Chromophobe renal cell carcinoma with rare distant metastasis

Metastasis accounts for the most common tumor of the central nervous system (CNS) in adults. Renal cell carcinoma (RCC) is one of the common carcinoma showing brain metastasis, with a predilection for clear cell variant. Chromophobe RCC (ChRCC) in contrast to clear cell RCC shows far less common distant metastasis. When they metastasize, commonly involve the liver, lungs, and lymph nodes. ChRCC metastasizing to the brain is extremely rare. Isolated brain metastasis from RCCs is also uncommon. We report an unusual case of a 54-year-old woman with ChRCC with isolated metastasis to the brain, 2 years after radical nephrectomy for renal mass.

Phase II trial of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost for treatment of brain metastases of lung cancer / 中华放射肿瘤学杂志

Objective:To evaluate the efficacy and safety of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost in the treatment of brain metastases of lung cancer.Methods:Forty lung cancer patients with brain metastases who received whole-brain radiotherapy with simultaneous integrated boost and hippocampal avoidance in Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2020 were enrolled in this study. Brain MRI, survival follow-up and evaluation of side effects were performed before radiotherapy and at 1, 3, 6 and 12 months after radiotherapy, respectively. Overall survival (OS), progression-free survival (PFS) and changes in cognitive function were analyzed. Continuous data were described as Mean ± SD. Categorical data were described by frequency and composition ratio or percentage. Survival analysis was conducted by Kaplan-Meier method. Influencing factors of survival were identified by univariate and multivariate Cox's regression analyses.Results:A total of 40 patients were enrolled in the study. The median follow-up time was 14.2 months and the median OS, PFS and intracranial PFS of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis showed that male gender and newly diagnosed stage Ⅳ disease were associated with worse OS and PFS, respectively. The Hopkins verbal learning test-revised (HVLT-R) scores at baseline and 1, 3 and 6 months after radiotherapy were 21.94±2.99, 20.88±3.12, 20.03±3.14, and 19.78±2.98, respectively. The HVLT-R score at 6 months after radiotherapy was decreased by approximately 9.8% compared with the baseline. No grade 3 or above toxic and side effect occurred in the entire cohort.Conclusion:Hippocampal avoidance whole-brain irradiation with simultaneous integrated boost is a safe and effective treatment for brain metastases of lung cancer, which is expected to reduce the impact of radiotherapy on cognitive function.

Application of the second derivative-based small monitor unit beam deletion optimization to CyberKnife planning of heads / 中华放射医学与防护杂志

Objective:To investigate the effects of different small monitor unit (MU) beam deletion optimization method in the CyberKnife treatment planning system on the calculated planned dose to brain tumors.Methods:A total of 17 patients with brain metastases treated in our hospital from June, 2021 to February, 2022 were selected for this study. A treatment plan was designed for each patient using the multiPlan system in the CyberKnife VSI system as the group without optimization. To improve the efficiency, the generated original plans should be optimized first by deleting some small MUs, forming an experience group and an optimization group for each patient. For the experience group, beams below 30 MU were deleted according to experience. For the optimization group, beams below the MU value calculated based on the second derivative method were deleted. Finally, the parameters of the two groups were statistically compared. The main evaluation parameters included the node number, the beam number, the total number of MUs, the estimated treatment duration, doses to 2% and 95% planning target volumes (PTV D2 and PTV D95), average dose to PTV ( Dmean), average dose to brain tissue ( Dmean-Brain), conformity index (CI), new conformity index (nCI), gradient index (GI), coverage, and the maximum doses to the brainstem and left and right lens ( Dmax-BS, Dmax-LL, and Dmax-RL), and the average doses to the dose shells 20 mm and 40 mm away from PTV (Shell20 and Shell40). Results:The two optimization method met the requirements for the prescription dose delivery to more than 98% PTV. There were statistical differences in the node number ( H = 7.97, P< 0.05) and estimated treatment duration ( H = 6.60, P < 0.05) among the group without MP optimization, the experience group, and the optimization group, with the estimated treatment duration and node number of the optimization group less than those of the group without MP optimization ( P < 0.05). There were no statistically significant differences in other parameters among the three groups ( P > 0.05). The PTV was moderately positively correlated with the treatment duration ( r=0.79, P < 0.01) and beam number ( r=0.78, P < 0.01) of the experience group, and was also moderately positively correlated with the treatment duration ( r=0.69, P < 0.01) and beam number ( r=0.71, P < 0.01) of the optimization group. Conclusions:For the CyberKnife planning of heads, the small MU beam deletion optimization method based on the second derivative can further shorten the treatment duration while ensuring no significant differences in the distribution of doses to organs at risk and targets. Moreover, this method is more effective in optimizing the plans for a large PTV volume.

All-stage targeted therapy for the brain metastasis from triple-negative breast cancer

Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood-brain barrier (BBB) and blood-tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a "Y-shaped" peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC. Inherited from the activated platelet, the hybrid liposomes still retain the native affinity toward CTCs. Further, the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo. The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions, and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug. Overall, this work provides a promising prospect for the comprehensive treatment of BM-TNBC, which could be generalized to other cell types or used in imaging platforms in the future.

Bizarre presentation of choriocarcinoma: A case report / Philippine Journal of Obstetrics and Gynecology

@#Choriocarcinoma is a malignant subtype of gestational trophoblastic disease that follows any type of pregnancy. It is characterized by rapid hematogenous spread to multiple organs, associated with high human chorionic gonadotropin levels with good response to chemotherapy. We present the case of a 31‑year‑old Filipina who initially presented with severe headaches and blurring of vision 3 years after an unremarkable term pregnancy. The transvaginal ultrasound was normal. After a series of diagnostic tests, the initial working impression was a primary brain tumor with metastases to the lungs, adrenal, kidney, and vulva. Emergency craniotomy was done due to deteriorating status secondary to an intracranial hemorrhage. The histopathology report showed choriocarcinoma. Chemotherapy using Etoposide‑Methotrexate‑Actinomycin D‑Cyclophosphamide‑Vincristine with high‑dose methotrexate and concomitant whole‑brain irradiation was then instituted with good response. This case highlights the importance of having a high index of suspicion for gestational trophoblastic neoplasia to prevent the performance of unnecessary procedures, leading to a delay in diagnosis and the institution of the appropriate treatment.

Research Progress in the Efficacy and Safety of ALK Inhibitors in the Treatment of NSCLC Brain Metastasis / 中国肺癌杂志

Lung cancer is one of the most lethal malignancies in the world, with non-small cell lung cancer (NSCLC) accounting for approximately 80%-85% of all pathological types. Approximately 30%-55% of NSCLC patients develop brain metastases. It has been reported that 5%-6% of patients with brain metastases harbor anaplastic lymphoma kinase (ALK) fusion. ALK-positive NSCLC patients have shown significant therapeutic benefits after treatment with ALK inhibitors. Over the past decade, ALK inhibitors have rapidly evolved and now exist in three generations: first-generation drugs such as Crizotinib; second-generation drugs including Alectinib, Brigatinib, Ceritinib, and Ensartinib; and third-generation drugs like Lorlatinib. These drugs have exhibited varying efficacy in treating brain metastases in ALK-positive NSCLC patients. However, the numerous options available for ALK inhibition present a challenge for clinical decision-making. Therefore, this review aims to provide clinical guidance by summarizing the efficacy and safety of ALK inhibitors in treating NSCLC brain metastases.
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Intraventricular metastasis from carcinoma breast masquerading as choroid plexus neoplasm: A case report

Metastatic tumors in the brain represent the most common type of intracranial neoplasm, comprising 8–10% of all brain tumors. 30% of such tumors are primarily of breast origin in females. Brain parenchymal metastasis is the more common presentation. Intraventricular spread is rare, seen in less than 5% of cases in a metastatic scenario. Here, we report a case of 41-year-old female presenting with intraventricular brain metastasis in a follow-up case of carcinoma breast. Five years post-surgery, the patient presented with complaints of headache. On evaluation, magnetic resonance imaging (MRI) brain showed an intraventricular lesion in the fourth ventricle. She was operated on for the same and the biopsy revealed a tumor with a complex papillary pattern resembling choroid plexus papilloma. On immunohistochemistry (IHC), the tumor cells were positive for cytokeratin 7 (CK7), Epithelial membrane antigen (EMA), GATA3, and mammaglobin favoring a metastasis from breast origin. Hence, a possibility of brain metastasis should be kept in mind in patients presenting with solitary ventricular masses due to the lack of definite radiological characteristics in such locations and histological overlap. Also, organ-specific IHC is a must in today's evidence-based era as is reflected in our case.

Role of apparent diffusion coefficient measurement in differentiating histological subtypes of brain metastasis of lung cancer

SUMMARY OBJECTIVE: The aim of this study was to investigate the role of apparent diffusion coefficient of diffusion-weighted imaging in differentiating histological subtypes of brain metastasis of lung cancer. METHODS: Diffusion-weighted imaging of 158 patients (mean age: 61.2±10.68 years) with brain metastasis of lung cancer (36 small cell lung cancer and 122 non-small cell lung cancer) were retrospectively evaluated. The minimum and mean apparent diffusion coefficient values of the metastasis, apparent diffusion coefficient of edema around the metastasis, and apparent diffusion coefficient of contralateral brain parenchyma were measured. Normalized apparent diffusion coefficient was calculated by proportioning the mean apparent diffusion coefficient of the metastasis to the apparent diffusion coefficient of the contralateral brain parenchyma. Minimum and mean apparent diffusion coefficient of the metastasis, apparent diffusion coefficient of edema around metastasis, and normalized apparent diffusion coefficient were compared between small cell lung cancer and non-small cell lung cancer metastases. RESULTS: Minimum apparent diffusion coefficient, mean apparent diffusion coefficient, and normalized apparent diffusion coefficient values of small cell lung cancer metastases (0.43±0.19×10−3mm2/s, 0.63±0.20×10−3mm2/s, and 0.81 [0.55-1.44], respectively) were significantly lower than those of non-small cell lung cancer metastases (0.71±0.26×10−3mm2/s, 0.93±0.29×10−3mm2/s, and 1.30 [0.60-3.20], respectively; p<0.001). Mean apparent diffusion coefficient of edema of small cell lung cancer metastases (1.21±0.28×10−3mm2/s) was significantly lower than that of non-small cell lung cancer metastases (1.39±0.26×10−3mm2/s, p=0.020). The best cutoff values of minimum apparent diffusion coefficient, mean apparent diffusion coefficient, normalized apparent diffusion coefficient, and apparent diffusion coefficient of edema for the differentiation of small cell lung cancer and non-small cell lung cancer were found to be 0.56×10−3mm2/s, 0.82×10−3mm2/s, 1.085, and 1.21×10−3mm2/s, respectively. The area under the receiver operating characteristic curve, sensitivity, and specificity values were, respectively, 0.812, 80.6, and 73.8% for minimum apparent diffusion coefficient; 0.825, 91.7, and 61.5% for mean apparent diffusion coefficient; 0.845, 80.6, and 73.8% for normalized apparent diffusion coefficient; and 0.698, 75.0, and 67.7% for apparent diffusion coefficient of edema. CONCLUSIONS: Minimum apparent diffusion coefficient, mean apparent diffusion coefficient, normalized apparent diffusion coefficient, and apparent diffusion coefficient of edema around metastasis can differentiate histological subtypes of brain metastasis of lung cancer.

Research Progress on Risk Factors of Brain Metastasis in Non-small Cell Lung Cancer / 中国肺癌杂志

Brain metastasis of non-small cell lung cancer (NSCLC) is a common treatment failure mode, and the median survival time of NSCLC patients with brain metastasis is only 1 mon-2 mon. Prophylactic cranial irradiation (PCI) can delay the occurrence of brain metastasis, but the survival benefits of NSCLC patients are still controversial. It is particularly important to identify the patients who are most likely to benefit from PCI. This article reviews the high risk factors of brain metastasis in NSCLC.
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Clinical features of patients with EGFR mutation-positive non-small cell lung cancer and brain metastases / 中华放射肿瘤学杂志

Advanced non-small cell lung cancer (NSCLC) patients are commonly with brain metastases, leading to poor survival and quality of life. Epidermal growth factor receptor (EGFR) is common sensitive mutation type in NSCLC. Compared with other molecular types, it has different molecular biological characteristics. For patients with brain metastases and EGFR-mutated advanced NSCLC, EGFR-tyrosine kinase inhibitors can prolong overall survival and improve intracranial and extracranial control rate. To understand the characteristics of brain metastases of patients with sensitively EGFR-mutated NSCLC, the incidence, onset time, site, number and size of lesions, symptoms, targeted treatment effect and disease outcomes were reviewed, which can provide reference for interventional timing and local treatment technology selection of local treatment for brain parenchymal metastases.

Analysis of risk factors associated with brain metastasis of limited small cell lung cancer after prophylactic cranial irradiation / 中华放射肿瘤学杂志

Small cell lung cancer (SCLC) has the biological characteristics of high recurrence and metastasis. The brain is the common site of SCLC extrapulmonary metastasis. Prophylactic cranial irradiation (PCI) can effectively reduce the incidence of brain metastasis and prolong the overall survival of patients with limited SCLC. Nevertheless, nearly one third of patients develop brain metastases after PCI. This article reviews the risk factors of brain metastasis after PCI, aiming to determine which subgroup of patients with limited SCLC can benefit from PCI and provide reference for the clinical application of PCI.

Single-fraction SRS and multi-fraction SRT for brain metastases from colorectal cancer / 中华放射肿瘤学杂志

Objective:To compare the efficacy and side effects of multi-fraction stereotactic radiotherapy (SRT) and single-fraction stereotactic radiosurgery (SRS) in the treatment of brain metastases from colorectal cancer.Methods:A total of 98 patients with brain metastases from colorectal cancer searched from the database of Professional Committee of Brain Metastasis of Shanghai Anticancer Association were recruited in this study. Among them, 46 patients weretreated with SRT and 52 patients with SRS. Clinical characteristics of all patients were analyzed between two groups and the local tumor control rate, median survival time and the incidence of radiation-induced brain injury were compared between two groups.Results:The objective remission rates (ORR) in the SRT and SRS groups were 76.1% and 67.3%, respectively. The 12-month local tumor control rates were 88.3% and 83.9% between two groups, with no statistical difference ( P=0.689). The median overall survival time of all patients was 11.6 months, 10.8 months in the SRT group and 12.7 months in the SRS group. There was no statistical difference between two groups ( P=0.129). Multivariate analysis showed that the main factors leading to poor prognosis included the number of tumors of >3( P=0.026), low GPA score ( P=0.035), and lack of systematic treatment mode and bevacizumab ( P=0.001). There was no statistical difference in the incidence of acute and late radiation-induced brain injury between two groups. Conclusions:Both SRT and SRS are effective therapies for brain metastases from colorectal cancer. The synergistic application of systematic treatment mode may be one of the main reasons affecting the survival time of the patients.

Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with different doses of whole brain radiotherapy / 中华放射肿瘤学杂志

Objective:To analyze the prognosis and influencing factors of patients with brain metastases from non-small cell lung cancer (NSCLC) treated with different doses of whole brain radiotherapy (WBRT).Methods:A total of 244 NSCLC patients with brain metastases who underwent WBRT in the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different doses of WBRT (EQD 2Gy), they were divided into the 30-39 Gy group ( n= 104) and ≥40 Gy group ( n= 140). The intracranial progression-free survival (iPFS) and overall survival (OS) were compared betweentwo groups. According to the number of brain metastases, GPA score, KPS score, chemotherapy and targeted therapy, the prognosis of different doses of WBRT was further analyzed. Results:The median iPFS and OS of all patients were 6.9 months and 11.8 months, respectively. Univariate survival analysis: the 1-year iPFS and 1-year OS between two groups were 22.5% and 25.4%( P=0.430) and 41.1% and 46.4%( P=0.068), respectively. Multivariate survival analysis: different doses of WBRT were not associated with the improvement of iPFS and OS; independent factors influencing iPFS included local boost, gender, number of brain metastases, chemotherapy and targeted therapy; independent factors influencing OS included gender, number of brain metastases, chemotherapy and targeted therapy. Subgroup analysis: in patients with KPS≥90, the 1-year iPFS and OS of patients with WBRT ≥ 40 Gy were seemingly better than those of their counterparts with 30-39 Gy, but the difference was statistically significant only in OS ( P=0.047), the difference was not statistically significant in iPFS ( P=0.068); in patients with chemotherapy, the 1-year iPFS and OS of patients with WBRT≥40 Gy were better than those of their counterparts with 30-39 Gy ( P=0.017, P=0.012); in patients with targeted therapy, the 1-year iPFS and OS in the WBRT≥40 Gy group were better than those in the 30-39 Gy group ( P=0.012, P=0.045). Conclusions:The 30-39 Gy may be the appropriate dose of WBRT for NSCLC patients with brain metastases. WBRT≥40 Gy does not bring more benefits. WBRT≥40 Gy may benefit NSCLC patients with brain metastases with high KPS score or active systemic therapy.

Risk assessment of brain metastasis after prophylactic cranial irradiation for 550 limited stage small cell lung cancer patients with remission after radiochemotherapy / 中华放射肿瘤学杂志

Objective:To evaluate the risk and prognostic factors of brain metastasis (BM) after prophylactic cranial irradiation (PCI) in limited stage small cell lung cancer (LS-SCLC) patients with complete and partial remission (CR/PR) after radiochemotherapy.Methods:Baseline data of 550 patients with LS-SCLC who obtained CR/PR after chemoradiotherapy and received PCI in Zhejiang Cancer Hospital between 2002 and 2017 were collected. The risk of BM and clinical prognosis were retrospectively analyzed. The survival analysis was performed by Kaplan-Meier method. Multivariate prognostic analysis was conducted byCox models.Results:The overall BM rate after PCI was 15.6%(86/550), with 9%(4/43), 13%(7/52), and 16.5%(75/455) for stage Ⅰ, Ⅱ and Ⅲ patients, respectively. The median overall survival (OS) for the entire cohort was 27.9 months, and the 5-year OS rate was 31.0%. The OS was 24.9 and 30.2 months for patients with or without BM, and the 5-year OS rates were 8.9% and 36.1%( P<0.001). BM was an independent factor of OS ( P<0.001). Clinical staging remained the influencing factor of OS and BM-free survival ( P<0.001, P=0.027). Having tumors of ≥5 cm in diameter significantly increased the risk of BM ( P=0.034) rather than the OS ( P=0.182). The median OS of patients aged<60 years was significantly longer than those aged ≥60 years (34.9 months vs. 24.6 months, P=0.001). The median OS of patients irradiated with 2 times/d was 29.8 months, significantly longer than 24.5 months of those irradiated with 1 time/d ( P=0.013). Age, sex, radiotherapy fraction and efficacy of radiochemotherapy (CR/PR) were not associated with the incidence rate of BM (all P>0.05). Conclusions:SCLC patients with tumors of ≥5 cm in diameter may have a higher risk of developing BM after PCI. Patients aged<60 years achieve better OS compared with their counterparts aged ≥60 years.

Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with supplemental radiotherapy under different prognostic scores / 中华放射肿瘤学杂志

Objective:To analyze the prognosis and influencing factors of different radiotherapy modes in patients with brain metastases from non-small cell lung cancer (NSCLC), and to explore the best benefit population with radiotherapy boost under different prognostic scores.Methods:634 patients with brain metastasis from NSCLC admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different radiotherapy modes, they were divided into three groups: no radiotherapy group ( n=330), whole-brain radiotherapy group (WBRT)( n=127) and whole-brain radiotherapy combined with boost group (WBRT+ boost)( n=177). The intracranial progression-free survival (iPFS) and overall survival (OS) were calculated by Kaplan-Meier method. The multivariate prognostic factors were analyzed by the Cox models. Results:The median iPFS and OS of all patients were 6.9 months and 9.0 months, respectively. In the no radiotherapy, WBRT and WBRT+ boost groups, the 1-year iPFS was 15.1%, 16.3% and 40.2%( P=0.002), and the 1-year OS was 33.7%, 38.2% and 48.1%( P<0.001), respectively. Multivariate survival analysis demonstrated that different radiotherapy modes were the independent factors affecting iPFS and OS. Subgroup analysis revealed that for patients with 1-3 brain metastases, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone ( P=0.026, P=0.044) when GPA score was 2.5-4.0; the 1-year OS and iPFSin the WBRT+ boost group were better than those of WBRT alone ( P=0.036, P=0.049) when there was no targeted therapy; for patients with ≥4 brain metastases, the 1-year iPFS in the WBRT+ boost group was better than that of WBRT alone ( P=0.019, P=0.012) when GPA score was 2.5-4.0 and there was no targeted therapy. When the GPA score was 0-2 or there was targeted therapy, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone, but the difference was not statistically significant (all P>0.05). Conclusions:Radiotherapy can significantly improve the iPFS and OS of NSCLC patients with brain metastases. When the number of brain metastases is 1-3, GPA score is 2.5-4.0 or no targeted therapy, boost may improve the iPFS and OS; when the number of brain metastases is more than 4, GPA score is 2.5-4.0 or no targeted therapy, boost may only bring iPFS benefit; when GPA score is 0-2 or targeted therapy, boost may not benefit significantly.

Progression of radiotherapy for brain metastases in non-small cell lung cancer / 国际肿瘤学杂志

Brain metastases are one of the most common distant metastases in patients with non-small cell lung cancer (NSCLC), and the prognosis will be extremely poor. The effect of chemotherapy and operation is limited. As a standard treatment, radiotherapy is widely used in clinical practice. Radiotherapy alone includes whole brain radiotherapy, stereotactic radiotherapy and whole brain radiotherapy combined with stereotactic radiotherapy. With the continuous development of radiotherapy and the progress of gene sequencing, radiotherapy has been combined with targeted drugs, anti-angiogenic drugs and immunodrugs in the treatment of NSCLC brain metastasis, which can improve the survival of patients with NSCLC brain metastasis.

A novel PI3K inhibitor XH30 suppresses orthotopic glioblastoma and brain metastasis in mice models

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.

Lower dose pembrolizumab monotherapy in the treatment of brain metastases from non-small cell lung carcinoma: A report of two cases

Introduction@#Lung cancer is the leading malignancy metastatic to the central nervous system with approximately 20% to 44% of all cases developing brain metastasis. Immunotherapy using pembrolizumab, an anti-PD1monoclonal antibody, is a novel method in lung cancer treatment and has shown favorable results in patients with metastatic brain lesions from non-small cell lung carcinoma (NSCLC). However, the cost of the recommended treatment dose limits its use especially in developing countries like the Philippines. @*Case Presentation@#The authors report two patients with lung cancer with brain metastasis upon diagnosis. The first patient is a 65-year-old male, non-smoker with PD-L1 expression of 60%. He was started on pembrolizumab 100 mg IV every three (3) weeks and a repeat CT scan after 11 cycles revealed a reduction of the two brain metastatic lesions and no fluoro-D-glucose (FDG) uptake on positron emission tomography (PET) scan even after one year into treatment. The second patient is a 67-year-old female, a previous smoker with PD-L1 expression of 50% with a metastatic solitary solid nodule in the cortex of the right cerebellum. After five cycles of pembrolizumab 100 mg IV every three weeks, there was noted complete resolution of brain metastasis on PET scan even after one year of treatment. @*Conclusion@#A lower dose of pembrolizumab (100 mg given every 3 weeks) was found to be effective in the management of advanced NSCLC with brain metastasis in the two patients. Further studies are recommended to investigate lower dose pembrolizumab as monotherapy without radiation therapy or surgery in patients with NSCLC with brain metastasis especially in the setting of a resource-limited country like the Philippines.

Advances in Treatment of Brain Metastasis from Lung Cancer / 肿瘤防治研究

Lung cancer is the malignant tumor with the highest incidence and mortality in China, and is prone to brain metastasis in the process of disease development, which seriously affects the quality of life and survival of patients. The treatment methods for brain metastasis of lung cancer include surgery, chemotherapy, whole brain radiotherapy, stereotactic radiosurgery, molecular targeted therapy, immunotherapy, anti-angiogenesis therapy, etc. It's one of the research hotspots to choose reasonable and effective treatment schemes for different patients. This paper reviews the research progress in the treatment of brain metastasis from lung cancer, to provide reference for selecting more reasonable clinical treatment for the patients.

Effects of flattening filter on dosimetry in fractionated stereotactic radiotherapy for brain metastases / 中国辐射卫生

@#<b>Objective</b> To investigate the dosimetric differences between volumetric modulated arc therapy (VMAT) with a flattening filter (FF) and flattening filter-free (FFF) VMAT in fractionated stereotactic radiotherapy for brain metastases. <b>Methods</b> Seventeen patients with brain metastases were divided into FF-VMAT group (VMAT plans with the FF mode) and FFF-VMAT group (VMAT plans with the FFF mode). The two groups were compared in terms of target volume dose parameters (<i>D</i>_98%, <i>D</i>_2% and <i>D</i>_mean), the conformal index (<i>CI</i>), the gradient index (<i>GI</i>), the gradient, normal brain tissue dose parameters (<i>V</i>_5Gy, <i>V</i>_10Gy, <i>V</i>_12Gy and <i>D</i>_mean), monitor units, and beam-on time. <b>Results</b> Compared with the FF-VMAT group, the FFF-VMAT group had significantly lower <i>GI</i> (3.33 ± 0.37 <i>vs</i> 3.27 ± 0.35, <i>P</i> = 0.001), a significantly lower gradient [(0.85 ± 0.20) cm <i>vs</i> (0.84 ± 0.19) cm, <i>P</i> = 0.002], a significantly shorter beam-on time [(177.05 ± 62.68) s <i>vs</i> (142.71 ± 34.59) s, <i>P</i> = 0.001], and significantly higher <i>D</i>_2% [(65.69 ± 2.15) Gy <i>vs</i> (66.99 ± 2.03) Gy, <i>P</i> = 0.001] and <i>D</i>_mean [(58.77 ± 1.60) Gy <i>vs</i> (59.95 ± 1.43) Gy, <i>P</i> <0.001]. There were no significant differences in the <i>CI</i>, the<i> D</i>_98%of the target volume, the <i>V</i>_5Gy, <i>V</i>_10Gy, <i>V</i>_12Gy and <i>D</i>_mean of the normal brain tissue, and monitor units between FFF-VMAT and FF-VMAT. <b>Conclusion</b> FFF-VMAT can better protect the normal tissue around the target volume, reduce the beam-on time, and improve treatment efficiency.