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Purpose: Malignant tumours in the parotid gland can originate either from the gland itself or as a result of metastatic spread of other tumours, such as cutaneous squamous cell carcinomas (CSCC) of the head and neck area. The aim of this study was to analyse and compare the clinical behaviour of primary as well as CSCC metastatic parotid cancers with special emphasis on therapy and oncologic outcome., Methods: Clinical and histopathological data of 342 patients with parotid gland malignomas surgically treated in a tertiary referral centre between 1987 and 2015 were retrospectively assessed. Oncologic outcomes of all cases with CSCC metastasis of the parotid gland (n = 49) were compared to those of primary parotid gland carcinomas (n = 293)., Results: Mean age at diagnosis was 72.3 years for CSCC patients versus 56.8 years in patients with primary parotid carcinoma. A total of 83.7% of CSCC patients were male, compared to 48.8% in the group of primary carcinomas. Forty-five out of 49 CSCC patients underwent total parotidectomy and neck dissection (91.8%). A total of 93.9% out of all CSCC patients received adjuvant radiotherapy. Five-year overall survival (OS) was 32.6% in CSCC patients versus 77.2% in primary parotid carcinoma patients., Conclusion: As compared to primary parotid cancers, we could show that patients suffering from CSCC metastases to the parotid gland presented with significantly higher age and worse survival., (© 2020. The Author(s).)

Radiotherapy plays an important role in the treatment of head and neck cancer. It represents the main curative option in advanced tumors. Due to technical progress of treatment appliances, the translation of radiobiological research into clinical praxis (altered fractionation), and the concurrent application of chemotherapy (radiochemotherapy), the efficacy of radiotherapy has markedly improved. Current developments focus on the integration of functional imaging into the treatment planning process to allow individualized dose prescription. Different systemic agents have shown to improve prognosis when applied concurrently with radiotherapy, whereas induction chemotherapy has not proven to be of further benefit. Treatment of human papillomavirus-related oropharyngeal carcinomas is challenging. Reduced treatment intensity for this entity is being investigated but cannot be recommended for clinical routine at this point. Adjuvant radiotherapy and radiochemotherapy improve the prognosis in high-risk head and neck cancer after surgical treatment. Further reductions in the treated neck volume in adjuvant radiotherapy need clinical investigation., (© 2017 S. Karger GmbH, Freiburg.)

It has been shown that podoplanin expression is associated with carcinoma of the aerodigestive tract. Recent studies indicate that podoplanin may serve as a prognostic biomarker in oral carcinoma. In order to provide evidence on the role of podoplanin in oropharyngeal squamous cell carcinoma, we evaluated the prognostic impact of podoplanin in these patients. We analyzed formalin-fixed tissue samples from 107 consecutive patients with oropharyngeal squamous cell carcinoma. HPV typing and immunohistochemical staining for both p16 and podoplanin were performed. Expression of podoplanin was seen in 38.3% of all cases. We found no correlation of the podoplanin scores with either p16 expression or with HPV status. There was no significant correlation of podoplanin expression with the staging variables T, N, M, and tumor grading. Podoplanin expression did neither influence the 5-year overall survival nor the 5-year disease-free survival. Concluding, we could not find a prognostic role of podoplanin expression neither in the HPV-positive cases nor in the HPV-negative cases. It appears that podoplanin is not expressed as often in oropharyngeal cancer compared to oral cancer. We could not show any relation of lymph node metastases and podoplanin expression in this homogenous cohort of tumors.

Combined analysis of diagnostic and therapeutic management of neck metastases of carcinoma of unknown primary origin ('true CUP') in two European tertiary referral centers (University Medical Centers of Maastricht, NL and Cologne, D) to contribute to the ongoing discussion on management in CUP. Retrospective analysis of 29 (Maastricht) and 22 (Cologne) true cervical CUP syndrome patients (squamous cell carcinoma). The diagnostic and therapeutic approaches were correlated with clinical follow-up data and HPV status. In total, 48 out of 51 true CUP patients received postsurgical adjuvant radiotherapy. In eight patients from Cologne, this was combined with concomitant platin-based chemotherapy. Neither in Cologne nor in Maastricht, radiotherapy of the pharyngeal mucosa was commonly performed (n = 6, 12.5 %) The percentage of patients who were irradiated ipsilaterally or bilaterally did not differ between both institutes (N = 21/27 in Maastricht vs. 11/21 in Cologne), nor did the 5-year overall survival differ significantly. Oncogenic HPV was only found in 4 out of 51 CUPs (7, 8 %). Therefore, no relation with overall and recurrence-free survival could be detected. No occult primary tumors were revealed during follow-up despite de-escalation of therapy by abandoning irradiation of the pharyngeal mucosa in both institutes. There were no significant differences between ipsilateral and bilaterally irradiated patients regarding overall and recurrence-free survival. The occurrence of distant metastases was more often noticed in ipsilaterally treated patients as compared to bilaterally radiated patients (8 vs. 2, p = 0.099). Those patients all had been classified N2b or higher. International guidelines still are not unified and there is an urgent need for a consented therapeutic regimen. Comparison of two international strategies on the management of CUP patients is presented and further research is recommended regarding the role of radiotherapy of the pharyngeal axis, the value of unilateral and bilateral radiotherapy and the role of concomitant or induction chemotherapy in CUP patients, particularly in N2b or higher-staged neck disease. The prevalence and role of HPV in true CUP after thorough diagnostic work-up seem limited in our case series, particularly when compared to the role in oropharyngeal carcinomas.

Background: The prognostic effect of neoadjuvant treatment in advanced oesophageal cancer is still debated because most studies included undefined T-stages, different radio/chemotherapies or different types of surgery., Objectives: To analyse the prognostic impact of neoadjuvant chemoradiation in patients with clinical T3 oesophageal cancer and oesophagectomy., Methods: In a retrospective study 768 patients from two centres with cT3/Nx/M0 oesophageal cancer and transthoracic en-bloc oesophagectomy were selected. Clinical staging was based on endoscopy, endosonography and spiral-CT scan. Propensity score matching using histology, location of tumour, age, gender and ASA-classification identified 648 patients (n=302 adenocarcinoma (AC), n=346 squamous cell carcinoma (SCC)) for the intention-to-treat analysis comparing group-I (n=324) patients with planned oesophagectomy and group-II (n=324) patients with planned neoadjuvant chemoradiation (40Gy, 5-FU, cisplatin) followed by oesophagectomy. The prognosis was analysed by univariate and multivariate analyses., Results: In the intention-to-treat analysis group-I had a 17% and group-II a 28% 5-year survival rate (5-YSR) (p<0.001). After excluding patients without oesophagectomy the 5-YSR of group-II increased to 30%. The results were more favourable for patients with AC (5y-SR of 38%) compared to SCC (22%) (p=0.060). In group-II patients with major response (n=128) had a 41% 5-YSR compared to 20% for those with minor response (n=155, p<0,001). In multivariate analysis neoadjuvant chemoradiation was a favourable independent prognostic factor., Conclusion: Neoadjuvant chemoradiation followed by oesophagectomy results in 11% higher 5-YSR than surgery alone for patients with cT3/Nx/M0 oesophageal cancer. This effect is due to the substantial prognostic benefit of the major responders., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To report outcome and toxicity of concurrent radiochemotherapy with carboplatin and paclitaxel in advanced squamous cell carcinomas of the oropharynx and hypopharynx., Patients and Methods: Advanced inoperable carcinomas of the oropharynx and hypopharynx were treated with either hyper-fractionated, accelerated radiotherapy (50.0 Gy/2.0 with concomitant boost to 69.2 Gy/1.6) or conventional fractionated radiotherapy (70.2-72 Gy/1.8) concurrent with paclitaxel 40 mg/m2 and carboplatin AUC 1 weekly for 6 weeks. Acute and long-term toxicity was measured according to WHO- and CTC-criteria., Results: A total of 84 patients were included between 2000 and 2008. Median follow-up time of patients alive was 36 months. Conventionally fractionated radiotherapy was given to 16 patients, while 68 patients were treated with concomitant boost. Finally, 88.1% of patients received full dose paclitaxel. Acute mucositis ≥ grade 3 was present in 51.2% of patients, while 6% of patients experienced ≥ grade 3 leucopenia and thrombopenia. A supportive gastric feeding tube was implanted in 89.1% of patients. Overall survival after 2 years was 46.3%, progression-free survival after 2 years was 41.0%. There was no significant survival difference between the different radiotherapy protocols., Conclusion: Concomitant carboplatin and paclitaxel is feasible and effective in advanced carcinomas of the head and neck.

Background: The epidermal growth factor receptor (EGFR) and the inhibitor of apoptosis protein survivin play important roles in the regulation of cellular proliferation and survival in squamous cell carcinomas. Their correlation in oropharyngeal squamous cell carcinoma (OSCC) has not been evaluated yet., Methods: In this multicenter study, we analyzed the expression of survivin and EGFR in tissue specimens from 73 selected patients with OSCC using immunohistochemistry., Results: Higher cytoplasmic survivin scores were significantly correlated with high scores of EGFR expression (p=.013). Nuclear survivin expression was associated with a poor overall survival rate with an estimated 3-year overall survival probability of 17.3% versus 87.4% for non-nuclear expression of survivin (p<.001). Multivariate analysis revealed that nuclear survivin expression was an independent negative prognostic factor (p=.008)., Conclusion: Considering the strong impact of nuclear survivin expression on survival, the survivin expression should be prospectively evaluated to select patients with an increased risk for disease recurrence., (Copyright (c) 2008 Wiley Periodicals, Inc. Head Neck 2008.)

The clinical management of patients with primary oropharyngeal squamous cell carcinoma remains controversial. The results of a combined approach involving surgery for the primary tumor, neck dissection, and postoperative radiotherapy were reviewed. A retrospective review was carried out for 211 patients meeting the inclusion criteria of resectable squamous cell carcinoma of the oropharynx. Overall survival and disease-free survival rates were calculated using the Kaplan-Meier method. Univariate (Log-rank test) and multivariate (Cox proportional hazards models) statistical analyses were carried out to investigate the role of clinical factors as significant prognostic markers. The 2- and 5-year disease-free survival rates were 79.8% and 68.8%, respectively. In univariate and multivariate analyses, positive resection margins were the only and independent significant prognostic markers for impaired disease-free survival (Log-rank: p=0.0238; Cox model: p=0.045; hazard ratio 2.48 [95% confidence interval 1.02-6.05]). In univariate analysis, male sex was the only significant negative prognostic factor for overall survival (Log-rank: p=0.0453), whereas Cox multivariate analysis identified extracapsular spread as an independent prognostics marker (p=0.049; hazard ratio 1.86 [95% confidence interval 1.00-3.43]). We conclude that the presented multimodal approach of surgery for the primary tumor and the neck followed by postoperative radio(chemo)therapy seems to be superior to non-surgical treatment protocols, as it results in better disease-free and overall survival. To assess this multimodal treatment approach, morbidity and economic considerations need to be further analyzed.

Objective/hypothesis: Tumor control and survival are considered the most important measures of treatment efficacy for patients with primary oropharyngeal squamous cell carcinoma. Furthermore, multimodal treatment protocols should be judged by their complication rates, morbidity, and therapy costs., Study Design: The results of a combined approach of primary surgery and neck dissection with postoperative radio(chemo)therapy were analyzed in retrospective chart review., Methods: Two hundred eleven patients' records were analyzed for surgical complications, therapeutic morbidity, and treatment costs., Results: The rate of postoperative hemorrhage was 4.7%. We observed no fatal complications. Ten percent of our patients required nutrition through percutaneous endoscopic gastrostomy (PEG). Twelve percent of all patients required long-term tracheostomy. The rates of PEG and tracheostomy were significantly higher in patients operated by the transcervical approach. The costs for the combined approach ranged from 10,587 euros (13,377 dollars) to 24,531 euros (30,996 dollars)., Conclusions: The presented multimodal approach provides a low rate of surgical complications and a tolerable morbidity. Considering the excellent oncologic results, this extensive and more cost-intensive multimodal approach is justified for patients with oropharyngeal cancer.