmax 5.4 vs 3.5; p=0.038). Receiver operating characteristic (ROC) curve analysis resulted in an area under the curve (AUC) of 0.78 for the detection of TC on SSTR PET/CT and of 0.73 for the detection of AC on [18F]FDG PET/CT. A total of 267 pathologically evaluated hilar and mediastinal lymph nodes were analyzed. ROC analysis of paired SSTR/[18F]FDG SUVmax values for the detection of metastasis of TC in 83 lymph nodes revealed an AUC of 0.91 for SSTR PET/CT and of 0.74 for [18F]FDG PET/CT (difference 0.17; 95% confidence interval: -0.03 to 0.38; p = 0.10). In a sub-cohort of 10 patients with 12 lesions suspicious for distant metastases on SSTR PET/CT that were investigated with biopsies, a positive predictive value (PPV) of 100% was observed. Conclusion Our findings confirm the higher SSTR ligand uptake in TC compared to AC and vice versa for the [18F]FDG uptake. More importantly, we found a good diagnostic performance of SSTR PET/CT for the detection of hilar and mediastinal lymph node metastases of TC. Finally, a PPV of 100% for SSTR PET/CT was found in a small sub-cohort of patients with pathologically investigated distant metastatic lesions. Taken together, SSTR PET/CT has a very high diagnostic value in the TNM assessment of pulmonary carcinoids, particularly in TC, which underscores its position in European guidelines.

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Recent Advances in the Management of Typical and Atypical Lung Carcinoids

Cited by 19 publications

References 113 publications

Prognostic nomogram for predicting long-term survival in bronchopulmonary carcinoid tumor patients receiving resection

Prognostic nomogram for predicting long-term survival in bronchopulmonary carcinoid tumor patients receiving resection

Bronchial Carcinoids: From Molecular Background to Treatment Approach

Value of [68Ga]Ga-Somatostatin Receptor PET/CT in the Grading of Pulmonary Neuroendocrine (Carcinoid) Tumours and the Detection of Disseminated Disease: Single Center Pathology-Based Analysis and Review of the Literature

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