Importance Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) has been a standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but with high acute toxic effects in CCRT phase. Whether CCRT can be safely replaced by radiation therapy with adjuvant chemotherapy (AC) is unknown. Objective To assess if sequential chemoradiotherapy (SCRT; IC, followed by radiotherapy alone, followed by AC) is noninferior to IC plus CCRT for LA-NPC in terms of efficacy, with less acute toxic effects. Design, Setting, and Participants This multicenter, open-label, phase 3 noninferiority randomized clinical trial was conducted from January 2018 to September 2021 in 6 centers in China. Patients aged 18 to 65 years with newly diagnosed stage III/IVA NPC were enrolled. The data cutoff date was June 30, 2024. Interventions Patients were randomly assigned 1:1 to receive 2 cycles of IC with a gemcitabine and cisplatin (GP) regimen (gemcitabine, 1000 mg/m(2), on days 1 and 8 plus cisplatin, 25 mg/m(2), on days 1, 2, and 3, repeated every 3 weeks) plus radiotherapy alone, followed by 2 cycles of AC with a GP regimen (SCRT group) or 2 cycles IC (GP regimen) followed by radiotherapy concurrent with weekly cisplatin, 30 mg/m(2) (IC plus CCRT group). Main Outcomes and Measures The primary end points were 3-year failure-free survival (FFS) with a noninferiority margin of 10% (hazard ratio [HR] less than 1.6) and the incidence of grade 3 or higher acute mucositis during radiotherapy. The secondary end points included overall survival, locoregional FFS, distant FFS, response rate, and toxic effects. Results Of 420 enrolled patients, 107 (25.5%) were women, and the median (IQR) age was 48 (41-54) years. A total of 210 patients were randomized to the SCRT group and 210 to the IC plus CCRT group. The median (IQR) follow-up time was 50 (40-61) months. In the intention-to-treat population, 3-year FFS was 83.7% (95% CI, 78.6-88.8) vs 79.5% (95% CI, 74.0-85.0) in the SCRT group vs the IC plus CCRT group, respectively (HR, 0.77; 95% CI, 0.50-1.19; P = .24), with the upper bound of the 95% CI less than 1.6. Identical outcomes were reported in the per-protocol population. Compared with the IC plus CCRT group, the SCRT group had significantly lower incidences of grade 3 or higher acute nonhematological toxic effects (acute mucositis, 61 [29.0%] vs 88 [41.9%], respectively; P < .001; nausea, 20 [9.5%] vs 38[18.1%], respectively; P = .01; vomiting, 8 [3.8%] vs 20 [9.5%], respectively; P = .02). No differences were observed in late toxic effects. Conclusions and Relevance Results from this noninferiority randomized clinical trial suggest that SCRT is noninferior to IC plus CCRT in terms of 3-year FFS in LA-NPC, with less severe acute nonhematological toxic effects.

CLINICAL TRIAL REGISTRATION:NCT06190782 (ClinicalTrials.gov).

Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) has been a standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but with high acute toxic effects in CCRT phase. Whether CCRT can be safely replaced by radiation therapy with adjuvant chemotherapy (AC) is unknown. To assess if sequential chemoradiotherapy (SCRT; IC, followed by radiotherapy alone, followed by AC) is noninferior to IC plus CCRT for LA-NPC in terms of efficacy, with less acute toxic effects. This multicenter, open-label, phase 3 noninferiority randomized clinical trial was conducted from January 2018 to September 2021 in 6 centers in China. Patients aged 18 to 65 years with newly diagnosed stage III/IVA NPC were enrolled. The data cutoff date was June 30, 2024. Patients were randomly assigned 1:1 to receive 2 cycles of IC with a gemcitabine and cisplatin (GP) regimen (gemcitabine, 1000 mg/m2, on days 1 and 8 plus cisplatin, 25 mg/m2, on days 1, 2, and 3, repeated every 3 weeks) plus radiotherapy alone, followed by 2 cycles of AC with a GP regimen (SCRT group) or 2 cycles IC (GP regimen) followed by radiotherapy concurrent with weekly cisplatin, 30 mg/m2 (IC plus CCRT group). The primary end points were 3-year failure-free survival (FFS) with a noninferiority margin of 10% (hazard ratio [HR] less than 1.6) and the incidence of grade 3 or higher acute mucositis during radiotherapy. The secondary end points included overall survival, locoregional FFS, distant FFS, response rate, and toxic effects. Of 420 enrolled patients, 107 (25.5%) were women, and the median (IQR) age was 48 (41-54) years. A total of 210 patients were randomized to the SCRT group and 210 to the IC plus CCRT group. The median (IQR) follow-up time was 50 (40-61) months. In the intention-to-treat population, 3-year FFS was 83.7% (95% CI, 78.6-88.8) vs 79.5% (95% CI, 74.0-85.0) in the SCRT group vs the IC plus CCRT group, respectively (HR, 0.77; 95% CI, 0.50-1.19; P = .24), with the upper bound of the 95% CI less than 1.6. Identical outcomes were reported in the per-protocol population. Compared with the IC plus CCRT group, the SCRT group had significantly lower incidences of grade 3 or higher acute nonhematological toxic effects (acute mucositis, 61 [29.0%] vs 88 [41.9%], respectively; P < .001; nausea, 20 [9.5%] vs 38[18.1%], respectively; P = .01; vomiting, 8 [3.8%] vs 20 [9.5%], respectively; P = .02). No differences were observed in late toxic effects. Results from this noninferiority randomized clinical trial suggest that SCRT is noninferior to IC plus CCRT in terms of 3-year FFS in LA-NPC, with less severe acute nonhematological toxic effects. ClinicalTrials.gov Identifier: NCT03366415

Background:Neoadjuvant concurrent chemoradiotherapy (CCRT) has become the preferred modality for patients with inoperable locally advanced esophageal squamous cell carcinoma (ESCC). To investigate whether the CCRT regimen of paclitaxel plus 5-fluorouracil (TF) increases the efficacy when compared with a regimen of cisplatin plus 5-fluorouracil (PF) in the locally advanced ESCC patient treatment. Methods:A total of 103 ESCC patients were randomly divided into study group (TF, n=52) and control group (PF, n=51), treated in Affiliated Hospital of Jiangnan University from July 2014 to June 2016. These patients were followed up for 2 years in our department by performing certain examinations to evaluate their survival state. The primary endpoint was overall survival (OS). Local control (LC), progression-free survival (PFS) and adverse effects were secondary endpoints. Results:A total of 103 patients were enrolled. The 1-, 2-year OS for TF group was 76.9%, 59.6% versus 74.5% (χ2=0.134, P=0.72), 56.9% (χ2=0.151, P=0.70) for PF group. The 1-, 2-year LPS for TF group and PF group were 71.2%, 61.5% and 66.7% (χ2=0.065, P=0.80), 58.8% (χ2=0.079, P=0.78) respectively. The serious leukopenia (grade 3-4) incidence rate for TF group was 36.5% versus 17.6% for PF group (χ2=4.642, P<0.05). Conclusions:When compared with the PF regimen, the TF regimen shows no survival benefit but exhibited a trend to a better control rate and a decreased distant metastasis rate. Both regimens showed tolerable toxicity. Trial Registration:Chinese Clinical Trial Registry ChiCTR2500100712.

6075 Background: Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) has been regarded as standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) due to its favorable disease control. Now, distant metastasis was the main cause of failure. However, concurrent cisplatin is associated with intolerable toxicities and ineffective in preventing distant metastasis. Since IMRT enhances the local control and chemotherapy before or after radiotherapy decreases the risk of distant failure, it is worth exploring whether sequential chemoradiotherapy (SCRT) regimen could replace IC+CCRT for patients with LA-NPC. Methods: This open-label, phase 3, non-inferiority clinical trial was conducted from January 2018 to September 2021 in 6 centers in China. Patients aged 18–65 years with stage T1-4N2-3 or T3-4N0-1 M0 NPC were randomly assigned (1:1) to receive 2 cycles of IC with GP regimen (gemcitabine 1000mg/m2 d1,8 + cisplatin 25 mg/m2 d1-3, q21d) plus IMRT, followed by 2 cycles of adjuvant chemotherapy (AC) with the same regimen or IC with GP regimen for 2 cycles followed by IMRT plus concomitant weekly cisplatin (30 mg/m²). The primary endpoint was 3-year failure-free survival (FFS) with non-inferiority margin of 10% (HR<1.6) and the incidence of grade ≥3 acute mucositis during radiotherapy. Efficacy analysis and safety analysis were dividedly performed in the intention-to-treat and safety population. Results: A total of 420 patients were randomly assigned to SCRT group (n = 210) or IC+CCRT group (n = 210). With a median follow-up of 47.0 months (IQR: 35.0-57.8), the 3-year FFS was 84.0% in SCRT group versus 79.8% in IC+CCRT group (log rank P=0.344), with an HR of 0.804 (95% CI, 0.510 to 1.266) and absolute difference of 4.2% (95% CI, -3.2 to 11.6). No significant differences were observed between groups in 3-year overall survival (97.4% vs. 94.5%; HR 0.413; 95% CI, 0.159 to 1.076; log rank P=0.061), locoregional control (91.7% vs. 88.8%; HR 0.767; 95% CI, 0.420 to 1.401; log rank P=0.386), or distant metastasis-free survival (93.6% vs. 91.5%; HR 0.756; 95% CI, 0.376 to 1.520; log rank P=0.430). Compared with IC+CCRT group, the SCRT group had significantly lower incidences of grade ≥3 acute nonhematological AEs due to the omission of concurrent chemotherapy (including acute mucositis 29.0% vs. 41.9%, P<0.001; nausea 9.5% vs. 18.1%, P=0.011; and vomiting 3.8% vs. 9.5%, P=0.019), and higher incidences of grade ≥3 acute hematological AEs (including thrombocytopenia and leukopenia) due to the additional AC. Conclusions: For LA-NPC, SCRT was not inferior in 3-year FFS to IC+CCRT. It might be an alternative treatment for LA-NPC patients with fewer sever nonhematological AEs during IMRT. Clinical trial information: NCT03366415 .

Background Anti-PD-1 therapy combined with or without chemotherapy is the standard regimen for metastatic esophageal cancer. Oligometastatic carcinoma is an intermediate state of tumor development between locally advanced and widespread metastasis, with potential long-term survival. The value of the addition of local intervention therapy to standard systemic therapy is still controversial for patients with oligometastasis. The ESO-Shanghai 13 trial demonstrated that systemic therapy combined with local intervention improved progression-free survival and overall survival in patients with oligometastatic esophageal squamous cell carcinoma. However, it is a phase II trial and has two systemic treatment regimens including chemotherapy and chemoimmunotherapy. There were only 43 patients treated with immunotherapy with or without local intervention therapy in ESO-Shanghai 13. To further assess the efficacy of Anti-PD-1 therapy with local intervention therapy in oligometastatic esophageal patients, we initiated a multicenter randomized controlled phase III clinical trial, ESO-Shanghai 20. Methods The ESO-Shanghai20 trial will recruit histology-proven esophageal squamous cell carcinoma patients with genuine oligometastasis (four or fewer metastatic lesions) and the eligible patients will be randomly assigned in a 2:1 ratio to receive either the combined local intervention therapy and systemic therapy (the combined group) or the systemic therapy only (the systemic group). Both groups receive anti-PD-1 with or without chemotherapy for 4 cycles every 21 days, followed by anti-PD-1 maintenance therapy every 21 days for 2 years. The local intervention therapy in this trial includes radiotherapy, surgery, and ablation, and allowed different metastases in the same patient to receive different local intervention treatment modes according to the characteristics of the metastatic site. The expected enrollment time is 36 months, and the follow-up time is 24 months. The combined treatment group and the systemic treatment group required 236 and 118 samples, respectively, and a total of 354 cases needed to be enrolled. The primary endpoint is progression free survival, and the second endpoint is overall survival and the toxicity and safety of the treatment. Discussion If the result of ESO-Shanghai20 shows that the combination of local intervention therapy with anti-PD-1 therapy is safe and promising for patients with oligometastatic esophageal squamous cell carcinoma, this study will provide a basis for the precise stratified treatment of patients with advanced esophageal squamous cell carcinoma. Trial registration NCT06190782.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Objective:To explore the efficacy of elective nodal irradiation (ENI) and involved field irradiation (IFI) combined with chemotherapy in treatment of esophageal cancer.Methods:A total of 104 patients with esophageal cancer in Affiliated Hospital of Jiangnan University from May 2018 to May 2020 were selected as subjects for prospective study. All patients were randomly divided into observation group and control group by lottery method with 52 cases in each group. The target volume of observation group was delineated with IFI, and the control group was delineated with ENI. The curative effects, the levels of serum tumor markers [carbohydrate antigen 50 (CA50), squamous cell carcinoma (SCC) and carcinoembryonic antigen (CEA)] before and after treatment, the 1-year overall survival (OS) rate, the incidence of adverse reactions and the scores of various dimensions of health survey summary (SF-36) after treatment were compared between the two groups.Results:The total effective rate in the observation group was 90.38% (47/52), the total effective rate in the control group was 84.62% (44/52), and the difference was not statistically significant ( χ2 = 0.79, P =0.374). There was no statistical difference in CA50, CEA, SCC levels between the two groups before and after treatment (all P > 0.05). After treatment, the CA50, CEA and SCC levels in the two groups were lower than those before treatment, and the differences were statistically significant (all P < 0.05). The 1-year OS rate of the observation group was 94.23%, the control group was 90.38%, and the difference in OS between the two groups was not statistically significant ( χ2 = 0.54, P = 0.462). The incidence of acute radiation esophagitis in the observation group was lower than that in the control group, and the difference was statistically significant ( P < 0.001). There was no statistical difference between the two groups in SF-36 scale scores of physical functioning, role-physical, bodily pain, mental health, vitality, social functioning, role-emotional, and general health after treatment (all P > 0.05). Conclusions:Both ENI and IFI are effective treatments for patients with esophageal cancer. There is no significant difference in the quality of life of patients between the two delineation methods, but the incidence of acute radiation esophagitis is lower in patients with IFI regimen.

Objective:To explore the healing mechanism of porcine small intestinal submucosa decorated with nano-silver (NS-PSIS) in the treatment of a model of fistula-in-ano.Methods:NS-PSIS was constructed. Animal models of fistula-in-ano were established using New Zealand rabbits and randomly divided into two groups according to random number table ( n=12 in each group). Rabbits in the experimental group were treated with NS-PSIS for anal fistulas, and those in the control group were treated with PSIS. The treated anal fistula tissue samples were obtained at 12, 24, 48 h and 14 d after surgery ( n=3 in each group). Hematoxylin-eosin staining was performed to observe the pathomorphological changes of the marginal tissues of the anal fistula. Masson staining was performed to assess collagen deposition in the marginal tissue of the anal fistula and quantitative analysis was performed. Immunohistochemical staining was performed to detect the expression of CD34 in the marginal tissue of the anal fistula and calculate the microvessel density (MVD). The expression of transforming growth factor (TGF)-β1, Smad2, collagen type Ⅰ (COL Ⅰ) and collagen type Ⅲ (COL Ⅲ) was detected. Real-time polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expression of TGF-β1, Smad2, COL Ⅰ and COL Ⅲ. For measurement data meeting normal distribution, independent sample t-test was used for comparison between two groups; otherwise, Wilcoxon rank sum test was used. Results:NS-PSIS was successfully constructed. A New Zealand rabbit model of fistula-in-ano was successfully established. In the early stage of treatment (12-48 h after surgery), significant inflammatory cell infiltration, fibroblast proliferation, collagen synthesis and neovascularization were observed around the fistula tract in both groups. Masson staining showed that collagen synthesis in the NS-PSIS group was significantly more than that in the PSIS group at 48 h after surgery [(29.40±2.80)% vs. (20.97±1.68)%, t=-7.752, P<0.01]. Immunohistochemistry showed that at 48 h after surgery, the MVD in NS-PSIS group was significantly higher than that in PSIS group [6.8 (5.2, 7.8) vs. 5 (4, 6.8), Z=-2.969, P<0.01]. At 24 h after surgery, the expression levels of COL Ⅰ [(22.06±2.83)% vs. (13.5±2.88)%, t=-6.342, P<0.01] and COL Ⅲ [(25.70±3.44)% vs. (20.02±2.45)%, t=-4.038, P<0.001] in NS-PSIS group were significantly higher than those in PSIS group. At 48 h after surgery, the expression levels of COL Ⅰ [(28.71±3.81)% vs. (20.09±3.07)%, t=-5.284, P<0.01] and COL Ⅲ [(30.59±1.41)% vs. (24.01±1.77)%, t=-710, P<0.01] in NS-PSIS group were significantly higher than those in PSIS group. In addition, the expression levels of TGF-β1 [19.71 (18.56, 20.90)% vs. (18.56±2.57)%, Z=-3.621, P<0.01] and Smad2 [(18.56±2.57)% vs. (12.22±2.55)%, t=-5.249, P<0.01] in the NS-PSIS group were significantly higher than those in the PSIS group at 48 h after surgery. RT-qPCR showed that the mRNA expression levels of TGF-β1 [8.62 (8.57, 9.05) vs. 6.87 (6.51, 7.14), Z=-3.621, P<0.01], Smad2 [13.44 (11.25, 13.59) vs. 10.05 (9.05, 10.37), Z=-3.616, P<0.01], COL Ⅰ [4.02 (3.84, 5.82) vs. 2.58 (2.08, 4.08), Z=-2.012, P<0.01] and COL Ⅲ [12.12 (11.60, 14.60) vs. 9.24 (7.25, 9.52), Z=-3.064, P<0.01] in the NS-PSIS group were significantly higher than those in the PSIS group at 48 h after surgery. Conclusion:The ability of NS-PSIS to promote neovascularization and collagen synthesis might be superior to PSIS in the early stage of therapy (48 h after surgery), and the mechanism might be related to the activation of TGF-β1/Smad2/COL Ⅰ/COL Ⅲ signaling pathway.

Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment, which are characterized by pro-tumor M2 phenotype and correlate with poor survival of nasopharyngeal carcinoma (NPC). Heme oxygenase-1 (HO-1) plays a crucial role in macrophage polarization toward M2 phenotype, but its prognosis significance in NPC has been rarely determined. To gain insights into the HO-1 expression profile and to determine the clinical significance of HO-1 in NPC, we performed immunohistochemistry analyses in 126 NPC specimens. CD163, a highly specific marker of M2 macrophages, was used as a surrogate for the polarization state of TAMs. Our results showed that high expression of HO-1 and CD163 were detected in TAMs for 57.9% (73/126) and 61.9% (78/126) of the studied patients, and both of them were significantly associated with worse survival. Additionally, a significant correlation between the intensities of HO-1 and CD163 was identified, and HO-1 exhibited a superior ability in predicting survival compared with CD163. Our study revealed for the first time that overexpression of HO-1 characterized a poor-prognosis subtype in NPC. Individualized therapy targeting HO-1 might serve as a promising treatment modality for NPC.

Gastric carcinoma (GC) is one of the most common cause of tumor-related death. Chemotherapy resistance usually occurs, leading to cancer relapse and poor survival of GC patients. To investigate the role of miRNAs in chemotherapy resistance for GC patients, we conducted an integrated analysis of miRNA expression and survival information using data obtained from The Cancer Genome Atlas project. Genome-wide screening of chemotherapy response-specific miRNAs was performed using Cox proportional hazards regression analyses for patients who received chemotherapy or those who had never received chemotherapy, respectively. A four-miRNA expression signature (involving two protective miRNAs, miR-200b and miR-103a, and two risk ones miR-199 and miR-152) was predicted as a specific indicator for GC chemoresistance (p = 0.00053; hazard ratio = 8.63), outperforming those clinicopathological factors. Functional experiments confirmed the roles of these signature miRNAs in regulation of chemotherapy response. Functional enrichment of these signature miRNAs and risk score revealed positive association with epithelial-mesenchymal transition (EMT), and negative association with cell cycle checkpoint and DNA damage response. Furthermore, the immune infiltration-miRNA functional network analysis revealed transformation from activated effector cells to resting immunosuppressive cells are preferred in GCs with adverse chemotherapy response. In summary, our work identifies a four-miRNA expression signature as a promising chemoresistance biomarker in GC, which provides novel insights into developing new strategies to overcome GC chemoresistance.

AbstractBackgroundThis study aimed to compare the efficacy and toxicity of raltitrexed (Saiweijian®) plus cisplatin (SP regimen) and 5‐fluorouracil plus cisplatin (FP regimen) as concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA‐NPC).MethodsEligible patients (N = 135) were allocated randomly in a ratio of 1:1 to receive CCRT with either SP or FP. At least 2 cycles of chemotherapy was administrated during radiotherapy. Progression free survival (PFS) was primary endpoint. Secondary endpoints included overall survival (OS), loco‐regional relapse free survival (LRRFS), distant metastasis free survival (DMFS) and toxicity.ResultsIn this study, 68 patients received SP as CCRT, and 67 received FP. Objective responses were noted in 97.1% of the patients in the SP group and in 97.0% of the patients in the FP group (P = 1.00). At the end of a median 36 months follow‐up period, the estimated 3‐year PFS rates were 70.1% for SP and 66.6% for FP, respectively. The 3‐year LRRFS, DMFS and OS rates were 88.9%, 74.7% and 84.0%, respectively, for the SP group, and 92.3%, 71.0% and 73.7%, respectively, for the FP group. Overall, there was no difference between treatment groups with regard to response or survival. The most frequent acute toxicities monitored in both groups were bone marrow suppression, gastrointestinal side effects and oral mucositis (OM). The overall incidence of grade 3‐4 OM in the FP group (47.8%) was higher than in the SP group (11.8%). However, the incidence of other adverse effects observed in both groups was similar (P > .05).ConclusionsThese data indicate that SP and FP therapies have similar efficacy in treating LA‐NPC. The SP regimen showed a tolerable safety profile along with a lower frequency of severe OM and therefore, an improved life quality. In conclusion, SP was a well tolerated, effective, regimen for LA‐NPC treatment.

Radiotherapy (RT) represents one of the major treatment methods for cancers. However, many studies have observed that in descendant surviving tumor cells, sublethal irradiation can promote metastatic ability, which is closely related to the tumor microenvironment. We therefore investigated the functions and mechanisms of sublethal irradiated liver nonparenchymal cells (NPCs) in hepatocellular carcinoma (HCC). In this study, primary rat NPCs and McA-RH7777 hepatoma cells were irradiated with 6 Gy X-ray. Conditioned media (CM) from nonirradiated (SnonR), irradiated (SR), or irradiated plus radiosensitizer celecoxib-treated (S[R + D]) NPCs were collected and added to sublethal irradiated McA-RH7777 cells. We showed that CM from sublethal irradiated NPCs significantly promoted the migration and invasion ability of sublethal irradiated McA-RH7777 cells, which was reversed by celecoxib. The differentially expressed genes in differently treated McA-RH7777 cells were enriched mostly in the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. SR increased the migration and invasion ability of HCC cells by inhibiting AMPK/mTOR signaling, which was enhanced by the AMPK inhibitor compound C and blocked by the AMPK activator GSK-621. Analyses of HCC tissues after neoadjuvant radiotherapy confirmed the effects of radiation on the AMPK/mTOR pathway. Cytokine antibody arrays and further functional investigations showed that matrix metalloproteinase-8 (MMP-8) partly mediates the promotion effects of SR on the migration and invasion ability of HCC cells by regulating AMPK/mTOR signaling. In summary, our data indicate that MMP-8 secreted by irradiated NPCs enhanced the migration and invasion of HCC by regulating AMPK/mTOR signaling, revealing a novel mechanism mediating sublethal irradiation-induced HCC metastasis at the level of the tumor microenvironment.

BACKGROUND Nasopharyngeal carcinoma (NPC), arising from nasopharynx epithelium, is a rare type of malignant carcinoma that has a specific geographical distribution and a high risk of distant metastases. For most of the diagnosed NPC patients, the total survival rate decreased significantly due to the high local recurrence rate and metastasis rate. Concurrent chemoradiotherapy (CCRT), as routine therapy strategy of NPC, usually accompanies with high-dosage cytotoxic agents and serious toxic side reaction. Therefore, there is an urgent need for update the existing therapy strategies. In this study, we sought to investigate the effects of a combined therapy strategy, erlotinib combined with cisplatin and radiotherapy, on biological characteristics of NPC CNE2 cells and the potential reasons. METHODS CNE2 cells in logarithmic phase seeding in 96-well plates received concentration gradients of erlotinib (at 0, 10, 20, 40, 80, 160, 320 mmol/L) or cisplatin (at 0, 0.25, 0.5, 1, 2, 4, 8 mg/L), in order to obtain the optimal working concentration of erlotinib and cisplatin via 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Then, cells were divided into control group and four treatment groups (Group I-IV). All treatment groups received irradiation of 4 Gy, moreover, Group II-IV respectively received erlotinib, cisplatin and erlotinib plus cisplatin at optimal working concentration. After 24 and 48 h of irradiation, growth inhibition rate was determined; invasion ability and migration ability was respectively detected by Boyden's chamber assay and cell scratch test; flow cytometry was performed for determining apoptosis rate and cell cycle distribution; the expression levels of epidermal growth factor receptor (EGFR) signal pathway proteins were semi-quantitatively analyzed by Western-blot. RESULTS Compared with Group I, all the other treatment groups showed better inhibition effect on cell viability, invasion and migration ability and higher apoptosis rate, while Group IV showed the strongest growth inhibition effect and highest apoptosis rate. In addition, EGFR signal pathway proteins of Group IV showed the lowest expression level. CONCLUSIONS In combined therapy with radiotherapy/chemotherapy, erlotinib could enhance radiotherapy/chemotherapy sensitivity, probably because it could suppress DNA damage repair after radiotherapy/chemotherapy, thus weakening radiotherapy/chemotherapy resistance of tumor cells.

Real-time assessment of therapeutic response in patients with advanced lung cancer presents a major challenge throughout the treatment process. Currently, computed tomography imaging is often used; however, it is radiation-based and hysteretic and is not suitable for repeated use as a real-time assessment. Blood biomarkers represent a novel solution for assessing therapeutic response in patients with advanced lung cancer. In the present study, the efficacy of a methylation marker [methylated prostaglandin E receptor 4 (mPTGER4)] and four protein markers [carcinoma antigen 125 (CA125), carcinoembryonic antigen (CEA), cytokeratin 19-fragments (cyfra21-1) and neuron-specific enolase (NSE)] were simultaneously evaluated to determine their potential in facilitating therapeutic response monitoring as well as their prognostic values in patients with stage IV lung cancer. The results indicated that, following treatment, the blood levels of methylated PTGER4 and NSE had significantly decreased, and mPRGER4, CA125, CEA and NSE exhibited a significant decrease in percentage level. Since mPTGER4 exhibited a higher rate of positive detection prior to therapy, and a greater response of sensitivity to therapy compared to the protein markers, it may represent an improved marker for the monitoring of therapeutic response. The efficacy of the markers in predicting the overall survival (OS) rate of patients with stage IV lung cancer was also assessed. Results from the follow-up of patients (up to 891 days) revealed that the blood levels of mPTGER4, CA125 and NSE before treatment were able to predict overall survival (OS) rate. Additionally, the percentage change in expression levels of CA125, CEA and NSE was also able to predict the OS rate. In conclusion, the present results indicate that mPTGER4 represents an improved biomarker for monitoring therapeutic efficacy compared with CA125, CEA, Cyfra21-1 and NSE. In predicting the long-term survival of patients with stage IV lung cancer; however, the pre-treatment levels of mPTGER4, CA125 and NSE and the percentage changes of CA125, CEA and NSE may be used as the markers.

Objective: To evaluate the impact of systematic nutrition management (SNM) on nutritional status, treatment-related toxicity, quality of life (QoL), response rates, and survival in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) treated by radiotherapy (RT). Methods: In this retrospective study, 56 patients with LA-NPC were selected as nutrition management group (NG) for SNM during RT till 1 month later. Another 56 patients with LA-NPC receiving RT without SNM as control group (CG) were identified from the hospital database and matched pairs with NG patients according to age, gender, stage, and body mass index (BMI) prior to RT. Results: At 1 month after RT, the percentage of malnourished patients with BMI <18.5 kg/m(2) was statistically significant reduced in NG as compared to the CG group (35.7% vs 58.9%, P=0.014). Nutritional indexes of body weight, hemoglobin, prealbumin, and lymphocyte in the NG were statistically significant higher than those in the CG group (P<0.05). NG patients had statistically significant less grade 3-4 oral mucositis during RT compared with the CG group (32.1% vs 51.8%, P=0.035). Furthermore, at 1 month after RT, an improved QoL was observed in NG patients with respect to physical, role and social functions, symptom scales of fatigue and pain, and the global health status as compared to the CG group (P<0.05). With a median follow-up of 24.8 months, there were no statistical differences between NG and CG (P>0.05) for the 2-year progression-free survival and overall survival (84.2% versus 79.5% and 94.7% versus 92.3%, respectively.). Conclusion: SNM for LA-NPC patients treated by RT resulted in better nutritional status, reduced treatment-related toxicity and improved QoL.

*These authors contributed equally to this work Objective: To evaluate the impact of systematic nutrition management (SNM) on nutritional status, treatment-related toxicity, quality of life (QoL), response rates, and survival in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) treated by radiotherapy (RT). Methods: In this retrospective study, 56 patients with LA-NPC were selected as nutrition management group (NG) for SNM during RT till 1 month later. Another 56 patients with LANPC receiving RT without SNM as control group (CG) were identified from the hospital database and matched pairs with NG patients according to age, gender, stage, and body mass index (BMI) prior to RT. Results: At 1 month after RT, the percentage of malnourished patients with BMI <18.5 kg/m was statistically significant reduced in NG as compared to the CG group (35.7% vs 58.9%, P=0.014). Nutritional indexes of body weight, hemoglobin, prealbumin, and lymphocyte in the NG were statistically significant higher than those in the CG group (P<0.05). NG patients had statistically significant less grade 3–4 oral mucositis during RT compared with the CG group (32.1% vs 51.8%, P=0.035). Furthermore, at 1 month after RT, an improved QoL was observed in NG patients with respect to physical, role and social functions, symptom scales of fatigue and pain, and the global health status as compared to the CG group (P<0.05). With a median follow-up of 24.8 months, there were no statistical differences between NG and CG (P>0.05) for the 2-year progression-free survival and overall survival (84.2% versus 79.5% and 94.7% versus 92.3%, respectively.). Conclusion: SNM for LA-NPC patients treated by RT resulted in better nutritional status, reduced treatment-related toxicity and improved QoL.

目的 局部晚期胃癌术后放化疗是胃癌综合治疗的重要组成部分,既往研究中术后放化疗主要针对淋巴结阳性和浆膜层受侵,按照术后组织学类型Lauren分型因素来选择的研究较少,术后Lauren分型临床容易获得,增加Lauren分型因素指导术后放化疗的选择具有重要临床意义.本研究分析和比较Lauren分型中肠型和弥漫型在局部晚期胃癌术后放化疗中的临床疗效和不良反应,为胃癌术后放化疗临床应用提供指导.方法 回顾性分析2012-05-10-2014-10-10江南大学附属医院肿瘤放疗科诊治的局部晚期胃癌患者80例,均接受D2根治术后放化疗,放化疗顺序为术后化疗2个周期后同期放化疗,放疗后辅助化疗4个周期,组织学按Lauren分型分为肠型组和弥漫型组各40例,放疗方法均为调强放疗(intensity modulated radiation therapy,IMRT)技术,放疗剂量为45 Gy/25次.比较两组患者3年总生存率(overall survival,OS)、3年无瘤生存率(disease-free survival,DFS)和3年局部区域复发率(loeoregional recurrence rate,LRR),以及两组不良反应及治疗后失败的分布情况.结果 肠型组与弥漫型组3年OS分别为72.5％和50.0％,差异有统计学意义,x2 =4.270,P=0.039;3年DFS分别为65.0％和42.5％,差异有统计学意义,x2=4.070,P=0.044;3年的LRR分别为12.5％和15.0％,差异无统计学意义,x2=0.110,P=0.745;两组不良反应差异无统计学意义,主要不良反应是1～2级消化道反应,血液学毒性及手足综合征,两组失败表型中腹膜转移肠型组发生6例,弥漫型组发生13例;远处脏器转移肠型组发生4例,弥漫型组发生8例,弥漫型组发生腹膜转移及远处脏器转移较肠型组有所增加.结论 局部晚期胃癌术后放化疗中肠型组较弥漫组3年OS和DFS明显延长,弥漫型组有远处转移倾向提示应加强全身治疗,Lauren分型对局部晚期胃癌术后放化疗选择有一定的指导作用,值得进一步研究.

目的 探讨同期加量调强放疗(SIB-IMRT)联合化疗治疗高级别脑胶质瘤的临床疗效和安全性.方法 回顾性分析2013年5月至2015年5月43例初治高级别胶质瘤术后患者的临床资料.患者全部采用术后瘤床区SIB-IMRT,予瘤床区60 Gy/25次,2.4 Gy/次,瘤床区外扩2 cm,50 Gy/25次.放疗期间接受同步化疗,从放疗第1天开始同步化疗,口服替莫唑胺75 mg/m2,放疗结束后4周予替莫唑胺(150 mg/m2)辅助化疗6个周期,观察1、2年生存率和无进展生存率及治疗期间的不良反应.结果 43例患者全部完成治疗,中位随访24个月,1、2年生存率分别为81.4％、55.8％,1、2年无进展生存率分别为65.1％、44.2％.其中,病理分级为Ⅲ级患者的1、2年生存率分别为88.0％、72.0％,1、2年无进展生存率分别为76.0％、60.0％;病理分级为Ⅳ级患者的1、2年生存率分别为72.2％、33.3％,1、2年无进展生存率分别为50.0％、22.2％.Ⅲ级患者的2年生存率和无进展生存率明显优于Ⅳ级患者,差异有统计学意义(P＜0.05).治疗期间主要不良反应为急性中枢神经毒性、血液学毒性、胃肠道反应,未观察到3级以上毒性反应及放射性脑坏死.结论 SIB-IMRT联合化疗治疗高级别脑胶质瘤术后患者的不良反应大部分能耐受,安全性良好,总的治疗时间有所缩短,值得临床上进一步研究.

目的 放疗为主的综合治疗是鼻咽癌的主要治疗手段,分子靶向治疗是近年研究的热点.本研究旨在评价诱导化疗序贯调强放疗同期联合尼妥珠单抗及塞来昔布,治疗局部晚期鼻咽癌的疗效及不良反应.方法 选取2013-06-01-2016-09-30江南大学附属医院就诊的31例局部晚期鼻咽癌患者,放疗前给予2个周期诱导化疗,采用IMRT技术,放疗同期给予尼妥珠单抗及塞来昔布治疗.根据RTOG评分标准评价放疗不良反应,NCI CTCAE 3.0标准评价化疗不良反应,RECIST实体瘤评价标准评价客观疗效.中位随访时间为30.5个月.采用Kaplan-Meier法绘制生存曲线.结果 放疗结束后3个月客观有效率100％.2年无进展生存率89.2％,95％CI为75.8％～98.5％,2年总生存率96.8％,95％CI为84.1％～100％.放疗期间不良反应3～4度发生率38.7％(12/13),其中口腔黏膜炎3～4度发生率25.8％(8/31),中性粒细胞减少3度发生率12.9％(4/31).所有患者均未出现尼妥珠单抗相关的皮疹、腹泻、过敏反应及塞来昔布相关的心血管不良反应.结论 诱导化疗序贯IMRT联合尼妥珠单抗及塞来昔布治疗局部晚期鼻咽癌耐受性良好,初步疗效满意,值得临床进一步研究.