Colorectal cancer and brain metastases: An aggressive disease with a different response to treatment

2018 ◽  
Vol 105 (5) ◽  
pp. 427-433 ◽  
Author(s):  
Georges Chahine ◽  
Tony Ibrahim ◽  
Tony Felefly ◽  
Abir El-Ahmadie ◽  
Pamela Freiha ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Brain Metastases ◽  
Median Survival ◽  
Metastatic Disease ◽  
Antiangiogenic Therapy ◽  
Response To Treatment ◽  
Aggressive Disease ◽  
Dismal Prognosis ◽  
Poor Outcomes ◽  
Different Response

Introduction: Brain metastases (BM) are rare in colorectal cancer (CRC) and are associated with a dismal prognosis. This work aims to report the rate of BM in CRC patients treated in a single institution, along with survival and prognostic factors. Methods: Medical charts for patients with histologically proven CRC were retrospectively reviewed. Results: A total of 538 patients were identified, of whom 33% developed any metastatic disease and 4.4% presented BM. Lung was the most frequently associated metastatic site (in 68% of the cases). The only factor independently associated with BM development was the presence of metastatic disease at the time of initial presentation. The median duration from initial diagnosis to BM development was 38.6 months (SD 29.1 months). Median survival after BM development was 62 days (95% confidence interval [CI] 56–68). Patients diagnosed with BM within 1 year of cancer diagnosis responded significantly better to treatment than those who acquired BM later, with a median survival after BM diagnosis of 261 days versus 61 days, respectively ( p = .002). Patients with BM who received antiangiogenic therapy had an improved median survival compared to those who did not (151 days vs 59 days, p = 0.02; hazard ratio for death 0.29 [95% CI 0.09–0.94]). Conclusion: CRC with BM is an aggressive disease resistant to standard treatment and is associated with poor outcomes. Adding antiangiogenic therapy might be of value for those patients. Patients with BM developing early in the disease course might respond better to treatment.

Response to induction or hypomethylating agent therapy among patients with myeloproliferative neoplasms progressing to accelerated or leukemic phase.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18561-e18561
Author(s):  
Gabriela Hobbs ◽  
Jennifer Lombardi Story ◽  
Maura A. Blaney ◽  
Philip C. Amrein ◽  
Amir Tahmasb Fathi ◽  
...  
Keyword(s):  
Median Survival ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Primary Myelofibrosis ◽  
Allogeneic Transplantation ◽  
Rank Test ◽  
Molecular Testing ◽  
Dismal Prognosis ◽  
Poor Outcomes

e18561 Background: Post-myeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) and accelerated phase disease (AP) are associated with poor outcomes; the optimal management of these patients at transformation is uncertain in the era of widely available molecular testing. Methods: We performed a retrospective analysis of adult patients with MPN that had transformed into AML (greater than 20% blasts) or AP (10-19% blasts and dysplastic features) from 2006-2016. Patients were 18 or older at AML/AP diagnosis. Outcomes were described by Kaplan and Meier and the Log rank test. Results: We identified 30 patients, with transformed MPN into AML (n = 23) or AP (n = 7), including one patient in AP at presentation. Most were male (73%). Disease evolved from polycythemia vera (n = 6), essential thrombocythemia (n = 11), primary myelofibrosis (n = 9) and other MPN diagnoses (MPN/MDS overlap, n = 3; MPN NOS, n = 1). The median age at MPN diagnosis was 67.5 yrs, and at transformation 72 yrs. The median time from MPN diagnosis to transformation was 5.6 yrs (range 0.3-36.0). 12 patients had JAK2 V617F testing both at MPN diagnosis and AML diagnosis; 6 had JAK2 mutations at both time points and 2 lost JAK2 at transformation. At AML/AP transformation, 11 patients had NGS mutation testing; the most common somatic mutations were NRAS (5/11), RUNX1 (2/11), and SRSF2 (2/11). 20 patients received treatment outside of supportive care. Of these, 8 achieved a CR or CRi (40%; 7/10 with induction and 1/8 with HMA). The only HMA response was on a trial of HMA+SGN33a. The median survival from AML/AP transformation was 5.8 mo. Of treated patients, median survival was 7.4 mo; 37% of treated patients were alive at 1 yr. Nine patients (31%; 7 with AML and 2 with AP) underwent allogeneic transplantation; 2 relapsed during follow-up. 74% of patients treated with allo-HCT were alive at 1 yr after AML/AP transformation. Conclusions: AML or accelerated phase disease arising out of MPN carries a dismal prognosis. HMA monotherapy had little efficacy in this group (0/7 achieved remission). Allogeneic transplantation offered the best chance of survival at one year, but fewer than a third of patients were able to proceed to transplant.

Tumor-informed assessment of molecular residual disease and its incorporation into practice for patients with early and advanced-stage colorectal cancer (CRC-MRD Consortia).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4108-4108 ◽  
Author(s):  
Pashtoon Murtaza Kasi ◽  
Farshid Dayyani ◽  
Van K. Morris ◽  
Scott Kopetz ◽  
Aparna Raj Parikh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Disease ◽  
Residual Disease ◽  
Early Stage ◽  
Circulating Tumor Dna ◽  
Response To Treatment ◽  
Chi Square ◽  
Multiplex Pcr Assay ◽  
Crc Management ◽  
First Time

4108 Background: Circulating tumor DNA (ctDNA) testing can be used for the assessment of molecular residual disease (MRD) in patients with early-stage or advanced colorectal cancer (CRC). Prospective evaluation of this methodology in clinical practice has been limited to-date. Methods: A personalized and tumor-informed multiplex PCR assay (Signatera 16-plex bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA for MRD assessment. We analyze and present results from an ongoing early adopter program of ctDNA testing across the spectrum of CRC management. Results: Here we present a total of 250 patients with colon (n=200), rectal (n=40), and other lower gastrointestinal cancers (n =10; anal, appendiceal, small bowel). MRD positivity rates and ctDNA quantification (mean tumor molecules/mL) are shown in Table. ctDNA detection was significantly associated with stage of disease (p<0.0001 Chi-square: 70.33). Additionally, in patients with radiologically measurable active metastatic disease, ctDNA detection rate was 100%. On the contrary, patients with advanced/metastatic disease who had partial response to treatment or no evidence of disease (NED) showed 28.5% and 19.2% of ctDNA-positivity, respectively. Conclusions: This is the first large, real-world study reporting on the results from a clinically validated MRD assay. For the first time we delineate MRD rates and quantify ctDNA concentration in patients with early-stage and advanced CRC. Furthermore, we provide an initial readout that effective ongoing treatment in patients with CRC may be correlated with ctDNA clearance. Ongoing analysis expanded to a cohort of 1200 clinical cases including correlation with genomic and serial testing will be presented. [Table: see text]

scholarly journals Distant Liver Metastases as a Major Factor Influencing Survival in Patients with Colorectal Cancer

Folia Medica ◽  
2016 ◽  
Vol 58 (3) ◽  
pp. 182-187
Author(s):  
Dimitar K. Penchev ◽  
Lilyana V. Vladova ◽  
Miroslav Z. Zashev ◽  
Radosvet P. Gornev
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Median Survival ◽  
Metastatic Disease ◽  
Descriptive Analysis ◽  
Distant Metastases ◽  
University Hospital ◽  
Rank Test ◽  
Hepatic Metastatic Disease

Abstract Aim: To assess the effect of the factor ‘hepatic metastatic disease’ on long-term outcomes in patients with colorectal cancer. Materials and methods: We analysed retrospectively 200 randomly selected patients. Forty-two of them were excluded from the study for different reasons so the study contingent was 158 patients over a period of 23 years. All were diagnosed and treated in the Lozenetz University Hospital, in the Department of General Surgery. 125 of the patients were diagnosed with colorectal cancer without distant metastases and 33 of the patients had liver metastases as a result of colorectal carcinoma. The statistical analysis was performed using SPSS 19 IMB, with a level of significance of P < 0.05 at which the null hypothesis is rejected. We also used descriptive analysis, Kaplan-Meier estimator, Log-Rank Test and Life-Table statistics models. Results: The median survival for patients without metastases was 160 months, and the median was 102 months. The median survival for patients with liver metastases was 28 months and the median was 21 months. One-year survival for patients without metastases was 92% versus 69% in patients with liver metastases. Conclusion: Average, annual and median survivals are influenced statistically significantly by the presence of liver metastases compared to overall survival and that of patients without metastatic colorectal cancer. Liver metastatic disease is a proven factor affecting long-term prognosis and survival in patients with colorectal cancer.

Treatment of unresectable or metastatic pancreatic cancer in the VA population: Does it improve survival?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15121-15121
Author(s):  
S. F. Mekan ◽  
R. S. Komrokji ◽  
M. S. Beg ◽  
Z. A. Nahleh ◽  
M. M. Safa
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Metastatic Disease ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Unresectable Disease ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Poor Outcomes

15121 Background: Locally advanced and metastatic pancreatic adenocarcinoma present as a treatment challenge because of poor outcomes with current treatment modalities. Therapy of unresectable or metastatic disease has not been studied in the VA population. Methods: We reviewed all cases of pancreatic cancer presenting to the system from 1995–2005. Cases were extracted from the VA Cancer Registry (VACCR). Results: There were 5522 cases identified; 5218 were adenocarcinomas. Out of these, there were 263 (5.1%) patients with unresectable locally advanced disease and 2778 (53.2%) patients with metastatic disease. Median survival for patients with unresectable disease was 5.6 months. Chemotherapy was administered to 94 patients and chemoradiation to 31 patients. No difference in survival was noted between the two groups (8.4 vs. 7.9 months, P = 0.434). In patients with metastatic disease, median survival was 2.2 months. Chemotherapy was administered to 760 (27%) patients in this group and showed improved survival as compared to patients who did not receive chemotherapy (5.3 vs. 1.5 months, p = 0.000). Conclusions: In VA patients with locally advanced unresectable disease, there is no difference in survival in patients treated with chemoradiation versus chemotherapy alone. In patients with metastatic disease, chemotherapy conferred a survival advantage. No significant financial relationships to disclose.

scholarly journals Epigenetic Biomarkers in Colorectal Cancer Patients Receiving Adjuvant or Neoadjuvant Therapy: A Systematic Review of Epidemiological Studies

2019 ◽  
Vol 20 (15) ◽  
pp. 3842 ◽  
Author(s):  
Barchitta ◽  
Maugeri ◽  
Destri ◽  
Basile ◽  
Agodi
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Adverse Effects ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
Epidemiological Studies ◽  
Response To Treatment ◽  
Epigenetic Biomarkers ◽  
Epigenetic Biomarker ◽  
Different Response

Colorectal cancer (CRC) represents the third-most common cancer worldwide and one of the main challenges for public health. Despite great strides in the application of neoadjuvant and adjuvant therapies for rectal and colon cancer patients, each of these treatments is still associated with certain adverse effects and different response rates. Thus, there is an urgent need for identifying novel potential biomarkers that might guide personalized treatments for specific subgroups of patients. However, until now, there are no biomarkers to predict the manifestation of adverse effects and the response to treatment in CRC patients. Herein, we provide a systematic review of epidemiological studies investigating epigenetic biomarkers in CRC patients receiving neoadjuvant or adjuvant therapy, and their potential role for the prediction of outcomes and response to treatment. With this aim in mind, we identified several epigenetic markers in CRC patients who received surgery with adjuvant or neoadjuvant therapy. However, none of them currently has the robustness to be translated into the clinical setting. Thus, more efforts and further large-size prospective studies and/or trials should be encouraged to develop epigenetic biomarker panels for personalized prevention and medicine in CRC cancer.

Survival advantage associated with palliative oophorectomy in patients with metastatic colorectal cancer (CRC) to the ovaries (mCRC-O): A single institution retrospective analysis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 539-539
Author(s):  
B. George ◽  
Y. You ◽  
C. Viswanathan ◽  
S. Wen ◽  
V. Baladandayuthapani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Median Survival ◽  
Metastatic Disease ◽  
Survival Data ◽  
Bilateral Oophorectomy ◽  
Single Institution ◽  
Ovarian Metastases ◽  
Disease Response ◽  
Resected Stage

539 Background: The ovaries are an uncommon site for secondary spread from metastatic CRC. We hypothesize that palliative oophorectomy improves survival among patients with mCRC-O. Methods: We undertook a single institution IRB-approved (DR-09-623) retrospective evaluation of women with mCRC-O from 2001-2008; 110 pts with ovarian metastases and follow-up information for survival analysis were identified out of 3,776 female pts with CRC (2.9%). Survival data was calculated from the date of diagnosis of ovarian metastases (by pathology or radiology) to date of death. Results: Median age of patients was 49 years (range 19-82); median duration of follow-up was 49 months. Twenty patients were identified from 1,758 female patients with CRC seen at our institution from 2001-2004 (1.1%) and ninety patients identified from 2,018 female CRC patients from 2005-2008 (4.5%). KRAS mutation was present in the primary tumor in 23 of 43 (54%). Sixteen evaluable patients who received systemic chemotherapy with mCRC-O and other sites of metastatic disease were identified; five (31%) had a mixed radiographic response (progression in the ovarian metastases with disease response in other sites of metastases). Seventy-one (64.5%) patients had metastatic disease at the time of initial presentation; 39 (35.5%) had completely resected stage II or III CRC with mCRC-O occurring at a later date. 86 (78.2%) underwent unilateral or bilateral oophorectomy for treatment of their disease. Patients who had metastatic disease at presentation and underwent oophorectomy had a median survival of 39.4 months versus 18.2 months for those with ovarian metastases left in situ (p < 0.0001); patients who developed ovarian relapse after prior colectomy and subsequently underwent oophorectomy had a median survival of 50 months versus 12 months for those patients who did not (p = 0.001). Patients with mCRC-O and peritoneal metastases had a significantly worse survival (p = 0.003). Conclusions: This single institution retrospective data analysis suggests that women with colorectal cancer metastatic to the ovaries may derive a survival benefit from palliative oophorectomy. No significant financial relationships to disclose.

scholarly journals SURG-06. MANAGEMENT OF HYDROCEPHALUS IN ADULT PATIENTS WITH BRAIN METASTASES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii204-ii204
Author(s):  
A Vaynerman ◽  
L Coombs ◽  
H Nickols ◽  
R LaRocca ◽  
K Sinicrope ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Median Survival ◽  
Systemic Therapy ◽  
Odds Ratio ◽  
Leptomeningeal Carcinomatosis ◽  
Third Ventriculostomy ◽  
Improved Outcomes ◽  
Poor Outcomes ◽  
Historical Controls

Abstract BACKGROUND Traditionally patients presenting with hydrocephalus in the setting of brain metastases were associated with poor outcomes. However, in the area of improved systemic therapies, the prognosis of brain metastases has improved, warranting investigation into the management of concomitant hydrocephalus. METHODS We conducted a retrospective review of 12 consecutive patients with brain metastases presenting with hydrocephalus treated with either endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunt (VPS) from June 2013 to December 2018. We then compared our outcomes to 77 historical controls from the literature to test the hypothesis that management of hydrocephalus in patients who respond to systemic therapy is associated with improved outcomes. RESULTS The medial overall survival in our cohort was 182 days compared with 91 days in the reported previous studies, with an odds ratio of 0.5 (95% CI 0.24-1.04). In the 5 patients who underwent ETV, the median survival was 182 days versus 77 days reported in the literature, an odds ratio of 0.42 (95% CI 1.28-1.40). Patients with one brain metastasis did not reach median survival with 4 of 5 patients alive at last follow up, while only 3 of 7 patients with at least two metastases were alive at follow up with a median survival of 182 days. Patients who had immunotherapy were associated with improved survival, while leptomeningeal carcinomatosis still was associated with a negative outcome. CONCLUSIONS Patients with brain metastases and hydrocephalus who underwent neurosurgical CSF diversion had improved survival compared with historical controls, particularly in patients with one metastasis or who received immunotherapy. This study supports initial interdisciplinary evaluation of patients with brain metastases by medical and radiation oncology together with neurosurgery to facilitate immediate systemic therapy after relief of hydrocephalus.

Gamma knife radiosurgery for renal cell carcinoma brain metastases

2002 ◽  
Vol 97 ◽  
pp. 489-493 ◽  
Author(s):  
Laura Hernandez ◽  
Lucia Zamorano ◽  
Andrew Sloan ◽  
James Fontanesi ◽  
Simon Lo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Gamma Knife ◽  
Median Survival ◽  
Renal Cell ◽  
Univariate Analysis ◽  
Gamma Knife Radiosurgery ◽  
Content Type ◽  
Fine Print

Object. The purpose of this study was to clarify the effectiveness of gamma knife radiosurgery (GKS) in achieving a partial or complete remission of so-called radioresistant metastases from renal cell carcinoma (RCC) and to propose guidelines for optimal treatment Methods. During a 5-year period, 29 patients (19 male and 10 female) with 92 brain metastases from RCC underwent GKS. The median tumor volume was 4.7 cm3 (range 0.5–14.5 cm3). Fourteen patients (48%) also underwent whole-brain radiotherapy (WBRT) before GKS, and two patients (6.8%) after GKS. The mean GKS dose delivered to the 50% isodose at the tumor margin was 16.8 Gy (range 13–30 Gy). All cases were categorized according to the Recursive Partitioning Analysis (RPA) classification for brain metastases. Univariate analysis was performed to determine significant prognostic factors and survival. The overall median survival was 7 months after GKS treatment. Age, sex, Karnofsky Performance Scale score, and controlled primary disease were not predictors of survival. Combined WBRT/GKS resulted in median survival of 18, 8.5, and 5.3 months for RPA Classes I, II, and III, respectively, compared with the median survival 7.1, 4.2, and 2.3 months for patients treated with WBRT alone. Conclusions. These results suggest that WBRT combined with GKS may improve survival in patients with brain metastases from RCC. Furthermore, this improvement in survival was seen in all RPA classes.

Long-Term Outcomes of Organ Preservation in Patients with Small Cell Carcinoma of the Bladder

2015 ◽  
Vol 94 (4) ◽  
pp. 401-405 ◽  
Author(s):  
Jairam R. Eswara ◽  
Niall M. Heney ◽  
Chin-Lee Wu ◽  
W. Scott McDougal
Keyword(s):  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Metastatic Disease ◽  
Advanced Disease ◽  
Chemical Exposure ◽  
Small Cell ◽  
Cancer Specific Survival ◽  
Entire Cohort ◽  
Aggressive Disease ◽  
Carcinoma Of The Bladder

Background: Small cell carcinoma of the bladder is an uncommon but clinically aggressive disease. There is no standard surgical or medical management for the disease. Methods: Between 1995 and 2009, 28 patients underwent transurethral resection (TUR) and/or cystectomy, chemotherapy, and/or radiation for small cell carcinoma of the bladder at our institution. Results: The median follow-up for survivors was 34 months. Patients presented most often with muscle-invasive disease (T2-4 - 89%), and 21% had lymph node/distant metastases. Tobacco use and chemical exposure were noted in 64 and 4% of patients, respectively. Patients with T1-2N0M0 had a median survival of 22 months compared to 8 months for those with more advanced disease (p = 0.03). Patients with T3-4 or nodal/metastatic disease who were given chemotherapy had an improved survival compared to those with T3-4 or nodal/metastatic disease who did not undergo chemotherapy (13 vs. 4 months, p = 0.005). The median time to recurrence of the entire cohort was 8 months, overall and cancer-specific survival was 14 months, and 5-year survival was 11%. Conclusions: Small cell carcinoma of the bladder is an aggressive disease with poor outcomes. Patients with T1-2N0M0 disease survived longer than those with advanced disease. Patients with T3-4 or nodal/metastatic disease had improved survival with chemotherapy.

scholarly journals Survival of patients with synchronous brain metastases: an epidemiological study in southeastern Michigan

2000 ◽  
Vol 9 (2) ◽  
pp. 1-5 ◽  
Author(s):  
Ajith J. Thomas ◽  
Jack P. Rock ◽  
Christine C. Johnson ◽  
Linda Weiss ◽  
Gordon Jacobsen ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Median Survival ◽  
Cancer Diagnosis ◽  
Systemic Disease ◽  
Primary Source ◽  
Primary Site ◽  
Unknown Primary ◽  
Primary Cancer ◽  
Significant Difference ◽  
Frequent Site

Object It has been suggested that synchronous brain metastases (that is, those occurring within 2 months of primary cancer diagnosis) are associated with a shorter survival time compared with metachronous lesions (those occurring greater than 2 months after primary cancer diagnosis). In this study the authors used data obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program to determine the incidence of synchronous brain metastases and length of survival of patients in a defined population of southeastern Michigan residents. Methods Data obtained in 2682 patients with synchronous brain metastases treated from 1973 to 1995 were reviewed. Study criteria included patients in whom at least one brain metastasis was diagnosed within 2 months of the diagnosis of primary cancer and those with an unknown primary source. The incidence per 100,000 increased fivefold, from 0.69 in 1973 to 3.83 in 1995. The most frequent site for the primary cancer was the lung (75.4%). The second largest group (10.7%) consisted of patients in whom the primary site was unknown. The median survival length was 3.3 months. There was no significant difference in the median survival in patients with primary lung/bronchus and those with an unknown primary site (3.2 months and 3.4 months, respectively). Conclusions Patients who present with synchronous lesions have a poor prognosis, and the predominant cause of death, in greater than 90% of cases, is related to systemic disease; however, despite poor median survival lengths, certain patients will experience prolonged survival.

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