Frontiers in Oncology
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2021 ◽  
Vol 11 ◽  
Author(s):  
Anusha Amaravathi ◽  
Janet L. Oblinger ◽  
D. Bradley Welling ◽  
A. Douglas Kinghorn ◽  
Long-Sheng Chang

The neurofibromatosis syndromes, including NF1, NF2, and schwannomatosis, are tumor suppressor syndromes characterized by multiple nervous system tumors, particularly Schwann cell neoplasms. NF-related tumors are mainly treated by surgery, and some of them have been treated by but are refractory to conventional chemotherapy. Recent advances in molecular genetics and genomics alongside the development of multiple animal models have provided a better understanding of NF tumor biology and facilitated target identification and therapeutic evaluation. Many targeted therapies have been evaluated in preclinical models and patients with limited success. One major advance is the FDA approval of the MEK inhibitor selumetinib for the treatment of NF1-associated plexiform neurofibroma. Due to their anti-neoplastic, antioxidant, and anti-inflammatory properties, selected natural compounds could be useful as a primary therapy or as an adjuvant therapy prior to or following surgery and/or radiation for patients with tumor predisposition syndromes, as patients often take them as dietary supplements and for health enhancement purposes. Here we review the natural compounds that have been evaluated in NF models. Some have demonstrated potent anti-tumor effects and may become viable treatments in the future.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yujie Li ◽  
Dengqiang Wu ◽  
Xuejia Yang ◽  
Sufang Zhou

Memory T cells include T memory stem cells (TSCM) and central memory T cells (TCM). Compared with effector memory T cells (TEM) and effector T cells (TEFF), they have better durability and anti-tumor immunity. Recent studies have shown that although TSCM has excellent self-renewal ability and versatility, if it is often exposed to antigens and inflammatory signals, TSCM will behave as a variety of inhibitory receptors such as PD-1, TIM-3 and LAG-3 expression, and metabolic changes from oxidative phosphorylation to glycolysis. These changes can lead to the exhaustion of T cells. Cumulative evidence in animal experiments shows that it is the least differentiated cell in the memory T lymphocyte system and is a central participant in many physiological and pathological processes in humans. It has a good clinical application prospect, so it is more and more important to study the factors affecting the formation of TSCM. This article summarizes and prospects the phenotypic and functional characteristics of TSCM, the regulation mechanism of formation, and its application in treatment of clinical diseases.


2021 ◽  
Vol 11 ◽  
Author(s):  
Hirva Mamdani ◽  
Bryan Schneider ◽  
Susan M. Perkins ◽  
Heather N. Burney ◽  
Pashtoon Murtaza Kasi ◽  
...  

BackgroundMost patients with resectable locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma (AC) receive concurrent chemoradiation (CRT) followed by esophagectomy. The majority of patients do not achieve pathologic complete response (pCR) with neoadjuvant CRT, and the relapse rate is high among these patients.MethodsWe conducted a phase II study (ClinicalTrials.gov Identifier: NCT02639065) evaluating the efficacy and safety of PD-L1 inhibitor durvalumab in patients with locally advanced esophageal and GEJ AC who have undergone neoadjuvant CRT followed by R0 resection with evidence of persistent residual disease in the surgical specimen. Patients received durvalumab 1500 mg IV every 4 weeks for up to 1 year. The primary endpoint was 1-year relapse free survival (RFS). Secondary endpoint was safety and tolerability of durvalumab following trimodality therapy. Exploratory endpoints included correlation of RFS with PD-L1 expression, HER-2 expression, and tumor immune cell population.ResultsThirty-seven patients were enrolled. The majority (64.9%) had pathologically positive lymph nodes. The most common treatment related adverse events were fatigue (27%), diarrhea (18.9%), arthralgia (16.2%), nausea (16.2%), pruritus (16.2%), cough (10.8%), and increase in AST/ALT/bilirubin (10.8%). Three (8.1%) patients developed grade 3 immune mediated adverse events. One-year RFS was 73% (95% CI, 56–84%) with median RFS of 21 months (95% CI, 14–40.4 months). Patients with GEJ AC had a trend toward superior 1-year RFS compared to those with esophageal AC (83% vs. 63%, p = 0.1534). There was a numerical trend toward superior 1-year RFS among patients with PD-L1 positive disease compared to those with PD-L1 negative disease, using CPS of ≥10 (100% vs. 66.7%, p = 0.1551) and ≥1 (84.2% vs. 61.1%, p = 0.1510) cutoffs. A higher relative proportion of M2 macrophages and CD4 memory activated T cells was associated with improved RFS (HR = 0.16; 95% CI, 0.05–0.59; p = 0.0053; and HR = 0.37; 95% CI, 0.15–0.93, p = 0.0351, respectively).ConclusionsAdjuvant durvalumab in patients with residual disease in the surgical specimen following trimodality therapy for locally advanced esophageal and GEJ AC led to clinically meaningful improvement in 1-year RFS compared to historical control rate. Higher PD-L1 expression may have a correlation with the efficacy of durvalumab in this setting. Higher proportion of M2 macrophages and CD4 memory activated T cells was associated with superior RFS.


2021 ◽  
Vol 11 ◽  
Author(s):  
Haochen Mou ◽  
Zhan Wang ◽  
Wenkan Zhang ◽  
Guoqi Li ◽  
Hao Zhou ◽  
...  

BackgroundSurgical therapy of breast cancer and bone metastasis can effectively improve the prognosis of breast cancer. However, after the first operation, the relationship between preoperative indicators and outcomes in patients who underwent metastatic bone surgery remained to be studied. Purpose 1. Recognize clinical and laboratory prognosis factors available to clinical doctors before the operation for bone metastatic breast cancer patients. 2. Develop a risk prediction model for 3-year postoperative survival in patients with breast cancer bone metastasis.MethodsFrom 2014 to 2020, patients who suffered from breast cancer bone metastasis and received therapeutic procedures in our institution were included for analyses (n=145). For patients who underwent both breast cancer radical surgery and bone metastasis surgery, comprehensive datasets of the parameters of interest (clinical features, laboratory factors, and patient prognoses) were collected (n=69). We performed Multivariate Cox regression to identify factors that were associated with postoperative outcome. 3-year survival prediction model and nomograms were established by 100 bootstrapping. Its benefit was evaluated by calibration plot, C-index, and decision curve analysis. The Surveillance, Epidemiology, and End Results database was also used for external validation.ResultsRadiotherapy for primary cancer, pathological type of metastatic breast cancer, lymph node metastasis, elevated serum alkaline phosphatase, lactate dehydrogenase were associated with postoperative prognosis. Pathological types of metastatic breast cancer, multiple bone metastasis, organ metastases, and elevated serum lactate dehydrogenase were associated with 3-year survival. Then those significant variables and serum alkaline phosphatase counts were integrated to construct nomograms for 3-year survival. The C-statistic of the established predictive model was 0.83. The calibration plot presents a graphical representation of calibration. In the decision curve analysis, the benefits are higher than those of the extreme curve. The receiver operating characteristic of the external validation of the model was 0.82, indicating a favored fitting degree of the two models.ConclusionOur study suggests that several clinical features and serological markers can predict the overall survival among the patients who are about to receive bone metastasis surgery after breast cancer surgery. The model can guide the preoperative evaluation and clinical decision-making for patients. Level of evidence Level III, prognostic study.


2021 ◽  
Vol 11 ◽  
Author(s):  
Shiqiang Ma ◽  
Jijun Tang ◽  
Fei Guo

Accurate automatic medical image segmentation technology plays an important role for the diagnosis and treatment of brain tumor. However, simple deep learning models are difficult to locate the tumor area and obtain accurate segmentation boundaries. In order to solve the problems above, we propose a 2D end-to-end model of attention R2U-Net with multi-task deep supervision (MTDS). MTDS can extract rich semantic information from images, obtain accurate segmentation boundaries, and prevent overfitting problems in deep learning. Furthermore, we propose the attention pre-activation residual module (APR), which is an attention mechanism based on multi-scale fusion methods. APR is suitable for a deep learning model to help the network locate the tumor area accurately. Finally, we evaluate our proposed model on the public BraTS 2020 validation dataset which consists of 125 cases, and got a competitive brain tumor segmentation result. Compared with the state-of-the-art brain tumor segmentation methods, our method has the characteristics of a small parameter and low computational cost.


2021 ◽  
Vol 11 ◽  
Author(s):  
Silin Chen ◽  
Ning Li ◽  
Yuan Tang ◽  
Bo Chen ◽  
Hui Fang ◽  
...  

PurposeTo create a prognostic prediction radiomics model for soft tissue sarcoma (STS) of the extremities and trunk treated with neoadjuvant radiotherapy.MethodsThis study included 62 patients with STS of the extremities and trunk who underwent magnetic resonance imaging (MRI) before neoadjuvant radiotherapy. After tumour segmentation and preprocessing, 851 radiomics features were extracted. The radiomics score was constructed according to the least absolute shrinkage and selection operator (LASSO) method. Survival analysis (disease-free survival; DFS) was performed using the log-rank test and Cox’s proportional hazards regression model. The nomogram model was established based on the log-rank test and Cox regression model. Harrell’s concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve analysis were used to evaluate the prognostic factors. The clinical utility of the model was assessed by decision curve analysis (DCA).ResultsThe univariate survival analysis showed that tumour location (p = 0.032), clinical stage (p = 0.022), tumour size (p = 0.005) and the radiomics score were correlated with DFS (p < 0.05). The multivariate analysis showed that tumour location, tumour size, and the radiomics score were independent prognostic factors for DFS (p < 0.05). The combined clinical-radiomics model based on the multivariate analysis showed the best predictive ability for DFS (C-index: 0.781; Area Under Curve: 0.791). DCA revealed that the use of the radiomics score-based nomogram was associated with better benefit gains relative to the prediction of 2-year DFS events than other models in the threshold probability range between 0.12 and 0.38.ConclusionThe radiomics score from pretreatment MRI is an independent prognostic factor for DFS in patients with STS of the extremities and trunk. The radiomics score-based nomogram could improve prognostic stratification ability and thus contribute to individualized therapy for STS patients.


2021 ◽  
Vol 11 ◽  
Author(s):  
Pai-Kai Chiang ◽  
Wei-Kung Tsai ◽  
Allen Wen-Hsiang Chiu ◽  
Jhen-Bin Lin ◽  
Feng-Yi Yang ◽  
...  

The changes in body composition are early adverse effects of androgen deprivation therapy (ADT); however, their prognostic impact remains unclear in prostate cancer. This study aimed to evaluate the association between body composition changes and survival in patients with high-risk prostate cancer. We measured the skeletal muscle index (SMI) and total adipose tissue index (TATI) at the L3 vertebral level using computed tomography at baseline and within one year after initiating ADT in 125 patients with high-risk prostate cancer treated with radiotherapy and ADT between 2008 and 2018. Non-cancer mortality predictors were identified using Cox regression models. The median follow-up was 49 months. Patients experienced an average SMI loss of 5.5% over 180 days (95% confidence interval: -7.0 to -4.0; p<0.001) and TATI gain of 12.6% over 180 days (95% confidence interval: 9.0 to 16.2; p<0.001). Body mass index changes were highly and weakly correlated with changes in TATI and SMI, respectively (Spearman ρ for TATI, 0.78, p<0.001; ρ for SMI, 0.27, p=0.003). As a continuous variable, each 1% decrease in SMI was independently associated with a 9% increase in the risk of non-cancer mortality (hazard ratio: 1.09; p=0.007). Moreover, the risk of non-cancer mortality increased 5.6-fold in patients with SMI loss ≥5% compared to those with unchanged SMI (hazard ratio: 5.60; p=0.03). Body mass index and TATI were not associated with non-cancer mortality. Muscle loss during ADT is occult, independent of weight change, and independently associated with increased non-cancer mortality in patients with high-risk prostate cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Junhao Wu ◽  
Yingwei Wang ◽  
Taiping Liao ◽  
Zijuan Rao ◽  
Weidong Gong ◽  
...  

PurposeThe present retrospective analysis sought to compare the relative diagnostic efficacy of [68Ga]Ga-DOTA-FAPI-04 to that of [18F]FDG PET/CT as a means of detecting bone metastases in patients with a range of cancer types.MaterialsIn total, 30 patients with bone metastases associated with different underlying malignancies were retrospectively enrolled. All patients had undergone [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT, and the McNemar test was used to compare the relative diagnostic performance of these two imaging modalities. The maximum standard uptake value (SUVmax) was used to quantify radiotracer uptake by metastatic lesions, with the relative uptake associated with these two imaging strategies being compared via the Mann-Whitney U test. The cohort was further respectively divided into two (osteolytic and osteoblastic bone metastases) and three clinical subgroups (lung cancer, thyroid cancer, and liver cancer).Results[68Ga]Ga-DOTA-FAPI-04 PET/CT was found to be significantly more sensitive as a means of diagnosing bone metastases relative to [18F]FDG PET/CT ([109/109] 100% vs [89/109] 81.7%; P< 0.01), consistent with the significantly increased uptake of [68Ga]Ga-DOTA-FAPI-04 by these metastatic lesions relative to that of [18F]FDG (n=109, median SUVmax, 9.1 vs. 4.5; P< 0.01). [68Ga]Ga-DOTA-FAPI-04 accumulation was significantly higher than that of [18F]FDG in both osteolytic (n=66, median SUVmax, 10.6 vs 6.1; P < 0.01), and osteoblastic metastases (n=43, median SUVmax, 7.7 vs 3.7; P < 0.01). [68Ga]Ga-DOTA-FAPI-04 uptakes were significantly higher than that of [18F]FDG in bone metastases from lung cancer (n = 62, median SUVmax, 10.7 vs 5.2; P < 0.01), thyroid cancer (n = 18, median SUVmax, 5.65 vs 2.1; P < 0.01) and liver cancer (n = 12, median SUVmax, 5.65 vs 3.05; P < 0.01). However, [68Ga]Ga-DOTA-FAPI-04 detected 10 false-positive lesions, while only 5 false-positive were visualized by [18F]FDG PET/CT.Conclusion[68Ga]Ga-DOTA-FAPI-04 PET/CT exhibits excellent diagnostic performance as a means of detecting bone metastases, and is superior to [18F]FDG PET/CT in this diagnostic context. Furthermore, [68Ga]Ga-DOTA-FAPI-04 tracer uptake levels are higher than those of [18F]FDG for most bone metastases. However, owing to the potential for false-positive bone lesions, it is critical that physicians interpret all CT findings with caution to ensure diagnostic accuracy.


2021 ◽  
Vol 11 ◽  
Author(s):  
Esperanza R. Matarredona ◽  
Natanael Zarco ◽  
Carmen Castro ◽  
Hugo Guerrero-Cazares

2021 ◽  
Vol 11 ◽  
Author(s):  
Foteinos-Ioannis D. Dimitrakopoulos ◽  
Anna G. Antonacopoulou ◽  
Anastasia E. Kottorou ◽  
Melpomeni Kalofonou ◽  
Nikolaos Panagopoulos ◽  
...  

BackgroundImmune system-related receptors CD40 (tumor necrosis factor receptor superfamily member 5), BAFFR (tumor necrosis factor receptor superfamily member 13C), and LTβR (tumor necrosis factor receptor superfamily member 3) play a pivotal role in non-small-cell lung cancer (NSCLC). To further evaluate their role in NSCLC, CD40 rs1883832 (T>C), BAFFR rs7290134 (A>G), and LTβR rs10849448 (A>G) single-nucleotide polymorphisms (SNPs) were investigated regarding their impact in risk and clinical outcome of NSCLC patients.MethodsThe three selected SNPs were evaluated in 229 NSCLC patients and 299 healthy controls, while CD40, BAFFR, and LTβR protein expression was assessed by immunohistochemistry in 96 tumor specimens from NSCLC patients.ResultsIn total, CD40 rs1883832 was associated with NSCLC risk, with the T allele, after adjusting for cofactors, being related to increased risk (p = 0.007; OR 1.701). Moreover, the CT genotype was associated with increased risk (p = 0.024; OR 1.606) and poorer 5-year overall survival (OS) after adjusting for cofactors (p = 0.001, HR 1.829), while CC was associated with higher CD40 expression in tumorous cells (p = 0.040) and in stromal cells (p = 0.036). In addition, AA homozygotes for the LTβR rs10849448 had increased risk for NSCLC in multivariate analysis (p = 0.008; OR, 2.106) and higher LTβR membranous expression (p = 0.035). Although BAFFR rs7290134 was associated with BAFFR membranous expression (p = 0.039), BAFFR rs7290134 was not associated with neither the disease risk nor the prognosis of NSCLC patients.ConclusionsIn conclusion, CD40 rs1883832 and LTβR rs10849448 seem to be associated with increased risk for NSCLC, while CD40 rs1883832 is also associated with OS of patients with NSCLC.


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