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Background: Adjuvant chemotherapy improves outcomes of pts with early breast cancer, but CINV have been regarded as two of the most disturbing side effects, affecting their quality of life (QoL). In this study, the primary objective was to compare the efficacy of olanzapine in addition to the standard aprepitant-based antiemetic regimen for CINV in pts receiving the 1st cycle of adjuvant AC chemotherapy (adriamycin 60mg/m2 and cyclophosphamide 600mg/m2). The secondary objective was to compare the tolerability and efficacy of such regimen in the 4 cycles of AC. Methods: This is a prospective single center, randomized study. Eligible pts had early stage breast cancer of Chinese ethnicity; they were chemotherapy- naive and treated with adjuvant AC chemotherapy. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomly allocated to Olanzapine (with olanzapine) or Standard (without olanzapine) arms. Individual patient filled in self-reported diary and visual analogue scale for nausea from which information on nausea, vomiting and use of rescue medication were collected; outcomes were compared during acute phase (0-24 hrs), delay (24-120 hrs) and overall time-frame (0-120 hrs) from initiation of AC. QoL was assessed by Functional Living Index-Emesis (FLIE). Results: 120 pts were randomized. For CINV in Cycle 1 AC, outcomes of Olanzapine vs Standard arms were: complete response (acute phase 70.0 vs 51.7%, p=0.0397; delay phase 75.0 vs 45.0%, p=0.0008; overall time-frame 65.0 vs 38.3%, p=0.0035), complete protection (acute phase 70.0 vs 50.0%, p=0.0253; delay phase 71.7 vs 40.0%, p=0.0005; overall 61.7 vs 36.7%, p=0.0062), total control (acute phase 65.0 vs 41.7%, p=0.0104; delay phase 60.0 vs 31.7%, p=0.0018; overall 51.7 vs 26.7%, p=0.0050), ‘no vomiting’ (acute phase 73.3 vs 51.7%, p=0.0142; delay phase 76.7 vs 48.3%, p=0.0013; overall 68.3 vs 40.0%, p=0.0018), ‘no significant nausea’ (acute phase 95.0 vs 75.0%, p=0.0017; delay phase 91.7 vs 65.0%, p=0.0004; overall 91.7 vs 63.3%, p=0.0002),‘no nausea’ (acute phase 76.7 vs 53.3%, p=0.0074; delay phase 65.0 vs 35.0%, p=0.0010; overall 58.3 vs 33.3%, p=0.0060), and need of rescue medication (acute phase 3.3 vs 11.7%, p=0.0654; delay phase 6.7 vs 21.7%, p=0.0133; overall 8.3 vs 23.3%, p=0.0244). Assessment of FLIE on Day 6 after Cycle 1 AC between the Olanzapine vs Standard arms revealed better QOL mean scores for nausea domain (p Conclusions: In this prospective study of Chinese women with breast cancer, the addition of olanzapine to standard antiemetic regimen increases the control of CINV and improves the QoL of pts during AC chemotherapy. Funding: Madam Diana Hon Fun Kong Donation for Cancer Research. Citation Format: Winnie Yeo, Thomas KH Lau, Vicky TC Chan, Li Leung, Dong Lai, Elizabeth Pang, Maggie Cheung, Ashley Wong, Winnie MT Soo, Vanessa TY Yeung, Teresa Tse, Eva WM Yeung, Daisy CM Lam, Kenneth CW Wong, David R Johnson, Kim PK Ng, Herbert Loong, Joyce TY Ng, Florence Mok, Mimi KM Lee, Darren MC Poon, Yvonne SH Yau, Macy Tong, Joyce JS Suen, Frankie KF Mo. Randomized study to determine the efficacy of Olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese breast cancer patients (PTS) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-09.

Background The prognostic impact of comorbidities in patients with sarcomas is not well defined. The aims of this study were to examine the implications of comorbidities and abnormal peripheral blood indices in patients with sarcomas.Methods A population-based database was assembled to extract patients with sarcoma in Hong Kong between January 2004 and March 2018. Charlson’s Comorbidity Index (CCI) score and prevalence of comorbidities, neutrophil, lymphocyte and platelet counts at diagnosis were assessed. The prognostic values of CCI, neutrophil-lymphocyte (NLR) and platelet-lymphocyte ratios (PLR) were estimated using Cox proportional hazard models. Restricted cubic spline plots were used to explore the association of baseline NLR and PLR with all-cause and cancer-specific mortality.Results Among 3358 eligible patients with sarcomas, 52.2% died after a median 26 months of follow-up. The most common comorbidities were diabetes mellitus (9.8%) and cerebrovascular disease (4.8%). Patients with higher CCI had higher mortality (CCI=3 vs CCI=2; HR 1.49; 95% CI 1.19 to 1.87; p

Objectives Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine. Patients and methods Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored. Results 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of “Complete Response” than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of “No significant nausea” and “No nausea” during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment. Conclusion The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted., Highlights • Olanzapine is reported to reduce nausea and vomiting after highly emetogenic chemotherapy. • Reported studies are limited by heterogeneous populations receiving diverse cytotoxic regimes. • This study enrolled Chinese breast cancer patients undergoing doxorubicin/cyclophosphamide. • Adding olanzapine to aprepitant/ondansetron/dexamethasone is superior in controlling nausea and vomiting. • Baseline investigations shows a surprisingly high rate of glucose and lipids abnormalities.

Background: Cutaneous Angiosarcoma (CAS) is a rare aggressive malignant tumour typically arising from skin or viscera. The incidence of AS appears more common in Asia, as compared with the West. The prognosis of patients (pts) advanced/inoperable CAS remains poor. The median PFS of first line systemic treatments of 3.8 months and overall survival (OS) of Methods: We investigated the potential effects of LBH589 and SAHA in ISO-HAS-B. IC50 of two pan-HDACi as single agents were tested, followed by synergism studies in combination with doxorubicin. Synergy effects were calculated by synergy-finder and evaluated by synergy score as follow scale: < -10 (antagonistic); -10 to 10 (additive); > 10 (synergistic).The cell death or cell growth inhibition were recorded by time lapse assay under microscope at 0, 24, 48 hours after treating with SAHA, doxorubicin (DOX) alone and in combination. The inhibitory effect on apoptosis pathway were studied by treating the ISO-HAS-B with two drugs alone and in combination at their respective IC50 concentrations for 48 hours. The detection of Caspase 3 and PARP by Western blotting was used to indicate apoptotic cell death. Results: IC50 of two pan-HDACi were determined by Graphpad PRISM 8.0. LBH589 and SAHA were shown to have anti-tumour effects and the combination of two pan-HDACi with doxorubicin showed synergistic growth inhibition than the single agents alone. A higher level of cell death can be seen in the combination of SAHA and DOX in ISO-HAS-B in a time-dependent manner .Cell shrinkage and pyknosis were visible by light microscopy after 48-hour treatment. Apoptosis was indicated by the increase level of cleaved PARP and Cleaved Caspase3, especially in the combination group from Western blot assays. Conclusions: The combination of SAHA and DOX induced higher level of apoptosis at 48h incubation. It significantly activated the apoptosis pathway by increasing the expression of Cleaved PARP and Cleaved Caspase3, which suggests its effectiveness in inhibition of protein synthesis. In-vivo experiments to validate these findings are currently on-going. Combination of HDACi and doxorubicin remains a promising treatment approach for CAS. Citation Format: Yingjun Zhang, Connie Hui, Chi Hang Wong, Chi Tung Choy, Teresa Tse, Teresa Tan, Sampson Kwan, Qian Tao, Herbert Loong. Synergistic activities of the histone deacetylase inhibitors with conventional cytotoxic chemotherapies in cutaneous angiosarcomas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3646.

Background Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been shown to be prognostic in various cancers. Prior reports of this in sarcomas have predominantly been made through smaller cohorts from single institutions. We investigated the prognostic implications of these indices in patients with soft-tissue (STS) and bone sarcomas using a large population-based database. Methods A population-based retrospective database was assembled to extract pts with sarcoma, as defined as ICD-9-CM codes of bone (170.x) or/and soft tissue (171.x) who have attended clinics or hospitals of the Hong Kong Hospital Authority between Jan 2004 and Mar 2018. Eligible patients (pts) with index presentation of bone sarcoma or/and STS on or after Jan 2005 were analysed to allow 1-year window. The most recent documented lymphocyte, neutrophil, and platelet counts from the index date of sarcoma diagnosis were retrieved, and the neutrophil-lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) were correlated with survival. Abnormal (abn) NLR and abn PLR are defined as NLR≥2.5 and PLR≥182 respectively. Restricted cubic spline plots were used to explore the shape of association between baseline NLR and PLR and all-cause mortality, fitting a restricted cubic spline function with four knots (5th, 35th, 65th, and 95th centiles). Results Of 3746 pts identified, 3358 pts satisfied eligibility: bone n = 661, STS n = 2576, both n = 121. NLR and PLR is available for 89.93% (n = 3020) of eligible pts, amongst which 65.9% (n = 1989) had abn NLR while 47.6% (n = 1438) had abn PLR., Abn NLR and abn PLR are each associated with higher all-cause mortality (abn NLR: HR 1.698, p Conclusions This is the largest assembled population-based sarcoma cohort in Asia. We show that NLR and PLR are robust prognostic factors, and abn NLR and PLR have negative effects on survival. More importantly, the relationship between NLR and PLR and mortality is shown to be non-linear. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Angiosarcomas (AS) are rare and aggressive tumors of endothelial cell origin. About half of patients present with a primary cutaneous lesion, most commonly over the scalp. Intravenous (IV) weekly paclitaxel (Pac) is the current accepted standard-of-care in inoperable or progressive disease. Median PFS is 3.8 months. IV Pac is associated with dose-limited toxicities including peripheral neuropathy, development of infusional reactions and anaphylaxis, in part due to the Cremophor EL formulation vehicle. Pac is a P-glycoprotein (P-gp) substrate. Pac is a substrate for the Pgp pump in the intestinal cells which leads to efflux of Pac back into the intestinal lumen, thereby making the drug nonbioavailable when taken orally. ORAXOL is a combination product of 2 separate drugs; oral Pac and a novel Pglycoprotein (Pgp) inhibitor, HM30181 methanesulfonate monohydrate (HM30181A). This allows for intestinal absorption and systemic exposure of Pac. ORAXOL has been studied in bioavailability and bioequivalence studies confirming its safety profile. A multi-center phase III study comparing ORAXOL and IV Pac in women with metastatic breast cancer is on-going. We are currently recruiting patients on a multi-center pilot study to determine the efficacy of ORAXOL in cutaneous AS. Trial design This is a multi-center, international, open-label, pilot study to evaluate the activity, safety, and tolerability of ORAXOL in subjects with cutaneous AS who have not been treated previously with taxanes. ORAXOL (15mg oral HM30181A & 205mg/m2 oral Pac) will be administered once daily for 3 consecutive days every week from Weeks 1 through 25; HM30181A is administered 1 hour before oral Pac on dosing days. Subjects who do not have disease progression at the end of treatment period are eligible to continue ORAXOL in the treatment extension phase. Primary objective is to determine the response rate (RR) within 6 months of initiation of treatment. Secondary objectives include (i) safety and tolerability, (ii) PFS and (iii) OS, (iv) duration of- and (v) time to-best response. Up to 25 evaluable subjects across 4 study sites will be enrolled in this study. The first patient has started dosing in December 2018. Clinical trial identification NCT03544567. Legal entity responsible for the study Athenex Inc. Funding Athenex Inc. Disclosure M.R. Kwan: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. D. Cutler: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. D. Kramer: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. W. Chan: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Athenex Inc. All other authors have declared no conflicts of interest.

Background The aims of this study were to understand the prevalence of chemotherapy (chemo) use and its associated impact on survival in patients (pts) with either bone- and soft-tissue sarcomas (STS) through a large real-world population dataset. Methods A population-based retrospective database was assembled to extract pts with sarcoma, as defined as ICD-9-CM codes of bone (170.x) or/and soft tissue (171.x) who have attended clinics or hospitals of the Hong Kong Hospital Authority (HA) between Jan 2004 and Mar 2018. Eligible pts with index presentation of bone or/and soft tissue sarcoma (STS) on or after Jan 2005 were analysed to allow 1-year window. Drug dispensing records of chemotherapy drugs (chemo) from the HA as categorized by the British National Formulary 8.x were extracted and correlated with all-cause and cancer specific mortality. Results Of 3746 pts identified, 3358 pts satisfied eligibility: bone: n = 661, STS n = 2576, both n = 121. 32.8% of pts (n = 1100) had chemo prescribed during the study period. The proportional use of chemo decreased with advancing age ( /=80y: 8.1%). Anthracyclines (AN) were the most commonly used class of chemo (19.8%), followed by alkylating drugs (17.3%), antimetabolites (11.9%) and vinca alkaloids & etoposide (8.7%). Comparing with pts who have not received chemo within the study period, the risk for death was higher in pts who have received AN either as first chemo (HR 1.51, 95%CI1.25-1.83; p 3months post diagnosis (log-rank p Conclusions This is one of the largest assembled population-based real-world sarcoma cohort. Chemo use and choice of chemo has implications on survival. The positive effect on survival was especially prominent in pts with bone sarcomas. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background The prognostic impact of comorbidities in patients (pts) with sarcomas is not well defined. The aims of this study were to examine the prevalence of comorbidities and its impact on overall survival in pts with sarcomas. Methods A population-based retrospective database was assembled to extract pts with sarcoma, as defined as ICD-9-CM codes of bone (170.x) or/and soft tissue (171.x) who have attended clinics or hospitals of the Hong Kong Hospital Authority between Jan 2004 and Mar 2018. Eligible pts with index presentation of bone or/and soft tissue sarcoma (STS) on or after Jan 2005 were analysed to allow 1-year window period. Comorbidities were obtained, and Charlson’s Comorbidity Score (CCS) defined by 19 medical conditions according to risk of mortality at the time of sarcoma diagnosis was calculated. CCS score and prevalence of comorbidities at diagnosis were assessed. Rate of all-cause mortality according to level of CCS were computed. The prognostic value of CCS was estimated using Cox proportional hazard models. Results Of 3746 pts identified, 3358 pts satisfied eligibility: bone: n = 661, STS: n = 2576; both: n = 121. Male: Female 52.6%: 47.4%. Proportional age group: /=80y: 11.0% (n = 370). Top 5 common co-morbidities: diabetes mellitus (9.8%); cerebrovascular disease (4.8%), ischaemic heart disease (3.8%), chronic lung disease (2.9%), congestive heart failure (2.6%). Mean age at presentation: 54.2y (bone: 46.8y, STS: 56.5y). Mean CCS: 4.6. Pts with higher CCS had higher mortality (CCS3 vs. CCS2; HR 1.49; 95% CI 1.19-1.87; p /=7 vs. CCS2; HR 3.20; 95% CI: 2.62-3.92; p Conclusions This is the largest population-based sarcoma cohort reported from Asia. Presence of comorbidities have significant negative prognostic impact on pts with sarcomas. Identification and treatment of relevant comorbidities may improve survival of sarcoma pts.

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental paradigms and analysis tools have been limited to constrained laboratory tasks and contexts due to technical limitations imposed by the available set of measuring and analysis techniques and the age of the subjects. These limitations severely limit the study of developmental neural dynamics and associated neural networks engaged in cognition, perception and action in infants performing “in action and in context”. This protocol presents a novel approach to study infants and young children as they freely organize their own behavior, and its consequences in a complex, partly unpredictable and highly dynamic environment. The proposed methodology integrates synchronized high-density active scalp electroencephalography (EEG), inertial measurement units (IMUs), video recording and behavioral analysis to capture brain activity and movement non-invasively in freely-behaving infants. This setup allows for the study of neural network dynamics in the developing brain, in action and context, as these networks are recruited during goal-oriented, exploration and social interaction tasks.

Together with surgery and radiotherapy, systemic treatment with cytotoxic chemotherapy and molecular targeted agents is one of the main therapeutic pillars in the treatment of soft-tissue sarcomas and is the mainstay of treatment in patients with advanced or metastatic disease. Unlike other more common malignancies such as breast and colorectal cancer, the role of chemotherapy when used in the adjuvant setting in soft-tissue sarcomas is less well defined. Results from prior studies have been conflicting, in part due to the heterogeneity and rarity of the disease, and large-scale meta-analysis has been performed to address this issue. Neoadjuvant chemotherapy, defined as the use of chemotherapy before definitive treatment with surgery or radiotherapy, has distinct theoretical and practical advantages, which can potentially be beneficial to the patient. However, the currently available evidence to support its use is even more scarce. In this review article, we describe the current established data behind the use of adjuvant chemotherapy in selected patients with localised soft-tissue sarcomas and, through extrapolation of available data, discuss the potential role of it when used in the upfront setting.

The mirror neuron system (MNS) in humans is thought to enable an individual's understanding of the meaning of actions performed by others and the potential imitation and learning of those actions. In humans, electroencephalographic (EEG) changes in sensorimotor -band at central electrodes, which desynchronizes both during execution and observation of goal-directed actions (i.e.,  suppression), have been considered an analog to MNS function. However, methodological and developmental issues, as well as the nature of generalized  suppression to imagined, observed, and performed actions, have yet to provide a mechanistic relationship between EEG - rhythm and MNS function, and the extent to which EEG can be used to infer intent during MNS tasks remains unknown. In this study we present a novel methodology using active EEG and inertial sensors to record brain activity and behavioral actions from freely-behaving infants during exploration, imitation, attentive rest, pointing, reaching and grasping, and interaction with an actor. We used -band (1-4Hz) EEG as input to a dimensionality reduction algorithm (locality- preserving Fisher's discriminant analysis, LFDA) followed by a neural classifier (Gaussian mixture models, GMMs) to decode the each MNS task performed by freely-behaving 6-24 month old infants during interaction with an adult actor. Here, we present results from a 20-month male infant to illustrate our approach and show the feasibility of EEG-based classification of freely occurring MNS behaviors displayed by an infant. These results, which provide an alternative to the-rhythm theory of MNS function, indicate the informative nature of EEG in relation to intentionality (goal) for MNS tasks which may support action-understanding and thus bear implications for advancing the understanding of MNS function.

Objective To study the mechanism of burn in hospitalized paediatric burn patients in order to develop a focused burn prevention campaign. Methods Acute paediatric burn patients were identified from the unit admission records. Detailed medical records were reviewed to identify the key demographic and management information including the country of residence, age, gender, extent of injury, specific treatment and hospital stay. Parents were then contacted to provide detailed information about the mechanism of the accident, first aid given, living density and parent's educational level. Results Two hundred and eighty-four admissions were identified in a 5-year period. Two hundred and twenty-four of these patients came from a defined regional population served by the hospital. The median age of patients was 3 and male to female ratio 1:0.74. The most common age group for burns was 1–2 years. The most common type of burns were scalds. Domestic burns accounted for 84.7% of admissions. Median burn area was 4% of the total body surface area with a range of 0.2–45%. Fifty percent of patients had no first aid treatment prior to presentation at the hospital. More accidents happened in homes with a high living density and the majority of parents had both completed secondary education. The most dangerous location in the house was the living room, followed by the bathroom, kitchen then bedroom. The majority of burns were related to hot drinks, followed by hot food and then bathing. Conclusion Detailed investigation of burn incidents can reveal repeated mechanisms of injury, which direct the focus of preventive strategies.