Reduction of Hematologic Toxicity in Locally Advanced Cervical Cancers

Cervical cancer is the fourth most common cancer among women and is mainly linked to infection with high-risk human papillomaviruses (HPV). Although most HPV infections resolve spontaneously, 570,000 women were diagnosed with cervical cancer in 2018, and more than half of them died from the disease. For locally advanced disease, concurrent chemoradiotherapy (RT-CT) followed by brachytherapy is considered the standard therapeutic treatment. Even though progress has been made in chemotherapy, external beam radiotherapy, and brachytherapy over the past decades-on the one hand by reducing the duration of chemotherapy-induced cytotoxicity, and on the other hand by decreasing radiation doses delivered to organs at risk-hematologic toxicity following concurrent chemoradiotherapy remains a frequent complication. The indication and benefit of chemotherapy have been demonstrated in phase III clinical trials; however, grade 3 hematologic toxicity (anemia, leukopenia, and thrombocytopenia) remains between 18.7% and 21.3%. Since total treatment duration is a prognostic factor for local control, brachytherapy must be administered near the end of or immediately after RT-CT so that total treatment time is as short as possible (≤ 50 days). If grade 3 hematologic toxicity persists after RT-CT (prior to brachytherapy), brachytherapy will be delayed, leading to a loss of disease control (Tanderup et al., 2016). Dose reduction to the bone marrow is possible, but to date no randomized trial has evaluated it. The objective of this multicenter French study is to assess whether bone-sparing-contouring of the pelvic and/or lumbosacral osseous structures as an organ at risk (OAR) during external radiotherapy planning-reduces the incidence of grade ≥ 3 hematologic toxicity and the use of leukocyte growth factors, platelet transfusions, and/or blood transfusions, while adhering to current recommendations and without compromising clinical outcomes in patients treated with RT-CT and brachytherapy for locally advanced cervical cancer.