Addition of chemotherapy to intensity-modulated radiotherapy does not improve survival in stage II nasopharyngeal carcinoma patients.

In this study, we examined whether combining neoadjuvant chemotherapy (NAC) and/or concurrent chemotherapy (CC) with intensity-modulated radiotherapy (IMRT) improved survival in patients with stage II nasopharyngeal carcinoma (NPC). Two hundred forty-two stage II NPC patients were enrolled between May 2008 and April 2014 and received radical IMRT with simultaneous integrated boost technique using 6 MV photons; some patient groups also received chemotherapy every 3 weeks for 2-3 cycles. The median follow-up duration was 69 months for all patients. At the last follow-up, 18 patients had experienced treatment failure; locoregional relapse among the IMRT alone, NAC+IMRT, NAC+CCRT, and CCRT occurred in 3, 3, 4 and 5, respectively; distant metastases in 0, 0, 2 and 1, respectively, and there was a statistically significant difference among four groups (P=0.019). The 5-year locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates for all patients were 94.7%, 98.7%, 92.9%, and 93.4%, respectively. Five-year LRRFS, DMFS, PFS, and OS were similar among the IMRT alone, NAC+IMRT, NAC+CCRT, and CCRT treatment groups. Univariate and multivariate analyses revealed that a combined regimen was not an independent prognostic factor for any survival outcome. However, patients who received IMRT plus chemotherapy experienced more acute adverse events than those who received IMRT alone. Thus, the addition of NAC and/or CC to IMRT did not improve survival outcomes, but was associated with higher incidences of acute treatment-associated toxicities than IMRT alone in patients with stage II NPC.

Gemcitabine/cisplatin induction chemotherapy before concurrent chemotherapy and intensity-modulated radiotherapy improves outcomes for locoregionally advanced nasopharyngeal carcinoma.

Addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CC) is an encouraging first-line treatment strategy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We evaluated the clinical efficacy and toxicity of addition of gemcitabine plus cisplatin (GP) IC to intensity-modulated radiotherapy (IMRT) and CC for patients with locoregionally advanced NPC. At a median follow-up duration of 48 months (10-59 months), 4-year local relapse-free survival (LRFS) was 86.9%, regional relapse-free survival (RRFS) was 90.6%, distant metastasis-free survival (DMFS) was 79.8%, progression-free survival (PFS) was 77.0%, and overall survival (OS) was 81.9%. Univariate analysis revealed that T stage, N stage, clinical stage, and CC correlated with OS, while N stage and clinical stage correlated with PFS. In multivariate analysis, T4 was a prognostic indicator of poor OS and PFS, and N3 was a prognostic indicator of poor OS. Having received ≥ 2 cycles of IC was prognostic of better RRFS. During IC, grade 3-4 thrombocytopenia occurred in 10 patients, and grade 3-4 leukocytopenia was observed in 16 patients. Two patients developed mild liver dysfunction. These findings indicate that GP-based IC followed by CC has promising efficacy with acceptable toxicities.

Association of the neoadjuvant chemotherapy cycle with survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma: a propensity-matched analysis.

Neoadjuvant chemotherapy (NAC) is widely used to treat locoregionally advanced nasopharyngeal carcinoma (NPC). To determine the optimal number of NAC cycles, we assessed the effect of NAC cycle on survival outcomes of locoregionally advanced NPC patients receiving NAC before concurrent chemotherapy and intensity-modulated radiotherapy. Clinical data from 1,188 non-metastatic NPC patients were retrospectively reviewed. All received ≥2 cycles of NAC added to concurrent chemoradiotherapy. Propensity score matching (PSM) was used to identify paired patients according to various covariates. In total, 297 pairs were selected. After a median follow-up time of 57 months (range: 7 to 104 months), the 5-year locoregional relapse-free survival, distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival rates in patients treated with 2 cycles vs. 3 to 4 cycles of NAC were 91.3% vs. 87.2% (P=0.149), 93.3% vs. 88.5% (P=0.043), 88.7% vs. 81.7% (P=0.037), and 94.0% vs. 92.6% (P=0.266), respectively. On multivariate analysis, 2 cycles of NAC were associated with improved DMFS (hazard ratio, 0.499; P=0.038) and PFS (hazard ratio, 0.585; P=0.049). NAC cycle was an independent prognosticator of DMFS and PFS in univariate and multivariate analyses. Thus, 2 cycles of NAC appear sufficient, as additional cycles were not associated with added survival benefit for locoregionally advanced NPC.

Addition of 5-fluorouracil to first-line induction chemotherapy with docetaxel and cisplatin before concurrent chemoradiotherapy does not improve survival in locoregionally advanced nasopharyngeal carcinoma.

Although a multicenter, randomized study indicated that induction chemotherapy (IC) with docetaxel/cisplatin/fluorouracil (TPF) before concurrent chemoradiotherapy (CCRT) improves survival outcomes, it remains unclear whether TPF is the best IC regimen for treating locoregionally advanced nasopharyngeal carcinoma (NPC). Our aim was to compare the efficacy and toxicities of TPF vs. docetaxel/cisplatin (TP) IC followed by CCRT in patients with locoregionally advanced NPC. One hundred thirty-two patients with locoregionally advanced NPC received 21-day cycles of IC with either TPF or TP. Both were followed by intensity-modulated radiotherapy concurrent with the cisplatin treatment every 3 weeks. Three-year rates of locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival were respectively 96.4%, 87.7%, 86.0%, and 94.7% for patients in the TPF arm patients and 90.3%, 91.9%, 85.2%, and 92.0% for patients in the TP arm. There were no differences in survival between the two arms. Multivariate analysis revealed the IC regimen was not an independent prognostic factor for any survival outcome. However, patients in the TP arm experienced fewer grade 3/4 toxicities. In sum, IC with docetaxel and cisplatin is associated with similar efficacy and less toxicity than the TPF regimen. Addition of fluorouracil to docetaxel plus cisplatin IC is therefore not recommended for patients with locoregionally advanced NPC.

Outcome and long-term efficacy of four facio-cervical fields conformal radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To evaluate the outcomes of 255 patients with nasopharyngeal carcinoma (NPC) treated with four facio-cervical fields conformal radiotherapy (4F-CRT). RESULTS: In one patient's 3 different RT treatment modalities, the 4F-CRT techniques resulted in sharper of the dose-volume histograms (DVHs) for primary gross tumor volume (PGTVnx) and planning target volume (PTVnx), similar to the intensity modulated radiation therapy (IMRT). The median follow-up duration was 43 months. Locoregional relapse and distant metastases as the first treatment failure events occurred in 32 (32/255, 12.5%) and 20 (30/255, 11.8%) patients, respectively. The 3-year and 5-year local control, disease-free survival, and overall survival rates were 83.3%, 82%, 83.8%, and 76.1%, 73.2%, 76.3% respectively. Univariate analysis displayed that clinical stage, T-stage, N-stage, and tumor response were related to prognosis. Multivariate analysis indicated that age, T-stage, N-stage, and combined chemotherapy were independent prognosticators. The incidence of grade 1-2 acute mucositis and leukocytopenia were 93.7% and 91.0%, respectively, with no cases of grade 4 toxicity detected. MATERIALS AND METHODS: From November 2007 to December 2011, 255 patients with histologically diagnosed, non-metastatic NPC were enrolled into this study and received 4F-CRT. Magnetic resonance imaging scans of the nasopharynx were performed on every patient. All patients received definitive radiotherapy with 6 MV X-rays using conventional fractions at 2 Gy daily, 5 fractions per week, and 231 patients with stage IIb-IV received concurrent chemotherapy and cisplatin-based adjuvant chemotherapy. The accumulated survival was calculated according to the Kaplan-Meier method; the log-rank test was used to compare survival differences. Multivariate analysis was performed using Cox's proportional hazard model. CONCLUSIONS: Compared with the conventional treatment plans, the 4F-CRT plan delivered more dose to cover the tumor volume and reduces the doses of the normal tissues including the parotid gland, TMJs and so on. The long-term efficacy of 4F-CRT is satisfactory and its toxicities are tolerable.

Optimization of the margin expanded from the clinical to the planned target volume during intensity-modulated radiotherapy for nasopharyngeal carcinoma.

During the radiotherapy process, the emergence of set-up errors is nearly inevitable. Because set-up errors were not detected and corrected daily, planned target volumes were formed by expanding the clinical target volume according to each unit's experience. We optimized the margins of clinical and planned target volumes during administration of intensity-modulated radiotherapy for nasopharyngeal carcinoma. A total of 72 patients newly diagnosed with non-metastatic nasopharyngeal carcinoma and treated with Tomotherapy were prospectively enrolled in the study. For each patient, one megavoltage computed tomography scan was obtained after conventional positioning, online correction, and daily tomotherapy delivery. The interfraction set-up errors were determined using a planning CT based on the registered scan. The mean interfraction errors were -2.437±2.0529 mm, 0.0652±2.3844 mm, 0.318±1.8314 mm, and 0.197±1.8721° for the medial-lateral, superior-inferior, and anterior-posterior directions, and the direction of rotation, respectively. The total MPTV in the three directions was 7.53 mm, 1.83 mm, and 2.08 mm, respectively. The 3-mm margins in the superior-inferior and anterior-posterior directions uniformly expanded from the clinical target volume should be sufficient, and the marging in the medial-lateral direction was up to 7.5 mm. These results suggest that personalized MPTV may be adopted for intensity-modulated radiotherapy planning.

Addition of 5-fluorouracil to docetaxel/cisplatin does not improve survival in locoregionally advanced nasopharyngeal carcinoma.

Addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) is a potentially effective approach for treating locoregionally advanced nasopharyngeal carcinoma (NPC). In this study, we compared the efficacy and toxicity of IC regimens consisting of docetaxel plus cisplatin with (TPF) or without (TP) 5-fluorouracil followed by CCRT in these patients. Clinical data from 245 propensity score-matched pairs of newly diagnosed non-metastatic NPC patients who received either TPF or TP IC before CCRT were retrospectively reviewed. After a median follow-up of 60 months, 5-year locoregional relapse-free, distant metastasis-free, progression-free, and overall survival rates were 95.6%, 94.7%, 90.4%, and 92.9% in TPF arm patients and 96.7%, 94.2%, 91.7%, and 91.0% in TP arm patients, respectively. There were thus no differences in survival between the two arms. Multivariate analysis revealed that IC regimen was not an independent prognostic factor for any of the survival outcomes. However, patients who received TP experienced lower incidences of grade 3/4 toxicities than those who received TPF. These results indicate that omission of 5-fluorouracil from TPF-based IC did not affect survival outcomes, but was associated with reduced toxicity, in patients with locoregionally advanced NPC.