Rules of parotid gland dose variations and shift during intensity modulated radiation therapy for nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is common in southern China [1]. Radiation therapy concurrently with chemotherapy is the definitive treatment for NPC [2,3]. Over the past decade, intensity-modulated radiotherapy (IMRT) has been widely delivered in clinic. Some patients receiving radiation therapy (RT) to the head and neck have significant anatomic changes during IMRT course, including shrinking nodal masses or primary tumors, resolving postoperative changes/edema, and changes in overall body habitus/weight loss [4-9]. It has been reported that replanning by using the second CT scan with an average interval of 19 fractions during the course of IMRT for head and neck cancer patients significantly reduced the normal organ dose and increased the target dose coverage compared with using the original plan on the new anatomy [8]. Our previous studies implicated that replanning was needed before the 25th fraction in 50% of IMRT plans to avoid the overdose to the normal sensitive structures [10,11]. We have recently reported that anatomic changes resulted in more predominant dosimetric effects in the first 15 fractions than those between fraction 16 and 25 [12].

Traditionally, IMRT plan was generated from single 3D anatomy prior to treatment. For the head and neck tumor, one of the most important roles of IMRT is to spare the function of parotid gland, which may potentially alleviate the degree and the rate of xerostomia [13,14]. Several studies have reported that bilateral parotid glands had a significantly variance of volume reduction over the treatment [11,12]. A recent study [15] investigated 10 patients with locally advanced oropharyngeal cancer treated with contralateral parotid-sparing IMRT concurrently with platinum-based chemotherapy. And it has been found that ipsilateral and contralateral parotids showed a mean reduction in volume of 29.7% and 28.4%, respectively. Those volume reductions resulted in significant dose changes. To date, there are very limited studies on parotid gland position and dose changes in IMRT of nasopharyngeal carcinoma. Therefore, we carried out this study to evaluate the rules of dose delivery changes and shift of parotid gland during IMRT for NPC.

IMRT has been used routinely in the treatment of NPC due to its anatomical position. The sharp dose gradient change around the target margin in IMRT requires accurate dose delivery to the target volume and critical organs. However, it has been demonstrated that most NPC patients will experience anatomic changes, mainly including shrinking of the primary tumor or nodal masses, parotid glands during IMRT [8,9,11]. Furthermore, anatomic changes could have a potential dosimetric impact when a highly conformal IMRT technique is used.

We have previously demonstrated that replanning during IMRT for NPC significantly improved 2-year local regional control rate. Replanning had a profound impact on the quality of life of NPC patients. Patients who did not receive replanning had significantly greater problems with speech, social contact, teeth, mouth opening, dry mouth and sticky saliva [17]. Furthermore, it has been reported that IMRT replanning improved the 3 years local progression–free survival for NPC patients with AJCC staged of late T or N, whereas patients at early stage could not benefit from IMRT replanning by retrospectively analyzing 33 patients [18]. Since protection of parotid glands function directly affects the quality of life, dose variation rule of parotid gland becomes the focus of research in the field of IMRT for nasopharyngeal carcinoma.

The changes of volume and dose of parotid gland by repeating simulation of KV-CT scans through the IMRT for nasopharyngeal carcinoma have been analyzed in our previously studies. A significant larger reduction of parotid volume was found between fraction 16 and 25 than in the first 15 fractions. However, the dose changes of the parotid gland were more prominent in the first 15 fractions than those between fractions 16 and 25 during IMRT [12]. Similarly, in the current study, we found that the variation of parotid glands V30 was more significantly decreased during the first 15 fractions than between fraction 16 and 25, particularly for the ipsilateral parotid glands. Several studies have suggested that the dose change of parotid gland may result from the parotid gland volume change [9]. However, Some other studies suggested that the dosimetric changes may be related with the positional shifts of the parotid glands during IMRT treatment [4,6]. Nishi T et al. reported that parotid glands and the retromandibular vein in parotid glands shifted medially an average of 4.2 mm and 2.4 mm separately at the third or fourth week of IMRT for NPC [4]. In our present study, we further demonstrated that the changes of parotid glands V30 variation may be associated with more significant shrinkage for GTVnx and the parotid glands moving into the high-dose region at the first 15 fractions.

In conclusion, our current study indicated that shrinking of gross tumor during IMRT treatment for NPC could lead to ipsilateral parotid glands move into the high-dose region at the first 15 fractions. Which subsequently leads to considerable inaccuracies in dose delivery to ipsilateral parotid glands during IMRT for nasopharyngeal carcinoma. Therefore, measurements of medial edges of parotid gland and GTVnx volume reduction may be a potential helpful strategy for optimizing treatment planning for IMRT and selecting patients who could benefit significantly from adaptive strategies.