Comparative effect of Tai Chi and aerobic exercise on cognitive function in advanced lung cancer survivors with perceived cognitive impairment: a three-arm randomized controlled trial with mediation analysis.

PURPOSE: Cancer-related cognitive impairment is prevalent in metastatic lung cancer survivors. This study aimed to compare the effectiveness of aerobic exercise and Tai Chi on perceived cognitive function and the mediating role of psychoneurological symptoms with perceived cognitive impairment. METHODS: In a subgroup of a parent randomized clinical trial, participants who reported cognitive impairment underwent a 16-week aerobic exercise (n = 49), Tai Chi (n = 48), and control (n = 54) groups. Measures included perceived cognitive function and psychoneurological symptoms (sleep disturbance, fatigue, anxiety, and depression) assessed at baseline (T0), 16-week (T1), and 1 year (T2). RESULTS: Participants in Tai Chi showed significant improvements compared to aerobic exercise and control groups in perceived cognitive function at T1 (AE: between-group difference, 6.52; P < 0.001; CG: 8.34; P < 0.001) and T2 (AE: between-group difference, 3.55; P = 0.05; CG: 5.94; P < 0.001). Sleep disturbance, fatigue, anxiety, and depression at month 12 explained 24%, 31%, 32%, and 24% of the effect of the intervention on cognitive function at month 12, respectively. Only anxiety at month 4 explained 23% of the intervention effect at month 12. CONCLUSIONS: Tai Chi demonstrated beneficial effects on cognitive function in advanced lung cancer survivors with perceived cognitive impairment. Improvement in cognitive function was mediated by reducing sleep disturbance, fatigue, anxiety, and depression, highlighting the importance of addressing these symptoms in future interventions to improve cognitive function, with anxiety playing a significant role at an earlier stage. IMPLICATIONS FOR CANCER SURVIVORS: Tai Chi is a potentially safe complementary therapeutic option for managing cognitive impairment in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04119778; retrospectively registered on 8 October 2019.

Tai Chi and Aerobic Exercise on Cancer-Related Dyspnea in Advanced Lung Cancer Patients: A Randomized Clinical Trial.

CONTEXT: Dyspnea, a prevalent and debilitating symptom in patients with advanced lung cancer, negatively affects symptom burden and prognosis. Physical activity has emerged as a promising non-pharmacological intervention for managing dyspnea. OBJECTIVES: This study compared the effectiveness of two widely-recognized physical activity modalities, namely Tai Chi (TC) and aerobic exercise (AE) for treating dyspnea in patients with advanced lung cancer. METHODS: Patients with advanced lung cancer (n=226) were randomized into TC, AE, or control groups. There was no baseline dyspnea requirement for patients. The AE group received two 60-minute supervised sessions and home-based exercises per month, the TC group received 60-minute sessions twice weekly, and the control group received exercise guidelines for 16 weeks. The primary outcome (sleep quality) of the study has been previously reported. In this secondary analysis, we focused on dyspnea outcomes, including overall and lung cancer-specific dyspnea. Assessments were conducted at baseline (T0), 16 weeks (T1), and one year (T2). RESULTS: Compared to the control group, TC significantly improved overall dyspnea at T1 (between-group difference, -8.69; P=0.03) and T2 (between-group difference, -11.45; P=0.01), but not AE. Both AE (between-group difference, -11.04; P=0.01) and TC (between-group difference, -14.19; P<0.001) significantly alleviated lung cancer-specific dyspnea at T2 compared with the control group. CONCLUSION: Both TC and AE alleviate dyspnea severity in patients with advanced lung cancer, and continuous exercise can yield substantial improvements. Due to its multi-component nature, Tai Chi has a greater effect on dyspnea.

Glioblastoma and Radiotherapy: a multi-center AI study for Survival Predictions from MRI (GRASP study).

BACKGROUND: The aim was to predict survival of glioblastoma at eight months after radiotherapy (a period allowing for completing a typical course of adjuvant temozolomide), by applying deep learning to the first brain MRI after radiotherapy completion. METHODS: Retrospective and prospective data were collected from 206 consecutive glioblastoma, IDH-wildtype patients diagnosed between March 2014-February 2022 across 11 UK centers. Models were trained on 158 retrospective patients from three centers. Holdout test sets were retrospective (n=19; internal validation), and prospective (n=29; external validation from eight distinct centers).Neural network branches for T2-weighted and contrast-enhanced T1-weighted inputs were concatenated to predict survival. A non-imaging branch (demographics/MGMT/treatment data) was also combined with the imaging model. We investigated the influence of individual MR sequences; non-imaging features; and weighted dense blocks pretrained for abnormality detection. RESULTS: The imaging model outperformed the non-imaging model in all test sets (area under the receiver-operating characteristic curve, AUC p=0.038) and performed similarly to a combined imaging/non-imaging model (p>0.05). Imaging, non-imaging, and combined models applied to amalgamated test sets gave AUCs of 0.93, 0.79, and 0.91. Initializing the imaging model with pretrained weights from 10,000s of brain MRIs improved performance considerably (amalgamated test sets without pretraining 0.64; p=0.003). CONCLUSIONS: A deep learning model using MRI images after radiotherapy, reliably and accurately determined survival of glioblastoma. The model serves as a prognostic biomarker identifying patients who will not survive beyond a typical course of adjuvant temozolomide, thereby stratifying patients into those who might require early second-line or clinical trial treatment.

Effectiveness of Aerobic Exercise and Tai Chi Interventions on Sleep Quality in Patients With Advanced Lung Cancer: A Randomized Clinical Trial.

Importance: Sleep disturbances prevalent among patients with advanced lung cancer can aggravate physical and psychological symptoms, contributing to decreased quality of life and survival. Objective: To compare the effectiveness of 2 physical activities of different modalities and intensities, namely aerobic exercise (AE) and tai chi (TC), on subjective sleep quality, physical and psychological outcomes, and survival in patients with advanced lung cancer. Design, Setting, and Participants: This assessor-blinded, randomized clinical trial was conducted in 3 public hospitals in Hong Kong between December 19, 2018, and September 7, 2022. A total of 226 patients with advanced lung cancer were recruited and randomized 1:1:1 to AE, TC, or the control group. Interventions: For 16 weeks, the AE group received two 60-minute supervised group exercise sessions and home-based exercises per month, and the TC group received 60-minute group sessions twice weekly. The control group received physical activity guidelines. Main Outcomes and Measures: The primary outcome was subjective sleep quality. Secondary outcomes included objective sleep measures, anxiety, depression, fatigue, quality of life, physical function, circadian rhythm, and 1-year survival. Assessments were conducted at baseline, 16 weeks (T1), and 1 year (T2). Results: The 226 participants had a mean (SD) age of 61.41 (8.73) years, and 122 (54.0%) were female. Compared with the control group, participants in the AE and TC groups showed statistically significant improvements in subjective sleep quality from baseline to T1 (AE: between-group difference, -2.72; 95% CI, -3.97 to -1.46; P < .001; TC: between-group difference, -4.21; 95% CI, -5.48 to -2.94; P < .001) and T2 (AE: between-group difference, -1.75; 95% CI, -3.24 to -0.26; P = .02; TC: between-group difference, -3.95; 95% CI, -5.41 to -2.49; P < .001), psychological distress, physical function, step count, and circadian rhythm. The TC group had a statistically significant greater improvement in sleep than the AE group at T1 (between-group difference, -1.49; 95% CI, -2.77 to -0.22; P = .02) and T2 (between-group difference, -2.20; 95% CI, -3.57 to -0.83; P < .001). Participants in the TC group showed statistically significant improvement in survival compared with the control group. Conclusions and Relevance: In this randomized clinical trial, AE and TC improved sleep, psychological distress, physical function, and circadian rhythm, with TC demonstrating greater benefits on sleep and survival. Both exercises, but particularly TC, can be incorporated into lung cancer survivorship care. Trial Registration: ClinicalTrials.gov Identifier: NCT04119778.

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, P = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses.

Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trial.

Background: The strategy of dual blockade of TGF-ß and PD-L1 pathways has not been previously tested in platinum-refractory recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients. This study aimed to evaluate the safety and efficacy of bintrafusp alfa in refractory R/M NPC patients. Methods: In this single-arm, single-centre phase II clinical trial, 38 histologically confirmed R/M NPC patients were enrolled and administered with bintrafusp alfa every 2 weeks. Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Findings: Thirty-eight patients were accrued (33 men; median age, 54 years). ORR was 23.7% (complete response, n = 2; partial response, n = 7). The median DOR was 19.2 months, median PFS was 2.3 months, median OS was 17.0 months, and 1-year OS rate was 63.2%. Unfortunately, 25 patients (65.7%) progressed within 8 weeks of treatment, 15 patients (39.5%) and 8 patients (21.1%) developed hyper-progressive disease (HPD) per RECIST v1.1 and tumor growth rate (TGR) ratio respectively. Sixteen patients (42.4%) experienced ≥ grade 3 treatment-related adverse events (TRAEs), most commonly anemia (n = 9, 23.7%) and secondary malignancies (n = 4, 10.5%). TRAEs led to permanent treatment discontinuation in 7 patients. Patients with strong suppression of plasma TGFß1 level at week 8 were unexpectedly associated with worse ORR (9.1% vs 44.4%, P = 0.046) and development of HPD. There was no correlation between PD-L1 expression and ORR. Interpretation: Bintrafusp alfa demonstrated modest activity in R/M NPC but high rates of HPD and treatment discontinuation secondary to TRAEs are concerning. Funding: The project was supported by Alice Ho Miu Ling Nethersole Charity Foundation Professorship Endowed Fund and Merck KGaA.

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.

Impact of weight loss on treatment interruption and unplanned hospital admission in head and neck cancer patients undergoing curative (chemo)-radiotherapy in Hong Kong.

PURPOSE: Malnutrition is highly prevalent in head and neck cancer (HNC) patients, with weight loss being one of the major nutritional indicators. The objective of this study was to investigate the impact of weight loss on treatment interruptions and unplanned hospital admissions in HNC patients undergoing radiotherapy (RT) with or without chemotherapy. METHODS: In this retrospective cohort study, consecutive HNC patients who started RT between January 2011 and December 2019 were included. Data from a total of 1086 subjects with 747 (68.8%) nasopharyngeal carcinomas (NPCs) and 31.2% (N=339) non-NPC patients were analysed. Body weight (BW) was measured before, during, and after RT treatment. Factors associated with ≥10% weight loss, treatment interruption, and unplanned admissions were analysed using multivariate logistic regression. RESULTS: The prevalence of ≥10% weight loss was 26.8% (N=288), with 32.7% (N=243) in NPC and 13.5% (N=45) in non-NPC patients. The prevalence of RT delay in patients with ≥10% vs. <10% weight loss was 6.2% vs. 7.0% (p=0.668) in NPC patients and 42.2% vs. 50.5% (p=0.300) in non-NPC patients. The prevalence of unplanned admissions in patients with ≥10% vs. <10% weight loss was 51.9% vs. 25.3% (p<0.001) in NPC patients and 68.9% vs. 27.0% (p<0.001) in non-NPC patients. CONCLUSION: In our study, ≥10% weight loss was found to be associated with a higher rate of unplanned admissions but not with RT delay or chemotherapy interruption. CLINICAL IMPLICATIONS: With the knowledge of the impact of weight loss on hospital admissions and the characteristics of patients with weight loss, nutritional intervention can be effectively focused on the stratification of patients for intensive nutritional support to reduce weight loss.

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.

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.

Background: Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and current indications for postoperative radiotherapy are controversial. Recent studies have proposed prognostic meningioma classification systems using DNA methylation profiling, copy number variants, DNA sequencing, RNA sequencing, histology, or integrated models based on multiple combined features. Targeted gene expression profiling has generated robust biomarkers integrating multiple molecular features for other cancers, but is understudied for meningiomas. Methods: Targeted gene expression profiling was performed on 173 meningiomas and an optimized gene expression biomarker (34 genes) and risk score (0 to 1) was developed to predict clinical outcomes. Clinical and analytical validation was performed on independent meningiomas from 12 institutions across 3 continents (N = 1856), including 103 meningiomas from a prospective clinical trial. Gene expression biomarker performance was compared to 9 other classification systems. Results: The gene expression biomarker improved discrimination of postoperative meningioma outcomes compared to all other classification systems tested in the independent clinical validation cohort for local recurrence (5-year area under the curve [AUC] 0.81) and overall survival (5-year AUC 0.80). The increase in area under the curve compared to the current standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval [CI] 0.07-0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% CI 0.37-0.78, P = 0.0001) and re-classified up to 52.0% meningiomas compared to conventional clinical criteria, suggesting postoperative management could be refined for 29.8% of patients. Conclusions: A targeted gene expression biomarker improves discrimination of meningioma outcomes compared to recent classification systems and predicts postoperative radiotherapy responses.

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.

Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma (START-FIT): a single-arm, phase 2 trial.

BACKGROUND: The synergy between locoregional therapies and immune checkpoint inhibitors has not been investigated as conversion therapy for unresectable hepatocellular carcinoma. We aimed to investigate the activity of sequential transarterial chemoembolisation (TACE) and stereotactic body radiotherapy followed by avelumab (an anti-PD-L1 drug) for locally advanced, unresectable hepatocellular carcinoma. METHODS: START-FIT was a single-arm, phase 2 trial in patients with locally advanced hepatocellular carcinoma who were not suitable for curative treatment, conducted in two hospitals in Hong Kong and one in Shenzhen, China. Eligible patients were those aged 18 years or older with an Eastern Cooperative Oncology Group performance status 0-1, Child-Pugh liver function score A5 to B7, tumour size of at least 5 cm, a maximum of three tumour lesions, and adequate hepatic, renal, and bone marrow function. Participants received TACE on day 1, followed by stereotactic body radiotherapy (27·5-40·0 Gy in five fractions) at day 28. Avelumab (10 mg/kg) was administered 14 days following stereotactic body radiotherapy and every 2 weeks thereafter. The primary endpoint was the proportion of patients deemed amenable to curative treatment, defined as those who had a sustained complete or partial treatment response for at least 2 months and if curative treatment could be performed (ie, resection, radiofrequency ablation, or transplantation), analysed by intention to treat. Safety was also analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT03817736) and has been completed. FINDINGS: Between March 18, 2019, and Jan 27, 2021, 33 patients (32 [97%] men and one [3%] woman) were enrolled. The median sum of the largest diameters of lesions was 15·1 cm (IQR 8·3-14·9). 21 (64%) patients had macrovascular invasion (hepatic vein [n=13], branched portal vein [n=3], or both [n=5]). Median follow-up was 17·2 months (IQR 7·8-25·8). 18 (55%) patients were deemed amenable to curative treatment: four (12%) of 33 patients had curative treatment (resection [n=2] or radiofrequency ablation [n=2]), and 14 (42%) had a radiological complete response and opted for close surveillance. 11 (33%) of 33 patients had treatment-related adverse events that were grade 3 or worse. The most common treatment-related grade 3 or worse adverse event was transient increase in alanine aminotransferase or aspartate aminotransferase (five [15%]) after TACE. Five (15%) patients developed immune-related adverse events of grade 3 or worse (three had hepatitis, two had dermatitis). INTERPRETATION: To our knowledge, this is the first prospective trial using the combination of immunotherapy and locoregional treatment as conversion therapy for locally advanced unresectable hepatocellular carcinoma, with promising results. Future randomised trials with larger cohorts of patients are warranted. FUNDING: Merck.

Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities.

Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities. Merlin-intact meningiomas (34%) have the best outcomes and are distinguished by NF2/Merlin regulation of susceptibility to cytotoxic therapy. Immune-enriched meningiomas (38%) have intermediate outcomes and are distinguished by immune infiltration, HLA expression and lymphatic vessels. Hypermitotic meningiomas (28%) have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. To translate these findings into clinical practice, we show cytostatic cell cycle inhibitors attenuate meningioma growth in cell culture, organoids, xenografts and patients.

Comparative Treatment Persistence with Bone-Targeting Agents Among Asian Patients with Bone Metastases from Solid Tumors: A Multinational Retrospective Cohort Study.

BACKGROUND: The efficacy of bone-targeting agents has been confirmed, but the generalizability of results to Asia is in question. OBJECTIVE: We aimed to evaluate and compare treatment persistence and re-initiation with different bone-targeting agents among patients with bone metastases from solid tumors. METHODS: This population-based cohort study included patients with bone metastasis with breast, lung, or prostate cancer who initiated bone-targeting agents, including denosumab, zoledronic acid, and pamidronate in Taiwan (2013-17), Hong Kong (2013-17), and Korea (2012-16). We described the patients' persistence with bone-targeting agents, by evaluating the interruption probability, and compared risks of treatment interruption. The rates of re-initiation with index bone-targeting agents were evaluated. RESULTS: We included 5127 patients (denosumab: 3440, zoledronic acid: 1210, pamidronate: 477) from Taiwan, 883 patients (denosumab: 458, zoledronic acid: 357, pamidronate: 68) from Hong Kong, and 4800 patients (zoledronic acid: 4068, pamidronate: 732) from Korea. Compared with zoledronic acid, denosumab had a lower risk of interruption in Taiwan (adjusted hazard ratio: 0.44; 95% confidence interval 0.40-0.48) and Hong Kong (0.36; 0.28-0.45). However, pamidronate was more likely to be interrupted than zoledronic acid in Taiwan (1.31; 1.11-1.54) and Korea (2.06; 1.83-2.32), but not in Hong Kong (1.13; 0.71-1.78). After discontinuation, original treatments with denosumab in Taiwan and zoledronic acid in Hong Kong were more likely to be resumed, while in Korea, the rates were similar among the bisphosphonates. CONCLUSIONS: Denosumab was associated with a lower risk of interruption than bisphosphonates in patients with bone metastases in Taiwan and Hong Kong. Further investigations may be required to verify patients' actual reasons for discontinuation.

A pilot randomized controlled trial using Baduanjin qigong to reverse frailty status among post-treatment older cancer survivors.

OBJECTIVES: To evaluate the feasibility and potential effects of qigong Baduanjin for reversing frailty status among older cancer survivors. MATERIALS AND METHODS: Twenty-eight older cancer survivors screened as pre-frail or frail were recruited. They were randomly assigned (1:1) to receive a sixteen-week Baduanjin intervention or an active control condition (light flexibility exercise). Frailty status (primary outcome) and secondary outcomes (physical performance, activities of daily living performance, psychological well-being, and health-related quality of life) were measured by physical performance tests and questionnaires. Qualitative interviews were conducted to explore participants' perspectives on the intervention. RESULTS: Twenty-one participants (75%) completed the study, with reasons of withdrawal mainly relating to the COVID-19 pandemic. Attendance at Baduanjin sessions and adherence to self-practice were satisfactory, with all retained participants attending all sessions and 81.8% practicing Baduanjin for more than 90 min per week. Qualitative findings demonstrated that participants accepted Baduanjin. The proportion of improvement in frailty status at post-intervention appeared to be higher in the intervention group (26.7%; 95% confidence interval [CI], 10.1% to 54.0%) than the control group (15.4%; 95% CI, 3.7% to 46.0%); yet the difference was not statistically significant (p = 0.461). CONCLUSIONS: Baduanjin qigong appears to be feasible and acceptable among older cancer survivors. To confirm the intervention effect, an adequately powered trial is warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04694066. Retrospectively registered 5 January 2021, https://clinicaltrials.gov/ct2/show/NCT04694066.

Bone-targeting agents in major solid tumour metastases: a multinational cohort study.

OBJECTIVE: To describe the epidemiology, clinical characteristics and utilisation patterns of bone-targeting agents (BTAs) in patients with bone metastases from breast, prostate and lung cancer. METHODS: This is a multinational retrospective cohort study including patients with three major solid tumours (breast, prostate and lung cancer) and newly initiated on BTAs (ie, denosumab, zoledronic acid and pamidronate). Records were retrieved from nationwide health databases from Hong Kong and Taiwan (HK and TW: 2013-2017) and Korea (KR: 2012-2016). Descriptive analyses included the annual incidence rates of bone metastases and the cumulative incidence curves of BTA initiation. We used Sankey diagrams to visualise the dynamic BTA utilisation patterns. RESULTS: The annual incidence rate of bone metastases ranged from 3.5% to 4.5% in TW, from 9.6% to 10.3% in HK and from 2.9% to 3.8% in KR. We identified 14.1% (5127), 9.3% (883) and 9.4% (4800) of patients with bone metastases newly initiated on BTAs in TW, HK and KR, respectively. The most frequently used BTA in TW (67.1%) and HK (51.9%) was denosumab, while in KR (84.8%) it was zoledronic acid. Sankey diagrams indicated the proportion of patients remaining on denosumab was highest in TW and HK, while it was zoledronic acid in KR. Specifically, in TW, patients who were on bisphosphonates or had discontinued treatment frequently switched to or reinitiated denosumab. CONCLUSIONS: We found the rate of BTA utilisation remained low across all sites and tumour types in recent years. The dynamic utilisation patterns of BTAs provide better understanding of the treatment landscape for future evaluation of associated outcomes of patients.

Patient-centred, self-administered acupressure for Chinese advanced cancer patients experiencing fatigue and co-occurring symptoms: A pilot randomised controlled trial.

OBJECTIVES: To evaluate the feasibility and potential effects of patient-centred self-administered acupressure for alleviating fatigue and co-occurring symptoms among Chinese advanced cancer patients receiving treatment. METHODS: Thirty advanced cancer patients who screened positive for moderate/severe fatigue with symptoms of insomnia and/or pain were recruited from a hospital in Hong Kong. They were randomly assigned (1:1) to receive a 4-week patient-centred self-administered acupressure intervention or health education. Fatigue (primary outcome) and secondary outcomes (sleep quality, pain, fatigue-sleep disturbance-pain symptom cluster severity, anxiety, depression and quality of life) were measured by questionnaires and actigraphy. RESULTS: Twenty-four participants (80%) completed the study. Adherence to self-administered acupressure practice was satisfactory, with all retained participants attending all sessions and 90.9% practising acupressure daily. All completers rated the class as very enjoyable or quite enjoyable. Fatigue, pain, symptom cluster severity, anxiety, depression and quality of life appeared to improve from baseline to post-intervention in the intervention group. Among these outcomes, only the between-group difference in anxiety post-intervention was significant. The group × time interaction effect was nonsignificant for all outcomes. CONCLUSIONS: Patient-centred self-administered acupressure appears to be feasible and acceptable among advanced cancer patients. A fully powered trial is warranted to confirm the intervention effect.

Using suicide notes to understand suicide among cancer patients: A mixed-method study.

BACKGROUND: Cancer patients are at risk of suicide. However, no studies have used suicide notes to investigate their expressed reasons for suicide. The objectives of this study were to compare the characteristics between note leavers and non-leavers among cancer suicide cases and to understand the patterns in expressed reasons for suicide using suicide notes. METHOD: Suicide cases (2012-2017) were identified from the Hong Kong Coroner's Court reports, which provide detailed information as well as the content of suicide notes. Bivariate tests and multiple logistic regression were performed to compare the characteristics of note leavers and non-leavers among suicide cases with cancer. Thematic analysis was performed on suicide notes to extract themes of expressed reasons for suicides by cancer status and age group. RESULTS: Among cancer suicide cases and compared to non-leavers, note leavers were younger, more likely to be male, use non-violent suicide methods, have better housing conditions, and live alone. Suffering from physical disease was a major theme identified among cancer note leavers across all age groups. Young and middle-aged non-cancer note leavers had various themes identified. Physical illness was the major theme for elderly non-cancer note leavers. CONCLUSIONS: Cancer note leavers had unique characteristics and suffering from physical illness was the major expressed reason identified in the suicide notes. Healthcare professionals should pay attention to the mental as well as the physical needs of patients. Improving quality of life and regaining control of life are vital for suicide prevention among cancer patients.

Suicidal/self-harm behaviors among cancer patients: a population-based competing risk analysis.

BACKGROUND: Cancer patients had elevated risk of suicidality. However, few researches studied the risk/protective factors of suicidal/self-harm behaviors considering the competing risk of death. The objective of this study is to systematically investigate the risk of suicidal/self-harm behaviors among Hong Kong cancer patients as well as the contributing factors. METHODS: Patients aged 10 or above who received their first cancer-related hospital admission (2002-2009) were identified and their inpatient medical records were retrieved. They were followed for 365 days for suicidal/self-harm behaviors or death. Cancer-related information and prior 2-year physical and psychiatric comorbidities were also identified. Competing risk models were performed to explore the cumulative incidence of suicidal/self-harm behavior within 1 year as well as its contributing factors. The analyses were also stratified by age and gender. RESULTS: In total, 152 061 cancer patients were included in the analyses. The cumulative incidence of suicidal/self-harm behaviors within 1 year was 717.48/100 000 person-years. Overall, cancer severity, a history of suicidal/self-harm behaviors, diabetes and hypertension were related to the risk of suicidal/self-harm behaviors. There was a U-shaped association between age and suicidal/self-harm behaviors with a turning point at 58. Previous psychiatric comorbidities were not related to the risk of suicidal/self-harm behaviors. The stratified analyses confirmed that the impact of contributing factors varied by age and gender. CONCLUSIONS: Cancer patients were at risk of suicidal/self-harm behaviors, and the impacts of related factors varied by patients' characteristics. Effective suicide prevention for cancer patients should consider the influence of disease progress and the differences in age and gender.

Understanding the impact of clinical characteristics and healthcare utilizations on suicide among cancer sufferers: a case-control study in Hong Kong.

BACKGROUND: Few studies have investigated whether hospital utilization patterns of cancer sufferers are associated with their suicide. This study aims to explore whether clinical profiles and healthcare utilization patterns are related to suicide among cancer sufferers. METHODS: Verified suicide cases with cancer (2012-2016) were identified. Each case was matched with two non-suicide controls suffering cancer, by birthyear, sex, and admission year. Cancer-related information, physical and psychiatric comorbidities, opioid-based painkiller usage, the number and length of inpatient admissions, and the number of outpatient and Accident & Emergency (A&E) attendances, in the six months leading up to the suicide, were identified. Conditional logistic regression models were constructed to explore the influence of clinical profiles and hospital utilization on suicide. These models were stratified by age and cancer stage. OUTCOMES: 383 cases and 766 controls were included in the analyses. Overall, younger age, metastasis/recurrent status, suffering head and neck cancer, having psychiatric comorbidities, using opioid-based painkillers, and high frequency of A&E attendances and inpatient admissions increased the odds of suicide. Being diagnosed with liver cancer, consuming high numbers of outpatient attendances, and high numbers of inpatient days decreased the odds of suicide. Stratified analyses confirmed the influence of young age and metastatic/recurrent cancer status on risk of suicide. INTERPRETATIONS: Suicidal cancer sufferers had distinctive clinical profiles and hospital utilization patterns. Detecting and mitigating suicidal risk should be incorporated as an important component in treatment of cancer sufferers in the clinical setting. FUNDING: Li Ka Shing Foundation and Hong Kong Research Grants Council.