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08 July 2022, Volume 49 Issue 7 Previous Issue    Next Issue

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Dosimetric study of volumetric modulated arc therapy and tomo direct simultaneous integrated boost for patients receiving breast-conserving surgery for left breast cancer Zhao Biao, Li Bo, Zhu Yupu, Ma Lishuang, Yuan Meifang, Yang Yi 2022, 49 (7):  385-389.  doi: 10.3760/cma.j.cn371439-20220330-00075 Abstract ( 437 )   HTML ( 49 )   PDF (784KB) ( 104 )   Save Objective To explore the dosimetry difference between volumetric modulated arc therapy （VMAT） and tomo direct （TD） in tumor bed simultaneous push radiotherapy after left breast-conserving surgery, and to provide more dosimetry reference for clinic. Methods A total of 22 patients with left breast cancer who underwent simultaneous quantitative radiotherapy after breast-conserving surgery were selected from the Department of Radiation Oncology, Yunnan Cancer Hospital from December 2018 to June 2020. The localized CT images and target organs at risk and other structural data were collected. Two radiotherapy plans, VMAT and TD, were designed for the same patient, and the dosimetry differences of target areas and organs at risk were compared and analyzed between the two groups.Results In terms of target dosimetry, there were statistically significant differences in the D2% [（59.99±0.19） Gy vs. （59.55±0.51） Gy, t=4.09, P<0.001], D98% [（57.19±0.08） Gy vs. （57.46±0.22） Gy, t=-5.10, P<0.001], conformal index （CI） （0.76±0.05 vs. 0.58±0.13, t=8.19, P<0.001） and homogeneity index （HI） （0.05±0.00 vs. 0.04±0.01, t=4.89, P<0.001） of the planning gross tumor volume （PGTV） between VMAT and TD plans. However, there was no statistically significant difference in the D50% [（58.73±0.10） Gy vs. （58.73±0.24） Gy, t=-0.03, P=0.974]. There were statistically significant differences in the D50% [（52.21±0.33） Gy vs. （53.00±0.72） Gy, t=-4.81, P<0.001], D98% [（48.44±0.43） Gy vs. （49.09±0.21） Gy, t=-6.80, P<0.001], CI （0.83±0.06 vs. 0.67±0.06, t=10.52, P<0.001） and HI （0.20±0.01 vs. 0.19±0.01, t=8.75, P<0.001） of the planned target volume （PTV） between the two plans. However, there was no statistically significant difference in the D2% [（59.01±0.45） Gy vs. （59.00±0.48） Gy, t=0.22, P=0.830]. In terms of organs at risk, there were statistically significant differences in the V20 [（18.81±2.86）% vs. （22.03±1.91）%, t=-5.36, P<0.001] and Dmean [（11.66±1.32） Gy vs. （12.85±1.46） Gy, t=-4.10, P=0.007] of left lung, V5 [（5.70±2.90）% vs. （0.30±0.13）%, t=16.44, P<0.001] and Dmean [（2.45±0.29） Gy vs. （0.43±0.14） Gy, t=9.09, P<0.001] of right lung, Dmean [（3.22±0.72） Gy vs. （1.69±0.80） Gy, t=5.41, P<0.001] of right breast, D2% [（5.37±1.97） Gy vs. （0.46±0.09） Gy, t=11.75, P<0.001] of cord between VMAT and TD plans. There were no significant differences in the V5 of left lung [（53.00±5.99）% vs. （50.00±7.69）%, t=1.91, P=0.061], V5 of right breast [（11.51±4.60）% vs. （8.06±3.49）%, t=1.59, P=0.120], V30 [（1.49±0.69）% vs. （1.51±0.71）%, t=-0.06, P=0.952] and Dmean [（3.99±0.97） Gy vs. （3.90±1.03） Gy,t=0.56, P=0.581] of heart between the two plans. Conclusion TD and VMAT can meet the clinical dosimetry requirements for patients with left breast cancer after breast-conserving surgery. However, the two techniques have their own characteristics. VMAT has better conformity and TD has better uniformity. TD is significantly better than VMAT in protecting the right lung, right breast and spinal cord of healthy organs at risk. VMAT is better in protecting the left lung. Both VMAT and TD basically achieve the same protection for heart. Figures and Tables | References | Related Articles | Metrics

Investigation of cerebrospinal fluid metabolites in patients with leptomeningeal metastases from lung adenocarcinoma based on untargeted metabolomics Lin Yongjuan, Li Huiying, Yin Zhenyu, Guo Aibin, Xie Yu 2022, 49 (7):  390-399.  doi: 10.3760/cma.j.cn371439-20220429-00076 Abstract ( 270 )   HTML ( 24 )   PDF (3077KB) ( 69 )   Save Objective To analyze the diagnostic value of metabolic makers in cerebrospinal fluid in advanced lung adenocarcinoma patients with leptomeningeal metastases （LM）. Methods A total of 46 cerebrospinal fluid samples （LM group） from lung adenocarcinoma patients with LM admitted to Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School from December 2019 to December 2021 were collected, and 48 cerebrospinal fluid samples （control group） from patients with benign neurological diseases during the same period were collected. Metabolomics analysis of cerebrospinal fluid was carried out by high-performance liquid chromatography-mass spectrometry. Principle component analysis （PCA） and orthogonal to partial least squares discriminant analysis （OPLS-DA） were used for modeling. Multi-criteria assessment was used to identify the different metabolites between the two groups. Receiver operating characteristic （ROC） curve, pathway enrichment analysis and other methods were used to screen metabolites and pathways related to LM from lung adenocarcinoma. Results There were no statistically significant differences in the proportions of age （Z=-0.41, P=0.210）, gender （χ2=1.19, P=0.275）, history of smoking （χ2=2.86, P=0.091）, Karnofsky performance status score （χ2=0.65, P=0.419） and increased intracranial pressure （χ2=0.65, P=0.419） between the LM group and control group. The models of PCA （R2X was 0.608 and 0.583, Q2 was 0.462 and 0.513 in electrospray ion positive and negative modes, respectively） and OPLS-DA （R2Y was 0.967 and 0.889, Q2 was 0.959 and 0.852 in electrospray ion positive and negative modes, respectively） showed that the overall data quality was good. Meanwhile, the model interpretation rate and prediction rate were effective. The permutation tests duplicated for 200 times and showed no over-fitting of the established model. The metabolic profiles of the two groups were significantly different. A total of 30 endogenously differential metabolites were screened by using multi-criteria assessment. Six potential biomarkers with larger area under the curve （AUC） were identified through ROC curve analysis, including tyrosine （AUC=0.967, 95%CI： 0.906-1.000）, phenylalanine （AUC=0.992, 95%CI： 0.973-1.000）, pyruvate （AUC=0.976, 95%CI： 0.935-1.000）, tryptophan （AUC=0.935, 95%CI： 0.880-0.973）, glucose （AUC=0.932, 95%CI： 0.880-0.975） and adenosine monophosphate （AUC=0.993, 95%CI： 0.987-1.000）. The 30 selected differential metabolites were enriched and analyzed for metabolic pathways, and 20 relevant metabolic pathways were matched. Among them, the four metabolic pathways most likely to cause changes in metabolites were glycolysis and glucose metabolic synthesis, pyruvate metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis. Conclusion Untargeted metabolomics analysis can effectively screen specific cerebrospinal fluid metabolites in lung adenocarcinoma patients with LM. Six potential metabolites such as tyrosine, phenylalanine, pyruvate, tryptophan, adenosine monophosphate, glucose and their metabolic pathways may be involved in the pathogenesis of LM from lung adenocarcinoma. Figures and Tables | References | Related Articles | Metrics

Efficacy and influencing factors of DEBIRI-TACE combined with regorafenib in the third-line or above treatment of colorectal cancer liver metastases Liu Song, Yu Guangji, Wang Qingdong 2022, 49 (7):  400-407.  doi: 10.3760/cma.j.cn371439-20220318-00077 Abstract ( 328 )   HTML ( 35 )   PDF (896KB) ( 70 )   Save Objective To explore the efficacy and influencing factors of irinotecan-loaded CalliSpheres drug-eluting bead-transcatheter arterial chemoembolization （DEBIRI-TACE） combined with regorafenib in the third-line or above treatment of unresectable colorectal cancer liver metastases. Methods From June 2018 to June 2020, 53 patients with unresectable colorectal cancer liver metastases admitted to Linyi Cancer Hospital of Shandong Province who had failed at least second-line systemic chemotherapy were retrospectively analyzed. The patients were divided into observation group （24 cases） and control group （29 cases） according to different treatment regimes. The control group only received regorafenib monotherapy, and the observation group received regorafenib combined with DEBIRI-TACE. According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate （ORR） and disease control rate （DCR） were evaluated, and the progression-free survival （PFS） and overall survival （OS） were estimated by Kaplan-Meier method. The Cox proportional hazards model was used to analyze the OS influencing factors in the observation group. The treatment related adverse reactions were observed. Results After 2 months of treatment, the ORR of the observation group was 75.0% （18/24）, and the DCR was 91.7% （22/24）, both were higher than those of the control group [6.9% （2/29） and 51.7% （15/29） respectively], with statistically significant differences （χ2=25.92, P<0.001; χ2=9.94, P=0.002）. There were no statistically significant differences in the incidences of regorafenib-related adverse reactions such as hand-foot skin reaction [62.5% （15/24） vs. 65.5% （19/29）, χ2=0.05, P=0.819], fatigue [41.7% （10/24） vs. 44.8% （13/29）, χ2=0.05, P=0.817], hypertension [29.2% （7/24） vs. 34.5% （10/29）, χ2=0.17, P=0.679], diarrhea [25.0% （6/24） vs. 27.6% （8/29）, χ2=0.04, P=0.832], hoarseness [16.7% （4/24） vs. 17.2% （5/29）, χ2=0.01, P=0.956] and proteinuria [8.3% （2/24） vs. 10.3% （3/29）, χ2=0.06, P=0.803] between the two groups. The main adverse reactions related to DEBIRI-TACE in the observation group were fever, pain, nausea and vomiting, etc., which were relieved after symptomatic treatment. No serious complications such as ectopic embolism of CalliSpheres drug eluting bead occurred. By the end of the follow-up,among the 24 patients in the observation group, the median OS of patients with simultaneous liver metastases was 12 months, and that of patients with metachronous liver metastases was 22 months, with a statistically significant difference （χ2=4.29, P=0.026）. The median OS of patients with 3-5 liver metastases was 21 months, and that of patients with more than 5 liver metastases was 14 months, with a statistically significant difference （χ2=3.35, P=0.040）. The median OS of Child-Pugh grade A patients was 22 months, and that of Child-Pugh grade B patients was 13 months, with a statistically significant difference （χ2=4.22, P=0.027）. The median OS was 16 months in patients with extrahepatic metastases and 23 months in patients without extrahepatic metastases, with a statistically significant difference （χ2=7.68, P=0.013）. Cox proportional hazards model analysis showed that simultaneous liver metastases （HR=1.59, 95%CI： 1.02-2.47, P=0.031） and extrahepatic metastases （HR=1.61, 95%CI： 1.29-2.01, P=0.020） were independent risk factors influencing OS of patients in the observation group. The median PFS of the observation group was 9 months, and that of the control group was 5 months, with a statistically significant difference （χ2=7.78, P=0.005）. The median OS of the observation group was 17 months, and that of the control group was 11 months, with a statistically significant difference （χ2=16.81, P<0.001）. Conclusion DEBIRI-TACE combined with regorafenib is effective in the third-line or above treatment of unresectable colorectal cancer liver metastases, with tolerable adverse reactions. It is a safe and feasible treatment method. The prognosis of patients with simultaneous liver metastases or extrahepatic metastases is worse. Figures and Tables | References | Related Articles | Metrics

Effects of chemotherapy dose intensity on short-term efficacy in patients with advanced colon cancer： a study based on real-world data Chu Xuelei, Mao Yun, Xue Peng, Li Linlu, Chen Meichi, Yuan Chunsheng, Qin Xiaoyan, Zhu Shijie 2022, 49 (7):  408-415.  doi: 10.3760/cma.j.cn371439-20220318-00078 Abstract ( 401 )   HTML ( 20 )   PDF (877KB) ( 60 )   Save Objective To investigate the effects of different chemotherapy dose intensity on the short-term efficacy and adverse reactions of patients with advanced colon cancer. Methods A real-world database of patients with advanced colon cancer in Wangjing Hospital of China Academy of Chinese Medical Sciences and China-Japan Friendship Hospital from January 2017 to December 2020 was established, including 105 patients treated with the same chemotherapy regimen for two consecutive cycles. The patients were grouped according to the average relative dose intensity （ARDI） of chemotherapy, and the population differences, treatment regimens, short-term efficacy and adverse reactions of different chemotherapy dose intensities were evaluated. The receiver operating characteristic （ROC） curve was used to analyze the predictive value of ARDI for short-term efficacy. Results There were 31 patients in the high dose intensity group （ARDI≥80%）, 34 patients in the medium dose intensity group （80%<ARDI<60%）, and 40 patients in the low dose intensity group （ARDI≤60%）. There were statistically significant differences in age （χ2=13.20, P=0.010） and Karnofsky functional status （KPS） score （χ2=7.99, P=0.008） among the high dose intensity group, medium dose intensity group and low dose intensity group. Compared with the low dose intensity group, the proportion of young and middle-aged patients in the high dose intensity group was higher, and the proportion of elderly patients was lower （χ2=12.63, P=0.002）. Compared with the medium dose intensity group, the proportion of patients with KPS score ≥60 was lower and the proportion of patients with KPS score <60 was higher in the low dose intensity group （P=0.013）. There was a statistically significant difference in the application of chemotherapy regimen among the three groups （χ2=22.88, P=0.027）, and there was a statistically significant difference in the application of chemotherapy regimen between the high dose intensity group and low dose intensity group （χ2=16.25, P=0.009）. The proportions of the high, medium and low dose intensity groups receiving combined chemotherapy were 96.77% （30/31）, 82.35% （28/34） and 80.00% （32/40） respectively. The incidences of chemotherapy drug reduction in the high, medium and low dose intensity groups were 93.55% （29/31）, 100% （34/34） and 100% （40/40） respectively, and the incidences of chemotherapy delay were 41.94% （13/31）, 79.41% （27/34） and 87.50% （35/40） respectively. The objective response rates of the high, medium and low dose intensity groups were 22.58% （7/31）, 14.71% （5/34） and 2.50% （1/40） respectively, with a statistically significant difference （χ2=7.11, P=0.027）. The disease control rates of the high, medium and low dose intensity groups were 93.55% （29/31）, 91.18% （31/34） and 87.50% （35/40） respectively, with no statistically significant difference （χ2=0.75, P=0.714）. The differences of carcinoembryonic antigen before and after treatment in the high, medium and low dose intensity groups were 2.09, 0.47 and -0.72 ng/ml respectively, with a statistically significant difference （χ2=10.09, P=0.006）. Compared with the low dose intensity group, the difference of carcinoembryonic antigen before and after treatment in the high dose intensity group was greater （χ2=23.12, P=0.005）. The differences of carbohydrate antigen 199 before and after treatment in the high, medium and low dose intensity groups were 2.30, 0.00 and -0.21 U/ml respectively, with a statistically significant different （χ2=8.85, P=0.012）. Compared with the low dose intensity group, the difference of carbohydrate antigen 199 before and after treatment in the high dose intensity group was greater （χ2=21.40, P=0.010）. No adverse reactions above grade 3 occurred in the three groups, and the safety was good. The most common adverse reactions were anemia （61.90%, 65/105）, leucopenia （39.05%, 41/105）, neutropenia （29.52%, 31/105） and nausea （36.19%, 38/105）. There were no statistically significant differences in the incidences of adverse reactions among the high, medium and low dose intensity groups （all P>0.05）. ROC curve analysis found that the area under the curve predicting objective response was 0.70, the sensitivity was 92.30%, and the specificity was 52.10% when the chemotherapy ARDI threshold was 64%. Conclusion In the real world, colon cancer patients receiving high dose intensive chemotherapy have better objective response rate,and tumor markers decreased significantly. The baseline status of colon cancer patients receiving low dose intensive chemotherapy is poor, but there is no statistically significant difference in disease control rate between patients receiving low dose intensive chemotherapy and patients receiving high dose intensive chemotherapy, and the adverse reactions are controllable. Figures and Tables | References | Related Articles | Metrics

Reviews

Roles of the SoxC family in tumor development and its clinical significance Zhang Dandan, Lin Gaoren, Xiao Qian, Liu Ying 2022, 49 (7):  416-419.  doi: 10.3760/cma.j.cn371439-20220408-00079 Abstract ( 213 )   HTML ( 19 )   PDF (732KB) ( 90 )   Save SoxC transcription factors are a group of important protein molecules involved in gene transcription, translation and expression, which can regulate gene expression by specifically binding to corresponding target genes or proteins. The SoxC gene family has unique molecular structure features. Its members Sox4, Sox11 and Sox12 are abnormally expressed in a variety of tumors, and can be used as diagnostic and prognostic markers for different tumors. Investigating the pathogenic mechanisms of the SoxC transcription factor family and their clinical significance can increase the evidence for SoxC as a therapeutic target for tumors. References | Related Articles | Metrics

Research status of glioblastoma-associated microglia Fei Wenjing, Wang Wenbao, Xie Huanhuan, Yan Jing, Yang Mi 2022, 49 (7):  420-424.  doi: 10.3760/cma.j.cn371439-20220429-00080 Abstract ( 163 )   HTML ( 19 )   PDF (768KB) ( 55 )   Save Microglia differ from macrophages with unique origin and role. In glioblastoma, microglia plays an important role in regulating tumor immune status, promoting tumor angiogenesis, destroying the blood-brain barrier, and reducing the sensitivity of treatment. Therefore, the combination of microglial therapy in the radiotherapy, chemotherapy and immunotherapy of glioblastoma has also become a clinically promising treatment. References | Related Articles | Metrics

Advances in the diagnosis and treatment of hepatocellular carcinoma with contrast-enhanced ultrasound Gao Junrong, Cao Manqing, Deng Yinghong 2022, 49 (7):  425-429.  doi: 10.3760/cma.j.cn371439-20220419-00081 Abstract ( 236 )   HTML ( 38 )   PDF (777KB) ( 107 )   Save Hepatocellular carcinoma （HCC） is a highly prevalent tumor in China. It has an insidious onset, rapid progression, early recurrence and poor prognosis. Most patients are already in the middle and late stages when they are diagnosed and lose the best time for surgery. Therefore, early diagnosis and treatment of HCC is crucial for patients. In recent years, contrast-enhanced ultrasound （CEUS） technology has been widely used in the diagnosis of liver diseases, especially in the diagnosis and treatment of HCC, which has an irreplaceable role. Meanwhile, the image fusion technology developed on the basis of CEUS can highlight the value of CEUS in the diagnosis and treatment of HCC. References | Related Articles | Metrics

Research progress of maintenance therapy for cervical cancer Peng Chen, Xie Yintong, Zhang Xin, Xie Peng 2022, 49 (7):  430-435.  doi: 10.3760/cma.j.cn371439-20220602-00082 Abstract ( 232 )   HTML ( 34 )   PDF (766KB) ( 83 )   Save Cervical cancer is a common malignant tumor that threatens women's life and health. Among them, the prognosis of recurrent or advanced cervical cancer is poor, and such patients often receive surgical treatment, radiotherapy, chemotherapy, etc., which makes it more difficult to choose a treatment plan. Even after the most effective treatment methods, the treatment failure rate of advanced cervical cancer is still high. Thanks to the research progress of tumor cell signaling pathway-related targets and immunotherapy, especially immune checkpoint inhibitors, new breakthroughs have been made in cervical cancer maintenance therapy. Targeted maintenance therapy, immune maintenance therapy, and multi-drug combination maintenance therapy are currently popular areas of cervical cancer maintenance therapy. References | Related Articles | Metrics

Research progress of metformin in non-Hodgkin lymphoma Wang Liuxue, Xi Xiaoping, Liu Jingjing, Shen Guomin, Yang Haiping 2022, 49 (7):  436-440.  doi: 10.3760/cma.j.cn371439-20220414-00083 Abstract ( 318 )   HTML ( 22 )   PDF (772KB) ( 67 )   Save Preclinical studies have shown that metformin, an activator of AMP-activated protein kinase （AMPK）, can inhibit the growth of lymphoma cells without affecting the function of normal lymphocytes, promote the apoptosis of lymphoma cells and improve the tumor immune environment. Clinical studies have shown that metformin can improve the efficacy of chemotherapy and prognosis of non-Hodgkin lymphoma （NHL）. Through the influence on glucose metabolism, it can improve blood glucose level and reduce the incidence of steroid diabetes. The main molecular mechanisms of metformin against NHL include activating AMPK in tumor cells, inhibiting mammalian target of rapamycin signal, inhibiting key cholesterol synthesis, improving glucose metabolism, enhancing highly cytotoxic T lymphocyte （CTL） activity and so on. Current research shows that metformin may become a new strategy for the treatment of NHL. References | Related Articles | Metrics