Clinical investigation: Head and neck
Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy: The Hong Kong experience

The material in this article was presented at the American Society of Therapeutic Radiology and Oncology, 45th Annual Meeting, Oct 2003, Salt Lake City, UT.
https://doi.org/10.1016/j.ijrobp.2004.05.022Get rights and content

Abstract

Purpose

To evaluate the efficacy of using intensity-modulated radiotherapy (IMRT) in the primary treatment of nasopharyngeal carcinoma (NPC), including the role of dose escalation above 66 Gy level.

Methods and materials

Between July 2000 and September 2002, 63 newly diagnosed NPC patients were treated with IMRT. The disease was Stage I in 9 (14%), Stage II in 18 (29%), Stage III in 22 (35%), and Stage IV in 14 (22%). The prescribed dose was 66 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the planning target volume (PTV), and 54–60 Gy to the clinically negative neck. All 20 (100%) patients with T1-2a tumors received intracavitary brachytherapy (ICB) boost, and 15/42 (36%) patients with T2b-T4 tumors received conformal boost (8 Gy/4 fractions). Nineteen patients with advanced stage disease also received either neoadjuvant or concurrent chemotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method.

Results

With a median follow-up of 29 months (range 8–45 months), 4 patients developed local in-field failure, 1 patient developed regional relapse, and 13 patients developed distant metastases. All 4 patients with local failure had either T3 or T4 disease before primary treatment and did not have ICB or conformal boost. The 3-year actuarial LRFS, NRFS, DMFS, and OS were 92%, 98%, 79%, and 90%, respectively. Multivariate analysis showed that dose escalation above 66 Gy was significantly associated with better PFS and DMFS, whereas GTV size was a significant adverse factor for OS. The worst acute mucositis was Grade 1 or 2 in 36 (59%), and Grade 3 in 25 (41%) patients. Acute dysphagia requiring tube feeding occurred in 5 (8%) patients. The proportion of patients with Grade 2-3 xerostomia was 57% at 3 months, and 23% at 2 years after IMRT. Within the subset of patients with a mean parotid dose of <31 Gy, the proportions with Grade 2-3 xerostomia were 30% and 17% at 3 months and 2 years, respectively.

Conclusion

Our experience of using IMRT in the primary treatment of NPC showed a very high rate of locoregional control and favorable toxicity profile. Furthermore, we found that dose escalation above 66 Gy of IMRT-based therapy was a significant determinant of progression-free survival and distant metastasis-free survival for advanced T-stage tumors. Distant metastases represent the predominant mode of treatment failure.

Introduction

Despite the recognized radiocurability and evidence of a dose–response relationship for nasopharyngeal carcinoma (NPC) 1, 2, 3, 4, radiotherapy (RT) treatment planning remains a great challenge in view of the close proximity of the tumor to the surrounding neural organs. Any attempt to perform dose escalation will be limited by the low radiation tolerance of the adjacent organs at risk (OAR)—namely, the brainstem, spinal cord, temporal lobes, and optic pathway. Strategies such as intracavitary brachytherapy (ICB) or stereotactic radiosurgery (STR) boost and altered fractionation RT regimens have been explored 3, 4, 5, 6, 7, 8, 9, 10, 11. However, regardless of the type of boost or fractionation regimen, treatment failure is expected to occur if target coverage is inadequate or normal tissue irradiation is excessive, a phenomenon not infrequently observed with conventional two-dimensional RT (2DRT). The reported 5-year local relapse-free survival after 2DRT is 75–95% and 45–80% in stage T1-T2 and T3-T4 patients, respectively 12, 13, 14.

Intensity-modulated radiation therapy (IMRT), by virtue of its dosimetric advantage, has gained increasing popularity in the treatment of cancers of the head-and-neck region. Although there is an appreciable number of dosimetric studies showing the advantage of IMRT over 2DRT in treatment of head-and-neck cancers, including NPC 15, 16, 17, 18, data on clinical outcome of primary treatment of NPC are limited. Encouraging results have been reported by the University of California-San Francisco (UCSF) group, with an impressive local control rate of 97% at 4 years when 70 Gy was delivered to the tumor 19, 20. Nevertheless, the question remains as to whether there is still a role of dose escalation beyond 66–70 Gy when target underdosing is no longer a confounding factor with IMRT. To address some of these issues, our center recruited 63 newly diagnosed nonmetastatic NPC patients for IMRT treatment between July 2000 and September 2002; these patients formed the basis of our analysis. In the present report, we describe our IMRT treatment technique and report on the early treatment outcome and toxicity profile of these patients. We also attempt to identify any significant prognostic factors, especially the dose–volume effect within the context of this high-precision therapy.

Section snippets

Pretreatment evaluation and patient characteristics

Between July 2000 and July 2002, 63 newly diagnosed nonmetastatic NPC patients underwent IMRT in our center. There were 48 males and 15 females, and the median age for the whole group was 48 years (range, 24–82 years). All patients were staged by a standard protocol comprising physical examination, fiber-optic nasopharyngoscopy, computed tomography (CT) of the nasopharynx and neck region, chest radiograph, and liver and bone profiles. Magnetic resonance imaging (MRI) of the nasopharynx was

Treatment outcomes

Analysis was performed in October 2003 and updated in March 2004, At a median follow-up time of 29 months (range, 7.7–44.7 months), 4 patients had developed local failure, 1 regional nodal failure, and 13 distant metastasis. The 3-year actuarial LRFS, NRFS, DMFS, and overall survival were 92%, 98%, 79%, and 90%, respectively (Fig. 2).

All 4 patients with local failures had advanced T3 or T4 disease initially. These were all in-field failures because the sites of local recurrence resided within

Discussion

Radiotherapy has been the mainstay of treatment for NPC for more than three decades. Until the early 1990s, the use of 2DRT to deliver a “tumoricidal” dose (66–70 Gy; 2 Gy per fraction; 6.6–7 weeks) to the target via laterally opposed fields had been the standard. This technique involved the manual projection of tumor volume and OARs onto the orthogonal simulation films based on bony anatomy and the employment of nonconformal shielding blocks to protect the critical structures. The obvious

Conclusion

Our experience of using IMRT treatment for a cohort of patients with early and advanced stage NPC showed a very high rate of locoregional control at early follow-up. All cases of local failures had occurred within the GTV. We found that dose escalation was possible for advanced T-stage tumors after 66 Gy delivered by IMRT, and dose escalation after 66 Gy-IMRT was a significant determinant of PFS and DMFS. Acute and late toxicities with IMRT were limited. Satisfactory dosimetric sparing of the

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Supported by the Clinical Oncology Department Fund, Prince of Wales Hospital, Hong Kong.

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