Fargo, ND, United States
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Bande D.,Roger Maris Cancer Center | Bande D.,University of North Dakota | Pillai A.K.,University of Texas Southwestern Medical Center | Blaszkowsky L.S.,Massachusetts General Hospital | And 5 more authors.
Frontiers in Oncology | Year: 2014

Liver metastases from colorectal cancer (CRC) result in substantial morbidity and mortality. The primary treatment is systemic chemotherapy, and in selected patients, surgical resection; however, for patients who are not surgical candidates and/or fail systemic chemotherapy, liver-directed therapies are increasingly being utilized. Yttrium-90 (Y-90) microsphere therapy, also known as selective internal radiation therapy (SIRT) or radioembolization, has proven to be effective in terms of extending time to progression of disease and also providing survival benefit. This review focuses on the use of Y-90 microsphere therapy in the treatment of liver metastases from CRC, including a comprehensive review of published clinical trials and prospective studies conducted thus far. We review the methodology, outcomes, and side effects of Y-90 microsphere therapy for metastatic CRC. © 2014 Raval, Bande, Pillai, Blaszkowsky, Ganguli, Beg and Kalva.


Bouton M.,Roger Maris Cancer Center | Raval M.,Essentia Health | Totzauer J.,North Dakota State University | Alberto N.,Roger Maris Cancer Center
Journal of Negative Results in BioMedicine | Year: 2014

Background: The ADAMs (A Disintegrin and Metalloproteinases) are a family of multi-domain, zinc-dependent metalloproteinase enzymes. ADAM 12 has been previously associated with the onset and progression of breast cancer, and elevated levels of ADAM 12 have been previously found in the urine of breast cancer patients. Aims of the current study are: 1) establish the viability of urinary ADAM 12 as a diagnostic marker for breast cancer, and 2) explore the effects of surgical tumor removal on the levels of urinary ADAM 12. Methods. A total of 96 patients have been recruited for this study, including 50 patients diagnosed with cancer, and 46 age-matched controls. Commercially available ELISA kits for ADAM 12 were used to quantify the presence and concentration of this enzyme in the urine from cancer patients with ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) both prior to any treatment and approximately two weeks following surgery, as well as from controls. Results: We find no statistically significant differences between the concentrations of ADAM 12 in the urine of breast cancer patients prior to treatment and that of their age-matched controls; however the concentration of ADAM 12, both alone and as a function of urine total protein, are significantly elevated following surgery (p < 0.0001). Patients who underwent a mastectomy have significantly higher urinary ADAM 12 concentrations than those who underwent a lumpectomy (significant at p = 0.0271). Conclusions: These findings suggest that urinary ADAM 12 may not correlate directly with the status and stage of breast cancer as previously thought; rather these increases may be a result of tissue injury and inflammation from biopsy and surgical resection. Results of this study may suggest a need for biomarkers to be evaluated carefully in the context of tissue damage. © 2014Nyren-Erickson et al.; licensee BioMed Central Ltd.


PubMed | Roger Maris Cancer Center, Dana-Farber Cancer Institute, Charleston Area Medical Center, Stanford University and 7 more.
Type: Journal Article | Journal: The Lancet. Oncology | Year: 2016

Erlotinib is approved for the treatment of all patients with advanced non-small-cell lung cancer (NSCLC), but is most active in the treatment of EGFR mutant NSCLC. Cabozantinib, a small molecule tyrosine kinase inhibitor, targets MET, VEGFR, RET, ROS1, and AXL, which are implicated in lung cancer tumorigenesis. We compared the efficacy of cabozantinib alone or in combination with erlotinib versus erlotinib alone in patients with EGFR wild-type NSCLC.This three group, randomised, controlled, open-label, multicentre, phase 2 trial was done in 37 academic and community oncology practices in the USA. Patients were eligible if they had received one or two previous treatments for advanced non-squamous, EGFR wild-type, NSCLC. Patients were stratified by performance status and line of therapy, and randomly assigned using permuted blocks within strata to receive open-label oral daily dosing of erlotinib (150 mg), cabozantinib (60 mg), or erlotinib (150 mg) and cabozantinib (40 mg). Imaging was done every 8 weeks. At the time of radiographic progression, there was optional crossover for patients in either single-drug group to receive combination treatment. The primary endpoint was to compare progression-free survival in patients given erlotinib alone versus cabozantinib alone, and in patients given erlotinib alone versus the combination of erlotinib plus cabozantinib. We assessed the primary endpoint in the per-protocol population, which was defined as all patients who were eligible, randomly assigned, and received at least one dose of treatment. The safety analysis population included all patients who received study treatment irrespective of eligibility. This trial is registered with ClinicalTrials.gov, number NCT01708954.Between Feb 7, 2013, and July 1, 2014, we enrolled and randomly assigned 42 patients to erlotinib treatment, 40 patients to cabozantinib treatment, and 43 patients to erlotinib plus cabozantinib treatment, of whom 111 (89%) in total were included in the primary analysis (erlotinib [n=38], cabozantinib [n=38], erlotinib plus cabozantinib [n=35]). Compared with erlotinib alone (median 18 months [95% CI 17-22]), progression-free survival was significantly improved in the cabozantinib group (43 months [36-74]; hazard ratio [HR] 039, 80% CI 027-055; one-sided p=00003) and in the erlotinib plus cabozantinib group (47 months [24-74]; HR 037, 025-053; one-sided p=00003). Among participants included in the safety analysis of the erlotinib (n=40), cabozantinib (n=40), and erlotinib plus cabozantinib (n=39) groups, the most common grade 3 or 4 adverse events were diarrhoea (three [8%] cases in the erlotinib group vs three [8%] in the cabozantinib group vs 11 [28%] in the erlotinib plus cabozantinib group), hypertension (none vs ten [25%] vs one [3%]), fatigue (five [13%] vs six [15%] vs six [15%]), oral mucositis (none vs four [10%] vs one [3%]), and thromboembolic event (none vs three [8%] vs two [5%]). One death due to respiratory failure occurred in the cabozantinib group, deemed possibly related to either drug, and one death due to pneumonitis occurred in the erlotinib plus cabozantinib group, deemed related to either drug or the combination.Despite its small sample size, this trial showed that, in patients with EGFR wild-type NSCLC, cabozantinib alone or combined with erlotinib has clinically meaningful, superior efficacy to that of erlotinib alone, with additional toxicity that was generally manageable. Cabozantinib-based regimens are promising for further investigation in this patient population.ECOG-ACRIN Cancer Research Group, National Cancer Institute of the National Institutes of Health.


Kumar R.,Mayo Medical School | Pruthi R.K.,Mayo Medical School | Pruthi R.K.,Comprehensive Hemophilia Center | Kobrinsky N.,Roger Maris Cancer Center | And 3 more authors.
Pediatric Blood and Cancer | Year: 2011

Development of pseudotumors is an unusual complication of hemophilia. Treatment is controversial, especially in patients with large proximal lesions. Surgery, while curative, can be associated with massive intra-operative bleeding, infection and amputation. Arterial embolization of blood vessels supplying the pseudotumor may reduce these complications. Herein, we report a 14-year-old patient with moderate hemophilia B with a pelvic pseudotumor and pseudoaneurysm that failed conservative management with factor replacement alone. He was successfully treated with Bead Block and coil embolization followed by surgical extirpation of the lesion 24 hr later. © 2010 Wiley-Liss, Inc.


Hayes J.J.,Roger Maris Cancer Center | Pfund J.,Roger Maris Cancer Center | Zouain N.,Roger Maris Cancer Center | Zouain N.,University of North Dakota
Health Physics | Year: 2010

Enhancements in radiation detection equipment at border crossings and airports resulted in a report to our institution from a 153 Sm-EDTMP therapy patient who was questioned after triggering radiation alarms. Using a clinical SPECT camera in its service mode, gamma-ray spectroscopy was performed on three patients whose 153 Sm-EDTMP injections were given between 4 mo and 2 y prior to this study. The spectra revealed the presence of high-energy photon peaks characteristic of those from 154Eu. While the presence of 154 Eu in 153 Sm injections is documented in the literature, the implications of its presence are not widely known. The results of this study show that 154Eu (t1/2 = 8.5 y) remains in the bones in detectable amounts for several years and may create concerning situations for post therapy patients at some security checkpoints. Institutions performing Sm-EDTMP therapy may want to inform their patients of this situation and provide a wallet card. Copyright © 2010 Health Physics Society.


Raval M.,Sanford Hospital | Raval M.,University of North Dakota | Raval M.,Roger maris cancer center | Kallamadi R.,Sanford Hospital | And 5 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2012

84 year old male with past medical history of myelodysplastic syndrome (MDS) presented with progressive subcutaneous and muscle bleed in the right forearm and arm. Workup revealed elevated activated partial thromboplastin time (aPTT) - 71.8 seconds (normal 23 - 32 seconds) which was persistently elevated after mixing study (37.1 seconds immediately and 51.1 seconds after 1 hour). Further laboratory work up revealed low factor VIII level (3%) and elevated factor VIII inhibitor by Bethesda assay (3 units/ml of blood). Acquired hemophilia A (AHA) diagnosis was established and patient was treated with recombinant factor VIIa (rFVlla) to control the bleeding and also prednisone for immunosuppression. Subsequent monitoring suggested reduction of factor VIII inhibitor - antibody levels to undetectable level in 3 days and increase of factor VIII level from 3% to 50% in 5 days. Despite of improvement in the laboratory values he continued to have progression of his bleeding which involved posterior chest wall and also left arm. Due to the progression of the condition and prior expressed wish family decided to stop the aggressive treatment and patient died nine days after the diagnosis. The case report describes a rare presentation of AHA in MDS (With bone marrow cytogenetics abnormality) patient with fatal outcome.


Al Hallak M.N.,University of North Dakota | Al Hallak M.N.,MeritCare Hospital | Al Hallak M.N.,Roger Maris Cancer Center | Hage-Nassar G.,MeritCare Hospital | Mouchli A.,MeritCare Hospital
Case Reports in Gastroenterology | Year: 2010

Primary colorectal squamous cell carcinoma (SCC) is one of the very rare malignancies of the gastrointestinal tract. The diagnosis cannot be made before ruling out other common primary sites. Using the endoscopic ultrasound (EUS) technique to get a tissue biopsy for submucosal tumors has not been demonstrated as the best diagnostic approach in the literature. Surgery is the gold standard treatment with arising evidence of good efficacy following conventional chemoradiation therapy. A 49-year-old male presented with rectal discomfort. Sigmoidoscopy revealed multiple submucosal masses in the rectosigmoid colon. Mucosal biopsies showed nonspecific inflammation. Subsequently, an EUS with fine needle biopsy was done and established the diagnosis of rectal SCC. There were no other primary sites noticed in the extensive evaluation. The patient chose to be treated only with chemoradiation without surgery. At the time of writing this report he had no evidence of recurrence achieving 2.5 years of survival. EUS is an emerging excellent approach to diagnose submucosal colorectal SCC. This case will add supportive evidence of having a complete response following combining treatment with squamous cell directed chemotherapy and external beam radiotherapy without preceded surgery. © 2010 S. Karger AG, Basel.


Sylvester R.K.,North Dakota State University | Steen P.,Roger Maris Cancer Center | Tate J.M.,University of Wisconsin - Madison | Mehta M.,University of Wisconsin - Madison | And 3 more authors.
Anti-Cancer Drugs | Year: 2011

Genotyping of putative determinants of temozolomide (TMZ)-induced life-threatening bone marrow suppression was performed in two patients with glioma treated with adjuvant TMZ and radiation therapy. DNA was extracted from the patients' mononuclear cells and genotyping of O-methylguanine-DNA- methyltransferase (MGMT), multidrug resistance (MDR1; also known as ABCB1), NQO1, and GSTP1 genes and analysis for the epigenetic silencing of specific MGMT gene promoters were carried out to evaluate the possible genetic determinants of increased risk of severe TMZ-induced myelosuppression. Although both patients were heterozygous for all ABCB1 single nucleotide polymorphisms and for rs12917 and rs1803965 in the MGMT gene, patient 1 was heterozygous for rs1695 in GSTP1 and rs2308327 in the MGMT gene. This patient also exhibited GG genotype for the MGMT single nucleotide polymorphisms, rs2308321, which is noteworthy for its 0.7% frequency globally. Epigenetic silencing of MGMT gene was not detected in either patient. Two single nucleotide polymorphisms identified in patient 1 (missense I143V and K178R polymorphisms; rs2308321 and rs2308327, respectively) have recently been shown to correlate with an increased risk of severe TMZ-induced myelosuppression. The polymorphisms identified in patient 2 have not been associated with an increased risk of severe TMZ-induced myelosuppression. Genotyping analyses of larger patient populations administered TMZ are required to validate the genetic determinants of severe TMZ-induced myelosuppression. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


PubMed | Roger Maris Cancer Center
Type: Journal Article | Journal: Health physics | Year: 2010

Enhancements in radiation detection equipment at border crossings and airports resulted in a report to our institution from a Sm-EDTMP therapy patient who was questioned after triggering radiation alarms. Using a clinical SPECT camera in its service mode, gamma-ray spectroscopy was performed on three patients whose Sm-EDTMP injections were given between 4 mo and 2 y prior to this study. The spectra revealed the presence of high-energy photon peaks characteristic of those from Eu. While the presence of Eu in Sm injections is documented in the literature, the implications of its presence are not widely known. The results of this study show that Eu (t1/2 = 8.5 y) remains in the bones in detectable amounts for several years and may create concerning situations for post therapy patients at some security checkpoints. Institutions performing Sm-EDTMP therapy may want to inform their patients of this situation and provide a wallet card.

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