Michael K.M. Kam

Prospective Randomized Study of Intensity-Modulated Radiotherapy on Salivary Gland Function in Early-Stage Nasopharyngeal Carcinoma Patients

PURPOSE 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). PATIENTS AND METHODS 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. RESULTS 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 patients 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. CONCLUSION 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 patients subjective xerostomia with parotid-sparing IMRT reflects the need to enhance protection of other salivary glands.

Intensity-modulated radiotherapy in nasopharyngeal carcinoma: dosimetric advantage over conventional plans and feasibility of dose escalation

PURPOSE 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. MATERIALS AND METHODS 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. RESULTS 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. CONCLUSIONS 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.

Survival outcome of patients with nasopharyngeal carcinoma with first local failure: A study by the Hong Kong nasopharyngeal carcinoma study group

The purpose of this article is to report the overall survival (OS) outcome of patients with nasopharyngeal carcinoma (NPC) with local failure who received salvage treatment and to identify prognostic factors for OS.

Nasopharyngectomy: Does the approach to the nasopharynx influence survival?

Objective To investigate whether the approach used to the nasopharynx to perform a salvage nasopharyngectomy for recurrent or residual nasopharyngeal carcinoma influences survival. Study Design A retrospective case series. Subjects and Methods 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. Results 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. Conclusion 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.

Clinical utility of plasma Epstein-Barr virus DNA and ERCC1 single nucleotide polymorphism in nasopharyngeal carcinoma.

Single nucleotide polymorphism (SNP) of the excision repair cross‐complementing group 1 (ERCC1) gene has been linked with sensitivity to platinum and radiation. The authors hypothesized that the ERCC1 genotype for the SNPs cytosine‐to‐thymine substitution at codon 118 (C118T) and cytosine‐to‐adenine substitution at codon 8092 (C8092A) is prognostic in patients with nasopharyngeal carcinoma (NPC) who receive either radiotherapy (RT) or cisplatin plus RT.

Surgical salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma: a multivariate analysis of prognostic factors.

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).

Validation of the modified radiosurgery-based arteriovenous malformation score in a linear accelerator radiosurgery experience in Hong Kong

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%; Spearmans 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.

Pattern of recurrence and factors associated with cerebrospinal fluid dissemination of glioblastoma in Chinese patients

Background: Pattern of recurrence of glioblastoma (GBM) seems to have undergone some shifts from distant metastasis as a rarity to a higher proportion, including disease disseminated via cerebrospinal fluid (CSF) pathway. There is still no report on the pattern of recurrence for Chinese population. Here, we evaluated the pattern of recurrence of GBM in Chinese patients along with factors that could affect the distribution of recurrence. Methods: Medical records of GBM patients with definite recurrence were reviewed. Local recurrence was defined as tumor regrowth within the preoperative abnormal signals on magnetic resonance imaging (MRI) T2 sequence. New recurrence was a new lesion away from the preoperative T2 abnormalities. New recurrence in contact with CSF pathways was registered as new CSF dissemination. Progress-free survival (PFS) and survival after progress were compared using the Kaplan–Meier survival curves. Potential risk factors for new CSF dissemination were assessed using univariate models followed by multivariate analysis. Results: Thirty-six patients were proven to have recurrence; 22 local and 14 new recurrences. Among the 14 patients, 11 had new CSF dissemination. Median PFS for local, new parenchymal recurrence, and new CSF dissemination were 5.5 months, 9.9 months, and 12.1 months, whereas survival after progress were 6.1 months, 5.7 months, and 16.9 months, respectively. The ventricular entry during surgery and the completion of concomitant chemoradiotherapy were risk factors for new CSF dissemination. O6-methylguanine-DNA methyltransferase methylation was associated with the development of CSF dissemination. Conclusion: The majority of recurrence remained local (22/36, 61%). However, CSF dissemination was up to 30% (11/36). PFS for patients with CSF dissemination was the longest, and paradoxically survival after progress was the shortest. Ventricular entry should be avoided. Whole craniospinal MRI surveillance should be included for these patients.

Prediction of distant metastases from nasopharyngeal carcinoma: Improved diagnostic performance of MRI using nodal volume in N1 and N2 stage disease

PURPOSE To determine if the magnetic resonance imaging (MRI) of the head and neck can predict distant metastases (DM) from nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS MRI examinations of 763 NPC patients were assessed for primary tumour stage (T), nodal stage (N), primary tumour volume (PTV) and total nodal volume (NV). The association between MRI and clinical parameters were examined in DM+ and DM- patients using logistic regression and for distant metastases free survival (DMFS) using cox regression. Optimum thresholds were assessed by receiver-operating characteristics analysis, and positive predictive value (PPV) and odds ratio (OR) calculated. RESULTS Distant metastases were present in 181/763 NPC patients (23.7%). Higher N stage and NV were the independent predictors of DM (p<0.001 and 0.018 respectively) and poor DMFS (p=0.001 and 0.030 respectively). Addition of NV (threshold≥32.8cm3) to the N stage improved the PPVs and ORs for DM in stage N1 (from 18.9% to 31.8% and 5.613 to 11.133 respectively) and stage N2 (from 40.4% to 60.8% and 16.189 to 36.979 respectively) but not in stage N3 (68.3% to 68.6% and 51.385 to 52.052 respectively). CONCLUSION MRI N stage and NV were independent predictors of DM and DMFS. The addition of NV in NPC patients with bulky N1 and N2 disease improved the ability of MRI to predict DM.

Non-surgical treatment of lung cancer: personalised stereotactic ablative radiotherapy

Stereotactic ablative radiotherapy has emerged as a standard treatment for medically inoperable stage I non-small-cell lung cancer and selected cases of lung metastasis. Techniques to freeze or limit tumour movement during treatment and image-guided radiation delivery are integral to a successful stereotactic ablative treatment without overdose of surrounding normal structures. In this article, the practice in a local oncology institution will be used to illustrate the concept of personalised stereotactic ablative radiotherapy.