Tõnu Vanakesa

PURPOSE: The MAGE-A3 protein is expressed in approximately 35% of patients with resectable non-small-cell lung cancer (NSCLC). Several immunization approaches against the MAGE-A3 antigen have shown few, but often long-lasting, clinical responses in patients with metastatic melanoma. PATIENTS AND METHODS: A double-blind, randomized, placebo-controlled phase II study was performed assessing clinical activity, immunologic response, and safety following immunization with recombinant MAGE-A3 protein combined with an immunostimulant (13 doses over 27 months) in completely resected MAGE-A3-positive stage IB to II NSCLC. The primary end point was disease-free interval (DFI). RESULTS: Patients were randomly assigned to either MAGE-A3 immunotherapeutic (n = 122) or placebo (n = 60). After a median postresection period of 44 months, recurrence was observed in 35% of patients in the MAGE-A3 arm and 43% in the placebo arm. No statistically significant improvement in DFI (hazard ratio [HR], 0.75, 95% CI, 0.46 to 1.23; two-sided P = .254), disease-free survival (DFS; HR, 0.76; 95% CI, 0.48 to 1.21; P = .248), or overall survival (HR, 0.81; 95% CI, 0.47 to 1.40; P = .454) was observed. Corresponding analysis after a median of 70 months of follow-up revealed a similar trend for DFI and DFS. All patients receiving the active treatment showed a humoral immune response to the MAGE-A3 antigen, although no correlation was observed with outcome. No significant toxicity was observed. CONCLUSION: In this early development study with a limited number of patients, postoperative MAGE-A3 immunization proved to be feasible with minimal toxicity. These results are being investigated further in a large phase III study.

OBJECTIVE: To review our experience using antero-superior approaches for resection of a heterogeneous group of tumors, both benign and malignant, involving the thoracic inlet and adjacent structures. These included Pancoast type bronchial carcinomas, primary neurogenic tumors, soft-tissue neoplasms, and metastases from a variety of primary sites. METHODS: Between October 1993 and January 1998 we undertook 22 operations on 21 patients using a variety of antero-superior approaches. The anterior cervical-transsternal approach was used in 11 operations, the Dartevelle technique was used in five cases, the modification described by Nazari in one patient and that described by Grunenwald in five cases. RESULTS: 21 of the 22 operations were considered to be complete resections with negative margins. There were no intraoperative or postoperative deaths. Major complications occurred in five patients; acute respiratory distress syndrome (n = 4), and thrombosis of the arterial graft and acute respiratory distress syndrome (n = 1). Chronic morbidity was observed in 12 patients; prolonged arm pain (n = 1), arm edema (n = 2), motor and sensory deficits (n = 2), phrenic nerve paresis (n = 1), disfigurement and instability of the pectoral girdle (n = 4), and disturbances in shoulder girdle function (n = 2). CONCLUSIONS: The anterior cervical-transsternal approach we previously described provides adequate exposure for the resection of neurogenic tumors originating in the brachial plexus and sympathetic chain, and for metastatic nodal disease at the base of the neck or in the superior mediastinum. We have found it to be associated with little morbidity, the postoperative stay has been short, and it has proven flexible enough to cope with the changed circumstances found at surgery. For Pancoast type bronchogenic carcinomas and other malignancies with extensive invasion of major structures at the thoracic inlet, we believe the best present option is the clavicle sparing antero-superior technique described by Grunenwald as a modification of the Dartevelle approach. When operating for lung cancer we presently feel that the antero-superior approach should be combined with a posterolateral thoracotomy, to accomplish complete intraoperative staging and undertake anatomical pulmonary resection under optimal conditions.

BACKGROUND: Thymic epithelial tumors are rare thoracic tumors for which pathological diagnosis is challenging due to the definition of multiple subtypes, tumor heterogeneity, and variations in interobserver reproducibility. In this study, we aimed at analyzing the quality of pathological reporting in line with the consistency between initial diagnosis and final diagnosis after expert review through a collaboration between the largest thoracic oncology center in Estonia, and one expert center in France. METHODS: Hospital electronic database and pathology databases from the Tallinn North Estonia Medical Centre were searched for thymic and mediastinal tumors from 2010 to 2017. Pathology specimens were referred to the Pathology Department of the Lyon University hospital. Overall, 55 tissue specimens from 49 patients were included. RESULTS: From pathology reports, tumor size, diagnosis, and invasion had been mentioned in ≥80% of cases, while resection status and staging were assessed in only 48% and 17% of cases, respectively. The initial diagnosis was consistent with that of the review in 60% of cases. Diagnostic concordance for thymoma subtypes was low (Cohen's kappa 0.34, 95% CI: 0.16-0.52). Overall, a major change in the management of 8 (16%) patients had to be made after pathological review: 3 patients had a normal thymus according to the reference centre, while thymoma B1 or B2 had been diagnosed locally; 5 additional patients had a final diagnosis of non-thymic tumor. CONCLUSIONS: Implementing structured pathology reports may help to decrease discrepancies in the diagnosis of thymic epithelial tumors. The development of expert networks is an opportunity to improve diagnosis and patient care, particularly in regard to rare cancers.