Issue 29Fall 2013
In this issue we present:
- Outpatient Induction Chemotherapy for AML or MDS: A New Model of Care Honed at SCCA
- Intensely Personalized Breast Cancer Treatment
- Cytoreductive Surgery for Metastatic Kidney Cancer
- SCCA Expands Cancer Care to North Seattle
- Provider Profile: Edmond Marzbani, MD
- Provider Profile: Janie Lee, MD
- Join the MoDAWGS in Support of Movember in November!
Although many cancer patients now receive chemotherapy as outpatients, most cancer treatment centers do not extend this practice to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndromes (MDS) who are receiving initial intensive induction therapy. This reluctance primarily reflects the propensity of such therapy to damage the GI tract and aggravate patients’ pre-existing low neutrophil counts, thus producing potentially life-threatening infections. AML and its treatment also cause a significant reduction in platelet counts and thus a significant risk of bleeding. The high-risk nature of AML and its initial treatment has traditionally led physicians to keep patients in the hospital until patients’ neutrophil and platelet counts recover four to five weeks after the initiation of chemotherapy.
But recently, based on growing experience with oral prophylactic antibiotics and transfusion support, physicians at Seattle Cancer Care Alliance (SCCA) have begun routinely discharging patients from its inpatient facility at the University of Washington Medical Center (UWMC) immediately following the completion of high-dose induction chemotherapy for AML and MDS. This allows patients to spend only five to seven days, rather than four to five weeks, in the hospital. This spring, SCCA researchers initiated a pilot clinical trial involving complete outpatient administration and monitoring of chemotherapy for AML and MDS. The trial’s principal goals are to assess the safety of this practice and its effects on quality of life and costs.
Building Confidence in Early Discharge
Clinicians at SCCA were pioneers in providing patients with outpatient care following moderately intensive treatments such as reduced-intensity allogeneic stem-cell transplantation. “The doctors at Fred Hutchinson Cancer Research Center started doing outpatient transplants a couple decades ago,” said Pamela S. Becker, MD, PhD, associate professor in the Division of Hematology at the University of Washington (UW) School of Medicine. “So it didn’t make a lot of sense that we were giving other patients with leukemia less intense chemotherapy and keeping them here longer. This is an inconsistency.”
Before joining UW and SCCA in 2008, Elihu Estey, MD, professor in the Division of Hematology at the UW School of Medicine, had gained experience with early discharge of newly diagnosed AML patients at the University of Texas MD Anderson Cancer Center in Houston. These patients were typically young and were discharged on an ad-hoc basis.
But changing the way things have always been done requires more formal evidence. Doctors, nurses, and patients had come to equate heavy-duty chemotherapy with hospitalization.
To build confidence in the potential switch, Roland B. Walter, MD, PhD, assistant professor in the Division of Hematology at the UW School of Medicine, built on Estey’s experience and led an SCCA pilot study exploring the medical and financial effects of early hospital discharge in patients who met medical criteria (e.g., good liver, kidney, and heart function; no bleeding; no need for intravenous antibiotics), lived within 30 minutes of SCCA, and had a routinely available caregiver.
The study results (published in Haematologica 2011;96:914-917) showed that even though many of the patients who were discharged early required readmission before recovery of their blood counts, no deaths or intensive care admissions resulted. Patients spent less time in the hospital and required less IV antibiotic treatment and fewer red blood cell transfusions than they would have without early discharge. The average daily cost of caring for the patient was also reduced.
Overall, the small SCCA study documented the feasibility and safety of outpatient management of selected AML/MDS patients and signaled a turning point in routine care for leukemia treatment in Seattle.
“We now have regimens that are given partly or almost entirely outpatient,” said Paul Hendrie, MD, PhD, associate professor in the UW hematology division and clinical medical director for the Inpatient Oncology Service. “What we tell new patients has definitely changed. In the past we would tell them to expect to stay in the hospital until their blood counts recovered from chemotherapy. Now it’s changed to ‘you will come in, receive chemotherapy, and then, if everything is going right, we should be able to discharge you to our outpatient clinics.’”
New Patient Benefits — and Responsibilities
While reducing the length of the hospital stay by two or three weeks can certainly improve the patient’s quality of life—most patients naturally prefer being at home—the prospect of an early discharge can cause unease in some patients. Certain patients expect to be hospitalized during their cancer treatment. “Some patients are hesitant, but we talk with them,” Hendrie said. “The nurses spend time with them. You have to be reassuring. And for some patients, maybe you wait an extra day. Then once they go home and see that nothing dramatic has happened, they feel more assured.”
Estey and Hendrie emphasize the importance of both the patient and the patient’s home caregiver hearing instructions before discharge. In particular, knowing that they must return to the hospital at the first sign of trouble—such as a fever—is critical. All patients and their caregivers at SCCA receive this mandatory training before discharge. The presence of good family support such as a spouse, parent, or child providing 24/7 care immediately after discharge also makes a difference.
Being ready for rapid readmission is another key to good outcomes, and that’s why patients must remain within 30 minutes of SCCA as they recover. For some, this means staying at a nearby hotel with their caregiver. SCCA House also provides patients and their families access to reasonably priced housing. Longer term, SCCA researchers hope their studies will help convince insurance companies to reimburse patients for the costs of chemotherapy-related lodging.
“I don’t think there is any question that in ten years this will be the standard of care,” Estey said. “Just look at other trends in medicine. For many years when people gave birth they stayed in the hospital for a week or several days. Now they go home. Surgery was totally inpatient. Now it’s routinely outpatient. Treatment of AML is often unpredictable. However, we can always strive to improve the patient’s quality of life as we treat them. That’s why we are moving increasingly toward outpatient chemotherapy.”
Next Step: Outpatient Chemotherapy for AML and MDS
Their experiences with early discharge have now led SCCA clinicians to explore the feasibility of outpatient-only induction therapy for newly diagnosed AML and high-risk MDS. The new SCCA pilot clinical trial #7910 started in June 2013 and will enroll 25 patients who are 18 to 59 years of age and in generally good condition. As in the early discharge trial, patients must have a caregiver and live within 30 minutes of SCCA during their treatment.
Read more about this new trial.
The study’s primary goals are no increase in mortality and to have at least half of the patients complete chemotherapy without the need for hospital admission. Patients will receive all of their induction chemotherapy in the outpatient infusion center at SCCA and will stay in a nearby private residence or hotel. Researchers will also monitor patients’ quality of life and the treatment costs.
According to Becker, who is the principal investigator on the trial, most community hospitals are not yet ready with the resources or staff to offer complete outpatient infusion chemotherapy for acute leukemia.
“This protocol requires having the clinical personnel and structure in place,” Becker said. “Even for us, we had to prepare our nurses and staff. It’s been a long process. I met many times with the nursing staff, nursing administration, and outpatient nurses to get everyone on board and set expectations.
“Our goal is to be able tell patients: We can give you induction chemotherapy as safely and effectively as any other induction chemotherapy… but at SCCA you have the bonus of not needing to be in the hospital,” Becker said. Study results, due by early 2015, will determine the feasibility of this next step in chemotherapy’s ongoing evolution from hospital to home.
Finding the vulnerabilities of a patient’s specific tumor could be a “magic button” in cancer treatment. A long line of physicians are anxious to see if such a button for tumor death exists, including V.K. Gadi, MD, PhD, associate professor of medicine at the UW School of Medicine.
“The idea will take more development, but I think it’s feasible,” Gadi said. In his latest trial, New Targets for Doxorubicin Resistant Breast Cancer, a tumor is cultured to determine on a functional level its vulnerabilities.
“We are doing this research study to develop a test to help predict which patients with breast cancer might need additional medicine to improve survival,” Gadi said. “This is needed because when the breast cancer has been surgically removed and adjuvant chemotherapy has been administered, there is still a chance that the cancer will return. We would like to take a closer look and develop this test to determine which cellular pathways protect cancer cells from anthracycline chemotherapy. This is a very different way of looking at treating tumors. It is intensely personalized. No other assay has this.”
Functional genetics and high throughput screening involve systematically testing large numbers of genes to identify weak points in cancer cells. “It’s essentially a very efficient search engine that quickly and precisely identifies genes required for survival of cancer cells,” said Christopher Kemp, MD, a member of the Fred Hutchinson Cancer Research Center’s divisions of Human Biology and Public Health Sciences.
The idea is that cancers are a result of uncontrolled cell proliferation with coinciding vulnerabilities. Kemp and Gadi are using functional genetics to find weaknesses they can then attack with existing or new drugs that will selectively kill cancer cells but not normal cells.
“We have eliminated several major bottlenecks in the traditional path to cancer drug development and have optimized a pipeline to finding better therapies,” Kemp said. “By teaming up with experts with a range of experience, we will be able to translate our findings to the clinic much faster.”
“The ultimate goal is in real-time to treat a patient with her own ‘functional genomic’ signature to identify treatments uniquely tailored to the cancer she is fighting,” Gadi said. “It seems counter-intuitive at a time when medicine is moving towards uniformity to propose combinations of treatments that may only work for the patient sitting in front of you, but then again, we’ve bucked the trend with success before and we are happy to do it again.”
To cut or not to cut? Cytoreductive nephrectomy, or removal of the tumor-bearing kidney, may benefit survival outcomes for men and women with newly diagnosed metastatic kidney cancer. But the surgery can be morbid and delay the start of medical therapies. Not all kidney cancer patients should undergo cytoreductive nephrectomy, so community physicians often turn to our university-based faculty to determine the best treatment course for their hardest-to-treat patients.
Approximately 65,000 new kidney cancer cases will be diagnosed in 2013, and 13,680 patients will die from their kidney cancers. About 20 percent of kidney cancer patients have distant metastases at diagnosis. Historically, immunotherapy with interferon-alpha or interleukin-2 had been the mainstays of kidney cancer therapy. More recently, the development of targeted therapies has substantially changed the treatment approach for most patients with kidney cancer. These therapies affect the cancer’s ability to grow new blood vessels, a key mechanism by which kidney cancers grow.
“Predominantly, good performance status patients do better with nephrectomy followed by either immune therapy using high-dose interleukin-2 or using the newer targeted agents,” Tykodi stated. “And most studies of targeted kidney agents are based heavily on nephrectomized patients. Nephrectomy doesn’t appear to be beneficial for patients.”
Cytoreductive nephrectomy helps palliate local symptoms such as pain or recurrent hematuria associated with the primary tumor and obviates concerns about progression of the main tumor if left in place. Randomized studies have also shown improvement in patient survival rates when treatment includes cytoreductive nephrectomy followed by systemic therapy with interferon.
Though interferon-alpha is no longer commonly used, the charts below indicate the potential therapeutic benefit of the addition of surgery to treatment for metastatic kidney cancer, and is one of several that Gore and Tykodi use to represent the benefits of cytoreductive nephrectomy. Ongoing trials will evaluate whether the survival benefit seen with interferon-alpha also applies to newer targeted therapies. The biological explanation for better survival associated with cytoreductive nephrectomy surgery is not well understood. Nephrectomy may remove endogenous pro-angiogenic proteins such as vascular endothelial growth factor (VEGF) that could promote tumor growth and metastases and/or affect response to subsequent anti-VEGF therapy. Nephrectomy may also help relieve immune suppression mediated by large tumor bulk.
SCCA continues to offer immunotherapy with high-dose interleukin-2 to select patients with metastatic kidney cancer. Interleukin-2 treatment can result in a complete response for a small percentage of kidney cancer patients and is invariably combined with cytoreductive nephrectomy. Patients who qualify for this combined treatment would have excellent performance status. Poor risk metastatic kidney cancer would not be treated with this regimen. To schedule an educational outreach talk at your location on this topic, contact the SCCA Physician Outreach office at (206) 288-1066 or firstname.lastname@example.org.
In early September, Seattle Cancer Care Alliance (SCCA) opened a medical oncology clinic at UW Medicine’s Northwest Hospital & Medical Center in North Seattle. This clinic joins SCCA Radiation Oncology at Northwest Hospital and Seattle Cancer Care Alliance Proton Therapy, A ProCure Center, located on the same campus, providing comprehensive cancer care and access to leading-edge cancer treatments and clinical studies to North Seattle residents.
SCCA Medical Oncology
UW Medicine physicians now treat patients at SCCA Medical Oncology at Northwest Hospital as well as at the SCCA Clinic at South Lake Union. Services include an on-site pharmacy, laboratory, diagnostic services, and infusion, physical therapy, nutrition counseling, with patient navigator assistance available. Lymphedema therapy and pain management, as well as support groups, classes, and a free hat and wig bank are available to patients.
SCCA Radiation Oncology
SCCA Radiation Oncology treats adult patients for any primary cancer, including breast, colon, lung, and prostate cancer. A new Elekta Synergy linear accelerator with electron and photon capability was installed in 2010. The facility uses a 16-slice, wide-bore GE LightSpeed CT simulator to target tumors and minimize damage to healthy tissue, the Philips Healthcare medical dosimetry treatment planning system, and Elekta MOSAIQ electronic medical record software.
SCCA Proton Therapy
SCCA Proton Therapy, A ProCure Center opened last March. An advanced form of radiation treatment, proton therapy can be calibrated with great precision to selectively kill cancer cells. Over the past seven months, proton therapy at SCCA has been used to treat a steady stream of patients including those with central nervous system cancers (adults and children), prostate and other genitourinary cancers, lung cancer, and recently liver cancer.
There are 12 proton therapy centers across the country. “Our disease experts are working toward identifying the cancer patients who will benefit the most from proton radiotherapy, often developing comparative treatment plans for both protons and conventional X-rays to identify the best treatment for each patient,” said associate medical director Ramesh Rengan, MD, PhD.
In many cases SCCA radiation oncologists have the option to treat patients with traditional X-ray (photon) treatment or with proton therapy. Rengan explains that often it isn’t clear whether patients would be better served with protons or photons, so comparative planning is used to model both options. If, during the comparative planning process, it is discovered that protons do not provide a meaningful benefit, SCCA radiation oncologists will recommend X-ray therapy. “Our goal is for the patient to be treated with the optimal modality for their cancer, whether that is X-rays or protons.
The comparative planning process helps us ensure that this happens. We then discuss with the referring physician the best way to deliver this care to the patient. It is not unusual for us to find X-rays to be equivalent and to recommend photons,” Rengan said.
Patients who clearly benefit from proton therapy include those with tumors near critical structures and those who require re-irradiation after initial treatment with X-rays. Often, these patients cannot be re-treated safely with conventional X-rays or photons because of excess dose to healthy tissue. For these patients, protons may offer the only therapeutic option for treatment.
Physicians referring patients to an SCCA clinic at Northwest Hospital will receive copies of consultation notes as well as copies of post-treatment summaries. SCCA physicians frequently have personal contact with referring providers as part of the treatment decision-making process. Normal follow-up occurs for patients four to six weeks after treatment is finished, according to follow-up algorithms. But who the patient ultimately sees for the follow-up visit(s) is determined with the referring provider.
SCCA Medical Oncology at Northwest Hospital
p: (206) 368-5800
SCCA Radiation Oncology at Northwest Hospital
p: (206) 368-5808
SCCA Proton Therapy, A ProCure Center
p: (877) 897-7628
Provider Profile: Edmond Marzbani, MD, Medical Director, SCCA Medical Oncology, UW Medicine Northwest Hospital & Medical Center
Edmond Marzbani, MD, became the medical director of SCCA Medical Oncology at UW Medicine’s Northwest Hospital and Medical Center in September 2013. He is also a clinical assistant professor at the UW School of Medicine.
Marzbani spent much of his fellowship with the UW’s Tumor Vaccine Group investigating the efficacy of a vaccine directed against HER-2/neu for the prevention and treatment of high-risk breast cancer. He hopes to continue his collaboration with the Tumor Vaccine Group and other SCCA-based research groups by facilitating high-priority clinical trials at Northwest Hospital.
In his lifetime Marzbani, like all oncologists, hopes to see the eradication of cancer. “This will require improvements both in the early prevention and diagnosis of cancer,” he said. “I anticipate there will be a shift from toxic chemotherapy to well-tolerated targeted therapies in the next 10 years, which will certainly improve the quality of life of patients receiving treatment. The SCCA clinic at Northwest Hospital will be at the forefront of using these new therapies as they are approved.”
Provider Profile: Janie M. Lee, MD, MSc, Medical Director, Breast Imaging Services, Seattle Cancer Care Alliance
In August 2013, Janie M. Lee, MD, MSc joined the University of Washington as an associate professor of radiology and SCCA as the clinical director of Breast Imaging. “I’ve always been interested in women’s health,” Lee said.
“I started my medical career at a time when including women and minorities in major clinical trials was being recognized as critical for understanding how treatments affect all of our patients.”
Lee completed her diagnostic radiology residency at the University of Pennsylvania, her clinical fellowship at Massachusetts General Hospital, and earned her master’s in health policy and management at the Harvard School of Public Health. She aims to advance women’s health through a combination of clinical, research, and educational efforts.
In the breast imaging clinic, Lee applies state-of-the-art technologies to diagnose breast cancer. Her research focuses on integrating information about patient risk factors, cancer biology, and new imaging tests to improve how new breast cancers and recurrences are diagnosed. “By tailoring screening approaches to patient characteristics such as breast density and family history, we may be able to apply screening more intensively in higher risk women to detect more early breast cancers,” Lee said. “At the same time, screening women at lower risk less intensively will minimize false-positive test results.”
Who are the MoDAWGS? It’s a team of folks from Seattle Cancer Care Alliance, University of Washington, VA Puget Sound, and Fred Hutchinson Cancer Research Center, including doctors, researchers, staff, patients, and caregivers, all supporting the efforts of the Movember organization in raising awareness and funds to combat prostate cancer, testicular cancer, and other men’s health issues.
Movember is the reason behind the millions of moustaches seen on men (and women) around the world in November. Men supporting Movember can grow a moustache in November and become a “Mo Bro,” bringing awareness to men’s health issues by prompting conversations wherever they go. And “Mo Sistas” can help raise funds and encourage the men in their lives to get involved.
To join MoDAWGS or support Movember, go to www.modawgs.com. Share this information and our latest prostate cancer screening guidelines with your patients, all located on our SCCA blog. To request Movember materials for your clinic, contact us at email@example.com or (206) 288-6396.
The SCCA Adult Bone Marrow Transplant News is a publication presenting the latest information on bone marrow transplant research at SCCA, providing up-to-date information for all health care professionals caring for transplant patients.
Read about important outcomes research at the Fred Hutch that may benefit your patients.
Each issue of Clinical Trials Monthly highlights several of the more than 200 clinical trials that are currently recruiting patients at SCCA.
Each quarterly Leading Edge newsletter will highlight a new topic to give you the latest news on leading-edge therapies that SCCA physicians are offering.