Weiwei Xiao

Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities.

BACKGROUND AND PURPOSE To evaluate the long-term survival outcomes and toxicity of NPC patients treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS From May 2001 to October 2008, 868 non-metastatic NPC patients treated by IMRT were analyzed retrospectively. The Radiation Therapy Oncology Group (RTOG) criteria were used to assess toxicity. RESULTS With a median follow-up of 50 months (range, 5-115 months), the 5-year estimated disease specific survival (DSS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) were 84.7%, 91.8%, 96.4% and 84.6%, respectively. Of the 868 patients, 186 (21.3%) developed failure after treatment. Distant metastasis was the major failure pattern after treatment. The 5-year OS rate in patients with stage I, II, III, and IVa-b were 100.0%, 94.3%, 83.6%, and 70.5%, respectively. The 5-year LRFS rate in patients with stage T1, T2, T3, and T4 disease were 100.0%, 96.0%, 90.4%, and 83.3%, respectively (χ(2) = 26.32, P<0.001). The 5-year DMFS for N0, N1, N2, and N3 patients were 96.1%, 85.6%, 73.7%, and 62.1%, respectively (χ(2) = 65.54, P<0.001). Concurrent chemotherapy failed to improve survival rates for patients with advanced locoregional disease. The most common acute toxicities were mainly in grade 1 or 2. Compared with IMRT alone, IMRT plus concurrent chemotherapy increased the severity of acute toxicities. The incidence of brain radiation damage was relatively high (5.5%, 48/868 cases), and was not observed in patients with stage T1-2. CONCLUSION IMRT for NPC yielded excellent survival outcomes, and distant metastasis was the most commonly seen failure pattern after treatment. The role of concurrent chemotherapy for advanced locoregional stage NPC patients needs to be further investigated. Treatment-related toxicities were well tolerable. However, the incidence of brain radiation damage was relatively high, especially for patients with advanced T-stage.

Late toxicities after intensity-modulated radiotherapy for nasopharyngeal carcinoma: patient and treatment-related risk factors

Background:The objective of this study is to analyse the factors affecting late toxicity for nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT).Methods:Seven hundred and eighty-nine consecutive NPC patients treated with IMRT at our centre from January 2003 to February 2008 were retrospectively analysed. Radiotherapy-related complications were categorised using the RTOG Late Radiation Morbidity Scoring Criteria and the Common Terminology Criteria for Adverse Events (Version 3.0). Two hundred and thirty-three patients were treated with IMRT alone (group 1) and 556 patients underwent cisplatin-based chemotherapy (group 2).Results:Median follow-up was 65 months (range, 4–106 months). The 5-year major late toxicity rate was significantly greater in group 2 than group 1 (63.2% vs 42.0%, P<0.001). Multivariate analyses showed that N category, T category and chemotherapy were significant factors. The maximal dose (Dmax) to the temporal lobe was a significant factor affecting temporal lobe injury (TLI), with a hazard ratio of 1.26 (95% confidence interval (CI), 1.18–1.35; P<0.001) per 1-Gy increase. The 5-year TLI rate increased from 0.8% for 284 lobes with Dmax <65.77 Gy to 27.1% for 176 lobes with greater doses (P<0.001). Logistic regression showed that the hazard ratio attributed to the parotid gland mean dose was 1.36 (95% CI, 1.21–1.53; P<0.001) per 1-Gy increase. Chemotherapy was not a significant factor (P=0.211).Conclusion:With the application of IMRT, the incidence of radiation-related complications has been reduced except for TLI. The significant factors affecting the risk of TLI included T category, chemotherapy and Dmax.

Primary small cell carcinoma of the esophagus: review of 64 cases from a single institution.

Primary small cell carcinoma of esophagus (SCCE) is a rare disease with poor prognosis. The aims of this study are to review the clinical characteristics, treatment modalities, and outcomes of SCCE and to investigate the prognostic factors and optimal treatment options. Sixty-four patients diagnosed as SCCE in Sun Yat-sen University Cancer Center from 1990 to 2011 were retrospectively reviewed. There were 46 patients with limited disease (LD) and 18 with extensive disease. The median survival time (MST) and overall survival rate were calculated and compared by the Kaplan-Meier method and log-rank test, respectively. The prognostic factors were calculated by Cox hazards regression model. With a median follow up of 11.6 months, the MST of all the 64 patients was 12.6 months, 16.5 months for LD and 9.0 months for extensive disease. The 1-, 3-, and 5-year overall survivals were 52.5%, 20.9%, and 7.5%, respectively. In univariate analysis, patients with ECOG performance score <2 (P = 0.009), lesion length ≤5 cm (P = 0.009), T stage ≤2 (P = 0.004), LD (P = 0.000), and multimodality treatment (P = 0.016) had significant associations with MST. Multivariate analysis showed that ECOG performance score (P = 0.001), T stage (P = 0.023), limited-extensive stage (P = 0.007), and treatment modality (P = 0.008) were independent prognostic factors. Locoregional treatment combined with chemotherapy had a trend to increase MST from 15.3 to 20.0 months in LD patients (P = 0.126), while combined chemotherapy had a significant impact on MST in extensive disease patients (P = 0.000). SCCE is a highly malignant disease with poor prognosis. Patients might obtain survival benefit from the combination of locoregional treatment and systemic therapy. Prospective studies are needed to validate these factors.

Positron emission tomography–computed tomography before treatment is highly prognostic of distant metastasis in nasopharyngeal carcinoma patients after intensity-modulated radiotherapy treatment: A prospective study with long-term follow-up

OBJECTIVES The utility of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the prediction of distant metastasis after definitive treatment for non-disseminated NPC patients is not clear. We prospectively investigated the prognostic significance of (18)F-FDG PET-CT performed before treatment for the distant metastasis-free survival (DMFS) of NPC patients treated with intensity-modulated radiotherapy (IMRT) ± chemotherapy. MATERIALS AND METHODS The results of PET-CT scans performed at initial diagnosis were recorded and analyzed prospectively. Patients then received standard treatment per protocol independent of the PET-CT result. IMRT was administered to the nasopharynx and neck. Early stage patients received IMRT alone, whereas loco-regionally advanced patients received concurrent chemoradiation. Patient outcomes were evaluated. RESULTS One hundred and seventy-nine patients were analyzable. DM occurred in 33 patients and the 3-year DMFS rate of the whole cohort was 84.1%. The cut-off of the SUVmax at the primary site (SUVmax-P) for DMFS was 10.22 by ROC curve. The 3-year DMFS rates of the higher and lower SUVmax-P groups (SUVmax-P⩽or>10.22) were 93.2% and 75.1%, respectively, with an 18.1% difference (P=0.003). Multivariate analysis indicated that SUVmax-P was a risk factor independently associated with DMFS (HR, 2.672; 95%CI, 1.236-5.776; P=0.012) and OS (HR, 2.417; 95%CI, 1.313-4.448; P=0.005). Subgroup analysis indicated that the 5-year DMFS and OS in loco-regionally advanced patients with SUVmax-P⩽10.22 were similar to those of early stage patients, whereas those of loco-regionally advanced patients with SUVmax-P>10.22 patients predicted worse outcome. CONCLUSION SUVmax-P is a useful biomarker to predict distant metastasis of NPC patients treated with IMRT. Combining SUVmax-P with tumor overall stage, a more precise picture could be obtained to predict treatment outcome.

Prognostic significance of tumor volume in locally recurrent nasopharyngeal carcinoma treated with salvage intensity-modulated radiotherapy.

Introduction To evaluate the prognostic value of gross tumor volume (TV) in patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma. Methods Between 2001 and 2012, 291 consecutive patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma underwent salvage IMRT were retrospectively reviewed. The correlations between TV and recurrent T classification were analyzed. Survival analyses were performed. Receiver operating characteristic (ROC) curves were calculated to identify cut-off point of TV. The Akaike information criterion and Harrell’s concordance index (c-index) were utilized to test the prognostic value. Results The median TV significantly increased with advancing recurrent T classification (P<0.001). The 5-year overall survival rate was 33.2% for the entire cohort. On multivariate analysis, TV was an independent negative prognostic factor for distant metastasis-free survival (hazard ratio =1.013, P =0.003), overall survival (hazard ratio = 1.015, P<0.001) and toxicity-related death (hazard ratio = 1.014, P<0.001). The 5-year overall survival rates were 63.1% and 20.8% for patients with a TV < 22 cm3 and TV ≥22 cm3, respectively (P < 0.001). In patient with TV <22 cm3, locoregional failure is the leading cause of death. In patients with TV≥22 cm3, distant metastasis rate is higher and occurred within short term after local recurrence; meanwhile, radiation-induced injuries became more common and led to half of deaths in this group. The Akaike information criterion and c-index analyses indicated that the predictive ability of recurrent T classification improved when combined with TV. Conclusions Our data suggests TV is a significant prognostic factor for predicting the distant metastasis, overall survival and toxicity-related death of patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma after salvage IMRT. TV should be considered when designing personalized salvage treatments for these patients. For patients with bulky local recurrent tumor, radiation may need to be de-emphasized in favor of systemic treatment or best supportive care.

The efficacy and safety of Endostar combined with chemoradiotherapy for patients with advanced, locally recurrent nasopharyngeal carcinoma

Purpose To evaluate the short-term efficacy and safety of recombinant human endostatin (Endostar) combined with chemoradiotherapy for the treatment of advanced, locally recurrent nasopharyngeal carcinoma (NPC). Materials and Methods Between March 2010 and October 2013, a total of 22 patients with stage rIII-IVb locally recurrent NPC underwent salvage radiotherapy with Endostar in Sun Yat-Sen University Cancer Center. Intensity-modulated radiotherapy (IMRT) was delivered. Platinum-based chemotherapy was used in a neoadjuvant protocol. Endostar was continuously administered intravenously (105 mg/m2) for 14 days (Days 1–14) from the first day of treatment during a 21-day cycle. Tumor response and treatment toxicities were observed. Results Until January 2014, the median follow-up time was 13 months (range, 4–41 months). All patients completed the planned radiotherapy. A complete response was achieved in 20 patients, and a partial response was achieved in 2 patients. The incidence of grade 3–5 late radiation injury in this study was 50% (11/22) and that of nasopharyngeal mucosal necrosis was 31.8% (7/22). Conclusions Endostar combined with chemoradiotherapy may be effective in decreasing both the incidence of nasopharyngeal mucosal necrosis. Studies with a larger sample size and longer follow-up are warranted.

Pathological Assessment of the AJCC Tumor Regression Grading System After Preoperative Chemoradiotherapy for Chinese Locally Advanced Rectal Cancer

Abstract We used American Joint Committee on Cancer (AJCC) Staging Manual system to assess the prognostic significance of tumor regression grading (TRG) for locally advanced rectal cancer (LARC) (T3/4 or N+) patients who were treated with preoperative chemoradiotherapy (CRT). The 4 AJCC-TRG classifications were evaluated on surgical specimens from 295 LARC patients receiving CRT. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated using Kaplan–Meier method and Cox regression model. Classifications of TRG 0, 1, 2, and 3 were found in 27.5%, 19.3%, 45.7%, and 7.5% of the resected specimens, respectively. Three-year OS was 95.5% for TRG0, 91.5% for TRG1, 84.8% for TRG2, and 85.7% for TRG3 (P = 0.035). Three-year DFS was 89.0% for TRG0, 74.4% for TRG1, 70.9% for TRG2, and 62% for TRG3 (P = 0.018). By multivariate analysis, AJCC-TRG (P = 0.033), residual lymph node metastasis (ypN+) (P < 0.001) and pretreatment CA19-9 level (P = 0.035) were significant predictors of OS. Pathological T category (P = 0.006) and nodal status (P < 0.001) after CRT were the most important independent prognostic factors for DFS. AJCC-TRG is a prognostic factor for LARC patients receiving CRT, independent of pathological staging.

CCR6 Is a Predicting Biomarker of Radiosensitivity and Potential Target of Radiosensitization in Rectal Cancer

Purpose This study aimed to explore the functions and mechanisms of C-C motif chemokine receptor 6 (CCR6), a gene associated with progression and metastasis of colorectal cancer (CRC), in radiosensitivity of rectal cancer (RC). Materials and Methods RNA sequencing and immunohistochemical analysis on CCR6 expression were performed in pretreatment tissues of RC patients exhibiting different therapeutic effects of radiotherapy. Colonogenic survival assay was conducted in different CRC cell lines to assess their radiosensitivity. And the impact of CCR6 expression on radiosensitivity was validated through RNA interference. The DNA damage repair (DDR) abilities of cell lines with different CCR6 expression were evaluated through immunofluorescence-based γH2AX quantification. Results The CCR6 mRNA level was higher in patients without pathologic complete remission (pCR) than in those with pCR (fold changed, 2.11; p=0.004). High-level expression of CCR6 protein was more common in the bad responders than in the good responders (76.3% vs. 37.5%, p < 0.001). The CRC cell lines with higher CCR6 expression (LoVo and sw480) appeared to be more radioresistant, compared with the sw620 cell line which had lower CCR6 expression. CCR6 knockdown made the LoVo cells more sensitive to ionizing radiation (sensitization enhancement ratio, 1.738; p < 0.001), and decreased their DDR efficiency. Conclusion CCR6 might affect the RC radiosensitivity through DDR process. These findings supported CCR6 as a predicting biomarker of radiosensitivity and a potential target of radiosensitization for RC patients.

The value of shear wave elastography in predicting for undiagnosed small cervical lymph node metastasis in nasopharyngeal carcinoma: A preliminary study

BACKGROUND To investigate the diagnostic value of shear wave elastography (SWE) in identifying cervical small lymph node metastases in nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS This prospective study was approved by the local institutional review board. From July 2014 to March 2016, 114 sLNs from 62 newly diagnosed NPC patients (47 men, 15 women) were assessed. Target small lymph nodes (sLNs), which were undiagnosed by magnetic resonance imaging (MRI), were defined as scattered cervical lymph nodes that had no evidence of central necrosis or extracapsular spread and exhibited a maximum transverse diameter ≥5 mm and <10 mm in MRI. The mean (Emean), minimum (Emin) and maximum (Emax) of the elasticity indices (EIs) were measured by SWE at the stiffest part of the sLN (kPa). Biopsy pathology was served as the reference standard. Diagnostic performances were assessed using receiver operating curve (ROC) analysis on a node-by-node basis. RESULTS Of the 114 small cervical lymph nodes, 88 (77.2%) were benign, and 26 (22.8%) were malignant. All SWE EIs were significantly higher in malignant sLNs than in benign sLNs (p < 0.001). Emean exhibited the highest diagnostic value (area under the curve = 0.879 ± 0.036) (p < 0.001) and the corresponding sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 84.6%, 83.0%, 59.5%, 94.8% and 83.3%, respectively. The intra-observer reproducibility of all SWE EIs were significant, with intra-class correlation coefficient (ICC) of 0.745 in Emean, 0.716 in Emax and 0.702 in Emin. CONCLUSION Shear wave elastography is an optional supplementary imaging modality to routine MRI examination to diagnose cervical lymph nodes in NPC patients.

Advantage of PET/CT in target delineation of MRI negative cervical lymph nodes in intensity-modulated radiation therapy planning for nasopharyngeal carcinoma

Introduction: In intensity-modulated radiation therapy (IMRT) planning for nasopharyngeal carcinoma (NPC), cervical lymph nodes (CLNs) that appear negative on magnetic resonance imaging (MRI) scans can be difficult to target. The purpose of this study was to assess the advantage of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) for distinguishing MRI-negative CLNs and the effect of 18F-FDG PET/CT on diagnosis, target delineation, and dose prescription in IMRT planning for NPC. Methods: Thirty-five NPC patients with 37 MRI-negative CLNs underwent 18F-FDG PET/CT imaging before treatment. Ultrasonography-guided fine-needle aspiration cytology (USgFNAC) was performed to examine the pathology of CLNs. The 18F-FDG PET/CT and cytopathological results were compared, and the diagnostic accuracy of 18F-FDG PET/CT was calculated. The cytopathologically confirmed CLNs were delineated and treated as the gross tumor volume of lymph nodes (denoted as GTVnd). Results: Nineteen of the 37 MRI-negative CLNs were positive on 18F-FDG PET/CT, and metastasis was confirmed by USgFNAC in 16 CLNs. Of the remaining 18 18F-FDG PET/CT-negative lymph nodes, metastasis was confirmed in one. The diagnostic accuracy, sensitivity, and specificity of 18F-FDG PET/CT were 89.2%, 94.1%, and 85.0%, respectively. The positive and negative predictive values were 84.2% and 94.4%, respectively. With a median follow-up of 48.3 months, no relapse was observed among the 18F-FDG PET/CT-positive CLNs with metastasis confirmed by USgFNAC and treated as GTVnd. Conclusion: 18F-FDG PET/CT had high accuracy, sensitivity, and specificity for distinguishing MRI-negative CLNs. 18F-FDG PET/CT-positive CLNs could reasonably be categorized as high-risk clinical tumor volume in IMRT planning for NPC.