Rosalie Ho

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.

Randomized Phase II Trial of Concurrent Cisplatin-Radiotherapy With or Without Neoadjuvant Docetaxel and Cisplatin in Advanced Nasopharyngeal Carcinoma

PURPOSE 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. PATIENTS AND METHODS 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. RESULTS 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). CONCLUSION 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.

Phase I Trial of Recombinant Modified Vaccinia Ankara Encoding Epstein–Barr Viral Tumor Antigens in Nasopharyngeal Carcinoma Patients

Epstein-Barr virus (EBV) is associated with several malignancies including nasopharyngeal carcinoma, a high incidence tumor in Chinese populations, in which tumor cells express the two EBV antigens EB nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2). Here, we report the phase I trial of a recombinant vaccinia virus, MVA-EL, which encodes an EBNA1/LMP2 fusion protein designed to boost T-cell immunity to these antigens. The vaccine was delivered to Hong Kong patients with nasopharyngeal carcinoma to determine a safe and immunogenic dose. The patients, all in remission more than 12 weeks after primary therapy, received three intradermal MVA-EL vaccinations at three weekly intervals, using five escalating dose levels between 5 × 10(7) and 5 × 10(8) plaque-forming unit (pfu). Blood samples were taken during prescreening, immediately before vaccination, one week afterward and at intervals up to one year later. Immunogenicity was tested by IFN-γ ELIspot assays using complete EBNA1 and LMP2 15-mer peptide mixes and known epitope peptides relevant to patient MHC type. Eighteen patients were treated, three per dose level one to four and six at the highest dose, without dose-limiting toxicity. T-cell responses to one or both vaccine antigens were increased in 15 of 18 patients and, in many cases, were mapped to known CD4 and CD8 epitopes in EBNA1 and/or LMP2. The range of these responses suggested a direct relationship with vaccine dose, with all six patients at the highest dose level giving strong EBNA1/LMP2 responses. We concluded that MVA-EL is both safe and immunogenic, allowing the highest dose to be forwarded to phase II studies examining clinical benefit.

Effects of a Care Protocol on Care Outcomes in Older Nursing Home Patients with Chronic Obstructive Pulmonary Disease

OBJECTIVES: To evaluate the effects of a care protocol used by community nurses to support nursing home staff in the care of patients with chronic obstructive pulmonary disease (COPD).

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.