Randomized trial of weekly docetaxel and cisplatin combined with concurrent 3DCRT in patients with locally advanced esophageal cancer

Abstract Objective： This randomized controlled clinical study was to assess and compare the efficacy and safety of two chemoradiotherapy regimens [cisplatin ＋ 5-fluorouracil ＋ 3 dimensional conformal radiation therapy （3DCRT） and cisplatin ＋ weekly docetaxel ＋ 3DCRT] in patients with locally advanced esophageal squamous cell carcinoma. Methods： A total of seventy-four patients with clinical stages liB to IIIB esophageal squamous cell carcinoma were enrolled. Chemotherapy for PF group comprised 5-fluorouracil at days 1-5 （250 mg/m2/d） and cisplatin （20 mg/m2） at days 1-3 of every 28-day cycle; full treatment course included 2 cycles. Chemotherapy for DP group comprised docetaxel （20 mg/m2） and cisplatin （20 mg/m2） at days 1,8, 15, 22, 29, and 36. Both groups treated with concurrent 60 Gy 3DCRT at 200 cGy/d. Results： Seventy-four patients were enrolled and 71 completed the planned treatment, with a follow-up rate of 95.94%. Short-term curative effect was not statistically significant between the two groups （P = 0.471）. The 2-year survival rates were 65.7% and 61.1%, respectively （P = 0.806）, 5 years survival rates were 34.29% and 27.78%, respectively （P = 0.221）, and there was no significant difference by Fisher test （P = 0.734）. As common side effects, incidence rates of radioactive esophagitis and hematological toxicity were lower in DP group. Conclusion： For locally advanced esophageal cancer patients, current chemoradiotherapy with chemo- therapy regimen of weekly docetaxel plus cisplatin has equal curative effect with 5-fluorouracil plus cisplatin, but well-tolerated by reducing side effects such as radioactive esophagitis and bone marrow suppression.

High power focused-beam microwave hyperthermia combined with intrapleural injection of Shapeilin in the treatment of patients with malignant hydrothorax

Objective:The aim of the study was to evaluate the efficacy and toxicity of high power focused-beam microwave hyperthermia with intrapleural injection of Shapeilin for patients with malignant hydrothorax.Methods:Fifty-eight patients with malignant hydrothorax were divided into group A and group B randomly.All patients underwent indwelling pleural catheter and were treated by intrapleural injection of Shapeilin once three days.Treatment was composed of 3 times injection.Patients of group B received high power focused-beam microwave hyperthermia after injection of Shapeilin.Results:The response rate of group B(79.3%) was higher than that of group A(48.3%)(P < 0.05).Incidence of main adverse reactions,associated with Shapeilin,of two groups including fever and thoracodynia were similar(P > 0.05).Patients of group B didn't encounter severe toxicities of microwave hyperthermia.Conclusion:High power focused-beam microwave hyperthermia combined with intrapleural injection of Shapeilin is effective and tolerable for patients with malignant hydrothorax.

The observation of single-agent gemcitabine maintenance therapy in patients with metastatic breast cancer

Objective:The aim of the study was to evaluate the efficacy and tolerability of single-agent gemcitabine in the maintenance treatment of histologically confirmed metastatic breast cancer cases.Methods:The 45 patients carried efficacious chemotherapy were divided into maintenance therapy group(n=23) and control group(n=22) according to the different treatment methods.Patients in the maintenance therapy group received gemcitabine therapy until 6 cycles,disease progression or adverse effect intolerance.Within the control group,the patients were given best supportive care.Follow-up was made until disease progression,death or 2 years.The short-term clinical efficacy and adverse effects,progression-free survival(PFS) and median survival of recurrence(MSR) of these two groups were compared and analyzed.Results:Compared with the control group,the experiment group had higher response rate(RR;73.9% vs 31.8%;P<0.05),and significantly progress of median PFS(13.1 vs 9.6 months;P<0.05).However,the progression of MSR had no statistically difference with the control group(23.3 vs 21.1 months;P>0.05).Most of the treatment-related adverse events were mild,and the most common adverse event was hematologic toxicity.The 3 cases occurred grades 3–4 neutropenia and 3 cases occurred grades 3–4 thrombocytopenia.The 1 patient stopped treatment because of grade 3 allergic reaction,and 4 patients required dose reduction for grade 4 adverse events.Other adverse effects were grades 1–2,and all were recovered after symptomatic treatment.There was no significant side effect which threatened the life.Conclusion:In the extension maintenance treatment,gemcitabine can consolidate the therapeutic effect in advance and significantly prolong median PFS of metastatic breast cancer patients.In conclusion,gemcitabine monotherapy with a favorable safety profile is an effective maintenance treatment in metastatic breast cancer patients.

Different response to neoadjuvant chemotherapy for different molecular subtypes in patients with locally advanced breast cancer

Objective： The aim of this study was to evaluate the impact of different molecular subtypes defined by immunohistochemistry （IHC） staining on the response rate for patients with locally advanced breast cancer received neoadjuvant chemotherapy. Methods： One hundred and seven breast cancer patients admitted from 2007 to 2011 who received 4 cycles of docetaxel/epirubicin-combined （TE） neoadjuvant chemotherapy were retrospectively reviewed, the patients were classified into 4 subtypes： luminal A, luminal B, HER-2 and triple negative breast cancer （TNBC） according to different combination patterns of estrogen receptor （ER）, progesterone receptor （PR） and human epidermal growth factor-2 （HER-2） expression defined by IHC method. The correlation between response rate and the molecular subtypes were analyzed. Results： The pathological complete response （PCR）, clinical complete response （CCR）, clinical partial response （CPR）, and clinical stable disease （CSD） rate of whole group was 15.89% （17/107）, 22.43% （24/107）, 63.55% （68/107）, 14.02% （15/107）, respectively, and the overall response rate （ORR） was 85.98% （92/107）. The PCR rate and ORR of luminal A, luminal B, HER-2 and TNBC subtypes was 4.76% and 73.81%; 16.67% and 83.33%;17.65% and 100.00%; 30.00% and 96.67%, respectively. The PCR and ORR rate of HER-2/TNBC subtypes was higher than that of luminal A/B subtypes （P = 0.019, P = 0.002, respectively）. Conclusion： Different molecular subtypes display different response rate for patients with locally advanced breast cancer received neoadjuvant TE chemotherapy, HER-2JTNBC subtypes have a higher PCR and ORR rate than that of luminal NB subtypes.

The side effects of docetaxel with cyclophosphamide as postoperative adjuvant chemotherapy for elderly breast cancer patients

Objective: The aim of this study was to investigate the side effects of docetaxel with cyclophosphamide as postoperative adjuvant chemotherapy for elderly breast cancer patients. Methods: Thirty-six operable elderly breast cancer patients at intermediate risk based on the St Gallen risk classification underwent modified radical mastectomy and then were given four cycles of TC regimen (docetaxel 75 mg/m2 i.v. on day 1; cyclophosphamide 600 mg/m2 i.v. on day 1; every 21 days ). Primary prophylaxis granulocyte colony stimulating factor (G-CSF) 200μg i.h. was administered on day 4-6. Results: The main side effect was neutropenia. Grade 3 neutropenia developed in 36.1% and G4 in 19.4%, respectively. Most of the other side effects were G1-2. Dose reduction occurred in 11.1% patients. The completion rate of chemotherapy was 100%. Conclu-sion: Docetaxel with cyclophosphamide as postoperative adjuvant chemotherapy regimen with G-CSF primary prophylaxis is tolerable for elderly patients in general good condition.

Effects of three-dimensional conformal radiotherapy on the esophageal carcinoma

Objective： Radiation therapy is an important component of the multidisciplinary management of esophageal carcinoma. Three-dimensional conformal radiation therapy requires the precise definition of the target volume. We aimed to compare the treatment results and radiation toxicities between three-dimensional conformal radiotherapy （3D-CRT） and conventional radiotherapy （CR） for patients with cervical and thoracic esophageal carcinoma. Methods： From June 2004 to December 2006, a random study was performed on 106 patients treated with 3D-CRT or CR, 53 patients in each group. The patients in CR group received conventional radiotherapy in 2.0 Gy/f, 5 f/week and total dose was 66-70 Gy in 6.5 or 7 weeks. The patients in 3D-CRT group were treated by 3D-CRT in 2.0 Gy/f, 5 f/week and total dose was 64-70 Gy in 6 weeks. The local control rates, survival rates and radiation toxicities for the two groups were investigated. Results： The 1-year and 3-year local control rates were 83.0% and 60.4% in 3D-CRT group and 64.2% （x^2 = 4.853, P = 0.028） and 32.1% （x^2 = 9.812, P = 0.002） in CR group. The 1-year and 3-year survival rates were 73.6% and 50.9% in 3D-CRT group and 54.7% （x^2 = 4.102, P = 0.043） and 32.1% （x^2 = 3.886, P = 0.049） in CR group. Between the two groups, there was no significant difference in radiation toxicities. Conclusien： The 1-year and 3-year local control rates and survival rates of patients with esophageal carcinoma treated by 3D-CRT is superior to CR. However, longer-term results and radiation toxicity need further study which involves more patients and prolonged follow-up.

A live attenuated virus-based intranasal COVID-19 vaccine provides rapid,prolonged,and broad protection against SARS-CoV-2

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);however,they are limited with respect to eliciting local immunity in the respiratory tract,which is the primary infection site for SARS-CoV-2.To overcome the limitations of intramuscular vaccines,we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain(RBD)of the spike protein of SARSCoV-2,named CA4-d NS1-n CoV-RBD(d NS1-RBD).A preclinical study showed that in hamsters challenged 1d after single-dose vaccination or 9 months after booster vaccination,d NS1-RBD largely mitigated lung pathology,with no loss of body weight.Moreover,such cellular immunity is relatively unimpaired for the most concerning SARS-Co V-2 variants,especially for the latest Omicron variant.In addition,this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses.The protective immune mechanism of d NS1-RBD could be attributed to the innate immune response in the nasal epithelium,local RBD-specific T cell response in the lung,and RBD-specific Ig A and Ig G response.Thus,this study demonstrates that the intranasally delivered d NS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection,compensating limitations of current intramuscular vaccines.

Histopathological Features and Viral Antigen Distribution in the Lung of Fatal Patients with Enterovirus 71 Infection

Dear Editor,Enterovirus 71(EV71)infection causes hand-foot-andmouth disease(HFMD)in infants and children.Patients with HFMD usually have good prognosis;however,in some extreme cases the infection can be accompanied by central nervous system diseases,eventually leading to cardiorespiratory failure,and even death.Currently。

Synthesis and application of near-infrared substituted rhodamines

Near infrared(NIR) fluorescent probes are highly attractive in the field of fluorescent imaging of living organisms for their outstanding signal-to-noise ratio, strong tissue penetration and low biotoxicity.Herein, we summarized some recent progress in the synthesis and application of NIR rhodamines by replacing the bridging oxygen atom with main group elements such as silicon and phosphorus.

A simplex method for the orbit determination of maneuvering satellites

A simplex method of orbit determination （SMOD） is presented to solve the problem of orbit determination for maneuvering satellites subject to small and continuous thrust. The objective function is established as the sum of the nth powers of the observation errors based on global positioning satellite （GPS） data. The convergence behavior of the proposed method is analyzed using a range of initial orbital parameter errors and n values to ensure the rapid and accurate convergence of the SMOD. For an uncontrolled satellite, the orbit obtained by the SMOD provides a position error compared with GPS data that is commensurate with that obtained by the least squares technique. For low Earth orbit satellite control, the precision of the acceleration produced by a small pulse thrust is less than 0.1% compared with the calibrated value. The orbit obtained by the SMOD is also compared with weak GPS data for a geostationary Earth orbit satellite over several days. The results show that the position accuracy is within 12.0 m. The working efficiency of the electric propulsion is about 67% compared with the designed value. The analyses provide the guidance for subsequent satellite control. The method is suitable for orbit determination of maneuvering satellites subject to small and continuous thrust.