Welcome to IBPRO.

Expanding the role of radiotherapy
Improving local control and reducing toxicity best combine physics and biology strategies.

Some of the important questions and issues we will address:

1. Is response variability a limiting factor to achieving a wider therapeutic window and improved outcomes?
2. Is normalized dose-response gradient actually useful in practice?
3. Are normal-tissue dose response curves always steeper than for malignancies?
4. What is the radiation dose-equivalent of adding chemotherapy?
5. Is Equivalent Uniform Dose actually useful, or are there better derived metrics?
6. Strategies for modification of normal-tissue responses based on the underlying pathobiology: How does that work?
7. What the biological risks versus gains from minimizing the target volume in different tumors/sites?
8. What possible interventions might we have in the processing of radiation damage?
9. Do we have to develop tumor-specific agents?
10. What modifying agents have been clinically tested?
11. What modifying agents are in the pipeline?
12. What trials of modifying agents are currently active?
13. What is the overall outlook for further biologically-based strategies for improving therapeutic ratio?
14. What is the value potential of using “big data”?

Target definition, treatment precision, and adaptive therapy
More rapid and precise imaging/treatment of the target volume and imaging the response to therapy are increasingly possible.

Some of the important questions and issues we will address:

1. Can we find fundamentally different and advantageous ways to deliver RT or are we stuck with mere incremental improvements in treatment plan quality resulting from improvements in technology?
2. How much “room for error” do we need to leave in treatment planning?
3. How much does motion management actually affect clinical outcome?
4. Does better precision of treatment delivery always give a better outcome?
5. Should increased precision in treatment delivery be used only with patients with a favorable prognostic profile?
6. When will it be practical and clinically advantageous to create adaptive treatment plans while patients are on the treatment couch?
7. Does adaptive therapy enable an increase in target volume without increased toxicity?
8. Is fractionation still important in adaptive therapy?
9. Can functional imaging provide a biophysical model for cancer treatment?
10. How does therapy “reprogram” the microenvironment?
11. How do we extract useful biological information from imaging?
12. How do improved image guidance using CT, PET and MRI make for improved geometrical sparing of normal tissues?
13. What can we best image in the tumor microenvironment that really matters?
14. Why has hypoxia not had a bigger impact clinically?
15. Is it that acute hypoxia is important and chronic hypoxia is irrelevant?
16. Is it that concurrent cisplatinum effectively “takes care” of the gain from using hypoxic sensitizers?
17. Does perfusion matter in other ways than controlling oxygenation?
18. Is dose painting for everyone?
19. Is individualized therapy really feasible and would it actually improve outcomes?
20. Is Head & Neck cancer a paradigm for improved precision in radiotherapy?

Hypofractionation
Increasing use of radiation doses per fraction >2.2 Gy and much higher: Where, how, when, and latest outcomes.

Some of the important questions and issues we will address:

1. Can animal models help us broadly understand the response to hypofractionation or must we focus only on clinical response data?
2. What are the human data-driven approaches to modeling responses to hypofractionation and SBRT?
3. Can modeling the human data be precise enough to guide decisions on treating individual patients?
4. Should we use BED or EQD2 as the common currency for expressing “biological dose equivalent”?
5. From the clinical data alone, can we say that “LQ cannot predict response to high doses per fraction”?
6. Must we invoke “new radiobiology” to understand response to high doses per fraction?
7. Is indirect cell death involved in the response to hypofractionation and SBRT?
8. Why are vascular-mediated effects more apparent at high doses per fraction than at 2 Gy per fraction?
9. Do hypofractionation and SBRT come automatically with a benefit of reduced overall treatment time?
10. Does the increasing use of large doses per fraction put hypoxia “back on the map”?
11. Why are we using clinical hypofractionation and SBRT effectively in 2015 and not in 1995?
12. In which sites is clinical application of hypofractionation/SBRT currently most successful?
13. Can we agree yet on an optimum number of fractions and total dose for each site?
14. Is chemotherapy less relevant within the context of SBRT?

Immunotherapy
How do inflammatory and immune responses to radiation damage influence outcome in different tumors, normal tissues and disseminated disease.

Some of the important questions and issues we will address:

1. What are the inflammatory responses induced by radiotherapy?
2. How do proimmunogenic and immunosuppressive effects of radiotherapy balance in different tumor types and sites/organs?
3. To what extent can radiation induce immune-mediated cell death compared with frank mitotic death?
4. Can immune-suppressive mediators yet be manipulated to therapeutic advantage?
5. Can immune-derived abscopal effects contribute significantly to patient cure?
6. Are immune responses more apparent with systemic (isotope) rather than local radiotherapy?
7. Does systemic chemotherapy also induce immunogenic cell death?
8. Where, if at all, does HPV fit into immune response?
9. How can treatment planning systems account for immune-modulated responses?
10. What is the dependence of immune-modulated responses on radiation dose or dose per fraction?
11. Are immune responses a significant cause of responses not conforming to a linear-quadratic relationship with higher radiation dose?
12. Can immune responses to primary local tumor irradiation lead to reduction in metastases and would this be more likely following higher dose-per fraction treatment of the primary, e.g. SBRT?
13. What clinical trials are currently underway to test efficacy of combining radiotherapy with immunotherapy?
14. Can/will the immune system really play a decisive role in radiation oncology?

Wrapping up
Reviewing what we have discovered during the past week, summarizing the clinical trial development activity, and a final closing discussion with faculty: “What is tomorrow?”