Neurological complications of modern radiotherapy for head and neck cancer.

Radiotherapy is one of the mainstay treatment modalities for the management of non-metastatic head and neck cancer (HNC). Notable improvements in treatment outcomes have been observed in the recent decades. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and charged particle therapy, have significantly improved tumor target conformity and enabled better preservation of normal structures. However, because of the intricate anatomy of the head and neck region, multiple critical neurological structures such as the brain, brainstem, spinal cord, cranial nerves, nerve plexuses, autonomic pathways, brain vasculature, and neurosensory organs, are variably irradiated during treatment, particularly when tumor targets are in close proximity. Consequently, a diverse spectrum of late neurological sequelae may manifest in HNC survivors. These neurological complications commonly result in irreversible symptoms, impair patients' quality of life, and contribute to a substantial proportion of non-cancer deaths. Although the relationship between radiation dose and toxicity has not been fully elucidated for all complications, appropriate application of dosimetric constraints during radiotherapy planning may reduce their incidence. Vigilant surveillance during the course of survivorship also enables early detection and intervention. This article endeavors to provide a comprehensive review of the various neurological complications of modern radiotherapy for HNC, summarize the current incidence data, discuss methods to minimize their risks during radiotherapy planning, and highlight potential strategies for managing these debilitating toxicities.

Multi-domain neurocognitive impairment following definitive intensity-modulated radiotherapy for nasopharyngeal cancer: A cross-sectional study.

INTRODUCTION: Neurocognitive impairment from inadvertent brain irradiation is common following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aimed to determine the prevalence, pattern, and radiation dose-toxicity relationship of this late complication. MATERIALS AND METHODS: We undertook a cross-sectional study of 190 post-IMRT NPC survivors. Neurocognitive function was screened using the Montreal Cognitive Assessment-Hong Kong (HK-MoCA). Detailed assessments of eight distinct neurocognitive domains were conducted: intellectual capacity (WAIS-IV), attention span (Digit Span and Visual Spatial Span), visual memory (Visual Reproduction Span), verbal memory (Auditory Verbal Learning Test), processing speed (Color Trail Test), executive function (Stroop Test), motor dexterity (Grooved Pegboard Test) and language ability (Verbal Fluency Test). The mean percentiles and Z-scores were compared with normative population data. Associations between radiation dose and brain substructures were explored using multivariable logistic regression. RESULTS: The median post-IMRT interval was 7.0 years. The prevalence of impaired HK-MoCA was 25.3 % (48/190). Among the participants, 151 (79.4 %) exhibited impairments in at least one neurocognitive domain. The predominantly impaired domains included verbal memory (short-term: mean Z-score, -0.56, p < 0.001; long-term: mean Z-score, -0.70, p < 0.001), processing speed (basic: mean Z-score, -1.04, p < 0.001; advanced: mean Z-score, -0.38, p < 0.001), executive function (mean Z-score, -1.90, p < 0.001), and motor dexterity (dominant hand: mean Z-score, -0.97, p < 0.001). Radiation dose to the whole brain, hippocampus, and temporal lobe was associated with impairments in executive function, verbal memory, processing speed, and motor dexterity. CONCLUSIONS: Neurocognitive impairment is prevalent and profound in post-IMRT NPC survivors. Cognitive assessment and rehabilitation should be considered part of survivorship care.

Circumvention of Gefitinib Resistance by Repurposing Flunarizine via Histone Deacetylase Inhibition.

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) for treating advanced non-small cell lung cancer (NSCLC). However, drug resistance seriously impedes the clinical efficacy of gefitinib. This study investigated the repositioning of the non-oncology drug capable of inhibiting histone deacetylases (HDACs) to overcome gefitinib resistance. A few drug candidates were identified using the in silico repurposing tool "DRUGSURV" and tested for HDAC inhibition. Flunarizine, originally indicated for migraine prophylaxis and vertigo treatment, was selected for detailed investigation in NSCLC cell lines harboring a range of different gefitinib resistance mechanisms (EGFR T790M, KRAS G12S, MET amplification, or PTEN loss). The circumvention of gefitinib resistance by flunarizine was further demonstrated in an EGFR TKI (erlotinib)-refractory patient-derived tumor xenograft (PDX) model in vivo. The acetylation level of cellular histone protein was increased by flunarizine in a concentration- and time-dependent manner. Among the NSCLC cell lines evaluated, the extent of gefitinib resistance circumvention by flunarizine was found to be the most pronounced in EGFR T790M-bearing H1975 cells. The gefitinib-flunarizine combination was shown to induce the apoptotic protein Bim but reduce the antiapoptotic protein Bcl-2, which apparently circumvented gefitinib resistance. The induction of Bim by flunarizine was accompanied by an increase in the histone acetylation and E2F1 interaction with the BIM gene promoter. Flunarizine was also found to upregulate E-cadherin but downregulate the vimentin expression, which subsequently inhibited cancer cell migration and invasion. Importantly, flunarizine was also shown to significantly potentiate the tumor growth suppressive effect of gefitinib in EGFR TKI-refractory PDX in vivo. The findings advocate for the translational application of flunarizine to circumvent gefitinib resistance in the clinic.

Comparison of Clinical Outcomes, Pathologic Characteristics, and Immune-Related Features of Postradiation vs Sporadic Oral Cavity Squamous Cell Carcinoma.

Importance: Postradiation oral cavity squamous cell carcinoma (OCSCC) is a common secondary malignant neoplasm affecting survivors of head and neck cancer who underwent radiotherapy. The clinical, pathologic, and immune-related features of postradiation OCSCC are poorly characterized, and treatment options are limited because of surgical difficulty and high morbidity associated with reirradiation. Objective: To determine whether postradiation OCSCC has distinctive clinical, pathologic, and immune-related features compared with demographic-matched sporadic OCSCC. Design, Setting, and Participants: This retrospective matched cohort study was conducted at a single tertiary oncology center in Hong Kong. Participants included consecutive patients with OCSCC diagnosed between 2000 and 2020. Patients with postradiation OCSCC were matched with patients with sporadic OCSCC using age, year of diagnosis, sex, and anatomic subsites. Data analysis was performed from July to December 2022. Exposure: Head and neck irradiation involving the oral cavity before the diagnosis of OCSCC. Main Outcomes and Measures: The primary outcomes were relapse pattern, survival, and causes of death. Pathologic features; immunohistochemical staining for programmed death-ligand 1, PD-1, MSH6, PMS2, FOXP3, and Ki67; and mRNA expression of 31 immune-related genes were also analyzed. Results: A total of 173 patients, 60 with postradiation OCSCC (median [IQR] age, 63.8 [53.0-71.7] years; 43 men [71.7%]) and 113 with sporadic OCSCC (median [IQR] age, 64.4 [52.8-70.6] years; 83 men [73.5%]), were included. Patients with postradiation OCSCC had a higher proportion of N0 disease than those with sporadic OCSCC (50 patients [83.3%] vs 56 patients [49.6%]). With a median (IQR) follow-up of 10.2 (1.2-20.5) years, the 10-year relapse-free survival rates were lower in patients with postradiation OCSCC than sporadic OCSCC (29.6% [95% CI, 17.1%-43.2%] vs 52.4% [95% CI, 41.8%-62.0%]; P = .04), and the same was true for overall survival (30.5% [95% CI, 17.6%-44.4%] vs 52.3% [95% CI, 41.4%-62.1%]; P = .03). All relapses in patients with postradiation OCSCC were locoregional, whereas 35.2% of relapses (12 of 34 patients) in patients with sporadic OCSCC were distant. Despite similar 10-year disease-specific survival rates between the 2 groups (68.8% [95% CI, 55.8%-81.0%] vs 67.1% [95% CI, 57.5%-76.5%]; P = .91), patients with postradiation OCSCC had excess mortality due to pneumonia and cerebrovascular events. Postradiation OCSCC exhibited more adverse pathologic features (perineural invasion, worse pattern of invasion, and tumor budding), higher PD-1 expression, and higher gene expression of CD4 and TGF-ß compared with sporadic OCSCC. Conclusions and Relevance: This retrospective matched cohort study found distinctive pathologic characteristics and relapse patterns of postradiation OCSCC compared with sporadic OCSCC, which may be attributable to the lack of adjuvant radiotherapy, aggressive biologic phenotype, and different host immune response. Further exploration of the role of immune checkpoint therapy may be justified.

Consensus Statements on Precision Oncology in the China Greater Bay Area.

BACKGROUND: Next-generation sequencing comprehensive genomic panels (NGS CGPs) have enabled the delivery of tailor-made therapeutic approaches to improve survival outcomes in patients with cancer. Within the China Greater Bay Area (GBA), territorial differences in clinical practices and health care systems and strengthening collaboration warrant a regional consensus to consolidate the development and integration of precision oncology (PO). Therefore, the Precision Oncology Working Group (POWG) formulated standardized principles for the clinical application of molecular profiling, interpretation of genomic alterations, and alignment of actionable mutations with sequence-directed therapy to deliver clinical services of excellence and evidence-based care to patients with cancer in the China GBA. METHODS: Thirty experts used a modified Delphi method. The evidence extracted to support the statements was graded according to the GRADE system and reported according to the Revised Standards for Quality Improvement Reporting Excellence guidelines, version 2.0. RESULTS: The POWG reached consensus in six key statements: harmonization of reporting and quality assurance of NGS; molecular tumor board and clinical decision support systems for PO; education and training; research and real-world data collection, patient engagement, regulations, and financial reimbursement of PO treatment strategies; and clinical recommendations and implementation of PO in clinical practice. CONCLUSION: POWG consensus statements standardize the clinical application of NGS CGPs, streamline the interpretation of clinically significant genomic alterations, and align actionable mutations with sequence-directed therapies. The POWG consensus statements may harmonize the utility and delivery of PO in China's GBA.

Role of patients' family members in end-of-life communication: an integrative review.

OBJECTIVES: To synthesise empirical findings on the role of family in end-of-life (EOL) communication and to identify the communicative practices that are essential for EOL decision-making in family-oriented cultures. SETTING: The EOL communication settings. PARTICIPANTS: This integrative review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Relevant studies published between 1 January 1991 and 31 December 2021 were retrieved from four databases, including the PsycINFO, Embase, MEDLINE and Ovid nursing databases, using keywords with meanings of 'end-of-life', 'communication' and 'family'. Data were then extracted and coded into themes for analysis. The search strategy yielded 53 eligible studies; all 53 included studies underwent quality assessment. Quantitative studies were evaluated using the Quality Assessment Tool, and Joanna Briggs Institute Critical Appraisal Checklist was used for qualitative research. PRIMARY AND SECONDARY OUTCOME MEASURES: Research evidence on EOL communication with a focus on family. RESULTS: Four themes emerged from these studies: (1) conflicts in family decision-making in EOL communication, (2) the significance of timing of EOL communication, (3) difficulty in identification of a 'key person' who is responsible for decisions regarding EOL care and (4) different cultural perspectives on EOL communication. CONCLUSIONS: The current review pointed towards the importance of family in EOL communication and illustrated that family participation likely leads to improved quality of life and death in patients. Future research should develop a family-oriented communication framework which is designed for the Chinese and Eastern contexts that targets on managing family expectations during prognosis disclosure and facilitating patients' fulfilment of familial roles while making EOL decision-making. Clinicians should also be aware of the significance of the role of family in EOL care and manage family members' expectations according to cultural contexts.

Patterns of care and survival of Chinese glioblastoma patients in the temozolomide era: a Hong Kong population-level analysis over a 14-year period.

Background: The aim of this study is to address the paucity of epidemiological data regarding the characteristics, treatment patterns and survival outcomes of Chinese glioblastoma patients. Methods: This was a population-level study of Hong Kong adult (>18 years) Chinese patients with newly diagnosed histologically confirmed glioblastoma between 2006 and 2019. The age standardized incidence rate (ASIR), patient-, tumor- treatment-related characteristics, overall survival (OS) as well as its predictors were determined. Results: One thousand and ten patients with a median follow-up of 10.0 months were reviewed. The ASIR of glioblastoma was 1.0 per 100 000 population with no significant change during the study period. The mean age was 57 + 14 years. The median OS was 10.6 months (IQR: 5.2-18.4). Independent predictors for survival were: Karnofsky performance score >80 (adjusted OR: 0.8; 95% CI: 0.6-0.9), IDH-1 mutant (aOR: 0.7; 95% CI: 0.5-0.9) or MGMT methylated (aOR: 0.7; 95% CI: 0.5-0.8) glioblastomas, gross total resection (aOR: 0.8; 95% CI: 0.5-0.8) and temozolomide chemoradiotherapy (aOR 0.4; 95% CI: 0.3-0.6). Despite the significant increased administration of temozolomide chemoradiotherapy from 39% (127/326) of patients in 2006-2010 to 63% (227/356) in 2015-2019 (P-value < .001), median OS did not improve (2006-2010: 10.3 months vs 2015-2019: 11.8 months) (OR: 1.1; 95% CI: 0.9-1.3). Conclusions: The incidence of glioblastoma in the Chinese general population is low. We charted the development of neuro-oncological care of glioblastoma patients in Hong Kong during the temozolomide era. Although there was an increased adoption of temozolomide chemoradiotherapy, a corresponding improvement in survival was not observed.

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.

Update on Molecular Diagnosis in Extranodal NK/T-Cell Lymphoma and Its Role in the Era of Personalized Medicine.

Natural killer (NK)/T-cell lymphoma (NKTCL) is an aggressive malignancy with unique epidemiological, histological, molecular, and clinical characteristics. It occurs in two pathological forms, namely, extranodal NKTCL (ENKTCL) and aggressive NK leukemia, according to the latest World Health Organization (WHO) classification. Epstein-Barr virus (EBV) infection has long been proposed as the major etiology of lymphomagenesis. The adoption of high-throughput sequencing has allowed us to gain more insight into the molecular mechanisms of ENKTCL, which largely involve chromosome deletion and aberrations in Janus kinase (JAK)-signal transducer and activator of transcription (STAT), programmed cell death protein-1 (PD-1)/PD-ligand 1 (PD-L1) pathways, as well as mutations in tumor suppressor genes. The molecular findings could potentially influence the traditional chemoradiotherapy approach, which is known to be associated with significant toxicity. This article will review the latest molecular findings in NKTCL and recent advances in the field of molecular diagnosis in NKTCL. Issues of quality control and technical difficulties will also be discussed, along with future prospects in the molecular diagnosis and treatment of NKTCL.

Dose-volume predictors of post-radiation primary hypothyroidism in head and neck cancer: A systematic review.

BACKGROUND AND PURPOSE: This systematic review aims to identify radiation dose-volume predictors of primary hypothyroidism after radiotherapy in patients with head and neck cancer (HNC). MATERIALS AND METHODS: We performed a systematic literature search of Medline, EMBASE and Web of Science from database inception to July 1, 2021 for articles that discuss radiation dose-volume predictors of post-radiation primary hypothyroidism in patients with HNC. Data on the incidence, clinical risk factors and radiation dose-volume parameters were extracted. A meta-analysis was performed using the random-effects model to estimate the pooled odds ratio (OR) of thyroid volume as a predictor of the risk of post-radiation hypothyroidism, adjusted for thyroid radiation dosimetry. RESULTS: Our search identified 29 observational studies involving 4,530 patients. With median follow-up durations ranging from 1.0 to 5.3 years, the average crude incidence of post-radiation primary hypothyroidism was 41.4 % (range, 10 %-57 %). Multiple radiation dose-volume parameters were associated with post-radiation primary hypothyroidism, including the thyroid mean dose (Dmean), minimum dose, V25, V30, V35, V45, V50, V30-60, VS45 and VS60. Thyroid Dmean and V50 were the most frequently proposed dosimetric predictors. The pooled adjusted OR of thyroid volume on the risk of post-radiation primary hypothyroidism was 0.89 (95 % confidence interval, 0.85-0.93; p < 0.001) per 1 cc increment. CONCLUSION: Post-radiation primary hypothyroidism is a common late complication after radiotherapy for HNC. Minimizing inadvertent exposure of the thyroid gland to radiation is crucial to prevent this late complication. Radiation dose-volume constraints individualized for thyroid volume should be considered in HNC radiotherapy planning.

Teaching end-of-life communication: priorities, challenges, scope-systematic review.

BACKGROUND: Without a well-rounded syllabus to teach end-of-life (EOL) communication, medical providers find it challenging to enhance their patients' quality of life at the final stage of life. AIM: The aim of this scoping review was to explore studies about the teaching of EOL communication and to detail how educators can approach the teaching of EOL communication. METHODS: A scoping review of both qualitative and quantitative studies was conducted according to the methodological framework of scoping review. The PsycINFO, PubMed, ERIC, CINAHL and EMBASE databases were searched for studies using the keywords 'teach', 'educat*', 'end of life', 'terminal care', 'communication' and 'palliative care'. Sixteen studies were appraised, and none was rejected on the grounds of quality. RESULTS: The search strategy yielded 22 278 entries and 16 studies were included. Two themes were identified from the priorities in teaching EOL communication: (1) challenges to teaching EOL communication and (2) methods of teaching EOL communication. To present a comprehensive overview of EOL communication teaching, we provide directions for priorities of topics and approaches when teaching EOL communication. CONCLUSIONS: The review detailed the complexity of teaching EOL communication, which indicates the need for a well-rounded syllabus that includes skills such as non-verbal social cues, communication strategies and understanding EOL communication in various cultural contexts to facilitate a well-rounded EOL communication experience for students' future practice.

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

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.

Application of hypoglossal nerve constraint in definitive radiotherapy for nasopharyngeal carcinoma: A dosimetric feasibility study.

PURPOSE: Radiation-induced hypoglossal nerve palsy is an infrequent but debilitating late complication after definitive radiotherapy for head and neck cancers. D1cc < 74 Gy (equivalent dose in 2 Gy fractions, EQD2) has been proposed as a potential dose constraint that limits 8-year palsy risk to < 5%. This study sets to perform detailed dosimetric assessments on the applicability of this novel dose constraint in advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: This is a retrospective single-institution dosimetry study. NPC radiotherapy plans were identified from an institutional database, with an aim to select 10 eligible cases. Bilateral hypoglossal nerves were retrospectively contoured following a standard atlas. Cases with either one, or both, hypoglossal nerves D1cc exceeded 74 Gy EQD2 were included. Dosimetry of hypoglossal nerves, planning target volumes (PTV) and normal structures before and after application of the new hypoglossal nerve constraint were compared and analyzed. RESULTS: Ten NPC cases were replanned. All hypoglossal nerve contours overlapped with high-dose PTV, predominantly at regions of gross nodal diseases. D1cc in 15 out of 20 hypoglossal nerves exceeded 74G y EQD2 at initial plans. All nerves fulfilled the pre-specified constraint of 74Gy EQD2 after re-plan. Median hypoglossal nerve D1cc reduced from 74.8Gy (range, 74.1 to 77.4Gy) to 73.5Gy (range, 72.4 to 74.0Gy) (p < 0.001), corresponded to a projected reduction in 8-year palsy risk from 5%-14% to 3%-5%. PTV V100 was maintained above 95% in all cases. Dose increments in near-maximum (D2) and decrements in near-minimum (D98) were < 1 Gy. Safety dosimetric parameters of standard head and neck organs-at-risk showed no significant changes. CONCLUSIONS: Hypoglossal nerve D1cc < 74 Gy EQD2 is a dosimetrically feasible constraint in definitive radiotherapy for NPC. Tumor target coverage and normal organ dosimetry were not compromised with its usage. Its routine application should be considered in definitive radiotherapy for head and neck cancers.

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

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.

Chinese perspective on end-of-life communication: a systematic review.

BACKGROUND: Palliative care providers serving Chinese patients lack a culture-specific model of communication, a strong evidence base for this and clear guidance on its application. Thus, providers find it challenging to address patients' dignity, and determine their priorities and preferences for treatments and care, at the patients' final stage of life. AIM: This study explores the culture-specific influences and current understanding of end-of-life (EOL) communication in the Chinese context. METHODS: A qualitative systematic review of qualitative studies was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PsycINFO, PubMed and ERIC databases were searched for studies between January 1994 and July 2019, using keywords 'end of life', 'terminal care', 'communication' and 'Chinese'. Included studies were appraised with Critical Appraisal Skills Programme criteria. RESULTS: The search strategy yielded 982 entries and 13 studies were included. Six themes were identified in EOL communication in the Chinese context: (1) Chinese philosophies on the meaning of 'good death'. (2) Negative attitudes towards communication on dying. (3) EOL communication as a taboo topic. (4) Clinician-centred approaches to treatment-decision making. (5) Family expectations being prioritised over patient self-autonomy in prognosis disclosure. (6) Care-providers expressing puzzlement over cultural preferences regarding EOL communication. CONCLUSIONS: The review detailed the complexity of EOL communication in the Chinese context, urging for a communication model distinct from Western-based practices. Future research could explore a validated communication framework that addresses the local culture, thus enabling an understanding of patients' priorities and interpreting EOL encounters from a cross-cultural perspective.

Radiation-induced hypoglossal nerve palsy after definitive radiotherapy for nasopharyngeal carcinoma: Clinical predictors and dose-toxicity relationship.

BACKGROUND AND PURPOSE: Radiation-induced hypoglossal nerve palsy is a debilitating and irreversible late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC) and other skull base tumors. This study sets to evaluate its incidence and clinical predictive factors, and to propose relevant dosimetric constraints for this structure to guide radiotherapy planning. MATERIALS AND METHODS: We undertook a retrospective review of 797 NPC patients who underwent definitive intensity-modulated radiotherapy (IMRT) between 2003 and 2011. Cumulative incidence and clinical predictors for radiation-induced hypoglossal nerve palsy were evaluated. Archived radiotherapy plans were retrieved and 330 independent hypoglossal nerves were retrospectively contoured following standardized atlas. Optimal threshold analyses of dosimetric parameters (Dmax, D0.5cc, D1cc, D2cc, Dmean) were conducted using receiver operating characteristic curves. Normal tissue complication probability was generated with logistic regression modeling. RESULTS: With a median follow-up of 8.1 years, sixty-nine (8.7%) patients developed radiation-induced hypoglossal nerve palsy. High radiotherapy dose, premorbid diabetes, advanced T-stage and radiological hypoglossal canal involvement were independent clinical risk factors. Maximum dose received by 1 cc volume (D1cc) was the best predictor for the development of radiation-induced nerve palsy (AUC = 0.826) at 8 years after IMRT. Hypoglossal nerves with D1cc of 74 Gy EQD2 had an estimated palsy risk of 4.7%. Nerves with D1cc <74 Gy EQD2 had significantly lower risk of palsy than those ≥74 Gy EQD2 (2.4% vs 20.8%, p <0.001). CONCLUSION: Incidence of radiation-induced hypoglossal nerve palsy was high after definitive IMRT for NPC. D1cc <74 Gy EQD2 can serve as a useful dose constraint to adopt during radiotherapy planning to limit palsy risk to <5% at 8 years after IMRT.

Risk, pattern and survival impact of second primary tumors in patients with nasopharyngeal carcinoma following definitive intensity-modulated radiotherapy.

AIM: Second primary tumor (SPT) is a serious late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC). We evaluated the incidence, pattern, risk factors and survival impact of SPT in NPC patients following definitive intensity-modulated radiotherapy (IMRT). METHODS: A retrospective review of 780 consecutive IMRT-treated NPC patients between February 2003 and September 2011 was conducted. Cumulative SPT incidence and overall survival after SPT diagnosis were estimated. Associations between clinical characteristics and SPT risk were analyzed. Standardized incidence ratios (SIR) were calculated using age, gender and calendar-year-specific cancer incidences from the Hong Kong Cancer Registry. RESULTS: At a median follow-up of 7.5 years, 51 SPTs (6.7%) were identified, 22 (43.1%) of which occurred within previous radiotherapy fields. Tongue cancers (31.8%) and sarcomas of the head and neck (31.8%) were the most common in-field SPTs. Age [hazard ratio (HR), 1.051; 95% confidence interval (CI), 1.025-1.078] and smoking status (HR, 1.755; 95% CI, 1.002-3.075) were independent risk factors associated with SPT development. Median overall survival after SPT diagnosis was 2.9 years. There was an 84% increase in cancer risk (SIR, 1.84; 95% CI, 1.37-2.42) compared with the general population. Significant excess risks were observed for sarcoma, tongue, oropharyngeal, prostate and liver cancer. Excess risks were higher beyond 5 years of follow-up. CONCLUSION: Substantial risk of SPT, especially for in-field sarcoma and tongue cancers, exists after definitive IMRT for NPC. SPT severely negates longevity of NPC survivors. High awareness and careful surveillance is warranted for this late lethal complication.