Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

Abstract

PURPOSE To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy (CRT), and to develop a normal tissue complication probability (NTCP) model for HT. METHODS AND MATERIALS We tested associations between hematologic nadirs during CRT and the volume of BM receiving ≥ 10 and 20 Gy (V10 and V20) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with 37 identically treated patients from a prior study, forming a cohort of 81 patients for NTCP analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. RESULTS In the validation cohort, significant negative correlations were observed between white blood cell count (WBC) nadir and V10 (regression coefficient (β)=−0.060, p=0.009) and V20 (β=−0.044, p=0.010). In the combined cohort, the (adjusted) β estimates for log(WBC) vs. V10 and V20 were: −0.022 (p=0.025) and −0.021 (p=0.002), respectively. Patients with V10 ≥ 95% were more likely to experience grade ≥ 3 leukopenia (68.8% vs. 24.6%, p<0.001) as were patients with V20 > 76% (57.7% vs. 21.8%, p=0.001). CONCLUSIONS These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V10 < 95% and V20 < 76% may reduce HT.

Dosimetric predictors of acute haematological toxicity in oesophageal cancer patients treated with neoadjuvant chemoradiotherapy

“…2,4,5 Furthermore, myelotoxicity has been identified as a significant poor prognostic factor in patients with T4 EC treated with CRT followed by curative resection. 6 Pelvic radiotherapy and chemotherapy are known to be myelosuppressive in patients with cervical and anal cancers, [7][8][9][10][11][12][13] and radiation oncologists have implemented efforts to mitigate the degree of haematological toxicity (HT) associated with these treatments. Given that the thorax contains approximately 35% of the functional BM, 14 irradiation of these thoracic structures could destroy radiosensitive BM stem cells and contribute to HT in patients with EC.…”

“…V x indicates the total organ volume percentage exceeding a radiation dose of x (Gy). Results: Greater thoracic vertebrae and rib irradiation doses, including mean vertebral dose (MVD), thoracic vertebrae V 5-30 (TVV ), mean rib dose and rib V [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] , were associated with increased leukopenia (grade $ 3) risk. Additional BM sites (sternum, scapulae and clavicles) did not influence HT.…”

Clinical value of concurrent radiochemotherapy in cervical cancer and comparison of ultrasonography findings before and after radiochemotherapy

“…Radiotherapy remains an important local treatment of malignant tumors, with about 70% of cancer patients requiring radiotherapy during treatment; about 40% of all cancers can be eradicated with radiotherapy (Taylor et al, 2005;Eifel, 2006;Forrest et al, 2010;Lim et al, 2011;Rose et al, 2011). In the treatment of cervical cancer, radiotherapy can kill residual tumor cells present after surgery, which effectively prevents recurrence and metastasis.…”

Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

“…Previous normal tissue complication probability modeling studies have found that acute HT is associated with increased radiation dose to the pelvic BM in patients undergoing CRT (14,15). Furthermore, sparing ABM using intensity modulated RT (IMRT) may be an effective strategy to reduce HT (16,17).…”