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.

Prospective evaluation of plasma Epstein-Barr virus DNA clearance and fluorodeoxyglucose positron emission scan in assessing early response to chemotherapy in patients with advanced or recurrent nasopharyngeal carcinoma.

BACKGROUND: Plasma Epstein-Barr virus (pEBV) DNA and fluorodeoxyglucose positron emission (PET) reflect tumour burden in advanced NPC. This study hypothesised that a dual endpoint based on assessing pEBV DNA clearance and PET response could predict early drug response. METHODS: Eligible patients underwent a computed tomography (CT) scan and dual PET-CT at baseline, a PET-CT at 4 weeks, and then a CT scan at 10 weeks after starting palliative or induction chemotherapy. Plasma EBV DNA clearance was determined. RESULTS: Fifty-eight out of 70 enrolled patients completed all imaging and 50/58 had falling pEBV DNA level, which allowed calculation of the clearance. At a median follow-up of 29.1 months, the dual endpoint (pEBV DNA clearance ≤ 10 days and > 50% drop in sum of SUVmax of target lesions) was an independent indicator of overall survival (hazard ratio (HR) = 0.135, 95% CI = 0.039 to 0.466, p = 0.0015) and progression-free survival (HR = 0.136, 95% CI = 0.048 to 0.385, p = 0002). This dual endpoint could predict subsequent response by Response Evaluation Criteria In Solid Tumours (RECIST) criteria at 10 weeks after chemotherapy. CONCLUSIONS: Early PET-CT response and pEBV DNA clearance could predict survival and subsequent response. This dual endpoint is an innovative tool for assessing early drug response.

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.

Evolution of radiation-induced brain injury: MR imaging-based study.

PURPOSE: To evaluate the temporal lobes in patients previously treated for nasopharyngeal carcinoma to provide a better understanding of delayed radiation-induced injury in the brain unaffected by the underlying tumor. MATERIALS AND METHODS: Retrospective analysis of the patient data was approved by the local ethics committee. Informed consent was waived. Magnetic resonance (MR) imaging results in patients with temporal lobe injury (TLI) after receiving radiation for nasopharyngeal carcinoma were analyzed. The appearance and change over time of white matter lesions (WMLs), contrast material-enhanced lesions, and cysts were assessed. The Mann-Whitney U test was used to compare interval time, and the chi(2) and Fisher exact tests were used to compare the pattern of TLI changes. RESULTS: The study group was 124 patients (95 men, 29 women; mean age, 51.4 years) with 192 injured temporal lobes; 62 of these patients with 103 injured temporal lobes underwent follow-up MR imaging at least once (range, one to five examinations). A total of 332 injured temporal lobes were revealed. WMLs, contrast-enhanced lesions, and cysts were present on 332 (100%), 274 (82.5%), and 42 (12.7%) studies, respectively. All contrast-enhanced lesions more than 2 cm in size showed necrosis, and those 3 cm or greater formed a rim-enhanced necrotic mass. WMLs were the only lesion to occur alone, contrast-enhanced lesions were always accompanied by WMLs, and cysts were always accompanied by WMLs and contrast-enhanced lesions. Detection of cysts was significantly later than detection of WMLs and contrast-enhanced lesions (P <.01). Regression or resolution was found in 27 (28%) of 96 WMLs, 37 (39%) of 94 contrast-enhanced lesions, and one (7%) of 15 cysts. CONCLUSION: TLI from radiation is not always an irreversible and progressive process but is one that can regress or resolve at MR imaging. In the evolution of radiation injury, WMLs are seen first and are followed by contrast-enhanced lesions, which have an increasing tendency to become necrotic with increasing size. Cysts are the least frequent manifestation and arise in the late stage of TLI.

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.

MRI findings in patients with severe trismus following radiotherapy for nasopharyngeal carcinoma.

The aim of the study was to document MRI findings in masticator structures in patients with trismus developing after radiotherapy for nasopharyngeal carcinoma (NPC). MRI neck examinations were reviewed in 35 patients with marked trismus, defined as an interincisal gap of 25 mm or less, post-radiotherapy for NPC. Patients with trismus before treatment, infiltration of masticator structures at the time of trismus, or previous surgery involving the masticator structures were excluded. Sixteen patients had no significant abnormality in their masticator structures (46%). Nineteen patients (54%) had abnormalities comprising radiotherapy-induced masticator muscle fibrosis (n = 19), denervation atrophy of the masticator muscles secondary to mandibular nerve damage (n = 1), mandibular ramus signal abnormalities (n = 5), mandibular condyle sclerosis with or without capsular thickening (n = 5), perimasticator fibrosis extending into the masticator space (n = 3) and inflammation secondary to severe sinusitis extending into the masticator space (n = 2). Nine patients (26%) had more than one type of abnormality. Twenty-two patients (63%) had concomitant skull base osteoradionecrosis which extended into the pterygoid bases in 16 patients (45%). The presence of several MRI abnormalities in the masticator structures of patients with trismus after radiotherapy suggests that trismus is multifactorial. This study advances the understanding of mechanisms behind this debilitating side effect of radiotherapy.

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.

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.

Quantitative analysis of the transrenal excretion of circulating EBV DNA in nasopharyngeal carcinoma patients.

PURPOSE: The existence of transrenal clearance of circulating cell-free DNA is controversial. In this study, we used NPC as a model to investigate if circulating EBV DNA can be excreted into urine and to quantify the contribution of renal excretion to the clearance of plasma EBV DNA. EXPERIMENTAL DESIGN: Quantitative analysis of urine EBV DNA was done for 74 NPC patients using real-time PCR with two different amplicon sizes. The urine concentration of EBV DNA was expressed as copies per millimole of creatinine (copies/mmol Cr) to minimize the effects of interindividual variations in hydration status. RESULTS: EBV DNA was detectable in the urine of 56% NPC patients using a 59-bp real-time PCR assay. The median urine EBV DNA concentrations measured by the 59- and 76-bp assays were 7,040 and 290 copies/mmol Cr, respectively. Patients with detectable urine EBV DNA had significantly higher plasma concentrations, with a positive correlation between the plasma and urine concentrations of EBV DNA. The fraction of plasma EBV DNA excreted into the urine was 0.0026% of that for creatinine. CONCLUSIONS: We have shown that circulating EBV DNA can be excreted transrenally into urine in NPC patient and the fraction of excretion is negatively associated with the size of the DNA molecules. Because there is a positive correlation between plasma and urine EBV DNA concentration, urine EBV DNA analysis may potentially be applicable as an ultra-noninvasive test for the monitoring and prognostication of NPC patients.