Bone Marrow Toxicity and Tolerance of Sandwich Therapy for Advanced-Stage Endometrial Cancer: A Single-Institution Experience

Abstract

<h3>Purpose/Objective(s)</h3> Adjuvant therapy for advanced-stage endometrial cancer (EC) involve chemotherapy (CT) and/or radiation therapy (RT). Institutional practices vary regarding the sequencing of these therapies. While recent trials favored concurrent chemoradiation followed by consolidating CT, there is no randomized comparison of efficacy between ‘sandwich' (ST) versus concurrent CT. Previous studies show BM dose is predictive of hematological toxicities (HT) in concurrent chemoradiation. In this study, we sought to determine whether bone marrow dose contributes to hematological toxicity in ST for treatment of advanced-stage EC. <h3>Materials/Methods</h3> Data for patients who received ST (CT with carboplatin/paclitaxel then 45 Gy external beam radiation therapy [EBRT] with/without paraaortic [PA] fields then additional CT) at a single academic institution for EC cases was abstracted. Full ST was defined as 3 CT cycles, then RT, followed by a final 3 CT cycles. Grade 3 (G3) higher hematologic toxicities (ANC <1000, Hgb <8.0, platelet count <50,000) were recorded for each patient based at the time of infusion or radiation therapy. T-test and Chi-square test were used as appropriate to determine association. <h3>Results</h3> 98 EC patients that underwent ST were included; 66.0% were stage IIIC. 84% of patients completed full ST, and 26.3% of cases experienced ≥1 treatment delay. Among cycle delays cases, 57.7% had ≥1 G3 hematologic toxicity: 10 neutropenia, 4 anemia, and 3 thrombocytopenia. HT rate was 49.0%: 34% neutropenia, 13% anemia, 12% thrombocytopenia. Frequency of cycle delay (31.3% vs. 21.6%) or ST non-completion (13.7% vs. 18.4%) were not significantly associated with HT presence (p>0.05, all). Significantly fewer patients who had HT both pre- and post-EBRT completed post-sandwich CT compared to toxicities occurring at other time intervals (Table). While patients with ≥2 HT during their treatment received a significant larger mean bone marrow radiation dose (69.0 vs 72.5%, p=0.037), overall dosimetric data were similar regardless of HT timing during treatment. PA boost did display more frequent HT following RT (21.1% vs. 51.7%, p = 0.033) but completed ST at similar rates (63.2% vs 36.8%, p=0.441). There was a 10% mortality rate; overall survival was similar despite presence of HT occurrence, or with HT requiring a cycle delay or cycle non-completion (p>0.05, all cases). <h3>Conclusion</h3> In our study, BM dose does matter in determining HT even in ST, but does not affect overall treatment completion. The treatment completion rate is comparable to those reported historically for CT only arm. Low rates of cycle interruption and similar overall survival point to a promising safety and efficacy profile with ST.