Efficacy of concurrent chemoradiotherapy alone for loco-regionally advanced nasopharyngeal carcinoma: long-term follow-up analysis.

BACKGROUND: To analysis the clinical outcomes of concurrent chemoradiotherapy (CCRT) alone based on 10-year results for loco-regionally advanced nasopharyngeal carcinoma (LANPC), so as to provide evidence for individualized treatment strategy and designing appropriate clinical trial for different risk LANPC patients. METHODS: Consecutive patients with stage III-IVa (AJCC/UICC 8th) were enrolled in this study. All patients received radical intensity-modulated radiotherapy (IMRT) and concurrent cisplatin chemotherapy (CDDP). The hazard ratios (HRs) of death risk in patients with T3N0 was used as baseline, relative HRs were calculated by a Cox proportional hazard model to classify different death risk patients. Survival curves for the time-to-event endpoints were analyzed by the Kaplan-Meier method and compared using the log-rank test. All statistical tests were conducted at a two-sided level of significance of 0.05. RESULTS: A total of 456 eligible patients were included. With 12-year median follow-up, 10-year overall survival (OS) was 76%. 10-year loco-regionally failure-free survival (LR-FFS), distant failure-free survival (D-FFS) and failure-free survival (FFS) were 72%, 73% and 70%, respectively. Based on the relative hazard ratios (HRs) of death risk, LANPC patients were classified into 3 subgroups, low-risk group (T1-2N2 and T3N0-1) contained 244 patients with HR < 2; medium-risk group (T3N2 and T4N0-1) contained 140 patients with HR of 2 - 5; high-risk group (T4N2 and T1-4N3) contained 72 patients with HR > 5. The 10-year OS for patients in low-, medium-, and high-risk group were 86%, 71% and 52%, respectively. Significantly differences of OS rates were found between each of the two groups (low-risk group vs. medium-risk group, P < 0.001; low-risk group vs. high-risk group, P < 0.001; and medium-risk group vs. high-risk group, P = 0.002, respectively). Grade 3-4 late toxicities included deafness/otitis (9%), xerostomia (4%), temporal lobe injury (5%), cranial neuropathy (4%), peripheral neuropathy (2%), soft tissue damage (2%) and trismus (1%). CONCLUSIONS: Our classification criteria demonstrated that significant heterogeneity in death risk among TN substages for LANPC patients. IMRT plus CDDP alone maybe suitable for low-risk LANPC (T1-2N2 or T3N0-1), but not for medium- and high-risk patients. These prognostic groupings provide a practicable anatomic foundation to guide individualized treatment and select optimal targeting in the future clinical trials.

The benefit of adjuvant radiotherapy on overall survival in resected stage I to II pancreatic cancer: A propensity-adjusted analysis.

BACKGROUND: The survival time of patients with early pancreatic cancer (PC) is still disappointing, even after surgical resection. PC has an extremely poor prognosis. Herein, we aimed to investigate the survival effect of postoperative radiotherapy (PORT) on resected stage I to II PC. MATERIAL AND METHODS: A large eligible sample of patients was identified from 2010 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) registry. Survival analysis was conducted to evaluate the efficiency of PORT. Propensity score matching (PSM) analysis was used to reduce selection bias and to make the groups comparable. RESULTS: A total of 3219 patients with resected stage I to II PC was included after rigid screening. The median overall survival (OS) was 26 months with PORT (n = 1055) versus 21 months with non-PORT (n = 2164) before matching (p<0.001). By multivariable analysis, PORT remained a favorable prognostic predictor for OS. In PSM analysis, receiving PORT was associated with improved OS (median, 26 months vs. 23 months; at 2 years, 51.7% vs. 46.7%; at 5 years, 23.3% vs. 17.4% (P = 0.006). After further meticulous exploration, only the stage IIB subgroup benefited from PORT (p<0.001). This result was due to the positive lymph node state (N+), whose mortality risk was cut by 23.4% (p<0.001) by PORT. CONCLUSION: Addition of PORT to the treatment of patients with resected stage I to II PC conveys a survival benefit, particularly among those with N-positive or stage IIB disease.

A Pilot Study: N-Staging Assessment of Shear Wave Elastrography in Small Cervical Lymph Nodes for Nasopharyngeal Carcinoma.

Purpose: To investigate N-staging Assessment of pretreatment Shear wave elastrography (SWE) in small cervical lymph nodes (0. 5 cm ≤ maximum diameter < 1 cm, intact capsule, no central necrosis, sCLNs) in nasopharyngeal carcinoma (NPC) patients. Methods: Pathological biopsy proven 28 NPC patients with sCLNs shown in pretreatment magnetic resonance (MR) images and 40 target lymph nodes were enrolled. All target lymph nodes were divided into metastasis and benign lymph node groups according to pathology. SWE was used to exam the real time SWE imaging of each target lymph nodes before conducting ultrasonography guided fine needle biopsy. The minimum (Emin), maximum (Emax), and mean (Emean) elasticity indices (kPa) of target lymph nodes were recorded. The SWE examination was repeated three times for the same target lymph node and each elasticity indices for statistic was determined by average of three measurements. SPSS 21.0 statistics software is used for statistical analysis. The receiver operating characteristic (ROC) curve was performed to obtain the cutoff value of elasticity indices of metastatic sCLNs. Statistical significance was assumed when the P < 0.05. Results: Nine lymph nodes were metastatic and 31 were benign. The Emin, Emax, and Emean of benign group were 8.15 ± 6.12, 25.05 ± 12.37, and 16.05 ± 8.29 kPa, respectively; Emin, Emax, and Emean of metastasis group were 11.5 ± 6.17, 41.38 ± 17.87, and 23.48 ± 6.50 kPa, respectively. The difference of the Emax and Emean between metastasis and benign group were statistically significant (P = 0.003 and 0.018). The area under the ROC curve of Emin, Emax, and Emean of metastasis lymph node were 0.685 (P = 0.095), 0.785 (P = 0.010), and 0.765 (P = 0.017), respectively. Emax of 27 kPa and Emean of 17 kPa were taken as the cutoff value of diagnosis for metastasis sCLNs: the sensitivity, specificity, and accuracy were 77.8 and 100%, 71.0 and 61.3%, 75.0 and 70.0%, respectively. Conclusions: Pretreatment SWE has high accuracy in evaluating the sCLNs in NPC patients and is helpful for accurate N-staging and survival prognosis. It can be used as a clinical supplementary examination.

Pathologic study of tumour extension for clinically localized unilateral nasopharyngeal carcinoma: Should the contralateral side be included in the clinical target volume?

INTRODUCTION: The clinical target volume (CTV) delineation is crucial for tumour control and normal tissue protection. This study investigated the contralateral extension of nasopharyngeal carcinoma (NPC) in patients with a clinically diagnosed unilateral tumour to pursue the possibility of CTV reduction. METHODS: Twenty NPC patients with localized tumours confined to only one side of the nasopharynx as shown by magnetic resonance imaging and fibreoptic endoscopy were selected for biopsy. The tissues of the contralateral pharyngeal recess (CPR) and the contralateral posterosuperior wall (CPSW) of the nasopharynx were obtained in each case and prepared for pathological examination. The factors associated with contralateral tumour infiltration were analysed. RESULTS: Five of 20 (25.0%) patients were pathologically confirmed to have carcinoma cell infiltration in the CPSW, including 2 (10.0%) that had carcinoma cell infiltration in the CPR. The T classification (P = 0.014) and primary tumour volume (P = 0.033) were positively associated with the infiltration of the CPSW, but none of the primary tumour factors affected the involvement of the CPR. The contralateral retropharyngeal lymph node (LN) metastasis (P = 0.016), but not the contralateral cervical LN, was significantly associated with the infiltration of the CPR. Positive Epstein-Barr virus DNA (EBV-DNA) was another factor that increased the probability of CPR invasion (P = 0.044). CONCLUSIONS: Contralateral pharyngeal recess infiltration is rare in patients with clinically diagnosed unilateral primary NPC. Reduced CTV coverage, including the CPSW but not CRP, is feasible for patients with unilateral cancer of the nasopharynx without contralateral LN metastasis or positive EBV-DNA. Further large-sample studies are needed.

The Feasibility Study of a Hybrid Coplanar Arc Technique Versus Hybrid Intensity-modulated Radiotherapy in Treatment of Early-stage Left-sided Breast Cancer with Simultaneous-integrated Boost.

This study demonstrated the feasibility and advantages of a hybrid, volumetric arc therapy technique that used two 90° coplanar arcs and two three-dimensional conformal tangential beams in the simultaneous-integrated boost radiotherapy of left-sided breast cancer after breast-conserving surgery. A total of nine patients with stage I, left-sided breast cancer who underwent breast-conserving surgery were selected for this retrospective study. For each patient, a hybrid arc plan was generated and then compared with two hybrid intensity-modulated radiotherapy plans. All plans were optimized using the same objectives and dose constraints. The prescription dose was 50.4 Gy to the planning target volume with simultaneous boost to 60 Gy to the expanded gross target volume in 28 fractions. The differences among these hybrid plans were analyzed by the Kolmogorov-Smirnov test or the Wilcoxon rank sum test. The hybrid arc plans achieved the clinical requirements of target dose coverage and normal tissue (NT) dose constraints. It was found that the hybrid arc plans showed advantages in the conformity index of the expanded gross target volume, the V5 of the heart, the D2 of the left ventricle, and the D2 and V50.4 of NTs. The average beam-on time and monitor units of the hybrid arc plans were significantly lower (P < 0.001).

Distant metastasis risk and patterns of nasopharyngeal carcinoma in the era of IMRT: long-term results and benefits of chemotherapy.

PURPOSE: To report the distant metastasis (DM) risk and patterns for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and to analyze the benefits of chemotherapy based on DM risk. MATERIALS AND METHODS: 576 NPC patients were analyzed. The DM rates were calculated using the Kaplan-Meier method, and the log-rank test was used to compare differences. The patients were divided into different risk subclassifications according to DM hazard ratios. RESULTS: 91 patients developed DM after treatment, with bone as the most common metastatic sites. 82.4% of DMs occurred within 3 years of treatment. Patients were classified as low-risk, intermediate-risk and high-risk, and the corresponding 5-year DM rates were 5.1%, 13.1% and 32.4%, respectively (P < 0.001). Chemotherapy failed to decrease the DM rate in the low-risk subclassification, but decreased the DM risk in the intermediate-risk subclassification (P = 0.025). In the high-risk subclassification, the DM rate was 31.9% though chemotherapy was used, which was significantly higher than that of other two subclassifications. CONCLUSIONS: DM is the dominant treatment failure in NPC treated by IMRT, with similar occurrence times and distributions to those that occurred in the era of conventional radiotherapy. Further studies on treatment optimization are needed in high-risk patients.

Risk factors and prediction-score model for distant metastasis in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

The objective of this study is to identify the risk factors and construct a prediction-score model for distant metastasis (DM) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). A total of 520 nonmetastatic NPC patients were analysed retrospectively. The independent risk factors for DM were tested by multivariate Cox regression analysis. The prediction-score model was established according to the regression coefficient. The median follow-up was 88.4 months. The 5-year DM rate was 15.1%. N2-3, primary tumour volume of nasopharynx (GTVnx) >24.56 cm(3), haemoglobin change after treatment (ΔHGB) >25.8 g/L, albumin-globulin ratio (AGR) ≤1.34, pretreatment neutrophil-lymphocyte ratio (NLR) >2.81 and pretreatment serum lactate dehydrogenase (LDH) >245 U/L were significantly adverse independent predictive factors for DM. Three subgroups were defined based on the prediction-score model: low risk (0-2), intermediate risk (3-4) and high risk (5-8). The 5-year DM rates were 4.6, 21.8 and 50.8%, respectively (P < 0.001). The areas under the curve for DM in the prediction-score model and the UICC/AJCC staging system seventh edition were 0.748 and 0.627, respectively (P < 0.001). The scoring model is useful in evaluating the risk of DM in IMRT-treated NPC patients and guiding future therapeutic trials. Further prospective study is needed.