Louis Constine’s Seminal Contribution to Radiation Oncology

Jun. 18, 2024
The “Agony of Victory” May No Longer Bring as much Anguish, Thanks to Decades of Research

Louis (Sandy) Constine, MD, FACR, FASTRO, has been a specialist in radiation and pediatric oncology for 50 years. This month, his career reached a high point when the premier journal in his field published a series of 30 landmark studies with Constine as the lead editor and frequent author.

headshot of L Sandy Constine MD in a white coat
Sandy Constine, MD

The research addresses the toxic side effects of radiation therapy for young people and will guide safer treatment planning for children with cancer around the world for decades to come.

The work is also a huge stepping stone for improving the outlook for survivors of childhood cancer. The team provides granular information on the causes of treatment toxicities, methodologies to better understand treatment injuries in the future, and insights into the best pathways for reducing side effects.

“It’s been a true honor to work on this project and a fulfilling chapter in my career, knowing that we are making a difference for young people with cancer,” said Constine, leader of the Wilmot Cancer Institute (Judy DiMarzo) Survivorship Program.

Years ago, Constine adopted the phrase “agony of victory,” to illustrate the double-edged sword of childhood cancer treatment in previous eras: While many children were cured of cancer, their exposure to radiation and chemotherapy also posed serious threats to their health as they age due to the “late effects” of treatment toxicities.

Overall, research shows, 60% to 90% of childhood cancer survivors treated in previous eras are likely to develop one or more chronic health conditions.

These risks cover a wide spectrum with the deadliest being second cancers and heart disease later in life. For example, young girls treated with radiation historically had a 30 percent chance of developing breast cancer — compared to a 13 percent lifetime risk for the average female — but that risk is decreasing with contemporary therapy.

The Constine-led coalition of researchers investigated the elements that led to this situation, thereby dissecting the genesis of the late effects.

“Now we are poised to celebrate our victories with less agony because the long-term side effects of treatment will diminish,” he said. “That’s a blessing to us all.”

Research Offers Blueprints for the Future

The 12-year project started after Constine established an international network of more than 150 physician-scientists, biostatisticians, physicists, and epidemiologists committed to investigating the toxicities of cancer therapy for children and adolescents.

The group is known as the PENTEC (Pediatric Normal Tissue Effects in Clinic) team, and Constine serves as chair.

One factor that makes the research so important, Constine said, is that the team investigated how cancer treatment impacts the organs of children as a function of their stage of development and how chemotherapy affects developing tissues.

Scientists also filled in knowledge gaps by establishing radiation dose and exposed-volume guidelines to inform radiation therapy planning and offer blueprints for future studies. This approach, for example, suggests that oncologists should avoid treating children as “small versions of adults” because sensitivity to radiation therapy relates to the stage of a child’s development.

The International Journal of Radiation Oncology, Biology, Physics (known as the Red Journal) spotlighted the PENTEC studies in a special edition with a preface that can be found here.

In the introduction section, of which Constine was the lead author, the team notes that despite a childhood cancer cure rate of 80 percent, studies reveal a nine-year gap in life expectancy for children diagnosed and treated in the 1990s. Since then, a more judicious and precise use of radiation therapy has improved long-term side effects.

A Distinguished Career

Constine’s career as a young scientist took off at Stanford University, where he credited remarkable mentors such as Henry Kaplan, MD, a pioneer in lymphoma radiation oncology; Saul Rosenberg, MD, a pioneer in treating Hodgkin lymphoma; and Sarah Donaldson, MD, who continues as a gigantic force in the field of pediatric radiation oncology. He moved to the University of Rochester to collaborate with another giant in the field, Philip Rubin, MD, who inspired him to dedicate his life to advancing the field of radiation oncology, and to ease the journey for all afflicted by cancer or impacted by therapies.

Constine is a long-standing member of the National Cancer Institute Physician’s Data Query panel for the treatment of all pediatric cancers, for which he received an award of merit. He was also a member of a four-person United Nations task force collating the adverse effects of radiation on children and distributing the information to all member nations.

As his career advanced, he also led numerous professional societies, and recently retired from his roles as the radiation chair of the Lymphoma Committee in the Southwest Oncology Group (SWOG), a large and prestigious network that conducts clinical research, and as chair of the American Radium Society Appropriateness Criteria Lymphoma Committee.

These words guide his professional life, he said: “For the survivor of cancer, the world is full, and each day is a celebration; for the physician, each patient is an inspiration; for the person fighting cancer, each day is precious and must be faced with courage.”