Association of sarcopenia with severe chemotherapy toxicities and survival in patients with advanced gastric cancer.

BACKGROUND: Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining sarcopenia have been found to have limitations when clinically applied. This study aimed to determine the optimal cutoff for SMI to predict severe toxicities of chemotherapy and overall survival (OS) in patients with advanced GC. METHODS: Patients with metastatic gastric adenocarcinoma who received first-line palliative chemotherapy between January 2014 and December 2021 at Queen Mary Hospital, Hong Kong, were included in this study. The SMI was determined via a pre-chemotherapy computed tomography scan. Optimal cutoff points of SMI were identified by recursive partitioning analysis. Univariate and multivariate analyses evaluating risk factors of severe chemotherapy toxicities and OS were also performed. RESULTS: A total of 158 patients (male: 108 (68.4%), median age: 65.3) were included. The SMI cutoff to define low SMI was ≤33 cm2/m2 for males and ≤28 cm2/m2 for females; 30 patients (19.0%) had low SMI. Patients with low SMI had a higher incidence of hematological toxicities (63.3% vs 32.0%, P = .001) and non-hematological toxicities (66.7% vs 36.7%, P = .003). Multivariable analysis indicated that low SMI and low serum albumin (≤28 g/L) were independent predictive factors of hematological toxicity, while low SMI and neutrophil-lymphocyte ratio ≥5 were predictive factors of non-hematological toxicity. Moreover, patients with low SMI had a significantly shorter OS (P = .011), lower response rate to chemotherapy (P = .045), and lower utilization of subsequent lines of treatment (P < .001). CONCLUSIONS: Using pre-chemotherapy SMI cutoff (≤33 cm2/m2 for males and 28 cm2/m2 for females) one can identify individuals with a higher risk of severe chemotherapy toxicities and worse prognosis.

Screening for Frailty Using the FRAIL Scale in Older Cancer Survivors: A Cross-sectional Comparison With the Fried Phenotype.

OBJECTIVES: To examine the diagnostic performance of the FRAIL Scale for frailty screening with reference to the Fried phenotype and investigate its association with health outcomes in older cancer survivors. DATA SOURCE: In this cross-sectional quantitative study, participants were post-treatment cancer survivors aged 65 or above. Measurements included the FRAIL Scale, Fried phenotype, Geriatric Depression Scale-15 item, Modified Barthel Inventory, and EORTC Core Quality of Life Questionnaire. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of the FRAIL Scale with reference to the Fried phenotype. Health outcomes associated with being frail as estimated by the FRAIL Scale and Fried phenotype were also examined using regressions. RESULTS: Based on 293 older cancer survivors, the area under curve (AUC) of the FRAIL Scale was 0.79, and the optimal cut-off of 1 yielded a sensitivity of 92% and specificity of 41%. According to regression results, the FRAIL Scale was modified by adding an item on time since cancer treatment completion (AUC = 0.81), and using a cut-off of 2 for older cancer survivors, which yielded a sensitivity of 74% and specificity of 67%. The modified FRAIL Scale was associated with depressive symptoms, functional independence, fatigue, dyspnea, physical functioning, and role functioning. CONCLUSIONS: The modified FRAIL Scale is proposed for use in older cancer survivors, and a cut-off of 2 should be used. IMPLICATIONS FOR NURSING PRACTICE: The modified FRAIL Scale can serve as a brief screening tool for identifying frailty among older cancer survivors in practice.

Limitations of GPT-4 as a geriatrician in geri-oncology case conference: A case series.

Generative pre-trained transformer 4 (GPT-4) is an artificial intelligence (AI) system with a chat interface. The number of studies testing GPT-4 in clinical applications has been increasing. We hypothesized that GPT-4 would be able to suggest management strategies for medical issues in elderly oncology patients, similar to those provided by geriatricians. We compared the responses of GPT-4 to those of a geriatrician for four oncological patients. After these case conferences, none of the patients required admission for medical consultation. In three out of four scenarios, GPT-4 was able to offer a multidisciplinary approach in the first prompt. In all three scenarios, GPT-4 identified medication-related side effects and suggested appropriate medications in the first prompt. However, GPT-4 was unable to suggest initial dosages of medications to be used in the first prompt and was unable to suggest a more humanistic and non-pharmacological approach to anorexia, even with a follow-up prompt. In conclusion, GPT-4 may be used as a screening tool to provide potential rudimentary directions for management, which can then be reviewed by medical professionals before considering a formal consultation for more tailored and refined opinions from specialists.

Cognitive frailty in older cancer survivors and its association with health-related quality of life.

PURPOSE: This study aimed (1) to estimate the prevalence of cognitive frailty, (2) to identify factors associated with cognitive frailty and (3) to examine the association of cognitive frailty with health-related quality of life (HRQOL) in older cancer survivors. METHODS: This was a cross-sectional study. Participants were aged 65 or above, diagnosed with cancer and had completed cancer treatment. Measures on physical frailty, cognitive functioning and HRQOL were administered. Multiple linear regression models were used to examine the association of cognitive frailty with HRQOL. RESULTS: Among 293 recruited participants, 18.8% had a cognitive functioning decline, 8.9% were physically frail and 8.2% were cognitively frail. Regular exercise (OR = 0.383, p = .035) and shorter time since treatment completion were associated with less likelihood of cognitive frailty (OR = 1.004, p = .045). Cognitive frailty was significantly associated with global health status (ß = -0.116; p = .044), physical functioning (ß = -0.177; p = .002), social functioning (ß = -0.123; p = .035) and fatigue symptoms (ß = 0.212; p < .001) after adjusting for potential confounding variables. CONCLUSIONS: Cognitive frailty, found in 8.2% of older cancer survivors, is associated with various dimensions of HRQOL. Longitudinal research examining the trajectory and impact of cognitive frailty on more diverse health outcomes in older cancer survivors is warranted. The findings improve service providers' knowledge of cognitive frailty in older cancer survivors and inform surveillance and care for geriatric cancer survivorship.

Adjuvant Chemotherapy in Older Patients with Gastric Cancer: A Population-Based Cohort Study.

(1) Background: The effectiveness of adjuvant chemotherapy in older patients with gastric cancer after D2-gastrectomy is unclear. This study investigated the efficacy of adjuvant chemotherapy in elderly patients with stage II/III gastric cancer. (2) Methods: A real-world population-based retrospective cohort of patients aged ≥65 with stage II/III gastric cancer (n = 2616; median age: 73.5; 12.2% aged >80 years) treated between 1 January 1997 and 31 December 2020 were included. All data was retrieved from the Hong Kong Hospital Authority Clinical Management System (CMS). Clinical characteristics of those patients with and without adjuvant chemotherapy treatment were balanced after propensity score matching (PSM). In total, 732 patients treated with adjuvant chemotherapy were matched with 732 patients treated with surgery alone. Hazard ratios (HRs) estimated via Cox proportional hazards regression models were used to compare the overall survival (OS) and cancer-specific survival (CSS) of the two patient groups. (3) Results: Adjuvant chemotherapy was associated with better OS (37 vs. 25 months; HR: 0.80; 95% CI: 0.75-0.84; p < 0.001) than surgery alone. The OS benefit was observed in both the 65-80 (44 vs. 27 months; HR: 0.79; 95% CI: 0.74-0.84; p < 0.001) and >80 (14 vs. 11 months; HR: 0.82; 95% CI: 0.71-0.96; p < 0.001) age groups. A better CSS was observed in patients who received adjuvant chemotherapy than those who only had surgery (5-year CSS: 64.1% vs. 61.1%, HR: 0.85; 95% CI: 0.79-0.93; p < 0.001). (4) Conclusions: adjuvant chemotherapy significantly improved OS and CSS in older patients with stage II/III gastric cancer.

Overexpression of BQ323636.1 contributes to anastrozole resistance in AR+ve/ER+ve breast cancer.

Aromatase inhibitors (Ais) are used as adjuvant endocrine therapy for oestrogen receptor-positive (ER+ve) post-menopausal breast cancer patients. Ais, by inhibiting the enzyme aromatase, block the conversion of androgen to oestrogen, reducing oestrogen levels. Resistance to Ais limits their clinical utilisation. Here, we show that overexpression of BQ323636.1 (BQ), a novel splice variant of nuclear co-repressor NCOR2, is associated with resistance to the non-steroidal aromatase inhibitor anastrozole in ER+ve post-menopausal breast cancer. Mechanistic study indicates that BQ overexpression enhances androgen receptor (AR) activity and in the presence of anastrozole, causes hyper-activation of AR signalling, which unexpectedly enhanced cell proliferation, through increased expression of CDK2, CDK4, and CCNE1. BQ overexpression reverses the effect of anastrozole in ER+ve breast cancer in an AR-dependent manner, whilst co-treatment with the AR antagonist bicalutamide recovered its therapeutic effect both in vitro and in vivo. Thus, for BQ-overexpressing breast cancer, targeting AR can combat anastrozole resistance. Clinical study of 268 primary breast cancer samples of ER+ve patients who had been treated with non-steroidal Ais showed 32.5% (38/117) of cases with combined high nuclear expression of BQ and AR, which were found to be significantly associated with Ai resistance. Non-steroidal Ai-treated patients with high nuclear expression of both BQ and AR had poorer overall, disease-specific, and disease-free survival. These findings suggest the importance of assessing BQ and AR expression status in the primary ER+ve breast tumour prior to Ai treatment. This may save patients from inappropriate treatment and enable effective therapy to be given at an early stage. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

SRSF5 Regulates the Expression of BQ323636.1 to Modulate Tamoxifen Resistance in ER-Positive Breast Cancer.

About 70% of breast cancer patients are oestrogen receptor-positive (ER +ve). Adjuvant endocrine therapy using tamoxifen (TAM) is an effective approach for preventing local recurrence and metastasis. However, around half of the patients will eventually develop resistance. Overexpression of BQ323636.1 (BQ) is one of the mechanisms that confer TAM resistance. BQ is an alternative splice variant of NCOR2. The inclusion of exon 11 generates mRNA for NCOR2, while the exclusion of exon 11 produces mRNA for BQ. The expression of SRSF5 is low in TAM-resistant breast cancer cells. Modulation of SRSF5 can affect the alternative splicing of NCOR2 to produce BQ. In vitro and in vivo studies confirmed that the knockdown of SRSF5 enhanced BQ expression, and conferred TAM resistance; in contrast, SRSF5 overexpression reduced BQ expression and, thus, reversed TAM resistance. Clinical investigation using a tissue microarray confirmed the inverse correlation of SRSF5 and BQ. Low SRSF5 expression was associated with TAM resistance, local recurrence and metastasis. Survival analyses showed that low SRSF5 expression was associated with poorer prognosis. We showed that SRPK1 can interact with SRSF5 to phosphorylate it. Inhibition of SRPK1 by a small inhibitor, SRPKIN-1, suppressed the phosphorylation of SRSF5. This enhanced the proportion of SRSF5 interacting with exon 11 of NCOR2, reducing the production of BQ mRNA. As expected, SRPKIN-1 reduced TAM resistance. Our study confirms that SRSF5 is essential for BQ expression. Modulating the activity of SRSF5 in ER +ve breast cancer will be a potential approach to combating TAM resistance.

SGLT2i reduces risk of developing HCC in patients with co-existing type 2 diabetes and hepatitis B infection: A territory-wide cohort study in Hong Kong.

BACKGROUND AND AIMS: Type 2 diabetes (T2D) and chronic hepatitis B infection (CHB) are risk factors of HCC. Sodium glucose co-transporter 2 inhibitors (SGLT2i) inhibit HCC oncogenesis in preclinical studies. However, clinical studies are lacking. This study aimed to evaluate the impact of SGLT2i use on incident HCC using a territory-wide cohort of exclusively patients with co-existing T2D and CHB. APPROACH AND RESULTS: Patients with co-existing T2D and CHB between 2015 and 2020 were identified from the representative electronic database of the Hong Kong Hospital Authority. Patients with and without SGLT2i use were 1:1 matched by propensity score for their demographics, biochemistry results, liver-related characteristics, and background medications. Cox proportional hazards regression model was used to assess the association between SGLT2i use and incident HCC. A total of 2,000 patients with co-existing T2D and CHB (1,000 in each SGLT2i and non-SGLT2i group; 79.7% on anti-HBV therapy at baseline) were included after propensity-score matching. Over a follow-up of 3,704 person-years, the incidence rates of HCC were 1.39 and 2.52 cases per 100 person-year in SGLT2i and non-SGLT2i groups, respectively. SGLT2i use was associated with a significantly lower risk of incident HCC (HR 0.54, 95%CI: 0.33-0.88, p =0.013). The association remained similar regardless of sex, age, glycemic control, diabetes duration, presence of cirrhosis and hepatic steatosis, timing of anti-HBV therapy, and background antidiabetic agents including dipeptidyl peptidase-4 inhibitors, insulin, or glitazones (all p interaction>0.05). CONCLUSIONS: Among patients with co-existing T2D and CHB, SGLT2i use was associated with a lower risk of incident HCC.

Trajectories of sleep disturbance in cancer survivors during the first 2 years post-treatment.

STUDY OBJECTIVES: To examine the trajectories of sleep disturbance in cancer survivors during the first 2 years post-treatment and to investigate whether psychological, cognitive, and physical factors differentiate trajectories. METHODS: A total of 623 Chinese cancer survivors of diverse cancer types participated in a 2-year-long prospective study after the completion of cancer treatment. Sleep disturbance was measured using Pittsburgh Sleep Quality Index at 3 (T2), 6 (T3), 12 (T4), 18 (T5), and 24 (T6) months after baseline (within 6-months post-treatment; T1). Latent growth mixture modeling identified distinctive sleep disturbance trajectories and tested if these longitudinal patterns were predicted by baseline psychological distress, attentional control, attentional bias and physical symptom distress and T2 cancer-related distress. Fully adjusted multinomial logistic regression then identified whether these factors differentiated trajectories. RESULTS: Two distinct sleep disturbance trajectories were identified, namely stable good sleepers (69.7%) and persistent high sleep disturbance (30.3%). Compared to those in the stable good sleep group, patients in the persistent high sleep disturbance group were less likely to report avoidant (OR=0.49, 95% CI = 0.26-0.90), while more likely to report intrusive thoughts (OR = 1.76, 95% CI = 1.06-2.92) and cancer-related hyperarousal (OR = 3.37, 95% CI = 1.78-6.38). Higher depression scores also predicted persistent high sleep disturbance group membership (OR = 1.13, 95% CI = 1.03-1.25). Attentional bias, attentional control, anxiety, and physical symptom distress did not predict sleep trajectory membership. CONCLUSIONS: One in three cancer survivors experienced persistent high sleep disturbance. Screening and managing depressive symptoms and cancer-related distress in early cancer rehabilitation may reduce risk of persistent sleep disturbance among cancer survivors.

Invasive or noninvasive? A systematic review and network meta-analysis of acupuncture and acupressure to treat sleep disturbance in cancer patients.

BACKGROUND: Both acupuncture and acupressure have been suggested beneficial for reducing sleep disturbance in cancer patients. While acupuncture is invasive involving needle insertion, acupressure is noninvasive. Their comparative effectiveness is unclear, hindering clinical recommendations. AIMS: This study aimed to explore the comparative effectiveness of acupuncture and acupressure on sleep in cancer patients. METHODS: This is a systematic review and Bayesian network meta-analysis. Eight key English and Chinese databases were searched. Twenty-four randomized controlled trials involving 2002 cancer patients comparing the effects of six treatments (manual acupuncture, electroacupuncture, acupressure, sham, enhanced usual care, and no treatment) on sleep were found. RESULTS: Compared with enhanced supportive care, acupressure demonstrated the largest effect size for reducing self-reported sleep disturbance (standardized mean difference [SMD] = -2.67, 95% CrI: -3.46 to -1.90; GRADE = moderate), followed by acupuncture (SMD = -1.87, 95% CrI: -2.94 to -0.81, GRADE = moderate) and electroacupuncture (SMD = -1.60, 95% CrI: -3 to -0.21; GRADE = low). The surface under the cumulative ranking curve indicates that acupressure is most likely to rank highest. LINKING EVIDENCE TO ACTION: Based on available evidence, acupressure can be recommended as the optimal treatment for reducing sleep disturbance in cancer patients. More rigorous trials are warranted to confirm whether different forms of acupuncture or acupressure have different effects on sleep in cancer patients. Particularly, studies examining acupuncture interventions alone instead of in combination with other therapies are needed.

Docetaxel, Cisplatin, and 5-FU Triplet Therapy as Conversion Therapy for Locoregionally Advanced Unresectable Esophageal Squamous Cell Carcinoma.

BACKGROUND: The standard treatment for locoregionally advanced unresectable esophageal squamous cell carcinoma was radical chemoradiotherapy. However, the prognosis was modest. Emerging evidence showed the concept of induction chemotherapy with a goal of conversion surgery. METHODS: We reviewed the long-term, clinical outcomes and safety data of induction chemotherapy using docetaxel-cisplatin-5FU (DCF) and subsequent definitive treatment, either surgery or radical chemoradiotherapy (CRT), in locally advanced unresectable esophageal cancer in Queen Mary Hospital, Hong Kong. A total of 47 patients (median age 62 years, male: 41 (87.2%)) with locoregionally advanced unresectable esophageal cancer received induction DCF. The response rate was 65.9% (complete/partial response: n = 31). After induction DCF, 24 patients (41.4%) had radical surgery and 7 (14.9%) had definitive CRT. RESULTS: The median overall survival (mOS) was significantly longer in patients received subsequent surgery compared with those with definitive CRT (mOS: 40.2 vs. 9.1 months, hazard ratio 3.33, 95% confidence interval 1.22-9.07, p = 0.02) and no definitive treatment (mOS: 40.2 vs. 6.3 months, hazard ratio 8.51, 95% confidence interval 3.7-19.73, p < 0.001). Patients who received surgery, female, and those with supraclavicular lymph node involvement had a better OS. Twenty-one patients (44.7%) developed grade 3/4 adverse events during induction DCF, and two died after chemotherapy because of trachea-esophageal fistula complicated with sepsis. Eleven patients who had surgery had postoperative complications and none had postoperative mortality. CONCLUSIONS: Induction DCF and subsequent conversion surgery offered a chance of cure with long-term survival benefit and manageable toxicities in patients with locoregionally advanced unresectable esophageal cancer.

Checkpoint Kinase 2 Inhibition Can Reverse Tamoxifen Resistance in ER-Positive Breast Cancer.

Breast cancer is a heterogeneous disease. Tamoxifen is frequently used to treat ER-positive breast cancer. Our team has identified a novel splice variant of NCOR2, BQ323636.1 (BQ), that mediates tamoxifen resistance. However, the upstream factors that modulate BQ expression are not apparent. This study reveals that tamoxifen treatment causes induction of DNA damage which can enhance BQ expression. We show that DNA damage can activate the ATM/CHK2 and ATR/CHK1 signalling cascades and confirm that ATM/CHK2 signalling is responsible for enhancing the protein stability of BQ. siRNA or a small inhibitor targeting CHK2 resulted in the reduction in BQ expression through reduced phosphorylation and enhanced poly-ubiquitination of BQ. Inhibition of CHK2 by CCT241533 could reverse tamoxifen resistance in vitro and in vivo. Using clinical samples in the tissue microarray, we confirmed that high p-CHK2 expression was significantly associated with high nuclear BQ expression, tamoxifen resistance and poorer overall and disease-specific survival. In conclusion, tamoxifen treatment can enhance BQ expression in ER-positive breast cancer by activating the ATM/CHK2 axis. Targeting CHK2 is a promising approach to overcoming tamoxifen resistance in ER-positive breast cancer.

Treatment Outcomes of Computer Tomography-Guided Brachytherapy in Cervical Cancer in Hong Kong: A Retrospective Review.

(1) Background: To report the long-term clinical outcomes of computer-tomography (CT)-guided brachytherapy (BT) for locally advanced cervical cancer. (2) Methods: A total of 135 patients with FIGO stage IB-IVA cervical cancer treated with definitive radiotherapy +/- chemotherapy with an IGABT boost at Queen Mary Hospital, Hong Kong, between November 2013 and December 2019 were included. Treatment included pelvic radiotherapy 40 Gy/20 Fr/4 weeks +/- chemotherapy then CT-guided BT (7 Gy × 4 Fr) and a sequential parametrial boost. The primary outcome was local control. Secondary outcomes were pelvic control, distant metastasis-free survival, overall survival (OS) and late toxicities. (3) Results: The median follow-up was 53.6 months (3.0-99.6 months). The five-year local control, pelvic control, distant metastasis-free survival and OS rates were 90.7%, 84.3%, 80.0% and 87.2%, respectively. The incidence of G3/4 long-term toxicities was 6.7%, including proctitis (2.2%), radiation cystitis (1.5%), bowel perforation (0.7%), ureteric stricture (0.7%) and vaginal stenosis and fistula (0.7%). Patients with adenocarcinomas had worse local control (HR 5.82, 95% CI 1.84-18.34, p = 0.003), pelvic control (HR 4.41, 95% CI 1.83-10.60, p = 0.001), distant metastasis-free survival (HR 2.83, 95% CI 1.17-6.84, p = 0.021) and OS (HR 4.38, 95% CI: 1.52-12.67, p = 0.003) rates. Distant metastasis-free survival was associated with HR-CTV volume ≥ 30 cm3 (HR 3.44, 95% CI 1.18-9.42, p = 0.025) and the presence of pelvic lymph node (HR 3.44, 95% CI 1.18-9.42, p = 0.025). OS was better in patients with concurrent chemotherapy (HR 4.33, 95% CI: 1.40-13.33, p = 0.011). (4) Conclusions: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes. (4) Conclusion: CT-guided BT for cervical cancer achieved excellent long-term local control and OS. Adenocarcinoma was associated with worse clinical outcomes.

Return to Work and Work Productivity During the First Year After Cancer Treatment.

Objectives: Working-age cancer patients face barriers to resuming work after treatment completion. Those resuming work contend with reduced productivity arising from persisting residual symptoms. Existing studies of return to work (RTW) after cancer diagnosis were done predominantly in Western countries. Given that employment and RTW in cancer survivors likely vary regionally due to healthcare provision and social security differences, we documented rates and correlates of RTW, work productivity, and activity impairment among Chinese cancer survivors in Hong Kong at one-year post-treatment. Methods: Of 1,106 cancer patients assessed at six-months post-cancer treatment (baseline), 593 previously worked; detailed work status, psychological distress (HADS), physical symptom distress (MSAS-SF), supportive care needs (SCNS-SF34-C), health-related quality of life (SF12), and illness perception (B-IPQ) were assessed. Six months later (follow-up), work productivity and activity impairment were assessed (WPAI; n = 402). Descriptive analyses examined RTW rate. Fully adjusted regressions determined RTW, work productivity, and activity impairment predictors. Results: At baseline, 39% (232/593) were working, 26% (153/593) on sick leave, and 35% (208/593) were unemployed. Compared to patients returning to work, unemployed participants were older, likely manual/service-oriented workers, and had lower family income, chemotherapy, fewer unmet health system and information needs, poorer physical functioning, and negative illness perceptions. Sick leave participants were likely service-oriented workers, who had head and neck cancer, chemotherapy, and poor physical functioning. At FU, baseline depressive symptoms, physical symptom distress, and negative illness perceptions predicted presenteeism and work productivity loss; gynecological cancer, fewer unmet health system and information needs, and greater unmet sexuality needs predicted absenteeism; physical symptom distress, negative illness perception, and poor physical functioning predicted activity impairment. Conclusion: Cancer survivors who had more physically demanding jobs and poorer physical functioning delayed RTW. Unmanaged physical symptom and psychological distress hindered work productivity.

Management of Nasopharyngeal Carcinoma in Elderly Patients.

Nasopharyngeal cancer (NPC) is one of the most difficult cancers in the head and neck region due to the complex geometry of the tumour and the surrounding critical organs. High-dose radical radiotherapy with or without concurrent platinum-based chemotherapy is the primary treatment modality. Around 10%-15% of NPC patients have their diagnosis at age after 70. The management of NPC in elderly patients is particularly challenging as they encompass a broad range of patient phenotypes and are often prone to treatment-related toxicities. Chronologic age alone is insufficient to decide on the management plan. Comprehensive geriatric assessment with evaluation on patients' functional status, mental condition, estimated life expectancy, comorbidities, risks and benefits of the treatment, patients' preference, and family support is essential. In addition, little data from randomized controlled trials are available to guide treatment decisions in elderly patients with NPC. In deciding which treatment strategy would be suitable for an individual elderly patient, we reviewed the literature and reviewed the analysis of primary studies, reviews, and guidelines on management of NPC. This review also summarises the current evidence for NPC management in elderly adults from early to late stage of disease.

Overexpression of BQ323636.1 Modulated AR/IL-8/CXCR1 Axis to Confer Tamoxifen Resistance in ER-Positive Breast Cancer.

NCOR2 is a co-repressor for estrogen receptor (ER) and androgen receptor (AR). Our group previously identified a novel splice variant of NCOR2, BQ323636.1 (BQ), that mediates tamoxifen resistance via interference of NCOR2 repression on ER. Luciferase reporter assay showed BQ overexpression could enhance the transcriptional activity of androgen response element (ARE). We proposed that BQ employs both AR and ER to confer tamoxifen resistance. Through in silico analysis, we identified interleukin-8 (IL-8) as the sole ERE and ARE containing gene responsiveness to ER and AR activation. We confirmed that BQ overexpression enhanced the expression of IL-8 in ER+ve breast cancer cells, and AR inhibition reduced IL-8 expression in the BQ overexpressing cell lines, suggesting that AR was involved in the modulation of IL-8 expression by BQ. Moreover, we demonstrated that IL-8 could activate both AKT and ERK1/2 via CXCR1 to confer tamoxifen resistance. Targeting CXCR1/2 by a small inhibitor repertaxin reversed tamoxifen resistance of BQ overexpressing breast cancer cells in vitro and in vivo. In conclusion, BQ overexpression in ER+ve breast cancer can enhance IL-8 mediated signaling to modulate tamoxifen resistance. Targeting IL-8 signaling is a promising approach to overcome tamoxifen resistance in ER+ve breast cancer.