A deep learning-based semiautomated workflow for triaging follow-up MR scans in treated nasopharyngeal carcinoma.

It is imperative to optimally utilize virtues and obviate defects of fully automated analysis and expert knowledge in new paradigms of healthcare. We present a deep learning-based semiautomated workflow (RAINMAN) with 12,809 follow-up scans among 2,172 patients with treated nasopharyngeal carcinoma from three centers (ChiCTR.org.cn, Chi-CTR2200056595). A boost of diagnostic performance and reduced workload was observed in RAINMAN compared with the original manual interpretations (internal vs. external: sensitivity, 2.5% [p = 0.500] vs. 3.2% [p = 0.031]; specificity, 2.9% [p < 0.001] vs. 0.3% [p = 0.302]; workload reduction, 79.3% vs. 76.2%). The workflow also yielded a triaging performance of 83.6%, with increases of 1.5% in sensitivity (p = 1.000) and 0.6%-1.3% (all p < 0.05) in specificity compared to three radiologists in the reader study. The semiautomated workflow shows its unique superiority in reducing radiologist's workload by eliminating negative scans while retaining the diagnostic performance of radiologists.

Genetic alterations in LEP and ADIPOQ genes and risk for breast cancer: a meta-analysis.

Introduction: Breast cancer has a strong genetic predisposition, and its genetic architecture is not fully understood thus far. In this study, we aimed to perform a meta-analysis to evaluate the association of genetic alterations in LEP and ADIPOQ genes, as well as their receptor-encoded genes with risk for breast cancer. Methods: Only published studies conducted in humans and written in English were identified by searching PubMed, SCOPUS, CINAHIL and Embase from their inception to October 2022. Eligibility assessment and data collection were completed independently by two researchers. Statistical analyses were done using the STATA software. Results: After literature search, 33 publications were eligible for inclusion. Overall, LEP gene rs7799039-G allele (odds ratio [OR]: 0.78, 95% confidence interval [CI]: 0.62 to 0.98) and ADIPOQ gene rs1501299-T allele (OR: 1.41, 95% CI: 1.06 to 1.88) were associated with the significant risk of breast cancer. In subgroup analyses, differences in menopausal status, obesity, race, study design, diagnosis of breast cancer, genotyping method and sample size might account for the divergent observations of individual studies. Circulating leptin levels were comparable across genotypes of LEP gene rs7799039, as well as that of LEPR gene rs1137101 (P>0.05). Begg's funnel plots seemed symmetrical, with the exception of LEPR gene rs1137100 and ADIPOQ gene rs1501299. Discussion: Taken together, we found, in this meta-analysis, that LEP gene rs7799039 and ADIPOQ gene rs1501299 were two promising candidate loci in predisposition to breast cancer risk.

Add-on individualizing prediction of nasopharyngeal carcinoma using deep-learning based on MRI: A multicentre, validation study.

In nasopharyngeal carcinoma, deep-learning extracted signatures on MR images might be correlated with survival. In this study, we sought to develop an individualizing model using deep-learning MRI signatures and clinical data to predict survival and to estimate the benefit of induction chemotherapy on survivals of patients with nasopharyngeal carcinoma. Two thousand ninety-seven patients from three independent hospitals were identified and randomly assigned. When the deep-learning signatures of the primary tumor and clinically involved gross cervical lymph nodes extracted from MR images were added to the clinical data and TNM staging for the progression-free survival prediction model, the combined model achieved better prediction performance. Its application is among patients deciding on treatment regimens. Under the same conditions, with the increasing MRI signatures, the survival benefits achieved by induction chemotherapy are increased. In nasopharyngeal carcinoma, these prediction models are the first to provide an individualized estimation of survivals and model the benefit of induction chemotherapy on survivals.

Artificial intelligence for assisting cancer diagnosis and treatment in the era of precision medicine.

Over the past decade, artificial intelligence (AI) has contributed substantially to the resolution of various medical problems, including cancer. Deep learning (DL), a subfield of AI, is characterized by its ability to perform automated feature extraction and has great power in the assimilation and evaluation of large amounts of complicated data. On the basis of a large quantity of medical data and novel computational technologies, AI, especially DL, has been applied in various aspects of oncology research and has the potential to enhance cancer diagnosis and treatment. These applications range from early cancer detection, diagnosis, classification and grading, molecular characterization of tumors, prediction of patient outcomes and treatment responses, personalized treatment, automatic radiotherapy workflows, novel anti-cancer drug discovery, and clinical trials. In this review, we introduced the general principle of AI, summarized major areas of its application for cancer diagnosis and treatment, and discussed its future directions and remaining challenges. As the adoption of AI in clinical use is increasing, we anticipate the arrival of AI-powered cancer care.

hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression.

BACKGROUND: Systematic profiling studies have implicated regulators of pre-mRNA splicing as important disease determinants in gastric cancer (GC), but the underlying mechanisms have remained elusive. Here we focused on hnRNPA2B1 splicing factor-dependent mechanisms governing GC development. METHODS: The expression of hnRNPA2B1 was analyzed among the Cancer Genome Atlas (TCGA) datasets of GC and validated at mRNA level. The function of hnRNPA2B1 in GC cells was analyzed and its downstream gene was identified using RNA immunoprecipitation. Further, effect of hnRNPA2B1 on BIRC5 alternative splicing was investigated. RESULTS: We show that overexpression of hnRNPA2B1 in GC is correlated with poor survival, and hnRNPA2B1 is required for maintaining GC malignant phenotype by promoting cell proliferation, inhibiting cell apoptosis and increasing cell metastasis. Mechanistically, hnRNPA2B1 co-expressed with several core spliceosome components and controls alternative splicing of anti-apoptotic factor BIRC5. BIRC5 isoform 202 (BIRC5-202) played the oncogenic function in GC cells, and overexpression of the BIRC5-202 transcript partly rescued the decrease in cisplatin resistance induced by downregulation of hnRNPA2B1. CONCLUSIONS: We demonstrate that hnRNPA2B1 regulates BIRC5 splicing and might act as a therapeutic target of chemo-resistant GC cells.

3-D RoI-Aware U-Net for Accurate and Efficient Colorectal Tumor Segmentation.

Segmentation of colorectal cancerous regions from 3-D magnetic resonance (MR) images is a crucial procedure for radiotherapy. Automatic delineation from 3-D whole volumes is in urgent demand yet very challenging. Drawbacks of existing deep-learning-based methods for this task are two-fold: 1) extensive graphics processing unit (GPU) memory footprint of 3-D tensor limits the trainable volume size, shrinks effective receptive field, and therefore, degrades speed and segmentation performance and 2) in-region segmentation methods supported by region-of-interest (RoI) detection are either blind to global contexts, detail richness compromising, or too expensive for 3-D tasks. To tackle these drawbacks, we propose a novel encoder-decoder-based framework for 3-D whole volume segmentation, referred to as 3-D RoI-aware U-Net (3-D RU-Net). 3-D RU-Net fully utilizes the global contexts covering large effective receptive fields. Specifically, the proposed model consists of a global image encoder for global understanding-based RoI localization, and a local region decoder that operates on pyramid-shaped in-region global features, which is GPU memory efficient and thereby enables training and prediction with large 3-D whole volumes. To facilitate the global-to-local learning procedure and enhance contour detail richness, we designed a dice-based multitask hybrid loss function. The efficiency of the proposed framework enables an extensive model ensemble for further performance gain at acceptable extra computational costs. Over a dataset of 64 T2-weighted MR images, the experimental results of four-fold cross-validation show that our method achieved 75.5% dice similarity coefficient (DSC) in 0.61 s per volume on a GPU, which significantly outperforms competing methods in terms of accuracy and efficiency. The code is publicly available.

Crowe Type IV Hip Dysplasia Treated by THA Comebined with Osteotomy to Balance Functional Leg Length Discrepancy: A Prospective Observational Study.

OBJECTIVE: To measure the factors that affect functional leg length of Crowe type IV Developmental dysplasia of the hip (DDH) patients and to review our own methods to balance leg length discrepancy (LLD) in Crowe type IV DDH patients. METHODS: This was a prospective observational study which started in June 2017 and ended in August 2019. Inclusion criteria included: (i) Crowe type I or Crowe type IV hip dysplasia patients who underwent total hip arthroplasty (THA) in the Department of Orthopaedics at our institution between July 2017 and June 2018; (ii) the patients were treated with our specific leg length balance strategy; and (iii) the related outcomes of patients were completely recorded. Finally, 18 consecutive Crowe type I patients (20 hips) and 14 consecutive Crowe type IV patients (18 hips) were selected and divided into two groups according to Crowe types. All patients received THA, and patients with a longer affected side and inferior anatomical acetabular positions in Crowe type IV group also received subtrochanteric osteotomy. During operation and after hip reduction, leg lengths were compared while two legs were in an extended position and the operative leg was on top of the non-operative one. Additional leg length adjustment was applied when leg length was considered to be unequal. Prior to surgery, subluxation height of the femoral head on the affected side, functional LLD, bony length of lower limbs, and distance from teardrops to the lowest point line of the sacroiliac joint were recorded. After surgery, cup sizes, functional LLD, and height of hip rotational centers were measured. Clinical evaluations, such as Harris Hip Score (HHS) and SF-12 scale, were also obtained before and after surgery for all patients. RESULTS: At the last follow-up, functional LLD and clinical measurements of both Crowe type IV group and Crowe type I group were significantly improved. Compared with Crowe type I patients, Crowe type IV patients had a significantly lower MCS, a significantly longer leg lengthening length and a significantly lower hip center height after surgery. Significant differences of tibia length, leg length, and teardrop position were found between affected side and healthy side of Crowe type IV patients. Only three of 14 Crowe type IV patients remained under 1 cm functional LLD. Five patients in the Crowe type IV group developed lower limb numbness immediately following surgery, and they all recovered within 6 months. The average follow-up period for either group was 14 months, and all patients were followed-up at 1, 3, 6, and 12 months then yearly after surgery until the final follow-up. CONCLUSION: After detailed leg length balance process, THA combined with transverse sub-trochanter osteotomy could be an effective method to achieve equal function leg length with most Crowe type IV patients.

hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing.

BACKGROUND: The high prevalence of alternative splicing among genes implies the importance of genomic complexity in regulating normal physiological processes and diseases such as gastric cancer (GC). The standard form of stem cell marker CD44 (CD44S) and its alternatives with additional exons are reported to play important roles in multiple types of tumors, but the regulation mechanism of CD44 alternative splicing is not fully understood. METHODS: Here the expression of hnRNPK was analyzed among the Cancer Genome Atlas (TCGA) cohort of GC. The function of hnRNPK in GC cells was analyzed and its downstream targeted gene was identified by chromatin immunoprecipitation and dual luciferase report assay. Finally, effect of hnRNPK and its downstream splicing regulator on CD44 alternative splicing was investigated. RESULTS: The expression of hnRNPK was significantly increased in GC and its upregulation was associated with tumor stage and metastasis. Loss-of-function studies found that hnRNPK could promote GC cell proliferation, migration, and invasion. The upregulation of hnRNPK activates the expression of the splicing regulator SRSF1 by binding to the first motif upstream the start codon (- 65 to - 77 site), thereby increasing splicing activity and expression of an oncogenic CD44 isoform, CD44E (has additional variant exons 8 to 10, CD44v8-v10). CONCLUSION: These findings revealed the importance of the hnRNPK-SRSF1-CD44E axis in promoting gastric tumorigenesis.

Total Hip Arthroplasty for Crowe Type IV Hip Dysplasia: Surgical Techniques and Postoperative Complications.

Total hip arthroplasty (THA) of Crowe type IV developmental dysplasia of the hip (DDH) is challenging. Although traditional (lateral, posterolateral, and posterior) THA approaches have been used with great anatomic success, they damage periarticular muscles, which are already quite weak in type IV DDH. The recently developed direct anterior approach (DAA) can provide an inter-nerve and inter-muscle approach for THA of type IV dysplasia hips. However, femur exposure with the DAA could be difficult during surgery and it is hard to apply femoral shortening osteotomy. THA techniques used for type IV DDH include anatomic hip center techniques (true acetabular reconstruction) and high hip center techniques, wherein an acetabulum is reconstructed above the original one. Although anatomic construction of the hip center is considered "the gold standard" treatment, it is impossible if the anatomical acetabular is too small and shallow. Procedures used to support type IV DDH reduction with anatomic hip center techniques include greater trochanter osteotomy, lesser trochanter osteotomy, and subtrochanteric osteotomy. However, these techniques have yet to be standardized, and it is unclear which is best for type IV DDH. One-state and two-state non-osteotomy reduction techniques have also been introduced to treat type IV DDH. Potential complications of THA performed in patients with type IV DDH include leg length discrepancy (LLD), peri-operative femur fracture, nonunion of the osteotomy site, and nerve injury. It is worth noting that nowadays an increasing number of Crowe type IV DDH patients are more sensitive to postoperative LLD.

Development and implementation of a dynamically updated big data intelligence platform from electronic health records for nasopharyngeal carcinoma research.

OBJECTIVE: To develop a big data intelligence platform for secondary use of electronic health records (EHRs) data to facilitate research for nasopharyngeal cancer (NPC). METHODS: This project was launched in 2015 and carried out by the cooperation of an academic cancer centre and a technology company. Patients diagnosed with NPC at Sun Yat-sen University Cancer Centre since January 2008 were included in the platform. Standard data elements were established to defined 981 variables for the platform. For each patient, data from 13 EHRs systems were extracted, integrated, structurized and normalized. Eight functional modules were constructed for the platform to facilitate the investigators to identify eligible patients, establish research projects, conduct statistical analysis, track the follow-up, search literature, etc. RESULTS: From January 2008 to December 2018, 54,703 patients diagnosed with NPC were included. Of these patients, 39,058 (71.4%) were male, and 15,645 (28.6%) were female; median age was 47 (interquartile range, 39-55) years. Of 981 variables, 341 were obtained from data structurization and normalization, of which 68 were generated by interacting multiple data sources via well-defined logical rules. The average precision rate, recall rate and F-measure for 341 variables were 0.97 ± 0.024, 0.92 ± 0.030, and 0.94 ± 0.027 respectively. The platform is regularly updated every seven days to include new patients and add new data for existing patients. Up to now, eight big data-driven retrospective studies have been published from the platform. CONCLUSION: Our big data intelligence platform demonstrates the feasibility of integrating EHRs data of routine healthcare, and offers an important perspective on real-world study of NPC. The continued efforts may be focus on data sharing among multiple hospitals and publicly releasing of data files. ADVANCES IN KNOWLEDGE: Our big data intelligence platform is the first disease-specific data platform for NPC research. It incorporates comprehensive EHRs data from routine healthcare, which can facilitate real-world study of NPC in risk stratification, decision-making and comorbidities management.

Preoperative Planning for Total Hip Arthroplasty for Neglected Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH) is accompanied by morphological alterations on both the acetabular and the femoral side. Total hip arthroplasty (THA) provides effective treatment in cases of neglected DDH but requires elaborate preoperative planning. To determine the morphological changes resulting from the dysplasia, the anatomic acetabular position, the height of the femur head dislocation, the height of the femur head dislocation, and the combined anteversion must all be established. In addition, a vital and complicated process of strategizing leg length balance must be conducted in cases of severe DDH. Each type of leg length discrepancy (LLD), including bony and functional and anatomical LLD, should be evaluated in the context of the presence or absence of a fixed pelvic tilt. Moreover, with severe unilateral dislocated hips, a more inferior change in the original rotational center of the hip must be accounted for. Due to these multiple morphological changes, the accurate size of the prosthesis and the cup position are difficult to predict. In comparison with other methods, CT scan-based 3-dimensional templating provides the best accuracy. Despite the presence of anatomic alterations, various types of acetabular and femoral prostheses have been developed to treat hip dysplasia. Both cemented and cementless cups are used in DDH cases. In DDH accompanied by insufficient acetabular bone stock, a cemented cup combined with bone graft provides a reliable treatment. Monoblock stems can be used when the combined anteversion is less than 55°, and a modular stem system when this parameter is greater than 55°. Customized stems can be designed for DDH coupled with severe proximal femoral distortion. A ceramic-on-ceramic bearing is considered optimal for young DDH patients.

Pretreatment MRI radiomics analysis allows for reliable prediction of local recurrence in non-metastatic T4 nasopharyngeal carcinoma.

BACKGROUND: To identify a radiomics signature to predict local recurrence in patients with non-metastatic T4 nasopharyngeal carcinoma (NPC). METHODS: A total of 737 patients from Sun Yat-sen University Cancer Center (training cohort: n = 360; internal validation cohort: n = 120) and Wuzhou Red Cross Hospital (external validation cohort: n = 257) underwent feature extraction from the largest axial area of the tumor on pretreatment magnetic resonance imaging scans. Feature selection was based on the prognostic performance and feature stability in the training cohort. Radscores were generated using the Cox proportional hazards regression model with the selected features in the training cohort and then validated in the internal and external validation cohorts. We also constructed a nomogram for predicting local recurrence-free survival (LRFS). FINDINGS: Eleven features were selected to construct the Radscore, which was significantly associated with LRFS. For the training, internal validation, and external validation cohorts, the Radscore (C-index: 0.741 vs. 0.753 vs. 0.730) outperformed clinical prognostic variables (C-index for primary gross tumor volume: 0.665 vs. 0.672 vs. 0.577; C-index for age: 0.571 vs. 0.629 vs. 0.605) in predicting LRFS. The generated radiomics nomogram, which integrated the Radscore and clinical variables, exhibited a satisfactory prediction performance (C-index: 0.810 vs. 0.807 vs. 0.753). The nomogram-defined high-risk group had a shorter LRFS than did the low-risk group (5-year LRFS: 73.6% vs. 95.3%, P < .001; 79.6% vs 95.8%, P = .006; 85.7% vs 96.7%, P = .005). INTERPRETATION: The Radscore can reliably predict LRFS in patients with non-metastatic T4 NPC, which might guide individual treatment decisions. FUND: This study was funded by the Health & Medical Collaborative Innovation Project of Guangzhou City, China.

[Expanded curettage and bone cement filling combined with internal fixation for the treatment of Campanacci III giant cell tumour of knee joint].

OBJECTIVE: To evaluate clinical effects of expanded curettage and bone cement filling combined with internal fixation in treating Campanacci III giant cell tumor of knee joint. METHODS: From January 2006 to December 2016, 21 patients with Campanacci III giant cell tumor of knee joint were treated by expanded curettage and bone cement filling combined with internal fixation, including 11 males and 10 females with an average age of(35.24±10.56) years old (ranged from 21 to 61 years old). The courses of disease ranged from 1.5 to 24.0 months with an average of(8.1±4.4) months. Among them, 8 patients were distal femur and 13 patients were proximal tibia. All patients were primary tumors. Musculoskeletal Tumor Society(MSTS) scores were used to evaluate lower limb function before and after operation. X-ray was used to observe healing of lesions and the occurrence of adverse reactions. RESULTS: All incisions were healed at grade A without complications such as infection and internal fixation failure. All patients were followed up from 8 to 56 months with an average of (29.62±9.48) months. MSTS score at the latest follow-up 26.71±2.35 was higher than that of before operation 15.24±1.14, and had statistical significance(t=20.160, P=0.000). The results of X-ray at final following-up showed internal fixation was well, and no loosening and fracture of subchondral bone. Three patients recurred giant cell tumor and replaced with tumor prosthesis. CONCLUSIONS: Expanded curettage and bone cement filling with internal fixation for the treatment of Campanacci III giant cell tumor of knee joint could effectively retain limb function and reduce tumor recurrence rate.

Universal screening for Lynch syndrome in a large consecutive cohort of Chinese colorectal cancer patients: High prevalence and unique molecular features.

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.

Beneficial effects of anti-EGFR agents, Cetuximab or Nimotuzumab, in combination with concurrent chemoradiotherapy in advanced nasopharyngeal carcinoma.

OBJECTIVE: This study aimed to evaluate the efficacy and safety in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) plus Cetuximab (CTX) or Nimotuzumab (NTZ) compared to those receiving induction chemotherapy (IC) plus CCRT. MATERIALS AND METHODS: From January 2008 to December 2013, 715 eligible patients were enrolled in the study. Using propensity scores to adjust for gender, age, Karnofsky performance status (KPS), tumor stage, node stage, and clinical stage, a well-balanced cohort was created by matching each patient who received CTX/NTZ plus CCRT (137 patients) with two patients who underwent IC plus CCRT (274 patients). The primary endpoint was overall survival (OS), and other outcome variables included disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional relapse-free survival (LRRFS). RESULTS AND CONCLUSION: The median follow-up was 57.0 months and 55.0 months for the CTX/NTZ plus CCRT group and IC plus CCRT group, respectively. No significant differences were found between the CTX/NTZ plus CCRT group and the IC plus CCRT group in 3-year OS (95.5% vs. 94.7%, P = 0.083), 3-year DFS (93.3% vs. 86.1%, P = 0.104), 3-year DMFS (96.2% vs. 92.5%, P = 0.243) and 3-year LRRFS (97.0% vs. 95.1%, P = 0.297). Patients undergoing IC plus CCRT suffered from severe hematologic toxicity and diarrhea compared with those treated with CTX/NTZ plus CCRT. The combination of CTX/NTZ with CCRT is comparable to IC plus CCRT treatment in survival outcomes for locoregionally advanced NPC patients but has a better safety profile than IC plus CCRT treatment.

A small heat shock protein 21 (sHSP21) mediates immune responses in Chinese oak silkworm Antheraea pernyi.

Small heat shock proteins (sHSPs) are conserved among insects and play an important role in the regulation of many biological processes, including temperature stress, abiotic stress, immune responses, metamorphosis, and embryo development. Antheraea pernyi is an economically valuable silk-producing moth and source of insect food containing high-quality protein. The aim of this study was to quantify expression of the ApsHSP21 gene in response to pathogen-associated molecular patterns (PAMPs) and nucleopolyhedrovirus (NPV) challenge. The deduced ApsHSP21 protein sequence consists of 186 residues with a calculated molecular mass of 21.0 kDa and an isoelectronic point (pI) of 6.63. The protein contains a conserved α-crystallin domain (ACD), and includes two casein kinase II phosphorylation sites, a protein kinase C phosphorylation site, two tyrosine kinase phosphorylation sites, and various polypeptide binding sites. Phylogenetic analysis revealed that ApsHSP21 is closely related to homologs from other insects. Real-time quantitative reverse transcription PCR (qRT-PCR) analysis revealed that expression of ApsHSP21 was significantly up-regulated at different timepoints following simulated pathogen challenge with lipopolysaccharide (LPS), peptidoglycan (PGN), glucan, and NPV. The results suggest sHSP21 is involved in innate immune responses in A. pernyi.

Pretreatment Serum Amyloid A and C-reactive Protein Comparing with Epstein-Barr Virus DNA as Prognostic Indicators in Patients with Nasopharyngeal Carcinoma: A Prospective Study.

PURPOSE: The measuring Epstein-Barr virus (EBV) DNA is an important predictor of nasopharyngeal carcinoma (NPC). This study evaluated the predictive value of pretreatment serum amyloid A (SAA) and C-reactive protein (CRP) comparing with EBV DNA in patients with NPC. MATERIALS AND METHODS: In an observational study of 419 non-metastatic NPC patients, we prospectively evaluated the prognostic effects of pretreatment SAA, CRP, and EBV DNA on survival. The primary endpoint was progress-free survival (PFS). RESULTS: The median level of SAA and CRP was 4.28 mg/L and 1.88 mg/L, respectively. For the highSAA group (> 4.28 mg/L) versus the low-SAA (≤ 4.28 mg/L) group and the high-CRP group (> 1.88 mg/L) versus the low-CRP (≤ 1.88 mg/L) group, the 5-year PFS was 64.5% versus 73.1% (p=0.013) and 65.2% versus 73.3% (p=0.064), respectively. EBV DNA detection showed a superior predictive result, the 5-year PFS in the EBV DNA ≥ 1,500 copies/mL group was obviously different than the EBV DNA < 1,500 copies/mL group (62.2% versus 77.8%, p < 0.001). Multifactorial Cox regression analysis confirmed that in the PFS, the independent prognostic factors were including EBV DNA (hazard ratio [HR], 1.788; p=0.009), tumour stage (HR, 1.903; p=0.021), and node stage (HR, 1.498; p=0.049), but the SAA and CRP were not included in the independent prognostic factors. CONCLUSION: The results of SAA and CRP had a certain relationship with the prognosis of NPC, and the prognosis of patients with high level of SAA and CRP were poor. However, the predictive ability of SAA and CRP was lower than that of EBV DNA.

Concurrent Chemoradiotherapy with or without Anti-EGFR-Targeted Treatment for Stage II-IVb Nasopharyngeal Carcinoma: Retrospective Analysis with a Large Cohort and Long Follow-up.

We examined the benefits of the combination of anti-EGFR targeted treatment, cetuximab (CTX) or nimotuzumab (NTZ) and concurrent platinum-based chemoradiotherapy (CCRT) compared with CCRT alone in patients with stage II - IVb nasopharyngeal carcinoma (NPC). A total of 1,628 eligible patients with stage II - IVb NPC, who received CCRT (three cycles of 100 mg/m2 cisplatin every 3 weeks with intensity-modulated radiotherapy) with or without CTX or NTZ between June 2009 and December 2013 were included in the analysis. Using propensity scores to adjust for potential prognostic factors, a well-balanced cohort of 878 patients was created by matching each patient who received CTX or NTZ plus CCRT with no more than four patients who received CCRT alone (1:4). Efficacy and safety were compared between CTX/NTZ plus CCRT and CCRT alone arms. Compared with CCRT alone, treatment with CTX/NTZ plus CCRT was associated with a significantly increased overall survival (3-year OS, 96.6% vs. 92.9%, P = 0.015), improved disease-free survival (3-year DFS, 93.5% vs 86.9%, P = 0.028), and improved distant metastasis-free survival (3-year DMFS, 94.6% vs 89.3%, P = 0.030). Increased rate of CTX related-skin reaction and mucositis was observed in the CTX plus CCRT arm. Multivariate analysis demonstrated the combination of CTX/NTZ was a significant protective factor for OS, DFS, and DMFS in patients treated with CCRT. Our analysis suggests that the addition of CTX/NTZ to CCRT is more effective for maximizing survival in patients with stage II-IVb NPC compared with CCRT alone.