Purpose: To investigate the role of prophylactic cranial irradiation (PCI) within a trimodality protocol (chemotherapy, chemoradiotherapy, surgery) for patients with operable stage IIIA non–small-cell lung cancer (NSCLC). Patients and Methods: After mediastinoscopic staging, patients with operable stage IIIA NSCLC were enrolled to a German multicenter trial and randomly assigned to receive either primary resection followed by adjuvant thoracic radiation therapy (50 to 60 Gy; arm A) or preoperative chemotherapy (cisplatin/etoposide [PE]; three cycles) followed by concurrent chemoradiotherapy (PE plus 45 Gy; 1.5 Gy twice per day) and definitive surgery (arm B), respectively. Patients in arm B were scheduled to receive PCI (30 Gy; 2 Gy daily fractions). Results: One hundred twelve patients were randomly assigned between November 1994 and July 2001. One hundred six patients were eligible (arm A: 51, arm B: 55), 90 males and 16 females, 50 with squamous cell, 16 with large cell, five with adenosquamous, and 35 with adenocarcenoma (median age, 57 years; range, 37 to 71 years). Forty-three patients received PCI as scheduled in arm B. Eleven long-term survivors (arm A: four; arm B: seven) underwent a comprehensive neuropsychological examination. PCI significantly reduced the probability of brain metastases as first site of failure (7.8% at 5 years v 34.7%; P = .02), the overall brain relapse rate was reduced comparably (9.1% at 5 years v 27.2%; P = .04). A slightly reduced neurocognitive performance in comparison with the age-matched normal population was found for patients in both treatment groups. No significant difference between patients who were treated with or without PCI could be noted. Conclusion: PCI is effective in preventing brain metastases following this aggressive trimodality approach. Neurocognitive late effects are not significantly different between patients treated with or without PCI.

Randomized trials were analyzed comparing surgery with definitive radiotherapy as local curative treatment options within the framework of different multimodality treatments for patients with locally advanced non-small cell lung cancer (NSCLC). Endpoints for comparison of treatment results were overall survival, progression-free survival, and toxicity.

Objectives: Prediction of histopathological response with PET/CT scans after neoadjuvant chemoradiotherapy is limited by confounding factors which have been evaluated in this analysis. Methods:¹⁸F-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT findings [standard uptake value (SUV), residual tumor volume] were correlated with histopathological parameters of the resection specimens (tumor cell density, necrosis, scar, macrophage infiltration) in patients with locally advanced non-small cell lung cancer (stage IIIA/IIIB) after neoadjuvant induction chemotherapy (platinum-based doublet) and concurrent chemoradiotherapy (cisplatin/vinorelbine/45 Gy). Results: Sixty patients [40 male/20 female, median age 56 years (34–78)] completed induction therapy, 46 patients (stage IIIA/IIIB: 16/30; squamous cell carcinoma 41%, adenocarcinoma 48%, large cell carcinoma 11%) were resected. Pathologic complete response of the primary tumor was observed in 19 patients (41%) with a broad range of SUV_mean (0.4–9.8, mean 3.0) after neoadjuvant therapy. A high rate of histopathological complete remissions (44%) was observed in tumors with a postinduction SUV >2.5 and volumes larger than the median (7.9 cm³) before resection. SUV_mean was positively correlated with the macrophage score (r = 0.39, p = 0.007) and tumor cell density (r = 0.32, p = 0.03). Conclusions: These observations suggest that postinduction FDG uptake should be interpreted with caution in larger residual tumor volumes, since high SUV levels may be due to macrophage infiltration and not viable tumor tissue.

In a previous report, we compared the conformity of robust intensity-modulated proton therapy (IMPT) plans with that of helical tomotherapy plans for re-irradiations of head and neck carcinomas using a fixed set-up error of 2 mm. Here, we varied the maximum set-up errors between 0 and 5 mm and compared the robust IMPT-plans with planning target volume (PTV) based intensity-modulated photon therapy (IMRT).

Outcome of consecutive patients with locally advanced non-small cell lung cancer and histopathologically proven mediastional lymph node metastases treated with induction chemotherapy, neoadjuvant radiochemotherapy and thoracotomy at the West German Cancer Center between 08/2000 and 06/2012 was analysed. A clinico-pathological prognostic model for survival was built including partial or complete response according to computed tomography imaging (CT) as clinical parameters as well as pathologic complete remission (pCR) and mediastinal nodal clearance (MNC) as histopathologic factors. Proportional hazard analysis (PHA) and recursive partitioning analysis (RPA) were used to identify prognostic factors for survival. Long-term survival was defined as survival ≥ 36 months. A total of 157 patients were treated, median follow-up was 97 months. Among these patients, pCR and MNC were observed in 41 and 85 patients, respectively. Overall survival was 56 ± 4% and 36 ± 4% at 24 and 60 months, respectively. Sensitivities of pCR and MNC to detect long-term survivors were 38% and 61%, specificities were 84% and 52%, respectively. Multivariable survival analysis revealed pCR, cN3 category, and gender, as prognostic factors at a level of α < 0.05. Considering only preoperative available parameters, CT response became significant. Classifying patients with a predicted hazard above the median as high risk group and the remaining as low risk patients yielded better separation of the survival curves by the inclusion of histopathologic factors than by preoperative factors alone (p < 0.0001, log rank test). Using RPA, pCR was identified as the top prognostic factor above clinical factors (p = 0.0006). No long term survivors were observed in patients with cT3-4 cN3 tumors without pCR. pCR is the dominant histopathologic response parameter and improves prognostic classifiers, based on clinical parameters. The validated prognostic model can be used to estimate individual prognosis and forms a basis for patient selection for treatment intensification.