21 Outcomes of resected SST after CRT Introduction In patients with clinically resectable Non-Small Cell Lung Cancer (NSCLC), the survival rates vary, ranging from an estimated median survival of 19 months for stage IIIA to 95 months for stage IA 20. In locoregionally-advanced NSCLC, combined modality treatments using concurrent chemo-radiotherapy (CRT) have been associated with an increase in survival rates 21,22. Superior Sulcus Tumours (SST), also called Pancoast tumours, are a rare sub-set comprising 3-5% of all NSCLC and are located in the lung apex. They are locally advanced with invasion of the chest wall, adjacent structures or vertebrae, reducing the likelihood of a radical (R0) resection with primary surgery. Pre-operative induction CRT followed by resection is now considered the standard treatment option in medically fit patients 23,24. This combined-modality approach is associated with 95% complete resection (R0) rates and up to 50% of tumours demonstrates pathologic complete regression (pCR) 25,26. Limited information is available about the histopathologic changes of such neoadjuvant regimes on tumour and adjacent normal lung parenchyma and their relation to prognosis 27,28,29. The aim of this study was to describe the histopathologic pulmonary and tumour related changes after concurrent CRT and relate these to clinical outcome. Patients and methods A retrospective analysis was performed on a consecutive series of patients with SST treated by concurrent CRT and subsequent surgical resection in the period 1997-2007 at the VU University Medical Center (VUmc) and the Netherlands Cancer Institute (NKI-AVL), both located in Amsterdam, the Netherlands. 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. A total of 50 patients were identified, after excluding 6 patients (13%) who started CRT, but had progressive disease or were no longer clinically fit for surgery. Four cases had to be excluded because of irretrievable histological slides and tissue blocks. All but one of the 19 NKI-AVL patients received an accelerated hypo-fractionated radiation schedule of 66 Gy delivered in 24 fractions and most of them (n=17, 89%) had concurrent single agent chemotherapy consisting of daily low dose Cisplatin. The treatment at the VUmc was one cycle of cisplatin-gemcitabine, followed by concurrent CRT consisting of cisplatin-etoposide and radiation doses ranging from 39 Gy in 13 fractions to 50 Gy in 25 fractions (mean 44 Gy). All VUmc patients received chemotherapy. Combining the data from both institutes the mean absolute radiation dose was 53 Gy. After completion of CRT, restaging (typically with some combination of CT and/or MRI of the thorax and upper abdomen, MRI scan of the brain, FDG-PET scanning and invasive mediastinal staging) and discussion in a multidisciplinary meeting, surgical resection was attempted in patients without disease progression. 2
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