Malignant Solitary Fibrous Tumours of the Pleura Are Not All the Same: Analysis of Long-Term Outcomes and Evaluation of Risk Stratification Models in a Large Single-Centre Series.

Introduction: Malignant solitary fibrous tumours of the pleura (mSFTP) are extremely rare diseases (<5% of all pleural neoplasms) with unpredictable behaviour. Surgery remains the standard of care for these tumours; however, estimating patient prognosis and planning follow-up remain challenging. Several risk stratification models have been proposed, but a classification with diagnostic and prognostic potential has not been well standardised yet. The aim of this study was to analyse the clinicopathological data of mSFTP to investigate their prognostic features and to compare the performance of three risk stratification models proposed in the literature. Methods: Observational retrospective cohort study on all proven cases of mSFTP surgically resected with radical intent between 2000 and 2019 in a single centre. Demographic, surgical and pathological data were examined. All patients were risk-stratified by using three prediction models: modified Demicco, De Perrot and Tapias. Overall survival (OS) and disease-free survival (DFS) were analysed. Results: There were 21 men and 13 women (median age, 67 years, range, 23-83 years). Twenty-one patients (62%) were symptomatic. The median follow-up was 111 months (range, 6-258 months). The 5-year OS and DFS were 81.2% and 77.4%, respectively. Nine patients (26.5%) experimented recurrences. At univariate analysis, the presence of necrosis (p = 0.019), nuclear atypia (p = 0.006), dimension greater than 11.5 cm (median value of our cohort) (p = 0.037) and relapse/disease progression (p = 0.001) were independent prognostic factor of worse OS. The administration of adjuvant treatment was a protective independent factor for survival (p = 0.001). Radicality of resection (p = 0.005); tumour dimension (p = 0.013), presence of necrosis (p = 0.041) and nuclear atypia (p = 0.007) and pleural pattern (p = 0.011) were independent prognostic factors of worse DFS. Analysing the three risk stratification models, the Tapias score was revealed as the best index to predict both OS (p = 0.002) and DFS (p = 0.047) in patients with mSFTP. Conclusions: Using the risk stratification model proposed by Tapias, patients with the highest risk of recurrence could be identified at the time of surgery to establish a more frequent imaging surveillance and longer follow-up. The role of adjuvant treatment in mSFTP therapy has not been established yet, but further analysis on patients with a high risk of recurrence, stratified according to risk models, along with biomolecular panels may tailor future post-surgical therapies.

Which Surgery for Stage II-III Empyema Patients? Observational Single-Center Cohort Study of 719 Consecutive Patients.

OBJECTIVE: Recent guidelines support the use of thoracoscopic surgery in stage II-III empyema; however, there is still debate regarding the best surgical approach. The aim of our study is to compare postoperative outcomes of VATS and open surgical approaches for the treatment of post-pneumonic empyema. METHODS: Observational cohort study on prospectively collected cases of post-pneumonic empyema surgically treated in a single center (2000-2020). Patients were divided into an open group (OT, posterolateral muscle sparing thoracotomy) and VATS group (VT, 2 or 3 port ± utility incision). The primary outcome of the study was empyema resolution, assessed by the recurrence rate. Secondary outcomes were mortality, complications, pain and return to daily life. All patients were followed up at 1, 3 and 6 months after surgery in the outpatient clinic with a chest radiograph/CT scan. RESULTS: In total, 719 consecutive patients were surgically treated for stage II-III empyema, with 644 belonging to the VT group and 75 to the OT group. All patients had a clinical history of pneumonia lasting no more than 6 months before surgery, and 553 (76.9%) had stage II empyema. Operative time was 92.7 ± 6.8 min for the OT group and 112.2 ± 7.4 for the VT group. The conversion rate was 8.4% (46/545) for stage II and 19.2% (19/99) for stage III. Twelve patients (1.86%) in the VT group and four patients (5.3%) in the OT group underwent additional surgery for bleeding. Postoperative mortality was 1.25% (9/719): 5.3% (4/75) in OT and 0.77% (5/644) in VT. Postoperative stay was 10 ± 6.5 days in OT and 8 ± 2.4 in VT. Overall morbidity was 14.7% (106/719): 21.3% (16/75) in OT and 13.9% (90/644) in VT. In VT, six patients (0.93%) showed recurrent empyema: five were treated with chest drainage and one with additional open surgery. CONCLUSIONS: Our findings suggest that the VATS approach, showing a 99% success rate, shorter length of stay and lower postoperative morbidity, should be considered the treatment of choice for thoracic empyema.

Impact of epidermal growth factor receptor and KRAS mutations on clinical outcome in resected non-small cell lung cancer patients.

OBJECTIVES: Surgery yields best results for non-small cell lung cancer (NSCLC) patients. Epidermal growth factor receptor (EGFR) and its downstream factor Kirsten rat sarcoma viral oncogene homolog (KRAS) are variably mutated in NSCLC. Such mutations predict clinical response to tyrosine kinase inhibitors. This study evaluated incidence and correlation of EGFR and KRAS mutations with clinicopathologic parameters and outcome in resected stage I to III NSCLC. METHODS: We analyzed the clinical characteristics and outcome data for 230 patients who underwent resection at our institution for stage I to III NSCLC. The tumors were assessed for both EGFR (exons 18 to 21) and KRAS (exons 2 and 3) mutations by nested polymerase chain reaction and sequenced in both sense and antisense direction. Kaplan-Meier estimates of overall survival and disease-free survival were calculated for clinical and biological variables using Cox model. RESULTS: EGFR and KRAS mutations were detected in 22 (9.6%) and 39 (16.9%) patients, respectively. In the whole population, both EGFR and KRAS mutations were significantly correlated with adenocarcinoma (ADC). Overall, EGFR mutations were more frequent in women (P<0.0001) and in nonsmokers (P<0.0001). In the ADC/BAC group, KRAS mutations were more frequent in man (P<0.02) and EGFR mutations (exon 19 deletion and L858R) demonstrated a tendency towards worse disease-free survival (P=0.056). No difference in outcome was seen between patients harboring KRAS mutations compared with KRAS wild type. CONCLUSIONS: EGFR and KRAS mutations are frequent in ADCs and are not prognostic factors for survival. EGFR mutations could be used to identify patients suitable for adjuvant treatment with targeted therapy resulting in potentially improved outcomes.

Primary neuroendocrine tumours of the thymus: a clinicopathologic and prognostic study in 19 patients.

BACKGROUND: We sought to evaluate factors influencing long-term survival in 19 patients with primary neuroendocrine tumours of the thymus. METHODS: From January 1990 to December 2004, 19 patients (14 males, 5 females; mean age 48.6 years) were surgically treated for a primary neuroendocrine tumour of the thymus. RESULTS: All patients underwent radical R0 thymomectomy and were followed up for a total of 1,459 months (median: 69 months; range: 8-180). Nine patients had associated paraneoplastic syndrome. No operative mortality occurred. Two patients underwent re-do surgery because of local recurrence, respectively, 25 and 35 months after surgery. Five patients died of disease, respectively, 51, 70, 95, 131 and 153 months after surgery. One patient died of myocardial infarction with no evidence of disease. Thirteen patients are alive, of which 10 are free from disease and three with disease. The overall 5-year and 10-year actuarial survival rates were 91.6% and 69.8%, respectively (median survival: 153 months). The 10-year survival was evaluated according to histology (typical carcinoid 100%; atypical carcinoid: 66.6%; large cell neuroendocrine tumours: 0%), Masaoka staging (stage I: 100%; stage II: 50%; stage III: 66.6%; stage IV: 0%), presence of paraneoplastic syndrome (no: 87.5%; yes: 0%) and postoperative radiotherapy (yes: 40%; no: 83.3%). CONCLUSIONS: The prognosis of primary neuroendocrine tumours of the thymus is related to the grading of the neoplasm, the presence of a paraneoplastic syndrome and to the Masaoka staging but not to the postoperative radiotherapy.

Surgical treatment of benign neurogenic tumours of the mediastinum: a single institution report.

OBJECTIVE: Neurogenic tumours of the mediastinum are uncommon neoplasms arising from nerve tissues within the thorax. We sought to evaluate and compare the outcome following surgical resection of such tumours by VATS, open thoracotomy, and by either combined with hemilaminectomy. METHODS: From February 1992 to March 2007, 93 patients underwent surgical resection of neurogenic tumours of the mediastinum in our institution. A videothoracoscopic approach was used in 57 cases (61.3%) (group V), of which 44 underwent VATS only and 13 required conversion to open approach. In the remaining 36 cases, 32 patients underwent thoracotomy (group T) and 4 had combined procedure with the neurosurgeons (group N). RESULTS: No postoperative mortality was reported. Postoperative morbidity rate was 23.6% (22/93; 14 of group T, 4 of group N, and 4 of group V; p<0.0001). Histology showed benign neurogenic tumours in all patients. Statistical analysis showed differences between the two groups (group V and T respectively) in mean operative time (111.3+/-58.2 min vs 149.06+/-77.05 min; p: 0.01), median postoperative stay (4 days vs 6 days p: 0.0009) and median postoperative pain on day 1, day 7 and 1 month after surgery (respectively p<0.0001, p<0.0001 and p: 0.001). At a mean follow-up of 73 months no patients showed recurrence of the tumour. CONCLUSIONS: VATS represents the gold standard for the treatment of benign neurogenic tumours of the mediastinum with better results in terms of morbidity, operative time, postoperative stay and postoperative pain compared to open approach. Dumbbell tumours require a combined thoracic and neurosurgical approach.

Gemcitabine, paclitaxel, and cisplatin as induction chemotherapy for patients with biopsy-proven Stage IIIA(N2) nonsmall cell lung carcinoma: a Phase II multicenter study.

BACKGROUND: The objective of the current study was to define the activity and tolerability, as well as the influence on resectability, of the combination of gemcitabine, paclitaxel, and cisplatin (GTP) as induction chemotherapy for patients with Stage IIIA(N2) nonsmall cell lung carcinoma (NSCLC). METHODS: Forty-nine chemotherapy-naïve patients (median age, 61 years; World Health Organization performance status, 0-1) with biopsy-proven Stage IIIA(N2) disease received 1000 mg/m(2) gemcitabine, 125 mg/m(2) paclitaxel, and 50 mg/m(2) cisplatin on Days 1 and 8 of every 3 weeks until reevaluation for surgery or definitive radiotherapy. RESULTS: Grade 3-4 neutropenia was the most common hematologic toxicity, occurring in 32.7% of patients; however, only 1 case of febrile neutropenia was reported. Grade 3-4 thrombocytopenia occurred in 12.2% of patients but was not associated with bleeding. Severe nonhematologic toxicities were uncommon; the only Grade 4 nonhematologic toxicity was diarrhea, which occurred in 4% of patients. One patient died after the first course of therapy, but this event was found to be unrelated to treatment. Thirty-six patients (73.5%) achieved an objective response, and an additional 4 patients had stable disease with clearance of mediastinal lymph nodes. Overall, 29 patients underwent thoracotomy and 27 (55%) underwent complete resection. Mediastinal nodes were free of tumor in 35% of all cases, and 8 pathologic complete responses (16%) were reported. Median survival was 23 months, with a 1-year survival rate of 85%. CONCLUSIONS: GTP is highly active as an induction chemotherapy regimen for Stage IIIA(N2) NSCLC and yields good toxicity results. The use of GTP in combination with radiotherapy and new biologic drugs should be explored.