Abstract
BackgroundTo identify dosimetric parameters associated with acute hematologic toxicity (HT) in rectal cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy.MethodsNinety-three rectal cancer patients receiving concurrent capecitabine and pelvic intensity-modulated radiation therapy (IMRT) were analyzed. Pelvic bone marrow (PBM) was contoured for each patient and divided into three subsites: lumbosacral spine (LSS), ilium, and lower pelvis (LP). The volume of each site receiving 5–40 Gy (V 5, V10, V15, V20, V30, and V40, respectively) as well as patient baseline clinical characteristics was calculated. The endpoint for hematologic toxicity was grade ≥ 2 (HT2+) leukopenia, neutropenia, anemia or thrombocytopenia. Logistic regression was used to analyze correlation between dosimetric parameters and grade ≥ 2 hematologic toxicity.ResultsTwenty-four in ninety-three patients experienced grade ≥ 2 hematologic toxicity. Only the dosimetric parameter V40 of lumbosacral spine was correlated with grade ≥ 2 hematologic toxicity. Increased pelvic lumbosacral spine V40 (LSS-V40) was associated with an increased grade ≥ 2 hematologic toxicity (p = 0.041). Patients with LSS-V40 ≥ 60 % had higher rates of grade ≥ 2 hematologic toxicity than did patients with lumbosacral spine V40 < 60 % (38.3 %, 18/47 vs.13 %, 6/46, p =0.005). On univariate and multivariate logistic regression analysis, lumbosacral spine V40 and gender was also the variable associated with grade ≥ 2 hematologic toxicity. Female patients were observed more likely to have grade ≥ 2 hematologic toxicity than male ones (46.9 %, 15/32 vs 14.8 %, 9/61, p =0.001).ConclusionsLumbosacral spine -V40 was associated with clinically significant grade ≥ 2 hematologic toxicity. Keeping the lumbosacral spine -V40 < 60 % was associated with a 13 % risk of grade ≥ 2 hematologic toxicity in rectal cancer patients undergoing concurrent chemoradiotherapy.
Highlights
Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is the standard of care for patients with locally advanced rectal cancer (LARC) [3, 10, 19, 20]
Guidelines for Pelvic bone marrow delineation For each patient, the external contour of all bones within the pelvis was used as a surrogate for pelvic bone marrow (PBM), and the PBM was further divided into three subsites, as described by Mell et al.: (1) ilium—including the iliac crests extending to the superior border of the femoral heads; (2) lower pelvis (LP)—consisting of the pubes, ischia, acetabula, and proximal femora, extending from the superior border of the femoral heads to the inferior border of the ischial tuberosities; and (3) lumbosacral spine (LSS)—extending from the most superior vertebral body contained in the planning treatment volume inferiorly to include the entire sacrum [16] (Fig. 2)
The LSS was the smallest subsite of the PBM (22 %), and the LP was the largest subsite (46 %)
Summary
Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is the standard of care for patients with locally advanced rectal cancer (LARC) [3, 10, 19, 20]. The delivery of 5-Fluorouracil (5-FU) based chemotherapy with radiotherapy reduces 5-year incidence of local recurrence compared with radiotherapy (RT) alone [11]. Park et al demonstrated tumor response to neoadjuvant CRT was associated with 5-year recurrence free survival (RFS) [18]. Pelvic radiotherapy may contribute to the development of HT. Reducing pelvic bone marrow (PBM) irradiation may reduce HT, enabling improved delivery of chemotherapy, and, treatment efficacy. To identify dosimetric parameters associated with acute hematologic toxicity (HT) in rectal cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy
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