A prospective, single-arm trial of PD-1 inhibitors plus chemoradiotherapy for solitary metachronous metastasis nasopharyngeal carcinoma.

PURPOSE: Initial treatment for Recurrent/Metastatic Nasopharyngeal Carcinoma (R/M NPC) often involves Gemcitabine plus cisplatin with or without PD-1 inhibitors. However, PD-1 inhibitors' effectiveness varies, prompting for better treatments. This study explores effect and safety of combining PD-1 inhibitors with chemoradiotherapy for oligometastatic NPC patients. METHODS: Oligometastatic NPC patients underwent radical treatment with PD-1 inhibitors and chemotherapy, followed by concurrent PD-1 inhibitors and chemoradiotherapy, and then maintenance PD-1 inhibitors. Objective response rate (ORR) and disease control rate (DCR) were calculated by irRECIST-1.1, and CTCAE-4.0 was used to evaluate the toxicity. RESULTS: The study enrolled 47 patients with a median age of 46. The median follow-up lasted 16.5 months, with metastatic lesions receiving a median radiation dose of 45 Gy. The median courses of PD-1 inhibitors and chemotherapy were 9.5 and 5 respectively. The metastasis sites included lung (40.8 %), liver (21.1 %), mediastinal lymph node (7.9 %), abdominal lymph nodes (3.9 %), bone (21.1 %), adrenal gland (3.9 %), and brain (1.3 %). ORR and DCR were 85.1 % and 100 % at 3 months after radiotherapy. The median survival was not reached yet, and 1 and 2-year OS rates were 93.1 % and 78.4 %. The median PFS was 18 months, with 1 and 2-year PFS rates of 70.2 % and 47.7 % respectively. PD-L1 expression showed a positive correlation for PFS. Twenty-five patients experienced grade 3 or 4 adverse events (AE) that were possibly related to chemotherapy. No grade 5 AE was observed. CONCLUSIONS: The synergy of concurrent PD-1 inhibitors and chemoradiotherapy shows promising efficacy and an acceptable toxicity for oligometastasis NPC patients.

A promising predictive biomarker combined EBV NDA with PNI for nasopharyngeal carcinoma in nonendemic area of China.

In endemic areas, EBV DNA is used to guide diagnosis, detect recurrence and distant metastasis of NPC. Until now, the importance of EBV DNA in the prediction of NPC has received little attention in non-endemic regions. To explore the prognostic value of EBV DNA alone or in combination with PNI in NPC patients from a non-endemic area of China. In this retrospective study, 493 NPC patients were enrolled. Clinical pathologic data, pre-treatment plasma EBV DNA, and laboratory tests were all performed. A standard anticancer treatment was prescribed, and follow up data were collected. EBV DNA was found to be positively related to clinical stage (r = 0.357, P < 0.001), T stage (r = 0.193, P < 0.001), N stage (r = 0.281, P < 0.001), and M stage (r = 0.215, P < 0.001). The difference in EBV DNA loads between clinical stage, T, N and M stage was statistically significant (P < 0.001). In this study, the best cutoff value for EBV-DNA to distinguish the prognosis of NPC was 262.7 copies/ml. The 5-year OS of patients in the EBV-DNA ≤ 262.7 copies/ml group and EBV-DNA > 262.7 copies/ml group was 88% and 65.3%, respectively (P < 0.001). EBV-DNA and PNI were found to be independent prognostic factors for OS in multivariate analysis (P < 0.05). EBV-DNA was independent prognostic factors for PFS. In predicting NPC patients OS, the novel combination marker of EBV DNA and PNI outperformed TNM staging (AUC: 0.709 vs. 0.675). In addition, the difference between EBV + PNI and EBV + TNM was not statistically significant for OS or PFS (P > 0.05). This novel combination biomarker was a promising biomarker for predicting NPC survival and may one day guide treatment option.

Initial analysis of the synergy of programmed cell death-1 (PD-1) inhibitor and concurrent chemoradiotherapy treatment for recurrent/metastatic head and neck squamous cell carcinoma patients.

BACKGROUND: Programmed cell death-1 (PD-1) inhibitor was proven to be useful for the recurrent/metastatic head and neck squamous carcinoma (R/M HNSCC) patients. Though both PD-1 inhibitor alone and combination with chemotherapy showed some benefit for PFS and OS, the survival outcome was still not satisfactory. Some studies showed the possible benefit for PD-1 inhibitors combination with radiation for head and neck squamous carcinoma, however there was few studies concerned about synergy of concurrent PD-1 inhibitor combination with chemoradiotherapy for R/M HNSCC. So, we aimed to explore the potential effect and toxicity of the concurrent PD-1 inhibitor and chemoradiotherapy for R/M HNSCC. METHODS: We consecutively enrolled the R/M HNSCC patients treated with concurrent PD-1 inhibitor and chemoradiotherapy from August 2018 to April 2022 in Sichuan Cancer hospital. All the patients received the combination of PD-1 inhibitor and chemotherapy, and followed with synergy of concurrent PD-1 inhibitor and chemoradiotherapy, then maintenance PD-1 inhibitor. ORR and DCR was calculated by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST-1.1), and Common terminology criteria for adverse events (CTCAE-4.0) was used to evaluate the toxicity.The Kaplan-Meier method was used to analyze OS and PFS. RESULTS: 40 R/M HNSCC patients were enrolled in our stuty. The median follow up time was 14 months. 22 patients had recurrent disease only, 16 patients had metastatic disease only, and 2 patients had both recurrence and metastasis disease. For the recurrent lesions, 23 patients received a median radiation dose of 64 Gy (range 50-70 Gy). 18 patients received a median dose of 45 Gy (range 30-66 Gy) for metastatic lesions. The median courses of PD-1 inhibitors and chemotherapy were 8 and 5 respectively. After the treatment, the ORR and DCR were 70.0% and 100%. The median OS was 19 months (range 6.3-31.7 months), with 1 and 2-years OS rates of 72.8% and 33.3%. The median PFS was 9 months (range 3.1-14.9 months), with 6 and 12 months PFS rates of 75.5% and 41.4% respectively. The PFS had no statistical significance in PD-L1 negative and positive group (7 vs 12 months, p = 0.059). The most common grade 3 or 4 adverse events(AE) were leucopenia (25.0%), neutropenia (17.5%), anemia (10.0%), thrombocytopenia (5.0%), hyponatremia (2.5%), and pneumonia(2.5%). No grade 5 AE was observed. CONCLUSIONS: The synergy of concurrent PD-1 inhibitor treatment with chemoradiotherapy shows promise as a treatment strategy and an acceptable toxicity for the R/M HNSCC patients.

Recurrent/metastatic head and neck squamous carcinoma (R/M HNSCC) patients face limited treatment choices and poor prognosis. As a new treatment method, immune checkpoint inhibitor plays an important role for the R/M HNSCC patients recently. However, there were still some controversies for the combination of chemoradiotherapy and immunotherapy, such as timing, radiation dose, fractionation, and et al. In our study, the synergy of concurrent chemoradiotherapy with PD-1 inhibitor showed a promising results for the R/M HNSCC patients, with improved objective response rate (ORR) (70.0%, 95% CI 55.8% to 84.2%) and disease control rate (DCR) (100%, 95% CI 100% to 100%). The median progression-free survival (PFS) and overall survival (OS) were prolonged to 9 months (range 3.1­14.9 months) and 19 months (range 6.3­31.7 months) respectively. The toxicity was tolerable during the treatment, the total incidence rate of grade 3 or 4 adverse events were 65%, similar with other study.

Preoperative diagnosis of solitary pulmonary nodules with a novel hematological index model based on circulating tumor cells.

Objective: Preoperative noninvasive diagnosis of the benign or malignant solitary pulmonary nodule (SPN) is still important and difficult for clinical decisions and treatment. This study aimed to assist in the preoperative diagnosis of benign or malignant SPN using blood biomarkers. Methods: A total of 286 patients were recruited for this study. The serum FR+CTC, TK1, TP, TPS, ALB, Pre-ALB, ProGRP, CYFRA21-1, NSE, CA50, CA199, and CA242 were detected and analyzed. Results: In the univariate analysis, age, FR+CTC, TK1, CA50, CA19.9, CA242, ProGRP, NSE, CYFRA21-1, and TPS showed the statistical significance of a correlation with malignant SPNs (P <0.05). The highest performing biomarker is FR+CTC (odd ratio [OR], 4.47; 95% CI: 2.57-7.89; P <0.001). The multivariate analysis identified that age (OR, 2.69; 95% CI: 1.34-5.59, P = 0.006), FR+CTC (OR, 6.26; 95% CI: 3.09-13.37, P <0.001), TK1 (OR, 4.82; 95% CI: 2.4-10.27, P <0.001), and NSE (OR, 2.06; 95% CI: 1.07-4.06, P = 0.033) are independent predictors. A prediction model based on age, FR+CTC, TK1, CA50, CA242, ProGRP, NSE, and TPS was developed and presented as a nomogram, with a sensitivity of 71.1% and a specificity of 81.3%, and the AUC was 0.826 (95% CI: 0.768-0.884). Conclusions: The novel prediction model based on FR+CTC showed much stronger performance than any single biomarker, and it can assist in predicting benign or malignant SPNs.

Automatic tumor segmentation and metachronous single-organ metastasis prediction of nasopharyngeal carcinoma patients based on multi-sequence magnetic resonance imaging.

Background: Distant metastases is the main failure mode of nasopharyngeal carcinoma. However, early prediction of distant metastases in NPC is extremely challenging. Deep learning has made great progress in recent years. Relying on the rich data features of radiomics and the advantages of deep learning in image representation and intelligent learning, this study intends to explore and construct the metachronous single-organ metastases (MSOM) based on multimodal magnetic resonance imaging. Patients and methods: The magnetic resonance imaging data of 186 patients with nasopharyngeal carcinoma before treatment were collected, and the gross tumor volume (GTV) and metastatic lymph nodes (GTVln) prior to treatment were defined on T1WI, T2WI, and CE-T1WI. After image normalization, the deep learning platform Python (version 3.9.12) was used in Ubuntu 20.04.1 LTS to construct automatic tumor detection and the MSOM prediction model. Results: There were 85 of 186 patients who had MSOM (including 32 liver metastases, 25 lung metastases, and 28 bone metastases). The median time to MSOM was 13 months after treatment (7-36 months). The patients were randomly assigned to the training set (N = 140) and validation set (N = 46). By comparison, we found that the overall performance of the automatic tumor detection model based on CE-T1WI was the best (6). The performance of automatic detection for primary tumor (GTV) and lymph node gross tumor volume (GTVln) based on the CE-T1WI model was better than that of models based on T1WI and T2WI (AP@0.5 is 59.6 and 55.6). The prediction model based on CE-T1WI for MSOM prediction achieved the best overall performance, and it obtained the largest AUC value (AUC = 0.733) in the validation set. The precision, recall, precision, and AUC of the prediction model based on CE-T1WI are 0.727, 0.533, 0.730, and 0.733 (95% CI 0.557-0.909), respectively. When clinical data were added to the deep learning prediction model, a better performance of the model could be obtained; the AUC of the integrated model based on T2WI, T1WI, and CE-T1WI were 0.719, 0.738, and 0.775, respectively. By comparing the 3-year survival of high-risk and low-risk patients based on the fusion model, we found that the 3-year DMFS of low and high MSOM risk patients were 95% and 11.4%, respectively (p < 0.001). Conclusion: The intelligent prediction model based on magnetic resonance imaging alone or combined with clinical data achieves excellent performance in automatic tumor detection and MSOM prediction for NPC patients and is worthy of clinical application.

Clinical relevance of plasma EBV DNA as a biomarker for nasopharyngeal carcinoma in non-endemic areas: A multicenter study in southwestern China.

BACKGROUND: Numerous clinical studies have validated plasma EBV DNA as a reliable biomarker for nasopharyngeal carcinoma (NPC) screening, tumor load monitoring, and prognosis prediction in endemic regions. However, the clinical relevance of plasma EBV DNA as a biomarker for NPC in non-endemic areas is still unclear. METHOD: The pretreatment plasma EBV DNA of 1405 newly diagnosed NPC patients from three major regional hospitals in non-endemic areas were analyzed retrospectively. The medical records of 244 age- and gender-matched healthy individuals were reviewed. EBV DNA was detected using Polymerase Chain Reaction (PCR). Based on the baseline of 400 and 0 copies/mL, the distribution characteristics of the pretreatment EBV DNA load in different clinical stages and geographic regions were analyzed. The diagnostic value of pretreatment plasma EBV DNA for NPC with two baselines was evaluated using the ROC curve. RESULTS: NPC patients had a significantly higher pretreatment EBV DNA level than healthy controls (P＜0.001). Pretreatment EBV DNA was closely associated with clinical and TNM stages in non-endemic areas, as it was in endemic areas. However, when 400 copies/mL set as the detection baseline, the sensitivity and specificity for NPC diagnosis were 40.8 % and 100 %, respectively (AUC = 0.704, cut off = 200.5 copies/mL). This sensitivity was lower than that reported in endemic regions (41.5 % - 97.1 %). Lower sensitivity may result in false negatives, missing diagnoses during NPC screening. Further investigation revealed that 39.7 % (558/1405) of NPC patients had detectable EBV DNA and S amplification curves. Optimizing the detection limit to 0 copies/mL, the sensitivity could be improved to 80.5 % (AUC = 0.901). CONCLUSIONS: In non-endemic areas, the clinical significance of plasma EBV DNA as a biomarker for NPC was restricted due to the low detection limit of 400 copies/mL. More efficient nucleic acid extraction and detection methods are needed to optimize the detection limit and increase the clinical application of plasma EBV DNA for NPC.

Stereotactic radiosurgery with whole brain radiotherapy combined with bevacizumab in the treatment of brain metastases from NSCLC.

OBJECTIVE: Non-small cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. Whole-brain radiotherapy (WBRT) is one of the standard treatment strategies for NSCLC. It is interesting to combine angiogenesis inhibitors such as bevacizumab with radiation therapy. This study aimed to explore the efficacy and safety of stereotactic radiosurgery (SRS) with WBRT combined with bevacizumab in the treatment of brain metastases. METHODS: A total of 21 patients with brain metastases from NSCLC were treated with bevacizumab and WBRT-SRS, while 28 patients were treated with WBRT-SRS only. The bevacizumab average dose was 5-7.5 mg/kg, approximately 2 cycles during radiotherapy. Tumor responses were evaluated every 3 months based on Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: The median follow-up time was 13.5 months (range 2.7-88.4 months). The ORR and DCR of patients who received WBRT-SRS with or without bevacizumab were similar (p = 0.458, p = 0.382). OS(42.63 years VS 25.23 years, p = 0.02)and LPFS (39.53 years VS 23 years, p = 0.047)were better in WBRT-SRS with bevacizumab groups. After radiotherapy and 3 months after radiotherapy, the volume of peritumoral edema was significantly reduced in WBRT-SRS with bevacizumab groups(45.62 ± 24.03 cm3 vs 63.03 ± 25.44 cm3, p = 0.036;8.63 ± 6.87 cm3 vs 15.62 ± 10.58 cm3, p = 0.021). The main adverse reactions were similar in the two groups except for Venous thrombosis with bevacizumab (0 patients vs 5 patients, p = 0.006). CONCLUSION: Bevacizumab with radiotherapy improved the overall efficacy and reduced the peritumoral edema of BM from NSCLC.

FJX1 as a candidate diagnostic and prognostic serum biomarker for colorectal cancer

Purpose: Colorectal cancer (CRC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of CRC. The aim of the present study was to screen candidate biomarkers in diagnosis and prognosis of CRC based on a novel strategy.Materials and methodsThe expression level of gene higher in cancer than in adjacent non-cancer tissue was defined as “positive”, and the top 10% genes with “positive rate” were filtered out as candidate diagnostic biomarkers in four Gene Expression Omnibus (GEO) datasets. Then, the prognostic value of candidate biomarkers was estimated Cox regression analysis. Moreover, the concentration of biomarker in serum was detected in CRC patients.ResultsEighteen candidate biomarkers were identified with efficient diagnostic value in CRC. As a prognostic biomarker, FJX1 (four-jointed box kinase 1) showed a good performance in predicting overall survivals in CRC patients. In serum levels, FJX1 showed high sensitivity and specificity in distinguishing CRC patients from controls, and the concentration of serum FJX1 was associated with distant metastasis in CRC. In addition, serum FJX1 was significantly decreased after surgery in CRC patients. Compared with traditional CRC biomarkers CEA and CA 19-9, FJX1 still showed good efficiency in diagnosis and prognosis. Moreover, inhibition of FJX1 expression by siRNA or neutralization of secreted FJX1 by antibody could suppress cell proliferation and migration in vitro.ConclusionOur findings provided a novel strategy to identify diagnostic biomarkers based on public datasets, and suggested that FJX1 was a candidate diagnostic and prognostic biomarker in CRC patients. (AU)

FJX1 as a candidate diagnostic and prognostic serum biomarker for colorectal cancer.

PURPOSE: Colorectal cancer (CRC) is one of the most common cancer worldwide. It is essential to identify non-invasive diagnostic and prognostic biomarkers of CRC. The aim of the present study was to screen candidate biomarkers in diagnosis and prognosis of CRC based on a novel strategy. MATERIALS AND METHODS: The expression level of gene higher in cancer than in adjacent non-cancer tissue was defined as "positive", and the top 10% genes with "positive rate" were filtered out as candidate diagnostic biomarkers in four Gene Expression Omnibus (GEO) datasets. Then, the prognostic value of candidate biomarkers was estimated Cox regression analysis. Moreover, the concentration of biomarker in serum was detected in CRC patients. RESULTS: Eighteen candidate biomarkers were identified with efficient diagnostic value in CRC. As a prognostic biomarker, FJX1 (four-jointed box kinase 1) showed a good performance in predicting overall survivals in CRC patients. In serum levels, FJX1 showed high sensitivity and specificity in distinguishing CRC patients from controls, and the concentration of serum FJX1 was associated with distant metastasis in CRC. In addition, serum FJX1 was significantly decreased after surgery in CRC patients. Compared with traditional CRC biomarkers CEA and CA 19-9, FJX1 still showed good efficiency in diagnosis and prognosis. Moreover, inhibition of FJX1 expression by siRNA or neutralization of secreted FJX1 by antibody could suppress cell proliferation and migration in vitro. CONCLUSION: Our findings provided a novel strategy to identify diagnostic biomarkers based on public datasets, and suggested that FJX1 was a candidate diagnostic and prognostic biomarker in CRC patients.

Predictive Value of Preoperative Neutrophil-to-Lymphocyte Ratio in Patients with Hepatocellular Carcinoma after Transarterial Chemoembolization Combined With Radiofrequency Ablation.

PURPOSE: To determine the predictive value of preoperative inflammatory markers in hepatocellular carcinoma (HCC) prognosis after transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA). MATERIALS AND METHODS: A total of 161 patients with HCC who underwent TACE combined with RFA were enrolled in this retrospective study. Receiver operating characteristic (ROC) curve analysis was used to decide the cutoff value of the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), the platelet-to-lymphocyte ratio (PLR), and the prognostic nutritional index (PNI). The relationship between preoperative NLR, LMR, PLR, PNI, and survival outcomes was analyzed using Kaplan-Meier curves and multivariate Cox regression analyses. RESULTS: The cutoff value of NLR for the best discrimination of HCC prognosis was 2.95. The median recurrence-free survival (RFS) of the low NLR (≤2.95) group was longer than that of the high NLR (>2.95) group (29 months vs. 20 months, p = 0.013). The median overall survival (OS) of the low NLR group was longer than that of the high NLR group (60 months vs. 38 months, p = 0.006). Multivariate analysis showed that the tumor size (≤3 cm vs. >3cm), tumor number (single vs. multiple), and NLR (≤2.95 vs. >2.95) were independent predictors of the PFS and OS. LMR, PLR, and PNI did not have any prognostic significance. CONCLUSION: NLR was confirmed as an independent predictive biomarker for hepatocellular carcinoma prognosis after TACE combined with RFA.

Dosimetric analysis of radiation-induced brainstem necrosis for nasopharyngeal carcinoma treated with IMRT.

BACKGROUND: Radiation-induced brainstem necrosis (RIBN) is a late life-threatening complication that can appear after treatment in patients with nasopharyngeal carcinoma (NPC). However, the relationship between RIBN and radiation dose is not still well-defined. METHODS: During January 2013 and December 2017, a total of 1063 patients with NPC were treated at Sichuan cancer hospital with IMRT. A total of 479 patients were eligible for dosimetric analysis. Dosimetric parameters of the RIBN, Dmax(the maximum dose), D0.1c (maximum average dose delivered to a 0.1-cc volume), D1cc, D2cc, D3cc, D5cc, D10cc and Dmean (mean does) were evaluated and recorded. ROC curve was used to analyze the area under curve (AUC) and cutoff points. Logistic regression for screening dose-volume parameter and logistic dose response model were used to predict the incidence of brainstem necrosis. RESULTS: Among the 479 patients with NPC, 6 patients were diagnosed with RIBN, the incidence of RIBN was 1.25% (6/479), and the median time to RIBN after treatment was 28.5 months (range 18-48 months). The dose of the brainstem in patients with RIBN were higher than that in patients without necrosis. ROC curve showed that the area under the curve (AUC) of Dmax was the largest (0.987). Moreover, logistic stepwise regression indicated that Dmax was the most important dose factor. The RIBN incidence at 5% over 5 years (TD5/5) and 50% incidence over 5 years (TD50/5) was 69.59 Gy and76.45 Gy, respectively. CONCLUSIONS: Brainstem necrosis is associated with high dose irritation. Dmax is the most significant predictive dosimetric factor for RIBN. Dmax of brainstem should be considered as the dose limitation parameter. We suggest that the limitation dose for brainstem was Dmax < 69.59 Gy.

Evaluation of the efficacy of the anti-ulcer oral mucosal protective agent RADoralex® in the prevention and treatment of radiation-induced oral mucosal reactions induced during treatment of nasopharyngeal carcinoma.

The aim of this study was to evaluate the efficacy and safety of antiulcer oral mucosal protectant-RADoralex® in the prevention and treatment of radiation-induced oral mucosal reactions elicited during intensity-modulated radiation therapy (IMRT). for locally advanced nasopharyngeal carcinoma (NPC). A total of 90 patients with locally advanced NPC who developed post-treatment grade 1 oral mucositis were selected for this study. They were randomly assigned to the experimental group (n = 44) treated by mouth rinsing with the RADoralex® during radiochemotherapy and the control group (n = 43) treated by mouth rinsing with sodium bicarbonate solution, and the patients' oral mucosal conditions, quality of life, weight change and oral pain levels were analyzed. The incidence of Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 2 and grade 3 oral mucositis were significantly lower in the experimental group than in the control group. Compared to the control group, the time to progression, and the time from the end of treatment to oral mucosa healing in the experimental group was significantly shorter. The experimental group lost 8.66 ± 3.543% of their body weight during treatment period, while the control group lost 12.53 ± 4.284% (p < .001). From the beginning the 3rd week of treatment to the 2nd week after the end of treatment, the Oral Mucositis Assessment Scale (OMAS) scores were lower in the experimental group than in the control group (p < .05). RADoralex® significantly reduced the incidence and severity of oral mucositis in patients with locally advanced NPC during radiochemotherapy, delayed the progression of oral mucositis.

DW-MRI-Guided Dose Escalation Improves Local Control of Locally Advanced Nasopharyngeal Carcinoma Treated with Chemoradiotherapy.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most highly radiosensitive malignancies; however, some locally advanced NPC patients experienced local recurrence even though they received aggressive treatment regimens. Defining the tumor volume precisely is important to escalate the total dose required for the primary tumor. In this study, we aimed to investigate the feasibility and efficacy of dose escalation guided by DW-MRI in patients with locally advanced NPC. PATIENTS AND METHODS: A total of 230 patients with locally advanced NPC treated with intensive modulated radiotherapy (IMRT) at Sichuan Cancer Hospital between January 2010 and January 2015 were enrolled in this retrospective study. All the patients were treated with all-course of simultaneous integrated boost-IMRT. DW-MRI-guided dose escalation with 2.2-2.5 Gy/F, qd for 1-3 days or 1.2-1.5 Gy/F, bid for 1-3 days were prescribed to 123 patients. Survival and complication of the patients were evaluated, and multivariate analysis was performed. RESULTS: The median follow-up of patients in the DW-MRI-guided dose-escalation group and the conventional group was 48 months (range 8-88 months) and 52 months (range 6-90 months), respectively. The 5-year overall survival rate, distant metastasis-free survival rate, progression-free survival, and local recurrence-free survival (LRFS) of patients in the dose-escalation group and the conventional group were 88% vs 82.5% (p = 0.244), 86.1% vs 83.3% (p = 0.741), 82.2% vs 76.6% (p = 0.286), and 89.1% vs 80.1% (p = 0.029), respectively. Multivariate analysis showed that dose escalation was independent prognostic factor for LRFS (HR 0.386, 95% CI 0.163-0.909, p = 0.03). CONCLUSION: DW-MRI-guided dose escalation is a feasible strategy to improve local control of patients with locally advanced NPC. The treatment-related complications are tolerable.

Hepatoid Adenocarcinoma Of The Lung Metastasizing To The Gingiva.

BACKGROUND: Hepatoid adenocarcinoma (HAC) of the lung, a very rare tumor, has been reported metastasizing to lymph nodes and distant tissue, with poor prognosis. We report a case of lung HAC metastasizing to the gingiva, which is a rare metastasis site. CASE REPORT: A 70-year-old, 50-pack-year, male smoker was diagnosed with a lung mass on a health examination. A chest CT showed a lung mass in the superior lobe of the right lung and enlarged lymph nodes in the right hilum and mediastinum. Liver and other digestive tumors were excluded. The lung mass was confirmed to be HAC by biopsy with positivity of HepPar-1. Despite erlotinib therapy, the tumor metastasized to the gingiva. Then, docetaxel and nedaplatin therapy, radiotherapy, and bevacizumab therapy were administered successively. The patient died of tumor progression 9 months after presentation. CONCLUSION: Gingival metastasis of lung HAC is rare. The patient had a poor outcome. Further studies need to be conducted on lung HAC.

A novel prognostic marker based on risk stratification with prognostic nutritional index and age for nasopharyngeal carcinoma patients who received neoadjuvant chemotherapy.

Aim: To evaluate the prognostic value of pretreatment prognostic nutritional index (PNI) in nasopharyngeal carcinoma (NPC) patients treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy. Materials & methods: We conducted a retrospective study on prognostic value of PNI in NPC patients. A new prognostic marker was explored based on risk stratification with PNI and age. Results: PNI and age were two independent prognostic factors for overall survival (OS) and progression free survival besides node stage and clinical stage. Low prognostic nutritional index and high age (LPNI-HAge) was identified as an independent prognostic factor for both OS (p < 0.001) and progression free survival (p = 0.008), which has a better predict value than sole PNI or age. Conclusion: The novel prognosis index LPNI-HAge provides prognostication of OS and progression free survival for NPC patients treated with neoadjuvant chemotherapy plus concurrent chemoradiotherapy.

Unresectable recurrence malignant sacrococcygeal teratoma in children treated with chemoradiotherapy: Case report and literature review.

Sacrococcygeal teratoma is the most common germ cell neoplasia that consists of tissues derived from primitive germ layers. Approximately 10-20% of patients are malignant. Because of the high rate of recurrence, treatment strategies for malignant sacrococcygeal teratomas are limited. Hence, we report a case of malignant sacrococcygeal teratoma treated with concurrent chemoradiotherapy plus adjuvant chemotherapy and review the literature. This case report indicates that chemoradiation plus adjuvant chemotherapy may be a treatment option for malignant SCT which is not technically resectable or with residual lesion after surgery.

A new marker based on risk stratification of human papillomavirus DNA and tumor size to predict survival of locally advanced cervical cancer.

OBJECTIVE: To assess the prognostic value of human papillomavirus (HPV) viral load in locally advanced cervical carcinoma treated with radical concurrent chemoradiotherapy. METHODS: From January 2012 to October 2013, a total of 246 locally advanced cervical carcinoma patients were included in this retrospective study. HPV DNA status was tested by Hybrid Capture 2 assay. Tumor size was measured on T2WI. All the patients in the study received concurrent cisplatin-based chemoradiotherapy with intensity-modulated radiotherapy and three-dimensional brachytherapy. Survival rate was calculated by the Kaplan-Meier method, and a log-rank test was used to compare the survival. Multivariate analysis employed the Cox regression model. RESULTS: The median follow-up time was 52 months. The median value of HPV DNA was 163.13 relative light unit/cut-off (RLU/CO) (range 1.65-2162.62 RLU/CO). The 5-year overall survival, distant metastasis-free survival of patients in the low HPV DNA group (HPV DNA ≤ 163.13 RLU/CO) and the high HPV DNA group (HPV DNA > 163.13 RLU/CO) were 46.3 % vs 58.5 % (p = 0.009) and 65.9 % vs 75.6% (p = 0.003), respectively. Multivariate analysis showed that the HPV DNA, tumor size, and International Federation of Gynecology and Obstetrics (FIGO) stage were independent prognostic factors for overall survival and distant metastasis-free survival. We choose the tumor size and HPV DNA as the risk stratification factors to build a new prediction marker which can better predict overall survival for locally advanced cervical cancer than can the FIGO stage. CONCLUSIONS: HPV DNA may be a useful biomarker for locally advanced cervical cancer. Low HPV load predicts a worse survival. The new marker based on risk stratification by combining HPV DNA and tumor size is better associated with overall survival of locally advanced cervical cancer treated with concurrent chemoradiotherapy.

Clinical outcome and prognostic analysis of young adults nasopharyngeal carcinoma patients of a nonendemic area in intensity-modulated radiotherapy era.

AIM: To investigate the clinical outcome and prognostic factors of young adults nasopharyngeal carcinoma (NPC) patients in the era of intensity-modulated radiotherapy. METHODS: We retrospectively analyzed the clinical outcome and the prognostic factors of young adults NPC patients who were admitted to our hospital from January 2010 to December 2013. COX regression model was used to identify factors associated with survival. The acute and late toxicities were also evaluated. RESULTS: A total of 165 patients were included; the median follow-up time for all the patients was 65 months (4-96 months). The 5-year overall survival (OS), distant metastasis-free survival, progression-free survival and local-regional recurrence-free survival were 85.9, 82.4, 76.4 and 92.4%, respectively. N stage was an independent prognostic factor for OS (p = 0.009) and distant metastasis-free survival (p = 0.008). Cumulative cisplatin >200 mg/m2 was an independent prognostic factor for OS (p = 0.032). CONCLUSION: Young adults with NPC can achieve a reasonable local-regional control and OS in the era of intensity-modulated radiotherapy with tolerable toxicities.

Dexamethasone Stimulates Hepatitis B Virus (HBV) Replication Through Autophagy.

BACKGROUND Reactivation of hepatitis B virus (HBV) is a fatal complication of chemotherapy. Occult HBV infection might be reactivated in patients undergoing chemotherapy or immunosuppression. However, the mechanism of HBV reactivation induced by chemotherapy or immunosuppression remains unclear. MATERIAL AND METHODS HepG2.2.15 cells were treated with an autophagy inducer (rapamycin), an inhibitor (3-methyladenine, 3-MA), and dexamethasone. Autophagosomes were observed by a transmission electron microscope (TEM). LC3-I, LC3-II, and P62 were analyzed by western blot. HBV replicative intermediates were detected by southern blot. HBV DNA expression was quantitated with real-time polymerase chain reaction (PCR). The level of HBV surface antigen (HBsAg) in culture medium was examined by ELISA. RESULTS In this study, we find that dexamethasone stimulates HBV replication and protein expression by inducing autophagy in HepG2.2.15 cells. In contrast, autophagy inhibitor (3-MA) abrogates HBsAg secretion stimulated by dexamethasone. CONCLUSIONS Our results suggest that dexamethasone stimulates HBV replication through autophagy. This might provide a novel insight into the mechanism of glucocorticoid-mediated HBV reactivation through autophagy, which might be a new therapeutic target.

Prognostic variables for temporal lobe injury after intensity modulated-radiotherapy of nasopharyngeal carcinoma.

To determine predictive factors for temporal lobe injury (TLI) in nasopharyngeal carcinoma patient (NPC) treated with intensity-modulated radiation therapy (IMRT). A total of 695 NPC cases treated with IMRT were retrospectively analyzed. TLI was diagnosed on MRI images. Volume-dose histograms for 870 evaluable temporal lobes were analyzed, and the predictive factors for the occurrence of TLI was evaluated. Receiver operating characteristic curve (ROC) and Logistic regression analysis was used to determine volume-dose parameters that predict temporal lobe injury (TLI). Univariate and multivariate analysis were used to analyze the predictive factors for TLI. The radiation dose-tolerance model of temporal lobe was calculated by logistic dose-response model. The median follow-up time was 73 months. A total of 8.5% patients were diagnosed with TLI. Among all the volume-dose parameters, logistic regression model showed D2cc (the dose Gray delivered to 2 cubic centimeter volume) was an only independent predictive factor. Multivariate analysis showed D2cc of temporal lobe, fraction size of prescription, T stage, and chemotherapy were the independent predictive factors for TLI. Logistic dose-response model has indicated the TD5/5 and TD50/5 of D2cc are 60.3 Gy and 76.9 Gy, respectively. D2cc of temporal lobe, fraction size of prescription, T stage, and chemotherapy were the possible independent predictive factors for TLI after IMRT of NPC. Biologic effective doses (TD5/5 and TD50/5 ) of D2cc are considered to prevent TLI.