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Bardhan, N. M.

Publications and source records attributed to Bardhan, N. M..

2 recordsLinked to original sources

Optimal Prescriptive Treatments for Ovarian Cancer with Genetic Data

Among the cancers affecting the female population, Ovarian Cancer (OC), while being relatively rare, is the leading cause of gynecological cancer-related deaths, with overall 5-year survival rates of approximately 50% for all stages combined. This is because of the challenges associated with the diagnosis, resulting in detection at advanced stages of OC, coupled with the slow progress in effective treatment options since the approval of platinum-based chemotherapy in the late 1970s. There has been a relative lack of sophisticated methods based on Machine Learning (ML) models that use genetic data for better prediction of Ovarian Cancer outcomes and result in more effective treatment recommendations. Therefore, there is an unmet clinical need to create models that allow physicians to make informed decisions based on all available data, including patient demographic, social, health, and genomic data. Hence, we develop new techniques for leveraging genetic information in prescribing optimal treatments for patients with OC, using a publicly available dataset from the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) trial. Our approach is able to transform genotype sequencing information into a simple tabular form that can then be used as the input to any ML model. Coupled with the recorded treatment regimen and clinical parameters of matched patients from the genetic dataset, we estimate the treatment effect in terms of mortality prediction and use it to prescribe the optimal treatment for any given patient. By including the genetic features engineered through our proposed method, our models have a higher accuracy than the models without genetic information embedded. The increase in predictive accuracy demonstrates the improved efficacy of our method in the predictive setting. Furthermore, in the prescriptive setting, the models including genetic features output different treatment choices for patients, showing the impact of their inclusion. This is further highlighted by the feature importance of the genetic features such as mutations in the FAT3, BRCA1, BRCA2, and NF1 genes, where they rank highly with a tighter aggregation of the top features, relative to the sharp drop-off in feature importance after the top feature in the models without genetic data. Taken together, in summary, our models will allow oncologists to make more informed and accurate decisions, incorporating a patients genetic data with all other available clinical information, which has the potential for improved prognosis and better long-term survival outcomes for Ovarian Cancer patients.

cancer biology↗

A Machine Learning-optimized system for on demand, pulsatile, photo- and chemo-therapeutic treatment using near-infrared responsive MoS2-based microparticles in a breast cancer model

Cancer therapy research is of high interest because of the persistence and mortality of the disease and the side effects of traditional therapeutic methods, while often multimodal treatments are necessary based on the patients needs. The development of less invasive modalities for recurring treatment cycles is thus of critical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation, by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation. The system is composed of poly(caprolactone) microparticles of 200 m size with incorporated molybdenum disulfide (MoS2) nanosheets as the photothermal agent and hydrophilic doxorubicin or hydrophobic violacein, as model drugs. Upon irradiation the nanosheets heat up to [≥]50 {degrees}C leading to polymer matrix melting and release of the drug. MoS2 nanosheets exhibit high photothermal conversion efficiency and allow for application of low power laser irradiation for the system activation. A Machine Learning algorithm was applied to acquire optimal laser operation conditions; 0.4 W/cm2 laser power at 808 nm, 3-cycle irradiation, for 3 cumulative minutes. In a mouse subcutaneous model of 4T1 triple-negative breast cancer, 25 microparticles were intratumorally administered and after 3-cycle laser treatment the system conferred synergistic phototherapeutic and chemotherapeutic effect. Our on-demand, pulsatile synergistic treatment resulted in increased median survival up to 40 days post start of treatment compared to untreated mice, with complete eradication of the tumors at the primary site. Such a system could have potential for patients in need of recurring cycles of treatment on subcutaneous tumors. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=56 SRC="FIGDIR/small/536750v1_ufig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@14ab0f3org.highwire.dtl.DTLVardef@a72649org.highwire.dtl.DTLVardef@1c28608org.highwire.dtl.DTLVardef@1ed9c06_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗