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Radiotherapy (RT) is the primary local treatment modality for brain metastases, which are common secondary malignancies. Image-guidance system such as cone beam computed tomography (CBCT) may be not applicable to adaptive radiotherapy (ART), as well as hypofractionated RT in brain metastases, because it cannot clearly show the shrinkage and deformation of intracranial tumors, and the peritumoral edema changes in a real-time manner. Magnetic resonance (MR) image has high spatial resolution and soft tissue contrast and no radiation dose burden compared with CBCT. MR-guided adaptive radiotherapy (MR-gART) allows real-time tracking of deformation and position changes of the intracranial tumors, and enables online planning reconstruction during the treatment process. MR-gART could deliver high dose irradiation to the tumors while reducing the radiation dose of important organs at risk around, which contributes to achieving precision RT. In this work, the application of MR-gART in brain metastases was reviewed.
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Whole brain radiotherapy (WBRT) is the standard radiotherapy regimen of preventive radiation for patients diagnosed with brain metastases and non-small cell lung cancer, which can improve intracranial control and prolong overall survival. However, neurocognitive functions (NCF) decline due to impaired hippocampal might occur thereafter. Recent studies have shown that hippocampal sparing WBRT (HS-WBRT) is capable of protecting neurocognitive function and improving quality of life (QOL). In this review, the authors described the methods and significance of hippocampal sparing, summarized the research progress on clinical trials related to HS-WBRT in combination with the development of radiotherapy technology and experimental drugs, and discussed the existing controversies and problems, aiming to provide reference for clinical work.
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Objective:To investigate the predictive value of enhanced CT-based radiomics for brain metastasis (BM) and selective use of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC).Methods:Clinical data of 97 patients diagnosed with LS-SCLC confirmed by pathological and imaging examination in Shanxi Provincial Cancer Hospital from January 2012 to December 2018 were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) Cox and Spearman correlation tests were used to select the radiomics features significantly associated with the incidence of BM and calculate the radiomics score. The calibration curve, the area under the receiver operating characteristic (ROC) curve (AUC), 5-fold cross-validation, decision curve analysis (DCA), and integrated Brier score (IBS) were employed to evaluate the predictive power and clinical benefits of the radiomics score. Kaplan-Meier method and log-rank test were adopted to draw survival curves and assess differences between two groups.Results:A total of 1272 radiomics features were extracted from enhanced CT. After the LASSO Cox regression and Spearman correlation tests, 8 radiomics features associated with the incidence of BM were used to calculate the radiomics score. The AUCs of radiomics scores to predict 1-year and 2-year BM were 0.845 (95% CI=0.746-0.943) and 0.878 (95% CI=0.774-0.983), respectively. The 5-fold cross validation, calibration curve, DCA and IBS also demonstrated that the radiomics model yielded good predictive performance and net clinical benefit. Patients were divided into the high-risk and low-risk cohorts based on the radiomics score. For patients at high risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 18.2% in the PCI group, and 61.8% and 75.4% in the non-PCI group, respectively ( P<0.001). In the PCI group, the 1-year and 2-year overall survival rates were 92.9% and 78.6%, and 85.3% and 36.8% in the non-PCI group, respectively ( P=0.023). For patients at low risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 0% in the PCI group, and 10.0% and 20.2% in the non-PCI group, respectively ( P=0.062). In the PCI group, the 1-year and 2-year overall survival rates were 100% and 77.0%, and 96.7% and 79.3% in the non-PCI group, respectively ( P=0.670). Conclusion:The radiomics model based on enhanced CT images yields excellent performance for predicting BM and individualized PCI.
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Objective:To evaluate the feasibility of magnetic resonance (MR) perfusion imaging for sub-region segmentation of brain metastases (BMs), and to provide reference for individualized radiotherapy based on blood flow perfusion heterogeneity in BMs patients.Methods:96 BMs patients were selected, including 55 patients with necrosis and 41 without necrosis. Each patient was scanned with CT simulation and MR simulation before radiotherapy. MIM Maestro 6.8.8 software was used to delineate the gross tumor volume (GTV) and necrosis GTV (GTV N) from enhanced T 1W images and T 2 Propeller images, respectively, and the solid GTV (GTV S) was obtained by the subtraction of the two. Then, the cerebral blood flow map of three dimensional arterial spin labeling (3D-ASL) was employed to determine the high perfused GTV (GTV H) and low perfused GTV (GTV L). The volume and proportion of sub-regions were counted and compared between two groups and the correlation of each sub-region was analyzed. Results:The volume of GTV in the necrosis and non-necrosis groups was 19.56 and 7.34 cm 3, respectively. Besides, the AUC of the ROC between GTV volume and necrosis was 0.749. In the necrosis group, the ratio of GTV N, GTV S, GTV H and GTV L to GTV was 20.47%, 79.53%, 33.03% and 46.50%, respectively (all P<0.05). Among them, the r value between GTV S and GTV was 0.963, 0.849 for GTV L and GTV, and 0.840 for GTV L and GTV S, significantly higher than 0.683 for GTV H and GTV and 0.764 for GTV H and GTV S (all P<0.05). In the non-necrosis group, the ratio of GTV H to GTV was higher than that in the necrosis group (58.95% vs. 33.03%, P<0.05). In addition, the ratio of GTV L to GTV was slightly lower than that in the necrosis group (41.05% vs. 46.50%, P>0.05). The r value between GTV H and GTV was 0.776, significantly higher than 0.574 between GTV L and GTV ( P<0.05). Conclusion:MR-3D-ASL can quantitatively analyze the heterogeneous blood perfusion of BMs, which could guide the sub-region segmentation and local dose escalation of tumors.
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Objective To evaluate the necessity of arc by arc setup verification in patients with brain metastases receiving stereotactic radiotherapy (SRT) by analyzing the inter-and intra-fraction setup errors and residual errors collected from the ExacTrac X-ray portal image.Methods Clinical data of brain metastases patients treated with SRT in the previous two years were retrospectively analyzed.The ExacTrac X-ray setup images were collected after the normal setup procedure.Setup errors were calculated by registering the cranial bony structures of the ExacTrac X-ray setup images to that of the digitally reconstructed setup images.The inter-and intra-fraction setup errors and residual errors were statistically analyzed.Results Seventy-five patients from 116 lesions received 337 cycles of SRT of the head.The inter-and intra-fraction translational setup errors in the x,y and z directions were (0.93±0.86) mm and (0.15±0.59) mm;(1.83± 1.27) mm and (0.25±0.73) mm;(0.96±0.80) mm and (0.14±0.56) mm,respectively.The inter-and intra-fraction rotational setup errors in the x,y,z directions were (0.65°± 0.62°) and (0.19°± 0.40°);(0.97°±0.94°) and (0.13°± 0.25°);(0.92°± 0.71°) and (0.10°± 0.29°),respectively.The residual translational setup errors in the x,y,z directions were (0.06±0.23) mm,(0.08±0.24) mm and (0.08±0.22)mm,and (0.12°± 0.27°),(0.09°± 0.18°) and (0.06°± 0.19°) for the residual rotational setup errors,respectively.For a reference setup error threshold of 0.7 mm/0.7°,99.1％ of the SRT exceeded the threshold and required setup correction.For 1 006 non-coplanar arcs,rotating the treatment couch from 0° to the treatment angle made 66.4％ of arcs exceed the threshold and require at least once setup correction.Conclusions During SRT for brain metastasis,the inter-and intra-fraction setup errors should be emphasized.It is necessary to perform arc by arc setup error verification.
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Objective To investigate the association between the timing of brain metastases and the prognosis of patients with small cell lung cancer (SCLC).Methods A retrospective analysis was performed in 131 patients with limited-stage SCLC firstly metastasized to the brain were admitted to our hospital from 2007 to 2015.According to the median bone metastasis-free survival (BMFS),all patients were divided into A group (BMFS ≤ 10 months,n =61) and B group (BMFS＞ 10 months,n=70).The survival rates were analyzed using the Kaplan-Meier method.Between-group comparison was performed by log-rank test.The Cox regression model was used for multivariate prognostic analysis.Results In all 131 patients,the median overall survival (OS) and 1-,2-,and 3-year OS rates were 22.5 months,87.3％,44.7％,and 20.8％,respectively.The median OS after brain metastases and 1-and 2-year OS rates were 9.3 months,39.3％ and 14.8％,respectively.No statistical significance was observed in the median OS after brain metastases between the A and B groups (8.6 vs.9.3 months,P=0.695).Moreover,the OS after brain metastases did not significantly differ in patients without PCI or those receiving different therapies after brain metastases between two groups (P=0.240-0.731).Conclusions The timing of SCLC with brain metastases is significantly correlated with the OS rather than the OS after brain metastases.Therefore,prevention of brain metastases may be an effective approach to prolong the OS of patients with SCLC.
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Objective To explore the effect of prognostic nutrition index (PNI) on the overall survival time of patients with brain metastases of lung adenocarcinoma.Methods A retrospective analysis was performed on the clinic data of 274 patients who were admitted to our hospital and confirmed with brain metastases of lung adenocarcinoma from May 2013 to May 2016.The prognosic factors for brain metastases such as PNI,gender,age,smoking history,epidermal growth factor receptor (EGFR) mutation status,Karnofsky performance status (KPS) score,the number of brain lesions,treatment of brain lesions,extracranial metastases and the status of primary disease were analyzed.The receiver operating characteristic (ROC) curve was drawn to determine the optimal cut-off value of PNI,and the patients were divided into high PNI group and low PNI group.The univariate and multivariate prognostic analyses were performed by the Log-rank test and the Cox proportional hazards model.Results The patients were divided into high PNI (＞ 50.45) group (n =72) and low PNI (≤50.45) group (n =202).The median overall survival (OS) was 11.20 months in all patients with brain metastases,and the median OS of the low PNI group and high PNI group were 10.13 months and 15.17 months respectively.The univariate analysis results showed that gender (x2 =5.459,P =0.019),age (x2 =3.986,P =0.046),smoking or not (x2 =6.878,P =0.009),EGFR mutation status (x2 =20.484,P＜0.001),KPS score (x2 =126.573,P ＜ 0.001),extracranial metastases or not (x2 =4.403,P =0.036),treatment on the brain lesions (x2 =40.444,P ＜ 0.001) and PNI (x2 =7.972,P =0.005) were related to the prognosis.The Cox multivariate analysis results showed that age (HR =1.580,95％ CI:1.104-2.295,P =0.012),EGFR mutation status (HR =0.549,95％ CI:0.408-0.738,P ＜ 0.001),KPS score (HR =0.077,95％CI:0.045-0.134,P ＜ 0.001),treatment on brain metastases (HR =0.882,95％ CI:0.789-0.987,P =0.029) and PNI (HR =0.614,95％ CI:0.437-0.861,P =0.005) were related to the prognosis.Conclusion PNI is an independent prognostic predictor of brain metastases in patients with lung adenocarcinoma,and the high-PNI is correlated to the long OS of patients with brain metastases of lung adenocarcinoma,which has certain clinical practical value.
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Objective To explore the association between epidermal growth factor receptor (EGFR) mutation subtypes and the prognosis of brain metastasis in patients with lung adenocarcinoma.Methods A retrospective analysis was performed on the clinical data of 256 patients who were admitted to our hospital and confirmed with brain metastases of lung adenocarcinoma by EGFR mutation detection from 2010 to 2015.The prognostic factors for brain metastases were analyzed.The survival rate was calculated by the Kaplan-Meier method and analyzed by the log-rank test.The univariate and multivariate prognostic analyses were performed by the log-rank test and the Cox proportional hazards model.Results The median survival time was 10.13 months in all patients.The univariate analysis showed that sex,EGFR mutation status,exon 19 deletion,the Karnofsky Performance Status (KPS) score of brain metastases,and targeted therapy were prognostic predictors (P=0.006,0.001,0.010,0.000,0.003).The multivariate analysis showed that the KPS score and exon 19 deletion were prognostic factors for brain metastases (P=O.000,0.045).When grouped into the recursive partitioning analysis classes,all the patients were split into three subgroups with significantly different prognosis (P =0.000).Conclusions Exon 19 deletion is a prognostic predictor of brain metastases in patieuts with lung adenocarcinoma,which can be integrated into the prognosis scoring system for brain metastases of lung adenocarcinoma.EGFR tyrosine kinase inhibitors improve the survival in patients with brain metastases of lung adenocarcinoma and EGFR mutation,particularly,in those with exon 19 deletion.
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Objective To assess the feasibility and outcomes of fractionated stereotactice radiation therapy(FSRT) for brain metastases more than 3 cm in diameter. Methods From September 1996 to July 2006,47 patients(34 male and 13 female)with brain metastases larger than 3 cm were treated with FSRT. The median age was 58(range,31-87) years old. Pathologic diagnosis was adenocarcinoma in 19 patients, squamacarcinoma in 7, small cell carcinoma in 7, adeno-squamacarcinoma in 3, melanoma in 2, poor differen-tiated carcinoma, clear cell carcinoma, transitional cell carcinoma each in 1, and unknown in 6. FSRT was delivered as initial treatment for 26 patients, and as salvage therapy for 21. The largest diameter of brain me-tastases was 3.1-6.0 cm(median, 3.8 cm). Planning target volume were 2.5-33.8 cm3(median, 9.4 cm3). The median dose of FSRT was 30(range,16-57)Gy in 5(range,2 - 11) fractions. The treatment for primary tumor was surgery in 23 patients, radiotherapy and/or chemotherapy in 22, and none in 2. Results The last follow up was in April 2008. All patients were followed up and 33 had follow up more than 5 years. The 1-,2- and 5-year local control rate was 49%, 44% and 44%, respectively. The median survival time was 11 months(range,0.5-88.0 months, 95% CI=8.1-13.8 months). The corresponding overall survival rate was 40%, 17% and 6%, respectively. There were 46 patients died by the last follow up,including 21 died from brain metastases, 17 died from extracranial progression, and 8 died from other causes. Conclusion FSRT is safe and beneficial for selected patients with brain metastases larger than 3 cm.
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Objective To retrospectively analyze clinical outcomes of brain metastases treated with Cyberknffe. Methods From Aug. 2006 to Aug. 2007, 40 patients with brain metastases treated with Cy-berknife in Tianjin Cancer Hospital were included. Totally 68 brain metastatic lesions were treated. The maximal diameter was 0.4 -7.5 cm (average 1.9 cm). The primary tumor of 35 patients was partial re-ponse or stable to the previous treatment at the diagnosis of brain metastasis. The geometric center of target volume was set as the isocenter and the nominal standard dose point. More than 95% target volume was cov-ered by 80% isodose surface. Hypofractionated radiation was 18 -36 Gy given in 1 -5 fractions of 5 -25 Gy. Results The Follow-up rate was 95%. The clinical symptom remission rate (including complete and partial remission) at one week after Cyberknife treatment was 90% (36/40). The therapeutic effective rate (CR + PR + SD) was 94% (64/68) after three months follow-up, which was evaluated by contrast-en-hanced CT or MRI. The 3-month local control and 1-year survival rates were 78% (53/68) and 68% (27/40). New brain metastatic lesions outside the radiation field occurred in 14 patients within 3 months, which was independent of age, whole brain irradiation, number or maximal diameter of original lesions, frac-tion dose, frequency or total dose of Cyberknife treatment. Conclusions Cyberknife, used as the primary treatment of brain metastases, can achieve good clinical outcomes.