Lois B. Travis, MD, ScD, an internationally recognized expert on cancer survivorship, leads the cancer survivorship research program at the IU Simon Cancer Center. In the program, researchers look at ways to predict who is susceptible to toxicities in cancer treatment and then alter treatment or develop preventive measures to protect the patient from long-term adverse side effects. This ground-breaking program has the potential to impact the nearly six million people worldwide who are eligible for treatment with a platinum-based agent.
Dr. Travis, the Lawrence H. Einhorn Professor of Cancer Research at IU School of Medicine and a researcher at the IU Simon Cancer Center, talked about cancer survivorship and the program in this Q&A.
Q: More than 15 million Americans are currently cancer survivors. What can be attributed to people surviving their cancer diagnosis?
Dr. Travis: These improvements in survival reflect earlier diagnosis (as the result of cancer screening), more effective treatment and better supportive care.
Q: What are some of the challenges that survivors face?
Dr. Travis: Cancer survivors face challenges in many areas. These include physical and psychosocial. The particular set of physical challenges will depend on the type of treatment that they received. For example, the late effects of cancer treatment can include life-threatening complications, such as second malignant neoplasms (cancerous tumors) and cardiovascular disease. Especially high risks for these complications have been reported following the extensive radiotherapy regimens that were used in the past to treat Hodgkin lymphoma. In addition, survivors can also face non-life threatening complications such as pulmonary toxicity, kidney problems, and neurologic issues. Psychosocial issues can include anxiety and depression. In addition, an increasing area of concern in the survivorship community is that of possible financial hardship experienced by some survivors.
Q: You often talk about the “cost of the cure.” What do you mean by that?
Dr. Travis: Curing cancer frequently comes at a cost. Regrettably, many of the applied cytotoxic treatments such as radiotherapy and chemotherapy also result in normal tissue damage, which can result in physical complications, including those that are noted above.
Q: What has the research team been able to learn thus far about lessening the cost of the cure?
Dr. Travis: For almost 20 years, my team and I conducted research at the National Cancer Institute that examined the late effects of cancer treatment. Based on this body of research and those by other research teams, we know that it is important to use the lowest doses and smallest fields of radiotherapy needed to cure the cancer. A goal here is to avoid unnecessary radiation exposure to normal tissue. Similarly, the long-term maintenance chemotherapy that was used in the past has been largely shown to be unnecessary, and it only exposed patients to more potential toxicity.
Q: You and the team are first focusing on testicular cancer survivors since IU is home to the largest database of information on that population, providing you and your colleagues the opportunity to track their quality of life. What have you and your colleagues learned so far about the cost of the cure for those survivors?
Dr. Travis: This research program, which is international in scope, is funded by a large grant from the National Cancer Institute. It includes testicular cancer survivors not only at IU, but also Memorial Sloan‐Kettering Cancer Center, Dana-Farber Cancer Institute, Princess Margaret Hospital (Canada), University of Pennsylvania, British Columbia Cancer Agency (Canada), the University of Rochester, and the Royal Marsden Hospital (Great Britain). To date, we have enrolled more than 1,800 testicular cancer survivors and published three papers in the high-impact journal, the Journal of Clinical Oncology (JCO), as well as publishing many other papers. Our first paper in JCO received an incisive editorial, “The Sound of Silence: A Proxy for Platinum Toxicity.” Our baseline results showed surprisingly that 80 percent of testicular cancer survivors had hearing loss on audiometric testing, with 1 in 5 classified as severe-to-profound. That’s a level at which hearing aids are recommended. Fifty-six percent had neuropathy, which is a nerve problem that causes pain, numbness, and tingling in the hands and feet; and 40 percent had tinnitus, which is ringing in the ears.
We found that a mutation in a specific gene was related to hearing loss and this showed a significant interaction with cisplatin dose, thus having potential clinical impact to predict susceptibility. In addition, we found that 38 percent of the survivors at a young median age of 37 years already had more than three adverse health outcomes. These included everything from hypertension to diabetes to cardiovascular disease and more. This is concerning since these men are young at diagnosis, have an overall 97 percent five-year survival rate, and could live upwards of 50 years or more.
Q: What can be done – or what is being done – to lessen the toxic effects for those men?
Dr. Travis: For patients with metastatic testicular cancer, in order to be cured, they must receive cisplatin-based chemotherapy. Our overarching goal is to set the foundation, through our genetic studies, to eventually develop otoprotectants — to prevent hearing loss and tinnitus — and other preventive agents to lessen the effects of neuropathy.
Q: IU’s Dr. Einhorn developed the cure for testicular cancer by combining the platinum-based chemotherapy drug cisplatin with two other drugs. Platinum-based drugs are used for more than a dozen other cancers, so what do you hope can be learned from testicular cancer survivors and applied to survivors of other cancers?
Dr. Travis: Testicular cancer survivors were chosen to study cisplatin-related toxicities because of their young age at diagnosis, homogeneity of cisplatin-based therapy (usually either cisplatin, etoposide and bleomycin), high cure rate (overall 97 percent five-year survival) followed by upwards of 50 years of survival, and eventual opportunities for intervention. Moreover, no other cytotoxic drugs that cause ototoxicity or neuropathy are given to testicular cancer survivors. Testicular cancer survivors are instrumental to learning about the long-term trajectory of cisplatin-related toxicities, and well as the underlying genetic underpinnings. Both of these facets of our research will be applied to the many other patients worldwide who receive cisplatin-based chemotherapy.
Q: Do you see a time on the horizon when your research will go beyond testicular cancer survivors?
Dr. Travis: My teams and I have conducted research in many other areas over the course of almost 30 years. For 20 years, our focus was on second malignant neoplasms among different groups of cancer survivors, including Hodgkin lymphoma, non-Hodgkin lymphoma, breast cancer, and cervical cancer. It is only in recent years that we turned our attention to testicular cancer survivors, since testicular cancer is the most common cancer in young men and is understudied. Given the success of Dr. Einhorn’s cisplatin-based chemotherapy regimen for testicular cancer, one in 600 men in the United States is now a survivor. Right now, our team’s focus is on continuing to follow our large international cohort now that it is established. However, we are also keenly interested in other areas, especially adolescent and young adult cancer survivors, since they are also understudied.
Q: Any last thoughts for cancer survivors and the people who love them?
Dr. Travis: We care about you. Please be pro-active and take responsibility for your health. When you finish your cancer therapy, ask your provider for a summary of your treatment and a survivorship care plan. Engage in a regular exercise program, eat a healthy diet, and maintain an ideal body weight. Avoid tobacco use and excess alcohol intake. Also, please ensure that you have adequate social support. If you feel any distress at any time, please reach out to your health care providers and ask for help.
