Metastasis In Cancer Patients Research Articles

P35.21 Comprehensive Genomic Profiling of Lung Metastases in Cancer Patients

P35.21 Comprehensive Genomic Profiling of Lung Metastases in Cancer Patients

The influence of brain metastases on the central nervous system effects of methylnaltrexone: a post hoc analysis of 3 randomized, double-blind studies

PurposePeripherally acting μ-opioid receptor antagonists such as methylnaltrexone (MNTX, Relistor®) are indicated for the treatment of opioid-induced constipation (OIC). The structural properties unique to MNTX restrict it from traversing the blood-brain barrier (BBB); however, the BBB may become more permeable in patients with brain metastases. We investigated whether the presence of brain metastases in cancer patients compromises the central effects of opioids among patients receiving MNTX for OIC.MethodsThis post hoc analysis of pooled data from 3 randomized, placebo-controlled trials included cancer patients with OIC who received MNTX or placebo. Endpoints included changes from baseline in pain scores, rescue-free laxation (RFL) within 4 or 24 h of the first dose, and treatment-emergent adverse events (TEAEs), including those potentially related to opioid withdrawal symptoms.ResultsAmong 356 cancer patients in the pooled population, 47 (MNTX n = 27; placebo n = 20) had brain metastases and 309 (MNTX n = 172; placebo n = 137) did not have brain metastases. No significant differences in current pain, worst pain, or change in pain scores from baseline were observed between patients treated with MNTX or placebo. Among patients with brain metastases, a significantly greater proportion of patients who received MNTX versus placebo achieved an RFL within 4 h after the first dose (70.4% vs 15.0%, respectively, p = 0.0002). TEAEs were similar between treatment groups and were generally gastrointestinal in nature and not related to opioid withdrawal.ConclusionFocal disruptions of the BBB caused by brain metastases did not appear to alter central nervous system penetrance of MNTX.

Enhanced lymphatic delivery of nanomicelles encapsulating CXCR4-recognizing peptide and doxorubicin for the treatment of breast cancer

Lymph node metastases in cancer patients are associated with high aggressiveness, poor prognosis, and short survival time. The chemokine receptor 4 (CXCR4)/stroma derived factor 1α (CXCL12) biological axis plays a critical role in the spread of cancer cells. Designing effective delivery systems that can successfully deliver CXCR4 antagonists to lymph nodes, which are rich in CXCR4-overexpressing cancer cells, for controlling cancer metastasis remain challenging. In this study, we demonstrated that such a challenge may be alleviated by developing nanometer-sized polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles for the co-delivery of the CXCR4 antagonistic peptide E5 and doxorubicin (M-E5-Dox). This nanomicelle platform enables the preferential accumulation of cargos into lymph nodes and thus can better inhibit cancer metastasis and enhance antitumor efficacy than either free drugs or single drug-loaded micelles in breast cancer-bearing mouse models. Hence, M-E5-Dox is expected to be a potential therapeutic agent that would improve the clinical benefits of breast cancer therapy and treatment of various CXCR4-overexpressing malignancies.

Clinical value of dual-phase F-18 sodium fluoride PET/CT for diagnosing bone metastasis in cancer patients with solitary bone lesion.

The present study aimed to investigate whether dual-phase F-18 sodium-fluoride (NaF) positron emission tomography/computed tomography (PET/CT) could improve the diagnostic accuracy of detecting bone metastasis in cancer patients with a solitary bone lesion compared to conventional F-18 NaF PET/CT. We retrospectively enrolled 113 cancer patients who underwent dual-phase F-18 NaF PET/CT for the differential diagnosis of a solitary bone lesion seen on bone scintigraphy. According to the dual-phase PET/CT protocol, an early-phase scan was acquired immediately after radiotracer injection and a conventional F-18 NaF PET/CT scan was performed. The diagnostic abilities of the visual analysis of conventional and dual-phase PET/CT scans and two quantitative parameters (lesion-to-blood pool uptake ratio on early-phase scan and lesion-to-bone uptake ratio on conventional scan) for detecting bone metastasis were compared. The final diagnosis of bone metastasis was made by histopathological confirmation or follow-up imaging studies. A metastatic bone lesion was diagnosed in 28 patients (24.8%). The sensitivity, specificity, and accuracy were 100.0%, 70.6%, and 77.9%, respectively, for visual analysis of conventional F-18 NaF PET/CT, 92.9%, 42.4%, 54.9%, respectively, for lesion-to-bone uptake ratio, 96.4%, 88.2%, and 90.3%, respectively, for visual analysis of dual-phase PET/CT, and 92.9%, 81.2%, and 83.2%, respectively, for lesion-to-blood pool uptake ratio. Visual analysis of dual-phase PET/CT was shown to have the highest area under the receiver operating characteristic curve value (0.923; 95% CI, 0.858-0.965) among all parameters. Dual-phase F-18 NaF PET/CT showed a high diagnostic ability for detecting bone metastasis with improved specificity and accuracy compared to conventional F-18 NaF PET/CT in cancer patients. Dual-phase F-18 NaF PET/CT might help diagnose bone metastasis in patients with malignancies who were shown to have a solitary bone lesion on bone scintigraphy.

The rise of metastatic bone disease in Ireland.

To describe the expected rise of metastatic bone disease in Ireland, the relative primary types, and the locations of spread within the skeleton. This was a population-based epidemiological study using cancer registry data. We included patients with known metastatic cancer to bone, within 1year of the primary diagnosis, during the years 1994 to 2012 inclusive. Our main outcome measures were age-specific, gender-specific and age-standardised incidence rates of bone metastasis, primary types and metastatic location within the skeleton. There were 14,495 recognised cases of bone metastasis in Ireland, 1994-2012 inclusive. Cases consistently rose over the time period, with 108% case increase and 51% age-standardised incidence rise. Annual percentage change increased across both genders and over all age groups. Most of this rise was not due to demographic population change. Breast, prostate and lung accounted for the majority of primary types. GI cancers were the fourth most common primary type. There were proportional increases in breast and lung, with proportional decreases in prostate. The spine was the major metastatic site. Bone metastasis is a significant and rising healthcare concern in Ireland. This rise is disproportionate to demographic changes. Breast, prostate and lung cancers account for the majority. GI cancers are implicated in an unexpectedly high number of cases. Spine is the most common location of bony metastasis, especially at presentation. Prudent healthcare planning is necessitated to prepare for the growing consequences of bone metastasis in cancer patients.

Advances in Exosome Analysis Methods with an Emphasis on Electrochemistry

Exosomes, small extracellular vesicles, are released by various cell types. They are found in bodily fluids, including blood, urine, serum, and saliva, and play essential roles in intercellular communication. Exosomes contain various biomarkers, such as nucleic acids and proteins, that reflect the status of their parent cells. Since they influence tumorigenesis and metastasis in cancer patients, exosomes are excellent noninvasive potential indicators for early cancer detection. Aptamers with specific binding properties have distinct advantages over antibodies, making them effective versatile bioreceptors for the detection of exosome biomarkers. Here, we review various aptamer-based exosome detection approaches based on signaling methods, such as fluorescence, colorimetry, and chemiluminescence, focusing on electrochemical strategies that are easier, cost-effective, and more sensitive than others. Further, we discuss the clinical applications of electrochemical exosome analysis strategies as well as future research directions in this field.

Advanced distal rectal cancer: possibilities of sphincter-sparing surgeries in combination with neoadjuvant therapy

Objective: to analyze the outcomes of sphincter-sparing surgeries in patients with advanced distal rectal cancer depending on the therapy they receive.Materials and methods. This study included 289 patients with advanced (stage T3N0–2M0) distal rectal cancer who have undergone sphincter-sparing surgeries. Patients were divided into three groups according to their treatment scheme. In group 1, we used combination treatment that included a short course of neoadjuvant radiotherapy supplemented by 3 multidirectional radiomodifiers (local microwave hyperthermia, rectal administration of a biopolymer composition containing metronidazole, and chemotherapy with capecitabine). Patients in group 2 received combination treatment that included neoadjuvant radiotherapy alone. Treatment outcomes in patients receiving combination therapy was compared to those of patients with similar characteristics and location of rectal tumors who have undergone surgery alone in N. N. Blokhin National Medical Research Center of Oncology (group 3).Results. We observed a significant decrease in the incidence of locoregional cancer metastasis in patients from group 1 compared to those from groups 2 and 3 (0.8 % vs 7.9 % and 18.2 % respectively). Moreover, patients in group 1 demonstrated better relapse-free survival than participants in groups 2 and 3 (79.6 % vs 52.6 % and 51 % respectively). The new scheme of combination therapy developed by our team (used in group 1) did not increase the incidence of postoperative complications. The best local disease control in group 1 was achieved in patients with middle rectal cancer who have undergone sphincter-sparing surgeries: none of 81 patients developed relapses, whereas the relapse-free survival rate reached 83 % compared to 56.9 % in group 1 and 41.7 % in group 3.Conclusions. The new treatment scheme that includes neoadjuvant radiotherapy supplemented by 3 multidirectional radiomodifiers can be used as one of the options increasing efficacy of radiotherapy and, therefore, efficacy of combination treatment in patients with advanced rectal cancer who undergo sphincter-sparing surgeries.

Pan-metastatic cancer analysis of prognostic factors and a prognosis-based metastatic cancer classification system

We aimed to perform a pan-metastatic cancer analysis on survival and prognostic factors and to create a prognosis-based classification system. We selected distant metastasis patients from the Surveillance, Epidemiology, and End Results (SEER) database. The associations between the characteristics of the patients at admission and overall survival were determined. A prognosis-based metastatic cancer classification was established based on the identified prognostic factors. The differences in prognosis among these categories were tested. The survival rate and prognostic factors were not consistent across cancers. Three metastatic cancer categories were generated, each with different prognoses. The prognostic differences among the categories were satisfactorily validated. Different metastatic cancer types had homogeneous and heterogeneous survival rates and prognostic factors. A prognosis-based classification system for synchronous distant metastasis cancer patients at admission was created. This classification system reflects the grade of malignancy in metastatic cancers and may guide the prediction of survival and individualized treatment. Moreover, it may have important implications for the management of synchronous metastatic cancers and aid clinicians in properly allocating medical resources to metastatic patients.

Distribution and predictive value of initial presenting symptoms in spinal metastases from primary cancer patients.

Primary cancer patients may have some symptoms and develop spinal metastases in their disease progression. This study was to report the distribution and predictive value of specific initial presenting symptoms in patients with spine metastatic disease. The clinical information about patients with primary cancers was retrospectively collected and analyzed at their initial diagnosis from January 2008 to December 2017. The distribution and specific value of initial presenting symptoms were analyzed in predicting spinal metastases. A total of 14,603 cancer patients were finally included, of whom 1665 (11.4%) cases were confirmed with spinal metastases. 41.55% (6067/14,603) patients had initial presenting symptoms, while 92.19% (1535/1665) patients with spinal metastases presented at least one initial presenting symptoms. Among 6269 patients with symptoms, 1535 (24.49%) were diagnosed with spinal metastases. Factors including primary tumor type, local pain, night-aggravating pain, limb numbness, limb weakness, unstable gait, claudication, loss of sphincter control, and weight loss are associated with the distribution of spinal metastases. The pooled sensitivity, specificity, positive predictive value, and negative predictive value were 90.9% (89.4-92.2%), 64.9% (64.0-65.7%), 24.99% (23.91-26.11%), and 98.23% (97.92-98.50%), respectively. Positive likelihood ratio of "night-aggravating pain" was 33.25 (12.65-87.36) and 17.26 (12.25-24.32) in patients < 45 and 45-64years old, respectively. The distribution of spinal metastases is associated with primary tumor type and initial presenting symptoms. The predictive value of initial presenting symptoms differs in age groups, but resembles in cancer types. The presence of night-aggravating pain had relative high value in predicting metastases in cancer patients under 65years old.

Clinical-morphological and laboratory predictors of «superscan» scintigraphy phenomenon in prostate cancer

Introduction. Detection of bone metastases in cancer patients is of great importance in the choice of treatment tactics and assessment of the disease prognosis. The article discusses the «superscan» phenomenon on bone scintigraphy in detecting skeletal metastases in prostate cancer (PC) patients. When analyzing published reports, we found only one large prospective study and a few case report publications on the detection of «superscan» in patients with generalized skeletal involvement. The purpose of the study was to determine the laboratory and clinical morphological parameters associated with «superscan» scintigraphic phenomenon in patients with prostate cancer. Material and Methods . Of 2474 prostate cancer patients who underwent bone scintigraphy, 48 had the «superscan» phenomenon. Clinical, laboratory and morphological parameters were: age of the patients, tumor stage by TNM (7th edition, 2010), histological type of the tumor, Gleason index, prostate specific antigen (PSA) level, pain syndrome (on a 5-point verbal scale of pain estimates, 1982), the presence of castration-resistant prostate cancer, hemoglobin level and erythrocyte sedimentation rate (ESR). Results . The «superscan» phenomen was found to occur most often in prostate cancer patients aged 60-69 years. Stage III and IV tumors were detected in 97.9 % of cases, lymphatic invasion in 20.8 %, and visceral metastases in 12.5 %. In addition, the phenomenon was associated with high PSA levels (the mean PSA level was 100 ng/ml, range: 26-4957) and the presence of moderately and poorly differentiated (Gleason ≥7)) tumors. Chronic pain syndrome at the time of detection of «superscan» was observed in 47.9% of patients, castration resistance - in 16.6 %. The median hemoglobin level was 114 (75-139) g/l and ESR was 34 (14-62) mm/h. Conclusion . The most significant factors associated with the «superscan» scintigraphy phenomenon in prostate cancer patients were the primary tumor extension, high PSA level and low-grade tumors. New data on the association between the «superscan» phenomenon and the levels of hemoglobin and ESR have been obtained. Further studies on the relationship between the «superscan» phenomenon and pain syndrome and castration resistance are required.

Distribution of Femoral Metastases; Potential Role for Extended FDG PET/CT Scanning

This study investigates the distribution of femoral metastases in cancer patients, specifically addressing the incidence of distal femoral metastases. PET/CT examinations routinely extend only to mid-thigh level, precluding detection of distal metastases. We found a total of 208 femoral metastases in 112 patients. 30% had distal femoral metastases in addition to other areas of involvement. 7% of patients with femoral metastases had only distal femur disease. 6 patients had distal pathologic fractures. Exclusion of the distal femur during PET/CT may result in a missed or delayed diagnosis that could contribute to the development of a pathologic fracture with increased morbidity.

Hypnosis in Women with Breast Cancer: Its Effects on Cytokines

The aim of the present study was to evaluate the effects of hypnosis on the cytokine levels of women with breast cancer during chemotherapy. Patients with a recent breast cancer diagnosis were assigned to either a control group (n = 20) or to a hypnosis group (n = 20). The control group received standard medical care, while the hypnosis group received 24 sessions of hypnosis over 6 months as an adjuvant therapy to standard medical care. Three blood samples were obtained, one before the initiation of chemotherapy, the second a month after beginning treatment, and the third at the end of treatment. At the end of chemotherapy treatment, the control group showed significantly higher levels of tumor necrosis factor alpha (TNF-α) and granulocyte colony stimulation factor (G-CSF) compared to the hypnosis group. Stabilized G-CSF and TNF-α levels during chemotherapy in the hypnosis group could be considered as beneficial because high levels of these cytokines have been associated with increased levels of tumor growth and metastasis in cancer patients.

Stage-specific expression analysis of MMP-2 &amp; MMP-9 in laryngeal carcinoma

Both matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) is involved in degradation of extracellular matrix and found to stimulate invasion and metastasis in cancer patients. However, studies on the stage-specific expression of MMPs at different stages of larynx carcinoma are still lacking. In the present study, we compare the expression level of MMP-2 and MMP-9 at different stages of laryngeal carcinoma. Tumor tissues samples were taken from larynx cancer patients by deep biopsy during direct laryngoscopy. Gene expression for MMP-2 and MMP-9 was analyzed using RT-PCR. Significantly high expression of MMP-2 was observed compared to the MMP-9 at stage IV compared to the less advanced stages of the disease. Present study concluded that the MMP-2 expressed with a greater magnitude as compared to the MMP-9 in advance stages of laryngeal carcinoma.

MLL3 Induced by Luteolin Causes Apoptosis in Tamoxifen-Resistant Breast Cancer Cells through H3K4 Monomethylation and Suppression of the PI3K/AKT/mTOR Pathway.

Tamoxifen is one of the most common hormone therapy drug for estrogen receptor (ER)-positive breast cancer. Tumor cells with drug resistance often cause recurrence and metastasis in cancer patients. Luteolin is a natural compound found from various types of vegetables and exhibit anticancer activity in different cancers. This study demonstrated that luteolin inhibits the proliferation and induces apoptosis of tamoxifen-resistant ER-positive breast cancer cells. Luteolin also causes cell cycle arrest at the G2/M phase and decreases mitochondrial membrane potential. Besides, luteolin reduces the levels of activated PI3K/AKT/mTOR signaling pathway. The combination treatment of luteolin and PI3K, AKT, or mTOR inhibitors synergistically increases apoptosis in tamoxifen-resistant ER-positive breast cancer cells. Ras gene family (K-Ras, H-Ras, and N-Ras), an activator of PI3K, was transcriptionally repressed by luteolin via induction of tumor suppressor mixed-lineage leukemia 3 (MLL3) expression. MLL3 increases the level of monomethylation of Histone 3 Lysine 4 on the enhancer and promoter region of Ras genes, thus causes repression of Ras expressions. Our finding implies that luteolin was a promising natural agent against tamoxifen resistance of breast cancer.

LINC02273 drives breast cancer metastasis by epigenetically increasing AGR2 transcription

BackgroundThe majority of breast cancer patients die of metastasis rather than primary tumors, whereas the molecular mechanisms orchestrating cancer metastasis remains poorly understood. Long noncoding RNAs (lncRNA) have been shown to regulate cancer occurrence and progression. However, the lncRNAs that drive metastasis in cancer patients and their underlying mechanisms are still largely unknown.MethodslncRNAs highly expressed in metastatic lymph nodes were identified by microarray. Survival analysis were made by Kaplan-Meier method. Cell proliferation, migration, and invasion assay was performed to confirm the phenotype of LINC02273. Tail vein model and mammary fat pad model were used for in vivo study. RNA pull-down and RIP assay were used to confirm the interaction of hnRNPL and LINC02273. Chromatin isolation by RNA purification followed by sequencing (ChIRP-seq), RNA-seq, ChIP-seq, and luciferase reporter assay reveal hnRNPL-LINC02273 regulates AGR2. Antisense oligonucleotides were used for in vivo treatment.ResultsWe identified a novel long noncoding RNA LINC02273, whose expression was significantly elevated in metastatic lesions compared to the primary tumors, by genetic screen of matched tumor samples. Increased LINC02273 promoted breast cancer metastasis in vitro and in vivo. We further showed that LINC02273 was stabilized by hnRNPL, a protein increased in metastatic lesions, in breast cancer cells. Mechanistically, hnRNPL-LINC02273 formed a complex which activated AGR2 transcription and promoted cancer metastasis. The recruitment of hnRNPL-LINC02273 complex to AGR2 promoter region epigenetically upregulated AGR2 by augmenting local H3K4me3 and H3K27ac levels. Combination of AGR2 and LINC02273 was an independent prognostic factor for predicting breast cancer patient survival. Moreover, our data revealed that LINC02273-targeting antisense oligonucleotides (ASO) substantially inhibited breast cancer metastasis in vivo.ConclusionsOur findings uncover a key role of LINC02273-hnRNPL-AGR2 axis in breast cancer metastasis and provide potential novel therapeutic targets for metastatic breast cancer intervention.

Comparison of hair medulla from lymph node metastasis and non-lymph node metastasis gastric cancer patients using synchrotron radiation infrared microspectroscopy

Lymph node metastasis often occurs in gastric cancer, hence it is important to explore new methods for diagnosing lymph node metastasis before surgery. In this study, synchrotron radiation infrared (SR-IR) microspectroscopy was used to compare hair medulla from lymph node metastasis and non-metastasis gastric cancer patients. Peak-area ratios indicated that significant alterations might occur in lipids, proteins and nucleic acids after lymph node metastasis. Discriminant analysis was implemented on the basis of peak-area ratios and obtained the following results: the sensitivity was 80.56%, the specificity was 82.76%, the positive predictive value was 85.29% and the accuracy was 81.54%. This study showed that biomacro-molecules in hair medulla were influenced by lymph node metastasis, indicating that IR spectra of hair medulla may be potentially used to diagnose lymph node metastasis before gastric cancer surgery.

Expression of Angiopoietin-like 4 Fibrinogen-Like Domain increases risk of brain metastases in women with breast cancer

Abstract Background Brain metastases challenge daily clinical practice, and the mechanisms by which cancer cells cross the blood-brain barrier remain largely undeciphered. Angiopoietin-like 4 (ANGPTL4) proteolytic fragments have controversial biological effects on endothelium permeability. Here, we studied the link between ANGPTL4 and the risk of brain metastasis in cancer patients. Methods From June 2014 to June 2015, serum samples from 86 cancer patients were prospectively collected, and ANGPTL4 concentrations were assessed. Using a murine model of brain metastases, we investigated the roles of nANGPTL4 and cANGPTL4 fragments in the occurrence of brain metastases. Results A positive ANGPTL4 serum concentration over 0.1ng/mL was associated with decreased overall-survival. Multivariate analyses found that only breast cancer brain metastases were significantly associated with elevated ANGPTL4 serum concentrations. 4T1 murine breast cancer cells were transfected with either nANGPTL4- or cANGPTL4-encoding cDNAs. Compared to mice injected with wild-type 4T1 cells, mice injected with nANGPTL4 cells had shorter median survival (p Conclusions This study opens the way for further translational research on the role of cANGPTL4 fragment in human breast cancer brain metastases.

Never Travel Alone: The Crosstalk of Circulating Tumor Cells and the Blood Microenvironment.

Commonly, circulating tumor cells (CTCs) are described as source of metastasis in cancer patients. However, in this process cancer cells of the primary tumor site need to survive the physical and biological challenges in the blood stream before leaving the circulation to become the seed of a new metastatic site in distant parenchyma. Most of the CTCs released in the blood stream will not resist those challenges and will consequently fail to induce metastasis. A few of them, however, interact closely with other blood cells, such as neutrophils, platelets, and/or macrophages to survive in the blood stream. Recent studies demonstrated that the interaction and modulation of the blood microenvironment by CTCs is pivotal for the development of new metastasis, making it an interesting target for potential novel treatment strategies. This review will discuss the recent research on the processes in the blood microenvironment with CTCs and will outline currently investigated treatment strategies.

Body Mass Index and prostatic-specific antigen are predictors of prostate cancer metastases in patients undergoing robot-assisted radical prostatectomy and extended pelvic lymph node dissection.

The aim of this study was to investigate the risk factors contributing to multiple lymph node invasion (LNI) in patients with prostate cancer (PCa) undergoing extended pelvic lymph node dissection (ePLND) during robot assisted radical prostatectomy (RARP). A total of 211 patients who underwent RARP and ePNLD from June 2013 to March 2017 were classified according to lymph node status in the surgical specimen (absent, single or multiple). Risk factors of LNI were evaluated by the multinomial logistic regression model. A receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the efficacy of factors and model evaluation. On multivariate analysis, the risk of multiple LNI, was independently increased by Body Mass Index (BMI) (odds ratio [OR] 1.194; P=0.026) and prostate-specific antigen (PSA) (OR=1.089; P=0.014) when compared to patients without LNI. ROC curves indicated that both BMI (AUC=0.702) and PSA (AUC=0.732) had fair discrimination power. For each unit of increase in PSA, the odds of multiple lymph node invasion increased by 8.9% and for each unit increase of BMI, the odds of multiple LNI increased by 19.4%. The risk of multiple LNI was independently predicted by PSA and BMI with fair discrimination power.

Effect of MRI-based semiautomatic size-assessment in cerebral metastases on the RANO-BM classification.

Evaluation of asemiautomatic software algorithm for magnetic resonance imaging (MRI)-based assessment of cerebral metastases in cancer patients. Brain metastases (n = 131) in 38patients, assessed by contrast-enhanced MRI, were retrospectively evaluated at two timepoints (baseline, follow-up) by two experienced neuroradiologists in ablinded manner. The response assessment in neuro-oncology (RANO) criteria for brain metastases (RANO-BM) were applied by means of asoftware (autoRANO-BM) as well as manually (manRANO-BM) at an interval of 3weeks. The average diameter of metastases was 12.03 mm (SD ± 6.66 mm) for manRANO-BM and 13.97 mm (SD ± 7.76 mm) for autoRANO-BM. Diameter figures were higher when using semiautomatic measurements (median = 11.8 mm) as compared to the manual ones (median = 10.2 mm; p = 0.000). Correlation coefficients for intra-observer variability were 0.993 (autoRANO-BM) and 0.979 (manRANO-BM). The interobserver variability (R1/R2) was 0.936/0.965 for manRANO-BM and 0.989/0.998 for autoRANO-BM. A total of 19 lesions (15%) were classified differently when using semiautomatic measurements. In 14cases with suspected disease progression by manRANO-BM astable course was found according to autoRANO-BM. Computerized measuring techniques can aid in the assessment of cerebral metastases by reducing examiner-dependent effects and may consequently result in adifferent classification according to RANO-BM criteria.