Moffitt Cancer Center: Cutting-Edge, Total Cancer Care

Moffitt Cancer Center

Located in Tampa, Florida, Moffitt Cancer Center enjoys a reputation as one of the world’s most sophisticated cancer centers and, as such, consistently attracts fellowship-trained physicians and medical researchers who are among the best in their fields. Moffitt has 14 partnerships in Florida, Puerto Rico, Georgia, and Pennsylvania, and is listed in US News & World Report as one of “America’s Best Hospitals” for cancer care.

Now in its 26th year of operation, the National Cancer Institute-designated center is using the latest innovations to uphold its commitment to comprehensive care. Indeed, Moffitt’s trademarked Total Cancer Care™ model, introduced in 2003 by Moffitt scientists and employees, is an evolving protocol that combines information technology, cutting-edge basic science, and stateof- the-art clinical care aimed at identifying and meeting all the needs of each patient in the most personalized way possible.

Among the programs that best exemplify this approach are Moffitt’s breast cancer program, which now offers its patients singledose intraoperative radiotherapy and low-dose mammography, and its new Personalized Medicine Institute.

Single-Dose Intraoperative Radiotherapy

for Early Breast Cancer

In November 2010, Moffitt became the first center in the Tampa Bay area to acquire INTRABEAM (Carl Zeiss Meditec), a radiation platform designed to replace as many as 6½ weeks of radiotherapy (typically administered 5 days per week) with a single 30- to 45-minute targeted intraoperative treatment administered while patients are anesthetized for lumpectomies.

INTRABEAM, which is cleared for use in most countries and was FDA-approved in 1999, is considered the least disruptive radiotherapy treatment available to patients with early-stage breast cancer. The system’s miniature x-ray source, highly flexible support stand, and full range of radiation applicator options enable targeted delivery of a precise dose of intraoperative radiation directly to the tumor bed immediately after excision. The intraoperative delivery method minimizes geographical misses and essentially eliminates the adverse effects associated with external-beam radiation therapy (EBRT), which can include skin reactions, irritation of healthy breast tissue, and exposure to the lungs and heart.

Eleanor Harris, MD

The benefits of INTRABEAM extend beyond symptom reduction and the convenience of onetime radiation, which in and of itself is highly significant to patients. Eleanor Harris, MD, clinical director and section chief for the Breast and Gynecological Clinical and Research Divisions within Moffitt’s Radiation Oncology Program, explained that intraoperative, singledose, partial-breast radiation can “eliminate treatment delay for patients who need to undergo chemotherapy. This dramatically reduces treatment time and will improve women’s access to breast conservation therapy.”

Potential Candidates

Moffitt’s decision to acquire the ground-breaking system was based largely on the findings of the landmark TARGeted Intraoperative radioTherapy (TARGIT-A) study, in which investigators showed that, based on local recurrence rates, postlumpectomy single-dose, targeted intraoperative radiotherapy was as effective as EBRT. The international, multicenter clinical trial followed 2232 patients for a median of four years and, to date, remains the largest randomized clinical trial ever conducted in the field of intraoperative radiotherapy for the treatment of early breast cancer.

Currently, patients eligible for treatment with accelerated partial-breast radiotherapy, including INTRABEAM, are postmenopausal women with small (<3.0 cm) tumors, negative excision margins, and negative lymph nodes. Harris explained that the postmenopausal criterion stems from recommendations put forth in radiation oncology guidelines for the use of accelerated partial-breast radiation, and reflects the limited data on such treatment for premenopausal women, who are at higher risk for local recurrence.

Harris went on to explain that because intraoperative assessment of sentinel lymph nodes and excisional margins is preliminary, patients need to be counseled extensively prior to treatment, ensuring that they understand that final processing of pathology samples may indicate the need for conventional whole-breast radiation. “Very occasionally, we’ll find something on final processing that wasn’t seen intraoperatively,” said Harris. “For this reason, we always obtain consent based on the understanding that, while unlikely, final pathology could demonstrate positive nodes or residual disease requiring additional radiotherapy. Even so, most patients opt to go ahead with the INTRABEAM treatment.”

The criteria for such treatment will continue to evolve as additional findings become available, said Harris, explaining that results from a trial of partial-breast radiotherapy that will include those at higher risk for local recurrence (premenopausal women and those with node-positive malignancies) will be forthcoming within the next one to two years. In the meantime, women who don’t meet the criteria for INTRABEAM may still be eligible for INTRABEAM boost treatment, which delivers a single dose of radiation directly to the tumor bed intraoperatively, prior to the start of whole-breast radiation, thereby potentially reducing the duration of the total radiotherapy regimen by five to eight days.

“When I was trained in the 1990s, there was essentially one way to treat breast cancer,” said Harris. “Today, we have 10 or 12 options, thanks, in large part, to our ability to better define risk levels and to customize recommendations and subsequent treatment.” Harris, who is confident that these recommendations and treatments will continue to be refined and improved, is especially excited about the opportunity to work toward personalizing radiation therapy in an era in which such endeavors have been aimed primarily at drug therapy.

Moffitt clinicians treated their first patient with INTRABEAM in January 2011, and 70 to 80 women have been treated subsequently. And because the technology is a “soft” radiation source that requires no significant shielding, Harris also envisions potential indications for other types of cancer. “This is a technology that can, essentially, be taken into any operating room,” she said. “I wouldn’t be surprised to see the development of new applicators for other parts of the body, enabling new and exciting capabilities.”

Kelley Irby, RN

Nursing Perspective

The first decision to be made in the preoperative assessment of a breast cancer patient is whether she might be a candidate for any type of breast conservation treatment, including a treatment such as INTRABEAM. Kelley Irby, RN, primarycare nurse for Harris, stressed the importance of preoperative counseling in this process. “Despite the potential benefits of such treatments—and perhaps because of those benefits&mdash;we run the risk of losing patients to follow-up if they’re not educated sufficiently prior to treatment,” said Irby.

Because, as explained by Harris, intraoperative pathology findings must always be confirmed by definitive results made available some days later, a sense of uncertainty is introduced into treatment, and must be recognized and dealt with effectively by those providing pre-treatment counseling. “Most patients tend to handle this quite well and elect to go ahead with the accelerated treatment,” said Irby. “But a patient’s mindset can change if, indeed, final pathology results indicate that partial-breast radiation was insufficient, making it critical that we ensure that patients really do understand and acknowledge the potential need for follow-up treatment with whole-breast radiation.”

Irby points out that loss to follow-up can also be a “side effect” of the convenience of singledose therapy. “Sometimes, a patient can be so relieved at the prospect of not having to undergo the traditional 6+ weeks of radiotherapy that they have a hard time comprehending that follow-up is still needed,” she said. “We need to explain, in no uncertain terms, that one treatment doesn’t mean ‘no follow-up.’”

“

We need to explain, in no uncertain terms, that one treatment doesn’t mean ‘no follow-up.’ ”

—Kelley Irby, RN

Referring to a very different type of “side effect,” Irby noted that the care of patients who undergo INTRABEAM therapy is made somewhat easier by the absence of the skin reactions typically seen with conventional radiotherapy. “Patients treated with conventional multidose radiotherapy need to be carefully monitored— and, frequently, treated&mdash;for a range of skin effects,” she said. “At this point, we’re seeing virtually no such reactions with INTRABEAM.”

Low-Dose Mammography

Only a year after acquiring INTRABEAM, Moffitt began offering patients the very latest in breast cancer diagnostic technology.

After approximately eight years of its use throughout Europe, Australia, New Zealand, and Japan, the FDA approved in 2011 a mammography technology, (MicroDose Mammography), that produces crystal-clear images with half the radiation dose of conventional mammography. In November 2011, Moffitt became the first academic center in the country and the only site in the Southeast to offer Micro- Dose Mammography.

Chris Flowers, MD

While touted as ideal for younger, highrisk women (eg, those with a family history of breast cancer) and those with dense breasts, Moffitt’s director of Breast Imaging and Research, Chris Flowers, MD, noted that the cancer center is beginning to use the technology for most patients in need of mammography.

“With breast-tissue images delivered at a 50- micron pixel size—resolution that is two times higher than that of some other full-field digital mammography systems&mdash;and at a radiation dose approximately 40% to 60% of that produced by conventional mammography, MicroDose gives us the ability to image breasts with the lowest possible radiation dose without having to sacrifice image quality,” Flowers said. He went on to note that the cost of the MicroDose machine is approximately the same as that of conventional mammography machines.

FDA approval of MicroDose comes at a time when popular media have contributed to a heightened concern about the longterm effects of radiation from all forms of diagnostic imaging. “Women have every right to be concerned about such issues,” said Flowers. “But the undeniable benefits of lowerdose mammography notwithstanding, it’s important that such information be given in a way that doesn’t scare patients, especially since the radiation dose from conventional mammography is already very low.”

In Europe, and especially in Ireland, MicroDose is routinely used for high-volume screening programs. It is hoped that Moffitt’s MicroDose machine, which is housed in the Outpatient Imaging and Oncology Center within the new Moffitt Cancer Center, will ultimately enable same-day screening/diagnostic workups for some 20 patients per day.

Moffitt Cancer Center Timeline

1986

1995

1999

2007

2011

Moffitt opens.

The Moffitt Research

Center opens.

The Moffitt Affiliate Network begins.

Ground is broken for M2Gen™.

Moffitt becomes the nation’s first academic center to offer MicroDose.

1989

1998

1998

2003

2010

2012

Moffitt’s Blood & Marrow Transplant Program is launched.

Moffitt is awarded a National Cancer Institute core grant.

Moffitt’s affiliate network program begins.

Total Cancer Care™ is created.

Moffitt becomes the first center in the Tampa Bay area to acquire INTRABEAM.

Moffitt announces the creation of the Personalized Medicine Institute.

Personalized Medicine Institute

Moffitt was already considered a national leader in personalized medicine when, in February, the center announced the creation of its Personalized Medicine Institute (PMI). The Institute, funded largely through philanthropy and grants, is headed by William S. Dalton, PhD, MD, Moffitt’s long-time president, chief executive officer (CEO), and director, who will now devote his focus to the establishment of the new institute, while also serving as CEO of Moffitt’s biotechnology subsidiary M2Gen™.

William S. Dalton, PhD, MD, CEO, President, and Director, Moffitt Cancer Center

It was during Dalton’s tenure as Moffitt’s CEO that the center’s Total Cancer Care approach to developing evidence-based, personalized cancer treatments and information/decision tools was launched. Far more than a concept, Total Cancer Care is a treatment path initiated by the mapping of genetic information from tumor samples and bodily fluids donated by patients who enroll at participating hospitals and physicians’ offices. The resulting data are stored and made available for analysis by researchers with the aim of creating individualized therapies for medical, nutritional, psychological, social, and physical symptoms. Physicians may use the database to inform patients of new information, including clinical trials, which might be pertinent to their care.

Moffitt leaders are making an effort to export the Total Cancer Care idea to their colleagues at other sites. Meanwhile, in their own center, they’re capitalizing on the approach through the PMI.

“The PMI is nine years in the making and is a natural product of the Moffitt culture,” said Dalton. “It will allow us to organize our Total Cancer Care efforts to create new resources and enhance the capability of existing resources, such as our basic science labs, all with the goal of making the right treatment for the right patient at the right time a reality.” Stated differently, the PMI will enable the generation of data aimed at determining the best therapy for a given patient based on comparisons to that patient’s cohort identity—an endeavor that has involved extensive work in the areas of data aggregation and health information technology (IT), and has even necessitated the creation of a new department of Information Shared Services.

Within the same nine-year period, Dalton also founded M2Gen, the world’s largest cancer-focused biorepository linked to longitudinal clinical data, with more than 86,000 patients enrolled and more than 40,000 tumor specimens collected.

“M2Gen commercializes the PMI’s efforts for industry, partners, and clients to identify unmet needs and develop new drugs, identifying patients doing well on treatment and those not doing well, while determining mechanisms of resistance that will ultimately provide new targets for treatment,” Dalton explained. In a clinical trial-matching process recognized by an issued patent, M2Gen is partnering with Merck and other pharmaceutical and biotechnology companies to launch the first clinical trials that will recruit patients via the world’s largest cancer-focused biorepository. A new IT platform developed in partnership with Oracle will expedite the clinical trial process and provide patients with more timely access to drugs that are a good match for their unique genetic characteristics.

“

The PMI and Total Cancer Care represent a true partnership with our patients. When we wanted to know how to identify our patients’ needs, we went straight to the source, asking them to partner with us throughout their lifetime.”

—William S. Dalton, PhD, MD

Looking ahead, Moffitt Cancer Center will soon collaborate with Sanford-Burnham Medical Research Institute and Florida Hospital on the creation of a Personalized Medicine Partnership of Florida (PMP of Florida). The resulting partnerships among Florida-based centers of excellence in medical research and clinical care will further the development and utilization of new molecular and genomic technologies to discover, translate, and personalize interventions designed to more effectively and efficiently prevent and treat cancer and other debilitating diseases.

In these ventures, Moffitt’s success is dependent upon its commitment to collaboration with patients.

“The PMI and Total Cancer Care represent a true partnership with our patients,” Dalton said. “When we wanted to know how to identify our patients’ needs, we went straight to the source, asking them to partner with us throughout their lifetime. A patient advocacy and ethics council was formed, and through it, patientmembers requested that their own information be made available to them in a format that would be useful in their decision-making. Moffitt responded by creating a patient portal for such access, and the satisfaction scores have been exceedingly high.”

That collaborative structure is expected to help patients long into the future.

“By following hundreds of thousands of patients over time,” Dalton said, “we will ultimately be able to predict future needs in newly diagnosed individuals, and intervene before those needs even manifest.”