Salvage treatment for locally recurrent nasopharyngeal carcinoma (NPC) is complicated and relatively limited. Radiotherapy, combined with effective concomitant chemotherapy, may improve clinical treatment outcomes. We conducted a phase II randomized controlled trial to evaluate the efficacy of intensity-modulated radiotherapy with concomitant weekly cisplatin on locally recurrent NPC. Between April 2002 and January 2008, 69 patients diagnosed with non-metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group (n = 34) or radiotherapy alone group (n = 35). All patients received intensity-modulated radiotherapy. The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days (range 23–53 days). The concomitant chemotherapy schedule was cisplatin 30 mg/m2 by intravenous infusion weekly during radiotherapy. The median follow-up period of all patients was 35 months (range 2–112 months). Between concomitant chemoradiotherapy and radiotherapy groups, there was only significant difference in the 3-year and 5-year overall survival (OS) rates (68.7% vs. 42.2%, P = 0.016 and 41.8% vs. 27.5%, P = 0.049, respectively). Subgroup analysis showed that concomitant chemoradiotherapy significantly improved the 5-year OS rate especially for patients in stage rT3–4 (33.0% vs. 13.2%, P = 0.009), stages III–IV (34.3% vs. 13.2%, P = 0.006), recurrence interval >30 months (49.0% vs. 20.6%, P = 0.017), and tumor volume >26 cm3 (37.6% vs. 0%, P = 0.006). Compared with radiotherapy alone, concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC, especially those with advanced T category (rT3–4) and stage (III–IV) diseases, recurrence intervals >30 months, and tumor volume >26 cm3.

Little is known about the nature of metastasis to small cervical lymph nodes (SCLNs) in the patients with nasopharyngeal carcinoma (NPC) examined by using 18-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). The present study aimed to evaluate the diagnostic values of PET/CT in identifying metastasis in SCLNs in NPC patients. Magnetic resonance images (MRI) and PET/CT scans for 470 patients with newly diagnosed, non-distant metastatic NPC were analyzed. Metastatic rates of SCLNs were defined by the positive number of SCLNs on PET/CT scans and total number of SCLNs on MRI scans. Receiver operating characteristic curve was applied to compare PET/CT-determined stage with MRI-determined stage. In total, 2082 SCLNs were identified, with 808 (38.8%) ≥ 5 and < 6 mm in diameter (group A), 526 (25.3%) ≥ 6 and < 7 mm in diameter (group B), 374 (18.0%) ≥ 7 and < 8 mm in diameter (group C), 237 (11.4%) ≥ 8 and < 9 mm in diameter (group D), and 137 (6.5%) ≥ 9 and < 10 mm in diameter (group E). The overall metastatic rates examined by using PET/CT for groups A, B, C, D, and E were 3.5%, 8.0%, 31.3%, 60.0%, and 83.9%, respectively (P < 0.001). In level IV/Vb, the metastatic rate for nodes ≥ 8 mm was 84.6%. PET/CT examination resulted in modification of N category and overall stage for 135 (28.7%) and 46 (9.8%) patients, respectively. The areas under curve of MRI-determined and PET/CT-determined overall stage were 0.659 and 0.704 for predicting overall survival, 0.661 and 0.711 for predicting distant metastasis-free survival, and 0.636 and 0.663 for predicting disease-free survival. PET/CT was more effective than MRI in identifying metastatic SCLNs, and the radiologic diagnostic criteria for metastatic lymph nodes in level IV/Vb should be re-defined.

Hepatitis B virus (HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B (hepatitis B surface antigen [HBsAg]-negative and hepatitis B core antibody [HBcAb]-positive). This study aimed to assess HBV reactivation and hepatitis occurrence in diffuse large B-cell lymphoma (DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reactivation and hepatitis occurrence and to analyze whether HBV reactivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B. We reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center, China. Predictive factors for HBV reactivation, hepatitis development, and survival were examined by univariate analysis using the chi-square or Fisher’s exact test and by multivariate analysis using the Cox regression model. Among the 278 patients, 165 were HBsAg-negative. Among these 165 patients, 6 (10.9%) of 55 HBcAb-positive (resolved HBV infection) patients experienced HBV reactivation compared with none (0%) of 110 HBcAb-negative patients (P = 0.001). Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients (21.8% vs. 8.2%, P = 0.013). HBcAb positivity and elevated baseline alanine aminotransferase (ALT) levels were independent risk factors for hepatitis. Among the 55 patients with resolved hepatitis B, patients with elevated baseline serum ALT or aspartate aminotransferase (AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels (P = 0.037, P = 0.005, respectively). An elevated baseline AST level was an independent risk factor for hepatitis in these patients. Six patients with HBV reactivation recovered after immediate antiviral therapy, and chemotherapy was continued. HBcAb positivity, HBV reactivation, or hepatitis did not negatively affect the survival of DLBCL patients. DLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reactivation and hepatitis than HBsAg-negative/HBcAb-negative patients. Close monitoring and prompt antiviral therapy are required in these patients.

Background: This prospective study was conducted to evaluate inter- and intra-fraction errors in nasopharyngeal carcinoma (NPC) patients undergoing volumetric modulated arc therapy (VMAT) using cone-beam computed tomography (CBCT) and to thus obtain planning target volume (PTV) margins to effectively guide treatment in the future. Methods: Fifteen NPC patients scheduled to undergo VMAT were prospectively enrolled in the study. For each patient, three CBCT scans were obtained; one after daily conventional positioning, one after online correction with 2 mm tolerance and one after 1 week of VMAT delivery. The scans were registered to the planning CT to determine the inter- and intra-fraction errors. Patient positioning errors were analyzed for time trends over the course of radiotherapy. PTV margins were calculated from the systematic (Σ) and random (σ) errors. Results: The average absolute values of the pre-correction, post-correction and intra-fraction errors (in order) were 1.1, 0.6 and 0.4 mm in the medial–lateral (ML) direction, 1.2, 0.7 and 0.5 mm in the superior–inferior (SI) direction and 1.1, 0.7 and 0.5 mm in the anterior–posterior (AP) direction. The corresponding Σ were 1.0–1.4 mm, 0.4–0.5 mm and 0.2–0.4 mm, while the corresponding σ were 0.7–0.8 mm, 0.6–0.7 mm and 0.5–0.6 mm. With time, gradual increases in both the inter- and intra-fraction three-dimensional displacements were observed (P = 0.019 and P = 0.044, respectively). The total PTV margins accounting for pre-correction and intra-fraction errors were 3.4–4.1 mm and those accounting for post-correction and intra-fraction errors were 1.7–2.2 mm. Conclusions: CBCT is an effective modality to evaluate and improve the accuracy of VMAT in NPC patients. Inter- and intra-fraction three-dimensional displacements increased as a function of time during the course of radiotherapy. In our institution, we recommend a PTV margin of 5 mm for NPC patients undergoing VMAT without CBCT and 3 mm for those treated with rigorous daily CBCT scans.

Background: Famitinib is a tyrosine kinase inhibitor against multiple targets, including vascular endothelial growth factor receptor 2/3, platelet‐derived growth factor receptor, and stem cell factor receptor (c‐kit). Previous studies have demonstrated anti‐tumour activities of famitinib against a wide variety of advanced‐stage solid cancers. We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We also evaluated the feasibility of contrast‐enhanced ultrasound (D‐CEUS) as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy. Methods: The trial was conducted in subjects with stage III or IVa‐b NPC using a 3 + 3 design of escalating famitinib doses. Briefly, subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT. D‐CEUS of the neck lymph nodes was performed at day 0, 8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy. End points included safety, tolerability and anti‐tumour activity. Results: Twenty patients were enrolled (six each for 12.5, 16.5 and 20 mg and two for 25 mg). Two patients in the 25 mg cohort developed dose‐limiting toxicities, including grade 4 thrombocytopenia and grade 3 hypertension. The most common grade 3/4 adverse events were leukopenia, neutropenia and radiation mucositis. D‐CEUS tests showed that more than 60% of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone, and the parameter response was associated with disease improvement. In the famitinib monotherapy stage, three patients (15%) showed partial responses. The complete response rate was 65% at the completion of treatment and 95% 3 months after the treatment ended. After a median follow‐up of 44 months, the 3‐year progression‐free survival (PFS) and distant metastasis‐free survival were 70% and 75%, respectively. Subjects with a decrease of perfusion parameter response, such as peak intensity decreased at least 30% after 1 week of famitinib treatment, had higher 3‐year PFS (90.9% vs. 44.4%, 95% CI 73.7%–100% vs. 11.9%–76.9%, P < 0.001) than those with an increase or a reduction of less than 30%. Conclusions: The recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC. D‐CEUS is a reliable and early measure of efficacy for famitinib therapies. Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.

P21-activated protein kinase 1 (PAK1), a main downstream effector of small Rho GTPases, is overexpressed in many malignancies. PAK1 overexpression is associated with poor prognosis in some tumor types, including breast cancer, gastric cancer, and colorectal cancer. However, the expression and clinical relevance of PAK1 expression in human pancreatic cancer remains unknown. The present study investigated the clinical and prognostic significance of PAK1 expression in pancreatic carcinoma. We examined and scored the expression of PAK1 by immunohistochemistry in 72 primary pancreatic carcinoma samples and 20 liver metastatic samples. The relationships between PAK1 and clinicopathological parameters and prognosis in primary and metastatic pancreatic cancer were analyzed. Among the total 92 cases, primary pancreatic cancer samples had a significantly higher rate (38/72, 52.8%) of high PAK1 expression than liver metastatic samples (5/20, 25.0%) (P = 0.028). Among the 72 primary pancreatic cancer patients, high PAK1 expression was associated with younger age (P = 0.038) and moderately or well differentiated tumor (P = 0.007). Moreover, a positive relationship was found between high PAK1 expression and overall survival (OS) (P < 0.005). Patients with high PAK1 expression had a better OS than those with low PAK1 expression. Univariate and multivariate analysis by Cox regression including PAK1 and other prognostic pathological markers demonstrated high PAK1 immunostaining as a prognostic factor for survival in pancreatic cancer patients (P < 0.005). We report for the first time that PAK1 is a novel prognostic marker for pathologically confirmed human pancreatic cancer. Reduced expression of PAK1 correlates with poor histological differentiation in pancreatic cancer.