Publications by authors named "Wai-Tong Ng"

90 Publications

Meta-analysis of chemotherapy in nasopharynx carcinoma (MAC-NPC): An update on 26 trials and 7080 patients.

Clin Transl Radiat Oncol 2022 Jan 26;32:59-68. Epub 2021 Nov 26.

Oncostat U1018 INSERM, labeled Ligue Contre le Cancer, Villejuif, France.

Purpose: Chemotherapy, when added to radiotherapy, improves survival in locally advanced nasopharyngeal carcinoma (NPC). This article presents the second update of the Meta-Analysis of Chemotherapy in NPC.

Methods: Published or unpublished randomized trials assessing radiotherapy (±a second chemotherapy timing) with/without chemotherapy in non-metastatic NPC patients were identified. Updated data were sought for studies included in the previous rounds of the meta-analysis. The primary endpoint was overall survival. All trials were analyzed following the intent-to-treat principle using a fixed-effects model. Treatments were classified in five subsets according to chemotherapy timing. The statistical analysis plan was pre-specified.

Results: Eighteen new trials were identified. Individual patient data were available for seven. In total, the meta-analysis now included 26 trials and 7,080 patients. The addition of chemotherapy reduced the risk of death, with a hazard ratio (HR) of 0.79 (95% confidence interval (CI) [0.73; 0.85]), and an absolute survival increase at 5 and 10 years of 6.1% [+3.9; +8.3] and + 8.4% [+5.7; +11.1], respectively. The largest effect was observed for concomitant + adjuvant, induction (with concomitant in both arms) and concomitant chemotherapy, with respective HR [95%CI] of 0.68 [0.59; 0.79] (absolute survival increase at 5 years: 12.3% (7.0%;17.6%)), 0.73 [0.63; 0.86] (6.0% (2.5%;9.5%)) and 0.81 [0.70; 0.92] (5.2% (0.8%;9.6%)). The benefit of chemotherapy was also demonstrated by improvement in progression-free survival, cancer mortality, locoregional control and distant control. There was a significant interaction between patient age and chemotherapy effect.

Conclusion: This updated meta-analysis confirms the benefit of concomitant chemotherapy and concomitant + adjuvant chemotherapy, and suggests that addition of induction or adjuvant chemotherapy to concomitant chemotherapy improves tumor control and survival. The benefit of chemotherapy decreases with increasing patient age.
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http://dx.doi.org/10.1016/j.ctro.2021.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660702PMC
January 2022

In Reply to Abbasi et al.

Int J Radiat Oncol Biol Phys 2022 Jan;112(1):262-263

Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China; Clinical Oncology Centre, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

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http://dx.doi.org/10.1016/j.ijrobp.2021.09.019DOI Listing
January 2022

Dose-Response Reduction in Risk of Nasopharyngeal Carcinoma From Smoking Cessation: A Multicenter Case-Control Study in Hong Kong, China.

Front Oncol 2021 27;11:699241. Epub 2021 Sep 27.

School of Public Health, University of Hong Kong, Hong Kong, China.

Background: Cigarette smoking is associated with nasopharyngeal cancer (NPC) risk. Whether quitting reduces the risk is unclear. We investigated the associations of NPC with duration of and age at quitting in an endemic region.

Methods: We investigated the associations between NPC and quitting in a multicenter case-control study in Hong Kong with 676 newly diagnosed NPC cases and 1,285 hospital controls between 2014 and 2017, using a computer-assisted self-administered questionnaire. Multivariable unconditional logistic regression yielded adjusted odds ratios (AORs) of NPC by quitting status, duration and age of quitting, combinations of duration and age of quitting, and quitting to smoking duration ratio, compared with current smoking.

Results: Quitting (AOR: 0.72; 95% CI: 0.53-0.98) and never smoking (0.73, 0.56-0.95) were associated with lower NPC risk. NPC risk decreased with (i) longer quitting duration ( < 0.01), reaching significance after 11-20 (0.62, 0.39-0.99) and 21+ years (0.54, 0.31-0.92) of quitting; (ii) younger quitting age ( = 0.01), reaching significance for quitting at <25 years (0.49, 0.24-0.97); and (iii) higher quitting to smoking duration ratio ( < 0.01), reaching significance when the ratio reached 1 (0.60, 0.39-0.93). Quitting younger (age <25) appeared to confer larger reductions (49% for ≤10 years of quitting, 50% for 11+ years) in NPC risk than quitting at older ages (25+) regardless of quitting duration (16% for ≤10 years, 39% for 11+ years).

Conclusions: We have shown longer duration and younger age of quitting were associated with lower NPC risk, with dose-response relations. Our findings support including smoking as a cause of NPC. Stronger tobacco control measures and quitting services are needed to prevent NPC.
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http://dx.doi.org/10.3389/fonc.2021.699241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503184PMC
September 2021

Prognostic Factors for Overall Survival in Nasopharyngeal Cancer and Implication for TNM Staging by UICC: A Systematic Review of the Literature.

Front Oncol 2021 2;11:703995. Epub 2021 Sep 2.

Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

This study aims to identify prognostic factors in nasopharyngeal carcinoma (NPC) to improve the current 8th edition TNM classification. A systematic review of the literature reported between 2013 and 2019 in PubMed, Embase, and Scopus was conducted. Studies were included if (1) original clinical studies, (2) ≥50 NPC patients, and (3) analyses on the association between prognostic factors and overall survival. The data elements of eligible studies were abstracted and analyzed. A level of evidence was synthesized for each suggested change to the TNM staging and prognostic factors. Of 5,595 studies screened, 108 studies (44 studies on anatomical criteria and 64 on non-anatomical factors) were selected. Proposed changes/factors with strong evidence included the upstaging paranasal sinus to T4, defining parotid lymph node as N3, upstaging N-category based on presence of lymph node necrosis, as well as the incorporation of non-TNM factors including EBV-DNA level, primary gross tumor volume (GTV), nodal GTV, neutrophil-lymphocyte ratio, lactate dehydrogenase, C-reactive protein/albumin ratio, platelet count, SUVmax of the primary tumor, and total lesion glycolysis. This systematic review provides a useful summary of suggestions and prognostic factors that potentially improve the current staging system. Further validation studies are warranted to confirm their significance.
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http://dx.doi.org/10.3389/fonc.2021.703995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445029PMC
September 2021

External Validation of a Nomogram to Predict Survival and Benefit of Concurrent Chemoradiation for Stage II Nasopharyngeal Carcinoma.

Cancers (Basel) 2021 Aug 25;13(17). Epub 2021 Aug 25.

Department of Clinical Oncology, Tuen Mun Hospital, Hospital Authority, Hong Kong, China.

A nomogram was recently published by Sun et al. to predict overall survival (OS) and the additional benefit of concurrent chemoradiation (CCRT) vs. radiotherapy (RT) alone, in stage II NPC treated with conventional RT. We aimed to assess the predictors of OS and to externally validate the nomogram in the IMRT era. We analyzed stage II NPC patients treated with definitive RT alone or CCRT between 2001 and 2011 under the territory-wide Hong Kong NPC Study Group 1301 study. Clinical parameters were studied using the Cox proportional hazards model to estimate OS. The nomogram by Sun et al. was applied with 1000 times bootstrap resampling to calculate the concordance index, and we compared the nomogram predicted and observed 5-year OS. There were 482 patients included. The 5-year OS was 89.0%. In the multivariable analysis, an age > 45 years was the only significant predictor of OS (HR, 1.98; 95%CI, 1.15-3.44). Other clinical parameters were insignificant, including the use of CCRT (HR, 0.99; 95%CI, 0.62-1.58). The nomogram yielded a concordance index of 0.55 (95% CI, 0.49-0.62) which lacked clinically meaningful discriminative power. The nomogram proposed by Sun et al. should be interpreted with caution when applied to stage II NPC patients in the IMRT era. The benefit of CCRT remained controversial.
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http://dx.doi.org/10.3390/cancers13174286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428339PMC
August 2021

Dosimetric comparison of intensity modulated radiotherapy and intensity modulated proton therapy in the treatment of recurrent nasopharyngeal carcinoma.

Med Dosim 2021 Aug 29. Epub 2021 Aug 29.

Department of Medical Physics, Pamela Youde Nethersole Eastern Hospital, Hong Kong.

Background And Purpose: To compare the dosimetric performance of Intensity Modulated Proton Therapy (IMPT) and Intensity Modulated Radiotherapy (IMRT) in terms of target volume coverage and sparing of neurological organs-at-risk (OARs) in salvaging recurrent nasopharyngeal carcinoma (rNPC). The maximum dose to the internal carotid artery (ICA) and nasopharyngeal (NP) mucosa, which are associated with potential carotid blowout and massive epistaxis, were also evaluated.

Materials And Methods: IMRT and IMPT treatment plans were created for twenty patients with locally advanced rNPC. Planning Target Volume (PTV) was used to account for the setup and spatial error/uncertainty in the IMRT planning. Robust optimization on Clinical Target Volume (CTV) coverage with consideration of range and setup uncertainty was employed to produce two IMPT plans with 3-field and 4-field arrangements. The planning objective was to deliver 60 Gy to the PTV (IMRT) and CTV (IMPT) without exceeding the maximum lifetime cumulative Biologically Effective Dose (BED) of the neurological OARs (applied to the Planning organs-at-risk volume). The target dose coverage as well as the maximum dose to the neurological OARs, ICA, and NP mucosa were compared.

Results: Compared with IMRT, 3-field IMPT achieved better coverage to GTV V100% (83.3% vs. 73.2%, P <0.01) and CTV V100% (80.5% vs. 72.4%, P <0.01), and lower maximum dose to the critical OARs including the spinal cord (19.2 Gy vs. 22.3 Gy, P <0.01), brainstem (30.0 Gy vs. 32.3 Gy, P <0.01) and optic chiasm (6.6 Gy vs. 9.8 Gy, P <0.01). The additional beam with the 4-fields IMPT plans further improved the target coverage from the 3-field IMPT (CTV V98%: 85.3% vs. 82.4%, P <0.01) with similar OAR sparing. However, the target dose was highly non-uniform with both IMPT plans, leading to a significantly higher maximum dose to the ICA (∼68 Gy vs. 62.6 Gy, P <0.01) and NP mucosa (∼72 Gy vs. 62.8 Gy, P <0.01) than IMRT.

Conclusion: IMPT demonstrated some dosimetric advantage over IMRT in treating rNPC. However, IMPT could also result in very high dose hot spots in the target volume. Careful consideration of the ICA and NP mucosal complications is recommended when applying IMPT on rNPC patients.
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http://dx.doi.org/10.1016/j.meddos.2021.07.002DOI Listing
August 2021

Low vitamin D exposure and risk of nasopharyngeal carcinoma: Observational and genetic evidence from a multicenter case-control study.

Clin Nutr 2021 09 8;40(9):5180-5188. Epub 2021 Aug 8.

School of Public Health, The University of Hong Kong, Hong Kong SAR, China.

Background & Aims: Little is known about the risk of nasopharyngeal carcinoma (NPC) in relation to vitamin D exposure. The aim of this study was to examine the associations of NPC risk with serum level of 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD, and potential effect modification by several putative risk factors of NPC.

Methods: Our multicenter case-control study in Hong Kong recruited 815 NPC cases and 1502 frequency-matched (by sex and age) hospital controls from five major regional hospitals, and recruited 299 healthy subjects from blood donation centers (2014-2017). Circulating level of 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD (rs12785878, rs11234027, rs12794714, rs4588 and rs6013897) were measured by validated enzyme immunoassay and the iPLEX assay on the MassARRAY System, respectively. Data were also collected on demographics, lifestyle factors, ultraviolet radiation exposure, and potential confounders using a computer-assisted, self-administered questionnaire with satisfactory test-retest reliability. Unconditional logistic regression models were used to estimate ORs and 95% CIs.

Results: Despite no significant association of NPC risk with circulating 25OHD and genetic predicted 25OHD, there was evidence for an inverse association in participants with normal body mass index (between 18.5 and 27.5) across categories of 25OHD (P = 0.003), and a positive association in those with low socioeconomic status across categories based on the genetic score (P = 0.005). In addition, risk of NPC diagnosed at an early stage was higher for genetically lower 25OHD level (adjusted OR = 3.09, 95% CI = 1.04-9.21, P = 0.022).

Conclusions: Findings of this first comprehensive study to investigate the positive association of NPC risk with vitamin D deficiency need to be confirmed and be best interpreted with results of further similar studies. Our findings may inform possible etiological mechanisms of the associations with several putative risk/protective factors of NPC.
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http://dx.doi.org/10.1016/j.clnu.2021.07.034DOI Listing
September 2021

Current Trends and Controversies in the Management of Warthin Tumor of the Parotid Gland.

Diagnostics (Basel) 2021 Aug 13;11(8). Epub 2021 Aug 13.

Coordinator of the International Head and Neck Scientific Group, 35125 Padua, Italy.

Purpose: To review the current options in the management of Warthin tumors (WTs) and to propose a working management protocol.

Methods: A systematic literature search was conducted using PubMed and ScienceDirect database. A total of 141 publications were selected and have been included in this review. Publications were selected based on relevance, scientific evidence, and actuality.

Results: The importance of parotid WTs is increasing due to its rising incidence in many countries, becoming the most frequently encountered benign parotid tumor in certain parts of the world. In the past, all WTs were treated with surgery, but because of their slow growth rate, often minimal clinical symptoms, and the advanced age of many patients, active observation has gradually become more widely used. In order to decide on active surveillance, the diagnosis of WT must be reliable, and clinical, imaging, and cytological data should be concordant. There are four clear indications for upfront surgery: uncertain diagnosis; cosmetic problems; clinical complaints, such as pain, ulceration, or recurrent infection; and the patient's wish to have the tumor removed. In the remaining cases, surgery can be elective. Active surveillance is often suggested as the first approach, with surgery being considered if the tumor progresses and/or causes clinical complaints. The extent of surgery is another controversial topic, and the current trend is to minimize the resection using partial parotidectomies and extracapsular dissections when possible. Recently, non-surgical options such as microwave ablation, radiofrequency ablation, and ultrasound-guided ethanol sclerotherapy have been proposed for selected cases.

Conclusions: The management of WT is gradually shifting from superficial or total parotidectomy to more conservative approaches, with more limited resections, and to active surveillance in an increasing number of patients. Additionally, non-surgical treatments are emerging, but their role needs to be defined in future studies.
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http://dx.doi.org/10.3390/diagnostics11081467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391156PMC
August 2021

Can Radiation Therapy Quality Assurance Improve Nasopharyngeal Cancer Outcomes in Low- and Middle-Income Countries: Reporting the First Phase of a Prospective International Atomic Energy Agency Study.

Int J Radiat Oncol Biol Phys 2021 12 19;111(5):1227-1236. Epub 2021 Aug 19.

Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital and the University of Hong Kong, Hong Kong, China.

Purpose: Most new nasopharyngeal cancer cases occur in low-income and middle-income countries, and these patients experience poorer overall survival than that of new nasopharyngeal cancer cases in high-income countries. The goal of this research project is to determine whether the introduction of a radiation therapy quality assurance program can ultimately improve outcomes for nasopharyngeal cancer patients in lower-income and middle-income countries. This study reports the results of the first phase of the International Atomic Energy Agency Coordinated Research Project (325-E3-TM-47712).

Methods And Materials: This prospective study has 2 phases. Phase 1 is a survey of radiation therapy resources, patient characteristics and treatment, and results of radiation therapy quality assurance performed by the expert panel. An educational workshop reviewing phase 1 results for each center was completed before accrual of patients for phase 2. The ultimate aim of the study is to compare the first and second cohort of patients to see if quality assurance can result in fewer major protocol deviations and a 15% improvement in patients' 3-year progression-free survival.

Results: Of 14 participating centers, 13 (93%) had computed tomography simulators and linear accelerators (LINAC) with intensity modulated radiation therapy (IMRT) capacity, median 3 LINAC (range, 1-13), and median 10 radiation oncologists (range, 5-51). The annual number of nasopharyngeal cancer cases irradiated was median 54 (range, 10-627). Five of 14 centers (36%) had no local radiation therapy quality assurance. For the current phase 1 study, 134 patients were evaluated, 82.1% had MRI staging, 99.3% had metastatic workup, 65.6% undifferentiated histology, 51% stage 3 and 49% stage 4. Radiation therapy quality assurance revealed 81 (60.4%) of 134 patients had major protocol violations in gross tumor volume and high dose planning target volume contours and/or dosimetry, 28.4% patients had borderline plans, 15 (11.2%) acceptable, and only 6 (4.2%) had inevitable compromise due to tumor extent.

Conclusions: This is the first International Atomic Energy Agency study to address the fundamental issue of treatment quality rather than altered treatment regimens. The high rate of unacceptable radiation therapy plans is a major concern, and we hope phase 2 will show a significant reduction and improved patient outcomes.
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http://dx.doi.org/10.1016/j.ijrobp.2021.08.013DOI Listing
December 2021

A systematic review and recommendations on the use of plasma EBV DNA for nasopharyngeal carcinoma.

Eur J Cancer 2021 08 18;153:109-122. Epub 2021 Jun 18.

Coordinator of International Head and Neck Scientific Group, Padua, Italy.

Introduction: Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Southeast Asia, particularly Southern China. The classical non-keratinising cell type is almost unanimously associated with latent Epstein-Barr virus (EBV) infection. Circulating plasma EBV DNA can be a useful biomarker in various clinical aspects, but comprehensive recommendations and international guidelines are still lacking. We conducted a systematic review of all original articles on the clinical application of plasma EBV DNA for NPC; we further evaluated its strengths and limitations for consideration as standard recommendations.

Methods: The search terms 'nasopharyngeal OR nasopharynx', and 'plasma EBV DNA OR cell-free EBV OR cfEBV' were used to identify full-length articles published up to December 2020 in the English literature. Three authors independently reviewed the article titles, removed duplicates and reviewed the remaining articles for eligibility.

Results: A total of 81 articles met the eligibility criteria. Based on the levels of evidence and grades of recommendation assessed, it is worth considering the inclusion of plasma EBV DNA in screening, pre-treatment work-up for enhancing prognostication and tailoring of treatment strategy, monitoring during radical treatment, post-treatment surveillance for early detection of relapse, and monitoring during salvage treatment for recurrent or metastatic NPC. One major limitation is the methodology of measurement requiring harmonisation for consistent comparability.

Conclusions: The current comprehensive review supports the inclusion of plasma EBV DNA in international guidelines in the clinical aspects listed, but methodological issues must be resolved before global application.
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http://dx.doi.org/10.1016/j.ejca.2021.05.022DOI Listing
August 2021

Re-irradiation versus surgery for locally recurrent nasopharyngeal carcinoma.

Lancet Oncol 2021 06;22(6):e217

Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Clinical Oncology Centre, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

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http://dx.doi.org/10.1016/S1470-2045(21)00143-1DOI Listing
June 2021

Standardization for oncologic head and neck surgery.

Eur Arch Otorhinolaryngol 2021 Dec 12;278(12):4663-4669. Epub 2021 May 12.

Coordinator of the International Head and Neck Scientific Group, Padua, Italy.

The inherent variability in performing specific surgical procedures for head and neck cancer remains a barrier for accurately assessing treatment outcomes, particularly in clinical trials. While non-surgical modalities for cancer therapeutics have evolved to become far more uniform, there remains the challenge to standardize surgery. The purpose of this review is to identify the barriers in achieving uniformity and to highlight efforts by surgical groups to standardize selected operations and nomenclature. While further improvements in standardization will remain a challenge, we must encourage surgical groups to focus on strategies that provide such a level.
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http://dx.doi.org/10.1007/s00405-021-06867-6DOI Listing
December 2021

Contemporary management of the neck in nasopharyngeal carcinoma.

Head Neck 2021 06 29;43(6):1949-1963. Epub 2021 Mar 29.

International Head and Neck Scientific Group, Padua, Italy.

Up to 85% of the patients with nasopharyngeal carcinoma present with regional nodal metastasis. Although excellent nodal control is achieved with radiotherapy, a thorough understanding of the current TNM staging criteria and pattern of nodal spread is essential to optimize target delineation and minimize unnecessary irradiation to adjacent normal tissue. Selective nodal irradiation with sparing of the lower neck and submandibular region according to individual nodal risk is now emerging as the preferred treatment option. There has also been continual refinement in staging classification by incorporating relevant adverse nodal features. As for the uncommon occurrence of recurrent nodal metastasis after radiotherapy, surgery remains the standard of care.
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http://dx.doi.org/10.1002/hed.26685DOI Listing
June 2021

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

Int J Radiat Oncol Biol Phys 2021 07 9;110(3):682-695. Epub 2021 Feb 9.

Department of Clinical Oncology, University of Hong Kong Shenzhen Hospital and University of Hong Kong, Hong Kong, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.041DOI Listing
July 2021

Dietary fiber intake from fresh and preserved food and risk of nasopharyngeal carcinoma: observational evidence from a Chinese population.

Nutr J 2021 02 2;20(1):14. Epub 2021 Feb 2.

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, G/F, Patrick Manson Building (North Wing), 7 Sassoon Road, Pok Fu Lam, Hong Kong, SAR, China.

Background: The role of dietary fiber intake on risk of nasopharyngeal carcinoma (NPC) remains unclear. We examined the associations of dietary fiber intake on the risk of NPC adjusting for a comprehensive list of potential confounders.

Methods: Using data from a multicenter case-control study, we included 815 histologically confirmed NPC incident cases and 1502 controls in Hong Kong, China recruited in 2014-2017. Odds ratios (ORs) of NPC (cases vs controls) for dietary fiber intake from different sources at different life periods (age 13-18, age 19-30, and 10 years before recruitment) were evaluated using unconditional logistic regression, adjusting for sex, age, socioeconomic status, smoking and drinking status, occupational hazards, family history of cancer, salted fish, and total energy intake in Model 1, Epstein-Barr virus viral capsid antigen serological status in Model 2, and duration of sun exposure and circulating 25-hydroxyvitamin D in Model 3.

Results: Higher intake of total dietary fiber 10 years before recruitment was significantly associated with decreased NPC risk, with demonstrable dose-response relationship (P-values for trend = 0.001, 0.020 and 0.024 in Models 1-3, respectively). The adjusted ORs (95% CI) in the highest versus the lowest quartile were 0.51 (0.38-0.69) in Model 1, 0.48 (0.33-0.69) in Model 2, and 0.48 (0.33-0.70) in Model 3. However, the association was less clear after adjustment of other potential confounders (e.g. EBV) in the two younger periods (age of 13-18 and 19-30 years). Risks of NPC were significantly lower for dietary fiber intake from fresh vegetables and fruits and soybean products over all three periods, with dose-response relationships observed in all Models (P-values for trend for age 13-18, age 19-30 and 10 years before recruitment were, respectively, 0.002, 0.009 and 0.001 for Model1; 0.020, 0.031 and 0.003 for Model 2; and 0.022, 0.037 and 0.004 for Model 3). No clear association of NPC risk with dietary fiber intake from preserved vegetables, fruits and condiments was observed.

Conclusion: Our study has shown the protective role of dietary fiber from fresh food items in NPC risk, but no association for total dietary fiber intake was observed, probably because total intake also included intake of preserved food. Further studies with detailed dietary information and in prospective settings are needed to confirm this finding, and to explore the possible underlying biological mechanisms.
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http://dx.doi.org/10.1186/s12937-021-00667-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856716PMC
February 2021

Nasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci.

Commun Biol 2020 12 11;3(1):759. Epub 2020 Dec 11.

Department of Clinical Oncology, University of Hong Kong, Hong Kong (Special Administrative Region), People's Republic of China.

Despite pronounced associations of major histocompatibility complex (MHC) regions with nasopharyngeal carcinoma (NPC), causal variants underlying NPC pathogenesis remain elusive. Our large-scale comprehensive MHC region deep sequencing study of 5689 Hong Kong Chinese identifies eight independent NPC-associated signals and provides mechanistic insight for disrupted transcription factor binding, altering target gene transcription. Two novel protective variants, rs2517664 (T = 4.6%, P = 6.38 × 10) and rs117495548 (G = 3.0%, P = 4.53 × 10), map near TRIM31 and TRIM39/TRIM39-RPP21; multiple independent protective signals map near HLA-B including a previously unreported variant, rs2523589 (P = 1.77 × 10). The rare HLA-B*07:05 allele (OR < 0.015, P = 5.83 × 10) is absent in NPC, but present in controls. The most prevalent haplotype lacks seven independent protective alleles (OR = 1.56) and the one with additional Asian-specific susceptibility rs9391681 allele (OR = 2.66) significantly increased NPC risk. Importantly, this study provides new evidence implicating two non-human leukocyte antigen (HLA) genes, E3 ubiquitin ligases, TRIM31 and TRIM39, impacting innate immune responses, with NPC risk reduction, independent of classical HLA class I/II alleles.
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http://dx.doi.org/10.1038/s42003-020-01487-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733486PMC
December 2020

Treatment of persistent/recurrent nodal disease in nasopharyngeal cancer.

Curr Opin Otolaryngol Head Neck Surg 2021 Apr;29(2):86-92

Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Purpose Of Review: Persistent or recurrent disease in the neck lymphatics is an unusual pattern of failure in nasopharyngeal carcinoma (NPC) after definitive radiotherapy or chemoradiotherapy. The purpose of this review is to critically synthesize the current knowledge regarding salvage treatment of this unique form of failure in NPC.

Recent Findings: Surgery in the form of radical neck dissection has been established as the standard salvage treatment with 5-year regional control of 60--86%. Recent shift in paradigm has resulted in the use of modified or selective neck dissection as salvage surgery in some centers. Risk factors for poor survival outcome include recurrent nodal disease, number of involved lymph nodes, extracapsular extension, high lymph node ratio, and positive resection margin. There are no well controlled studies on the role of additional radiotherapy or chemotherapy to improve local control or survival after salvage neck dissection in this group of patients with regional failure.

Summary: There is limited literature regarding the extent of surgical dissection in treating nodal persistent or recurrent disease. Prospective studies are also needed to determine whether adjuvant therapy improves treatment outcomes.
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http://dx.doi.org/10.1097/MOO.0000000000000687DOI Listing
April 2021

Solar Ultraviolet Radiation and Vitamin D Deficiency on Epstein-Barr Virus Reactivation: Observational and Genetic Evidence From a Nasopharyngeal Carcinoma-Endemic Population.

Open Forum Infect Dis 2020 Oct 12;7(10):ofaa426. Epub 2020 Sep 12.

School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region (SAR), China.

Background: We investigated the relationship of Epstein-Barr virus viral capsid antigen (EBV VCA-IgA) serostatus with ambient and personal ultraviolet radiation (UVR) and vitamin D exposure.

Methods: Using data from a multicenter case-control study, we included 1026 controls subjects in 2014-2017 in Hong Kong, China. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between UVR exposure and EBV VCA-IgA (seropositivity vs seronegativity) were calculated using unconditional logistic regression models adjusted for potential confounders.

Results: We observed a large increase in seropositivity of EBV VCA-IgA in association with duration of sunlight exposures at both 10 years before recruitment and age 19-30 years (adjusted OR = 3.59, 95% CI = 1.46-8.77; and adjusted OR = 2.44, 95% CI = 1.04-5.73 for ≥8 vs <2 hours/day; for trend = .005 and .048, respectively). However, no association of EBV VCA-IgA serostatus with other indicators of UVR exposure was found. In addition, both circulating 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD were not associated with EBV VCA-IgA serostatus.

Conclusions: Our results suggest that personal UVR exposure may be associated with higher risk of EBV reactivation, but we did not find clear evidence of vitamin D exposure (observational or genetic), a molecular mediator of UVR exposure. Further prospective studies in other populations are needed to confirm this finding and to explore the underlying biological mechanisms. Information on photosensitizing agents, and serological markers of EBV, and biomarkers related to systemic immunity and inflammation should be collected and are also highly relevant in future studies.
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http://dx.doi.org/10.1093/ofid/ofaa426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585328PMC
October 2020

Second primary cancer after intensity-modulated radiotherapy for nasopharyngeal carcinoma: A territory-wide study by HKNPCSG.

Oral Oncol 2020 12 24;111:105012. Epub 2020 Sep 24.

Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong.

Objectives: Long-term risk of second primary cancer (SPC) after definitive intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) remains unclear. This study aims to evaluate the risk, predictive factors and survival impact of SPC in a large territory-wide cohort of NPC survivors in an endemic region.

Materials And Methods: In this multicenter study, consecutive NPC patients (n = 3166) who underwent definitive IMRT in all six public oncology centers in Hong Kong between 2001 and 2010 were included. SPC risks were quantified by standardized incidence ratios (SIRs) and absolute excess risks (AERs) estimated from corresponding age-, sex-, and calendar year-specific population cancer incidence data from the Hong Kong Cancer Registry. Predictive factors and SPC-specific mortality were analyzed.

Results: Over a median follow-up period of 10.8 years, 290 cases of SPC were observed with a crude incidence of 9.2%. Cancer risk in NPC survivors was 90% higher than that in general population [SIR, 1.9; 95% confidence interval (CI), 1.7-2.2], with an AER of 52.1 (95% CI, 36.8-67.3) per 10,000 person-years at risk. Significant excess cancer risks were observed for oral cavity, sarcoma, oropharynx, paranasal sinus, salivary gland, thyroid, skin and lung. Advanced age, smoking, hepatitis B status, and re-irradiation were independent predictive factors. SPC accounted for 9.4% of all deaths among NPC survivors during the study period, and 10-year SPC-specific mortality was 3.4%.

Conclusions: Second cancer risk after IMRT was substantial among NPC patients. SPC impairs long-term survival, and close surveillance is warranted as part of survivorship care.
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http://dx.doi.org/10.1016/j.oraloncology.2020.105012DOI Listing
December 2020

Radiotherapy in the management of glottic squamous cell carcinoma.

Head Neck 2020 12 8;42(12):3558-3567. Epub 2020 Sep 8.

International Head and Neck Scientific Group, Padua, Italy.

Introduction: Our purpose is to review the role radiotherapy (RT) in the treatment of glottic squamous cell carcinoma (SCC).

Methods: A concise review of the pertinent literature.

Results: RT cure rates are Tis- T1N0, 90% to 95%; T2N0, 70% to 80%; low-volume T3-T4a, 65% to 70%. Concomitant cisplatin is given for T3-T4a SCCs. Severe complications occur in 1% to 2% for Tis-T2N0 and 10% for T3-T4a SCCs. Patients with high-volume T3-T4 SCCs undergo total laryngectomy, neck dissection, and postoperative RT. Those with positive margins and/or extranodal extension receive concomitant cisplatin. The likelihood of local-regional control at 5 years is 85% to 90%. Severe complications occur in 5% to 10%.

Conclusions: RT is a good treatment option for patients with Tis-T2N0 and low-volume T3-T4a glottic SCCs. Patients with higher volume T3-T4 cancers are best treated with surgery and postoperative RT.
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http://dx.doi.org/10.1002/hed.26419DOI Listing
December 2020

NPC-0501 trial on the value of changing chemoradiotherapy sequence, replacing 5-fluorouracil with capecitabine, and altering fractionation for patients with advanced nasopharyngeal carcinoma.

Cancer 2020 08 4;126(16):3674-3688. Epub 2020 Jun 4.

Department of Clinical Oncology, The University of Hong Kong, Hong Kong, Hong Kong.

Background: A current recommendation for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy (RT) with concurrent cisplatin followed by adjuvant cisplatin and 5-fluorouracil (PF). This randomized NPC-0501 trial evaluated the therapeutic effect of changing to an induction-concurrent sequence or accelerated-fractionation sequence, and/or replacing 5-fluorouracil with capecitabine (X).

Methods: Patients with American Joint Committee on Cancer/International Union Against Cancer stage III to stage IVB NPC initially were randomly allocated to 1 of 6 treatment arms (6-arm full-randomization cohort). The protocol was amended in 2009 to permit centers to opt out of randomization regarding fractionation (3-arm chemotherapy cohort).

Results: A total of 803 patients were accrued (1 of whom was nonevaluable) from 2006 to 2012. Based on the overall comparisons, neither changing the chemotherapy sequence nor accelerated fractionation improved treatment outcome. However, secondary analyses demonstrated that when adjusted for RT parameters and other significant factors, the induction-concurrent sequence, especially the induction-PX regimen, achieved significant improvements in progression-free survival (PFS) and overall survival. Efficacy varied among different RT groups: although no impact was observed in the accelerated-fractionation group and the 3-arm chemotherapy cohort, a comparison of the induction-concurrent versus concurrent-adjuvant sequence in the conventional-fractionation group demonstrated a significant benefit in PFS (78% vs 62% at 5 years; P = .015) and a marginal benefit in overall survival (84% vs 72%; P = .042) after adjusting for multiple comparisons. Comparison of the induction-PX versus the adjuvant-PF regimen demonstrated better PFS (78% vs 62%; P = .027) without an increase in overall late toxicity.

Conclusions: For patients irradiated using conventional fractionation, changing the chemotherapy sequence from a concurrent-adjuvant to an induction-concurrent sequence, particularly using induction cisplatin and capecitabine, potentially could improve efficacy without an adverse impact on late toxicity. However, further validation is needed for confirmation of these findings.
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http://dx.doi.org/10.1002/cncr.32972DOI Listing
August 2020

Clinical utility of serial analysis of circulating tumour cells for detection of minimal residual disease of metastatic nasopharyngeal carcinoma.

Br J Cancer 2020 07 6;123(1):114-125. Epub 2020 May 6.

Department of Clinical Oncology, University of Hong Kong, Hong Kong (Special Administrative Region), People's Republic of China.

Background: Nasopharyngeal carcinoma (NPC) is an important cancer in Hong Kong. We aim to utilise liquid biopsies for serial monitoring of disseminated NPC in patients to compare with PET-CT imaging in detection of minimal residual disease.

Method: Prospective serial monitoring of liquid biopsies was performed for 21 metastatic patients. Circulating tumour cell (CTC) enrichment and characterisation was performed using a sized-based microfluidics CTC chip, enumerating by immunofluorescence staining, and using target-capture sequencing to determine blood mutation load. PET-CT scans were used to monitor NPC patients throughout their treatment according to EORTC guidelines.

Results: The longitudinal molecular analysis of CTCs by enumeration or NGS mutational profiling findings provide supplementary information to the plasma EBV assay for disease progression for good responders. Strikingly, post-treatment CTC findings detected positive findings in 75% (6/8) of metastatic NPC patients showing complete response by imaging, thereby demonstrating more sensitive CTC detection of minimal residual disease. Positive baseline, post-treatment CTC, and longitudinal change of CTCs significantly associated with poorer progression-free survival by the Kaplan-Meier analysis.

Conclusions: We show the potential usefulness of application of serial analysis in metastatic NPC of liquid biopsy CTCs, as a novel more sensitive biomarker for minimal residual disease, when compared with imaging.
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http://dx.doi.org/10.1038/s41416-020-0871-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341819PMC
July 2020

COVID-19 pandemic: Effects and evidence-based recommendations for otolaryngology and head and neck surgery practice.

Head Neck 2020 06 15;42(6):1259-1267. Epub 2020 Apr 15.

International Head and Neck Scientific Group, Udine, Italy.

The 2019 novel coronavirus disease (COVID-19) is a highly contagious zoonosis produced by SARS-CoV-2 that is spread human-to-human by respiratory secretions. It was declared by the WHO as a public health emergency. The most susceptible populations, needing mechanical ventilation, are the elderly and people with associated comorbidities. There is an important risk of contagion for anesthetists, dentists, head and neck surgeons, maxillofacial surgeons, ophthalmologists, and otolaryngologists. Health workers represent between 3.8% and 20% of the infected population; some 15% will develop severe complaints and among them, many will lose their lives. A large number of patients do not have overt signs and symptoms (fever/respiratory), yet pose a real risk to surgeons (who should know this fact and must therefore apply respiratory protective strategies for all patients they encounter). All interventions that have the potential to aerosolize aerodigestive secretions should be avoided or used only when mandatory. Health workers who are: pregnant, over 55 to 65 years of age, with a history of chronic diseases (uncontrolled hypertension, diabetes mellitus, chronic obstructive pulmonary diseases, and all clinical scenarios where immunosuppression is feasible, including that induced to treat chronic inflammatory conditions and organ transplants) should avoid the clinical attention of a potentially infected patient. Health care facilities should prioritize urgent and emergency visits and procedures until the present condition stabilizes; truly elective care should cease and discussed on a case-by-case basis for patients with cancer. For those who are working with COVID-19 infected patients' isolation is compulsory in the following settings: (a) unprotected close contact with COVID-19 pneumonia patients; (b) onset of fever, cough, shortness of breath, and other symptoms (gastrointestinal complaints, anosmia, and dysgeusia have been reported in a minority of cases). For any care or intervention in the upper aerodigestive tract region, irrespective of the setting and a confirmed diagnosis (eg, rhinoscopy or flexible laryngoscopy in the outpatient setting and tracheostomy or rigid endoscopy under anesthesia), it is strongly recommended that all health care personnel wear personal protective equipment such as N95, gown, cap, eye protection, and gloves. The procedures described are essential in trying to maintain safety of health care workers during COVID-19 pandemic. In particular, otolaryngologists, head and neck, and maxillofacial surgeons are per se exposed to the greatest risk of infection while caring for COVID-19 positive subjects, and their protection should be considered a priority in the present circumstances.
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http://dx.doi.org/10.1002/hed.26164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262203PMC
June 2020

Current management of stage IV nasopharyngeal carcinoma without distant metastasis.

Cancer Treat Rev 2020 Apr 21;85:101995. Epub 2020 Feb 21.

International Head and Neck Scientific Group, Padua, Italy.

Up to one in four patients with nasopharyngeal carcinoma present with non-metastatic stage IV disease (i.e. T4 or N3). Distinct failure patterns exist, despite the routine adoption of contemporary treatment modalities such as intensity modulated radiotherapy and systemic chemotherapy. Concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy or induction chemotherapy followed by CCRT are commonly employed in this setting, with the latter emerging as the preferred option. Additionally, emerging radiation technologies like proton therapy has become available offering new opportunities for prevention of radiation-induced side effects. This article reviews not only the current treatment strategies, but also discusses novel ways to tackle this challenging disease with respect to the patterns of failure.
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http://dx.doi.org/10.1016/j.ctrv.2020.101995DOI Listing
April 2020

Dose volume effects of re-irradiation for locally recurrent nasopharyngeal carcinoma.

Head Neck 2020 02 16;42(2):180-187. Epub 2019 Oct 16.

Department of Clinical Oncology, Li Ka Shing Faulty of Medicine, The University of Hong Kong, Hong Kong, China.

Background: This study analyzed the dose volume effects of re-irradiation for locally recurrent nasopharyngeal carcinoma (NPC) and attempts to determine the optimal dose for the best survival.

Methods: Ninety-one patients were studied. The local control, fatal complication, and overall survival were analyzed against the dose (in Equivalent Dose at 2 Gy/fractions) and recurrent gross tumor volume (GTV).

Results: The local control and fatal complication rate appear to increase with prescribed dose. The overall survival peaks at around 60 Gy . Local control decreases significantly with increasing GTV (P < .001) while overall survival shows similar trend (P = .06). No correlation was observed between the fatal complication rate and GTV volume. The dose response of local control appears to be stronger for smaller tumors.

Conclusion: GTV volume plays a significant role in local control. A 60 Gy appears to be optimal for the best survival outcome; higher doses might be considered for small tumors.
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http://dx.doi.org/10.1002/hed.25988DOI Listing
February 2020

Management of locally recurrent nasopharyngeal carcinoma.

Cancer Treat Rev 2019 Sep 21;79:101890. Epub 2019 Aug 21.

Coordinator of the International Head and Neck Scientific Group, Padua, Italy.

As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10-20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC.
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http://dx.doi.org/10.1016/j.ctrv.2019.101890DOI Listing
September 2019

Crucifera sulforaphane (SFN) inhibits the growth of nasopharyngeal carcinoma through DNA methyltransferase 1 (DNMT1)/Wnt inhibitory factor 1 (WIF1) axis.

Phytomedicine 2019 Oct 29;63:153058. Epub 2019 Jul 29.

Department of Biology, Hong Kong Baptist University, Kowloon, Hong Kong, China. Electronic address:

Background: Sulforaphane (SFN), a natural compound present in cruciferous vegetable, has been shown to possess anti-cancer activities. Cancer stem cell (CSC) in bulk tumor is generally considered as treatment resistant cell and involved in cancer recurrence. The effects of SFN on nasopharyngeal carcinoma (NPC) CSCs have not yet been explored.

Purpose: The present study aims to examine the anti-tumor activities of SFN on NPC cells with CSC-like properties and the underlying mechanisms.

Methods: NPC cells growing in monolayer culture, CSCs-enriched NPC tumor spheres, and also the NPC nude mice xenograft were used to study the anti-tumor activities of SFN on NPC. The population of cells expressing CSC-associated markers was evaluated using flow cytometry and aldehyde dehydrogenase (ALDH) activity assay. The effect of DNA methyltransferase 1 (DNMT1) on the growth of NPC cells was analyzed by using small interfering RNA (siRNA)-mediated silencing method.

Results: SFN was found to inhibit the formation of CSC-enriched NPC tumor spheres and reduce the population of cells with CSC-associated properties (SRY (Sex determining Region Y)-box 2 (SOX2) and ALDH). In the functional study, SFN was found to restore the expression of Wnt inhibitory factor 1 (WIF1) and the effect was accompanied with the downregulation of DNMT1. The functional activities of WIF1 and DNMT1 were confirmed using exogenously added recombinant WIF1 and siRNA knockdown of DNMT1. Moreover, SFN was found to inhibit the in vivo growth of C666-1 cells and enhance the anti-tumor effects of cisplatin.

Conclusion: Taken together, we demonstrated that SFN could suppress the growth of NPC cells via the DNMT1/WIF1 axis.
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http://dx.doi.org/10.1016/j.phymed.2019.153058DOI Listing
October 2019

Patterns of care and treatment outcomes for local recurrence of NPC after definite IMRT-A study by the HKNPCSG.

Head Neck 2019 10 27;41(10):3661-3669. Epub 2019 Jul 27.

Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China.

Background: This study evaluates the contemporary care for patients with locally recurrent nasopharyngeal carcinoma after failure of the primary course of intensity modulated radiotherapy.

Methods: Eligible patients were identified through the Hong Kong Cancer Registry database. Patterns of care and treatment outcomes were analyzed.

Results: Two hundred seventy-two patients with locally recurrent tumors were identified. Of them, 30.9% received surgery, whereas 35.7% received re-irradiation (re-RT). The 5-year overall survival (OS) for the whole group was 30.2%. Old age and advanced rT classification were adverse prognostic factors, whereas surgery (mainly in resectable recurrence) was associated with favorable survival outcome. The 5-year OS rates for patients who received surgery and re-RT were 56.3% and 21.8%, respectively.

Conclusions: Early detection of resectable recurrence is of paramount importance as surgery for resectable tumors offers the potential to achieve excellent outcomes. Re-RT could be considered in selected patients with unresectable disease and favorable prognostic features.
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http://dx.doi.org/10.1002/hed.25892DOI Listing
October 2019

Automatic segmentation for adaptive planning in nasopharyngeal carcinoma IMRT: Time, geometrical, and dosimetric analysis.

Med Dosim 2020 Spring;45(1):60-65. Epub 2019 Jul 23.

Department of Clinical Oncology, Pamela Youde Nethersole Easter Hospital, 3 Lok Man Road, Chai Wan, Hong Kong.

The aim of this study was to quantify the geometrical differences between manual contours and autocontours, the dosimetric impacts, and the time gain of using autosegmentation in adaptive nasopharyngeal carcinoma (NPC) intensity-modulated radiotherapy (IMRT) for a commercial system. A total of 20 consecutive Stages I to III NPC patients who had undergone adaptive radiation therapy (ART) re planning for IMRT treatment were retrospectively studied. Manually delineated organs at risks (OARs) on the replanning computed tomography (CT) were compared with the autocontours generated by VelocityAI using deformable registration from the original planning CT. Dice similarity coefficients and distance-to-agreements (DTAs) were used to quantify their geometric differences. IMRT test plans were generated with the assistance of RapidPlan based on the autocontours of OARs and manually segmented target volumes. The dose distributions were applied on the manually delineated OARs, their dose volume histograms and dose constraints compliances were analyzed. Times spent on target, OAR contouring, and IMRT replanning were recorded, and the total time of replanning using manual contouring and autocontouring were compared. The averaged mean DTA of all structures included in the study were less than 2 mm, and 90% of the patients fulfilled the mean distance agreement tolerance recommended by AAPM 132. The averaged maximum DTA for brainstem, cord, optic chiasm, and optic nerves were all less than 4 mm, whereas temporal lobes and parotids have larger average maximum DTA of 4.7 mm and 6.8 mm, respectively. It was found that large contour discrepancies in temporal lobes and parotids were often associated with large magnitude of deformation (warp distance) in image registrations. The resultant maximum dose of manually segmented brainstem, cord, and temporal lobe and the median dose of manually segmented parotids were found to be statistically higher than those to their autocontoured counter parts in test plans. Dose constraints of the manually segmented OARs in test plans were only met in 15% of the cases. The average time of manual contouring and autocontouring were 108 and 10 minutes, respectively (p < 0.001). More than 30% of the total replanning time would be spent in manual OAR contouring. Manual OAR delineation takes up a significant portion of time spent in ART replanning and OAR autocontouring could considerably enhance ART workflow efficiency. Geometrical discrepancies between auto- and manual contours in head and neck OARs were comparable to typical interobserver variation suggested in various literatures; however, some of the corresponding dosimetric differences were substantial, making it essential to carefully review the autocontours.
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http://dx.doi.org/10.1016/j.meddos.2019.06.002DOI Listing
December 2020

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

Int J Radiat Oncol Biol Phys 2019 11 2;105(3):567-580. Epub 2019 Jul 2.

Division of Radiation Oncology, National Cancer Centre Singapore, Oncology ACP, Duke-NUS Medical School, Singapore. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ijrobp.2019.06.2540DOI Listing
November 2019
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