Model-Based Evaluation of Spontaneous Tumor Regression in Pilocytic Astrocytoma
Thomas Buder1,2, Andreas Deutsch1, Barbara Klink3
1Zentrum für Informationsdienste und Hochleistungsrechnen (ZIH), Technische Universität Dresden, Dresden, Germany.
Insights
Pilocytic astrocytoma (PA) behavior after partial resection is predictable using a mathematical model. Tumor regression probability depends linearly on residual size, suggesting any tumor removal improves prognosis.
Area of Science:
- Pediatric neuro-oncology
- Mathematical modeling of tumors
- Cancer biology
Background:
- Pilocytic astrocytoma (PA) is the most common pediatric brain tumor, typically benign with a good prognosis after total resection.
- Partial resection is often necessary due to tumor location, leading to unpredictable outcomes like regression, regrowth, or progression.
- Current management strategies for unresectable PA vary, highlighting the need for better prognostic tools.
Purpose of the Study:
- To develop a mathematical model to understand the growth and progression of pilocytic astrocytoma after partial resection.
- To investigate the relationship between residual tumor size and spontaneous regression.
- To provide a quantitative prediction of regression probability for partially resected PAs.
Main Methods:
- Development of a Markov chain model incorporating cell proliferation, death, and mutations.
- Analysis of tumor behavior based on a deduced risk coefficient (γ) from epidemiological data.
- Quantitative prediction of regression probability as a function of residual tumor size.
Main Results:
- Tumor behavior after partial resection is primarily determined by a risk coefficient (γ).
- A linear dependency between residual tumor size and regression probability was hypothesized.
- Removing any amount of tumor mass is predicted to improve the prognosis for benign PA.
Conclusions:
- The mathematical model provides quantitative predictions for PA regression post-partial resection.
- The findings suggest a linear relationship, contrasting with diffuse malignant gliomas.
- Residual tumor volume should be considered a crucial prognostic factor in future PA therapeutic studies.
Abstract:
Pilocytic astrocytoma (PA) is the most common brain tumor in children. This tumor is usually benign and has a good prognosis. Total resection is the treatment of choice and will cure the majority of patients. However, often only partial resection is possible due to the location of the tumor. In that case, spontaneous regression, regrowth, or progression to a more aggressive form have been observed. The dependency between the residual tumor size and spontaneous regression is not understood yet. Therefore, the prognosis is largely unpredictable and there is controversy regarding the management of patients for whom complete resection cannot be achieved. Strategies span from pure observation (wait and see) to combinations of surgery, adjuvant chemotherapy, and radiotherapy. Here, we introduce a mathematical model to investigate the growth and progression behavior of PA. In particular, we propose a Markov chain model incorporating cell proliferation and death as well as mutations. Our model analysis shows that the tumor behavior after partial resection is essentially determined by a risk coefficient γ, which can be deduced from epidemiological data about PA. Our results quantitatively predict the regression probability of a partially resected benign PA given the residual tumor size and lead to the hypothesis that this dependency is linear, implying that removing any amount of tumor mass will improve prognosis. This finding stands in contrast to diffuse malignant glioma where an extent of resection threshold has been experimentally shown, below which no benefit for survival is expected. These results have important implications for future therapeutic studies in PA that should include residual tumor volume as a prognostic factor.
