Concurrent chemotherapy and radiation therapy is the standard treatment approach for patients with locally advanced cervical carcinoma. With standard cisplatin based chemotherapy, acute and late toxicity remain significant problem, and the incidence of loco-regional failure, distant metastasis, and cancer mortality remain high. Therefore, strategies to reduce toxicity and permit treatment intensification are needed. 

Methods to reduce toxicity during chemoradiotherapy, particularly gastrointestinal and hematologic, could mitigate this toxicity and take advantage of the therapeutic benefits of intensive concurrent chemotherapy.

Multiple studies in gynecologic cancer have shown that IMRT plans reduce dose to pelvic organs while maintaining acceptable target coverage. Comparisons of IMRT to conventional treatments in patients have found reduced acute and late GI toxicity and hematologic toxicity with IMRT. Studies have also shown that IMRT plans can be optimized to intensively reduce normal tissue dose and have established evidence-based guidelines for dosimetric planning to reduce toxicity. 

To our kowledge, however, detailed QOL data for cervical cancer patients treated with IMRT + cisplatin is lacking, particularly in the international setting. This trial provides an ideal mechanism to collect and analyze cross-cultural patient -reported longitudianl data. We will explore the impact of IMRT on QOL using two validated instruments: the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C 30 form and QLQ-CX24 module. 

Hematologic toxicity (HT) is a key barrier to intensifying chemoradiotherapy in patients with pelvic malignancies. It is well - known that both radiation and chemotherapy are myelosuppressive, but the extent to which pelvic radiation contributes to HT in  patients undergoing CRT is unknown. 

Qualitative MR has long been used to detect fat in tissues from the change in signal intensity caused by the characteristic short T1 of fat or the chemical shift difference between fat and water.  Within BM there is considerable heterogeneity in fat content that varies with age and disease status. A quantitative technique called Iterative Decomposition of water and fat with Echo Asymmetry and Least-Squares Estimation (T2*-IDEAL), can distinguish red and yellow BM based on their fat signal fraction, providing a quantitative assessment of BM in response to treatments.  [18F]- deoxyfluorothymidine (¹⁸F-FLT) is an effective PET imaging tracer for proliferating BM. FLT is a DNA precursor that is phosphorylated and sequestered intracellularly by the enzyme thymidine kinase 1, which is active during DNA synthesis, leading to specific tracer uptake in BM after irradiation with doses as low as 2 Gy, and complete absence of uptake after 10-20 Gy.  ¹⁸F-FLT appears superior to ¹⁸F-FDG to discriminate between proliferating cells and metabolically active non-proliferating cells.

In a sub-study of this protocol, we will test the hypothesis that BM-sparing IMRT plans designed to avoid active that subregions identified by PET can further reduce HT. This technique could improve patients tolerance to chemotherapy and increase the therapeutic ration of CRT for pelvic malignancies in general.

Recently, gantry-mounted kV cone beam computed tomography (CBCT) has been used to acquire daily volumetric images of patients in the treatment position. The target volume can be drawn on the daily CBCT and the CBCT registered to the planning CT to determine the daily target position relative to planning CT. The margin that would be needed to encompass the target each day for a given degree of accuracy in target coverage can then be determined.

Compared to conventional RT techniques, IMRT will reduce acute hematologic and gastrointestinal toxicity for cervical cancer patients treated with concurrent cisplatin.

1. To test whether IMRT will reduce the rate of acute grade â‰¥ hematologic or clinically significant grade â‰¥ 2 gastrointestinal toxiciy compared to conventional RT techniques for cervical cancer patients treated with concurrent cisplatin.