Real-world hypothesis-generating cohort of pancreatic cancer patients with brain metastases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16720-e16720
Author(s):  
Derek Cridebring ◽  
David Hadley ◽  
Timothy S Scott ◽  
Alex B Vilner ◽  
Tammy M Heckman ◽  
...  

e16720 Background: Pancreatic cancer (PC) is the third most lethal form of cancer in the United States, and is most often diagnosed having already metastasized, making its 5-year survival rate one of the lowest. Metastatic PC (mPC) is most common at sites such as liver, lymph nodes, and lung while, in contrast, brain metastases from PC are rare. Brain metastases present a major challenge for future oncological research, as they are difficult to treat. If PC patients most likely to develop brain metastases can be identified earlier, there is an opportunity for rapid therapeutic intervention. There is limited research and understanding of the relationship between pancreatic cancer and brain metastases. Methods: We performed a retrospective, non-interventional study using deidentified data. Inteliquet’s data was aggregated from its consortium of 175 US healthcare locations, which includes a variety of source systems at each site. These sources include electronic medical record systems, laboratory information management systems, and other sources. A subset of the adult mPC data originally treated at HonorHealth was identified as an exploratory cohort. Results: 833 patient records were identified with drug treated mPC, 33 (4%) of which had metastasized to the brain. The PC dataset had a median diagnosis age of 65 and was 46% female. The site of the primary tumor within the pancreas was acquired from ICD10 code: 35% were in the head, 14% in the tail, 15% in the body, 5% in overlapping sites, 6% in other parts and 26% where location was unspecified. Metastatic locations came from secondary malignancy ICD10 codes: 63% had liver and 25% had lung metastases, which aligns with prior studies. For patients with brain metastases, the gender distribution was 42% female, while the distribution of primary PC site was: 33% head, 9% tail, 6% body, 6% in overlapping locations, 12% in other parts and 33% with unspecified location. The median age of diagnosis in the brain metastasis group was 67 years. Conclusions: This is the largest study of PC patients with brain metastases that we could find. 33 patients out of 833 had brain metastases compared to a recent review which had 25 cases. Our data suggests that specification of the primary pancreatic site is more difficult, aside from the head of the pancreas. Analyses are underway to explore correlations between other clinical factors and brain metastases, and to calculate the time in between the initial pancreatic cancer diagnosis and detection of the brain metastasis. This hypothesis-generating cohort will be tested in patient data from the rest of the consortium.

2014 ◽  
Vol 14 (4) ◽  
pp. 372-385 ◽  
Author(s):  
Dima Suki ◽  
Rami Khoury Abdulla ◽  
Minming Ding ◽  
Soumen Khatua ◽  
Raymond Sawaya

Object Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. Methods Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990–2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. Results Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2–77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan-Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24–34 months) and 9 months (95% CI 6–11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3–1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6–11 months). Conclusions The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14510-e14510
Author(s):  
Rebecca Levin-Epstein ◽  
Joshua Rusheen ◽  
Preetham Kumar ◽  
Rubine Gevorgyan ◽  
Zoe McWatters ◽  
...  

e14510 Background: Brain metastases can lead to significant morbidity and mortality in patients with advanced cancer. Preventing metastatic disease to the brain could thus substantially improve outcomes. The mechanism of brain metastasis is incompletely understood. Circulating tumor cells drain to the right heart and through the pulmonary circulation, where they may manifest as lung metastases, and can circulate further to the left heart and then to the brain. However, in patients who develop brain metastases without prior lung involvement, metastatic cells may take an alternate route. We hypothesized that cancer cells may pass directly from the right to left heart via a patent foramen ovale (PFO), akin to paradoxical embolism. The prevalence of PFO is approximately 20-30% in the general population; if further elevated in this population, PFO may play a role in brain metastasis development, and ultimately, prophylactic PFO closure may provide benefit. We conducted a pilot study to investigate whether PFO is associated with brain metastases in patients without prior lung involvement. Methods: We prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding lung metastases. Participants underwent a transcranial Doppler study to assess for PFO. Agitated saline was injected intravenously at rest and with Valsalva maneuver. High intensity signals were counted in the middle cerebral arteries for 1 minute after each injection. Spencer grade ≥3 indicated a positive study, consistent with the presence of PFO. Results: We accrued 9 participants who met inclusion criteria. Primary cancers were breast (6 participants), upper gastrointestinal (2 participants), and thyroid (1 participant). A positive study was identified in 2/9 (22.2%) participants. One individual was a female with breast cancer who had no preceding extracranial metastases, and the other individual was a male with duodenal adenocarcinoma whose only prior metastatic disease was distant lymphadenopathy, not active at brain metastasis diagnosis. No participants have developed lung metastases as of their most recent imaging. Conclusions: In this prospective pilot study, we found no increased prevalence of PFO in patients who develop brain metastases without preceding lung involvement compared to estimates for the general population. Though a larger study is needed, the development of brain metastases in these patients may reflect tumors’ biological factors directing metastasis organotropism, rather than a structural pathway.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi198-vi198
Author(s):  
Ruchi Raval ◽  
Aadi Pandya ◽  
Jaspreet Behl ◽  
Sumul Raval

Abstract PURPOSE As more information is gathered about brain metastases, it still remains that the current prognosis of brain metastases is very poor. Due to this, it is imperative that physicians are aware of the most important components regarding brain metastases. This literature review will encompass the most current literature in order to highlight the most crucial information. METHODS All mentioned studies and literature reviews cited in the paper were obtained through various sites, and were published between 1996 and 2017. The main components that were required from the papers reviewed included where in the body the brain metastases originated from, where in the brain they tended to spread to, what the signs and symptoms typical of patients with brain metastases are, and what the options are in terms of treatment. RESULTS Using the results from a variety of studies performed within the past three decades, it is apparent that brain metastases most commonly originate from, in order of increasing frequency, lung cancer, breast cancer, melanoma, and colorectal cancer. In addition, it is reaffirmed that the magnetic resonance imaging (MRI) is the best diagnostic tool to be used when dealing with brain metastases. The most frequent signs and symptoms of a brain metastases include cognitive changes, headaches, weakness, and seizures. Finally, supportive treatment includes use of corticosteroids, antiepileptic drugs (AEDs), and anticoagulation therapy. Definitive treatment for brain metastases varies based on size, location, and prevalence in the brain, but the most effective options include chemotherapy, radiation therapy, and surgery. CONCLUSIONS The study’s results confirm the need for more research to be done regarding brain metastases, and better options to increase the survival of patients.


2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i3-i3
Author(s):  
Katie Thies ◽  
Anisha Hammer ◽  
Blake Hildreth ◽  
Luke Russell ◽  
Steven Sizemore ◽  
...  

Abstract Stromal platelet-derived growth factor receptor-beta (PDGFRβ) has emerged as an actionable mediator of breast tumor-stromal communication. As a receptor tyrosine kinase, PDGFRβ is activated by its ligand, PDGFB, which is released by neighboring tumor epithelium and endothelium. However, how PDGF signaling mediates breast cancer (BC) initiation, progression, and metastasis remains unclear. To evaluate PDGFRβ in this disease, we developed a mouse model of stromal-specific PDGFRβ activation using the Fsp-cre transgene previously published by our group. Mesenchymal-specific activation of PDGFRβ promotes preferential experimental brain metastasis of PDGFB-expressing mammary tumor cells when injected intravenously and accelerates intracranial tumor growth of these cells. Mammary tumor cells expressing low levels of PDGFB do not exhibit a similar increase in brain metastases in PDGFRβ mutant mice. To our knowledge, this is the first example where genetic manipulation of the stroma leads to an increased incidence of BCBM. Our pre-clinical data suggests that primary breast tumors that express high PDGFB could preferentially metastasize to the brain. To test this in patients, we analyzed PDGFB protein expression in a tissue microarray comprised of HER2-positive and triple negative BC primary tumors. While high PDGFB did not correlate with site-independent metastatic recurrence, it was prognostic of brain metastasis, mirroring our mouse data. Our findings suggest that high primary tumor PDGFB expression defines a subset of BC patients predisposed to brain metastases. These patients may benefit from therapeutic intervention of PDGFRβ signaling. To test this pre-clinically, we treated mice harboring intracranial tumors with the PDGFR-specific inhibitor, crenolanib. Excitingly, crenolanib treatment significantly inhibited the brain tumor burden in these mice. Combined, our findings (1) advocate that primary tumor expression of PDGFB is a novel prognostic biomarker for the development of BCBM and (2) support clinical trial evaluation of PDGFR inhibitors for the prevention and treatment of BCBM.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi245-vi245
Author(s):  
Rupesh Kotecha ◽  
Muni Rubens ◽  
Sergio Gonzalez-Arias ◽  
Vitaly Siomin ◽  
Matthew Hall ◽  
...  

Abstract OBJECTIVE Up to 30% of cancer patients will develop brain metastasis during the course of their systemic disease with a significant proportion undergoing resection of at least one lesion. The objective of the present study was to characterize the rates, predictors, and costs of 30-day readmissions following craniotomy for brain metastases using a nationally representative database. METHODS This study was a retrospective analysis of data from the Nationwide Readmissions Database (NRD) from 2010–2014. We included patients who underwent craniotomy for brain metastasis, identified using ICD-9-CM diagnosis (198.3) and procedure (01.59) codes. The primary outcome of the study was unplanned 30-day all-cause readmission rates. Secondary outcomes included predictors and costs of readmissions. RESULTS During the study period, there were 44,846 index hospitalizations for patients who underwent resection of brain metastasis. Among this cohort, 17.8% (n=7,965) had unplanned readmissions within the first 30 days after discharge from the index hospitalization. The readmission rate did not change significantly during the study period (P=0.286). The odds of unplanned readmission were significantly greater in patients with thromboembolic complications (aOR, 1.53; 95% CI: 1.18–2.01), patients with Elixhauser comorbidities >3 (aOR, 1.35; 95% CI: 1.22–1.50), male patients (adjusted odds ratio [aOR], 1.29; 95% CI: 1.17–1.42), patients with an initial length of stay ≥5 days (aOR, 1.02; 95% CI: 1.01–1.03). The median per-patient cost for 30-day unplanned readmission was $11,109 and this accounted for a total cost of $132.1 million during the study period. CONCLUSIONS Unplanned readmissions after resection for brain metastases involve substantial healthcare expenditures. Though there have been many interventions for improving surgical quality, post-operative care, and cost metrics, unplanned readmission rates have not changed. Key patient-specific variables and high rates of comorbidities should be considered to focus our efforts on patient selection for resection, and for strengthening existing interventions for high-risk patients.


2019 ◽  
Vol 20 (12) ◽  
pp. 3080 ◽  
Author(s):  
Fan Wu ◽  
Robert D. McCuaig ◽  
Christopher R. Sutton ◽  
Abel H. Y. Tan ◽  
Yoshni Jeelall ◽  
...  

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.


2020 ◽  
Vol 39 (3) ◽  
pp. 711-720 ◽  
Author(s):  
Mari Hosonaga ◽  
Hideyuki Saya ◽  
Yoshimi Arima

Abstract Metastasis of cancer cells to the brain occurs frequently in patients with certain subtypes of breast cancer. In particular, patients with HER2-positive or triple-negative breast cancer are at high risk for the development of brain metastases. Despite recent advances in the treatment of primary breast tumors, the prognosis of breast cancer patients with brain metastases remains poor. A better understanding of the molecular and cellular mechanisms underlying brain metastasis might be expected to lead to improvements in the overall survival rate for these patients. Recent studies have revealed complex interactions between metastatic cancer cells and their microenvironment in the brain. Such interactions result in the activation of various signaling pathways related to metastasis in both cancer cells and cells of the microenvironment including astrocytes and microglia. In this review, we focus on such interactions and on their role both in the metastatic process and as potential targets for therapeutic intervention.


Sarcoma ◽  
2005 ◽  
Vol 9 (3-4) ◽  
pp. 147-150 ◽  
Author(s):  
Tejpal Gupta ◽  
Siddhartha Laskar ◽  
Sumeet Gujral ◽  
Mary Ann Muckaden

Background and purpose:Brain metastasis is a relatively uncommon event in the natural history of soft tissue sarcomas. The increasing use of chemotherapy may have caused a reduction in local relapses as well as distant failures leading to an improvement in survival, thereby allowing metachronous seeding of the brain, a sanctuary site. The purpose of this report is to increase awareness amongst clinicians regarding such a possibility.Patients and methods:A review of the departmental sarcoma database following the presentation of this index case in the clinic.Results and discussion:An adolescent male who had previously been treated with surgery and radiotherapy for a spindle cell sarcoma of the left thigh developed a space-occupying lesion in the brain within 6 months of treatment of the primary tumor. He subsequently underwent resection of the presumed solitary brain metastasis followed by whole brain radiotherapy. On radiation he was detected to have pulmonary metastases too, for which he was offered palliative chemotherapy. The patient died of brain metastasis within 4 months. A review of the departmental sarcoma database, restricted to soft tissue sarcomas purely, maintained prospectively from 2000 till date, could not identify any other such case.Conclusion:Brain metastases from soft tissue sarcomas are rare. Patients with neurological symptoms, however, should be appropriately investigated. Surgical resection of brain metastasis could be considered for solitary brain metastasis in non-eloquent areas. Palliative radiotherapy is appropriate for patients with multiple brain metastases or co-existing extra-cranial disease.


Neurosurgery ◽  
1988 ◽  
Vol 23 (6) ◽  
pp. 777-780 ◽  
Author(s):  
Harold Haft ◽  
George C. Wang

Abstract Metastatic liposarcomas to the brain are rare. The authors describe a patient with a 20-year history of liposarcoma originating in the thigh and metastatic to the brain 18 years later. The brain metastasis was removed by surgery. Nine months later, the patient developed metastases to the retroperitoneum and liver. At that same time, she had recurrent brain metastasis. She was then treated with chemotherapy. The abdominal mass shrank considerably in the beginning, and the recurrent brain metastases totally disappeared. The patient eventually succumbed to widespread liposarcoma. Autopsy revealed extensive liposarcoma involving the retroperitoneum, liver, and lung, but no trace of tumor was found in the brain.


2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Yoji Shido ◽  
Yukihiro Matsuyama

Alveolar soft part sarcoma (ASPS) is a rare malignant tumor that generally occurs in adolescents and young adults. It progresses slowly, but lung and brain metastases often occur in the early phase of the clinical course, and chemotherapy has been reported as not being effective for ASPS. Pazopanib is a multitargeted tyrosine kinase inhibitor that has been clinically available from November 2012 in Japan. This is a case report of a patient presented with multiple lung metastases and unresectable primary abdominal ASPS. We initially treated this patient by systemic chemotherapy with combination use of ifosfamide and doxorubicin. Stable disease was observed without any objective response. Then, we finally started to administrate pazopanib 800 mg/day. After 25 months of pazopanib administration, slight tumor reduction and a decrease of enhancement were observed. Objective responses were achieved for both the primary tumor and metastatic lung tumor; however, a newly developed brain metastasis was subsequently identified. Based on this case, pazopanib appears effective against ASPS, except for brain metastases. This case suggests that pazopanib may be useful as a first-line drug against unresectable ASPS and that longitudinal assessment of brain metastasis should be performed in similar cases.


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