Dosimetric parameters predict radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma patients: A systematic review and meta-analysis.

This systematic review examines the role of dosimetric parameters in predicting temporal lobe necrosis (TLN) risk in nasopharyngeal carcinoma (NPC) patients treated with three-dimensional conformal RT (3D-CRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). TLN is a serious late complication that can adversely affect the quality of life of NPC patients. Understanding the relationship between dosimetric parameters and TLN can guide treatment planning and minimize radiation-related complications. A comprehensive search identified relevant studies published up to July 2023. Studies reporting on dosimetric parameters and TLN in NPC patients undergoing 3D-CRT, IMRT, and VMAT were included. TLN incidence, follow-up duration, and correlation with dosimetric parameters of the temporal lobe were analyzed. The review included 30 studies with median follow-up durations ranging from 28 to 110 months. The crude incidence of TLN varied from 2.3 % to 47.3 % and the average crude incidence of TLN is approximately 14 %. Dmax and D1cc emerged as potential predictors of TLN in 3D-CRT and IMRT-treated NPC patients. Threshold values of >72 Gy for Dmax and >62 Gy for D1cc were associated with increased TLN risk. However, other factors should also be considered, including host characteristics, tumor-specific features and therapeutic factors. In conclusion, this systematic review highlights the significance of dosimetric parameters, particularly Dmax and D1cc, in predicting TLN risk in NPC patients undergoing 3D-CRT, IMRT, and VMAT. The findings provide valuable insights that can help in developing optimal treatment planning strategies and contribute to the development of clinical guidelines in this field.

Governing cross-border healthcare in mainland China: a scoping review of national policies from 2002 to 2022.

This study reviews national-level policies regulating cross-border healthcare in mainland China after it acceded to the World Trade Organization (WTO). Policy documents from official websites of the State Council and 19 ministries were screened, from which 487 policy documents were analyzed. WTO's five modes of trade and WHO's six building blocks of healthcare system were used to guide the analysis of policymaking patterns, charting of policy evolution process, identification of key policy areas, differentiation of 29 detailed policy themes, and identification of major countries/regions involved in cross-border healthcare. The findings lead to four policy recommendations: (1) to establish a national-level committee to govern cross-border healthcare, (2) to build an information system to comprehensively integrate various information on cross-border healthcare consumption and provision, (3) to take more proactive policy actions in healthcare internationalization, and (4) to carry out reform experiments in key sub-national regions to fully explore various possibilities in developing and regulating cross-border healthcare.

Treatment strategy for de novo metastatic nasopharyngeal carcinoma: a literature review.

BACKGROUND AND OBJECTIVE: Nasopharyngeal carcinoma (NPC) with de novo distant metastasis (M1) is classified as stage IVB in the 8th edition of the staging system jointly adopted by the American Joint Committee on Cancer and the International Union against Cancer Control. Patients with M1 disease generally have a relatively short life expectancy. This review discusses the personalized and intensified treatment strategies for de novo metastatic NPC. METHODS: A literature search was conducted on PubMed to identify peer-reviewed publications on subdivisions of M1 disease and treatment of de novo metastatic NPC. Clinicaltrials.gov and Chinese Clinical Trial Register were searched to identify ongoing clinical trials evaluating systemic or local therapy of previously untreated metastatic NPC. KEY CONTENT AND FINDINGS: M1 encompasses a diverse group of diseases. Several important factors, including tumor burden, EBV-DNA levels, location of involvement, the number of metastasis, and treatment strategies, influence the prognosis of NPC patients. Researchers have attempted to define M1 subcategorization to reflect the underlying risk profile and tailor personalized treatment. Recent advancements have brought new hope for this otherwise incurable condition. In the era of immunotherapy, checkpoint inhibitors have become the first-line systemic treatment for metastatic NPC in JUPITER-02, CAPTAIN-1st, and RATIONALE-309. Additionally, the value of radical locoregional radiation therapy and ablative treatment to distant metastatic sites should not be overlooked in patients with de novo metastatic diseases. Locoregional radiation with concurrent chemotherapy, maintenance chemotherapy, and radical local treatment to metastatic sites are emerging as potential treatment options. CONCLUSIONS: Given the diversity of metastatic NPC, a multimodality approach incorporating chemotherapy, immunotherapy, locoregional radiation and ablative treatment to metastatic sites has been shown to improve overall control. Further research is needed to determine the efficacy and optimal duration of maintenance therapy.

The impact of the multi-disciplinary molecular tumour board and integrative next generation sequencing on clinical outcomes in advanced solid tumours.

Background: The integration of next-generation sequencing (NGS) comprehensive gene profiling (CGP) into clinical practice is playing an increasingly important role in oncology. Therefore, the HKU-HKSH Multi-disciplinary Molecular Tumour Board (MTB) was established to advance precision oncology in Hong Kong. A multicenter retrospective study investigated the feasibility of the HKU-HKSH MTB in determining genome-guided therapy for treatment-refractory solid cancers in Hong Kong. Methods: Patients who were presented at the HKU-HKSH MTB between August 2018 and June 2022 were included in this study. The primary study endpoints were the proportion of patients who receive MTB-guided therapy based on genomic analysis and overall survival (OS). Secondary endpoints included the proportion of patients with actionable genomic alterations, objective response rate (ORR), and disease control rate (DCR). The Kaplan-Meier method was used in the survival analyses, and hazard ratios were calculated using univariate Cox regression. Findings: 122 patients were reviewed at the HKU-HKSH MTB, and 63% (n = 77) adopted treatment per the MTB recommendations. These patients achieved a significantly longer median OS than those who did not receive MTB-guided therapy (12.7 months vs. 5.2 months, P = 0.0073). Their ORR and DCR were 29% and 65%, respectively. Interpretation: Our study demonstrated that among patients with heavily pre-treated advanced solid cancers, MTB-guided treatment could positively impact survival outcomes, thus illustrating the applicability of NGS CGPs in real-world clinical practice. Funding: The study was supported by the Li Shu Pui Medical Foundation. Dr Aya El Helali was supported by the Li Shu Pui Medical Foundation Fellowship grant from the Li Shu Pui Medical Foundation. Funders had no role in study design, data collection, data analysis, interpretation, or writing of the report.

Optimal time for early therapeutic response prediction in nasopharyngeal carcinoma with functional magnetic resonance imaging.

Background and Purpose: Physiological changes in tumour occur much earlier than morphological changes. They can potentially be used as biomarkers for therapeutic response prediction. This study aimed to investigate the optimal time for early therapeutic response prediction with multi-parametric magnetic resonance imaging (MRI) in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemo-radiotherapy (CCRT). Material and Methods: Twenty-seven NPC patients were divided into the responder (N = 23) and the poor-responder (N = 4) groups by their primary tumour post-treatment shrinkages. Single-voxel proton MR spectroscopy (1H-MRS), diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI were scanned at baseline, weekly during CCRT and post-CCRT. The median choline peak in 1H-MRS, the median apparent diffusion coefficient (ADC) in DW-MRI, the median influx rate constant (Ktrans), reflux rate constant (Kep), volume of extravascular-extracellular space per unit volume (Ve), and initial area under the time-intensity curve for the first 60 s (iAUC60) in DCE-MRI were compared between the two groups with the Mann-Whitney tests for any significant difference at different time points. Results: In DW-MRI, the percentage increase in ADC from baseline to week-1 for the responders (median = 11.39%, IQR = 18.13%) was higher than the poor-responders (median = 4.91%, IQR = 7.86%) (p = 0.027). In DCE-MRI, the iAUC60 on week-2 was found significantly higher in the poor-responders (median = 0.398, IQR = 0.051) than the responders (median = 0.192, IQR = 0.111) (p = 0.012). No significant difference was found in median choline peaks in 1H-MRS at all time points. Conclusion: Early perfusion and diffusion changes occurred in primary tumours of NPC patients treated with CCRT. The DW-MRI on week-1 and the DCE-MRI on week-2 were the optimal time points for early therapeutic response prediction.

Recommendations for Epstein-Barr virus-based screening for nasopharyngeal cancer in high- and intermediate-risk regions.

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.

Current Radiotherapy Considerations for Nasopharyngeal Carcinoma.

Radiotherapy is the primary treatment modality for nasopharyngeal carcinoma (NPC). Successful curative treatment requires optimal radiotherapy planning and precise beam delivery that maximizes locoregional control while minimizing treatment-related side effects. In this article, we highlight considerations in target delineation, radiation dose, and the adoption of technological advances with the aim of optimizing the benefits of radiotherapy in NPC patients.

Post-radiation primary hypothyroidism in patients with head and neck cancer: External validation of thyroid gland dose-volume constraints with long-term endocrine outcomes.

BACKGROUND: Post-radiation primary hypothyroidism is a common late complication in head and neck cancer (HNC) survivors. No radiation dose-volume constraint of the thyroid gland has been externally validated for predicting long-term thyroid function outcomes. MATERIALS AND METHODS: This external validation study evaluated the diagnostic properties of 22 radiation dose-volume constraints of the thyroid gland proposed in the literature. Radiation dosimetric data from 488 HNC patients who underwent neck irradiation from January 2013 to December 2015 at two tertiary oncology centers were reviewed. The diagnostic metrics of candidate constraints were computed by inverse probability of censoring weighting and compared using time-dependent receiver operating characteristic (ROC) curves with death designated as a competing event. Multivariable regression analyses were performed using the Fine-Gray sub-distribution hazard model. RESULTS: Over a median follow-up period of 6.8 years, 205 (42.0 %) patients developed post-radiation primary hypothyroidism. The thyroid volume spared from 60 Gy (VS60) had the largest area under ROC curve of 0.698 at 5 years after radiotherapy. Of all evaluated constraints, VS60 at a cutoff value of 10 cc had the highest F-score of 0.53. The 5-year hypothyroidism risks of patients with thyroid VS60 ≥ 10 cc and < 10 cc were 14.7 % and 38.2 %, respectively (p < 0.001). The adjusted sub-hazard ratio for post-radiation primary hypothyroidism for VS60 < 10 cc was 1.87 (95 % confidence interval, 1.22-2.87; p < 0.001). CONCLUSION: Thyroid VS60 is the best radiation dose-volume parameter to predict the long-term risk of primary hypothyroidism in patients with HNC who underwent neck irradiation. VS60 ≥ 10 cc is a robust constraint that limits the 5-year primary hypothyroidism risk to less than 15 % and should be routinely employed during radiotherapy optimization.

Particle beam therapy for nasopharyngeal cancer: A systematic review and meta-analysis.

Background/purpose: A systematic review and meta-analysis were performed to better understand the benefits of particle beam therapy for nasopharyngeal cancer (NPC) treatment. The survival outcomes and toxicity of primary and recurrent NPC patients treated with proton or carbon ion beam therapy were investigated. Method: PubMed, Scopus, and Embase were searched between 1 January 2007 to 3 November 2021. The inclusion and exclusion criteria included studies with either primary or recurrent NPC patients, sample size of ≥10 patients, and proton or carbon ion beam therapy as interventions. Twenty-six eligible studies with a total of 1502 patients were included. We used a random-effect meta-analysis to examine the impact of particle beam therapy on primary NPC patients and qualitatively described the results among recurrent patients. The primary outcome was overall survival (OS), while secondary outcomes included progression-free survival (PFS), local control (LC) and toxicity. Results: The pooled OS at 1-year, 2-year and 3-year and 5-year for primary NPC patients who received particle beam therapy were 96 % (95 % confidence interval (CI) = 92 %-98 %), 93 % (95 % CI = 83 %-97 %), 90 % (95 % CI = 73 %-97 %) and 73 % (95 % CI = 52 %-87 %) respectively. The pooled 1-year and 2-year PFS, and LC for these patients were above 90 %. For locally recurrent NPC patients, the 1-year OS rate ranged from 65 % to 92 %, while the 1-year LC rate ranged from 80 % to 88 %. Both proton and carbon ion beam therapy were generally safe among primary and recurrent patients, with ≥G3 late toxicity rates of 20 % or less. Approximately a 5 % mortality rate was reported among recurrent patients. Conclusions: This systematic review and meta-analysis demonstrated particle beam therapy has great potential in treating NPC, yielding excellent survival outcomes with low toxicity. However, further investigations are needed to assess the long-term outcomes and cost-effectiveness of this newer form of radiotherapy.

Correlations of tumour permeability parameters with apparent diffusion coefficient in nasopharyngeal carcinoma.

Background and Purpose: Functional imaging has an established role in therapeutic monitoring of cancer treatments. This study evaluated the correlations of tumour permeability parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and tumour cellularity derived from apparent diffusion coefficient (ADC) in nasopharyngeal carcinoma (NPC). Material and Methods: Twenty NPC patients were examined with DCE-MRI and RESOLVE diffusion-weighted MRI (DW-MRI). Tumour permeability parameters were quantitatively measured with Tofts compartment model. Volume transfer constant (Ktrans), volume of extravascular extracellular space (EES) per unit volume of tissue (Ve), and the flux rate constant between EES and plasma (Kep) from DCE-MRI scan were measured. The time-intensity curve was plotted from the 60 dynamic phases of DCE-MRI. The initial area under the curve for the first 60 s of the contrast agent arrival (iAUC60) was also calculated. They were compared with the ADC value derived from DW-MRI with Pearson correlation analyses. Results: Among the DCE-MRI permeability parameters, Kep had higher linearity in inverse correlation with ADC value (r = -0.69, p = <0.05). Ktrans (r = -0.60, p=<0.05) and iAUC60 (r = -0.64, p = <0.05) also had significant inverse correlations with ADC. Ve showed a significant positive correlation with ADC (r = 0.63, p = <0.05). Conclusions: Nasopharyngeal tumour vascular permeability parameters derived from DCE-MRI scan were correlated linearly with tumour cellularity measured by free water diffusability with ADC. The clinical implementations of these linear correlations in the quantitative assessments of therapeutic response for NPC patients may be worth to further explore.

Epstein-Barr virus directed screening for nasopharyngeal carcinoma in individuals with positive family history: A systematic review.

OBJECTIVES: Evidence to support Epstein-Barr virus (EBV)-directed population nasopharyngeal carcinoma (NPC) screening has been growing. Familial aggregation is a well-recognized phenomenon in endemic regions. This systematic review summarizes the role of EBV-directed screening in individuals with a positive family history (FH+) of NPC. METHODS: We searched four electronic databases from their inception to October 2021. We included studies on individuals with FH+ of NPC who had undergone EBV-directed investigations, with no restriction in the testing methods or analytic techniques. The primary and secondary outcomes were EBV positivity rates and NPC incidence rates, respectively. Meta-analyses were performed using the random-effect model. RESULTS: Ten cross-sectional studies (n = 7436) and three cohort studies (n = 4306) were included. The pooled relative risk (RR) of EBV positivity between individuals with and without FH+ of NPC were 2.79 (95 % CI 1.37-5.68, p = 0.005) for viral capsid antigen (VCA) IgA, 3.09 (95 % CI 0.65-14.83, p = 0.16) for Epstein-Barr nuclear antigen (EBNA1) IgA, and 1.76 (95 % CI 1.04-2.96, p = 0.03) for combined EBNA1/VCA IgA. In the three cohort studies, the NPC incidence rates ranged from 90.2 to 266 per 100 000 person-years with high proportions of early-stage diseases. FH+ individuals who were EBV-positive had a 2.5 to 30.7-fold risk of NPC development compared to their EBV-negative counterparts. CONCLUSION: Family members of NPC patients had significantly higher EBV positivity rates than the general population. FH+ individuals who are EBV-positive had high risks of developing NPC. Familial screening using EBV serology may facilitate early NPC detection in endemic areas.

A Single-Arm Phase 2 Trial on Induction Chemotherapy Followed by Concurrent Chemoradiation in Nasopharyngeal Carcinoma Using a Reduced Cumulative Dose of Cisplatin.

Background: We conducted this study to evaluate if a reduced cumulative dose of induction and concurrent cisplatin conferred similar favorable outcomes when compared to trial NPC-0501. Methods: Newly diagnosed nasopharyngeal carcinoma (NPC) with stage III-IVA were prospectively recruited from January 2015 to September 2019. Induction chemotherapy (IC) consisted of cisplatin 80mg/m2 on day 1 and capecitabine 1000mg/m2 twice daily from day 1 to 14 every 3 weeks for 3 cycles followed by concurrent chemoradiotherapy (CCRT) with 2 cycles of cisplatin 100mg/m2 given every 3 weeks. Tumor response was evaluated according to RECIST v1.1. Acute and late adverse events (AEs) were graded with CTCAE v4.0 and Late Radiation Morbidity Scoring of the RTOG, respectively. Results: 135 patients were recruited. At 16 weeks after CCRT, all 130 patients who completed the entire course of radiotherapy (RT) had a complete response upon final assessment. With a median follow-up of 36.2 months, 22 treatment failures and 8 deaths were observed. The 3-year progression-free survival, overall survival, locoregional recurrence-free survival, and distant recurrence-free survival were 83.7%, 94.1%, 94.1%, and 85.9%, respectively. Our survival data outcomes were similar to those reported in the cisplatin and capecitabine (PX) induction arm of the 0501 trial. 103 patients (76.3%) reported acute grade 3-4 AEs. Two patients (1.5%) had late grade 3-4 complications, numerically fewer than those reported in the NPC-0501 trial. Conclusions: Induction PX and concurrent cisplatin with a reduced cumulative cisplatin dose yield survival outcomes comparable to those reported in the NPC-0501 trial with excellent tolerability. Therefore, a reduced cumulative dose of cisplatin is a promising treatment scheme for nasopharyngeal carcinoma.

Exploratory Study of NPC-0501 Trial: Optimal Cisplatin Dose of Concurrent and Induction/Adjuvant Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma.

PURPOSE: The current recommendation for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is cisplatin-based induction chemotherapy (IC) or adjuvant chemotherapy (AC) plus concurrent chemoradiotherapy (CRT). However, data on the optimal platinum doses for each phase of combined regimens are lacking. EXPERIMENTAL DESIGN: 742 patients with NPC in the NPC-0501 trial treated with CRT plus IC/AC and irradiated with intensity-modulated radiotherapy (IMRT) were analyzed. The optimal platinum dose to achieve the best overall survival (OS) in the concurrent and induction/adjuvant phases was studied. RESULTS: Evaluation of the whole series shows the optimal platinum dose was 160 mg/m2 in the concurrent and 260 mg/m2 in the induction/adjuvant phase. Repeating the analyses on 591 patients treated with cisplatin throughout (no replacement by carboplatin) confirmed the same results. The cohort with optimal platinum doses in both phases had better OS than the cohort suboptimal in both phases (stage III: 90% vs. 75%; stage IVA-B: 80% vs. 56%, at 5-year). Multivariable analyses confirmed optimal platinum doses in both phases versus suboptimal dose in each phase are significant independent factors for OS, with HR of 0.61 [95% confidence interval (CI), 0.41-0.91] and 0.67 (95% CI, 0.48-0.94), respectively. Treatment sequence was statistically insignificant after adjusting for platinum doses. CONCLUSIONS: Both concurrent and IC/AC are needed for locoregionally advanced NPC, even for patients irradiated by IMRT; the concurrent platinum dosage could be set at ≥160 mg/m2 when coupled with adequate induction/adjuvant dosage at ≥260 mg/m2 (or at least ≥240 mg/m2). To achieve these optimal dosages, IC-CRT at conventional fractionation is favored.

The Selective Role of Open and Endoscopic Approaches for Sinonasal Malignant Tumours.

Endoscopic endonasal surgery has been demonstrated to be effective in the treatment of selected cases of sinonasal cancers. However, in cases of locally advanced neoplasms, as well as recurrences, the most appropriate approach is still debated. The present review aims to summarize the current state of knowledge on the utility of open approaches to resect sinonasal malignant tumours. Published comparative studies and meta-analyses suggest comparable oncological results with lower morbidity for the endoscopic approaches, but selection biases cannot be excluded. After a critical analysis of the available literature, it can be concluded that endoscopic surgery for selected lesions allows for oncologically safe resections with decreased morbidity. However, when endoscopic endonasal surgery is contraindicated and definitive chemoradiotherapy is not appropriate, craniofacial and transfacial approaches remain the best therapeutic option.