Publications by authors named "Anthony Kong"

73 Publications

COVID-19 and Aphasia.

Curr Neurol Neurosci Rep 2021 Oct 21;21(11):61. Epub 2021 Oct 21.

Academic Unit of Human Communication, Development, and Information Sciences (CDIS), The University of Hong Kong, Pokfulam Road, Hong Kong, SAR, Hong Kong.

Purpose Of Review: Aphasia is an acquired neurological language disorder after brain damages. Persons with aphasia (PWA) are more susceptible to behavioral and emotional implications due to inherent communication and/or cognitive difficulties. Currently, little is known regarding the impact of COVID-19 on PWA.

Recent Findings: There are now growing reports with evidence of neurological and dysexecutive syndromes subsequent to interference of brain functions in acute patients with COVID-19, leading to variable aphasia-like symptoms. COVID-19 affected chronic PWA more in terms of disrupted communication and daily routines, worsened psychosocial well-being, and difficulties getting aphasia services that adequately addressed their needs. Acute versus chronic PWA were disproportionately affected by COVID-19. Recognizing, examining, and managing COVID-19-related neurological and behavioral problems in PWA is not straightforward. As we passed the 1-year mark and approaching the 2-year mark of the onset of COVID-19, more research is necessary to prioritize strategies for improving current evidence-based care and rehabilitation of aphasia.
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http://dx.doi.org/10.1007/s11910-021-01150-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529864PMC
October 2021

A phase II study of monalizumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: The I1 cohort of the EORTC-HNCG-1559 UPSTREAM trial.

Eur J Cancer 2021 Oct 9;158:17-26. Epub 2021 Oct 9.

Service d'Oncologie Médicale, Institut Roi Albert II, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, 1200 Brussels, Belgium. Electronic address:

Purpose: Monalizumab is a monoclonal antibody targeting the inhibitory natural killer group 2A (NKG2A) receptor localised on natural killer (NK) and T cells. Its ligand, the human leukocyte antigen E (HLA-E), is overexpressed in squamous cell carcinoma of the head and neck (SCCHN). By targeting the HLA-E-NKG2A pathway, monalizumab may enhance NK and T cell activity.

Experimental Design: The UPSTREAM trial is a biomarker-driven umbrella trial studying targeted therapies and immunotherapies in patients with recurrent/metastatic (R/M) SCCHN progressing after platinum therapy. The immunotherapy 1 (I1) cohort was a phase II, single-arm substudy evaluating monalizumab (10 mg/kg intravenously on day 1 of a 14-day cycle). The primary end-point was the objective response (OR) rate (Response Evaluation Criteria in Solid Tumours 1.1) over the first 16 weeks. A two-stage Simon design was used (H1 15%, H0 3%, α 8%, power 90%) with pre-planned interruption of accrual if no OR was observed after the first 25 patients.

Results: Twenty-six eligible patients were enrolled. Seventeen (65%) patients had received ≥2 previous lines of systemic treatment, and 15 (58%) patients were PD(-L)1 inhibitor pretreated. No OR was observed. Stable disease was observed in 6 patients (23%) with a median duration of 3.8 months (95% confidence interval [CI]: 2.7-NE). The median progression-free survival and overall survival were 1.7 months (95% CI: 1.5-1.8) and 6.7 months (95% CI: 3.0-9.6), respectively. The most frequent treatment-related adverse event was grade I/II fatigue (19%).

Conclusions: Monalizumab monotherapy has limited activity in R/M SCCHN. The I1 cohort did not meet its primary objective. Monalizumab combined with durvalumab is under investigation within UPSTREAM.
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http://dx.doi.org/10.1016/j.ejca.2021.09.003DOI Listing
October 2021

Sentence types and complexity of spontaneous discourse productions by Cantonese-speakers with traumatic brain injury- a preliminary report.

Clin Linguist Phon 2021 Oct 6:1-17. Epub 2021 Oct 6.

Speech Therapy Department, Ruttonjee Hospital, Hong Kong SAR.

Previous investigations on sentence production in English-speaking individuals with traumatic brain injury (TBI) have yielded mixed conclusions based on their findings. While some studies found comparable sentence complexity between speakers with TBI and control speakers, others reported more syntactic and lexical errors, reduced sentence complexity, and erroneous word order transpositions in the sentence production of speakers with TBI. These contradictory findings could possibly be due to the use of language measures that were less sensitive to subtle syntactic impairments among speakers with TBI. In this preliminary report, the language samples obtained from 11 Cantonese-speaking participants with mild-moderate TBI in Guangzhou, with a mean age of 37.6 and mean years of education of 10 years, and nine control speakers with a similar age range and education background were analyzed using in-depth linguistic-oriented frameworks adopted from pervious works in Cantonese. The results indicated that the TBI group produced more errors, different varieties of sentence types, and lower syntactic complexity in their sentence production compared with the control group. The findings suggested that the more refined and linguistic-oriented measures used in the present study were more sensitive in identifying the subtle syntactic impairments produced by the participants with TBI.
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http://dx.doi.org/10.1080/02699206.2021.1984582DOI Listing
October 2021

Centralised RECIST Assessment and Clinical Outcomes with Lenvatinib Monotherapy in Recurrent and Metastatic Adenoid Cystic Carcinoma.

Cancers (Basel) 2021 Aug 27;13(17). Epub 2021 Aug 27.

Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK.

Adenoid cystic carcinoma (ACC) is a rare cancer of secretory glands. Recurrent or metastatic (R/M) ACC is generally considered resistant to cytotoxic chemotherapy. Recent phase II studies have reported improved objective response rates (ORR) with the use of the multi-kinase inhibitor lenvatinib. We sought to evaluate real-world experience of R/M ACC patients treated with lenvatinib monotherapy within the UK National Health Service (NHS) to determine the response rates by Response Evaluation Criteria of Solid Tumour (RECIST) and clinical outcomes. Twenty-three R/M ACC patients from eleven cancer centres were included. All treatment assessments for clinical decision making related to drug therapy were undertaken at the local oncology centre. Central radiology review was performed by an independent clinical trial radiologist and blinded to the clinical decision making. In contrast to previously reported ORR of 12-15%, complete or partial response was not observed in any patients. Eleven patients (52.4%) had stable disease and 5 patients (23.8%) had progression of disease as the best overall response. The median time on treatment was 4 months and the median survival from discontinuation was 1 month. The median PFS and OS from treatment initiation were 4.5 months and 12 months respectively. Multicentre collaborative studies such as this are required to evaluate rare cancers with no recommended standard of care therapy and variable disease courses.
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http://dx.doi.org/10.3390/cancers13174336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431195PMC
August 2021

Clinical outcomes in relapsed oropharyngeal cancer after definitive (chemo) radiotherapy.

Oral Dis 2021 Aug 2. Epub 2021 Aug 2.

Department of Clinical Oncology, Guy's and St Thomas' NHS Trust, London, UK.

Objectives: To report clinical outcomes of relapsed oropharyngeal squamous cell carcinoma (OPSCC) after definitive intensity-modulated (chemo)radiotherapy [(C)RT].

Materials And Methods: Data for all relapsed patients treated for OPSCC with definitive (C)RT between 2010 and 2016 were collected. Primary end-point was post-failure survival (PFS).

Results: Overall, 273 OPSCC patients completed definitive (C)RT. Of these, 42 cases (n = 26 human papilloma virus (HPV)-negative; n = 16 HPV-positive) had relapsed (n = 23 persistent disease; n = 19 recurrent disease) and were included in the final analysis. Two-year PFS for the entire population was 30.6%; 20.5% for HPV-negative and 43.8% for HPV-positive patients. Salvage curative surgery was associated with a significantly higher 2 years PFS rate (56.2%) compared with palliative treatment (22.9%) and best supportive care (0%) (p < 0.001). A positive trend in 2 years PFS was recorded in the early complete response cases (49.5%) versus patients who did not achieve a complete response within 3 months of the end of (C)RT (23.0%) (p = 0.11).

Conclusion: A higher PFS rate is achieved when relapsed OPSCC cases are treated with salvage curative intent. HPV-positive disease and early complete response within 3 months from the end of (C)RT may be related to better PFS.
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http://dx.doi.org/10.1111/odi.13985DOI Listing
August 2021

Comprehensive Genomic and Transcriptomic Analysis of Three Synchronous Primary Tumours and a Recurrence from a Head and Neck Cancer Patient.

Int J Mol Sci 2021 Jul 15;22(14). Epub 2021 Jul 15.

TRON-Translational Oncology, University Medical Center, Johannes Gutenberg University Mainz, Freiligrathstraße 12, 55131 Mainz, Germany.

Synchronous primary malignancies occur in a small proportion of head and neck squamous cell carcinoma (HNSCC) patients. Here, we analysed three synchronous primaries and a recurrence from one patient by comparing the genomic and transcriptomic profiles among the tumour samples and determining the recurrence origin. We found remarkable levels of heterogeneity among the primary tumours, and through the patterns of shared mutations, we traced the origin of the recurrence. Interestingly, the patient carried germline variants that might have predisposed him to carcinogenesis, together with a history of alcohol and tobacco consumption. The mutational signature analysis confirmed the impact of alcohol exposure, with Signature 16 present in all tumour samples. Characterisation of immune cell infiltration highlighted an immunosuppressive environment in all samples, which exceeded the potential activity of T cells. Studies such as the one described here have important clinical value and contribute to personalised treatment decisions for patients with synchronous primaries and matched recurrences.
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http://dx.doi.org/10.3390/ijms22147583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305204PMC
July 2021

WEE1 Inhibitor: Clinical Development.

Curr Oncol Rep 2021 Jul 16;23(9):107. Epub 2021 Jul 16.

Institute of Head and Neck Studies (InHANSE), University of Birmingham, Birmingham, UK.

Purpose Of Review: WEE1 inhibitor has been shown to potential chemotherapy or radiotherapy sensitivity in preclinical models, particularly in p53-mutated or deficient cancer cells although not exclusively. Here, we review the clinical development of WEE1 inhibitor in combination with chemotherapy or radiotherapy with concurrent chemotherapy as well as its combination with different novel agents.

Recent Findings: Although several clinical trials have shown that WEE1 inhibitor can be safely combined with different chemotherapy agents as well as radiotherapy with concurrent chemotherapy, its clinical development has been hampered by the higher rate of grade 3 toxicities when added to standard treatments. A few clinical trials had also been conducted to test WEE1 inhibitor using TP53 mutation as a predictive biomarker. However, TP53 mutation has not been shown to be the most reliable predictive biomarker and the benefit of adding WEE1 inhibitor to chemotherapy has been modest, even in TP53 biomarker-driven studies. There are ongoing clinical trials testing WEE1 inhibitor with novel agents such as ATR and PAPR inhibitors as well as anti-PDL1 immunotherapy, which may better define the role of WEE1 inhibitor in the future if any of the novel treatment combination will show superior anti-tumor efficacy with a good safety profile compared to monotherapy and/or standard treatment.
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http://dx.doi.org/10.1007/s11912-021-01098-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285350PMC
July 2021

The Dutch Main Concept Analysis: Translation and Establishment of Normative Data.

Am J Speech Lang Pathol 2021 07 8;30(4):1750-1766. Epub 2021 Jun 8.

Department of Rehabilitation Sciences, Ghent University, Belgium.

Purpose The main concept analysis (MCA; Kong, 2009) quantifies the effectiveness and efficiency of information transfer during verbal discourse by means of four sets of sequential pictorial stimuli. This test was originally developed for a Cantonese-speaking population. The main goals of this study were (a) to translate and adapt the MCA to Dutch; (b) to establish normative data for healthy native Dutch-speaking adults; (c) to assess the effect of age, education level, and gender on MCA outcome; and (d) to establish inter- and intrarater reliability of the Dutch MCA. Method Language samples were collected from 60 healthy native Dutch speakers, equally recruited in different age (20-39 years, 40-59 years, 60-79 years) and education (middle and highly educated) categories through administration of the MCA. Utterances produced by at least 75% of the participants were included as a main concept in the Dutch MCA. Subsequently, age-specific normative data were established for each of the MCA parameters. Finally, an ICC was calculated in order to verify inter- and intrarater reliability of the Dutch MCA. Results The translated MCA consisted of 19 main concepts. Age-specific normative data were obtained. Both age and education level had a significant effect on MCA outcome. Information transfer in elderly was both less effectively and efficiently compared to young- and middle-aged adults. In addition, highly educated participants transferred information less efficiently compared to middle educated participants. Based on inter- and intrarater reliability measures, the Dutch MCA proved to be a reliable measuring instrument. Conclusions The MCA was translated to Dutch, and age-specific normative data were established for a healthy, Dutch-speaking population. The Dutch MCA is a reliable tool for eliciting and quantifying discourse production. Validation of the test for people with aphasia is necessary in order for the test to be useful in a clinical practice.
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http://dx.doi.org/10.1044/2021_AJSLP-20-00285DOI Listing
July 2021

Adaptation and validation of the main concept analysis of spoken discourse by native Japanese adults.

Clin Linguist Phon 2021 May 14:1-17. Epub 2021 May 14.

Department of Oto-Rhino-Laryngology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

Many people with aphasia demonstrate problems of oral production at the discourse level. The Main Concept Analysis (MCA) for oral discourse production is a published evidence-based battery for quantifying the degree of presence, accuracy, completeness, and efficiency of targeted main concepts in oral discourse. In Japan, such a standardized tool specialized for assessing spoken discourse is currently lacking. The purpose of this study was to adapt the Japanese version of MCA for oral discourse production (the Japanese-MCA) and examine its validity and reliability. Stage 1 of the study involved the establishment of linguistically-specific main concepts (MCs) of the Japanese-MCA. Ten speech-language-hearing therapists and 60 healthy participants who were native monolingual Japanese speakers were recruited to determine MCs. Stage 2 examined the criterion validity and reliability of the Japanese-MCA. Language samples of 20 participants with aphasia, as verified by Standard Language Test of Aphasia (SLTA), and 20 healthy older participants were used. Results of Stage 1 of the study yielded normative data with a set of target MCs that were geographically and linguistically specific for use in Japan. The results also revealed the comparability of the Japanese-MCA and previously reported versions of other languages. Stage 2 findings indicated not only a high correlation of criterion validity, but also good reliability of the test. With established norms and specific scoring criteria of the Japanese-MCA, it is believed that this new tool will become a useful addition to clinical management and research of aphasia in Japan.
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http://dx.doi.org/10.1080/02699206.2021.1915385DOI Listing
May 2021

TNM 8 staging is a better prognosticator than TNM 7 for patients with locally advanced oral cavity squamous cell carcinoma treated with surgery and post-operative radiotherapy.

Radiother Oncol 2021 07 3;160:54-60. Epub 2021 May 3.

Department of Clinical Oncology, Guy's and St Thomas, NHS Trust London, UK; King's College London, UK.

Purpose: To assess TNM 8 staging in discriminating overall survival (OS) amongst patients with locally advanced oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative radiotherapy (PORT), compared to TNM 7.

Material And Methods: Data from OCSCC patients treated with surgery and PORT between January 2010 and December 2018 were reviewed. Demographics, tumour characteristics and treatment response data were collected, and patients staged according to both TNM 7 and TNM 8. OS and disease free survival (DFS) were estimated using the Kaplan Meier method. Univariate and multivariable analyses were conducted for factors affecting OS, DFS and early disease recurrence within 12 months.

Results: Overall 172 patients were analyzed. Median follow up was 32 months for all patients and 48 months for surviving patients. TNM 8 staging demonstrated significant stratification of OS and DFS amongst the entire cohort, whereas TNM 7 staging did not. On multivariable analysis, TNM 8 stage, performance status (PS) and a positive surgical margin were prognostic for OS. Looking at disease recurrence within 12 months, TNM 8 stage IVB, presence of lymphovascular invasion (LVSI), younger age and lesser smoking history were predictive factors on multivariable analysis.

Conclusion: TNM 8 is a good development of its predecessor in terms of predicting survival for patients with locally advanced OCSCC. We have also identified younger age (<60 years) and a smoking history of <10 pack years as risk factors for early disease recurrence, potentially representing a separate biological cohort within OCSCC patients.
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http://dx.doi.org/10.1016/j.radonc.2021.04.003DOI Listing
July 2021

Safety and Treatment Outcomes of Nivolumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Retrospective Multicenter Cohort Study.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Guys Cancer Centre, Guy's and St. Thomas NHS Foundation Trust, London SE1 9RT, UK.

Nivolumab is an anti-PD-1 monoclonal antibody currently used as immunotherapy for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with evidence of disease progression after platinum-based chemotherapy. This study evaluates real-world safety and treatment outcomes of non-trial nivolumab use. A retrospective multicenter cohort study of patients with recurrent/metastatic HNSCC treated with nivolumab between January 2017 and March 2020 was performed. Overall, 123 patients were included. The median age was 64 years, the majority of patients were male (80.5%) and had a smoking history (69.9%). Primary outcomes included overall response rate (ORR) of 19.3%, median progression-free survival (PFS) of 3.9 months, 1-year PFS rate of 16.8%, a median overall survival (OS) of 6.5 months and 1-year OS rate of 28.6%. These results are comparable to the CHECKMATE-141 study. Of 27 patients who had PD-L1 status tested, positive PD-L1 status did not significantly affect PFS ( = 0.86) or OS ( = 0.84). Nivolumab was well tolerated with only 15.1% experiencing immune-related toxicities (IRT) and only 6.7% of patients stopping due to toxicity. The occurrence of IRT appeared to significantly affect PFS ( = 0.01) but not OS ( = 0.07). Nivolumab in recurrent/metastatic HNSCC is well tolerated and may be more efficacious in patients who develop IRT.
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http://dx.doi.org/10.3390/cancers13061413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003537PMC
March 2021

The Impact of COVID-19 on Speakers With Aphasia: What Is Currently Known and Missing?

J Speech Lang Hear Res 2021 01 11;64(1):176-180. Epub 2020 Dec 11.

School of Communication Sciences and Disorders, University of Central Florida, Orlando.

Purpose Enhancing social participation and reducing emotional distress in persons with aphasia (PWA) are a critical rehabilitation goal. Social relationships and meaningful activities performed by PWA are also crucial to promote positive psychosocial well-being. As a precautionary measure specific to the COVID-19 pandemic, most PWA worldwide have generally followed the guidelines of going out less, restricting when and where to gather with friends and peers, reducing social activities, and maintaining appropriate social distance; these acts are contrary to the traditional principles of managing aphasia. This article aims to (a) highlight and add to our understanding of issues related to the impact of the currently evolving COVID-19 pandemic on PWA, (b) direct readers to relevant reports in the literature of telerehabilitation for aphasia to look for useful information regarding remote assessment and therapy to be considered during the pandemic, (c) summarize support initiatives developed and resources compiled thus far as well as provide links for caregivers and PWA to find more information about COVID-19 in their communities, and (d) offer recommendations to potentially move the field of aphasia research and clinical PWA services forward in a positive way to endure the pandemic and in the forthcoming post-COVID world. Conclusions At present, there are significant knowledge gaps regarding the short and long-term impacts of COVID-19 on PWA and their caregivers. It is crucial that different stakeholders be sensitive and flexible when addressing the psychosocial and rehabilitation needs of PWA to mitigate the negative effects during and after the COVID-19 era.
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http://dx.doi.org/10.1044/2020_JSLHR-20-00371DOI Listing
January 2021

The Effect of Metalinguistic Sentence Combining on Eighth-Grade Students' Understanding and Written Expression of Comparison and Contrast in Science.

J Speech Lang Hear Res 2020 09 5;63(9):3068-3083. Epub 2020 Aug 5.

School of Communication Sciences and Disorders, University of Central Florida, Orlando.

Purpose The purpose of this study was to examine whether sentence combining with an explicit metalinguistic approach in comparison to typical science instruction was effective in improving written expression and understanding of comparison/contrast in science for eighth-grade students who struggle with literacy. Method Eighty-four eighth-grade students who struggle with literacy participated in this study. The experimental group ( = 36) received the writing intervention of metalinguistic sentence combining (MSC) during their science class for a total of 400 min (20 intervention sessions, 20 min each), while the comparison group ( = 48) participated in their typical science instruction. Total science instruction time was held constant for both groups. All students completed pretests and posttests to determine an increase in (a) syntactic factors of academic science text such as longer sentence length and use of syntactic forms of connectives, targeted connectives, left embeddedness, and agentless passive voice when responding to a science compare and contrast writing prompt; and (b) listing similarities and differences between two science concepts on a graphic organizer. Results Treatment was effective in improving the experimental group's score in listing similarities and differences between two science concepts on a graphic organizer. There were no significant differences between the two groups in their use of syntactic factors typical of academic text when responding to a science compare and contrast writing prompt. Conclusions MSC was effective in improving the experimental student's ability to demonstrate understanding of comparison and contrast in science. Modifications to the MSC intervention may yield better results in the experimental group's posttreatment writing in future studies. Supplemental Material https://doi.org/10.23641/asha.12735950.
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http://dx.doi.org/10.1044/2020_JSLHR-19-00086DOI Listing
September 2020

Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study.

Clin Cancer Res 2020 10 15;26(19):5153-5161. Epub 2020 Jul 15.

Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Purpose: The prognosis for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is poor, and only a minority of patients benefit from checkpoint immunotherapy. Talimogene laherparepvec (T-VEC), an oncolytic immunotherapy approved for advanced melanoma, in combination with pembrolizumab may yield enhanced antitumor activity over either agent alone.

Patients And Methods: This was a phase Ib/III, multicenter trial testing intratumoral T-VEC combined with intravenous pembrolizumab in R/M HNSCC refractory to platinum-based chemotherapy. For phase Ib, primary endpoint was incidence of dose-limiting toxicity (DLT). Key secondary endpoints included objective response rate and progression-free survival per irRECIST, overall survival, and safety.

Results: Thirty-six patients were enrolled into the phase Ib study. The data cut-off date was August 28, 2018. Median follow-up was 5.8 months (range, 0.3-24.2). One DLT of T-VEC-related fatal arterial hemorrhage was reported. Twenty (55.6%) and 21 (58.3%) patients experienced adverse events (AE) related to T-VEC and pembrolizumab, respectively. Besides the DLT, there were no treatment-related fatal AEs. A confirmed partial response was observed in 5 (13.9%) patients. Ten (27.8%) patients were unevaluable for response due to early death. Median PFS and OS were 3.0 months [95% confidence interval (Cl), 2.0-5.8] and 5.8 months (95% Cl, 2.9-11.4), respectively.

Conclusions: The combination of T-VEC and pembrolizumab demonstrated a tolerable safety profile in R/M HNSCC. The efficacy with the combination was similar to that with pembrolizumab monotherapy in historical HNSCC studies. Phase III part of this study was not further pursued (ClinicalTrials.gov Identifier: NCT02626000).
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1170DOI Listing
October 2020

Automatic Assessment of Speech Impairment in Cantonese-speaking People with Aphasia.

IEEE J Sel Top Signal Process 2020 Feb 28;14(2):331-345. Epub 2019 Nov 28.

School of Communication Sciences and Disorders, University of Central Florida, Orlando, FL, USA.

Aphasia is a common type of acquired language impairment resulting from dysfunction in specific brain regions. Analysis of narrative spontaneous speech, e.g., story-telling, is an essential component of standardized clinical assessment on people with aphasia (PWA). Subjective assessment by trained speech-language pathologists (SLP) have many limitations in efficiency, effectiveness and practicality. This paper describes a fully automated system for speech assessment of Cantonese-speaking PWA. A deep neural network (DNN) based automatic speech recognition (ASR) system is developed for aphasic speech by multi-task training with both in-domain and out-of-domain speech data. Story-level embedding and Siamese network are applied to derive robust text features, which can be used to quantify the difference between aphasic speech and unimpaired one. The proposed text features are combined with conventional acoustic features to cover different aspects of speech and language impairment in PWA. Experimental results show a high correlation between predicted scores and subject assessment scores. The best correlation value achieved with ASR-generated transcription is .827, as compared with .844 achieved with manual transcription. The Siamese network significantly outperforms story-level embedding in generating text features for automatic assessment.
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http://dx.doi.org/10.1109/JSTSP.2019.2956371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271834PMC
February 2020

Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: the trial protocol.

BMJ Open 2020 03 16;10(3):e033009. Epub 2020 Mar 16.

Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK

Introduction: Patients with head and neck squamous cell carcinoma with locally advanced disease often require multimodality treatment with surgery, radiotherapy and/or chemotherapy. Adjuvant radiotherapy with concurrent chemotherapy is offered to patients with high-risk pathological features postsurgery. While cure rates are improved, overall survival remains suboptimal and treatment has a significant negative impact on quality of life.Cell cycle checkpoint kinase inhibition is a promising method to selectively potentiate the therapeutic effects of chemoradiation. Our hypothesis is that combining chemoradiation with a WEE1 inhibitor will affect the biological response to DNA damage caused by cisplatin and radiation, thereby enhancing clinical outcomes, without increased toxicity. This trial explores the associated effect of WEE1 kinase inhibitor adavosertib (AZD1775).

Methods And Analysis: This phase I dose-finding, open-label, multicentre trial aims to determine the highest safe dose of AZD1775 in combination with cisplatin chemotherapy preoperatively (group A) as a window of opportunity trial, and in combination with postoperative cisplatin-based chemoradiation (group B).Modified time-to-event continual reassessment method will determine the recommended dose, recruiting up to 21 patients per group. Primary outcomes are recommended doses with predefined target dose-limiting toxicity probabilities of 25% monitored up to 42 days (group A), and 30% monitored up to 12 weeks (group B). Secondary outcomes are disease-free survival times (groups A and B). Exploratory objectives are evaluation of pharmacodynamic (PD) effects, identification and correlation of potential biomarkers with PD markers of DNA damage, determine rate of resection status and surgical complications for group A; and quality of life in group B.

Ethics And Dissemination: Research Ethics Committee, Edgbaston, West Midlands (REC reference 16/WM/0501) initial approval received on 18/01/2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences.

Trial Registration Number: ISRCTN76291951 and NCT03028766.
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http://dx.doi.org/10.1136/bmjopen-2019-033009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076237PMC
March 2020

Concurrent cisplatin or cetuximab with radiotherapy for HPV-positive oropharyngeal cancer: Medical resource use, costs, and quality-adjusted survival from the De-ESCALaTE HPV trial.

Eur J Cancer 2020 01 30;124:178-185. Epub 2019 Nov 30.

Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK. Electronic address:

Background: The De-ESCALaTE HPV trial confirmed the dominance of cisplatin over cetuximab for tumour control in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Here, we present the analysis of health-related quality of life (HRQoL), resource use, and health care costs in the trial, as well as complete 2-year survival and recurrence.

Materials And Methods: Resource use and HRQoL data were collected at intervals from the baseline to 24 months post treatment (PT). Health care costs were estimated using UK-based unit costs. Missing data were imputed. Differences in mean EQ-5D-5L utility index and adjusted cumulative quality-adjusted life years (QALYs) were compared using the Wilcoxon signed-rank test and linear regression, respectively. Mean resource usage and costs were compared through two-sample t-tests.

Results: 334 patients were randomised to cisplatin (n = 166) or cetuximab (n = 168). Two-year overall survival (97·5% vs 90·0%, HR: 3.268 [95% CI 1·451 to 7·359], p = 0·0251) and recurrence rates (6·4% vs 16·0%, HR: 2·67 [1·38 to 5·15]; p = 0·0024) favoured cisplatin. No significant differences in EQ-5D-5L utility scores were detected at any time point. At 24 months PT, mean difference was 0·107 QALYs in favour of cisplatin (95% CI: 0·186 to 0·029, p = 0·007) driven by the mortality difference. Health care costs were similar across all categories except the procurement cost and delivery of the systemic agent, with cetuximab significantly more expensive than cisplatin (£7779 [P < 0.001]). Consequently, total costs at 24 months PT averaged £13517 (SE: £345) per patient for cisplatin and £21064 (SE: £400) for cetuximab (mean difference £7547 [95% CI: £6512 to £8582]).

Conclusions: Cisplatin chemoradiotherapy provided more QALYs and was less costly than cetuximab bioradiotherapy, remaining standard of care for nonsurgical treatment of HPV-positive OPSCC.
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http://dx.doi.org/10.1016/j.ejca.2019.10.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947474PMC
January 2020

Analysing coherence of oral discourse among Cantonese speakers in Mainland China with traumatic brain injury and cerebrovascular accident.

Int J Speech Lang Pathol 2020 02 21;22(1):37-47. Epub 2019 Mar 21.

Department of Chinese and Bilingual Studies, The Hong Kong Polytechnic University, Hong Kong, Hong Kong.

: Coherence can reflect subtle language deficits in individuals with traumatic brain injury (TBI) and cerebrovascular accident (CVA). This study aimed at investigating whether global and local coherence in Cantonese-speaking adults with CVA and TBI differ from non-brain-injured (NBI) speakers. Factors contributing to the coherence ratings and impacts of elicitation tasks on coherence were examined.: Two clinical groups with fluent aphasia (7 CVA and 11 TBI) and 18 controls matched in age and education, who were Cantonese speakers living in China participated. Language samples of single and sequential picture description and storytelling were elicited, and subsequently analysed on global and local coherence, content sequence, and informativeness.: TBI speakers had impaired global and local coherence, while CVA speakers had poor global coherence. Sequence of main events produced by the three groups correlated significantly with global coherence. Attention and visuospatial skills were also significantly related to global coherence in both clinical groups. Finally, impaired language integrity was associated with problems of local coherence. The results were consistent with previous studies. Linguistic deficits of coherence in discourse in the two clinical groups and possible impacts of elicitation tasks on the cognitive demands and coherence ratings were discussed.
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http://dx.doi.org/10.1080/17549507.2019.1581256DOI Listing
February 2020

Use of co-verbal gestures during word-finding difficulty among Cantonese speakers with fluent aphasia and unimpaired controls.

Aphasiology 2019 16;33(2):216-233. Epub 2018 Apr 16.

Division of Speech and Hearing Sciences, University of Hong Kong, Hong Kong.

Background: Co-verbal gestures refer to hand or arm movements made during speaking. Spoken language and gestures have been shown to be tightly integrated in human communication.

Aims: The present study investigated whether co-verbal gesture use was associated with lexical retrieval in connected speech in unimpaired speakers and persons with aphasia (PWA).

Methods & Procedures: Narrative samples of 58 fluent PWA and 58 control speakers were extracted from Cantonese AphasiaBank. Based on the indicators of word-finding difficulty (WFD) in connected speech adapted from previous research, and a gesture annotation system with independent coding of gesture forms and functions, all WFD instances were identified. The presence and type of gestures accompanying each incident of WFD were then annotated. Finally, whether the use of gesture was accompanied by resolution of WFD, i.e., the corresponding target word could be retrieved, was examined.

Outcomes & Results: Employment of co-verbal gesture did not seem to be related to the success of word retrieval. PWA's naming ability at single-word level and their overall language ability (as reflected by the aphasia quotient of the Cantonese version of the Western Aphasia Battery) were found to be the two strongest predictors of success rate of resolving WFD.

Conclusions: The Lexical Retrieval Hypothesis highlighting the facilitative functions of iconic and metaphoric gestures in lexical retrieval was not supported. Challenges in conducting research related to WFD, and the clinical implications in gesture-based language intervention for PWA were discussed.
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http://dx.doi.org/10.1080/02687038.2018.1463085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402778PMC
April 2018

Overcoming acquired resistance to HSP90 inhibition by targeting JAK-STAT signalling in triple-negative breast cancer.

BMC Cancer 2019 Jan 24;19(1):102. Epub 2019 Jan 24.

Department of Oncology, University of Oxford, Oxford, UK.

Background: Due to the lack of effective therapies and poor prognosis in TNBC (triple-negative breast cancer) patients, there is a strong need to develop effective novel targeted therapies for this subtype of breast cancer. Inhibition of heat shock protein 90 (HSP90), a conserved molecular chaperone that is involved in the regulation of oncogenic client proteins, has shown to be a promising therapeutic approach for TNBC. However, both intrinsic and acquired resistance to HSP90 inhibitors (HSP90i) limits their effectiveness in cancer patients.

Methods: We developed models of acquired resistance to HSP90i by prolonged exposure of TNBC cells to HSP90i (ganetespib) in vitro. Whole transcriptome profiling and a 328-compound bioactive small molecule screen were performed on these cells to identify the molecular basis of acquired resistance to HSP90i and potential therapeutic approaches to overcome resistance.

Results: Among a panel of seven TNBC cell lines, the most sensitive cell line (Hs578T) to HSP90i was selected as an in vitro model to investigate acquired resistance to HSP90i. Two independent HSP90i-resistant clones were successfully isolated which both showed absence of client proteins degradation, apoptosis induction and G2/M cell cycle arrest after treatment with HSP90i. Gene expression profiling and pathway enrichment analysis demonstrate significant activation of the survival JAK-STAT signalling pathway in both HSP90i-resistant clones, possibly through IL6 autocrine signalling. A bioactive small molecule screen also demonstrated that the HSP90i-resistant clones showed selective sensitivity to JAK2 inhibition. Inhibition of JAK and HSP90 caused higher induction of apoptosis, despite prior acquired resistance to HSP90i.

Conclusions: Acquired resistance to HSP90i in TNBC cells is associated with an upregulated JAK-STAT signalling pathway. A combined inhibition of the JAK-STAT signalling pathway and HSP90 could overcome this resistance. The benefits of the combined therapy could be explored further for the development of effective targeted therapy in TNBC patients.
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http://dx.doi.org/10.1186/s12885-019-5295-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345040PMC
January 2019

Evidence for the approach to the diagnostic evaluation of squamous cell carcinoma occult primary tumors of the head and neck.

Oral Oncol 2019 01 30;88:145-152. Epub 2018 Nov 30.

Institute of Head and Neck Studies and Education (InHANSE), Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom. Electronic address:

Metastases to the cervical lymph nodes from a occult primary (CUP) of head and neck squamous carcinomas has been increasing in presentation (HNSCC). Modern diagnostic workup, including clinical evaluation, conventional imaging, FDG-PET/CT and panendoscopy/tonsillectomy enables detection of the primary site in over half of all cases, and is associated with significantly improved survival rates. Recent studies have demonstrated the utility of novel molecular pathology and transoral surgical techniques in improving diagnosis and treatment. We present a new, evidence-based protocol incorporating these novel diagnostic modalities. It aims to identify the site of the primary tumor, and determine the stage of the disease, including extranodal extension. This information can personalise treatment recommendations, rationalise combinations of treatment modalities, and thereby potentially minimise toxicity and improving functional outcomes.
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http://dx.doi.org/10.1016/j.oraloncology.2018.11.020DOI Listing
January 2019

An Integrative Analysis of Spontaneous Storytelling Discourse in Aphasia: Relationship With Listeners' Rating and Prediction of Severity and Fluency Status of Aphasia.

Am J Speech Lang Pathol 2018 11;27(4):1491-1505

Department of Special Education and Counselling, The Education University of Hong Kong.

Purpose: This study investigated which of the three analytic approaches of oral discourse, including linguistically based measures, proposition-based measures, and story grammar, best correlated with aphasia severity and with naïve listeners' ratings on aphasic productions. The predictive power of these analytic approaches to aphasia severity and fluency status of people with aphasia (PWA) was examined. Finally, which approach best discriminated fluent versus nonfluent PWA was determined.

Method: Audio files and orthographic transcriptions of the storytelling task "The Boy Who Cried Wolf" from 68 PWA and 68 controls were extracted from the Cantonese AphasiaBank. Each transcript was analyzed using these 3 systems.

Results: The linguistic approach of discourse analysis best correlated with aphasia severity and naïve listeners' subjective ratings. Although both linguistically based and proposition-based measures significantly predicted aphasia severity, a subset of linguistic measures focusing on the quantity and efficiency of production were particularly useful for clinical estimation of the fluency status of aphasia.

Conclusions: The linguistically based measures appeared to be the most clinically effective and powerful in reflecting PWA's performance of spoken discourse.
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http://dx.doi.org/10.1044/2018_AJSLP-18-0015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436460PMC
November 2018

Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial.

Lancet 2019 01 15;393(10166):51-60. Epub 2018 Nov 15.

University of Oxford, Oxford, UK.

Background: The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy.

Methods: We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m loading dose followed by seven weekly infusions of 250 mg/m). The primary outcome was overall severe (grade 3-5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080.

Findings: Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3-5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2-5·4] with cisplatin vs 4·8 [4·2-5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3-31·0] with cisplatin vs 30·1 [28·3-31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7-14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6-7·2]; p=0·0007).

Interpretation: Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin.

Funding: Cancer Research UK.
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http://dx.doi.org/10.1016/S0140-6736(18)32752-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319250PMC
January 2019

The Expanding Role of Radiosurgery for Brain Metastases.

Medicines (Basel) 2018 Aug 14;5(3). Epub 2018 Aug 14.

Hall-Edwards Radiotherapy Research Group, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham B15 2TH, UK.

Stereotactic radiosurgery (SRS) has become increasingly important in the management of brain metastases due to improving systemic disease control and rising incidence. Initial trials demonstrated SRS with whole-brain radiotherapy (WBRT) improved local control rates compared with WBRT alone. Concerns with WBRT associated neurocognitive toxicity have contributed to a greater use of SRS alone, including for patients with multiple metastases and following surgical resection. Molecular information, targeted agents, and immunotherapy have also altered the landscape for the management of brain metastases. This review summarises current and emerging data on the role of SRS in the management of brain metastases.
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http://dx.doi.org/10.3390/medicines5030090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165316PMC
August 2018

The clinical impact of using complex molecular profiling strategies in routine oncology practice.

Oncotarget 2018 Apr 17;9(29):20282-20293. Epub 2018 Apr 17.

Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests. The resulting information was interpreted and personalized treatments for each patient were suggested. Our data showed that NGS alone provided the oncologist with useful information in 10-50% of cases (depending on cancer type), whereas the addition of IHC/other tests increased extensively the usefulness of the information provided. Using internet surveys, we investigated how therapy recommendations influenced treatment choice of the oncologist. For patients who were still alive after the provision of the molecular information (76.8%), 60.4% of their oncologists followed report recommendations. Most treatment decisions (93.4%) were made based on the combination of NGS and IHC/other tests, and an approved drug- rather than clinical trial enrolment- was the main treatment choice. Most common reasons given by physicians to explain the non-adherence to recommendations were drug availability and cost, which remain barriers to personalised precision medicine. Finally, we observed that 27% of patients treated with the suggested therapies had an overall survival > 12 months. Our study demonstrates that the combination of NGS and IHC/other tests provides the most useful information in aiding treatment decisions by oncologists in routine clinical practice.
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http://dx.doi.org/10.18632/oncotarget.24757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945513PMC
April 2018

Cantonese AphasiaBank: An annotated database of spoken discourse and co-verbal gestures by healthy and language-impaired native Cantonese speakers.

Behav Res Methods 2019 06;51(3):1131-1144

Division of Speech and Hearing Sciences, University of Hong Kong, Pok Fu Lam, Hong Kong SAR.

This article reports the construction of a multimodal annotated database of spoken discourse and co-verbal gestures by native healthy speakers of Cantonese and individuals with language impairment: the Cantonese AphasiaBank. This corpus was established as a foundation for aphasiologists and clinicians to use in designing and conducting research investigations into theoretical and clinical issues related to acquired language disorders in Chinese. Details in terms of the purpose, structure, and levels of annotation of the database (containing part-of-speech-annotated orthographic transcripts with Romanization and the corresponding videos) are described. The discussion presents the challenges of building a spoken database of a language that is not linguistically well-researched and that does not have a standardized written form for many of its lexical items, as well as presenting how these issues were addressed. Most importantly, the article highlights the potential of Cantonese AphasiaBank as a powerful research tool for linguists and psycholinguists.
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http://dx.doi.org/10.3758/s13428-018-1043-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200664PMC
June 2019

Circulating tumor DNA as a biomarker and liquid biopsy in head and neck squamous cell carcinoma.

Head Neck 2018 07 15;40(7):1598-1604. Epub 2018 Mar 15.

Institute of Head and Neck Studies and Education, Department of Head and Neck Surgery, University of Birmingham, Birmingham, United Kingdom.

The use of circulating biochemical molecular markers in head and neck cancer holds the promise of improved diagnostics, treatment planning, and posttreatment surveillance. In this review, we provide an introduction for the head and neck surgeon of the basic science, current evidence, and future applications of circulating tumor DNA (ctDNA) as a biomarker and liquid biopsy to detect tumor genetic heterogeneity in patients with head and neck squamous cell carcinoma (HNSCC).
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http://dx.doi.org/10.1002/hed.25140DOI Listing
July 2018

Research and clinical services in Chinese aphasia: A recent update.

Aphasiology 2018 14;32(1 Suppl):115-116. Epub 2018 Aug 14.

Department of Communication Sciences and Disorders St Johns University.

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http://dx.doi.org/10.1080/02687038.2018.1486372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749830PMC
August 2018

The use of free non-dementia-specific Apps on iPad to conduct group communication exercises for individuals with Alzheimer's disease (Innovative Practice).

Dementia (London) 2020 May 1;19(4):1252-1264. Epub 2017 Sep 1.

Department of Communication Sciences and Disorders, University of Central Florida, Orlando, FL, USA.

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http://dx.doi.org/10.1177/1471301217727630DOI Listing
May 2020

An analysis of topics and vocabulary in Chinese oral narratives by normal speakers and speakers with fluent aphasia.

Clin Linguist Phon 2018 13;32(1):88-99. Epub 2017 Jul 13.

a Division of Speech and Hearing Sciences , University of Hong Kong , Hong Kong SAR.

This study analysed the topic and vocabulary of Chinese speakers based on language samples of personal recounts in a large spoken Chinese database recently made available in the public domain, i.e. Cantonese AphasiaBank ( http://www.speech.hku.hk/caphbank/search/ ). The goal of the analysis is to offer clinicians a rich source for selecting ecologically valid training materials for rehabilitating Chinese-speaking people with aphasia (PWA) in the design and planning of culturally and linguistically appropriate treatments. Discourse production of 65 Chinese-speaking PWA of fluent types (henceforth, PWFA) and their non-aphasic controls narrating an important event in their life were extracted from Cantonese AphasiaBank. Analyses of topics and vocabularies in terms of part-of-speech, word frequency, lexical semantics, and diversity were conducted. There was significant overlap in topics between the two groups. While the vocabulary was larger for controls than that of PWFA as expected, they were similar in distribution across parts-of-speech, frequency of occurrence, and the ratio of concrete to abstract items in major open word classes. Moreover, proportionately more different verbs than nouns were employed at the individual level for both speaker groups. The findings provide important implications for guiding directions of aphasia rehabilitation not only of fluent but also non-fluent Chinese aphasic speakers.
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http://dx.doi.org/10.1080/02699206.2017.1334092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114172PMC
August 2018
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