2010 Research Wrap-up
CCH Newsletter - Fall 2010
Brain Tumors and Neuroblastoma
Preclinical study shows new chemotherapy combination promotes cell death in neuroblastomaHigh-risk cases of neuroblastoma have poor survival rates and novel therapies are needed. AZ623 is an inhibitor of the Trk receptor tyrosine kinases, which have been implicated in neuroblastoma growth. Researchers Peter Zage, M.D., Ph.D., left, and Patrick Zweidler-McKay, M.D., Ph.D., right, studied AZ623 combined with topotecan, an agent already used in most current neuroblastoma treatment regimens, to test their effectiveness against neuroblastoma tumor models.
The pre-clinical study showed that AZ623 induces neuroblastoma tumor cell death in vitro and reduces tumor growth and vascularity in vivo. The combination of AZ623 and topotecan was more effective in reducing tumor growth than either treatment alone. The antitumor effects of AZ623 plus topotecan suggest a novel combination for use in neuroblastoma patients. Published in Cancer
Intensive chemotherapy improves survival in pediatric high-grade glioma after gross total resection
Research led by Johannes Wolff, M.D., found that HIT-GBM-C chemotherapy after complete tumor resection for high-grade gliomas was superior to previous protocols. A previous HIT-GBM protocol consisted of intensive chemotherapy and simultaneous radiation followed by interferon gamma maintenance treatment. HIT-GBM-C evaluated the effect of a prolongation of the same type of treatment with the addition of valproic acid.
The most important finding in this study is that the overall survival of patients with total gross tumor resection was improved by the HIT-GBM-C treatment regimen, while there was no improvement for treated patients with less than total gross resection. The finding that some treatment protocols resulted in increased survival after complete resection indicates that the infiltrating cells are sensitive to certain types of chemotherapy but not to others. The collective experience shows that complete resection is an important step in treatment but so is chemotherapy, in particular after complete resection, and that resection alone is not enough. Published in Cancer
Reirradiation for progressive diffuse intrinsic pontine glioma
MD Anderson radiation oncologists have found a way to safely alleviate symptoms in patients with progressive diffuse intrinsic pontine glioma, an aggressive and fatal pediatric brain cancer. Pontine glioma accounts for 10% to 15% of pediatric brain tumors and usually targets children under the age of 10. The median survival for this disease is less than one year, and patients are subject to multiple neurologic deficits.
Radiation oncologists at MD Anderson led by Anita Mahajan, M.D., have found that giving an additional round of radiation in selected patients after progression is not only feasible, but it can improve painful symptoms and may delay the growth of the tumor for a short time. Presented at 42nd Annual Congress of International Society of Pediatric Oncology
Prognostic factor discovered for pediatric bone cancer survival and ways to lower costs of care
A recent study from the Children’s Cancer Hospital has shown the importance of the absolute lymphocyte count (ALC) in predicting the prognosis of pediatric bone cancer patients. This is built on previous studies of other MD Anderson pediatric populations confirming ALC as a prognostic factor.
Peter Anderson, M.D., and other researchers discovered that pediatric osteosarcoma patients with a high ALC after two weeks of chemotherapy had a 92% survival rate compared to patients with a low ALC who had a 33% survival rate. For Ewing’s sarcoma patients with a high ALC at two weeks, their overall survival was 68% compared to an overall survival of 32% for patients with a low ALC. Dexamethasone is often given as an anti-nausea regimen to bone cancer patients. Since it has shown to possibly reduce ALC recovery, MD Anderson clinicians have recommended using other anti-nausea medications that won’t affect the ALC negatively.
Also as a part of their study, researchers compared inpatient chemotherapy regimens to outpatient regimens and found that outpatient treatment for osteosarcoma and Ewing’s sarcoma was 25% to 35% lower in cost than having the same chemotherapy given inpatient. Presented at 42nd Annual Congress of International Society of Pediatric Oncology
Comparison shows inpatient chemotherapy more costly than outpatient delivery
Improvements in the delivery of anti-nausea medication and fluid hydration have allowed for some chemotherapy regimens to be administered in an outpatient setting. Although surveys have shown patients prefer outpatient care compared to inpatient care, a new pilot study conducted by the Children’s Cancer Hospital has further quantified the benefits of outpatient care, says Winston Huh, M.D.
The study showed that the costs associated with administering some outpatient chemotherapy are significantly less than delivering a similar therapy in the inpatient setting. Nursing interventions and paperwork were also less in the outpatient setting. The study results showed that some chemotherapy can be delivered to outpatients safely while cutting down on nursing paperwork and overall hospital costs. Presented at 42nd Annual Congress of International Society of Pediatric Oncology
Signaling pathway impacts spread of bone cancer and overall survival
Researchers have identified an important signaling pathway that, when blocked, significantly decreases the spread of pediatric bone cancer.
In their pre-clinical study, Dennis Hughes, M.D., and other researchers at MD Anderson’s Children’s Cancer Hospital found that blocking the Notch pathway in bone tumors in mice decreased metastases in the lungs 15-fold. Their research showed that the Notch pathway and Hes1 gene play a key role in promoting the invasion and metastasis of osteosarcoma, the most common form of bone cancer in children.
In addition to Notch and Hes1’s role in metastasis, the study unveiled that Hes1 expression can be correlated with a patient’s prognosis. The researchers conducted a small retrospective study looking at patient samples, and 39% of patients with high expression levels of Hes1 survived 10 years versus the 60% survival rate for patients who had lower levels. Presented at 42nd Annual Congress of International Society of Pediatric Oncology
Pre-clinical study of Imatinib and TRAIL combination shows growth inhibition of Ewing’s sarcoma
There is a crucial need for better therapeutic approaches for the treatment of Ewing’s sarcoma. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in Ewing’s sarcoma cells in vitro. However, in vivo, acquired resistance to TRAIL is a major limiting factor. Platelet-derived growth factor receptor-beta (PDGFR-beta) is highly expressed on Ewing’s cells.
Andrea Hayes-Jordan, M.D., and Children’s Cancer Hospital researchers were able to show pre-clinically that using imatinib mesylate (Gleevac) to inhibit PDGFR-beta in Ewing’s cells enhanced the effects of TRAIL, both in vitro and in vivo. The combination of imatinib mesylate and TRAIL significantly inhibited the growth of primary tumors and decreased the incidence of spontaneous Ewing’s pulmonary metastasis compared with either drug alone. The study supports the possibility that combining these treatments will improve anti-cancer therapy for Ewing’s sarcoma. Published in Cancer
MD Anderson zeroes in on better way to predict prognosis in pediatric leukemia patients
Patrick Zweidler-McKay, M.D., Ph.D., and other researchers may have found a way to more accurately predict treatment outcomes in young leukemia patients using information from a common and simple complete blood count test, also known as a CBC. The results of a retrospective study illustrated that measuring residual disease (MRD) indicator and the absolute lymphocyte count (ALC) together enable physicians to better predict which patients with acute lymphocytic leukemia (ALL) will remain disease free and who will most likely relapse.
The study was based on 171 pediatric ALL patients and showed that after a month of treatment, patients who were MRD positive with a low ALC had an event-free survival rate of 33% and an overall five-year survival outcome of 41%. However, those who were MRD positive but with a high ALC had an event-free survival rate of 69% and overall five-year survival of 92%. The most positive outcomes come from patients who are MRD negative and have high ALC. These patients have a 99% overall five-year survival. Presented at the American Society of Pediatric Hematology/Oncology Annual Meeting
Novel HDAC inhibitor initiates cell death in pre-clinical studies of acute leukemia
Histone deacetylase inhibitors (HDACi) have become a promising new avenue for cancer therapy, and many are currently in Phase I/II clinical trials for various tumor types. In a recent study led by Joya Chandra, Ph.D., findings show that apoptosis induction and histone alterations by PCI-24781, a novel hydroxamic acid-based HDAC inhibitor, require caspase-8 and the adaptor molecule, Fas-associated death domain (FADD), in acute leukemia cells.
PCI-24781 treatment also causes an increase in superoxide levels, which has been reported for other HDACi. However, an antioxidant does not reverse histone alterations caused by PCI-24781, indicating that ROS generation is likely downstream of the effects that PCI-24781 exerts on histone H3. Taken together, these results provide insight into the mechanism of apoptosis induction by PCI-24781 in leukemia by highlighting the roles of caspase-8, FADD and increased superoxide levels. Published in the International Journal of Cell Biology
Children’s Cancer Hospital faculty selected as endocrine tumor experts for prestigious textbook
Pediatric endocrinologists Steven Waguespack, M.D., left, and Anita Ying, M.D., along with pediatric oncologist, Winston Huh, M.D., authored a chapter on pediatric endocrine tumors in the Principles and Practice of Pediatric Oncology textbook edited by Philip Pizzo and David Poplack. The chapter appears in the newest edition of the book, viewed as one of the most credible resources in pediatric oncology.
Multiple endocrine neoplasia virtual clinic opens for families
MD Anderson has opened a new virtual clinic for multiple endocrine neoplasia (MEN) that will offer families a multidisciplinary approach for MEN risk assessment and treatment. Children of parents with the hereditary disease will have access to a team of pediatric endocrinologists, genetic counselors and endocrine surgeons who can monitor children for any signs of the disease and treat it if diagnosed.
First national MEN patient education conference hosted at MD Anderson
Pediatric endocrinologists Steven Waguespack, M.D., and Anita Ying, M.D., presented at the first Multiple Endocrine Neoplasia (MEN) patient education conference in the nation. The conference, hosted by MD Anderson, was geared toward families and offered education of genetic testing, diagnosis and treatment for adult and pediatric patients.
Waguespack and Ying were also authors on a comprehensive review of pediatric pheochromocy and paraganglioma published in the May 2010 edition Journal of Clinical Endocrinology and Metabolism. Both continue to speak nationally and internationally on a variety of topics related to endocrine tumors and endocrine sequelae of cancer care.
Neurofibromatosis Clinic opens new clinical trials for patients
MD Anderson is home to the largest neurofibromatosis program in the country, seeing more than 1,000 pediatric and adult patients a year. Neurologist John Slopis, M.D., above, and neuropsychologist Bartlett Moore, Ph.D., below, have collaborated on numerous research studies on the biology of cognitive abilities in neurofibromatosis patients. As a result, they were able to standardize cognitive testing for school-age patients and develop a guide for school interventions.
Currently, Slopis and Razelle Kurzrock, M.D., have clinical trials under way to test two different drugs, one targeting skin tumors and one targeting NF2. In addition, Dina Chelouche-Lev, M.D., is conducting molecular genetics research investigating the drivers of malignant transformation of neurofibromas.
Patients who receive care at MD Anderson for neurofibromatosis benefit from a comprehensive team including experienced surgeons, pain management experts, nurse practitioners, psychologists, cognitive testing specialists, education specialists, sarcoma oncologists and researchers.
Problem-Solving Skills Training helps mothers of newly diagnosed patients cope with stress
Mothers who have children diagnosed with cancer now have a better approach to address and cope with stresses associated with their child’s disease. A new certified intervention, called Problem-Solving Skills Training (PSST), has proven to be more effective long term compared to other psychological methods, such as reflective listening.
Three months after their child’s initial diagnosis, the stress levels of mothers receiving PSST had decreased twice as much as mothers who had no intervention. Martha Askins, Ph.D., from the Children’s Cancer Hospital, is a collaborator on the multi-institution study. Her next goal is to adapt the training method to an online program that parents can access from home or when psychological support is unavailable. Presented at 42nd Annual Congress of International Society of Pediatric Oncology
Psychosocial and functional comparison of limb-salvage surgery and amputationResearchers at MD Anderson Children’s Cancer Hospital have completed a study of 57 osteosarcoma patients who received either a limb-salvage surgery or amputation while under treatment at the children’s hospital. When comparing emotional and physical outcomes from the surgeries, they found that better leg function was significantly related to better emotional well-being in long-term osteosarcoma patients. In the study, led by Winston Huh, M.D., above left, Rhonda Robert, Ph.D., above right, and Norman Jaffe, M.D., below right, physical function outweighed the impact of other variables on emotional well-being, including age at diagnosis, duration of treatment, hip involvement, rotationplasty and gender. Late amputation was associated with body image concerns.
The researchers concluded that anticipated physical function outcomes should be emphasized throughout treatment-related decision making for patients with osteosarcoma. Informing patients of long-term survivorship issues and projecting functional needs across their lifespans may inform and guide treatment. Published in the Journal of Pediatric Blood and Cancer
AYA and Survivorship
Factors influencing adherence to follow-up care in childhood cancer survivors
Despite their increased risk for late effects and secondary cancers, nearly half of childhood cancer survivors at the Children’s Cancer Hospital did not continue follow-up care seven years after their diagnosis.
In their study, Children’s Cancer Hospital researchers, led by Joann Ater, M.D., found that patients treated with only surgery were highly less likely to return for follow-up care five years after treatment. Survivors of central nervous system cancers or solid tumors other than bone cancers were less likely to adhere to follow-up standards, as well as survivors over the age of 18 without private health insurance. At five years post-diagnosis, African-Americans were significantly less likely to not return for follow-up care. The findings from the study showed the primary factors that influenced compliance to follow-up care.
As a result, a more in-depth analysis of a larger survivor population will be studied. All patients will receive a survivor’s guide from MD Anderson called Passport for Care that will include essential information needed for follow-up care. More education will also be given to patients and families before the child turns 18 about the importance of continuity of insurance coverage. Presented at 42nd Annual Congress of International Society of Pediatric Oncology
Health behaviors and preferences of childhood cancer survivors
Approximately 40% of childhood cancer survivors are overweight or obese, according to researchers at the Children’s Cancer Hospital. Led by Joann Ater, M.D., researchers recently studied the health behavior and preferences of Children’s Cancer Hospital survivors to determine what can be done to encourage healthier lifestyles.
The study showed that childhood cancer survivors who were overweight or obese were significantly less likely to view their health as good and were much more likely to be worried about their cancer. Overall education about late effects and the importance of maintaining healthy behaviors was low for all survivors, but those who were overweight expressed interest in weight control and getting in shape. Of the 157 survey participants, most preferred a computer-based intervention. As a result, the Children’s Cancer Hospital is planning a web-based diet and exercise intervention targeting survivors. Presented at 42nd Annual Congress of International Society of Pediatric Oncology
Starting an Adolescent and Young Adult (AYA) Program: some success stories and some obstacles to overcome
MD Anderson’s Anna Franklin, M.D., recently collaborated with multiple institutions to review the best practices used by cancer centers that have implemented an AYA program.
This particular age group has unique needs that are not often met by traditional pediatric and adult cancer programs.
The analysis unveiled that the most important factors for the successful establishment of an AYA oncology service are the degree of engagement of both pediatric and adult medical oncologists, the philanthropic support of charities, and the role of dedicated professionals across a range of disciplines in driving the development of services for AYA patients. To improve the patient experience for its AYA patients, MD Anderson has established an AYA Advisory Council of patients and staff, a fertility clinic, young adult social programs, as well as targeted clinical studies. Published in the Journal of Clinical Oncology
- Pediatric Clinical Trials
- Children's Cancer Hospital