R Timmerman¹*, Y Prezado²*, S Chang³*, K Sheng⁴*, (1) The University of Texas Southwestern Medical Ctr, Indianapolis, IN, (2) Institut Curie, Paris Cedex 5, (3) University of North Carolina, School of Medicine, Chapel Hill, NC, (4) UCLA School of Medicine, Los Angeles, CA

• 
  R Timmerman
• 
  Y Prezado
• 
  S Chang
• 
  K Sheng

TU-EF-TRACK 7-0 (Tuesday, 7/27/2021) 3:30 PM - 5:30 PM [Eastern Time (GMT-4)]

Speaker 1: Prof. Robert Timmerman, UT Southwestern
Presentation Title: “PULSAR: The adaptation of SAbR toward personalized medicine.”

Radiotherapy dogma, based on conventional daily dosing, insists that treatments be completed without interruption. In fact, randomized trials conducted in the 70’s and 80’s with a “split” inserted into a course of conventional daily dose treatment resulted in improved toxicity (as predicted), but poorer tumor control (tumor control penalty) leading to abandonment. The implementation of Stereotactic Ablative Radiotherapy (SAbR) successfully challenged another radiotherapy dogma condemning hypo-fractionation by showing higher rates of tumor control WITHOUT increasing late toxicity. Building on this reality, we and others have hypothesized that potential benefits of a “split course” might be re-examined with SAbR where more potent dosing could avoid the tumor control penalty while providing other opportunities to exploit for improving therapy. New radiotherapy platforms with sophisticated on-board imaging and software are capable of rapid re-planning enabling an “adaptive” approach where change triggers a modified treatment. The benefit of adaptive radiotherapy using conventional small dose daily fractionation is marginal because little changes. So here we introduce a new treatment paradigm called Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy (PULSAR). PULSAR uses independently planned, potent SAbR treatments called “pulses” to trigger change in the tumor, in its microenvironment and in the patient as a whole. Pulses are separated by ample time (weeks to months) hoping for ample changes to occur. Multiple interrogations proceed between pulses to guide the next pulse which is independently planned (adapted). Interrogations might include imaging (anatomical and functional), blood/urine tests, assays, history and physical exam, toxicity assessments and even repeat biopsy. With time, these tests are likely to uniquely change for each patient facilitating adaptions personalizing the therapy. Much work needs to be done to guide the adaptions as this is much more than just adapting to position and shape. Treatments may be altogether changed combining different drugs with different pulses depending on the evolution of change, perhaps even abandoning the original treatment altogether. PULSAR defines both opportunities and complicated assessments. Artificial intelligence tools will likely be helpful in making PULSAR a revolutionary new treatment paradigm

Learning objectives

1. Learn about the concept and the advantages of Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy (PULSAR) for adaptative radiotherapy
2. Learn about potential changes in the tumor and its microenvironment triggered by PULSAR and how to use them to optimize the treatments.



Speaker 2: Dr. Yolanda Prezado, Institut Curie (France), EFOMP’s representative
Presentation Title: “Overview of Spatially Fractionated Radiation Therapy: from photons to charged particles.”


Despite remarkable advancements, the dose tolerances of normal tissues continue to be the main limitation in radiation therapy (RT). One possible solution could be to employ distinct dose delivery methods, activating different biological processes from those ones in standard RT. Along this line, the strong spatial modulation used in techniques such as GRID, Lattice therapy or minibeam radiation therapy (MBRT), has already demonstrated a significant reduction of normal tissue toxicity and an important increase of the therapeutic index for some (radio-resistant) tumors. While spatially fractionated radiation therapy (SFRT) has mainly used photon beams, the alliance of SFRT and the benefits of charged particles for therapy has recently started. This presentation will provide a general overview on SFRT and how it is evolving from the use of photons to charged particles.


Learning objectives

1. Learn about spatial fractionation of the dose in radiation therapy and its advantages
2. Learn about radiobiology in SFRT



Speaker 3: Prof. Sha Chang, University of North Carolina
Presentation Title: “Understanding the correlation between dosimetric parameters and treatment responses for spatially fractionated radiation therapy”

A solid understanding of correlation between dosimetry and treatment response is crucial for radiation therapy for cancer. We have gained such an understanding for conventional seamless radiation therapy but it may not apply for spatially-fractionated radiation therapy (SFRT).

SFRT is a nonconventional radiation therapy where dose distribution is highly fractionated in space. Decades of clinical and preclinical data have shown that SFRT has promising potentials as a very high therapeutic ratio radiation therapy, especially when used as a neoadjuvant therapy and for cancers that cannot be adequately managed by conventional therapies. These cancers include large late stages cancers, in- or near-field reoccurrences, refractory cancers, and cancer within or near highly radiosensitive critical organs.

Two major obstacles for broad SFRT clinical application are lack of understanding of working mechanism and of the correlation between complex SFRT dosimetric parameters and treatment responses. The key questions to be answered include what is the most proper dosimetric parameter to be used for SFRT treatment prescription and what is an “apple to apple” comparison between a SFRT treatment and the “gold standard” conventional radiation therapy for a given endpoint. In this presentation we intend to shed lights on these and other important questions by reviewing and analyzing available data and discuss directions for future research.

Learning Objectives:
1. Recognize that understanding the correlation between dosimetric parameters and treatment response is crucial to advance SFRT.
2. Understand that preclinical SFRT studies indicate that peak dose may not be closely correlated with treatment response.
3. Learn methods to conduct research on SFRT dosimetry vs. treatment response.



Speaker 4: Prof. Ke Sheng, University of California,
Presentation Title: “Radiotherapy beyond 4pi”


Despite the potential for significantly improve the dose conformity, OAR sparing, and target dose escalation, gaps exist to prevent 4π radiotherapy from being widely used in the clinic. The gaps include the complexity of the optimization, the cumbersomeness of the C-arm gantry system to achieve the non-coplanar angles, and the long time needed for treatment delivery. The presentation will discuss the technical roadmaps to overcome these challenges. Artificial intelligence can be used to streamline treatment planning in two aspects. First, the plan dose can be individually predicted based on previously treated patients. Second, Artificial intelligence methods can be used to simplify dose calculation and optimization or circumvent certain steps of the optimization to speed up the calculation. A new robotic hardware platform is expected to effectively and efficiently access the non-coplanar angles without rotating the patient couch. The reduction in the form factor afforded by cutting-edge linear accelerator affords additional beam angles that were unavailable previously. The new many-isocenter optimization methods blur the traditional definitions of field of view and intensity modulation resolution. Ultimately, the combination of hardware and software innovations will move 4π closer to clinical reality.

Learning objectives:

1. Learn the challenges that exist in 4π radiotherapy and the hardware development to overcome the challenges.
2. Learn the optimization methods that allow the same system to treat both small targets with high intensity modulation resolution in SRS and large tumors with conventional fractionation.

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