Clinical investigation: head and neck
Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience

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Abstract

Purpose: To update our experience with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC).

Methods and Materials: Between April 1995 and October 2000, 67 patients underwent IMRT for NPC at the University of California-San Francisco (UCSF). There were 20 females and 47 males, with a mean age of 49 (range 17–82). The disease was Stage I in 8 (12%), Stage II in 12 (18%), Stage III in 22 (33%), and Stage IV in 25 (37%). IMRT was delivered using three different techniques: 1) manually cut partial transmission blocks, 2) computer-controlled auto-sequencing segmental multileaf collimator (SMLC), and 3) sequential tomotherapy using a dynamic multivane intensity modulating collimator (MIMiC). Fifty patients received concomitant cisplatinum and adjuvant cisplatinum and 5-FU chemotherapy according to the Intergroup 0099 trial. Twenty-six patients had fractionated high-dose-rate intracavitary brachytherapy boost and 1 patient had gamma knife radiosurgery boost after external beam radiotherapy.

The prescribed dose was 65–70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), 50–60 Gy to the clinically negative neck, and 5–7 Gy in 2 fractions for the intracavitary brachytherapy boost. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. The local progression-free, local-regional progression-free, distant metastasis-free rates, and the overall survival were calculated using the Kaplan-Meier method.

Results: With a median follow-up of 31 months (range 7 to 72 months), there has been one local recurrence at the primary site. One patient failed in the neck. Seventeen patients developed distant metastases; 5 of these patients have died. The 4-year estimates of local progression-free, local-regional progression-free, and distant metastases-free rates were 97%, 98%, and 66% respectively. The 4-year estimate of overall survival was 88%. The worst acute toxicity documented was as follows: Grade 1 or 2 in 51 patients, Grade 3 in 15 patients, and Grade 4 in 1 patient. The worst late toxicity was Grade 1 in 20 patients, Grade 2 in 15 patients, Grade 3 in 7 patients, and Grade 4 in 1 patient. At 3 months after IMRT, 64% of the patients had Grade 2, 28% had Grade 1, and 8% had Grade 0 xerostomia. Xerostomia decreased with time. At 24 months, only one of the 41 evaluable patients had Grade 2, 32% had Grade 1, and 66% had Grade 0 or no xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.3 Gy, 74.5 Gy, and 49.4 Gy to the GTV, and 78.9 Gy, 68.7 Gy, and 36.8 Gy to the CTV. An average of only 3% of the GTV and 3% of the CTV received less than 95% of the prescribed dose.

Conclusion:Excellent local-regional control for NPC was achieved with IMRT. IMRT provided excellent tumor target coverage and allowed the delivery of a high dose to the target with significant sparing of the salivary glands and other nearby critical normal tissues.

Introduction

Nasopharyngeal carcinoma (NPC) is common among Asians, especially the Southern Chinese. However, it is rarely seen among the Caucasian population, representing less than 1% of all cancers in the United States (1). The standard treatment for NPC is radiotherapy alone for early (T1N0) disease, and combined radiotherapy and chemotherapy for more advanced lesions, including those with nodal involvement or T2–4 disease 2, 3. The local control rate for American Joint Committee on Cancer (AJCC) 1992 Stage T1 and T2 tumors ranged from 64% to 95%. However, the control rate decreased to 44–68% in AJCC 1992 Stage T3/T4 tumors. Five-year survival was between 36% and 58% 4, 5, 6, 7, 8, 9, 10.

Tumor control for carcinoma of the nasopharynx is highly correlated with the dose delivered to the tumor. In a series of 107 patients with NPC, local control was significantly improved when >67 Gy was delivered to the tumor target (11). In another series of 118 patients, the improvement of tumor control was attributed not only to the prescription of higher doses of radiation, but also to improvements in technical accuracy (12). Because the nasopharynx is surrounded by many critical normal tissues, accuracy in dose delivery is essential in any dose escalation study.

Intensity-modulated radiation therapy (IMRT) has recently gained popularity in the treatment of head-and-neck cancer. With this technique, the intensity of the radiation beams can be modulated so that a high dose can be delivered to the tumor while significantly reducing the dose to the surrounding normal tissues 13, 14, 15, 16. Xia et al. (17) compared IMRT treatment plans with conventional treatment plans for a case of locally advanced NPC. They concluded that IMRT provided improved tumor target coverage with significantly better sparing of sensitive normal tissue structures in the treatment of locally advanced NPC. Two recent papers also substantiated this finding. The authors stated that because of a lack of major benefit with conventional 3-dimensional treatment planning used only during the boost phase of treatment for NPC, they are currently using IMRT to deliver the entire course of radiation 18, 19.

At our medical center, we have been using IMRT for the treatment of NPC since 1995. Local-regional control rate was 100% in our initial clinical experience of 35 patients (20). These patients were treated primarily with forwardly planned IMRT. Over the past 4 years, we have been using inverse planning for all our patients because this technique allows better sparing of the surrounding normal critical structures (17). The majority of the radiation beams were delivered using either computer-controlled auto-sequencing static multileaf collimator (MLC) or the Peacock system using a dynamic multivane intensity-modulating multileaf collimator, called the MIMiC. In this report, we update our results, and describe the evolution of our techniques in the treatment planning and delivery of IMRT for NPC.

Section snippets

Patient and staging evaluation

Between April 1995 and November 2000, 67 patients underwent IMRT for NPC in the Department of Radiation Oncology, University of CaliforniaSan Francisco. For this analysis, the records of these 67 patients, including the first 35 patients that were reported previously, were reviewed and updated (20).

Pretreatment evaluation included a complete history and physical examination, direct flexible fiberoptic endoscopic examination, complete blood counts, liver function tests, chest X-ray, magnetic

Patient characteristics

There were 20 females and 47 males, with a mean age of 49 (range 17–82). Table 1 shows the T- and N-stage distribution of the patient population according to the 1997 AJCC staging classification. The disease was Stage I in 8 (12%), Stage II in 12 (18%), Stage III in 22 (33%), and Stage IV in 25 (37%). There were 55 Chinese, 3 African-American, 2 Hispanic, 6 white, and 1 Saudi Arabian. Thirty-four patients had nonkeratinizing carcinoma (WHO II), and 33 patients had undifferentiated carcinoma

Discussion

Radiotherapy ± chemotherapy is the primary treatment modality for NPC, preferred over surgery due to its anatomic location. The reported local control rate for T1/T2 tumors ranges between 64% and 95% whereas for T3/T4 tumors, the control rate drops to 44–68% according to the 1992 AJCC staging classification 4, 5, 6, 7, 8, 9, 10. Studies have shown that local control rate increased with dose 11, 12. However, due to the anatomic location of the nasopharynx in proximity to many critical normal

Conclusion

Excellent local-regional control for NPC was achieved with intensity-modulated radiotherapy. IMRT provided excellent tumor target coverage and allowed the delivery of a high dose to the target with significant sparing of the salivary glands and other nearby critical normal tissues. Future trials evaluating more effective chemotherapy regimens ± anti-angiogenic agents in decreasing the rate of distant metastasis in NPC are warranted.

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