BackgroundImmunotherapy can become a crucial therapeutic option to improve prognosis for lung cancer patients. First clinical trials with therapies targeting the programmed cell death receptor PD-1 and its ligand PD-L1 have shown promising results in several solid tumors. However, in lung cancer the diagnostic, prognostic and predictive value of these immunologic factors remains unclear.MethodThe impact of both factors was evaluated in a study collective of 321 clinically well-annotated patients with non-small lung cancer (NSCLC) using immunohistochemistry.ResultsPD-1 expression by tumor infiltrating lymphocytes (TILs) was found in 22%, whereas tumor cell associated PD-L1 expression was observed in 24% of the NSCLC tumors. In Fisher’s exact test a positive correlation was found for PD-L1 and Bcl-xl protein expression (p = 0.013). Interestingly, PD-L1 expression on tumor cells was associated with improved overall survival in pulmonary squamous cell carcinomas (SCC, p = 0.042, log rank test), with adjuvant therapy (p = 0.017), with increased tumor size (pT2-4, p = 0.039) and with positive lymph node status (pN1-3, p = 0.010). These observations were confirmed by multivariate cox regression models.ConclusionOne major finding of our study is the identification of a prognostic implication of PD-L1 in subsets of NSCLC patients with pulmonary SCC, with increased tumor size, with a positive lymph node status and NSCLC patients who received adjuvant therapies. This study provides first data for immune-context related risk stratification of NSCLC patients. Further studies are necessary both to confirm this observation and to evaluate the predictive value of PD-1 and PD-L1 in NSCLC in the context of PD-1 inhibition.

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Adjuvant therapy of local soft tissue sarcomas (STS) after wide surgical excision still is a topic under controversial scientific debate. In this single center report we have offered an adjuvant “sandwich” therapy protocol consisting of 4 cycles of doxorubicin (75 mg/m2 i.v. over 1 h on day 1) followed by ifosfamide (5 g/m2 i.v. over 24 h starting on day 1) and local radiotherapy scheduled between chemotherapy cycles 2 and 3 to 104 consecutive patients after wide surgical excision (R0) of histologically proven high-grade STS. After a mean follow-up of 39 months (range 5–194 months) relapse free survival (RFS) at 2 and 5 years was 68.1% (95% CI, 58.5–77.7%) and 61.2% (95% CI, 50.4–71.6%). When analyzing the 82 STS cases of the extremities only 2- and 5-year RFS was 74.0% (95% CI, 64.0–84.0%) and 65.3% (95% CI, 53.7–76.9%). By intent-to-treat analysis, the overall survival (OS) at 2 years was 87.3% (95% CI, 80.5–94.1%) and 75.6% (95% CI, 65.2–86.0%) at 5 years, while OS for STS of the extremities only cohort was 90.5% (95% CI, 83.7–97.3%) and 79.0% (95% CI, 68.4–89.6%), respectively. Tolerability of the treatment was good. This analysis demonstrates the feasibility of adjuvant chemoradiotherapy and reflects the results of the long lasting intensive multidisciplinary team approach at our “high-volume” sarcoma center. The long-term survival in our patients is among the highest reported and the low local and distant recurrence rate in high-risk STS is at least comparable to the published data.

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