37 Prognostic value of MIB-1, PD-L1 and nuclear size in SST after CRT Introduction In patients with resectable non-small cell lung cancer (NSCLC), survival rates drop with higher clinical stage, ranging from an estimated median survival of 95 months for stage IA to 19 months for stage IIIA 20. In locally-advanced NSCLC (LA-NSCLC), combined modality treatments using concurrent chemo-radiotherapy (CRT) have led to increased survival rates21,22. For superior sulcus tumours (SST), also called Pancoast tumours, comprising 3-5% of all NSCLC, and typically invade the chest wall, induction CRT followed by resection is considered the standard treatment in medically fit patients23,24,30. This combined modality approach is associated with 95% complete resection (R0) rates and up to 50% of tumours demonstrate pathologic complete regression25,26. The presence of complete pathological regression was found predictive for favourable clinical outcome after tri-modality therapy in these patients43. Other morphological characteristics found in pretreatment biopsies and resection specimen, such as Ki-67, MIB-1, nuclear size and PD-L1 expression, have been investigated for prognostic value in resected NSCLC, but their role in patients treated with induction and resection (trimodality treatment), and their relation to clinical outcome, is currently unknown44. This lack of knowledge was noticed by the members of the International Association Lung Cancer (IASLC), who recently published multidisciplinary recommendations for pathologic assessment of lung cancer resection specimens after neoadjuvant therapy, stating that future studies to explore the role of immunohistochemistry on resected tumours in the neoadjuvant setting are encouraged45. Against this background, the aim of this study was to examine whether changes in nuclear size, expression of MIB-1 and PD-L1 in the residual tumour compared to baseline, are prognostically relevant for patients with SST treated with concurrent CRT, followed by resection. Patients and methods A retrospective analysis was performed on a consecutive series of patients with SST treated with concurrent CRT and subsequent surgical resection in the period 2005-2014 at Amsterdam University Medical Center, location VU Medical Center in Amsterdam. SST was defined as a tumour growing into the thoracic wall at the apex of the lung, above the level of the second rib 30. Patients were selected on basis of residual tumour being present in the resection specimen. For all 33 patients, a pre-treatment diagnostic biopsy was included for morphometric evaluation. Clinical data on follow-up were retrieved from the patient medical records. Part of this patient population has previously been described43. 3
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