Timing Is Everything


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I look forward to a time when it doesn’t matter when or where a patient is diagnosed and when every patient has a 100% chance of being cured of his or her cancer…. This is ASCO’s vision and mission—and mine.
— Daniel F. Hayes, MD, FACP, FASCO

In 1959, my 5-year-old cousin, Kim, was diagnosed with acute lymphocytic leukemia (ALL). As an 8-year-old, I didn’t really understand what was happening to him, except that he had to go to the Riley Hospital for Children in Indianapolis, Indiana, for treatment. The haunting vision of his looking out the window of his hospital room as we walked to our car after what turned out to be our last visit sticks with me to this day. He passed away the next week.

Nearly twenty years later, when I was a third-year medical student at Indiana University School of Medicine, my wife introduced me to John Cleland, the husband of her coworker. Over dinner that evening, John learned I was just starting my clinical years. He informed me that he was a patient of Lawrence Einhorn, MD, and that Dr. Einhorn had treated him for widespread, metastatic testicular cancer a few years before. As we all now know, Dr. Einhorn had been testing a platinum-based chemotherapy regimen of cisplatin, vinblastine, and bleomycin in the treatment of testicular cancer. John said the therapy appeared to have cured him, and he sure looked good to me. I was subsequently assigned to the oncology ward at the medical center and met Dr. Einhorn. It was then that I realized I was destined to become a medical oncologist.

These two cases, so intimately involved in my own personal life, represent the importance of timing. Had Kim been diagnosed with ALL in the mid-1960s, he would have had a small chance of being cured of his cancer. If he had been diagnosed in 2000, his odds of living a reasonably normal life span would have increased to nearly 90%.

Advances in Cure Rates

Figure 1, from a paper by Stephen P. Hunger, MD, and Charles G. Mullighan, MD, published in The New England Journal of Medicine,1 illustrates the remarkable increase in expected overall survival and subsequent cure rates in cohorts of children with ALL from 1968 to 2009. The respective Kaplan-Meier curves increase stepwise from an approximate cure rate of 10% in the first cohort treated from 1968 to 1970, which was a huge step above the 0% chance a decade earlier, to 90% in the cohort diagnosed from 2000 to 2005. Importantly, these advances in cure rates for pediatric ALL have been accompanied by a reassuring reduction in late treatment-related mortality, as recently reported by Armstrong et al.2

Fig. 1: Overall survival among children with acute lymphoblastic leukemia (ALL) who were enrolled in Children’s Cancer Group and Children’s Oncology Group clinical trials, 1968–2009. Reprinted with permission from Hunger SP, Mullighan CG: N Engl J Med 373:1541-1552, 2015.

In contrast, my friend John was much more fortunate than my cousin. He had been treated with a series of less effective regimens in the early 1970s, prior to meeting Dr. Einhorn, and had been told there was not much left to do. However, due to a coincidence of both geography and timing, he became Dr. Einhorn’s first patient cured with a cisplatin-containing drug regimen.

Of course, now, like childhood ALL, nearly 90% of men with metastatic testicular cancer can expect to live normal life spans with a high quality of life.3,4 In fact, John has run several marathons since his diagnosis and fathered three lovely children. Had John’s cancer been diagnosed 5 years earlier, it is unlikely he would have lived to share his wonderful story.

Role of NCI in Cancer Advances

Taken together, these two stories highlight the exhilarating, yet too slow, progress we have made in the treatment of many cancers. They also highlight the importance of federally funded cancer research and the visionary foresight of the National Cancer Act of 1971, which was signed into law by President Richard Nixon.

Prior to the National Cancer Act, cancer treatment depended very much on geography, because there were only a few well-trained medical oncologists in the country, and they were mostly clustered in a few large academic centers in major cities. Encouraged by the work of philanthropist and cancer research advocate Mary Lasker and chemotherapy pioneer Sidney Farber, MD, the National Cancer Act led to establishment of the National Cancer Institute (NCI) and a nationwide system of cancer centers. The training programs in these NCI-designated centers have placed highly trained oncologists throughout the country and provided access to cancer care to patients in big cities and small towns alike. Now, if you have cancer, you do not have to travel to New York or Houston or Bethesda to get state-of-the-art treatment.

The National Cancer Act also led to a huge infusion of sustained financial support for extramural funding of cancer research grants and jump-started highly effective research programs in such diverse areas as understanding the biology of cancer, diagnosis and treatment, screening and prevention strategies, and long-term survivorship. Furthermore, the law provided much-needed support for the cooperative group clinical trial system, which continues to generate practice-changing results.

Growing Number of Survivors

Although we have made much progress in cancer advancements since 1971, the war on cancer has not been won. Over the past decade, advances in early detection and more effective therapies have led to a reduction in cancer mortality and more than 15.5 million survivors, according to the American Cancer Society (ACS). By 2026, the ACS estimates that number will grow to more than 20 million.5

As I look back on my early days as a clinical oncologist, I recall the frequent plea of my patients, “Doctor, can you keep me alive long enough for the next big change in treatment to come along?” My cousin Kim’s death and John’s survival still resonating in my memory, I would paternalistically respond, “Yeah, sure,” while thinking, “It seems unlikely.”

However, in the past 10 years, in breast cancer alone (my particular specialty), the explosion of new treatments for patients with metastatic disease, some of which have moved into the adjuvant setting, have me shaking my head in wonder. In fact, I cannot count the number of patients with metastatic breast cancer who, like John, have done just well enough on one therapy to be able to enjoy the benefits of a subsequent treatment, which was only entering clinical trials when they were initially diagnosed.

Again, timing is everything.

Improving Survivors’ Quality of Life

But these advances are not enough. Losing one patient to cancer is one too many. ASCO advocated strongly for the passage of the recent 21st Century Cures Act, which was signed into law on December 13, 2016. The bill includes support for former Vice President Joe Biden’s National Cancer Moonshot Initiative, which endeavors to make a decade’s worth of cancer research progress in 5 years. I am optimistic that the Vice President’s extraordinary efforts to constructively direct his grief to real action, will greatly improve the chances of survival for greater numbers of patients diagnosed in the next decade, which brings me to the issues of long-term survivorship.

In 1985, when I was in a medical oncology fellowship program, no one taught us about long-term cancer survivorship; we were too busy trying to keep as many patients from dying as we could. However, due to the success in more effective therapies over the past 30 years and the subsequent increase in the number of cancer survivors, we’ve seen the emergence of the field of cancer survivorship.

As a young faculty member, I was invited to be the discussant at a plenary session at the 2000 ASCO Annual Meeting. Charles L. Loprinzi, MD, who was just beginning his career as a leader in research in cancer care management, was the presenter. Dr. Loprinzi reported that a commonly used antidepressant, venlafaxine, was quite effective in reducing hot flashes in breast cancer survivors receiving antiestrogen therapies. I remember being struck by how his presentation represented a turning point in our field, taking us from the question of, “Can we cure some patients?” to “Can we cure more patients and improve their quality of life?”

To address the many complicated physical, emotional, and financial issues experienced by many cancer survivors, this past year, ASCO launched the Cancer Survivorship Symposium: Advancing Care and Research. The Symposium provides a unique opportunity for clinicians across disciplines and professions to get together and learn about the rapidly evolving research to guide the best care for cancer survivors. This year’s program was held on January 27–28 in San Diego. I hope you were able to attend and, if not, I encourage you to attend next year’s meeting. You will not be disappointed.

I wish my cousin Kim had lived long enough to reap the benefits of the hard-won advances in ALL treatment that occurred just a few years after his death and to have witnessed the improvements in survivorship care made possible by our colleagues in pediatric research. Over the past 3 decades, I have felt a vicarious sense of professional pride, and a personal debt of gratitude, for Dr. Einhorn’s groundbreaking research in testicular cancer that cured my friend John of his disease.

I look forward to a time when it doesn’t matter when or where a patient is diagnosed and when every patient has a 100% chance of being cured of his or her cancer and can look forward to a long and quality life. The Moonshot is but one more step toward this goal. It is ASCO’s vision and mission—and mine.

Acknowledgments: I would like to thank Richard Schilsky, MD, FASCO, FACP, Senior Vice President and Chief Medical Officer of ASCO, for his helpful comments in crafting this column. I would also like to thank my aunt, Martha Yarling, and John Cleland for allowing me to share their experiences with cancer. Their stories and the stories of all my patients provide me with inspiration in all my professional activities. ■

Disclosure: Dr. Hayes is President of ASCO.

References

1. Hunger SP, Mullighan CG: Acute lymphoblastic leukemia in children. N Engl J Med 373:1541-1552, 2015.

2. Armstrong GT, Chen Y, Yasui Y, et al: Reduction in late mortality among 5-year survivors of childhood cancer. N Engl J Med 374:833-842, 2016.

3. Einhorn LH, Donohue J: Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 87:293-298, 1977.

4. Hanna NH, Einhorn LH: Testicular cancer—Discoveries and updates. N Engl J Med 371:2005-2016, 2014.

5. American Cancer Society: Cancer Facts & Figures 2016. Available at www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf. Accessed January 19, 2017.


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