Publications by authors named "Wei-Han Hu"

50 Publications

Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

Lancet 2021 07 7;398(10297):303-313. Epub 2021 Jun 7.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.

Background: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options.

Methods: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111.

Findings: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group.

Interpretation: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma.

Funding: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S0140-6736(21)01123-5DOI Listing
July 2021

A Gene-Expression Predictor for Efficacy of Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma.

J Natl Cancer Inst 2021 Apr;113(4):471-480

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC.

Methods: We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided.

Results: We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed.

Conclusions: The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients.
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http://dx.doi.org/10.1093/jnci/djaa100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023816PMC
April 2021

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.

N Engl J Med 2019 09 31;381(12):1124-1135. Epub 2019 May 31.

From the Departments of Radiation Oncology (Y.Z., L.C., Y.-P.C., W.-H.H., W.-F.L., L.-L.T., Y.-P.M., G.-Q.Z., R.S., X.L., R.G., F.H., J.-W.L., X.-J.D., C.X., N.L., Y.-Q.L., F.-Y.X., Ying Sun, J.M.), Medical Oncology (Y.-H.L.), and Nasopharyngeal Carcinoma (H.-Y.M.) and the Clinical Trials Center (Y.G.), Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy (Y.Z., L.C., Y.-P.C., W.-H.H., W.-F.L., L.-L.T., Y.-P.M., G.-Q.Z., R.S., X.L., R.G., F.H., J.-W.L., X.-J.D., C.X., N.L., Y.-Q.L., F.-Y.X., Ying Sun, J.M.), and the Department of Radiation Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University (X.-C.W., Q.-F.S.), Guangzhou, the Cancer Center, Tongji Hospital Affiliated to Tongji Medical College (G.-Q.H., G.-X.L.), and the Cancer Center, Union Hospital, Tongji Medical College (K.-Y.Y., J.H.), Huazhong University of Science and Technology, Wuhan, the Department of Radiation Oncology, First People's Hospital of Foshan, Foshan (N.Z., S.-Q.L.), the Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning (X.-D.Z., L.L.), the Department of Head and Neck Oncology, Affiliated Hospital of Guizhou Medical University, Guizhou Cancer Hospital, Guiyang (F.J., J.-H.L.), the Department of Radiation Oncology, XiJing Hospital of Fourth Military Medical University, Xi'an (M.S., J.Z.), the Cancer Center (Z.-B.C.), and the Department of Head and Neck Oncology (S.-Y.W., Q.-D.L.), Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, the Department of Radiation Oncology, Second Affiliated Hospital of Soochow University, Suzhou (Y.T., L.Z.), the Department of Radiation Oncology, Peking University Cancer Hospital, Beijing (Yan Sun, B.-M.Z.), and the Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang (J.-G.L., Y.X.) - all in China; and the Divisions of Radiation Oncology and Medical Sciences, National Cancer Center Singapore, and the Oncology Academic Program, Duke-National University of Singapore Medical School - both in Singapore (M.L.K.C.).

Background: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials.

Methods: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety.

Results: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group.

Conclusions: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).
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http://dx.doi.org/10.1056/NEJMoa1905287DOI Listing
September 2019

Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Long-term results of phase 3 randomized controlled trial.

Int J Cancer 2019 07 24;145(1):295-305. Epub 2019 Jan 24.

Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, People's Republic of China.

To report long-term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III-IVB (except T3-4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m d1), cisplatin (60 mg/m d1), and fluorouracil (600 mg/m /d civ d1-5) every 3 weeks. Patients from both groups received intensity-modulated radiotherapy concurrently with three cycles of 100 mg/m cisplatin every 3 weeks. After a median follow-up of 71.5 months, the IC plus CCRT group showed significantly better 5-year failure-free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure-free survival (88% vs. 79.8%, p = 0.030), and locoregional failure-free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein-Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long-term follow-up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.
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http://dx.doi.org/10.1002/ijc.32099DOI Listing
July 2019

The efficacy of induction chemotherapy in the treatment of stage II nasopharyngeal carcinoma in intensity modulated radiotherapy era.

Oral Oncol 2018 10 7;85:95-100. Epub 2018 Sep 7.

Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China; Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, People's Republic of China. Electronic address:

Purpose: To evaluate the efficacy of induction chemotherapy in the treatment of stage II nasopharyngeal carcinoma (NPC) in era of intensity modulated radiotherapy (IMRT).

Methods And Materials: A total of 173 patients with American Joint Committee on Cancer (AJCC) 7th stage II NPC from two institutions were included. All patients were divided into two groups: induction chemotherapy + concurrent chemoradiotherapy group (ICRT) group and concurrent chemoradiotherapy group (CCRT). Induction chemotherapy was consisted of one to three cycles of cisplatin plus fluorouracil (PF) or paclitaxel plus cisplatin (TP). Concurrent chemotherapy included one to three cycles of cisplatin. We retrospectively assessed overall survival (OS), progression-free survival (PFS), locoregional failure free survival (LRFFS) and distant metastasis free survival (DMFS) in patients of both groups. T-test, Chi-square test, Kaplan-Meier methodology and Cox proportional hazards model were used to analyze.

Results: With a median follow up of 64.7 months, no significant difference was found in grade 3-4 hematologic toxicity, liver dysfunction and renal impairment between ICRT and CCRT group. Univariable analyses shown adding induction chemotherapy to CCRT significantly decreased 5-year OS (87.9% vs 95.5%, P = 0.033), 5-year PFS (74.0% vs 86.1%, P = 0.035), 5-year LRFFS (80.0% vs 91.2%, P = 0.016), but there was no statistically significant difference in 5-year DMFS (87.1% vs 94.7%, P = 0.095). In multivariable analyses, we found the consistent results that induction chemotherapy was a negative factor associated with OS (HR of death = 3.768, 95% CI = 1.117-12.709; P = 0.032), PFS (HR of progression = 2.156, 95% CI = 1.060-4.386; P = 0.034), LRFFS (HR of locoregional relapse = 2.435, 95% CI = 1.009-5.874; P = 0.048) and also DMFS (HR of metastasis = 2.873, 95% CI = 1.005-8.211; P = 0.049), in stage II NPC patients.

Conclusion: In present study, we found that induction chemotherapy caused deleterious effect on stage II NPC patients. However, this is a retrospective study and the adverse effects of induction chemotherapy has not been previously reported. It warrants further investigation.
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http://dx.doi.org/10.1016/j.oraloncology.2018.08.016DOI Listing
October 2018

10-Year Results of Therapeutic Ratio by Intensity-Modulated Radiotherapy Versus Two-Dimensional Radiotherapy in Patients with Nasopharyngeal Carcinoma.

Oncologist 2019 01 6;24(1):e38-e45. Epub 2018 Aug 6.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China

Background: The purpose of this study was to verify 10-year results of survival and late toxicities and assess the ultimate therapeutic ratio of intensity-modulated radiotherapy (IMRT) versus two-dimensional radiotherapy (2DRT) in patients with nasopharyngeal carcinoma (NPC).

Materials And Methods: We retrospectively reviewed the data from 1,276 patients with nonmetastatic NPC who received IMRT or 2DRT from January 2003 to December 2006.

Results: Of the 1,276 patients, 512 were treated with IMRT and 764 with 2DRT. Median follow-up was 115 months. At 10 years, the IMRT group demonstrated significantly better results than the 2DRT group in local failure-free survival (L-FFS; 90% vs. 84%; hazard ratio [HR], 0.57, 95% confidence interval [CI], 0.40-0.81;  = .001), failure-free survival (FFS; 69% vs. 58%; HR, 0.69, 95% CI, 0.57-0.83;  < .001), and overall survival (OS; 75% vs. 63%; HR, 0.62, 95% CI, 0.51-0.77;  < .001). Subgroup multivariate analyses showed that radiotherapeutic technique (IMRT vs. 2DRT) remained an independent prognostic factor for L-FFS in the T1 subgroup (HR, 0.30; 95% CI, 0.11-0.80;  = .02); for FFS in the stage II subgroup (HR, 0.42; 95% CI, 0.24-0.73;  = .002); and for OS in the stage I (HR, 0.20; 95% CI, 0.04-0.96;  = .04), stage II (HR, 0.39; 95% CI, 0.21-0.75;  = .004), and stage IVA-B (HR, 0.74, 95% CI, 0.56-0.98;  = .04) subgroups. The incidence of grade 3-4 temporal lobe necrosis, cranial neuropathy, eye damage, ear damage, neck soft tissue damage, trismus, and dry mouth was significantly lower in the IMRT group than in the 2DRT group.

Conclusion: IMRT demonstrated an improved ultimate therapeutic ratio compared with 2DRT in patients with NPC after a 10-year follow-up, with significant improvement of L-FFS, FFS, and OS and decrease in most late toxicities.

Implications For Practice: The ultimate therapeutic ratio of intensity-modulated radiotherapy versus two-dimensional radiotherapy in patients with nasopharyngeal carcinoma is unclear. In this retrospective study of 1,276 patients with nonmetastatic nasopharyngeal carcinoma with a follow-up of 115 months, intensity-modulated radiotherapy demonstrated an improved ultimate therapeutic ratio compared with two-dimensional radiotherapy, with significant improvement of local failure-free survival, failure-free survival, and overall survival and decrease in most late toxicities and noncancer deaths. However, distant control remains insufficient with this treatment modality.
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http://dx.doi.org/10.1634/theoncologist.2017-0577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324627PMC
January 2019

Role of sequential chemoradiotherapy in stage II and low-risk stage III-IV nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy: A propensity score-matched analysis.

Oral Oncol 2018 03 20;78:37-45. Epub 2018 Feb 20.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China. Electronic address:

Objectives: To investigate the role of sequential chemoradiotherapy (SCRT; induction chemotherapy [IC] followed by intensity-modulated radiotherapy [IMRT]) in stage II and low-risk stage III-IV nasopharyngeal carcinoma (NPC).

Materials And Methods: Four well-matched groups were individually generated using propensity score matching in patients (n = 689) with stage II (SCRT vs. concurrent chemoradiotherapy [CCRT], SCRT vs. IMRT alone) and low-risk stage III-IV NPC (SCRT vs. CCRT, SCRT vs. IC + CCRT). Five-year overall/disease-free/locoregional relapse-free/distant metastasis-free survival (OS/DFS/LRRFS/DMFS) and acute hematological toxicities were compared between groups. The value of SCRT was further investigated in multivariate analysis and subgroup analysis by adjusting for covariates and limiting IC-to-IMRT time interval, respectively.

Results: SCRT led to equivalent survival outcomes compared to CCRT/IMRT alone and CCRT/IC + CCRT in stage II and low-risk stage III-IV NPC, respectively (all P > .050). In multivariate analysis, patients with stage II NPC treated by SCRT obtained higher DMFS (AHR = 0.22, 95% CI = 0.05-1.00, P = .050), but not OS, DFS or LRRFS, compared to patients receiving CCRT; non-significant differences were observed between SCRT and other treatments. SCRT with short IC-to-IMRT time interval (≤70 days) achieved higher 5-year survival rates than IMRT alone (DMFS: P = .046), CCRT (stage II NPC; OS: P = .047; DMFS: P = .020) and IC + CCRT (DFS: P = .041). Moreover, SCRT was associated with higher, equivalent and lower frequencies of acute hematological toxicities than IMRT alone, CCRT and IC + CCRT, respectively.

Conclusion: SCRT is mainly beneficial in stage II NPC, leading to better DMFS and/or equivalent acute hematological toxicities compared to CCRT/IMRT alone. CCRT is still the best choice for low-risk stage III-IV NPC.
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http://dx.doi.org/10.1016/j.oraloncology.2018.01.008DOI Listing
March 2018

A comparison of weekly versus 3-weekly cisplatin during concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma using intensity modulated radiation therapy: a matched study.

J Cancer 2018 1;9(1):92-99. Epub 2018 Jan 1.

Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.

To compare the long-term survival outcomes and acute toxicity between locoregionally advanced nasopharyngeal carcinoma (NPC) patients who received either weekly or 3-weekly cisplatin during concurrent chemoradiotherapy (CCRT). Between November 2008 and August 2011, 241 biopsy-proved NPC patients receiving concurrent cisplatin with intensity modulated radiotherapy (IMRT) were included. 90 patients treated with 4-7 weeks of 30-40 mg/m cisplatin weekly were matched with 90 patients who received two or three cycles of 80 mg/m cisplatin three-weekly by sex, age, T stage, N stage, Karnosky performance score (KPS). IMRT was presented to the nasopharyngeal gross target volume at 66-72 Gy/30-32 fractions and those involved neck area at 60-66 Gy/30-32 fractions. The median follow-up time was 69 months (range, 2-91 months), and the 5-year overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 85.6% vs. 90.0% ( = 0.207), 85.6% vs. 92.6% ( = 0.152), 94.4% vs. 96.7% ( = 0.411), and 88.9% vs. 95.6% ( = 0.107) for the group treated weekly and 3-weekly cisplatin, respectively. No statistically significant survival differences were found between the two treatment groups in both univariate and multivariate analyses. The similar incidence of acute toxicities was observed between two groups. Concurrent cisplatin-based chemotherapy administered weekly or three-weekly in combination with IMRT leads to similar acute toxicities and long-term survival outcomes in locoregionally advanced NPC patients.
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http://dx.doi.org/10.7150/jca.21357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743715PMC
January 2018

Loss of LKB1 Expression Decreases the Survival and Promotes Laryngeal Cancer Metastasis.

J Cancer 2017 30;8(17):3548-3554. Epub 2017 Sep 30.

State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou.

Given recent results indicating that diminished LKB1 expression in laryngeal cancer correlates with shorter survival. We aim to perform an analysis estimate the role of decreased liver kinase B1(LKB1) and in the prognostication of human laryngeal squamous cell carcinoma (LSCC). We conducted a retrospective study and evaluate the expression of LKB1 and p16INK4a (p16) in 208 clinical advanced-stage LSCC tissue samples by using immunohistochemistry. The specimens were received at Sun Yat-sen University Cancer Center (Guangzhou, China). To evaluate the independent prognostic relevance of LKB1, univariate and multivariate Cox regression models were used, overall survival (OS) and distant metastasis-free survival (DMFS) were compared using the Kaplan-Meier method. Immunohistochemical analyses revealed that 80/208 (38.5%) of the LSCC tissue samples expressed high LKB1. Low LKB1 expression was associated with a significantly shorter OS and DMFS than high LKB1 expression ( = 0.041 and 0.028, respectively; log-rank test), and there was a poorer OS in the p16-positive than p16-negative group. In the subgroup stratified by p16 status, the shorter OS were also seen with low LKB1 expression. Multivariate survival analysis indicated that high LKB1 expression was an independent prognostic factor for OS (hazard ratio [HR]: 1.628, 95% confidence interval [CI]: 1.060-2.500, = 0.026) and DMFS (HR: 2.182, 95% CI: 1.069-4.456, = 0.032). : Our data indicated that low expression of LKB1 was significantly associated with poor prognosis and it may represent a marker of tumor metastasis in patients with LSCC. When combined with p16, LKB1 was also of prognostic value.
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http://dx.doi.org/10.7150/jca.20535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687170PMC
September 2017

Meta-analysis of the clinical characteristics and prognostic relevance of NOTCH1 and FBXW7 mutation in T-cell acute lymphoblastic leukemia.

Oncotarget 2017 Sep 19;8(39):66360-66370. Epub 2017 Jun 19.

State Key Laboratory of Oncology in South China, Guangzhou, China.

The NOTCH1 signaling pathway is crucial for T-cell development, and NOTCH1 and/or FBXW7 mutations are frequently detected in T-cell acute lymphoblastic leukemia (T-ALL). We performed a systematic review and meta-analysis of 18 randomized controlled trials (RCTs) to assess the prognostic impact of mutations in the NOTCH1 pathway. After retrieving relevant articles from PubMed, EMBASE, and the Cochrane Library, we investigated overall survival (OS) and event-free survival (EFS) with hazard ratios (HRs) using fixed-effects or random-effects models and conducted subgroup analyses based on population and mutation status. NOTCH1/FBXW7 mutations correlated significantly with better prognosis (5-year EFS: HR, 0.57; 95% confidence interval [CI], 0.46 to 0.68; < 0.001 and 5-year OS: HR, 0.61; 95% CI, 0.51 to 0.74; < 0.001). The HR for 5-year EFS and OS with NOTCH1 mutations were 0.63 (95% CI, 0.53 to 0.75) and 0.76 (95% CI, 0.60 to 0.95), respectively; with FBXW7 mutations, they were 0.82 (95% CI, 0.60 to 1.11) and 0.79 (95% CI, 0.55 to 1.12), respectively. However, differences between children and adults showed no significance. We conclude that the presence of NOTCH1/FBXW7 mutations is an independent prognostic factor for 5-year EFS and 5-year OS.
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http://dx.doi.org/10.18632/oncotarget.18576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630418PMC
September 2017

DNA-dependent protein kinase catalytic subunit functions in metastasis and influences survival in advanced-stage laryngeal squamous cell carcinoma.

J Cancer 2017 22;8(12):2410-2416. Epub 2017 Jul 22.

State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known to function in several types of cancer. In this study, we investigated the expression and clinicopathologic significance of DNA-PKcs in laryngeal squamous cell carcinoma (LSCC). We conducted a retrospective study of 208 patients with advanced-stage LSCC treated at Sun Yat-sen University Cancer Center, Guangzhou, China. We assessed DNA-PKcs and p16INK4a (p16) status using immunohistochemistry. We examined the association between DNA-PKcs expression and clinicopathologic features and survival outcomes. To evaluate the independent prognostic relevance of DNA-PKcs, we used univariate and multivariate Cox regression models. We estimated overall survival (OS) and distant metastasis-free survival (DMFS) using the Kaplan-Meier method. Immunohistochemical analyses revealed that 163/208 (78.4%) of the LSCC tissue samples exhibited high DNA-PKcs expression. High DNA-PKcs expression was significantly associated with survival outcomes ( = 0.016) and distant metastasis ( = 0.02; chi-squared test). High DNA-PKcs expression was associated with a significantly shorter OS and DMFS than low DNA-PKcs expression ( = 0.029 and 0.033, respectively; log-rank test), and was associated with poor OS in the p16-positive subgroup ( = 0.047). Multivariate analysis identified DNA-PKcs as an independent prognostic indicator of OS and DMFS in all patients ( = 0.039 and 0.037, respectively). : Our results suggest that patients with LSCC in whom DNA-PKcs expression is elevated have a higher incidence of distant metastasis and a poorer prognosis. DNA-PKcs may represent a marker of tumor progression in patients with p16-positive LSCC.
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http://dx.doi.org/10.7150/jca.20069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560160PMC
July 2017

ABO blood group is a predictor of survival in patients with laryngeal cancer.

Chin J Cancer 2016 10 13;35(1):90. Epub 2016 Oct 13.

State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.

Background: Whether the ABO blood group is associated with the survival of patients with laryngeal cancer remains unknown. The purpose of this study was to investigate the association between the ABO blood group and clinicopathologic characteristics of patients with laryngeal cancer and assess whether the ABO blood group was associated with prognosis.

Methods: We analyzed the records of 1260 patients with laryngeal cancer who underwent curative treatment at Sun Yat-sen University Cancer Center between January 1993 and December 2009. The Chi-square test was used to assess the relationship between the ABO blood group and clinicopathologic characteristics. The Kaplan-Meier method was used to estimate 3-, 5-, and 10-year overall survival (OS) rates. The Cox proportional hazards model was used in univariate and multivariate analyses of OS.

Results: No significant association was found between the ABO blood group and clinicopathologic characteristics except for primary tumor site. The median OS for patients with blood groups A, B, AB, and O were 87.0, 80.0, 90.0, and 72.5 months, respectively. The 3-, 5-, and 10-year OS rates were 82.4%, 76.0%, and 67.5% for patients with blood group A; 77.4%, 69.8%, and 58.4% for patients with blood group B; 82.2%, 73.1%, and 65.6% for patients with blood group AB; and 71.7%, 66.4%, and 55.5% for patients with blood group O, respectively. Univariate and multivariate analyses showed that the ABO blood group had significant effects on prognosis in patients with laryngeal cancer.

Conclusions: The ABO blood group is associated with survival in patients with laryngeal cancer. Patients with blood group O had significantly shorter OS than patients with other ABO blood groups.
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http://dx.doi.org/10.1186/s40880-016-0152-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062923PMC
October 2016

Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial.

Lancet Oncol 2016 Nov 27;17(11):1509-1520. Epub 2016 Sep 27.

Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Background: The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial.

Methods: We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III-IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18-59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m on day 1), intravenous cisplatin (60 mg/m on day 1), and continuous intravenous fluorouracil (600 mg/m per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT01245959.

Findings: Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38-49), 3-year failure-free survival was 80% (95% CI 75-85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66-78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48-0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 [42%] vs 17 [7%]), leucopenia (98 [41%] vs 41 [17%]), and stomatitis (98 [41%] vs 84 [35%]).

Interpretation: Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities.

Funding: Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000).
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http://dx.doi.org/10.1016/S1470-2045(16)30410-7DOI Listing
November 2016

Management of the N0 neck in recurrent laryngeal squamous cell carcinoma.

Mol Clin Oncol 2016 Jan 29;4(1):70-76. Epub 2015 Oct 29.

Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China; Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang 310022, P.R. China.

The most effective therapeutic approach for the node-negative (N0) neck in patients with recurrent laryngeal squamous cell carcinoma (SCC) remains a subject of dispute. In the present study, the records of 163 patients with recurrent laryngeal SCC were retrospectively reviewed. All patients had a N0 neck at recurrence. At the time of recurrence, the N0 neck was managed using a wait-and-see strategy (observation group) or treatment (treatment group). A total of 125 (76.7%) patients accepted the wait-and-see strategy and 38 (23.3%) patients underwent treatments, including surgery, radiotherapy and/or chemotherapy. The Kaplan-Meier method with the computation of log-rank was used for analysis of survival. The t-test, χ test or Fisher's exact test was used for comparisons of non-survival data in the groups. P<0.05 was considered to indicate a statistically significant difference in the two-sided tests. The 3- and 5-year overall survival rates after recurrence were 64.5 and 54.6% for the observation group, and 49.9 and 42.5% for the treatment group, respectively (P=0.011). The present study suggests that a wait-and-see policy is a satisfactory management option for the N0 neck in recurrent laryngeal SCC.
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http://dx.doi.org/10.3892/mco.2015.663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726969PMC
January 2016

Effect of Prolonged Radiotherapy Treatment Time on Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma.

PLoS One 2015 27;10(10):e0141332. Epub 2015 Oct 27.

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

Purpose: To estimate the influence of prolonged radiation treatment time (RTT) on survival outcomes in nasopharyngeal carcinoma after continuous intensity-modulated radiation therapy.

Methods And Materials: Retrospectively review 321 patients with NPC treated between October 2009 and December 2010 and all of them underwent simultaneous accelerated intensity-modulated radiation therapy. The fractionated dose was 2-2.47 Gy/F (median 2.27 Gy), and the total dose for nasopharyngeal region was 64-74 Gy/ 28-33 fractions. The association of prolonged RTT and treatment interruption with PFS, LRFS and DFFS were assessed by univariate analysis and multivariate analysis. Survival analyses were carried out using Kaplan-Meier methodology and the log-rank test was used to assess the difference. The Cox regression proportional hazard model was used for multivariate analyses and evaluating the prognostic parameters for PFS, LRFS and DFFS.

Results: Univariate analysis revealed no significant associations between prolonged RTT and PFS, LRFS, DFFS when dichotomized using various cut-off values (all P>0.05). In multivariate analysis, RTT (range, 36-63 days) as a continuous variable, had no influence on any survival outcome as well (P>0.05). T and N classification were independent prognostic factors for PFS, LRFS and DFFS (all P<0.05, except T classification for LRFS, P = 0.057). Age was an independent prognostic factor for PFS (hazard ratio [HR], 1.033; P = 0.008) and DFFS (HR, 1.032; P = 0.043).

Conclusion: We conclude that no such association between survival outcomes and radiation treatment duration (range: 36-63 days) can be found in the present retrospective study, however, we have to remind that prolongation in treatment should be limited in clinical application and interruptions caused by any reason should be minimized as much as possible.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0141332PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624640PMC
June 2016

Erratum to: Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma.

J Cancer Res Clin Oncol 2015 Apr;141(4):767

Department of Medical Oncology, Zhejiang Cancer Hospital, 38 Guang Ji Road, Hangzhou, China.

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http://dx.doi.org/10.1007/s00432-015-1926-1DOI Listing
April 2015

HPV Infection and Anemia Status Stratify the Survival of Early T2 Laryngeal Squamous Cell Carcinoma.

J Voice 2015 May 4;29(3):356-62. Epub 2014 Dec 4.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, China; State Key Laboratory of Oncology in South China, Sun Yat-sen University, Guangzhou, Guangdong Province, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, China. Electronic address:

Objective: This study was designed to investigate the potentially prognostic indicators of early laryngeal squamous cell carcinomas (LSCCs), including human papillomavirus (HPV) status.

Methods: A total of 336 patients with T2N0-1M0 LSCC were included in this study. Clinical data were collected from archival documents, and HPV infection and p16(INK4A) expression were detected.

Results: A total of 32/318 cases of high-risk HPV infection and 10/336 cases of p16(INK4A) overexpression were found. Three hundred eighteen tumors were classified into a three-class model according to HPV infection and p16(INK4A) expression: class I, HPV+/p16+; class II, HPV+/p16-; and class III, HPV-/p16-. Class III had a trend of decreased overall survival (OS) (P = 0.076) and a markedly low relapse-free survival (RFS) (P = 0.022) compared with class I and class II. HPV-positive cases (class I plus class II) had a significantly longer OS (P = 0.038) and RFS (P = 0.006). In multivariate analysis, HPV-positive (P = 0.020), nonanemia (P = 0.011), and N0 stage (P = 0.005) were significant predictors for high RFS. But only HPV-positive (P = 0.047) and nonanemia (P < 0.001) were significant predictors for superior OS.

Conclusion: A trend of discrete survival among HPV+/p16+, HPV+/p16-, and HPV-/p16 classes was found in early LSCCs. We suggest that HPV infection and hemoglobin level are the potential factors that can stratify outcome of early LSCCs.
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http://dx.doi.org/10.1016/j.jvoice.2014.08.016DOI Listing
May 2015

P16INK4A as a surrogate biomarker for human papillomavirus-associated oropharyngeal carcinoma: consideration of some aspects.

Cancer Sci 2013 Dec 8;104(12):1553-9. Epub 2013 Nov 8.

Sun Yat-sen University Cancer Center, Guangdong, China; State Key Laboratory of Oncology in South China, Guangdong, China; Collaborative Innovation Center for Cancer Medicine, Guangdong, China.

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) frequently show different clinical and pathological features, which tend to be younger age, better performance status, less tobacco and alcohol consumption, more poorly differentiated histopathology, but usually with better treatment response and prognosis compared with HPV-negative OPSCCs. In tumor tissue, HPV infection is closely correlated with p16(INK4A) expression, which has been suggested to be a surrogate biomarker of HPV infection. However, there is diversity of sensitivity and specificity about p16(INK4A) in surrogate detection of HPV status. Herein, we summarize the current knowledge and note some aspects for consideration concerning p16(INK4A) as a surrogate biomarker for HPV-associated OPSCC.
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http://dx.doi.org/10.1111/cas.12287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653521PMC
December 2013

Plasma uric acid and tumor volume are highly predictive of outcome in nasopharyngeal carcinoma patients receiving intensity modulated radiotherapy.

Radiat Oncol 2013 May 15;8:121. Epub 2013 May 15.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangdong Province, Guangzhou 510060, China.

Background: The combined predictive value of plasma uric acid and primary tumor volume in nasopharyngeal carcinoma (NPC) patients receiving intensity modulated radiation therapy (IMRT) has not yet been determined.

Methods: In this retrospective study, plasma uric acid level was measured after treatment in 130 histologically-proven NPC patients treated with IMRT. Tumor volume was calculated from treatment planning CT scans. Overall (OS), progression-free (PFS) and distant metastasis-free (DMFS) survival were compared using Kaplan-Meier analysis and the log rank test, and Cox multivariate and univariate regression models were created.

Results: Patients with a small tumor volume (<27 mL) had a significantly better DMFS, PFS and OS than patients with a large tumor volume. Patients with a high post-treatment plasma uric acid level (>301 μmol/L) had a better DMFS, PFS and OS than patients with a low post-treatment plasma uric acid level. Patients with a small tumor volume and high post-treatment plasma uric acid level had a favorable prognosis compared to patients with a large tumor volume and low post-treatment plasma uric acid level (7-year overall OS, 100% vs. 48.7%, P <0.001 and PFS, 100% vs. 69.5%, P <0.001).

Conclusions: Post-treatment plasma uric acid level and pre-treatment tumor volume have predictive value for outcome in NPC patients receiving IMRT. NPC patients with a large tumor volume and low post-treatment plasma uric acid level may benefit from additional aggressive treatment after IMRT.
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http://dx.doi.org/10.1186/1748-717X-8-121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679939PMC
May 2013

Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma.

J Cancer Res Clin Oncol 2012 Oct 10;138(10):1717-25. Epub 2012 Jun 10.

Department of Medical Oncology, Zhejiang Cancer Hospital, 38 Guang Ji Road, Hangzhou, China.

Background And Objective: No randomized trial has been reported comparing different chemotherapy regimens on disseminated nasopharyngeal carcinoma (NPC). This study aims to compare five cisplatin-based regimens including cisplatin + 5-fluororacil (PF), paclitaxel + cisplatin (TP), gemcitabine + cisplain (GP), paclitaxel + cisplatin + 5-fluororacil (TPF), and bleomycin + cisplatin + 5-fluororacil (BPF) regimen most frequently used as the first-line protocols for metastatic NPC retrospectively.

Methods: Eight hundred and twenty-two patients with metastatic NPC were divided into five groups according to the regimen they received. Then, their response rate, toxicity, and long-term survival outcome as well as the prognostic factors were analyzed.

Results: The higher response rates in GP and TPF regimens comparing to PF regimen were achieved (Χ (2) = 4.57, P = 0.033; Χ (2) = 7.04, P = 0.008), as well as in TPF regimen comparing to TP regimen (Χ (2) = 5.579, P = 0.018). The occurrence rate of the major III-IV grade toxicity was significantly different between the five groups. However, no statistically significant difference was observed in progression-free survival (PFS; P = 0.247) and overall survival (P = 0.127) among the five groups. Cox multivariate analysis identified the following independent prognostic factors: liver metastases, plasma Epstein Barr Virus (EBV)-DNA level, cycles of chemotherapy, and second-line chemotherapy.

Conclusions: PF, TP, and GP are all effective regimens as the first-line chemotherapy for metastatic NPC, which can be well tolerated. Over four cycles of chemotherapy are recommended under no contraindication. Patients should transfer to the second-line regimen after the treatment failure of the first-line chemotherapy.
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http://dx.doi.org/10.1007/s00432-012-1219-xDOI Listing
October 2012

Primary nasopharyngeal adenocarcinoma: a review.

Asia Pac J Clin Oncol 2012 Jun 12;8(2):123-31. Epub 2012 Mar 12.

Department of Radiation Therapy, First People's Hospital of Foshan Affiliated to Sun Yat-sen University, China.

Primary nasopharyngeal adenocarcinoma (NAC) accounts for approximately 0.5% of all nasopharyngeal cancer. The diagnosis, staging and treatment of NAC has not been well described. This article presents a literature review on NAC and identifies its characteristics and management. The NAC group of diseases contains various pathological types and has a series of specific clinical characteristics, including slow progression, a low incidence of neck masses and frequent cranial neuropathy. The Epstein-Barr virus may not play an important role in NAC carcinogenesis. The rarity of the disease makes the staging classification and treatment strategies of NAC parallel to those recommended for nasopharyngeal squamous carcinoma. Some patients might benefit from surgery, and radiotherapy using precise techniques might achieve good control for treating NAC, but the roles of chemotherapy and target therapy are not clear. The proper staging system and optimal treatment strategies need to be established in NAC.
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http://dx.doi.org/10.1111/j.1743-7563.2011.01499.xDOI Listing
June 2012

Expression TGM2 and BNIP3 have prognostic significance in laryngeal cancer patients receiving surgery and postoperative radiotherapy: a retrospective study.

J Transl Med 2012 Mar 30;10:64. Epub 2012 Mar 30.

Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China.

Background: This study was designed to determine the pattern and correlation between expression of the HIF-1α transcriptional targets TGM2 and BNIP3 in laryngeal cancer, and investigate the association of BNIP3 and TGM2 with clinical outcome in laryngeal squamous cell carcinoma (SCC) patients receiving postoperative radiotherapy.

Methods: Immunostaining with antibodies specific to BNIP3 and TGM2 was performed in formalin-fixed, paraffin-embedded specimens from 148 laryngeal SCC patients. BNIP3 and TGM2 expression was scored as high or low, based on the number of tumor cells stained and the staining intensity. All patients received postoperative radiotherapy. Patient follow up and clinicopathological data were compared using the Chi-squared test, univariate and multivariate analyses, and survival curves were generated using the Kaplan-Meier method and log-rank test.

Results: The 3, 5 and 10-year overall survival rates (OS) for all patients were 77.7%, 71.6%, 56.4%, respectively. Primary tumor site, T stage, overall stage, lymph-node metastasis, BNIP3 expression and TGM2 expression were significant prognostic factors for OS in univariate analysis. Negative cervical lymph nodes, high BNIP3 expression and low TGM2 expression were independent prognostic factors of improved OS in multivariate analysis. BNIP3 expression correlates with TGM2 expression in laryngeal SCC (P = 0.012).

Conclusions: This study indicates that lymph-node metastasis, BNIP3 expression and TGM2 expression are independent prognostic factors in laryngeal SCC patients receiving postoperative radiotherapy. Further studies are required to investigate how BNIP3 and/or TGM2 influence the prognosis of laryngeal SCC patients treated with postoperative radiotherapy, and to determine how TGM2 and BNIP3 expression are regulated.
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http://dx.doi.org/10.1186/1479-5876-10-64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362769PMC
March 2012

Treatment results and prognostic factors of patients undergoing postoperative radiotherapy for laryngeal squamous cell carcinoma.

Chin J Cancer 2011 Jul;30(7):482-9

State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.

Postoperative radiotherapy (PRT) is widely advocated for patients with squamous cell carcinomas of the head and neck that are considered to be at high risk of recurrence after surgical resection. The aims of this study were to evaluate the treatment outcomes of PRT for patients with laryngeal carcinoma and to identify the value of several prognostic factors. We reviewed the records of 256 patients treated for laryngeal squamous cell carcinoma between January 1993 and December 2005. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Log-rank test was employed to identify significant prognostic factors for DFS and OS. The Cox proportional hazards model was applied to identify covariates significantly associated with the aforementioned endpoints. Our results showed the 3-, 5-, and 10-year DFS for all patients were 69.9%, 59.5%, and 34.9%, respectively. The 3-, 5-, and 10-year OS rates were 80.8%, 68.6%, and 38.8%, respectively. Significant prognostic factors for both DFS and OS on univariate analysis were grade, primary site, T stage, N stage, overall stage, lymph node metastasis, overall treatment times of radiation, the interval between surgery and radiotherapy, and radiotherapy equipment. Favorable prognostic factors for both DFS and OS on multivariate analysis were lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment. In conclusion, our data suggest that lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment are favorable prognostic factors for DFS and OS and that reducing the overall treatment times of radiation to 6 weeks or less and the interval between surgery and radiotherapy to less than 3 weeks are simple measures to remarkably improve treatment outcome.
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http://dx.doi.org/10.5732/cjc.010.10527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013423PMC
July 2011

Surgery alone provides long-term survival rates comparable to those of surgery plus postoperative radiotherapy for patients with adenoid cystic carcinoma of the palate.

Oral Oncol 2011 Mar 22;47(3):170-3. Epub 2011 Jan 22.

State Key Laboratory for Cancer Research in Southern China, Guangzhou 510060, Guangdong Province, People's Republic of China.

We compared the outcomes and rates of survival provided by surgery alone and surgery combined with postoperative radiotherapy for patients with adenoid cystic carcinoma of the palate (ACP), a rare, low-grade malignant tumor arising within the salivary glands. Fifty-eight patients with ACP were included in this retrospective study. ACP at stages T(1), T(2), T(3,) and T(4) was found in 11, 32, 5, and 10 patients, respectively. The patients were treated with surgery alone or underwent surgery combined with postoperative radiotherapy. The 5, 10, and 15year survival rates were 75%, 37.5%, and 25%, respectively, among the 24 patients who underwent surgery alone. These were not significantly different from the rates of 70.6%, 35.3%, and 20.8%, respectively, among the 34 patients who underwent surgery plus postoperative radiotherapy (P=0.21). The 5 and 10year survival rates were significantly greater among patients receiving ⩾60Gy of radiotherapy than those among patients receiving <60Gy of radiotherapy (83.3% and 45.8% vs. 40.0% and 10.0%, respectively) (P=0.04). ACP exhibited good long-term survival rates when treated with surgery alone. Addition of postoperative radiotherapy at doses of ⩾60Gy had no effect on survival, but postoperative radiotherapy at doses of <60Gy reduced survival. Recurrence within the palate was the main cause of treatment failure.
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http://dx.doi.org/10.1016/j.oraloncology.2010.12.005DOI Listing
March 2011

Prognostic significance of Oct4 and Sox2 expression in hypopharyngeal squamous cell carcinoma.

J Transl Med 2010 Oct 12;8:94. Epub 2010 Oct 12.

State Key Laboratory of Oncology in South China, Cancer Center of Sun Yat-Sen University, Guangzhou 510060, China.

Background: Oct4 and Sox2 are two major transcription factors related to the stem cell self-renewal and differentiation. The aim of this study was to examine the association between Oct4 and Sox2 expression levels with both the clinicopathological characteristics and prognoses of patients with hypopharyngeal squamous cell carcinoma.

Method: Tumor tissue samples from 85 patients with hypopharyngeal squamous cell carcinoma were collected, and the clinical follow-up data of these patients were recorded, and expression status of Oct4 and Sox2 were examined in these tissue samples by immunohistochemistry (IHC).

Results: Oct4 expression was found to be an independent predictive factor for overall survival (p = 0.004) in patients with hypopharyngeal squamous cell carcinoma and was independently related to loco-regional control (p = 0.001). Although Sox2 expression status showed no significant association with overall survival (p = 0.166), disease-free survival (p = 0.680) or loco-regional control (p = 0.383), when using a subgroup analysis, the subgroup with both high Oct4 and Sox2 expression had the best prognosis (p = 0.000). Sox2 expression could be a potential prognostic predictor for patients with hypopharyngeal squamous cell carcinoma. Simultaneous analyses of Oct4 and Sox2 expression could be more effective in evaluating the prognoses of patients with hypopharyngeal squamous cell carcinoma.

Conclusion: Oct4 expression is an independent predictive factor for patients with hypopharyngeal squamous cell carcinoma, suggesting that Oct4 expression may be a useful indicator for predicting the prognosis of hypopharyngeal squamous cell carcinoma.
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http://dx.doi.org/10.1186/1479-5876-8-94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958910PMC
October 2010

[Tonsillar carcinoma: analyses of the therapy and prognostic factors].

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2009 Oct;44(10):848-52

State Key Laboratory of Oncology in South China, Department of Radiation Oncology, Guangzhou 510060, China.

Objective: To retrospectively analyze the therapeutic effect on patients with tonsillar carcinoma and factors affecting their prognosis.

Methods: Clinical data of 61 patients pathologically confirmed with tonsillar carcinoma without distant metastasis were analyzed. All the patients were treated in Cancer Center of Sun Yat-sen University from April 1997 to April 2008. There were 2 patients with undifferentiated carcinoma, 26 with poorly differentiated squamous cell carcinoma and 33 with median-well differentiated squamous cell carcinoma. According to the AJCC 2002 staging criteria for head-neck cancers, there were 9 staged I cases, 7 staged II cases, 23 staged III cases and 22 staged IV cases. The treatment was radiotherapy alone in 27 cases, radiotherapy combined with chemotherapy in 23 cases, surgery combined with postoperative radiotherapy in 6 cases, neoadjuvant chemotherapy plus surgery combined with postoperative radiotherapy in 3 cases, radiotherapy with salvage surgery in 2 cases.

Results: The overall 5-year survival rate was 50.2%. For 16 cases with staged I-II staged, there were 8 cases with radiotherapy alone, 5 years survival was 50.0%, 6 cases with surgery combined with postoperative radiotherapy, 5 years survival was 83.3%. The difference between the two treatments was not significant in statistics (P = 0.318). For III-IV staged 45 cases, there were 19 cases with simple radiotherapy, 5 years survival was 51.5%, 21 cases with radiotherapy combined with chemotherapy, 5 years survival was 36.4%, 5 cases with surgery combined with postoperative radiotherapy, 5 years survival was 75.0%. The difference among the three treatments was not significant in statistics (P = 0.239). According to T stages, the 5-year survival rates of stage T1-T4 cases were 91.8%, 46.8%, 29.1%, 0% respectively (chi(2) = 30.168, P < 0.001). Multivariate analysis demonstrated that T stage, therapeutic effect of primary site and cervical metastatic lymph node were the independent prognostic factors (P < 0.05).

Conclusions: T stage, the therapeutic effect of primary site and cervical metastatic lymph node were the independent prognostic factors. For I-II staged tonsillar tumor cases, based on organ preservation, were tendency to choice simple radiotherapy. For III-IV staged cases, yet the relationships between therapeutic mode and therapeutic effect still need further researches.
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October 2009

[Prophylactic irradiation of cervical lymph nodes for Stage-N0 nasopharyngeal carcinoma].

Chin J Cancer 2010 Jan;29(1):106-10

State Key Laboratory of Oncology, South China, Guangzhou, Guangdong 510060, People's Republic of China.

Background And Objective: It is controversial for the irradiation level and dose of the regional prevention for naspharyngeal cancer (NPC) with one or both cervical lymph node-negative neck. The study was to analyze the proophylactic irradiation of cervical lymph nodes for Stage -N0 NPC patients.

Methods: From January 2002 and December 2004, 205 NPC patients with negative lymphadenopathy diagnosed by imaging, were retrospectively analyzed. Before treatment, each patient underwent CT or MRI. Facial-cervical portals and 6-8 MV photons were used in radiotherapy. Doses applied were 60-80 Gy to the nasopharynx and 46-64 Gy to the neck without lymphadenopathy. Consecutive radiotherapy was performed employing conventional fractionation of 2 Gy/fraction, once a day, for a total of five fractions per week. Chemotherapy was administered to 60 patients. Median follow-up was 44 months. The survival function was calculated according to the Kaplan-Meier method. A log-rank test was used to compare the differences in survival. The Cox proportional hazards model was used for multivariate analysis. A total of 205 patients with stage-N0 NPC were divided into an upper-neck irradiation group and an entire-neck group.

Results: The 3-year overall survival rate (OS) was 92.9% and the 3-year disease-free survival rate (DFS) was 91.9%. A total of 88 patients received irradiation to the upper neck and 117 to the entire neck. The rate of regional failure for the upper-neck group and the entire-neck group were 2.27% and 0%, respectively (P>0.05). The rates of regional failure in patients with T1-, T2-, T3- and T4-stage disease were 0, 3.08%, 0, and 0, respectively (P>0.05). The rates of regional failure in the patients both without and with local failure were 1.03% and 0, respectively (P>0.05). The 1-and 3-year OS for the upper-neck group were 97.7% and 94.2%, and the 1- and 3-year OS for the entire-neck group were 97.4% and 91.9% (P=0.950). The 1- and 3-year DFS for the upper-neck group were 96.6% and 92.9%, and the 1- and 3-year DFS for the entire-neck group were 95.6% and 90.9% (P= 0.730). In multivariate analysis, sex (P=0.039) and T stage (P=0.004) were independent prognosis factors for patients with stage-N0 NPC.

Conclusions: Prophylactic irradiation to the upper neck does not influence regional failure or long-term survival in the patients with stage-N0 NPC. Radiotherapy to the upper neck (levels II, III, VA) is recommended for the patients with stage-N0 NPC. Involvement of the parapharyngeal space, T stage, and the rates of local failure do not influence regional failure in these patients. Sex and T stage were independent prognosis factors of stage-N0 NPC patients.
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http://dx.doi.org/10.5732/cjc.009.10297DOI Listing
January 2010

[Target volume including the nasopharynx for radiotherapy of hypopharyngeal squamous cell carcinoma: whether or not].

Ai Zheng 2009 May;28(5):515-9

State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, China.

Background And Objective: There is controversy in whether the nasopharynx should be included in target volume for radiotherapy of hypopharyngeal squamous cell carcinoma. This study was to analyze the necessity of radiotherapy including the nasopharynx for patients with hypopharyngeal squamous cell carcinoma.

Methods: Clinical data of 196 patients with hypopharyngeal squamous cell carcinoma treated in Cancer Center of Sun Yat-sen University from May 1994 to August 2006 were analyzed. Of the 196 cases of hypopharyngeal carcinoma, three were at stage I, 26 at stage II, 38 at stage III, and 129 at stage IV. Ninety-four patients received radiotherapy, 49 received surgery and 53 received surgery combined with radiotherapy. The nasopharynx was included in target volume in 78 patients, but excluded in 69 patients. The prognosis of the two groups were compared.

Results: The 3-year and 5-year overall survival rates were 38.57% and 21.69%. The 5-year survival rates were 100% in stage I patients, 43.08% in stage II patients, 27.57% in stage III patients, and 13.99% in stage IV patients, and were 13.90% in surgery group, 10.60% in radiotherapy group, and 44.08% in combined therapy group. Between nasopharynx-included and nasopharynx-excluded groups, there was no significant difference in 5-year overall survival rate (24.44 % vs. 20.68%, kappa2=0.10,P=0.76),5-year progression-free survival rate (15.99% vs. 10.91%, kappa2=0.65, P=0.42), relapse rate and metastasis rate (kappa2=1.56, P=0.21). Relapse in cervical lymph nodes occurred in 39 patients; no relapse in the nasopharynx was observed.

Conclusions: Combined therapy is recommended for advanced hypopharyngeal squamous cell carcinoma. The target volume including the nasopharynx is not recommended. Controlling cervical lymph node metastasis may be helpful for prolonging survival.
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May 2009

[Induction chemotherapy with docetaxel plus cisplatin (TP regimen) followed by concurrent chemoradiotherapy with TP regimen versus cisplatin in treating locally advanced nasopharyngeal carcinoma].

Ai Zheng 2009 Mar;28(3):279-85

State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, P. R. China.

Background And Objective: Clinical trials on docetaxel plus cisplatin (DDP) (TP regimen) in treating nasopharyngeal carcinoma (NPC) are still uncertain due to limited samples. This study was to compare the short-term efficacy and toxicity of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen versus DDP in treating locally advanced NPC.

Methods: Fifty-seven patients with stage T3-4N2-3M0 NPC diagnosed pathologically from December 2005 to December 2006 were randomized into TP group (30 patients) and DDP group (27 patients). Both groups received TP regimen as induction chemotherapy with docetaxel (70 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2, repeating every 21 days for 2 cycles. For concurrent chemotherapy, TP group were administered docetaxel (60 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2; DDP group were administered DDP (80 mg/m(2)) on Day 1. Both schedules were repeated every 21 days for 2 cycles. Linear accelerator was used as radioactive source. Irradiation field was designed with CT-simulation and conventional fractions.

Results: The 57 patients received 111 cycles of induction chemotherapy, and 53 of them received 103 cycles of concurrent chemotherapy; four patients ceased induction chemotherapy and three ceased concurrent chemotherapy. All patients completed radiotherapy. The major toxicity of induction chemotherapy was hematologic toxicity; the main toxicities of concurrent chemoradiotherapy were hematologic toxicity and mucositis. The occurrence rates of Grade 3-4 leucopenia and Grade 3-4 neutropenia were significantly higher in TP group than in DDP groups (p <0.05). In concurrent chemoradiotherapy, the application rate of granulocyte colony stimulating factor (G-CSF) was significantly higher in TP group than in DDP group (100% vs. 72.0%, p<0.05). After concurrent chemoradiotherapy, the complete remission (CR) rates of the nasopharynx and regional lymph nodes were 93.3% and 92.9% in TP group, and were 96.3% and 91.3% in DDP group (p>0.05).

Conclusions: The short-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen on locally advanced NPC is similar to that of TP regimen followed by concurrent chemoradiotherapy with DDP. The toxicity of the former schedule is severer than that of the latter, but it is tolerable with the use of G-CSF. The long-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen need to be further studied.
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March 2009

[Long-term efficacy of induction chemotherapy plus concurrent radiochemotherapy on advanced nasopharyngeal carcinoma].

Ai Zheng 2007 Aug;26(8):885-9

State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, PR China.

Background & Objective: Induction chemotherapy plus concurrent radiochemotherapy may prolong disease-free and overall survival of advanced nasopharyngeal carcinoma (NPC) patients. This study was to compare the long-term efficacy of induction chemotherapy plus concurrent radiochemotherapy and radiotherapy alone on advanced NPC.

Methods: Clinical data of 535 advanced NPC patients, treated in Cancer Center of Sun Yat-sen University from Jan. 1997 to Dec. 1998, were analyzed. Of the 535 patients, 75 were treated with 3-5 cycles of induction and concomitant chemotherapy of PF regimen (cisplatin combined 5-fluorouracil) plus radiotherapy, 460 were treated with radiotherapy alone. The survival statuses of the 2 groups were compared. Prognostic factors were analyzed by Cox regression analysis. Cumulative survival rate was analyzed by Kaplan-Meier method.

Results: The 5-year overall and disease-free survival rates were significantly higher in radiochemotherapy group than in radiotherapy group (78.15% vs. 55.27%, 71.55% vs. 48.99%, P<0.05). For the patients with stage III tumors, the median overall and disease-free survival term were significantly longer in radiochemotherapy group than in radiotherapy group (94.5 months vs. 85.1 months, 89.5 months vs. 82.9 months, P<0.05). For the patients with stage IVa tumors, the same results were obtained (82.4 months vs. 44.4 months, 69.6 months vs. 40.3 months, P<0.05). Cox regression analysis showed that clinical stage and chemotherapy were dependent prognostic factors of advanced NPC.

Conclusion: Induction chemotherapy plus concurrent radiochemotherapy could prolong the survival of patients with advanced NPC.
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August 2007
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