P Teo

The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Publications (69)302.51 Total impact

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    ABSTRACT: Epstein Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia, and the plasma level of EBV DNA is a highly sensitive marker of disease recurrence following radiotherapy. Leptomeningeal recurrence from NPC is extremely rare and difficult to diagnose; only 4 cases have been reported in the literature. We report a case of leptomeningeal recurrence in NPC that was diagnosed using imaging and plasma and cerebrospinal fluid EBV DNA assays, followed by a review of the literature.
    Oncology 02/2008; 74(1-2):119-22. · 2.17 Impact Factor
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    ABSTRACT: This randomized trial compared the rates of delayed xerostomia between two-dimensional radiation therapy (2DRT) and intensity-modulated radiation therapy (IMRT) in the treatment of early-stage nasopharyngeal carcinoma (NPC). Between November 2001 and December 2003, 60 patients with T1-2bN0-1M0 NPC were randomly assigned to receive either IMRT or 2DRT. Primary end point was incidence of observer-rated severe xerostomia at 1 year after treatment based on Radiotherapy Oncology Group /European Organisation for the Research and Treatment of Cancer late radiation morbidity scoring criteria. Parallel assessment with patient-reported outcome, stimulated parotid flow rate (SPFR), and stimulated whole saliva flow rate (SWSFR) were also made. At 1 year after treatment, patients in IMRT arm had lower incidence of observer-rated severe xerostomia than patients in the 2DRT arm (39.3% v 82.1%; P = .001), parallel with a higher fractional SPFR (0.90 v 0.05; P < .0001), and higher fractional SWSFR (0.41 v 0.20; P = .001). As for patient's subjective feeling, although a trend of improvement in patient-reported outcome was observed after IMRT, recovery was incomplete and there was no significant difference in patient-reported outcome between the two arms. IMRT is superior to 2DRT in preserving parotid function and results in less severe delayed xerostomia in the treatment of early-stage NPC. Incomplete improvement in patient's subjective xerostomia with parotid-sparing IMRT reflects the need to enhance protection of other salivary glands.
    Journal of Clinical Oncology 11/2007; 25(31):4873-9. · 18.04 Impact Factor
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    ABSTRACT: The aim of this study is to evaluate the deficiencies in target coverage and organ protection of 2-dimensional radiation therapy (2DRT) in the treatment of advanced T-stage (T3-4) nasopharyngeal carcinoma (NPC), and assess the extent of improvement that could be achieved with intensity modulated radiation therapy (IMRT), with special reference to of the dose to the planning organ-at-risk volume (PRV) of the brainstem and spinal cord. A dosimetric study was performed on 10 patients with advanced T-stage (T3-4 and N0-2) NPC. Computer tomography (CT) images of 2.5-mm slice thickness of the head and neck were acquired with the patient immobilized in semi-extended-head position. A 2D plan based on Ho's technique, and an IMRT plan based on a 7-coplanar portals arrangement, were established for each patient. 2DRT was planned with the field borders and shielding drawn on the simulator radiograph with reference to bony landmarks, digitized, and entered into a planning computer for reconstruction of the 3D dose distribution. The 2DRT and IMRT treatment plans were evaluated and compared with respect to the dose-volume histograms (DVHs) of the targets and the organs-at-risk (OARs), tumor control probability (TCP), and normal tissue complication probabilities (NTCPs). With IMRT, the dose coverage of the target was superior to that of 2DRT. The mean minimum dose of the GTV and PTV were increased from 33.7 Gy (2DRT) to 62.6 Gy (IMRT), and 11.9 Gy (2DRT) to 47.8 Gy (IMRT), respectively. The D(95) of the GTV and PTV were also increased from 57.1 Gy (2DRT) to 67 Gy (IMRT), and 45 Gy (2DRT) to 63.6 Gy (IMRT), respectively. The TCP was substantially increased to 78.5% in IMRT. Better protection of the critical normal organs was also achieved with IMRT. The mean maximum dose delivered to the brainstem and spinal cord were reduced significantly from 61.8 Gy (2DRT) to 52.8 Gy (IMRT) and 56 Gy (2DRT) to 43.6 Gy (IMRT), respectively, which were within the conventional dose limits of 54 Gy for brainstem and of 45 Gy for spinal cord. The mean maximum doses deposited on the PRV of the brainstem and spinal cord were 60.7 Gy and 51.6 Gy respectively, which were above the conventional dose limits. For the chiasm, the mean dose maximum and the dose to 5% of its volume were reduced from 64.3 Gy (2DRT) to 53.7 Gy (IMRT) and from 62.8 Gy (2DRT) to 48.7 Gy (IMRT), respectively, and the corresponding NTCP was reduced from 18.4% to 2.1%. For the temporal lobes, the mean dose to 10% of its volume (about 4.6 cc) was reduced from 63.8 Gy (2DRT) to 55.4 Gy (IMRT) and the NTCP was decreased from 11.7% to 3.4%. The therapeutic ratio for T3-4 NPC tumors can be significantly improved with IMRT treatment technique due to improvement both in target coverage and the sparing of the critical normal organ. Although the maximum doses delivered to the brainstem and spinal cord in IMRT can be kept at or below their conventional dose limits, the maximum doses deposited on the PRV often exceed these limits due to the close proximity between the target and OARs. In other words, ideal dosimetric considerations cannot be fulfilled in IMRT planning for T3-4 NPC tumors. A compromise of the maximal dose limit to the PRV of the brainstem and spinal cord would need be accepted if dose coverage to the targets is not to be unacceptably compromised. Dosimetric comparison with 2DRT plans show that these dose limits to PRV were also frequently exceeded in 2DRT plans for locally advanced NPC. A dedicated retrospective study on the incidence of clinical injury to neurological organs in a large series of patients with T3-4 NPC treated by 2DRT may provide useful reference data in exploring how far the PRV dose constraints may be relaxed, to maximize the target coverage without compromising the normal organ function.
    Medical Dosimetry 02/2007; 32(4):263-70. · 1.01 Impact Factor
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    ABSTRACT: To define the dose-response relationship of nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of 66 Gy when the basic radiotherapy (RT) course was given by the 2D Ho's technique. Data from all five regional cancer centers in Hong Kong were pooled for this retrospective study. All patients (n = 2426) were treated with curative-intent RT with or without chemotherapy between 1996 and 2000 with the basic RT course using the Ho's technique. The primary endpoint was local control. The prognostic significance of dose-escalation ('boost') after 66 Gy, T-stage, N-stage, use of chemotherapy, sex and age (< or =40 years vs >40 years) was studied. Both univariate and multivariate analyses were performed. On multivariate analysis, T-stage (P < 0.01; hazard ratio [HR], 1.58) and optimal boost (P = 0.01; HR, 0.34) were the only significant factors affecting local failure for the whole study population, and for the population of patients treated by radiotherapy alone, but not for patients who also received chemotherapy. The following were independent determinants of local failure for patient groups with different T-stages treated by radiotherapy alone: use of a boost in T1/T2a disease (P = 0.01; HR, 0.33); use of a boost (P < 0.01; HR, 0.60) and age (P = 0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors treated by radiotherapy alone and given a boost, the use of a 20 Gy-boost gave a lower local failure rate than a 10 Gy-boost. There was no apparent excess mortality attributed to RT complications. Within the context of a multi-center retrospective study, dose-escalation above 66 Gy significantly improved local control for T1/T2a and T3/4 tumors when the primary RT course was based on the 2D Ho's technique without additional chemotherapy. 'Boosting' in NPC warrants further investigation. Caution should be taken when boosting is considered because of possible increase in radiation toxicity.
    Radiotherapy and Oncology 05/2006; 79(1):27-33. · 4.52 Impact Factor
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    ABSTRACT: This phase III randomized study compared concurrent cisplatin-radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m(2) weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval [CI] = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT (P = .049, hazard ratio [HR] = 0.71 [95% CI = 0.5 to 1.0]). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage (P = .74, HR = 0.93 [95% CI = 0.59 to 1.4]), whereas there was a difference between the arms for T3/T4 stage (P = .013, HR = 0.51 [95% CI = 0.3 to 0.88]), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.
    CancerSpectrum Knowledge Environment 05/2005; 97(7):536-9. · 14.07 Impact Factor
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    ABSTRACT: To analyze the treatment results achievable for nasopharyngeal carcinoma in the modern era to identify the key failures for future improvement and to provide an updated baseline for future trials. The results of 2687 consecutive patients treated at all public oncology centers in Hong Kong during 1996-2000 were retrospectively analyzed. The stage distribution (by American Joint Committee on Cancer and International Union Against Cancer staging system, 1997) was 7% Stage I, 41% Stage II, 25% Stage III, and 28% Stage IVA-B. All patients were irradiated with 6-MV photons and the median total dose was 66 Gy. Only 23% of patients had additional treatment with chemotherapy. The 5-year local, nodal, and distant failure-free rates were 85%, 94%, and 81%, respectively; patients with local failure had significantly higher risk of nodal and distant failures. The 5-year progression-free, overall, and cancer-specific survival rates were 63%, 75%, and 80%, respectively. The presenting stage was the most important prognostic factor for all endpoints: with overall survival decreasing from 90% for Stage I to 58% for Stage IVA-B. The results achieved by the 2070 patients treated by radiotherapy alone were almost identical to that of the whole series, the distant failure-free rate among patients with locoregional control was 89% for Stage I-II and 75% for Stage III-IVB. The 860 patients (32%) staged with magnetic resonance imaging achieved significantly better results than those staged by computed tomography, the overall survival being 93% vs. 83% for Stages I-II, and 72% vs. 63% for Stages III-IVB (p = 0.001). Treatment results for nasopharyngeal carcinoma have substantially improved in the modern era; future trials should be based on updated baseline results. Further reduction of distant failure is important for future breakthrough, particularly for patients with advanced disease.
    International Journal of Radiation OncologyBiologyPhysics 04/2005; 61(4):1107-16. · 4.52 Impact Factor
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    ABSTRACT: Nasopharyngeal carcinoma (NPC), an endemic tumor in southern China, has three unique etiologic factors, including genetic susceptibility, chemical carcinogens, and association with Epstein-Barr virus (EBV) infection. Recent identification of critical genetic changes in this cancer has allowed the description of a multistep model for the pathogenesis of NPC. NPC is highly radiosensitive and chemosensitive. Attempts have been made to improve treatment results by integrating radiotherapy with some form of chemotherapy. Here, we review the current evidence available on the various chemotherapy-radiotherapy sequencing approaches and seek to define the optimal integration of radiotherapy and chemotherapy. Despite consistently high response rates to platinum-based neoadjuvant chemotherapy, none of six randomized studies of neoadjuvant and/or adjuvant chemotherapy showed any improvement in overall survival, although two did demonstrate significant improvement in local control rates and progression-free survival. However, three randomized studies of concurrent cisplatin-radiotherapy one with, and two without, adjuvant chemotherapy demonstrated significant improvement in progression-free survival and two of these have demonstrated improvement in overall survival. Preliminary data on the use of neoadjuvant chemotherapy followed by concurrent chemoradiation have been highly encouraging. Concurrent cisplatin-radiation with or without adjuvant chemotherapy should be considered as standard practice for locoregionally advanced NPC. The addition of neoadjuvant chemotherapy warrants further investigation and appears to be the most likely approach to further improve treatment results.
    Seminars in Oncology 01/2005; 31(6):794-801. · 4.33 Impact Factor
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    ABSTRACT: This review describes the clinical background that underlies the transition from two-dimensional to three-dimensional (3D) planning techniques in the treatment of nasopharyngeal cancer (NPC). A systematic search of the Medline was performed using 'nasopharyngeal carcinoma', 'radiotherapy', '3-dimensional conformal radiotherapy', 'stereotactic radiosurgery/radiotherapy' and 'intensity-modulated radiotherapy' as keywords. Citing evidence from the published literature and their own institutional experience, the authors critically examined the positive impact of 3D methods--with emphasis on intensity-modulated radiotherapy (IMRT)--on target coverage and geometric accuracy, sparing of normal organs, and dosimetric homogeneity. Potential problems related to the widespread practice of IMRT such as quality assurance, utilization of medical resources and the risk of developing radiation-induced secondary cancers were highlighted. Application of IMRT within the context of altered fractionation, dose escalation and concurrent chemotherapy were discussed. The article concluded with a suggested treatment approach and research direction for different stages of NPC.
    Radiotherapy and Oncology 12/2004; 73(2):163-72. · 4.52 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    International Journal of Radiation OncologyBiologyPhysics 12/2004; 60(5):1440-50. · 4.52 Impact Factor
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    ABSTRACT: PURPOSE: To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. PATIENTS AND METHODS: Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. CONCLUSION This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC.
    Journal of Clinical Oncology 09/2004; 22(15):3053-60. · 18.04 Impact Factor
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    ABSTRACT: To evaluate the current UICC/AJCC Staging System for nasopharyngeal carcinoma and to search for ways of improving the system. This is a retrospective analysis of 2687 consecutive patients treated in five public centres in Hong Kong during the period 1996-2000. All patients were staged by computed tomography, magnetic resonance imaging, or both. The prognostic significance of the current stage assignment on various aspects of tumour control was evaluated. T-category, N-category and stage-group were all significant prognostic factors for major end points (P < 0.01). However, the distinction of prognosis between Stage I and II was insignificant (5-year cancer-specific survival being 92% vs 95%; P = 0.13). Multivariate analyses (corrected for age and sex) revealed lack of significance between T2a and T1 in hazards of local and distant failures, N3a and N2 in distant failure and subgroups of T1-2N0 in cancer-specific deaths. Corresponding down-staging of T2a to T1, N3a to N2, and subgroup T2N0 to stage I, resulted in more even and orderly increase in the hazard ratio of cancer-specific deaths (from 1 for stage I to 1.98 for II, 3.5 for III, 6.08 for IVA and 8.62 for IVB), better hazard consistency among subgroups of the same stage and more balanced stage distribution. The current UICC/AJCC Staging System could be further improved by the modifications suggested; validation of the current proposal by external data is urgently awaited.
    Clinical Oncology 06/2004; 16(4):269-76. · 2.86 Impact Factor
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    ABSTRACT: This pilot study assesses the psychosocial impact of different modalities of breast cancer surgery in Chinese patients and their husbands. Thirty-six patients who underwent conservative breast therapy (BCT) for breast cancer were compared with 36 women who underwent total mastectomy (TM) on four aspects of psychosocial adjustment. They were matched in pairs in terms of stage of disease, age and time since surgery. Where available, their husbands were also consented for similar assessment. Women who underwent BCT showed a significantly better response to their body and sexual image than those who underwent TM. This difference did not translate into any significant difference in terms of emotional and symptomatic aspects, daily activities, or fear of recurrences. The husbands of patients in the TM group showed significantly more emotional and symptomatic distress and greater change in the perception of their wives' body and sexual images. This is the first of such study conducted in a Chinese population. The lack of differences in certain psychosocial aspects may indicate a generally good adjustment in the TM patients after their surgery. It may also relate to the fact that volunteers for the study were themselves representative only of the patient population who adapted well to the surgery, and those patients who were emotionally distressed tended to decline to participate. Psychosocial disruption in the patients' families is reflected in our study where patients' husbands in the TM group were significantly more disturbed. However, due to the limited number of patients studied, the findings are not yet conclusive and require further studies for confirmation.
    Psycho-Oncology 03/2004; 13(2):132-9. · 3.51 Impact Factor
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    ABSTRACT: This study prospectively examines the prognostic role of p53 oncoprotein (p53), Ki67-antigen (Ki67), tumor angiogenesis (MVD), epidermal growth factor receptor (EGFR), and HER2 receptor protein (HER2) expression in Chinese with undifferentiated nasopharyngeal carcinoma (NPC). Seventy-eight Chinese were recruited from October 1995 to July 1997 at the Prince of Wales Hospital, Hong Kong. Pretreatment immunohistochemical preparations of the primary tumor were made, and clinical data were collected prospectively until October 30, 2000. The markers were correlated with overall survival (OS), disease-free survival (DFS), time to progression (TTP), and UICC stage. On univariate analysis, EGFR expression correlated with poorer OS (p =.0001), DFS (p =.01), shorter TTP (p =.0001), and advanced T stage (p =.036). Strong EGFR expression, when compared with weak or moderate, was associated with poorer OS (p =.04) and shorter TTP in a subgroup of patients with UICC stage III-IV disease. HER2 expression was associated with advanced UICC stage (p =.006). The presence of p53 expression correlated with poorer DFS (p =.01) and a trend toward shorter TTP (p =.06). No correlation was found with Ki67-antigen or MVD. On multivariate analysis, only EGFR expression was significantly linked to shorter OS and TTP. EGFR expression in undifferentiated NPC is associated with a poor clinical outcome. A prognostic role of p53 and HER2 expression is suggestive but not consistently defined in this study. The relatively high prevalence of positive staining for EGFR supports the use of molecular targeted therapy in this disease.
    Head & Neck 11/2003; 25(10):864-72. · 2.83 Impact Factor
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    ABSTRACT: To study pre-treatment cell kinetics and their clinical correlations in nasopharyngeal carcinoma (NPC). Ninety newly diagnosed NPC patients were studied using in vivo Bromodeoxyuridine (BrdU) labeling and flow cytometric analysis. Immunohistochemical staining for BrdU and Ki 67 was also performed. The median S-phase duration (Ts) was 6.2 h (range 3.5-18.7 h), median flow cytometric labeling index (FCM-LI) was 7.4% (1.3-37.6%), and median potential doubling time (Tpot) was 3.6 days (0.5-19.9 days). The median histologic labeling index (H-LI) was 12.4% (1.2-43.3%), and median histologic Tpot (H-Tpot) was 2.1 days (0.5-33.3 days). FCM-LI and H-LI were both positively correlated with Ki67 whereas Tpot and H-Tpot were both negatively correlated with Ki67 and N-stage. In univariate analysis, Tpot and H-Tpot showed a trend for progression free survival. Tpot was significantly associated with local relapse free survival, but lost its significance in multivariate analysis. N-stage was the only significant prognostic factor for all radiotherapy outcomes in both univariate and multivariate analyses. Tpot was the only pre-treatment cell kinetic parameter for which some evidence was found for an association with survival in NPC patients. Future studies should aim to combine cell kinetic parameters together with other biological markers and clinical parameters to provide more useful prognostic information to guide individual patient's therapy.
    Radiotherapy and Oncology 11/2003; 69(1):53-62. · 4.52 Impact Factor
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    ABSTRACT: To compare intensity-modulated radiotherapy (IMRT) with two-dimensional RT (2D-RT) and three-dimensional conformal radiotherapy (3D-CRT) treatment plans in different stages of nasopharyngeal carcinoma and to explore the feasibility of dose escalation in locally advanced disease. Three patients with different stages (T1N0M0, T2bN2M0 with retrostyloid extension, and T4N2M0) were selected, and 2D-RT, 3D-CRT, and IMRT treatment plans (66 Gy) were made for each of them and compared with respect to target coverage, normal tissue sparing, and tumor control probability/normal tissue complication probability values. In the Stage T2b and T4 patients, the IMRT 66-Gy plan was combined with a 3D-CRT 14-Gy boost plan using a 3-mm micromultileaf collimator, and the dose-volume histograms of the summed plans were compared with their corresponding 66-Gy 2D-RT plans. In the dosimetric comparison of 2D-RT, 3D-CRT, and IMRT treatment plans, the T1N0M0 patient had better sparing of the parotid glands and temporomandibular joints with IMRT (dose to 50% parotid volume, 57 Gy, 50 Gy, and 31 Gy, respectively). In the T2bN2M0 patient, the dose to 95% volume of the planning target volume improved from 57.5 Gy in 2D-RT to 64.8 Gy in 3D-CRT and 68 Gy in IMRT. In the T4N2M0 patient, improvement in both target coverage and brainstem/temporal lobe sparing was seen with IMRT planning. In the dose-escalation study for locally advanced disease, IMRT 66 Gy plus 14 Gy 3D-CRT boost achieved an improvement in the therapeutic ratio by delivering a higher dose to the target while keeping the normal organs below the maximal tolerance dose. IMRT is useful in treating all stages of nonmetastatic nasopharyngeal carcinoma because of its dosimetric advantages. In early-stage disease, it provides better parotid gland sparing. In locally advanced disease, IMRT offers better tumor coverage and normal organ sparing and allows room for dose escalation.
    International Journal of Radiation OncologyBiologyPhysics 06/2003; 56(1):145-57. · 4.52 Impact Factor
  • Cancer treatment and research 02/2003; 114:275-93.
  • Peter M L Teo, Anthony T C Chan
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) is highly radiosensitive and patients presenting with early disease have a high cure rate after radiotherapy. For patients presenting with locoregionally advanced disease, despite a high initial control rate with radiotherapy, the subsequent failure rates are significant. Concurrent cisplatin-radiotherapy with or without adjuvant chemotherapy have been demonstrated to significantly improve survival and is currently the standard treatment strategy for patients with locoregionally advanced disease. Encouraging phase II trials have been reported on the use of neoadjuvant chemotherapy followed by concurrent chemotherapy-radiotherapy, which may provide the optimal way to deliver chemoradiation in NPC. Improved radiotherapy techniques using intensity modulated methods or three-dimensional conformal methods may further improve local control by reducing geographical misses while preserving normal organ functions.
    Seminars in Cancer Biology 01/2003; 12(6):497-504. · 7.44 Impact Factor
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    ABSTRACT: Tumor hypoxia is known to be associated with resistance to chemotherapy, radiotherapy, and poorer survival. Recently, it is shown that hypoxia induces the expression of hypoxia-inducible factor-1alpha and 2alpha (HIF-1alpha and HIF-2alpha), which then up-regulates the expression of downstream genes such as carbonic anhydrase IX (CA IX) and vascular endothelial growth factor (VEGF). We examined the expression of HIF-1alpha, HIF-2alpha, CA IX, and VEGF by immunohistochemistry in nasopharyngeal carcinoma (NPC) biopsies from 90 consecutive patients recruited between 1994 and 1997 in a randomized controlled trial of chemoradiation in locally advanced NPC and investigated their relationship with survival. HIF-1alpha was expressed in 52 of 90 (58%), HIF-2alpha in 6 of 89 (7%), CA IX in 51 of 90 (57%), and VEGF in 54 of 90 (60%) of tumors. Tumor HIF-1alpha expression correlated significantly with that of CA IX (P = 0.008) and VEGF (P = 0.003). High tumor HIF-1alpha expression was associated with a trend for poor overall survival (P = 0.06). Tumors with a positive hypoxic profile (defined as high expression of both HIF-1alpha and CA9) were associated with worse progression-free survival (P = 0.04). Tumors with both hypoxic and angiogenic profile (defined as high VEGF expression) were associated with a worse progression-free survival (P = 0.0095). Overexpression of HIF-1alpha, CA IX, and VEGF is common in NPC, which is probably related to hypoxia up-regulated expression involving a HIF-dependent pathway, and is associated with poor prognosis. Targeting the hypoxia pathway may be useful in the treatment of NPC.
    Clinical Cancer Research 09/2002; 8(8):2595-604. · 7.84 Impact Factor
  • A T C Chan, P M L Teo, P J Johnson
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) is endemic in southern China where genetic abnormalities and Epstein-Barr virus (EBV) infection are critical in the pathogenesis of the disease. Circulating EBV-DNA has been shown to improve prognostication and monitoring of NPC patients. Radiotherapy is the mainstay treatment for early disease and concurrent cisplatin/radiotherapy has been demonstrated to prolong survival in locoregionally advanced disease. Ongoing studies of targeting agents and immunotherapeutic approaches may further improve treatment results.
    Annals of Oncology 08/2002; 13(7):1007-15. · 7.38 Impact Factor
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    ABSTRACT: To study the factors affecting the risk of symptomatic temporal lobe necrosis after different fractionation schedules. One thousand thirty-two patients with T1-2 nasopharyngeal carcinoma treated with radical radiotherapy in Hong Kong during 1990-1995 were studied. They were treated at four different centers with similar techniques but different fractionation schedules: 984 patients were given 1 fraction daily throughout (q.d.), and 48 patients were irradiated twice daily (b.i.d.) for part of the course. The median total dose was 62.5 Gy (range 50.4-71.2), dose per fraction was 2.5 Gy (range 1.6-4.2), and overall treatment time (OTT) was 44 days (range 29-70). In addition, 500 patients received supplementary doses for parapharyngeal extension, 113 received booster doses by brachytherapy, and 114 received sequential chemotherapy using cisplatin-based regimes. Altogether, 24 patients developed symptomatic temporal lobe necrosis: 18 from the q.d. group and 6 from the b.i.d. group. The 5-year actuarial incidence ranged from 0% (after 66 Gy in 33 fractions within 44 days) to 14% (after 71.2 Gy in 40 fractions within 35 days). Multivariate analyses showed that the risk was significantly affected by the fractional effect of the product of total dose and dose per fraction (hazard ratio [HR] = 1.04, 95% confidence interval [CI] 1.02-1.05), OTT (HR 0.88, 95% CI 0.80-0.97), and b.i.d. scheduling (HR 13, 95% CI 3-54). Repeating the analyses for patients treated with the q.d. schedules confirmed the independent significance of OTT in addition to the product of total dose and dose per fraction. The tentative results suggest that in addition to fractional dose, the OTT also had significant impact on the risk of temporal lobe necrosis, and b.i.d. scheduling increased the hazard further.
    International Journal of Radiation OncologyBiologyPhysics 06/2002; 53(1):75-85. · 4.52 Impact Factor

Publication Stats

3k Citations
302.51 Total Impact Points

Institutions

  • 1991–2008
    • The Chinese University of Hong Kong
      • Prince of Wales Hospital
      Hong Kong, Hong Kong
  • 2004–2007
    • Hong Kong Sanatorium & Hospital
      Hong Kong, Hong Kong
  • 1987–2005
    • Prince of Wales Hospital, Hong Kong
      Chiu-lung, Kowloon City, Hong Kong
    • Queen Mary Hospital
      Hong Kong, Hong Kong