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Purpose: Oral mucositis (OM) is one of the most prevalent and crippling treatment-related toxicities experienced by nasopharyngeal carcinoma (NPC) patients receiving radiotherapy (RT), posing a tremendous adverse impact on quality of life. This multi-center study aimed to develop and externally validate a multi-omic prediction model for severe OM., Methods: Four hundred and sixty-four histologically confirmed NPC patients were retrospectively recruited from two public hospitals in Hong Kong. Model development was conducted on one institution (n = 363), and the other was reserved for external validation (n = 101). Severe OM was defined as the occurrence of CTCAE grade 3 or higher OM during RT. Two predictive models were constructed: 1) conventional clinical and DVH features and 2) a multi-omic approach including clinical, radiomic and dosiomic features., Results: The multi-omic model, consisting of chemotherapy status and radiomic and dosiomic features, outperformed the conventional model in internal and external validation, achieving AUC scores of 0.67 [95% CI: (0.61, 0.73)] and 0.65 [95% CI: (0.53, 0.77)], respectively, compared to the conventional model with 0.63 [95% CI: (0.56, 0.69)] and 0.56 [95% CI: (0.44, 0.67)], respectively. In multivariate analysis, only the multi-omic model signature was significantly correlated with severe OM in external validation (p = 0.017), demonstrating the independent predictive value of the multi-omic approach., Conclusion: A multi-omic model with combined clinical, radiomic and dosiomic features achieved superior pre-treatment prediction of severe OM. Further exploration is warranted to facilitate improved clinical decision-making and enable more effective and personalized care for the prevention and management of OM in NPC patients., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethics approval and consent to participate: The use of data was approved by the Research Ethics Committee (Kowloon Central/Kowloon East), reference number KC/KE-18–0085/ER-1, and the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee, reference number CRE-2022.689. Due to the retrospective nature of the study, patient consent to participate was waived., (© 2024. The Author(s).)

Introduction: Alongside the improved survival of nasopharyngeal cancer (NPC), late radiation toxicities are alarmingly hampering survivors' quality of life. A patient-reported symptom burden survey is lacking to address the unmet need for symptom management among local NPC survivors., Methods: A single-center cross-sectional survey was conducted on 211 NPC survivors who had completed radiation therapy for three to 120 months. We employed the Chinese version M. D. Anderson Symptom Inventory - Head & Neck Module (MDASI-HN-C), Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN-C), and a question extracted from the Cancer Survivors' Unmet Needs Measure (CaSUN)., Results: Two hundred valid responses were collected. Participants suffered from at least four moderate to severe symptoms (mean = 4.84, SD = 4.99). The top five severe symptoms were dry mouth, mucus problems, difficulty swallowing or chewing, teeth or gum problems, and memory problems. MDASI-HN-C subscales were negatively correlated with the physical, emotional, functional, and HN-specific domains of the FACT-HN-C. The unmet need for symptom management was positively associated with symptom burden, either general symptoms (Adjusted odds ratio [OR adj ] = 1.566, 95% CI = 1.282 - 1.914, p < 0.001) or top-5 symptoms (OR adj = 1.379, 95% CI = 1.185 - 1.604, p < 0.001), while negatively associated with post-RT time (OR adj = 0.981, 95% CI [0.972, 0.991], p < 0.001)., Conclusion: Virtually all NPC survivors suffer from late toxicities, which interplay with survivors' perceptions intricately to affect their unmet needs for symptom management. Personalized supportive care strategies with regular assessments and stratifications are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tam, Ching, Yip, Kwong, Chan, Wong and Lee.)

Background: Androgen deprivation therapy (ADT) is the foundational treatment for metastatic prostate cancer (PCa). Androgen receptor (AR) axis-targeted therapies are a new standard of care for advanced PCa. Although these agents have significantly improved patient survival, the suppression of testosterone is associated with an increased risk of cardiometabolic syndrome. This highlights the urgency of multidisciplinary efforts to address the cardiometabolic risk of anticancer treatment in men with PCa., Methods: Two professional organizations invited five urologists, five clinical oncologists, and two cardiologists to form a consensus panel. They reviewed the relevant literature obtained by searching PubMed for the publication period from April 2013 to April 2023, to address three discussion areas: (i) baseline assessment and screening for risk factors in PCa patients before the initiation of ADT and AR axis-targeted therapies; (ii) follow-up and management of cardiometabolic complications; and (iii) selection of ADT agents among high-risk patients. The panel convened four meetings to discuss and draft consensus statements using a modified Delphi method. Each drafted statement was anonymously voted on by every panelist., Results: The panel reached a consensus on 18 statements based on recent evidence and expert insights., Conclusion: These consensus statements serve as a practical recommendation for clinicians in Hong Kong, and possibly the Asia-Pacific region, in the management of cardiometabolic toxicities of ADT or AR axis-targeted therapies in men with PCa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Poon, Tan, Chan, Chan, Chan, Kan, Lam, Leung, Wong, Kam, Ng and Chiu.)

Objective: To evaluate and validate the recent and emerging data for prognostic and predictive biomarkers with therapeutic targets in breast cancer., Data Sources: A literature search from January 2015 to March 2022 was performed using the key terms breast cancer , clinical practice guidelines , gene mutations , genomic assay , immune cancer therapy , predictive and/or prognostic biomarkers , and targeted therapies ., Study Selection and Data Extraction: Relevant clinical trials, meta-analyses, seminal articles, and published evidence- and consensus-based clinical practice guidelines in the English language were identified, reviewed and evaluated., Data Synthesis: Breast cancer is a biologically heterogeneous disease, leading to wide variability in treatment responses and survival outcomes. Biomarkers for breast cancer are evolving from traditional biomarkers in immunohistochemistry (IHC) such as estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor type 2 (HER2) to genetic biomarkers with therapeutic implications (e.g. breast cancer susceptibility gene 1/2 [ BRCA1/2 ], estrogen receptor α [ ESR1] gene mutation, HER2 gene mutation, microsatellite instability [MSI], phosphatidylinositol 3-kinase catalytic subunit 3Cα [ PIK3CA ] gene mutation, neurotrophic tyrosine receptor kinase [ NTRK ] gene mutation). In addition, current data are most robust for biomarkers in immunotherapy (e.g. programmed cell death receptor ligand-1 [PD-L1], microsatellite instability-high [MSI-H] or deficient mismatch repair [dMMR]). Oncotype DX assay remains the best validated gene expression assay that is both predictive and prognostic whereas MammaPrint is prognostic for genomic risk., Conclusions: Biomarker-driven therapies have the potential to confer greater therapeutic advantages than standard-of-care therapies. The purported survival benefits associated with biomarker-driven therapies should be weighed against their potential harms.

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD)., Design: Retrospective cohort study., Methods: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005-2019., Findings: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months' follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5-17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies., Conclusion: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.

Objective. To study the effects of magnetic field gradients on the dose deposition in an inhomogeneous medium and to present the benefits offered by magnetic-field-modulated radiotherapy (MagMRT) under multiple radiation beams. Approach. Monte Carlo simulations were performed using the Geant4 simulation toolkit with a 7 MV photon beam from an Elekta Unity system. A water cuboid embedded with material slabs of water, bone, lung or air was used to study the effects of MagMRT within inhomogeneous medium. Two cylindrical water phantoms, with and without a toroidal lung insert embedded, were used to study the effects of MagMRT under single, opposing or four cardinal radiation beams. Optimized magnetic field variations in the form of a wavelet were used to induce dose modulation within the material slabs or at the iso-center of the phantoms. Main results. The magnitudes of the dose enhancement and reduction induced by the magnetic field gradients become more prominent in a medium of lower density. A maximum dose increase of 6.5% and a decrease of 4.8% were found inside bone, while an increase of 20.4% and a decrease of 13.9% were found in lung tissue. Under multiple radiation beams, the dose enhancement can be induced at the iso-center while the dose reduction occurs in regions around the tumor. For the case with four cardinal beams irradiating a homogeneous water cylinder, an 8.4% of dose enhancement and a 2.4% of dose reduction were found. When a toroidal lung insert was embedded, a maximum dose enhancement of 9.5% and a reduction of 17.0% were produced for anterior-posterior opposing fields. Significance. With an optimized magnetic field gradient, MagMRT can induce a dose boost to the target while producing a better sparing to the surrounding normal tissue, resulting in a sharper dose fall-off in all directions outside the target volume., (© 2022 IOP Publishing Ltd.)

Background: Quantitative measurement of plasma Epstein-Barr virus (EBV) DNA by real-time PCR at the end of primary treatment is a robust prognostic marker for nasopharyngeal carcinoma (NPC) patients. However, up to 40% of patients who would later develop disease recurrence had undetectable post-treatment plasma EBV DNA. Targeted sequencing for the entire EBV genome potentially allows a more comprehensive and unbiased detection of plasma EBV DNA and enables the use of other parameters such as fragment size as biomarkers. Hence, we explored if plasma EBV DNA sequencing might allow more accurate prognostication of NPC patients., Patients and Methods: Plasma samples collected from 769 patients with stage IIB-IVB NPC at 6-8 weeks after radiotherapy were analysed using targeted sequencing for EBV DNA., Results: The sensitivities of the PCR-based analysis, at a cut-off of any detectable levels of plasma EBV DNA, for prediction of local and distant recurrences were 42.3% and 85.3%, respectively. The sequencing-based analysis (involving quantitation and size profiling) achieved better performance for both local and distant recurrences than PCR. Using a cut-off of the proportion of plasma EBV DNA deduced by sequencing at 0.01%, the sensitivities of the sequencing-based analysis for local and distant recurrences were 88.5% and 97.1%, with the resultant negative predictive values of 99.1% and 99.4%, respectively. Among patients with undetectable EBV DNA on quantitative PCR, sequencing could further define a subgroup that enjoyed superior survival outcomes based on the proportion of plasma EBV DNA, with a 5-year progression-free survival (PFS) approaching 90%. On multivariate analysis, sequencing-based quantitative level of plasma EBV DNA was the independent prognostic factor with the highest hazard ratio for prediction of overall survival and PFS., Conclusion: NPC prognostication using post-treatment plasma EBV DNA could be enhanced through sequencing., Competing Interests: Disclosure KCAC and YMDL hold equities in DRA, Take2 and Grail/Illumina; were consultants to Grail and previously received research funding from Grail. YMDL is a scientific cofounder of Grail. WKJL holds equities in Grail/Illumina. PJ holds equities in DRA and Grail/Illumina; is a consultant to Take2; is a Director of KingMed Future. DCTC, WKJL, KCAC and YMDL have filed patent applications based on the data generated from this work. EPH receives speaker’s honoraria from Merck Sharp & Dohme (MSD) and Merck Serono and serves as a consultant or in the advisory board from MSD. BBYM serves in the advisory board and receives speaker’s honorarium from Novartis, Bristol-Myers Squibb and MSD and receives research grant from Novartis and is a consultant to Viracta Therapeutics and Y-Biologics. ATCC receives research funding from Merck Serono, MSD, Novartis, Pfizer and Eli Lily, speaker's honorarium from Beigene, Springer and Pfizer, travel funding from BMS, MSD, Pfizer, Roche, Novartis and AstraZeneca, and is an advisory board member for MSD, Tessa Therapeutics. BZ is the founder and shareholder of Health View Bioanalytic Limited. QTL is a consultant to MSD and serves in the advisory boards of Nanobiotics, Roche and Coherus. Patent royalties are received from Grail, Illumina, Sequenom, DRA, Take2 and Xcelom. All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Locally advanced and recurrent/ metastatic (R/M) head and neck cancers have poor prognosis generally. Radiotherapy (RT) is known to have multiple immunomodulatory effects, and various immune checkpoint inhibitors (ICIs) have been shown to be efficacious in the R/M setting in recent years. Hence, it is logical to combine RT and ICIs to improve the outlook for such patients, especially in view of the promising pre-clinical data on this novel combination. In this review, we highlighted the key mechanisms underlying the immunostimulatory and immunoinhibitory effects of RT, with a view to suggesting strategies to overcome radioresistance. We also discussed how the unique immune landscapes of virus-induced cancers, namely Epstein-Barr virus-induced nasopharyngeal carcinoma and human papillomavirus-mediated oropharyngeal cancer, could be exploited with ICIs. The landmark clinical trials in both the locally advanced and R/M settings were reviewed, and these trials showed that the combination of RT and ICIs is generally well tolerated. The potential reasons behind the largely negative results of these studies were also explored, focusing on various parameters including dose fractionation, sequencing, irradiated volume and the use of predictive biomarkers., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Progression to metastatic disease occurs in about half of all men who develop prostate cancer (PC), one of the most common cancers in men worldwide. Androgen deprivation therapy has been the mainstay therapy for patients with metastatic PC (mPC) since the 1940s. In the last decade, there has been unprecedented advancement in systemic therapies, e.g., taxane, androgen-signalling pathway inhibitors, and biomarker-driven targeted therapies for various stages of disease, resulting in overall survival improvement. Adding to ongoing controversies over how best to treat these patients is the recognition that ethnicity may influence prognosis and outcomes. This review discusses recent evidence for the impacts of Asian ethnicity specifically, which includes environmental, sociocultural, and genetic factors, on the approach to pharmacological management of mPC. Clear inter-ethnic differences in drug tolerability, serious adverse events (AEs), and genetic heterogeneity must all be considered when dosing and scheduling for treatment, as well as designing future precision studies in PC.

Background: Stereotactic body radiotherapy (SBRT) has potential radiobiologic and economic advantages over conventional fractionated radiotherapy (CFRT) in localized prostate cancer (PC). This study aimed to compare the effects of these two distinct fractionations on patient-reported quality of life (PRQOL) and tolerability., Methods: In this prospective phase II study, patients with low- and intermediate-risk localized PC were randomly assigned in a 1:1 ratio to the SBRT (36.25 Gy/5 fractions/2 weeks) or CFRT (76 Gy/38 fractions/7.5 weeks) treatment groups. The primary endpoint of variation in PRQOL at 1 year was assessed by changes in the Expanded Prostate Cancer Index Composite (EPIC) questionnaire scores and analysed by z-tests and t -tests., Results: Sixty-four eligible Chinese men were treated (SBRT, n = 31; CFRT, n = 33) with a median follow-up of 2.3 years. At 1 year, 40.0%/46.9% of SBRT/CFRT patients had a >5-point decrease in bowel score ( p = 0.08/0.28), respectively, and 53.3%/46.9% had a >2-point decrease in urinary score ( p = 0.21/0.07). There were no significant differences in EPIC score changes between the arms at 3, 6, 9 and 12 months, but SBRT was associated with significantly fewer grade ≥ 1 acute and 1-year late gastrointestinal toxicities (acute: 35% vs. 87%, p < 0.0001; 1-year late: 64% vs. 84%, p = 0.03), and grade ≥ 2 acute genitourinary toxicities (3% vs. 24%, p = 0.04) compared with CFRT., Conclusion: SBRT offered similar PRQOL and less toxicity compared with CFRT in Chinese men with localized PC.

The past three decades have borne witness to many advances in the understanding of the molecular biology and treatment of nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer endemic to southern China, southeast Asia and north Africa. In this Review, we provide a comprehensive, interdisciplinary overview of key research findings regarding NPC pathogenesis, treatment, screening and biomarker development. We describe how technological advances have led to the advent of proton therapy and other contemporary radiotherapy approaches, and emphasize the relentless efforts to identify the optimal sequencing of chemotherapy with radiotherapy through decades of clinical trials. Basic research into the pathogenic role of EBV and the genomic, epigenomic and immune landscape of NPC has laid the foundations of translational research. The latter, in turn, has led to the development of new biomarkers and therapeutic targets and of improved approaches for individualizing immunotherapy and targeted therapies for patients with NPC. We provide historical context to illustrate the effect of these advances on treatment outcomes at present. We describe current preclinical and clinical challenges and controversies in the hope of providing insights for future investigation., (© 2021. Springer Nature Limited.)

Objective. The feasibility of magnetic-field-modulated radiotherapy (MagMRT) with an MR-LINAC was investigated by studying the effects of dose enhancement and reduction using a transverse magnetic field with a longitudinal gradient applied along a photon radiation beam. Approach. Geant4 simulation toolkit was used to perform Monte Carlo simulations on a water phantom with the energy spectrum of a 7 MV flattening-filter-free photon beam from an Elekta Unity system as the source of radiation. Linear magnetic field gradients with magnitudes ranged from 1 to 6 T cm -1 and spatial extents of 1-3 cm were used to study the dependence of dose modulation on these two parameters. The effects of radiation field size and the ability of dose modulation through optimizing the waveform of magnetic field variation were also explored. Main results. Our results show that dose enhancement and reduction can be achieved by applying a transverse magnetic field with a longitudinal field gradient along a photon beam. The steeper the gradient, the more prominent is the effect. A dose enhancement of 33% and a dose reduction of 22% are found for a magnetic gradient of 6 T cm -1 and -6 T cm -1 respectively. The spatial extent of the dose modulation effect which is greater than 3% is found to be around 1-2 cm. Both the dose enhancement and reduction effects are independent of the radiation field sizes, but they exhibit different behaviors with the spatial extents of the gradient. Multiple locations of dose enhancement and reduction can be produced by modulating the waveform of the magnetic field variation along the radiation beam, demonstrating a vast degree of freedom in the modulation aspect of MagMRT. Significance. MagMRT is a conceptually feasible and promising new radiotherapy modulation technique along the direction of the radiation beam., (© 2021 Institute of Physics and Engineering in Medicine.)

Purpose: To study the dynamic changes in plasma Epstein-Barr virus (pEBV) DNA after radiotherapy in nasopharyngeal cancer (NPC)., Experimental Design: We conducted a randomized controlled trial of adjuvant chemotherapy versus observation in patients with NPC who had detectable pEBV DNA at 6 weeks post-radiotherapy. Randomized patients had a second pEBV DNA checked at 6 months post-randomization. The primary endpoint was progression-free survival (PFS)., Results: We prospectively enrolled 789 patients. Baseline post-radiotherapy pEBV DNA was undetectable in 573 (72.6%) patients, and detectable in 216 (27.4%) patients, of whom 104 (13.2%) patients were eligible for randomization to adjuvant chemotherapy ( n = 52) versus observation ( n = 52). The first post-radiotherapy pEBV DNA had a sensitivity of 0.48, specificity of 0.81, area under receiver-operator characteristics curve (AUC) of 0.65, false positive (FP) rate of 13.8%, and false negative (FN) rate of 14.4% for disease progression. The second post-radiotherapy pEBV DNA had improved sensitivity of 0.81, specificity of 0.75, AUC of 0.78, FP rate of 14.3%, and FN rate of 8.1%. Patients with complete clearance of post-radiotherapy pEBV DNA (51%) had survival superior to that of patients without post-radiotherapy pEBV DNA clearance (5-year PFS, 85.5% vs. 23.3%; HR, 9.6; P < 0.0001), comparable with patients with initially undetectable post-radiotherapy pEBV DNA (5-year PFS, 77.1%), irrespective of adjuvant chemotherapy or observation., Conclusions: Patients with NPC with detectable post-radiotherapy pEBV DNA who experienced subsequent pEBV DNA clearance had superior survival comparable with patients with initially undetectable post-radiotherapy pEBV DNA. Post-radiotherapy pEBV DNA clearance may serve as an early surrogate endpoint for long-term survival in NPC., (©2021 American Association for Cancer Research.)

Background and Purpose: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China and the first-line treatment is radiotherapy. Intensity-modulated radiation therapy (IMRT) can deliver high dose to cancer and low dose to normal tissue, but xerostomia is still one of the complications after IMRT. However, how the concentration of saliva electrolytes be affected by IMRT and the effects on the quality of life are still unknown. In this prospective study, 76 NPC patients were recruited from hospitals in Hong Kong to identify the change of saliva electrolytes and xerostomia-related quality of life before and after IMRT., Methods and Materials: Saliva and questionnaire were collected before IMRT, 1 month, 3 months, 6 months and 12 months after IMRT. The concentration of saliva electrolytes was detected using inductively coupled plasma-optical emission spectroscopy (ICP-OES)., Results: Saliva flow rate significantly decreased after IMRT. Decrease in the mean value of pH was observed but the difference is not statistically significant. The concentrations of potassium, iodine, and calcium decreased and chloride concentration increased after IMRT, while the concentrations of sodium, magnesium, copper or zinc were kept at the same level before and after treatment. Xerostomia-related quality of life was adversely affected by IMRT, but partially recovered after 1 year., Conclusions: Our study revealed the change of saliva electrolytes and xerostomia-related quality of life in patients undergone IMRT for NPC., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: After curative radiotherapy (RT) or chemoradiation (CRT), there is no validated tool to accurately identify patients for adjuvant therapy in nasopharyngeal carcinoma (NPC). Post-RT circulating plasma Epstein-Barr virus (EBV) DNA can detect minimal residual disease and is associated with recurrence and survival independent of TNM (tumor-lymph node-metastasis) stage. We aimed to develop and validate a risk model for stratification of NPC patients after completion of RT/CRT to observation or adjuvant therapy., Patients and Methods: The prospective multicenter 0502 EBV DNA screening cohort (Hong Kong NPC Study Group 0502 trial) enrolled from 2006 to 2015 (n = 745) was used for model development. For internal validation, we pooled independent patient cohorts from prospective clinical studies enrolled from 1997 to 2006 (n = 340). For external validation, we used retrospective cohort of NPC patients treated at Sun Yat-sen University Cancer Center from 2009 to 2012 (n = 837). Eligible patients had histologically confirmed NPC of Union for International Cancer Control (UICC) 7th Edition stage II-IVB who completed curative RT/CRT with or without neoadjuvant chemotherapy, had post-RT EBV DNA tested within 120 days after RT and received no adjuvant therapy. The primary end point was overall survival (OS). We used recursive-partitioning analysis (RPA) to classify patients into groups of low, intermediate, and high risk of death., Results: Combining post-RT EBV DNA level (0, 1-49, 50-499, and ≥500 copies/ml) and TNM stage (II, III, IVAB), RPA model classified patients into low-, intermediate-, and high-risk groups with 5-year OS of 89.4%, 78.5% and 37.2%, respectively. The RPA low-risk group had comparable OS to TNM stage II (5-year OS 88.5%) but identified more patients (64.8% versus stage II 28.1%) that could potentially be spared adjuvant therapy toxicity. The RPA model (c-index 0.712) showed better risk discrimination than either the TNM stage (0.604) or post-RT EBV DNA alone (0.675) with improved calibration and consistence. These results were validated in both internal and external cohorts., Conclusion: Combining post-RT EBV DNA and TNM stage improved risk stratification in NPC., Competing Interests: Disclosure EPH, speaker's honoraria from Merck Sharp & Dohme (MSD), Merck Serono; consultant/advisory board from MSD. BBYM, advisory board and speaker's honorarium from Novartis, Bristol-Myers Squibb, MSD; research grant from Novartis, Boehringer Ingelheim; WKJL holds equity in Grail; KCAC, grant support from the Research Grants Council of Hong Kong, Kadoorie Charitable Foundation and Cirina/Grail; royalties from Sequenom, Illumina, Grail/Cirina, Xcelom, DRA and Take2; holds equities of DRA and Take2; YMDL, received sponsored research agreement from Grail; research grant from Hong Kong Research Grants Council; endowed professorship: Li Ka Shing Foundation; shareholding, membership of scientific advisory board, sponsored research agreement, licensing, royalties from Grail; shareholding, licensing, royalties from Take2; consultancy to Decheng Capital: licensing, royalties from Sequenom, DRA Limited and Illumina; ATCC, received research and travel grants: MSD, Pfizer, Roche. All remaining authors have declared no conflicts of interest., (Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Aims: Recently published international guidelines recommended using the stimulated thyroglobulin (sTg) post-radioactive iodine (RAI) ablation, in conjunction with tumour stage, as a risk stratification factor. The choice of cut-off values for sTg, namely 1 and 10 ng/ml, was, however, largely based on the functional sensitivities of the assays used, with relatively few published data addressing the prognostic impact of alternative cut-off values. Our study aims to provide data on the prognostic value of sTg at different levels of sensitivities and specificities., Materials and Methods: We conducted a retrospective review of all adult cases of differentiated thyroid carcinoma receiving RAI ablation at our centre from 2008 to 2010. All patients had sTg measured at around 6 months post-ablation. The functional sensitivity of our assay was 0.5 ng/ml. The outcome was adverse clinical event, defined as cancer-related death, persistent macroscopic disease demonstrable on imaging (including radioisotope scan) and/or receiving further treatment for persistent or recurrent disease. A receiver operating characteristic (ROC) analysis was carried out., Results: We identified 140 patients treated in the review period, with 106 of them suitable for further analysis. The reasons for exclusion included the presence of anti-thyroglobulin antibodies and medullary or anaplastic histological subtypes. Most (54.7%) had intermediate-risk disease as per the American Thyroid Association classification (2009). The median follow-up duration was 6.4 years; the minimum, excluding deaths, was 5.0 years. ROC analysis showed that the optimal cut-off value of sTg for predicting adverse clinical events was >1.0 ng/ml, associated with a sensitivity of 90.9%, a specificity of 81.0%, a positive predictive value of 55.6% and a negative predictive value of 97.1%., Conclusion: Based on ROC analysis of sensitivities and specificities, our data showed that a post-ablation sTg value of 1 ng/ml is the optimal cut-off in prognostication of adverse clinical events., (Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Folate level was proposed to be a predictor for fluoropyrimidine-related toxicity. We conducted a prospective study to determine the association between serum and red-cell folate and capecitabine-related toxicity in patients with colorectal cancers., Materials and Methods: Eligibility criteria included diagnosis of colorectal cancers; eligible patients who were scheduled to undergo capecitabine monotherapy or capecitabine-oxaliplatin (CAPOX) for adjuvant or palliative purposes. Exclusion criteria included concomitant radiotherapy or chemotherapy other than capecitabine or CAPOX and creatinine clearance <30 mL/min. Fasting serum and red-cell folate were measured prior to chemotherapy. Capecitabine was administered at 2,500 mg/m 2 per day (monotherapy) or 2,000 mg/m 2 per day (CAPOX) for 14 days every 3 weeks. The toxicity of the first four cycles was documented by clinical investigators who were blinded to folate levels., Results: A total of 144 patients were recruited, of whom 126 were eligible; 40 patients had capecitabine alone, and 86 patients received CAPOX. The rates of grade 2 and grade 3 toxicity were 63.5% and 14.3%, respectively. Nausea and vomiting were the most common grade ≥2 adverse event (47.7%), followed by hand-foot syndrome (25.4%), diarrhea (23.1%), and neutropenia (22.3%). Combination with oxaliplatin (odds ratio [OR], 2.77; p  = .043) and serum folate (OR, 10.33; p  = .002) were independent predictors of grade ≥2 toxicity. Red-cell folate was not predictive of toxicity. For every 10 nmol/L increment in serum folate, the risk of grade ≥2 toxicity increased by 9%., Conclusion: Serum folate level, but not red-cell folate, was associated with higher rate of grade ≥2 toxicity during capecitabine-based treatment. Excessive folate intake may be avoided before and during capecitabine-based chemotherapy., Implications for Practice: This is the first prospective study to evaluate the association between serum folate level and capecitabine-related toxicity in patients with colon cancers. It shows that higher serum folate level is associated with increased risks of moderate to severe toxicity during capecitabine-based treatment. Excessive folate intake should be avoided before and during capecitabine-based chemotherapy., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Background: The present study retrospectively evaluated the efficacy and safety of enzalutamide in different lines of metastatic castration-resistant prostate cancer (mCRPC) treatment in a real-world setting., Patients and Methods: The clinical records of patients with mCRPC treated with enzalutamide between August 2015 and October 2017 were retrieved from all 7 public oncology centers in Hong Kong and reviewed. The primary endpoint was progression-free survival (PFS) in first (1L), second (2L), and third or fourth lines (3L or 4L) of CRPC treatment. Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and tolerance., Results: Among a total of 117 patients (median age of 73 years [range, 52-90 years]), 34 (29.1%), 57 (48.7%), and 26 (19.3%) patients had enzalutamide as their 1L (chemo-naive), 2L (post-docetaxel or -abiraterone), and 3L or above treatment options. The overall PSA response rates were 43.6%, and were 73.5%, 35.1%, and 19.2% for 1L, 2L, and 3L or 4L treatment, respectively. PFS and OS were significantly associated with the line of treatment in the univariate survival analysis (1L/2L/3L and 4L; PFS, 7.1/3.9/2.2 months; OS, not reached/15.8/7.4 months; both P = .0002) but not in the multivariate analysis. The observed incidence of any fatigue (grade 1 or 2, 54.7%; grade 3 or 4, 9.4%) was much higher than reported in the AFFIRM (A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100 [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 34%) and PREVAIL (A Multinational Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy And Safety Study Of Oral Mdv3100 In Chemotherapy-naïve Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 36%) trials; as well, grade ≥ 2 fatigue was significantly associated with 3L or 4L treatment (P = .01 in both univariate and multivariate analyses)., Conclusion: In the real-life setting, there was a higher incidence of enzalutamide-related fatigue than reported in the trials. Earlier lines of enzalutamide treatment were associated with longer PFS and OS, more frequent PSA response, and less fatigue., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)