14 Chapter 1 cant association with loco-regional recurrence and disease-specific survival in early stage OSCC, it is advised to assess whether WPOI type 5 is present or absent (15, 44). Tumor dispersion in the form of WPOI type 5 goes predominately through soft tissue. However, it can also occur in the form of extratumoral perineural van lymphovascular invasion. It should be mentioned that throughout this thesis tumors have been scored for cohesive (WPOI type 1-3) versus non-cohesive (WPOI type 4, 5) growth pattern, which can be considered as the outdated not precisely defined alternative for WPOI (15, 38, 41, 43). Extranodal extension, being the growth of carcinomatous tissue through the capsule of metastatic lymph nodes (45), occurs in aggressive carcinoma, is associated with poor prognosis (41), and should be recorded as present or not identified (38). The distance between carcinoma and deep resection margin should be measured in mm (15, 38). The margin is clear, when the distance is > 5 mm; close when the margin is 1-5 mm; and involved, when the distance is < 1 mm. Involved margins are significantly associated with any form of recurrence (local, regional and distant metastasis) (20). Post-operative radiation and/or chemotherapy Primary radiotherapy is not routinely used for OSCC, as its high-dose is associated with osteoradionecrosis (46). On the other hand, post-operative radiotherapy is well-established for locally advanced disease and histopathological risk factors – such as pN2-3, ENE, close or involved surgical margins, or perineural invasion – and is known to improve loco-regional control and survival (5, 12, 47-50). Although advances were made with surgery and postoperative radiotherapy, disease control and overall survival remained challenging. Therefore, studies have been performed to examine the efficacy of CRT. It is now established that post-operative CRT is beneficial for patients with ENE and positive margins (5, 12, 16, 17, 51). Management of recurrent and metastatic disease Some patients with recurrent or metastatic OSCC, may be cured by salvage resection, re-irradiation or metastasectomy. However, the majority of this patient population is amendable for systemic therapy (5, 9). Traditionally recurrent and/or metastatic OSCC are treated with cytotoxic chemotherapy consisting of cisplatin with 5-fluorouracill and/or a taxane. For toxicity reasons cisplatin is sometimes replaced with carboplatin, yet this results in reduced tumoricidal activity (52).
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