Objective:To explore the effects of Onodera′s prognostic nutritional index (PNI) on the prognosis of locally advanced oropharyngeal squamous cell carcinoma (LA-OPSCC) after induction chemotherapy followed by sequential chemoradiotherapy.Methods:A retrospective analysis was conducted on the clinical data of 52 LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy in The Affiliated Cancer Hospital of Guizhou Medical University during 2014-2018. The PNI values of all the patients at different treatment phases were statistically analyzed, and the ROC curve was employed to determine the optimal critical value of PNI. The patients in this study were divided into a well-nourished group ( n = 27) and a poorly-nourished group ( n = 25). The Kaplan-Meier method was used for survival analysis. The Cox proportional hazards model was utilized to analyze the relationships between different nutritional status and prognosis. Clinical features and adverse reactions were compared between the two groups. Results:The PNI values decreased significantly after radiotherapy, with an optimal critical value of 42.4. The 5-year overall survival (OS) and progression-free survival (PFS) of the well-nourished group (PNI ≥ 42.4) were 62.6% and 60.9%, respectively, which were significantly higher than those (30.1% and 29.7%) of the poorly-nourished group (PNI < 42.4, χ2 = 11.12, 5.74, P < 0.05). The multivariate analysis showed that PNI was an independent prognostic factor for the OS after radiotherapy ( HR = 2.752, 95% CI: 1.095-6.917, P = 0.031). The LA-OPSCC patients aged over 60 years or those who did not respond to induction chemotherapy accounted for a higher proportion of malnutrition after chemoradiotherapy ( χ2 = 4.89, 5.05, P < 0.05). Conclusions:PNI after radiotherapy can be used as a prognostic factor in the evaluation of LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy. The LA-OPSCC patients aged over 60 years or those who do not respond to induction chemotherapy should receive more nutritional support during the chemoradiotherapy.

Objective:To explore the clinical significance and prognostic value of fibrinogen (FIB) in the treatment of locally advanced head and neck squamous cell carcinoma with induction chemotherapy combined with radiotherapy.Methods:A retrospective analysis was conducted for the clinical data of 114 patients with locally advanced head and neck squamous cell carcinoma receiving non-surgical treatment in the Department of Head and Neck Oncology, the Affiliated Cancer Hospital of Guizhou Medical University from May 2011 to May 2021. The FIB critical value was determined based on the median FIB level before induction chemotherapy, by which patients were divided into high-FIB and low-FIB groups. The ROC curves were used to determine the optimal cut-off value for other hematologic-related parameters such as neutrophils, lymphocytes, and platelets. Statistical methods were used to analyze the results. The enumeration data were analyzed by Chi-square test or Fisher exact probability method. Survival curves for OS and PFS were plotted by Kalplan-Meier method and tested by Log-rank method. Prognostic factors were evaluated by Cox proportional hazard regression model.Results:There were 59 cases in the high-FIB group (FIB > 3.6 g/L) and 55 cases in the low-FIB group (FIB ≤ 3.6 g/L). The high FIB group had higher neutrophils, platelets, NLR, and PLR ( χ2= 7.84, 12.80, 15.04, 9.14; P<0.05) than the low FIB group. The 3- and 5-year overall survival (OS) rates were significantly longer in the low FIB group than those in the high-FIB group (62.9% vs. 39.6%; 46.9% vs. 25.8%), and progression-free survival (PFS) rates of the low FIB group significantly longer than those of the high-FIB group (63.3% vs. 40.3%; 48.1% vs. 26.2%). The univariate analysis showed that the OS and PFS in patients with locally advanced head and neck squamous cell carcinoma were related to FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes. The multivariate analysis showed that FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes were independent prognostic factors of the OS [ HR (95% CI): 1.89 (1.08-3.31), 3.76 (1.12-12.65), 2.14 (1.09-4.21), P < 0.05]and PFS HR (95% CI): 1.92 (1.90-3.36), 3.93 (1.01-11.34), 2.15 (1.09-4.22), P < 0.05]of patients with locally advanced head and neck squamous cell carcinoma. Conclusions:Patients with low FIB receive high OS and PFS rates after induction chemotherapy combined with radiotherapy. Therefore, FIB can be used as a prognostic factor in the evaluation of non-surgical treatment of patients with locally advanced head and neck squamous cell carcinoma.

Objective: To evaluate the long-term effect and safety of chrono-chemotherapy combined with intensity modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma (NPC). Methods: 160 patients with locally advanced NPC were randomly divided into a chrono group and conventional group according to random number table. In the first stage, all patients underwent two cycles of induced chemotherapy, consisting of docetaxel, cisplatin and 5-Fu every 21 days. Notably, patients received chrono-moduated chemotherapy according to circadian rhythm in the chrono group, and conventional chemotherapy in the conventional group. Then, 21 days after the completion of first stage, three cycles of concurrent cisplatin chemotherapy every 21 days were given to all patients during IMRT. The median follow-up after the completion of radiotherapy was 31 months. Long-term side effects and the survival of patients were observed. Results: Patients in the chrono group had significantly lower rates of hearing loss (22.72%), dysphagia (0) and neck fibrosis (4.54%) compared with those in the conventional group (39.13%、8.69%, 15.94%, respectively, all P<0.05). Meanwhile, the 1- year overall survival rates (97.0% vs 92.8%), 3-year overall survival rates (80.3% vs 81.2%), 1-year progression free survival rates (95.5% vs 87.0%), 3-year progression free survival rates (71.2% vs 73.9%), 1-year locoregional relapse-free survival rates (97.0% vs 95.7%), 1-year locoregional relapse-free survival rates (92.4% vs 92.8%), 1-year distant metastasis-free survival rates (97.0% vs 98.6%) and 3-year distant metastasis-free survival rates (90.9% vs 91.3%) between the chrono group and the conventional group were not statistically significant (all P>0.05). Conclusions Compared with conventional chemotherapy, chrono-chemotherapy combined with IMRT didn′t affect long-term survival, but reducing the incidence of adverse events in patients with locally advanced NPC.

Objective: To compare the adverse events, immune status, and short-term efficacy between chronomodulated chemotherapy (CCR) and routine chemotherapy (RCR) combined with intensity modulated radiotherapy (IMRT)in the treatment of patients with locally advanced nasopharyngeal carcinoma. Methods: A total of 159 patients with newly diagnosed locally advanced nasopharyngeal carcinoma were randomized into the CCR group and the RCR group to evaluate the short-term efficacy and adverse events. Results: No significant difference was found in CR, PR, SD, and PD between the CCR group and the RCR group (P>0.05), and no significant difference was observed in the response rate (CR+ PR) between the two groups (P>0.05). The incidence of leukopenia(Z=-2.222, P<0.05), neutropenia(Z=-1.999, P<0.05), vomiting(Z=-2.298, P<0.05), and oral mucositis(Z=-3.571, P<0.05)of the CCR group was lower than those of the RCR group with statistical significance. The CD16+ 56+ lymphocyte cell count was higher in the CCR group than that in the RCR group(Z=-2.332, P<0.05). Conclusions As a novel invention, CCR combined with IMRT can reduce the incidence and severity of treatment-related adverse events and improve immune status without diminishing clinical efficacy, therefore deserving clinical application.

Objective To explore efficacy and safety of simulated artificial pancreas in modulating stress hyperglycemia in critically ill patients. Methods A prospective randomized controlled study was performed. Seventy-two critically ill patients with stress hyperglycemia, aged 18-85 years, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score over 15, two consecutive random blood glucose 11.1 mmol/L or higher, glycated hemoglobin (HbA1C) below 0.065, unable to eat food for 3 days after inclusion, or only accepting parenteral nutrition, admitted to intensive care unit (ICU) in Shanghai Punan Hospital of Pudong New District from January 1st, 2015 to June 30th, 2017 were enrolled. The patients were divided into three groups according to the random number table method, high-intensity group and low-intensity group were injected Novolin R (high-intensity group 2/3 dosage, low-intensity group 1/3 dosage) to modulate stress hyperglycemia by simulated artificial pancreas. Simulated artificial pancreas consisted of Guardian real time glucose monitoring system (GRT system), close-circle control algorithm and micro-pump;subcutaneous injection of Humulin 70/30 was applied to modulate stress hyperglycemia in humulin group. Real-time glucose levels of interstitial fluid in abdominal wall, equivalent to blood glucose levels, 10 minutes each time, were monitored by using of GRT system for all patients in three groups. Fasting serum levels of stress hormones including epinephrine and cortisol and insulin resistance index (IRI) were recorded within 24 hours after inclusion. Mean blood glucose, blood glucose variation coefficient, blood glucose target-reaching rate, blood glucose target-reaching time, hypoglycemia rate and 6-month mortality were measured. Twenty healthy adults from health administration department of the hospital were recruited as healthy control group. Results A total of 60 eligible critically ill patients were included in this study, each group with 20 patients. There was no significant difference in gender, age, APACHE Ⅱ scores among three groups. The levels of serum epinephrine, cortisol and IRI within 24 hours after inclusion in the three groups were significantly higher than those in healthy control group. The mean blood glucose levels of humulin group, low-intensity group, high-intensity group were decreased (mmol/L: 10.2±3.2, 8.4±2.6, 8.1±2.2), the blood glucose target-reaching rate were increased [40.2% (3 295/8 196), 71.1% (5 393/7 585), 80.4% (6 286/7 818)], the blood glucose target-reaching time were shortened (hours: 49.1±5.8, 24.6±4.6, 17.5±4.2), the hypoglycemia rates were increased respectively [1.3% (108/8 196), 2.8% (211/7 585), 4.0% (313/7 818)], with statistically significant differences (all 1 = 0.000). There was no significant difference in blood glucose variation coefficient and 6-month mortality among three groups [blood glucose variation coefficient: (29.4±3.7)%, (28.5±5.3)%, (26.1±4.6)%, 6-month mortality: 55.0%, 45.0%, 40.0%, all 1 > 0.05]. Conclusions Simulated artificial pancreas could effectively and safely modulate stress hyperglycemia in critically ill patients, high-intensity modulation could bring about better efficacy in the regulation of hyperglycemia. High-frequency blood glucose monitoring by using GRT system could promptly identify hypoglycemia and help it to be corrected.

Objective To assess the antiangiogenic role of recombinant human endostatin combined with chemoradiotherapy and the capacity,and to explore the early tumor response as measured by comparing the change of MRI perfusion parameter.Methods From May 2012 to March 2013,22 locally advanced nasopharyngeal carcinoma patients who received recombinant human endostatin combined with chemoradiotherapy following induction chemotherapy,were included in the prospective study group.The other 25 patients,who received chemoradiotherapy following induction chemotherapy alone in the same period,were included in the control group.The perfusion parameters including blood volume(BV),blood flux(BF),mean transit time (MTT) were obtained by carrying out MR perfusion scanning at 3 time points:before induction chemotherapy,after induction chemotherapy,the end of concurrent chemoradiotherapy.Results Compared with before induction chemotherapy,the perfusion parameters including BV and BF obviously decreased in the study group (F =3.05,3.85,P ＜ 0.05).The parameter of MTT had no obviously change in the study group(P ＞0.05).In the control group,the change of BV,BF and MTT of nasopharyngeal lesions area during the treatment showed no significant difference (P ＞ 0.05).To make comparison between the two groups,at the end of concurrent chemoradiotherapy,BF of nasopharyngeal lesions area in the study group was 0.72 ± 0.56 and 1.92 ± 1.26 in the control group,the former showing significantly declined results (t =-3.056,P =0.012).Conclusions Recombinant human endostatin might be a good indicator of local tumor microvascular changes and the treatment-related toxicity could be tolerated.Magnetic resonance perfusion imaging maybe assessed the capacity of anti-angiogenesis therapy to induce early tumor response.Clinical trial registration Chinese clinical trial registry,ChiCRTONRC-12002394.

Objective:To investigate the outcomes of the regimen with docetaxel, cisplatin, and 5-fluorouracil (TPF regimen) in chrono-chemotherapy, and evaluate the feasibility of reducing the toxicity and immunological damage in nasopharyngeal carcinoma (NPC) patients with distant metastasis at preliminary diagnosis, then to compare the advantages and disadvantages between chrono-che-motherapy and traditional chemotherapy. Methods:A total of 46 NPC patients with distant metastasis at preliminary diagnosis (UICC 2010 stage IVc) were enrolled in this study. These NPC patients were randomly divided into chrono-chemotherapy and conventional chemotherapy groups, with 23 cases for each group. TPF neo-adjuvant chemotherapy was conducted in both groups for two cycles, with 21 days to 28 days for each cycle. The following regimen was used for the chrono-chemotherapy group:docetaxel 75 mg/m2, infu-sion, d1;cisplatin 75 mg/m2, 10:00 a.m.-10:00 p.m., continuous infusion, d1-d5;and fluorouracil 750 mg/(m2 · d), 10:00 p.m.-10:00 a. m., continuous intravenous infusion, d1-d5. The following regimen was used for the conventional chemotherapy group:docetaxel 75 mg/m2, infusion, d1;cisplatin 75 mg/m2, infusion, d1;and fluorouracil 750 mg/(m2· d), continuous infusion, d1-d5, 120 h. Patients who obtained therapeutic efficacy via induction chemotherapy were provided with intensity-modulated radiotherapy as a concurrent radio-therapy and chemotherapy (DDP 100 mg/m2, infusion, d1-d2, with 21 days each cycle and a total of two courses). One month after con-current chemoradiation, an adjuvant chemotherapy with the same regimen as the induction chemotherapy was employed for a total of two courses. Acute and late toxicities were graded in accordance with the Common Terminology Criteria for Adverse Events v3.0 scor-ing. Tumor response was evaluated using the 2000 Response Evaluation Criteria in Solid Tumors. The effective rates included complete and partial responses. Relevant data were analyzed by SPSS16.0 statistical software. Results:More emesis was observed at Grade 2 or above in the conventional chemotherapy group than in the chrono-chemotherapy group, with statistical significance between the two groups (P=0.035). After chemotherapy, the value of CD4/CD8 increased in the chrono-chemotherapy group and decreased in the con-ventional chemotherapy group, with statistical significance between the two groups (P=0.033). Conclusion:The proposed chrono-che-motherapy outperforms conventional chemotherapy in reducing the occurrence of severe vomiting. This chrono-chemotherapy may be advantageous in reducing severe bone marrow depression and may play a positive role in the immune function of NPC patients.

OBJECTIVETo compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC).

METHODSSeventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle.

RESULTSSixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in both of the two groups. The PR was 80.6% in the chronochemotherapy group and 50.0% in the conventional chemotherapy group (P=0.009). After concurrent chemoradiotherapy, the CR rate in the chronocheotherapy group was 45.5%, significantly higher than 20.7% in the conventional chemotherapy group (P=0.040). Secondly, the incidence rates of adverse reactions including bone marrow suppression, nausea, vomiting, diarrhea, constipation, oral mucositis, fatigue, anorexia in the chrono-chemotherapy group were significantly lower than that in the conventional group (P<0.05 for all). Finally, compared the two groups, the CD4+ /CD8+ ratio was significantly lower in the chronochemotherapy group than that in the conventional chemotherapy group (P<0.05). The lymphocytes CD19+ and CD4+/CD8+ were decreased and CD3+, CD4+, CD8+, CD16++CD56+ were increased in the chronochemotherapy group, while only CD3+ and CD8+ were increased in the conventional chemotherapy group.

CONCLUSIONSCompared with the conventional chemotherapy, the chronochemotherapy may be more favorable in the treatment of NPC, with a better therapeutic effects and effectiveness than that of conventional chemotherapy after induction chemotherapy, with less side effects, and can improve the immune function in the patients.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Carcinoma ; Chemoradiotherapy ; Cisplatin ; administration & dosage ; Drug Chronotherapy ; Fluorouracil ; administration & dosage ; Humans ; Induction Chemotherapy ; methods ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Nausea ; Neoplasm Staging ; Radiotherapy, Intensity-Modulated ; Taxoids ; administration & dosage ; Treatment Outcome

OBJECTIVETo compare the short-term efficacy and observe the tolerability and safety of recombinant human endostatin combined with induction chemotherapy followed by chemoradiotherapy for locally advanced nasopharyngeal carcinoma.

METHODSFifty-three patients with locally advanced nasopharyngeal carcinoma, who received recombinant human endostatin combined with induction chemotherapy followed by chemoradiotherapy, treated in our department from December 2011 to March 2013 were included in the study group of this study. Another 48 patients, who received induction chemotherapy followed by chemoradiotherapy alone in the same period, were chosen as a control group. The short-term outcome, overall survival (OS), progression-free survival (PFS), and acute side effects of the two groups were compared.

RESULTSThe complete remission rates of nasopharyngeal tumor in the study and control groups were 77.4% and 72.9%, respectively (P=0.154). The complete remission rates of patients with and without cervical lymph node metastasis were 75.5% and 62.6%, respectively, showing a significant difference (P=0.037). The 2-year OS, PFS, and DMFS rates for the study group were 82.3%, 77.2%, and 82.2%, respectively, versus 87.2%, 84.3% and 84.2% for the control group, showing a non-significant differences between the two groups (P=0.938, P=0.551, and P=0.725).

CONCLUSIONSThe short-term results of recombinant human endostatin (Endostar) combined with induction chemotherapy followed by concurrent chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma are slightly better than that of induction chemotherapy followed by concurrent chemoradiotherapy alone, with tolerable treatment-related toxicity and no more side effects.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma ; Chemoradiotherapy ; Cisplatin ; Disease-Free Survival ; Endostatins ; therapeutic use ; Humans ; Induction Chemotherapy ; Lymphatic Metastasis ; Nasopharyngeal Neoplasms ; drug therapy ; radiotherapy ; Remission Induction

Objective To analyze the long?term efficacy of intensity?modulated radiotherapy (IMRT) with or without chemotherapy in treatment of 454 patients with nasopharyngeal carcinoma (NPC) and its influencing factors. Methods A retrospective analysis was performed on the clinical data of 454 patients with non?metastatic NPC who received IMRT with or without chemotherapy in our center from 2007 to 2012. Prescribed doses of 69. 96?73. 92 Gy in 33 fractions, 69. 96 Gy in 33 fractions, 60. 06 Gy in 33 fractions, and 50. 96 Gy in 28 fractions were applied to nasopharyngeal gross tumor volume, cervical metastatic lymph nodes, high?risk drainage area, and low?risk drainage area, respectively. In all patients, 438 received induction chemotherapy, 420 concurrent chemotherapy, and 216 adjuvant chemotherapy, most of which were based on cisplatin and taxol. The Kaplan?Meier method was used for calculating survival rates and the log?rank test was used for survival difference analysis and univariate prognostic analysis. The Cox model was used for the multivariate prognostic analysis. Results The 3?year sample size was 210. The 3?year overall survival ( OS ) , local recurrence?free survival, nodal relapse?free survival, progression?free survival, and distant metastasis?free survival ( DMFS) rates were 88. 1%, 91. 0%, 90. 7%, 80. 5%, and 85. 1%, respectively. Age, T stage, and N stage were influencing factors for the OS rate ( P=0. 011;P=0. 005;P=0. 033);T stage and N stage were influencing factors for the disease progression?free survival ( P=0. 017;P=0. 005) and DMFS ( P=0. 012;P=0. 019) . The grade≥3 acute and late adverse reactions included hematological toxicity , oral mucositis , xerostomia , dysphagia , and brain injury . Conclusions IMRT promotes the long?term survival rates in patients with NPC. The distant metastasis is the major reason for treatment failure. The adverse reactions induced by IMRT combined with chemotherapy are tolerable.