Leptomeningeal carcinomatosis in colorectal cancer: The Mayo Clinic experience.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 710-710
Author(s):  
Gretchen E Taylor ◽  
Nina J. Karlin ◽  
Thorvardur Ragnar Halfdanarson ◽  
Kyle Coppola ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Disease ◽  
Mayo Clinic ◽  
Treatment Options ◽  
Palliative Radiotherapy ◽  
Leptomeningeal Metastasis ◽  
Leptomeningeal Carcinomatosis ◽  
Mri Findings ◽  
Lower Extremity Weakness ◽  
Neurologic Symptoms

710 Background: Leptomeningeal metastasis (LM) has been described as a rare form of metastatic disease progression in colorectal cancer (CRC). There remains a paucity of literature with regards to the course and management of LM in CRC. The aim of this study was to estimate the incidence of LM in CRC patients seen at our institution over a 15-year period, and to describe the clinical course and outcome of these cases. Methods: LM in CRC primary cases between 2000 and 2014 were identified in the Mayo Clinic databases. The charts were retrospectively reviewed. Results: Of 17,095 CRC primaries, we identified 10 patients with LM (0.058%) in this 15-year period. Nine cases were included in the analysis. Four had metastatic disease at the time of their initial CRC diagnosis. One patient also had a lung adenocarcinoma diagnosed during initial staging for the CRC primary. Median overall survival after CRC diagnosis was 25.7 months (range 4.7-74.8). Median time to diagnosis of LM after CRC diagnosis was 25.3 months (range 1-68.1). All patients had MRI findings consistent with LM: 3 patients with spinal LM, 5 patients with intracranial LM, 1 with both. One of three CSF analyses at the time of LM workup was positive for malignant cells; all had elevated protein. Neurologic symptoms correlated with site of the lesions, with headache, cranial nerve palsy, lower extremity weakness, and gait disturbance among the most frequently reported. However, not all patients had neurologic findings, with LM lesions found incidentally in two cases. Seven patients (78%) had palliative radiotherapy (RT) for LM. Three patients continued to receive systemic chemotherapy after diagnosis of LM. No patients underwent intrathecal chemotherapy. Median survival after LM diagnosis was 7 weeks (range 2-39). Conclusions: The diagnosis of LM is an exceedingly rare development in the natural course of CRC. It continues to confer an extremely poor prognosis with limited treatment options. At our institution, most patients had their disease addressed by palliative means, with many receiving RT to control their neurologic symptoms. Based on our series, supportive care remains a sensible approach to the management of LM in CRC.

scholarly journals A Case of Leptomeningeal Carcinomatosis from Aggressive Metastatic Prostate Cancer

2019 ◽  
Vol 12 (1) ◽  
pp. 311-316 ◽  
Author(s):  
Ryan David Carroll ◽  
E. Cindy Leigh ◽  
Zachary Curtis ◽  
Anthony Thorpe ◽  
Jason Ballengee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Brain Mri ◽  
Altered Mental Status ◽  
Leptomeningeal Carcinomatosis ◽  
Cancer Therapies ◽  
Csf Cytology ◽  
Lower Extremity Weakness ◽  
Confirmatory Tests ◽  
Technological Improvements

Leptomeningeal carcinomatosis (LC) is a rare leptomeningeal spread of diffusely metastatic tumors. It occurs more commonly with hematologic tumors, less commonly with solid tumors, and is exceedingly rare in prostate cancer. Due to its scarcity, it has traditionally been difficult to diagnose LC but advancement of MRI has helped considerably. However, even with technological improvements, pre-mortem diagnosis of LC remains difficult and controversial. Our case is a 71-year-old male with prostate cancer with bone metastases who presented to our facility with altered mental status (AMS), lower extremity weakness, and worsening diarrhea. The diarrhea was responsive to antibiotic therapy, but his AMS did not resolve. A head CT without contrast was negative but follow-up brain MRI revealed leptomeningeal enhancement highly suggestive of LC. Cerebrospinal fluid (CSF) cytology results were negative and other CSF studies were inconclusive. Although further studies were planned, the patient continued to deteriorate, and the family elected to withdraw care. He passed away without beginning treatment for the LC. Despite advances in cancer therapies, LC remains difficult to diagnose and treat. Imaging may be suggestive of the condition but the confirmatory tests such as repeated CSF cytology or meningeal biopsy are not only invasive but also usually occur postmortem. Additional methods of CSF testing have been studied to evaluate their role in accurately diagnosing LC but low specificity for LC has somewhat limited their use. Although treatment options are mainly palliative in nature, prompt recognition and early treatment could grant valuable time for patients and families.

Efficacy of temozolomide in pretreated patients with metastatic sarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23550-e23550
Author(s):  
Nail Paksoy ◽  
Izzet Dogan ◽  
Meltem Ekenel ◽  
Mert Basaran
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Metastatic Disease ◽  
De Novo ◽  
Treatment Options ◽  
Palliative Radiotherapy ◽  
Progression Free Survival ◽  
Primary Treatment Modality ◽  
Heavily Pretreated ◽  
Metastatic Sarcoma

e23550 Background: Sarcoma is a rare heterogeneous group malignancy and most commonly arises from soft tissue. The primary treatment modality is surgery. However, in metastatic disease, treatment options are limited. Cytotoxic chemotherapy is preferred for palliative treatment. This study aimed to assess the efficacy of temozolomide in heavily pretreated soft tissue sarcoma. Methods: We evaluated the patients with a metastatic various types of soft tissue sarcoma retrospectively. The patients with gastrointestinal stromal tumors and bone sarcomas were excluded from the study. We recorded the clinical, pathological, and treatment data of the patients. SPSS 25v was used for statistical analysis. Survival analysis was performed with the Kaplan-Meier method. Results: Sixteen patients were included in this study. The median age was 48 (range, 21-73) years. Six (37.5%) patients were de-novo metastatic. Tumor localizations were intra-abdominal (43.8%), extremity (31.2%), intrathoracic (12.5%), and head-and-neck (12.5%). The most common metastatic sites were lung (75%), bone (31.8%), liver (18.8%), respectively. For metastatic disease, the patients received at least two different chemotherapy regimens (75%), pazopanib (50%) and palliative radiotherapy (31.3%). Metastasectomy was also performed on five (31.3%) patients. Median progression-free survival was 3.5 (95% CI, 2.6-4.3) months. Partial response was observed in one (6.3%) patients, stable disease in four (25 %) patients. Eleven (68.8%) patients had progressive disease. Grade 1-2 adverse events were observed in nine (56.3%) patients, grade 3-4 in one (6.3%) patients. Conclusions: We showed that temozolomide was well-tolerated but had a limited efficacy for the treatment of patients with metastatic sarcoma. Treatment options for metastatic sarcomas are limited. Temozolomide may be considered a treatment option in patients with heavily pretreated soft tissue sarcoma.

scholarly journals Response to Olaparib in a Patient with Germline BRCA2 Mutation and Breast Cancer Leptomeningeal Carcinomatosis

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Pedro Exman ◽  
Robert M. Mallery ◽  
Nancy U. Lin ◽  
Heather A. Parsons
Keyword(s):  
Breast Cancer ◽  
Metastatic Cancer ◽  
Parp Inhibitor ◽  
Treatment Options ◽  
Brca2 Mutation ◽  
Leptomeningeal Metastasis ◽  
Complete Response ◽  
Parp Inhibitors ◽  
Leptomeningeal Carcinomatosis ◽  
Response To Treatment

AbstractLeptomeningeal carcinomatosis (LC) is a devastating complication of metastatic cancer that disproportionately affects patients with advanced breast cancer. Moreover, those with BRCA1/2-mutated disease more often experience leptomeningeal metastasis. Treatment options for LC are limited and often include significant toxicities. PARP inhibitors offer an important potential treatment for patients with BRCA1/2-mutated breast and ovarian cancers, but clinical studies excluded patients with central nervous system (CNS) metastases, including LC. Efficacy data in this area are therefore limited, although a phase I study of olaparib in glioblastoma did show CNS penetration. Here we report a case of a patient with BRCA2-mutated breast cancer and solitary recurrence in the leptomeninges with ongoing complete response to treatment with the PARP inhibitor olaparib. PARP inhibitors may be an important treatment option for patients with BRCA-mutated disease and LC, and warrant further study.

scholarly journals Thumb metastases in a patient with colorectal cancer

2007 ◽  
Vol 15 (3-4) ◽  
pp. 97-98 ◽  
Author(s):  
Ivan Nikolic ◽  
Aleksandar Patrnogic ◽  
Bratislav Stojiljkovic ◽  
Bogdan Bogdanovic ◽  
Biljana Kukic
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Disease ◽  
Proximal Phalanx ◽  
Lumbar Vertebra ◽  
Palliative Radiotherapy ◽  
Metastatic Colorectal Carcinoma ◽  
Primary Surgery ◽  
History Of ◽  
Histopathologic Analysis ◽  
Hand Radiography

Bone metastases from colorectal cancer are not common and most frequently are manifesting in late history of metastatic disease. We present a 67-old man who had first symptoms of metastatic disease manifested with edema and decreased mobility of thumb of right hand. Radiography showed complete osteolysis of proximal phalanx of thumb, which appeared 30 months after primary surgery for colorectal cancer. Histopathologic analysis of amputated thumb confirmed diagnosis of metastatic colorectal carcinoma and excluded osteolysis of other reasons. Metastatic changes in the first and second lumbar vertebra, which were treated with palliative radiotherapy, were confirmed by additional diagnostics.

Leptomeningeal Carcinomatosis in Colorectal Cancer: The Mayo Clinic Experience

2018 ◽  
Vol 17 (2) ◽  
pp. e183-e187 ◽  
Author(s):  
Gretchen Taylor ◽  
Nina Karlin ◽  
Thorvardur R. Halfdanarson ◽  
Kyle Coppola ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Mayo Clinic ◽  
Leptomeningeal Carcinomatosis ◽  
Clinic Experience

scholarly journals Isolation and Enumeration of Circulating Tumor Cells (CTC) as Prognostic and Predictive Biomarkers in Post-Operative m-CRC

2021 ◽  
pp. 1-6
Author(s):  
Swaroop G
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Disease ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
Liquid Biopsies ◽  
Prognostic Information ◽  
Clinical Prognosis

Circulating Tumor Cells (CTCs) presents non-invasive, repeatable investigation of patient‘s disease. In metastatic Colorectal Cancer (m-CRC) patients, CTC enumerations have been comprehensively studied in evaluating metastatic disease. CTC analysis has been shifting from enumeration to more sophisticated molecular depiction of tumor cells, which is used for liquid biopsy of the tumor, reflecting cytological and molecular changes in metastatic patients over time. In this study, CTC enumeration in advanced and localized metastatic colorectal cancer, highlights the vital gains as well as the challenges posed by various approaches, and their implications for advancing disease management. Detection of circulating tumor cells (CTC‘s) or circulating free tumor DNA (ctDNA) to conduct chemotherapy and reporting prognosis is extremely important, In view of the detail CTC has the potential to offer multiple samples by way of sequential minimally-invasive liquid biopsies. In fastidious, there is escalating evidence for the efficacy of CTC‘s in the clinical management of metastatic colorectal cancer (CRC). With most studies confirming the association of elevated CTC counts with worse prognosis. CTC‘s were first identified by Ashworth in 1869. CTC research has been vulnerable by the failure to constantly detect these typical cells. While the normal range of WBCs in human blood is 4.5-119/L, there may only be a few CTC‘s. The most widely used CTC enumeration platform, Cell-Search (Veridex LLC, NJ, USA) was approved for clinical use. As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. Investigations were carried out that Circulating Tumor Cells (CTCs) could predict clinical prognosis in patients with mCRC. This pilot study, demonstrates that CTCs can serve as both prognostic and predictive factor for patients with mCRC. The presence of at least three CTCs at baseline and follow-up is a strong independent prognostic factor for inferior PFS and OS. When utilized in combination with imaging studies, CTCs provide additional prognostic information. There are several studies for which CTCs could have efficacy inmetastatic colorectal cancer. The statistics suggests that CTCs may be used as a stratification feature in metastatic disease treatment trials. The current list of validated prognostic factors is short, with only routine status being universally recognized. Further study should prospectively deal with modification of regimens based on unfavorable CTCs early in the course of treatment will result in enhancement in PFS or OS. As treatment has become more effective for metastatic disease, decision making has become more complicated. Five classes of drugs are on hand for treatment. The most common initial chemotherapy is a fluoropyrimidine with oxaliplatin or irinotecan. CTC levels drawn at 3 to 5 weeks and 6 to 12 weeks, before PET imaging, may lead to prospective regimen choices and standby patients from unnecessary drug toxicity by suggesting that an early change in treatment is defensible.

scholarly journals Landscape of Current Targeted Therapies for Advanced Colorectal Cancer

2021 ◽  
Author(s):  
Ana João Pissarra ◽  
Catarina Abreu ◽  
André Mansinho ◽  
Ana Lúcia Costa ◽  
Sara Dâmaso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Disease ◽  
Targeted Therapies ◽  
High Throughput Sequencing ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Her2 Overexpression ◽  
Braf Mutations ◽  
Therapeutic Landscape ◽  
Cancer Types

Colorectal cancer (CRC) is one of the most frequent and lethal cancer types worldwide. While surgery with chemotherapy and radiotherapy remains the only curative approach for localized CRC, for metastatic disease the therapeutic landscape has significantly evolved over the last years. Development and approval of novel targeted therapies, such as monoclonal antibodies against EGFR and VEGF, have significantly increased the median survival of patients with metastatic disease, with some trials reporting a benefit over 40 months. Increasing accessibility of high throughput sequencing has unraveled several new therapeutic targets. Actionable alterations, such as HER2 overexpression, BRAF mutations, and NTRK fusions, are currently available in metastatic disease, providing significant therapeutic opportunities for these patients, while new emerging agents, as immune checkpoint inhibitors, promise better treatment options in the near future. In this chapter, an overview of established and future CRC targeted therapies in the clinical setting is provided, as well as their mechanism of action, limitations, and future applicability.

Change of clinical features and outcomes of adolescents and young adults (AYA) with colorectal cancer over time: Pooled analysis of 26,768 patients in the National Cancer Database (NCDB).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 256-256
Author(s):  
Sally Jeanne Trufan ◽  
William Mills Worrilow ◽  
Kunal C. Kadakia ◽  
Reza Nazemzadeh ◽  
Laura W. Musselwhite ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Features ◽  
Metastatic Disease ◽  
Treatment Options ◽  
Stage Iv ◽  
Pooled Analysis ◽  
Primary Tumor Site ◽  
Disease Etiology ◽  
Health Insurance Status ◽  
Over Time

256 Background: The incidence of colorectal cancer (CRC) in younger patients (pts) is rising. The underlying etiology is unknown, and it is uncertain if disease biology and clinical features are changing over time. Methods: A retrospective study of pts data in the NCDB was performed to compare the clinicopathological features and outcomes of AYA with CRC over a 12-year period. Pts diagnosis period was dichotomized into older (2004 – 2009) and newer (2010 – 2015) eras. Uni- and multi-variable chi-square, logistic regression, and survival analyses were used for comparisons. Survival differences were assessed using Kaplan-Meier curves. Results: In total, 26,768 AYA (18-40yrs) with CRC were identified and included in the analysis: 45.8% (n = 12,268) from the older and 54.2% (n = 14,500) from the newer era. There were no differences between the 2 groups in gender distribution or levels of income and education. However, in the newer vs. older era, there was a greater proportion of non-white, non-black pts (7.2% vs. 6%; p = 0.0005) and pts diagnosed between the ages of 18-30 (21.1% vs. 18.8%; p < .0001). Pts in the newer era tended to have more comorbidities (8.6 vs 7.5%; p = 0.0012), left-sided tumors (77.5% vs. 76.1%; p = 0.04), and well-differentiated histology (12.0% vs. 8.3%; p < 0.0001). Newer era pts also had lower rates of metastatic disease at presentation (15.3% vs. 18.2%; p < 0.001%) and nodal involvement (54.9 vs. 58.4%; p < 0.001%). Median OS of pts with stage IV disease appears to have improved over time (24.1 vs. 22.5 mos; p = 0.014). After controlling for age, race, primary tumor site and grade, presence of comorbidities, and health insurance status, older era pts with stage IV CRC were at a 15.1% greater risk of all-cause death by year 5 compared to newer era pts (HRadj= 1.15 (1.07-1.24, p = 0.0001). Conclusions: Our data suggest that AYA with CRC in more recent years tend to present at a younger age and have a lower rate of metastatic disease. They also have improved survival. Further investigation of AYA disease etiology and biology are warranted. Continued efforts to increase awareness, promote early detection, and improve treatment options are essential.

scholarly journals Dedicated MRI staging versus surgical staging of peritoneal metastases in colorectal cancer patients considered for CRS-HIPEC; the DISCO randomized multicenter trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
M. P. Engbersen ◽  
C. J. V. Rijsemus ◽  
J. Nederend ◽  
A. G. J. Aalbers ◽  
I. H. J. T. de Hingh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Diagnostic Laparoscopy ◽  
Controlled Trial ◽  
Peritoneal Metastases ◽  
Surgical Staging ◽  
Mri Findings ◽  
Mri Staging ◽  
Multicenter Randomized Controlled Trial ◽  
Colorectal Cancer Patients

Abstract Background Selecting patients with peritoneal metastases from colorectal cancer (CRCPM) who might benefit from cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is challenging. Computed tomography generally underestimates the peritoneal tumor load. Diagnostic laparoscopy is often used to determine whether patients are amenable for surgery. Magnetic resonance imaging (MRI) has shown to be accurate in predicting completeness of CRS. The aim of this study is to determine whether MRI can effectively reduce the need for surgical staging. Methods The study is designed as a multicenter randomized controlled trial (RCT) of colorectal cancer patients who are deemed eligible for CRS-HIPEC after conventional CT staging. Patients are randomly assigned to either MRI based staging (arm A) or to standard surgical staging with or without laparoscopy (arm B). In arm A, MRI assessment will determine whether patients are eligible for CRS-HIPEC. In borderline cases, an additional diagnostic laparoscopy is advised. The primary outcome is the number of unnecessary surgical procedures in both arms defined as: all surgeries in patients with definitely inoperable disease (PCI > 24) or explorative surgeries in patients with limited disease (PCI < 15). Secondary outcomes include correlations between surgical findings and MRI findings, cost-effectiveness, and quality of life (QOL) analysis. Conclusion This randomized trial determines whether MRI can effectively replace surgical staging in patients with CRCPM considered for CRS-HIPEC. Trial registration Registered in the clinical trials registry of U.S. National Library of Medicine under NCT04231175.

scholarly journals Hypoxia-inducible Factor 2α: A Key Player in Tumorigenesis and Metastasis of Pheochromocytoma and Paraganglioma?

2021 ◽  
Author(s):  
Nicole Bechmann ◽  
Graeme Eisenhofer
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathways ◽  
Metastatic Disease ◽  
Therapeutic Intervention ◽  
Treatment Options ◽  
Hypoxia Inducible Factor ◽  
Germline Mutations ◽  
Driver Mutations ◽  
Mesenchymal Transition ◽  
Therapeutic Relevance

AbstractGermline or somatic driver mutations linked to specific phenotypic features are identified in approximately 70% of all catecholamine-producing pheochromocytomas and paragangliomas (PPGLs). Mutations leading to stabilization of hypoxia-inducible factor 2α (HIF2α) and downstream pseudohypoxic signaling are associated with a higher risk of metastatic disease. Patients with metastatic PPGLs have a variable prognosis and treatment options are limited. In most patients with PPGLs, germline mutations lead to the stabilization of HIF2α. Mutations in HIF2α itself are associated with adrenal pheochromocytomas and/or extra-adrenal paragangliomas and about 30% of these patients develop metastatic disease; nevertheless, the frequency of these specific mutations is low (1.6–6.2%). Generally, mutations that lead to stabilization of HIF2α result in distinct catecholamine phenotype through blockade of glucocorticoid-mediated induction of phenylethanolamine N-methyltransferase, leading to the formation of tumors that lack epinephrine. HIF2α, among other factors, also contributes importantly to the initiation of a motile and invasive phenotype. Specifically, the expression of HIF2α supports a neuroendocrine-to-mesenchymal transition and the associated invasion-metastasis cascade, which includes the formation of pseudopodia to facilitate penetration into adjacent vasculature. The HIF2α-mediated expression of adhesion and extracellular matrix genes also promotes the establishment of PPGL cells in distant tissues. The involvement of HIF2α in tumorigenesis and in multiple steps of invasion-metastasis cascade underscores the therapeutic relevance of targeting HIF2α signaling pathways in PPGLs. However, due to emerging resistance to current HIF2α inhibitors that target HIF2α binding to specific partners, alternative HIF2α signaling pathways and downstream actions should also be considered for therapeutic intervention.

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