Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with different doses of whole brain radiotherapy / 中华放射肿瘤学杂志

Objective:To analyze the prognosis and influencing factors of patients with brain metastases from non-small cell lung cancer (NSCLC) treated with different doses of whole brain radiotherapy (WBRT).Methods:A total of 244 NSCLC patients with brain metastases who underwent WBRT in the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different doses of WBRT (EQD 2Gy), they were divided into the 30-39 Gy group ( n= 104) and ≥40 Gy group ( n= 140). The intracranial progression-free survival (iPFS) and overall survival (OS) were compared betweentwo groups. According to the number of brain metastases, GPA score, KPS score, chemotherapy and targeted therapy, the prognosis of different doses of WBRT was further analyzed. Results:The median iPFS and OS of all patients were 6.9 months and 11.8 months, respectively. Univariate survival analysis: the 1-year iPFS and 1-year OS between two groups were 22.5% and 25.4%( P=0.430) and 41.1% and 46.4%( P=0.068), respectively. Multivariate survival analysis: different doses of WBRT were not associated with the improvement of iPFS and OS; independent factors influencing iPFS included local boost, gender, number of brain metastases, chemotherapy and targeted therapy; independent factors influencing OS included gender, number of brain metastases, chemotherapy and targeted therapy. Subgroup analysis: in patients with KPS≥90, the 1-year iPFS and OS of patients with WBRT ≥ 40 Gy were seemingly better than those of their counterparts with 30-39 Gy, but the difference was statistically significant only in OS ( P=0.047), the difference was not statistically significant in iPFS ( P=0.068); in patients with chemotherapy, the 1-year iPFS and OS of patients with WBRT≥40 Gy were better than those of their counterparts with 30-39 Gy ( P=0.017, P=0.012); in patients with targeted therapy, the 1-year iPFS and OS in the WBRT≥40 Gy group were better than those in the 30-39 Gy group ( P=0.012, P=0.045). Conclusions:The 30-39 Gy may be the appropriate dose of WBRT for NSCLC patients with brain metastases. WBRT≥40 Gy does not bring more benefits. WBRT≥40 Gy may benefit NSCLC patients with brain metastases with high KPS score or active systemic therapy.

Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with supplemental radiotherapy under different prognostic scores / 中华放射肿瘤学杂志

Objective:To analyze the prognosis and influencing factors of different radiotherapy modes in patients with brain metastases from non-small cell lung cancer (NSCLC), and to explore the best benefit population with radiotherapy boost under different prognostic scores.Methods:634 patients with brain metastasis from NSCLC admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different radiotherapy modes, they were divided into three groups: no radiotherapy group ( n=330), whole-brain radiotherapy group (WBRT)( n=127) and whole-brain radiotherapy combined with boost group (WBRT+ boost)( n=177). The intracranial progression-free survival (iPFS) and overall survival (OS) were calculated by Kaplan-Meier method. The multivariate prognostic factors were analyzed by the Cox models. Results:The median iPFS and OS of all patients were 6.9 months and 9.0 months, respectively. In the no radiotherapy, WBRT and WBRT+ boost groups, the 1-year iPFS was 15.1%, 16.3% and 40.2%( P=0.002), and the 1-year OS was 33.7%, 38.2% and 48.1%( P<0.001), respectively. Multivariate survival analysis demonstrated that different radiotherapy modes were the independent factors affecting iPFS and OS. Subgroup analysis revealed that for patients with 1-3 brain metastases, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone ( P=0.026, P=0.044) when GPA score was 2.5-4.0; the 1-year OS and iPFSin the WBRT+ boost group were better than those of WBRT alone ( P=0.036, P=0.049) when there was no targeted therapy; for patients with ≥4 brain metastases, the 1-year iPFS in the WBRT+ boost group was better than that of WBRT alone ( P=0.019, P=0.012) when GPA score was 2.5-4.0 and there was no targeted therapy. When the GPA score was 0-2 or there was targeted therapy, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone, but the difference was not statistically significant (all P>0.05). Conclusions:Radiotherapy can significantly improve the iPFS and OS of NSCLC patients with brain metastases. When the number of brain metastases is 1-3, GPA score is 2.5-4.0 or no targeted therapy, boost may improve the iPFS and OS; when the number of brain metastases is more than 4, GPA score is 2.5-4.0 or no targeted therapy, boost may only bring iPFS benefit; when GPA score is 0-2 or targeted therapy, boost may not benefit significantly.

Application value of contrast-enhanced ultrasound with SonoLiver software in intraoperative diagnosis of glioma / 中华超声影像学杂志

Objective:To explore the application value of contrast-enhanced ultrasound with SonoLiver software including quantitative analysis and dynamic vascular pattern (DVP) in the intraoperative diagnosis of glioma.Methods:SonoLiver software was used to analyze the contrast-enhanced ultrasound (CEUS) process of 252 cases with different grades of gliomas in General Hospital of Southern Theatre Command of PLA from 2006 to 2016. Among them, 144 were in the low-grade gliomas (LGG) group and 108 were in the high-grade gliomas (HGG) group. The quantitative parameters included maximum intensity (IMAX), time to peak (TTP) and mean transit time (mTT). The images of each CEUS were obtained, and the microvessel density (MVD) of corresponding pathology was compared, so as to analyze their correlations and characteristics.Results:There were significant differences in IMAX, TTP and mTT between the CEUS parameters of gliomas with different grades. IMAX in HGG group was significantly higher than that in LGG group( P<0.001), while TTP was shorter ( P=0.017) and mTT was longer( P=0.030). By correlation analysis between MVD and the CEUS parameters, MVD was positively correlated with IMAX ( r s=0.736, P<0.001) and mTT( r s=0.184, P=0.003), but negatively correlated with TTP( r s=-0.186, P=0.003). Compared with DVP images, the tumor areas of LGG group were mainly warm and black colors with small spots of cool-colored areas, and most of the surrounding areas were more obvious black areas. In HGG group, the tumor areas were mainly warm colors. Most of which were scattered in patchy cold colors areas, and the surrounding black areas were less ( P<0.05). There were significant differences in differentiating gliomas boundary before and after using DVP technique ( P<0.05). After using DVP, the boundary of glioma was clearer and more discernible. The discernibility of HGG group was up to 99%, and that of LGG group reached 97%. Conclusions:SonoLiver software can effectively and quantitatively analyze the CEUS parameters of gliomas with different grades, and its DVP images can directly reflect the contrast perfusion characteristics of gliomas, providing a new way to distinguish the boundary of gliomas and a new imaging method for the differential diagnosis of high and low grades of gliomas.

Association of postoperative radiotherapy and body mass index with the incidence of breast cancer related lymphedema in Chinese patients / 中国肿瘤临床

Objective: To investigate the correlation between body mass index (BMI) and the incidence of breast cancer (BC) related lymphedema (BCRL) in Chinese patients over the period following postoperative radiotherapy (RT). Methods: This study included 281 female patients with single-sided BC who were treated at The Fourth Hospital of Hebei Medical University between November 2013 and February 2015. The clinical data of these patients were collected prospectively and analyzed. Based on their BMI, the patients were classified into three subgroups: low BMI (BMI BMI>25, n=89), and high BMI (BMI≥28, n=98). The upper limb volume difference (ULVD) was compared between the diseased and healthy one. Univariate and multivariate generalized estimating equations (GEE) and linear logistic regression models were used to estimate the effects of RT and BMI on BCRL (defined as a ULVD ≥200 mL). In addition, these results were compared among the three BMI subgroups. Results: The mean ULVD before and after RT were 40.6 and 42.9 mL, respectively. The median ULVD before and after therapy remained constant at 30.0 mL; no significant difference was observed (P>0.05). Two and single patient respectively lacked one arm volume measurement before and after RT. The BCRL incidence rates in the low, middle, and high BMI subgroups before RT were 2.2% (2/93), 6.8% (6/88), and 13.3% (13/98); the corresponding rates after RT were 1% (1/93), 12.4% (11/89), and 12.2% (12/98), respectively. The GEE model indicated that RT did not cause an increase in the incidence rate of BCRL (P=0.529). Multivariable logistic regression for the middle and high BMI subgroups before RT (RR=4.199, P=0.693 and RR=10.999, P=0.002, respectively) and after RT (RR=13.287, P=0.047 and RR=14.308, P=0.029, respectively) indicated a significantly higher risk of BCRL in the high BMI subgroup . Similar results were obtained from the subgroup analyses of the middle BMI subgroup. Conclusions: The incidence and severity of BCRL do not decrease during the period following postoperative RT. Among Chinese BC patients, a lower threshold BMI of 28 kg/m2 appears to be associated with BCRL after RT. This is distinctly different from the commonly reported BMI threshold of 30 kg/m2 in most European and American studies.

Effect of whole-brain radiotherapy and TKIs on suvival of patients with brain metastases from non-small cell lung cancer stratified by EGFR mutation status / 中国肿瘤临床

Objective: To compare overall survival (OS) and intracranial progression-free survival (iPFS) effects of whole-brain radiotherapy (WBRT) and tyrosine kinase inhibitors (TKIs) in NSCLC patients with brain metastases (BM) stratified by EGFR mutation status (mutant, wild-type). Methods: We performed a retrospective analysis of 215 NSCLC BM patients diagnosed in January 2013 to January 2015 with known EGFR status and followed up to December 1, 2016. Stratified Kaplan-Meier curves and multivariate Cox models were used to evaluate the effects of WBRT (defined as≥30 Gy, "W") and TKIs (after BM, "T") on OS and iPFS independently and jointly. Two-sided P>0.20 was considered non-significant (ns). Results: In patients with BM, the mean age was 58 years, 52% were female, and 93% had adenocarcinoma. Those with EGFR mutations (114 patients) had "W" (35 patients) and "T" (87 patients) with adjusted hazard ratios (HRs) (P) of 1.135 (ns) and 0.202 (P<0.001) for OS, respectively, and 1.122 (ns) and 0.275 (P<0.001) for iPFS, respectively. "W+T" (22 patients), "T only" (65 patients), "W only"(13 patients), and "neither" (14 patients) had OS-median survival time (MST) of 14.1, 15.3, 7.1, and 4.3 months, respectively; their iPFS-MST were 14.1, 13.4, 6.8, and 4.5 months, respectively. Their adjusted HRs (P) were 0.196 (P=0.003), 0.114 (P<0.001), 0.434 (ns), 1.000 (ref) for OS, respectively, and 0.272 (P=0.012), 0.200 (P<0.001), 0.622 (ns), 1.000 (ref) for iPFS, respectively. Compared with "T only," "W+T" was not associated with better survival and "W only" had adjusted HRs (P) of 3.804 (P=0.025) for OS and 3.114 (P=0.032) for iPFS. The EGFR wild-type (101 patients) used "W" in 43 patients with OS-MST of 11.3 (7.1) and iPFS of 11.2 (4.8) months; the adjusted HRs (P) of "W"were 0.539 (P=0.105) for OS and 0.485 (P=0.048) for iPFS. Conclusions: In EGFR-mutant NSCLC BM patients, TKIs are associated with improved survival, whether, WBRT alone or combined are not. In cases of EGFR wild-type, WBRT confers the improved the iPFS.

The study of relationship between intelligence impairment and interictal epileptiform discharges spreading in mesial temporal lobe epilepsy / 中国神经精神疾病杂志

Objective To investigate the relationship between intelligence impairment and interictal epileptiform discharges spreading in mesial temporal lobe epilepsy(mTLE)patients. Method We assessed 145 patients diagnosed as mTLE and their general materials, analyzed the relationship between intelligence impairment and interictal epileptiform discharges spreading. Results ①Patients with mTLE with longer disease course and higher frequencies of epilepsy tended to have a severe impairment in the total intelligence quotient (IQ), verbal intelligence quotient (vIQ) and performance intelligence quotient (pIQ). ② IQ of was negatively correlated with the condition that interictal epileptiform discharges spreading to the ipsilateral central and parietal region in patients with left lesion; pIQ was negatively correlated with the condition that interictal epileptiform discharges spreading to the ipsilateral frontal region, while positively correlated with the condition that interictal epileptiform discharges spreading to the ipsilateral occipital region in patients with right lesion. Conclusion ①Intelligence impairment of mTLE patients is related with courses and frequencies.②Total IQ is more severely impaired by interictal epileptiform discharges spreading to the ipsilateral central and parietal region in left mTLE patients, and the pIQ is more severely impaired by interictal epileptiform discharges spreading to the ipsilateral frontal region in right mTLE patients.

Radiation boost does not help whole-brain radiotherapy further improve survivals of SCLC brain metastasis patients / 中华放射肿瘤学杂志

Objective To investigate the effect of radiation boost ( Boost ) on further improving overall survival ( OS) and intracranial progression-free survival ( IPFS) of small-cell lung cancer ( SCLC) brain metastases (BM) patients treated by whole-brain radiotherapy (WBRT). Methods A retrospective analysis of 142 consecutive SCLC BM patients admitted between 2013 and 2015 was conducted after excluding those with historical prophylactic cranial irradiation (n=16) or SRT (n=10) or local RT alone (n=1).The Kaplan-Meier curve was utilized to calculate the survival rate. The log-rank test and multivariate Cox proportional hazard regression model were utilized to evaluate clinical prognosis. Results All patients were aged 59. 6 years old on average, and the female proportion was 23％. The quantity of brain metastasis lesion was 1 in 35％, 2-3 in 23％ and ≥4 in 42％, respectively. The proportion of patients receiving chemotherapy was 70％. The median OS was 9. 0 months and the median IPFS was 7. 3 months. The accumulative mortality rate in the non-radiation ( n=53 ) , WBRT ( n=33 ) and WBRT+ Boost ( n=56 ) groups was 92％, 79％ and 73％, and the accumulative failure rate ( death or new/relapsed brain metastasis) was 94％, 82％ and 80％, respectively. Compared with the non-radiation group, WBRT and WBRT+Boost therapies exerted significant effect upon OS ( P=0. 000 and 0. 000) and IPFS ( P=0. 000 and 0. 000) . Compared with WBRT alone, WBRT+ Boost treatment exerted no significant effect upon OS ( P=0. 41 and 0. 51) . Conclusions WBRT can significantly improve OS and IPFS of patients with SCLC-BM. However, concurrent and additional radiation boost does not further improve the survival rate.

Effects of Lianhua Qingwen on Pulmonary Oxidative Lesions Induced by Fine Particulates (PM2.5) in Rats / 中国医学科学杂志(英文版)

Objective To investigate the antagonistic effects of different doses of Lianhua Qingwen on pulmonary injury induced by fine particulates PM2.5 in rats. Methods Fine particulates suspended in the environment were collected. Forty-eight healthy adult wistar rats were randomly divided into 6 groups with 8 rats in each group. Four groups of rats were exposed to PM2.5 by intratracheally dripping suspensions of fine particulates PM2.5 (7.5 mg/kg) as dust-exposed model rats. Among them 24 rats in three groups received Lianhua Qingwen treatment (crude drug) at a dose of 2 g/kg, 4 g/kg, 8 g/kg per day for 3 days before dust exposure and were defined as low-dose, middle-dose and high-dose Lianhua Qingwen treatment groups respectively. The other dust-exposed model rats without treatment were assigned as PM2.5 control group. The un-exposed rats were set as saline control group (1.5 ml/kg saline) and blank control group. All rats were killed after 24 hours of the exposure. Lung tissue, serum and bronchoalveolar lavage fluid (BALF) were collected. The levels of malonaldehyde (MDA), lactate dehydrogenase (LDH), and glutathione peroxidase (GSH-PX) in blood serum and BALF, and superoxide dismutase (SOD) in blood surum were measured using fluorescent quantitation PCR; Expression of NF-E2-related factor 2(NRF-2), heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO1) in lung tissues were measured using Western blot. Pathological changes of lung tissues in each group were also examined. Results Pathology revealed thickened alveolar septum, congestion of capillary, interstitial edema and infiltration of lymphocyte and neutrophil surrounding bronchiole in the PM2.5 control group, which were significantly relieved in the Lianhua Qingwen treatment groups. Compared to the blank and saline control groups, the PM2.5 control group had significantly higher levels of LDH and MDA (p<0.01) and lower level of GSH-PS (p<0.01) in BALF, significantly higher levels of LDH and MDA (p<0.05) and lower level of GSH-PS (p<0.05) in rat serum. The levels of MDA in blood serum and BALF were significantly lower in each treatment group than that in PM2.5 control group (all P<0.05). In both middle-dose and high-dose treatment group the measurements of LDH in serum and BALF as well as GSH-PX in serum were significant difference from those of PM2.5 control group (all P<0.05). Expressions of NRF-2, HO-1 and NQO1 in lung tissues were significantly different among middle-dose and high-dose treatment group compared with those in PM2.5 control group (all P<0.05). Conclusion Fine particulates PM2.5 in environment may induce pulmonary oxidative lesions in rats. Middle-dose and high-dose Lianhua Qingwen has antagonist effece on the injuries induced by fine particulates.

Impact of postoperative radiotherapy on the relationship between molecular subtype and prognosis in patients with breast cancer / 中华放射肿瘤学杂志

Objective To retrospectively investigate the impact of postoperative radiotherapy ( RT) on the relationship between molecular subtype and survival in patients with breast cancer ( BC ) . Methods A total of 716 women who were admitted to our hospital in 2008 and newly received unilateral mastectomy were divided into Luminal A ( LA ) , Luminal B?HER?2?negative ( LB1 ) , Luminal B?HER?2?positive ( LB2) , HER?2 overexpression ( HER?2+) , triple?negative ( TN) , and unassigned subtypes according to the 2011 St. Gallen Consensus. The Cox model was used to analyze the differences in overall survival ( OS) and disease?free survival ( DFS ) rates between subtypes in all patients, RT group, or non?RT group. The Kaplan?Meier method was used to calculate OS and DFS rates. The Cox model was used to perform the factor analysis. Results In all patients, the median follow?up time was 71?4 months;the overall mortality rate was 10?5%;the incidence of treatment failure ( death+relapse+metastasis) was 14?9%;217 patients ( 30?3%) received RT. The multivariate analysis showed that there was no significant difference in OS between subtypes in any group ( all P>0?05 ) . In all patients, patients with LB1 subtype or unassigned subtype had significantly poorer DFS rates than those with LA subtype ( HR= 1?881, P= 0?035;HR= 1?907, P=0?049) . In the non?RT group, patients with LB1 subtype had significantly poorer DFS rates than those with LA subtype (HR=3?324, P=0?01). In the RT group, there was no significant difference in DFS rate between subtypes ( all P>0?05) . The two?dimensional cross analyses of RT and subtype demonstrated that patients with LB1 subtype in the non?RT group had lower OS and DFS rates than patients with LA subtype in the RT group ( P=0?09,0?06) . Conclusions Patients with LB1 subtype have lower OS and DFS rates than patients with LA subtype, especially in the non?RT patients. RT has no impact on the relationship between subtype and prognosis.