Optimization of radiation dosing schedules for proneural glioblastoma
H Badri1, K Pitter2, E C Holland3
1Department of Industrial and Systems Engineering, University of Minnesota, Minneapolis, MN, 55455, USA. badri019@umn.edu.
Abstract:
Glioblastomas are the most aggressive primary brain tumor. Despite treatment with surgery, radiation and chemotherapy, these tumors remain uncurable and few significant increases in survival have been observed over the last half-century. We recently employed a combined theoretical and experimental approach to predict the effectiveness of radiation administration schedules, identifying two schedules that led to superior survival in a mouse model of the disease (Leder et al., Cell 156(3):603-616, 2014). Here we extended this approach to consider fractionated schedules to best minimize toxicity arising in early- and late-responding tissues. To this end, we decomposed the problem into two separate solvable optimization tasks: (i) optimization of the amount of radiation per dose, and (ii) optimization of the amount of time that passes between radiation doses. To ensure clinical applicability, we then considered the impact of clinical operating hours by incorporating time constraints consistent with operational schedules of the radiology clinic. We found that there was no significant loss incurred by restricting dosage to an 8:00 a.m. to 5:00 p.m. window. Our flexible approach is also applicable to other tumor types treated with radiotherapy.
Insights
Optimizing radiation schedules for glioblastoma treatment can improve survival. This study found that fractionated radiotherapy schedules, even within standard clinic hours, effectively minimize toxicity while maintaining efficacy.
Area of Science:
- Oncology
- Radiation Oncology
- Medical Physics
Background:
- Glioblastomas are aggressive primary brain tumors with poor prognoses despite current treatments.
- Significant survival improvements for glioblastoma have been limited over the past 50 years.
- Previous research identified superior radiation schedules in a mouse model using theoretical and experimental methods.
Purpose of the Study:
- To extend theoretical and experimental approaches to optimize fractionated radiotherapy schedules for glioblastoma.
- To minimize toxicity in early- and late-responding tissues.
- To assess the impact of clinical operating hours on radiotherapy schedule efficacy.
Main Methods:
- Decomposition of the optimization problem into radiation dose per fraction and inter-fraction time intervals.
- Modeling of fractionated radiotherapy schedules.
- Incorporation of clinical time constraints (8:00 a.m. to 5:00 p.m.) into the optimization model.
Main Results:
- Identified optimized fractionated radiotherapy schedules.
- Demonstrated that restricting radiation delivery to standard clinical operating hours (8:00 a.m. to 5:00 p.m.) did not significantly compromise efficacy.
- The approach successfully minimized toxicity in normal tissues.
Conclusions:
- Optimized fractionated radiotherapy schedules can improve glioblastoma treatment outcomes.
- Radiotherapy can be effectively delivered within standard clinical operating hours without significant loss of therapeutic benefit.
- The flexible optimization approach is applicable to various tumor types treated with radiotherapy.
