**4. Conclusion**

172 Carcinogenesis, Diagnosis, and Molecular Targeted Treatment for Nasopharyngeal Carcinoma

Ramsden et al (1975) classified osteoradionecrosis of the temporal bone as either localized or diffuse. In localized osteoradionecrosis, the disease is generally confined to the external auditory canal, and symptoms manifest according to the site and stage of the disease. In diffuse osteoradionecrosis it extends beyond the temporal bone to the base of the skull and its surrounding structures. The affected patients presented with more severe symptoms of profuse and pulsatile otorrhea and significant pain. The diffuse form is associated with a greater likelihood of complications, including trismus, intracranial infection, facial nerve palsy, labyrinthitis, chronic mastoiditis, CSF leak, and internal carotid artery aneurysm.

The type that is more commonly seen is the localized type where the ORN is heralded by unhealed ulcer, foul discharge, exposed bone and accompanying granuloma. It is typically seen in the lower external canal skin, an area predisposed to downward pressure-induced trauma from wearing hearing aids or iatrogenically traumatized during aural toileting or ear-picking. Sometimes, it involves the middle ear (Figure 4). As suggested by Hao et al, treatment ranges from thorough aural toilet, otic drops, hyperbaric oxygen (Rudge 1993) that reverses the ill effects of radiation induced skin changes, and finally sequestrectomy. Most important though rare, high degree of suspicion and awareness is the key in detection and early management of this condition before serious complication ensues. Lim et al (2005) reported an interesting case of a 44-year-old Chinese man with a history of nasopharyngeal carcinoma that was treated with radiotherapy presented with fluid in the middle ear. A myringotomy was performed and subsequently a diagnosis of cerebrospinal fluid leakage

Radiation-associated tumours (RATS) are rare complications of radiotherapy. Goh et al (1999) studied RATs in the temporal bones of patients who were previously irradiated for cancers of the nasopharynx. Of the 7 patients studied, 5 had squamous cell carcinomas, 1 osteogenic sarcoma and 1 chondrosarcoma. This distribution of the type of cancer is interesting as radiation-induced cancers are more associated with sarcoma than with squamous cell carcinoma. A possible reason for this observation may be related to the chronic ear infections that are commonly present in post-irradiated ears. The combined long-term effects of radiation and chronic infections may well predispose the ear to squamous cell carcinoma. In another study of patients with malignant tumors of the external auditory canal and temporal bone, the 1-year cumulative recurrence for the RAT group was 100%, but there was no recurrence in the non-RAT group (P = 0.001) suggesting a poorer

Delayed diagnosis is not uncommon in this condition. Almost two thirds of the patients in the series reported by Lim et al. (2000) had T3 disease at the time of presentation. One reason could be that otorrhea, the most common presentation, was often mistaken to be due

Another reason for misdiagnosis is difficulty in getting histological confirmation in the Clinic. Lim et al (2000) gave the example of a patient with an initial diagnosis of pseudoepitheliomatous hyperplasia. This was based on superficial small punch biopsy

secondary to osteoradionecrosis of the temporal bone was made.

**3.5 Radiation-associated tumors** 

prognosis in RATS patients (Lim et al 2000)

to chronic otitis externa.

(John et al., 1993)

Because of the close relation between the nasopharynx and ear structures, NPC frequently has Otological manifestations. Attending Physicians must be mindful of these manifestations as they may aid early diagnosis with consequently better treatment outcomes.

Treatment of NPC with radiotherapy or chemo-radiation also has great impact on the practice of Otology. Improved RT techniques have reduced unnecessary radiation exposure to ear structures, with lesser chances of developing ear complications. Nevertheless, it is inevitable in many instances. With greater emphasis in the use of chemo-RT in advanced head and neck cancers, chemo-radiation-induced SNHL has also assumed greater significance. Although recent technology such as cochlear implants have been highly successful in rehabilitating profound hearing loss, prevention is still the best practice in the management of radiation-induced SNHL. A proposed ROS-dependent apoptotic model of hair-cell damage offers the prospect of prevention at a molecular level in the near future.
