Publications by authors named "B A Vellayappan"

57 Publications

Cardiovascular diseases among diffuse large B-cell lymphoma long-term survivors in Asia: a multistate model study.

ESMO Open 2022 Jan 10;7(1):100363. Epub 2022 Jan 10.

Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; Department of Non-Communicable Disease and Cancer Epidemiology, Instituto de Investigacion Biosanitaria de Granada (ibs.GRANADA), Andalusian School of Public Health, Granada, Spain. Electronic address:

Background: We modeled the clinical course of a cohort of diffuse large B-cell lymphoma (DLBCL) patients with no prior cardiovascular diseases (CVDs) using a multistate modeling framework.

Patients And Methods: Data on 2600 patients with DLBCL diagnosed between 2000 and 2018 and had received chemotherapy with or without radiotherapy were obtained from a population-wide electronic health database of Hong Kong. We used the Markov illness-death model to quantify the impact of doxorubicin and various risk factors (therapeutic exposure, demographic, comorbidities, cardiovascular risk factors, and lifestyle factors which included smoking) on the clinical course of DLBCL (transitions into incident CVD, lymphoma death, and other causes of death).

Results: A total of 613 (23.6%) and 230 (8.8%) of 2600 subjects died of lymphoma and developed incident CVD, respectively. Median follow-up was 7.0 years (interquartile range 3.8-10.8 years). Older ages [hazard ratio (HR) for >75 versus ≤60 years 1.88; 95% confidence interval (CI) 1.25-2.82 and HR for 61-75 versus ≤60 years 1.60; 95% CI 1.12-2.30], hypertension (HR 4.92; 95% CI 2.61-9.26), diabetes (HR 1.43; 95% CI 1.09-1.87), and baseline use of aspirin (HR 5.30; 95% CI 3.93-7.16) were associated with an increased risk of incident CVD. In a subgroup of anticipated higher-risk patients (aged 61-75 years, smoked, had diabetes, and received doxorubicin), we found that they remained on average 7.9 (95% CI 7.2-8.8) years in the DLBCL state and 0.1 (95% CI 0.0-0.4) years in the CVD state, if they could be followed up for 10 years. The brief time in the CVD state is consistent with the high chance of death in patients who developed CVD. Other causes of death have overtaken DLBCL-related death after about 5 years.

Conclusions: In this Asian population-based cohort, we found that incident CVDs can occur soon after DLBCL treatment and continued to occur throughout survivorship. Clinicians are advised to balance the risks and benefits of treatment choices to minimize the risk of CVD.
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http://dx.doi.org/10.1016/j.esmoop.2021.100363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760397PMC
January 2022

Stereotactic radiosurgery in alveolar soft part sarcoma brain metastases: Case series and literature review.

J Clin Neurosci 2021 Nov 24;93:227-230. Epub 2021 Sep 24.

Division of Neurosurgery, Department of Surgery, National University Hospital, Singapore.

Alveolar soft part sarcoma (ASPS) has the highest incidence of brain metastasis amongst sarcomas. There is a paucity of literature published focusing on radiation therapy for this condition. This is a single centre retrospective review of the treatment of three patients with 12 ASPS brain metastasis using single dose stereotactic radiosurgery (SRS). Five lesions were treated with low (<25 Gy) and seven with high (≥25 Gy) dose. Four lesions had a volume of >1.5 cm and were defined as large, while seven had a volume of ≤0.5 cm and were defined as small. The local tumor control as well as the clinical complication rates were studied. There was a statistically significant relation between treatment dose and tumor control rate. All large tumors treated with low dose recurred and required surgical removal within two months following SRS, while the large lesion treated with high dose recurred after 11 months. Five of the six small tumors treated with high doses were controlled, while the sixth required retreatment and was stable thereafter. No patient suffered from undue symptomatic radiation effects. The success rate following SRS for small ASPS metastases treated with high doses seems to be sufficient to justify the treatment. The short time for large tumor to recur, significant increase in tumor size requiring surgical removal of the tumors, makes low dose SRS unattractive. Based on this limited patient population, it seems that high dose SRS should be used for all ASPS brain metastases except for large tumors deemed surgically accessible.
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http://dx.doi.org/10.1016/j.jocn.2021.09.002DOI Listing
November 2021

H3K27M-mutant, hemispheric diffuse glioma in an adult patient with prolonged survival.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab135. Epub 2021 Sep 17.

Department of Pathology, National University Health System, Singapore.

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http://dx.doi.org/10.1093/noajnl/vdab135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500686PMC
September 2021

Comparison of diagnostic performance and inter-reader agreement between PI-RADS v2.1 and PI-RADS v2: systematic review and meta-analysis.

Br J Radiol 2021 Sep 14:20210509. Epub 2021 Sep 14.

Department of Radiology, Tan Tock Seng Hospital, Singapore, Singapore.

Objectives: To perform a systematic review and meta-analysis comparing diagnostic performance and inter reader agreement between PI-RADS v. 2.1 and PI-RADS v. 2 in the detection of clinically significant prostate cancer (csPCa).

Methods: A systematic review was performed, searching the major biomedical databases (Medline, Embase, Scopus), using the keywords "PIRADS 2.1" or "PI RADS 2.1" or "PI-RADS 2.1". Studies reporting on head-to-head diagnostic comparison between PI-RADS v. 2.1 and v. 2 were included. Pooled sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were compared between PI-RADS v. 2.1 and v. 2. Summary receiver operator characteristic graphs were plotted. Analysis was performed for whole gland, and pre-planned subgroup analysis was performed by tumour location (whole gland transition zone (TZ)), high b-value DWI (b-value ≥1400 s/mm), and reader experience (<5 years vs ≥5 years with prostate MRI interpretation). Inter-reader agreement and pooled rates of csPCa for PI-RADS 1-3 lesions were compared between PI-RADS v. 2.1 and v. 2. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool v. 2 (QUADAS-2).

Results: Eight studies (1836 patients, 1921 lesions) were included. Pooled specificity for PI-RADS v. 2.1 was significantly lower than PI-RADS v. 2 for whole gland (0.62 0.66, = 0.02). Pooled sensitivities, PPVs and NPVs were not significantly different ( = 0.17, 0.31, 0.41). Pooled specificity for PI-RADS v. 2.1 was significantly lower than PI-RADS v. 2 for TZ only (0.67 0.72, = 0.01). Pooled sensitivities, PPVs and NPVs were not significantly different ( = 0.06, 0.36, 0.17). Amongst studies utilising diffusion-weighted imaging with highest b-value of ≥1400 s/mm, pooled sensitivities, specificities, PPVs and NPVs were not significantly different ( = 0.52, 0.4, 0.5, 0.47). There were no significant differences in pooled sensitivities, specificities, PPVs and NPVs between PI-RADS v. 2.1 and PI-RADS v. 2 for less-experienced readers ( = 0.65, 0.37, 0.65, 0.81) and for more experienced readers ( = 0.57, 0.90, 0.91, 0.65). For PI-RADS v. 2.1 alone, there were no significant differences in pooled sensitivity, specificity, PPV and NPV between less and more experienced readers ( = 0.38, 0.70, 1, 0.48). Inter-reader agreement was moderate to substantial for both PI-RADS v. 2.1 and v. 2. There were no significant differences between pooled csPCa rates between PI-RADS v. 2.1 and v. 2 for PI-RADS 1-2 lesions (6.6% vs  7.3%, = 0.53), or PI-RADS 3 lesions (24.1% vs  26.8%, = 0.28).

Conclusions: Diagnostic performance and inter-reader agreement for PI-RADS v. 2.1 is comparable to PI-RADS v. 2, however the significantly lower specificity of PI-RADS v. 2.1 may result in increased number of unnecessary biopsies.

Advances In Knowledge: 1. Compared to PI-RADS v. 2, PI-RADS v. 2.1 has a non-significantly higher sensitivity but a significantly lower specificity for detection of clinically significant prostate cancer.2. PI-RADS v. 2.1 could potentially result in considerable increase in number of negative targeted biopsy rates for PI-RADS 3 lesions, which could have been potentially avoided.
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http://dx.doi.org/10.1259/bjr.20210509DOI Listing
September 2021

Evolution of materials for implants in metastatic spine disease till date - Have we found an ideal material?

Radiother Oncol 2021 10 19;163:93-104. Epub 2021 Aug 19.

Department of Radiation Oncology, National University Health System, Singapore.

"Metastatic Spine Disease" (MSD) often requires surgical intervention and instrumentation with spinal implants. Ti6Al4V is widely used in metastatic spine tumor surgery (MSTS) and is the current implant material of choice due to improved biocompatibility, mechanical properties, and compatibility with imaging modalities compared to stainless steel. However, it is still not the ideal implant material due to the following issues. Ti6Al4V implants cause stress-shielding as their Young's modulus (110 gigapascal [GPa]) is higher than cortical bone (17-21 GPa). Ti6Al4V also generates artifacts on CT and MRI, which interfere with the process of postoperative radiotherapy (RT), including treatment planning and delivery. Similarly, charged particle therapy is hindered in the presence of Ti6Al4V. In addition, artifacts on CT and MRI may result in delayed recognition of tumor recurrence and postoperative complications. In comparison, polyether-ether-ketone (PEEK) is a promising alternative. PEEK has a low Young's modulus (3.6 GPa), which results in optimal load-sharing and produces minimal artifacts on imaging with less hinderance on postoperative RT. However, PEEK is bioinert and unable to provide sufficient stability in the immediate postoperative period. This issue may possibly be mitigated by combining PEEK with other materials to form composites or through surface modification, although further research is required in these areas. With the increasing incidence of MSD, it is an opportune time for the development of spinal implants that possess all the ideal material properties for use in MSTS. Our review will explore whether there is a current ideal implant material, available alternatives and whether these require further investigation.
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http://dx.doi.org/10.1016/j.radonc.2021.08.007DOI Listing
October 2021
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