Integration of stereotactic radiosurgery or whole brain radiation therapy with immunotherapy for treatment of brain metastases

The prognosis of brain metastases(BM)is traditionally poor.BM are mainly treated by local radiotherapy,including stereotactic radiosurgery(SRS)or whole brain radiation therapy(WBRT).Recently,immunotherapy(i.e.,immune checkpoint inhibitors,ICI)has demonstrated a survival advantage in multiple malignancies commonly associated with BM.Individually,radiotherapy and ICI both treat BM efficiently;hence,their combination seems logical.In this review,we summarize the existing preclinical and clinical evidence that supports the applicability of radiotherapy as a sensitizer of ICI for BM.Further,we discuss the optimal timing at which radiotherapy and ICI should be administered and review the safety of the combination therapy.Data from a few clinical studies suggest that combining SRS or WBRT with ICI simultaneously rather than consecutively potentially enhances brain abscopal-like responses and survival.However,there is a lack of conclusion about the definition of"simultaneous";the cumulative toxic effect of the combined therapies also requires further study.Thus,ongoing and planned prospective trials are needed to further explore and validate the effect,safety,and optimal timing of the combination of immunotherapy with radiotherapy for patients with BM.

Value of serial magnetic resonance imaging in the assessment of brain metastases volume control during stereotactic radiosurgery

AIM To evaluate brain metastases volume control capabilities of stereotactic radiosurgery(SRS) through serial magnetic resonance(MR) imaging follow-up. METHODS MR examinations of 54 brain metastases in 31 patients before and after SRS were reviewed. Patients were included in this study if they had a pre-treatment MR examination and serial follow-up MR examinations at 6 wk, 9 wk, 12 wk, and 12 mo after SRS. The metastasis volume change was categorized at each follow-up as increased(> 20% of the initial volume), stable(± 20% of the initial volume) or decreased(< 20% of the initial volume). RESULTS A local tumor control with a significant(P < 0.05) volume decrease was observed in 25 metastases at 6-wk follow-up. Not significant volume change was observed in 23 metastases and a significant volume increase was observed in 6 metastases. At 9-wk followup, 15 out of 25 metastases that decreased in size at 6 wk had a transient tumor volume increase, followed by tumor regression at 12 wk. At 12-wk follow-up there was a significant reduction in volume in 45 metastases, and a significant volume increase in 4 metastases. At 12-mo follow-up, 19 metastases increased significantly in size(up to 41% of the initial volume). Volume tumor reduction was correlated to histopathologic subtype.CONCLUSION SRS provided an effective local brain metastases volume control that was demonstrated at follow-up MR imaging.

Whole-brain radiation therapy alone vs. combined therapy with stereotactic radiosurgery for the treatment of limited brain metastases: A systematic review

Objective The aim of the study was to compare the efficacy and safety of whole brain radiotherapy(WBRT) used alone and combined with stereotactic radiosurgery(SRS) in the treatment of limited(1–4)brain metastases. Methods We searched for randomized controlled and matched-pair analysis trials comparing WBRT plus SRS versus WBRT alone for brain metastases. The primary outcomes were the overall survival(OS), intracranial control(IC), and localcontrol(LC). The secondary outcome was radiation toxicity. The log hazard ratios(lnHRs) and their variances were extracted from published Kaplan-Meier curves and pooled using the generic inverse variance method in the RevMan 5.3 software. The non-pooled outcome measures were evaluated using descriptive analysis. Results Three randomized controlled trials and two matched-pair analysis studies were included. There was no difference in the OS for limited brain metastases between the two groups [lnHR 0.91(95% CI 0.76–1.09, P = 0.32) vs. 0.72(95% CI 0.44–1.19, P = 0.20)]. The LC and IC were significantly higher in the combined treatment group [lnHR 0.69(95% CI 0.55–0.86, P = 0.001) vs. 0.41(95% CI 0.29–0.58, P < 0.0001)]. For patients with a single lesion, one trial showed a higher survival in the combined treatment group(median OS: 6.5 months vs. 4.9 months, P = 0.04). The combined treatment was not associated with significantly higher incidence of radiation toxicity. Conclusion Combined treatment with WBRT plus SRS should be recommended for patients with limited brain metastases based on the better LC and IC without increased toxicity. It should also be considered a routine treatment option for patients with solitary brain metastases based on the prolonged OS.

Therapeutic Effect of First-line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI)Combined with Whole Brain Radiotherapy on Patients with EGFR Mutation-positive Lung Adenocarcinoma and Brain Metastases

This study compared the therapeutic effect of first-line epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)with that of EGFR-TKI plus whole brain radiotherapy(WBRT)on patients with EGFR mutation-positive lung adenocarcinoma and brain metastases.A total of 139 patients with lung adenocarcinoma and brain metastases treated with first-line EGFR-TK1therapy from September 2008 to December 2017 were enrolled in this study.The study endpoints were intracranial time to progression(TTP)and overall survival(OS).The effects of clinical pathological parameters and EGFR gene status on the study endpoints were compared.The results showed that the intracranial TTP was significantly longer in EGFR-TKI plus WBRT group than in EGFR-TKI group (median 30.0 vs.18.2 months,χ2=10.824,P=0.001),but no significant difference in the OS was noted between the two groups (median 48.0 vs.41.1 months,χ2=0.012, P=0.912).Also,there was no statistically significant difference in the OS between patients treated with early and late radiotherapy (P=0.849)and between those with asymptomatic and those with symptomatic intracranial metastases (P=0.189).The OS and intracranial TTP of patients with intracranial oligometastases (≤3metastatic sites)were not significantly different from those of patients with multiple intracranial metastases (P=0.104 and P=0.357,respectively),and exon 19 and exon 21 mutations didn't show significant effects on the OS and intracranial TTP of patients (P=0.418 and P=0.386,respectively).In conclusion,there was no statistically significant difference in the OS between the EGFR-TKI alone group and EGFR-TK1 plus WBRT group.However, simultaneous use of WBRT was found to significantly prolong intracranial TTP and improve cerebral symptoms,and thus EGFR-TKI and WBRT combined may be clinically beneficial for patients with EGFR mutation-positive lung adenocarcinoma and brain metastases.

Treatment of patients with multiple brain metastases by isolated radiosurgery:Toxicity and survival

BACKGROUND Radiosurgery for multiple brain metastases has been more reported recently without using whole-brain radiotherapy.Nevertheless,the sparsity of the data still claims more information about toxicity and survival and their association with both dosimetric and geometric aspects of this treatment.AIM To assess the toxicity and survival outcome of radiosurgery in patients with multiple(four or more lesions)brain metastases.METHODS In a single institution,data were collected retrospectively from patients who underwent radiosurgery to treat brain metastases from diverse primary sites.Patients with 4-21 brain metastases were treated with a single fraction with a dose of 18 Gy or 20 Gy.The clinical variables collected were relevant to toxicity,survival,treatment response,planning,and dosimetric variables.The Spearman’s rank correlation coefficients,Mann-Whitney test,Kruskal-Wallis test,and Log-RESULTS From August 2017 to February 2020,55 patients were evaluated.Headache was the most common complaint(38.2%).The median overall survival(OS)for patients with karnofsky performance status(KPS)>70 was 8.9 mo,and this was 3.6 mo for those with KPS≤70(P=0.047).Patients with treated lesions had a median progression-free survival of 7.6 mo.There were no differences in OS(19.7 vs 9.5 mo)or progression-free survival(10.6 vs 6.3 mo)based on prior irradiation.There was no correlation found between reported toxicities and planning,dosimetric,and geometric variables,implying that no additional significant toxicity risks appear to be added to the treatment of multiple(four or more)lesions.CONCLUSION No associations were found between the evaluated toxicities and the planning dosimetric parameters,and no differences in survival rates were detected based on previous treatment status.

Efficacy and nursing of stereotactic radiotherapy in lung cancer patients with brain metastases

Objective: To observe the efficacy of stereotactic radiotherapy (SRT) in lung cancer patients with brain metas-tases and explore the nursing for those patients. Methods: From June 2002 to December 2006, 43 patients of lung cancer with brain metastases were treated with SRT, 8 of them were treated with the association of whole-brain radiotherapy (WBRT) and 6 of them were treated with combination of chemotherapy. During the period of SRT, the patients were applied with active psychological nursing and diet nursing. We also tried to prevent patients from epicranium injury, and meanwhile, patients were asked to took active convalesce exercise. Results: All patients finished SRT without serious reaction and complication. Local control rate was 81.4%, nervous system symptoms relief rate was 76.7% and KPS score was raised significantly. Survival time ranged from 2 to 34 months, median survival time was 8.5 months, and 6-month, 1-and 2-year survival rates were 58.9%, 26.2%, and 6.0% respectively. Conclusion: SRT was one of the effective palliation treatments for the lung cancer patients with brain metastases, and with the assistance of effective nursing, which would prolong their survival time and improved quality of life.

Could helical tomotherapy do whole brain radiotherapy and radiosurgery?

Whole brain radiotherapy (WBRT) remains the standard management of breast cancer patients with brain metastases, allowing for symptomatic improvement and good local control in most patients. However, its results remain suboptimal in terms of both efficacy and toxicity. In highly selected breast cancer patients, stereotaxic radiotherapy demonstrates a very good local control with a low toxicity. With the purpose of improving the efficacy/toxicity ratio, we report the association of integrated boost with WBRT in a breast cancer patient with brain metastases. Two and a half years after completion of helical tomotherapy (HT), the patient experienced clinical and radiological complete remission of her brain disease. No delayed toxicity occurred and the patient kept her hair without need of radiosurgical procedure. The HT provided a high dosimetric homogeneity, delivering integrated radiation boosts, and avoiding critical structures involved in long-term neurological toxicity. Further assessment is required and recruitment of breast cancer patients into clinical trials is encouraged.

Efficacy of Temozolomide Combined with Whole Brain Radiotherapy in the Treatment of Cerebral Metastases from Lung Cancer

[Objectives] To observe the clinical efficacy,adverse reaction and survival time of temozolomide combined with whole brain radiotherapy in the treatment of lung cancer. [Methods] A total of 43 patients with lung cancer and cerebral metastases were reviewed and analyzed. Three-dimensional conformal radiotherapy(3D-CRT) technique was used to perform whole brain radiotherapy,one time a day and5 times a week. At the same time of radiotherapy,temozolomide chemotherapy was performed,150 mg/( m2·d),continuous oral administration of 5 d,every 28 days were a cycle( those patients who continue receiving temozolomide chemotherapy did not receive other related antitumor therapy,such as systemic chemotherapy and molecular targeted therapy,etc.),and drugs were administered for 4-6 cycles according to tolerance of patients. Kaplan-Meier method was used to calculate the survival rate. [Results]The objective response rate of 43 patients was79. 0%(34/43),in which CR was 6/43,PR was 28/43,and 9 cases had PD. By December 31,2016,7 patients in 43 cases died,one patient died of cerebral hernia due to intracranial lesions and 6 patients died of failure of other important organs due to metastasis. The OS and PFS of the whole group of patients in one year were 49. 1% and 56. 9% respectively. The adverse reactions were mild and the patients could tolerate such treatment. [Conclusions] Temozolomide combined with whole brain radiotherapy in the treatment of lung cancer with cerebral metastases has excellent clinical efficacy,while patients can tolerate such treatment.

Pre-operative stereotactic radiosurgery treatment is preferred to post-operative treatment for smaller solitary brain metastases

Background:While the optimal combination of whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) and surgical resection in the treatment of brain metastases, is controversial, the addition of SRS to surgical resction of solitary metastasis may enhance local control while potentially minimizing toxicity associated with adjuvant WBRT. This study seeks to determine whether pre-operative SRS to the lesion versus post-operative SRS to the resection bed may reduce irradiation of adjacent normal brain tissue. Methods:A retrospective study of 12 patients with 13 surgically resected cerebral metastases was performed. The pre-operative contrast-enhancing tumors and post-operative resection cavities plus any enhancing residual disease were contoured to yield the gross target volume (GTV). In turn these GTV''''s were uniformly expanded by 3-mm to generate the pre-operative, as well as post-operative planning target volume (PTV.) For each lesion, a 7-static-conformal-beam, non-coplanar plan utilizing 6 MV photons was generated to encompass the PTV within the 85％isodose line. Excess normal brain volume irradiated was defined as the volume outside the GTV receiving the prescribed dose. Results:When lesions were divided into two groups-Group A (pre-operative GTV''''s<15 cc, n=9) and Group B (pre-operative GTV''''s>15 cc, n=4)-the average volume of normal brain irradiated was significantly smaller if pre-operative SRS was used for treatment of lesions in Group A (9.5 vs. 16.8 cc, paired t-test, p=0.0045). In contrast, this volume was smaller for Group B lesions if post-operative SRS was used for treatment of these lesions (27.6 vs. 51.2 cc, p=0.252). A comparison of groups with respect to mean volume differences between pre-and post-operative SRS was significantly different (two-sample t-test p=0.016). GTV and the difference between pre-and post-operative volume were highly correlated (Pearson correlation=?0.875, p<0.0001). Conclusions:Pre-operative treatment of smaller metastases may result in reduced radiation dose to normal tissue and, thus, reduced treatment-related morbidity compared to post-operative irradiation of the resection cavity.

Observations on the role of brain stereotactic radiosurgery

As a research paradigAs a research paradigm （1） evaluated measures of animal performance correlated with markers of microglia activation and inflammation as they sought to see the effects of more focused radiation in two-month-old male athymic nude rats.The authors used intensity modulated radiation therapy （IMRT） and volumetric modulated arc therapy （VMAT） to irradiate the hippocampus either unilaterally or bilaterally.Treatment plans delivered a total dose of 10 Gy to either one or both hemispheres of the rat brain.Their data suggests that specific behavioral tasks could be reduced by focused radiation delivered to the hippocampus,and in unilaterally treated animals,the contralateral brain seemed to up-regulate repair mechanisms.This report provides additional information relative to the mechanisms of radiobiological effect using targeted radiation.

Research of radiosurgery for brain metastases

Objective To explore the efficacy of gamma knife radiosurgery for brain metastases. Methods 112 cases with brain metastases were treated by gamma knife. Among them,most cases were performed with surgery combined with whole brain radiation therapy and chemotherapy. Results 85 cases were followed-up

Stereotactic radiosurgery in the era of novel systemic therapy for lung cancer brain metastases

The emergence of novel systemic therapies has spurred a dramatic paradigm shift in lung cancer treatment.Research has revealed greater intracranial efficacy in targeted agents and immune checkpoint inhibitors(ICI)compared to conventional chemotherapy.Concurrently,advances in stereotactic radiosurgery(SRS)have contributed to the increased use of this highly localized,minimally-invasive treatment modality for local tumor control.In this era of precision medicine,the combination of these novel agents and SRS demands further prospective exploration-particularly as questions regarding their sequence of administration and the risk of neurotoxicity remain unanswered.Presently,although data are limited and largely retrospective,literature supports the concurrent administration of ICI and radiation,with no observed increases in immune-related adverse events or acute neurologic toxicities.In the case of patients with driver mutations,newer generations of tyrosine kinase inhibitors(TKI)display improved intracranial efficacy and are currently preferred alone upfront in patients with asymptomatic brain metastases(BM)due to lack of data.Evidence of combining TKI and SRS is limited with mixed results.In this review,we explore the evidence regarding the use of novel systemic agents and SRS for treatment of lung cancer BM.Clinical practice will continue to be refined as larger,prospective studies yield results.

Brain metastases from hepatocellular carcinoma after hepatectomy

Hepatocellular carcinoma is a highly malignant neoplasm and frequently involves extrahepatic organs but decidedly rarely occurs in brain. We describe 3 cases of brain metastases in patients suffering from post-HBV hepatocarcinoma. The ＂stroke-like＂ presentation of the cerebral localization of the disease can be explained by both the important vascularization of the tumor and the frequent hemocoagulative alterations caused by the cirrhosis. The importance of diagnostic neuroradiology is briefly addressed, with reference to the fundamental role played by MRI. Surgery of these lesions does not present any particular technical problems as long as they are located in accessible areas and the patient＇s general and neurological conditions allow it. Postoperative radiotherapy seems to improve the quality and quantity of residual life, although the number of patients described in the literature was too small to draw any definite conclusion in this regard.

HyperArc performance in radiotherapy and its correlations with number and volume of multiple brain metastases

Objective:To assess the performance and advantages of HyperArc for radiotherapy of multiple brain metastases with dosimetric parameters with respect to coplanar volumetric modulated arc radiotherapy(c-VMAT),and characterize implicit correlations between tumor features and dosimetric parameters.Methods:This retrospective study involved 40 patients with multiple brain metastases(4–16 tumors,12.8–240.8 cm3)who received simultaneous radiotherapy at the Department of Radiation Oncology,Shenzhen People's Hospital from January 2019 to December 2022.Both HyperArc and c-VMAT plans were designed by the same and qualified physicist using the Eclipse system with Truebeam.A single isocenter and a 6 MV flattening filter-free(6FFF)photon beam were used for radiotherapy of multiple brain metastases in each plan.Dosimetric parameters of tumors and organs at risk(OARs)were compared between HyperArc and c-VMAT plans.Corre-lations between tumor features(number and volume)and dosimetric parameters were revealed and analyzed.Furthermore,monitor units(MUs)of both plan types were recorded to assess rays utilization and delivery efficiency.Results:Compared to c-VMAT plans,HyperArc plans achieved higher maximum dose(D_(max))(5.23%,t=7.87,P<0.01),but lower minimum dose(Dmin)(3.94%,t=-2.12,P=0.04)and mean dose(D_(mean))(1.05%,t=-3.29,P<0.01)for planning gross tumor volumes(PGTVs).The conformity index(CI),homogeneity index(HI),gradient index(GI)and R50%of PGTVs with HyperArc were better than those with c-VMAT,with the improve-ments of 20.78%,1.68%,19.83%and 36.20%,respectively(P<0.01).The dosimetric parameters of OARs were significantly improved in HyperArc plans compared to c-VMAT plans.Specifically,the D_(max)and the D_(mean)to the brainstem decreased by 16.14%and 11.37%,respectively.The D_(max)for eye_L decreased by 16.88%,for eye_R decreased by 11.67%,for optical nerve_L decreased by 12.56%,and for chiasm decreased by 18.12%.Few correlations were observed between the differences of CI/HI/GI/R50%and the number of PGTVs between the two plan types.Whereas,regression analysis indicated that the differences of CI/GI/R50%were negatively correlated with the volume of PGTVs,respectively.Moreover,although HyperArc plans reduced the MUs by 4.74%compared to c-VMAT,no significant difference was observed(P>0.05).Conclusions:This study demonstrates the promising performance of HyperArc for radiotherapy of multiple brain metastases,including better dose conformity for the tumors,more rapid dose drop and less dose spillage outside the tumors area,effective reduction of dose bridges among close tumors,and sparing OARs.It also reveals the correlations between the number or volume of tumors and dose parameters,which can help optimize the use of HyperArc and predict clinical benefits.

BRAIN METASTASES FROM CARCINOMA OF UTERINE CERVIX

Objective: To study the mechanism, clinical characteristics, therapy regimens, and survival of cervical carcinoma metastases to the brain. Methods: We retrospectively analyzed 11 patients with brain metastases from cervical carcinoma. Results: Two cases were at stage lb, two at IIa, and seven at IIIb, respectively. Histologically, they were squamous cell carcinoma (6 cases), adenosquamous carcinoma (2 cases), small cell carcinoma (2 cases), or adenocarcinoma (1 cases), poorly differentiated. Eight were accompanied with lung, liver, and bone metastases disease and three had no any other systemic metastases at the time of the brain metastases diagnosis. Two had controlled, and other nine were uncontrolled or progressive primary disease. The median interval from the diagnosis of the primary carcinoma to the detection of brain lesion was 14.6 months. Headache was the most common symptom of brain metastases. Eight of 11 patients developed multiple lesions and other 3 cases had a solitary lesion in brain. The patients were treated by combination of surgery and whole brain radiation therapy (WBRT) (3 cases), stereotactic radiosurgery (SRS) (3 cases), or WBRT (5 cases). The patients had a median survival of 6.6 months. Conclusion: Brain metastases are not always a late complication of cervical carcinoma. The development of the metastases is related to pathological type, poorly differentiation, and advanced stage. Surgery and SRS are the appropriate therapy regimen for these patients.

Therapeutic Effects of Stereotactic Radiotherapy on 389 Cases of Brain Glioma

Objective： To investigate the treatment effectiveness and side effects of stereotactic radiotherapy for brain glioma. Methods： From Jun. 1995 to Dec. 1998, 389 cases of brain gliomas were treated by stereotactic radiotherapy, among which 151 cases were treated by stereotactic radiosurgery （SRS） and the other 238 cases, by fractionated stereotactic radiotherapy （FSRT）. In the SRS group, the marginal tumor dose was 20 to 30 Gy （median, 2.6 Gy）. One to 6 isocenters （median, 2.48） and 5 to 21 irradiation arcs （median, 8.45） were applied. In the FSRT group, the per-fraction marginal tumor dose was 8 to 12 Gy with 1 to 6 isocenters （median, 2.53）, 6 to 20 irradiation arcs （median, 8.25） and 2-5 fractions delivered everyday or every other day. Results： Three months after treatment, the complete and partial response rates were 13.9% and 45.7% in SRS group respectively. The stable disease rate was 17.2%. The total effective rate was 76.8%. In FSRT group, the complete and partial remission rates were 19.7% and 47.9% respectively. The stable disease rate was 20.6%. The total effective rate was 88.2%. The total effective rate of FSRT group was higher than that in SRS group （X^2=9.874, P=0.020）. The 1-year, 3-year and 5-year survival rate of all patients was 54.3%, 29.3%, 16.5% respectively. The 1-year, 3-year and 5-year survival rate in SRS group and FSRT group was 52.3% vs 26.5%, 11.9% vs 55.5%, and 31.1 vs 19.3% respectively. There was no significant difference between the two groups （X^2=2.16, P=0.1417）. The brain edema caused by the main radiation was more severe in the SRS group than in FSRT group （X^2=4.916, P=0.027）. Conclusion： It is effective for brain glioma to be treated by stereotactic radiotherapy. Compared with SRS, the FSRT has the advantage of good effect and less side response.

Radiotherapy of brain metastases from non-small cell lung cancer

Brain metastases risk at the time of diagnosis or during the course of disease is high in non-small cell lung cancer (NSCLC). Even the incidence of brain metastases has increased in recent years, due to detection of smaller asymptomatic lesions with MRI screening as well as improved survival as a consequence of developments in systemic therapies. In the last decade, there have been many trials in the management of NSCLC patients with brain metastases, questioning the role of adjuvant whole brain radiotherapy (WBRT) after surgery or stereotactic radiosurgery (SRS), WBRT, compared to best supportive care in patients not amenable to surgery, aggressive local therapies in solitary brain metastases, postsurgical cavity SRS, SRS in non-oligometastatic patients, cranial radiotherapy in patients with driver mutations, thyrosine kinase inhibitors, immune check point inhibitors and the impact of therapies on neurocognitive functions and quality of life. The main objective of this review is to provide an update on current trends in radiotherapy in the management of newly diagnosed brain metastases from NSCLC.

Systemic Therapy after Radiotherapy Significantly Reduces the Risk of Mortality of Patients with 1-3 Brain Metastases： A Retrospective Study of 250 Patients

Background：For patients with a brain metastasis （BM）,systemic therapy is usually administered after the completion of radiotherapy,especially in cases of multiple BMs.However,the role of systemic therapy in patients with a limited number of BMs is not clear.Therefore,we conducted a retrospective study to explore this question.Methods：Consecutive patients with a pathologically confirmed malignancy and 1-3 intracranial lesions that had been documented within the last decade were selected from the databases of three hospitals in China.Results：A total of 250 patients were enrolled;of them,135 received radiotherapy alone and 115 received radiotherapy plus systemic therapy.In patients receiving whole-brain radiation therapy （WBRT） as radiotherapy,28 received WBRT alone and 35 patients received WBRT plus systemic therapy.Of the patients treated with stereotactic radiosurgery （SRS）,107 received SRS alone and 80 received SRS plus systemic therapy.Multivariate analysis revealed that systemic therapy significantly reduced the risk of mortality compared with radiotherapy alone （hazard ratio [HR] =0.294,95% confidence interval [CI] =0.158-0.548）.Further,when the analysis was conducted in subgroups ofWBRT （HR =0.230,95% CI =0.081-0.653） or SRS （HR=0.305,95% CI=0.127-0.731）,systemic therapy still showed the ability to reduce the risk of mortality in patients with BMs.Conclusion：Systemic therapy after either SRS or WBRT radiotherapy may significantly reduce the risk of mortality of patients with 1-3 BMs.

Radiotherapy of brain metastases from small-cell lung cancer: standards and controversies

Small-cell lung cancer (SCLC) has a high propensity to metastasize into the brain. Radiotherapy plays a major role in the treatment of brain metastases (BM) from SCLC. Whole-brain radiotherapy (WBRT) is the standard treatment of BM from SCLC. However, the neurocognitive toxicity and modest efficacy of this approach have led to the increased use of stereotactic radiosurgery. We have no strong evidence for the use of different forms of radiation (WBRT vs. radiosurgery) in SCLC, because BM from this primary tumor were excluded from clinical trials. In this review, the use of radiation in form of WBRT or radiosurgery is discussed in distinct clinical indications: as a primary treatment and at relapse;without prior use of prophylactic cranial irradiation (PCI);and after PCI. Combinations of radiotherapy with chemotherapy are discussed as BM in SCLC occur rarely as a sole event.

Diagnosis and management of brain metastases:an updated review from a radiation oncology perspective

Brain metastasis are the most common intracranial malignancy in the adult population. Their incidence has increased dramatically over the last 20 years, as a result of the increasing number of cases stemming from lung and breast cancer together with the higher cancer survival rates due to diagnostic and therapeutic advances. More than 40%of cancer patients develop brain metastases during the course of their disease: specifically, they appear in 50%of patients with lung cancer, more than 25% of patients with breast cancer, and 20% of patients with melanoma. Diagnosis is made using different imaging approaches, such as computed tomography and magnetic resonance imaging, accompanied by clinical manifestations and a history of malignancy supporting the diagnosis of a brain metastasis. Current treatment options should be oriented to the patient's current performance, the number of intracranial and extracranial lesions, and related factors. Although surgical resection and whole-brain radiotherapy have been standard treatments for many years, numerous treatment modalities have become more easily available and accepted worldwide, producing more favorable and reliable results. Among these is stereotactic radiosurgery, and the latest clinical trials support this treatment.