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Background and purpose This multicenter, phase 3 trial investigates whether the incorporation of concurrent paclitaxel and cisplatin together with a reduced total dose of radiotherapy is superior to standard fluorouracil–cisplatin based CRT. Materials and methods Patients with SCCHN, stage III–IVB, were randomized to receive paclitaxel/cisplatin (PacCis)–CRT (arm A; paclitaxel 20 mg/m2 on days 2, 5, 8, 11 and 25, 30, 33, 36; cisplatin 20 mg/m2, days 1–4 and 29–32; RT to a total dose of 63.6 Gy) or fluorouracil/cisplatin (CisFU)–CRT (arm B; fluorouracil 600 mg/m2; cisplatin 20 mg/m2, days 1–5 and 29–33; RT: 70.6 Gy). Endpoint was 3-year-disease free survival (3y-DFS). Results A total of 221 patients were enrolled between 2010 and 2015. With a median follow-up of 3.7 years, 3y-DFS in the CisFU arm and PacCis arm was 58.2% and 48.4%, respectively (HR 0.82, 95% CI 0.56–1.21, p = 0.52). The 3y-OS amounted to 64.6% in the CisFU arm, and to 59.2% in the PacCis arm (HR 0.82, 95% CI 0.54–1.24, p = 0.43). In the subgroup of p16-positive oropharyngeal carcinomas, 3y-DFS and 3y-OS was 84.6% vs 83.9% (p = 0.653), and 92.3% vs. 83.5% (p = 0.76) in arm A and B, respectively. Grade 3–4 hematological toxicities were significantly reduced in arm A (anemia, p = 0.01; leukocytopenia, p = 0.003), whereas grade 3 infections were reduced in arm B (p = 0.01). Conclusion Paclitaxel/cisplatin–CRT with a reduced RT-dose is not superior to standard fluorouracil/cisplatin–CRT. Subgroup analyses indicate that a reduced radiation dose seems to be sufficient for p16+ oropharyngeal cancer or non-smokers. Clinical trial information: NCT01126216; EudraCT Number 2005-003484-23.

The tissue-specific glycosylation of the carcinoma (CA)-associated antigen epithelial cell adhesion molecule (EpCAM) was studied in 60 patients suffering from head and neck CAs, and 26 pairs of autologous healthy thyroid and CA biopsies. EpCAM was glycosylated in all tumor samples in which its expression was detectable (73%). Additionally, in 80.7% of patients, tumor-derived EpCAM was heavily glycosylated while EpCAM derived from autologous thyroid was not (76.2%) or weakly (23.8%). Four cases showed a similar glycosylation pattern (15.3%) and one case displayed a reverse pattern (3.8%). Additionally, the expression and glycosylation of EpCAM were assessed in tumor adjacent and distant tissue. EpCAM was glycosylated in tumor-adjacent while it was not or only weakly expressed in tumor distant tissue where it was unglycosylated. Thus, EpCAM is differentially glycosylated in healthy tissue and tumor cells of the head and neck area.

6016 Background: Concurrent CRT with 70.6 Gy is the standard treatment for locally advanced head and neck cancer (LA-SCCHN). There exist no prospective data on safety and efficacy of a reduced radiation (RT) dose. Methods: Pts with stage III-IVB LA-SCCHN were randomized 1:1 to receive 70.6 Gy with concurrent cisplatinum (20mg/m²/d IV on days 1-5 and 29-33) and fluorouracil (600 mg/m²/d CIV on days 1-5 and 29-33) (standard arm A) versus 63,6 Gy with intensified chemotherapy using concurrent cisplatinum (20mg/m²/d IV on days 1-4 and 29-32) and paclitaxel (20mg/m²/d IV on days 2, 5, 8, 11 and 25, 30, 33, 36) (experimental arm B). After a planned interim analysis recruitment was stopped due to statistical reasons. Results: Between 06/2010 and 02/2015 a total of 221 pts were randomized with 105 pts receiving treatment in arm A and 112 in arm B (4 pts dropped out). Median follow-up was 38 months. Pts’ characteristics: Oral cavity (15%), oropharynx (54%), hypopharynx (28%), larynx (14%); 17 pts had more than one primary site; tumor stage: III (14%), IV (86%); HPV-status (p16) was positive in 20%, negative in 38%, currently pending in 42%. A total of 96 PFS-related events occurred. 3-year PFS (ITT) was 58% in the standard arm A and 48% in experimental arm B (p = 0.454). 3-year OS (ITT) was 64% in arm A and 59% in arm B (p = 0.688). 3-year rates of distant metastases, loco-regional recurrences and death were 10% vs 12%, 17% vs 21% and 15% vs 19% for pts in arm A and B, respectively. As for the p16-positive subgroup, 3-year PFS/OS were 77%/76% in arm A (n = 21) and 69%/80% in arm B (n = 22), respectively. Grade 3+ hematologic adverse events during therapy (arm A/arm B): Anemia 11%/4% (p = 0.038); neutropenia 40%/16% (p < 0.001); thrombocytopenia 8%/3% (p = 0.130). Conclusions: These preliminary results indicate that pts receiving concurrent CRT for LA-SCCHN did not benefit from a lower total RT dose of 63.6Gy despite intensified chemotherapy. However, in the subgroup of p16-positive pts a reduced RT dose may be sufficiently effective. Clinical trial information: NCT01126216.

Elevated levels of u-PA Ag and scu-PA preoperatively and before revascularization of the graft are explained by an impaired clearance function by the diseased liver. They are parallel preoperatively and in the beginning of OLT by increased tcu-PA activity. This may reflect a role of the intrinsic fibrinolytic system in the "hyperfibrinolytic state" observed in patients with end stage liver disease. u-PA Ag and scu-PA normalize following reperfusion. The increase in tcu-PA observed during the anhepatic phase coincided with greatly increased fibrinolysis, as demonstrated by thrombelastography. This indicates that u-PA seems to be involved in the development of fibrinolysis during OLT. It had been demonstrated in previous investigations that a significant increase of t-PA activity was seen in the late anhepatic phase leading to an elevated plasmin generation. Since plasmin is a major activator of scu-PA, a t-PA mediated scu-PA activation would explain the concomitant increase in both plasminogen activators.