Deshields T.L.,Siteman Cancer Center |
Potter P.,Barnes Jewish Hospital |
Olsen S.,Barnes Jewish Hospital |
Liu J.,University of Washington
Supportive Care in Cancer | Year: 2014
Purpose: The purpose of this longitudinal study was to track the symptom experience in a sample of cancer patients, determine the persistence of cancer symptoms and symptom burden, and examine the relationship between symptoms and QOL over time. Methods: Five hundred forty-two patients provided longitudinal data, completing surveys over a 12-month period. Patients had breast, colorectal, gynecologic, lung, or prostate cancer with stage 1, 2, or 3 disease. Surveys included the Memorial Symptom Assessment Scale and the Functional Assessment of Cancer Therapy-General Scale and were administered every 3 months. Demographic and clinical information and comorbidities were collected from the tumor registry. Results: The number and type of symptoms experienced by patients varied by cancer type, but about 90 % of patients reported one or more symptoms-with prostate cancer patients reporting fewer symptoms and colorectal patients, more symptoms. Prostate patients also had the lowest symptom burden at every time point. Overall, symptom burden decreased over time, as did the Physical subscale for the MSAS. Quality of life was stable over time, except for physical well-being, which improved. Quality of life was negatively correlated with symptom burden at every time point. Conclusions: The differences in symptom experience by cancer type suggest that assessment and management of symptoms must be individually tailored or at least adjusted by cancer type. While symptom burden decreased over time, residual symptom burden was still noteworthy. As quality of life was persistently negatively correlated with symptom burden, the results suggest the need for comprehensive symptom assessment and management. © 2013 Springer-Verlag.
Hamilton N.A.,Washington University in St. Louis |
Liu T.-C.,Washington University in St. Louis |
Cavatiao A.,Washington University in St. Louis |
Mawad K.,Washington University in St. Louis |
And 5 more authors.
Surgery (United States) | Year: 2012
Background: Pancreatic neuroendocrine neoplasms are rare malignancies for which the ideal staging method remains controversial. Ki-67 is a cell proliferation marker that has been shown to have some utility in predicting prognosis in neuroendocrine neoplasms. We sought to test the predictive ability of Ki-67 staining for disease recurrence and overall survival (OS) in pancreatic neuroendocrine neoplasms. Methods: The medical records of patients who underwent pancreatic resection for pancreatic neuroendocrine neoplasms at a tertiary referral hospital from 1994 to 2009 were reviewed. The pathologic specimens of all were stained for Ki-67 and recorded as percentage of cells staining positive per high-powered field. The 10-year disease-free and OSs were analyzed. Results: We identified 140 patients. Gender and age were not associated with increased risk of disease recurrence. Patients with tumors >4 cm or with Ki-67 staining >9% were more likely to have disease recurrence (P = .0454 and .047) and have decreased OS (P < .0001 and .0007). Conclusion: Increasing tumor size and increasing Ki-67 staining both correlate with increased risk of disease recurrence and decreased OS. Designing a staging system that incorporates both of these clinical variables will enable better identification of patients at risk for recurrent pancreatic neuroendocrine neoplasms.
Frith A.E.,Washington University in St. Louis |
Hirbe A.C.,Washington University in St. Louis |
Van Tine B.A.,Washington University in St. Louis |
Van Tine B.A.,Siteman Cancer Center
Current Oncology Reports | Year: 2013
Sarcomas collectively represent over 100 different subtypes of bone and soft tissue tumors of mesenchymal origin. The low response rate to cytotoxic chemotherapies has necessitated the need for development of either histologically driven or pathway-specific targeted therapies. As our understanding of the molecular mechanisms driving certain subtypes is rapidly advancing, the number of targeted therapies is also increasing. Recently identified novel druggable targets include the MDM2 amplifications in well-differentiated and dedifferentiated liposarcomas, the new translocation NAB2:STAT6 of solitary fibrous tumors, the angiopoeitin-TIE2 pathway in angiosarcoma, the suppression of Mcl1 in X:18/synovial sarcomas, the mTOR pathway in malignant peripheral nerve sheath tumors, CDK4 in alveolar rhabdomyosarcoma, cMET regulation in alveolar soft parts sarcoma, the metabolic abnormalities in wild-type/SHD GIST, and the lack of argininosuccinate synthetase 1 expression seen in most sarcomas. It is through a fundamental understanding of sarcoma biology that clinical trials based on molecular targets can be developed. © 2013 Springer Science+Business Media New York.
News Article | September 2, 2016
Quitting smoking improves health and lowers odds of developing lung cancer. But a new study shows that even among smokers with a genetic predisposition to smoking heavily and developing lung cancer at a young age, the benefits of quitting are significant. An international study led by researchers at Washington University School of Medicine in St. Louis and the Siteman Cancer Center indicates that in these high-risk smokers, quitting smoking cuts lung cancer risk in half and delays the age at which the disease is diagnosed. The findings suggest that in the future, doctors may request a DNA analysis from smokers to employ more effective therapies to help them quit. The new study is available online in the journal eBioMedicine. The researchers analyzed data from 15 studies involving more than 12,000 current and former smokers. They found that even those with DNA variations that elevated their cancer risk had better outcomes if they kicked the habit. “When people with the risky gene variants quit smoking, it cuts their odds of getting lung cancer in half,” said first author Li-Shiun Chen, M.D., an assistant professor of psychiatry. “We also found that although some patients will go on to develop lung cancer even after quitting, stopping smoking can delay their diagnosis by an average of seven years.” The same research team previously had found that smokers with variations in a nicotine receptor gene were likely to continue smoking longer than those without the DNA variants. Those with the risky gene profile also were likely to be diagnosed with lung cancer about four years earlier than smokers without the risky variety of the gene, called CHRNA5. The researchers also repeatedly have found that it’s more difficult to quit for people with the high-risk genetic profile. But if they can manage it, Chen said, quitting can significantly lower their risk of lung cancer, on par with smokers who don’t have gene variations that make it harder to quit. “Some people believe that genes determine everything,” Chen said. “They might think there’s no use in even trying to quit, but these findings directly contradict that myth. Although a person may be genetically vulnerable to conditions such as smoking, obesity or metabolic syndrome, the situation isn’t hopeless. Our health may be altered by certain genes, but we still can manage to make healthier choices, and if we do that, there can be big benefits.” Lung cancer is the most common cancer in the world, making up about 13 percent of cancer cases worldwide and contributing to more than a quarter of all cancer-related deaths. About half of those diagnosed with lung cancer will die within a year of that diagnosis. In past research, Chen and her colleagues have found that a risky genetic profile can make a smoker more likely to respond to nicotine-replacement therapy. Because those with high-risk genes are more likely to benefit from nicotine patches and other medications, Chen’s colleague, Laura Jean Bierut, MD, the Alumni Endowed Professor of Psychiatry, explained that doctors might want to identify smokers who have risky genetic variants. That, she explained, could make it possible to match smokers to therapies that are most likely to help them kick the habit. “Normally, those with a risky genetic profile have difficulty quitting,” Bierut explained. “They are successful only about one-third as often as those who don’t have a risky gene profile. Because we also know they are more likely to respond to certain therapies, such as nicotine patches or lozenges, we should be able to use precision medicine therapies that match individual smokers to the treatments most likely to help them.” Chen is studying smokers to learn what combinations of treatments work best in those with and without risky DNA variants. Her team is recruiting 720 smokers from the St. Louis area who are trying to quit. Those in the study are randomly assigned to receive either counseling only or counseling and one of two smoking-cessation therapies. The researchers will try to determine which therapeutic strategies work best and how to match those therapies to an individual smoker’s DNA by comparing success in smoking cessation with the DNA of individual smokers.
New research shows that current approaches to genome analysis systematically miss detecting a certain type of complex mutation in cancer patients’ tumors. Further, a significant percentage of these complex mutations are found in well-known cancer genes that could be targeted by existing drugs, potentially expanding the number of cancer patients who may benefit. The study, from Washington University School of Medicine in St. Louis, appears Dec. 14 in the journal Nature Medicine. “The idea of not catching a targetable mutation in a patient’s tumor is devastating,” said senior author Li Ding, Ph.D., associate professor of medicine and assistant director of the McDonnell Genome Institute at Washington University. “We developed a software tool for finding a certain type of genetic error that has been consistently missed by cancer genome studies. We identified a large number of such events in critical cancer genes. The ability to discover such events is crucial for cancer research and for clinical practice.” Mutations in the genome happen in a variety of ways. Perhaps the simplest is a change in a single “letter” of the DNA code. Among the more complex types of mutations are those that involve deleting or inserting a few letters. In the new study of 8,000 cancer cases, the investigators focused on mutations involving letters that are inserted at the same time that other letters are deleted. “We call this type of mutation a complex indel because insertion and deletion is happening at the same time, in the same genomic location,” said Ding, who also is a research member of the Siteman Cancer Center at the School of Medicine and Barnes-Jewish Hospital. “It is very difficult to capture such events because conventional approaches were designed to catch one or the other, not both types at the same time and place.” To find the complex indels, the researchers developed specialized computer software and verified its accuracy in genome sequences into which they purposely introduced these complex mutations. Then, the researchers looked at cancer genomes that already had been sequenced and found 285 complex indels in genes known to be associated with cancer. About 81 percent of these complex indel events had been missed on the first analysis using conventional approaches. And another 18 percent had been misidentified as some other type of mutation. Ding emphasized the importance of developing special tools to find these complex indels, as the data suggest they go almost completely undetected by existing tools and appear to cluster in important cancer genes more often than can be attributed to random chance. This information is particularly valuable when indels are found in genes that already have drugs designed to counter the effects of mutation. In particular, the researchers identified complex indels in the gene EGFR, which is implicated in lung cancer. If such an indel is found in this gene, Ding and her colleagues suggest a patient may benefit from an EFGR inhibitor, such as erlotinib, regardless of the tumor type. The investigators also found complex indels in a gene called KIT, which appears to play a role in melanoma. The analysis suggests that patients with complex indels in KIT would benefit from drugs such as imatinib, sunitnib and sorafenib, which target mutations in this gene. The new software the investigators developed specifically to find complex indels is called Pindel-C. It was built on top of existing software called Pindel, which was published in 2009 by the study’s first author, Kai Ye, Ph.D., assistant professor of genetics. Both versions of the software are freely available online for download.