Food Avoidance Beliefs and Behaviors Among Chinese Cancer Patients: Validation of a New Measurement Tool.

OBJECTIVE: Restrictive food avoidance behavior among Chinese cancer patients is common. Yet, to the authors' knowledge, no study has investigated factors associated with such behavior. This study attempted to validate a new measurement tool, the Cancer Patients Food Avoidance Behaviors Scale (CPFAB), that assessed cancer patients' belief regarding 5 perceived benefits of practicing food avoidance, and to test its applicability. DESIGN: Cross-sectional face-to-face interviews. SETTING: Two outpatient oncology clinics in 2 different districts of Hong Kong. PARTICIPANTS: A total of 245 patients with nasopharyngeal and colorectal cancer. MAIN OUTCOME MEASURES: Assessment of psychometric properties of the CPFAB. ANALYSIS: Principal components method with oblique (Promax) rotations was performed to investigate the factor structure of the CPFAB. RESULTS: Psychometric properties, which included test-retest intraclass correlations (mean = 0.72; SD = 0.12), Cronbach α (.88-.94), floor (0.4% to 5.7%) and ceiling (0% to 7.3%) effects, and item-subscale (0.67-0.79) and subscale-total (0.68-0.89) correlations, were satisfactory. CONCLUSIONS AND IMPLICATIONS: The CPFAB, a new instrument used to assess food avoidance, was developed and validated. It showed satisfactory psychometric properties and can be used to evaluate interventions that seek to modify food avoidance attitudes among cancer patients.

Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer.

BACKGROUND: Circulating cell-free Epstein-Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons. METHODS: We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI). RESULTS: A total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently positive results on the repeated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of these participants, 34 had nasopharyngeal carcinoma. A significantly higher proportion of participants with nasopharyngeal carcinoma that was identified by screening had stage I or II disease than in a historical cohort (71% vs. 20%, P<0.001 by the chi-square test) and had superior 3-year progression-free survival (97% vs. 70%; hazard ratio, 0.10; 95% confidence interval, 0.05 to 0.18). Nine participants declined to undergo further testing, and 1 of them presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing. The sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively. CONCLUSIONS: Analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort. (Funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government; ClinicalTrials.gov number, NCT02063399 .).

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

BACKGROUND: 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. METHODS: The authors tested their hypothesis using biomarker screening samples from the Hong Kong NPC Study Group 0502 trial, which was a prospective, multicenter clinical trial that used post-RT plasma Epstein-Bar virus (EBV) DNA (pEBV) levels to screen patients with high-risk NPC for adjuvant chemotherapy. RESULTS: ERCC1 SNPs were analyzed in 576 consecutive patients who were screened by pEBV. In the total biomarker population, there was no significant association of ERCC1 C118T or C8092A genotype with relapse-free survival (RFS) or overall survival (OS). There also was no correlation between ERCC1 genotype and ERCC1 protein or messenger RNA expression in a subset of patients who had available paired biopsies. Post-RT pEBV status was the only independent prognosticator for RFS and OS in multivariate analyses. However, there was a significant interaction between ERCC1 C118T genotype and post-RT pEBV status (RFS, P = .0106; OS, P = .0067). The ERCC1 C118T genotype was significantly associated with both RFS (hazard ratio, 1.67; 95% confidence interval, 1.07-2.61; P = .024) and OS (hazard ratio, 2.31; 95% confidence interval, 1.22-4.40; P = .0106) in the post-RT pEBV-negative population, but not in the pEBV-positive population. CONCLUSIONS: The current results prospectively validate pEBV as the most significant prognostic biomarker in NPC that can be used to select high-risk patients for adjuvant therapy. The ERCC1 C118T genotype may help to identify a favorable subgroup (approximately 7%) of pEBV-negative patients with NPC who have an excellent prognosis and can be spared the toxicities of further therapy.

Early detection of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA analysis in a surveillance program.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia. Over the last decade, plasma Epstein-Barr virus (EBV) DNA has been developed as a tumor marker for NPC. In this study, the authors investigated whether plasma EBV DNA analysis is useful for NPC surveillance. METHODS: In total, 1318 volunteers ages 40 to 60 years were prospectively recruited. Plasma EBV DNA and serology for viral capsid antigen immunoglobulin A (IgA) were measured. Participants who had detectable plasma EBV DNA or positive IgA serology underwent nasal endoscopic examination and a follow-up plasma EBV DNA analysis in approximately 2 weeks. All participants were followed for 2 years to record the development of NPC. RESULTS: Three individuals with NPC were identified at enrolment. All of them were positive for EBV DNA and remained positive in follow-up analysis. Only 1 of those patients was positive for EBV serology. In 1 patient who had NPC with a small tumor confined to the mucosa, the tumor was not detectable on endoscopic examination. Because of a 2-fold increase in plasma EBV DNA on the follow-up analysis, that patient underwent magnetic resonance imaging, which revealed the tumor. Among the participants who did not have NPC but had initially positive plasma EBV DNA results, approximately 66% had negative EBV DNA results after a median of 2 weeks. CONCLUSIONS: Plasma EBV DNA analysis proved useful for detecting early NPC in individuals without a clinical suspicion of NPC. Repeating the test in those who had initially positive results differentiated those with NPC from those who had false-positive results. Cancer 2013. © 2013 American Cancer Society.

Prognostic significance of the total dose of cisplatin administered during concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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 40 mg/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. RESULTS: 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 56.5 months (range 4.2-200.2 months), 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). CONCLUSION: Number of cycles of cisplatin delivered is an independent prognostic factor in patients with stage II-III NPC undergoing CRT with weekly cisplatin.

A randomized trial on addition of concurrent-adjuvant chemotherapy and/or accelerated fractionation for locally-advanced nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To evaluate the therapeutic benefits by adding chemotherapy (+C) and/or accelerated-fractionation (AF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma. MATERIALS AND METHODS: From 1999 to 2004, 189 eligible patients were randomized to one of four treatment groups (CF/CF+C/AF/AF+C). The number of fractions/week was 5 for the CF groups and 6 for the AF groups. Patients in the +C groups were given concurrent cisplatin plus adjuvant cisplatin and fluorouracil. RESULTS: The AF+C group achieved significantly higher failure-free rate (88% at 5-year) than the CF group (63%; p=0.013), the AF group (56%; p=0.001) and the CF+C group (65%; p=0.027). As compared with CF alone, the increase in late toxicity was statistically insignificant (36% vs. 20%; p=0.25). Deaths due to cancer progression decreased (7% vs. 33%; p=0.011) but deaths due to incidental causes increased (9% vs. 2%; p=0.62). Improvement in overall survival reached borderline significance (85% vs. 66%; p=0.058). CONCLUSIONS: Concurrent-adjuvant chemotherapy combined with AF significantly reduced failure and cancer-specific deaths. Although the increase in major late toxicity and incidental deaths were statistically insignificant, a subtle increase in non-cancer deaths narrowed the overall survival gain.

Dosimetric comparison of intensity-modulated stereotactic radiotherapy with other stereotactic techniques for locally recurrent nasopharyngeal carcinoma.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSION: 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.

14-3-3sigma expression as a prognostic marker in undifferentiated nasopharyngeal carcinoma.

In this study, we investigated the expression of 14-3-3sigma tumor suppressor gene in a panel of NPC cell lines, xenografts and primary tumors. Our objective was to determine the correlation between 14-3-3sigma expression and clinical outcome in NPC. We detected reduced 14-3-3sigma expression in 5/6 NPC tumor lines by quantitative RT-PCR and Western blotting. By immunohistochemical staining, significant down-regulation of 14-3-3sigma was also found in 26/72 (36.1%) primary tumors of NPC patients, who were treated with curative radiotherapy. Promoter methylation was confirmed in a subset of primary tumors by methylation-specific PCR analysis. Importantly, we demonstrated that 14-3-3sigma expression is significantly associated with both overall survival (OS) and cancer-specific survival (CSS), but not with the clinical staging of NPC patients. The low 14-3-3sigma expression was associated with improved overall (p=0.029) and cancer-specific survival (p=0.042) on univariate analysis. 14-3-3sigma expression and staging were also independent variables to all the prognostic factors under multivariate analysis. In conclusion, low expression of 14-3-3sigma appears to be a valuable marker for better survival in patient with NPC. These results provide the evidence that 14-3-3sigma expression is a significant prognostic factor for NPC patients.

Risk of second primary malignancies following nasopharyngeal carcinoma in Hong Kong.

Nasopharyngeal carcinoma (NPC) is rare in most of the world but common among southeast Asians. Since NPC is usually diagnosed at relatively young ages and most patients now survive, the issue of second primary tumors (SPTs) has become important. Previous studies of SPTs among NPC survivors have given conflicting results. Data on patients with NPC diagnosed between 1996 and 2002 were abstracted from the medical records of two Hong Kong oncology centers. SPT incidence in these patients was compared to that of Hong Kong's general population using standardized incidence ratios (SIR). Eight-four patients were observed to have at least 1 SPT and 92 total additional cancers (SIR = 1.93, 95% CI = 1.55-2.37). The excess risk was greater for women and patients under 40 at diagnosis. Significant excesses were found for tongue, lung, nasal and middle ear, and brain cancers. The pattern of sites at which the greatest excess risk occurred is consistent with the hypothesis that much of the excess is due to treatment effects. The greater excess risk among patients diagnosed before 40 points to possible genetic influences. More research is needed to determine the reasons for greater excess risk among women.

Laryngopharyngeal sensory deficits and impaired pharyngeal motor function predict aspiration in patients irradiated for nasopharyngeal carcinoma.

OBJECTIVES/HYPOTHESIS: To assess the contribution of laryngopharyngeal sensory deficits and impaired pharyngeal motor function to aspiration in patients irradiated for nasopharyngeal carcinoma. STUDY DESIGN: A retrospective study at a tertiary referral university teaching hospital. METHODS: One hundred consecutive patients who underwent radiotherapy for nasopharyngeal carcinoma referred to a dysphagia clinic underwent sensory testing of their laryngopharynx and endoscopic evaluation of their swallowing. The sensory threshold of the laryngopharynx was determined, the pharyngeal contraction assessed, and the status of the larynx and hypopharynx documented before and after swallowing. The presence of laryngeal penetration and aspiration was noted. RESULTS: The average time from radiation therapy to assessment was 10.2 years, and the mean duration of swallowing symptoms was 27 months. Laryngopharyngeal sensation was deficient in 89% of patients and the pharyngeal contraction impaired in 93% patients. Laryngeal penetration and aspiration occurred in 87% and 74% of patients, respectively. Aspiration was associated with food residue in the pyriform fossae after swallowing (P < .001) and impaired pharyngeal contraction (P < .001), but not with laryngopharyngeal sensory deficiency. There was no association between a laryngopharyngeal sensory deficit and impaired pharyngeal contraction. CONCLUSIONS: Impaired pharyngeal contraction and food bolus clearance from the hypopharynx during swallowing are more important than laryngopharyngeal sensory deficiency in predicting aspiration in patients who underwent radiotherapy for nasopharyngeal carcinoma.

Osteoradionecrosis of the upper cervical spine: MR imaging following radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To document the MRI appearances of radiation-induced abnormalities in the cervical spine following treatment for nasopharyngeal carcinoma (NPC). METHODS: Patients with radiation-induced abnormalities in the upper cervical spine were identified from a retrospective analysis of reports from patients undergoing MRI follow-up. Imaging and clinical records of these patients were reviewed. Symmetrical distribution of abnormalities at C1 (anterior arch+/-adjacent aspect of the lateral masses) and C2 (dens+/-body especially with a characteristic horizontal rim of marrow preservation above the inferior endplate) were considered typical for osteoradionecrosis (ORN). RESULTS: Abnormalities of C1/2 were identified in 9/884 (1%) patients. The MRI distribution of abnormalities was typical for ORN in four and atypical in five patients. Abnormal soft tissue was present in the atlantoaxial joint in eight patients, forming a florid mass in six. This soft tissue was in direct continuity with the posterior nasopharyngeal wall ulceration via the retropharyngeal region. The final clinical diagnosis was ORN in eight, five of whom had clinical factors which suggested infection could have played a contributory role, and osteomyelitis in one patient. All patients had undergone additional radiotherapy treatment comprising of brachytherapy (7), stereotactic radiotherapy (1) or radiotherapy boost (2) and three had undergone nasopharyngectomy. CONCLUSION: ORN of the upper cervical spine following radiotherapy for NPC is more common than previously suspected and is seen in patients with additional treatment, especially brachytherapy. MRI features are often atypical and a contributory role of infection in the development of some cases of ORN is postulated.

The BAHA hearing system for hearing-impaired postirradiated nasopharyngeal cancer patients: a new indication.

BACKGROUND: Radiation for patients who have nasopharyngeal cancer (NPC) often renders them hearing challenged and facing difficulties from treatment sequelae such as chronic suppurative otitis media and osteoradionecrosis. Conventional hearing aids aggravate otorrhea, and ear moulds traumatize osteoradionecrosis ulcers in the ear canal. The bone-anchored hearing aid (BAHA) hearing system might represent an excellent hearing solution. OBJECTIVE: To investigate the BAHA benefit and osseointegration results for hearing-impaired postirradiated NPC patients. STUDY DESIGN: A prospective longitudinal study. SETTING: Tertiary university center. PATIENTS: Eleven hearing-impaired postirradiated NPC patients were studied from October 2002 to October 2006. METHODS: Two-stage BAHA surgeries were performed. Assessments include pure-tone and speech audiometry, implant integrity, periabutment audit, and patient satisfaction analysis during a 24-month period. Radiation dosimetric analysis and bone sampling at the fixture implant sites were studied. RESULTS: No implant fixtures were lost (follow-up, 13-58 mo). Average patient satisfaction scores were 84.4%, with 80% using their BAHA everyday and 90% using their devices for more than 8 hours. Dosimetric analysis of the implant site revealed that all fixtures were outside the irradiated field. There was a reduction in otorrhea rates after BAHA use over the course of the study. CONCLUSION: Successful osseointegration was demonstrated in postirradiated NPC patients. Improved subjective hearing clarity, reduced ear discharge rates, and extended BAHA usage times accounted for high patient satisfaction with the BAHA hearing system. This is the first study to demonstrate long-term osseointegration and hearing benefit in postirradiated NPC patients. We recommend the BAHA hearing system for the treatment of chronic suppurative otitis media-related hearing problems in NPC patients.

MRI of radiation-induced tumors of the head and neck in post-radiation nasopharyngeal carcinoma.

The aim of this study was to document the sites and MRI features of radiation-induced tumors (RITs) in the head and neck following treatment for nasopharyngeal carcinoma (NPC). The MRI examinations and clinical records of 20 patients with 21 RITs were reviewed retrospectively. RITs developed 3-30 years after radiotherapy and included eleven squamous cell carcinomas, six sarcomas, two neuroendocrine carcinomas, one mucoepidermoid carcinoma and one meningioma. RITs arose in the maxillary region (9), oro/hypopharynx and oral cavity (5), external auditory canal (4), nasopharynx and sphenoid sinus (2) and brain (1). Radiation-induced carcinoma and sarcoma had MRI features that were useful to distinguish them from recurrent NPC. To improve early detection of RITs, the check areas on an MRI of a patient with previous NPC treated by radiation should always include the maxillary region, tongue, and external auditory canal/temporal bone.

A broadly adaptive array of dose-constraint templates for planning of intensity-modulated radiation therapy for advanced T-stage nasopharyngeal carcinoma.

PURPOSE: To develop and validate adaptive dose-constraint templates in intensity-modulated radiotherapy (IMRT) planning for advanced T-stage nasopharyngeal carcinoma (NPC). METHOD AND MATERIALS: Dose-volume histograms of clinically approved plans for 20 patients with advanced T-stage NPC were analyzed, and the pattern of distribution in relation to the degree of overlap between targets and organs at risk (OARs) was explored. An adaptive dose constraint template (ADCT) was developed based on the degree of overlap. Another set of 10 patients with advanced T-stage NPC was selected for validation. Results of the manual arm optimization protocol and the ADCT optimization protocol were compared with respect to dose optimization time, conformity indices, multiple-dose end points, tumor control probability, and normal tissue complication probability. RESULTS: For the ADCT protocol, average time required to achieve an acceptable plan was 9 minutes, with one optimization compared with 94 minutes with more than two optimizations of the manual arm protocol. Target coverage was similar between the manual arm and ADCT plans. A more desirable dose distribution in the region of overlap between planning target volume and OARs was achieved in the ADCT plan. Dose end points of OARs were similar between the manual arm and ADCT plans. CONCLUSIONS: With the developed ADCT, IMRT treatment planning becomes more efficient and less dependent on the planner's experience on dose optimization. The developed ADCT is applicable to a wide range of advanced T-stage NPC treatment and has the potential to be applied in a broader context to IMRT planning for other cancer sites.

Persistent aberrations in circulating DNA integrity after radiotherapy are associated with poor prognosis in nasopharyngeal carcinoma patients.

PURPOSE: Aberrations of circulating nucleic acid integrity have been observed in cancer patients. However, the clinical significance of such changes has not been completely elucidated. In this study, we investigated the plasma DNA integrity in nasopharyngeal carcinoma (NPC) patients and its association with patients' survival after radiotherapy. EXPERIMENTAL DESIGN: Plasma DNA integrity was analyzed for 105 NPC patients before and after curative-intent radiotherapy and for 40 healthy controls. The plasma DNA concentration of each sample was measured by two real-time PCRs targeting the leptin gene. The amplicon sizes of the two assays were 105 and 201 bp. The integrity index was calculated as the ratio of the two concentrations (201 bp/105 bp). More intact circulating DNA would give a higher integrity index. RESULTS: The plasma DNA integrity index of the NPC patients was significantly higher than that of the healthy controls (median, 0.356 versus 0.238; P < 0.001). After radiotherapy, a reduction in plasma DNA integrity index was observed in 70% NPC patients. Patients with persistent aberrations of plasma DNA integrity had significantly poorer survival probability than those with reduced DNA integrity after treatment (P < 0.001, Kaplan-Meier). CONCLUSIONS: NPC is associated with disturbances in the integrity of circulating cell-free DNA. The persistence of DNA integrity aberrations after radiotherapy is associated with reduced probability of disease-free survival. Therefore, the measurement of plasma DNA integrity may serve as a useful marker for the detection and monitoring of malignant diseases.

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 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. 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 patient's subjective xerostomia with parotid-sparing IMRT reflects the need to enhance protection of other salivary glands.

Nasopharyngeal cancers: which method should be used to measure these irregularly shaped tumors on cross-sectional imaging?

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSION: 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.

Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma.

PURPOSE: To evaluate the effect of combining circulating Epstein-Barr viral (EBV) DNA load data with TNM staging data in pretherapy prognostication of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Three hundred seventy-six patients with all stages of NPC were studied. Pretreatment plasma/serum EBV DNA concentrations were quantified by a polymerase chain reaction assay. Determinants of overall survival were assessed by multivariate analysis. Survival probabilities of patient groups, segregated by clinical stage (I, II, III, or IV) alone and also according to EBV DNA load (low or high), were compared. RESULTS: Pretherapy circulating EBV DNA load is an independent prognostic factor for overall survival in NPC. Patients with early-stage disease were segregated by EBV DNA levels into a poor-risk subgroup with survival similar to that of stage III disease and a good-risk subgroup with survival similar to stage I disease. CONCLUSION: Pretherapy circulating EBV DNA load is an independent prognostic factor to International Union Against Cancer (UICC) staging in NPC. Combined interpretation of EBV DNA data with UICC staging data leads to alteration of risk definition of patient subsets, with improved risk discrimination in early-stage disease. Validation studies are awaited.

Clinical studies of immunomodulatory activities of Yunzhi-Danshen in patients with nasopharyngeal carcinoma.

OBJECTIVES: Nasopharyngeal carcinoma (NPC) is a prevalent tumor in Hong Kong. The immune system of such patients could be adversely affected during the course of conventional chemotherapy or radiotherapy. We investigated the immunomodulatory effects of Traditional Chinese Medicine (TCM) Yunzhi-Danshen capsules in NPC patients treated with radiotherapy. DESIGN: Randomized, double-blind, placebo-controlled 16-week study. SETTING/LOCATION: The Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong. SUBJECTS: Twenty-seven (27) patients with histologically proven NPC, at least 18 years of age. METHODS: Twenty-seven patients with histologically proven NPC were recruited to take Yunzhi (3.6 g daily) and Dangshem (1.4 g daily) in the form of 12 combination capsules (TCM group) or placebo (12 capsules) daily for 16 weeks, respectively. Flow cytometry was used to assess the percentages and absolute counts of human lymphocyte subsets in whole blood. Plasma concentration of soluble interleukin-2 receptor and soluble tumor necrosis factor receptor 2 was measured by enzyme-linked immunosorbent assay (ELISA). Ex vivo production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-10 in the whole blood assay culture supernatant was measured by ELISA. RESULTS: The decreases in percentage and absolute count of T lymphocytes in the TCM group were less than those in the placebo group after they took the capsules for 16 weeks (both p < 0.05). Furthermore, the decreases in absolute count of T suppressor cells plus cytotoxic T lymphocytes, and T helper cells in the TCM group were significantly lower than those in the placebo group after they took the capsules for 16 weeks (both p < 0.05). CONCLUSION: These results suggest that Yunzhi-Danshen can exert an immunomodulating effect in alleviating lymphopenia during radiotherapy in NPC patients.