Program Information

In Memoriam of John "Jack" F. Fowler: The Mathematics of Dose-Fractionation Effects

C Orton

M Ritter

S Bentzen

C Orton¹*, M Ritter²*, S Bentzen³*, (1) Wayne State University, Grosse Pointe, MI, (2) University of Wisconsin School of Medicine and Public Health, Madison, WI, (3) University of Maryland, Baltimore, MD

Presentations

1:45 PM : Jack’s early career and achievements - C Orton, Presenting Author
2:25 PM : A research example - working with Jack on hypofractionation - M Ritter, Presenting Author
3:05 PM : Linear-quadratic modeling - current status and where to next? - S Bentzen, Presenting Author

WE-F-FS4-0 (Wednesday, August 2, 2017) 1:45 PM - 3:45 PM Room: Four Seasons 4

Bhudatt Paliwal came to know Jack as an invited faculty to our conference on Time-Dose relationships held in Madison in 1974. His dynamic personality immediately produced a spark!  This relationship continued over the last forty years. He was the inspiration and the fuel for nine conferences on related themes. Like many of his generation, his early education and training was in physics (B.Sc. in 1944, M.Sc. in 1946). After receiving his Ph.D. in Radiation Physics in 1955, he spent several years in hospital physics, before joining the MRC Radio-therapeutic Research Unit at Hammersmith Hospital in 1959 where he made his presence and expertise known and felt. 

Colin Orton notes that although best known as a radiobiologist, Professor Fowler actually started out as a radiation physicist. His early research was on the effect of x rays on the conductivity of plastics and on solid-state and ionization dosimetry. He also published some of the first studies on arc therapy dose distributions and it was while working on this as a physicist at King’s College Hospital in London that he began to get interested in biological effects of radiation. He published many articles on the effects of dose rate and fractionation as early as the late ‘50s, and was one of the very first to propose using the linear-quadratic formula to account for the effects of fractionation.
This initiated a lifetime interest in this topic and he was still publishing articles on this 50 years later.

After his retirement from the Gray Laboratory, Jack joined the University of Wisconsin in Madison as a Visiting Professor, where I continued to collaborate with him. Jack focus his energies exclusively on reading, writing, teaching, and collaborating with researchers in Madison and across the globe. He worked closely and published with a variety of clinicians, physicists. A short list would include Dolores Buchler, Judith Stitt, Daniel Petereit, Bruce Thomadsen, Thomas “Rock” Mackie, Timothy Kinsella, Mark Ritter, Paul Harari, Richard Chappell, Mary Lindstrom, Minesh Mehta, Wolfgang Tome and many more. He collaborated on clinical fractionation schedules for external beam and high-dose-rate, tumor cell proliferation, and overall treatment time. As an engaging teacher, he energized Madison’s graduate school’s radiobiology curriculum and also held extended teaching engagements in Belgium and Sweden, during the same timeframe. Jack seems to tap a source of endless energy and enthusiasm to foster his passion for linear-quadratic model. He has been an outstanding advisor and analyst of clinical fractionation.

One of the topics that came from these collaborations was hypofractionation for prostate cancer, which Mark Ritter will discuss. Hypofractionation for prostate cancer was originally carried out in the pursuit of efficiency and convenience but has now attracted greatly renewed interest based upon a hypothesis, formulated by Brenner, Fowler and others, that prostate cancers have a higher sensitivity to fraction size, reflected in a low alpha/beta ratio, than do late responding organs at risk such as the rectum or bladder. Tumor control and acceptable toxicity outcomes from a majority of hypofractionation analyses indeed appear to support the usefulness of LQ modeling and these yield alpha/beta ratios for prostate cancer that appear to be low. Prospective prostate trials employing moderate hypofractionation will be reviewed and the rationale for and early outcomes from newer trials employing extreme hypofractionation (≥6 Gy/fraction) will be summarized as well. Hypofractionation's significant potential for therapeutic gain, cost savings, and improved patient convenience appears increasingly positioned to profoundly impact the future management of localized prostate.

In this session, Søren Bentzen will discuss the simple LQ formalism and how Jack taught it. A number of developments have changed the research field of dose-fractionation biology in recent years. Among these are the realization that recovery half-times in human normal tissues are much longer than in rodents, the realization of the interaction between dose distribution and dose fractionation, the use of combined modalities, and the increased focus on patient-level risk factors on radiation toxicity. As short review of how these developments will be presented.

Joe Deasy notes that recent tumor control probability modeling that takes a more mechanistic approach has found good agreement with the LQ + time model used by Jack Fowler

Colin observes that without question, Professor Jack Fowler was probably the best known, most highly respected radiation biologist of his time and for this he received numerous honors, far too many to relate here, but some of the most prestigious were the Rontgen Prize and the Barclay Medal of the British Institute of Radiology, the Klaas Breur Medal of ESTRO, Marie Skłodowska Curie Medal of the Polish Society for Radiation Research, the Gold Medal of the Gilbert Fletcher Society, and the ASTRO Gold Medal, to name just a few.

Paliwal reflects that he has, and many of us in the AAPM have, been very fortunate to have had the opportunity to work with this energetic and innovative researcher. His willingness to listen, advise, and propose new solutions made him an outstanding. We hope the AAPM members will continue to cherish Jack’s creativity and enthusiasm for generations to come. Jack is known to most of us professionally but one could not help but be touched by him personally.  Jack’s guidance and collaboration continued throughout his life. Like so many of our colleagues he energized and inspired me. The profession will miss him.  All of his colleagues and friends will miss him.

Learning Objectives:
1. Learn about Jack Fowler's life and contributions to medical physics and radiation biology.
2. Learn the fundamentals of the linear-quadratic (LQ) model for biological response to radiation dose and some examples of how it has been used in clinical applications.
3. Learn how the model has developed over the last decade.

Handouts

• 127-35245-418554-126770.pdf (C Orton)

• 127-35246-418554-127411-2090127787.pdf (M Ritter)

• 127-35247-418554-127412.pdf (S Bentzen)

Contact Email: