CLINICAL INVESTIGATION
Salvage brachytherapy for patients with locally persistent nasopharyngeal carcinoma

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Abstract

Purpose: Locally persistent nasopharyngeal carcinoma (NPC) carries an increased risk of local failure if additional treatment is not given. This study was conducted to evaluate the outcomes of patients with locally persistent NPC as treated by high-dose-rate (HDR) intracavitary brachytherapy, and to explore whether routine brachytherapy boost could improve the local control.

Methods and Materials: Eighty-seven patients with locally persistent NPC treated during 1990–1998 with HDR intracavitary brachytherapy were retrospectively analyzed. Fibreoptic nasopharyngoscopy was performed 3–6 weeks after completion of the primary external radiation therapy (ERT). Biopsies were only taken from suspicious areas. Those with complete regression of local disease were put on observation. Eighty-seven patients were shown to have persistent viable disease at a median time of 6 weeks post-RT. The distribution according to Ho’s staging system at initial diagnosis was as follows: Stage I—8, II—33, III—41, IV—5; T1—19, T2—48, T3—20; N0—32, N1—22, N2—28, N3—5. CT scan for restaging was not performed after the documentation of persistent disease. Our policy was to treat all patients with persistent disease with brachytherapy irrespective of the extent of disease just prior to brachytherapy. They were treated with HDR intracavitary brachytherapy, with either cobalt sources or an iridium source, giving 22.5–24 Gy in 3 weekly sessions in all but 4 patients. This dose was prescribed at a distance of 1.5 cm from the center of the surface as defined by the sources in the first six patients and subsequently reduced to 1 cm for the others. Twelve patients were treated with neoadjuvant chemotherapy. To compare the efficacy of brachytherapy, another 383 consecutive nonmetastatic patients, treated with curative intent by ERT, during the years 1990–1993, were evaluated. Multivariate analysis was performed using the Cox regression proportional hazards model.

Results: The 5-year actuarial local failure–free survival (LFFS) rates and disease-specific survival rates for the brachytherapy group and ERT group were 85% and 76.6% (p = 0.15), and 72% and 67.8% (p = 0.2), respectively. The corresponding 5-year actuarial LFFS rates for T1, T2, and T3 disease were 94.7%, 88.2%, 67.4%, and 84.1%, 79.8%, 62.6%. In assessing the local control, only the T staging was significant on multivariate analysis (p = 0.0004). Other parameters such as age, sex, and persistence of disease (giving brachytherapy) were all nonsignificant. Complications were comparable between the two groups. In the persistent group, the local failure rates of the patients treated with and without neoadjuvant chemotherapy were 17% (2/12) and 13% (10/75) respectively. When analyzed according to different brachytherapy sources, the 5-year LFFS rates of the T1, T2, and T3 patients treated with iridium and cobalt sources were 100% vs. 85.7 (p = 0.19), 93.6% vs. 70% (p = 0.04), and 67.7% vs. 60% (p = 0.72). The difference was statistically significant for the T2 groups. When early T-stage (T1 and T2) patients were grouped together for analysis, the iridium group again showed a statistically significant improvement in 5-year LFFS rate when it was compared with the cobalt group (95.3% vs. 76.5%, p = 0.03) and the ERT alone group (95.3% vs. 81.5%, p = 0.03). The improvement of local control is attributed to a higher nasopharyngeal mucosal dose that is achieved by using small-size flexible applicators with an iridium source. It is interesting to note that the 5-year LFFS rates for the ERT alone group (T1: 84.1%, T2: 79.8%, T3: 62.6%) are comparable to the corresponding rates of the cobalt group. This information supports our speculation that an adequate booster treatment could compensate for inadequate primary treatment. The prognosis of patients with locally recurrent NPC is grave. Maximizing the local control is therefore crucial for the survival of the patients. The good local control of early T-stage locally persistent NPC patients receiving brachytherapy supports the incorporation of brachytherapy into the primary treatment program. The 5-year LFFS rates for T3 disease treated with and without brachytherapy were unsatisfactory (iridium group: 67.7%; cobalt group: 60%; ERT alone group: 62.6%). A more aggressive approach to improve the local control of Ho’s T3 disease should be explored.

Conclusion: Our experience suggests that locally persistent NPC can be effectively salvaged by brachytherapy. The local control of patients with early T-stage NPC at initial diagnosis is even better than those having clinical remission of local disease at the completion of ERT. Furthermore, it is possible that routine brachytherapy boost, after the completion of ERT, could improve the local control. The exact benefit, however, can only be elucidated by prospective randomized studies.

Introduction

Persistent nasopharyngeal carcinomas (NPC) remain a challenge. Yan et al. showed that 36% (5/14) of the patients with histologically proven residual disease within 2 weeks of completion of external radiation therapy (ERT) would subsequently develop local recurrence if a booster dose was not given (1). Likewise, experience on the regression patterns of other head and neck tumors also showed that failure to achieve complete remission at or shortly after the completion of RT was associated with an increased risk of local failure 2, 3. Therefore, it is fair to speculate that a patient with locally persistent NPC carries an increased risk of developing local failure if a booster dose is not given.

Despite advances in imaging technology and treatment techniques, local failure still occurs in 20–37% of patients receiving adequate treatment to the nasopharynx in several contemporary series 4, 5, 6, 7. The treatment results of locally recurrent NPC are unsatisfactory, with a 5-year actuarial local control rate in the region of 15–36% 7, 8, 9. Patients with early-stage local recurrences, who are more amenable to nasopharyngectomy 7, 10, 11 or interstitial implants 6, 12, 13, tend to have a better chance of subsequent local control. This illustrates the importance of early detection of local failure. Given the poor outcome and high associated complications with retreatment, more aggressive primary treatment to secure high local control seems to be the approach with the least toxicity.

The present study is a retrospective analysis of a series of patients with locally persistent NPC treated by high-dose-rate (HDR) intracavitary brachytherapy with curative intent. Treatment results of the earlier patients have been reported elsewhere (14). In this series we update our earlier report by adding 48 cases. With a larger patient number and a longer follow-up period, the treatment results can provide some grounds for exploration of any possible therapeutic gain on dose escalation with brachytherapy.

Section snippets

Methods and materials

In the Department of Clinical Oncology at the Tuen Mun Hospital, 83 patients with locally persistent NPC, following a radical course of ERT, were treated with HDR intracavitary remote afterloading brachytherapy during the period March 1990 to February 1998. These 83 patients represented approximately 10% of our NPC patients treated during the same period. Another four patients with locally persistent disease were treated elsewhere with ERT and referred to our department for brachytherapy. Thus,

Results

The 5-year actuarial LFFS rates and DSS rates for the brachytherapy group and ERT alone group were 85% and 76.6% (p = 0.15) (Fig. 3), and 72% and 67.8% (p = 0.2), respectively. The corresponding 5-year actuarial LFFS rates for T1, T2, and T3 disease were 94.7%, 88.2%, 67.4%, and 84.1%, 79.8%, 62.6%. A trend of improvement in the local control of the brachytherapy group was seen, and the local control of T1 and T2 patients was in the region of 90%. In assessing local control, only the T staging

Discussion

One may criticize that not all the patients treated during the years 1990–1998 were included in the present analysis. Their inclusion could certainly add more valuable information. Nevertheless, we managed to include 383 consecutive nonmetastatic NPC patients treated during the years 1990–1993 as a control group for evaluating the role of brachytherapy. More detailed analysis of this control group was beyond the scope of the current discussion.

In the present study, patients with local

Conclusion

We have reasons to believe that locally persistent NPC carries an increased risk of local recurrence if adequate additional treatment is not given. In this study, we have shown an improvement in local control for early T-stage NPC patients after receiving salvage brachytherapy treatment.

Acknowledgements

The authors thank Prof. J. F. Fowler for his advice on the fractionation schedule and all the staff of the Department of Clinical Oncology for their contribution in the management of this series of patients.

References (30)

  • J.T. Chang et al.

    The role of brachytherapy in early-stage nasopharyngeal carcinoma

    Int J Radiat Oncol Biol Phys

    (1996)
  • J.P. Batami et al.

    Significance and therapeutic implications of tumor regression following radiotherapy in patients treated for squamous cell carcinoma of the oropharynx and pharyngolarynx

    Head Neck Surg

    (1990)
  • H.T. Barkley et al.

    The significance of residual disease after external irradiation of squamous cell carcinoma of the oropharynx

    Radiology

    (1977)
  • L.V. Johansen et al.

    Carcinoma of the nasopharynxAnalysis of treatment results in 167 consecutively admitted patients

    Head Neck Surg

    (1992)
  • W.E. Fee et al.

    Long-term survival after surgical resection for recurrent nasopharyngeal cancer after radiotherapy failure

    Arch Otolaryngol Head Neck Surg

    (1991)
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