A systematic review to summarize treatment patterns, guidelines, and characteristics of patients with renal cell carcinoma in the Asia-Pacific region.

INTRODUCTION: This systematic review evaluated treatment patterns and guidelines in advanced/metastatic and adjuvant renal cell carcinoma (RCC) in the Asia-Pacific region. AREAS COVERED: Embase, PubMed, and congresses were searched for observational studies and guidelines in accordance with PRISMA. Records published during 2016-2021 (2019-2021 for congresses) were included. EXPERT OPINION: Nine studies and three guidelines were identified overall. In advanced/metastatic RCC, the most common treatments were tyrosine kinase inhibitors (TKIs) (notably sunitinib: 33-100%) for first-line, and everolimus (13-85%) or axitinib (2-89%) for second-line therapy. In adjuvant RCC, sunitinib was most used (54%), followed by mammalian target of rapamycin inhibitors (mTORis, 27%) with immunotherapy being less common (16%). The guidelines provided varying recommendations for advanced/metastatic RCC. For first-line in advanced/metastatic clear cell RCC (the most common subtype), guidelines recommended mTORis (everolimus for poor-risk patients) (India, 2016); clinical study enrollment for high-risk patients or TKIs for low- to medium-risk patients (China, 2019); or immunotherapy based on survival benefits over sunitinib; dose adjustment was also recommended to manage TKI toxicities (Hong Kong, 2019). The landscape remained more static in the adjuvant setting, but best practice was uncertain. No clear trends were identified in patient characteristics.

Acupuncture for chemotherapy-associated insomnia in breast cancer patients: an assessor-participant blinded, randomized, sham-controlled trial.

BACKGROUND: Insomnia is a highly prevalent symptom occurred during and post-chemotherapy. Acupuncture may have beneficial effects in the management of chemotherapy-associated insomnia. This study was conducted to determine the efficacy and safety of acupuncture in improving chemotherapy-associated insomnia in breast cancer patients. METHODS: This assessor-participant blinded, randomized, sham-controlled trial was conducted from November 2019 to January 2022 (follow-up completed July 2022). Participants were referred by oncologists from two Hong Kong hospitals. Assessments and interventions were conducted at the outpatient clinic of School of Chinese Medicine, the University of Hong Kong. The 138 breast cancer patients with chemotherapy-associated insomnia were randomly assigned to receive either 15 sessions of active acupuncture regimen by combining needling into body acupoints and acupressure on auricular acupoints or sham acupuncture control (69 each) for 18 weeks, followed by 24 weeks of follow-up. The primary outcome was measured using Insomnia Severity Index (ISI). Secondary outcomes included the Pittsburgh Sleep Quality Index, Actiwatch and sleep diary for sleep parameters, depression and anxiety, fatigue and pain, and quality of life. RESULTS: There were 87.7% (121/138) participants who completed the primary endpoint (week-6). The active acupuncture regimen was not superior to the sham control in reducing ISI score from baseline to 6 weeks (mean difference: - 0.4, 95% CI - 1.8-1.1; P = 0.609), but produced short-term treatment and long-term follow-up better outcomes in improving sleep onset latency, total sleep time, sleep efficiency, anxiety, depression, and quality of life. Participants of the active acupuncture group had a pronouncedly higher cessation rate of sleeping medications than the sham control (56.5% vs. 14.3%, P = 0.011). All treatment-related adverse events were mild. No participants discontinued treatments due to adverse events. CONCLUSION: The active acupuncture regimen could be considered as an effective option for the management of chemotherapy-associated insomnia. It also could serve as a tapering approach to reduce and even replace the use of sleeping medications in breast cancer patients. Trial registration Clinicaltrials.gov : NCT04144309. Registered 30 October 2019.

Refining TNM-8 M1 categories with anatomic subgroups for previously untreated de novo metastatic nasopharyngeal carcinoma.

PURPOSE: To propose a refined M1 classification in de novo metastatic nasopharyngeal carcinoma (NPC) based on pooled data from two academic institutions. METHODS: Previously untreated de novo M1 NPC patients prospectively treated at The University of Hong Kong (N = 69) and Fujian Cancer Hospital (N = 114) between 2007 and 2016 were recruited and randomized in a 2:1 ratio to generate training (N = 120) and validation (N = 63) cohorts, respectively. Multivariable analysis (MVA) was performed for the training and validation cohorts to identify anatomic prognostic factors for overall survival (OS). Recursive partitioning analysis (RPA) was performed which incorporated the anatomic prognostic factors identified in the MVA to derive Anatomic-RPA groups which stratified OS in the training cohort, and were then validated in the validation cohort. RESULTS: Median follow-up for the training and validation cohorts was 27.2 and 30.2 months with 3-year OS of 51.6% and 51.1%, respectively. MVA revealed that co-existing liver-bone metastases was the only factor prognostic for OS in both the training and validation cohorts. Anatomic-RPA separated M1 disease into M1a (no co-existing liver-bone metastases) and M1b (co-existing liver-bone metastases) with median OS 39.5 and 23.7 months, respectively (p = 0.004) in the training cohort. RPA for the validation cohort also confirmed good segregation with co-existing liver-bone metastases with median OS 47.7 and 16.0 months, respectively (p = 0.008). CONCLUSION: Our proposal to subdivide de novo M1 NPC into M1a (no co-existing liver-bone metastases) vs. M1b (co-existing liver-bone metastases) provides better OS segregation.

Electroacupuncture Plus Auricular Acupressure on Chemotherapy-Related Insomnia in Patients With Breast Cancer (EACRI): Study Protocol for a Randomized, Sham-Controlled Trial.

OBJECTIVE: Insomnia is a highly prevalent and disturbing symptom in breast cancer patients under or post chemotherapy. If not appropriately treated, it can persist for years after the completion of cancer treatments. Acupuncture has been widely used for alleviating insomnia. The aim of this study is to examine the feasibility, efficacy and safety of acupuncture for chemotherapy-related insomnia among patients with breast cancer. MATERIALS AND METHODS: This is a trial protocol for a randomized, sham-controlled, subject- and assessor-blinded clinical trial. A total of 138 eligible participants will be assigned randomly to acupuncture or sham control group at a ratio of 1:1. Participants in acupuncture group will receive electroacupuncture (EA) plus auricular acupressure (AA) treatment, while subjects in sham acupuncture group will receive sham EA plus sham AA. Both acupuncture and sham treatments will be given twice weekly for 6 weeks, followed by maintenance treatments once every 4 weeks for 12 weeks (15 sessions totally). The primary outcome is the change of Insomnia Severity Index score between baseline and the end of 6-week treatment. Secondary outcome measurements include Actiwatch, sleep diary, Pittsburgh Sleep Quality Index, Functional Assessment of Cancer Therapy-Breast Cancer, Hospital Anxiety and Depression Scale, Brief Pain Inventory-Short Form, Brief Fatigue Inventory, Acupuncture Expectancy Scale, credibility, and adverse events. Participants will be followed up to 42 weeks. CONCLUSIONS: This trial will expand our understanding of the feasibility, efficacy, and safety of acupuncture as a treatment for alleviating chemotherapy-related insomnia in patients with breast cancer. EA plus AA, if proven to be effective, can be implemented into routine settings to play a role in insomnia management for patients with breast cancer.

Systematic Review with Meta-Analysis: Effectiveness and Safety of Acupuncture as Adjuvant Therapy for Side Effects Management in Drug Therapy-Receiving Breast Cancer Patients.

OBJECTIVE: To investigate the potential benefits and safety of acupuncture on managing side effects induced by drug therapies in patients with breast cancer using a PRISMA standard systematic review and meta-analysis. METHODS: Published randomised controlled trials from nine databases in English and Chinese language were searched. Trials with a real acupuncture treatment group and a control group with sham acupuncture, no treatment, or waitlist control were included. The primary outcome of this study was the therapeutic effects on five symptoms induced by drug therapies, including gastrointestinal disorder, neuropathy, arthralgia, joint symptoms, and cognitive impairment. The quality of life was assessed as a secondary outcome. The risk of bias of each study was analysed according to the Cochrane Handbook. RESULTS: Sixteen randomised controlled trials with 1189 participants were included in the meta-analysis. The primary outcome and all subgroup analyses showed statistically significant improvements in the management of side effects by real acupuncture. The quality of life of patients has enhanced during the treatment. CONCLUSION: Although the number of publications is limited, a clear preliminary conclusion could be drawn by the meta-analysis, suggesting the beneficial adjuvant role of acupuncture in patients with breast cancer who receive drug therapies. No serious adverse events were observed from all the RCTs, and the safety of acupuncture is ascertained. More standardised and sophisticated large-scale randomised controlled trials are needed to evaluate the findings further.

Efficacy and Safety of Chinese Herbal Medicine on Treatment of Breast Cancer: A Meta-analysis of Randomized Controlled Trials.

Breast cancer is currently the most common cancer in women, and it accounts for 11.6% of all cancer diagnoses in 2018. Breast cancer patients frequently resort to alternative medicine in addition to conventional Western therapy. This study is to evaluate clinical effectiveness of Chinese herbal medicine (CHM) on breast cancer by conducting meta-analyses on 81 randomized controlled trials (RCTs) with a total of 7215 subjects from eight databases. All RCTs compared patients using Western therapy alone and those using additional CHM therapy to evaluate the difference of primary (tumor response, mean time to progression (mTTP), overall survival (OS) and progression free survival (PFS)) and secondary outcome measures (tumor markers). Results showed that under the RECIST1.1 criteria, 52% patients with additional CHM therapy (67%, under WHO criteria) achieved either a complete response (CR) or a partial response (PR), compared to 38% patients with Western therapy alone (53%, under the WHO criteria). The risk ratio was 1.31 ([Formula: see text] < 0.00001, 95% CI = 1.15-1.50) for patients with CHM plus Western therapy and 1.25 ([Formula: see text] < 0.00001, 95% CI = 1.18-1.98) for those with Western therapy. Moreover, patients with complementary CHM therapy were associated with an mTTP of 2.79 months longer ([Formula: see text] < 0.00001) and an OS of 1.90 months longer ([Formula: see text] < 0.00001); they also had an increase in 3-year PFS ([Formula: see text]= 0.002), 2- ([Formula: see text]= 0.0002) and 5-year ([Formula: see text]= 0.006) OS rates. Therefore, complementary CHM therapy might demonstrate clinical benefits for breast cancer patients in terms of tumor response and survival. Clinical studies with further stratification of tumor stages and intervention types are highly warranted.

The Adjunctive Effect of Acupuncture for Advanced Cancer Patients in a Collaborative Model of Palliative Care: Study Protocol for a 3-Arm Randomized Trial.

BACKGROUND: Cancer is the second leading cause of death before the age of 70. Improved cancer survival has put increasing demands on cancer care. Palliative care is the specialized multi-disciplinary care providing relief from the pain, symptoms, and stress of serious illness. The study aims to evaluate the adjunctive effect of acupuncture for advanced cancer patients in a collaborative model of palliative care. METHODS/DESIGN: This is a single-blinded, randomized, sham-controlled trial. One hundred twenty advanced cancer patients undergoing palliative care will be randomized in a ratio of 2:1:1 to manual acupuncture plus standard care group (ASC), sham acupuncture plus standard care group (SSC), and standard care group (SC). Patients in ASC and SSC will receive 9 sessions of acupuncture or sham acupuncture for 3 weeks, and will be followed up for 2 months. The primary measure is the change from baseline score of the Edmonton Symptom Assessment System at 3 weeks. The secondary measures include the Brief Fatigue Inventory, Hospital Anxiety and Depression Scale, Insomnia Severity Index, Numeric Rating Scale, and European Organization for Research and Treatment of Cancer Quality of Life 15 items Questionnaire for Palliative Care. DISCUSSION: The finding of this trial will provide high-quality evidence on the adjunctive effect of acupuncture to standard care on advanced cancer patients undergoing palliative care. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04398875 (https://www.clinicaltrials.gov/ct2/show/NCT04398875), Registered on 21 May 2020.

Electroacupuncture Plus Auricular Acupressure for Chemotherapy-Associated Insomnia in Breast Cancer Patients: A Pilot Randomized Controlled Trial.

OBJECTIVE: Chemotherapy-associated insomnia is a highly prevalent complaint in breast cancer patients. This study was undertaken to evaluate the safety, feasibility, and preliminary effectiveness of electroacupuncture plus auricular acupressure for chemotherapy-associated insomnia in patients with breast cancer. MATERIALS AND METHODS: In this randomized, wait-list controlled trial, thirty breast cancer patients under or post chemotherapy with insomnia were randomly allocated to the acupuncture or wait-list control group. Participants in acupuncture group received electroacupuncture plus auricular acupressure treatment twice weekly for 6 weeks. Participants in wait-list group received the same regimen of treatment after 6-week of waiting period. Insomnia Severity Index (ISI) served as the primary outcome measurement. Secondary outcomes were sleep parameters recorded with sleep diary and actiwatch, as well as the scores of Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B). RESULTS: Twenty-eight participants completed study (13 in the acupuncture group vs 15 in the wait-list control group). At week-6 post-intervention, ISI score change from baseline showed significant between-group difference favoring acupuncture group of -2.9 points (95% CI: -5.2 to -0.6, P = .014). The acupuncture group showed greater improvements in the total sleep time recorded by sleep diary (P = .026), scores of PSQI (P = .012), HADS-depression (P = .020), and FACT-B (P < .001) compared with the control group. Improvements were maintained at week-10 and week-14 follow-ups. CONCLUSIONS: Acupuncture is safe, feasible, and effective for chemotherapy-associated insomnia in breast cancer patients under or post chemotherapy. A larger sample size randomized clinical trial is warranted to confirm the present findings. CLINICAL TRIAL REGISTRATION: NCT03762694.

A Cost-Effectiveness Analysis of Systemic Therapy for Metastatic Hormone-Sensitive Prostate Cancer.

BACKGROUND: Currently, approved first-line treatment options of metastatic hormone-sensitive prostate cancer (mHSPC) include (1) androgen deprivation therapy (ADT) alone, ADT plus one of the following: (2) docetaxel, (3) abiraterone, (4) enzalutamide, and (5) apalutamide. The high cost of novel androgen receptor pathway inhibitors warrants an understanding of the combinations' value by considering both efficacy and cost. OBJECTIVE: This study aimed to compare the cost-effectiveness of these five treatment options in mHSPC from the US payer perspective to guide treatment sequence. METHODS: A Markov model was developed to compare the lifetime cost and effectiveness of these five first-line treatment options for mHSPC using outcomes data from published literature. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were obtained from the Veterans Affairs Pharmaceutical Catalog. We extrapolated survival beyond closure of the trials. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Life-years, QALYs, lifetime costs, and incremental cost-effectiveness ratios (ICERs) were estimated. Univariable, 2-way, and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty. A willingness-to-pay (WTP) threshold of US$100,000 per QALY was used. RESULTS: Compared to ADT alone, docetaxel plus ADT provided a 0.28 QALY gain at an ICER of US$12,870 per QALY. Abiraterone plus ADT provided an additional 1.70 QALYs against docetaxel plus ADT, with an ICER of US$38,897 per QALY. Compared to abiraterone plus ADT, enzalutamide plus ADT provided an additional 0.87 QALYs at an ICER of US$509,813 per QALY. Apalutamide plus ADT was strongly dominated by enzalutamide plus ADT. Given the WTP threshold of US$100,000 per QALY, abiraterone plus ADT represented high-value health care. CONCLUSIONS: Abiraterone plus ADT is the preferred treatment option for men with mHSPC at a WTP threshold of US$100,000 per QALY.

Chinese Herbal Medicine for Reducing Chemotherapy-Associated Side-Effects in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Chemotherapy usually induces a variety of side-effects in cancer treatment as it cannot tell normal cells apart from cancer cells and kills both. Chinese herbal medicine (CHM) has been regarded as a potential effective intervention for relieving the side-effects of chemotherapy in breast cancer patients. OBJECTIVE: This study aims to conduct a comprehensive systematic review and meta-analysis to evaluate the efficacy of CHM as adjuvant therapy for reducing the chemotherapy-induced side-effects in the treatment of breast cancer. METHODS: Main electronic databases were searched up to May 2020 for Randomized Controlled Trials (RCTs) evaluating the effect of CHM on breast cancer patients with chemotherapy. The PRISMA statement was adopted in this study and meta-analyses were performed. RESULTS: The included studies showed unsatisfied quality. Results based on available literature indicated that the adjunctive use of CHM with chemotherapy may reduce the chemotherapeutic agents-associated adverse events, including nausea and vomiting, diarrhea, alopecia, myelosuppression, and impaired immune function. CONCLUSION: A confident conclusion could not be have due to the lack of large scale and high quality trials.

Lymphopenia and Radiation Dose to Circulating Lymphocytes With Neoadjuvant Chemoradiation in Esophageal Squamous Cell Carcinoma.

PURPOSE: We hypothesized that radiation-induced lymphopenia could be predicted by the effective dose to the circulating immune cells (EDIC) in advanced esophageal squamous cell carcinoma treated with trimodality therapy according to the Dutch ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial regimen. To test this hypothesis, we examined the effect of EDIC on the degree of lymphocyte drop (lymphocyte nadir). METHODS AND MATERIALS: Patients with advanced nonmetastatic esophageal squamous cell carcinoma treated in a single tertiary cancer center from 2012 to 2018 were eligible for this study. All patients had to have a radiation therapy plan available for EDIC computation and received neoadjuvant chemoradiation according to the Dutch CROSS trial regimen before radical esophagectomy. The EDIC was calculated as a function of integral doses to the lung, heart, and total body with a verified mathematical model. The association between EDIC and lymphocyte nadir was studied, and the relationships of overall survival (OS) with lymphocyte nadir and EDIC were assessed using multivariable Cox regression model. RESULTS: This analysis included 92 eligible consecutive patients (77 men and 15 women). The mean EDIC was 2.8 Gy (range, 0.6-4.4). EDIC was significantly correlated with lymphocyte nadir (Spearman coefficient = -0.505; P < .01), and lymphocyte nadir was a significant independent factor for shorter OS (hazard ratio = 0.63; P < .001). Lymphocyte nadir was also the most significant factor in determining OS among other clinical parameters. Exploratory analysis showed significant OS differences between EDIC groups (<2, 2-4, and >4 Gy). The 2-year OS rates were 66.7%, 42.7%, and 16.7% for EDIC <2, 2 to 4, and >4 Gy, respectively. CONCLUSIONS: There was a significant correlation between radiation dose to circulating immune cells and lymphocyte nadir, which in turn affected OS in patients with advanced nonmetastatic esophageal squamous cell carcinoma treated by trimodality therapy.

Real-world Scenario: CROSS Regimen as Preoperative Therapy for Oesophageal Squamous Cell Carcinoma.

BACKGROUND: Preoperative chemoradiation (CROSS regimen) has been widely adopted worldwide. The survival advantage imparted is especially impressive for oesophageal squamous cell carcinoma (OSCC). This study aimed at investigating the efficacy of the CROSS regimen in real-world scenario. METHODS: This is a retrospective study of all patients with OSCC intended for preoperative treatment using the CROSS regimen during 2012-2017. Patients were divided into two groups: those within the selection criteria in the CROSS trial and those beyond criteria, namely age > 75 years old, tumour length > 8 cm or clinical M1 stage of lymph node involvement (AJCC 6th edition). Clinical outcome and survival data were compared. RESULTS: Eighty-eight patients were included. There were 46 patients in the "CROSS eligible" group and 42 in the "CROSS ineligible" group. By intention-to-treat, the estimated median survival was 24.2 months vs. 12.7 months, respectively (p = 0.047). The results were much inferior compared to that published in the original CROSS trial. Univariable and multivariable analyses showed tumour length and resectability as independent variables affecting survival. DISCUSSION: In a real-world scenario, the clinical outcome remains suboptimal and the excellent results in the trial setting were not reproducible in this Asian cohort. Patient selection is one key element accountable for the difference. The efficacy of the CROSS regimen may not be adequate for patients with more advanced disease. The optimal multimodal therapy for this group of patients remains undefined.

Comparing the efficacy of integrative body-mind-spirit intervention with cognitive behavioral therapy in patient-caregiver parallel groups for lung cancer patients using a randomized controlled trial.

Purposes/objectives: This paper reports the comparative efficacies of integrative body-mind-spirit intervention (I-BMS) and cognitive behavioral therapy (CBT) in patient-caregiver parallel groups for Chinese patients with lung cancer.Design: Randomized controlled trial (RCT).Methods: One hundred and fifty-seven patient-caregiver dyads with no marked functional impairment were randomized into one of the two interventions with eight weekly patient-caregiver parallel groups. Assessments were conducted at baseline, within one, eight- and sixteen-weeks post-intervention. Effects of treatment group across time were analyzed by multilevel modeling.Findings: CBT led to greater reduction in emotional vulnerability than I-BMS. I-BMS resulted in greater increase in overall QoL and spiritual self-care, and more reduction in depression than CBT. Patients in both interventions experienced improvement in physical, emotional and spiritual, except social, domains of QoL.Conclusion: I-BMS was more efficacious for diverse domains of QoL, and CBT was more effective for emotional well-being, despite the relatively small between-group effect sizes.Implications for psychosocial providers/policy: (1) With the expanding repertoire of psychosocial interventions for families facing lung cancer, it has become imperative to investigate the comparative efficacies of empirically supported and culturally adapted interventions. (2) Our findings show that I-BMS was more effective for diverse domains of QoL, while CBT was more efficacious with emotional well-being, although both interventions led to significant improvements in physical, emotional and spiritual domains of patient QoL. (3) Patient-caregiver parallel groups have been shown to be effective for enhancing QoL of Chinese lung cancer patients. (4) Care professionals are encouraged to dispense interventions based on the idiosyncratic needs and preferences of the patients to maximize the treatment effects.

Systemic Therapy for Esophageal Squamous Cell Carcinoma.

With more understanding of the tumor biology, esophageal squamous cell carcinoma (ESCC) and adenocarcinoma are increasingly recognized as different disease entities and are managed with different treatment approaches. Most patients with ESCC need systemic treatment at some point of their disease course, but only until recently, the progress in systemic treatment has been relatively stagnant compared with its adenocarcinoma counterpart. Platinum-based regimens remain the standard of care, while taxanes have been increasingly used upfront and in later lines of treatment. The attempts to personalize treatment for ESCC with various target therapies have been futile. Immune checkpoint inhibitors are now coming into play with promising activity and potentials to combine with different treatment modalities. The current chapter overviews the systemic treatment for ESCC and highlights the recent development.

Comparing dyadic cognitive behavioral therapy (CBT) with dyadic integrative body-mind-spirit intervention (I-BMS) for Chinese family caregivers of lung cancer patients: a randomized controlled trial.

PURPOSE: The study adopted a randomized controlled trial to compare the effect of culturally compatible psychosocial interventions on multiple aspects of quality of life (QoL) for family caregivers of lung cancer patients. METHODS: 157 Chinese informal caregivers of lung cancer patients were recruited together with the family members for whom they were providing care, and randomly assigned to either integrative body-mind-spirit intervention (I-BMS) or cognitive behavioral therapy (CBT). Patient-caregiver dyads attended the same arm of intervention in separate groups for 8 weeks. Assessments of generic QoL, anxiety, depression, perceived stress, insomnia, and caregiving burden were measured before intervention (T0), within 1-week (T1), 8-week (T2), and 16-week (T3) post-intervention. RESULTS: Adopting the intention-to-treat analysis, family caregivers in receipt of both I-BMS and CBT exhibited a statistically significant improvement in generic QoL immediately following intervention and at follow-up assessments, with moderate effect size. Improvement of insomnia was found at T1 for both modes, which deteriorated at follow-up; both modes reduced anxiety and perceived stress at follow-up. No intervention effect was observed in depression and domains of caregiving burden. There was no significant interaction effect between intervention type and time. No main or interaction effect between sample background variables and intervention type was found to predict symptomatic changes at T1 and T3. CONCLUSIONS: Culturally attuned I-BMS and CBT exhibited equivalent effectiveness in improving psychological distress and generic QoL for family caregivers of lung cancer patients. To improve the evaluation of outcomes, future study could benefit from incorporating a usual care control.

Cost-effectiveness analysis of Abiraterone Acetate versus Docetaxel in the management of metastatic castration-sensitive prostate cancer: Hong Kong's perspective.

BACKGROUND: Several randomized control trials (RCTs) have showed that adding either abiraterone acetate (AA) or docetaxel (D) to androgen-deprivation therapy (ADT) improves survival of metastatic castration-sensitive prostate cancer patients (mCSPC). Yet, the cost-effectiveness of these treatment options has not been fully compared under Hong Kong's setting. This cost-effectiveness analysis (CEA) serves as the first study in Hong Kong to compare the economic value of these two combinations ADT + AA vs. ADT + D. METHODS: A deterministic Markov model is used to project cost-effectiveness of each treatment until death. Survival curves for progression/death were extracted and digitized from the five RCTs (CHAARTED, LATITUDE, two STAMPEDE (2016/2017), and GETUG-AFU15). Clinically significant adverse events (AEs) were modeled; utility values were obtained from the literature. Primary outcomes were the quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). We used the societal perspective from Hong Kong and considered three times of local gross domestic product per capita (GDPpc) as the willingness-to-pay (WTP) threshold (i.e., US$138,649). We estimated the break-even cost of AA in case ADT + AA is not a cost-effective strategy under this WTP threshold. While considering the standard AA dosage (1000 mg) as the main analysis, we also examined the potential impact of the low-dose AA (250 mg) strategy. RESULTS: Integrating simulations with probabilistic sensitivity analysis, ADT + D returns 0.79 (median; 95% credible interval 0.56-0.97) QALY with an ICER of US$14,397/QALY ($7824-22,632) compared to ADT-alone. A head-to-head comparison indicates that ADT + AA further gains 0.79 (0.45-1.17) QALY but with an ICER of $361,439/QALY ($260,615-599,683) when compared to ADT + D. Considering three times of GDPpc as WTP threshold, ADT + D is more cost-effective in all simulations; while ADT + AA is more cost-effective than ADT + D only if the cost of AA is reduced by at least 63%. The low-dose AA (250 mg) strategy is potentially cost-effective when it generates equivalent efficacy as the standard dosage (1000 mg). CONCLUSIONS: ADT + D is therefore shown to be a more cost-effective strategy than ADT + AA in metastatic castration-sensitive prostate cancer patients in developed economies. Addition of AA substantially improved QALY compared to D but at a significant cost.

Negative plasma Epstein-Barr virus DNA nasopharyngeal carcinoma in an endemic region and its influence on liquid biopsy screening programmes.

BACKGROUND: Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in endemic regions may have undetectable plasma EBV DNA. METHODS: We prospectively recruited 518 patients with non-metastatic NPC and measured their pre-treatment plasma EBV DNA. The stage distribution and prognosis between pre-treatment plasma EBV DNA-negative (0-20 copies/ml) and EBV DNA-positive (>20 copies/ml) patients following radical treatment were compared. RESULTS: Seventy-eight patients (15.1%) were plasma EBV DNA-negative, and 62 in this subset (12.0%) had 0 copy/ml. Only 23/78 (29.5%) plasma EBV DNA-negative patients with advanced NPC (stage III-IVA) had strong EBV encoded RNA (EBER) positivity (score 3) in their tumours compared to 342/440 (77.7%) EBV DNA-positive patients of the same stages (p < 0.001). Though EBV DNA-negative patients had more early-stage disease (p < 0.001) and smaller volumes of the primary tumour and the positive neck nodes (p < 0.001), they had similar 5-year overall survival and cancer-specific survival to those EBV DNA-positive counterparts by stage. Similar results were also seen when plasma EBV DNA cut-off was set at 0 copy/ml. CONCLUSIONS: Patients with low-volume NPC may not be identified by plasma/serum tumour markers and caution should be taken in its utility as a screening tool for NPC even in endemic regions. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02476669.

Literature Review of Traditional Chinese Medicine Herbs-Induced Liver Injury From an Oncological Perspective With RUCAM.

Traditional Chinese medicine (TCM) herbs are commonly regarded to be safe with minimal toxicities in Chinese communities. Cancer patients who are receiving Western oncology therapy often concurrently take TCM herbs for anticancer and symptom relief purposes. We performed a literature review for current evidence on TCM herb-induced liver injury from an oncological perspective. A literature search on PubMed was performed to identify publications regarding TCM herbs and concoctions with hepatoprotective or hepatotoxic properties. Lists of commonly used herbs and their causality levels were compiled. In view of the wide range of evidence available, cases assessed by the well-established RUCAM (Roussel Uclaf Causality Assessment Method) algorithm were categorized as the highest level of evidence. More than one case of TCM herb-induced liver injury was confirmed by RUCAM in the following herbs and concoctions: Lu Cha (Camellia sinensis), Bai Xian Pi (Dictamnus dasycarpus), Tu San Qi (Gynura segetum), Jin Bu Huan (Lycopodium serratum), He Shou Wu (Polygoni multiflora), Ge Gen (Pueraria lobata), Dan Lu Tong Du tablet, Shou Wu Pian, Xiao Chai Hu Tang, Xiao Yin pill, and Yang Xue Sheng Fa capsule. Finally, TCM with anticancer or symptom relief uses were discussed in detail with regard to their hepatotoxic or hepatoprotective properties.