Raman spectroscopy as a promising noninvasive tool in brain cancer detection

Despite intensive therapy regi men,brain cancers present with a poor prognosis,with an esti-mated median survival time of less than 15 months in case of glioblastoma.Early detection and improved surgical resctions are suggested to enhance prognosis;several tools are being explored to achieve the purpose.Raman spectroscopy(RS),a nondestructive and noninv asive technique,has been extensively explored in brain cancers.This review summarizes RS based studies in brain cancers,categorized into studies on animal models,ex tivo human samples,and in tito human subjects.Findings suggest RS as a promising tool which can aid in improving the accuracy of brain tumor surgery.Further adv ancements in instrumentation,market assessment,and clinical trials can facilitate translation of the technology as a noninvasive intraopenative guidance tool.

Gold-based nanomaterials for the treatment of brain cancer

Brain cancer,also known as intracranial cancer,is one of the most invasive and fatal cancers affecting people of all ages.Despite the great advances in medical technology,improvements in transporting drugs into brain tissue have been limited by the challenge of crossing the blood-brain barrier(BBB).Fortunately,recent endeavors using gold-based nanomaterials(GBNs)have indicated the potential of these materials to cross the BBB.Therefore,GBNs might be an attractive therapeutic strategy against brain cancer.Herein,we aim to present a comprehensive summary of current understanding of the critical effects of the physicochemical properties and surface modifications of GBNs on BBB penetration for applications in brain cancer treatment.Furthermore,the most recent GBNs and their impressive performance in precise bioimaging and efficient inhibition of brain tumors are also summarized,with an emphasis on the mechanism of their effective BBB penetration.Finally,the challenges and future outlook in using GBNs for brain cancer treatment are discussed.We hope that this review will spark researchers'interest in constructing more powerful nanoplatforms for brain disease treatment.

Optimal Fusion-Based Handcrafted with Deep Features for Brain Cancer Classification

Brain cancer detection and classification is done utilizing distinct medical imaging modalities like computed tomography(CT),or magnetic resonance imaging(MRI).An automated brain cancer classification using computer aided diagnosis(CAD)models can be designed to assist radiologists.With the recent advancement in computer vision(CV)and deep learning(DL)models,it is possible to automatically detect the tumor from images using a computer-aided design.This study focuses on the design of automated Henry Gas Solubility Optimization with Fusion of Handcrafted and Deep Features(HGSO-FHDF)technique for brain cancer classification.The proposed HGSO-FHDF technique aims for detecting and classifying different stages of brain tumors.The proposed HGSO-FHDF technique involves Gabor filtering(GF)technique for removing the noise and enhancing the quality of MRI images.In addition,Tsallis entropy based image segmentation approach is applied to determine injured brain regions in the MRI image.Moreover,a fusion of handcrafted with deep features using Residual Network(ResNet)is utilized as feature extractors.Finally,HGSO algorithm with kernel extreme learning machine(KELM)model was utilized for identifying the presence of brain tumors.For examining the enhanced brain tumor classification performance,a comprehensive set of simulations take place on the BRATS 2015 dataset.

Proteogenomics for pediatric brain cancer

Pediatric central nervous system tumors are the most common tumors in children,it constitute 15%–20%of all malignancies in children and are the leading cause of cancer related deaths in children.Proteogenomics is an emerging field of biological research that utilizes a combination of proteomics,genomics,and transcriptomics to aid in the discovery and identification of biomarkers for diagnosis and therapeutic purposes.Integrative proteogenomics analysis of pediatric tumors identified underlying biological processes and potential treatments as well as the functional effects of somatic mutations and copy number variation driving tumorigenesis.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Classification of Brain Tumors Using Hybrid Feature Extraction Based on Modified Deep Learning Techniques

According to the World Health Organization(WHO),Brain Tumors(BrT)have a high rate of mortality across the world.The mortality rate,however,decreases with early diagnosis.Brain images,Computed Tomography(CT)scans,Magnetic Resonance Imaging scans(MRIs),segmentation,analysis,and evaluation make up the critical tools and steps used to diagnose brain cancer in its early stages.For physicians,diagnosis can be challenging and time-consuming,especially for those with little expertise.As technology advances,Artificial Intelligence(AI)has been used in various domains as a diagnostic tool and offers promising outcomes.Deep-learning techniques are especially useful and have achieved exquisite results.This study proposes a new Computer-Aided Diagnosis(CAD)system to recognize and distinguish between tumors and non-tumor tissues using a newly developed middleware to integrate two deep-learning technologies to segment brain MRI scans and classify any discovered tumors.The segmentation mechanism is used to determine the shape,area,diameter,and outline of any tumors,while the classification mechanism categorizes the type of cancer as slow-growing or aggressive.The main goal is to diagnose tumors early and to support the work of physicians.The proposed system integrates a Convolutional Neural Network(CNN),VGG-19,and Long Short-Term Memory Networks(LSTMs).A middleware framework is developed to perform the integration process and allow the system to collect the required data for the classification of tumors.Numerous experiments have been conducted on different five datasets to evaluate the presented system.These experiments reveal that the system achieves 97.98%average accuracy when the segmentation and classification functions were utilized,demonstrating that the proposed system is a powerful and valuable method to diagnose BrT early using MRI images.In addition,the system can be deployed in medical facilities to support and assist physicians to provide an early diagnosis to save patients’lives and avoid the high cost of treatments.

Carbon Nanotubes-based Drug Delivery to Cancer and Brain

Current treatments for cancer and the central nervous system diseases are limited, partly due to the difficulties posed by the insolubility, poor distribution of drugs among cells and lack of selectivity of drugs, the inability of drugs to cross cellular barriers and blood brain barrier（BBB）. Carbon nanotubes（CNTs） possess many distinct properties including good electronic properties, remarkably penetrating capability on the cell membrane, high drug-loading and pH-dependent therapeutic unloading capacities,thermal properties, large surface area and easy modification with molecules, which render them as a suitable candidate to deliver drugs to cancer and brain. CNTs as a drug delivery could achieve a high efficacy, enhance specificity and diminish side effects. Whereas CNTs have been primarily employed in cancer treatment, a few studies have focused on the treatment and diagnosis of the central nervous system diseases using CNTs. Here, we review the current progress of in vitro and in vivo researches of CNTs-based drug delivery to cancer involving CNTs-based tumor-targeted drug delivery systems（DDS）, photodynamic therapy（PDT） and photothermal therapy（PTT）. Meanwhile, we also review the current progress of in vitro and in vivo researches of CNTs-based drug delivery to brain.

Brain metastasis in advanced colorectal cancer： results from the South Australian metastatic colorectal cancer (SAmCRC) registry

Objective:Brain metastasis is considered rare in metastatic colorectal cancer(mCRC);thus,surveillance imaging does not routinely include the brain.The reported incidence of brain metastases ranges from 0.6% to 3.2%.Methods:The South Australian mCRC Registry(SAmCRC)was analyzed to assess the number of patients presenting with brain metastasis during their lifetime.Due to small numbers,a descriptive analysis is presented.Results:Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis(1.4%).The clinical characteristics of those with brain metastasis were as follows:the median age was 65.3 years and 51% were female.Where the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation status of the tumor was known,the majority harbored a KRAS mutation(55%);31(53%)underwent craniotomy and 55(93%)underwent whole-brain radiotherapy.The median survival time from diagnosis of brain metastasis was 4.2 months(95% confidence interval 2.9–5.5).Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy(8.5 months vs.2.2 months,respectively).Data from the SAmCRC(a population-based registry)confirm that brain metastases are rare and the median time to development is approximately 2 years.Conclusions:Brain metastasis is a rare outcome in advanced CRC.Patients within the registry tended to be female,young in age,and harbored with higher rates of KRAS mutations.Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately,most patients with central nervous system involvement die from their extracranial disease.

High plasma fibrinogen concentration and platelet count unfavorably impact survival in non–small cell lung cancer patients with brain metastases

High expression of fibrinogen and platelets are often observed in non–small cell lung cancer(NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age ≥ 65 years(P = 0.011), smoking status(P = 0.009), intracranial symptoms(P = 0.022), clinical T category(P = 0.010), clinical N category(P = 0.003), increased partial thromboplastin time(P < 0.001), and platelet count(P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration(median, 17.3 months versus 11.1 months; P ≤ 0.001). A similar result was observed for platelet counts(median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases(R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

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.

Retrospective Review for Prevalence and Survival in Metastatic Breast Cancer with Brain Metastasis in Two Patient Cohorts: One Collected 2000-2005 and the Second Collected 2006-2011

Purpose: To determine whether the new treatments for breast cancer CNS metastases improve survival by comparing the survival between two cohorts: 2000-2005 and 2006-2011. Patients and Methods: A retrospective, comparative, correlational chart review was performed. Data from 172 women diagnosed with CNS metastases between 2000 and 2011, was evaluated. Results: Approximately 10% of patients diagnosed with invasive breast cancer between 2000 and 2011 developed CNS metastases. The cohort was separated into four groups: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), HER2+ (ER -, PR-, HER2+) and TN (ER-, PR-, HER2-). There was a statistically significant difference in the overall survival between luminal A and luminal B (5.55 months vs. 15.3 months, respectively, p = 0.048). There was also a statistically significant difference in the overall survival between luminal B and TN (15.3 months vs. 7.49 months, respectively, p = 0.0181). There was no significant difference in overall survival between luminal B and HER2+ (15.3 months vs. and 10.98 months, respectively, p = 0.105), TN and HER2+ (7.49 months vs. 10.98 months, respectively, p = 0.514), and between luminal A and TN or HER2+ (5.55 months vs. 7.49 months, respectively, p = 0.428, or 5.55 months vs. 10.98 months, respectively, p = 0.491). Overall median survival of the patients in 2000-2005 and 2006-2011 were 6.64 months vs. 10.58 months, respectively (p = 0.0592). Conclusion: The results of our study showed that despite the new therapies there is little improvement in survival for brain metastasis in breast cancer.

Role of the brain-gut axis in gastrointestinal cancer

Several studies have largely focused on the significant role of the nervous and immune systems in the process of tumorigenesis, including tumor growth, proliferation, apoptosis, and metastasis. The brain-gut-axis is a new paradigm in neuroscience, which describes the biochemical signaling between the gastrointestinal (GI) tract and the central nervous system. This axis may play a critical role in the tumorigenesis and development of GI cancers. Mechanistically, the bidirectional signal transmission of the brain-gut-axis is complex and remains to be elucidated. In this article, we review the current findings concerning the relationship between the brain-gut axis and GI cancer cells, focusing on the significant role of the brain-gut axis in the processes of tumor proliferation, invasion, apoptosis, autophagy, and metastasis. It appears that the brain might modulate GI cancer by two pathways: the anatomical nerve pathway and the neuroendocrine route. The simulation and inactivation of the central nervous, sympathetic, and parasympathetic nervous systems, or changes in the innervation of the GI tract might contribute to a higher incidence of GI cancers. In addition, neurotransmitters and neurotrophic factors can produce stimulatory or inhibitory effects in the progression of GI cancers. Insights into these mechanisms may lead to the discovery of potential prognostic and therapeutic targets.

Prognostic scoring system for synchronous brain metastasis at diagnosis of colorectal cancer: A population-based study

BACKGROUND Brain metastasis(BM)from colorectal cancer(CRC)is rarely encountered clinically,and its prognosis has not been fully evaluated.AIM To construct a scoring system and accurately predict the survival of patients with synchronous BM at diagnosis of CRC.METHODS A retrospective study of 371 patients with synchronous BM from CRC was performed,using the data from 2010 to 2014 from the Surveillance,Epidemiology,and End Results database.Survival time and prognostic factors were statistically analyzed by the Kaplan-Meier method and Cox proportional hazards models,respectively.A scoring system was developed using the independent prognostic factors,and was used to measure the survival difference among different patients.RESULTS For the 371 patients,the median overall survival was 5 mo,survival rates were 27%at 1 year and 11.2%at 2 years.Prognostic analysis showed that age,carcinoembryonic antigen level and extracranial metastasis to the liver,lung or bone were independent prognostic factors.A scoring system based on these three prognostic factors classified the patients into three prognostic subgroups(scores of 0-1,2-3,and 4).The median survival of patients with scores of 0-1,2-3 and 4 was 14,5 and 2 mo,respectively(P<0.001).Subgroup analysis showed that there were significant differences in prognosis among the groups.Score 2-3 vs 0-1:hazard ratio(HR)=2.050,95%CI:1.363-3.083;P=0.001;score 4 vs 0-1:HR=3.721,95%CI:2.225-6.225;P<0.001;score 2-3 vs 4:HR=0.551,95%CI:0.374-0.812;P=0.003.CONCLUSION The scoring system effectively distinguishes long-term and short-term survivors with synchronous BM from CRC.These results are helpful in providing a reference for guiding therapy.

Successful outcome after combined chemotherapeutic and surgical management in a case of esophageal cancer with breast and brain relapse

Esophageal cancer (EC) is a highly lethal disease. Approximately 50% of patients present with metastatic EC and most patients with localized EC will have local recurrence or develop metastases, despite potentially curative local therapy. The most common sites of distant recurrence are represented by lung, liver and bone while brain and breast metastases are rare. Usually patients with advanced disease are not treated aggressively and their median survival is six months. We report a woman patient who developed breast and brain metastases after curative surgery. We treated her with a highly aggressive chemotherapeutic and surgical combination resulting in a complete remission of the disease even after 11-year follow-up. We think that in super selected patients with more than one metastasis, when functional status is good and metastases are technically resectable, a surgical excision may be considered as a salvage option and chemotherapy should be delivered to allow a systemic control.

Recursive Partitioning Analysis Classification and Graded Prognostic Assessment for Non-Small Cell Lung Cancer Patients with Brain Metastasis:A Retrospective Cohort Study

Objective：To assess prognostic factors and validate the effectiveness of recursive partitioning analysis （RPA） classes and graded prognostic assessment （GPA） in 290 non-small cell lung cancer （NSCLC） patients with brain metastasis （BM）.Methods：From Jan 2008 to Dec 2009,the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation,systemic chemotherapy and tyrosine kinase inhibitors （TKIs） in two institutes were analyzed.Survival was estimated by Kaplan-Meier method.The differences of survival rates in subgroups were assayed using log-rank test.Multivariate Cox＇s regression method was used to analyze the impact of prognostic factors on survival.Two prognostic indexes models （RPA and GPA） were validated respectively.Results：All patients were followed up for 1-44 months,the median survival time after brain irradiation and its corresponding 95% confidence interval （95% CI） was 14 （12.3-15.8） months.1-,2-and 3-year survival rates in the whole group were 56.0%,28.3%,and 12.0%,respectively.The survival curves of subgroups,stratified by both RPA and GPA,were significantly different （P0.001）.In the multivariate analysis as RPA and GPA entered Cox＇s regression model,Karnofsky performance status （KPS） ≥ 70,adenocarcinoma subtype,longer administration of TKIs remained their prognostic significance,RPA classes and GPA also appeared in the prognostic model.Conclusion：KPS ≥70,adenocarcinoma subtype,longer treatment of molecular targeted drug,and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.

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.

Surgery Versus Stereotactic Radiosurgery for Single Synchronous Brain Metastasis from Non-Small Cell Lung Cancer

Objective： The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery （SRS） for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer. Methods： Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years （range, 32-85 years）. At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients （21.4%）, lobectomies in 30 （71.4%）, and wedge resection in 3 （7.2%）. 48 patients （90.5%） underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS. Results： There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients （28.3%） had no evidence of lymph node metastases （No）, 20 patients （37.7%） had hilar metastases （N1）, and 18 patients （34%） had mediastinal metastases （N2）. The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant （P〉0.05）. In lymph node negative patients （No）, the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases （N1-2）. The difference was significant （P〈0,01）. For adenocarcinomas, the 5-year survival rate was 5%. The correspondent data for squamous cell lung cancers was 3%. The difference was not significant （P〉0.05）. Conclusion： Although the overall survival rate for patients who have brain metastases from NSCLC is poor, surgical resection or radiosurgery may be beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.

Profile of Patients with Breast Cancer Brain Metastasis in Abidjan

Patients with breast cancer will develop brain metastases in 15% - 25% of cases. Objective: To identify the profile of patients with breast cancer brain metastasis. Method: Retrospective study over 4 years in the oncology department of Treichville Hospital. All patients with breast carcinoma who had a brain metastasis during their cancer management were included. Results: 41 cases of breast carcinoma brain metastasis were collected. Patients were older than 40 years in 78% of cases. Family history of breast cancer was found in 7% of patients. More than 80% of patients had consulted with T3 and T4 tumor masses, with 100% of cases of node involvement. The brain was the second site of metastasis. The tumors were Triple negative in 48%, Her2 positive in 36% and luminal in 16%. Brain metastases were of late onset in the majority of cases (68%). They were clinically characterized by headaches (100%), most often included in an intracranial hypertension syndrome (52%). They were multiple (60%). Therapeutically, no surgery was performed on the metastases. Three patients received whole brain radiation therapy. All patients received systemic therapy. In terms of response, 30 cases of progression were observed after treatment and 2 cases of complete response were obtained. Survival from onset of brain metastasis was of 75% at 3 months and 2% at 12 months. Patients with longer survival rates were over 40 years old with triple negative breast cancer. Conclusion: Brain metastasis from breast cancer most often occurs in a particular clinical and pathological context in our countries.

Clinicopathological Evaluation and Prognostic Analysis in Breast Cancer Patients with Brain Metastasis

Background: Brain metastases are diagnosed in 5% - 15% of patients with breast cancer. Clinical management of brain metastases appears to be crucial in improving the prognosis of patients with breast cancer that has metastasized to the brain. However, few studies have investigated whether treatment of metastatic brain tumors would lead to improved prognosis. Methods: A total of 41 breast cancer patients whose tumors metastasized to the brain and who were diagnosed and treated at our hospital were enrolled. This study was conducted to determine the characteristics of brain metastases and to identify the factors that may affect the treatment and prognosis of patients with brain metastases. Results: There were more patients with HER2 and triple negative subtypes than of the luminal subtype. The median time from the initiation of breast cancer treatment to the onset of brain metastasis was 31 months (range, 7 - 134 months). Significantly greater disease-specific survival (DSS) was observed in patients who had a performance status of 0 - 2 at the time of diagnosis of metastatic brain tumors than those with a performance status of 3 - 4 (p = 0.04). DSS was also significantly greater in patients who underwent surgery to remove brain metastases and in patients treated with systemic therapy (p = 0.0007 and 0.0001, respectively). Conclusions: It may be possible to improve the prognosis of patients with brain metastases if lesions are detected early enough when the patients’ performance status is still good. In order for these findings to be definitive, however, results of future prospective studies are eagerly awaited.

Predictive Factors of Intracranial Response of Immune Checkpoint Inhibitors in Patients with Brain Metastasis from Non-Small Cell Lung Cancer

Background: Immune checkpoint inhibitors (ICI)s were recently approved for the treatment of advanced non-small cell lung cancer (NSCLC). Whereas brain metastases (BM) are frequent in NSCLC patients, data are missing regarding ICIs intracranial efficacy and tolerance in patients with BM from NSCLC. Methods: This retrospective study was performed in the Multidisciplinary Oncology and Therapeutic Innovation department, Marseille, France between April 2013 and February 2016. Data from patients with NSCLC with at least one BM, and treated with ICIs (anti-PD1, anti-PDL1 or anti-CTL4) were analyzed. Clinical, biological data and outcomes were retrieved from electronic patients’ records. We assessed ICIs intracranial efficacy and tolerance. Results: Data from 55 patients were analyzed. Objective Response Rate (ORR) and Disease Control Rate (DCR) were respectively of 1.8 and 36.4%. Median overall survival was 17.2 months and median progression free survival was 2.9 months. Intracranial ORR (icORR) and intracranial DCR (icDCR) were respectively 16.4% and 45.5%. Both were independent of smoking status, intracranial treatment, performance status, pathology, molecular profile and the presence or number of BM at diagnosis. However, there was a trend towards an association between icORR and ECOG PS (p = 0.05), tobacco status (p = 0.057) and intracranial treatment. Adverse events were seen in 38.2% patients without identified predictive factor. Neurological symptoms appeared in 5.5% patients during immunotherapy and improved in 3.63% patients. Conclusions: ICIs can be used safely on patients with BM from NSCLC. However, intracranial response is heterogeneous in such patients and we showed ECOG PS, tobacco smoking and intracranial treatment to be associated with an improved icORR. This is the first study looking for predictive factors of intracranial response of ICIs in patients with BM from NSCLC.