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C. Barrios

Moderator of

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    MS 07 - Neuroendocrine Tumors other than SCLC: Pathology to Patient Management (ID 529)

    • Event: WCLC 2017
    • Type: Mini Symposium
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 6
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      MS 07.01 - Pathology of Neuroendocrine Tumors other than SCLC (ID 7669)

      15:45 - 16:00  |  Presenting Author(s): Mary Beth Beasley

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Neuroendocrine tumors (NET) of the lung comprise approximately 20% of all primary lung carcinomas overall and consist primarily of four malignancies: Typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma(SCLC) using 2015 World Health Organization (WHO) nomenclature. The four tumors have historically been regarded as a spectrum; however, there are significant differences between TC/AC and LCNEC/SCLC on many levels. Additionally, while most TC and AC arise de novo, a small percentage of cases with arise in the setting of diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH), a rare pre-neoplastic condition. DIPNECH has not been associated with the development of LCNEC or SCLC. TC and AC, comprise 1-2% of primary lung cancers with the vast majority being TC. Both TC and AC may occur in either a central or peripheral location, with central tumors resulting in symptoms related to obstruction while peripheral tumors are often asymptomatic and discovered incidentally. TC is considered a “low grade” or “well-differentiated” tumor; however, 5-20% of TC are associated with regional lymph node or distant metastases. AC, considered an “intermediate grade” or “moderately-differentiated” tumor, is associated with metastases in up to 40% of cases. The five and 10 year survival for TC is approximately 90% whereas it drops to 70% and 50% for AC. By current WHO criteria, TC is defined as a neuroendocrine tumor greater than 5mm in size with fewer than 2 mitoses per 2mm[2] and lacking necrosis, whereas AC is defined as a neuroendocrine tumor with 2-10 mitoses per 2mm[2] or necrosis. As mitotic activity and necrosis may be focal, the distinction between TC and AC can generally not be made on a small sample. Both tumors classically show an organoid or trabecular pattern of growth and are composed of a relatively uniform population of round to oval cells with granular nuclear chromatin, but may show a wide range of histologic growth patterns, particularly in TC. Given that the main feature distinguishing AC from TC is mitotic activity, one would expect that proliferation markers such as Ki-67 would be of potential value in discriminating these two tumors. Numerous studies have attempted to evaluate this parameter with various cut offs being proposed; however, ultimately there is too much overlap between the Ki-67 scores of TC and AC for it to be reliably useful in discriminating between the two tumors. The Ki-67 score can be useful in separating high-grade from low-grade tumors on small distorted biopsies, and some studies have shown it to have utility as a prognostic marker in TC/AC. As such it may be used to potentially guide treatment and is included as a parameter in the European Neuroendocrine Tumor Society (ENETS) guidelines. Surgery remains the only curative treatment option for TC/AC but there is a lack of consensus in regard to treatment of un-resectable or metastatic disease. Results of the RADIANT-4 trial have led to the approval of everolimus for advanced TC/AC. There is additional evidence that somatostain analogs may be useful in selected patients. Molecular analysis of TC and AC demonstrate distinctly different molecular profiles compared to the high grade NET’s, with MEN1 alterations found essentially exclusively in carcinoids whereas alteration of RB1 cell cycle regulation genes and the PI3K/AKT/mTOR pathway were found less frequently in TC/AC and enriched in the higher grade tumors. TC/AC also tend to show frequent mutations of chromatin remodeling genes, as well as mutations of PSIP1 and ARID1A. Actionable mutations such as EGFR mutations and ALK rearrangements are not found in TC/AC and thus far evaluation of PD-L1 in carcinoids has been negative, suggesting a lack of a role for current targeted therapy or immunotherapeutic agents used in non-small cell lung carcinomas (NSCLC). Several clinical trials are either ongoing or currently recruiting to evaluate the efficacy of several small molecular inhibitors. LCNEC was originally described in 1991 and was initially included as a subtype of large cell carcinoma in subsequent WHO classification, but in the current WHO it is classified as a type of neuroendocrine carcinoma. The tumor is defined as a tumor with neuroendocrine morphology with large cell morphology and greater than 10 mitoses/2mm[2], although most cases have substantially higher mitotic rates. By definition, tumors must show evidence of neuroendocrine differentiation, usually identified by immunohistochemical methods. While distinction of LCNEC from SCLC may appear straightforward on the surface, in reality LCNEC can be heterogeneous and the distinction is not always clear cut. Currently, there is no immunostain or other definitive test to discriminate between the two and distinction ultimately rests of subjective evaluation of the tumor morphology. The extreme rarity of this tumor, combined with the tumor heterogeneity and resultant subjectivity inherent in classification has likely contributed to conflicting reports in the literature regarding prognosis, although it is generally agreed that LCNEC is a high-grade tumor with a poor prognosis. Similarly, variable results have been reported in regard to the responsiveness of LCNEC to treatment regimens typically used for SCLC leading to a lack of consensus regarding whether LCNEC should be managed similar to SCLC or similar to other non-small cell carcinomas. Molecular studies have additionally shown variable results. The majority of studies have shown overlapping features with SCLC. Some studies, however, have shown alterations characteristic of other tumor types, most notably occasional EGFR, ALK and KRAS mutations even in the absence of an overt mixed adenocarcinoma component, which have not been found in SCLC. Interestingly, in 2016, Rekhtman, et al, evaluated 45 LCNEC and pared normal tissue by NGS with 241 cancer gene analysis. This study demonstrated that LCNEC, while having some commonly altered genes, largely fell into two major and one minor subset (SCLC-like, NSCLC-like and a small number of “carcinoid like” tumors). These findings may explain the variability of results in treatment trials and may indicate that more comprehensive analysis of this rare groups of tumors may yield more optimal treatment strategies.

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      MS 07.02 - Novel Chemotherapy for LCNEC (ID 7670)

      16:00 - 16:15  |  Presenting Author(s): Seiji Niho

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Given that large cell neuroendocrine carcinoma (LCNEC) of the lung is rare and histological diagnosis from small samples is difficult, no large-scale clinical trials has yet evaluated the optimal chemotherapy for LCNEC. In a retrospective study of 45 consecutive patients with advanced LCNEC, response rates for small cell lung cancer (SCLC; n=11) and non-small cell lung cancer (NSCLC; n=34) regimen groups receiving first-line chemotherapy were 73% and 50% (P=0.19), median progression-free survival (PFS) was 6.1 and 4.9 months (P=0.41), and median overall survival (OS) was 16.5 and 9.2 months (P=0.19), respectively. SCLC regimens included platinum plus paclitaxel (PTX) and irinotecan plus platinum, while NSCLC regimens included pemetrexed, erlotinib, and gemcitabine[1]. A second retrospective study of the efficacy of first-line chemotherapies in 22 consecutive patients with advanced LCNEC reported an objective response in five of nine patients receiving CDDP+irinotecan (56%) and in three of five receiving carboplatin (CBDCA)+PTX (60%) [2]. Of the two prospective phase II studies of platinum-based chemotherapies for LCNEC (Table), a French study (GFPC 0302) used a chemotherapy regimen comprising CDDP+etoposide (ETP), while a Japanese study used CDDP+irinotecan. Objective response rate (ORR) was about 40% and median PFS was 5 to 6 months in both studies. Central pathological reviews in both studies demonstrated that about a quarter of patients had SCLC or undifferentiated NSCLC [3, 4]. Everolimus is an oral mTOR inhibitor that has been approved for the treatment of well-differentiated neuroendocrine tumors of the lung. A recent phase II study of CBDCA+PTX+everolimus as first-line chemotherapy for advanced LCNEC was discontinued prematurely due to low recruitment after enrolling only 49 patients versus a planned sample size of 71. Among them, ORR was 45%, disease control rate was 74%, median PFS was 4.4 months, and median OS was 9.9 months [5]. Ongoing studies include a randomized phase II study comparing CBDCA+ETP and CBDCA+PTX for advanced LCNEC and a randomized phase II/III study of CDDP+ETP with or without veliparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in patients with extensive stage SCLC or metastatic LCNEC.

      Study GFPC 0302 Japanese study German study
      Regimen CDDP+ETP CDDP+Irinotecan CBDCA+PTX+Everolimus
      N 42 44 49
      ORR (%) (95%CI) 38 55 (39-70) 45 (31-60)
      Median PFS (months) (95%CI) 5.2 (3.1-6.6) 5.9 (5.5-6.3) 4.4 (3.2-6.0)
      Median OS (months) (95%CI) 7.7 (6.0-9.6) 15.1 (11.2-19.0) 9.9 (6.9-11.7)
      Reference 1. Sun JM, Ahn MJ, Ahn JS, et al. Chemotherapy for pulmonary large cell neuroendocrine carcinoma: similar to that for small cell lung cancer or non-small cell lung cancer? Lung Cancer 2012;77:365-370. 2. Fujiwara Y, Sekine I, Tsuta K, et al. Effect of platinum combined with irinotecan or paclitaxel against large cell neuroendocrine carcinoma of the lung. Jpn J Clin Oncol 2007;37:482-486. 3. Niho S, Kenmotsu H, Sekine I, et al. Combination chemotherapy with irinotecan and cisplatin for large-cell neuroendocrine carcinoma of the lung: a multicenter phase II study. J Thorac Oncol 2013;8:980-984. 4. Le Treut J, Sault MC, Lena H, et al. Multicentre phase II study of cisplatin-etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study. Ann Oncol 2013;24:1548-1552. 5. Christopoulos P, Engel-Riedel W, Grohe C, et al. Everolimus with paclitaxel and carboplatin as first-line treatment for metastatic large-cell neuroendocrine lung carcinoma: a multicenter phase II trial. Ann Oncol 2017.

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      MS 07.03 - Novel Systemic Therapy for Carcinoid of the Lung (ID 7671)

      16:15 - 16:30  |  Presenting Author(s): Primo Lara

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Carcinoid tumors of the lung belong to a broad group of neoplasms called neuroendocrine tumors (NETs). These tumors are highly heterogeneous and represent a broad spectrum of phenotypes and clinical behavior. Often, the clinical behavior of these tumors corresponds with their underlying pathologic features. For example, in those tumors deemed as “typical carcinoid/NETs”, clinical behavior is often very indolent. At the other end of the spectrum, NETs can present as small cell lung cancer (SCLC) which is characterized by virulent and highly metastatic behavior. Those tumors deemed as “atypical carcinoid/NETs” usually have an intermediate clinical phenotype. Lung NETs are rare: the annual incidence rate is estimated to be approximately 1 in 100,000. In those patients whose lung NETs are no longer surgically resectable and/or have metastasized distantly, the treatment goals are principally disease control and symptom palliation. Because of their rarity, there are very limited prospective Level 1 data to guide optimal management of lung NETs. Treatment recommendations are often based on extrapolation from clinical experience in gastrointestinal NETs (specially pancreatic NET), subset analyses from other NET trials, anecdotal reports (case series), and expert opinion (e.g., consensus panels). Thus, the optimal management strategy for Lung NETs is not yet fully defined. Systemic therapy options range from somatostatin analog therapy, mTOR inhibitor therapy, and cytotoxic chemotherapy. Somatostatin analog therapy is offered in selected patient subsets that have slowly progressing disease and whose tumors express somatostatin receptors as detected by nuclear medicine scanning (Octreoscan). Somatostatin analog therapy is only modestly efficacious, with disease stabilization as the expected clinical benefit. Inhibition of the mTOR with everolimus has demonstrated efficacy in randomized trials. In the RADIANT-2 trial of everolimus+octreotide vs. placebo+octreotide in NETs, a small subset of patients with lung NETs (n=44) was analyzed. This showed an improvement in progression free survival with everolimus+octreotide vs. the control arm (median PFS 8.8 months vs 2.8; Hazard Ratio (HR) = 0.62; p=0.1). Subsequently, the phase III RADIANT-4 trial of everolimus vs placebo in non-functional lung and GI NETs was conducted. In this trial, approximately 30% of the 302 randomized patients had lung NETs. RADIANT-4 showed a PFS and overall survival (OS) benefit in favor of everolimus (PFS HR=0.39, p<0.0001; OS HR=0.64, p=0.037). More recently, a randomized phase II trial (LUNA) of pasitreotide alone, everolimus alone, or the combination showed a trend for improved PFS for the combination arm (PFS at 9 months was 39.0% for pasitreotide alone, 33.3% for everolimus alone, and 58.5% for the combination). In patients who are not candidates for somatostatin analog therapy or everolimus, or have failed these therapies, cytotoxic chemotherapy is often considered. The most commonly used regimens include platinum-etoposide (similar to that employed for SCLC) and temozolomide. Response rates to chemotherapy are reportedly much lower in lung NETs (vs SCLC) in retrospective studies; for example, platinum-etoposide is reported to yield response rates of 20-30% in lung NETs compared to rates greater than 50% in SCLC. It is thought that tumor responses are possibly influenced by the degree of tumor de-differentiation. Other agents with anecdotal activity include 5FU, capecitabine, oxaliplatin, and anthracyclines. Prospective trials of systemic therapy in lung NETs are essential to define the optimal standards of care. Selected References: 1. Hendifar, AE et al. J Thor Oncol 2016; 12(3):425-436 2. Yao, J. et al. Lancet 2016; 387: 968-77 3. Fazio N, et al. Chest 2013; 143(4):955-962

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      MS 07.04 - Surgical Treatment for Neuroendocrine Tumors other than SCLC (ID 7672)

      16:30 - 16:45  |  Presenting Author(s): Akira Iyoda  |  Author(s): Yoko Azuma, T. Makino, H. Otsuka, S. Koezuka, N. Tochigi, K. Shibuya, T. Mikami, Kazutoshi Isobe, S. Homma

      • Abstract
      • Presentation
      • Slides

      Abstract:
      In the 1970s, pulmonary neuroendocrine tumors were classified into three histologically defined categories: typical carcinoid (TC), atypical carcinoid (AC) and small cell lung carcinoma (SCLC) [1]. In 1999, the World Health Organization (WHO) classified large cell neuroendocrine carcinoma (LCNEC) as a fourth neuroendocrine tumor of the lung. Although LCNEC was classified as a variant of large cell carcinoma in 1999 [2], it was classified as a neuroendocrine tumor in 2015. To date, for neuroendocrine tumors of the lung, the major categories of morphologically identifiable neuroendocrine tumors are TC, AC, LCNEC, and SCLC. Analyses of molecular markers revealed that low-grade TC and intermediate-grade AC exhibit a low proliferative rate compared with high-grade LCNEC and SCLC [3], and TC and AC have different genetic alterations from high-grade LCNEC and SCLC [4]. Analyses of their genetic alterations show that neuroendocrine lung tumors may represent a spectrum ranging from low-grade TC and intermediate-grade AC to highly malignant LCNEC and SCLC tumors [4]. TC is classified as a malignant epithelial tumor of the lung [2, 5]. However, the overall survival rate is better for TC than for AC [5, 6], and the frequency of lymph node metastases in TC is lower than in high-grade LCNEC and SCLC [6]. Therefore, some investigators have advocated limited resection in patients with TC [7]. Some reports revealed that sublobar resection was noninferior to lobectomy for survival in patients with TC tumor [7]. However, other reports advised that radical oncologic surgery with radical node dissection was needed, and segmental and other limited procedures had to be avoided because of the high frequency of lymph node involvement and multicentric forms [8]. Moreover, preoperative diagnoses and/or diagnoses from intraoperative frozen sections are often difficult for differentiating AC from TC, because small amounts of necrosis or few mitoses are sometimes unclear in those specimens. A randomized controlled trial is the best method to compare surgical efficacy. However, it may be impractical due to the rarity of carcinoid tumors. Moreover, AC has a poorer prognosis and a higher frequency of lymph node metastases than TC. Therefore, sublobar resection for TC might be the optimal surgical method because of lung preservation and lower mortality than lobectomy; however, limited resection for TC remains an area of controversy. Several reports [9] revealed that the clinical behavior, morphology, and prognosis of LCNEC were similar to those of SCLC, even though there might be several clinicopathological differences between SCLC and LCNEC in peripheral, small-sized, and high-grade neuroendocrine tumors [10]. Because it is difficult to diagnose patients with LCNEC pre-operatively, and most cases have been diagnosed postoperatively from surgically resected specimens, many reports on LCNEC have referred to surgical cases, of which the majority [9] revealed that patients with LCNEC had poor prognoses. Even patients with pathological stage I LCNEC have had poor prognoses, with five-year survival rates of 27-67% [9]. In patients with LCNEC who underwent radical surgery and complete resection, many recurrent tumors were observed as distant metastases [10]. Therefore, surgery alone is not sufficient to treat patients with LCNEC, and subsequent adjuvant therapy may be necessary [10]. Although there were high response rates with platinum-based and SCLC-based chemotherapies in patients with LCNEC, almost all patients had only partial responses [9, 10]. Patients with LCNEC may not be able to expect complete responses with platinum-based and SCLC-based chemotherapies compared with patients with SCLC, even though these chemotherapies are as effective as adjuvant treatment. Therefore, patients with advanced-stage LCNEC had a poor prognosis because they could not always achieve a complete response. Although the indication for surgery is limited to stage I in patients with SCLC, surgery and adjuvant chemotherapy may achieve satisfactory results in terms of survival for patients with LCNEC with not only stage I but also stage II/III [10]. Therefore, surgical indications for patients with LCNEC may not be limited to clinical stage I cases, and surgery with adjuvant chemotherapy should be attempted for resectable LCNEC. References [1] Arrigoni MG, Woolner LB, Bernatz PE. Atypical carcinoid tumors of the lung. J Thorac Cardiovasc Surg. 1972;64:413-21. [2] Travis WD, Colby TV, Corrin B, Shimosato Y, Brambilla E, editors. Histological Typing of Lung and Pleural Tumours. World Health Organization International Histological Classification of Tumors, XIII, 3rd ed. Berlin/Heidelberg: Springer-Verlag; 1999. [3] Rusch VW, Klimstra DS, Venkatraman ES. Molecular markers help characterize neuroendocrine lung tumors. Ann Thorac Surg. 1996;62:798-810. [4] Onuki N, Wistuba II, Travis WD, Virmani AK, Yashima K, Brambilla E, Hasleton P, Gazdar AF. Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer. 1999;85:600-7. [5] Travis W.D, Brambilla E, Müller-Hermelink H.K, Harris C.C (Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumors of the Lung, Pleura, Thymus and Heart. IARC Press:Lyon 2004. [6] Iyoda A, Hiroshima K, Baba M, Saitoh Y, Ohwada H, Fujisawa T. Pulmonary large cell carcinomas with neuroendocrine features are high grade neuroendocrine tumors. Ann Thorac Surg. 2002;73:1049-54. [7] Fox M, Van Berkel V, Bousamra M II, Sloan S, Martin RC II. Surgical management of pulmonary carcinoid tumors: sublobar resection versus lobectomy. Am J Surg. 2013;205:200-8. [8] Daddi N, Ferolla P, Urbani M, Semeraro A, Avenia N, Ribacchi R, Puma F, Daddi G. Surgical treatment of neuroendocrine tumors of the lung. Eur J Cardiothorac Surg. 2004;26:813-7. [9] Iyoda A, Hiroshima K, Nakatani Y, Fujisawa T. Pulmonary large cell neuroendocrine carcinoma- its place in the spectrum of pulmonary carcinoma. Ann Thorac Surg. 2007;84:702-7. [10] Iyoda A, Makino T, Koezuka S, Otsuka H, Hata Y. Treatment options for patients with large cell neuroendocrine carcinoma of the lung. Gen Thorac Cardiovasc Surg. 2014;62:351-6.

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      MS 07.05 - ESTS Registration for Neuroendocrine Tumors (ID 7673)

      16:45 - 17:00  |  Presenting Author(s): Pier Luigi Filosso  |  Author(s): F. Guerrera, P. Lyberis, E.L.N.S. Committee

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Lung Neuroendocrine Tumors (NETs) are rare neoplasms derived from the neuroendocrine cells of the bronchopulmonary epithelium. They represent about 25% of all the neuroendocrine tumors, and no more than 2%-3% of all the primary tumors of the lung. Their incidence has recently increased by approximately 6% per year, probably due to the improved awareness as well as for the diffusion of lung cancer screening programs worldwide. NETs’ incidence now ranges from 0.2 to 2 per 100,000 individuals per year in the United States. Their rarity, along with the lack of randomized clinical trials, make lung NETs’ global management still questioned, especially in case of advanced diseases, and only few clinical recommendations currently exist. In 2012, during the Annual Meeting in Essen (Germany), the European Society for Thoracic Surgeons (ESTS) created a new Working Group (WG) specifically dedicated to the Lung NETs. The Steering Committees was composed by the following Thoracic Surgeons: Pier Luigi Filosso (Torino, Italy-Chair), Pascal Alexandre Thomas (Marseille, France), Mariano Garcia-Yuste (Valladolid, Spain), Eric Lim (London, UK), Federico Venuta (Rome, Italy), Alessandro Brunelli and Konstantinos Papagiannopoulos (Leeds, UK), Hisao Asamura (Tokyo, Japan). The aim of this WG was to create a group of physicians expert on Lung NETs in order to improve scientific knowledge on such rare neoplasms, and disseminate it among the scientific community. A specific database was rapidly designed, to retrospectively collect data of patients operated for lung NETs, and it was sent to all the ESTS Members who expressed their interest to this project. Moreover, a survey concerning lung NETs’clinical management was prepared and its results were recently published (Future Oncol. 2016;12:1985-1999). Up to now, 2040 operated NETs patients have been collected amongst 17 high-volume International Thoracic Surgery Institution worldwide. This retrospective database was used for several studies about lung NETs clinical behavior and outcome. In particular, the outcome and prognostic factors of two aggressive lung NETs: atypical carcinoids (ACs) and large-cell neuroendocrine carcinomas (LCNCs) were the object of the first publication (Eur.J.Cardiothorac Surg. 2015;48:55-64). For ACs, age (P<0.001), tumour size (P=.015) and sub-lobar resections (P=0.005) were independent negative prognostic factors; for LCNCs, only pTNM stage III tumors (P=0.016) negatively affected outcome in the multivariate analysis. Local recurrences and distant metastases were statistically more frequent in LCNCs (P=0.02), as expected. A prognostic model of survival for typical carcinoids (TCs) was the matter of the second publication (Eur.J.Cardiothorac Surg. 2015;48:441-447): an analysis of 1109 TC patients was performed. A prediction model for mortality, evaluating age, gender, previous malignancies, peripheral tumour location, TNM stage and ECOG PS was elaborated, and the final model showed a good discrimination ability with a C-statistic equal to 0.836 (bootstrap optimism-corrected 0.806). Moreover, this model has been recently validated by Cattoni and Coll. The treatment of biologically aggressive/advanced lung NETs was recently investigated in a paper published by the Journal of Thoracic Disease (J.Thorac. Dis. 2015;7:S163-S171). Surgery, whenever feasible, remains the mainstay of treatment, and chemo/radiotherapy should be reserved to progressive diseases. In case of resected N1-N2 carcinoids, a "watch and see" policy and a close clinical/radiological follow-up is also recommended. Surgery alone is not sufficient to treat high-grade NETs (e.g.: LCNC): adjuvant CT is suggested even in early stages. Platinum-Etoposide regimen demonstrated to be the most effective; Irinotecan and other biological drugs are also regarded to be very promising. The management of advanced lung NETs should be tailored by multidisciplinary teams including Medical and Radiation Oncologists, Surgeons, Pathologists, Pulmonologists, Endocrinologists, Interventional Radiologists; patients’ prognosis is mainly dependent on tumor grade and its anatomical extent. Large-cell neuroendocrine carcinoma (LCNC) is a rare tumor characterized by an aggressive biological behaviour and poor prognosis; its optimal treatment is still under debate. Some recent reports indicate that adjuvant chemotherapy (CT) may have a beneficial effect on survival. Data from 400 patients with resected LCNC were analyzed. The 3- and 5-year survival rates were 54.1% and 45%, respectively. With the multivariable model, increasing age, ECOG ≥2 and advanced TNM stage were indicators of poor prognosis. Weak evidence of a higher overall survival in patients receiving adjuvant CT (adjusted hazard ratio 0.73; 95% confidence interval: 0.56-0.96, P  = 0.022) was also observed (Eur.J.Cardio-Thorac.Surg. 2017;52:339-345). In Stage I TCs (SITCs) non-anatomical resections (wedge) are sometimes advocated because of their indolent behavior. An analysis on effect of surgical procedure on SITC patients’ survival was therefore done (Eur.J.Cardiothorac.Surg. 2017 submitted paper). Eight-hundred seventy-six SITC patients (569 females,65%) were included in this study; the 5-year OS rate was 94.3% (95%CI:92.2 –95.9). At univariable analysis, wedge resection resulted to be associated with a poor prognosis (5-year OS 82%,95%CI:0.71-0.89,P<.001) compared to other anatomical resections. At multivariable score-adjusted analysis, wedge resection confirmed to be an independent predictor of poor prognosis (HR2.17,95%CI: 1.19-3.96,P=.012). Since 2106, a lung NETs prospective database is active through the official ESTS European Database, and up to now, more than 150 new cases have been collected. Through this new platform, very easy to be used, we are confident to collect, in few years, more data especially on possible tumor recurrences and their treatment, as well as on the role of emerging biological drugs used in the adjuvant setting in advanced diseases. An active participation of Medical/Radiation Oncologists to this scientific project would be also desirable. The active role of the most important Scientific Societies could strongly support the success of this scientific project.

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      MS 07.06 - Which Chemotherapy or Targeted Therapy is Better for Treatment of LCNEC Patients: SCLC-based versus Non-SCLC-based Regimens? (ID 7674)

      17:00 - 17:15  |  Presenting Author(s): Sumitra Thongprasert

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Staging of large cell neuroendocrine carcinoma (LCNEC) was classified based on non-small cell type (TNM stage). The treatment of early stage (I, II) was mainly surgery; the use of neo - adjuvant and adjuvant chemotherapy are in consideration but there's not a standard approach; for stage III which limited to the thoracic area, the role of concurrent chemotherapy and radiotherapy is one of the options. Whether the regimen of chemotherapy should be similar to small cell lung cancer (SCLC) or the regimen of non -small cell lung cancer (NSCLC) is not clear. Most of the data are in favor of SCLC regimen which is Cisplatin plus etoposide; however the data came from retrospective and small numbers of patients, thus there's an unmet need to improve the treatment of LCNEC. Large Cell Neuroendocrine Carcinoma and Small Cell Lung Cancer are both consider high grade neuroendocrine carcinoma of the lung. Small cell is the most frequent type of lung neuroendocrine tumor, occurs around 15% of lung cancer while Large Cell neuroendocrine carcinoma was only about 3% of lung cancer. According to WHO classification in 2004 LCNEC was classified as a variant of large-cell carcinoma; however in 2015 WHO classification LCNEC was classified into a group of neuroendocrine tumor which includes SCLC, typical carcinoid, atypical carcinoid and LCNEC. According to genomic analysis, LCNEC was separated into two groups. Some have genomic characteristic of SCLC and some have genomic characteristic of NSCLC. The new modalities such as anti-angiogenesis and in the case of EGFR mutation the treatment with EGFR inhibitor should be considered. The role of met inhibitors in LCNEC should be explored. Thus there is a long way to go in order to improve the outcome of this rare lung cancer type.

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Author of

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    P3.13 - Radiology/Staging/Screening (ID 729)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P3.13-018 - CT-Guided Percutaneous Barium Marking Prior to Video-Assisted Thoracoscopic Surgery (VATS) for the Localization of Small Pulmonary Nodules (ID 9497)

      09:30 - 09:30  |  Author(s): C. Barrios

      • Abstract
      • Slides

      Background:
      Widespread CT scan availability generates the challenge of managing small pulmonary lesions generally undetected on chest radiographs. Preoperative nodule localization is critical for adequate diagnosis and an accurate resection. Metallic hook wire localization under CT is a widely used method but can be associated with pneumothorax, hook related discomfort, and dislodgement. CT-guided percutaneous barium marking (CT-GPBM) can be simpler, low cost procedure, without risk of dislodgement, and radiopaque on fluoroscopy, increasing resection accuracy. Barium marking through bronchoscopy has been previously reported. This study describes our experience with CT-GPBM in the diagnosis and management of ground glass abnormalities and small pulmonary nodules.

      Method:
      Between January 2013 and May 2017, 36 patients underwent preoperative CT-GPBM and VATS resections at our institution, and were retrospectively reviewed. All cases were discussed in multidisciplinary rounds. After CT localization and local anesthesia, a 21-gauge Chiba needle was utilized, under CT guidance, to inject 0,2 mL of 140% barium sulfate suspension. A control CT confirms the marking and verifies possible complications. CT-GPBM and VATS resection are performed in the same day. VATS resection is performed under fluoroscopy guidance. Finally, the specimen is submitted to fluoroscopy to confirm a complete resection.

      Result:
      Thirty-six different cases were analyzed (41.7% male / 58.3% female). Median age was 65 (ranging from 32 to 91). 18/36 were never smokers. Most lesions were identified on routine follow-up CT (21/36 - 58.3%). Many had previous history of cancer (24/36 - 66.7%). 31/36 (86.1%) were single nodules - median size of 14mm (ranging from 5 to 47). Solid lesion was the most common radiologic finding (21/36 - 61,8%), while the others were semi-solid or ground glass abnormalities. Pathological findings confirmed primary lung cancer in 41,6% of cases (15/36). Adenocarcinoma was the most common histology. Nine patients had benign diseases. Metastatic lesions represented 33,3% (12/36), most derived from colorectal cancer. No patient had reported complications.

      Conclusion:
      This analysis shows that CT-GPBM is an effective, easy and safe pre-operative (VATS) localization procedure, allowing accurate diagnosis and resection of small or faint pulmonary nodules, avoiding thoracotomies in benign diseases and metastatic tumors. Data will be updated for presentation.

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