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Aims: Programmed death‐ligand 1 (PD‐L1) immunostaining is used to predict which non‐small‐cell lung cancer (NSCLC) patients will respond best to treatment with programmed cell death protein 1/PD‐L1 inhibitors. PD‐L1 immunostaining is sometimes performed on alcohol‐fixed cytological specimens instead of on formalin‐fixed paraffin‐embedded (FFPE) biopsies or resections. We studied whether ethanol prefixation of clots from endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) results in diminished PD‐L1 immunostaining as compared with formalin fixation. Methods and results: FFPE cell blocks from EBUS‐TBNA specimens of 54 NSCLC patients were identified. For each case, paired samples were available, consisting of clots directly immersed in formalin and clots prefixed in Fixcyt (50% ethanol). Serial sections were immunostained for PD‐L1 by use of the standardised SP263 assay and the 22C3 antibody as a laboratory‐developed test (LDT). PD‐L1 positivity was determined with two cut‐offs (1% and 50%). Concordance of PD‐L1 positivity between the formalin‐fixed (gold standard) and ethanol‐prefixed material was assessed. When the 22C3 LDT was used, 30% and 36% of the ethanol‐prefixed specimens showed false‐negative results at the 1% and 50% cut‐offs, respectively (kappa 0.64 and 0.68). When SP263 was used, 22% of the ethanol‐prefixed specimens showed false‐negative results at the 1% cut‐off (kappa 0.67). At the 50% cut‐off, concordance was higher (kappa 0.91), with 12% of the ethanol‐prefixed specimens showing false‐negative results. Conclusion: Ethanol fixation of EBUS‐TBNA specimens prior to formalin fixation can result in a considerable number of false‐negative PD‐L1 immunostaining results when a 1% cut‐off is used and immunostaining is performed with SP263 or the 22C3 LDT. The same applies to use of the 50% cut‐off when immunostaining is performed with the 22C3 LDT. [ABSTRACT FROM AUTHOR]

• Platinum-based CRT for HPV-neg HNSCC has unique treatment course and outcome pattern. • CRT is often too toxic, in ∼35% of patients the cisplatin-dose plan needed changes. • Switching to carboplatin when cisplatin is too toxic seems not beneficial for OS (HR 1.49 vs HR 1.59). • Development of DM was strongly associated with boosting method (SEQ vs SIB; OR 1.91). Definitive concomitant cisplatin-based chemoradiotherapy (CRT) is the current gold standard for most patients with advanced stage head and neck squamous cell carcinoma (HNSCC) of the pharynx and larynx. Since previous meta-analysis on CRT outcomes in HNSCC have been reported, advances have been made in radiotherapy techniques and clinical management, while HPV-status has been identified as a strong confounding prognostic factor in oropharyngeal cancer. Here, we present real-world outcome data from a large multicenter cohort of HPV-negative advanced stage HNSCC treated with CRT using contemporary IMRT-based techniques. Retrospective data were collected from a multicenter cohort of 513 patients treated with definitive concurrent platinum-based CRT with curative intent between January 2009 and August 2017. Only patients with HPV-negative advanced stage (III-IV) HNSCC were included. A prognostic model for outcome was developed based on clinical parameters and compared to TNM. Nearly half of the 513 patients (49%) had an oropharyngeal tumor, often locally advanced (73.3% T3-T4b) and with involvement of the regional lymph nodes (84%). Most patients (84%) received cisplatin as single agent. In total 66% received the planned number of cycles and 75% reached a cumulative cisplatin dose of ≥200 mg/m2. Locoregional control was achieved in 324 (63%) patients during follow-up, and no association with tumor sites was observed (p = 0.48). Overall survival at 5 year follow-up was 47%, with a better survival for laryngeal cancer (p = 0.02) compared to other sites. A model with clinical variables (gender, high pre-treatment weight loss, N2c/N3-stage and <200 mg/m2 dose of cisplatin) provided a noticeably stronger association with overall survival than TNM-staging (C- index 0.68 vs 0.55). Simultaneous Integrated Boosting (SIB) significantly outperformed Sequential Boosting (SEQ) to reduce the development of distant metastasis (SEQ vs SIB: OR 1.91 (1.11–3.26; p = 0.02). Despite advances in clinical management, more than a third of patients with HPV-negative HNSCC do not complete CRT treatment protocols due to cisplatin toxicity. A model that consists of clinical variables and treatment parameters including cisplatin dose provided the strongest association with overall survival. Since cisplatin toxicity is a major obstacle in completing definitive CRT, the development of alternative and less toxic radiosensitizers is therefore warranted to improve treatment results. The association of RT-boost technique with distant metastasis is an important finding and requires further study. [ABSTRACT FROM AUTHOR]