Study Population
The ethics committee of Sun Yat-sen University Cancer Center approved this prospective study and all patients signed written informed consent before the first treatment. We enrolled 122 newly diagnosed NPC patients with no prior treatment and referred to NAC from September 2017 to December 2019. However, we excluded three patients from the study for the following reasons: two patients were due to the small thickness, and one had inadequate image quality due to serious motion on MRI examination. Ultimately, the final study population consisted 119 patients. All enrolled patients were candidates to receive cisplatin-based NAC for 2 cycles every 21 days, and then underwent follow-up MRI. In each cycle, 100 patients received cisplatin (DDP, Qilu Pharmaceutical, Shandong, China) 100 mg/m2 plus Taxol (PTX, Hainan Chuntch Pharmaceutical, Hainan, China) 135 mg/m2 given on day 1. The other 19 patients received cisplatin 100 mg/m2 given on days 1 plus Gemcitabine (GEM, Jiangsu Hansoh Pharmaceutical, Jiangsu, China) 1000 mg/m2 given on days 1 and 8. All patients were hydrated one day before the application of Cisplatin and two days after the application of Cisplatin in order to protect the patients’ renal function
MRI Acquisition
All of the examinations were performed using a 1.5 T MRI scanner (Aera, Siemens Healthcare, Germany) with a 20-channel head and neck combined coil. Routine clinical MRI examination contained RESOLVE-DWI sequence, and the parameters were as follows: field of view, 24 cm × 24 cm; section thickness, 5 mm; intersection gap, 1 mm; number of sections, 30; repetition time, 6100 milliseconds; echo time, 84 milliseconds; matrix, 208 × 208; number of readout segment, 5; fat suppression, fat sat. Strong; b value, 0 and 1000s/mm2; acquisition time, 2 minutes 45 seconds. Every patient enrolled was done the MRI examinations above before the treatment and after two cycles of NAC.
Images Analysis
The T2-weighted and DWI images were evaluated independently by three radiologists with more than 10 years experiences, and any differences were resolved by consensus. The morphological regression of tumors was measured according to T2-weighted images from the both MRI examinations. Meanwhile, at the first MRI examination, three region of interests (ROIs) were drawn manually at the largest section of the tumor and its adjacent up/down sections on ADC maps referring to T2-weighted images, avoiding the hemorrhagic and necrotic region, and the ADC values obtained from the above three ROIs were averaged to obtained the final results (Fig. 1).
The patients were classified into responders and non-responders based on Response Evaluation Criteria in Solid Tumors (RECIST)[20]. Responders were defined as completed response (CR) and partially response (PR) patients, while non-responders were referred to as stable response (SD) or progressed on the follow-up MRI.
All patients’ TNM stage were determined by radiologists with reference to the 8th edition of the International Union against Cancer/ American Joint Committee on Cancer (UICC/AJCC) manual.
Statistical Analysis
The consistency between observers was evaluated by intra-class correlation coefficient (ICC), and an ICC of 1.0 was considered to indicate perfect agreement; 0.81–0.99 indicated almost perfect agreement; 0.61–0.80, substantial agreement; 0.41–0.60, moderate agreement; 0.21–0.40, fair agreement; and ≤ 0.20, slight agreement[21]. The data of ADC values was assessed for normality with the Shapiro-Wilk test. The Independent sample t-test was used to compare the ADC values of responders and non-responders. Categorical or continuous variables (age, gender, T classification, N classification and clinical stage) were compared using the Chi-square test. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) and 95% confidence intervals (CI) were calculated to evaluate the diagnostic efficiency of the ADC values in distinguishing responders and non-responders. All of the analyses were performed using the SPSS 25.0 statistical software package (https://www.ibm.com/support/pages/node/589145), with a value of two-tailed p < 0.05 considered to be a significant difference.