In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival and pathological complete response (primary endpoints; modified ITT [mITT] population, which excluded patients with known EGFR/ALK aberrations) with a manageable safety profile in patients with resectable (R)-NSCLC. Here, we report surgical outcomes from AEGEAN. Patients with treatment-naïve R-NSCLC (stage II-IIIB[N2]) and ECOG PS 0/1 were randomized (1:1) to platinum-based chemotherapy plus durvalumab or placebo IV (Q3W, 4 cycles) before surgery, followed by durvalumab or placebo (Q4W, 12 cycles). Surgical outcomes were summarized for the mITT population using descriptive statistics. 737/740 mITT patients received treatment, 366 and 371 in the durvalumab and placebo arms, respectively; 80.6% and 80.7% underwent surgery, 77.6% and 76.7% completed surgery, and, of the 295 and 302 patients who underwent surgery, 17.3% and 22.2% had delayed surgery. Median time from last neoadjuvant dose to surgery was 34.0 days in both arms. Of patients who underwent surgery, similar proportions had open (49.2% vs 50.7%) and minimally invasive (49.2% vs 47.0%) procedures; lobectomy was the most common procedure (88.1% vs 85.4%). R0 resection rates were numerically higher in the durvalumab versus placebo arm (94.7% vs 91.3%). Median time from surgery to first adjuvant dose was 50.0 versus 52.0 days. In exploratory analyses, a numerically higher proportion of patients in the durvalumab versus placebo arm with baseline N2 nodal status had downstaging from N2 to N0 (47.3% vs 40.2%) or, with baseline N1 nodal status, from N1 to N0 (53.6% vs 46.2%) after surgery. Similar proportions had surgical complication(s) (59.1% vs 60.1%), primarily grade 1/2 (53.0% vs 51.8%, modified safety analysis set). The addition of durvalumab to neoadjuvant chemotherapy had no detrimental effect on the feasibility, approach, type, or timing of surgery and was associated with a tolerable surgical safety profile, versus neoadjuvant chemotherapy alone. NCT03800134.

Integrin-linked kinase (ILK) is a protein kinase that links integrins and growth factors to a range of signalling pathways. ILK expression and activity are increased in a variety of human cancers. However, little is known regarding the role of ILK in malignant pleural mesothelioma (MPM). In this study, we assessed the expression of ILK in samples of human MPM, and compared it with the expression of epidermal growth factor receptor (EGFR). Thirty-four samples of human malignant mesothelioma were stained with a polyclonal antibody against ILK. Two independent observers evaluated the morphological pattern and intensity of staining. The findings have been compared with the patient's characteristics. Most MPM and mesothelial cell proliferation samples (87.9%) showed cytoplasmic ILK staining of varying intensity. Normal mesothelial cells and normal lung parenchyma did not stain for ILK at all. Conversely, the percentage of positive EGFR staining was somewhat lower (75.8%). The ILK-positive patients were significantly older than the ILK-negative patients. Here we report for the first time that ILK is indeed expressed in malignant mesothelioma. For further validation of a causal association between ILK and neoplastic mesothelial transformation, these immunohistochemical results should be supplemented with clinical and molecular biological data.

Objective: Integrin-linked kinase (ILK) is a cell membrane-bound molecule implicated in the metastatic progression of many tumour types. It phosphorylates the downstream target AKT (phosphorylated AKT, pAKT), and, by doing this, it activates anti-apoptotic pathways. We have recently shown ILK expression in malignant pleural mesothelioma (MPM). To determine whether ILK expression in MPM is connected with pAKT expression, and whether ILK and pAKT expression have any influence on the patient’s prognosis, we correlated ILK and pAKT expression, as assessed by immunohistochemistry, with disease-related survival in a retrospective cohort of 80 MPM patients. Material and methods: The paraffin specimens of 80 MPM cases treated from 1990 to 2006 (52 surgical cases, 28 conservative cases) have been retrieved from the archive. The median (range) patients’ age was 62 (28–83 years) years; the male-to-female ratio was 3:1. Fifty percent of the patients had an epitheloid subtype. The samples have been stained with anti-ILK as well as with anti-pAKT and scored by two independent pathologists. Intensity of ILK and pAKT expression has been correlated with disease-related survival. Results: In total, 73 of 80 (91%) MPM samples expressed ILK; 65 of 74 (88%) MPM samples expressed pAKT. Comparing the 5-year disease-related survival according to ILK or pAKT expression, no statistically significant difference could be found between ILK and pAKT expressing or non-expressing patients. However, in the subgroup of conservatively treated MPM patients, those with strong ILK expression had a longer 5-year disease-related survival (p ≪ 0.0001). In total, the only prognostic factor across all ILK, pAKT and therapy subgroups was the histological subtype (p = 0.01). The prognostic significance of the histological subtype has been confirmed in multivariate analysis (p = 0.005). Conclusion: The expression of ILK in MPM is connected with the expression of the downstream target pAKT, but neither ILK nor pAKT expression has a measurable influence on the patient’s prognosis, except for certain subgroups of MPM. However, to shed light on the true prognostic impact of ILK and pAKT expression in MPM, prospective trials are needed.

Objective: Increased immunoreactivity of integrin-linked kinase (ILK) in the primary tumour is an adverse prognostic factor in a variety of preclinical and clinical models of human cancer. Here, we investigate the relationship between ILK immunoreactivity in primary non-small-cell lung cancer (NSCLC) and the survival after curative lung resection. Methods: Tumour specimens of 138 radically operated NSCLC patients have been retrieved from the pathology archive, mounted in tissue microarrays and immunostained against ILK. The immunoreactivity against ILK has been graded in a semi-quantitative manner (negative or 1–3 positive) by two observers blinded to any patient data, and correlated to the survival data. Results: In total, 88 of 138 tumours (64%) showed an ILK immunoreactivity, which varied significantly between various histological subtypes as it ranged from 46% (squamous cell carcinoma (SCC)) to 79% (adenocarcinoma) (p = 0.019). The 5-year cancer-related survival of ILK-positive SCC patients was at 42 ± 10% versus 72 ± 9% significantly shorter than in ILK-negative patients (p = 0.011). In addition, the recurrence-free survival (RFS) of ILK-positive SCC patients was also significantly shorter than of ILK-negative patients (38 ± 10% vs 60 ± 10%) (p = 0.005). In multivariate analysis, ILK expression was a significant prognostic factor for RFS in squamous cell carcinoma (p = 0.018), but not in adenocarcinoma or in the rare histology group. Conclusions: Primary NSCLC tumours show a variable ILK immunoreactivity, dependent on the histological subtype. In SCC, ILK immunoreactivity is a significantly adverse prognostic factor.

Synovial sarcoma of the lung (SSL) is a very rare but aggressive primary lung tumor. Due to its unusual histological features, it can easily be misdiagnosed, if only small biopsies of the tumor are investigated. Here, we review two recent cases of SSL diagnosed and treated in our institution. The first case is a 37-year-old male with a round nodule in the right lower lobe; he underwent a lobectomy. Histologically, the nodule resembled a biphasic tumor. Cytogenetic analysis revealed a translocation t (X; 18), and the diagnosis of primary SSL could be established. The patient is alive and disease-free since 45 months following surgery. The second case is a 41-year-old male with a cystic lesion in the right lower lobe, removed by video-assisted thoracic surgery (VATS) segmentectomy. In the tumor tissue, spindle cell-rich and cystic structures could be found, together with epithelial elements. Because the tumor contained also a translocation t (X; 18), it could be diagnosed as monophasic SSL. The patient is alive and disease-free since 11 months. Since rare diseases of the lung may present as subtle and focal changes, complete removal of suspect pulmonary lesions is always advisable.