Penn State Cancer Institute: Pioneering Research Unites with Advanced Care in Central Pennsylvania

By Thomas Crocker
Friday, November 18, 2016
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ESTABLISHED IN 2000, Penn State Cancer Institute, recognized as an American College of Surgeons Commission on Cancer-accredited facility, has evolved into a premier academic oncology center that encompasses clinical care, research, education and outreach. Since 2009, the 178,000-square-foot facility on the Milton S. Hershey Medical Center campus has served as the hub for nearly 160 clinicians, researchers and faculty members based in Hershey and University Park, State College in Centre County. The Cancer Institute care teams see nearly 2,000 individual cases annually.

Representing nine Penn State colleges and 36 departments, the Cancer Institute clinicians and faculty serve a 27-county catchment area. Partnering closely with referring physicians, specialists provide advanced, collaborative care locally to nearly a third of Pennsylvania’s population, comprising a diverse demographic mix.

“Eighteen of the counties we serve are designated as parts of Appalachia by the federal government,” says Ray Hohl, MD, PhD, director, Penn State Cancer Institute. “Individuals in all of the counties we serve have unique health considerations. For example, patients who develop lung cancer in our catchment area have a different panel of mutations than patients in other parts of the country.”

Many counties in the Penn State Cancer Institute catchment area are quite rural and medically underserved. “Sullivan County, for example, has had no primary care physicians. On the other hand, our service area also includes Harrisburg, Lancaster, Reading and York — urban areas with a much higher minority population,” Dr. Hohl continues. “Our partners at Penn State Health St. Joseph in Reading care for the fastest-growing Hispanic population of any urban center in the commonwealth.”

Multidisciplinary, Multimodal Care

The Cancer Institute’s 10 multidisciplinary disease teams include surgeons, medical oncologists, radiation oncologists, pathologists, other medical specialists and basic scientists.

“While the clinicians handle direct patient care, the scientists unravel the cancer. There is a robust interplay between the two groups; the partnership of these teams and their work is vital for our patients.” Dr. Hohl says.

The coordination among Cancer Institute disease teams allows the scientists access to cancer tumor tissue samples. As a result, scientists can test hypotheses about how certain cancers develop and how laboratory research applies to people.

“By having direct access to information from individuals with cancer, our scientists can form the proof-of-concept needed to develop clinical trials which in turn help to advance the treatment of cancer. We are fortunate to have a growing group of Cancer Institute members who wear both hats as clinician-scientists,” Dr. Hohl says.

Complementing this team approach to patient care is an array of leading-edge therapeutic modalities, especially radiosurgery and radiotherapy. Accredited by the American College of Radiology for Radiation Oncology Practice, Penn State Cancer Institute features Leksell Gamma Knife® IconTM, TrueBeam and RapidArc technologies.

Dr. Hohl shares that the team is at work on the development of a stereotactic radiosurgery program on the Milton S. Hershey Medical Center campus that utilizes the latest instruments and techniques: “At Penn State Health St. Joseph, we place a strong emphasis on liver-directed therapies, in which yttrium-90-linked microspheres are injected into the blood vessels that feed liver tumors. These microspheres have the ability to reduce malignancies by precisely delivering radiation to certain areas of the tumors. Navesh Sharma, DO, PhD, Penn State Cancer Institute radiation oncologist, authored the initial study that secured approval for this technology in the United States. This is something in which we possess clear expertise.”

In Focus: Thoracic Oncology

The Cancer Institute’s thoracic oncology team exemplifies the multidisciplinary model of care: a dozen clinicians representing medical oncology, radiation oncology, surgery, pulmonology, radiology and pathology, as well as midlevel practitioners and five basic science and translational researchers. In addition to the value of a multidisciplinary team, referred patients are a priority. If a patient is referred to any member of the team, such as a pulmonologist, the clinician sees that patient the same day. Finally, the Cancer Institute survivorship clinic provides more support as these patients move on in their lives beyond diagnosis and treatment.

“To understand the intricacies of cancer development, prevention, management and treatment, our team’s work extends from the clinic to the lab, and vice versa,” says Chandra Belani, MD, director, thoracic oncology program, Penn State Cancer Institute. “We care for nearly 600 new patients every year, primarily for lung cancer, but also treat individuals with mesothelioma, carcinoid tumors, new endocrine tumors and rare malignancies of the chest.” Various diagnostic procedures are offered, including navigational bronchoscopy, percutaneous needle biopsy and endobronchial ultrasound. CT screening is also available for individuals at risk for lung cancer.

“In addition, because of the prevalence of patients in our region presenting with various types of lung nodules, we also offer a nodule clinic,” Dr. Belani says. “Not all nodules are malignant. However, when they do transform from benign to malignant, our expert specialists use algorithmic characterizations to best determine next steps for treatment. Our thoroughly comprehensive and multidisciplinary approach enables us to diagnose and treat all stages of lung cancer: early-stage malignancies typically receive surgical intervention; locally advanced cancer may result in surgery and radiation; advanced disease typically warrants chemotherapy, immunotherapy and targeted therapy.”

Like many of their colleagues within the Cancer Institute, the thoracic oncology team meets twice weekly in a multidisciplinary clinic meeting and a tumor board meeting to discuss the cases of each patient seen in clinic with the entire team.

Thoracic oncology research is intimately connected to the team’s clinical work. For three decades, Dr. Belani has worked tirelessly with his peers to develop most of the treatments for lung cancer that are now widely used worldwide, including targeted therapies that focus on a triad of mutations associated with lung cancer.

“Translational researchers characterize the tissue samples we collect from patients and look for biomarkers, driver mutations and abnormalities that can be targeted,” Dr. Belani says. “Unfortunately, we have found that lung cancer tumors have developed a resistance, and therefore, we cannot cure this disease, as is. To accomplish such a feat, we must go further and do more. From patients’ tumors, we are able to pull what causes the resistance, and from there, develop second- and third-generation drugs to target those mutations.”

Basic biologists are researching the biology of tumors. The Cancer Institute boasts bioinformatics and basic scientists who develop animal models of tumors to study them further and determine if treatments can be improved.

Seeking Better Understanding of Gynecologic Cancers

The Penn State Cancer Institute’s gynecologic malignancies group addresses both common and rare female reproductive cancers at the intersection of bench and bedside, with benefits that reverberate across a broad range of cancer care.

“Focusing on gynecologic malignancies not only helps the women they affect, it can also give hope to individuals with other cancers, such as pancreatic cancer,” says Rébécca Phaëton, MD, gynecologic oncologist, Penn State Cancer Institute, assistant director for residency research in the department of obstetrics and gynecology, Penn State Health Milton S. Hershey Medical Center, and the Department of Microbiology and Immunology, Penn State College of Medicine.

Dr. Phaëton and her colleagues focus their therapeutic and investigative efforts on ovarian, cervical and endometrial cancers, as well as less common malignancies, such as vulvar, vaginal and fallopian tube cancers. Each patient population has different areas of priority for researchers and clinicians, according to Dr. Phaëton.

“Ovarian cancer has been widely studied, but little has been done to impact overall survival,” she says. “Although we have new drugs and are learning more about genetic predispositions, we need to do more to impact the early detection and survivability of this disease. Most ovarian cancers are found in Stage III.”

“Treating endometrial cancer more effectively,” Dr. Phaëton advises, “requires partnering with nutritionists and gynecologists to address one of its most serious risk factors: obesity.”

In contrast, the United States’ low rates of cervical cancer represent a (not yet complete) victory for researchers and clinicians. “I think gynecologic oncology has the widest range of treatment impacts when diseases are studied,” Dr. Phaëton says. “We have done so much related to screening and early detection of cervical cancer that women are rarely diagnosed with this disease in the U.S. anymore. At the other end of the spectrum, however, is ovarian cancer, for which we still have a lot to do.”

Taking Discovery to the Bank

The gynecologic malignancies group consists of surgeons, anatomic pathologists, basic scientists, geneticists, social workers and nurse practitioners. Prior to surgery, the team seeks patient consent to bank an excess portion of tumor that is not necessary for diagnosis; investigators then study this tissue in the lab.

“Our goal is to translate lab findings to develop more specific clinical trials,” Dr. Phaëton says. “We study if immunotherapy being developed in our lab with monoclonal antibodies is effective against actual patient samples. Classically, we purchased cell lines that had been stored in tissue banks for research purposes. To be able to study actual tissue from the patient in a dynamic setting allows us access beyond just the cancer cells. It includes other immune cells and tissue, to really understand the impact of treatment and to establish a stronger case for translation to a Phase I trial.”

She adds, “The anatomic pathologists also work with banked specimens where tumor tissue is embedded in paraffin blocks to look at genomic expression. Genetic precursors can tell us if a lesion actually harbors a chromosome or DNA derangement to indicate cancer on a final surgery or diagnosis, even when not initially identified as cancer by a pathologist. For endometrial cancer, this allows for greater diagnostic perspective by looking at genomic changes in the tissues; we can then identify individuals who require surgical intervention versus observation.”

The work of Dr. Phaëton and her colleagues illustrates the recent expansion of goals within the cancer treatment and research communities.

“In the past, cancer treatment focused primarily on survival,” Dr. Phaëton says. “The goal was to give individuals some disease-free intervals when they were not fighting cancer or undergoing chemotherapy. Now, the bar is so much higher, beyond just survival. We want quality-of-life, recurrence-free intervals, and then — prevention. We need to do more, so we have to investigate more. We cannot investigate cancer from just one perspective.”

Robust Research

Research at the Cancer Institute is divided into three umbrella programs — mechanisms of carcinogenesis, experimental therapeutics, and population health and cancer control. The first research program, mechanisms of carcinogenesis, focuses on the underpinnings of cancer development.

Many of the clinical trials and novel approaches to cancer management are developed under the second research program, experimental therapeutics. From this program, many scientists have seen their research on brain tumors, melanoma and lymphoma advance into active clinical trials.

The final umbrella research program, population health, focuses on epidemiologic issues, such as colorectal cancer screening and detection, and smoking-related cell mutations.

Throughout all of these research programs, the investigators and clinicians at the Cancer Institute are working to better understand the development of cancer, the treatment of cancer and the impact of cancer on local communities.

The Penn State Cancer Institute lung cancer investigations mentioned here are only a few of the nearly 100 active treatment clinical trials that are open to patients at any given time. In addition, the Cancer Institute has screening- and diagnosis-geared studies, as well as research that tackles supportive care for patients.

“We take pride in opening various types of clinical trials, whether they are pharmaceutical industry-sponsored or investigator-initiated. They help us to investigate new treatments, novel approaches to cancer management, and many other avenues that could ultimately bring us closer to our goal: a cure,” says Monika Joshi, MD, MRCP, hematologist and oncologist, Penn State Cancer Institute, assistant professor of medicine, Penn State Health Milton S. Hershey Medical Center.

“Many agents work well in pre-clinical settings, but applying them to humans is a different endeavor. We partner with pre-clinical researchers who are adept at working with mice or cell cultures. They develop and establish mechanisms to support our efforts, and then they are on to Phase I and Phase II clinical trials to test specific drugs in patients. These are the earliest human studies that are done to develop new therapies.”

“Cancer cells are probably 100 times smarter than humans,” Dr. Joshi says. “As we work to identify new targets and develop agents against them, the cancer cells escape them. We are working to find new pathways of identifying cancer cells’ mechanisms of resistance; determining how they evade our treatments.”

A critical ally and resource in the Cancer Institute’s investigations is the Big Ten Cancer Research Consortium (BTCRC), which includes 12 of the cancer centers of the Big Ten Conference’s 14 full member institutions. In addition to access to a much larger patient population, the BTCRC allows researchers to collect invaluable insight about the structure of prospective clinical trials from a cadre of experts.

“Completing a trial at a single center could take ages if the patient population is not big enough,” Dr. Joshi says. “With the BTCRC, a researcher can present his or her trial idea on one of the organization’s regular conference calls and open it at 10 centers. That provides an added bonus of speed-to-market given the breadth and depth of these studies, once they are expanded to other institutions. A study that could take four or five years to complete at one institution might finish in a year if it’s conducted through the BTCRC.”

For example, Dr. Joshi is involved in a BTCRC study that investigated the use of an anti-PD-1 antibody in combination with another agent for the treatment of metastatic renal cancer. She and the Cancer Institute were involved in designing and conducting the 60-plus patient study, Phase II of which closed in May. “We only had six patients enrolled in the study at our institute,” Dr. Joshi says. “But, with the help of multiple sites, it accrued very fast.” Results are pending.

Dr. Joshi adds, “A trial I initiated investigating a combination of radiation therapy and immunotherapy for locally advanced bladder cancer is getting ready to open at six BTCRC centers. The BTCRC is an important platform for clinicians like me who have ideas they want to take further.”

Membership in the BTCRC not only helps to advance the important cancer research happening at Penn State Cancer Institute, but the partnership with other academic medical centers helps to advance another key area of focus: education.

“We are focused on grooming young, outstanding scientists,” Dr. Hohl says. “Doing trials at the national level requires a lot of expertise and time in the system. Membership in the BTCRC affords us opportunities to develop junior scientists because the experience of conducting trials within the framework of the organization is more user-friendly.”

Looking Ahead

If one thing about the future of cancer care is certain, it is that it will be characterized by discovery and disruption. The Cancer Institute is fueling both. During the next decade, Dr. Hohl envisions more unified research efforts across the Penn State campuses.

“We have been focusing on Hershey and University Park, but we also have research going on at Penn State’s campus in Harrisburg,” he says. “Penn State Dickinson Law in Carlisle is interested in exploring how certain policy issues might relate to changes in cancer therapy. As membership in the Cancer Institute grows, it will be more balanced throughout Penn State’s many sites.”

As the Cancer Institute progresses forward and members continue to focus on the key research programs and the multidisciplinary science and practice of patient care. Dr. Hohl also expects to shape the future with a number of specific initiatives:

  • Additional alignment with community hospitals and health systems, similar to the Cancer Institute’s relationships with Penn State Health St. Joseph and Mount Nittany Medical Center
  • Deeper collaboration with the Pennsylvania Department of Health and the Cancer Institute’s fellow commonwealth-supported cancer centers: University of Pittsburgh Cancer Institute, Northeast Regional Cancer Institute and Penn Medicine’s Abramson Cancer Center
  • Increased emphasis on survivorship
  • Returning patients to their primary care providers following successful cancer treatment
  • Collaboration with primary care physicians and community oncologists throughout Pennsylvania, an indispensable part of the Cancer Institute’s work

“Oncology services have become incredibly sophisticated,” Dr. Hohl says. “Individuals with cancer are treated in both academic and community health care settings. Community clinicians and the Cancer Institute experts have unique, respective strengths that should be recognized and partnered with each other. Our academic clinicians want to get to know patients early in their disease courses so they can be better resources to their community colleagues (and those patients) if challenges arise throughout the course of each patient’s journey.”

The Penn State Cancer Institute physicians, surgeons, scientists and staff are fighting cancer on every front. With the seamless integration of clinical care and research, the expansive team is focused on decreasing the impact of cancer in Pennsylvania. They are doing more each and every day with their increasing resources both within their walls and beyond to ensure that patients receive the right diagnosis and the right therapy at the right time.

A Pivotal Moment

Where does the battle against cancer stand? Four Penn State Cancer Institute clinicians weigh in.


Ray Hohl, MD, PhD, director, Penn State Cancer Institute:


Ray Hohl, MD, PhD

“I believe we have reached a turning point. We’ve gone from personalized medicine to precision medicine, which has caught the attention of politicians. President Obama, for example, announced the launch of the Precision Medicine Initiative in his 2015 State of the Union address. We have made enormous strides in the basic science world in understanding the genetic abnormalities and unique mutations of cancer. We talk about lung, colon and pancreatic cancers as individual malignancies, for example, but more often, we refer to them as p53-related cancers that can cross organ system boundaries.

“We have a lot of new drugs out there that are very effective at targeting certain molecular abnormalities in certain cancers. Now, we have to get those drugs and treatments to patients. Treating individuals with cancer has become much more complicated. It is not just about what the cancer looks like under the microscope, but also about what it looks like once its genome has been sequenced. This tells us a lot about whether it will respond to therapy. Thankfully, in recent years, the FDA has greatly accelerated its approval of oncology drugs. We have had periods where one or more new agents a week are being approved, or an old agent is being approved for a new cancer indication. The field is changing so quickly that it challenges how we apply these changes to patient care.”


Monika Joshi, MD, MRCP, hematologist-oncologist, Penn State Cancer Institute, assistant professor of medicine, Division of Hematology and Oncology, Penn State Health Milton S. Hershey Medical Center:


Monika Joshi, MD, MRCP

“This is an exciting era for cancer treatment, overall. Two treatment categories, specifically, have exploded in recent years: precision medicine with targeted therapies and immunotherapy.

“Regardless of histology, if there is a target, these targeted therapies work for certain cancers, specifically in the case of lung cancer. Targeted therapies have really evolved beautifully in lung cancer, and we are seeing some of them beginning to impact other cancer types, as well. For example, we have an open study here at Penn State Cancer Institute focused on fibroblast growth factor receptors (FGFR) and bladder cancer. Preliminary results suggest FGFRs may be a very real target for treating bladder cancer.

“The other important category is immunotherapy. Lung, bladder, renal, and head and neck cancers have all seen the rise of immunotherapies. In my focus area, I primarily treat genitourinary cancer — a form of renal cancer — and we’ve used immunotherapy for a long time. However, we need to do a lot more for patients who don’t respond to these therapies. We have definitely reached a turning point where we’re combining agents to enhance immunotherapies and turning away from chemotherapy a bit.”


Chandra Belani, MD, director, thoracic oncology program, Penn State Cancer Institute:


Chandra Belani, MD

I think we are approaching an inflection point. The emphasis, the ultimate goal, is to develop personalized and precise therapies with better understanding of the biology of cancer. If we are going to develop these therapies that are individualized to patients and their tumors, we need to understand patients’ characteristics and tumors’ biology. We have made strides, and overall outcomes are getting better. But, we still have a lot of questions to answer and much more ground to cover to get to where we want to be in this battle.”


Rébécca Phaëton, MD, gynecologic oncologist, Penn State Cancer Institute, assistant director for residency research, department of obstetrics and gynecology, Penn State Health Milton S. Hershey Medical Center, and Department of Microbiology and Immunology, Penn State College of Medicine:


Rébécca Phaëton, MD

“Cancer researchers, whether they are basic, clinical or translational scientists, have adjusted their focus to be much more patient-centric than years ago. Basic scientists, for example, who had been focused on specific proteins or modulators, cannot successfully advance their science without a patient care translation. Researchers must ensure a relevant patient-related application; they cannot undertake medicine or science for its own sake. Focusing on themes to inform patient care, such as understanding mechanisms or improving outcomes, is critical, whether it is in drug discovery, novel chemotherapy or preventive strategies.”

Visit PennStateHershey.org/Cancer for further information regarding the Cancer Institute. To refer a patient, call 717-531-6585 and select option 1.

For more information about clinical trials at Penn State Cancer Institute, Penn State Health Milton S. Hershey Medical Center and Penn State College of Medicine, visit studyfinder.psu.edu or call the clinical trials office at 866-905-1872.