EGFR tyrosine kinase inhibitors (TKIs) treatment has been established as standard therapy for EGFR-mutated adenocarcinomas. In the studies which published prospective randomized trials comparing EGFR TKIs with chemotherapy, a very low percentage of EGFR-mutated non-adenocarcinomas was enrolled in clinical trials. The efficacy of TKIs treatment for EGFR-mutated non-adenocarcinomas and their relationship with clinicopathological characteristics remain debatable. The results of retrospective studies show that the frequency of EGFR mutation is lower in non-adenocarcinoma than that of adenocarcinoma and efficacy of TKIs treatment for non-adenocarcinoma is inferior to adenocarcinoma. Smoking status is significantly associated with the efficacy of TKIs treatment for EGFR-mutated non-adenocarcinomas. The EGFR mutation rate and efficacy of TKIs treatment in adenosquamous cell carcinoma are higher than those of squamous cell carcinoma or large cell lung carcinoma. It may be concluded that the incidence of EGFR mutations in patients with non-adenocarcinoma NSCLC from mainland China is not very low and it is reasonable that EGFR TKIs could be an option for the treatment of EGFR-mutated non-adenocarcinoma NSCLC, especially for patients with adenosquamous histology and non-smokers. It is necessary to conduct a large-sample prospective study to understand the clinicopathological characteristics of non-adenocarcinomas and to evaluate the efficacy of EGFR TKI treatment or/and chemotherapy for EGFR-mutated non-adenocarcinoma NSCLC.

OBJECTIVETo evaluate the accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy (NAC) with three-dimensional (3D) reconstruction technique.

METHODSThis was a prospective study. The data of 61 patients with pathologically proven solitary invasive ductal carcinoma (IIA-IIIC) who had received 6 to 8 cycles of NAC from July 2010 to August 2013 was analyzed. All the patients were female, aging from 31 to 70 years with a median of 49 years. Breast specimen after surgery was prepared with part-mount sub-serial section, and residual tumors were microscopically outlined, scanned and registered by Photoshop software. The 3D model of pathological and MRI residual tumors was reconstructed with 3D-DOCTOR software. The longest diameter, maximum cross-section area and volume of the residual tumors determined using 3D MRI were compared with 3D pathological findings, and the associations between MRI and pathology were analyzed by Spearman rank correlation and Bland-Altman analysis.

RESULTSThe longest diameter, maximum cross-section area and volume of the residual tumors after NAC measured by MRI and pathology was highly correlated (r=0.942, 0.941, 0.903, all P=0.00). MRI appears to underestimate pathology in the longest diameter, maximum cross-section area, but slightly overestimate in volume, and two methods had a good consistence (MD=0.3 cm, 95% CI: -1.43 to 1.9 cm; MD=1.39 cm², 95% CI: -9.55 to 12.34 cm²; MD=-0.433 cm³, 95% CI: -7.065 to 6.199 cm³).

CONCLUSION3D MRI reconstruction after NAC could accurately detects the residual tumors after neoadjuvant chemotherapy, and contribute to select patients who received breast conserving therapy after NAC with tumor downstaging.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; diagnosis ; drug therapy ; Female ; Humans ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm, Residual ; diagnosis ; Prospective Studies ; Tomography, X-Ray Computed

AIM: To examine the effects of salidroside on choroidal thickness, hypoxia-inducible factor-1α(HIF-1α), dopamine(DA)and its D1 receptor expression in guinea pigs with lens-induced myopia(LIM).METHODS: A total of 18 two-week-old guinea pigs were randomly divided into the normal control(NC)group, the LIM group, and the LIM + salidroside(LIM+SA)group, with 6 guinea pigs in each group. The guinea pigs in the NC group were fed normally and intragastrically administered with 2 mL/d saline; those in the LIM group wore a -5D lens in front of their right eyes to establish a myopia model, then they were intragastrically administered with 2 mL/d saline. Finally, those in the LIM+SA group wore glasses along with intragastric administration of 2 mL/d salidroside at a dose of 100 mg/kg. The refraction, axial length, and choroidal thickness of guinea pigs in each group were measured 4wk following the establishment of the model. In addition, the relative mRNA expression and protein content of HIF-1α in the choroid and retina of guinea pigs in each group were detected by real-time quantitative PCR(qPCR)and immunohistochemistry(IHC). Finally, the DA concentration and its D1 receptor expression were detected by enzyme-linked immunosorbent assay(ELISA)and Western blot.RESULTS: At 4wk after model establishment, guinea pigs of LIM group and LIM+SA group exhibited increased negative refraction of the right eye, prolonged axial length, and decreased choroidal thickness compared to the NC group. The relative mRNA expression and protein content of HIF-1α in the choroid and retina of the guinea pigs increased. The concentration of DA and the expression of its D1 receptor both decreased. Moreover, compared to the LIM group, the diopter of the right eye of guinea pigs in LIM+SA group significantly reduced, the axial length was shorter, the thickness of choroid increased, the relative mRNA expression and protein content of HIF-1α in the choroid and retina decreased and the concentration of DA and the expression of its D1 receptor both increased.CONCLUSION: Salidroside can delay myopia progression in myopic guinea pigs by affecting choroidal thickness and the expression of HIF-1α, DA and its D1 receptor.

OBJECTIVEThe aim of this study was to determine the impact of routinely performed internal mammary sentinel lymph node biopsy (IM-SLNB) on the staging and treatment, and to analyze the success rate, complications and learning curve.

METHODSAll patients with biopsy-proven breast cancer who underwent sentinel lymph node biopsy between 2012 and 2014 were included in a prospective analysis. Internal mammary sentinel lymph node biopsy (IM-SLNB) was performed in all patients with IM-SLN visualized on preoperative lymphoscintigraphy and/or detected by intraoperative gamma probe detection. The adjuvant treatment plan was adjusted according to the current guidelines.

RESULTSIn a total of 349 patients, 249 patients (71.1%) showed internal mammary drainage. IM-SLNB was performed in 153 patients with internal mammary drainage, with a success rate of IM-SLNB of 97.4% (149/153). Pleural lesion and internal mammary artery bleeding were found in 7.2% and 5.2% patients, respectively. In 8.1% of patients (12/149) the IM-SLN was tumor positive. In the group of patients who underwent IM-SLNB, lymph node staging was changed in 8.1% of patients, and IMLNs radiotherapy was guided by these results, however, systemic treatment was changed in only 0.7% of the patients.

CONCLUSIONSIM-SLNB has a high successful rate and good safety. Identification of internal mammary metastases through IM-SLNB may provide more accurate staging and guide the tailored internal mammary radiotherapy.

TRIAL REGISTRATIONClinicalTrials. gov, NCT01642511.

Breast ; pathology ; Breast Neoplasms ; pathology ; Female ; Humans ; Learning Curve ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Mammary Arteries ; Neoplasm Staging ; methods ; Neoplasms, Second Primary ; Prospective Studies ; Sentinel Lymph Node Biopsy ; methods

Objective To optimize the measurement and analysis method for carbon-14 in environmental biological samples, and to provide technical support for the formulation of standard methods for carbon-14 measurement in environmental biological samples. Methods Through the optimization research on the carbon dioxide absorption method, the moisture content and carbon content of biological samples were measured with the moisture meter and the element analyzer according to the simplified personnel operation and the optimized process steps of the method, and intra- and inter-laboratory validation of the method was carried out. Results Under typical conditions, the lower limit of detection of the method reached 3 Bq/kg, and there were a relative standard deviation within laboratories of less than 17% and a relative standard deviation between laboratories of less than 14%, with a relative error of less than 19%. Most of the sample pretreatment was directly completed by the instrument and equipment, which improved the precision and accuracy of the measurement of moisture content and carbon content in samples, and reduced the influence of experiment personnel’s operation differences on the test results. Conclusion The lower limit of detection, precision, and accuracy of the optimized method meet the relevant requirements for the determination of carbon-14 in biological samples.

Objective To experimentally verify the precision and accuracy of determining tritiated water in ambient air using the desiccant adsorption sampling–high temperature negative pressure desorption of liquid water (containing HTO)–liquid Scintillation counter method, and to provide technical support for developing standard methods for monitoring tritiated water in ambient air. Methods The relative standard deviation and recovery of multi-group samples were verified by collecting, testing, and analyzing environmental samples with different activity concentrations. The uncertainty of the method was evaluated, the main uncertainty components were identified, and the reliability of measurement results was analyzed. Through experimental comparison of different methods, the differences in the test results of different methods were examined. Results The relative standard deviation of multiple samples ranged from 6.7% to 7.9%, the recovery ranged from 95.7% to 97.3%, and the uncertainty was greatly affected by the sample counting rate, with no significant difference as compared to condensation sampling method. Conclusion The precision and accuracy of this method meet the requirements of environmental authorities for monitoring tritiated water in ambient air, and it can be widely used in the monitoring of tritiated water in ambient air.

OBJECTIVETo explore the differences in volume and localization of the internal gross target volume and planning target volume delineated by clips and/or seroma based on four-dimensional computed tomography (4D-CT) during free-breathing in breast cancer patients after breast conserving surgery.

METHODSFifteen breast cancer patients after breast-conserving surgery (BCS) were recruited for external-beam partial breast irradiation (EB-PBI). On the ten sets CT images, the gross tumor volumes (GTV) formed by the clips, the seroma, and both the clips and seroma were delineated and defined as GTVc, GTVs and GTVc+s, respectively. Ten GTVc, GTVs and GTVc+s on the ten sets CT images produced the IGTVc, IGTVs, IGTVc+s. The PTVc, PTVs, PTVc+s were created by adding 15 mm to the IGTVc, IGTVs, IGTVc+s, respectively. The IGTV and PTV volume and distance between the centers of IGTVc, IGTVs, IGTVc+s and PTVc, PTVs, PTVc+s were all recorded. Conformity index (CI) and degree of inclusion (DI) were calculated for IGTV/IGTV and PTV/PTV, respectively.

RESULTSThe volume of IGTVc+s[(35.73 ± 19.77) cm³] was significantly larger than the IGTVc [(28.35 ± 17.54) cm³] and IGTVs [(24.19 ± 21.53) cm³] (P < 0.05), and the volume of PTVc+s [(191.59 ± 69.74) cm³] was significantly larger than that of the PTVc [(161.53 ± 61.07) cm³] and PTVs [(148.98 ± 62.22)cm³] (P < 0.05). There were significant differences between the DIs of IGTVc in IGTVc+s and IGTVc+s in IGTVc, the DIs of IGTVs in IGTVc+s and IGTVc+s in IGTVs, the DIs of PTVc in PTVc+s and PTVc+s in PTVc, and the DIs of PTVs vs. PTVc+s and PTVc+s in PTVs (P < 0.05 for all). The CI of IGTVc/IGTVc+s (0.63 ± 0.14) and the CI of IGTVs/IGTVc+s (0.54 ± 0.17) were significant larger than that of the CI of IGTVc/IGTVs (0.40 ± 0.14)(P < 0.05). There were non-significant differences among the CI of PTVc/PTVs, PTVc/PTVc+s and PTVs/PTVc+s (0.73 ± 0.12, 0.78 ± 0.13 vs. 0.75 ± 0.17). The DIs and CIs of IGTV/IGTV and PTV/PTV were negatively correlated with their centroid distance (P < 0.05).

CONCLUSIONSThere are volume difference and spatial mismatch between the target volumes delineated on the basis of surgical clips and seroma. The DI and CI between the PTVs are larger than that between the IGTV. External-beam partial breast irradiation should be implemented based on the PTV that is defined based on both seroma and surgical clips.

Breast Neoplasms ; diagnostic imaging ; radiotherapy ; Female ; Four-Dimensional Computed Tomography ; Humans ; Mastectomy, Segmental ; methods ; Radiotherapy Dosage ; Respiration ; Seroma ; diagnostic imaging ; radiotherapy ; Surgical Instruments

OBJECTIVETo explore the clinical value and efficacy of reduced field intensity modulated radiation therapy (RF-IMRT) for patients with advanced cervical cancer.

METHODSSeventy-one patients with stage IIB-IIIB cervical cancer, who underwent reduced field IMRT (RF-IMRT group) and 72 patients treated with conventional radiotherapy (c-RT group) in Shandong Cancer Hospital between 2005 August and 2011 August, were enrolled in this study. The RF-IMRT plans were as follows: whole pelvic IMRT plan was performed to deliver an initial dose of 30 Gy, then the irradiated volume was reduced to lymphatic drainage region as well as paracervix and parametrium for an additional 30 Gy boost. Conventional 2-field RT plan was performed in these patients using ADAC Pinnacle 3 planning system, to be given the same prescription dose, and to compare the irradiation dose of organs at risk (OARs). At the same time, conventional 2-field RT was performed in 72 patients of the c-RT group. Concurrent chemotherapy and intracavitary brachytherapy were also performed in the two groups. The treatment response, toxicities, normal tissue avoidance, and survival were assessed.

RESULTSSixty-six patients of the RF-IMRT group and 65 patients of the c-RT group fulfilled the treatment plan. IMRT plans yielded better dose conformity to the target (0.711 ± 0.057 vs. 0.525 ± 0.062, P = 0.032) and better sparing of the rectum, bladder and small intestine (rectum: 41.6 ± 6.8 vs. 50.8 ± 3.2, P = 0.016; bladder: 40.2 ± 2.9 vs. 51.4 ± 1.8, P = 0.007; small intestine: 22.3 ± 2.6 vs. 35.8 ± 3.9, P = 0.004). The mean dose delivered to the planning target volume (PTV) was significantly higher in the RF-IMRT group than that in the c-RT group (60.8 vs. 51.2 Gy, P = 0.006). The RF-IMRT patients experienced significantly lower acute and chronic toxicities with comparable short-term effects than did those treated with conventional RT (P > 0.05). No significant differences were found between the two groups for 1-, 3-, and 5-year overall survival (OS) rates, while a significantly higher progression-free survival (PFS, 65.2% vs. 46.2%, P = 0.031) rate was observed in the RF-IMRT group.

CONCLUSIONSRF-IMRT yields higher dose distributions and lower toxicities compared with conventional RT, and both the tumor target volume and pelvic lymphatic drainage region achieve curative dose irradiation, the adjacent organs at risk are well protected, and with tolerable adverse reactions. Yet, RF-IMRT provides comparable clinical outcomes and higher PFS.

Adenocarcinoma ; drug therapy ; pathology ; radiotherapy ; Brachytherapy ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; radiotherapy ; Chemoradiotherapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; Organs at Risk ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated ; adverse effects ; methods ; Remission Induction ; Survival Rate ; Uterine Cervical Neoplasms ; drug therapy ; pathology ; radiotherapy

Objective: To investigate the potential dosimetric benefits of four-dimensional computed tomography (4DCT) compared to three-dimensional CT (3DCT) in the planning of radiotherapy for external-beam partial breast irradiation (EB-PBI). Methods: Three-DCT and 4DCT scan sets were acquired for 20 patients who underwent EB-PBI. For each patient a conventional 3D conformal plan (3D-CRT) was generated based on end-inhalation phase (EI). The treatment plan based on the 4DCT EI phase images was copied and applied to the end-exhalation phase (EE) and 3DCT images (defined as EB-PBI_EI, EB-PBI_EE, EB-PBI_3D, respectively). Results: The median volumes of the tumour bed based on 3DCT, EI and EE were 20.99 cm^3, 19.28 cm^3, and 18.78 cm^3, respectively. The tumour bed volume based on 3DCT was significantly greater than that of EI and EE volumes (P<0.05). The planning target volumes (PTV) coverage of EB-PBI_3D, EB-PBI_EI and EB-PBI_EE were 96.85%, 97.51%, 97.03%, respectively. The planning target volume (PTV) coverage of EB-PBI_3D was significantly less than that of EB-PBI_EI and EB-PBI_EE (P<0.05). The median homogeneity indexs (HI) based on 3DCT, EI and EE were 0.13, 0.13, 0.13, respectively. The median conformal indexs (CI) based on 3DCT, EI and EE were 0.68, 0.69, 0.68, respectively. The median mean doses (D_mean) based on 3DCT, EI and EE were 36.20 Gy, 36.20 Gy, 36.22 Gy, respectively. However there were no significant differences in the homogeneity index, conformity index and the mean dose of PTV between the three treatment plans (P>0.05). The EB-PBI_3D plan resulted in the largest organs at risk dose (P<0.05). Conclusion There was a significant benefit when using 4DCT to plan 3D-CRT for EB-PBI with regard to reduced non-target organ exposure, and might result in poor dose coverage when the PTV is determined using 3DCT.

OBJECTIVETo compare the methods of delineating the whole breast target volume based on surface marks, palpation and glandular tissue on CT images, and to explore the contouring criteria after breast-conserving surgery.

METHODSIn 15 patients with breast cancer after breast-conserving surgery, the whole breast target was delineated in 3D CT simulation images each by three different methods. The target volume delineated according to anatomical marks were named CTVan, according to breast palpation named CTVpa, and according to glandular mammary tissue showing by CT images named CTVgl. The volumes of CTVan, CTVpa and CTVgl, and the degree of inclusion (DI) and conformal index (CI) between the targets were measured.

RESULTSThe mean volumes of CTVan, CTVpa and CTVgl were (792.23 ± 282.25) cm(3), (618.33 ± 295.90) cm(3) and (196.83 ± 117.62) cm(3), respectively. The differences among the three methods were statistically significant (P < 0.001). The difference between CTVan and CTVpa had no statistical significance (P = 0.08), and both the differences between CTVan and CTVgl, and between CTVpa and CTVgl had statistical significance (both P < 0.001). The CI between CTVan and CTVpa (0.644 ± 0.122) was significantly larger than the CI between CTVan and CTVgl (0.264 ± 0.108), and the CI between CTVpa and CTVgl (0.328 ± 0.115)(P < 0.001). The DI of CTVan to CTVpa was 0.709 ± 0.144,DI of CTVgl to CTVan was 0.994 ± 0.005 and DI of CTVgl to CTVpa was 0.989 ± 0.008. The differences of inner, outer, upper and lower boundaries of CTVpa and CTVan were (3.35 ± 7.23) mm, (5.57 ± 13.37) mm, (1.75 ± 11.62) mm, and (11.25 ± 4.07)mm, respectively. The cranial and medial boundaries had a negative correlation with CTVpa (P < 0.05 for all).

CONCLUSIONSThe differences among the three methods in the delineation of whole breast target volume are statistically significant. The target volume delineated according to the glandular mammary tissue displayed by CT scan is significantly smaller than that by the other two methods. Combination of breast palpation and anatomical marks may be helpful in delineating the whole breast target volume is relatively reasonable at present.

Breast ; pathology ; Breast Neoplasms ; diagnostic imaging ; Female ; Humans ; Imaging, Three-Dimensional ; Mastectomy, Segmental ; Palpation ; Tomography, X-Ray Computed