To see the other types of publications on this topic, follow the link: Atherosclerosis – Chemotherapy.
Journal articles on the topic 'Atherosclerosis – Chemotherapy'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Atherosclerosis – Chemotherapy.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Min, San S., and Anthony S. Wierzbicki. "Radiotherapy, chemotherapy and atherosclerosis." Current Opinion in Cardiology 32, no. 4 (July 2017): 441–47. http://dx.doi.org/10.1097/hco.0000000000000404.
Full text
2
Paulenka, Yuliya, Maritza Cotto, Christine Rickette, and Krystal Hunter. "Latent atherosclerosis as a risk factor in chemotherapy-induced cardiomyopathy." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e12525-e12525. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e12525.
Full textAbstract:
e12525 Background: Anthracyclines and monoclonal antibodies targeting HER2/neu receptors are widely used antineoplastic agents in breast cancer treatment. Both therapies have been known to cause cardiovascular adverse effects, notably chemotherapy-induced congestive heart failure, especially if used in combination. Multiple factors have been postulated to increase the risk of doxorubicin and trastuzumab-associated cardiotoxicity, including a pre-existing coronary artery disease, but the role of latent atherosclerosis has not been widely studied. Methods: We retrospectively reviewed health records of female breast cancer patients at our institution treated with doxorubicin or trastuzumab between 2012 and 2017. Using echocardiography, we identified patients with underlying atherosclerotic lesions at the start of the treatment and those who subsequently developed cardiotoxicity. Chemotherapy-induced cardiomyopathy was defined as a drop in the ejection fraction (EF) to < 50% from the normal EF of > 53% pre-therapy. We used a χ2 test to search for the relationship between atherosclerosis and subsequent cardiotoxicity. Results: A total of 518 patient records were reviewed. Of 518 patients with breast cancer, 93 (18%) received doxorubicin or trastuzumab-based chemotherapy. The median age for breast cancer diagnosis was 58. Sixty-one patients (66%) were identified to have atherosclerosis on echocardiography at the time of the first chemotherapy cycle. The most common location for atherosclerotic lesions was in the aortic arch and proximal upper abdominal aorta. Of 61 patients with atherosclerosis, ten (16.4%) subsequently developed chemotherapy-induced cardiomyopathy (p = 0.77). A post hoc analysis was performed to compare the two cohorts aged 40 to 50 (p = 0.49) and 51 to 75 (p = 1.00) as they represented the majority of breast cancer cases. Conclusions: The role of atherosclerosis in doxorubicin and trastuzumab-induced toxicity remains unclear. We did not observe any statistical correlation between atherosclerosis at the start of chemotherapy and increased rates of cardiac injury. A younger population may be more susceptible to cardiotoxicity, but further research is needed as the study has limitations. Although we identified patients with latent atherosclerosis, additional evaluation via carotid artery intima-media thickness measurements would yield more precision. Other methods such as the use of computed tomography and coronary artery calcium scores would also allow for assessing atherosclerotic plaque burden. Still, not all patients were subjected to these techniques. Furthermore, the study was challenged by the small sample size and its retrospective nature. Larger prospective studies are essential to explore this area further. Identifying the means of reducing cardiovascular complications remains a priority as heart disease is currently the leading cause of death among breast cancer survivors.
3
Mukai, Mikio, Keiko Komori, and Toru Oka. "Mechanism and Management of Cancer Chemotherapy-Induced Atherosclerosis." Journal of Atherosclerosis and Thrombosis 25, no. 10 (October 1, 2018): 994–1002. http://dx.doi.org/10.5551/jat.rv17027.
Full text
4
Levine, Jennifer M., Michael A. Weiner, Tatjana Rundek, Mitchell S. V. Elkind, Deborah Hughes, Romel Ramas, Ken Cheung, and Kara M. Kelly. "Subclincal Atherosclerosis as Measured by CIMT Is Present in Patients with Hodgkin’s Disease." Blood 106, no. 11 (November 16, 2005): 4646. http://dx.doi.org/10.1182/blood.v106.11.4646.4646.
Full textAbstract:
Abstract Cardiovascular disease is a well-described late effect of treatment for Hodgkin’s Disease (HD), generally attributed to high dose radiation therapy (RT) to the mediastinum and neck. Increased carotid artery intima-media thickness (CIMT), measured by ultrasound, is a valid marker of subclinical atherosclerosis and is associated with an increased risk of future vascular disease. We evaluated CIMT in 31 patients with HD, (22 males, 9 females), mean age 21 (range 9–39) years, between 2 and 241 months from diagnosis. Thirty patients received chemotherapy, including anthracyclines. Sixteen patients were treated with RT to the bilateral neck and mediastinum; 4 received high dose (36Gy) RT and 12 received lower dose (21–25Gy) RT. One patient received lower dose RT only to the bilateral neck. Fourteen patients were treated with chemotherapy alone. CIMT was assessed using a standardized scanning and reading protocol. The CIMT was calculated as the mean of the maximum measurement at 12 sites; near and far walls of the common carotid, bifurcation and internal carotid arteries bilaterally. The mean CIMT for the total cohort was 0.757mm. Among 5 patients (mean age 13, range 9–16 years), evaluated while actively receiving therapy or within one year from completion of therapy, mean CIMT was 0.715, equivalent to the mean CIMT found in healthy 30 year old adults (Stein, Stroke 2004). In a multivariate linear regression analysis CIMT was significantly associated with increasing time since diagnosis (p=0.035), age (p=0.016), and male gender (p=0.014). There was no difference in CIMT between those patients treated with chemotherapy alone vs. chemotherapy and radiation therapy. Subclinical atherosclerosis in patients with HD may evolve early in the course of treatment and survivorship and then increase with age and time from diagnosis. Type of treatment was not a significant predictor of CIMT in our cohort suggesting that factors other than RT play a role in the development of subclinical atherosclerosis. Further studies are needed to better elucidate the etiology of atherosclerotic disease in HD survivors. Screening with CIMT may detect subclinical atherosclerosis and allow for earlier intervention to prevent cardiovascular disease in this population.
5
Sekijima, T., A. Tanabe, R. Maruoka, N. Fujishiro, S. Yu, S. Fujiwara, H. Yuguchi, Y. Yamashita, Y. Terai, and M. Ohmichi. "Impact of platinum-based chemotherapy on the progression of atherosclerosis." Climacteric 14, no. 1 (February 2011): 31–40. http://dx.doi.org/10.3109/13697137.2010.522278.
Full text
6
Ren, Yan, Wei Qiao, Dongliang Fu, Zhiwei Han, Wei Liu, Weijie Ye, and Zunjing Liu. "Traditional Chinese Medicine Protects against Cytokine Production as the Potential Immunosuppressive Agents in Atherosclerosis." Journal of Immunology Research 2017 (2017): 1–8. http://dx.doi.org/10.1155/2017/7424307.
Full textAbstract:
Atherosclerosis is a chronic inflammatory disease caused by dyslipidemia and mediated by both innate and adaptive immune responses. Inflammation is a critical factor at all stages of atherosclerosis progression. Proinflammatory cytokines accelerate atherosclerosis progression, while anti-inflammatory cytokines ameliorate the disease. Accordingly, strategies to inhibit immune activation and impede immune responses towards anti-inflammatory activity are an alternative therapeutic strategy to conventional chemotherapy on cardiocerebrovascular outcomes. Since a number of Chinese medicinal plants have been used traditionally to prevent and treat atherosclerosis, it is reasonable to assume that the plants used for such disease may suppress the immune responses and the resultant inflammation. This review focuses on plants that have immunomodulatory effects on the production of inflammatory cytokine burst and are used in Chinese traditional medicine for the prevention and therapy of atherosclerosis.
7
Gomes, Fernando L. T., Raul C. Maranhão, Elaine R. Tavares, Priscila O. Carvalho, Maria L. Higuchi, Fernando R. Mattos, Fabio G. Pitta, Sergio A. Hatab, Roberto Kalil-Filho, and Carlos V. Serrano. "Regression of Atherosclerotic Plaques of Cholesterol-Fed Rabbits by Combined Chemotherapy With Paclitaxel and Methotrexate Carried in Lipid Core Nanoparticles." Journal of Cardiovascular Pharmacology and Therapeutics 23, no. 6 (May 20, 2018): 561–69. http://dx.doi.org/10.1177/1074248418778836.
Full textAbstract:
In previous studies, it was demonstrated that lipid core nanoparticles (LDE) resemble the low-density lipoprotein structure and carrying the antiproliferative agent paclitaxel (PTX) strongly reduced atherosclerosis lesions induced in rabbits by cholesterol feeding. Currently, the aim was to verify whether combining LDE-PTX treatment with methotrexate (MTX) associated with LDE (LDE-MTX) could accelerate the atherosclerosis regression attained with single LDE-PTX treatment, after withdrawing the cholesterol feeding. Thirty-eight rabbits were fed 1% cholesterol chow for 8 weeks. Six of these rabbits were then euthanized for analyses of the aorta (controls). In the remaining rabbits, cholesterol feeding was withdrawn, and those 32 animals were allocated to 3 groups submitted to different 8-week intravenous treatments, all once/week: LDE-PTX (n = 10; 4 mg/kg), LDE-PTX + LDE-MTX (n = 11; 4 mg/kg), and LDE-alone (n = 11). Rabbits were then euthanized and aortas were excised for morphometric, immunohistochemical, and gene expression analyses. After cholesterol feeding withdrawal, in comparison with LDE-alone group, both LDE-PTX and LDE-PTX + LDE-MTX treatments had the ability to increase the regression of plaque areas: −49% in LDE-PTX and −59% for LDE-PTX + LDE-MTX. However, only LDE-PTX + LDE-MTX treatment elicited reduction in the intima area, estimated in −57%. Macrophage presence in aortic lesions was reduced 48% by LDE-PTX and 43% by LDE-PTX + LDE-MTX treatment. Matrix metalloproteinase 9 was reduced by either LDE-PTX (74%) or LDE-PTX + LDE-MTX (78%). Tumor necrosis factor α gene expression was reduced 65% by LDE-PTX and 79% by LDE-PTX + LDE-MTX. In conclusion, treatment with LDE-PTX indeed accelerated plaque reduction after cholesterol feeding; LDE-PTX + LDE-MTX further increased this effect, without any observed toxicity. These results pave the way for the use of combined chemotherapy to achieve stronger effects on aggravated, highly inflamed atherosclerotic lesions.
8
Vitorio, T., M. Higuchi, and R. Maranhão. "Abstract: P476 COMBINED CHEMOTHERAPY ASSOCIATED WITH LIPIDIC NANOEMULSIONS ACHIEVES MARKED ATHEROSCLEROSIS REGRESSION IN THE RABBIT." Atherosclerosis Supplements 10, no. 2 (June 2009): e787. http://dx.doi.org/10.1016/s1567-5688(09)70771-8.
Full text
9
Morrow, Andrew J., Alan C. Cameron, Alexander R. Payne, Jeff White, and Ninian N. Lang. "Cisplatin related cardiotoxicity – acute and chronic cardiovascular morbidity in a testicular cancer survivor." Scottish Medical Journal 65, no. 1 (December 30, 2019): 24–27. http://dx.doi.org/10.1177/0036933019897347.
Full textAbstract:
Testicular germ cell tumours are the most common malignancy in men aged 20 to 40 years. They are subdivided into seminoma and non-seminomatous germ cell tumours (NSGCTs). Both seminoma and NSGCT occur at about the same rate, however some tumours contain a combination of both. Cisplatin-based chemotherapy is used adjuvantly in high-risk stage 1 mixed and NSGCT patients and contributes towards oncological cure in almost all metastatic cases, regardless of histology. However, cardiovascular toxicity is a major concern. In addition to acute endothelial toxicity and associated risk of arterial thrombosis, accelerated atherosclerosis may be the result of chemotherapy-associated latent cardio-metabolic dysfunction. A 45-year-old man began treatment with cisplatin-based chemotherapy for testicular cancer. On day 9, he suffered an anterior ST segment elevation myocardial infarction (STEMI). There was proximal occlusion of the left anterior descending (LAD) artery but otherwise normal coronary arteries. Ten months following chemotherapy, he had another STEMI. There was a fresh obstructive lesion in the previously angiographically normal mid LAD, new diffuse coronary atheroma elsewhere and a deterioration in lipid profile despite statin therapy. Acute and longer-term cardiovascular risks of cisplatin-based chemotherapy may have different underlying pathophysiological mechanisms. These issues are of growing relevance in a population of patients expected to have excellent cancer-related outcomes.
10
Altena, R., H. Boer, C. Meijer, J. Nuver, A. M. van Roon, N. Zwart, E. De Vries, J. D. Lefrandt, A. J. Smit, and J. A. Gietema. "Association of Raynaud's phenomenon after bleomycin etoposide cisplatin (BEP) chemotherapy for testicular cancer (TC) with accelerated atherosclerosis." Journal of Clinical Oncology 29, no. 15_suppl (May 20, 2011): 4631. http://dx.doi.org/10.1200/jco.2011.29.15_suppl.4631.
Full text
11
Lik, Przemyslaw, and Dariusz Nejc. "Management of hard-to-heal wounds arising as a result of surgical oncology treatment- usage of the modern wound dressings." Polish Journal of Surgery 91, no. 1 (January 3, 2019): 1–5. http://dx.doi.org/10.5604/01.3001.0012.8304.
Full textAbstract:
The problem of hard-to-heal wounds concerns 1-1.5% of the total population and about 3% of the population above 60 years of age. The risk factors associated with impaired wound healing are diabetes, arterial and venous insufficiency, advanced atherosclerosis, obesity, and inadequate wound supply. As a result of these pathological processes may develop localized wound infection, disseminated infection, tissue necrosis, and even chronic inflammation carcinogenesis. In the group of patients with malignant tumors, there are wounds arising in the course of the underlying disease and as a result of medical treatment. Wound healing is a significant problem and is often complicated due to the patient’s general condition, comorbidities and complex treatment of cancer, which includes surgery, radiotherapy, and chemotherapy. Radiotherapy used for local-regional control of disease after surgical treatment has a negative effect on healing by causing fibrosis of tissues and blood vessels damage, while chemotherapy interferes with the process of cell proliferation.
12
Bang, Oh Young, Jong-Won Chung, Mi Ji Lee, Woo-Keun Seo, Gyeong-Moon Kim, and Myung-Ju Ahn. "Cancer-Related Stroke: An Emerging Subtype of Ischemic Stroke with Unique Pathomechanisms." Journal of Stroke 22, no. 1 (January 31, 2020): 1–10. http://dx.doi.org/10.5853/jos.2019.02278.
Full textAbstract:
Systemic cancer and ischemic stroke are common conditions and two of the most frequent causes of death among the elderly. The association between cancer and stroke has been reported worldwide. Stroke causes severe disability for cancer patients, while cancer increases the risk of stroke. Moreover, cancer-related stroke is expected to increase due to advances in cancer treatment and an aging population worldwide. Because cancer and stroke share risk factors (such as smoking and obesity) and treatment of cancer can increase the risk of stroke (e.g., accelerated atherosclerosis after radiation therapy), cancer may accelerate conventional stroke mechanisms (i.e., atherosclerosis, small vessel disease, and cardiac thrombus). In addition, active cancer and chemotherapy may enhance thrombin generation causing stroke related to coagulopathy. Patients with stroke due to cancer-related coagulopathy showed the characteristics findings of etiologic work ups, D-dimer levels, and infarct patterns. In this review, we summarized the frequency of cancer-related stroke among patients with ischemic stroke, mechanisms of stroke with in cancer patients, and evaluation and treatment of cancer-related stroke. We discussed the possibility of cancer-related stroke as a stroke subtype, and presented the most recent discoveries in the pathomechanisms and treatment of stroke due to cancer-related coagulopathy.
13
Leite, Antonio C. A., Tatiana V. Solano, Elaine R. Tavares, and Raul C. Maranhão. "Use of Combined Chemotherapy with Etoposide and Methotrexate, both Associated to Lipid Nanoemulsions for Atherosclerosis Treatment in Cholesterol-fed Rabbits." Cardiovascular Drugs and Therapy 29, no. 1 (February 2015): 15–22. http://dx.doi.org/10.1007/s10557-014-6566-1.
Full text
14
Lamberti, Giuseppe, Francesco Gelsomino, Stefano Brocchi, Antonio Poerio, Barbara Melotti, Francesca Sperandi, Mauro Gargiulo, Claudio Borghi, Michelangelo Fiorentino, and Andrea Ardizzoni. "New disappearance of complicated atheromatous plaques on rechallenge with PD-1/PD-L1 axis blockade in non-small cell lung cancer patient: follow up of an unexpected event." Therapeutic Advances in Medical Oncology 12 (January 2020): 175883592091380. http://dx.doi.org/10.1177/1758835920913801.
Full textAbstract:
Atherosclerosis is considered an irreversible process, with crucial contribution of inflammation and immune cells. Impact of cancer immunotherapy on a partly immune-driven disease, such as atherosclerosis, is poorly understood, but preclinical models suggest its worsening on programmed death/ligand-1 (PD-1/PD-L1) inhibitors. In a previously reported cohort of 11 patients with non-small cell lung cancer (NSCLC) treated with nivolumab and pre-existing complicated atheromatous plaques, 3 patients had a dramatic radiologic reduction of aortic plaques while on nivolumab; of these 3, 2 died receiving no further treatment. The remaining patient was an 83-year-old woman with history of arterial hypertension and hypothyroidism who was diagnosed with locally advanced squamous NSCLC. At relapse, complicated aortic atheromatous plaques were demonstrated on scans. The patient was then treated with nivolumab obtaining stable disease at radiological assessment, which also demonstrated almost complete vanishing of aortic plaques. After relapse and interval treatment with chemotherapy, she experienced new development of aortic atheromatous plaques. At further relapse she received atezolizumab, which yielded disease response and new reduction in aortic plaques, until nearly complete resolution. The observation of a repeated improvement of atheromatous plaques on treatment with PD-1/PD-L1 inhibitors favors the protective role of T cells on atheromatous plaques that is impaired by PD-L1 expression by plaque-associated macrophages. Validation by independent and prospective observation is needed.
15
Yang, Jiayin, Xiaohong Liao, Jerry Yu, and Ping Zhou. "Role of CD73 in Disease: Promising Prognostic Indicator and Therapeutic Target." Current Medicinal Chemistry 25, no. 19 (May 30, 2018): 2260–71. http://dx.doi.org/10.2174/0929867325666180117101114.
Full textAbstract:
CD73, also known as ecto-5’-nucleotidase (eN, NT5E, EC3.13.5), is the ratelimiting enzyme for adenosine generation and is expressed on multiple cells. Its expression is significantly influenced by hypoxia and inflammatory factors. During inflammation, CD73 protects endothelial barrier function and inhibits leukocyte trafficking. CD73 also promotes M2 macrophages (anti-inflammatory phenotype). In addition, CD73 is expressed on Treg cells and mediates immune suppression through adenosine. CD73 serves as an essential regulator for the immunity and inflammation. Its expression is related to many diseases, such as autoimmune diseases, ischemia-reperfusion injuries, arterial calcifications, and atherosclerosis. CD73 is overexpressed in many cancers. Its expression is positively associated with tumor growth, metastasis, angiogenesis, poor prognosis and resistance to chemotherapy. Thus, CD73 may be used for prognostic indicator and therapeutic target in diseases such as cancers.
16
Kalábová, Hana, Bohuslav Melichar, Leoš Ungermann, Jiří Doležal, Lenka Krčmová, Markéta Kašparová, Jiří Plíšek, Radomír Hyšpler, Miroslav Pecka, and Dagmar Solichová. "Intima-media thickness, myocardial perfusion and laboratory risk factors of atherosclerosis in patients with breast cancer treated with anthracycline-based chemotherapy." Medical Oncology 28, no. 4 (June 22, 2010): 1281–87. http://dx.doi.org/10.1007/s12032-010-9593-1.
Full text
17
Weinstein, Jason S., Csanad G. Varallyay, Edit Dosa, Seymur Gahramanov, Bronwyn Hamilton, William D. Rooney, Leslie L. Muldoon, and Edward A. Neuwelt. "Superparamagnetic Iron Oxide Nanoparticles: Diagnostic Magnetic Resonance Imaging and Potential Therapeutic Applications in Neurooncology and Central Nervous System Inflammatory Pathologies, a Review." Journal of Cerebral Blood Flow & Metabolism 30, no. 1 (September 16, 2009): 15–35. http://dx.doi.org/10.1038/jcbfm.2009.192.
Full textAbstract:
Superparamagnetic iron oxide nanoparticles have diverse diagnostic and potential therapeutic applications in the central nervous system (CNS). They are useful as magnetic resonance imaging (MRI) contrast agents to evaluate: areas of blood–brain barrier (BBB) dysfunction related to tumors and other neuroinflammatory pathologies, the cerebrovasculature using perfusion-weighted MRI sequences, and in vivo cellular tracking in CNS disease or injury. Novel, targeted, nanoparticle synthesis strategies will allow for a rapidly expanding range of applications in patients with brain tumors, cerebral ischemia or stroke, carotid atherosclerosis, multiple sclerosis, traumatic brain injury, and epilepsy. These strategies may ultimately improve disease detection, therapeutic monitoring, and treatment efficacy especially in the context of antiangiogenic chemotherapy and antiinflammatory medications. The purpose of this review is to outline the current status of superparamagnetic iron oxide nanoparticles in the context of biomedical nanotechnology as they apply to diagnostic MRI and potential therapeutic applications in neurooncology and other CNS inflammatory conditions.
18
Scudiero, Laura, Francesco Soriano, Nuccia Morici, Giovanni Grillo, Oriana Belli, Alice Sacco, Manlio Cipriani, et al. "Allogeneic peripheral blood stem cell transplantation and accelerated atherosclerosis: An intriguing association needing targeted surveillance. Lessons from a rare case of acute anterior myocardial infarction." European Heart Journal: Acute Cardiovascular Care 9, no. 7 (May 24, 2016): NP3—NP7. http://dx.doi.org/10.1177/2048872616652311.
Full textAbstract:
We report the case of a 23-year-old man who developed an acute ST-elevation myocardial infarction secondary to acute thrombotic occlusion of the proximal left anterior descending coronary artery five years after undergoing chemotherapy, radiotherapy, haematopoietic stem cell transplantation for acute lymphoblastic leukaemia and bulky mediastinal mass involving the pleura and pericardium. His medical history also included Graft versus Host Disease developed 13 months after transplantation and acute myocarditis three months before the actual hospital admission. To the best of our knowledge, coronary artery disease as a complication of haematopoietic stem cell transplantation and low-dose mediastinal radiation therapy in young patients has been rarely reported in the medical literature. Clinicians should have a high degree of suspicion of coronary artery disease in patients treated with allogeneic haematopoietic stem cell transplantation, especially in patients previously treated with target mediastinal radiotherapy, as a group at risk of premature and significantly accelerated atherosclerosis, in order to make a timely and correct diagnosis.
19
Sarkar, Swaimanti, Aindrila Chattopadhyay, and Debasish Bandyopadhyay. "Multiple strategies of melatonin protecting against cardiovascular injury related to inflammation: A comprehensive overview." Melatonin Research 4, no. 1 (January 1, 2021): 1–29. http://dx.doi.org/10.32794/mr11250080.
Full textAbstract:
The onset and progression of baneful chronic diseases are often accompanied by a torrent of uncontrolled inflammatory reactions. Although inflammation is a natural response to detect, eliminate, and counterpoise the harmful insults to physiological integrity, a persistent inflammation causes tissue damage or more serious disorders, for example, the atherosclerosis and myocardial infarction. Inflammation often occurs in the cardiovascular system, but are also caused by other disorders including metabolic syndrome, autoimmune diseases, AIDS, and cancer that can affect the cardiac health. To effectively treat heart diseases a potent remedy is necessary which not only suppresses the inflammation but also prevents inflammation-associated cardio-pathogenesis. The ubiquitous antioxidant molecule melatonin has both anti-inflammatory and cardioprotective activities. Melatonin executes its anti-inflammatory activity by its antioxidant function or by targeting multiple intracellular signalling cascades such as modulating cytokine profile, blocking inflammasome activation and apoptosis. Lipid dysregulation and endothelial dysfunction that play a crucial role in the pathogenesis of atherosclerosis, insulin resistance, and diabetes are prevented by melatonin. Attenuation of mitochondrial and ER stress by melatonin is also pertinent to its cardioprotective action. Additionally, melatonin by its immuno-stimulatory activity can suppress inflammaging and immuno-senescence in HIV patients and thereby averts chronic inflammation-induced cardiovascular abnormality in these subjects. Modulation of cytokine profile and decrease in MMP-9 secretion by melatonin is beneficial in autoimmune conditions. In addition to its anti-tumour potency, melatonin can reduce chemotherapy-induced cardio-toxicity in cancer patients. This review, therefore, provides a concise summary of the currently available information appertaining to the roles of melatonin in mitigation of chronic inflammation and its effect on cardiovascular integrity.
20
Plokhova, E. V., A. V. Sorokin, A. V. Staferov, and D. P. Dundua. "Methods of diagnosis in cardio-oncology." Journal of Clinical Practice 9, no. 1 (December 25, 2018): 50–62. http://dx.doi.org/10.17816/clinpract09150-62.
Full textAbstract:
Early diagnosis and advances in treatment have led to improved survival of patients with cancer, but have also increased morbidity and mortality due to treatment side effects. Cardiovascular diseases (CVDs) are one of the most frequent of these side effects. As a result of the direct effects of radiation therapy and chemotherapy on heart and vessels сan be: acceleration of atherosclerosis, damage of cardiomyocytes and endothelium, and arterial and venous thrombosis. The direct effect of the cancer treatment on the heart is called cardiotoxicity. Early diagnosis and identification of patients at high risk of cardiotoxicity is the first step towards successful prevention of CVD in cancer patients without compromising cancer care, which ultimately leads to a reduction in mortality. Echocardiography is the method of choice for the detection of myocardial dysfunction during and after cancer therapy. New methods of imaging like three-dimensional echocardiography, speckle-tracking echocardiography, cardiac magnetic resonance show a higher sensitivity in detecting of early myocardial dysfunction during cancer therapy. This review outlines the main diagnostic algorithms and approaches used in cardiooncology.
21
Zaborowska-Szmit, Magdalena, Maciej Krzakowski, Dariusz M. Kowalski, and Sebastian Szmit. "Cardiovascular Complications of Systemic Therapy in Non-Small-Cell Lung Cancer." Journal of Clinical Medicine 9, no. 5 (April 27, 2020): 1268. http://dx.doi.org/10.3390/jcm9051268.
Full textAbstract:
Cardiovascular diseases may determine therapy outcomes of non-small-cell lung cancer (NSCLC). The evidence for how iatrogenic cardiovascular complications contribute to ceasing anticancer treatment, decreasing the quality of life or even premature death, is unclear. Older patients and smokers are at risk of atherosclerosis and arterial thromboembolic events (TE), such as myocardial infarction or stroke. Venous TE can be observed in up to 15% of NSCLC patients, but the risk increases three to five times in ALK (anaplastic lymphoma kinase)-rearranged NSCLC. ALK inhibitors are associated with electrophysiological disorders. Cytotoxic agents and anti-VEGF inhibitors mainly cause vascular complications, including venous or arterial TE. Cardiac dysfunction and arrhythmias seem to be less frequent. Chemotherapy is often administered in two-drug regimens. Clinical events can be triggered by different mechanisms. Among epidermal growth factor inhibitors, erlotinib and gefitinib can lead to coronary artery events; however, afatinib and osimertinib can be associated with the development of heart failure. During anti-PD1/anti-PDL1 therapy, myocarditis is possible, which must be differentiated from acute coronary syndrome and heart failure. Awareness of all possible cardiovascular complications in NSCLC encourages vigilance in early diagnostics and treatment.
22
Cacciotti, Chantel, Christine Chordas, Kate Valentino, Rudy Allen, Peter Manley, and Natasha Pillay-Smiley. "QOL-41. CARDIAC DYSFUNCTION IN MEDULLOBLASTOMA SURVIVORS TREATED WITH PHOTON IRRADIATION." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii438—iii439. http://dx.doi.org/10.1093/neuonc/noaa222.699.
Full textAbstract:
Abstract BACKGROUND Medulloblastoma is an aggressive central nervous system (CNS) tumor that occurs mostly in the pediatric population. Treatment includes surgical resection, craniospinal radiation (CSI) and chemotherapy. Children who receive standard photon radiation (RT) are at risk for cardiac toxicities. Potential late effects include coronary artery disease, left ventricular scarring and dysfunction, valvular damage and atherosclerosis. Current survivorship guidelines recommend routine ECHO surveillance for these patients but this comes at significant health care costs over a lifetime. We describe the experience of cardiac dysfunction in medulloblastoma survivors in a multi-institution study. METHODS A retrospective chart review of medulloblastoma patients treated between 1980 and 2010 with radiation at Lurie Children’s Hospital and Dana-Farber/ Boston Children’s Hospital who had an echocardiogram done following completion of therapy. RESULTS 168 patients were treated for medulloblastoma during the study time. Of whom, 80 patients had echocardiogram follow up and 76 received photon irradiation. The latter were included in the study. The mean age at CSI was 8.6 years (range 2.9- 20), and mean number of years post RT at echocardiogram 7.4 years (range 2–16). Mean ejection fraction (EF) was 60.03% and shortening fraction (SF) 33.8%. Four patients (5%) had abnormal results, all of which had EF<50%. CONCLUSION Patients who received craniospinal irradiation for medulloblastoma therapy have relatively normal echocardiograms post treatment. Although RT may result in cardiac risks, echocardiograms may not be the most cost effective or efficacious mode to evaluate the risk in these survivors long term.
23
Anwar, Syaiful, Purwanto Adhipireno, Ria Triwardhani, and Edward Kurnia Setiawan Limijadi. "The Correlation between Serum Amyloid A, Mean Platelet Volume, and Creatine Kinase Myocardial B in Acute Coronary Syndrome." Open Access Macedonian Journal of Medical Sciences 9, B (May 20, 2021): 286–89. http://dx.doi.org/10.3889/oamjms.2021.5922.
Full textAbstract:
BACKGROUND: Atherosclerosis causes acute myocardial necrosis and inflammation characterized by increased mean platelet volume (MPV) and serum amyloid A (SAA). Creatine Kinase Myocardial Band (CKMB) is known as myocardial necrosis marker commonly used in daily practice to help diagnosing acute coronary syndrome. AIM: The purpose of this study was to determine the correlation between MPV, SAA, and CKMB in patients with acute coronary syndrome. METHODS: An analytic observational study with a cross-sectional approach was conducted from May to July 2019. This study involved 32 patients with ACS at the Emergency Department of Dr Kariadi Public Hospital. The inclusion criteria of this study were patients with chest pain, aged 30–75 years, and normal body temperature while the exclusion criteria were malignancy, undergoing chemotherapy/radiation, renal failure, hypertension, and liver disease. Examination of CKMB was done using the spectrophotometry method, MPV value was measured using a hematology analyzer, and SAA level was measured using the ELISA method. Statistical test was done using Spearman correlation. RESULTS: The median (min-max) of MPV and SAA values was 9.85 (2.78-11.7) fL and 40.454 (5.879–66.059) μg/ml, while the mean ± SD (min-max) value of CKMB was 115.47 ± 155.97 (10–608) U/L. The correlation coefficient between CKMB level with MPV and SAA levels were r = −0.244 (p = 0.179) and r = 0.442 (p = 0.011), respectively. CONCLUSION: There was a significant positive moderate correlation between CKMB and SAA levels which could be used as a marker of acute inflammation in ACS, whereas inflammatory marker of MPV did not have a significant correlation.
24
Lenihan, Daniel J., Ravi Potluri, Hitesh Bhandari, Sandip Ranjan, and Clara Chen. "Evaluation of Cardiovascular Comorbidities Among Patients with Multiple Myeloma in the United States." Blood 128, no. 22 (December 2, 2016): 4794. http://dx.doi.org/10.1182/blood.v128.22.4794.4794.
Full textAbstract:
Abstract Background: Multiple myeloma (MM) is typically diagnosed in older adults, with a median age at diagnosis of 69 years and the majority diagnosed between ages 65 and 74 years. It might be expected that cardiovascular disease (CVD) would be common in this patient population but currently there is little data about CVD in this population. CVD events may be consequences of age-related comorbidities, CVD itself, or anti-MM treatment received. Anthracycline chemotherapy, certain proteasome inhibitors and immunomodulatory drugs have been reported to increase the risk of CVD complications. Objective: To determine the prevalence of CVD comorbidities among MM patients in the period prior to receiving anti-MM treatment as observed in a US claims database, in order to understand the magnitude of these risks in a 'real-world' practice setting. Methods: Patients with a diagnosis ICD-9 code for MM were identified in MarketScan Commercial and Medicare claims databases from 7/1/2012 to 9/30/2014. The index date was the first claim of an anti-MM drug in this period, which was preceded by a 6-month baseline period with continuous medical and prescription drug coverage and no claims for another anti-MM drug. CVD comorbidities included cardiac arrhythmia, cardiac failure, stroke, ischemic heart disease, hypertension, venous thromboembolism (VTE), angina, coronary atherosclerosis and myocardial infarction (MI). Descriptive statistics were used to measure and report demographics and patient characteristics. Prevalence of CVD in MM patients was adjusted for the age and sex profile of the general US population and compared with prevalence reported in the literature for the US population. Patients were also divided into subgroups according to the anti-MM regimen received, and the prevalence of CVD by subgroup was assessed. Results: 4,635 patients met the study eligibility criteria (median age 64 years, 57% male, 42% with Charlson Comorbidity Index ≥2). Of these, 28%, 21%, 32% and 18% were in the North Central, Northeast, South and West regions, respectively. During the baseline period, CVD was present in 66% (n=3,048) of patients with MM. Relative to the general US adult population, annual standardized prevalence rates in this MM population were 22.0, 12.0, 2.8, 2.1 and 1.1 times higher for arrhythmia, VTE, cardiac failure, coronary atherosclerosis and hypertension, respectively, while being 82%, 73% and 32% lower for angina, stroke and MI, respectively. It is possible that patients with a history of these acute CVD events were less likely to receive an anti-MM drug (Table). Further, the prevalence of baseline CVD events in patients receiving carfilzomib was 34%, 52%, 43%, 30% and 47% lower for arrhythmia, cardiac failure, ischemic heart disease, hypertension and coronary atherosclerosis, respectively, than in those not receiving carfilzomib. Conclusion: Compared with the general US adult population, patients with MM appear to have a higher prevalence of CVD comorbidities relevant to anti-MM treatment. The lower rates of baseline CVD events suggests clinicians may avoid using carfilzomib in MM patients who are at risk of CVD. Given the chronic nature of MM and the need for long-term care, CVD comorbidities should be ascertained and taken into consideration when selecting appropriate treatment to manage the clinical and economic burden associated with such conditions. Table Table. Disclosures Lenihan: BMS, Roche, Amgen (Consultancy); Takeda (Research Funding): Consultancy, Research Funding. Potluri:Janssen Research & Development, LLC: Other: Contracted to perform research; SmartAnalyst, Inc.: Employment. Bhandari:SmartAnalyst India Pvt. Ltd.: Employment. Ranjan:SmartAnalyst India Pvt. Ltd.: Employment. Chen:Bristol-Myers Squibb: Employment.
25
Diplas, Bill, Ryan Ptashkin, Andrea Cercek, Rona Yaeger, Kelly L. Bolton, Sree Bhavani Chalasani, Avni Mukund Desai, et al. "Clinical relevance of clonal hematopoiesis in metastatic gastrointestinal malignancies." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e16082-e16082. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e16082.
Full textAbstract:
e16082 Background: Clonal hematopoiesis (CH) represents non-random clonal selection of bone marrow-derived cells marked by somatic mutations in certain genes. The presence of CH is associated with development of atherosclerosis and leukemia, and accelerated by toxic exposures (chemotherapy, radiation, smoking) and aging (Jaiswal et al. NEJM 2017; Abelson et al. Nature 2018). The impact of these genetic alterations on cellular function is unknown, especially in the broader context of immunity and in response to cancer therapy. To determine the contribution of CH to therapeutic response and hematologic toxicity in cancer patients, we examined the outcomes of patients treated with cytotoxic and immunotherapy in relationship to CH status. Methods: We evaluated patients with metastatic colorectal cancer (CRC) or esophagogastric cancer (EGC). DNA extracted from whole blood and tumor tissue were sequenced in tandem as part of the MSK-IMPACT hybridization capture-based sequencing assay. CH was defined as any mutation with a VAF of at least 2%, present in at least 10 reads, with at least 2:1 blood:tumor reads, or 1.5:1 blood:lymph node that was not found in gnomAD with a frequency > 0.005. Additional filtering and putative driver definitions (CH-PD) were described by Bolton et al. Nature Genetics 2020. Multivariate survival analyses were performed using a Cox Proportional Hazard model correcting for CH, CH-PD, prior smoking, prior chemotherapy, prior radiation, MSI status, and age at cancer diagnosis. Results: 654 patients with EGC (n = 348) and CRC (n = 306) who began treatment between 2006 and 2020 were included in the analysis. CH was present in 34.5% and 24.4% of each group, and 17.2% and 12.9% harbored CH-PD, respectively. CH and CH-PD were both associated with older age and smoking history, and CH was also associated with prior radiation and MSI-high status (p < 0.05). Patients with CH or CH-PD receiving first-line (1L) therapy for CRC or EGC demonstrated no difference in mPFS after multivariate analysis, though 1L EGC patients with CH-PD had inferior mOS (p = 9e-5). There was no difference in pre-1L WBC, ANC, or ALC, nor in G-CSF or PEG-G-CSF doses administered during 1L therapy between patients with CH or CH-PD versus those without. Similarly, presence of CH or CH-PD had no impact on mPFS or mOS in patients receiving immune checkpoint blockade (ICB) without concurrent chemotherapy after multivariate survival analysis. Conclusions: We confirmed that the mere presence of CH is not prognostic for overall survival, but that EGC patients with CH-PD mutations have inferior overall survival, which is consistent with previous findings. Presence of CH or CH-PD was not associated with differences in baseline leukocyte counts nor need for G-CSF support, nor did it impact PFS in either tumor type, suggesting limited utility of CH in solid tumor clinical decision-making.
26
Tilija Pun, Nirmala, and Chul-Ho Jeong. "Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance." Pharmaceuticals 14, no. 5 (May 16, 2021): 470. http://dx.doi.org/10.3390/ph14050470.
Full textAbstract:
Cancer is incurable because progressive phenotypic and genotypic changes in cancer cells lead to resistance and recurrence. This indicates the need for the development of new drugs or alternative therapeutic strategies. The impediments associated with new drug discovery have necessitated drug repurposing (i.e., the use of old drugs for new therapeutic indications), which is an economical, safe, and efficacious approach as it is emerged from clinical drug development or may even be marketed with a well-established safety profile and optimal dosing. Statins are inhibitors of HMG-CoA reductase in cholesterol biosynthesis and are used in the treatment of hypercholesterolemia, atherosclerosis, and obesity. As cholesterol is linked to the initiation and progression of cancer, statins have been extensively used in cancer therapy with a concept of drug repurposing. Many studies including in vitro and in vivo have shown that statin has been used as monotherapy to inhibit cancer cell proliferation and induce apoptosis. Moreover, it has been used as a combination therapy to mediate synergistic action to overcome anti-cancer drug resistance as well. In this review, the recent explorations are done in vitro, in vivo, and clinical trials to address the action of statin either single or in combination with anti-cancer drugs to improve the chemotherapy of the cancers were discussed. Here, we discussed the emergence of statin as a lipid-lowering drug; its use to inhibit cancer cell proliferation and induction of apoptosis as a monotherapy; and its use in combination with anti-cancer drugs for its synergistic action to overcome anti-cancer drug resistance. Furthermore, we discuss the clinical trials of statins and the current possibilities and limitations of preclinical and clinical investigations.
27
Habib, N., H. Daaboul, G. Hajj, A. Jabbour, and N. Kassem. "Antitumor activity of a new cholesterol derivative (24-ethyl-cholestane- 3β, 5α,6α-triol) in solid tumors." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e13541-e13541. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e13541.
Full textAbstract:
e13541 Oxysterols are oxygenated derivatives of cholesterol. They have nuclear receptors and have been shown to pass cell membranes and the blood-brain barrier at a faster rate than cholesterol itself. In addition, oxysterols have been ascribed a number of important roles in connection with cholesterol turnover, atherosclerosis, apoptosis, and necrosis. Oxysterols have been shown to have antitumor effects on experimental models. These compounds however may be toxic and to our knowledge, although some derivatives have been tested in animals, none have reached the clinical level. 24-ethyl-cholestane- 3β,5α,6α-triol is a new oxysterol developed in our lab. An oral form of this compound has been tested in mice and rats and has shown neither acute nor chronic toxicity. It has also been tested on animal tumor models and on human cancer xenografts. The results of these tests were very promising showing an anti-tumor activity on a panel of tumor cell lines. Our experiments on humans have shown no toxicity for this drug. Many patients with a variety of solid tumors all of whom have received many lines of chemotherapy and considered refractory to any conventional therapy have received this new drug. We observed in most of these patients a rapid and dramatic improvement in their quality of life and a fast pain control. Some patients could stop taking high doses of opioids within 1 or 2 days. A high rate of clinical benefit has also been observed in a variety of solid tumors including lung, breast, pancreatic, ovarian and uterine cancers, associated in some cases with a sharp decrease in tumor markers. Some patients with brain tumors (glioblastomas) have also responded to this therapy. No significant financial relationships to disclose.
28
Ivanova, Victoria Aleksandrovna, Galina Nerodo, and Ekaterina Alekseevna Nerodo. "Peculiarities of clinical characteristics in different aged patients with vulvar cancer." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e16512-e16512. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e16512.
Full textAbstract:
e16512 Background: Comparison of vulvar cancer clinical flow in patients of reproductive and old age. Methods: The studying of vulvar cancer clinical delopment included 64 patients of reproductive age and 775 patients of old age. Results: The patients were from 20 to 90 years old; 64 (7.6%) of them were from 20 to 50 years old; the other 92.4% were more than 50 years old. The patients of reproductive age at early stages made up 70.3%; the patients of old age at early stages made up 70.3%. Hypertensive disease (13.5%), obesity (13.5%), diseases of liver and stomach (11.8%) and the sole case of diabetes mellitus (1.6%) were among the concomitant diseases of the reproductive age patients. Among the seniors,: hypertensive disease (77.7%), atherosclerosis (42.9%), obesity (62.8%), osteochondrosis (18.3%), diabetes mellitus (9.1%), diseases of liver and gall bladder (29.95%). Only 16% of the patients from the younger group had leukokeratosis and kraurosis; among the seniors, 62% had those diseases. At the same time, the younger the group of patients with vulvar cancer, the more often they had papilloma, condyloma on vulva in their anamnesis, and infection of human papilloma virus. In the group under 50 such patients made up 87.5%, and in the group of seniors there was one case of infection of human papilloma virus – 0.48%. All the patients undergone different types of complex curing; more than half of the patients undergone chemotherapy. 17% of the patients of the reproductive age, and 23.3% of the seniors had the relapses of the disease. Conclusions: Our study proved the statement about existence of two pathogenetic variants of vulvar cancer appearance: the first variant is HPV– positive, diagnosed in young women; the second variant is HPV– negative, diagnosed in women of elderly age, associated with neurodystrophic processes and chronic infection.
29
Rachel, Q. M. N., K. Mamun, and M. H. Nguyen. "603 CHALLENGES IN THE MANAGEMENT OF SEVERE ORTHOSTATIC HYPOTENSION ASSOCIATED WITH SUPINE HYPERTENSION IN A PATIENT WITH AUTONOMIC DYSFUNCTION ON BACKGROUND OF NASOPHARYNGEAL CARCINOMA AND TYPE II DIABETES MELLITUS." Age and Ageing 50, Supplement_2 (June 2021): ii14—ii18. http://dx.doi.org/10.1093/ageing/afab119.16.
Full textAbstract:
Abstract Introduction Combined chemotherapy and radiotherapy increases long term survival in patients with nasopharyngeal carcinoma. However, radiotherapy of the carotid sinus or brain stem can evolve labile hypertension and orthostatic intolerance from chronic baroreflex failure. Diabetes would also cause this neuropathy. Management of patients with Supine hypertension-Orthostatic hypotension can be very challenging. Methods A case report was done on a 71-year-old man with metastatic nasopharyngeal carcinoma status post radiation therapy who was admitted with severe supine hypertension-orthostatic hypotension. Patient was managed with both non-pharmacological and pharmacological methods, and monitored for postural symptoms, complications of severe supine hypertension—which has been linked to left ventricular hypertrophy and kidney dysfunction, and placed on 24 hour ambulatory blood pressure monitoring to aid in management so as to prevent hypertension induced organ damage. Results This review outlines the pathophysiology of Supine hypertension-Orthostatic hypotension, treatment complications and potential management strategies recommendations for this group of patients. It revealed the benefit of having a 24 hour ambulatory blood pressure monitoring, which provides insight on the timing and magnitude of an individual’s blood pressure fluctuations throughout the day so as to further guide management. Conclusion Chronic baroreflex failure is a late sequela of neck irradiation for naso-pharyngeal carcinoma due to accelerated atherosclerosis in the region of the carotid sinus baroreceptor. Treatment goal is achieved with adequate control of pre-syncopal symptoms and prevention of long term complications. Non-pharmacological interventions remain the first line of therapy, followed by pharmacological interventions as necessary. Nonetheless, management of blood pressure in these elderly patients with baroreflex dysfunction remains challenging and should be individualized. Moving forward, a prospective study on the incidence of late onset, iatrogenic baroreflex failure as a late complication of neck irradiation and its particular relationship to carotid arterial rigidity should be conducted to increase awareness, timely diagnosis and management of the condition among physicians.
30
Mok, Tony S. K., Pilar Garrido Lopez, Edward S. Kim, Cagatay Arslan, Jean-Louis Pujol, Yuanbo Song, Cecile Blin, et al. "Randomized phase II study of canakinumab (CAN) or pembrolizumab (PEM) as monotherapy or in combination as neoadjuvant therapy in patients (Pts) with surgically resected (Stage IB-IIIA) non-small cell lung cancer (NSCLC): CANOPY-N." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): TPS9626. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.tps9626.
Full textAbstract:
TPS9626 Background: Complete surgical resection is the standard treatment (tx) for pts with stage I-IIIA NSCLC. 5-year survival rates range from 19-50%, with most pts dying from distant recurrence. Neoadjuvant or adjuvant chemotherapy improves overall survival (OS) by only 5% in pts with NSCLC, and new tx options are needed. Preliminary data with PD-1 or PD-L1 inhibitors as neoadjuvant therapy has shown major pathologic responses (MPR) or pathologic complete responses (pCR) in pts with early stage NSCLC. CANTOS study demonstrated reduced incidence of NSCLC and decreased lung cancer-related mortality with CAN (IL-1β inhibitor) versus placebo, in a dose-dependent manner for pts with atherosclerosis. In pre-clinical NSCLC humanized models, tx with CAN±anti PD-1 inhibitor could lead to anti-tumor activity. Combination of CAN and PEM is expected to enhance the efficacy of PD-1 inhibition by inhibiting dysregulated inflammation in tumor microenvironment. Based on available evidence, CANOPY-N study was designed to evaluate effect of CAN and PEM as monotherapy or in combination as neoadjuvant tx for pts with resectable NSCLC. Methods: CANOPY-N (NCT03968419) is a phase II, randomized, open-label study evaluating effect of CAN or PEM monotherapy or in combination as neoadjuvant tx in resectable NSCLC pts. Histologically confirmed stage IB-IIIA, tx-naive, ECOG PS 0-1 NSCLC pts eligible for surgery and with a planned surgical resection in approximately 4-6 weeks (after 1st dose of study tx), are eligible to participate. An archival (if obtained up to 6 months before 1st day of tx) or new biopsy is required. Approximately 110 pts will be randomized in 2:2:1 ratio (stratified by histology [squamous/non-squamous]) to one of the tx arms to receive a total of 2 doses (200 mg Q3w) of CAN alone (n = 44) or in combination with PEM (n = 44) or PEM (n = 22) with safety follow-up up to 130 days from last study drug dose. Primary endpoint is to determine MPR rate (≤10% of residual viable tumor cells at time of surgery), secondary endpoints include determination of ORR, MPR rate based on local review, surgical feasibility rates, anti-drug antibodies incidence and PK parameters. Clinical trial information: NCT03968419 .
31
Haugnes, Hege S., Torgeir Wethal, Nina Aass, Olav Dahl, Olbjørn Klepp, Carl W. Langberg, Tom Wilsgaard, Roy M. Bremnes, and Sophie D. Fosså. "Cardiovascular Risk Factors and Morbidity in Long-Term Survivors of Testicular Cancer: A 20-Year Follow-Up Study." Journal of Clinical Oncology 28, no. 30 (October 20, 2010): 4649–57. http://dx.doi.org/10.1200/jco.2010.29.9362.
Full textAbstract:
Purpose To evaluate the prevalence of cardiovascular risk factors and long-term incidence of cardiovascular disease (CVD) in survivors of testicular cancer (TC). Methods Overall, 990 men treated for unilateral TC (1980 to 1994) were included in this national follow-up study (2007 to 2008). They were categorized into four treatment groups: surgery (n = 206), radiotherapy only (RT; n = 386), chemotherapy only (n = 364), and combined RT/chemotherapy (n = 34). Age-matched male controls from the general population (ie, NORMs) were included (n = 990). Survivors of TC who were diagnosed with CVD before or within 2 years after the TC diagnosis were excluded from analyses of CVD end points. Results Median observation time was 19 years (range, 13 to 28 years). All cytotoxic treatment groups had significantly increased prevalences of antihypertensive medication, and survivors in the RT and RT/chemotherapy groups had higher prevalences of diabetes (RT: odds ratio [OR], 2.3; 95% CI, 1.5 to 3.7; RT/chemotherapy: OR, 3.9; 95% CI, 1.4 to 10.9) compared with NORMs. Overall 74 survivors of TC (8.0%) experienced atherosclerotic disease during follow-up. Increased risks for atherosclerotic disease were observed in age-adjusted Cox regression analyses after any cytotoxic treatment when compared with surgery only (RT: hazard ratio [HR], 2.3; 95% CI, 1.04 to 5.3; chemotherapy: HR, 2.6; 95% CI, 1.1 to 5.9; RT/chemotherapy: HR, 4.8; 95% CI, 1.6 to 14.4). Treatment with cisplatin, bleomycin, and etoposide (BEP) alone had a 5.7-fold higher risk (95% CI, 1.9 to 17.1 fold) for coronary artery disease compared with surgery only and a 3.1-fold higher risk (95% CI, 1.2 to 7.7 fold) for myocardial infarction compared with NORMs. Conclusion Treatment with infradiaphragmatic RT and/or cisplatin-based chemotherapy, particularly the BEP regimen, increases the long-term risk for CVD in survivors of TC.
32
Nakazato, Tomonori, Chisako Ito, Kengo Shimazaki, Hideki Arakaki, and Yoshinobu Aisa. "Evaluation of Oxidative Stress Markers in Hematopoietic Stem Cell Transplantation Patients." Blood 126, no. 23 (December 3, 2015): 1925. http://dx.doi.org/10.1182/blood.v126.23.1925.1925.
Full textAbstract:
Abstract [Introduction] Oxidative stress caused by the increased production of reactive oxygen species (ROS) or decreased efficacy of the antioxidant system is implicated in the pathogenesis of various disease entities, such as atherosclerosis, cardiovascular disease, renal failure, malignant tumors, and autoimmune diseases. Chemotherapy and radiation therapy are associated with increased formation of ROS. Conditioning regimens preceding hematopoietic stem cell transplantation (HSCT) usually consist of high-dose chemotherapy and/or total body irradiation (TBI). A limited number of studies demonstrated that the conditioning therapy given to HSCT patients creates a high oxidative stress and decreases the antioxidant defense system. The objective of this study was to look for further evidence of oxidative stress status in HSCT patients. [Methods] In this study, urine samples were collected from 32 HSCT patients before and after conditioning therapy and from 15 healthy controls. The patients included 19 male and 13 female with a median age of 58 years (27-68 years). Twenty patients received allogeneic HSCT (9 uBMT, 1 rPBSCT and 10 CBT) and 12 patients received autologous PBSCT. The conditioning regimens for allo-HSCT included TBI12Gy+Ara-C+G-CSF (n=3), TBI12Gy+Ara-C+CY (n=1), TBI12Gy+VP-16+CY (n=1), Flu+L-PAM+TBI3Gy (n=6), Flu+BU+TBI3Gy (n=1), Flu+Ara-C+G-CSF+BU+TBI4Gy (n=3), Flu+L-PAM (n=2), and BU+CY (n=3). The diagnosis included AML (n=9), MDS (n=5), DLBCL (n=1), FL (n=2), T-ALL (n=1) and MM (n=2). Fifteen patients (75%) had high-risk disease at transplantation. Twelve multiple myeloma (MM) patients received L-PAM 200mg/m2 + autologous PBSCT. We measured urinary 8-hydroxydeoxyguanosine (8-OHdG) by competitive immunochromatography using a novel automatic oxidative stress analyzer, ICR-001 (Techno-Medica). 8-OHdG, which originates from damaged DNA repaired by non-specific endonucleases and specific glycosylates and is eliminated into urine, is widely used as a sensitive biomarker of oxidative stress. [Results] Urinary 8-OHdG significantly increased immediately after conditioning therapy. In 20 allo-HSCT patients, urinary 8-OHdG levels on day 0 were significantly higher than pre-conditioning levels and healthy controls (mean: 458.2 vs. 90.9 vs. 15.7 ng/mgCr). In 12 auto-HSCT patients, urinary 8-OHdG levels on day 0 were also higher than pre-conditioning levels (mean: 273.6 vs. 107.2 ng/mgCr). No significant correlation was found between urinary 8-OHdG levels and serum ferritin levels during pre- and post-transplant period. Allo-HSCT patients with high urinary 8-OHdG levels on day 0 (over 300ng/mg/Cr; N=10) had significantly shorter survival than those with low urinary 8-OHdG levels on day 0 (under 300ng/mg/Cr; N=10) (1-year OS, 11.1% vs. 80.0%, respectively; P=0.01) (Figure. 1). On the other hand, post-conditioning urinary 8-OHdG levels were not associated with outcome in auto-HSCT patients. In univariate analysis, a high 8-OHdG level on day 0, CBT, and RIC regimen were associated with poor OS in allo-HSCT patients. [Conclusion] In the present study we demonstrated that conditioning therapy results in increased oxidative stress in HSCT patients. In particular, our data proved that high urinary 8-OHdG levels on day 0 were associated with poor prognosis in allo-HSCT patients. These results suggest that oxidative stress may have an important role in allo-HSCT and also may be a useful prognostic biomarker. Since our results are based on a small-sized analysis, further large prospective studies are warranted to verify this conclusion. Disclosures No relevant conflicts of interest to declare.
33
Jordan, Jennifer H., Sujethra Vasu, Tim Morgan, Ralph D’Agostino, Giselle C. Melendez, Michael Hall, Craig Hamilton, et al. "MYOCARDIAL EXTRACELLULAR VOLUME IS ELEVATED IN CANCER SURVIVORS TREATED WITH ANTHRACYCLINE-BASED CHEMOTHERAPY COMPARED TO CANCER-FREE PEERS AND NEWLY DIAGNOSED AND UNTREATED CANCER PATIENTS: A SINGLE-CENTER OBSERVATIONAL STUDY OF THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) AND CARDIO-ONCOLOGY CARDIOVASCULAR MAGNETIC RESONANCE IMAGING STUDIES." Journal of the American College of Cardiology 65, no. 10 (March 2015): A1081. http://dx.doi.org/10.1016/s0735-1097(15)61081-6.
Full text
34
Rao, Uttam K., Heidi Chen, Katie S. Gatwood, Michael T. Byrne, Salyka M. Sengsayadeth, Stacey A. Goodman, Bhagirathbhai Dholaria, et al. "Reduced Insulin Sensitivity in Patients with Myeloid Malignancies and Clonal Hematopoiesis Mutations." Blood 136, Supplement 1 (November 5, 2020): 27–28. http://dx.doi.org/10.1182/blood-2020-137712.
Full textAbstract:
Cancer survivors are at increased risk for insulin resistance, which can lead to diabetes mellitus, dyslipidemia, and cardiovascular disease. Whether susceptibility to insulin resistance is due to shared onco-metabolic risk factors, like obesity and older age, or if it originates from malignancy and its treatment is unknown. We investigated metabolic and malignancy-associated risk factors and their effect on insulin sensitivity in patients with treated hematological malignancies. Due to previous glucocorticoid exposure, we hypothesized that patients with lymphoid malignancies would be less insulin sensitive. Nineteen adult patients with treated hematological malignancies but without diabetes mellitus were evaluated with a 2-hour, 75-gram, oral glucose tolerance test (OGTT) and a hyperinsulinemic-euglycemic clamp. Hyperinsulinemic-euglycemic clamps were performed to measure steady-state glucose infusion rate (M-value) as an indicator of whole-body glucose utilization during high-dose insulin stimulation. Decreasing M-values reflect increasing insulin resistance. Patient characteristics were analyzed and compared with OGTT and clamp results. The majority of individuals had myeloid malignancies [MDS/AML (n=7) and CML/MPN (n = 4)]. The remainder were diagnosed with NHL (n=7) and CML lymphoid blast crisis (n=1). All patients were treated before metabolic testing. Sixteen individuals (84%) received cytotoxic chemotherapy and 3 (16%) were administered only tyrosine kinase inhibitors. Median lines of systemic treatment were 2 (range, 1-6), and median time from cancer diagnosis to metabolic testing was 10 months (range, 3-132). Immediately before OGTTs and clamps, 10 (53%) patients were in a complete response, and 9 (47%) had persistent/stable disease. During OGTTs, impaired fasting glucose (plasma glucose 100-125 mg/dL) and impaired glucose tolerance (2-hour plasma glucose 140-199 mg/dL) were respectively observed in 5 (26%) and 6 (32%) patients. M-values were decreased in patients with impaired glucose tolerance. Overweight and obese cancer patients also had lower M-values than individuals with normal body mass indices (BMI) (Table 1). There were otherwise no differences in insulin resistance per age, sex, performance status, ethnicity, or diabetes family history. Differences in insulin resistance were not observed based on exposure to cytotoxic chemotherapy, non-cranial irradiation, numbers of lines of treatment, response, or malignancy duration. Previous glucocorticoid exposure did not impact insulin sensitivity. Surprisingly, patients with myeloid malignancies demonstrated lower M-values (6.92 + 0.54 vs. 12.11 + 1.89; p=0.026) than did those with lymphoid cancers. Acquired mutations involved with myeloid malignancies and clonal hematopoiesis (CH) can increase the risk for atherosclerosis and cardiovascular disease, which are sequelae of insulin resistance. Accordingly, insulin resistance was increased in patients with both a myeloid malignancy and mutations involving either DNMT3A, TET2, ASXL1, or JAK2 compared to myeloid malignancies with unknown/absent CH mutations or lymphoid cancers (6.71 + 0.77 vs. 7.28 + 0.72 vs. 12.11 + 1.89; p=0.031). After adjustment for interaction effect in linear regression modeling, both myeloid malignancy and elevated BMI continued to predict lower insulin sensitivity (Table 2). Pre-diabetes was diagnosed by fasting glucose or OGTT in 26-32% of patients with treated hematological cancers, more than double the prevalence of impaired fasting glucose or impaired glucose tolerance reported by the National Health and Nutrition Examination Survey III. Contrary to our hypothesis, lymphoid cancers and short-term steroids did not contribute to insulin resistance. Instead, myeloid malignancies and CH mutations were associated with reduced insulin sensitivity. Interventions targeting energy balance and obesity will be needed to prevent the harmful sequelae of insulin resistance in long-term cancer survivors. Alternatively, elimination of CH mutations could prove to be a novel treatment of insulin resistance. Disclosures Dholaria: bms: Research Funding; Poseida: Research Funding; Angiocrine: Research Funding; Takeda: Research Funding; J&J: Research Funding.
35
Arvedson, Tara L., George Doellgast, Hossein Salimi-Moosavi, Chadwick King, Ian Foltz, Ching Chen, Hongyan Li, and Barbra J. Sasu. "Development of a Sandwich ELISA to Detect Hepcidin in Human Serum." Blood 114, no. 22 (November 20, 2009): 2000. http://dx.doi.org/10.1182/blood.v114.22.2000.2000.
Full textAbstract:
Abstract Abstract 2000 Poster Board I-1022 Hepcidin is a 25 amino acid peptide that is the central mediator of iron metabolism. Iron excess, deficiency and maldistribution have been implicated in the etiology of many diseases including atherosclerosis, diabetes, neurodegeneration and the anemia of inflammation. Determination of hepcidin levels may be useful in diagnosis and treatment decisions for some or all of these diseases. Serum hepcidin measurement has so far been limited to a prohepcidin (60 amino acid hepcidin precursor) ELISA, mass spectrometry (MS)-based assays or competition ELISAs using polyclonal anti-hepcidin antibodies. The current work describes the generation of a sandwich ELISA using monoclonal antibodies to detect human hepcidin (hHepc) and optimization of assay conditions to resolve inconsistencies between MS- and ELISA-based detection. The ability of two anti-hHepc antibodies to sandwich (bind simultaneously) with hHepc was demonstrated using a rabbit polyclonal antibody preparation from hHepc-immunized animals. The same polyclonal antibody preparation was used for both hHepc capture and detection. The limit of detection achieved with this assay was O.D.450<1, suggesting that only a small proportion of the total antibodies could bind concurrently. To improve hHepc detection, a panel of monoclonal antibodies was screened for the ability to sandwich. Antibody epitope characterization studies using purified antibodies and >1000 hybridoma supernatants identified three classes of antibodies: classes 1 and 2 each recognized epitopes found in both full length mature hHepc (hHepc 25) and a shorter version (hHepc 20); class 3 bound a different epitope and demonstrated an increased affinity for hHepc 25 over hHepc 20. The majority of antibodies characterized were in class 1 while antibodies in classes 2 and 3 were rare (∼1% of antibody panel) highlighting the difficulty in achieving a sandwiching event. Antibodies 19D12 (class 1) and 23F11 (class 2) were identified as the optimal sandwich pair with a detection range of approximately 0.2-1000 ng/ml using synthetic hHepc. Initial comparisons of data generated using the sandwich ELISA and a fully-quantitative MS-based assay demonstrated a lack of consistent agreement. This issue was somewhat addressed by introduction of an alkaline treatment step to dissociate any protein/hHepc complexes in serum. Subsequent comparison of the two assays using sera from several different patient populations (anemia of cancer, chemotherapy-induced anemia, kidney disease) as well as healthy donors demonstrated good correlation (R2 range = 0.83-0.92; n=237). This sandwich ELISA may represent a tool for aligning the MS and ELISA-generated results in a format that has the potential to be high throughput and widely available. Disclosures: Arvedson: Amgen: Employment. Doellgast:Amgen: Employment. Salimi-Moosavi:Amgen: Employment. King:Amgen: Employment. Foltz:Amgen: Employment. Chen:Amgen: Employment. Li:Amgen: Employment. Sasu:Amgen: Employment.
36
Ghanem, Riede, Uhrmeister, Weigang, and Altehoefer. "Epithelioides Angiosarkom der Aorta." Vasa 31, no. 4 (November 1, 2002): 269–73. http://dx.doi.org/10.1024/0301-1526.31.4.269.
Full textAbstract:
Primary malignant tumors of the aorta are extremely rare. Review of the literature indicates that there are nearly 100 recorded cases of primary malignant tumors of the aorta. The purpose of this article is to present an additional case of the primary malignant tumors of the aorta which initially has been misinterpretated as atherosclerosic disease. This aortic tumor was of endothelial origin and immunohistochemical studies classified the tumor as an epithelioid angiosarcoma. The treatment resulted in an abdominal aortic repair. MRI of the spine revealed multifocal metastastic disease of the axial skeleton and a subsequent chemotherapy was performed. The patient died 17 months after the initial diagnosis.
37
Gangaraju, Radhika, Yanjun Chen, Lindsey Hageman, Jessica Wu, Wendy Landier, Liton F. Francisco, Andrew McDonald, et al. "Stroke Risk in Blood or Marrow Transplant (BMT) Survivors - a Report from the BMT Survivor Study (BMTSS)." Blood 134, Supplement_1 (November 13, 2019): 3298. http://dx.doi.org/10.1182/blood-2019-124564.
Full textAbstract:
BACKGROUND: BMT recipients are vulnerable to accelerated atherosclerosis due to prior exposure to radiation with or without chemotherapy, and consequent long-term cardiovascular morbidity, such as stroke. A comprehensive evaluation of the risk of late-occurring stroke in adult BMT survivors and the associated risk factors has not been performed. We addressed this gap using the resources offered by the BMTSS. METHODS: BMTSS includes patients transplanted between 1974 and 2014 at 3 US sites who survived ≥2y after BMT, were alive and ≥18y at BMTSS survey completion. The survey asked participants to report if a healthcare provider had diagnosed specific chronic health conditions (including stroke), or relapse of primary cancer or development of new cancer, along with age at diagnosis. The participants provided information on sociodemographics, health behaviors and medication use. Medical record abstraction was used for information regarding primary cancer diagnosis, therapeutic exposures (pre-BMT chemotherapy/radiation, transplant preparative regimens), stem cell source (autologous, allogeneic), graft type (bone marrow, cord blood or peripheral blood stem cells), and history of chronic graft vs. host disease (GvHD). A cohort of 908 siblings also completed the BMTSS survey and served as a comparison group. Informed consent was obtained from all participants. RESULTS: The study included 3,479 BMT survivors; 50.3% had received an allogeneic BMT, 54.8% were males; 71.4% were non-Hispanic whites. Median age at study participation was 59y (range: 18-89y) for BMT survivors and 57y (range: 18-90y) for siblings. Patient characteristics are shown in Table 1. BMT survivors were followed for a median of 9y (range: 2-41 y) from BMT. Stroke was reported by 136 BMT survivors (67 allogeneic, 69 autologous); of these, 75 (55%) patients developed stroke ≥2y after BMT. Conditional on surviving ≥2y after BMT, the 10y cumulative incidence of stroke was 3.8% (Fig 1), and was comparable for allogeneic (3.4±0.5%) and autologous (4.2±0.6%) BMT recipients, p=0.3. Stroke in BMT recipients compared with siblings: Using logistic regression, and after adjusting for sociodemographics, physical activity and relevant comorbidities, we found that allogeneic BMT survivors were at a 2.1-fold higher odds of reporting stroke as compared to siblings (95%CI: 1.2-3.7, p=0.01), and autologous BMT recipients were at a 1.7-fold higher odds of reporting stroke compared to siblings (95%CI: 0.9-3.0, p=0.09). Stroke after Allogeneic BMT: History of hypertension (HR=2.2, 95%CI: 1.2-3.9, p=0.007), venous thromboembolism (HR=3.4, 95%CI: 1.6-7.1, p=0.002), diagnosis of acute lymphoblastic leukemia (HR=4.9, 95%CI: 1.6-15.0, p=0.006), acute myeloid leukemia/ myelodysplastic syndrome (HR=5.2, 95%CI: 1.4-19.0, p=0.013) (ref: non Hodgkin lymphoma), pre-BMT exposure to alkylating agents (HR=3.3, 95%CI: 1.3-8.5, p=0.01) and pre-BMT neck radiation (HR=5.4, 95%CI: 1.2-23.8, p=0.03) were associated with increased stroke risk. Exercise was associated with lower stroke risk (HR: 0.5, 95%CI: 0.3-0.9, p=0.01). Stroke after Autologous BMT: The risk factors for stroke in autologous BMT survivors included: increasing age at BMT (HR=1.02/y, 95%CI: 1.0-1.1, p=0.05), history of hypertension (HR=1.8, 95%CI: 1.1-3.2, p=0.03), coronary heart disease (HR=2.8, 95%CI: 1.3-6.4, p=0.01) and venous thromboembolism (HR=2.3, 95%CI: 1.1-4.7, p=0.02). Relapse of primary disease or development of new cancer were not associated with increased stroke risk in either autologous or allogeneic BMT recipients. CONCLUSION: In this large study, we found that the incidence of stroke was 4% among BMT survivors, and that they are at an increased risk of developing stroke when compared to an unaffected comparison group. The study also identified subgroups among BMT survivors at increased risk of stroke such as those who received neck radiation and those with cardiovascular comorbidity. These findings suggest a need for increased awareness of stroke as a late complication of BMT, such that aggressive management of cardiovascular risk factors can be instituted among those at highest risk. Disclosures Weisdorf: Incyte: Research Funding; Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy.
38
Zakai, Neil, Pamela Lutsey, Aaron Folsom, and Mary Cushman. "Black-White Differences In Venous Thrombosis Risk: the Longitudinal Investigation of Thromboembolism Etiology (LITE)." Blood 116, no. 21 (November 19, 2010): 478. http://dx.doi.org/10.1182/blood.v116.21.478.478.
Full textAbstract:
Abstract Abstract 478 Black-White Differences in Venous Thrombosis Risk: The Longitudinal Investigation of Thromboembolism Etiology (LITE). Neil A. Zakai, Pamela L. Lutsey, Aaron R. Folsom, Mary Cushman. Introduction: Venous thrombosis (VT) is more common in blacks than whites. The reasons for this difference and whether it is explained by racial differences in VT risk factors is not known. Methods: VT was ascertained by physician review of medical records in the Longitudinal Investigation of Thromboembolism Etiology (LITE), a prospective observational study of 21,680 men and women age 45–100 years participating in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) cohorts. VT was classified as provoked if preceded within 90 days by major surgery, trauma, immobility, or associated with active cancer or chemotherapy. We used age- and sex-adjusted Cox models to evaluate whether certain VT risk factors explained the increased risk of VT in blacks vs whites. We also tested if the impact of VT risk factors differed by race using interaction terms. Most risk factors were assessed in both ARIC and CHS cohorts (body mass index (BMI), diabetes, hypertension, chronic kidney disease (CKD), factor VIII, and education) except the activated partial thromboplastin time (aPTT), von Willebrand factor (vWF), and protein C were measured in ARIC only and C-reactive protein was measured in CHS only. Results: With up to 15 years of follow up, among 20,964 participants (5,054 blacks) without VT at baseline, 648 developed new VT (200 blacks). The age- and sex-standardized incidence of VT per 1000 person-years was higher in blacks than whites for all VT (3.18 vs 1.96), whether the VT was provoked (2.11 vs. 1.24) or unprovoked (1.12 vs. 0.74), all p <0.01. Blacks and whites had a similar incidence of pulmonary embolism (PE) (0.83 vs. 0.76, p = 0.56). Blacks had more adverse levels of many VT risk factors except CKD and a lower aPTT: BMI (29.3 vs. 26.8 kg/m2), diabetes (21 vs 11%), hypertension (59 vs 38%), CKD (5 vs. 12%), high school graduation (58 vs 80%), factor VIII (146 vs 124%), vWF (134 vs 113%), CRP (2.4 vs 1.8 mg/L) protein C (3.13 vs. 3.18 mg/L), all p <0.01. In age- and sex-adjusted Cox models, the relative risk of total VT for blacks vs. whites was 1.67 (95% CI 1.41, 1.97). When risk factors were added to age-, sex- and race-adjusted Cox models, BMI explained 36% of the excess risk of VT in blacks, factor VIII 58%, and vWF 54%. The other risk factors had a minimal impact on the HR for race. When all risk factors measured in both cohorts were considered in the same model, the association of black race with VT was attenuated (HR 1.15; 95% CI 0.94, 1.42). Of the risk factors evaluated, there were significant interactions between race and hypertension, CKD, and aPTT below the median (29s). The table lists the HR for each of these risk factors stratified by race; hypertension and CKD were stronger risk factors for VT in blacks while an aPTT less than the median was a stronger risk factor for VT in whites. Conclusions: Blacks have a higher incidence of VT than whites, whether provoked or unprovoked. The increased risk in blacks was largely explained by a greater prevalence of VT risk factors among blacks, particularly obesity, higher factor VIII and higher vWF. Further, CKD and hypertension were stronger risk factors for VT in blacks, while a shorter aPTT was a weaker risk factor for VT in blacks. Larger studies of VT in blacks addressing environmental and genetic risk factors and health-care disparities are needed to fully understand reasons for these ethnic differences in VT incidence. Disclosure: No relevant conflicts of interest to declare.
39
Panciu, Traian Constantin, Bianca Masgras, Catrinel Ciuca, Raluca Ciomag, Anca Mihăilescu, and Adriana Gurghean. "Acute Coronary Syndrome Following Long-Term Erlotinib Treatment." Internal Medicine 15, no. 3 (July 1, 2018): 61–66. http://dx.doi.org/10.2478/inmed-2018-0023.
Full textAbstract:
AbstractIntroduction. The treatment of neoplasia has advanced due to targeted molecular therapies. Erlotinib, a tyrosine kinase inhibitor that acts by blocking epidermal growth factor receptor (EGFR), is used to treat advanced or metastatic chemotherapy-resistant non-small cell lung cancers (NSCLC).Erlotinib is a safe and well tolerated medication. Although the most common adverse effects are cutaneous or gastrointestinal, its cardiotoxicity is an important topic in the treatment and follow-up of neoplastic patients.Clinical case. A 76-year-old male patient with 40 Pack Year history of smoking that has quitted 20 years ago, was admitted in 2009 for night sweats, dry cough and weight loss. He is diagnosed with lung cancer in the right upper lobe (T4N2M1), with the histopathological diagnosis of clear cell adenocarcinoma. The patient performs radiotherapy and chemotherapy with 6 series of Gemcitabine and Cisplatin with partial response, followed by Erlotinib treatment with favorable progression with regression of tumor size.In December 2017, he presents recurrent episodes of atypical angina lasting about 2 weeks. The electrocardiographic examination reveals ST segment elevation, with tall T waves and Q waves are present in the lower branches, associated with the increase of myocardial necrosis enzymes. Echocardiography highlights inferior hypokinesia with left ventricle ejection rate estimated at 45%. The patient has a favorable evolution during admission without recurrence of pain. Coronary angiography is performed at distance with evidence of vascular atherosclerotic lesions and the installation of active pharmacodynamic stents.Discussions. Tyrosine kinase inhibitors may be the cause of acute coronary events both by affecting myocardiocytes following EGFR inhibition, but also by increasing atheromatic plaque instability and by prolonging theQT segment.In conclusion a systemic cardiologic assessment of Erlotinib-treated patients may be recommended throughout the course of therapy.
40
Gangaraju, Radhika, Yanjun Chen, Lindsey Hageman, Jessica Wu, Liton F. Francisco, Michelle Kung, Daniel J. Weisdorf, et al. "Coronary Heart Disease Risk in Blood or Marrow Transplant Survivors." Blood 136, Supplement 1 (November 5, 2020): 17–18. http://dx.doi.org/10.1182/blood-2020-137731.
Full textAbstract:
INTRODUCTION: Exposure to total body irradiation (TBI) increases the risk for cardiovascular risk factors (CVRFs) such as diabetes, hypertension and dyslipidemia in Blood or Marrow Transplant (BMT) survivors with the potential to increase the risk of post-BMT Coronary Heart Disease (CHD). Chest radiation is associated with accelerated atherosclerosis in conventionally treated patients. These factors, with or without additional factors such as smoking likely place BMT survivors at a high risk for CHD. Yet, a comprehensive evaluation of the risk of late-occurring CHD in BMT survivors is lacking. We addressed this gap using the resources offered by the BMT survivor study (BMTSS). METHODS: BMTSS includes patients transplanted between 1974 and 2014 at 3 US sites, and who had survived ≥2 years after BMT, and were alive and ≥18 years at BMTSS survey completion. The BMTSS survey asked participants to report chronic health conditions diagnosed by their healthcare provider (including CHD, diabetes, hypertension and dyslipidemia), along with age at diagnosis. The participants self-reported sociodemographics and health behaviors. Information regarding primary cancer diagnosis, therapeutic exposures, donor type, stem cell source, and history of chronic graft vs. host disease (GvHD; for allogeneic BMT recipients) was abstracted from medical records. A cohort of 1,131 siblings completed the BMTSS survey and served as a comparison group. We obtained informed consent from all participants. RESULTS: The study included 3,479 BMT survivors; 50.3% had received an allogeneic BMT, 54.8% were males, and 71.4% were non-Hispanic whites. Median age at study participation was 59 years (interquartile range [IQR]: 48-66 years) for BMT survivors and 57 years (IQR: 46-64 years) for siblings. BMT survivors were followed for a median of 9 years (range: 2-41 years) from BMT. CHD developed after BMT in 122 BMT survivors (52 allogeneic, 70 autologous). BMT recipients compared with siblings: After adjusting for sociodemographics and comorbidities, allogeneic BMT survivors were at a 7.2-fold higher odds (95%CI: 4.0-13.0, p<0.0001) and autologous BMT recipients at a 11.7-fold higher odds (95%CI: 6.8-20.2, p<0.0001) of reporting CHD as compared to siblings. Allogeneic BMT survivors: The 20 year cumulative incidence of CHD was 4.7% for allogeneic BMT recipients. Increasing age at BMT (HR=1.05/year, 95%CI: 1.02-1.07, p<0.0001), male sex (HR=2.09, 95%CI: 1.14-3.82, p=0.017), history of CVRFs (HR=3.6, 95%CI: 1.72-7.41, p=0.0006), and pre-BMT targeted chemotherapy such as tyrosine kinase inhibitors (HR=2.7, 95%CI: 1.10-6.77, p=0.030) were associated with increased CHD risk. The 20 year cumulative incidence of CHD among patients with CVRFs was 6.6% vs. 1.9% (p=0.005) among those who did not have CVRFs (Fig 1). Autologous BMT survivors: The 20 year cumulative incidence of CHD was 9.1% for autologous BMT recipients. The risk factors for CHD in autologous BMT survivors included: increasing age at BMT (HR=1.06/year, 95%CI: 1.03-1.09, p<0.0001), male sex (HR=2.3, 95%CI: 1.30-3.90, p=0.004), history of smoking (HR=1.66, 95%CI: 1.03-2.67, p=0.038), CVRFs (HR=1.77, 95%CI: 1.04-3.01, p=0.036), arrhythmia (HR=1.85, 95%CI: 1.01-3.42, p=0.048) and history of pre-BMT chest radiation (HR=4.56, 95%CI: 2.1-9.88, p=0.0001). For every 1 Gray increase in the dose of chest radiation, there was a 4% increase in the risk of CHD, p=0.0002. The 20 year cumulative incidence of CHD among patients with CVRFs was 10.2% vs. 7.4% among those who did not have CVRFs (p=0.04) (Fig 2). CONCLUSION: BMT survivors are at a 7-fold to 12-fold higher risk of CHD compared with a sibling comparison group. CVRFs are independent risk factors for CHD both among allogeneic and autologous BMT recipients. Pre-BMT chest radiation further increases this risk in autologous BMT recipients. These findings suggest a need for aggressive management of CVRFs in BMT recipients to prevent CHD-related morbidity. Disclosures Gangaraju: Sanofi Genzyme, Consultant for Cold Agglutinin Disease: Consultancy. Weisdorf:FATE Therapeutics: Consultancy; Incyte: Research Funding. Arora:Pharmacyclics: Research Funding; Kadmon: Research Funding; Syndax: Research Funding; Fate Therapeutics: Consultancy.
41
Groen, H., M. M. Hochstenbag, J. W. van Putten, A. Vincent, O. Dalesio, B. Biesma, H. J. Smit, A. Termeer, B. E. van den Borne, and F. M. Schramel. "A randomized placebo-controlled phase III study of docetaxel/carboplatin with celecoxib in patients (pts) with advanced non-small cell lung cancer (NSCLC): The NVALT-4 study." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 8005. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.8005.
Full textAbstract:
8005 Background: Cox-2 is overexpressed in NSCLC tumors and has a negative impact on survival. It is involved in proliferation and angiogenesis. The hypothesis is that celecoxib by inhibiting Cox-2 enzyme will prolong survival and may increase response to chemotherapy. Methods: We performed a phase III study with planned sample size of 540 pts. Included were pts with pathologically proven NSCLC, no prior chemotherapy, PS=0–2, measurable disease, adequate organ functions. Excluded were pts with CHF NYHA class II-IV, atherosclerotic diseases, gastrointestinal bleeding, symptomatic brain metastases and chronic use of NSAIDs (defined as 1 wk for >3 wks per yr or more than 21 days throughout the year). Acetylsalicylic acid (ASA) ≤ 150 mg/d was allowed. Pts were treated with docetaxel 75 mg/m2;, carboplatin (AUC = 6 mg/ml.min) every 3 wks for 5 cycles and randomized for celecoxib (cel) 400 mg bd, starting on day 1 for 3 years or placebo (plac) 400 mg bd. Stratification was by WHO PS (0–1 vs. 2), stage (IIIB vs. IV), ASA (yes vs. no) and hospital. Primary endpoint was overall survival. Results: From July 2003 until Dec 2007 561 pts were randomized (cel 281 pts, plac 280 pts). Median follow-up was 36 months (mo). Median (range) age 61 yrs(33–84), M/F 63/37%, PS 0/1/2 45/48/6%, adeno/large cell/squamous/other 48/27/18/7%, stage IIIB/IV 17/83%, 11% of pts used acid ≤ 150 mg/day. Reason to end treatment (cel/plac arm) was therapy completed (51/45%), PD (17/22%), adverse events (8/10%), death (8/8%). Toxicity was mild and no increase in cardiovascular events were observed in cel arm. CR, PR, SD, PD in cel/plac arm was 0/1%, 33/26%, 35/40%, 14/19%, respectively. Response rate in evaluable pts was better in the cel arm (p=0.05). Median PFS (95% CI) was 5,5 mo ( 4,3 - 6,8), OS was 8,3 mo (7,5 - 8,8), not different for both arms. HR stratified by ASA and PS for PFS and OS was 0,94 (0.79–1.13) and 0.95 (0.79–1.15), respectively. Conclusions: Addition of celecoxib to first line chemotherapy improves response rate but not progression-free interval or overall survival. No significant financial relationships to disclose.
42
Chitu, Monica, Theodora Benedek, S. Condrea, C. Blendea, and I. Benedek. "An unusual case of cardiac syncope and acute coronary syndrome – a case report." Acta Medica Marisiensis 60, no. 6 (December 1, 2014): 285–87. http://dx.doi.org/10.1515/amma-2015-0011.
Full textAbstract:
Abstract Introduction: We aimed to present a case of acute coronary syndrome with unexpected etiology complicated by syncope and arrhythmias, confirmed by imagistic examinations as cardiac parasitosis. Cardiac parasitic diseases are rare diseases, whose diagnosis and therapy should be adapted to each case. Imaging techniques allow precise diagnosis of cardiac echinococcosis, providing essential structural details on the damage degree of heart structures, allowing optimization of complex treatment in these cases. Case presentation: A 67-year old, obese and diabetic woman presented with cardiac syncope, arrhythmias and acute chest pain. Imagistic examinations excluded intracoronary thrombosis and confirmed a severe structural damage of myocardial tissue, consisting in replacement of the myocardial structure by many cysts caused by parasitic infestation with echinococcus multilocularis and echinoccocus granulosus originating from the liver. CT scan confirmed severe distruction of the left ventricular myocardium by policysts, that led to thinning of inferior and apical left ventricle wall without any possibility of surgical excision. Therefore a specific chemotherapy with albendazole was initiated. Follow up at 2 months indicated a favorable evolution, with serological decrease of echinococcal antibodies and reduction of cysts volume. Conclusion: In cases of angina and arrhythmias with non-atherosclerotic etiology, imaging techniques can diagnose the anatomopathological substrate of the disease and represent a valuable tool for the follow up.
43
Alsara, Osama, Ahmad Alsarah, Jagadeesh K. Kalavakunta, Heather Laird-Fick, and George S. Abela. "Isolated Left Main Coronary Artery Stenosis after Thoracic Radiation Therapy: To Operate or Not to Operate." Case Reports in Medicine 2013 (2013): 1–5. http://dx.doi.org/10.1155/2013/834164.
Full textAbstract:
Radiation therapy of neoplasms involving the chest or mediastinum results in a wide spectrum of cardiac complications including coronary artery disease, which can present in patients with few or no traditional cardiac risk factors. We report a case of radiation induced coronary artery disease in a 60-year-old female with a history of stage IIIA nonsmall cell lung carcinoma which was diagnosed eight years earlier and treated with chemotherapy and radiotherapy. She presented to the hospital with atypical chest pain that had occurred intermittently over the preceding week. Her initial electrocardiogram and cardiac enzymes were within normal limits. However, following an indeterminate exercise nuclear stress test, she developed chest pain and elevated cardiac enzymes. Coronary angiography demonstrated 90% stenosis of the left main coronary artery ostium, without any evidence of atherosclerotic disease or stenosis in other coronary arteries. She underwent surgical revascularization, which revealed dense adhesions surrounding the heart. During surgery, she developed severe bleeding and died. Coronary artery disease can present within years of radiation exposure, and ostial lesions are typical. Treatment is often challenging because of the effects of radiation on other tissues and the risks of revascularization procedures. Therefore, a multidisciplinary team approach should be considered.
44
Snelling, Brian M., Samir Sur, Sumedh S. Shah, Justin Caplan, Priyank Khandelwal, Dileep R. Yavagal, Robert M. Starke, and Eric C. Peterson. "Transradial Approach for Complex Anterior and Posterior Circulation Interventions: Technical Nuances and Feasibility of Using Current Devices." Operative Neurosurgery 17, no. 3 (November 28, 2018): 293–302. http://dx.doi.org/10.1093/ons/opy352.
Full textAbstract:
AbstractBACKGROUNDDespite several studies analyzing the safety of transradial access (TRA) for neurointervention compared to transfemoral approach (TFA), neurointerventionalists are apprehensive about implementing TRA. From our positive institutional experience, we now utilize TRA first line for a majority of our cases. Here, we present our single-institution experience.OBJECTIVETo determine safety and feasibility of TRA for neurointervention.METHODSThrough retrospective review of patients receiving TRA for anterior and posterior circulation cerebrovascular interventions at our institution between December 2015 and January 2018, we present our experience regarding this transition, while focusing on technique, complications, feasibility, indications, and limitations.RESULTSOne hundred five procedures were performed on 92 patients (anterior circulation: 77%; posterior circulation: 23%). Radial artery access was achieved in all patients. Twenty-nine cases constituted mechanical thrombectomy, 33 cases represented intracranial aneurysms treatments, and 33 cases included interventions like angioplasty, balloon test occlusion, chemotherapy delivery, and thrombolysis. TRA was used as second-line access to TFA in 5 instances due to aortic arch anomalies and atherosclerotic disease. Minor access-site complications were seen in 2.85% of patients. Ten procedures (9.0%) could not be completed with TRA, with crossover to TFA occurring in 7 cases.CONCLUSIONTRA is safe and feasible for the majority of neurointerventional procedures and provides decreased risk of major access-site complications compared to TFA. Perceived limitations of TRA can likely be eliminated via operator experience and engineering ingenuity; thus, there is a role for TRA for neurointervention, especially in patients with increased risk of access-site complications from TFA.
45
Giffen, Mark A., and Jerri L. McLemore. "Hyperoxalosis Secondary to Intravenous Vitamin C Administration as a Non-Allopathic Treatment for Cancer." Academic Forensic Pathology 9, no. 1-2 (March 2019): 118–26. http://dx.doi.org/10.1177/1925362119851129.
Full textAbstract:
Vitamin C (ascorbic acid) has long been known to have antioxidant properties, with associated claims that it can boost the immune system, fight off infection, and help in the treatment of cancer. Similar to many other over-the-counter and herbal medicines, vitamin C can cause potential side effects with significant morbidity and rarely mortality. We discuss a case of an elderly woman with metastatic adenocarcinoma of the lung that was treated with several rounds of allopathic chemotherapy; however, treatment was stopped because of worsening quality of life and disease progression. She was treated with 10 courses of intravenous high-dose vitamin C at a local homeopathic medical center as an alternative treatment method. Five days after the last vitamin C administration, she was admitted to an allopathic hospital due to acute renal failure and oliguria culminating in a myocardial infarct due to underlying atherosclerotic disease. Workup revealed dehydration secondary to poor oral intake and acute renal failure which was clinically concerning for calcium oxalate– induced kidney injury. At the time of autopsy, in addition to her widely metastatic adenocarcinoma and myocardial damage, hyperoxalosis of the kidney with acute kidney injury was present. Hyperoxalosis of the kidney is a documented phenomenon related to administration of intravenous and oral vitamin C at superphysiologic doses as recommended by some natural and homeopathic practitioners and is, therefore, a significant complication of treatment. This case highlights the renal complications of supertherapeutic vitamin C administration and the associated morbidity which can contribute to death.
46
Chen, John H., Daniel J. Lenihan, Sharon E. Phillips, Madan H. Jagasia, Stacey A. Goodman, Adetola A. Kassim, Shelton L. Lacy, et al. "Risk Factors for Cardiac Toxicities Associated with Proteasome Inhibitor Chemotherapy during Treatment of Multiple Myeloma." Blood 126, no. 23 (December 3, 2015): 5363. http://dx.doi.org/10.1182/blood.v126.23.5363.5363.
Full textAbstract:
Abstract Introduction Proteasome inhibitors (PI) bortezomib (B) and carfilzomib (C) are cornerstone therapies for multiple myeloma (MM). An increased incidence of PI-induced cardiac adverse events (CAEs) has been reported in patients receiving C. However, risk factors for cardiac toxicity in this population remain unclear. Our objective is to evaluate the incidence of CAEs associated with C compared with B and identify risk factors for developing events. Patients and Method This was a retrospective analysis of 96 consecutive patients treated for MM at Vanderbilt University from 2011 to 2014 who received B (n=44) and/or C (n=52). Patients in the C group had been previously treated with B, whereas patients in the B group did not have exposure to C. No patients studied were included in both cohorts. We evaluated the clinical features and frequency of CAEs (grade II-IV heart failure, acute coronary syndrome, left ventricular dysfunction, atrial fibrillation/flutter, thromboembolism, systemic hypertension, pulmonary hypertension, orthostatic hypotension, or sudden cardiac death). To identify factors that predisposed patients to CAEs, we analyzed duration of PI therapy, 10-year atherosclerotic cardiovascular disease (ASCVD) risk (calculated risk of myocardial infarction or stroke), gender, use of antithrombotic (antiplatelet/anticoagulant) and antihypertensive medications, prior history of cardiac events, and disease cytogenetic profile. Patients with a prior history of cardiac events were followed by a cardio-oncologist during the course of treatment. Results Table 1 shows patient characteristics. Twenty-five patients experienced CAEs (B, 13% (n=12); C, 25% (n=13)). Cumulative incidence (CI) of CAEs was not significantly different in patients on C compared with B (log-rank test P = 0.41) (Figure 1). Heart failure was the most common type of CAE (Table 2). CAEs occurred after a median of 90 days (range, 4-456) with C and 63.5 days (range, 5-336) with B. By univariate analysis, more patients in the C group were prior smokers, underwent stem cell transplantation and had more prior lines of therapy. More patients in the B group used antithrombotic and ACE inhibitor agents. There were no other significant differences in the use of antihypertensive, antiarrhythmic, and lipid-lowering medications between cohorts. Multivariate analysis showed that male gender (HR 5.3, 95% CI 1.5-18.0, P = 0.007) was an independent risk factor for developing CAEs. Patients taking antithrombotic agents had a lower risk of CAE compared with those not on these therapies (HR 0.1, 95% CI 0.04-0.54, P = 0.004). While ASCVD risk was not predictive of CAEs, patients with a prior history of cardiac events who were followed by a cardio-oncologist experienced fewer CAEs (HR 0.2, 95% CI 0.05-0.72, P = 0.014). Longer duration of PI use resulted in decreasing risk of CAE (HR 0.8, 95% CI 0.7-0.9, P = 0.010). There were no interactions between these outcomes. Conclusions In this series, the incidence of CAEs associated with C did not differ significantly from that of B. We found that events occurred early in therapy. Male gender was an independent risk factor for CAEs. Use of antithrombotic therapy was associated with significantly reduced risk of CAEs. These data suggest that patients may benefit from antithrombotic therapy and follow-up by a cardio-oncologist while on PI therapy, particularly if there is a prior history of cardiac events. Table 1. Bortezomib % (n=44) Carfilzomib % (n=52) P-value ASCVD Risk 0.43 0-10% 46 50 10-20% 29 36 >20% 26 14 Male Gender 57 71 0.82 Median Age, y 61 (38-91) 60 (36-86) 0.20 Past Smoker 26 51 0.02 Type II Diabetes 11 17 0.41 Hyperlipidemia 27 27 0.97 Kidney Disease 9 12 0.70 Prior History of Cardiac Event 59 60 0.96 Median Duration on Bortezomib, d 229 203 0.67 Median Duration on Carfilzomib, d 87.5 ACE Inhibitor Use 32 13 0.03 Antithrombotic Use 48 23 0.01 ISS Stage 0.72 III 34 25 FISH Risk 0.13 Standard/Intermediate 93 85 High 7 15 Median Prior Lines of Therapy 0 (0-4) 2 (0-8) <0.001 Stem Cell Transplant 45 65 0.05 Table 2. Cardiac adverse events Bortezomib Carfilzomib P-value Total Cardiac Adverse Events* 19 17 0.08 Heart Failure 9 6 Acute Coronary Syndrome 1 2 Left Ventricular Dysfunction 0 1 Atrial Fibrillation/Flutter 2 2 Thromboembolism 2 2 Systemic Hypertension 3 3 Pulmonary Hypertension 0 1 Orthostatic Hypotension 2 0 Sudden Cardiac Death 0 0 *Some patients had multiple events Figure 1. Cumulative incidence of cardiac adverse events Figure 1. Cumulative incidence of cardiac adverse events Disclosures No relevant conflicts of interest to declare.
47
Peravali, Monica, Chidera Nosiri, Christopher S. Hourigan, Christopher Gallagher, and Aarthi Shenoy. "A Prospective Pilot Study to Evaluate Molecular Changes in the Hematopoietic System after Receipt of Chemotherapy or Radiotherapy and Its Clinical Implications Among Racially Diverse Breast Cancer Survivors: Breast Survivorchip Study." Blood 136, Supplement 1 (November 5, 2020): 34–35. http://dx.doi.org/10.1182/blood-2020-138740.
Full textAbstract:
Background: Clonal hematopoiesis (CH) increases in inflammatory states, and in retrospective epidemiological studies, has been associated with increased rates of atherosclerotic coronary artery disease, ischemic stroke, neurocognitive disorders, and hematologic malignancies.Previous data in non-cancer patients reported approximately 5% incidence of CH in patients aged 60-69. Next-generation sequencing (NGS) has demonstrated CH in 25% of predominantly white cancer survivors (21% in breast cancer patients) following chemotherapy and radiotherapy and 16% in a subset of patients prior to treatment suggesting a higher incidence of CH at baseline with malignancy and an increase in incidence following cancer treatment. The variance in CH rate among racially diverse cancer patients has not been well reported. The purpose of this prospective pilot investigator-initiated translational study is to characterize baseline profiles of existing CH, patterns of clonal evolution, and clinical implications of CH in a racially diverse population of breast cancer patients in a longitudinal fashion prior to and one year after receiving cancer directed therapy. This study will be performed at MedStar Washington Hospital Center (MWHC). MWHC is a not-for-profit, 912-bed, teaching and research hospital caring for a racially and socioeconomically diverse population in Washington, D.C. Study Design: Newly diagnosed breast cancer patients stages 0-III, who are candidates for surgery, chemotherapy and/or radiation, and/or endocrine therapy and/or Her2 directed therapy at WHC will be eligible. Baseline demographic data, comprehensive history, quality of life and cognitive assessments will be obtained at baseline and at 12 ± 1 months post initiation of therapy.Clinical data including blood counts, treatment delays, dose adjustments, and echocardiography results will be collected throughout treatment and entered into RedCap database. Blood will be collected in Paxgene tubes for each timepoint. Error-corrected NGS will be performed in a NIH laboratory on regions of genes known to be recurrently mutated in CH allowing for the sensitive and reproducible detection of low-level variants and accurate quantification of changes over time. Research sequencing results will not be returned to treating physicians or patients. Study Outcomes: The primary outcome of this study is to determine baseline rate of CH in a cohort of 100 breast cancer patients. We expect 50-60% of our patients to be black and therefore, can specifically evaluate CH in this group of patients compared to whites. Secondary outcome is to describe change in mutational profile after cancer-directed therapy. Descriptive analysis of the relationship of CH to treatment tolerance including prolonged myelosuppression or organ dysfunction leading to dose reductions and treatment delays as well as reduction in quality of life and cognition will be conducted as part of the exploratory analysis. Statistical methods: Descriptive statistics would be presented using frequency and proportions for categorical data and means and standard deviation for continuous data. Medians and quartiles will be presented for continuous data with non-normal distribution. Proportion of CH in breast cancer patients pre-treatment would be compared to proportion of CH post treatment using McNemar test for comparison of marginal proportions in paired data. Difference in baseline incidence of CH among different race categories would be evaluated using chi-squared test of independence. Effect of CH on delay in treatment would be evaluated using Kaplan Meier method for comparison of time to treatment between patients with CH and patients without CH. Clinical Significance: Life expectancy of breast cancer survivors is inferior to the general population and more so for black women. These differences may extend beyond psychosocial disparities and may have their foundation in genomic differences. Understanding clonal hematopoiesis in our racially diverse breast cancer patients will have significant implications both during the delivery of cancer directed therapy and in their long-term survivorship care. We currently have 25 patients enrolled in our study with their samples awaiting processing for NGS at NIH. Disclosures Gallagher: Seattle Genetics:Membership on an entity's Board of Directors or advisory committees;Daiichi Sankyo:Membership on an entity's Board of Directors or advisory committees.
48
Armenian, Saro, Can-Lan Sun, George Mills, Jennifer Berano Teh, Liton Francisco, Lennie Wong, Stephen J. Forman, and Smita Bhatia. "Late Cardiovascular Events in Survivors of Hematopoietic Cell Transplantation (HCT)." Blood 114, no. 22 (November 20, 2009): 2252. http://dx.doi.org/10.1182/blood.v114.22.2252.2252.
Full textAbstract:
Abstract Abstract 2252 Poster Board II-229 Introduction: HCT is increasingly offered as a therapeutic option for hematological malignancies. Improvement in therapeutic and supportive care strategies has resulted in a growing population of long-term survivors. These survivors are at a substantial risk of morbidity, contributed to by therapeutic exposures, and development of comorbidities. For example, HCT survivors are potentially at increased risk of atherosclerotic disease of large and small vessels, due to the higher risk of dyslipidemia, diabetes, and hypertension in HCT survivors (Blood 2007;109:1765-72) as well as prior exposures to atherogenic therapeutic exposures (pre-HCT, during conditioning and post-HCT). However, cardiovascular disease (CVD) has not been well-characterized in HCT survivors, in part because of the long latency of clinically overt disease, requiring extended follow-up of large cohorts. The current report addresses this gap in literature by comprehensively evaluating the role of pre- and post-HCT therapeutic exposures (chemotherapy, radiation), transplant-related conditioning regimens, and comorbidities (pre- and post-HCT) in the development of late CVD after HCT. Methods: Utilizing a nested case-control design, individuals with late CVD (diagnosed ≥1 year after HCT) were identified from a cohort of 3,287 1+ year survivors who underwent HCT at a single institution. This cohort formed the sampling frame for selecting controls (without CVD) matched for age and year of HCT, donor source (allogeneic vs. autologous), and length of follow-up. All episodes of CVD (cases) were clinically validated, and included coronary artery disease (CAD) or cerebrovascular events (stroke). Results: Sixty-three patients with late CVD were identified; 44 (69.8%) had CAD and 19 (30.2%) had stroke. Median age at HCT was 49.0 years (range, 18.6 to 78.9 years); median time to CVD was 4.1 years (range, 1.15 to 19.45 years); 66.7% received autologous HCT. Compared to matched controls (N=183), patients with late CVD were more likely to be male (68.3% vs. 51.6%; p=0.02), had greater body mass index at HCT (28.5 vs. 26.6 kg/m2; p=0.03), and were more likely to have multiple comorbidities after HCT (47.6% vs. 13.4%; p<0.01). Conditioning with total body irradiation (TBI), cyclophosphamide, and TBI + cyclophosphamide were associated with incremental increased risk (Odds Ratio [OR]=1.2, 2.5, 2.9, respectively; p for trend=0.04). Multivariate logistic regression revealed that having 2 of 4 cardiovascular risk factors (obesity, dyslipidemia, hypertension, and diabetes) was independently associated with a 5-fold risk of developing late CVD (OR=5.2; p<0.01). Multivariate analyses restricted to CAD cases and their matched controls revealed the following risk factors: pre-HCT exposure to mediastinal radiation (OR=9.3; p=0.04), and presence of 2 of 4 cardiovascular risk factors (OR=4.6, p=<0.01). No interactions were observed between therapeutic exposures and presence of comorbidities. Conclusions: The current study represents the most comprehensive experience to date describing risk factors for late CVD following HCT, and demonstrates that mediastinal radiation and presence of comorbidities are primarily responsible for the risk of late CVD. These data form the basis for identifying high-risk individuals for targeted surveillance, as well as developing preventive strategies in the form of aggressive management of comorbidities. Disclosures: No relevant conflicts of interest to declare.
49
Ivovic, Miomira, Biljana Radojkovic, Zorana Penezic, Mirjana Stojkovic, Milina Tancic, Svetlana Vujovic, Andrija Bogdanovic, and Milka Drezgic. "Agranulocytosis and acute coronary syndrom in apathetic hyperthyreoidism." Srpski arhiv za celokupno lekarstvo 131, no. 5-6 (2003): 249–53. http://dx.doi.org/10.2298/sarh0306249i.
Full textAbstract:
INTRODUCTION Tissue expose to excessive levels of circulating thyroid hormones results in thyrotoxicosis. In most cases, thyrotoxicosis is due to hyper-activity of the thyroid gland. Cardiovascular and myopathic manifestations are predominant clinical features in most hyperthyroid patients, aged 60 years and older. Some of patients have apathetic hyperthyreoidism which presents with weight loss, small goiter, severe depression and without clinical features of increased sympathetic activity [3, 6]. About 50% of patients with cardiovascular manifestations have no evidence of underlying heart disease. Cardiac problems resolve when euthyreoid state is established [3]. Three treatment modalities are available in hyperthyreodism, namely medicament therapy, surgery and radioactive iodine. Antithyroid drug therapy complications, can be mild such as rash, which is managed without cessation of therapy by antihistamines administration. On the other hand, very serious complications such as agranulocytosis, necessitate immediate discontinuation of the medication and appropriate treatment. Although extremely rear, it is life-threatening with highly variable recovery time. CASE REPORT A 62-year-old woman with recurrent hyperthyroidism was admitted after treatment of agranu locytosis due to antithyroid drugs in another institution with G-CSF. The patient presented with clinical features of apathetic hyperthyroidism with extremely elevated thyroid hormone levels (total and free T4) and suppressed TSH. Radioactive iodine (5 mCi) was administered after increased thyroid uptake was confirmed. Echocardiography on admission was normal. ECG revealed moderately inverted T waves in standard and V1, V2 precordial leads. Laboratory analysis revealed mild normocytic anemia with normal white blood cell count, hypokaliemia and normal concentration of creatine phosphokinase lactic dehidrogenase and mildly elevated aspartate transaminase in sera. Chest X-ray was consistent with pulmonary emphysema. Because the worsening of ECG changes she was transferred to Coronary unit. The diagnosis of non-Q myocardial infarction was confirmed and treatment with nitrates and beta-adrenergic antagonists was instituted. Four weeks later she became euthyroid and coronarography was performed. Subepicardial coronary arteries were normal (Figure 1). She was dismissed, and still euthyroid three months later. DISCUSSION Agranulocytosis is very rare but very serious complication of antithyroid drug therapy. It can be detected in about 0.1 -1 % patients during the first three months of treatment. Sudden appearance, heralded by sore throat and fever, prompt physicians to seek white blood cell and differential count [1-3]. Confirmation of diagnosis urges cessation of drug therapy and appropriate antibiotic treatment. Recently, it was reported that recombinant human granulocyte colony-stimulating factor (rhG-CSF) is to be effective in shortening the recovery time in the neutropenic patients undergoing chemotherapy and also in patients with other types of neutropenia [5]. Tamai at al. [7] confirmed positive outcome in 34 patients treated with rhG-CSF compared to corticosteroid treatment. Hematologic laboratory abnormalities disappear 7-10 days after secession of therapy. Patients completely recover two to three weeks later. Fatal outcome was also described [1 -5]. Thyroid hormones have profound effects on cardiovascular physiology, especially on heart rate, cardiac output and systemic vascular resistance. In patients with hyperthyroidism, cardiac output is much higher than in normal persons. This is the result of direct effect of thyroid hormones on cardiac muscle contractility, heart rate and decrease in systemic vascular resistance. Excessive thyroid hormone secretion increases cardiac Na-K-activated plasma membrane ATP-ase and sarcoplasmic reticulum Ca-activated ATP-ase with resultant in increase myocardial contractility [6 9]. Sinus tachycardia is the most common rhythm disorder in hyperthyroidism but paroxysmal tachycardia and atrial fibrillation are not rare. This can be explained by increased heart rate, cardiac output, blood volume, coronary artery flow and peripheral oxygen consumption in thyreotoxicosis [9]. Patients with coronary arteriosclerosis can develop angina pectoris during thyreotoxic stage, which can be explained by imbalance between cardiac demand and supply. Myocardial damage is often in thyrotoxic patients with chronic hart failure, together with myocardial infarction in patients without coronary disease [2,6]. Congestive heart failure and atrial fibrillation are relatively resistant to digitalis treatment because of high metabolic turn over of medication and excessive myocardial irritability in hyperthyro-idism [6]. Cardiovascular and myopathic manifestations predominate in older hyperthyroid patients (over 60 years) and some of them can have only few symptoms of hyperthyroidism [1-3]. Thyrotoxic state characterized by fatigue, apathy, extreme weakness, low-grade fever and sometimes congestive heart failure are designated as apathetic hyperthyroidism. Such patients have small goiters, mild tachycardia and often cool and dry skin with few eye signs [6]. Patients with subclinical hyperthyroidism are at increased risk for atrial fibrillation [9]. Unstable angina and non-Q myocardial infarction (non ST elevation) are acute manifestation of coronary artery disease. The acute coronary syndrome of unstable angina, non-Q myocardial infarction and Q-wave myocardial infarction have atherosclerotic lesions of the coronary arteries as a common pathogenic substrate. Errosions or ruptures of unstable atherosclerotic plaque triggered pathophysiologic processes, resulted in thrombus formation at the site of arterial injury. This leads to abrupt reduction or cessation through the affected vessel. Clinical manifestations of unstable angina and non-Q myocardial infarction are similar and diagnosis of non-Q myocardial infarction is made on the basis of elevated serum markers indicative of cardiac necrosis, detected in peripheral circulation. Acute coronary syndrome ranging from unstable angina to myocardial infarction an non-Q myocardial infarction represents increasingly severe manifestations of the same pathophysiologic processes [10,11]. In conclusion, these 62-year-old woman presented with apathetic form of recurrent hyperthyroidism associated with two serious complications life-threatening agranulocytosis and acute coronary syndrome.
50
Solomou, E., I. Koutagiar, N. Ioakimidis, D. Terentes-Printzios, A. Georgakopoulos, A. Pouli, A. Sioni, et al. "The effects of chemotherapy on arterial inflammation assessed by 18 FDG PET-CT in patients with Lymphoma." European Heart Journal 41, Supplement_2 (November 1, 2020). http://dx.doi.org/10.1093/ehjci/ehaa946.0297.
Full textAbstract:
Abstract Introduction Anti-cancer treatment can lead to increased cardiovascular morbidity among lymphoma survivors. This may be the result of direct effect of treatment on heart function, or indirect acceleration of atherosclerosis. 18F-fluorodeoxyglucose (FDG) uptake is a sensitive and robust marker for assessment of atherosclerotic inflammation. Purpose To investigate the effects of chemotherapy on arterial inflammation using FDG-PET CT in patients with lymphoma. Methods Fifty nine (mean age 58±17 years) patients with Hodgkin (n=39) or non-Hodgkin lymphomas (n=20) underwent 18FDG PET-CT imaging at baseline, interim and after completion of chemotherapy as part of their routine protocol. Arterial inflammation was assessed by arterial target to background ratio (TBR) of the aortic wall along the entire aorta. The index vessel TBR (the vessel with the higher value at baseline) was used for assessment of arterial inflammation. Patients with Hodgkin Lymphomas (HL) underwent therapy with Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The interim of their treatment was set at 1 to 3 days prior to initiating the 3rd chemotherapy cycle. Patients with non Hodgkin Lymphomas (NHL) underwent therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone+rituximab (R-CHOP). The interim of their treatment was set at 2 weeks post the 4th chemotherapy cycle. All patients we reassessed 6 weeks after chemotherapy completion. Results There were no differences in age and atherosclerotic risk factors (hypertension, diabetes, dyslipidemia and smoking), between the two groups (all P>0.05). Similarly, there were no differences in mean (±SD) index vessel TBR between HL and NHL patients (2.4±0.7 vs 2.7±0.9, respectively, P=0.65). In the whole study population the index vessel TBR progressively decreased after the end of therapy (by 0.53±0.11, from baseline to 6 weeks following the end of therapies) (F=10.94, P<0.001, ANOVA). The index vessel TBR decreased in both HL and NHL patients at 6 weeks after therapy compared to baseline level (all P<0.01, ANOVA, figure). The decrease at the interim scan was more pronounced in NHL compared to HL patients, however at 6 weeks after chemotherapy completion the index vessel TBR decreased further in patients with HL, while it increased slightly compared to interim levels in NHL patients (figure 1). Conclusion Arterial inflammation is reduced during and post-chemotherapy in patients with lymphoma. The index vessel TBR changes at the interim phase and 6 weeks after therapy completion indicate a different effect of specific treatment regimes in arterial inflammation between HL and NHL patients. Figure 1 Funding Acknowledgement Type of funding source: None