PD-L1 and HIF-2α Upregulation in Head and Neck Paragangliomas after Embolization

Hypoxia activates pathways associated with tumor progression, metastatic spread, and alterations in the immune microenvironment leading to an immunosuppressive phenotype. In particular, the upregulation of PD-L1, a target for therapy with checkpoint inhibitors, is well-studied in several tumors. However, the relationship between hypoxia and PD-L1 regulation in pheochromocytomas and paragangliomas (PPGL), and especially in paragangliomas treated with embolization, is still largely unexplored. We investigated the expression of the hypoxia-marker HIF-2α and of PD-L1 in a PPGL-cohort with and without embolization as potential biomarkers that may predict the response to treatment with HIF-2α and checkpoint inhibitors. A total of 29 tumor samples from 25 patients who were operated at a single center were included and analyzed utilizing immunohistochemistry (IHC) for PD-L1 and HIF-2α. Embolization prior to surgery was performed in seven (24%) tumors. PD-L1 expression in tumor cells of head and neck paragangliomas (HNPGLs) receiving prior embolization (median PD-L1 positivity: 15%) was significantly higher as compared to PD-L1 expression in HNPGLs without prior embolization (median PD-L1 positivity: 0%) (p = 0.008). Consistently, significantly more HNPGLs with prior embolization were positive for HIF-2α (median nuclear HIF-2α positivity: 40%) as compared to HNPGLs without prior embolization (median nuclear HIF-2α positivity: 0%) (p = 0.016). Our results support the hypothesis that embolization with subsequent hypoxia leads to the upregulation of both PD-L1 and HIF-2α in HNPGLs, and could thus facilitate targeted treatment with HIF-2α and checkpoint inhibitors in the case of inoperable, locally advanced, or metastatic disease

Impact of the new TNM Staging System (8th edition) on oral tongue cancers

AIM OF THE STUDY For tumours of the oral tongue, the most recent 8th edition of the AJCC/UICC staging system has introduced depth of infiltration (DOI) as a novel parameter. With this study we wanted to investigate its impact regarding this risk stratification compared with the preceding 7th edition. METHODS Between 2008 and 2017, 161 patients of two tertiary referral centres in Switzerland (Kantonsspital St. Gallen and University Hospital Zurich) with T1 N0 or T2 N0 tongue cancers were enrolled in this study. The primary tumours were restaged according to the 8th edition of the TNM classification. Kaplan-Meier curves for overall and disease-specific survival were calculated. RESULTS According to the 7th edition, of the 161 patients, 102 were staged after surgery as pT1 (stage I) and 59 as pT2 (stage II). According to the 8th edition, 36 patients (22.4%) were re-staged to a higher stage. Of these 36 patients, 8 (22.2%) experienced a recurrence, and 9 (25%) died. In the remaining, not re-staged group, 20 patients (16.0%) experienced a recurrence (p = 0.55) and 14 (11.2%) died (p = 0.025*). The 7th edition showed a statistically significant difference between pT1 and pT2 tumours for overall survival (p = 0.025), but not for disease-specific survival (p = 0.091), whereas the 8th edition was able to well discriminate between pT1, pT2 and pT3 for both overall (pT1 vs pT2, p = 0.016*; pT2 vs pT3, p = 0.031*) and disease-specific survival (pT1 vs pT2, p = 0.037*; pT2 vs pT3, p = 0.023*). CONCLUSION The recent TNM 8th edition provides a more accurate prediction of overall and disease-specific survival for this subgroup of patients. Hence, a more aggressive treatment should be considered for patients re-staged to pT3 due to depth of infiltration

Long-term Speech and Swallowing Function after Primary Resection and Sentinel Node Biopsy for Early Oral Squamous Cell Carcinoma

OBJECTIVES: Analysis of long-term speech and swallowing function and subjective quality of life (QOL) after primary resection and sentinel node biopsy (SNB) in patients with early stage (cT1/T2) oral squamous cell carcinomas (OSCC). MATERIAL AND METHODS: Eighty-one consecutive patients treated primarily by transoral resection without flap reconstruction and SNB for a cT1/T2 OSCC were included. Completion neck dissection (CND) was indicated in case of occult disease in the sentinel nodes. Adjuvant radiation (aRT) was administered according to the ultimate lymph node status. All patients showed no evidence of disease at time of analysis. Speech and swallowing function were assessed using standardized clinical examinations (11-item, articulation test) and validated questionnaires on subjective QOL (MDADI, FIGS). Median follow-up was 60 months (range 13-159 months) after initial treatment. RESULTS: In all assessments for speech and swallowing, the entire study cohort achieved very high scores, with mean values located in the highest 10% of the scales. Neither tumor size nor site, age, pN-category, CND, and aRT had significant impact on functional outcomes and subjective QOL with the exception of lower scores in the global and physical scores of MDADI after CND or aRT, and articulation in the population over 60 years of age. CONCLUSION: Transoral resection without reconstruction and SNB for early OSCC achieves excellent outcome with regard to speech, swallowing and subjective QO

Impact of the new TNM Staging System (8th edition) on oral tongue cancers

AIM OF THE STUDY For tumours of the oral tongue, the most recent 8th edition of the AJCC/UICC staging system has introduced depth of infiltration (DOI) as a novel parameter. With this study we wanted to investigate its impact regarding this risk stratification compared with the preceding 7th edition. METHODS Between 2008 and 2017, 161 patients of two tertiary referral centres in Switzerland (Kantonsspital St. Gallen and University Hospital Zurich) with T1 N0 or T2 N0 tongue cancers were enrolled in this study. The primary tumours were restaged according to the 8th edition of the TNM classification. Kaplan-Meier curves for overall and disease-specific survival were calculated. RESULTS According to the 7th edition, of the 161 patients, 102 were staged after surgery as pT1 (stage I) and 59 as pT2 (stage II). According to the 8th edition, 36 patients (22.4%) were re-staged to a higher stage. Of these 36 patients, 8 (22.2%) experienced a recurrence, and 9 (25%) died. In the remaining, not re-staged group, 20 patients (16.0%) experienced a recurrence (p = 0.55) and 14 (11.2%) died (p = 0.025*). The 7th edition showed a statistically significant difference between pT1 and pT2 tumours for overall survival (p = 0.025), but not for disease-specific survival (p = 0.091), whereas the 8th edition was able to well discriminate between pT1, pT2 and pT3 for both overall (pT1 vs pT2, p = 0.016*; pT2 vs pT3, p = 0.031*) and disease-specific survival (pT1 vs pT2, p = 0.037*; pT2 vs pT3, p = 0.023*). CONCLUSION The recent TNM 8th edition provides a more accurate prediction of overall and disease-specific survival for this subgroup of patients. Hence, a more aggressive treatment should be considered for patients re-staged to pT3 due to depth of infiltration