*2.2.1 Nasopharynx*

Radiotherapy is the major treatment modality for nasopharyngeal carcinoma (NPC). It is because the primary tumor site of NPC is difficult to be accessed by surgical intervention, and the tumor cells of NPC are sensitive to radiation [5]. The use of radiotherapy alone is effective to treat stage I to II NPC, while concurrent chemotherapy is added for higher stages disease to achieve better local-regional control and survival outcome [6]. IMRT is the preferred radiotherapy technique and the late side effect of xerostomia in patients receiving IMRT was significantly reduced [7]. The current standard of the prescribed total dose to the primary tumor is to give 70 Gy in 33–35 fractions [8]. With the use of simultaneous integrated boost, the prophylactic dose which is lower than the dose to the primary tumor is prescribed for the potential microscopic spread of the primary tumor and selected cervical lymph nodes

regions. The prophylactic prescription can be varied in different local practices, it was reported that the prescriptions for the intermediate and low-risk cervical lymph nodes were about 60 Gy and 50 Gy, respectively [8, 9].

#### *2.2.2 Oral cavity*

The cancer of the oral cavity includes various sub-sites such as the anterior tongue, buccal mucosa, hard palate, soft palate, alveolus, and floor of the mouth. The primary treatment of the cancer of the oral cavity varied according to the stage, which can be briefly divided into early and advanced. For early-stage which refers to T1 and early T2 tumors, radiotherapy entirely or partly delivered by brachytherapy can result in similar local control as in surgery [10, 11]. However, a recent retrospective study reported that primary radiotherapy to early-stage oral cavity cancer patients resulted in higher mortality as compared with those who received primary surgery [12]. It has also been reported in the same article that the majority (more than 95%) of early-stage oral cavity cancer patients received primary surgery. The small proportion of patients receiving primary radiotherapy in this group of patients was attributed to the fact that brachytherapy services were not available due to lack of expertise and suitability of applicator for insertion [10]. Hence, most early-stage oral cavity cancer patients receive surgery for primary treatment, although radiotherapy is also an alternative. Postoperative radiotherapy is only indicated for positive or close margins after resection [13]. For advanced oral cavity cancer, surgery is often the standard primary treatment whenever resectable [14], and then followed by adjuvant radiotherapy or chemo-radiotherapy. For non-resectable advanced oral cavity cancer, radical radiotherapy is offered in conjunction with chemotherapy or targeted therapy to improve disease control [15]. The total prescribed dose is 70 Gy to the gross tumor or 66 Gy to the tumor bed after resection, delivered with 2 Gy per fraction. Similar to NPC, prophylactic irradiation to the cervical lymph nodes regions is also used, where 60 Gy and 54 Gy are prescribed to the intermediate-risk and lowrisk regions, respectively [16].

#### *2.2.3 Larynx*

A specific consideration when treating cancer of the larynx is preserving organs and function. Radiotherapy alone or concurrent chemoradiotherapy is the most widely applied approach in organ preservation therapy [17]. Radical surgery is the rival choice for the patients, the outcome would lead to sub-optimal quality of life because it would result in loss of voice, swallowing problem, and often a permanent tracheostomy. To achieve a better quality of life after treatment, organ preservation therapy using radiotherapy or chemoradiotherapy is recommended for early-stage disease and some advanced cases of T3 and T4 [17, 18]. The consideration of offering surgery instead of radical chemoradiotherapy for advanced cases includes patients' condition and the extent of the disease and should be assessed by an expert panel of clinicians from different disciplines [19, 20]. Even when surgery is chosen as the treatment option, radiotherapy still has the role in providing postoperative adjuvant treatment for high-grade tumors, positive margins, cervical lymph nodes involvement, and tumor invasion beyond the larynx [21]. The prescribed dose ranged from 66 Gy to 76 Gy to the primary tumor site and involved lymph node, and the prescription for the selective lymph node with suspected microscopic involvement is at least 50 Gy [22].

#### *2.2.4 Maxillary sinus*

Although the primary treatment of the cancer of the maxillary sinus is surgery, postoperative radiotherapy is indicated for stage 2 and stage 3 disease, and for stage 1 disease when the surgical margin is insufficient [20]. For locally advanced disease, induction chemotherapy and then concurrent chemoradiotherapy have been suggested for non-resectable patients [23]. The treatment outcome for these patients would be better if the tumor can be down-staged and subsequent resection is possible [23]. The concern of the radiotherapy to the maxillary sinus includes the preservation of the optic apparatus which are near to the tumor [20]. It has been reported that 37% of the patients who received conventional radiotherapy developed radiotherapyinduced blindness [24]. IMRT is the preferred technique. It has been reported that IMRT could significantly spare nearby organs than those in 3DCRT. The dose to the optic chiasm can be significantly reduced from over 60 Gy in 3DCRT to less than 40 Gy in IMRT [25], while the tumor coverage by the prescribed dose is increased from 83% in 3DCRT to 95% in IMRT. The prescribed dose to the primary tumor site ranged from 66 to 70 Gy.
