WITHDRAWN: Radiation-induced acute injury of intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy in induction chemotherapy followed by concurrent chemoradiotherapy for nasopharyngeal carcinoma: a prospective cohort study

Abstract

Background: Induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) was the new standard treatment for nasopharyngeal carcinoma (NPC). We aimed to address whether the addition of intensity-modulated radiotherapy (IMRT) compared to three-dimensional conformal radiotherapy (3D-CRT) aggravate radiation-induced acute injury of these patients. Methods: We conducted a prospective study of consecutive patients with biopsy-proven nonmetastatic NPC who newly underwent radiotherapy and sequentially received IC, followed by CCRT at our institution. Among the 224 patients included, 108 (48.21%) were treated with IMRT and 116 (51.78%) with 3D-CRT. Clinicians evaluated routinely acute injury each day during radiotherapy according to the Radiation Therapy Oncology Group (RTOG). Radiation-induced dermatitis, oral mucositis, bone marrow toxicity and gastrointestinal toxicity were compared using the Kaplan-Meier method and the Log-rank test. Overall survival (OS), locoregional progression-free survival (LRFS) distant metastasis-free survival (DMFS) and progression-free survival (PFS) were analyzed during standard follow-up consultations. Results: There was no difference in patient characteristics between groups; however, IMRT plans had higher docetaxel and nedaplatin compared with 3D-CRT plans. The most severe acute toxicities included oral mucositis in 96.43% and dermatitis in 88.84%. Subset analysis revealed that Grade 3-4 acute dermatitis, oral mucositis and bone marrow toxicity were not significantly lower in the IMRT than 3D-CRT (P>0.05). Patients in IMRT group achieved significantly lower risk of bone marrow toxicity (Hazard ratio [HR]=2.557, P=0.0029) in Kaplan-Meier test, but higher risk of leukopenia (HR=0.492, P=0.0165) and gastrointestinal injury (HR=0.432, P=0.0011). Multivariate analyses also demonstrated that IMRT, male gender and hepatitis were the independent prognostic factor for bone marrow toxicity (HR=2.557, P=0.0032). No significant difference was found between the 3D-CRT and IMRT groups in terms of survival. The use of IMRT was a predictive factor of significantly better short-term efficacy, whereas anemia was a significant independent predictor. Conclusions: In a combined regimen of IC followed by CCRT for the treatment of NPC, IMRT seems to be an aggressive technique with a trend towards increased gastrointestinal and hematological toxicities than those treated with 3D-CRT. Predicting the occurrence time of various side effects is beneficial to early protection and focus on to coherent treatment.