Abstract
Low-grade gliomas (LGGs) are brain tumors characterized by their slow growth and infiltrative nature. Treatment options for these tumors are surgery, radiation therapy and chemotherapy. The optimal use of radiation therapy and chemotherapy is still under study. In this paper, we construct a mathematical model of LGG response to combinations of chemotherapy, specifically to the alkylating agent temozolomide and radiation therapy. Patient-specific parameters were obtained from longitudinal imaging data of the response of real LGG patients. Computer simulations showed that concurrent cycles of radiation therapy and temozolomide could provide the best therapeutic efficacy in-silico for the patients included in the study. The patient cohort was extended computationally to a set of 3000 virtual patients. This virtual cohort was subject to an in-silico trial in which matching the doses of radiotherapy to those of temozolomide in the first five days of each cycle improved overall survival over concomitant radio-chemotherapy according to RTOG 0424. Thus, the proposed treatment schedule could be investigated in a clinical setting to improve combination treatments in LGGs with substantial survival benefits.
Highlights
Adult supratentorial WHO grade II diffuse low-grade gliomas (LGGs) are slowgrowing primary brain tumors that are, in general, incurable due to their infiltrative nature.active surgical and oncological treatment may lead to patient survival exceeding years following diagnosis [1].Treatment typically consists of surgery followed by observation, radiotherapy, chemotherapy, or chemoradiation [2]
Our results show that concurrent cycles of TMZ and RT could provide substantial survival improvements over concomitant radio-chemotherapy according to Radiation Therapy Oncology Group (RTOG) 0424 [12]
Best fits for all patients are shown in the Supplementary Information (SI) Section S2
Summary
Adult supratentorial WHO grade II diffuse low-grade gliomas (LGGs) are slowgrowing primary brain tumors that are, in general, incurable due to their infiltrative nature.active surgical and oncological treatment may lead to patient survival exceeding years following diagnosis [1].Treatment typically consists of surgery followed by observation, radiotherapy, chemotherapy, or chemoradiation [2]. Active surgical and oncological treatment may lead to patient survival exceeding years following diagnosis [1]. The decision as to the specific combination of therapies to be used on each patient is based on the qualitative consideration of different variables including age, tumor grade, performance status, tumor histology and location [3]. Systemic treatments play an important role in the management of LGGs. Procarbazine, lomustine, and vincristine (PCV) and temozolomide (TMZ) have been shown to be effective against low grade gliomas [4,5,6]. Procarbazine, lomustine, and vincristine (PCV) and temozolomide (TMZ) have been shown to be effective against low grade gliomas [4,5,6] Today, both therapies are widely recommended by recent clinical practice guidelines [7,8]. Due to its favorable toxicity profile, prolonged TMZ treatment is a relevant option either as upfront or as adjuvant treatment [9]
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