Michael K M Kam

Prince of Wales Hospital, Hong Kong, Chiu-lung, Kowloon City, Hong Kong

Are you Michael K M Kam?

Claim your profile

Publications (32)143.11 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The modified radiosurgery-based arteriovenous malformation (AVM) score (modified AVM score or Pollock-Flickinger AVM score [PFAS]) is a simplified grading system developed to predict outcome after gamma knife radiosurgery for cerebral AVM. The purpose of this study was to test the PFAS in a cohort of patients managed with linear accelerator (LINAC) radiosurgery. We analyzed 70 consecutive patients with cerebral AVM treated with LINAC radiosurgery in Hong Kong. The scores were determined by the following equation: Modified AVM score=(0.1×volume [cm(3)])+(0.02×age [years])+(0.5×location). The location values are as follows: hemispheric/corpus callosum/cerebellar=0; basal ganglia/thalamus/brainstem=1. A total of 74% of patients presented with ruptured AVM before radiosurgery. The overall obliteration rate was 86%. Five (7%) patients developed new permanent neurological deficits from delayed bleeding or radiation-induced complications. Modified AVM score correlated with the percentage of patients with AVM obliteration without new neurological deficits (≤1, 96%; 1.01-1.50, 78%; 1.51-2.00, 90%; >2, 50%; Spearman's rho 0.354, p=0.003). In conclusion, the modified AVM score is a good predictor of patient outcome after LINAC radiosurgery in our cohort. The modified AVM score can be used to guide treatment selection for cerebral AVM and stratify patients for future comparative analyses.
    Journal of Clinical Neuroscience 07/2012; 19(9):1252-4. · 1.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the frequency of pseudoprogression of glioblastoma in Chinese patients receiving concomitant chemoradiotherapy and investigate its association with pseudoprogression and tumour molecular marker O(6)-methylguanine-DNA methyltransferase promoter methylation status. Case series with internal comparisons. University teaching hospital, Hong Kong. Patients with glioblastoma treated with concomitant chemoradiotherapy during April 2005 to June 2010 were reviewed. Magnetic resonance imaging brain scans, pre- and post-concomitant chemoradiotherapy and 3-monthly thereafter were reviewed by an independent neuroradiologist according to Macdonald's criteria. Relevant patient information (clinical condition, performance score, development of new neurological deficits, use of steroids, and survival) was retrieved. For each patient, O(6)-methylguanine-DNA methyltransferase methylation status was investigated with genomic DNA from formalin-fixed or paraffin-embedded sections of tumour tissues by methylation-specific polymerase chain reaction. During the study period, 28 primary glioblastoma patients underwent concomitant chemoradiotherapy. The mean age of the patients was 48 (range, 16-71) years. Thirteen patients (13/28, 46%) developed early radiological progression of the tumour after completion of concomitant chemoradiotherapy, of whom five (39%) were subsequently found to have had pseudoprogression. Patients with pseudoprogression showed a trend towards longer survival (22 months in pseudoprogression vs 17 months in all others vs 11 months in those with genuine progression). Among the 27 patients tested for O(6)-methylguanine-DNA methyltransferase promoter status, 12 (44%) were methylated. Two (2/12, 17%) in the methylated group had pseudoprogression, while three (3/15, 20%) in the unmethylated group had pseudoprogression. Nearly half of all patients (46%) developed early radiological progression (within 3 months of completing concomitant chemoradiotherapy). Moreover, about one in three of such patients had pseudoprogression. Pseudoprogression is an important clinical condition to be aware of to prevent premature termination of an effective treatment.
    Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine 06/2012; 18(3):221-5.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Concurrent chemoradiotherapy (CRT) confers survival benefit over radiotherapy (RT) alone in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). This study explored the prognostic significance of the total dose of cisplatin delivered during CRT. A retrospective analysis was performed in patients with stage II to IVB NPC (AJCC 6th edition) who participated in 3 prospective studies. All patients received cisplatin at a fixed dose of 40mg/m(2)/week during a 6-7-weeks course of CRT. Chi-square test was used in the univariate analysis. Relationship between prognostic factors, the total dose of cisplatin administered and time-to-event endpoints were analyzed with the Cox Hazards model. Two hundred and forty-one patients were identified with the following stage distribution: Stage II=13.7%, III=45.2%, IV=41.1%. The median total number of cycles of cisplatin administered per patient was 5 cycles (range 1-8 cycles). At a median follow-up of 56.5months (range 4.2-200.2months), 93 patients (38.6%) had relapsed and 85 patients (35.2%) died. For all patients, the total number of cycles of cisplatin delivered was significantly associated with survival in the univariate but not the multivariate analysis. In a sub-group analysis of 142 patients with stage II and III NPC, patients who received more than 5 cycles of cisplatin had significantly better overall survival than those who did not (hazard ratio 0.44; 95% confidence interval, 0.23-0.85; p=0.02). Number of cycles of cisplatin delivered is an independent prognostic factor in patients with stage II-III NPC undergoing CRT with weekly cisplatin.
    Radiotherapy and Oncology 01/2012; 104(3):300-4. · 4.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: (1) To review the patient profile, management outcome and prognostic factors of brain abscess; (2) To compare the neurological outcome of nasopharyngeal carcinoma (NPC)-related brain abscess with non-NPC related brain abscess. Retrospective review of consecutive patients diagnosed (radiologically and/or microbiologically) with brain abscess in a regional neurosurgical center in Hong Kong over a nine year period. Fifty-four patients were recruited into this study. There were 37 male and 17 female patients. Eighteen (33%) patients had previous radiotherapy for nasopharyngeal carcinoma. Only 31 (57%) patients had fever on presentation. White cell count and/or C-reactive protein, was raised in 41 (76%) patients on admission. Surgical drainage was carried out in 49 (91%) patients, either by aspiration through a craniotomy, by drainage with corticotomy, or excision of the abscess. Abscess culture was positive in 45 (83%) patients. Common organisms isolated included Streptococcus species (35%) and Peptostreptococcus species (18%). Anaerobes were isolated in 50% of the NPC-related abscesses. The mean follow-up time was 34 months. At the 6 months interval, 24 (44%) patients had good recovery. Favorable outcome was achieved in 30 (55%) patients. NPC-related brain abscess was associated with unfavorable neurological outcome (33%, p = 0.04). There was also a trend towards higher in-patient mortality in patients with NPC-related brain abscess (22%, p = 0.08). Brain abscess carried a substantial morbidity and mortality despite aggressive surgical and medical treatment. Patients with NPC-related brain abscess had a higher mortality and unfavorable neurological outcome.
    Clinical neurology and neurosurgery 12/2011; 114(6):560-3. · 1.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Based on our previous work on the clinical activity of cetuximab in recurrent nasopharyngeal carcinoma (NPC), we evaluated the feasibility of adding cetuximab to concurrent cisplatin and intensity-modulated radiotherapy (IMRT) in locoregionally advanced NPC. Patients with American Joint Committee on Cancer stage III-IVB NPC were given an initial dose of cetuximab (400 mg/m(2)) 7-10 days before receiving concurrent IMRT, weekly cisplatin (30 mg/m(2)/week) and cetuximab (250 mg/m(2)/week). Thirty patients (median age of 45 years) with stage III (67%), IVA (30%) and IVB (3%) nonkeratinizing NPC were enrolled. Grade 3-4 oropharyngeal mucositis occurred in 26 (87%) patients and 10 (33%) patients required short-term nasogastric feeding. Grade 3 radiotherapy-related dermatitis occurred in six patients (20%) and three patients (10%) had grade 3 cetuximab-related acneiform rash. These grade 3-4 skin and mucosal toxic effects were manageable and reversible. At a median follow-up of 31.8 months [95% confidence interval (CI) 26.2-32.1 months], the 2-year progression-free survival was 86.5% (95% CI 74.3% to 98.8%). Concurrent administration of cetuximab, weekly cisplatin and IMRT is a feasible strategy against locoregionally advanced NPC. Preliminary survival data compare favorably with historic data and further follow-up is warranted.
    Annals of Oncology 09/2011; 23(5):1287-92. · 7.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background The purpose of this study was to identify independent prognostic factors that influenced local relapse-free survival (LRFS) and overall survival (OS) of patients who underwent salvage surgery for residual or recurrent nasopharyngeal carcinoma (NPC).Methods Ninety-seven patients who had been treated with radiotherapy or chemoradiotherapy for NPC underwent a nasopharyngectomy for a residual or recurrent local tumor between November 1987 and June 2007. The subsequent minimum follow-up was 2 years. Univariate and multivariate analyses were performed to identify prognostic factors for LRFS and OS.ResultsThe 5-year LRFS and OS was 46.7% and 51.9%, respectively. On multivariate analysis for LRFS and OS, respectively, recurrent regional disease (hazard ratio [HR], 3.245; p = .008) and (HR, 4.990; p = .001), and positive surgical margins (HR, 5.963; p = .000), and (HR, 4.912; p = .000) were independent prognostic factors.Conclusion In patients undergoing surgical salvage nasopharyngectomy for residual or recurrent NPC, positive surgical margins have an independent negative influence on LRFS and OS. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
    Head & Neck 07/2011; 33(8):1126 - 1131. · 2.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: (1) To compare the survival of concomitant chemotherapy and radiotherapy with radiotherapy alone in Chinese patients with primary glioblastoma. (2) To determine the methylation status of O(6)Methylguanine DNA methyltransferase in Chinese primary glioblastoma, and to assess the prognostic value of O(6)Methylguanine DNA methyltransferase methylation status in such patients. Retrospective correlative analysis. University teaching hospital, Hong Kong. Patients diagnosed with histologically proven primary glioblastoma in the period of March 2005 to June 2007 were recruited. Genomic DNA was isolated from formalin-fixed and paraffin-embedded sections of glioblastoma tissues. Methylation-specific polymerase chain reaction for O(6)Methylguanine DNA methyltransferase was performed. Patients' information at presentation was collected (age, performance status, steroid use, extent of resection, complications, radiotherapy data, use of chemotherapy). Primary outcome was measured by overall survival while secondary outcome was measured by progression-free survival. Overall and progression-free survivals were estimated by the Kaplan-Meier technique. Outcomes were assessed for groups with and without concomitant chemoradiotherapy and for groups with and without O(6)Methylguanine DNA methyltransferase methylation. A total of 35 glioblastoma patients were recruited; 27 were male and 8 female. Their mean age was 50 years. In all, 17 received concomitant chemoradiotherapy, and 18 received radiotherapy only. Their median overall survival was 12 (range, 7-17) months and the median progression-free survival was 5 (range, 3-6) months. In the radiotherapy alone group, the median progression-free survival and overall survival was 4 (range, 3-5) months and 6 (range, 2-10) months, respectively. In the concomitant radiochemotherapy group, the median progression-free survival and overall survival was 6 (range, 2-10) months and 13 (range, 8-18) months, respectively. Fifteen (43%) of the tumour samples showed methylation of O(6)Methylguanine DNA methyltransferase. There was a trend towards overall longer survival in the group with methylated tumours compared to those with unmethylated tumours; respective values for median survival (ranges) were 17 (13-21) versus 10 (6-14) months (P=0.105). Our single-centre results indicated that Chinese glioblastoma patients who had received concomitant chemoradiotherapy showed a trend towards longer overall survival compared to those receiving radiotherapy alone. Approximately 43% of our Chinese glioblastoma samples showed methylation of O(6)Methylguanine DNA methyltransferase. O(6)Methylguanine DNA methyltransferase methylation may be a significant prognostic factor in Chinese glioblastoma patients.
    Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine 06/2011; 17(3):184-8.
  • [Show abstract] [Hide abstract]
    ABSTRACT: We aimed to evaluate the safety and efficacy of single-agent sunitinib in nasopharyngeal carcinoma (NPC). Eligible patients had progressive disease after prior platinum-based chemotherapy. Sunitinib was given as continuous once-daily dosing of 37.5 mg in 4-week cycles until progression. Thirteen patients were enrolled. Recruitment was stopped after two patients died of hemorrhagic events. All patients had previously received curative radiotherapy (RT) to nasopharynx/neck (including nine patients who had chemoradiotherapy). Patients received a median of three cycles of sunitinib. One patient was still on sunitinib with stable disease after 24 cycles. Hemorrhagic events occurred in nine patients (64%), including epistaxis in six, hemoptyses in three and hematemesis in two patients. Prior RT to thorax was significantly associated with hemoptyses (P = 0.03). Two patients with local tumor invasion into the carotid sheath developed fatal epistaxis/hematemesis within the first cycle of sunitinib, likely due to internal carotid blowout after tumor shrinkage. Sunitinib demonstrated modest clinical activity in heavily pretreated NPC patients. However, the high incidence of hemorrhage from the upper aerodigestive tract in NPC patients who received prior high-dose RT to the region is of concern. Direct vascular invasion by tumors appeared to increase the risk of serious bleeding.
    Annals of Oncology 02/2011; 22(6):1280-7. · 7.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Locally recurrent nasopharyngeal carcinoma (NPC) patients can be salvaged by reirradiation with a substantial degree of radiation-related complications. Stereotactic radiotherapy (SRT) is widely used in this regard because of its rapid dose falloff and high geometric precision. The aim of this study was to examine whether the newly developed intensity-modulated stereotactic radiotherapy (IMSRT) has any dosimetric advantages over three other stereotactic techniques, including circular arc (CARC), static conformal beam (SmMLC), and dynamic conformal arc (mARC), in treating locally recurrent NPC. Computed tomography images of 32 patients with locally recurrent NPC, previously treated with SRT, were retrieved from the stereotactic planning system for contouring and computing treatment plans. Treatment planning of each patient was performed for the four treatment techniques: CARC, SmMLC, mARC, and IMSRT. The conformity index (CI) and homogeneity index (HI) of the planning target volume (PTV) and doses to the organs at risk (OARs) and normal tissue were compared. All four techniques delivered adequate doses to the PTV. IMSRT, SmMLC, and mARC delivered reasonably conformal and homogenous dose to the PTV (CI <1.47, HI <0.53), but not for CARC (p < 0.05). IMSRT presented with the smallest CI (1.37) and HI (0.40). Among the four techniques, IMSRT spared the greatest number of OARs, namely brainstem, temporal lobes, optic chiasm, and optic nerve, and had the smallest normal tissue volume in the low-dose region. Based on the dosimetric comparison, IMSRT was optimal for locally recurrent NPC by delivering a conformal and homogenous dose to the PTV while sparing OARs.
    International journal of radiation oncology, biology, physics 04/2010; 79(1):71-9. · 4.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To review the experience with Onyx embolisation of cerebral arteriovenous malformation. Prospective study. A regional neurosurgical centre in Hong Kong. Data of patients with cerebral arteriovenous malformation who underwent Onyx embolisation over a 14-month period were prospectively collected. Eleven sessions of Onyx embolisation were performed in nine patients with cerebral arteriovenous malformations, seven of which had ruptured. Total occlusion was achieved in three (33%) of the patients, and subtotal occlusion (over 80% occlusion) in three out of four with Spetzler-Martin grade-III/IV malformations. One patient developed mild permanent neurological deficit. Onyx embolisation of cerebral arteriovenous malformations is feasible in Hong Kong. Careful patient and target selection are important.
    Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine 10/2009; 15(5):359-64.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nasopharyngeal carcinoma (NPC) is a platinum-sensitive cancer and excision repair cross-complementing group 1 (ERCC1) polymorphisms have been shown to predict survival in several cancers following platinum therapy. This multicenter study evaluated the activity of oxaliplatin and prolonged infusion of gemcitabine ('GEMOX' regimen) in recurrent NPC. Baseline blood samples were genotyped for the presence of ERCC1-118 gene polymorphisms. Forty-two patients were recruited, of whom most (61%) had metastatic disease. Of the 40 patients evaluated for response, the respective overall response and disease control rates were 56.1% and 90.2%. At a median follow-up of 14.8 months, the respective median overall survival and time to progression were 19.6 months [95% confidence interval (CI) = 12.8-22 months] and 9 months (95% CI = 7.3-10 months). Grade 3-4 toxic effects were uncommon. The distribution of ERCC1-118 genotypes from 29 patients was C/C (n = 17, 40.5%), C/T (n = 10, 23.8%) and T/T (n = 2, 4.8%). No differences in survival or response rates were found between genotypes. GEMOX is active in the treatment of recurrent NPC. Detection of single-nucleotide gene polymorphisms from genomic DNA in peripheral blood is feasible in NPC and further studies are warranted.
    Annals of Oncology 07/2009; 20(11):1854-9. · 7.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To compare the toxicities, tumor control, survival, and quality of life of nasopharyngeal cancer (NPC) patients treated with sequential neoadjuvant chemotherapy followed by concurrent cisplatin-radiotherapy (CRT) or CRT alone. Previously untreated stage III to IVB NPC were randomly assigned to (1) neoadjuvant docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks for two cycles, followed by cisplatin 40 mg/m(2)/wk concurrent with radiotherapy, or (2) CRT alone. Planned accrual was 30 patients per arm to detect 20% difference of toxicities based on 95% CIs. From November 2002 to November 2004, 65 eligible patients were randomly assigned to neoadjuvant chemotherapy followed by CRT (n = 34) or CRT alone (n = 31). There was a high rate of grade 3/4 neutropenia (97%) but not neutropenic fever (12%) during neoadjuvant chemotherapy. No significant differences in rates of acute toxicities were observed between the two arms during CRT. Dose intensities of concurrent cisplatin, late RT toxicities and quality of life scores were comparable in both arms. The 3-year progression-free survival for neoadjuvant versus control arm was 88.2% and 59.5% (hazard ratio = 0.49; 95% CI, 0.20 to 1.19; P = .12). The 3-year overall survival for neoadjuvant versus control arm was 94.1% and 67.7% (hazard ratio = 0.24; 95% CI, 0.078 to 0.73; P = .012). Neoadjuvant docetaxel-cisplatin followed by CRT was well tolerated with a manageable toxicity profile that allowed subsequent delivery of full-dose CRT. Preliminary results suggested a positive impact on survival. A phase III study to definitively test this neoadjuvant-concurrent strategy is warranted.
    Journal of Clinical Oncology 01/2009; 27(2):242-9. · 18.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate whether the approach used to the nasopharynx to perform a salvage nasopharyngectomy for recurrent or residual nasopharyngeal carcinoma influences survival. A retrospective case series. Eighty patients underwent a nasopharyngectomy via a transpalatal, maxillary swing, or midfacial degloving approach. Local progression-free, locoregional progression-free, and overall survival rates were calculated for each approach. For the whole group (N = 80), there were no significant differences in the survival rates between the three approaches. For the subgroup of patients with recurrent T1 and T2 tumors (n = 68), the local progression-free and locoregional progression-free survival rates were significantly better when a maxillary swing approach was used than when a midfacial degloving approach was used. The maxillary swing approach is associated with significantly better survival rates than the midfacial degloving approach when used to perform a salvage nasopharyngectomy for residual or recurrent T1 and T2 nasopharyngeal carcinoma.
    Otolaryngology Head and Neck Surgery 08/2008; 139(1):40-6. · 1.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The epidermal growth factor receptor (EGFR) is commonly overexpressed in nasopharyngeal carcinoma (NPC) and gefitinib inhibits NPC growth in vitro. Patients who progressed after prior platinum-based chemotherapy for recurrent NPC were given gefitinib orally at 500 mg/day at a 28-day cycle. Plasma Epstein-Barr virus (pEBV) DNA levels were obtained at specific intervals. Sixteen patients enrolled and 15 were evaluable for response. The median age was 49 years (range 34-64 years), and most patients were males with metastatic NPC. No objective response was seen and three patients had stable disease (SD) for 2.8 to 8.5 months. Radiological progression of disease coincided with rising levels of pEBV DNA in most patients, while the level of a patient with the longest duration of SD fell to an undetectable level at study completion. The mean time to progression and overall survival was 2.7 (standard error, SE +/- 0.5 months) and 12 months (SE +/- 1.7 months), respectively. No unexpected drug-related toxicities were seen. The study was prematurely terminated because there was insufficient activity to warrant progression to the second stage of accrual. This study found limited activity of gefitinib in recurrent NPC. Further evaluation of pEBV DNA as a biomarker of response in clinical trials of target-based agents is warranted.
    Cancer Chemotherapy and Pharmacology 07/2008; 62(1):59-64. · 2.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to determine whether the use of whole-body (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET)/CT alters staging and management of nasopharyngeal carcinoma (NPC) when compared with current staging practice. 52 patients with Stage III-IV NPC without distant metastases on chest X-ray/CT, abdominal ultrasound or bone scan were recruited for the study. Whole-body (18)F-FDG PET/CT and MRI of the head and neck were performed. The scans were compared for extent of the primary tumour (PT), cervical nodal metastases (CNM) and distant metastases (DM). Any discordance in results was assessed with respect to staging and impact on management. MRI and (18)F-FDG PET/CT scans were discordant in 28 (54%) patients. There was discordance in the extent of PT at 28 sites; in all sites, MRI showed more extensive tumour involving the nasopharynx (n = 8), skull base (n = 14), brain (n = 4) and orbit (n = 2). There was also variation among the extent of CNM in four nodes of the retropharyngeal region, with the nodes being positive on MRI. (18)F-FDG PET /CT did not identify any additional distant metastases but did identify a second primary tumour in the colon. The additional use of (18)F-FDG PET/CT did not "up-stage" the overall stage or change management in any patient. In conclusion, there is discordance between MRI and (18)F-FDG PET/CT, and the additional use of (18)F-FDG PET/CT for the current assessment of NPC at diagnosis does not appear to be justified in this cohort of patients.
    The British journal of radiology 05/2008; 81(964):291-8. · 2.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess the dosimetric effect of using a split-organ delineation approach during intensity-modulated radiotherapy (IMRT) treatment planning for advanced T-stage nasopharyngeal carcinoma (NPC). Twenty NPC patients with T3-4 tumours were studied. A reference (REF) IMRT plan was generated based on a standard treatment planning protocol, with a set of user-defined dose constraints for optimisation. An investigative (INV) IMRT plan was then generated based on the same protocol, but treating several organs at risk (OARs; parotid glands, temporal lobes, cochlea, auditory nerves and planning organ at risk volume [PRV] of the brainstem) as split organs consisting of target-overlapping and non-target-overlapping sub-segments. These sub-segments were assigned independent dose constraints. The REF and INV plans were compared with respect to target coverage and OAR sparing. Target coverage was evaluated by the Dmin (minimum dose), V66/V60 (percentage volume of gross target volume [GTV]/planning target volume [PTV] receiving 66 Gy/60 Gy), target conformity index (CI), and tumour control probability (TCP). The sparing of OARs was evaluated by the commonly used dose end points for the respective OAR, and normal tissue complication probability (NTCP). For PTV coverage, the INV plan was superior to the REF plan in terms of Dmin (P=0.000), CI (P=0.005) and TCP (P=0.002). This is attributed to an increase in dose to the PTV-OAR overlapping sub-segments. Regarding the sparing of OARs, there was a significant reduction in the mean dose of the parotid glands (P=0.002), and a slight, but non-significant, increase in NTCP of the temporal lobes, cochlea and brainstem. Using a split-organ delineation approach in IMRT treatment planning for advanced T-stage NPC, a significant improvement in the target coverage and TCP could be achieved, whereas the mean dose of the parotid was reduced significantly. There was insignificant change in the NTCP of the temporal lobe, parotid gland, cochlea and brainstem, but a significant change in the NTCP of the auditory nerve. The approach provides the planner extra room to manipulate the dose constraints during optimisation, and to obtain the desired result in less attempts. This approach also has the potential to be used in a broader context for IMRT planning for other tumour sites.
    Clinical Oncology 04/2008; 20(2):134-41. · 2.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To explore whether the margin status at surgical salvage nasopharyngectomy for local residual or recurrent nasopharyngeal carcinoma affects patient survival. Retrospective case series review. Academic tertiary referral center. Seventy-nine consecutive patients with operable local residual or recurrent nasopharyngeal carcinoma after failure of primary treatment with radiotherapy with or without chemotherapy underwent surgical salvage nasopharyngectomy with curative intent between November 28, 1987, and November 17, 2003. Sixty-one patients were men and 18 were women. Their mean age was 48 years (age range, 26-70 years). Surgical salvage nasopharyngectomy. The status of the closest margin at surgery was assessed as clear, close, or positive. Survival time was measured from the date of surgery to the date of the last follow-up, to the date of an event occurrence, or to the date of death. The Kaplan-Meier method was used to estimate the probability of local progression-free survival and overall survival at 5 years. Differences in survival rates between surgical margin statuses were assessed using the log-rank test. Five-year overall survival for patients with clear margins was 77%, for patients with close margins was 46% (P = .05), and for patients with positive margins was 23% (P < .001). Clear surgical margins at the time of surgical salvage nasopharyngectomy for residual or recurrent nasopharyngeal carcinoma positively affect patient survival.
    Archives of Otolaryngology - Head and Neck Surgery 12/2007; 133(12):1296-301. · 1.78 Impact Factor
  • [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine whether the standard techniques of measuring tumor size and change in size after treatment could be applied to the measurement of nasopharyngeal cancers, which are often irregular in shape. The standard measurements of bidimensional (BDM) (World Health Organization criteria) and unidimensional (UDM) (Response Evaluation Criteria in Solid Tumors [RECIST] criteria), together with the maximum depth of the tumor perpendicular to the pharyngeal wall (DM), were acquired from axial magnetic resonance images of primary nasopharyngeal carcinoma in 44 patients at diagnosis and in 29 of these patients after treatment. Tumor volume measurements (VM), acquired from the summation of areas from the axial magnetic resonance images, were used as the reference standard. There was a significant association between VM and BDM with respect to tumor size at diagnosis (p = 0.002), absolute change in tumor size after treatment (p < 0.001), and percentage change in tumor size after treatment (p = 0.044), but not between VM and UDM. There was also a significant association between VM and DM with respect to percentage change in tumor size after treatment (p = <0.0001) but not absolute change (p = 0.222). When using simple measurements to assess irregularly shaped nasopharyngeal cancers, the BDM should be used to measure size at diagnosis and the BDM and percentage change in size with treatment. Unidimensional measurement does not reflect size or change in size, and therefore the RECIST criteria may not be applicable to all tumor shapes. The use of DM requires further evaluation.
    International Journal of Radiation OncologyBiologyPhysics 09/2007; 69(1):148-54. · 4.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cycloxygenase-2 (COX-2), hypoxia inducible factor 1-alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) can be induced by the Epstein-Barr virus oncoprotein latent membrane protein-1 (LMP-1) in nasopharyngeal cancer (NPC) cell lines. This study examined the prognostic relevance of COX-2 and its relationship with HIF-1alpha and VEGF expression in NPC biopsies. Primary tumor biopsies were obtained from 78 participants of a randomized trial who received radiotherapy (RT) with or without concurrent chemotherapy for locoregionally advanced NPC. These were analyzed for COX-2 expression and then correlated with age, sex, disease stage, treatment arm, survival and disease recurrence, VEGF and HIF-1alpha expression in a regression model. 83% of tumors expressed COX-2, 47% co-expressed COX-2 and VEGF, 38% co-expressed COX-2 and HIF-1alpha. On univariate analysis, COX-2 expression did not correlate with survival and recurrence, but moderate to high COX-2 expression was associated with advanced nodal stage (p=0.03). Although univariate analysis showed that COX-2-HIF-1alpha co-expression was associated with worse progression-free survival (p=0.046), time to local (p=0.004) and regional recurrence (p=0.007), multivariate analysis failed to confirm any correlation between COX-2-HIF-1alpha or COX-2-VEGF co-expression and survival or disease recurrence. Contrary to previous report, this study failed to demonstrate any prognostic significance of COX-2 expression alone or co-expression with HIF-1alpha or VEGF in advanced NPC.
    Oral Oncology 05/2007; 43(4):373-8. · 2.70 Impact Factor