Alvarez Plays Leadership Role in Gynecologic Cancer Field

Ronald D. Alvarez, MD

Whether it involves the minutiae of preclinical studies or the broad perspective of group leadership, if the work concerns gynecologic oncology, Ronald D. Alvarez, MD, has likely tried it.

As a translational researcher and senior scientist at the University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, Alvarez spends half of each week treating patients with gynecologic cancers in the clinic and operating room, and much of the rest of his time conducting preclinical and clinical research aimed at developing gene therapies and vaccines for diseases, including ovarian and cervical cancers.

As a professor at UAB, the Ellen Gregg Shook Culverhouse Chair of Gynecologic Oncology, and director of the Division of Gynecologic Oncology, Alvarez also juggles administrative duties with the time he spends teaching residents and fellows.

Outside the school, he’s helped shepherd his field through changes in the healthcare and cooperativegroup systems by holding high-profile leadership posts, including last year’s stint as president of the Society of Gynecologic Oncology (SGO).

His latest achievement is earning a master’s degree in business administration from Auburn University, with the idea that he might eventually turn even more toward the administrative side of medicine.

The variety isn’t something Alvarez planned, but it has defined the 56-year-old’s journey thus far.

“When I started my residency, I really intended to be delivering babies, but then I was exposed to the specialty of gynecologic oncology and was immediately enamored by it,” Alvarez recalled. “I consider myself sort of an accidental academician, because I really thought I’d go into private practice. That ended up not being the chosen path for me and, as a result, I have ended up doing a lot of different things. I still consider myself a grand experiment, a work in progress.”

Developing New Treatments

To conduct his research, Alvarez collaborates with basic bench scientists, seeking to move the gene therapies they create for the treatment of gynecologic cancers out of the laboratory and into the clinic.

Such therapies, Alvarez said, are designed to provide a number of different ways by which cell death can be caused selectively in tumor cells. A subject of oncologic research mainly since the 1990s, gene therapy has been tested only on a small scale, so far, in humans. While his collaborators have continued to work at the bench to tweak viral-based gene therapies so they are better able to target and kill gynecologic cancers, Alvarez has been at the forefront of conducting clinical trials of such treatments in patients.

In 2010, he conducted the first study ever to evaluate an infectivityenhanced conditionally replicative adenovirus (CRAd) in patients with malignant gynecologic diseases.¹ The phase I study of the tropismmodified CRAd known as Ad5-Δ24- RGD showed “the feasibility, safety, potential antitumor response, and biological activity of this approach in ovarian cancer,” Alvarez and coauthors wrote. “Further evaluation of infectivity enhanced virotherapy approaches for malignant gynecologic diseases is warranted.” Since then, Alvarez has completed two phase I trials of other adenoviruses in this population with promispromising results, one of them this year.²

Another area of keen interest for Alvarez has been the development of vaccines against the human papillomavirus (HPV), a condition the doctor said is a prerequisite to the development of cervical cancer, and is implicated in most cases of other genital-tract malignancies including vulvar and vaginal cancers.

Although preventive HPV vaccines Gardasil and Cervarix are already on the market, Alvarez hopes to address gaps in what those vaccines can accomplish. He’s working toward that goal as co-principal investigator of a $2.6 million cervical neoplasm vaccine project that is part of a Cervical Specialized Program of Research Excellence (SPORE). SPORE is funded by the National Cancer Institute and includes collaborators at UAB, Johns Hopkins University, and the University of Colorado at Boulder.

“We’re looking at lower-cost vaccines that don’t need to be refrigerated, that cover a number of different HPV types, not just 16 and 18, and, instead of being strictly preventive, will be more therapeutic for patients who have cervical dysplasia and cancer,” he said.

Alvarez, who has also written a number of papers that shed light on how best to apply and combine current treatment strategies for gynecological cancers, has participated in trials looking at new applications for medications approved in other tumor types—including imatinib, cetuximab, lapatinib, and ixabepilone—in the treatment of gynecologic cancers.

In a look at herbal treatments for such diseases, Alvarez and colleagues showed this year in an in vitro study that components of green tea and cruciferous vegetables, epigallocatechin gallate and sulforaphane, induce apoptosis in paclitaxel-resistant ovarian cancer cells.³

Over the years, he has also collaborated on a number of studies of patients with AIDS, drawn in by the fact that some of them develop cervical dysplasia, one of his long-time research interests. As a result, Alvarez is a senior scientist in the Center for AIDS Research at UAB, and has been involved in several clinical trials of agents designed to protect against the transmission of AIDS.

Overall, Alvarez sees his body of work as a foundation for other scientists.

“My research focuses on developing new ways to prevent and treat really significant gynecological cancers,” he said. “Hopefully, somebody will be able to build on that and achieve greater success.”

Shaping His Field

Alvarez has offered broader insights into his field through a variety of leadership roles.

He is immediate past president of the SOG, and in that position oversaw the drafting of a white paper asserting that women with gynecologic cancers often receive uncoordinated, fragmented care and treatment, leading to deviation from guidelines and, ultimately, added cost.⁴ The paper calls for changes in the medical management of women with gynecologic cancers—beginning with their referral to doctors who specialize in treating those diseases.

“When care is provided by people who are knowledgeable and have training in this area, and who treat a large volume of patients with these diseases, outcomes are better,” Alvarez said. “We’re trying to ensure that the medical system at least meets the minimum standards for how patients with gynecologic cancers should be managed.”

Alvarez is also on the committee that writes guidelines for practice in ovarian cancer on behalf of the National Comprehensive Cancer Network, something he’s done for years.

While he believes the guidelines are useful and reliable, he cautioned that practitioners should not take them as gospel.

“Sometimes the guidelines are too loose, and sometimes they’re too restrictive,” he said. “They were just meant to be guidelines, but what they’ve turned into is something that is linked to what Centers for Medicare & Medicaid Services will approve in terms of what’s covered. It’s still a process that needs to continue to evolve with time as we move forward in the very complex healthcare reform environment in which we’ll be living.”

In addition to those posts, Alvarez is a past board member of the Gynecologic Oncology Group and co-chair of its Protocol Development Committee, his name appearing on a number of reports and studies published by the nonprofit research organization.

Among several additional posts are his current service in the Gynecologic Oncology Division of the American Board of Obstetrics and Gynecology and his past membership on an Ovarian Cancer Research Program panel for the US Department of Defense.

“Rarely do I say ‘no’ to any opportunity,” Alvarez said. “It’s been amazing to have this broad experience along a number of different aspects of the whole healthcare continuum, from the clinical side to education to research to administrative, at the national and local levels. I’ve been blessed with a lot of opportunities. I haven’t taken any of these opportunities for granted and have done my best to excel at all of them. It’s been kind of a fun ride.”

Ronald D. Alvarez, MD. . . Briefly Speaking

• Is married and has three children—a daughter who is married with a child, a son who just finished medical school, and another daughter who is nearly finished college.
• Enjoyed the book The Presidents Club: Inside the World’s Most Exclusive Fraternity, by Nancy Gibbs and Michael Duffy, which details how former US presidents interacted with sitting presidents during the 1900s. “It was useful for me, as president of the Society of Gynecologic Oncology, to put into perspective my relationship with former presidents,” he said, “and now to see how I can help, rather than be a hindrance, to the current president.”
• Appreciates the expression “short-term losses for long-term gains.” “I see the value of perseverance, whether in raising kids, doing research, or hanging in there with a sick patient,” he said.
• When he’s not working, likes to spend time with his family, play golf, travel, read, and work out.
• Recalls a summer working in the oil fields of Louisiana as his worst job ever. “It was hot and stinky work, hard labor,” he said. “It was a job that inspired me to keep going to school and doing my best.”
• Has published more than 250 papers in his field.
• Was honored by the Gynecologic Cancer Foundation with the Margaret Greenfield/Carmel Cohen, MD, Excellence in Ovarian Cancer Research Prize in 2009; was inducted into Louisiana State University’s Basic Sciences Hall of Distinction in 2011; and won the Ovarian Cancer National Alliance’s Rosalind Franklin Excellence in Ovarian Cancer Research Award in 2012.
• Believes that antiangiogenic agents and PARP inhibitors are some of the more exciting treatments being developed to treat ovarian cancer.
• Has “grave concern” that federal funding restraints will slow the progress of oncologic research. “We have all these wonderful capabilities to do incredible research, yet our resources are limited,” he said. “We have to make sure we use the resources we have wisely, pursuing only those treatments that can be developed in a cost-effective manner and that seem likely to garner substantial gains for patients.”

Putting Down Roots

While Alvarez’s career has been eclectic, one thing has remained constant: his home base.

After earning his BS in Zoology from Louisiana State University in Baton Rouge in 1979 and his MD from Louisiana State University School of Medicine in New Orleans in 1983, Alvarez completed a residency in Obstetrics and Gynecology and a fellowship in Gynecologic Oncology at UAB. Today, he’s finishing his 30th year at the institution.

“The first seven years were trainingrelated, and then, over the past 20-plus years as a faculty member, I was able to get exposure to different things that allowed me to transition in my career and take on different degrees of responsibility,” he said. “I’ve been able to grow in one place, which is kind of rare.”

Alvarez has had a number of mentors who helped him grow professionally. When he first arrived at UAB, Hugh M. Shingleton, MD, was directing the Division of Gynecologic Oncology, the position Alvarez holds now. Other mentors at UAB included Kenneth D. Hatch, MD; J. Maxwell Austin Jr, MD; and Edward E. Partridge, MD, director of the institution’s Comprehensive Cancer Center.

Drawing on His Faith

“They all had unique attributes,” said Alvarez, adding that there were too many mentors to mention in one sentence. “Either they were great clinicians, great academicians, great writers, or great surgeons. They were all very supportive of me and my development, and I try to pay it forward by being that kind of person to my junior faculty and trainees. I tell them to respect that others may have a different opinion than they do, and to realize the value of a team.”Alvarez was raised in New Orleans by his insurance salesman father and his mother, a homemaker. There were no doctors in his family.

Still, he was very interested in medicine, and followed news about emerging techniques in cardiovascular surgery while he was a student at an all-boys’ Catholic high school.

“From an early age,” he said, “I knew I was destined to be a physician.”

Alvarez was already on that path when he lost his college roommate, and then his father and father-in-law, to cancer, terrible experiences that, nevertheless, contributed to his ability to be a successful oncologist.

“It’s a matter of understanding your own mortality,” he said. “I come from a faith-based approach to managing patients with terminal illnesses, so I can help walk that path with them that eventually we all will walk. Because I’ve had some personal experiences with this, I can at least commiserate with family members who have deathly ill people in their families.”

Alvarez added a master’s degree in business administration to his educational credentials in June after being inspired by a discussion at a men’s church group.

“We were asked to look introspectively at our personalities and consider what we would want to do in the latter chapters of our lives,” Alvarez said. “I came up with getting another degree because I’ve always been interested in business and am running my division. As I get to be older, I could see moving out of a clinical role and more into an administrative role. One of my long-term goals is to see how I can be more involved in making adjustments to what is going on at the national level in terms of healthcare reform and changes in the way research is done.”

As he looks ahead to broader responsibilities, though, Alvarez, in typical fashion, refuses to let go of the more minute details of his work—especially when it comes to his patients.

“I keep a list of all the patients I took care of who passed away, and I usually submit it at church on All Souls’ Day together with a monetary contribution,” he said. “My last list goes back to 2002. I look at it a lot, and for almost all the patients on that list, I can think about something special they have said or done that helps me remember some unique aspect about them.

“We don’t take care of cancer, we take care of people with cancer—real people with real lives and real family members,” he noted. “That’s always an important thing to remember.”

References

1. Kimball KJ, Preuss MA, Barnes MN, et al. A phase I study of a tropism-modified conditionally replicative adenovirus for recurrent malignant gynecologic diseases [published online ahead of print October 26, 2010]. Clin Cancer Res. 2010;16(21):5277-5287.
2. Kim KH, Dmitriev IP, Saddekni S, et al. A phase I clinical trial of Ad5/3-Δ24, a novel serotype-chimeric, infectivity-enhanced, conditionally-replicative adenovirus (CRAd), in patients with recurrent ovarian cancer [published online ahead of print June 10, 2013]. Gynecol Oncol. 2013;130(3):518-524.
3. Chen H, Landen CN, Li Y,et al. Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and Bcl-2 down-regulation [published online ahead of print January 16, 2013]. Exp Cell Res. 2013;319(5):697-706.
4. Creating a new paradigm in gynecologic cancer care: policy proposals for delivery, quality and reimbursement. Society of Gynecologic Oncology website. http://www.sgo. org/wp-content/uploads/2012/09/Practice_ Summit_Report_FINAL.pdf. Published February 2013. Accessed July 24, 2013.