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P.L. Filosso
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ED04 - Bronchopulmonary Carcinoids (ID 267)
- Event: WCLC 2016
- Type: Education Session
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:V. Gorbunova, J. Hutter
- Coordinates: 12/05/2016, 14:30 - 15:45, Lehar 1-2
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ED04.01 - Surgery in Bronchopulmonary Typical and Atypical Carcinoids (ID 6440)
14:30 - 15:00 | Author(s): P.L. Filosso
- Abstract
- Presentation
Abstract:
Complete surgical resection of the tumor is the treatment of choice for Bronchopulmonary Carcinoids (BCs). The goal is to resect the lesion, saving as much lung parenchyma as possible. The type of surgical approach and resection are strictly depend on: a) tumor’s location, b) tumor’s histology and c) presence of lymphnodal metastases. In case of peripheral small BC (Figure 1), the type of surgical resection (wide wedge resection vs segmentectomy or lobectomy) is still matter of debate. Few scientific evidences (1,2) report that a wedge resection could be safely proposed since, in multivariate analysis, long-term survival is not compromised when this approach is used. However, those studies are retrospective, sometimes with limited data on the patients’ follow-up and the number of wedge resections is limited: therefore it is very difficult to draw definitive conclusions with those potential biases. The statement that a wedge resection should be reserved to a small peripheral N0 Typical Carcinoid (TC) seems to be more prudent. An anatomical resection (segmentectomy/lobectomy) should be proposed in case of an Atypical Carcinoid (AC), or whenever the tumor can not be resected in a less invasive manner (e.g: centroparenchymal lesion or when the lobe is totally occupied by the tumor – Figure 2-). The aim to preserve as much lung tissue as possible is the cause of the development of tissue-sparing surgical techniques (the so called “bronchial sleeve resections” and the “sleeve lobectomies”). The first contemplates a bronchial resection with the tumor, without any lung parenchyma exeresis; in the latter, a formal lobectomy with bronchoplastic procedure, is performed to avoid major pulmonary resections (e.g.: bilobectomy or pneumonectomy). An intraoperative frozen section of the bronchial margin has to be performed in all bronchoplastic procedures to confirm that no neoplastic cells are present in the anastomosis (3). Contrariwise, a pneumonectomy should be reserved to patients with a “destroyed lung”, usually caused by long-term obstructive pneumonia, a phenomena caused by an endobronchial tumor growth which completely obstructs the bronchial lumen, or when a tissue sparing resection can not be safely performed. The type of surgical approach (thoracotomy vs. minimally invasive one) must be decided based on tumor’s size and location, as well as the type of surgical resection planned. In general, VATS approach is currently indicated for small and peripheral BCs, while a posterolateral thoracotomy is generally used when a bronchoplastic procedure must be performed. Lymphadenectomy, and in particular, systematic hilar and mediastinal lymphadenectomy, must be always performed, in accordance with the European Society of Thoracic Surgeons (ESTS) recommendations for intraoperative lymph node assessment (4). A minimum of six nodal stations, three of which mediastinal, have to be harvested, including the subcarenal ones. Lymph nodal metastases, in fact, may be present in up to 25% of TCs and in less than 50% of ACs (5,6). In case of N positive (N+) BCs, and whenever feasible, upfront surgery may be proposed: a complete resection (R0) must be performed, whilst debulking interventions are not recommended. A satisfactory overall survival for BCs with lymph nodal metastases has been reported in several papers (7,8): those patients, in fact, survive longer than those with N+ NSCLC. An endobronchial resection (usually through rigid bronchoscopy) has been sometimes advocated for purely endobronchial tumors (3): it is mandatory to determine whether the tumor may present with an extrabronchial growth, in which case a local treatment alone is not sufficient, and should be followed by surgery (with or without bronchoplastic techniques). A palliative endobronchial treatment may be offered to those patients unfit for surgery, in which severe obstructive phenomena caused by the endoluminal tumor growth cause infective and respiratory consequences. Post-resectional tumor relapses may occur approximately in 20% of ACs and in 5% TCs (3,8): the risk of recurrence is strictly dependent from the histologic tumor subtype, the presence of lymph nodal metastases and the completeness of resection (9,10). Most recurrences are distant (liver, adrenal gland, bone), but sometimes, local relapses (lung and/or mediastinum) have also been reported. Surgery, with the same aim of the elective one, may be offered to those patients, improving their survival. REFERENCES 1 Yendamuri S, Gold D, Jayaprakash V, Dexter E, Nwogu C, Demmy T: Is sublobar resection sufficient for carcinoid tumors? Ann Thorac Surg. 2011;92:1774-1778 2 Ferguson MK, Landreneau RJ, Hazelrigg SR, Altorki NK, Naunheim KS, Zwischenberger JB, Kent M, Yim AP: Long-term outcome after resection for bronchial carcinoid tumors. Eur J Cardiothorac Surg. 2000;18:156-61 3 Detterbeck FC: Management of carcinoid tumors. Ann Thorac Surg 2010;89:998-1005 4 Lardinois D, De Leyn P, Van Schil P, Porta RR, Waller D, Passlick B, Zielinski M, Lerut T, Weder W: ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer. Eur J Cardiothorac Surg. 2006;30:787-792 5 Lim E, Yap YK, De Stavola BL, Nicholson AG, Goldstraw P: The impact of stage and cell type on the prognosis of pulmonary neuroendocrine tumors. J Thorac Cardiovasc Surg. 2005;130:969-972 6 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;26:813-817 7 Filosso PL, Ferolla P, Guerrera F, Ruffini E, Travis WD, Rossi G, Lausi PO, Oliaro A; European Society of Thoracic Surgeons Lung Neuroendocrine Tumors Working-Group Steering Committee: Multidisciplinary management of advanced lung neuroendocrine tumors. J Thorac Dis. 2015;7(Suppl 2):S163-S171 8 Filosso PL, Oliaro A, Ruffini E, Bora G, Lyberis P, Asioli S, Delsedime L, Sandri A, Guerrera F: Outcome and prognostic factors in bronchial carcinoids: a single-center experience. J Thorac Oncol. 2013;8:1282-1288 9 Caplin ME, Baudin E, Ferolla P, Filosso P, Garcia-Yuste M, Lim E, Oberg K, Pelosi G, Perren A, Rossi RE, Travis WD; ENETS consensus conference participants: Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids. Ann Oncol. 2015;26:1604-1620 10 Öberg K, Hellman P, Ferolla P, Papotti M; ESMO Guidelines Working Group: Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 Suppl 7:vii120-vii123Figure 1 Figure 2
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P1.05 - Poster Session with Presenters Present (ID 457)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.05-050 - External Validation of a Prognostic Model for Squamous-Cell Lung Cancer and Impact of Adjuvant Treatment in >1,300 Patients (ID 5297)
14:30 - 14:30 | Author(s): P.L. Filosso
- Abstract
Background:
A risk classification model able to powerfully discriminate the prognosis of resected squamous-cell lung cancer (R-SqCLC) patients (pts) was developed (Pilotto JTO 2015). Herein, we validate the model in a larger multicenter series of >1,300 R-SqCLC pts (AIRC project 14282).
Methods:
R-SqCLC pts in 6 different institutions (01/2002 - 12/2012) were considered eligible. Each patient was assigned with a prognostic score to identify the individual risk of recurrence, on the basis of the clinico-pathological data according to the develop model (age, T-descriptor according to TNM 7th edition, nodes, and grading). Kaplan-Meier analysis for disease-free/cancer-specific/overall survival (DFS/CSS/OS) was performed according to the published 3-class risk model (Low: score 0-2; Intermediate: score 3-4; High: score 5-6). Harrell’s C-statistics was adopted for model validation. The effect of adjuvant chemotherapy (ACT) was adjusted with the Propensity Score (PS).
Results:
Data from 1,375 pts from 6 institutions were gathered (median age: 68 years; male/female: 86.8%/13.2%; T-descriptor 1–2/3–4: 73.3%/26.7%; nodes 0/>0: 53.4%/46.6%; stages I-II/III-IV: 71.7%/28.3%); 384 pts (34.5%) underwent ACT. With a median follow-up of 55 months (95% CI 51-59), pts at Low-Risk had a significantly longer DFS in comparison with Intermediate- (HR 1.67, 95% CI 1.40-2.01) and High-Risk (HR 2.46, 95% CI 1.90-3.19) pts, as well as for CSS (HR 1.79, 95% CI 1.48-2.17; HR 2.33, 95% CI 1.76-3.07) and OS (HR 2.46, 95% CI 1.80-3.36; HR 4.30, 95% CI 2.92-6.33). C-statistics was 68.3 (95% CI 63.5-73.1), 68.0 (95% CI 63.2-72.9), and 66.0 (95% CI 61.6-71.1), for DFS, CSS and OS, respectively. 60-months DFS for Low-, Intermediate- and High-Risk pts was 51.0%, 33.5% and 25.8%, respectively (p<0.0001). 60-months CSS for Low-, Intermediate- and High-Risk pts was 82.7%, 64.7% and 53.3%, respectively (p<0.0001). 60-months OS for Low-, Intermediate- and High-Risk pts was 56.7%, 37.9% and 30.9%, respectively (p<0.0001). A significant benefit in DFS was found in favor of ACT (p=0.005), with no difference in CSS (p=0.57), although a trend in OS (p=0.16). Overall, no significant differences for ACT were found in DFS, CSS and OS when survival was corrected with PS analysis, although CSS and OS curves visually separate with a trend for ACT in Intermediate- and High-Risk pts.
Conclusion:
The prognostic performance of the previously developed model was validated in a larger R-SqCLC pts’ series. Considering the overall dismal prognosis of such disease, the efficacy of ACT requires to be clearly established for Intermediate- and High-Risk pts, as well as that should be questioned for Low-Risk pts.
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-019 - Large Cell Neuroendocrine Carcinoma of the Lung: Prognostic Factors of Survival and Recurrence after R0 Surgical Resection (ID 4928)
14:30 - 14:30 | Author(s): P.L. Filosso
- Abstract
Background:
Large cell neuroendocrine carcinomas (LCNEC) represent approximately 3% of all lung cancers. Due to this rarity, little knowledge exists about their outcome, prognosis or optimal treatment strategy. The objective of this study is to evaluate the outcomes of patients undergoing lung resection for LCNEC to identify the factors affecting survival and recurrence to help refine the optimal treatment strategy.
Methods:
We retrospectively reviewed 116 patients who underwent lung resection at 8 centers between 2000-2015. We excluded 18 patients: pNX(3), stage IV(5), R1-2(10). Univariate and multivariate analysis were performed to identify factors influencing disease-specific survival, overall survival and recurrence. The variables included age, gender, smoking habit, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, tumor location, tumor size, pT, pleura invasion, pN, pStage and neo/adjuvant treatments. Kaplan-Meier, Cox regression and ROC curve were used.
Results:
A total of 98 patients (M/F:60/38) were analyzed with a median age of 66 years (IQR=58-72). Prior to resection, 11 (11%) received induction therapy. Resections included pneumonectomy (8), bilobectomy (3), lobectomy (76) and sublobar (11) with an associated lymph node sampling (N=52, 55%) and lymphadenectomy (N=43, 45%). Adjuvant therapy was delivered in 28 (30%). Pathologic stages were I (N=40, 41%), II (N=33, 34%) and IIIA (N=25, 25%). Median follow-up was 62 (IQR=19-120) months. The 5-year disease-specific and overall survival rates were 51.6% and 42.7%. On univariate analysis, pT was associated with disease-specific and overall survival (p=0.011, p=0.028). Similarly pT was also associated on multivariate analysis with disease-specific and overall survival (p=0.044, p=0.034). The recurrence rate was 55% (2% local, 10% regional, 32% systemic, 11% not-specified). The median disease-free interval was 16 (IQR=6-80) months. Local-regional recurrence wasn’t associated with any factor on univariate analysis. Systemic recurrence was correlated with tumor size (p=0.002), pT (p=0.003) and pStage (p=0.024) on univariate analysis. Tumor size was an independent prognostic factor of systemic recurrence on multivariate analysis (p=0.001) with a threshold value of 3 cm (AUC=0.712). The 5-year disease-free survival for systemic recurrence in tumors < 3 cm or >3 cm was 75.4% and 37.8% (p=0.001). The 5-year disease-specific survival was 56.7% and 47.3% (p=0.088).
Conclusion:
Treatment of LCNEC with predominately surgical resection results in a respectable 5-year survival. However, a high proportion of systemic recurrence occurs. Tumors >3 cm have a higher rate of systemic recurrence and lower rate of survival suggesting that adjuvant chemotherapy may be indicated for completely resected LCNEC >3 cm.
