Current Management Strategy of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma is an unique head and neck cancer. It is common among the southern Chinese and is closely associated with the Epstein Barr virus (EBV). To diagnose the disease in its early stage is infrequent as the symptoms are usually trivial and patients only present in late stages. Testing the blood for elevated EBV DNA has now become a screening test for the high risk group of patients, aiming to diagnose the disease in its early stages. Imaging studies, positron emission tomography scans in addition to clinical examination provide information on the extent of the disease. The confirmation of the disease still depends on endoscopic examination and biopsy. Radiotherapy with or without chemotherapy has been the primary treatment modality. The application of intensity modulated radiotherapy and the use of concomitant chemoradiation have improved the control of nasopharyngeal carcinoma together with the reduction of long term side effects. The early detection of residual or recurrence tumor in the neck or at the primary site has allowed delivery of salvage treatment. The choice of the optimal surgical salvage, either for neck disease or primary tumor depends on the extent of the residual or recurrent disease. The outcome of these patients have improved with the application of the appropriate surgical salvage

Measurement invariance of the Functional Assessment of Cancer Therapy—Colorectal quality-of-life instrument among modes of administration

OBJECTIVES: To test for the measurement invariance of the Functional Assessment of Cancer Therapy—Colorectal (FACT-C) in patients with colorectal neoplasms between two modes of administration (self- and interviewer administrations). It is important to establish the measurement invariance of the FACT-C across different modes of administration to ascertain whether it is valid to pool FACT-C data collected by different modes or to assess each group separately. METHODS: A cross-sectional sample of 391 Chinese patients with colorectal neoplasms was recruited from specialist outpatient clinics between September 2009 and July 2010. Confirmatory factor analysis (CFA) was used to test the original five-factor model of the FACT-C on data collected by self- and interviewer administrations in single-group analysis. Multiple-group CFA was then used to compare the factor structure between the two modes of administration using chi-square tests and other goodness-of-fit statistics. RESULTS: The hypothesized five-factor model of FACT-C demonstrated good fit in each group. Configural invariance and metric invariance were fully supported in multiple-group CFA. Some item intercepts and their corresponding error variances were not identical between administration groups, suggesting evidence of partial strict factorial invariance. CONCLUSIONS: Our results confirmed that the five-factor structure of FACT-C was invariant in Chinese patients using both self- and interviewer administrations. It is appropriate to pool or compare data in the emotional well-being and colorectal cancer subscale scores collected by both administrations. Measurement invariance in three items, one from each of the other subscales, may be contaminated by response bias between modes of administration

Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma

© 2014 American Cancer Society. BACKGROUND A current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy with concurrent cisplatin plus adjuvant cisplatin and fluorouracil (PF). In this randomized trial, the authors evaluated the potential therapeutic benefit from changing to an induction-concurrent chemotherapy sequence, replacing fluorouracil with oral capecitabine, and/or using accelerated rather than conventional radiotherapy fractionation. METHODS Patients with stage III through IVB, nonkeratinizing NPC were randomly allocated to 1 of 6 treatment arms. The protocol was amended in 2009 to permit confining randomization to the conventional fractionation arms. The primary endpoint was progression-free survival. Secondary endpoints included overall survival and safety. RESULTS In total, 803 patients were accrued, and 706 patients were randomly allocated to all 6 treatment arms. Comparisons of induction PF versus adjuvant PF did not indicate a significant improvement. Unadjusted comparisons of induction cisplatin and capecitabine (PX) versus adjuvant PF indicated a favorable trend in progression-free survival for the conventional fractionation arm (P = .045); analyses that were adjusted for other significant factors and fractionation reflected a significant reduction in the hazards of disease progression (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.36-0.80) and death (HR, 0.42; 95% CI, 0.25-0.70). Unadjusted comparisons of induction sequences versus adjuvant sequences did not reach statistical significance, but adjusted comparisons indicated favorable improvements by induction sequence. Comparisons of induction PX versus induction PF revealed fewer toxicities (neutropenia and electrolyte disturbance), unadjusted comparisons of efficacy were statistically insignificant, but adjusted analyses indicated that induction PX had a lower hazard of death (HR, 0.57; 95% CI, 0.34-0.97). Changing the fractionation from conventional to accelerated did not achieve any benefit but incurred higher toxicities (acute mucositis and dehydration). CONCLUSIONS Preliminary results indicate that the benefit of changing to an induction-concurrent sequence remains uncertain; replacing fluorouracil with oral capecitabine warrants further validation in view of its convenience, favorable toxicity profile, and favorable trends in efficacy; and accelerated fractionation is not recommended for patients with locoregionally advanced NPC who receive chemoradiotherapy.postprin

International Recommendations on Reirradiation by Intensity Modulated Radiation Therapy for Locally Recurrent Nasopharyngeal Carcinoma

Purpose: Reirradiation for locally recurrent nasopharyngeal carcinoma (NPC) is challenging because prior radiation dose delivered in the first course is often close to the tolerance limit of surrounding normal structures. A delicate balance between achieving local salvage and minimizing treatment toxicities is needed. However, high-level evidence is lacking because available reports are mostly retrospective studies on small series of patients. Pragmatic consensus guidelines, based on an extensive literature search and the pooling of opinions by leading specialists, will provide a useful reference to assist decision-making for these difficult decisions. Methods and Materials: A thorough review of available literature on recurrent NPC was conducted. A set of questions and preliminary draft guideline was circulated to a panel of international specialists with extensive experience in this field for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the whole panel for review and reconsideration. The current guideline was based on majority voting after repeated iteration for final agreement. Results: The initial round of questions showed variations in clinical practice even among the specialists, reflecting the lack of high-quality supporting data and the difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of reirradiation (including patient selection, targets contouring, dose prescription, and constraints). Conclusion: This paper provides useful reference on radical salvage treatment strategies for recurrent NPC and optimization of reirradiation through review of published evidence and consensus building. However, the final decision by the attending clinician must include full consideration of an individual patient's condition, understanding of the delicate balance between risk and benefits, and acceptance of risk of complications. (C) 2021 Elsevier Inc. All rights reserved

International Guideline on Dose Prioritization and Acceptance Criteria in Radiation Therapy Planning for Nasopharyngeal Carcinoma

Purpose: The treatment of nasopharyngeal carcinoma requires high radiation doses. The balance of the risks of local recurrence owing to inadequate tumor coverage versus the potential damage to the adjacent organs at risk (OARs) is of critical importance. With advancements in technology, high target conformality is possible. Nonetheless, to achieve the best possible dose distribution, optimal setting of dose targets and dose prioritization for tumor volumes and various OARs is fundamental. Radiation doses should always be guided by the As Low As Reasonably Practicable principle. There are marked variations in practice. This study aimed to develop a guideline to serve as a global practical reference. Methods and Materials: A literature search on dose tolerances and normal-tissue complications after treatment for nasopharyngeal carcinoma was conducted. In addition, published guidelines and protocols on dose prioritization and constraints were reviewed. A text document and preliminary set of variants was circulated to a panel of international experts with publications or extensive experience in the field. An anonymized voting process was conducted to rank the proposed variants. A summary of the initial voting and different opinions expressed by members were then recirculated to the whole panel for review and reconsideration. Based on the comments of the panel, a refined second proposal was recirculated to the same panel. The current guideline was based on majority voting after repeated iteration for final agreement. Results: Variation in opinion among international experts was repeatedly iterated to develop a guideline describing appropriate dose prioritization and constraints. The percentage of final agreement on the recommended parameters and alternative views is shown. The rationale for the recommendations and the limitations of current evidence are discussed. Conclusions: Through this comprehensive review of available evidence and interactive exchange of vast experience by international experts, a guideline was developed to provide a practical reference for setting dose prioritization and acceptance criteria for tumor volumes and OARs. The final decision on the treatment prescription should be based on the individual clinical situation and the patient's acceptance of optimal balance of risk. (C) 2019 Elsevier Inc. All rights reserved

Genomic Sequencing and Comparative Analysis of Epstein-Barr Virus Genome Isolated from Primary Nasopharyngeal Carcinoma Biopsy

Whether certain Epstein-Barr virus (EBV) strains are associated with pathogenesis of nasopharyngeal carcinoma (NPC) is still an unresolved question. In the present study, EBV genome contained in a primary NPC tumor biopsy was amplified by Polymerase Chain Reaction (PCR), and sequenced using next-generation (Illumina) and conventional dideoxy-DNA sequencing. The EBV genome, designated HKNPC1 (Genbank accession number JQ009376) is a type 1 EBV of approximately 171.5 kb. The virus appears to be a uniform strain in line with accepted monoclonal nature of EBV in NPC but is heterogeneous at 172 nucleotide positions. Phylogenetic analysis with the four published EBV strains, B95-8, AG876, GD1, and GD2, indicated HKNPC1 was more closely related to the Chinese NPC patient-derived strains, GD1 and GD2. HKNPC1 contains 1,589 single nucleotide variations (SNVs) and 132 insertions or deletions (indels) in comparison to the reference EBV sequence (accession number NC007605). When compared to AG876, a strain derived from Ghanaian Burkitt's lymphoma, we found 322 SNVs, of which 76 were non-synonymous SNVs and were shared amongst the Chinese GD1, GD2 and HKNPC1 isolates. We observed 88 non-synonymous SNVs shared only by HKNPC1 and GD2, the only other NPC tumor-derived strain reported thus far. Non-synonymous SNVs were mainly found in the latent, tegument and glycoprotein genes. The same point mutations were found in glycoprotein (BLLF1 and BALF4) genes of GD1, GD2 and HKNPC1 strains and might affect cell type specific binding. Variations in LMP1 and EBNA3B epitopes and mutations in Cp (11404 C>T) and Qp (50134 G>C) found in GD1, GD2 and HKNPC1 could potentially affect CD8+ T cell recognition and latent gene expression pattern in NPC, respectively. In conclusion, we showed that whole genome sequencing of EBV in NPC may facilitate discovery of previously unknown variations of pathogenic significance

Clinical correlates of health preference and generic health-related quality of life in patients with colorectal neoplasms.

BACKGROUND: The aims of the study were to assess the health preference and health-related quality of life (HRQOL) in patients with colorectal neoplasms (CRN), and to determine the clinical correlates that significantly influence the HRQOL of patients. METHODS: Five hundred and fifty-four CRN patients, inclusive of colorectal polyp or cancer, who attended the colorectal specialist outpatient clinic at Queen Mary Hospital in Hong Kong between October 2009 and July 2010, were included. Patients were interviewed with questionnaires on socio-demographic characteristics, and generic and health preference measures of HRQOL using the SF-12 and SF-6D Health Surveys, respectively. Clinical information on stage of disease at diagnosis, time since diagnosis, primary tumour site was extracted from electronic case record. Mean HRQOL and health preference scores of CRN patients were compared with age-sex matched controls from the Chinese general population using independent t-test. Multiple linear regression analyses were conducted to explore the associations of clinical characteristics with HRQOL measures with the adjustment of socio-demographic characteristics. RESULTS: Cross-sectional data of 515 eligible patients responded to the whole questionnaires were included in outcome analysis. In comparison with age-sex matched normative values, CRN patients reported comparable physical-related HRQOL but better mental-related HRQOL. Amongst CRN patients, time since diagnosis was positively associated with health preference score whilst patients with rectal neoplasms had lower health preference and physical-related HRQOL scores than those with sigmoid neoplasms. Health preference and HRQOL scores were significantly lower in patients with stage IV colorectal cancer than those with other less severe stages, indicating that progressive decline from low-risk polyp to stage IV colorectal cancer was observed in HRQOL scores. CONCLUSION: In CRN patients, a more advanced stage of disease was associated with worse HRQOL scores. Despite potentially adverse effect of disease on physical-related HRQOL, the mental-related HRQOL of CRN patients were better than that of Chinese general population