The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round.

BACKGROUND: Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings. METHODS: High-risk subjects were defined as being >55 years of age and active smokers or formers who had quit within 15 years (>30 pack/y). A PLCOm2012 threshold >2% was chosen. Subject outreach was streamlined through media campaign and general practitioners' engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the "Maisonneuve risk re-calculation model", and a threshold <0.6% was chosen for the biennial round. RESULTS: In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M/F 62/38%), with a mean PLCOm2012 of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers. CONCLUSIONS: LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.

Postoperative Radiation Therapy for Thymic Carcinoma: An Analysis of the International Thymic Malignancy Interest Group/European Society of Thoracic Surgeons Database.

INTRODUCTION: R0 resection and radiation therapy have been associated with improved overall survival (OS) in patients with thymic carcinoma (TC). Here, we analyzed which subgroups of patients derive the greatest benefit from postoperative radiation therapy (PORT). METHODS: Clinical, pathologic, treatment, and survival information of 462 patients with TC from the International Thymic Malignancy Interest Group/European Society of Thoracic Surgeons database were analyzed. Variables included age, sex, continent of treatment, paraneoplastic syndrome, carcinoma subtype, tumor size, pathologic Masaoka stage, resection status, and use of chemotherapy. OS was the primary end point using the Kaplan-Meier method. Time to recurrence (TTR) was the secondary end point using a competing risk analysis. A 3-month landmark analysis was performed. RESULTS: PORT was associated with a significant OS benefit (5-y OS 68% versus 53%, p = 0.002). In patients with R0 resection, PORT was associated with increased OS for advanced (stages III-IV, p = 0.04), but not early (stages I-II, p = 0.14) stage TC. In patients with an R1/2 resection of advanced-stage TC, PORT was associated with significantly longer OS (5-y OS 53% versus 38%; p < 0.001). Subset analyses did not reveal clear associations of PORT with TTR. On multivariable analysis, lower pathologic stage, PORT, and R0 resection status were associated with an OS benefit, whereas only higher age and lower pathologic stage had an association with longer TTR. CONCLUSIONS: In the largest individual patient data set on patients with TC reported to date, PORT was associated with a meaningful OS benefit in patients with advanced-stage TC after an R0 or R1/2 resection.

Chest Drainage Therapy: What Comes out of Pandora's Box Can Affect Patient Outcomes.

Background: Over the last 100 years, the original three-bottle chest drainage system has been variously engineered into compact disposables and electronic units. Clinicians are now surrounded by a plethora of different types of systems, but little is known about the way that they work and perform. Thus, we sought to test the performance of the most commonly used chest drainage units under conditions that are relevant to clinical practice. Methods: A pleural space environment simulator was built. Thirty-two units were tested under four clinical scenarios: air leak interpretation during quiet breathing and after obstructed inspiration (−5 to −150 cmH2O), a buildup of negative pressure (−100 cmH2O), a bronchopleural fistula (10 L/min) and the need for effective external suction in the presence of air leakage. Twenty-five units were "traditional" thoracic drainages, five were "digital" low-flow/low-vacuum pumps and two were hybrids (a combination of the two). According to the design of the seal and of the suction control, the units were classified as wet-wet, wet-dry and dry-dry. Results: All wet units showed reverse air flow, with the potential to mimic an air leak when there was none. Ten wet units showed no automatic negative pressure relief features, while five dry-dry did but were slow to react. Ten wet and five dry-dry units showed no capability to handle a 10 L/min leak, as they were restrictive to flow (peak pressure up to 55 cmH2O). Only seven dry-suction units were able to maintain the set suction at high airflow rates (>20 L/min). Conclusions: Different chest drainage unit designs lead to different performances, some of which may negatively impact patient outcomes. This sounds the call to tailor our clinical practice for the individual patient. A paradigm shift to better understand all components of pleural physiology post-surgical intervention on this relatively neglected topic is needed to improve our daily practice.

Bronchoscopic Intra-Pleural Instillation of Fibrin Glue and Autologous Blood to Manage Persistent Air Leaks after Lung Resection.

Background: Persistent air leak is a common complication after lung resection causing prolonged length of stay and increased healthcare costs. Surgical intervention can be an option, but other more conservative approaches should be considered first. Here, we describe the use of flexible bronchoscopy to apply fibrin glue and autologous blood sequentially to the damaged lung. We named the technique "flexible thoracoscopy". METHODS: Medical records from patients with persistent air leaks after lung resection were collected retrospectively. Depending on the type of aerostasis that was performed, two groups were created: flexible thoracoscopy and surgery (thoracotomy). Flexible thoracoscopy was introduced at our institution in 2013. We entered the pleural space with a bronchoscope following the same surgical pathway that was used for tube thoracostomy. Perioperative characteristics and outcomes were analyzed using R software (ver. 3.4.4). RESULTS: From 1997 to 2021, a total of 23 patients required an intervention for persistent air leaks. Aerostasis was performed via flexible thoracoscopy in seventeen patients (69%) and via thoracotomy in six patients (31%). The median age was 70 years (22-82). Twenty patients were males (87%). There was no difference in age, sex distribution, BMI, comorbidities and FEV1%. An ASA score of 3 was more represented in the flexible thoracoscopy group; however, no evidence of a difference was found when compared to the thoracotomy group (p = 0.124). Length of in-hospital stay and chest tube duration was also similar between groups (p = 1 and p = 0.68, respectively). CONCLUSIONS: Aerostasis achieved either by flexible thoracoscopy or by thoracotomy showed similar results. We believe that flexible thoracoscopy could be a valid alternative to facilitate minimally invasive treatments for persistent air leaks. Further studies are needed to confirm these results.

EWSR1 translocation in primary hyalinising clear cell carcinoma of the thymus.

AIMS: In thymic carcinomas, focal clear cell change is a frequent finding. In addition to a prominent, diffuse clear cell morphology, some of these carcinomas show an exuberant hyalinised extracellular matrix, and therefore probably represent a separate entity. However, a characteristic genomic alteration remains elusive. We hypothesised that, analogous to hyalinising clear cell carcinomas of the salivary gland, hyalinising clear cell carcinomas of the thymus might also harbour EWSR1 translocations. METHODS AND RESULTS: We identified nine archived cases of thymic carcinoma with focal clear cell features and two cases that showed remarkable hyalinised stroma and prominent, diffuse clear cell morphology. These two cases expressed p40 and were negative for Pax8, CD5, and CD117. Programmed death-ligand 1 was highly positive in one case (70%), and negative in the other one. EWSR1 translocation was identified in both cases of hyalinising clear cell carcinoma, and was absent in all nine carcinomas that showed clear cell features without substantial hyalinisation. In one of the EWSR1-translocated cases, a fusion between exon 13 and exon 6 of EWSR1 and ATF1, respectively was identified by next-generation sequencing. CONCLUSIONS: These findings suggest that the EWSR1 translocation and possibly the EWSR1-ATF1 fusion might be unifying genomic alterations for thymic clear cell carcinomas with prominent hyalinised stroma, for which we propose the term 'hyalinising clear cell carcinoma of the thymus'. Because the immunophenotype is unspecific, testing for the EWSR1 translocation might be helpful in discriminating this entity from other thymic neoplasms or metastases, in particular those with clear cell change.

Paraneoplastic Syndromes and Thymic Malignancies: An Examination of the International Thymic Malignancy Interest Group Retrospective Database.

INTRODUCTION: Thymic epithelial tumors (TETs) are associated with paraneoplastic/autoimmune (PN/AI) syndromes. Myasthenia gravis is the most common PN/AI syndrome associated with TETs. METHODS: The International Thymic Malignancy Interest Group retrospective database was examined to determine (1) baseline and treatment characteristics associated with PN/AI syndromes and (2) the prognostic role of PN/AI syndromes for patients with TETs. The competing risks model was used to estimate cumulative incidence of recurrence (CIR) and the Kaplan-Meier method was used to calculate overall survival (OS). A Cox proportional hazards model was used for multivariate analysis. RESULTS: A total of 6670 patients with known PN/AI syndrome status from 1951 to 2012 were identified. PN/AI syndromes were associated with younger age, female sex, thymoma histologic type, earlier stage, and an increased rate of total thymectomy and complete resection status. There was a statistically significant lower CIR in the group with a PN/AI syndrome than in the group without a PN/AI syndrome (10-year CIR 17.3% versus 21.2%, respectively [p = 0.0003]). The OS was improved in the group with a PN/AI syndrome compared to the group without a PN/AI syndrome (median OS 21.6 years versus 17.0 years, respectively [hazard ratio = 0.63, 95% confidence interval: 0.54-0.74, p < 0.0001]). However, in the multivariate model for recurrence-free survival and OS, PN/AI syndrome was not an independent prognostic factor. DISCUSSION: Previously, there have been mixed data regarding the prognostic role of PN/AI syndromes for patients with TETs. Here, using the largest data set in the world for TETs, PN/AI syndromes were associated with favorable features (i.e., earlier stage and complete resection status) but were not an independent prognostic factor for patients with TETs.

Comparison of surgical approach and extent of resection for Masaoka-Koga Stage I and II thymic tumours in Europe, North America and Asia: an International Thymic Malignancy Interest Group retrospective database analysis.

OBJECTIVES: Surgeons at different institutions worldwide choose different types of operations for thymic tumours. It is not known whether these differences affect the outcomes of the patients. METHODS: A total of 1430 patients with Masaoka-Koga pathological Stage I-II thymic tumours without myasthenia gravis or pre-treatment were identified from the International Thymic Malignancy Interest Group retrospective database. Outcomes of patients from 3 major continents (Europe, North America and Asia) were compared. RESULTS: Patients from the 3 continents were comparable in gender and performance status. More European patients had more paraneoplastic syndromes; North American patients had the smallest tumour sizes and less adjuvant therapy; and Asian patients were younger and had more Stage I disease but higher grade tumours. Partial thymectomy was performed more often in Asian patients (31.7%) than in European (2.4%) and North American (5.4%; P < 0.001) patients. The median approach (sternotomy/clamshell) was the major approach in Europe (75.3%) and North America (76.6%). In contrast, the median approach was applied significantly less frequently in Asia (45.6%, P < 0.001); unilateral open (thoracotomy/hemi-clamshell, 23.3%) and minimally invasive approaches (video-assisted thoracoscopic surgery/robot, 31.1%) were used more often with similar rates of complete resection. The 10-year overall survival rate was 82% for Europe, 78% for North America and 90% for Asia ( P = 0.005), respectively. The 10-year cumulative recurrence rates were similar among the geographic groups (European 0.08, North American 0.07, and Asian 0.06, P = 0.61). Age was the only independent predictive factor for overall survival ( P < 0.001, HR = 1.089, 95% CI 1.056-1.123) in multivariable analysis. Types B3 and thymic carcinoma ( P = 0.003, HR = 3.932, 95% CI 1.615-9.576) were independent risk factors for increased recurrence. CONCLUSIONS: This study shows that the selection of the surgical approach and the extent of resection for Stage I and II thymic tumours differ by geographic region. However, these differences seem to have little impact on outcomes.

Determinants of Complete Resection of Thymoma by Minimally Invasive and Open Thymectomy: Analysis of an International Registry.

INTRODUCTION: Minimally invasive thymectomy (MIT) is a surgical approach to thymectomy that has more favorable short-term outcomes for myasthenia gravis than open thymectomy (OT). The oncologic outcomes of MIT performed for thymoma have not been rigorously evaluated. We analyzed determinants of complete (R0) resection among patients undergoing MIT and OT in a large international database. METHODS: The retrospective database of the International Thymic Malignancy Interest Group was queried. Chi-square and Wilcoxon rank sum tests, multivariate logistic regression models, and propensity matching were performed. RESULTS: A total of 2514 patients underwent thymectomy for thymoma between 1997 and 2012; 2053 of them (82%) underwent OT and 461 (18%) underwent MIT, with the use of MIT increasing significantly in recent years. The rate of R0 resection among patients undergoing OT was 86%, and among those undergoing MIT it was 94% (p < 0.0001). In propensity-matched MIT and OT groups (n = 266 in each group); however, the rate of R0 resection did not differ significantly (96% in both the MIT and OT groups, p = 0.7). Multivariate analyses were performed to identify determinants of R0 resection. Factors independently associated with R0 resection were geographical region, later time period, less advanced Masaoka stage, total thymectomy, and the absence of radiotherapy. Surgical approach, whether minimally invasive or open, was not associated with completeness of resection. CONCLUSIONS: The use of MIT for resection of thymoma has been increasing substantially over time, and MIT can achieve rates of R0 resection for thymoma similar to those achieved with OT.

Postoperative Radiation Therapy Is Associated with Longer Overall Survival in Completely Resected Stage II and III Thymoma-An Analysis of the International Thymic Malignancies Interest Group Retrospective Database.

OBJECTIVES: The aim of this study was to determine whether postoperative radiation therapy (PORT) is associated with an overall survival (OS) benefit in patients with completely resected Masaoka or Masaoka-Koga stage II and III thymoma. METHODS: All patients with completely resected (R0) stage II or III thymoma were identified in a large database of the International Thymic Malignancy Interest Group. Clinical, pathologic, treatment, and follow-up information were extracted. OS was the primary end point. A univariate analysis using the log-rank test was performed, and a multivariate Cox model was created to identify factors associated with OS. RESULTS: Of 1263 patients meeting the selection criteria, 870 (69%) had stage II thymoma. The WHO histologic subtype was A/AB in 360 patients (30%) and B1/B2/B3 in 827 (70%). PORT was given to 55% of patients (n = 689), 15% (n = 180) received chemotherapy, and 10% (n = 122) received both. The 5- and 10-year OS rates for patients having undergone an operation plus PORT were 95% and 86%, respectively, compared with 90% and 79% for patients receiving an operation alone (p = 0.002). This OS benefit remained significant when patients with stage II (p = 0.02) and stage III thymoma (p = 0.0005) were analyzed separately. On multivariate analysis, earlier stage, younger age, absence of paraneoplastic syndrome, and PORT were significantly associated with improved OS. CONCLUSIONS: We observed an OS benefit with the use of PORT in completely resected stage II and III thymoma. In the absence of a randomized trial, this represents the most comprehensive analysis of individual patient data and strong evidence in favor of PORT in this patient population.

Comparison of outcomes between neuroendocrine thymic tumours and other subtypes of thymic carcinomas: a joint analysis of the European Society of Thoracic Surgeons and the International Thymic Malignancy Interest Group.

OBJECTIVES: The latest World Health Organization (WHO) histological classification divides thymic epithelial tumours in thymomas and thymic carcinomas (TCs), the latter also including the neuroendocrine thymic tumours (NETTs). NETTs and other TC histotypes have been described to have a significantly lower survival than thymomas, but these two groups of tumours have rarely been compared directly. Using the European Society of Thoracic Surgeons and the International Thymic Malignancy Interest Group datasets, we wanted to study this issue. METHODS: This is a retrospective multicentre cohort study of patients operated for TC. Outcome measures were overall survival (OS) and recurrence-free survival (RFS). OS was analysed using the Kaplan-Meier method and RFS was assessed using competing risk analysis. The association with clinical and prognostic factors for OS and RFS was evaluated with log-rank test and Gray's test, respectively. RESULTS: A total of 1247 tumours (1042 TCs) were collected between 1984 and 2012. A R0 resection was performed in 363 TCs and in 52 NETTs. The median follow-up was 4.4 years for TCs and 4.1 years for NETTs. Owing to the missing values for survival information, a total of 728 TC patients and 132 NETTs were included in the OS analysis. Among them, 262 TC and 39 NETT patients died. The median OS was 6.6 years for TC and 7.5 years for NETTs. The overall 5-year survival rates were 60% for TC and 68% for NETTs; 10-year survival rates were 40% for TCs and 39% for NETTs (P = 0.19). Five-year RFS was 0.35 and 0.34 for TCs and NETTs (P = 0.36). On multivariate analysis, histology did not influence either OS (P = 0.79) or RFS (P = 0.59). CONCLUSIONS: This represents the largest clinical series of TCs and NETTs collected. Despite the biological aggressiveness of these rare neoplasms, the 5-year survival rate after resection is over 60% and TCs and NETT showed a similar rate of survival and recurrences after surgery.

What's new in thymic neoplasms.

PURPOSE OF REVIEW: The past 5 years have been marked with major developments in the field of thymic malignancies. RECENT FINDINGS: A lack of progress over decades has been transformed into dramatic advancements over the past 5 years through the creation of the International Thymic Malignancy Interest Group (ITMIG). ITMIG has brought together an engaged worldwide community interested in this field. An unprecedented global database has been developed and is being actively analyzed. Standard definitions have been established to allow collaboration; the histologic classification has been revised and the first formal stage classification system developed. Clinical trials and innovative research approaches are being implemented. The creation of the ITMIG infrastructure has yielded many successes and provides a solid foundation for future progress. SUMMARY: Clinicians and researchers should be aware of the knowledge, structure and tools that have been established. ITMIG provides an engaged community for collaboration and progress.

The impact of thymoma histotype on prognosis in a worldwide database.

INTRODUCTION: The rarity of thymomas and lack of multi-institutional studies have hampered therapeutic progress for decades. To overcome this, the members of the International Thymic Malignancy Interest Group created a worldwide retrospective database. This database was analyzed regarding the demographic and geographic distribution of thymomas and the impact of different variables on survival and recurrence. METHODS: This study analyzed 4221 thymomas diagnosed between 1983 and 2012 with World Health Organization histotype information from the International Thymic Malignancy Interest Group database. Associations to survival and recurrence were studied by univariate and multivariate analyses. RESULTS: Type B2 thymoma is the most common (28%) and type A the least common (12%) histotypes. They are significantly more frequent in Europe and the United States than Asia. Type A and AB occur at significantly higher age than other thymomas (64 and 57 years, respectively). There are no differences in gender distribution. Stage is lower in type A (90% in stages I-II) and AB than B1 to B3 thymomas (38% of type B3 in stage III). In univariate analysis, recurrence is significantly less frequent among stage I/II tumors, in type A and AB (recurrence rates, 1-2%) than B1 to B3 thymomas (2-7%). Multivariate analysis reveals an impact of age, stage, and resection status on survival and recurrence, whereas for histology there is only a significant impact on recurrence. CONCLUSION: New findings are (1) geographic differences such as a lower incidence of type A and B2 thymoma in Asia; and (2) impact of stage and histology, the latter partially limited to early stage disease, on recurrence.

Outcome of primary neuroendocrine tumors of the thymus: a joint analysis of the International Thymic Malignancy Interest Group and the European Society of Thoracic Surgeons databases.

OBJECTIVE: Primary neuroendocrine tumors of the thymus (TNET) are exceedingly rare. We studied a large series of TNET identified through the International Thymic Malignancy Interest Group and the European Society of Thoracic Surgeons databases. METHODS: This was a retrospective multicenter study of patients undergoing operation for TNET between 1984 and 2012. Outcome measures were: overall survival (OS) and cumulative incidence of recurrences (CIR). OS was analyzed using the Kaplan-Meier method and CIR was analyzed using competing risk analysis. Associations with clinical and prognostic factors for OS and CIR were evaluated using the log rank test and Gray test. RESULTS: Two hundred five patients with TNET were treated: 25 patients received induction therapy (19 chemotherapy [CT] and 6 radiotherapy [RT]). Data about resection status were available in 47% of cases: complete resection was performed in 52 patients (54%). Masaoka-Koga stages I, II, III, and IV were observed in 12, 33, 56, and 47 patients, respectively. Atypical carcinoid was the commonest histologic subtype (71 cases; 40%). One hundred one patients with TNET received adjuvant treatment; 52 patients died and 36 experienced a recurrence. The median OS was 7.5 years; 5-year OS was 68%, and 5-year CIR was 39%. OS was significantly influenced by Masaoka-Koga stage (P = .02) and completeness of resection (P = .03). CIR significantly increased in high Masaoka-Koga stages (P = .04). Histologic subtype was not associated with either OS or CIR. CONCLUSIONS: Our results confirm the high biologic aggressiveness of these rare neoplasms; pathologic stage and completeness of resection were demonstrated to be strong prognostic factors, whereas histology did not influence patients outcome.

Impact of adjuvant treatment for microscopic residual disease after non-small cell lung cancer surgery.

BACKGROUND: Incomplete resection of non-small cell lung cancer (NSCLC) portends a dramatic decline in survival. Historically, postoperative radiation and chemotherapy have been offered to treat residual disease at the surgical margins, yet the efficacy is unknown. We examined the survival among incompletely resected NSCLC patients to identify the optimal response to positive NSCLC surgical margins. METHODS: The National Cancer Data Base was queried for surgically managed pathologic stage I-III NSCLC between 2003 and 2006 (n = 54,512). The prevalence, predictors, impact, and optimal treatment approaches to positive surgical margins were investigated. RESULTS: A positive surgical margin was identified in 3,102 NSCLC patients (5.7% of resections), including 1,688 with microscopically positive (R1) margins (3.1%). Compared with complete resections, patients with R1 resections had a worse 5-year survival; stage pI (62% vs 37%; p < 0.0001), stage pII (41% vs 29%; p < 0.0001), and stage pIII (33% vs 19%; p < 0.0001). Postoperative administration of both chemotherapy and radiation were associated with superior survival compared with surgery alone at all stages; stage pI (44% vs 35%; p = 0.05), stage pII (33% vs 21%; p = 0.0013), and stage pIII NSCLC (30% vs 12%; p < 0.0001). Administration of chemotherapy or radiation alone was less consistently associated with improved outcome in R1 patients. Of note, radiation alone did not improve survival for stage pI patients with R1 resections (26% vs 35%; p = 0.0399). CONCLUSIONS: The administration of both chemotherapy and radiation is associated with an improved survival in patients with microscopically positive surgical margins, irrespective of stage. Further study is needed to clarify the optimal stage-specific adjuvant approach to incompletely resected NSCLC.

Thymic carcinoma outcomes and prognosis: results of an international analysis.

OBJECTIVES: The objectives of this collaborative study were to characterize patients with thymic carcinoma, their treatment patterns, and association with overall survival (OS) and recurrence-free survival (RFS). METHODS: Clinical, pathologic, treatment, and follow-up information were analyzed. OS and RFS were the primary outcome measures. RESULTS: In 1042 cases of thymic carcinoma, 42 (5%) patients had pathologic Masaoka stage I, 138 (17%) had stage II, 370 (45%) had stage III, and 274 (33%) had stage IV disease. Overall, 166 patients (22%) underwent induction chemotherapy and 48 (6%) had preoperative radiation therapy. An R0 resection was performed in 447 cases (61%), R1 in 102 cases (14%), and R2 in 184 cases (25%). Squamous cell carcinoma was the predominant histologic subtype (n = 560; 79%). Adjuvant chemotherapy was administered to 237 (31%) patients, and 449 (60%) received adjuvant radiation therapy. The median OS was 6.6 years (95% confidence interval [CI], 5.8-8.3) and the cumulative incidence of recurrence at 5 years was 35% (95% CI, 30%-40%). In univariate analysis, early Masaoka stage, R0 resection, chemotherapy, and radiation therapy were associated with OS. Early Masaoka stage and R0 resection were also associated with RFS. On multivariable analysis, R0 resection and radiation therapy were associated with prolonged OS. Radiation therapy and male gender were associated with prolonged RFS. CONCLUSIONS: R0 resection and radiation therapy are associated with improved OS, whereas radiation therapy and male gender are associated with longer RFS.

Development of the international thymic malignancy interest group international database: an unprecedented resource for the study of a rare group of tumors.

BACKGROUND: Our knowledge of thymic malignancies has largely been derived from small, single-institution series. Recognition of the need for broad collaboration led to the creation of the International Thymic Malignancy Interest Group (ITMIG) and the development of a large, centralized database to advance knowledge of these rare tumors. METHODS: A multidisciplinary Database Committee was convened to define a common set of data elements a priori. Retrospective data were solicited from ITMIG members and collated using standardized fields. Patients with thymoma, thymic carcinoma, or thymic carcinoid were included. RESULTS: Over a 6-month period, 47 institutions spanning 15 countries contributed a total of 6097 cases (mean, 129 [range, 10-1209]). The sex distribution was equal for thymomas, but there was a greater proportion of men with thymic carcinoma and thymic carcinoid (p < 0.0001). Nearly all cases (99%) were treated surgically. WHO type B2 was the most frequent histologic classification among thymomas, whereas squamous was the most common among thymic carcinomas. In total, 38% of patients with thymoma had myasthenia gravis compared with less than or equal to 5% for thymic carcinoma and thymic carcinoid. Median overall survival was 18.9 years (95% confidence interval [CI], 17.4-20.3) for thymoma, 6.8 years (95% CI, 5.5-7.9) for thymic carcinoma, and 7.5 years (95% CI, 6.5-8.5) for thymic carcinoid. CONCLUSIONS: The rapid creation of the ITMIG database demonstrates the feasibility of international collaboration for this rare set of malignancies and attests to the engagement of its membership. This database represents the largest collective data set ever assembled and provides an unprecedented resource for research of these tumors.

EGFR-targeted therapy for non-small cell lung cancer: focus on EGFR oncogenic mutation.

The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. Actually, the value of EGFR expressed in patients with NSCLC in predicting a benefit in terms of survival from treatment with an epidermal growth factor receptor targeted therapy is still in debate, while there is a convincing evidence on the predictive role of the EGFR mutational status with regard to the response to tyrosine kinase inhibitors (TKIs).This is a literature overview on the state-of-the-art of EGFR oncogenic mutation in NSCLC. It is designed to highlight the preclinical rationale driving the molecular footprint assessment, the progressive development of a specific pharmacological treatment and the best method to identify those NSCLC who would most likely benefit from treatment with EGFR-targeted therapy. This is supported by the belief that a rationale for the prioritization of specific regimens based on patient-tailored therapy could be closer than commonly expected.