Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

Small Animal Radiation Research Platform (SARRP): Aiding the optimisation of combined therapy for brain cancer (#143)

Kelly McKelvey 1 2 3 , Amanda Hudson 1 2 3 , Helen Wheeler 1 2 3 4 , Connie Diakos 2 3 4 , Michael Back 1 4 , Viive Howell 1 2 3
  1. Sydney Neuro-Oncology Group, North Shore Private hospital, St Leonards, NSW, Australia
  2. Sydney Vital, Translational Cancer Research, Royal North Shore Hospital, St Leonards, NSW, Australia
  3. Bill Walsh Translational Cancer Research Laboratory, NCS-SMS University of Sydney & NSLHD Research (Kolling Institute), St Leonards, NSW, Australia
  4. Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, NSW, Australia

Aims:

The Small Animal Radiation Research Platform (SARRP; Xstrahl, USA) is a miniaturised version of irradiators used in Oncology Departments around the world. Our aim is to use the SARRP on laboratory animals to replicate patient radiation therapy regimens and examine how radiation affects the inflammatory response during treatment.

Methods:

The SARRP uses cone-beam computed tomography (CBCT) and bioluminescent tomography (BLT) to pinpoint the precise anatomical location of a tumour in laboratory animals. Focal irradiation from a 0.5 mm diameter circle to whole body irradiation can be applied in fixed or dynamic X, Y, Z, θ (360o) planes to replicate conformal patient therapy.

Using a bioluminescent intracranial mouse model of glioblastoma (called Gl261-Fluc) we will assess the inflammatory response to combined radiation, chemotherapy and check point immunotherapy. For example, 2 Gy/day X-ray radiation for 5 days, 200 mg/m2/day Temozolomide for 5 days, and 10 mg/kg anti-PD-1mAb every 2 weeks to mimic patient regimens. We are also developing a biopsy and surgical resection method to complete this model for all treatment modalities currently available to patients.

Results:

We expect to utilise this mouse model of glioblastoma and the SARRP to advance knowledge of the tumour microenvironment and inflammatory response to cancer; optimise and tailor therapies for brain cancer; and to develop treatment regimens that minimise tissue damage and immune-related adverse events to combined therapy, which are associated with poorer patient outcomes.

Conclusions:

The SARRP is an integral piece of pre-clinical research technology to aid in the development of combined therapy for brain cancer and guide clinical trial protocols. Incorporation into a research pipeline will accelerate preclinical studies to improve the cancer experience, quality of life, and survival of patients.