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SummaryNeoadjuvant checkpoint inhibition in resectable non-small-cell lung cancer (NSCLC) is safe and high major pathologic response (MPR) and pathologic complete response (pCR) rates can be achieved in combination with chemotherapy. The Checkmate 816 trial gives evidence that pathologic response also leads to EFS benefit. This opens new opportunities in the curative setting but also raises questions: What is the value of adjuvant treatment with checkpoint inhibitors? Or should we treat our patients peri-operatively? Which biomarkers can we use for treatment decisions and monitoring of curative patients? Targeted therapies in the neoadjuvant setting lead to promising response rates and data for EFS and overall survival are eagerly awaited.

SummaryMalignant pleural mesothelioma (MPM) is a rare tumour that originates from the inner linings of the pleural cavity. The majority of cases are associated with exposure to asbestos for what was banned in the European Union in 1991. Due to the long latency between exposure and onset (20–40 years) the peak of MPM in Western Europe will be reached within the next years. Often diagnosed at an unresectable stage, treatment options remain palliative in the majority of cases. The highly aggressive nature of MPM leads to a dismal prognosis with a median overall survival of approximately one year.Platinum-based chemotherapy in combination with pemetrexed has been the mainstay of first line treatment in unresectable MPM for many years. Only recently, check point inhibitors have found their way into MPM treatment. The results of the phase III CheckMate 743 trial last year have finally led to a paradigm shift in the treatment of unresectable MPM. This trial showed a significant overall survival benefit for the combination of nivolumab and ipilimumab over standard chemotherapy, especially in nonepithelioid histology. Apart from histology, predictive biomarkers have not been identified for the treatment of MPM so far. Several trials investigating combination therapies with checkpoint inhibitors are currently ongoing and give hope to further improve prognosis for our patients.

Purpose Radiochemotherapy (RCT) is an effective standard therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Nonetheless, toxicity is common, with patients often requiring dose modifications. Methods To investigate associations of RCT toxicities according to CTCAE version 5.0 and subsequent therapy modifications with short- and long-term treatment outcomes, we studied all 193 patients with HNSCC who received RCT (70 Gy + platinum agent) at an academic center between 03/2010 and 04/2018. Results During RCT, 77 (41%, 95% CI 34–49) patients developed at least one ≥ grade 3 toxicity, including seven grade 4 and 3 fatal grade 5 toxicities. The most frequent any-grade toxicities were xerostomia (n = 187), stomatitis (n = 181), dermatitis (n = 174), and leucopenia (n = 98). Eleven patients (6%) had their radiotherapy schedule modified (mean radiotherapy dose reduction = 12 Gy), and 120 patients (64%) had chemotherapy modifications (permanent discontinuation: n = 67, pause: n = 34, dose reduction: n = 7, change to other chemotherapy: n = 10). Objective response rates to RCT were 55% and 88% in patients with and without radiotherapy modifications (p = 0.003), and 84% and 88% in patients with and without chemotherapy modifications (p = 0.468), respectively. Five-year progression-free survival estimates were 20% and 50% in patients with and without radiotherapy modifications (p = p = 0.88), respectively. Conclusions Reductions of radiotherapy dose were associated with impaired long-term outcomes, whereas reductions in chemotherapy intensity were not. This suggests that toxicities during RCT should be primarily managed by modifying chemotherapy rather than radiotherapy.

Diabetes mellitus (DM) and hyperglycemia are known predictors of adverse outcome in different tumor entities. The present study investigated the effect of DM and pre-surgery blood glucose levels on cancer specific survival (CSS), overall survival (OS), and disease-free survival (DFS) in non-metastatic soft tissue sarcoma (STS) patients. A total of 475 STS patients who underwent curative resection were included in this retrospective study. CSS, DFS, and OS were assessed using Kaplan–Meier curves. The association between pre-existing DM as well as mean pre-surgery blood glucose levels and all 3 survival endpoints was analyzed using Cox-hazard proportional (for OS and DFS) and competing risk regression models (for CSS). In unadjusted analysis, DM was significantly associated with adverse CSS (sub-hazard ratio [SHR]: 2.14, 95% confidence interval [CI] 1.18–3.90, p = 0.013) and OS (hazard ratio [HR]: 2.05, 95% CI 1.28–3.28) and remained significant after adjusting for established prognostic factors (CSS: adjusted SHR 2.33, 95% CI 1.21–4.49, p = 0.012; OS: adjusted HR 1.96, 95% CI 1.17–3.28, p = 0.010), respectively. There was no significant association of DM with DFS (p = 0.149). The mean pre-surgery glucose levels were not significantly associated with inferior outcome (CSS: p = 0.510, OS: p = 0.382 and DFS: p = 0.786). This study shows, that DM represents a negative prognostic factor for clinical outcome in STS patients after curative resection.