Primary colon cancer site as a predictor of bevacizumab effectiveness in metastatic colon cancer patients.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 574-574
Author(s):  
R. Islam ◽  
P. Chyou ◽  
H. Ege ◽  
A. Deedon ◽  
J. K. Burmester

574 Background: Bevacizumab has been approved by the FDA for first-line treatment in combination with chemotherapy for metastatic colon cancer. Although bevacizumab extends progression free survival and overall survival for many metastatic colon cancer patients, primary cancer site has not been examined as a predictor of its effectiveness. Methods: Data regarding bevacizumab treatment for colorectal cancer were abstracted from the medical record of 175 patients treated at a large multi-specialty clinic. Data were collected regarding demographics, body mass index, weight loss, lifestyle variables (smoking status, drinking habit), history of colon polyps, family history of cancer, primary site of tumor in the colon, tumor stage, lymph node involvement, metastasis, tumor grade of metastasis, cancer cell type, symptoms related to the cancer, and other comorbidities (cardiovascular disease, diabetes mellitus, Crohn's disease, diverticulitis, and irritable bowel syndrome).Tumor response was measured by radiologic and biochemical markers. Univariate and multivariate analyses were performed using Fisher's exact test, Wilconox rank sum test, and unconditional logistic regression modeling. Results: Univariate analysis demonstrated that positive tumor response was positively correlated with blood in stool (p=0.0301), advanced lymph node stage (p=0.048), and adenocarcinoma cancer cell type (p=0.0387), but negatively correlated with chemotherapy treatment of the primary tumor (p=0.0387) and primary site of the colon cancer (p=0.0328). Multivariate stepwise logistic regression analysis demonstrated that patients with primary tumor located in the transverse or descending/sigmoid colon were more likely (odds ratio=5.88, 95% confidence interval: 1.72–20.00; p=0.0046) to have a positive tumor response than patients whose primary tumor site was cecal/ascending colon. Conclusions: Primary site of metastatic colon cancer may influence the effectiveness of bevacizumab therapy. Future randomized, controlled trials are needed to examine the primary site as a predictor of tumor response in metastatic colon cancer patients using bevacizumab therapy. No significant financial relationships to disclose.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15147-e15147
Author(s):  
Mahvish Muzaffar ◽  
Abdul Rafeh Naqash ◽  
Darla K. Liles ◽  
Sumyra Kachru

e15147 Background: Tumor side has emerged as an important prognostic and predictive factor in metastatic colon cancer. We sought to study its impact on the metastatic pattern of colorectal cancer. Methods: The SEER database (version 8.3.5) was reviewed for patients with Stage IV colorectal cancer diagnosed between 2004-2015. We only included patients with labeled primary site, and excluded appendiceal, unlabeled and autopsy alone cases. Variables included in the analysis were: age, race, gender, grade, primary tumor side and sites of metastasis at diagnosis. Primary outcome analyzed was overall survival and disease specific survival.Cox proportional hazard regression model was employed to test the association between survival and side of cancer/ site of metastasis. Results: A total of 74,768 cases were identified who met the eligibility criteria. The mean age was 68.5 yrs. for right colon cancer (RCC),64.0 yrs. for left colon cancer (LCC). and 62.9 yrs. for rectal cancer. White race was predominant group for RCC, LCC and rectum. More females were vs men in RCC (52% vs 48%), LCC (44% vs 56%) and rectum (60% vs 40%). (The cox regression model suggested inferior outcome for black race HR 1.05(1.03-1.07) (<0.001), high grade HR 1.32(1.30-1.35) p<.0001, right side tumors HR 1.23(1.21-1.250, p <.0001 (table). Conclusions: Over last few years tumor sidedness has emerged as an important prognostic and predictive factor in colon cancer. Our study also highlights the impact of sidedness on survival irrespective of distant metastatic pattern. This analysis contributes to the ongoing discussion that right and left colon cancer are two distinct disease entities. Impact of primary tumor side and metastatic site on survival in colorectal cancer. [Table: see text]


2016 ◽  
Vol 22 (6) ◽  
pp. 628-639 ◽  
Author(s):  
Andinet Woldemichael ◽  
Eberechukwu Onukwugha ◽  
Brian Seal ◽  
Nader Hanna ◽  
C. Daniel Mullins

2012 ◽  
Vol 30 (26) ◽  
pp. 3223-3228 ◽  
Author(s):  
Laurence E. McCahill ◽  
Greg Yothers ◽  
Saima Sharif ◽  
Nicholas J. Petrelli ◽  
Lily Lau Lai ◽  
...  

Purpose Major concerns surround combining chemotherapy with bevacizumab in patients with colon cancer presenting with an asymptomatic intact primary tumor (IPT) and synchronous yet unresectable metastatic disease. Surgical resection of asymptomatic IPT is controversial. Patients and Methods Eligibility for this prospective, multicenter phase II trial included Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1, asymptomatic IPT, and unresectable metastases. All received infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) combined with bevacizumab. The primary end point was major morbidity events, defined as surgical resection because of symptoms at or death related to the IPT. A 25% major morbidity rate was considered acceptable. Secondary end points included overall survival (OS) and minor morbidity related to IPT requiring hospitalization, transfusion, or nonsurgical intervention. Results Ninety patients registered between March 2006 and June 2009: 86 were eligible with follow-up, median age was 58 years, and 52% were female. Median follow-up was 20.7 months. There were 12 patients (14%) with major morbidity related to IPT: 10 required surgery (eight, obstruction; one, perforation; and one, abdominal pain), and two patients died. The 24-month cumulative incidence of major morbidity was 16.3% (95% CI, 7.6% to 25.1%). Eleven IPTs were resected without a morbidity event: eight for attempted cure and three for other reasons. Two patients had minor morbidity events only: one hospitalization and one nonsurgical intervention. Median OS was 19.9 months (95% CI, 15.0 to 27.2 months). Conclusion This trial met its primary end point. Combining mFOLFOX6 with bevacizumab did not result in an unacceptable rate of obstruction, perforation, bleeding, or death related to IPT. Survival was not compromised. These patients can be spared initial noncurative resection of their asymptomatic IPT.


2022 ◽  
Vol 20 (4) ◽  
pp. 25-31
Author(s):  
A. A. Parshina ◽  
N. N. Tsybikov ◽  
P. P. Tereshkov ◽  
T. M. Karavaeva ◽  
M. V. Maksimenya

Aim. To investigate formation of neutrophil extracellular traps (NETs) and their impact on fibrinolysis in patients with colon cancer.Materials and methods. The study was performed in two groups. The experimental group consisted of patients with stage 2–3 non-metastatic colon cancer (n = 17, average age – 67 years). The control group included healthy volunteers matched by sex and age (n = 30, average age – 68 years). An experimental model was created from the whole blood. It included platelet-poor plasma and an isolated culture of neutrophils, previously induced to NETosis by adding 100 nmol PMA. The samples were incubated for 4 hours, then the test tubes were centrifuged to pellet cells and their remnants, and the plasma was transferred for subsequent examination. The plasma incubated with intact neutrophils was used as a control. The levels of interleukin-8 (IL-8) and P-selectin glycoprotein ligand-1 (PSGL-1) were used to determine the degree of cell activation. NETosis was confirmed by enzyme-linked immunosorbent assay (ELISA) and fluorescent microscopy. Fibrinolysis was assessed using the thrombodynamics test. The results were compared with the levels of fibrinolytic system components measured by flow cytometry.Results. In the control group, NETosis induction contributed to pronounced neutrophil activation that was accompanied by an increase in the IL-8, PSGL-1, and plasminogen levels, a decrease in PAI-1, and enhancement of fibrinolysis, compared with the intact samples. Higher levels of IL-8, PSGL-1, plasminogen, and PAI-1 and intensified fibrinolysis were detected in the intact samples. However, PMA-induced NETosis did not result in an increase in the degree of activation and significant changes in the given parameters.Conclusion. NETosis promotes both formation and lysis of fibrin clots. However, in cancer patients, suicidal NETosis does not contribute to fibrinolysis due to intracellular protease depletion, which may be one of the mechanisms causing hypercoagulation and insufficient fibrinolysis in cancer. 


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15535-e15535
Author(s):  
Mehmet Artac ◽  
Ayca Ceylan ◽  
Melek Karakurt Eryılmaz ◽  
Murat Araz ◽  
Mustafa Karaagac ◽  
...  

e15535 Background: VEGF receptors have an important role for inhibiting adaptive immun response in colon cancer. Therefore, we analyzed VEGF receptors in circulating T cell subsets according to stage in colon cancer patients. Methods: The prospective study group consisted of 50 patients with histologically confirmed colon cancer and 30 person without any cancer history as a control group. Peripheral blood specimens were collected from the patients after the diagnosis before inducing chemotherapy and radiotherapy. Patients with active infections or autoimmune disorders, who were treated with steroids and antibiotics in the last four weeks before the study enrollment were excluded from the study group. VEGFR2 expressions in circulating T cell subsets (Th1, Th2, Th17, CTL) were analyzed by flow cyctometry. Results: Age and gender were not different between the all study groups. Mean circulating CD4+ folicullar cells were less in colon cancer patients (9.54%±3.99) than the control group (12.03%±4.34), (p < 0.01). Mean circulating CD8+ follicular cells were higher in metastatic colon cancer (n = 26) 2.48% ± 1.68, than the non-metastatic colon cancer patients (n = 24) 1.63% ± 1.37, (p = 0.02). Mean VEGFR2 expressions in Th1 cells were higher in colon cancer patients 248.8 (Mean Flourescein intensity-MFI) than the control group 224.6, (P = 0.006). Mean VEGFR2 expressions in CTL were higher in colon cancer patients (381.8) than the control group (284.7), (p < 0.001). PD-1 expressions were not different between the colon cancer patients and the control group in all circulating T cell subsets. Mean VEGFR2 expressions in Th17 cells were higher non-metastatic colon cancer patients than the metastatic colon cancer patients (326.5 and 268.4 MFI, respectively, p = 0.02). Conclusions: VEGFR2 expressions are increased in circulating Th1 and CTL subsets in colon cancer patients. Whereas PD-1 expressions were not different in circulating T cell subsets than the control. VEGFRs may play an important role for the inhibition of circulating T cell subsets in colon cancer.


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