Proton therapy can allow for superior avoidance of normal tissues. A widespread consensus has been reached that proton therapy should be used for patients with curable pediatric brain tumor to avoid ...critical central nervous system structures. Brainstem necrosis is a potentially devastating, but rare, complication of radiation. Recent reports of brainstem necrosis after proton therapy have raised concerns over the potential biological differences among radiation modalities. We have summarized findings from the National Cancer Institute Workshop on Proton Therapy for Children convened in May 2016 to examine brainstem injury.
Twenty-seven physicians, physicists, and researchers from 17 institutions with expertise met to discuss this issue. The definition of brainstem injury, imaging of this entity, clinical experience with photons and photons, and potential biological differences among these radiation modalities were thoroughly discussed and reviewed. The 3 largest US pediatric proton therapy centers collectively summarized the incidence of symptomatic brainstem injury and physics details (planning, dosimetry, delivery) for 671 children with focal posterior fossa tumors treated with protons from 2006 to 2016.
The average rate of symptomatic brainstem toxicity from the 3 largest US pediatric proton centers was 2.38%. The actuarial rate of grade ≥2 brainstem toxicity was successfully reduced from 12.7% to 0% at 1 center after adopting modified radiation guidelines. Guidelines for treatment planning and current consensus brainstem constraints for proton therapy are presented. The current knowledge regarding linear energy transfer (LET) and its relationship to relative biological effectiveness (RBE) are defined. We review the current state of LET-based planning.
Brainstem injury is a rare complication of radiation therapy for both photons and protons. Substantial dosimetric data have been collected for brainstem injury after proton therapy, and established guidelines to allow for safe delivery of proton radiation have been defined. Increased capability exists to incorporate LET optimization; however, further research is needed to fully explore the capabilities of LET- and RBE-based planning.
Background
Radiopharmaceutical targeted therapy (RPT) has been studied for decades; however, recent clinical trials demonstrating efficacy have helped renewed interest in the modality.
Methods
This ...article reviews National Cancer Institute (NCI)’s support of RPT through communication via workshops and interest groups, through funding extramural programs in academia and small business, and through intramural research, including preclinical and clinical studies.
Results
NCI has co-organized workshops and organized interest groups on RPT and RPT dosimetry to encourage the community and facilitate rigorous preclinical and clinical studies. NCI has been supporting RPT research through various mechanisms. Research has been funded through peer-reviewed NCI Research and Program Grants (RPG) and NCI Small Business Innovation Research (SBIR) Development Center, which funds small business-initiated projects, some of which have led to clinical trials. The NCI Cancer Therapy Evaluation Program (CTEP)’s Radiopharmaceutical Development Initiative supports RPT in NCI-funded clinical trials, including Imaging and Radiation Oncology Core (IROC) expertise in imaging QA and dosimetry procedures. Preclinical targeted a-emitter therapy (TAT) research at the NCI’s intramural program is ongoing, building on foundational work dating back to the 1980s. Ongoing “bench-to-bedside” efforts leverage the unique infrastructure of the National Institutes of Health’s (NIH) Clinical Center.
Conclusion
Given the great potential of RPT, our goal is to continue to encourage its development that will generate the high-quality evidence needed to bring this multidisciplinary treatment to patients.
With external beam radiation therapy, uncertainties in treatment planning and delivery can result in an undesirable dose distribution delivered to the patient that can compromise the benefit of ...treatment. Techniques including geometric margins and probabilistic optimization have been used effectively to mitigate the effects of uncertainties. However, their broad application is inconsistent and can compromise the conclusions derived from cross-technique and cross-modality comparisons.
Conventional methods to deal with treatment planning and delivery uncertainties are described, and robustness analysis is presented as a framework that is applicable across treatment techniques and modalities.
This report identifies elements that are imperative to include when conducting a robustness analysis and describing uncertainties and their dosimetric effects.
The robustness analysis approach described here is presented to promote reliable plan evaluation and dose reporting, particularly during clinical trials conducted across institutions and treatment modalities.
This chapter describes interactive evolutionary design, a powerful technique where one marries the exploratory capabilities of evolutionary computation with the esthetic skills and sensibility of the ...human as selective agent. Interactive evolutionary design has the potential to be an enormously useful tool to graphic designers. However, in order for it to become commonly used, a number of barriers to use must be overcome, including making it both simpler to understand (e.g., more intuitive genotype-phenotype mappings) and with greater user-control (e.g., allow the user to lock “perfect” elements of a design). In this study we explore these ideas—how can one make interactive evolutionary design more appealing, useful and practical?—by developing a design tool “evoDesign” that employs a genetic algorithm to evolve designs. As an illustrative test case, evoDesign is used to evolve tiles used for walls or floors or as a repeating unit for fabrics and wallpapers.
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