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"Kim, Hyun S"
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Oncolytic virus immunotherapy: future prospects for oncology
2018
Background
Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques.
Main body
The ability to deliver therapy tailored to specific cellular targets at the precise locus in which it would have its greatest impact is a profound development in anti-cancer treatment. Although immune checkpoint inhibitors have an improved tolerability profile relative to cytotoxic chemotherapy and whole beam radiation, severe immune-related adverse events have emerged as a potential limitation. These include pneumonitis, pancreatitis, and colitis, which are relatively infrequent but can limit therapeutic options for some patients. Intratumor injection of oncolytic viruses, in contrast, has a markedly lower rate of serious adverse effects and perhaps greater specificity to target tumor cells. Early stage clinical trials using oncolytic viruses show induction of effector anti-tumor immune responses and suggest that such therapies could also morph and redefine both the local target cells’ niche as well as impart distant effects on remote cells with a similar molecular profile.
Conclusion
It is imperative for the modern immuno-oncologist to understand the biological processes underlying the immune dysregulation in cancer as well as the effects, uses, and limitations of oncolytic viruses. It will be with this foundational understanding that the future of oncolytic viral therapies and their delivery can be refined to forge future horizons in the direct modulation of the tumor bed.
Journal Article
Immuno-thermal ablations – boosting the anticancer immune response
2017
The use of immunomodulation to treat malignancies has seen a recent explosion in interest. The therapeutic appeal of these treatments is far reaching, and many new applications continue to evolve. In particular, immune modulating drugs have the potential to enhance the systemic anticancer immune effects induced by locoregional thermal ablation. The immune responses induced by ablation monotherapy are well documented, but independently they tend to be incapable of evoking a robust antitumor response. By adding immunomodulators to traditional ablative techniques, several researchers have sought to amplify the induced immune response and trigger systemic antitumor activity. This paper summarizes the work done in animal models to investigate the immune effects induced by the combination of ablative therapy and immunomodulation. Combination therapy with radiofrequency ablation, cryoablation, and microwave ablation are all reviewed, and special attention has been paid to the addition of checkpoint blockades.
Journal Article
Epidemiology, treatment and outcomes of gastroenteropancreatic neuroendocrine neoplasms
2024
To investigate incidence, treatment patterns and outcomes of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) in the United States. The 2019 National Cancer Database was searched for adult GEP-NEN patients. Main outcomes included overall and site-specific incidence, treatment patterns, and overall survival (OS). Overall survival was evaluated using averaged Cox regression. 86,324 GEP-NEN patients were included (6.33% of all GEP malignancies). From 2004 to 2016, annual GEP-NEN cases increased (
n
= 4,010 to
n
= 9,379), largely driven by low-stage, low-grade disease. Most patients received surgery, either alone (72.9%) or in combination with systemic therapy (4.9%). Longest overall survival (OS) was evident in patients with low stage and low grade GEP-NEN of the small intestine and rectum (
p
< 0.001). Patients undergoing surgical resection demonstrated longest OS. The addition of systemic therapy was most effective in high stage G3 NEN. Having higher income (
≥
$63,333) and private insurance or Medicare, but not Medicaid, was associated with improved survival. GEP-NEN incidence increases, likely due to improved detection and diagnosis. Treatment patterns have evolved to follow the latest international guidelines and site-specific improvement in survival is noted. In addition to disease specific factors, insurance access and socioeconomic factors emerged as potential targets for improving outcomes.
Journal Article
Development of a CNN+LSTM Hybrid Neural Network for Daily PM2.5 Prediction
2022
A CNN+LSTM (Convolutional Neural Network + Long Short-Term Memory) based deep hybrid neural network was established for the citywide daily PM2.5 prediction in South Korea. The structural hyperparameters of the CNN+LSTM model were determined through comprehensive sensitivity tests. The input features were obtained from the ground observations and GFS forecast. The performance of CNN+LSTM was evaluated by comparison with PM2.5 observations and with the 3-D CTM (three-dimensional chemistry transport model)-predicted PM2.5. The newly developed hybrid model estimated more accurate ambient levels of PM2.5 compared to the 3-D CTM. For example, the error and bias of the CNN+LSTM prediction were 1.51 and 6.46 times smaller than those by 3D-CTM simulation. In addition, based on IOA (Index of Agreement), the accuracy of CNN+LSTM prediction was 1.10–1.18 times higher than the 3-D CTM-based prediction. The importance of input features was indirectly investigated by sequential perturbing input variables. The most important meteorological and atmospheric environmental features were geopotential height and previous day PM2.5. The obstacles of the current CNN+LSTM-based PM2.5 prediction were also discussed. The promising result of this study indicates that DNN-based models can be utilized as an effective tool for air quality prediction.
Journal Article
Prospective longitudinal quality of life and survival outcomes in patients with advanced infiltrative hepatocellular carcinoma and portal vein thrombosis treated with Yttrium-90 radioembolization
2018
Background
To determine the effect of Yttrium-90 (Y90) radioembolization on health-related quality of life (HRQOL) and its effect on overall survival advanced, unresectable infiltrative hepatocellular carcinoma (HCC) patients with concurrent portal vein thrombosis (PVT).
Methods
Consecutive patients with unresectable infiltrative HCC and PVT were recruited. The Short-Form 36 (SF-36) questionnaire was used to assess HRQOL for consecutive patients treated with glass-based Y90 based on a prospective phase II trial. MR imaging was used to determine tumor progression every 3 months post-treatment. Overall survival (OS) from treatment and time to progression (TTP) was analyzed using Kaplan-Meier estimation and log-rank test.
Results
Thirty patients were treated and followed for 17.4 months; physical and mental component summary scores (PCS & MCS) remained unchanged at one, three, and six months. While no difference was observed in baseline SF-36 scores for patients with prolonged TTP (≥4 months) and OS (≥ 6 months), corresponding 1-month PCS were significantly higher than those with TTP < 4 months and OS < 6 months. At 1 month, patients with normalized Physical Function (PF), Role Physical (RP) and PCS within 2 standard deviations (SD) of US normalized baseline scores had a significantly prolonged median OS (15.7 vs. 3.7 months;
p
< 0.001) and TTP (12.4 vs. 1.8 mo;
p
< 0.001) compared those with physical component scores greater than 2SD below normalized US population values.
Conclusion
Y90 radioembolization for HCC demonstrated long-term preservation of HRQOL. Lower baseline HRQOL scores were predictive of poorer OS. Early (1 month post-treatment) significant decreases in PCS were independent predictors of poorer OS and TTP.
Trial registration
ClinicalTrials.gov identifier
NCT01556282
, registered March 16, 2012.
Journal Article
Epidemiology, treatment and outcomes of primary renal sarcomas in adult patients
2024
To assess epidemiology, clinical presentation, treatment and overall survival of adult patients with renal sarcomas, the 2004–2016 SEER and NCDB databases were queried for adult patients diagnosed with renal sarcoma, calculating average annual age-adjusted incidence rates (AAIR) and average annual percentage change (AAPC) as well as overall survival (OS). In n = 1279 included renal sarcoma patients, AAIR remained constant over the study period (average 0.53 cases/1million; AAPC = 0.7,
p
= 0.6). Leiomyosarcoma (AAIR 0.14 cases/1 million) and malignant rhabdoid tumors (0.06 cases/1 million) were most common. Sarcoma histiotypes demonstrated considerable heterogeneity regarding demographic and cancer-related variables. Patients presented with advanced local extent (T3 33.3%; T4 14.2%) or distant metastases (29.1%) and commonly underwent surgical resection (81.6%). Longer OS was independently associated with younger age, female sex, lower comorbidity index, low T stage, negative surgical margins, absence of tumor necrosis or distant metastases and leiomyosarcoma histiotype (multivariable
p
< 0.05 each). Treatment efficacy varied according to sarcoma histiotype (interaction
p
< 0.001). Accounting for 0.25% of renal malignancies, renal sarcomas include 43 histiotypes with distinct epidemiology, clinical presentation, outcomes and sensitivity to systemic therapy, thereby reflecting soft-tissue sarcoma behavior. Renal sarcoma treatment patterns follow recommendations by renal cancer guidelines with surgical resection as the cornerstone of therapy.
Journal Article
Stage IA papillary and chromophobe renal cell carcinoma: effectiveness of cryoablation and partial nephrectomy
2024
ObjectivesTo evaluate the effectiveness of cryoablation compared to partial nephrectomy in patients with stage IA papillary and chromophobe renal cell carcinoma (pRCC; chRCC).Material and methodsThe 2004–2016 National Cancer Database was queried for adult patients with stage IA pRCC or chRCC treated with cryoablation or partial nephrectomy. Patients receiving systemic therapy or radiotherapy, as well as those with bilateral RCC or prior malignant disease were excluded. Overall survival (OS) was assessed using Kaplan–Meier plots and Cox proportional hazard regression models. Nearest neighbor propensity matching (1:1 cryoablation:partial nephrectomy, stratified for pRCC and chRCC) was used to account for potential confounders.ResultsA total of 11122 stage IA renal cell carcinoma patients were included (pRCC 8030; chRCC 3092). Cryoablation was performed in 607 (5.5%) patients, and partial nephrectomy in 10515 (94.5%) patients. A higher likelihood of cryoablation treatment was observed in older patients with non-private healthcare insurance, as well as in those with smaller diameter low-grade pRCC treated at non-academic centers in specific US geographic regions. After propensity score matching to account for confounders, there was no statistically significant difference in OS comparing cryoablation vs partial nephrectomy in patients with pRCC (HR = 1.3, 95% CI: 0.96–1.75, p = 0.09) and those with chRCC (HR = 1.38, 95% CI: 0.67–2.82, p = 0.38).ConclusionAfter accounting for confounders, cryoablation, and partial nephrectomy demonstrated comparable OS in patients with stage IA papillary and chromophobe RCC. Cryoablation is a reasonable treatment alternative to partial nephrectomy for these histological RCC subtypes when radiologically suspected or diagnosed after biopsy.Critical relevance statementCryoablation might be considered as an upfront treatment alternative to partial nephrectomy in patients with papillary and chromophobe stage IA renal cell carcinoma, as both treatment approaches yield comparable oncological outcomes.Key PointsThe utilization of cryoablation for stage IA papillary and chromophobe RCC increases.In the National Cancer Database, we found specific patterns of use of cryoablation.Cryoablation and partial nephrectomy demonstrate comparable outcomes after accounting for confounders.
Journal Article
Inflammatory markers in intrahepatic cholangiocarcinoma: Effects of advanced liver disease
by
Uhlig, Johannes
,
Sellers, Cortlandt M.
,
Kim, Hyun S.
in
Aged
,
Bile Duct Neoplasms - blood
,
Bile Duct Neoplasms - mortality
2019
Background To investigate the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII) as prognostic biomarkers in intrahepatic cholangiocarcinoma (ICC) with a focus on viral hepatitis and liver status. Methods In this retrospective cohort study, patients from the institutional cancer registry with ICC from 2005 to 2016 were stratified by treatment group. Baseline inflammatory markers were dichotomized at the median. Overall survival (OS) was assessed via Kaplan‐Meier curves and Cox proportional hazard models. Multiple patient, liver, and tumor factors were included in the multivariable analysis (MVA). Results About 131 patients (median age 65 years, 52% male, 76% Caucasian) had a median OS of 13.0 months. Resection/interventional oncology with/without systemic therapy had improved survival vs systemic therapy alone in Child‐Pugh A patients (P < 0.01). In Child‐Pugh B/C patients, this survival difference became nonsignificant (P = 0.22). Increased NLR and SII were associated with decreased survival (P < 0.01), while dichotomized PLR was not (P = 0.3). On MVA, increased NLR remained an independent prognostic factor (HR 1.6, P < 0.05). In Child‐Pugh class A (n = 94), low‐NLR had higher OS vs high‐NLR (25.4 vs 12.2 months, P < 0.01). In Child‐Pugh class B/C (n = 28), NLR did not have a significant effect on median OS (low‐ vs high‐NLR: 6.7 vs 2.9 months, P = 0.2). Child‐Pugh class acted as an effect modifier on MVA for NLR (P = 0.0124). Conclusions The NLR has a stronger impact as a prognostic marker in ICC over the PLR and SII. This survival effect is decreased in advanced liver disease. The neutrophil‐to‐lymphocyte ratio (NLR) has the strongest impact as a prognostic marker in intrahepatic cholangiocarcinoma (ICC) versus the platelet‐to‐lymphocyte ratio and systemic immune‐inflammation index, and increased NLR is associated with decreased survival in ICC. The NLR has decreased prognostic utility in patients with advanced liver disease.
Journal Article
Development of a Hybrid Attention Transformer for Daily PM2.5 Predictions in Seoul
2025
A hybrid attention transformer (HAT) was developed for accurate daily PM2.5 predictions in Seoul. The performance of the HAT was evaluated through a comparative analysis of its predictions against ground-based observations and those from a three-dimensional chemical transport model (3-D CTM). The results demonstrated that the HAT outperformed the 3-D CTM, achieving a 4.60% higher index of agreement (IOA). Additionally, the HAT exhibited 22.09% fewer errors and 82.59% lower bias compared to the 3-D CTM. Diurnal variations in PM2.5 predictions from both models were also analyzed to explore the characteristics of the proposed model further. The HAT predictions closely aligned with observed PM2.5 throughout the day, whereas the 3-D CTM exhibited significant diurnal variability. The importance of the input features was evaluated using the permutation method, which revealed that the previous day’s PM2.5 was the most influential feature. The robustness of the HAT was further validated through a comparison with the long short-term memory (LSTM) model, which showed 18.50% lower errors and 95.91% smaller biases, even during El Niño events. These promising findings highlight the significant potential of the HAT as a cost-effective and highly accurate tool for air quality prediction.
Journal Article