ORIGINAL ARTICLE BRACHYTHERAPY BOOST FOR T1/T2 NASOPHARYNGEAL CARCINOMA

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1 ORIGINAL ARTICLE BRACHYTHERAPY BOOST FOR T1/T2 NASOPHARYNGEAL CARCINOMA Richard Yeo, FRCR, 1 Kam Weng Fong, FRCR, 1 Siew Wan Hee, MSc, 2 Eu Tiong Chua, FRCR, 1 Terence Tan, FRCR, 1 Joseph Wee, FRCR 1 1 Department of Radiation Oncology, National Cancer Centre Singapore, Singapore. richard.yeo.m.c@nccs.com.sg 2 Department of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore Accepted 18 February 2009 Published online 17 June 2009 in Wiley InterScience ( DOI: /hed Abstract: Background. The aim of this study was to review our experience and demonstrate the safety of intracavitary brachytherapy (ICB) in patients with nasopharyngeal carcinoma (NPC). Methods. Hundred seventy-eight patients with early T1-2b disease underwent radical external beam radiation therapy (EBRT) followed by ICB boost. The primary tumor received 66 Gy of EBRT over 33 fractions using 6 or 10 MV photons. ICB insertions were performed 1 week later, delivering 10 Gy in 2 fractions over 8 days. Kaplan-Meier survival analyses were used to calculate the actuarial 5-year overall survival (OS), cause-specific survival, local control, and disease-free survival (DFS). Results. Five-year local control rates were 91.6%. OS, DFS, and cause-specific survival were estimated to be 85.25%, 81.7%, and 87.9%, respectively. Median follow-up was 86 months. There were no documented serious complications noted with ICB. Conclusion. ICB boost supplementing radical EBRT is an excellent method of enhancing local control for patients with NPC with early T1-2b disease. VC 2009 Wiley Periodicals, Inc. Head Neck 31: , 2009 Keywords: brachytherapy; radiotherapy; nasopharyngeal carcinoma; local control Correspondence to: R. Yeo VC 2009 Wiley Periodicals, Inc. The incidence of nasopharyngeal carcinoma (NPC) varies worldwide, with rates in the West quoted as low as 0.3 per 100,000 in Los Angeles, California, USA, 1 to the rates in Southern China with estimates as high as 30 to 50 per 100, In Singapore, the age standardized incidence for NPC in men is 12.5 per 100,000 making it the sixth most frequent cancer in men. 3 The histological subtype of NPC also varies worldwide, squamous cell carcinoma (WHO type I) constitutes the main histological subtype in the West, whereas undifferentiated carcinoma (WHO type III) is found predominantly in the East. In our local context, Fong et al 4 noted the incidence of NPC with the undifferentiated subtype to be 92%. The primary treatment modality for NPC is radiotherapy. Supplementation of intracavitary brachytherapy (ICB) to boost the total dose around the nasopharynx, and enhance local control, have been well described From 1996 to 2000, our center adopted a protocol to routinely use ICB boosts for all T1/2 tumors treated with radical intent. This study aimed to describe our brachytherapy technique and illustrate its efficacy and safety Brachytherapy for Nasopharyngeal Carcinoma HEAD & NECK DOI /hed December 2009

2 PATIENTS AND METHODS Patients with biopsy-proven NPC underwent routine staging investigations: CT/MRI of the posterior nasal space, chest X-ray, ultrasound of the hepatobiliary system, bone scan, full blood count, and renal and liver function tests. All patients were referred for dental assessment. Patients were initially staged according to Ho s classification, the Union Internationale Contre le Cancer (UICC)/American Joint Committee on Cancer (AJCC) 1997 classification system. For the purposes of this study, patients treated before 1998 were retrospectively assigned an UICC 1997 stage from the clinical records. All patients with nonmetastatic T1 and T2 tumors were offered external beam radiotherapy (EBRT) followed by ICB. Patients with more locally advanced tumors were not treated with ICB and were excluded from this analysis. EBRT was prescribed to 66 Gy in 2 Gy fractions for 6 1 = 2 weeks. Details of our technique are described later. ICB followed after a 1-week break. EBRT Technique. Patients were treated with either a standard 3-field technique or a longfield technique, 4 the latter designed to encompass any bulky level in 2/5 lymph nodes and the primary site in 1 contiguous volume. Both techniques required an anterior neck field matched at its superior margin with the primary volume and bordered inferiorly by the base of the suprasternal notch and are described previously. 16 In essence, EBRT was treated in 2 phases, delivering 66 Gy in 33 fractions over 6.5 weeks to the posterior nasal space and the adjacent tissues using a 6 MV LINAC. Bulky neck nodes were boosted via electrons for a total dose of 70 to 76 Gy at the discretion of the attending physician. both ETTs are inserted, they are secured with a clamp and the positions of our applicators are adjusted with the help of fluoroscopy till an ideal placement was achieved. The ETT cuffs are then simultaneously inflated with the radiographic contrast. Following a final check, orthogonal films are then taken. The radiation oncologist marks out the length of the treatment volume on the lateral film. The prescription point is marked 0.5 cm beyond the surface of the inflated cuff (surrogate for mucosal surface). The Gammadot computer planning program uses a dose-point optimization algorithm to optimize dwell time. Isodose plots are generated and superimposed on the simulator films to check distribution in the sagital and coronal planes (Figure 1). Once the distribution was satisfactory, the dummy source trains were removed and the source applicator was inserted and connected to the Iridium-192 Gammamed high-dose-rate (HDR) remote after loading machine (RAL). The applicators were removed after treatment and a separate set of insertions and simulations were performed for the next treatment a week later. A typical dose of 10 Gy was prescribed to 0.5 cm, delivered in 2 fractions over 8 days. This gave a nominal cumulative dose of 76 Gy to the nasopharynx, taking into account the EBRT dose. Brachytherapy Details. This technique is largely modeled after Wang s, 13 with a few modifications. After administering a local anesthetic to the nasal passages, we inserted a pediatric endotracheal tube (ETT) along the middle or inferior turbinates. Passage along the former should place the tubes nearer the roof of the posterior nasal space which is ideal. Closed end catheters are then introduced into the ETT. The ideal position is obtained when the tip of the catheter is approximately 0.5 to 1.0 cm below the free edge of the soft palate. The dummy source train is then inserted and held by tape to the catheter. When FIGURE 1. Simulation film with isodoses plotted. [Color figure can be viewed in the online issue, which is available at www. interscience.wiley.com.] Brachytherapy for Nasopharyngeal Carcinoma HEAD & NECK DOI /hed December

3 Study Design. Study approval was obtained after application from our Institutional Review Board (IRB) to conduct this retrospective review. Our NPC database records were reviewed, and all patients who underwent ICB from January 1, 1997, to December 31, 1998, had their records retrieved. Baseline data for descriptive statistics as well as doses, techniques, and complications of radiotherapy treatment were noted. All patient follow-up records of events were noted until our censoring date of April 30, 2006, was reached. Patients were staged according to the 1997 UICC/AJCC system. Inclusion criteria included all T1-T2 histologically proven NPC (WHO Types I III), regardless of nodal status, nonmetastatic disease, completion of full course of EBRT, and completion of at least 1 fraction of ICB. Exclusion criteria included patients who received ICB as salvage therapy for recurrent disease, patients who had previous head and neck radiotherapy, either EBRT or ICB, previous cancers except basal cell carcinoma of the skin, inadequate staging investigations/missing data as detailed earlier, and patients who were not resident in Singapore and had no follow-up beyond the first year after completion of radiotherapy. Regular follow-up appointments were scheduled in accord with our local NPC protocol, which alternates consultations with our radiation oncologist and our ENT colleagues. The patient sees a doctor monthly for the first year, every 2 months for the second, quarterly for the third, half yearly for the fourth, then yearly thereafter. Follow-up CT/MRI scans of the posterior nasal space, chest X-ray, and blood investigations were routinely done at 3 months after the completion of radiotherapy and thereafter yearly until 5 years. Relevant investigations such as liver scans, bone scans, and other blood tests were done at the discretion of the doctor. Statistical Analysis. Categorical patient characteristics were presented in frequency and percentage. Comparisons between categorical characteristics were compared by Pearson s chi-square test or Fisher s exact test. The overall survival (OS) interval was calculated from the date of histological and/or radiological proof of diagnosis to time of death from any cause, whereas the cause-specific survival interval was until time of death from the cancer. Patients who were lost to follow-up were considered as censored cases. Time to disease recurrence was documented from the date of histological and/or radiological proof of diagnosis to date of discovery of local, regional, and/or distant recurrence or death from any cause (as first event). Patients who were still free from disease at last follow-up were considered as censored cases. Local control interval was calculated from 4 weeks after the date of the last EBRT treatment as this was usually the date of the first follow-up session when the radiation oncologist would review the posterior nasal space endoscopically to the time of local recurrence. Patients who did not experience local recurrence were censored. Kaplan-Meier estimator was used to obtain estimates for overall disease-free survival and local control survival functions. A 2-sided p value of <.05 was considered to be statistically significant. All analyses were performed using the SPPS program. RESULTS Our records show that 231 patients had undergone ICB for our study period of January 1, 1997, to December 31, Fifty-three patients were excluded for the following reasons: 19 patients notes were untraceable; 20 patients were treated for recurrent/persistent disease; 9 patients were non-singaporean residents with less than 1 year of follow-up; 3 patients were non-npc in origin; 2 patients in which ICB was interrupted or delayed by more than 1 month. A total of 178 patients were deemed eligible for our study. Descriptive Statistics. Male-to-female ratio was 2.5:1; 95% were Chinese patients. Only 4% of patients had a positive family history of NPC. Median age at presentation was 47 years. Ninety-five percent of patients had the undifferentiated (WHO III) histology. One hundred four (58.4%) had T1 tumors, 73 (41.0%) had T2b tumors, and only 1 had a T2a tumor. (For ease of data analysis, the singular T2a case was merged with the T2b cases to form the T2 group.) In accord with the UICC/AJCC 1997 classification of NPC, 52 (29.2%) had stage 1 disease, 79 (44.4%) had stage 2 disease, 38 (21.3%) had stage 3 disease, and 9 (5.1%) had stage 4 disease. Median follow-up was 86 months (range, ). All the patients underwent 6.5 to 7 weeks of EBRT followed by ICB 1 week later. The 1612 Brachytherapy for Nasopharyngeal Carcinoma HEAD & NECK DOI /hed December 2009

4 patients underwent radical neck dissection successfully; 1 had further interstitial brachytherapy to the neck. Unfortunately, 1 died of disease exactly 2 years after relapse, whereas another died of cardiovascular disease. A third developed distant metastases 2.5 years later and was referred for chemotherapy. Seventeen patients with distant metastases were noted: 10 have died, 6 have defaulted follow-up, and the remaining 1 is still on regular follow-up. FIGURE 2. Local control stratified according to T classification. majority of patients (97.2%) tolerated the 2 insertions well, only 5 patients (2.8%) had 1 insertion. Mean dose delivered per insertion was 5.01 Gy (range, , pooled SD 0.19). Five patients had concomitant chemoradiotherapy. Local and Regional Control. The 5-year local control rate was 91.6%. There appeared to be no difference in local control rate between patients who had T1 versus T2 disease (90.1% vs 94.2%, respectively, p ¼.766; Figure 2). Overall stage stratified local control rates were 89.1%, 93.2%, and 90.6% for stages 1, 2, and 3, respectively. All of the 9 patients who were seen with stage 4 disease were still free of local recurrence at time of follow-up. Of the 33 patients who had relapse, 14 failed locally (including 1 who had distant relapse concomitantly). After restaging, it was determined that 4 relapsed with T1 disease, 3 with T2, 5 with T3, and 2 with T4 disease. All 14 had received radiotherapy for salvage, except the 1 with distant relapse who was referred for chemotherapy only. Median time to local relapse was months (range, ). Eleven (78%) of these patients were successfully salvaged with combinations of surgery, chemotherapy, and reirradiation. Two patients received further chemotherapy; 1 died because of disease progression and the other is still on regular follow-up. The last patient declined further treatment and died 2 months later. There were only 4 nodal disease failures (including 1 who failed after 71 months) and crude nodal disease control was 97.7%; 3 relapsed with N1 disease and 1 with N3 disease. All Overall Survival, Cause-Specific Survival, and Disease- Free Survival. At the time of analysis, there were altogether 26 recorded deaths. Twenty deaths were attributed by NPC, whereas 6 patients died of other causes. Information on deaths was obtained from the National Registry of Births and Deaths by running a query on the entire cohort against the registry database. The 5-year OS rate was 85.25%, and there was no significant difference between stages (p ¼.197). The 5-year stage-specific OS rates were 91.5%, 85.9%, 76.7%, and 77.8% for stages 1, 2, 3, and 4, respectively (Figure 3). Patients seen with T1 disease had marginally higher 5-year OS rate (86.4%) than those seen with T2 disease (83.7%, p ¼.480). The 5-year cause-specific survival rate was 87.9%. Although patients seen with earlier stage had better cause-specific survival than did those seen with later stage, the difference was not significant (p ¼.269). The 5-year cause-specific survival rates were 93.3%, 87.1%, 84.7%, and 77.8% for stages 1, 2, 3, and 4, respectively. Similar observations were noted for T classification in which the FIGURE 3. Overall survival stratified to UICC stage. Brachytherapy for Nasopharyngeal Carcinoma HEAD & NECK DOI /hed December

5 Foul smell and dry mucoid crusting were the most common complaint noted by both patient and physician alike. Additionally, chronic serous otitis media was also noted in about 20% of the patients. Self-limiting epistaxis was noted in a few patients, not necessitating hospital admission. Other chronic complications, in ascending order of frequency, were temporal lobe necrosis, cranial nerve palsy, endocrine dysfunction, and soft tissue fibrosis. These ranged from 1% to 9% (Table 1). Complications of treatment more likely due to ICB itself, such as nasal mucosal synechiae and nasopharyngeal ulceration, were occasionally noted although these were largely asymptomatic. The 5-year complication-free rate was 82.9%. There were no documented cases of soft tissue fistula formation. FIGURE 4. A: Disease-free survival stratified according to T classification. B: Disease-free survival stratified according to UICC stage. 5-year cause-specific survival rates were 90.1% and 85.1% for T1 and T2, respectively (p ¼.152). The 5-year disease-free survival (DFS) rate was 81.7% and similar to OS and cause-specific survival functions, there were no significant difference by UICC/AJCC and T classification. The T classification specific 5-year DFS rates were 84.0% and 78.7% for T1 and T2, respectively (p ¼.302; Figure 4A) and 87.1%, 81.5%, 72.7%, and 87.5% for stages 1, 2, 3, and 4, respectively (p ¼.574; Figure 4B). Complications. Xerostomia was noted universally in all patients attributable to the EBRT. DISCUSSION Most major centers around the world with experience in treating large numbers of patients with NPC have advocated the use ICB. Our initial experience with ICB was primarily for disease relapse. We found it safe and tolerable; patients also experienced relatively few side effects. As more evidence emerged of a tumor dose response relationship, our center s NPC protocol was altered to incorporate adjuvant ICB after EBRT as a standard for early T disease patients. The dose to tumor relationship was noted by Yan et al 17 who described the enhancement of local control beyond the conventional 70 Gy with EBRT. In their retrospective analysis, tumors boosted with reduced fields beyond 70 Gy had significantly higher local control and survival rates. Additionally, Lee et al 18 proposed that there was a 9% decrease in local control rate for each Gray below the conventional 66 to 70 Gy. Other dose response studies have also concluded that higher radiation dose affords better local control. 19 Table 1. Complication rates. Complication Rate, % Temporal lobe necrosis 1.1 Cranial neuropathy 7.9 Serous otitis media 19.7 Soft tissue fibrosis 9 Endocrine dysfunction 5.6 Nasopharyngeal ulceration 1.1 Palatal fibrosis Brachytherapy for Nasopharyngeal Carcinoma HEAD & NECK DOI /hed December 2009

6 In an article by Teo et al, 20 the authors described the use of ICB after EBRT for T1/T2 tumors in 2 instances, the first for locally persistent disease (n ¼ 126) and the second for adjuvant treatment (n ¼ 62). EBRT was treated to 60 Gy in 24 fractions over 6 weeks (uncorrected biologically equivalent dose (BED) 75 Gy). Endoscopic evaluation with or without biopsy was performed 4 to 6 weeks after the completion of EBRT to determine response. ICB was delivered by a HDR after loading machine to 24 Gy in 3 fractions over 15 days for locally persistent disease or 18 Gy in 3 fractions over 15 days for adjuvant treatment. This was compared with historical data (n ¼ 555) treated with EBRT alone. Five-year actuarial free of local failure rate (FLF) was significantly higher in the ICB group compared with the EBRT only group, 94.2% versus 88.3%, respectively. A comparison between the 2 indications for ICB (local persistence vs adjuvant) did not differ significantly in the statistical analysis: FLF 94.3% versus 94.5%, respectively. In separate analyses, the presence of a dose tumor control relationship above 60 Gy was realized and the administration of ICB was shown to be the only significant factor in determining local control. Levandag et al 10,21 has also published extensively about their experience using ICB. In accord with the Rotterdam NPC Protocol ( ), all patients (T1 T4) were treated with EBRT followed by ICB less than 1 week later. EBRT was given to 60 Gy for T1 to T2a and 70 Gy for T2b to T4. ICB was applied by a computerized after loading machine, HDR doses of 17 Gy in 5 fractions (6 hours apart) for T1 to T2a tumors (cumulative dose 77 Gy) and 11 Gy in 3 fractions for T2b-4 tumors (cumulative dose 81 Gy). The multivariate analysis revealed that 5-year local control and OS for T1-T2N0-1 tumors were 92% and 62%, respectively. For T3-4 tumors (without chemotherapy), 5-year local control and OS were 57% and 12%, respectively. Dose distribution comparisons for a subset of 18 patients (stages 1 4) between ICB and various conformal EBRT techniques (including intensity modulated radiotherapy [IMRT] and stereotactic radiotherapy [SRT]) were analyzed using CT-based programs. Dosimetrically, it was noted that ICB produced a significant underdosing of the clinical target volume (CTV) for patients with larger tumor bulk, ie, T3-T4 as compared with the alternative 3-dimensional conformal EBRT techniques. This led them to the conclusion that ICB is only suitable for patients with early T-stage tumors. This was further confirmed by Leung et al, 22 after analysis of 1070 patients with NPC. Ninety-seven patients (T3 and T4 were included) had ICB after EBRT for biopsy-proven persistent disease. ICB consisted of an Ir-192 source delivering 22.5 to 24 Gy of ICB in 3 weekly sessions. A comparison with T-classification matched patients treated in the same period found that 5-year actuarial local failure-free survival for T1-2 disease was 92.8% versus 83.7% (p ¼.064) in favor of ICB; T3-4 was 66.1% versus 69.4% (p ¼.59). The authors concluded that ICB is indeed beneficial and that routine ICB boost following EBRT for T1-2 tumors could improve local control. Chang et al 6 compared various EBRT doses with or without brachytherapy among 192 patients staged (UICC/AJCC 1987) T1-2N0M0. EBRT was given in 1.8 Gy fractions from 64.8 to 68.4 Gy for EBRT with brachytherapy or 68.4 to 72 Gy for EBRT only. Brachytherapy was given 1 week after the completion of EBRT using a Co-60 remote after loading system. One to 3 fractions of 5 to 5.5Gy were given with 1-week intervals between each fraction. Group I consisted of patients treated with EBRT <72.5 Gy, no brachytherapy; group II had EBRT with 1 to 2 fractions of brachytherapy to a cumulative dose of 72.5 to 75Gy; group III had EBRT and 3 fractions of brachytherapy to a cumulative dose of >75 Gy. Five-year local control was reported at 73.7%, 93.9%, and 79.5%, 5-year disease-specific survival was 77%, 95.5%, and 82.4% for groups I, II, and III, respectively. From these results, it was concluded that the addition of 1 to 2 fractions of brachytherapy improved the local control and survival. However, it was noted that there were more severe complications seen in patients who had brachytherapy. These included palate perforation and sphenoid floor perforation. In an effort to decrease such serious complications, a reduction to 2 to 2.5 Gy per fraction for brachytherapy was implemented and preliminary observations have noted no major complications so far. Lee and Syed 23,24 have both reported their long-term experiences with ICB for managing NPC. Doses of EBRT ranged from 50 to 72 Gy and 50 to 60 Gy, respectively. Lee s institution delivered brachytherapy with various techniques including low dose rate (LDR) Cs-137/Ra-226/Co- 60 from 1000 to 5400 cgy; HDR Ir-192 boost was prescribed in 1 or 2 fractions to 5 to 7 Gy. Fortythree patients were treated for primary NPC, Brachytherapy for Nasopharyngeal Carcinoma HEAD & NECK DOI /hed December

7 Table 2. Patient and tumor characteristics EBRT þ ICB EBRT only N Percentage N Percentage p value Age < Sex Male Female Race Chinese Malay Indian Other Histology Undifferentiated Squamous Other T classification T T2a T2b N classification N N N N UICC/AJCC stage b b Chemotherapy No Yes Abbreviations: EBRT, external beam radiation therapy; ICB, intracavitary brachytherapy; UICC, Union Internationale Contre le Cancer; AJCC, American Joint Committee on Cancer. and 5-year local control rate and OS were 89% and 86%, respectively. Syed used Ir-192 radioactive seeds to treat 15 patients after EBRT with mean maximum tumor dose Gy (cumulative dose Gy). He reported 5-year local control and OS to be 93% and 61%, respectively. Both authors have noted minimal side effects with excellent results following brachytherapy. An excellent publication by Leung et al 25 recently compared a large cohort of T1-T2b patients who were routinely boosted with ICB. This was compared with a historical group who only had EBRT. All patients received 66 Gy in 33 fractions of EBRT and the ICB group received 10 to 12 Gy in 2 fractions over 8 days. A significant 5-year local control rate of 95.8% versus 88.3% (p ¼.02) in favor of ICB was proven. In our experience, using ICB with an Ir-192 HDR RAL machine as an adjunct to EBRT for early T1-T2b tumors has yielded excellent results with our 5-year local control at 91.6% and survival at 85.25%. For our discussion, we took a further step to compare this against historical data from a cohort of patients, treated at our center with EBRT only. 4 Patients from our historical data were restaged according to the 1997 AJCC/UICC classification, and characteristics from the 2 cohorts are presented in Table 2. Patients from the cohort appeared to have more advanced T classification. They also had significantly higher N classification and hence, overall stage. Figure 5 shows the actuarial local control rates of the 2 cohorts; the 5- year local control for the current (EBRT þ ICB) versus historical (EBRT) cohort was 91.6% versus 86.3%, respectively (p ¼.050). However, the marginal difference was no longer significant after adjusted for T classification (p ¼.061). On the other hand, the current treatment seemed to be able to control the local recurrence better for patients seen with T2 disease (5-year local control rates were 94.2% against 83.3%, p ¼.051). As advanced nodal status does not directly impact on local control, it was not analyzed as an explanatory variable. This comparison suggests that supplementing EBRT with ICB enhances local control, with a trend toward significance. Our local control rate is largely reflective of the experiences observed in numerous centers worldwide FIGURE 5. Comparison between EBRT and EBRT þ ICB Brachytherapy for Nasopharyngeal Carcinoma HEAD & NECK DOI /hed December 2009

8 Table 3. Comparison of brachytherapy results. Time Local Control T/N classification No. EBRT ICB (after) EBRT only With ICB Teo et a 20 T1 2 (Ho s classification)* Gy/24# Gy/3# 4 6 wk 88.3% 94.2% Levendag et al 10 T1 2b, N Gy/30 35# Gy/3 5# <1 wk 92% Chang et al 6 T1 2N Gy/36 38# 5 11 Gy/1 2# 1 wk 73.7% 93.9% Lee et al 23 T1 T Gy/25 40# 5 7 Gy/1 2# 1 2 wk 91% Leung et al 25 T1 2b Gy/33# Gy/2# 1 wk 88.3% 95.8% Yeo et al T1 T2b Gy/33# 10 Gy/2# 1 wk 86.3% 91.6% Abbreviations: EBRT, external beam radiation therapy; ICB, intracavitary brachytherapy. *Ho s classification of T1/T2 is equivalent to Union Internationale Contre le Cancer (UICC)/American Joint Committee on Cancer (AJCC) 1997 T1 T2. UICC/AJCC 1987 T1 2 is T1 in updated 1997 staging. # Fractions. summarized in Table 3. We did not note any serious complications with the use of adjuvant ICB in this retrospective analysis. As noted by Teo et al, 20 the usual problems of nasopharyngeal ulceration and necrosis were occasionally noted, but these did not bother the patients so much as the foul smell and dry mucoid crusting of the nasopharynx which were common. We have found that strict adherence to regular nasal douching using a sodium bicarbonate solution has solved this problem for the majority of patients. Chang et al 6 also noted palatal perforation in some patients. In our experience, apart from some patients who have palatal fibrosis, we have not noted any patients with such serious complications. A crude estimate of our mean palatal dose from ICB (for both insertions) was 29.5 Gy (range, Gy). In the era of IMRT and the excellent local control rates achievable, 26,27 the additional efficacy, if any, of routine ICB boost is unknown. However, ICB is an effective and tolerable procedure that is simpler and more economical than IMRT. Hospitals without the benefit of IMRT could certainly utilize this as an adjuvant boost to achieve better local control. With the large patient cohort presented in this study, it is our hope that we may be able to further establish the role of ICB as an adjunct to 2-dimensional EBRT routinely in the treatment of early T1-T2b NPC. REFERENCES 1. Parkin DM, Muir CS, Whelan SL, Gao YT, Ferlay J, Powell J. Cancer incidence in five continents. Vol VI. IARC Scientific Publication. Lyon: IARC; p 6(120). 2. National Cancer Control Office, Nanjing Institute of Geography. Atlas of cancer in the People s Republic of China. Shanghai: China Map Press; A Seow, WP Koh, KS Chia, LM Shi, Lee HP, Shanmugaratnam K. Trends in cancer incidence in Singapore, 1968 to In Singapore Cancer Registry Report No. 6. Singapore Cancer Registry, data/hpb.home/files/edu/report_1968_2002.pdf pp Fong KW, Chua EJ, Chua ET, et al. Patient profile and survival in 270 computer tomography staged patients with nasopharyngeal cancer treated at the Singapore General Hospital. Ann Acad Med Singapore; 25: Amornmarn R, Prempree T, Sewchand W, et al. Radiation management of advanced nasopharyngeal cancer. Cancer 1983;52: Chang JTC, See LC, Tang SG, et al. The role of brachytherapy in early-stage nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 1996;36: Choy D, Sham JST, Wei WI, et al. Transpalatal insertion of radioactive gold grain for the treatment of persistent and recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 1993;25: Lee AWM, Poon YF, Foo W, et al. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during : overall survival and patterns of failure. Int J Radiol Oncol Biol Phys 1992;23: Lin ZX, Li DR. Preliminary experience of HDR brachytherapy for nasopharyngeal carcinoma. Abstract of the 8th International Brachytherapy Conference, Nice, France, Nov , Levendag PC, Schmitz PI, Jansen PP, et al. Fractionated high-dose-rate brachytherapy in primary carcinoma of the nasopharynx. J Clin Oncol 1998;16: Teo PML, Kwan WH, Yu P, et al. A retrospective study of the role of intracavitary brachytherapy and the prognosticators determining local tumor control after primary radical radiotherapy in 903 non-disseminated nasopharyngeal carcinoma. Clin Oncol 1996;8: Vikram B, Mishra UB, Strong EW, et al. Patterns of failure in carcinoma of the nasopharynx. I. Failure at the primary site. Int J Radiat Oncol Biol Phys 1985;11: Wang CC. Improved local control of nasopharyngeal carcinoma after intracavitary brachytherapy boost. Am J Clin Oncol 1991;14: Yamashita S, Kondo M, Inuyama Y, et al. Improved survival of patients with nasopharyngeal squamous cell carcinoma. Int J Radiat Oncol Biol Phys 1986;12: Zhang YW, Liu TF, Fi CX. Intracavitary radiation treatment of nasopharyngeal carcinoma by high dose rate afterloading technique. Int J Radiat Oncol Biol Phys 1989;16: Chong VFH, Tsao SY. Nasopharyngeal carcinoma. Singapore: Armour Publishing; pp Brachytherapy for Nasopharyngeal Carcinoma HEAD & NECK DOI /hed December

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