USC Norris Comprehensive Cancer Center and Hospital: Groundbreaking Programs, Innovative Treatments

USC Norris Comprehensive Cancer Center and Hospital

The University of Southern California (USC) Norris Comprehensive Cancer Center and Hospital has long enjoyed a national reputation as a leading resource for cancer research, treatment, prevention, and education. Located in Los Angeles, the Center was named one of the nation’s first eight comprehensive cancer centers in 1973, and has held this National Cancer Institute (NCI) designation ever since.

The USC Norris Comprehensive Cancer Center maintains affiliations with several hospitals in the Los Angeles area, including the USC Norris Cancer Hospital, Children’s Hospital Los Angeles, Keck Hospital of USC, and Los Angeles County USC Medical Center. Patients who visit the Center’s outpatient clinics and affiliated hospitals reap the benefits of the ground-breaking work of nearly 200 scientists and physicians, with access to a wide range of already-approved novel agents and hundreds of clinical trials.

Research at Norris is organized into five thematic programs (molecular genetics, epigenetics and regulation, tumor microenvironment, cancer epidemiology, and cancer control research) and five translational research programs (genitourinary cancers, gastrointestinal cancers, women’s cancers, leukemia and lymphoma, and developmental therapeutics). The overall goal of “fostering collaborative research in the areas of basic, clinical, epidemiological, cancer control, and translational research” is evident throughout the Center and its affiliated sites, and is especially apparent in the USC Norris Melanoma Program and soon-to-be-launched Adolescent and Young Adult (AYA) Cancer Program.

Adolescent and Young Adult Cancer Program

In the coming year, the USC / Norris Cancer Center, the Norris Cancer Hospital, and Children’s Hospital Los Angeles will launch the AYA Cancer Program, bringing together teams of specialists from all areas of oncology to advance both research and comprehensive care for patients with cancer between the ages of 15 to 39 years. With this undertaking, Norris and Children’s Hospital join what is only a handful of centers nationwide with dedicated programs for patients in this age group.

The need for an AYA program is pressing. Cancer is this age group’s leading disease-related cause of death, and more than 70,000 adolescents and young adults are diagnosed in the United States each year. Despite impressive survival-related advances in other age groups, progress in the AYA population has lagged, and clinical trial enrollment during initial treatment averages only 3% to 4%, versus nearly 60% for pediatric populations. This lag stems largely from AYA patients’ distinct needs related to shifting personal relationships, employment, and education, often resulting in a gap in medical care. The problem is further compounded by clinical care that is characterized by frequently fragmented and non-age-appropriate services. When combined, these problems often manifest as an increased likelihood of misdiagnosis or late-stage diagnosis, as well as suboptimal adherence to treatment and follow-up plans.

A key initiative of the new program is to create a central AYA database into which each patient’s diagnostic-, therapeutic-, and outcome-related data will be automatically entered and then tracked and updated long-term by a case manager. The program is also planning to create a biorepository for patients’ tumors and other biological materials. In addition, AYA-specific clinical trials will be designed for the most common cancers affecting this population.

In an effort to meet the physical, emotional, and psychosocial needs of those in this age group, team leaders and nurse facilitators will coordinate each patient’s experience from diagnosis, to treatment, and on to recovery, ensuring that needs are met effectively and efficiently. To this end, patients will be offered a variety of AYA-specific services, including fertility preservation/ family planning, genetic counseling, education, employment and financial counseling, referral to AYA survivor and/or cancer-specific support groups, physical and occupational therapy, nutritional assessment and counseling, legal assistance, and psychological counseling.

Melanie Goldfarb, MD

Thyroid Cancer as a Major Focus

As one of the five most common malignancies in adolescents and young adults, thyroid cancer will be an area of intense interest among AYA Cancer Program researchers and clinicians. Despite the prevalence of the disease, research on its biology and treatment decisions specific to the AYA age group has been lacking, leaving several questions unanswered. “We know that adolescents and young adults tend to do very well in terms of survival, but recurrence remains a major issue, as does the lack of consensus about the wisdom of adjuvant oral radioactive iodine (I 131) therapy after surgery,” said Melanie Goldfarb, MD, assistant professor of Surgery and head of Endocrine Surgery at USC’s Keck School of Medicine.

According to Goldfarb, multicenter clinical trials on the use of postthyroidectomy radioiodine are needed, and is an area that AYA Cancer Program researchers hope to pursue. “Some studies conducted with older adults suggest that those with very low-risk tumors tend not to benefit from such treatment while those with high-risk tumors do,” she explained. “Unfortunately, studies have failed to address the pros and cons of the treatment in what is a large population of low- to intermediate-risk patients—especially adolescents and young adults, most of whom have stage I disease and some of whom have stage II disease—leaving endocrinologists and oncologists to make this decision without the benefit of sound evidence, “ said Goldfarb.

Goldfarb also anticipates that the launch of the AYA program will enable closer examination of a second issue: namely, how best to manage patients who develop thyroid nodules after radiotherapy administered previously for other cancers. “Some of these patients do develop thyroid malignancies but many others do not, and there are currently no evidence-based recommendations with regard to screening, diagnosis, and referral for surgical thyroidectomy,” she said.

Cosmetic Needs Addressed

As research continues, thyroidectomy will continue to be performed via a minimally invasive approach at the Center and within the new AYA program, with special attention paid to the cosmetic needs of younger patients with thyroid cancer. Rather than the historically large incisions made across the neck, the goal today is to accomplish the surgery through much smaller incisions with cosmetic surgery—type closures hidden in the crease of the neck. In experienced hands, such incisions can sometimes be as small as 4 cm in young patients with small thyroids. “Younger single patients tend to be especially concerned with cosmetic outcomes,” said Goldfarb, “and most have been more than pleased with the results achieved here at Norris.”

Goldfarb, who will serve as the “point person” in the new AYA Center, expects that adolescents and young adults will comprise roughly half of her patients. “What I envision is an environment of comprehensive care in which patients’ needs will be met more effectively and expeditiously. There will also be new opportunities for research that will provide much needed data that will ultimately promote a new understanding of the needs specific to the AYA age group.”

Melanoma Program

Both research and patient care are also at the forefront of the work being conducted within the the Center’s Melanoma Program, which combines the skills of medical, surgical, and radiation oncologists with those of laboratory scientists to configure highly individualized treatment plans that address each patient’s needs at both the molecular and “human” levels. Patients have access to the most current and ground-breaking therapies via clinical trials and a leading novel therapeutics phase I program at the Center.

Michael K. Wong, MD,PhD, FRCPC

Melanoma Program leader Michael K. Wong, MD, PhD, FRCPC, noted that the ability to handle highly complex cases sets USC Norris apart from other melanoma programs. “Where we excel is in situations involving truly advanced tumors, multiple organ involvement, and life-threatening metastases,” said Wong, who is professor of Medicine at the Keck School of Medicine and head of the Solid Tumors Section at USC Norris Comprehensive Cancer Center and Hospital.

Course-Changing Drug Approvals

Only one year ago Wong described his specialty as “one of the dark rooms in the oncology house,” characterized by multiple failed trials, treatment resistance, and poor outcomes. “Melanoma is the disease that gives cancer its bad name,” he said. Recently, however, the FDA approved three new drugs in 2011: peginterferon alfa-2b (Sylatron), ipilimumab (Yervoy), and vemurafenib (Zelboraf).

The promise of these new agents notwithstanding, Wong stressed that their successful use depends upon the skill and knowledge of those administering these agents. While patients experience almost no side effects during outpatient administration, ipilimumab works by inducing what is essentially unabated autoimmunity, which can cause severe and even fatal immune-mediated adverse reactions related to T-cell activation and proliferation, including enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. “Without a highly skilled and experienced team, an agent can turn from promising to deadly,” Wong cautioned. He went on to note that resistance to vemurafenib has already been seen, and that the agent is associated with adverse effects such as arthralgias, rash, fatigue, and hair loss, as well as the development of other skin cancers.

USC Norris Comprehensive Cancer Center and Hospital

1973

1983

1996

2007

2009

2012

USC Norris Comprehensive Cancer Center and Hospital is designated a National Cancer Institute comprehensive cancer center.

USC Norris Comprehensive Cancer Center and Hospital (then the USC Kenneth Norris Jr Cancer Hospital and Research Institute), including Marshall Ezralow Tower, is dedicated.

Dr Norman Topping Tower opens

The Harlyne J. Norris Research Tower opens its doors.

USC purchases USC Norris Cancer Hospital and Keck Hospital of USC from Tenet Healthcare Corporation.

The new Adolescent and Young Adult Cancer Program is scheduled to be launched in July.

1980

1988

1998

2008

2011

Peter Jones, PhD, discovers the links between DNA methylation and cancer (development of the concept of epigenetic therapy for the treatment of myelodysplastic syndrome).

Brian Henderson, MD, et al discover the links between steroid hormones and prostate, breast, and ovarian cancer, leading to therapies including tamoxifen and Lupron.

The Harold E. and Henrietta C. Lee Breast Center opens.

The definition of key mechanisms for DNA changes in lymphoma is attributed to Michael Lieber, MD, PhD.

Stephen B. Gruber is named director of the USC Norris Comprehensive Cancer Center, succeeding Peter Jones.

High-Dose Immunotherapy

Despite dealing with extremely advanced disease, the goal is to find a complete and permanent cure, said Wong. To this end, USC Norris has long served as a regional center of excellence for the use of high-dose immunotherapy with interleukin- 2, with clinicians who are highly experienced in the treatment.

Described by Wong as “a bit outside the mainstream,” such treatment requires the right team with the right expertise, operating within the right infrastructure. “Only a limited number of facilities offer this treatment because it’s difficult to administer and potentially dangerous, as it mimics a state of septic shock,” he said. Patients undergo inpatient treatment for a week, go home for a week, and then return for an additional week of treatment. The ideal candidate is someone healthy enough to mount a robust immune response, and to tolerate dose-related stress on the heart and lungs. For this reason, patient selection and appropriate pre-treatment testing (including cardiopulmonary evaluation and brain imaging, depending upon the agent) are essential. “These procedures require a great deal of effort on the part of all involved,” stated Wong, “but we can consistently deliver complete responses in a small number of these patients.”

Although each of these drugs is effective as a single-agent treatment, trials are being designed to evaluate a number of protocols. “When it works as we hope, it can melt away tumors like ice cream on a hot day,” said Wong.

The Basic Science

Wong’s laboratory has three primary areas of focus; namely, antiangiogenesis (blood vessels), the tumor’s need to invade adjacent tissue in order to proliferate, and tumor’s active barriers to destruction by host immune recognition (the “molecular invisibility cloak”) and agents, such as IL-2, with the potential to break down those barriers through changes in all these factors. “These tumors need to co-opt the body in order to exist and metastasize, so our focus needs to be on the host-tumor interface,” said Wong. “This essentially amounts to a balancing act not unlike a battle, in which the emergence of a victor (host or disease) determines the entire consequence of the ‘war.’ Working alongside the research group, our goal is to develop innovative approaches that can deliver nothing less than cures to patients with melanoma.”