Management of locally advanced non-small cell lung cancer in the modern era: A national Italian survey on diagnosis, treatment and multidisciplinary approach.

Concurrent chemotherapy and radiotherapy (cCRT) is considered the standard treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Unfortunately, management is still heterogeneous across different specialists. A multidisciplinary approach is needed in this setting due to recent, promising results obtained by consolidative immunotherapy. The aim of this survey is to assess current LA-NSCLC management in Italy. From January to April 2018, a 15-question survey focusing on diagnostic/therapeutic LA-NSCLC management was sent to 1,478 e-mail addresses that belonged to pneumologists, thoracic surgeons, and radiation and medical oncologists. 421 answers were analyzed: 176 radiation oncologists, 86 medical oncologists, 92 pneumologists, 64 thoracic surgeons and 3 other specialists. More than a half of the respondents had been practicing for >10 years after completing residency training. Some discrepancies were observed in clinical LA-NSCLC management: the lack of a regularly planned multidisciplinary tumor board, the use of upfront surgery in multistation stage IIIA, and territorial diffusion of cCRT in unresectable LA-NSCLC. Our analysis demonstrated good compliance with international guidelines in the diagnostic workup of LA-NSCLC. We observed a relationship between high clinical experience and good clinical practice. A multidisciplinary approach is mandatory for managing LA-NSCLC.

ACTH-producing tumorlets and carcinoids of the lung: clinico-pathologic study of 63 cases and review of the literature.

Adrenocorticotropic hormone (ACTH)-secreting lung carcinoids represent the principal cause of ectopic Cushing syndrome, but the prevalence of ACTH expression and the association between ACTH production and Cushing syndrome in lung carcinoids have scarcely been investigated. In addition, available information on the prognostic meaning of ACTH production is controversial. The aims of this multicentric retrospective study, also including a review of the literature, were to describe the clinico-pathologic features of ACTH-producing lung carcinoids, to assess recurrence and specific survival rates, and to evaluate potential prognostic factors. To identify ACTH production in 254 unselected and radically resected lung carcinoids, we used a double approach including RT-PCR (mRNA encoding for pro-opiomelanocortin) and immunohistochemistry (antibodies against ACTH and ß-endorphin). Sixty-three (24.8%) tumors produced ACTH and 11 of them (17.4%), representing 4.3% of the whole series, were associated with Cushing syndrome. The median follow-up time was 71 months. The 10-year overall and specific survival rates were 88.5% and 98.2%, respectively, with difference neither between functioning and nonfunctioning tumors nor between ACTH-positive and ACTH-negative carcinoids. At univariate analysis, histological type (typical or atypical) and Ki67 index significantly correlated with tumor recurrence. The literature review identified 172 previously reported patients with functioning ACTH-secreting lung carcinoids, and the meta-analysis of survival showed that 92% of them were alive after a mean follow-up time of 50 months. Our results demonstrate that ACTH-producing lung carcinoids are not rare, are not always associated with Cushing syndrome, and do not represent an aggressive variant of lung carcinoid.

Current Practices in the Management of Pulmonary Ground-Glass Opacities: A Survey of SICT Members.

BACKGROUND: Several gray areas and controversies exist concerning the management of pulmonary ground-glass opacities (GGOs), and there is a lack of consensus among clinicians on this topic. One of the main aims of the Italian Society of Thoracic Surgery is to promote education and research, so we decided to perform a survey on this topic to estimate current trends in practice in a large sample of thoracic surgeons. METHODS: A total of 160 thoracic surgeons responded, namely, completed our questionnaire (response rate, 53%; 160 of 302). The survey was composed of 36 questions divided into six subsections: (1) demographic characteristics of the respondents; (2) terminology and taxonomy; (3) radiologic and radiometabolic evaluation; (4) diagnostic approach and indications for surgery; (5) surgical management; and (6) radiologic surveillance. RESULTS: We observed some divergence of opinion regarding the definition of mixed GGOs, the role of 18F fluorodeoxyglucose positron emission tomography and computed tomography scans, indications for nonsurgical biopsy, intraoperative techniques for localizing GGOs, indications for surgery, extension of lung resection and lymph node dissection according to the radiologic scenario, use of intraoperative frozen section analysis, and radiologic surveillance of pure GGOs. CONCLUSIONS: This topic warrants more investigation in the future. An upcoming consensus conference of Italian Society of Thoracic Surgery experts (also open to experts in other specialties) could provide updated indications for GGO management based on the literature, expert opinions, and the results of the present survey.

Analysis of risk factors in the development of bronchopleural fistula after major anatomic lung resection: experience of a single centre.

BACKGROUND: The bronchopleural fistula (BPF) is a rare but potentially fatal complication of major thoracic surgery. The purpose of this work is to investigate the risk factors associated with the development of fistulas after lobectomy and pneumonectomy. METHODS: We retrospectively reviewed the records of 835 patients who underwent major anatomic lung resection at our centre from January 2003 to December 2013. Of these, 49 underwent pneumonectomy (P group) and 786 lobectomy (L group). RESULTS: A total of 18 patients (2.6%) developed a BPF in the postoperative period, of which there were 11 in the L group (1.3%) and seven in the P group (14.28%). The 30-day mortality was 0.05% (one patient after right pneumonectomy). In the L group, three patients developed a fistula after a left lobectomy and eight after a right one, of which four developed after bilobectomy. Univariate analysis showed that induction therapy, lower lobectomy, manual suture of the bronchus, 'not covered' bronchial stump, empyema, postoperative anaemia and pulmonary infections and mechanical ventilation >24 h are associated with the development of fistulas after lobectomy. Multivariate analysis confirmed that induction therapy, manual closure of the bronchus, postoperative pulmonary infections and anaemia are the main risk factors involved in our series. In the P group, four patients developed a fistula after a right pneumonectomy and three after a left one. Postoperative empyema and pulmonary infections, mechanical ventilation >24 h and female gender emerged as the main risk factors on univariate analysis, while on multivariate analysis, only the female gender presented a trend towards significance. CONCLUSIONS: Postoperative pulmonary infections, empyema and mechanical ventilation >24 h are strongly associated with the development of BPFs after both pneumonectomy and lobectomy in our series.

Prognostic Impact of Node-Spreading Pattern in Surgically Treated Small-Cell Lung Cancer: A Multicentric Analysis.

OBJECTIVE: Although surgery in selected small-cell lung cancer (SCLC) patients has been proposed as a part of multimodality therapy, so far, the prognostic impact of node-spreading pattern has not been fully elucidated. To investigate this issue, a retrospective analysis was performed. METHODS: From 01/1996 to 12/2012, clinico-pathological, surgical, and oncological features were retrospectively reviewed in a multicentric cohort of 154 surgically treated SCLC patients. A multivariate Cox proportional hazard model was developed using stepwise regression, in order to identify independent outcome predictors. Overall (OS), cancer-specific (CSS), and Relapse-free survival (RFS) were calculated by Kaplan-Meier method. RESULTS: Overall, median OS, CSS, and RFS were 29 (95 % CI 18-39), 48 (95 % CI 19-78), and 22 (95 % CI 17-27) months, respectively. Lymphadenectomy was performed in 140 (90.9 %) patients (median number of harvested nodes: 11.5). Sixty-seven (47.9 %) pN0-cases experienced the best long-term survival (CSS: 71, RFS: 62 months; p < 0.0001). Among node-positive patients, no prognostic differences were found between pN1 and pN2 involvement (CSS: 22 vs. 15, and RFS: 14 vs. 10 months, respectively; p = 0.99). By splitting node-positive SCLC according to concurrent N1-invasion, N0N2-patients showed a worse CSS compared to those cases with combined N1N2-involvement (N0N2: 8 months vs. N1N2: 22 months; p = 0.04). On the other hand, the number of metastatic stations (p = 0.80) and the specific node-level (p = 0.85) did not affect CSS. At multivariate analysis, pN+ (HR: 3.05, 95 % CI 1.21-7.67, p = 0.02) and ratio between metastatic and resected lymph-nodes (RL, HR: 1.02, 95 % CI 1.00-1.04, p = 0.03) were independent predictors of CSS. Moreover, node-positive patients (HR: 3.60, 95 % CI 1.95-6.63, p < 0.0001) with tumor size ≥5 cm (HR: 1.85, 95 % CI 0.88-3.88, p = 0.10) experienced a worse RFS. CONCLUSIONS: In selected surgically treated SCLC, the long-term survival may be stratified according to the node-spreading pattern.

CT-guided fine-needle ago-biopsy of pulmonary nodules: predictive factors for diagnosis and pneumothorax occurrence.

OBJECTIVE: To evaluate variables that could predict diagnosis during CT-guided fine-needle aspiration. METHODS: Data from 249 patients who underwent FNAB from January 2010 to December 2012 were analyzed in a retrospective observational study. RESULTS: Mean age was 66.7 ± 11.5 years, male/female ratio 158/91 (63 vs. 37 %). The nodules were in right lung in 123 patients (49 %), in left lung in 126 patients (51 %), the upper, lower and middle lobe localizations were, respectively in 122 (49 %), 100 (40 %) and 17 (6 %) patients. Mean nodule-chest wall distance was 63.89 ± 21.38 mm. The tumor location, the needle diameter, the presence of necrosis or cavitation, the node-chest wall distance and the number of passages were not related to the diagnostic outcome (p = NS). The nodule diameter was predictive of diagnosis. Odds ratio for a 10-30 mm tumor was 2.51 (95 % OR: 1.24-5.08, p value = 0.011), the odds ratio for a 30-50 mm tumor was 2.39 (95 % OR: 1.22-4.69, p value = 0.011), and the odds ratio for a tumor larger than 50 mm was 4.44 (95 % OR: 1.89-10.44, p value = 0.001). Post-procedure pneumothorax occurred in 62 cases (25 %). The determinant factors for pneumothorax occurrence were emphysema, odds ratio 6.87 (95 % CI 1.07-44.10, p value = 0.04), and the number of pleural passages, odds ratio of 5.47 (95 % OR: 1.92-15.58), 7.44 (95 % OR: 2.58-21.5), 6.13 (95 % OR: 2.07-18.11) p value = 0.001 for one, two, three or more of three passages, respectively. CONCLUSIONS: In our experience, nodule size is the most important diagnostic factor during fine-needle aspiration, while the number of passages and the presence of emphysema constitute risk factors for pneumothorax occurrence.

Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma.

BACKGROUND: The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series. METHODS: We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes. RESULTS: We found two prevalent CA-SSR-1 genotypes: a homozygous 16 CA repeat and a heterozygous genotype, bearing alleles with 16 and 20 CA repeats. The average combined allele length was correlated with tumor subtype: shorter sequences were significantly associated with the more aggressive WHO thymoma subtype group including B2/B3, B3 and B3/C histotypes. Four out of 29 informative cases analysed for somatic CA-SSR-1 loss of heterozygosity showed allelic imbalance (AI), 3/4 with loss of the longer allele. By egfr-FISH analysis, 9 out of 33 cases were FISH positive. Moreover, the two integrated techniques demonstrated that 3 out of 4 CA-SSR-1-AI positive cases with short allele relative prevalence showed significantly low or high chromosome 7 "polysomy"/increased gene copy number by egfr-FISH. CONCLUSIONS: Our molecular and genetic and follow up data indicated that CA-SSR-1-allelic imbalance with short allele relative prevalence significantly correlated with EGFR 3+ immunohistochemical score, increased egfr Gene Copy Number, advanced stage and with relapsing/metastatic behaviour in thymomas.

Incidence and Management of Post-Lobectomy and Pneumonectomy Bronchopleural Fistula.

INTRODUCTION: Bronchopleural fistula is a rare but potentially fatal complication of pulmonary resections and proper management is essential for its resolution. In this study, we analyzed the incidence of fistula after pulmonary resection and reported data about endoscopic and conservative treatments of this complication. METHODS: From January 2003 to December 2013, 835 patients underwent anatomic lung resections: 786 (94.1 %) had a lobectomy and 49 (5.9 %) a pneumonectomy. Bronchopleural fistula was suspected by clinical signs and confirmed by endoscopic visualization. RESULTS: Eighteen patients (2.2 %) developed a bronchopleural fistula, 11 in lobectomy group (1.4 %) and 7 in pneumonectomy group (14.3 %). The fistula size ranged between <1 mm and 6 mm and mean time of fistula onset was 33.9 ± 54.9 days after surgery. Of 18 patients who developed fistula, one died due to acute respiratory failure and another one was reoperated and then died to causes unrelated to the treatment. All the remaining 16 patients were treated with a conservative therapy that consisted in keeping or replacing a drainage chest tube. Nine of them underwent also endoscopic closure of the fistula using biological or synthetic glues. The mean period of time elapsed for the resolution of this complication was shorter with combined (conservative + endoscopic) than with conservative treatment alone (15.4 ± 13.2 vs. 25.8 ± 13.2 days, respectively), but without significant difference between the two methods (p: 0.299). CONCLUSION: Endoscopic therapy, associated with a conservative treatment, is a safe and useful option in the management of the postoperative bronchopleural fistula.

Surgical treatment of recurrent thymoma: is it worthwhile?†.

OBJECTIVES: Radical resection of thymoma is the most important predictor of survival; despite a complete resection, 10-30% of patients develop a recurrence. The surgical treatment of thymic relapses is an accepted therapeutic approach; however, no clear data are available yet regarding the indication for surgery and the long-term prognosis of this subset of patients. The aim of our work was to review the data of a group of recurrent thymomas treated by surgery, comparing it with non-surgical therapy, and analysing the outcome and the prognostic factors. METHODS: Between 1980 and 2010, 880 patients with thymoma underwent complete macroscopical resection and were followed up for recurrence. Masaoka stage IVa and type C thymic tumours were excluded from the study. A total of 82 (9.3%) patients developed a recurrence, and 52 (63.4%) were reoperated. The other 21 patients, originally operated outside, underwent surgical resection of recurrence. Finally, 73 patients were operated on for recurrent thymoma and 30 received medical treatment. This entire cohort represents the subject of the study. RESULTS: There were 57 (55.3%) males and 46 (44.7%) females. The median time to relapse was 50 months. Sixty-three (61.2%) recurrences were regional, 17 (16.5%) local, 14 (13.6%) distant, 6 (5.8%) regional and distant, and 3 (2.9%) local, regional and distant. No operative mortality was observed. In 50 (68.5%) patients, a macroscopic complete resection was accomplished. The 5- and 10-year overall survival rates from recurrence were 63 and 37%, respectively. Complete surgical resection was associated with a significant better survival when compared with incomplete surgical resection and non-surgical treatment (P < 0.0001). A significant poorer prognosis was observed for multiple versus single relapses (P < 0.0001), Masaoka stage III primary tumour versus Masaoka stage I-II primary tumour (P = 0.02), distant versus loco-regional relapses (P = 0.05) and B3 histotype versus other (P = 0.02). On multivariate analysis, completeness of resection, number of metastases, Masaoka stage of primary tumour and site of relapse were identified as the only independent predictors of prognosis. CONCLUSION: Reoperation for recurrent thymoma is effective and safe, achieving a prolonged survival. Complete macroscopic resection and single recurrence are associated with better prognosis.

Chest wall tumors and prosthetic reconstruction: A comparative analysis on functional outcome.

BACKGROUND: To address the question of how much chest-wall (CW) resections and prosthetic reconstructions influence functional outcome. METHODS: We retrospectively reviewed 175 patients who underwent surgery for CW tumors. The clinical, histological, surgical, oncological, and functional factors were analyzed. RESULTS: We performed: 75 rib resections; 20 sternal resections; 15 combined resections; and 27 lung resections. In 39 cases (22.2%) CW was stabilized with non-rigid prosthesis (Vicryl-mesh: 8 patients; Goretex-mesh: 31 patients). Postoperative complications occurred in 22 cases (12.6%): a correlation with lung resection was evidenced by multivariate analysis (P = 0.025). Five-year survival for primary and secondary tumors was 50% and 36%, respectively: multivariate analysis (P = 0.048) showed a worse survival in men only. In the prosthesis subset, pulmonary function tested as percentage of forced expiratory volume in one second (%FEV1) (pre: 87.1 ± 18.9%; post: 82.3 ± 23.0%, P = ns), percentage of forced vital capacity (pre: 94.1 ± 19.3%; post: 82.0 ± 21.6%, P = ns), diffusing capacity of the lungs for carbon monoxide (pre: 15.7 ± 7.4; post: 12.1 ± 4.1, P = ns) and paO2 (pre: 82.6 ± 10.9 mmHg; post: 83.9 ± 7.3 mmHg, P = ns) was slightly modified from pre to postoperative. Interestingly, the decline of FEV1% was lower in the prosthesis-subset (4.1 ± 15.9%) compared with the subgroup who did not undergo prosthetic stabilization (17.5 ± 16.2%), but this difference was not statistically significant (P = ns). CONCLUSION: Because of the low decrease of lung parameters, CW prosthetic reconstruction could be helpful for avoiding postoperative worsening of functional outcome, mostly in patients with pre-existing pulmonary diseases.

Multicenter comparison of 18F-FDG and 68Ga-DOTA-peptide PET/CT for pulmonary carcinoid.

PURPOSE: The aims of this study were to retrospectively evaluate and compare the detection rate (DR) of 68Ga-DOTA-peptide and 18F-FDG PET/CT in the preoperative workup of patients with pulmonary carcinoid (PC) and to assess the utility of various functional indices obtained with the 2 tracers in predicting the histological characterization of PC, that is, typical versus atypical. METHODS: Thirty-three consecutive patients with confirmed PC referred for 18F-FDG and 68Ga-DOTA-peptide PET/CT in 2 centers between January 2009 and April 2013 were included. The semiquantitative evaluation included the SUV max, the SUV of the tumor relative to the maximal liver uptake for 18F-FDG (SUV T/L) or the maximal spleen uptake for 68Ga-DOTA-peptides (SUV T/S), the ratio between SUV max of 68Ga-DOTA-peptides PET/CT, and the SUV max of 18F-FDG PET/CT (SUV max ratio). Histology was used as reference standard. RESULTS: Definitive diagnosis consisted of 23 typical carcinoids (TCs) and 10 atypical carcinoids. 18F-FDG PET/CT was positive in 18 cases and negative in 15 (55% DR). 68Ga-DOTA-peptide PET/CT was positive in 26 cases and negative in 7 (79% DR). In the subgroup analysis, 68Ga-DOTA-peptide PET/CT was superior in detecting TC (91% DR; P < 0.001), whereas 18F-FDG PET/CT was superior in detecting atypical carcinoid (100% DR; P = 0.04). The SUV max ratio was the most accurate semiquantitative index in identifying TC. CONCLUSIONS: Overall diagnostic performance of PET/CT in detecting PC is optimal when integrating 18F-FDG and 68Ga-DOTA-peptide PET/CT findings. In the subgroup analysis, the SUV max ratio seems to be the most accurate index in predicting TC. Both methods should be performed when PC is suspected or when the histological subtype is undefined.

Long-term results after treatment for recurrent thymoma: a multicenter analysis.

OBJECTIVES: The treatment for recurrent thymoma remains a very controversial issue. This study aims to investigate the long-term outcomes in patients with relapse according to treatment strategies and clinicopathological features. METHODS: We retrospectively analyzed the database of three tertiary centers of thoracic surgery with the aim of reviewing the clinical records of 81 patients who experienced a recurrent thymoma after radical thymectomy, in the period between January 2001 and June 2013. The staging of both primitive and recurrent thymomas were based on the surgical and pathological criteria described by Masaoka. Experienced pathologists reassessed independently the histology of the initial thymoma and its relapse, according to the WHO classification. To the purposes of this study R+ resection or thymic carcinoma were considered as exclusion criteria. The overall outcome for long-term (5 years and 10 years) survival and disease-free survival after initial thymectomy and after treatment of recurrent thymoma were analyzed using standard statistics. RESULTS: The population was gender balanced (41 M, 40 F), mean age: 46.4 ± 12.3 years. Fifty-four patients (66.7%) were affected by myasthenia gravis, while the other 14 by other paraneoplastic conditions. Surgery was performed in 61 patients (75.3%,), and radiotherapy and/or chemotherapy in 14 patients (17.3%). The mean follow-up duration after recurrence onset was 66.3 ± 56.4 months. Adjuvant therapy had no effect on prolonging the disease-free survival: no differences were found when investigating the administration of adjuvant chemotherapy (no CHT = 91.5 ± 76.4 months versus yes CHT=64.0 ± 41.3) and radiotherapy (no RT=86.2 ± 72.8 months versus yes RT= 93.0 ± 62.3; p = 0.8). Relapses were mostly local (mediastinum: 15 cases, pleura: 44 cases); hematogenous distant recurrences were observed in 15 cases (lung: 12; liver: 1; bone: 2 cases). An upgrade in the WHO class (defined as the "migration" of WHO class at initial thymectomy to more aggressive WHO class assigned at thymic recurrence resection) was found in 25/61 cases (40.9%), but this phenomenon apparently did not influence patient's prognosis. Overall, the 5- and 10-year survival rates after the initial thymectomy were 94.8% and 71.7%, respectively, while the 5- and 10-year survival rates after the treatment of the recurrence at the thymic level were 73.6% and 48.3%, respectively (82.4% at 5 years and 65.4% at 10 years when a R0-re-resection was obtained). The analysis on the trends of disease-free survival indicated that the site of recurrence (hematogenous diffusion) seems to be associated to a higher risk of re-relapse (p = 0.01). CONCLUSIONS: Even following a thymectomy performed with radical intent, thymoma may recur several years later, usually as a locoregional relapse. A rewarding long-term survival may be expected after treatment, especially when a re-resection (radical) is performed (82.4% at 5 years). An histopathological "WHO upgrade" (from "low-risk" WHO classes at thymectomy to "high-risk classes" at relapse) may be observed in a remarkable percentage of patients (nearly 40% in this series), but this phenomenon seems to be not correlated with any worsening of the prognosis.

Diagnostic features and subtyping of thymoma lymph node metastases.

AIM: The purpose of the present study was to characterize the morphological features of thymoma metastases in lymph nodes and to evaluate the possibility of their subtyping according to the 2004 WHO classification of thymus tumors. MATERIALS AND METHODS: We reviewed 210 thymoma cases in our series of thymic epithelial tumors (TET), including their recurrences and lymphogenous metastases. Three cases of lymph node metastases, one case occurring synchronously with the primary tumor and one synchronously with the first relapse (both in intrathoracic location) and one case of metastasis observed in a laterocervical lymph node subsequently to two thymoma relapses were found. RESULTS: The metastatic nodes were variably but extensively involved in all cases. The histological features were similar in both primary tumors and metastases. Thymoma metastases were subtyped according to the WHO classification as B3 (one case) and B2 (two cases), and distinctive features in comparison to metastatic epithelial neoplasias from other sites were observed. CONCLUSION: Thymoma lymph node metastases, although rare, can be subtyped according to the WHO classification on the basis of their morphological and immunohistochemical features. Clinically, the presence of nodal metastases may herald subsequent relapses and further metastases even in extrathoracic sites.

Is sleeve lobectomy comparable in terms of short- and long-term results with pneumonectomy after induction therapy? A multicenter analysis.

BACKGROUND: Sleeve lobectomy (SL) is considered a valid therapeutic option in untreated, centrally located non-small cell lung cancer (NSCLC) even in patients "fit" for pneumonectomy (PN). Nevertheless, SL feasibility and long-term results after induction therapy (IT) have been only rarely investigated. We herein report the results of a multicenter retrospective study on NSCLC patients who underwent PN or SL after IT for locally advanced NSCLC. METHODS: From January 1992 to January 2012, 119 consecutive patients (94 males, 25 females) underwent in three tertiary referral centers either SL (bronchial, arterial, or both) or PN for locally advanced NSCLC after IT (chemotherapy alone or combined chemoradiotherapy). The indication for SL was based on technical feasibility. Clinical and pathologic variables were retrospectively reviewed, and treatment results were assessed and compared in both groups. Survival was calculated by Kaplan-Meier method and compared by the log-rank test as well the Cox regression model. RESULTS: Sleeve lobectomy was performed in 51 patients and PN, in 68 patients. Thirty-day mortality and morbidity rates were 3.9% and 9.8% for SL and 2.9% and 22.1% for PN, respectively. Five-year survival rates were 53.8% after SL and 43.1% after PN, respectively (p = 0.28). Overall recurrence rate was 42.8% after SL and 47.0% after PN (p = 0.34); relapse was locoregional in 22.4% of SL cases and 12.1% after PN, respectively (p = 0.011). The Cox analysis suggested pN status and right side as independent risk factors for death in the SL group (hazard ratio, 1.96; 95% confidence interval, 1.12 to 3.44; p = 0.018; and hazard ratio, 2.96; 95% confidence interval, 1.13 to 8.66; p = 0.047, respectively). As well, pN status and right side were a strong predictor of relapse (hazard ratio, 2.33; 95% confidence interval, 1.17 to 4.64; p = 0.016; and hazard ratio, 2.96; 95% confidence interval, 1.13 to 8.66; p = 0.046, respectively) in SL patients. CONCLUSIONS: For locally advanced NSCLC, SL represents a safe and effective surgical option when compared with PN even after IT, with substantially comparable early and long-term results. Nevertheless, further investigations on a large cohort of patients are needed.

Thymic epithelial tumors express vascular endothelial growth factors and their receptors as potential targets of antiangiogenic therapy: a tissue micro array-based multicenter study.

OBJECTIVES: Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity. To ascertain the presence of potential therapeutic targets, we analyzed by immunohistochemistry the expression of angiogenesis-related biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA). MATERIALS AND METHODS: We assessed by immunohistochemistry the expression of the possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, and PDGFRß, in a TMA series of 200 TET collected in the framework of a multi-institutional collaborative project for Rare Diseases. RESULTS: When compared to the low-risk tumors, high-risk TET (B2, B3, carcinomas) contained higher proportion of cancer cells expressing VEGFA, VEGFC and VEGFD (P<0.001, P<0.001, and P<0.001) growth factors, and their receptors VEGFR1 (P=0.002), VEGFR2 (P=0.013), and VEGFR3 (P=0.041). No differences were observed in terms of PDGFRß expression. CONCLUSIONS: According to our data, it is possible to hypothesize the existence of multiple paracrine and/or autocrine loops in TET, particularly in the high-risk ones, involved in TET growth and progression. Anti-angiogenic agents, directed to inhibit these loops, are therefore to be considered as potential tools in advanced TET therapy.