Extracranial Sites Research Articles

Abstract IA020: Improving treatment of primary and metastatic brain tumors: Emerging insights and novel strategies

Abstract Approximately 200,000 patients develop metastasis each year in US alone. This incidence is approximately 20 times higher than glioblastoma – a uniformly fatal disease where all Phase III immune-checkpoint trials have failed to date. Patients diagnosed with metastatic breast cancer have a median survival of two years and account for approximately 40,000 deaths annually in the US alone. About 1/3rd of women with advanced breast cancer are at risk of developing brain metastases (BMs). A notable example is human epidermal growth factor receptor 2 (HER2)-positive breast cancer, where BMs from this disease are refractory to drugs that otherwise control disease in extracranial sites, for two reasons: i) the blood-brain/blood-tumor barrier (BBB/BTB) hinders the delivery of drugs to BMs, and ii) the brain tumor microenvironment (TME) reduces the efficacy of these therapies even when they accrue in BMs (Arvanitis et al, Nature Reviews Cancer 2020). By employing clinically relevant murine models, we demonstrated that theanti-HER2 antibody trastuzumab can upregulate VEGF in the microenvironment of BM (Izumi et al, Nature 2002), and thus, adding anti-VEGF/R agents can improve the efficacy of anti-HER2 therapies (Kodack et al, PNAS 2012). We further showed that HER3 is overexpressed in BMs and confers de novo resistance to anti-HER2 therapies. Blocking HER3 enhanced the efficacy of FDA-approved targeted therapies including trastuzumab and neratinib - a finding supported by independent clinical trials (Kodack et al, Science Translational Medicine 2017). In our attempt to improve survival further, we discovered that breast cancer cells implanted in the brain exhibit increased de novo lipid synthesis compared to breast cancer cells implanted in the breast or liver. Genetic or pharmacological inhibition of fatty acid synthase (FASN) reducesHER2+ breast tumor growth in the brain – unlike those grown in the breast or liver, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies (Ferraro et al, Nature Cancer 2021). In parallel, we have employed focused ultrasound to improve delivery of various therapeutics to BMs by transiently disrupting BBB/BTB (Arvanitis et al, PNAS 2018). Finally, by recognizing the similarities between the TME of BM and glioblastoma, we have developed 3 new strategies to reprogram the immunosuppressive microenvironment of glioblastoma to improve the efficacy of immune-check point blockers against these uniformly fatal tumors (Amoozgar et al, Nature Communications 2021, Amoozgar et al, bioarxiv 2022, Datta et al. bioarxiv 2022). These strategies are likely to also benefit patients with brain metastases that have now become a leading cause of morbidity and mortality with improved detection and extracranial treatments. Citation Format: Rakesh K. Jain. Improving treatment of primary and metastatic brain tumors: Emerging insights and novel strategies [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr IA020.

Outcomes and prognostic factors in metastatic renal cell carcinoma patients with brain metastases.

To evaluate the outcomes and prognostic factors in patients with brain metastatic renal cell carcinoma (bmRCC). The data of 322 patients with metastatic renal cell carcinoma, taken between 2012 and 2020, were retrospectively reviewed. Overall survival (OS) and prognostic factors were evaluated with Kaplan-Meier analysis and Cox regression analysis. Forty (12.4%) of the patients had bmRCC. Seventeen (42.5%) of the patients were de novo metastatic, and nine (22.5%) of the patients had brain metastases at presentation. Twenty-four (60%) patients previously had received various therapies (tyrosine kinase inhibitor or checkpoint inhibitors). After brain metastases developed, 35 (87.5%) of the patients received brain radiotherapy (whole-brain radiotherapy or stereotactic radiosurgery), and twenty-five (62.5%) patients received different systemic therapies. Nine patients received sunitinib, nine received pazopanib, five received nivolumab, and two received axitinib. The median OS was 8.8 months (range: 2.9-14.6) for all patients with bmRCC. In univariate analysis, the number of brain metastasis (P = 0.35), the site of brain metastasis (left, right or bilateral) (P = 0.79), the largest size of brain metastasis (P = 0.45), the number of extracranial metastatic sites (P = 0.81), de novo metastatic disease (P = 0.17), primary tumor site (left or right) (P = 0.90), and tumor grade (P = 0.09) were not statistically significant factors on OS. However, age (P = 0.02), a history of nephrectomy (P < 0.001), receiving brain radiotherapy (P = 0.005), and type of systemic treatment (P = 0.04) were statistically significant. Only, the effect of brain radiotherapy on OS (P = 0.01) was confirmed in multivariate analysis. In this study, we observed that the prognosis of patients with bmRCC was poor. Despite a small number of patients, we detected that the effect of tyrosine kinase inhibitors and nivolumab was comparable, and receiving brain radiotherapy was a prognostic factor for OS.

Metastatic high-grade meningioma: A case report and review of risk factors for metastasis.

Abstract Meningiomas are the most common primary tumor of the CNS, and although they usually have a good prognosis, meningiomas can metastasize to extracranial sites, greatly worsening the prognosis. Due to its infrequency, the clinical and molecular risk factors associated with this event are poorly characterized in the literature. A 69-year-old man was found to have a meningioma in the left parieto-occipital parafalcine region. Over the subsequent decade, the patient experienced multiple local tumor recurrences, including with invasion through the scalp and superior sagittal sinus. The tumor was WHO grade 2-3 and next-generation sequencing was notable for TERT promoter mutation, homozygous deletion of CDKN2A, and high variant allele frequency of NF2. The tumor metastasized to the axial and appendicular skeleton, liver, kidney, and lung, and the patient ultimately succumbed to disease. In summary, this is the first report of multiple simultaneous and anatomically-distinct extracranial metastases from a primary intracranial meningioma.

HER2 amplification in colorectal cancer with brain metastasis: A propensity score matching study

BackgroundThe association between human epidermal growth factor receptor-2 (HER2) amplification and brain metastasis (BM) in patients having colorectal cancer (CRC) has been suggested but not yet established. This study investigated the expression patterns of HER2, its association with BM, and its prognostic value in patients having CRC. MethodsWe retrospectively identified 99 patients having metastatic CRC (mCRC) and BM (the BM cohort) and compared them with a cohort of 249 patients having mCRC and without BM (the stage IV cohort) by propensity score matching. Immunohistochemical studies of HER2 on all available paraffin-embedded tumour samples, either from the primary tumour, the metastasis (brain and/or extracranial sites) or both, were performed and analysed. HER2 fluorescent in situ hybridisation was applied when necessary. The expression of HER2 was compared and correlated with survival. ResultsHER2 amplifications were detected in 16 (18.4%) of 87 and 9 (3.6%) of 249 patients who had specimens available in the BM and stage IV cohorts, respectively (P < .001). After propensity score matching, HER2 amplification was significantly associated with BM (odds ratio: 5.38, P = .003). HER2 heterogeneity was frequently observed not only at the single tumour level but also in paired tumour samples. A marginally significant longer survival since BM was found in patients having HER2-amplified mCRC than in those without (P = .07). ConclusionsHER2 amplification was significantly associated with BM in patients having mCRC and might have prognostic value for survival since BM. Given the heterogeneity of HER2 expression, the testing of HER2 status on available tissues from both primary and metastatic tumours should be encouraged.

HISTOPATHOLOGICAL APPROACH TO THE DIAGNOSIS OF BENIGN PERIPHERAL NERVE SHEATH TUMORS AT UNCOMMON LOCATION

Peripheral nerve sheath tumors are relatively common lesions that exhibit a wide morphological and biological spectrum. In the presence of classical morphological and immunohistochemical features, the histological diagnosis is usually straightforward, but they may represent diagnostic challenges. Schwannoma is a slow growing encapsulated tumor of neuroectodermal derivation that originates from the Schwann cells of the neural sheath. Most commonly presents as cerebellopontine angle mass but extracranial sites are known and needs to be considered in the differential diagnosis. Intraparotid and penile schwannomas are extremely rare. Their diagnosis could be missed on cytology due to cystic changes. Isolated plexiform neurofibroma of the tongue is again a rare tumor. Plexiform pattern recognition is important for the pathologist as these varients might show malignant transformation. Overall Fine needle aspiration cytology though inconclusive at times, help a lot initially to delineate between benign Vs malignant lesions. Moreover its minimally invasive so can be performed easily at the uncommon locations. Histopathology remains the gold standard. Clinicopathological and imaging correlation is must for definite diagnosis and treatment.

CTIM-02. TIP: PHASE I/II STUDY OF STEREOTACTIC RADIOSURGERY WITH CONCURRENT OLAPARIB FOLLOWED BY ADJUVANT DURVALUMAB AND PHYSICIAN’S CHOICE SYSTEMIC THERAPY IN SUBJECTS WITH BREAST CANCER BRAIN METASTASES

Abstract BACKGROUND Despite progress in the treatment of brain metastasis (BrM) for HER2+ breast cancer (BC), outcomes for patients with HER2-negative BC BrM remain poor. Current standard of care consists of local therapies, including surgery and radiotherapy, followed by systemic therapy. Preclinical studies show inhibitors of poly(ADP-ribose) polymerase (PARP) are effective with radiation therapy as a DNA damage response inhibitor. Triple negative BC (TNBC) has higher rates of homologous recombination deficiency compared to other BC subtypes, and together with HER2-negative, BRCA-mutated BC would be particularly sensitive to PARP inhibition. PARP inhibition also shows promising efficacy combined with immunotherapy in patients with germline BRCA-mutant and metastatic TNBC in clinical trials (MEDIOLA, TOPACIO). In addition, immunotherapy with stereotactic radiosurgery (SRS) is associated with favorable intracranial control and survival in patients with BrM. We hypothesize that this biologically-rational combination will enhance local control of SRS-treated BrM through synergy with PARP inhibition, while controlling micrometastatic disease in the brain and extracranial sites via potentiation of the immune response. METHOD We are conducting a multi-institution, Phase I/II trial of SRS plus olaparib, followed by durvalumab (with physician’s choice systemic therapy), for patients with TNBC (any BRCA status) or HER2-negative with BRCA-mutated (germline or somatic) BC BrM [NCT04711824]. The primary objectives are to evaluate safety and tolerability (Phase I) and determine intracranial disease control at 6 months (Phase II) of this treatment combination. Secondary objectives include determining clinical activity via intracranial and global progression-free survival, overall survival, and intracranial and extracranial response rate. Exploratory objectives will assess potential biomarkers of treatment response, including changes in circulating tumor cells and DNA in blood and cerebrospinal fluid, germline and tumor mutations in DNA repair pathway genes, and PD-L1 expression, as well as quality of life and patient-reported outcomes. A surgical sub-study will evaluate olaparib concentration/distribution in resected BrM.

Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures.

Outcomes following andexanet alfa reversal of factor Xa inhibitors in patients requiring urgent or emergent invasive procedures are lacking. This study aimed to describe efficacy and safety outcomes following andexanet alfa administration within 24h of an invasive procedure. This single-center, observational, retrospective study included patients who received andexanet alfa within 24h of an invasive or surgical procedure. The primary outcome was hemostatic efficacy graded as excellent, good, or poor using similar definitions to the ANNEXA-4 criteria. Secondary outcomes included hospital discharge disposition, intensive care unit (ICU) and hospital length of stay, 30-day mortality, 30-day thromboischemic event rates, and serum coagulation assay changes pre- and postreversal. Forty-four patients met inclusion criteria; of these, 27 (62.8%) received apixaban and 16 (37.2%) were treated with rivaroxaban prior to admission. The indications for reversal were categorized as intracranial (n=20 [45.5%]) or extracranial (n=24 [54.5%]) sites. Majority of patients required emergent operative procedures (18 [40.9%]), followed by invasive device placement (10 [22.7%]) or arterial embolization (9 [20.5%]). Thirty-eight (86.4%) patients were able to be adequately graded for hemostatic efficacy. Overall, 30 (78.9%) patients achieved excellent or good hemostasis within 24h after periprocedural administration of andexanet alfa (19 [82.6%] apixaban vs. 11 [78.6%] rivaroxaban; 12 [80.0%] intracranial events vs. 18 [78.3%] extracranial events). Discharge disposition was most often to a short- or long-term care facilities (27 [61.4%]). Thirty-day mortality and thromboischemic complications occurred in 15 (34.1%) and 12 (27.3%) patients, respectively. Prothrombin time and antifactor Xa assay results were significantly decreased after andexanet alfa administration (p < 0.05) while thromboelastogram assay values (reaction time, kinetic time, and activated clotting time) showed nonsignificant changes pre- versus postreversal. Andexanet alfa may be used for urgent or emergent reversal of apixaban and rivaroxaban peri-procedurally with promising hemostatic outcomes. Further prospective, comparative clinical research is warranted.

Does diploic venous flow drain extracranially in the pterional area? A magnetic resonance imaging study.

To the best of our knowledge, no study using neuroimaging modalities has documented calvarial diploic veins (DVs) connected to the extracranial sites. This study aimed to characterize them using magnetic resonance imaging (MRI). A total of 88 patients underwent thin-sliced contrast MRI. In addition, the DVs coursing through the pterional area were observed on three injected cadaver heads. On postcontrast MRI, the DVs of the pterional area directly drained into the temporalis muscle or supplied branches coursing into the muscle in 43% on the right side and 40% on the left. The DVs and their branches were highly variable in diameter and number. In 9% of cases, the DV of the pterional area was found to drain into an extracranial site and connected to large venous channels distributed in the temporalis muscle. Furthermore, in 17% of cases, the DVs drained into the extracranial sites in the frontal skull region, followed by 9% in the parietal, 2% in the occipital, and 1% in the temporal regions. The DVs coursed superficially in the pterional area on both sides of all three cadaver heads. On one side, the DV in the area was open to an extracranial site. Part of the diploic venous flow drains extracranially in the pterional area. This area may provide an important interface between the calvarial DVs and the extracranial venous system.

The impact of stereotactic ablative radiotherapy on oligoprogressive metastases from renal cell carcinoma.

Renal cell carcinoma (RCC) represents 80-90% of all kidney tumors and about 15-25% of patients will develop distant metastases. Systemic therapy represents the standard of care for metastatic patients, but stereotactic ablative radiotherapy (SABR) may play a relevant role in the oligoprogressive setting, defined as the progression of few metastases during an ongoing systemic therapy on a background of otherwise stable disease. Aim of the present study was to analyze the outcome of RCC patients treated with SABR on oligoprogressive metastases. In this monocenter study, we analyzed patients affected by RCC treated with SABR on a maximum of 5 cranial or extracranial oligoprogressive sites of disease. Endpoints were overall survival (OS), progression-free survival (PFS), and toxicity. We included 74 oligoprogressions (26 intracranial and 48 extracranial) and 57 SABR treatments in 44 patients. Most common concomitant treatments were sunitinib (28, 49.1%), pazopanib (12, 21.0%) and nivolumab (11, 19.3%). Median follow-up was 19.0months, and 1- and 2-year OS rates were 79.2% and 57.3%, respectively. Repeated SABR was a positive predictive factor for OS (p = 0.034). Median PFS was 9.8months, with 1- and 2-year rates of 43.2% and 25.8%. At multivariable analysis, disease-free interval (p = 0.022) and number of treated metastases (p = 0.007) were significant for PFS. About 80% of patients continued the ongoing systemic therapy 1- and 2-years after SABR with no grade 3 or 4 toxicities. we confirmed the efficacy and safety of SABR for oligoprogression from RCC, with the potential to ablate resistant metastases and to prolong the ongoing systemic therapy.

Glial Heterotopia Presenting as Lesion at Bridge of Nose, An Exemplary Case of Displacement of Neuroglial Tissue at Extracranial Sites

Glial Heterotopia Presenting as Lesion at Bridge of Nose, An Exemplary Case of Displacement of Neuroglial Tissue at Extracranial Sites

Outcomes and Molecular Features of Brain Metastasis in Gastroesophageal Adenocarcinoma

Brain metastasis (BrM) in gastroesophageal adenocarcinoma (GEA) is a rare and poorly understood phenomenon associated with poor prognosis. To examine the clinical and genomic features of patients with BrM from GEA and evaluate factors associated with survival. In this single-institution retrospective cohort study, 68 patients with BrM from GEA diagnosed between January 1, 2008, and December 31, 2020, were identified via review of billing codes and imaging reports from the electronic medical record with follow-up through November 3, 2021. Genomic data were derived from the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets clinical sequencing platform. Treatment with BrM resection and/or radiotherapy. Overall survival after BrM diagnosis. Sixty-eight patients (median age at diagnosis, 57.4 years [IQR, 49.8-66.4 years]; 59 [86.8%] male; 55 [85.9%] White) participated in the study. A total of 57 (83.8%) had primary tumors in the distal esophagus or gastroesophageal junction. Median time from initial diagnosis to BrM diagnosis was 16.9 months (IQR, 8.5-27.7 months). Median survival from BrM diagnosis was 8.7 months (95% CI, 5.5-11.5 months). Overall survival was 35% (95% CI, 25%-48%) at 1 year and 24% (95% CI, 16%-37%) at 2 years. In a multivariable analysis, an Eastern Cooperative Oncology Group performance status of 2 or greater (hazard ratio [HR], 4.66; 95% CI, 1.47-14.70; P = .009) and lack of surgical or radiotherapeutic intervention (HR, 7.71; 95% CI, 2.01-29.60; P = .003) were associated with increased risk of all-cause mortality, whereas 3 or more extracranial sites of disease (HR, 1.85; 95% CI, 0.64-5.29; P = .25) and 4 or more BrMs (HR, 2.15; 95% CI, 0.93-4.98; P = .07) were not statistically significant. A total of 31 patients (45.6%) had ERBB2 (formerly HER2 or HER2/neu)-positive tumors, and alterations in ERBB2 were enriched in BrM relative to primary tumors (8 [47.1%] vs 7 [20.6%], P = .05), as were alterations in PTPRT (7 [41.2%] vs 4 [11.8%], P = .03). This study suggests that that a notable proportion of patients with BrM from GEA achieve survival exceeding 1 and 2 years from BrM diagnosis, a more favorable prognosis than previously reported. Good performance status and treatment with combination surgery and radiotherapy were associated with the best outcomes. ERBB2 positivity and amplification as well as PTPRT alterations were enriched in BrM tissue compared with primary tumors; therefore, further study should be pursued to identify whether these variables represent genomic risk factors for BrM development.

Nasal Glioma Presenting as Cystic Lesion at Bridge of Nose, an Exemplary Case of Displacement of Neuroglial Tissue in Extracranial Sites

Nasal Glioma Presenting as Cystic Lesion at Bridge of Nose, an Exemplary Case of Displacement of Neuroglial Tissue in Extracranial Sites

Molecular Heterogeneity in Pediatric Malignant Rhabdoid Tumors in Patients With Multi-Organ Involvement

Rhabdoid tumors (RTs) of the brain (atypical teratoid/rhabdoid tumor; AT/RT) and extracranial sites (most often the kidney; RTK) are malignant tumors predominantly occurring in children, frequently those with SMARCB1 germline alterations. Here we present data from seven RTs from three pediatric patients who all had multi-organ involvement. The tumors were analyzed using a multimodal molecular approach, which included exome sequencing of tumor and germline comparator and RNA sequencing and DNA array-based methylation profiling of tumors. SMARCB1 germline alterations were identified in all patients and in all tumors. We observed a second hit in SMARCB1 via chr22 loss of heterozygosity. By methylation profiling, all tumors were classified as rhabdoid tumors with a corresponding subclassification within the MYC, TYR, or SHH AT/RT subgroups. Using RNA-seq gene expression clustering, we recapitulated the classification of known AT/RT subgroups. Synchronous brain and kidney tumors from the same patient showed different patterns of either copy number variants, single-nucleotide variants, and/or genome-wide DNA methylation, suggestive of non-clonal origin. Furthermore, we demonstrated that a lung and abdominal metastasis from two patients shared overlapping molecular features with the patient’s primary kidney tumor, indicating the likely origin of the metastasis. In addition to the SMARCB1 events, we identified other whole-chromosome events and single-nucleotide variants in tumors, but none were found to be prognostic, diagnostic, or offer therapeutic potential for rhabdoid tumors. While our findings are of biological interest, there may also be clinical value in comprehensive molecular profiling in patients with multiple rhabdoid tumors, particularly given the potential prognostic and therapeutic implications for different rhabdoid tumor subgroups demonstrated in recent clinical trials and other large cohort studies.

A first-in-human study of [68Ga]Ga-CDI: a positron emitting radiopharmaceutical for imaging tumour cell death

PurposeThis study assesses human biodistribution, radiation dosimetry, safety and tumour uptake of cell death indicator labelled with 68Ga ([68Ga]Ga-CDI), a novel radiopharmaceutical that can image multiple forms of cell death.MethodsFive participants with at least one extracranial site of solid malignancy > 2 cm and no active cancer treatment in the 8 weeks prior to the study were enrolled. Participants were administered 205 ± 4.1 MBq (range, 200–211 MBq) of [68Ga]Ga-CDI and 8 serial PET scans acquired: the first commencing immediately and the last 3 h later. Participants were monitored for clinical, laboratory and electrocardiographic side effects and adverse events. Urine and blood radioactivity was measured. Spherical volumes of interest were drawn over tumour, blood pool and organs to determine biodistribution and calculate dosimetry. In one participant, tumour specimens were analysed for cell death using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining.Results[68Ga]Ga-CDI is safe and well-tolerated with no side effects or adverse events. [68Ga]Ga-CDI is renally excreted, demonstrates low levels of physiologic uptake in the other organs and has excellent imaging characteristics. The mean effective dose was 2.17E − 02 ± 4.61E − 03 mSv/MBq. It images constitutive tumour cell death and correlates with tumour cell death on histology.Conclusion[68Ga]Ga-CDI is a novel cell death imaging radiopharmaceutical that is safe, has low radiation dosimetry and excellent biodistribution and imaging characteristics. It has potential advantages over previously investigated radiopharmaceuticals for imaging of cell death and has progressed to a proof-of-concept trial.Trial registrationACTRN12621000641897 (28/5/2021, retrospectively registered)

P63-1 Safety and efficacy of stereotactic body radiotherapy in patients with early stage NSCLC: systematic review

Stereotactic Body Radiotherapy (SBRT) is a non-invasive cancer treatment that uses many small, precise rays to deliver large doses to tumors at extracranial sites in 1 to 5 treatments. Currently, SBRT has become an alternative treatment for early-stage Non-Small Lung Cancer (NSCLC) if patients are inoperable. It provides high rates of local control and increase survival rates at the population level. This systematic review aims to evaluate the safety and efficacy of SBRT treatment in patient with early-stage NSCLC.

Outcomes and prognostic factors in patients with HER2-positive metastatic breast cancer with brain metastasis.

e14002 Background: Breast cancer is the most common malignancy in females. Brain metastasis is a poor prognostic factor in breast cancer. Brain metastasis can develop in about half of the HER2- positive metastatic breast cancer patients. The study was aimed to determine outcomes and prognostic factors in HER2 positive metastatic breast cancer patients who had brain metastasis. Methods: We evaluated the HER2-positive metastatic breast cancer patients with brain metastasis between 2008 and 2018. Data of the patients were recorded retrospectively. Kaplan Meier and Cox regression analysis were used for survival analysis and prognostic factors. Results: Eighty-three patients were included in the study. The median age was 49 (range, 25-76). Thirty-two (38.6%) patients had de-novo metastatic disease at diagnosis. The most common histopathological type was invasive ductal carcinoma (88.4%). The estrogen receptor and progesterone receptor positivity ratios were 42.2% and 28.9%, respectively. At the beginning of brain metastasis, the median number of extra-cranial metastasis was 2 (range, 0-4). The most common extra-cranial metastasis sites were bone (63.9%), liver (41%), and lung (34.9%), respectively. Twenty-eight patients (41.8%) had solitary brain metastasis. The median size of brain metastasis was 16 mm (range, 5-63) at diagnosis. All patients had treated with trastuzumab-based chemotherapy, 29 patients (34.9%) TDM-1, and 73 patients (88%) lapatinib+capesitabine combination. Seventeen patients (20.5%) had undergone craniotomy, and 82 patients (98.8%) received brain radiotherapy. The patients also received hormonotherapy (41%) and bisphosphonates (56.6%). At a median follow-up of 36 months (range 5.9-177.7) from beginning metastasis, the median overall survival was 34.9 months (95% CI, range 24.6-45.2). In multivariate analysis, age at diagnosis (p = 0.005), presence of five and over brain metastasis (p = 0.016), the number of chemotherapy used with trastuzumab (p = 0.017), and receiving three different HER2-targetted therapy (p = 0.032) were statistically significant for overall survival. However, size of brain metastasis (p = 0.091), lung metastasis (p = 0.428), liver metastasis (p = 0.338), bone metastasis (p = 0.132), and hormone positivity of tumor (p = 0.238) were not. Conclusions: Real-life outcomes of HER2-positive breast cancer patients with brain metastases were presented in this study. We showed that age at diagnosis, number of brain metastasis, number of chemotherapy received with trastuzumab, and had received three different HER2 targetted therapy was prognostic factors for overall survival.

Brain metastases in the setting of stable extracranial disease: A systematic review and meta-analysis.

2022 Background: Intracranial metastatic disease (IMD) is a life-altering complication for many patients with cancer. Improvements in systemic therapies have transformed the epidemiology of IMD, with some patients presenting with IMD in the context of stable extracranial disease (IMD-SECD). Among patients with metastases in other sites with similarly stable systemic disease, surgical resection and targeted therapy can result in long-term disease control and extended overall survival (OS), yet little is known about the clinical outcomes for patients with IMD-SECD. Methods: We searched MEDLINE, EMBASE, CENTRAL, and grey literature sources up to June 21, 2021 for studies reporting brain metastasis (BrM) with controlled extracranial disease (ECD) as well as IMD-SECD secondary to any primary cancer (criteria: presence of BrM and ≤2 extracranial metastatic sites, with no prior second-line chemotherapy and second-line brain-directed therapy). In studies comparing IMD-SECD and IMD patients, hazard ratios (HR) for OS and intracranial progression-free survival (iPFS) were pooled using random-effects meta-analysis, while medians for OS were estimated from single-arm IMD-SECD studies based on distribution-free summary survival curves. Results: Of 1067 records identified, 68 studies involving 5325 patients with IMD-SECD were included. Patients with IMD-SECD had prolonged OS (HR 1.93; 95% CI, 1.44-2.59; n = 10 studies; n = 877 patients) and iPFS (HR 1.59; 95% CI 1.31-1.92; n = 4 studies; n = 673 patients) compared with IMD patients. Subgroup analysis of patients with BrM and controlled versus uncontrolled ECD found prolonged OS with controlled ECD (HR 2.46; 95% CI, 1.36-4.44; n = 4 studies; n = 135 patients). Pooled median OS for all IMD-SECD patients was 20.85 months (mo) (95% CI, 16.35-25.98; n = 27 studies; n = 2159 patients). Stratification by primary cancer type showed median OS 20.18 mo (95% CI, 10.43-38.20; n = 2 studies; n = 109 patients) and 27.46 mo (95% CI, 18.27-49.66; n = 13 studies; n = 497 patients) for patients with IMD-SECD secondary to breast cancer and non-small cell lung cancer, respectively. Conclusions: Patients with IMD-SECD demonstrate prolonged OS and iPFS compared with patients with IMD, who may have more extensive systemic disease. Our results suggest that patients with IMD-SECD may represent a distinct subpopulation of patients with IMD with a uniquely favourable prognosis. It is possible that aggressive and timely treatment may significantly prolong survival for these patients. Future prospective trials should aim to investigate the efficacy of current treatment regimens in patients with IMD-SECD to further clarify optimal treatment pathways in this unique population of patients.

Extracranial guiding structures for navigation to specific topographical sectors of the equine neopallium: an anatomical investigation performing three-dimensional distance measurements in adult warm-blooded horses.

This basically anatomical study focuses on two items; firstly, the establishment of a system for the cartographic subdivision of the neopallium; secondly, the topographical correlation of extracranial landmarks and intracranial sites on the neopallium. The surface of the neopallium was subdivided into 15 sectors with reference to a newly introduced pattern of Primary Sulci. The topographical link between extracranial landmarks and certain intracranial sites (i.e. neopallium sectors) was elaborated by using a simple stereotactic device and a computer-assisted measurement device. Measurements were performed between points on the head's outer surface and on the isolated brain. The introduction of an anatomical three-dimensional coordinate system was an essential key issue for this investigation. This setting facilitated the measurements and calculations of the so-called indirect distances that were characterised by their alignment along the three orthogonal axes (x, y, z) of the anatomical coordinate system. The inter-individual comparison (16 adult horses [Equus caballus]) of the indirect distances revealed that each sector centre lay within a distinct morphometric residence area. The measured and calculated data also showed that each sector centre could be assigned to its proper extracranial landmark that - in comparison with other landmarks - was best suited for the optimal allocation of the sector centre point.

Clinical factors and association with treatment modalities in patients with breast cancer and brain metastases who develop leptomeningeal metastases.

Leptomeningeal metastases (LM) are an aggressive complication of metastatic breast cancer (MBC) with brain metastases (BM), with a short survival of weeks to months. Studies suggest that surgical resection of BM may increase the risk of LM, especially in infratentorial metastases. In this retrospective study, we examine this and other factors which may be associated with increased risk of LM. A database search at a single institution identified 178 patients with MBC and treated BM between 2007 and 2020. We collected demographic, clinical, radiographic, and other treatment data. LM was diagnosed by cerebrospinal fluid (CSF) cytology, neuroimaging, or both. Cox proportional hazards model was used. After a median follow-up of 8.5months, 41 out of 178 patients (23%) with BM developed LM. Median time to develop LM was 130days. Mean age was 51.3years. The number and size of the BM, hemorrhagic/cystic lesions, progressive/stable systemic disease, and extracranial metastases sites other than liver did not pose a higher risk of LM. Infratentorial lesions (HR = 5.41) and liver metastases (HR = 2.28) had a higher risk of LM. Patients who had any surgery did not have a higher risk for LM (HR 1.13). The LM group had a worse overall survival as compared to the non-LM group. Among MBC patients with BM, infratentorial BM and visceral liver lesions increase the risk of LM, whereas local treatment modalities such as surgery and radiation do not. These data imply that local treatment strategy should not differ based on potential risk for LM.

Retrospective Comparative Analysis of Clinical and Imaging Features of Craniocervical Artery Dissection: Spontaneous CAD vs. Minor Traumatic CAD.

Background and ObjectivesCraniocervical artery dissection (CAD) is the most common cause of ischemic stroke in young adults. The etiologies of CAD can be classified into three types, such as spontaneous (sCAD), minor traumatic (mtCAD), and genetic origin. Recent studies indicated that clinical presentations and imaging features could guide management and inform prognosis. This retrospective analysis sought to compare the clinical and imaging features of sCAD vs. mtCAD in providing evidence-based advice on medical treatment, functional rehabilitation, secondary stroke prevention, and prognosis, ultimately formulating clinical guidelines in managing CAD.MethodsIn total, 148 patients with CAD were identified from the medical records database and subdivided into sCAD and mtCAD based on the clinical presentations and imaging features. A retrospective comparative analysis was performed according to their clinical presentations and imaging features.ResultsPatients with mtCAD are significantly younger than sCAD with 120 cases of sCAD average aged 43.61 ± 12.75, while 28 cases of mtCAD average aged 35.68 ± 14.54. Patients with mtCAD had more cases of neck pain compared to sCAD. Patients with mtCAD had more cases of CAD at extracranial locations compared to sCAD. Patients with mtCAD had more cases of multiple site dissection compared to sCAD. Double lumen and intramural haematoma are the most common imaging findings with mtCAD patients having statistical significantly more cases of intramural haematoma and long tapering stenosis.ConclusionPatients with mtCAD were presented at a much younger age with symptoms of neck pain compared to sCAD. Patients with mtCAD predominantly presented at extracranial sites with more prominent features of multiple site dissection, intramural haematoma, and long tapering stenosis. These clinical and imaging features can translate into clinical practice guidelines for patients with CAD to improve the optimal functional outcome and reduce both morbidity and mortality.