Proposed The functional and biological properties of the tumor microenvironment are fundamentally important determinants of tumor response and therapy outcome in cancer.  Oxygenation status and vascularity and are known to influence radiation response, and molecular energy metabolism and proliferation impact on recurrence and metastatic progression.  However, with the current standard clinical diagnostic approaches, such as biopsy or anatomic/morphologic tumor imaging, assessment of the known intra-tumoral heterogeneity of functional and biological tumor properties is limited.  Specifically, the functional characteristics within the microenvironmental environment throughout the entire tumor have been challenging to assess spatially for tumor heterogeneity and temporally for clinical correlation before and during treatment.  While histologic tissue sampling is widely used clinically, sampling of the entire tumor with extensive biopsies, or biopsies at various time points during therapy for intra-treatment assessment are impractical and generally pose unacceptable clinical risk. 

Functional/molecular imaging offers the opportunity to assess biological heterogeneity across the entire tumor volume (spatially) and longitudinally across the treatment course (temporally).  In advanced cervical cancer, the tumor gradually undergoes radiation/chemotherapy induced functional and biological changes within its heterogeneous volume that can be assessed by sequential imaging before and during treatment.  

Advanced cervical cancer is an ideal disease to study – in clinical patients – the vascular, cellular and molecular tumor properties that can provide essential information to monitor therapeutic responsiveness, facilitate treatment planning and may provide early prediction of ultimate success or failure of an ongoing treatment.

Advanced cervical cancer is treated with cytotoxic therapy: radiation and concurrent chemotherapy.  It is a highly prevalent disease globally, and treatment failure is common.  The propensity of cervical cancer for hypoxia and poor vasculature within the often bulky heterogenous tumor volume is well-recognized.  Because advanced cervical cancer is not surgically resected, functional/molecular imaging provides unique opportunities for non-invasive assessment across the treatment course.