P16 positivity and regression grade predict survival after neoadjuvant radiotherapy of OSCC.

OBJECTIVES: Survival after preoperative radiotherapy in locally advanced head and neck squamous cell cancer is associated with pathological response. The prognostic importance of p16 expression in these patients has not been established yet. MATERIALS AND METHODS: Ninety-seven patients with oral squamous cell carcinoma, treated preoperatively with radiotherapy in combination with chemotherapy or cetuximab, were included in this retrospective analysis. Survival rates were estimated by the Kaplan-Meyer method. Pathological response was evaluated by histological analysis and p16 expression by immunohistochemistry. RESULTS: Overall survival after 2 years was 66% for the entire group, 92% in the p16-positive and 62% in the p16-negative group, respectively. 12.4% of the tumours were p16-positive. P16 expression (HR 6.98, p = .05) and regression grade (HR 2.94, p = .001) had a statistically significant impact on prognosis. 83.3% of p16-expressing tumours were pathological responders. All p16-positive patients with pathological response were alive within the observation period. CONCLUSION: P16 expression is associated with prognosis in preoperatively irradiated OSCC patients. The association between p16 positivity, regression grade and improved survival provides a rationale for de-intensification strategies in patients with head and neck cancer who respond well to neoadjuvant therapy, a concept that is being tested in prospective clinical trials.

Tricalcium phosphate-based biocomposites for mandibular bone regeneration--A histological study in sheep.

The present study investigated the suitability of three different absorbable biocomposites for the repair of critical sized bone defects created at the mandibular angle of adult sheep. Each biocomposite was composed of a three-dimensional individualized polylactide scaffold, containing a tricalcium phosphate biomaterial (chronOS). Either autologous bone marrow (chOS/BoneMarrow) or coagulation factor XIII (chOS/FactorXIII) was added to the biomaterial for osteopromotion. Venous whole blood (chOS/Blood) added to the biomaterial served as a control. A total of 18 adult sheep were used for implantation studies, subdivided into three groups of six animals each. After 12 weeks of observation, the animals were sacrificed and the mandibles were retrieved for qualitative and quantitative histologic assessment within three regions of interest (transitional zone, center, and periphery) throughout the biocomposites. Successful bone regeneration was defined by the absence of scaffold deformation and the presence of new bone formation within the biocomposites. In histomorphometry, only chOS/BoneMarrow showed elevated area fractions of newly formed bone in all regions of interest (transitional zone 50.7 ± 7.5, center 31.9 ± 9.3, periphery 23.1 ± 13.5). This led to preservation of the macroscopic scaffold structure in all specimens. Zero hurdle regression confirmed this by validating the factor biocomposite as significant (p < 0.001) for regeneration success. In our experiment, chOS/BoneMarrow was the only biocomposite passing the hurdle of regeneration in all three regions of interest. In contrast, bone formation was less pronounced and uniform in chOS/FactorXIII and chOS/blood-containing specimens. In these groups, scaffolds showed obvious to significant deformation. Overall, autologous bone marrow showed the most promising results in our experimental setting. As opposed to reports in the literature, we could not confirm the suitability of coagulation factor XIII to promote bone formation, since bone formation rates were comparable only to those of the control venous blood.