circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC).

BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

Genome-wide gene expression profiling of tongue squamous cell carcinoma by RNA-seq.

OBJECTIVE: Tongue squamous cell carcinoma (TSCC) is significantly more malignant than other type of oral squamous cell carcinoma (OSCC). In this study, we aimed to identify specific global gene expression signatures of TSCC to investigate the more invasive behavior of the deeply infiltrating cancer. METHODS: Using RNA-seq technology, we detected gene expression of 20 TSCCs, 20 matched paratumor tissues, and 10 healthy normal mucosa tissues. Enrichment analysis of gene ontology (GO) and pathway was conducted using online tools DAVID for the dysregulated genes. Additionally, we performed the quantitative real-time RT-PCR (qRT-PCR) to validate the findings of RNA-Seq in 10 samples of TSCC, matched paratumor, and normal mucosa, respectively. RESULTS: We detected 252 differentially expressed genes (DEGs) between TSCC and matched paratumor tissue, including 117 up-regulated and 135 down-regulated genes. For comparison between TSCC and normal mucosa, 234 DEGS were identified, consisting of 67 up-regulated and 167 down-regulated genes. For both two comparisons, GO categories of muscle contraction (GO: 0006936), epidermis development (GO: 0008544), epithelial cell differentiation (GO: 0030855), and keratinization (GO: 0031424) were commonly enriched. Altered gene expression affected some cancer-related pathways, such as tight junction. The qRT-PCR validation showed that gene expression patterns of FOLR1, NKX3-1, TFF3, PIGR, NEFL, MMP13, and HMGA2 were fully in concordance with RNA-Seq results. CONCLUSION: Findings in this study demonstrated the genetic and molecular alterations associated with TSCC, providing new clues for understanding the molecular mechanisms of TSCC pathogenesis.

[Effect of down-regulation of growth arrest and DNA damage inducible protein 45ß on PC9 lung adenocarcinoma cells].

OBJECTIVE: To explore the effect of down-regulation of growth arrest and DNA damage inducible protein 45ß (GADD45ß) on the PC9 lung adenocarcinoma cells.
 Methods: GADD45ß gene siRNA sequence was designed and synthesized, which was transfected into PC9 lung adenocarcinoma cells through lentivirus transfection. Quantitative real-time PCR (qRT-PCR) and Western blot are used to examine the mRNA and protein levels of GADD45ß in PC9 cells before and after the transfection. Annexin V-allophycocyanin (APC) double-staining flow cytometry was used to detect the apoptosis level after the transfection. The intracellular DNA content after transfection was detected by flow cytometry. The percentage of the cells at each period of cell cycle was calculated, and the effect of RNA interference on the cell growth were analyzed. The effects of RNA interference on the tumor-formation ability of cells were tested by counting the number of clones. MTT assay was used to test the half maximal inhibitory concentration (IC50) of PC9 cells for gefitinib. 
 Results: The 5'-AAATCCACTTCACGCTCAT-3' sequence was identified as the effective sequence for GADD45ß gene RNA interference. The mRNA and protein expression levels of GADD45ß were markedly decreased (both P<0.05) at 48 h after transfection of GADD45ß-siRNA, which resulted in the increased apoptosis rate (P<0.05), decreased tumor clone number (P<0.05) and increased percentage of PC9 cell at the S stage and G2/M stage (P<0.05). The IC50 for gefitinib was decreased obviously (P<0.05).
 Conclusion: Down-regulation of GADD45ß can reduce the colony-forming ability of PC9 cells, promote the cell apoptosis, and enhance the sensitivity of PC9 cells to gefitinib.

Economic evaluation of nivolumab as a second-line treatment for advanced renal cell carcinoma from US and Chinese perspectives.

BACKGROUND: Nivolumab is a new standard of care for patients with metastatic renal cell carcinoma (mRCC) and provides an overall survival benefit of 5.40 months in comparison with everolimus. This study evaluated the cost-effectiveness of nivolumab for the second-line treatment of mRCC from the perspective of US payers and identified the range of drug costs for which the addition of nivolumab to standard therapy could be considered cost-effective from a Chinese perspective. METHODS: A partitioned survival model was constructed to estimate lifetime costs, life-years, and quality-adjusted life-years (QALYs). Costs were estimated for the US and Chinese health care systems. One-way and probabilistic sensitivity analyses were performed. RESULTS: Nivolumab provided an additional 0.29 QALYs at a cost of $151,676/QALY in the United States. The probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of $100,000/QALY, at the current cost of nivolumab, the chance of nivolumab being cost-effective was 3.10%. For China, when nivolumab cost less than $7.90 or $9.70/mg, there was a nearly 90% likelihood that the incremental cost-effectiveness ratio for nivolumab would be less than $22,785 or $48,838/QALY, respectively. CONCLUSIONS: For the United States, nivolumab is unlikely to be a high-value treatment for mRCC at the current price, and a price reduction appears to be justified. In China, value-based prices for nivolumab are $7.90 and $9.70/mg for the country and Beijing City, respectively. This study could and should inform the multilateral drug-price negotiations in China that may be upcoming for nivolumab. Cancer 2017;123:2634-41. © 2017 American Cancer Society.

[Effect of jianpi-jiedu formula on tumor angiogenesis-relevant genes expression in colorectal cancer].

OBJECTIVE: To investigate the effect of the jianpi-jiedu formula (JPJD) on the expression of angiogenesis-relevant genes in colon cancer.
 Methods: Crude extract was obtained from JPJD by water extract method. The effect of JPJD crude extract on colon cancer cell proliferation capacity was determined by MTT assays. The IC50 value was calculated by GraphPad Prism5 software. Affymetrix gene expression profiling chip was used to detect significant differences in expressions of genes after JPJD intervention, and pathway enrichment analysis was performed to analyze the differentially expressed genes. Ingenuity Pathway Analysis software was applied to analyze differentially expressed genes relevant to tumor angiogenesis based on mammalian target of rapamycin (mTOR) signaling pathway and then the network diagram was built. Western blot was used to verify the protein levels of key genes related to tumor angiogenesis.
 Results: JPJD crud extract inhibited the proliferation capacity in colon cancer cells. The IC50 values in 24, 48, and 72 hours after treatment were 13.060, 9.646 and 8.448 mg/mL, respectively. The results of chip showed that 218 genes significantly upgraded, and 252 genes significantly downgraded after JPJD treatment. Most of the genes were related to the function of biosynthesis, metabolism, cell apoptosis, antigen extraction, angiogenesis and so on. There were 12 differentially expressed angiogenesis genes. IPA software analysis showed that the JPJD downregulated expression of sphingomyelin phosphodiesterase 3 (SMPD3), VEGF, vascular endothelial growth factor A (VEGFA), integrin subunit alpha 1 (ITGA1), cathepsin B (CTSB), and cathepsin S (CTSS) genes, while upregulated expressions of GAB2 and plasminogen activator, urokinase receptor (PLAUR) genes in the colorectal cancer cell. Western blot results demonstrated that JPJD obviously downregulated expressions of phospho-mTOR (P-mTOR), signal transducer and activator of transcription 3 (STAT3), hypoxia inducible factor-1α (HIF-1α), and VEGF proteins, while obviously upregulated the level of phospho-P53 (P-P53) protein.
 Conclusion: JPJD may inhibit colorectal tumor angiogenesis through regulation of the mTOR-HIF-1α-VEGF signal pathway.

[Inhibitory effect of jianpi-jiedu prescription-contained serum on colorectal cancer SW48 cell proliferation by mTOR-P53-P21 signalling pathway].

OBJECTIVE: To investigate the effect of jianpi-jiedu (JPJD) prescription-contained serum on colorectal cancer SW48 cell proliferation and the underlying mechanisms.
 Methods: Crude extract from JPJD was made by water extract method and the main components of crude extract from JPJD were analyzed by ultra-performance liquid phase high resolution time of flight mass spectrometry (UPLC-Q-TOF/MS). The low, medium, and high-concentration of JPJD-contained serum were prepared by the serum pharmacological method. The effect of serum containing JPJD on SW48 cell proliferation was determined by MTT assay. The cell cycle was detected by flow cytometric method. The protein levels of mammalian target of rapamycin (mTOR), phospho-mTOR, P-P53, and -P21, and the mRNA level of mTOR were examined by Western blot and RT-PCR, respectively.
 Results: Seven compounds including calycosin-7-glucoside, astragaloside, ginsenoside-Re, ginsenoside-Rb1, glycyrrhizinic acid, apigenin, atractylenolide-II were identified. MTT assays demonstrated that the SW48 cell proliferation was inhibited by medium and high concentration of JPJD-contained serum and the percentages of cells at G1 phase in SW48 cell cultured in the medium and high concentration of JPJD serum group were significantly higher than those in the control group (P<0.05). Meanwhile, the levels of mTOR mRNA and phospho-mTOR protein in the medium and high concentration of JPJD serum groups were substantially lower than those in the control group (P<0.05). Conversely, the expressions of phospho-P53 and P21 protein were significantly increased in the medium and high concentration of JPJD serum group compared with those in the control group.
 Conclusion: JPJD prescription-contained serum can inhibit SW48 cell proliferation, which may be related to mTOR-P53-P21 signaling pathways.

Disproportional signal of pericarditis with biological diseasemodifying antirheumatic drugs (bDMARDs) in patients with ankylosing spondylitis: a disproportionality analysis in the FAERS database.

Objective: This study aimed to investigate the potential association between biological disease-modifying antirheumatic drugs (bDMARDs) and pericarditis and uncover relevant clinical characteristics in ankylosing spondylitis (AS). Methods: Reports of pericarditis recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004-December 2022) were identified through the preferred term "pericarditis." Demographic and clinical characteristics were described, and disproportionality signals were assessed through the reporting odds ratio (ROR) and information component (IC). A significant signal was detected if the lower bound of IC (IC025) was more than zero. Results: We found 1,874 reports of pericarditis with bDMARDs (11.3% of cases with fatal outcomes). Adalimumab (IC025 3.24), infliximab (IC025 4.90), golimumab (IC025 5.40), certolizumab (IC025 5.43), etanercept (IC025 3.24), secukinumab (IC025 3.97), and ustekinumab (IC025 7.61) exhibit significant disproportionality signals compared to other medications in the FAERS database. After excluding pre-existing diseases and co-treated drugs that may increase the susceptibility of pericarditis, the disproportionality signal associated with infliximab, certolizumab, etanercept, secukinumab, and ustekinumab remained strong. Pericarditis cases associated with all bDMARDs were predominantly recorded in women aged 25-65 years. Conclusion: More reports of pericarditis were detected with AS patients on bDMARDs than with other drugs in the overall database. Further studies are warranted to investigate the underlying mechanisms and identify patient-related susceptibility factors, thus supporting timely diagnosis and safe(r) prescribing of bDMARDs.

Nedaplatin-based chemotherapy or cisplatin-based chemotherapy combined with intensity-modulated radiotherapy achieve similar efficacy for stage II-IVa nasopharyngeal carcinoma patients.

This retrospective study compared the efficacy and safety of nedaplatin-based chemoradiotherapy and cisplatin-based chemoradiotherapy in stage II-IVa nasopharyngeal carcinoma (NPC) patients. Patients treated with cisplatin-based or nedaplatin-based chemoradiotherapy between January 2012 and December 2015 were evaluated. Survival was estimated by the Kaplan‒Meier method and compared by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model. A cohort of 538 NPC patients was enrolled. There were no significant differences in the 5-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), or distant metastasis-free survival (DMFS) between the cisplatin and nedaplatin groups. During the whole treatment course, patients in the cisplatin group had higher incidences of grade 3‒4 vomiting and anorexia, while patients in the nedaplatin group had higher incidences of grade 3‒4 leucopenia and mucositis. In terms of late toxicities, patients in the cisplatin group had a higher incidence of xerostomia. In multivariate analysis, T stage, N stage, and clinical stage were prognostic factors for OS, PFS, and DMFS. In subgroup analyses, nedaplatin-based chemotherapy achieved comparable treatment outcomes in specific populations stratified by age, sex, ECOG PS score and clinical stage. Cisplatin and nedaplatin are effective choices for stage II-IVa NPC patients, with a different spectrum of side effects.

Corrigendum: Alpha Thalassemia/Intellectual Disability X-Linked Deficiency Sensitizes Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors.

[This corrects the article DOI: 10.3389/fonc.2020.608300.].

The Role of the SOX9/lncRNA ANXA2P2/miR-361-3p/SOX9 Regulatory Loop in Cervical Cancer Cell Growth and Resistance to Cisplatin.

Cervical cancer is a highly prevalent female malignancy. Presently, cisplatin (DDP) is a first-line agent for cervical cancer chemotherapy. However, its curative effect is limited because of chemo-resistance. It has been previously reported that SOX9 targeted and activated oncogenic genes, enhancing cervical cancer cell resistance to DDP. The effects of the SOX9/lncRNA ANXA2P2/miR-361-3p/SOX9 regulatory loop on cervical cancer cell growth and resistance to DDP have been demonstrated. miR-361-3p expression was decreased in DDP-resistant cervical cancer cells and tissues. Moreover, miR-361-3p overexpression inhibited the growth of resistant cervical cancer cells and the resistance to DDP, whereas miR-361-3p inhibition exerted opposite effects. miR-361-3p inhibited SOX9 expression through binding; the effects of miR-361-3p inhibition were partially reversed by SOX9 knockdown. LncRNA ANXA2P2 expression was elevated in DDP-resistant cervical cancer cells and tissues. LncRNA ANXA2P2 inhibited miR-361-3p expression by binding, thereby upregulating SOX9. LncRNA ANXA2P2 knockdown inhibited DDP-resistant cervical cancer cell growth and resistance to DDP, whereas the effects of lncRNA ANXA2P2 knockdown were partially reversed by miR-361-3p inhibition. SOX9 expression was elevated in DDP-resistant cervical cancer cells and tissues, and SOX9 activated lncRNA ANXA2P2 transcription by binding. Collectively, SOX9, lncRNA ANXA2P2, and miR-361-3p form a regulatory loop, modulating DDP-resistant cervical cancer cell growth and response to DDP treatment.

Systemic Inflammation Response Index (SIRI) Independently Predicts Survival in Advanced Lung Adenocarcinoma Patients Treated with First-Generation EGFR-TKIs.

BACKGROUND: Systemic inflammation response index (SIRI) has been reported to be an effective blood-based biomarker for predicting prognosis in various kinds of cancer patients. However, the prognostic role of SIRI in advanced lung adenocarcinoma patient remains unclear. METHODS: The aim of the present study is to evaluate the prognostic role of SIRI in EGFR-mutant advanced lung adenocarcinoma patients treated with first-generation EGFR-TKIs. A total of 245 patients who received gefitinib, erlotinib, or icotinib at the Second Xiangya Hospital were retrospectively evaluated. SIRI was defined as neutrophil count×monocyte/lymphocyte count. The optimal cut-off value was determined according to receiver operation characteristic curve analysis. Characteristics of patients were compared via chi-square test or Fisher's exact test. Survivals were estimated by the Kaplan-Meier method and compared by the Log rank test. Multivariate analysis was estimated using the Cox proportional hazards model. RESULTS: It is showed that high SIRI was associated with male patient, smoker, worse ECOG PS, 19-DEL mutation. Kaplan-Meier survival analysis showed that ECOG PS, brain metastasis, SIRI were significantly correlated with progression-free survival (PFS), and gender, ECOG PS, brain metastasis, NLR and SIRI were significantly correlated with overall survival (OS). Multivariate analysis showed that SIRI and ECOG PS independently predict PFS and OS. CONCLUSION: Our findings indicate that SIRI is an effective and convenient marker for predicting prognosis in advanced EGFR-mutant lung adenocarcinoma patients treated with first-generation TKI.

Cancer vaccines: Targeting KRAS-driven cancers.

Introduction: Mutant KRAS is a genetic driver of multiple cancers that has challenged clinical anti-cancer therapeutics in the last 3 decades. Neo-antigens encoded by KRAS mutations have been identified as tumor-specific with high immunogenicity and can be used to deliver precision cancer vaccines to promote anti-tumor immune responses. KRAS mutation-based cancer vaccines have produced encouraging preclinical and clinical results. Cancer vaccines represent a promising approach to treat KRAS-driven cancers.Areas covered: In this review, we summarize the development and progress of vaccines targeting KRAS and evaluate their potential benefits and obstacles in the current landscape of therapy for KRAS-driven cancers.Expert opinion: KRAS mutation-based cancer vaccines can induce immunogenicity in patients with KRAS-driven cancers. However, the mechanisms of tumor suppression including cellular and molecular factors within the tumor microenvironment may limit vaccine efficacy. Combining KRAS-driven therapeutic cancer vaccines with other methods and adjuvants can circumvent immunosuppression and promote therapeutic successes.

Guillain-Barre syndrome induced by pembrolizumab and sunitinib: A case report.

Pembrolizumab, an immune checkpoint inhibitor against the programmed death-1 pathway, has been used in combination with acitinib for the first-line treatment of advanced renal cell carcinoma. Neurotoxicity is a rare immune-related adverse event (irAE). The present study reports a case of Guillain-Barre syndrome (GBS) induced by pembrolizumab and sunitinib, and reviews other previous studies to elucidate the clinical characteristics and suitable management of this rare irAE. An advanced renal cell carcinoma patient who received several cycles of pembrolizumab combined with sunitinib developed limb weakness and numbness of the extremities, and was diagnosed with GBS by electrodiagnostic and cerebrospinal fluid examination. The patient improved after treatment with intravenous immunoglobulin along with prednisone. To the best of our knowledge, this is the first case of GBS during treatment with pembrolizumab in combination with sunitinib in advanced renal cell carcinoma.

A promising treatment option for refractory male primary choriocarcinoma: report of two cases.

Male primary choriocarcinoma is a rare and invasive malignant neoplasm for which traditional chemotherapy has limited efficacy. Pembrolizumab is a humanized monoclonal anti-programmed death-1 antibody that has antitumor activity in numerous malignancies. The diagnosis and treatment of two cases of advanced male primary choriocarcinoma were retrospectively analyzed and relevant literature was reviewed to discuss the prognosis and the efficacy of different treatments, including pembrolizumab. The first patient, who presented with cough and hemoptysis, was diagnosed with primary mediastinal choriocarcinoma. He initially responded to the first-line chemotherapy of etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine, but eventually developed brain metastases. The patient did not respond to the second-line chemotherapy comprising paclitaxel and cisplatin, and he died 6.5 months after diagnosis. The second patient experienced repeated episodes of abdominal pain and was diagnosed with primary neck choriocarcinoma. He received chemotherapy regimens similar to those of the first patient. However, imaging showed no significant changes and his clinical symptoms were not improved. Immunohistochemistry showed that the expression of programmed death ligand 1 on the tumor cells was 40%, and he was administered pembrolizumab combined with chemotherapy. He achieved complete response and was subsequently switched to pembrolizumab maintenance monotherapy. He is still alive without evidence of disease 36 months after diagnosis. To our knowledge, this is the first case of advanced male primary choriocarcinoma successfully treated with pembrolizumab combined with chemotherapy. Advanced male primary choriocarcinoma is highly aggressive and insensitive to chemotherapy. Pembrolizumab may provide a promising treatment option to improve patient outcomes.

Alpha Thalassemia/Intellectual Disability X-Linked Deficiency Sensitizes Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors.

BACKGROUND: The immune checkpoint inhibitors (ICIs) have achieved great success in the treatment of non-small cell lung cancer (NSCLC) patients. However, the response rate is low. The molecular mechanism involved in the effectiveness of ICIs remains to be elucidated. METHODS: ATRX mutation incidence among human cancers was analyzed from TCGA database. Atrx-deficient Lewis lung cancer cell line (LLC-sgAtrx) was established via AAV-CRISPR. Subcutaneous and metastasis models were established by subcutaneous and intravenous injection of LLC-sgAtrx and LLC-sgNTC cells into female C57BL/6 mice. The mice were treated with anti-PD1, anti-CLTA4 or Rat IgG2a. Tumor volume was determined by Vernier calipers and the IVIS imaging system. The proportions of CD3+ T cells, CD45+ immune cells, and the expression of pMHC I and PDL1 were determined by flow cytometry. The T cell cytotoxicity was determined by co-culture experiment. RESULTS: TCGA data showed that Atrx is a tumor suppressor mutated at high frequency among various human cancers. The tumor volume of mice bearing LLC-sgAtrx was significantly shrinked and the median survival of mice was significantly longer after anti-PD1 and anti-CTLA4 treatment. Flowcytometry results showed that Atrx deficiency increase the penetration of CD3+ T cell into the tumor microenvironment and enhanced antigen presentation after IFNγ stimulation. Additionally, the tumor cells with Atrx deficiency were more easily to be damaged by T cells under IFNγ stimulation. CONCLUSION: The present study demonstrated that Atrx deficiency sensitize lung cancer cells to ICIs by multiple mechanisms. And ATRX may serve as a promising biomarker for ICIs which helps patient stratification and decision making.

Systemic Inflammation Response Index Is a Predictor of Poor Survival in Locally Advanced Nasopharyngeal Carcinoma: A Propensity Score Matching Study.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a common malignancy in China and known prognostic factors are limited. In this study, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) were evaluated as prognostic factors in locally advanced NPC patients. MATERIALS AND METHODS: NPC patients who received curative radiation or chemoradiation between January 2012 and December 2015 at the Second Xiangya Hospital were retrospectively reviewed, and a total of 516 patients were shortlisted. After propensity score matching (PSM), 417 patients were eventually enrolled. Laboratory and clinical data were collected from the patients' records. Receiver operating characteristic curve analysis was used to determine the optimal cut-off value. Survival curves were analyzed using the Kaplan-Meier method. The Cox proportional hazard model was used to identify prognostic variables. RESULTS: After PSM, all basic characteristics between patients in the high SIRI group and low SIRI group were balanced except for sex (p=0.001) and clinical stage (p=0.036). Univariate analysis showed that NLR (p=0.001), PLR (p=0.008), SII (p=0.001), and SIRI (p<0.001) were prognostic factors for progression-free survival (PFS) and overall survival (OS). However, further multivariate Cox regression analysis showed that only SIRI was an independent predictor of PFS and OS (hazard ratio (HR):2.83; 95% confidence interval (CI): 1.561-5.131; p=0.001, HR: 5.19; 95% CI: 2.588-10.406; p<0.001), respectively. CONCLUSION: Our findings indicate that SIRI might be a promising predictive indicator of locally advanced NPC patients.

Concordance Study Between IBM Watson for Oncology and Real Clinical Practice for Cervical Cancer Patients in China: A Retrospective Analysis.

Watson for Oncology (WFO) is a artificial intelligence clinical decision-support system with evidence-based treatment options for oncologists. WFO has been gradually used in China, but limited reports on whether WFO is suitable for Chinese patients. This study aims to investigate the concordance of treatment options between WFO and real clinical practice for Cervical cancer patients retrospectively. We retrospectively enrolled 300 cases of cervical cancer patients. WFO provides treatment options for 246 supported cases. Real clinical practice were defined as concordant if treatment options were designated "recommended" or "for consideration" by WFO. Concordance of treatment option between WFO and real clinical practice was analyzed statistically. The treatment concordance between WFO and real clinical practice occurred in 72.8% (179/246) of cervical cancer cases. Logistic regression analysis showed that rural registration residences, advanced age, poor ECOG performance status, stages II-IV disease have a remarkable impact on consistency. The main reasons attributed to the 27.2% (67/246) of the discordant cases were the substitution of nedaplatin for cisplatin, reimbursement plan of bevacizumab, surgical preference, and absence of neoadjuvant/adjuvant chemotherapy and PD-1/PD-L1 antibodies recommendations. WFO recommendations were in 72.8% of concordant with real clinical practice for cervical cancer patients in China. However, several localization and individual factors limit its wider application. So, WFO could be an essential tool but it cannot currently replace oncologists. To be rapidly and fully apply to cervical cancer patients in China, accelerate localization and improvement were needed for WFO.