Concurrent chemotherapy is the standard of care for locally advanced NSCLC treated with definitive radiotherapy. The optimal chemotherapy regimen for use with concurrent therapy is not known. In this secondary analysis we evaluated the role of different chemotherapy regimens in patients treated in the phase III PET Plan trial. The prospective randomized controlled phase-III-type PET-Plan trial was conducted in 24 centers in Germany, Austria and Switzerland. Patients with inoperable locally advanced NSCLC suitable for radio-chemotherapy were randomized at a 1:1 ratio concerning the target volume (TV) definition and received quality-assured isotoxically dose-escalated IMRT or 3D-RT (60–74 Gy, 2 Gy per fraction) was applied to the respective TVs. Concurrent platinum-based chemotherapy was mostly conducted according to Vokes et al.(Vokes, II et al. 2002), using cisplatin 80mg/m2 (day 1 and 22) and vinorelbin 15mg/m2 (day 1+8 and 22+29) (protocol 1, P1) or cisplatin 20mg/m2 (day 1-5 and 29-33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15 and 29, 36, 43) (protocol 1, P2) or carboplatin AUC1 (day 1-5 and 29-33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15 and 29, 36, 43) (protocol 1, P3) according to Semrau et al. (Semrau, Klautke et al. 2008), at the discretion of the treating physician. Between 05/2009 and 11/2016, 172 patients in the per-protocol (PP) analysis (A: n = 84, B: n = 88). 30 patients were treated according to P1, 92 according to P2 and 28 according to P3 (1 patient did not receive any treatment and 21 patients received different treatments). All three protocols were well tolerated. Patients in P1 (17%) und P2 (15%) developed more grade 3 leucopenia than P3 (4%) but less grade 3 renal toxicities 0% (P1,2) vs 4% (P3). Only patients in P1 developed grade 4 hematologic toxicities (7% leucopenia, 3% anemia and 3% thrombocytopenia). Patents treated with P1 or P2 had a better OS as opposed to P3 (p = 0.008 and p = 0.009 respectively) but there was no difference between P1 and P2 (p = 0.6). There was no difference observed concerning PFS between the different protocols. Patients treated with cisplatin (n = 122) had a better OS as opposed to carboplatin (n = 28) (p = 0,003), which remained also adjusting for age, ECOG, ejection fraction using cardiac ultrasound and creatinine at baseline. Vinorelbin in combination with cisplatin either as a single dose of 80mg/m2 per cycle or daily doses of 20mg/m2 (5 days per cycle) for concurrent chemoradiation show similar efficacy in this patient cohort. Patients treated with carboplatin had a significant worse survival. This may be due to the selection of the drug due to restriction in normal tissue function, which may also cause an impaired prognosis.

Advanced medical imaging offers a chance for target volume reduction in modern radiotherapy, which may lead to more effective local treatments with reduced toxicity and offer the protection of draining lymph nodes and large vessels, possibly of importance for the upcoming combination of radiotherapy and immunotherapy. Locally advanced non-small cell lung cancer (NSCLC) with improvable local control and high toxicity is an excellent model to investigate this topic. In the prospective randomised controlled PET-Plan trial (NCT00697333), patients with inoperable stage II/III NSCLC and an indication for radiochemotherapy were randomized at a 1:1 ratio. In conventional arm A target volumes were informed by FDG-PET and CT plus elective nodal irradiation and in experimental arm B they were solely informed by FDG-PET. In both arms, quality assured isotoxically dose-escalated IMRT or 3D-CRT (60 - 74Gy, 2Gy per fraction) was planned and applied to the respective target volumes along with simultaneous platinum-based chemotherapy. The primary objective was time to locoregional progression (LRP) in terms of non-inferiority of experimental arm B. 311 patients were recruited, 205 patients included in the intent to treat (ITT) (A: n=99, B: n=106) and 172 patients in the per protocol (PP) analysis (A: n=84, B: n=88). Median FU time in the PP set was 16 months. Non-inferiority of experimental arm B was confirmed for the pre-specified non-inferiority margin. The risk of LRP was lower in the experimental arm B (2y-LRP 0.20 vs. 0.39; HR=0·57; 95% CI: 0·30–1·06; p=0·039) with no difference between study arms concerning survival (2y-OS 0.57 vs. 0.54), out-field recurrence and toxicity. In radiochemotherapy for locally advanced NSCLC PET-Imaging based reduction of radiotherapy target volumes is feasible and may improve local control without increasing toxicity. However, in this trial there was no impact on survival. The procedures established in this clinical trial provide a radiotherapy standard for future NSCLC-trials including immunotherapy and may furthermore inspire trials on imaging based target volume reduction for other types of tumours.

Erfassung möglicher Perfusionsdefekte des Myokards mittels 99mTc-MIBI-SPECT/CT (single photon emission computerized tomography – computed tomography) nach Bestrahlung bei linksseitigem Mammakarzinom.