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.

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.

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.

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.

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.

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.

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.

Brain metastases from hepatocellular carcinoma after hepatectomy

Hepatocellular 癌是一个高度恶意的瘤并且经常包含 extrahepatic 机关，但是很少坚决地发生在大脑。我们在受不了 post-HBV hepatocarcinoma 的病人描述大脑转移的 3 个案例。疾病的服的本地化的像击的演讲能被两个解释肿瘤和肝硬化引起的经常的 hemocoagulative 改变的重要 vascularization。诊断 neuroradiology 的重要性简短被探讨，与 MRI 起的基本作用的参考。只要他们位于可存取的区域，病人的一般、神经病学的条件允许它，这些损害的外科不导致任何特别技术问题。手术后的放射疗法似乎改进剩余生活的质量和数量，尽管在文学描述的病人的数字太小，不能得出任何明确的结论在这方面。

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.

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.

SIMULTANEOUS THORACO－CRANIAL OPERATION FOR THE TREATMENT OF LUNG CANCER WITH BRAIN METASTASES

We performed simultaneous one-stage thoraciccranial surgery on ten cases of lung cancer with brain metastases during the period of 1990 to 1994. Surgical mortality was 0% with low morbidity. By the end of the follow-up in February 1995, 4 patients died, with a mean survival of 8.25 months, and 6 patients survived, with a mean survival of 16 months and the longest one being approximately 36 months. Our results showed that, if patient's general condition permits, simultaneous onestage thoraco-cranial operation is feasible for the treatment of lung cancer involved the Periphery with solitary intracranial metastasis. Postoperative adjuvant chemotherapy is indicated to achieve better results.

Long-term control of melanoma brain metastases with co-occurring intracranial infection and involuntary drug reduction during COVID- 19 pandemic: A case report

BACKGROUND Melanoma brain metastasis is a common cause of death in melanoma patients andis associated with a poor prognosis. There are relatively few reports onintracranial infections after brain metastasis resection.CASE SUMMARY Here we report a case of melanoma brain metastases in a patient harboring aBRAF V600E mutation, who experienced intracranial tumor progression despiteprevious combined treatment with a programmed death (PD)-1 inhibitor, axitinib,and vemurafenib. She repeatedly underwent local therapy, including stereotacticradiosurgery and intracranial surgery, and developed central nervous systeminfection. Treatment with vemurafenib combined with cobimetinib resulted in anintracranial progression-free survival of 10 mo. During the coronavirus disease2019 (COVID-19) pandemic, the patient did not visit the hospital for regularvemurafenib treatment, and experienced intracranial progression afterinvoluntary drug reduction for 1 mo. The patient subsequently received varioussystemic treatments including vemurafenib, PD-1 inhibitor, and chemotherapy,with an overall survival of 29 mo as of September 2020.CONCLUSION We report the first case of melanoma brain metastases with co-occurringintracranial infection and unintended drug reduction during the COVID-19outbreak. Long-term control of the intracranial lesions was achieved withsystemic and local therapies.

Icotinib, an EGFR-TKI, for the treatment of brain metastases in non-small cell lung cancer:a retrospective study

Objective Treatment of brain metastases from non-small cell lung cancer(NSCLC) is a challenge because of the poor prognosis. Icotinib is a new type of oral epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI) used in the treatment of advanced NSCLC. The aim of this study was to evaluate the efficacy of icotinib in NSCLC patients with brain metastasis.Methods This study reviewed records of 51 NSCLC patients with brain metastases who took icotinib 125 mg, 3 times a day. Response rate, progression free survival, and overall survival were analyzed. SPSS software version 17.0 was used for univariate analysis, and Cox regression analysis to analyze factors affecting survival. Results Thirty-six cases had partial response, 6 cases had stable disease, and 10 cases had progressive disease. In 31 cases, EGFR gene mutation test were performed. EGFR was mutated in 26 cases and was with wild-type in 5 cases. In patients with EGFR mutations, 23 patients responded to icotinib [the disease control rate(DCR) was 88.5%], significantly higher than in patients with wild-type EGFR(1 patient, DCR 20%)(P = 0.005). The overall median progression-free survival(PFS) was 7.6 months. PFS was longer in the patients with EGFR mutations than in those with wild type EGFR(7.8 months vs 1.2 months, P = 0.03). The overall median overall survival(OS) time was 10.7 months. OS was longer in patients with EGFR mutations than in those with wild type EGFR(15.1 months vs 6.7 months, P = 0.003). The main side effects of the treatment were skin rash and diarrhea; no stage 3 or 4 toxic effects occurred. Univariate analysis demonstrated that OS was related to sex, Eastern Cooperative Oncology Group performance status(ECOG PS), smoking history, and EGFR mutation. Multivariate analysis showed that OS was independently related to sex, ECOG PS, and EGFR mutations.Conclusion Icotinib has a favorable effect on NSCLC patients with brain metastases harboring EGFR mutations. Icotinib can be a new choice of treatment for brain metastases in patients with NSCLC harboring EGFR mutations.

Brain Metastases: Epidemiological, Clinical, Diagnosis, Treatment and Outcome Features in Dakar

Brain metastases (BM) are the most frequent brain cancer. There are few studies on BM in Senegal. The aim of this study was to describe epidemiological, clinical, diagnosis, treatment and outcome features of patients diagnosed with BM. We conducted a retrospective and descriptive study of patients diagnosed with brain tumors and regularly followed at the neurosurgery department of the “Fann Teaching Hospital (CHNU-Fann)” of Dakar (Senegal) between from January 2010 to December 2017. The medical records of all the patients with evidence histologically diagnosed with BM were reviewed. In our study, 682 medical records of patients with brain tumors were reviewed, and only 20 showed histological evidence of BM (2.9%). The mean age was 45.45 years. The sex-ratio was 0.43. Brain CT scan was performed in all the patients (100%) and brain MRI in 3 patients. The brain lesions were multiple in 70% of the patients and single in 30%. The histological type of BM was adenocarcinoma (55%) and squamous cell carcinoma (45%). Five types of primary cancers were found: lung cancer (50%), breast cancer (30%), colorectal cancer (10%), melanoma (5%) and one undetermined cancer. All the patients had extirpation surgery;50% of the patients died 7 days after the surgery;25% had a survival of 3 months after the surgery and 25% of the patients were lost of sight. Conclusion: The improvement of the screening and diagnosis tests, and the use of the radiation treatment and chemotherapy could allow early management and decrease the death’s frequency of the patients with BM in Senegal.

Science Letters:Brain metastases of melanoma-mechanisms of attack on their defence system by engineered stem cells in the microenvironment

This report gives a better emphasis on the role of targeted effectors (e.g. a combination of 5-FC with CD-NSPCs as compared to the application of NSPCs alone) and how such delivery of pro-drug activating enzymes and other tumor-killing substances may overcome melanocytic defence system, interact with and promote the host defence and immune response modulations not only in melanoma but, potentially, in other highly-metastatic cancers.

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.

Treatment progress of brain metastases from lung cancer

Objective:Lung cancer is one of malignant tumors with the highest incidence in the world, and 30%-65% of the patients develop brain metastases in the progression of the disease. Brain metastases seriously affect the patient's cognitive function, survival time and quality of life, the prognosis is extremely poor and the natural course of disease is about 1-3 months. The main therapies for brain metastases from NSCLC include surgical resection, radiotherapy, chemotherapy, and so on. In recent years, with the improvement of surgical methods, the improvement of radiotherapy technology, the emergence of targeted drugs and the combined use of various treatments, the survival time of patients has been greatly extended, and the quality of life has also been significantly improved. In this paper, the current main treatment strategies for brain metastases are reviewed.