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.

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.

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.

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.

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.

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.

Cranial neuropathies in advanced nasopharyngeal carcinoma: Neurological recovery after modern radiotherapy and systemic chemotherapy.

OBJECTIVES: Cranial neuropathy is a common presenting symptom of advanced T4 nasopharyngeal carcinoma (NPC). Data on neurological outcomes after modern intensity-modulated radiotherapy (IMRT) and chemotherapy are scarce. MATERIALS AND METHODS: Case records of consecutive T4 NPC patients who received definitive IMRT in two tertiary oncology centers in 2004-2019 were reviewed. Patterns of cranial neuropathies at disease presentation were recorded. Time to neurological recovery and the rate of subsequent re-palsy were estimated by the Kaplan-Meier method. Clinical predictors were analyzed using multivariable Cox regression. RESULTS: During the study period, 257 T4 NPC patients presented with 504 individual cranial neuropathies. The median time from neuropathy onset to NPC diagnosis was two months (IQR, 1-4 months). Cranial nerves (CN) VI (56.4%), V2 (47.9%), and V3 (29.2%) were most frequently involved. At a median follow-up of 6.4 years, the crude partial and full recovery rates of neuropathies were 111 (22%) and 289 (57.3%), respectively. CN III, IV, and VI had the highest 5-year full recovery rate (72.7%), followed by CN V1-3 (60.3%), XII (48.6%), and II (18.2%) (p < 0.001). Positive smoking history, optic nerve involvement, and longer duration of neuropathy were independent negative predictors for neurological recovery. After full recovery, re-palsy was observed in 6.9% (20/289) of the nerves, 60% of which co-occurred with local NPC recurrences. CONCLUSION: Durable recovery of most cranial neuropathies in advanced T4 NPC was observed in the era of modern IMRT and effective systemic chemotherapy. Both patient and disease factors affected the chance of neurological recovery. Re-palsy of recovered nerves should prompt careful evaluation for local recurrence.

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.

Treatment Deescalation Strategies for Nasopharyngeal Cancer: A Review.

IMPORTANCE: Since the advent of modern radiotherapy techniques and incorporation of systemic chemotherapy for nasopharyngeal cancer, locoregional control has been excellent. However, the rate of treatment-related complications, many of which are irreversible, remains high. New approaches are being explored to determine whether the toxic effects of treatment can be relieved while maintaining disease control. This review presents the current state of deescalation strategies for nasopharyngeal cancer. OBSERVATIONS: A review of the literature shows that deescalation approaches can be generally categorized into deescalating systemic therapy vs deescalating radiotherapy. This review discusses studies that have explored sparing chemotherapy in selected patients with stage II cancer as well as altering the chemotherapy scheduling, dosing, and agent from the current standard of care, cisplatin. Deescalating radiotherapy has involved decreasing the dose and the treatment volume. In many cases, these approaches are being guided by measuring Epstein-Barr virus DNA levels, which is a robust biomarker for screening, treatment monitoring, and surveillance. Ongoing work with various imaging modalities, such as fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced or diffusion-weighted magnetic resonance imaging sequences, have shown promise as another biomarker to safely guide practitioners toward deescalation. CONCLUSIONS AND RELEVANCE: Various strategies to deescalate treatment in nasopharyngeal cancer have been explored, and outcomes have remained excellent in most approaches. Patient selection remains key, and long-term outcomes and late complications are still to be determined. Continued investigation with prospective, multi-institutional studies are needed to better elucidate how treatment for nasopharyngeal carcinoma can best be individualized and deescalated.

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.

Temporal Lobe Necrosis in Head and Neck Cancer Patients after Proton Therapy to the Skull Base.

PURPOSE: To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base. MATERIALS AND METHODS: Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with <3 months of follow-up, receiving <45 GyRBE or nonconventional fractionation, and/or no follow-up magnetic resonance imaging (MRI) were excluded. TLN was determined using MRI and graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Clinical (gender, age, comorbidities, concurrent chemotherapy, smoking, radiation techniques) and dose-volume parameters were analyzed for TLN correlation. The receiver operating characteristic curve and area under the curve (AUC) were performed to determine the cutoff points of significant dose-volume parameters. RESULTS: Between 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2-69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume [aV]); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm3 volume receiving the maximum dose (D0.5cm3, D1cm3, and D2cm3, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm3 gave the highest AUC (0.935) among dose parameters. The 11-cm3 cutoff value for aV50 and 62 GyRBE for D2cm3 showed maximum specificity and sensitivity. CONCLUSION: The estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm3, D2cm3 ≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy.

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

BACKGROUND: This study evaluates the contemporary care for patients with locally recurrent nasopharyngeal carcinoma after failure of the primary course of intensity modulated radiotherapy. METHODS: Eligible patients were identified through the Hong Kong Cancer Registry database. Patterns of care and treatment outcomes were analyzed. RESULTS: Two hundred seventy-two patients with locally recurrent tumors were identified. Of them, 30.9% received surgery, whereas 35.7% received re-irradiation (re-RT). The 5-year overall survival (OS) for the whole group was 30.2%. Old age and advanced rT classification were adverse prognostic factors, whereas surgery (mainly in resectable recurrence) was associated with favorable survival outcome. The 5-year OS rates for patients who received surgery and re-RT were 56.3% and 21.8%, respectively. CONCLUSIONS: Early detection of resectable recurrence is of paramount importance as surgery for resectable tumors offers the potential to achieve excellent outcomes. Re-RT could be considered in selected patients with unresectable disease and favorable prognostic features.

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.