Publications by authors named "Jason Chan"

314 Publications

Myoclonus and cerebellar ataxia associated with COVID-19: a case report and systematic review.

J Neurol 2021 Feb 22. Epub 2021 Feb 22.

Department of Clinical Neurosciences, University of Calgary, Calgary, AB, T2N 1N4, Canada.

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic in December 2019, neurological manifestations have been recognized as potential complications. Relatively rare movement disorders associated with COVID-19 are increasingly reported in case reports or case series. Here, we present a case and systematic review of myoclonus and cerebellar ataxia associated with COVID-19.

Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline using the PubMed and Ovid MEDLINE databases, from November 1, 2019 to December 6, 2020.

Results: 51 cases of myoclonus or ataxia associated with COVID-19, including our case, were identified from 32 publications. The mean age was 59.6 years, ranging from 26 to 88 years, and 21.6% were female. Myoclonus was multifocal or generalized and had an acute onset, usually within 1 month of COVID-19 symptoms. Myoclonus occurred in isolation (46.7%), or with ataxia (40.0%) or cognitive changes (30.0%). Most cases improved within 2 months, and treatment included anti-epileptic medications or immunotherapy. Ataxia had an acute onset, usually within 1 month of COVID-19 symptoms, but could be an initial symptom. Concurrent neurological symptoms included cognitive changes (45.5%), myoclonus (36.4%), or a Miller Fisher syndrome variant (21.2%). Most cases improved within 2 months, either spontaneously or with immunotherapy.

Conclusions: This systematic review highlights myoclonus and ataxia as rare and treatable post-infectious or para-infectious, immune-mediated phenomena associated with COVID-19. The natural history is unknown and future investigation is needed to further characterize these movement disorders and COVID-19.
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http://dx.doi.org/10.1007/s00415-021-10458-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897737PMC
February 2021

Droplet digital PCR of tumor suppressor gene methylation in serial oral rinses of patients with head and neck squamous cell carcinoma.

Head Neck 2021 Feb 17. Epub 2021 Feb 17.

Department of Otorhinolaryngology - Head and Neck Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.

Background: Head and neck squamous cell carcinoma (HNSCC) currently lacks sensitive approaches to detect cancer-related traits in body fluid.

Methods: Methylation of tumor suppressor genes (TSGs) (PAX5, EDNRB, and DCC) were measured in the oral rinses from 50 HNSCC and 58 control subjects using droplet digital PCR (ddPCR). Diagnostic accuracies in detecting HNSCC and the detection rate of recurrence in the post-treatment monitoring were analyzed.

Results: ddPCR TSG methylation detection in oral rinses for diagnosis of HNSCC had an AUC of 0.892 for PAX5, 0.753 for EDNRB, and 0.729 for DCC. Significant drop of TSG methylation was observed after completion of surgery (p < 0.01). 76.9% of the relapse cases had a pre-emptive rebound of methylation above presurgery levels in at least one of the tested markers before confirmed recurrence.

Conclusions: Utilizing ddPCR for TSG methylation detection in oral rinses shows potential for detection and monitoring of HNSCC.
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http://dx.doi.org/10.1002/hed.26647DOI Listing
February 2021

Clinical implications of systemic and local immune responses in human angiosarcoma.

NPJ Precis Oncol 2021 Feb 12;5(1):11. Epub 2021 Feb 12.

Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore.

Angiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes. In this study, we investigated the clinical relevance of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic immune response, as well as its correlation with intra-tumoral immune profiles in a subgroup of cases (n = 35) using the NanoString PanCancer IO360 panel and multiplex immunohistochemistry. In the overall cohort (n = 150), angiosarcomas of the head and neck (AS-HN) comprised most cases (58.7%) and median overall survival (OS) was 1.1 year. NLR, classified as high in 78 of 112 (70%) evaluable patients, was independently correlated with worse OS (HR 1.84, 95%CI 1.18-2.87, p = 0.0073). Peripheral blood NLR was positively correlated with intra-tumoral NLR (tNLR) (Spearman's rho 0.450, p = 0.0067). Visualization of tumor-infiltrating immune cells confirmed that tNLR scores correlated directly with both neutrophil (CD15 cells, rho 0.398, p = 0.0198) and macrophage (CD68 cells, rho 0.515, p = 0.0018) cell counts. Interestingly, tNLR correlated positively with oncogenic pathway scores including angiogenesis, matrix remodeling and metastasis, and cytokine and chemokine signaling, as well as myeloid compartment scores (all p < 0.001). In patients with documented response assessment to first-line chemotherapy, these pathway scores were all significantly higher in non-responders (47%) compared to responders. In conclusion, systemic and local immune responses may inform chemotherapy response and clinical outcomes in angiosarcomas.
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http://dx.doi.org/10.1038/s41698-021-00150-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881182PMC
February 2021

Absence of meaningful neurocognitive recovery in comatose patients with primary central nervous system lymphoma despite an effective response to chemotherapy: Case reports.

Mol Clin Oncol 2021 Mar 13;14(3):44. Epub 2021 Jan 13.

Division of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Republic of Singapore.

Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that occurs in patients who are elderly and immunocompromised. The most common treatment for PCNSL is high-dose methotrexate-based chemotherapy. Studies have suggested that the radiological response to high-dose methotrexate-based chemotherapy is associated with improved neurocognitive ability that remains stable upon follow-up. However, no study involving patients with an extremely poor neurological status before chemotherapy initiation has been reported, and the neurological prognosis of this group of patients remains unknown. The current case study described 3 patients with PCNSL diagnosed via biopsy who had comatose neurological states due to disease progression prior to treatment. All patients were treated with high-dose methotrexate-based chemotherapy. However, although effective radiological responses to treatment were achieved, no meaningful neurological or cognitive recovery was documented. Patients with PCNSL exhibiting a baseline comatose state have a poor neurological prognosis even with an effective tumour response to chemotherapy. Therefore, rapid detection and prompt treatment are crucial in patients with this disease.
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http://dx.doi.org/10.3892/mco.2021.2206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818097PMC
March 2021

Clinical and economic evaluation of a surveillance protocol to manage hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

Pharmacotherapy 2021 Feb 6. Epub 2021 Feb 6.

Division of Medical Oncology, National Cancer Centre Singapore, Singapore City, Singapore.

Study Objective: To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

Design: Prospective, single-arm study.

Setting: National Cancer Centre, Singapore.

Patients: Lymphoma patients with resolved HBV infection and scheduled to receive rituximab-based treatment.

Intervention: Close monitoring of HBV DNA levels, ie. every 4-6 weeks during rituximab treatment, every 6-8 weeks in the first year post-treatment, and every 3-4 months in the second year post-treatment.

Measurements: The efficacy of the surveillance protocol was examined by evaluating the rates of reactivation-related events. Feasibility was evaluated based on patient adherence. An economic analysis using a cost-minimization approach was conducted to compare the costs between the surveillance protocol and universal prophylaxis with entecavir 0.5 mg daily up to 1 year after cessation of rituximab.

Main Results: A total of 66 patients provided analyzable data with a follow-up period of 966.6 months. No hepatitis flare or reactivation-related events were detected. The median adherence rate to the surveillance protocol was 90.5%. Cost savings of US$946.40 per patient over the entire surveillance period were achieved if the surveillance protocol was adopted and was most affected by changes in prophylaxis duration and the cost of antiviral prophylaxis.

Conclusions: The surveillance protocol is an effective, feasible and cost-saving strategy to manage HBV reactivation among lymphoma patients with resolved HBV infection receiving rituximab.
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http://dx.doi.org/10.1002/phar.2508DOI Listing
February 2021

Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002).

J Clin Oncol 2021 Jan 28:JCO2003128. Epub 2021 Jan 28.

Stanford University, Stanford, CA.

Purpose: Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven.

Patients And Methods: In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI).

Results: Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% ( = .04). For IMRT, 2-year PFS was 87.6% ( = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% 52.4%; < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% ( = .56).

Conclusion: The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.
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http://dx.doi.org/10.1200/JCO.20.03128DOI Listing
January 2021

Profiling of extracellular vesicles in oral cancer, from transcriptomics to proteomics.

Semin Cancer Biol 2021 Jan 15. Epub 2021 Jan 15.

Department of Otorhinolaryngology, Head and Neck Surgery, Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address:

Oral cancers occurring in different subsites can have distinct etiologies' and are a significant problem worldwide. In general, the incidence of oral cancers has declined over the last decade due to improvements in modifiable risk factors (tobacco and alcohol consumption). However, recent data suggest that the incidence of squamous cell carcinomas in the oral tongue and oropharynx are increasing. Human papilloma virus (HPV) is an important risk factor for oropharyngeal cancer and is associated with better treatment responses when compared with HPV-unrelated oropharyngeal cancer. Regardless of the subsite, there are no clinically available biomarkers for the early detection of these cancers and many are detected at an advanced stage and are associated with poor 5-year survival rates. Tumor tissue and serial needle biopsies are used to diagnose and prognosticate oral cancers but have important limitations. Besides being invasive and physically painful, these types of biopsies offer a limited view of a complex tumor due to inter- and intra-tumoral heterogeneity and a dynamic tumor microenvironment. Liquid biopsies offer a promising and alternative way to measure disease in real-time. Extracellular vesicles (EVs) are small particles that are secreted by all cells types and can be readily isolated from a wide range of biofluids. EVs are structurally stable and can horizontally transfer bioactive molecules to distant sites throughout the body in concentrated forms that exceed what can be delivered in a soluble format. As EVs represent their cell of origin, biofluid derived EVs are heterogeneous and are comprised of a complex repertoire of host- and cancer-derived particles. This review article has focused on studies that have used transcriptomics and proteomics to explore the function and clinical significance of EVs in oral cavity and oropharyngeal cancers.
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http://dx.doi.org/10.1016/j.semcancer.2021.01.002DOI Listing
January 2021

Genomic Landscapes of Acral Melanomas in East Asia.

Cancer Genomics Proteomics 2021 Jan-Feb;18(1):83-92. Epub 2021 Jan 8.

Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore;

Background/aim: Acral melanomas (AM) represent a rare subgroup of melanomas with poor clinical outcomes and are enriched in Asian populations. Recent advances in next generation sequencing have provided opportunities to apply precision medicine to AM.

Patients And Methods: Here, we present a series of 13 patients with melanomas from Taiwan and Singapore, including 8 patients with AM profiled using whole exome sequencing and summarize the recent studies on the genomic landscape of AM.

Results: We identified mutually exclusive mutations in BRAF, NRAS, HRAS, NF1 and KIT in 6 AM cases. In addition, recurrent copy number gains in CCND1 and CDK4, as well as recurrent deletions in CDKN2A/CDKN2B, ATM and RAD51 were observed, supporting the potential use of CDK4/6 or PARP inhibitors in the treatment of these patients.

Conclusion: The genomic landscape of AM provides an important resource for applying novel targeted therapies in this rare disease.
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http://dx.doi.org/10.21873/cgp.20243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796820PMC
January 2021

Profiling severe acute respiratory syndrome coronavirus 2 and its relevance to otolaryngologic examinations during the coronavirus disease 2019 pandemic.

Curr Opin Allergy Clin Immunol 2021 02;21(1):38-45

Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China.

Purpose Of Review: The WHO announced the coronavirus disease 2019 (COVID-19) outbreak as a pandemic in February 2020 with over 15 million confirmed cases of COVID-19 globally to date. Otolaryngologists are at a high risk of contracting COVID-19 during this pandemic if there is inadequate and improper personal protective equipment provision, as we are dealing with diseases of the upper-aerodigestive tract and routinely engaged in aerosol-generating procedures.

Recent Findings: This article discusses the background and transmission route for severe acute respiratory syndrome coronavirus 2, its viral load and temporal profile as well as precaution guidelines in outpatient and operative setting in otorhinolaryngology.

Summary: As it is evident that COVID-19 can be transmitted at presymptomatic or asymptomatic period of infections, it is essential to practice ear, nose, and throat surgery with high vigilance in a safe and up-to-standard protection level during the pandemic. This article provides a summary for guidelines and recommendations in otorhinolaryngology.
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http://dx.doi.org/10.1097/ACI.0000000000000709DOI Listing
February 2021

Audio-Visual Training in Older Adults: 2-Interval-Forced Choice Task Improves Performance.

Front Neurosci 2020 12;14:569212. Epub 2020 Nov 12.

School of Applied Psychology, University College Cork, Cork, Ireland.

A growing interest in ameliorating multisensory perception deficits in older adults arises from recent evidence showing that impaired multisensory processing, particularly in the temporal domain, may be associated with cognitive and functional impairments. Perceptual training has proved successful in improving multisensory temporal processing in young adults, but few studies have investigated this training approach in older adults. In the present study we used a simultaneity (or synchronicity) judgement task with feedback, to train the audio-visual abilities of community-dwelling, cognitively healthy older adults. We recruited 23 older adults ( = 74.17, = 6.23) and a group of 20 young adults ( = 24.20, = 4.23) who served as a comparison. Participants were tested before and after perceptual training using a 2-Interval Forced Choice Task (2-IFC); and the Sound-Induced Flash Illusion (SIFI). After 3 days of training, participants improved on the 2-IFC task, with a significant narrowing of the temporal window of integration (TWI) found for both groups. Generalization of training effects was not found, with no post-training differences in perceptual sensitivity to the SIFI for either group. These findings provide evidence perceptual narrowing can be achieved in older as well as younger adults after 3 days of perceptual training. These results provide useful information for future studies attempting to improve audio-visual temporal discrimination abilities in older people.
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http://dx.doi.org/10.3389/fnins.2020.569212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693639PMC
November 2020

The Intersection between Oral Microbiota, Host Gene Methylation and Patient Outcomes in Head and Neck Squamous Cell Carcinoma.

Cancers (Basel) 2020 Nov 18;12(11). Epub 2020 Nov 18.

Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China.

The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of and in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes and , for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host-microbe interactions between enrichment and clinical outcomes or host gene methylation imply a potential role of as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.
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http://dx.doi.org/10.3390/cancers12113425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698865PMC
November 2020

Fear of hypoglycemia in children with type 1 diabetes and their parents: Effect of pump therapy and continuous glucose monitoring with option of low glucose suspend in the CGM TIME trial.

Pediatr Diabetes 2021 Mar 27;22(2):288-293. Epub 2020 Nov 27.

Division of Endocrinology and Metabolism, Children's Hospital of Eastern Ontario, Ottawa, Canada.

To determine if pump therapy with continuous glucose monitoring offering low glucose suspend (LGS) decreases fear of hypoglycemia among children with type 1 diabetes and their parents. The CGM TIME trial is a multicenter randomized controlled trial that enrolled 144 children with type 1 diabetes for at least 1 year (mean duration 3.4 ± 3.1 years) starting pump therapy (MiniMed™ Veo™, Medtronic Canada). CGM (MiniMed™ Enlite™ sensor) offering LGS was introduced simultaneously or delayed for 6 months. Hypoglycemia Fear Scale (HFS) was completed by children ≥10 years old and all parents, at study entry and 12 months later. Simultaneous and Delayed Group participants were combined for all analyses. Subscale scores were compared with paired t-tests, and individual items with paired Wilcoxon tests. Linear regression examined association with CGM adherence. 121/140 parents and 91/99 children ≥10 years had complete data. Mean Behavior subscale score decreased from 21.1 (SD 5.9) to 17.2 (SD 6.1) (p < .001) for children, and 20.7 (SD 7.5) to 17.4 (7.4) (p < .001) for parents. Mean Worry subscale score decreased from 17.9 (SD 11.9) to 11.9 (SD 11.4) (p < .001) for children, and 23.1 (SD 13.2) to 17.6 (SD 10.4) (p < .001) for parents. Median scores for 10/25 child items and 12/25 parent items were significantly lower at 12 months (p < .001). Linear regression found no association between HFS scores and CGM adherence. Insulin pump therapy with CGM offering LGS significantly reduced fear of hypoglycemia not related to CGM adherence in children with type 1 diabetes and their parents.
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http://dx.doi.org/10.1111/pedi.13150DOI Listing
March 2021

Bizarre giant cells in human angiosarcoma exhibit chemoresistance and contribute to poor survival outcomes.

Cancer Sci 2021 Jan 29;112(1):397-409. Epub 2020 Nov 29.

Division of Medical Oncology, National Cancer Centre Singapore, Singapore City, Singapore.

Giant cells (GC) are a poorly understood subset of tumor cells that have been increasingly recognized as a potential contributor to tumor heterogeneity and treatment resistance. We aimed to characterize the biological and clinical significance of GC in angiosarcoma, an aggressive rare cancer of endothelial origin. Archival angiosarcoma samples were examined for the presence of GC and compared with clinicopathological as well as NanoString gene expression data. GC were examined in angiosarcoma cell lines MOLAS and ISOHAS using conventional and electron microscopy, single cell whole genome profiling, and other assays. In the cell lines, GC represented a rare population of mitotically active, non-senescent CD31 cells, and shared similar genomic profiles with regular-sized cells, consistent with a malignant endothelial phenotype. GC remained viable and persisted in culture following exposure to paclitaxel and doxorubicin. In patient samples, GC were present in 24 of 58 (41.4%) cases. GC was correlated with poorer responses to chemotherapy (25.0% vs 73.3%, P = 0.0213) and independently contributed to worse overall survival outcomes (hazard ratio 2.20, 95% confidence interval 1.17-4.15, P = 0.0142). NanoString profiling revealed overexpression of genes, including COL11A1, STC1, and ERO1A, accompanied by upregulation of immune-related metabolic stress and metastasis/matrix remodeling pathways in GC-containing tumors. In conclusion, GC may contribute to chemoresistance and poor prognosis in angiosarcoma.
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http://dx.doi.org/10.1111/cas.14726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780052PMC
January 2021

Extracellular Vesicles in Head and Neck Cancer: A Potential New Trend in Diagnosis, Prognosis, and Treatment.

Int J Mol Sci 2020 Nov 4;21(21). Epub 2020 Nov 4.

Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.

Head and neck cancer (HNC) is a fatal and debilitating disease that is characterized by steady, poor survival rates despite advances in treatment. There is an urgent and unmet need to improve our understanding of what drives this insidious cancer and causes poor outcomes. Extracellular vesicles (EVs) are small vesicles that originate from tumor cells, immune cells, and other cell types and are secreted into plasma, saliva, and other bio-fluids. EVs represent dynamic, real-time changes of cells and offer an exciting opportunity to improve our understanding of HNC biology that may translate to improved clinical practice. Considering the amplified interest in EVs, we have sought to provide a contemporary review of the most recent and salient literature that is shaping the field. Herein, we discuss the functionality of EVs in HNCs and their clinical potential with regards to biomarker and therapeutic capabilities.
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http://dx.doi.org/10.3390/ijms21218260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662588PMC
November 2020

Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or naturalkiller/T-cell lymphoma.

Haematologica 2020 11 5;Online ahead of print. Epub 2020 Nov 5.

Division of Medical Oncology, National Cancer Centre Singapore.

Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose (MTD) of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory (R/R) T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with R/R TCL and NKTL were treated with standard dose ICE, dexamethasone 20mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose level (DL) 1, 2 and 3 were 40, 60 and 80mg respectively. Eleven patients with a median age of 60 were enrolled; 6 at DL1 and 5 at DL2. Patients had received a median of 2 (range 1-4) prior lines of treatment and 7 had primary refractory disease at study entry. Patients received a median of 3 cycles (range 1-6) of selinexor-DICE. The most common grade (G) 1/2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common G 3/4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed doselimiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the 10 evaluable patients, the overall and complete response rates were 91% and 82% respectively. The MTD of selinexor was 40mg when combined with DICE. The combination showed promising CR rates in patients with R/R TCL and NKTL but was poorly tolerated.
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http://dx.doi.org/10.3324/haematol.2020.251454DOI Listing
November 2020

Timing of CGM initiation in pediatric diabetes: The CGM TIME Trial.

Pediatr Diabetes 2021 Mar 4;22(2):279-287. Epub 2020 Nov 4.

Clinical Research Unit, CHEO Research Institute, Ottawa, Ontario, Canada.

Objective: To determine whether timing of CGM initiation offering low glucose suspend (LGS) affects CGM adherence in children and youth starting insulin pump therapy.

Methods: A 5-site RCT of pump-naïve subjects (aged 5-18 years) with type 1 diabetes (T1D) for at least 1 year compared simultaneous pump and CGM initiation offering LGS vs standard pump therapy with CGM initiation delayed for 6 months. Primary outcome was CGM adherence (hours per 28 days) (MiniMed™ Paradigm™ Veo™ system; CareLink Pro™ software) over 6 months after CGM initiation. Secondary outcome HbA1c was measured centrally. Linear mixed-models and ordinary least squares models were fitted to estimate effect of intervention, and covariates baseline age, T1D duration, HbA1c, gender, ethnicity, hypoglycemia history, clinical site, and association between CGM adherence and HbA1c.

Results: The trial randomized 144/152 (95%) eligible subjects. Baseline mean age was 11.5 ± 3.3(SD) years, T1D duration 3.4 ± 3.1 years, and HbA1c 7.9 ± 0.9%. Six months after CGM initiation, adjusted mean difference in CGM adherence was 62.4 hours per 28 days greater in the Simultaneous Group compared to Delayed Group (P = .007). There was no difference in mean HbA1c at 6 months. However, for each 100 hours of CGM use per 28-day period, HbA1c was 0.39% (95% CI 0.10%-0.69%) lower. Higher CGM adherence was associated with reduced time with glucose >10 mmol/L (P < .001).

Conclusion: CGM adherence was higher after 6 months when initiated at same time as pump therapy compared to starting CGM 6 months after pump therapy. Greater CGM adherence was associated with improved HbA1c.
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http://dx.doi.org/10.1111/pedi.13144DOI Listing
March 2021

Gallium-68 prostate-specific membrane antigen ([Ga]Ga-PSMA-11) PET for imaging of thyroid cancer: a feasibility study.

EJNMMI Res 2020 Oct 22;10(1):128. Epub 2020 Oct 22.

Department of Radiology and Biomedical Imaging, University of California San Francisco, 185 Berry Street, Suite 350, Lobby 6, Box 0946, San Francisco, CA, 94143, USA.

Background: Prostate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer. This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. The purpose of the current study was to determine the feasibility and utility of [Ga]Ga-PSMA-11 PET/MRI in thyroid cancer patients.

Methods: Eligible patients for this prospective pilot study were adults with a history of pathology-proven thyroid cancer who had abnormal radiotracer uptake on an 2-[F]FDG PET and/or I scintigraphy performed in the 12 months prior to study enrollment. Patients underwent a [Ga]Ga-PSMA-11 PET/MRI, and comparison was made to the prior qualifying 2-[F]FDG PET CT/MRI for lesion location and relative intensity.

Results: Twelve patients underwent [Ga]Ga-PSMA-11 PET/MRI, one of which was excluded from analysis due to debulking surgery prior to the PSMA PET. Of the remaining patients, 7/11 had differentiated disease (3 papillary, 2 follicular, 2 Hurthle cell) and 4/11 had dedifferentiated disease (2 poorly differentiated papillary, 2 anaplastic). Out of 43 lesions, 41 were visually 2-[F]FDG positive (uptake greater than background, detection rate 95.3%) and 28 were PSMA positive (uptake greater than background, detection rate 65.1%). Uptake was heterogeneous between patients, and in some cases within patients. 3/11 patients (1 poorly differentiated papillary, 2 follicular) had PSMA uptake which was greater than FDG uptake. For the remaining 8 patients, 2-[F]FDG uptake was greater than PSMA. Using one eligibility guideline in the prostate cancer literature for PSMA radioligand therapy (RLT), 8/11 could be considered eligible for possible future PSMA RLT. This was not predictable based on thyroid cancer subtype.

Conclusions: [Ga]Ga-PSMA-11 PET demonstrated lower detection rate when compared to 2-[F]FDG PET for thyroid cancer lesion visualization. Thyroid cancer subtype alone may not be sufficient to predict PSMA uptake, and radiotracer uptake may vary between patients and even within patients.
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http://dx.doi.org/10.1186/s13550-020-00720-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581659PMC
October 2020

External validation of the Canadian Syncope Risk Score for patients presenting with undifferentiated syncope to the emergency department.

Emerg Med Australas 2020 Oct 13. Epub 2020 Oct 13.

Emergency Department, Redcliffe Hospital, Brisbane, Queensland, Australia.

Objective: To validate the accuracy and safety of the Canadian Syncope Risk Score (CSRS) for patients presenting with syncope.

Methods: Single centre prospective observational study in Brisbane, Australia. Adults presenting to the ED with syncope within the last 24 h were recruited after applying exclusion criteria. Study was conducted over 1 year, from March 2018 to March 2019. Thirty-day serious adverse events (SAE) were reported based on the original derivation study and standardised outcome reporting for syncope. Individual patient CSRS was calculated and correlated with 30-day SAE and disposition status from ED.

Results: Two hundred and eighty-three patients were recruited to the study. Average age was 55.6 years (SD 22.7 years), 37.1% being male with a 39.9% admission rate. Thirty-day SAE occurred in seven patients (2.5%) and no recorded deaths. The CSRS performed with a sensitivity of 71.4% (95% confidence interval [CI] 30.3-94.9%), specificity 72.8% (95% CI 67.1-77.9%) for a threshold score of 1 or higher.

Conclusion: Syncope patients in our study were predominantly very low to low risk (72%). The prevalence of 30-day SAE was low, majority occurring following hospital discharge. Sensitivity estimates for CSRS was lower than the derivation study but lacked robustness with wide CIs because of a small sample size and number of events observed. However, the CSRS did not miss any clinically relevant outcomes in low risk patients making it potentially useful in aiding their disposition. Larger validation studies in Australia are encouraged to further test the diagnostic accuracy of the CSRS.
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http://dx.doi.org/10.1111/1742-6723.13641DOI Listing
October 2020

The use of pre-operative virtual reality to reduce anxiety in women undergoing gynecological surgeries: a prospective cohort study.

BMC Anesthesiol 2020 10 9;20(1):261. Epub 2020 Oct 9.

Department of Women's Anesthesia, KK Women's and Children's Hospital, 100 Bukit Timah Road Singapore, Singapore City, 229899, Singapore.

Background: Pre-operative anxiety is common and is associated with negative surgical outcomes. Virtual reality (VR) is a promising new technology that offers opportunities to modulate patient experience and cognition and has been shown to be associated with lower levels of anxiety. In this study, we investigated changes in pre-operative anxiety levels before and after using VR in patients undergoing minor gynecological surgery.

Methods: Patients who underwent elective minor gynecological surgeries in KK Women's and Children's hospital, Singapore were recruited. The VR intervention consisted of 10-min exposure via a headset loaded with sceneries, background meditation music and breathing exercises. For the primary outcome of pre-operative anxiety, patients were assessed at pre- and post-intervention using the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes of self-reported satisfaction scores and EuroQol 5-dimension 3-level (EQ-5D-3L) were also collected.

Results: Data analysis from 108 patients revealed that HADS anxiety scores were significantly reduced from 7.2 ± 3.3 pre-intervention to 4.6 ± 3.0 post-intervention (p < 0.0001). Furthermore, HADS depression scores were significantly reduced from 4.7 ± 3.3 pre-intervention to 2.9 ± 2.5 post-intervention (p < 0.0001). Eighty-two percent of the patients self-reported VR intervention as 'Good' or 'Excellent'. EQ-5D-3L showed significant changes in dimensions of 'usual activities' (p = 0.025), 'pain/discomfort' (p = 0.008) and 'anxiety/ depression' (p < 0.0001).

Conclusions: For patients undergoing minor gynecological procedures, the VR intervention brought about a significant reduction in pre-operative anxiety. This finding may be clinically important to benefit patients with high pre-operative anxiety without the use of anxiolytics.

Trial Registration: This study was registered on clinicaltrials.gov registry ( NCT03685422 ) on 26 Sep 2018.
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http://dx.doi.org/10.1186/s12871-020-01177-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547504PMC
October 2020

Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic mutation.

NPJ Genom Med 2020 18;5:39. Epub 2020 Sep 18.

Cancer Genetics Service, Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.

Gitelman syndrome is a rare, recessively inherited disease characterized by chronic hypokalemia and hypomagnesemia as a result of defective electrolyte co-transport at the level of the distal convoluted tubule of the kidney. Here, we present the first report of a patient with Gitelman syndrome who developed multiple neoplasia including colorectal polyposis, synchronous colorectal cancers, recurrent breast fibroadenomata and a desmoid tumor. Whole-exome sequencing confirmed germline compound heterozygous mutations of c.179C > T and c.1326C > G in , and in addition, identified a monoallelic germline c.934-2A > G splice site mutation in . , magnesium deficiency potentiated oxidative DNA damage in lymphoblastoid cell lines derived from the same patient. We postulate that monoallelic mutations may manifest in the presence of cooperative non-genetic mechanisms, in this case possibly magnesium deficiency from Gitelman syndrome.
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http://dx.doi.org/10.1038/s41525-020-00146-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501863PMC
September 2020

Technical considerations for positioning and placement of a transperineal ultrasound probe during prostate radiotherapy.

J Med Radiat Sci 2020 Oct 5. Epub 2020 Oct 5.

Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore.

This technical evaluation aims to provide practice 'how to' guidelines for radiation therapists (RTs) when positioning a transperineal ultrasound (TPUS) probe during prostate radiotherapy. Recommendations and practical tips will be provided for the best practice in TPUS-guided workflow to obtain optimal ultrasound images for accurate interpretation and registration of the prostate gland. This will assist the RTs in making consistent and accurate clinical decision in an ultrasound-guided radiotherapy workflow for prostate treatment. The implementation process and the associated successes and challenges will also be described to assist institutions who may be investigating the potential of implementing this system.
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http://dx.doi.org/10.1002/jmrs.439DOI Listing
October 2020

Multiomic analysis and immunoprofiling reveal distinct subtypes of human angiosarcoma.

J Clin Invest 2020 11;130(11):5833-5846

Division of Surgical Oncology, National Cancer Centre Singapore, Singapore.

Angiosarcomas are rare, clinically aggressive tumors with limited treatment options and a dismal prognosis. We analyzed angiosarcomas from 68 patients, integrating information from multiomic sequencing, NanoString immuno-oncology profiling, and multiplex immunohistochemistry and immunofluorescence for tumor-infiltrating immune cells. Through whole-genome sequencing (n = 18), 50% of the cutaneous head and neck angiosarcomas exhibited higher tumor mutation burden (TMB) and UV mutational signatures; others were mutationally quiet and non-UV driven. NanoString profiling revealed 3 distinct patient clusters represented by lack (clusters 1 and 2) or enrichment (cluster 3) of immune-related signaling and immune cells. Neutrophils (CD15+), macrophages (CD68+), cytotoxic T cells (CD8+), Tregs (FOXP3+), and PD-L1+ cells were enriched in cluster 3 relative to clusters 2 and 1. Likewise, tumor inflammation signature (TIS) scores were highest in cluster 3 (7.54 vs. 6.71 vs. 5.75, respectively; P < 0.0001). Head and neck angiosarcomas were predominant in clusters 1 and 3, providing the rationale for checkpoint immunotherapy, especially in the latter subgroup with both high TMB and TIS scores. Cluster 2 was enriched for secondary angiosarcomas and exhibited higher expression of DNMT1, BRD3/4, MYC, HRAS, and PDGFRB, in keeping with the upregulation of epigenetic and oncogenic signaling pathways amenable to targeted therapies. Molecular and immunological dissection of angiosarcomas may provide insights into opportunities for precision medicine.
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http://dx.doi.org/10.1172/JCI139080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598061PMC
November 2020

Clinical features and survival outcomes of ocular melanoma in a multi-ethnic Asian cohort.

Sci Rep 2020 10 1;10(1):16367. Epub 2020 Oct 1.

Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, 169610, Singapore.

Ocular melanomas are uncommon cancers in Southeast Asia unlike in the West. We conducted a retrospective review of patients (n = 44) with histologically-proven ocular melanoma within a multi-ethnic Asian cohort from Singapore. Clinicopathological features and relapse patterns were examined, and survival outcomes of interest included recurrence-free survival (RFS) and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional regression. The study cohort included 18 male and 26 female patients, with a median age of 52 years (range 8-78). Median follow-up was 154 months. For uveal melanomas (n = 29), the 5-year RFS and OS was 56.8% and 76.6%, respectively; whilst for conjunctival melanomas (n = 15), the 5-year RFS and OS was 30.1% and 68.8%, respectively. Fifteen patients (38.5%) eventually developed metastasis, following which the median survival was only 17 months. Multivariate analysis demonstrated that higher T stage was a significant independent predictor for both OS (HR 8.69, 95% CI 1.03 to 73.09, p = 0.047) and RFS (HR 11.62, 95% CI 2.45 to 55.00, p = 0.002). Smoking history was independently predictive of better RFS (HR 0.08, 95% CI 0.01 to 0.78, p = 0.030). In conclusion, our study demonstrates the poor ocular melanoma outcomes in Southeast Asians, highlighting the necessity for urgent research in this area of unmet clinical need.
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http://dx.doi.org/10.1038/s41598-020-73534-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529790PMC
October 2020

Evaluation of a National Comprehensive Cancer Network Guidelines-Based Decision Support Tool in Patients With Non-Small Cell Lung Cancer: A Nonrandomized Clinical Trial.

JAMA Netw Open 2020 09 1;3(9):e209750. Epub 2020 Sep 1.

Department of Radiation Oncology, University of California, San Francisco.

Importance: The association of guideline-based decision support with the quality of care in patients with non-small cell lung cancer (NSCLC) is not known.

Objective: To evaluate the association of exposure to the National Comprehensive Cancer Center (NCCN) guidelines with guideline-concordant care and patients' decisional conflict.

Design, Setting, And Participants: A nonrandomized clinical trial, conducted at a tertiary care academic institution, enrolled patients from February 23, 2015, to September 28, 2017. Data analysis was conducted from July 19, 2019, to April 22, 2020. A cohort of 76 patients with NSCLC seen at diagnosis or disease progression and a retrospective cohort of 157 patients treated before the trial were included. Adherence to 6 NCCN recommendations were evaluated: (1) smoking cessation counseling, (2) adjuvant chemotherapy for patients with stage IB to IIB NSCLC after surgery, (3) pathologic mediastinal staging in patients with stage III NSCLC before surgery, (4) pathologic mediastinal staging in patients with stage III NSCLC before nonsurgical treatment, (5) definitive chemoradiotherapy for patients with stage III NSCLC not having surgery, and (6) molecular testing for epidermal growth factor receptor and anaplastic lymphoma kinase alterations for patients with stage IV NSCLC. Subgroup analysis was conducted to compare the rates of guideline concordance between the prospective and retrospective cohorts. Secondary end points included decisional conflict and satisfaction.

Interventions: An online tool customizing the NCCN guidelines to patients' clinical and pathologic features was used during consultation, facilitated by a trained coordinator.

Main Outcomes And Measures: Concordance of practice with 6 NCCN treatment recommendations on NSCLC and patients' decisional conflict.

Results: Of the 76 patients with NSCLC, 44 were men (57.9%), median age at diagnosis was 68 years (interquartile range [IQR], 41-87 years), and 59 patients (77.6%) had adenocarcinoma. In the retrospective cohort, 91 of 157 patients (58.0%) were men, median age at diagnosis was 66 years (IQR, 61-65 years), and 105 patients (66.9%) had adenocarcinoma. After the intervention, patients received more smoking cessation counseling (4 of 5 [80.0%] vs 1 of 24 [4.2%], P < .001) and less adjuvant chemotherapy (0 of 7 vs 7 of 11 [63.6%]; P = .012). There was no significant change in mutation testing of non-squamous cell stage IV disease (20 of 20 [100%] vs 48 of 57 [84.2%]; P = .10). There was no significant change in pathologic mediastinal staging or initial chemoradiotherapy for patients with stage III disease. After consultation with the tool, decisional conflict scores improved by a median of 20 points (IQR, 3-34; P < .001).

Conclusions And Relevance: The findings of this study suggest that exposure to the NCCN guidelines is associated with increased guideline-concordant care for 2 of 6 preselected recommendations and improvement in decisional conflict.

Trial Registration: ClinicalTrials.gov Identifier: NCT03982459.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.9750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527870PMC
September 2020

Risk Factors Associated with Development of Acute and Sub-Acute Post-Cesarean Pain: A Prospective Cohort Study.

J Pain Res 2020 18;13:2317-2328. Epub 2020 Sep 18.

Department of Women's Anesthesia, KK Women's and Children's Hospital, Singapore.

Background: Although cesarean delivery is one of the most commonly performed surgical procedures, robust data regarding post-cesarean pain is still lacking. Recent studies showed an association between pain upon local anesthetic (LA) injection for spinal anesthesia, or the use of a "three simple questions", and acute post-cesarean pain. Nevertheless, these assessments have yet to be validated further, despite their relative ease of use. We aimed to assess the association between pain score upon LA injection with acute post-cesarean pain after 24 hours at rest (primary outcome) and sub-acute post-cesarean pain lasting for 4 weeks or more (secondary outcome).

Methods: Women undergoing cesarean delivery under spinal anesthesia were given pre-operative questionnaires on pain and psychological vulnerability. We also assessed the pain score upon LA injection and mechanical temporal summation. Univariate and multivariable logistic regressions were performed.

Results: The incidence of moderate-to-severe acute post-cesarean pain at 24 hours was 21.0% (95% CI=16.6-27.6%) (48 of 217 patients). Pain score upon LA injection was not significantly associated with acute post-cesarean pain after 24 hours at rest (unadjusted OR=1.10, 95% CI=0.95-1.27, =0.21). However, pain score upon LA injection was significantly associated with sub-acute post-cesarean pain (adjusted OR=1.29, 95% CI=1.07-1.55, =0.0089) with significant covariate of increased pre-operative central sensitization inventory (CSI) scores (adjusted OR=1.05, 95% CI=1.01-1.09, =0.0111; area under the curve (AUC)=0.691).

Conclusion: There was no association between increased pain score upon LA injection and acute post-cesarean pain, but it was associated with sub-acute post-cesarean pain. Further work is needed to define pain score upon LA injection as a convenient pragmatic measure of risk stratifying patients predisposed to sub-acute post-cesarean pain.
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http://dx.doi.org/10.2147/JPR.S257442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509311PMC
September 2020

Delivering CaRMS Transparency: Applicant Review and Selection Process of a Single-Center Diagnostic Radiology Residency Training Program.

Can Assoc Radiol J 2020 Sep 22:846537120957621. Epub 2020 Sep 22.

Department of Radiology, Faculty of Medicine, 6363University of Ottawa, Ontario, Canada.

Purpose: To report the current application review and selection process in our Canadian diagnostic radiology program at the University of Ottawa for both Canadian and international medical graduates.

Application Review And Selection Process: Submitted applications fulfilling institutional requirements were selected for a detailed file review after preliminary screening. A diverse group of file reviewers and interviewers was selected. Interviews were offered based on file review score sheet outcomes. Each interviewer generated a postinterview rank list. Applicants were reviewed and discussed from highest to lowest rank based on a preliminary compiled rank list generated from the average of the postinterview rank lists. Group discussion and a consensus model were used to create a final applicant rank list.

Conclusions: We outlined our systematic, consistent selection process which aligns with current best practices. This description may inform other programs wishing to adopt or optimize strategies to improve candidate assessments and selection processes.
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http://dx.doi.org/10.1177/0846537120957621DOI Listing
September 2020

Survival in Patients With Brain Metastases: Summary Report on the Updated Diagnosis-Specific Graded Prognostic Assessment and Definition of the Eligibility Quotient.

J Clin Oncol 2020 11 15;38(32):3773-3784. Epub 2020 Sep 15.

Miami Cancer Institute, Miami, FL.

Purpose: Conventional wisdom has rendered patients with brain metastases ineligible for clinical trials for fear that poor survival could mask the benefit of otherwise promising treatments. Our group previously published the diagnosis-specific Graded Prognostic Assessment (GPA). Updates with larger contemporary cohorts using molecular markers and newly identified prognostic factors have been published. The purposes of this work are to present all the updated indices in a single report to guide treatment choice, stratify research, and define an eligibility quotient to expand eligibility.

Methods: A multi-institutional database of 6,984 patients with newly diagnosed brain metastases underwent multivariable analyses of prognostic factors and treatments associated with survival for each primary site. Significant factors were used to define the updated GPA. GPAs of 4.0 and 0.0 correlate with the best and worst prognoses, respectively.

Results: Significant prognostic factors varied by diagnosis and new prognostic factors were identified. Those factors were incorporated into the updated GPA with robust separation ( < .01) between subgroups. Survival has improved, but varies widely by GPA for patients with non-small-cell lung, breast, melanoma, GI, and renal cancer with brain metastases from 7-47 months, 3-36 months, 5-34 months, 3-17 months, and 4-35 months, respectively.

Conclusion: Median survival varies widely and our ability to estimate survival for patients with brain metastases has improved. The updated GPA (available free at brainmetgpa.com) provides an accurate tool with which to estimate survival, individualize treatment, and stratify clinical trials. Instead of excluding patients with brain metastases, enrollment should be encouraged and those trials should be stratified by the GPA to ensure those trials make appropriate comparisons. Furthermore, we recommend the expansion of eligibility to allow for the enrollment of patients with previously treated brain metastases who have a 50% or greater probability of an additional year of survival (eligibility quotient > 0.50).
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http://dx.doi.org/10.1200/JCO.20.01255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655019PMC
November 2020

Will the COVID Pandemic Lead to Uncounted Cancer Deaths in the Future?

Int J Radiat Oncol Biol Phys 2020 Oct;108(2):351-352

Department of Clinical Oncology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

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http://dx.doi.org/10.1016/j.ijrobp.2020.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462880PMC
October 2020

Clinical Features of Plasmablastic Lymphoma: Case Series From an Asian Tertiary Cancer Center and Literature Review.

J Hematol 2020 Sep 14;9(3):71-78. Epub 2020 Aug 14.

Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.

Background: Plasmablastic lymphoma (PBL) is an aggressive subtype of mature B-cell non-Hodgkin lymphoma. Given its rarity, there remains a lack of clinicopathological data to guide its management, particularly on Asian patients.

Methods: We conducted a retrospective chart review of 10 patients diagnosed with PBL at the National Cancer Centre Singapore and performed a literature review of similar studies on Asian cohorts.

Results: Most patients were male (n = 9), with median age at diagnosis of 55 years (range, 33 - 91 years). Seven (70%) patients were considered to be immunocompromised. In the overall cohort, the median overall survival (OS) was 19.4 months with 5-year survival estimates given at 60% and 36% for OS and progression-free survival (PFS), respectively. At diagnosis, patients with HIV/AIDS (n = 5) were younger compared to others (median, 43 vs. 61 years; P = 0.0278), had greater number of nodal site involvement (median, 6 vs. 0; P = 0.0333), and higher international prognostic index (IPI) scores (P = 0.034 for trend). Amongst different chemotherapy used, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH)-based regimens (n = 6) elicited prominent complete response rates (83%) and led to durable responses even in the setting of advanced stage, high-risk IPI score and immunodeficiency.

Conclusions: In conclusion, our study describes the features of PBL in an Asian cohort and highlights disease features unique to HIV-associated PBL.
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http://dx.doi.org/10.14740/jh672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430862PMC
September 2020