Clinicians and researchers from throughout the United States gathered at The University of Texas MD Anderson Cancer Center in February to discuss emerging trends in cancer survivorship. “The field has bloomed to the point that we need to discuss the science of survivorship,” said Ethan Dmitrovsky, M.D., MD Anderson’s provost and executive vice president, in his opening remarks at the Fifth State of the Science Cancer Survivorship Research Symposium.
Among the research discussed at the symposium were three reports of preliminary research done at MD Anderson to address major health issues in cancer survivors.
BK virus affects survival after stem cell transplant
BK virus occurs in an estimated 70% of allogeneic stem cell transplant recipients. Although typically indolent in healthy individuals, BK virus can become active and cause hemorrhagic cystitis, nephritis, and ureteral stenosis in immunocompromised patients such as those who have undergone allogeneic stem cell transplant. To assess the characteristics associated with BK virus and its effect on survival after stem cell transplant in cancer patients, researchers conducted a retrospective review of nearly 2,500 patients who underwent allogeneic stem cell transplant for any malignancy from 2004 to 2012. “Currently, there are no protocols for screening and preventing the virus in these patients,” said Ala Abudayyeh, M.D., an assistant professor in the Section of Nephrology in the Division of Internal Medicine, who led the study.
Because patients typically are tested for BK virus only if they develop urinary symptoms, only 901 of the study’s 2,477 patients had been tested for BK virus; of these 901 patients, 629 tested positive.
The researchers conducted multivariable analyses to compare the characteristics and outcomes of the patients who tested positive for the virus with those of patients who tested negative as well as the untested patients.
Compared with BK virus–negative and untested patients, BK virus–positive patients had worse overall survival outcomes. Among BK virus–positive patients, higher viral loads were associated with worse overall survival outcomes.
The researchers also found that risk factors for symptomatic BK virus included diagnosis with a solid tumor, receipt of myeloablative conditioning regimens, and an HLA (human leukocyte antigen) mismatch between the donor and patient. Using these three factors, Dr. Abudayyeh and colleagues developed a grading scale to identify allogeneic stem cell transplant recipients at high risk of complications related to BK virus.
Currently, the researchers are working to validate the scale in another retrospective patient cohort. Because experimental treatments for BK virus are now available (Virus-Specific T Cells Treat Posttransplant Infections, OncoLog, March 2017), Dr. Abudayyeh hopes the scale will lead to the establishment of screening criteria that will enable patients with BK virus infections to be diagnosed and treated before severe symptoms occur.
Heart failure medications can be withdrawn in some cancer survivors after recovery from chemotherapy-induced left ventricular dysfunction
Chemotherapy-induced left ventricular dysfunction can occur acutely or many years after cancer treatment. Although heart failure medications—beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers—can restore left ventricular ejection fraction in patients with chemotherapy-induced left ventricular dysfunction, how long such patients must remain on heart failure medication is unclear because the general guidelines for these medications are based on clinical trials that excluded cancer patients.
In an ongoing clinical trial, Recovery of Left Ventricular Dysfunction in Cancer Patients (RECAP, No. 2012-0379), cancer survivors with chemotherapy-induced left ventricular dysfunction whose left ventricular ejection fraction has recovered (i.e., left ventricular ejection fraction of at least 50% for at least 6 months) are being weaned off their heart failure medications. Patients who had ongoing heart disease or a history of myocardial ischemia, diabetes, palpitations, or hypertension were excluded from the trial, which recently completed enrollment.
Patients in the trial are gradually weaned off their beta-blockers, ACE inhibitors, or angiotensin receptor blockers under close supervision and then monitored by echocardiography and symptom questionnaires at regular intervals. Although the trial is still on-going, early results are promising. Anecita Fadol, Ph.D., an assistant professor in the Department of Nursing and the trial’s principal investigator, said, “We’re seeing that heart failure medications can be withdrawn in selected patients and those patients will maintain their left ventricular ejection fraction.”
Expiratory muscle exercise reduces aspiration in head and neck cancer survivors
Radiation therapy for cancers of the head and neck often leaves patients with swallowing dysphagia and chronic aspiration, which increases the risk of pneumonia. A strategy to reduce aspiration, expiratory muscle strength training (EMST), has been shown to benefit patients who aspirate or are at risk to aspirate because of conditions such as Parkinson disease, stroke, or amyotrophic lateral sclerosis. An ongoing clinical trial (No. 2015-0238) is investigating whether EMST can also benefit head and neck cancer survivors with chronic aspiration due to radiation therapy.
EMST is done using a hand-held device, into which the patient blows to open a spring-loaded valve. This resistance training is designed to build the patient’s expiratory force and enable the patient to cough out liquid that is aspirated, thus reducing the risk of pneumonia. Data from the prior studies suggest that EMST also decreases aspiration by building muscles related to swallowing.
The trial in cancer survivors is led by Katherine Hutcheson, Ph.D., an associate professor in the Department of Head and Neck Surgery. The primary endpoints of the trial are to clarify the relationship between aspiration and expiratory function and to evaluate the clinical benefit from EMST in patients with chronic aspiration resulting from radiation therapy for head and neck cancer.
Before launching the trial, Dr. Hutcheson and colleagues obtained pilot data from a series of 64 patients with head and neck cancer, all of whom were evaluated for swallowing and expiratory function after completing radiation therapy and 26 of whom underwent EMST. In their study of patients’ expiratory function, the researchers found that patients who aspirated had lower than normal respiratory force. Furthermore, the 23 patients who completed the EMST protocol (three did not complete the exercise program) had 57% improvement in mean maximum expiratory pressure from baseline. In addition, 30% of these patients had a reduction in their aspiration severity, as measured by a barium swallow study.
“EMST appears to be well tolerated with excellent adherence,” Dr. Hutcheson said. “Patients also had improved scores on quality-of-life questionnaires.”
For more information, physicians can contact MD Anderson’s Office of Cancer Survivorship at firstname.lastname@example.org.
OncoLog, April 2017, Volume 62, Issue 4