Incidence,Risk Factors,and Prognosis of Patients with Hepatocellular Carcinoma and Brain Metastases

Objective Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma(HCC).This study aimed to examine the age-related incidence,demographics,and survival of patients with HCC and brain metastases.Methods Data of HCC patients from 2010 to 2015 in the Surveillance,Epidemiology,and End Results(SEER)Registry were screened for the presence of brain metastases.They were stratified by age and ethnicity.Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival(OS)and liver cancer-specific survival(CSS),respectively.Results A total of 141 HCC patients presenting with brain metastases were identified,accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease.Among all HCC patients,the incidence rate was the highest among patients aged 30-49 years old(0.47%).Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis.However,African-American patients presented with a significantly lower disease-specific survival[median time:1 month;interquartile range(IQR):0-3.0 months].Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases[odds ratio(OR):12.62,95% confidence interval(CI):8.40-18.97]but was not associated with a worse OS or CSS among those with brain metastases.Conclusion This study identified the age-related incidence and risk factors of brain metastases in HCC patients.These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases,and influence the counseling of this patient population regarding their prognosis.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Planning Target Volume Margin in Linac-Based Stereotactic Radiosurgery for Brain Metastases

Background: The treatment of brain metastases with radiotherapy has shifted to the use of Stereotactic Radio-surgery (SRS). The technical issue of expanding the treatment volume around the Gross Tumor Volume (GTV) is a current debate. Radiotherapy centers use variable GTV-PTV margins, ranging from one to 2 mm. Material and Methods: We performed a dosimetric comparison in plans of twenty patients using three margins: PTV zero, PTV1, and PTV2. We also developed imaginary Peel volumes. These volumes are described as follows: Peel1 = PTV1 − GTV, Peel2 = PTV2 − GTV. Results: Our results showed that the mean PTV volume differed significantly across the different margins (p = 0.000). The V12 of the brain significantly varied as a function of PTV margin (p = 0.000). The target coverage and plan quality indices were not significantly different. The Peel volume dosimetric analysis showed that the mean dose was significantly higher in the nearby normal brain tissue: Peel1 (p = 0.022) and Peel 2 (p = 0.013). Conclusion: According to our dosimetric analysis, expanding the GTV into a PTV by 1 mm margin is more convenient than 2 mm.

Stage Ⅳ non-small cell lung cancer with multiple metastases to the small intestine leading to intussusception: A case report

BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.

Impacts of radiation therapy on quality of life and pain relief in patients with bone metastases

Bone metastases(BM)are a common complication in advanced cancer patients,significantly contributing to morbidity and mortality due to their ability to cause pain,fractures,and spinal cord compression.Radiation therapy(RT)is vital in managing these complications by targeting metastatic lesions to ease pain,improve mobility,and reduce the risk of skeletal-related events such as fractures.Evidence supports the effectiveness of RT in pain relief,showing its ability to provide significant palliation and lessen the need for opioid painkillers,thereby enhancing the overall quality of life(QoL)for patients with BM.However,optimizing RT outcomes involves considerations such as the choice of radiation technique,dose fractionation schedules,and the integration of supportive care measures to mitigate treatment-related side effects like fatigue and skin reactions.These factors highlight the importance of personalized treatment planning tailored to individual patient needs and tumor characteristics.This mini-review aims to provide comprehensive insights into the multifaceted impacts of RT on pain management and QoL enhancement in BM patients,with implications for refining clinical practices and advancing patient care through the synthesis of findings from various studies.

Bridging the gap: Predicting brain metastasis in breast cancer

Chen et al explored clinicopathological features and prognostic factors,revealing advanced tumor stage,lung metastases,HER-2 overexpression,and triple-negative status as key contributors.Recent research connects astrocytes'role in brain metastasis with signaling pathways and the impact of Trastuzumab on HER-2 tumor survival.Factors such as positive HER2 status,lack of estrogen receptor expression,and liver metastasis are identified as additional risk factors.The routine use of magnetic resonance imaging,insights into gene mutations associated with metastasis,and the role of radiotherapy,including prophylaxis possibilities,is controversial in clinical practice.Understanding these risk factors in a multidisciplinary collaboration is precise for local treatments and targeted therapies,particularly for HER2+tumors,impacting directly on longer survival.

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.

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.

Radiotherapy for multiple brain metastases from hepatocellular carcinomas

A 78-year-old man with liver cirrhosis was found to have multiple hepatocellular carcinomas （HCCs） and underwent 3 sessions of transcatheter arterial chernoernbolization. Fourteen months after diagnosis, the patient presented with left herniparesis. Contrast- enhanced magnetic resonance imaging showed multiple metastases with ring-shaped enhancement in the cerebrum and cerebellum. There were no metastases to other organs. The metastatic lesions almost completely disappeared after whole-brain radiotherapy with a total dose of 50 Gy. Neurologic symptoms decreased, and the patient＇s quality of life improved. The patient underwent 2 more sessions of transcatheter arterial chemoembolization. Twelve months after the diagnosis of brain metastasis, the patient remains alive. The present case indicates that radiotherapy can improve quality of life and prolong survival in some patients with brain metastases from HCCs.

Whole brain radiotherapy concomitant or sequential Vm26/DDP in treating small cell lung cancer patients with brain metastases

Objective： The aim of the study was to compare efficacies and safeties of 2 different treatments of whole brain radiotherapy （WBRT） sequential or concomitant Vm26/DDP for small cell lung cancer （SCLC） patients with brain metastases. Methods： A total of 39 patients were randomly divided into sequential chemoradiotherapy regime （A group, 20 patients） and concomitant chemoradiotherapy regime （B group, 19 patients）. The close of WBRT was 36 Gy in 18-20 fractions, chemotherapy of Vm26/DDP regimen with teniposide 60 mg/m^2 on dl to d3 and cisplatin 20 mg/m^2 on dl to d5, repeating every 3 weeks. The response was evaluated after WBRT and 2 cycles of chemotherapy. Results： Total response rates of A and B groups were 70.0% and 78.9% respectively （P = 0.520）. The median survival was 11 months in A group and 10 months in B group. Six, twelve and eighteen months cumulative survival rates of A and B groups were 75.0%, 42.5%, 26.2%, and 81.6%, 26.4%, 10.5%, respectively （χ^2 = 0.383, P 〉 0.05）. Response rate and the number of brain metastases were independent prognostic factors. Conclusion： Both sequential and concomitant chemoradiotherapy groups are effective, and the main toxicity with myelosuppression is tolerable after therapy. It can be applied firstly and effectively to the SCLC patients with brain metastases in clinic.

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.

The effects of three-dimensional conformal radiotherapy combined with whole brain irradiation on brain metastases

Objective： To observe the recently therapeutic effects and toxicity of three-dimensional conformal radiotherapy combined with whole brain irradiation for patients with brain metastasis. Methods： 33 cases were treated by whole brain irradiation at first, the dose of which was 36-40 Gy （18-20 f）. Then three-dimensional conformal radiotherapy was added to the focus with a total dose of 20-25 Gy, whose fractionated dose was 2-5 Gy/time, 5 times/week or 3 times/week. Results： Within 1 month after radiotherapy, according to imaging of the brain, the CR of all patients was 45.5%, PR 36.4%, NC 15.1%, and PD 3%. For the 32 cases with neural symptoms before radiation, the CR of the symptoms was 40.6% and PR 59.4%. All patients gained different increases in KPS grade. By the end of the follow-up period, there were 22 deaths with the mean survival time up to 9.3 months. Conclusion： Three-dimensional conformal radiotherapy combined with whole brain irradiation can not only effectively control brain metastases and improve life quality, but also tends to prolong survival time.

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.

Temozolomide for treatment of brain metastases: A review of 21 clinical trials

Brain metastases from solid tumours are associated with poor prognosis despite aggressive treatment. Temozolomide can be used for the treatment of glioblastoma multiforme as well as melanoma. It has also been shown to have activity in patients with brain metastases from various malignancies, since it can cross the blood-brain barrier. To better understand the efficacy of temozolomide in the treatment of brain metastases, we carried out a review of 21 published clinical trials to determine whether temozolomide would benefit patients with brain metastases from solid tumours. Information regarding complete response, partial response, stable disease, objective response and objective response rate were collected to assess clinical outcomes. A modest therapeutic effect was observed when temozolomide was used as a single agent, however, the combination of temozolomide with whole-brain radiotherapy and/or other anticancer drugs exhibited encouraging activity. Thus, future high quality studies are warranted to confirm our findings.

Cabazitaxel in castration resistant prostate cancer with brain metastases: 3 case reports

Prostate cancer is the most common non-cutaneous malignancy for men. The skeleton is the most common metastatic site but, following an improvement in survival, metastases in uncommon sites are being found more frequently in clinical practice, especially brain metastases. Despite the new drugs now available for metastatic castration resistant prostate cancer, no clinical evidence exists about their effectiveness on brain metastases. We describe the clinical history of 3 patients treated with cabazitaxel plus whole brain radiotherapy. These case reports demonstrate that cabazitaxel is highly active and well tolerated in brain metastases.

Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis

Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma(NPC); however, it is not known whether locoregional radiotherapy targeting the primary tumor and regional lymph nodes affects the survival of patients with metastatic NPC. Therefore, we aimed to retrospectively evaluate the benefits of locoregional radiotherapy. A total of 408 patients with metastatic NPC were included in this study. The mortality risks of the patients undergoing supportive treatment and those undergoing chemotherapy were compared with that of patients undergoing locoregional radiotherapy delivered alone or in combination with chemotherapy. Univariate and multivariate analyses were conducted. The contributions of independent factors were assessed after adjustment for covariates with significant prognostic associations (P<0.05). Both locoregional radiotherapy and systemic chemotherapy were identified as significant independent prognostic factors of overall survival(OS). The mortality risk was similar in the group undergoing locoregional radiotherapy alone and the group undergoing systemic chemotherapy alone [multi-adjusted hazard ratio(HR)=0.9, P=0.529]; this risk was 60% lower than that of the group undergoing supportive treatment(HR=0.4, P=0.004) and 130% higher than that of the group undergoing both systemic chemotherapy and locoregional radiotherapy(HR=2.3, P<0.001). In conclusion, locoregional radiotherapy, particularly when combined with systemic chemotherapy, is associated with improved survival of patients with metastatic NPC.

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.

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.

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.

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.