Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

Background

N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT).

Patients and Methods

Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy.

Results

With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ² = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups.

Conclusion

IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute toxicity rate.     

Outcomes of Induction Chemotherapy Plus Intensity-Modulated Radiotherapy (IMRT) Versus IMRT Plus Concurrent Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Study

PURPOSE: It deserves investigation whether induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) is inferior to the current standard of IMRT plus concurrent chemotherapy (CC) in locoregionally advanced nasopharyngeal carcinoma. METHODS: Patients who received IC (94 patients) or CC (302 patients) plus IMRT at our center between March 2003 and November 2012 were retrospectively analyzed. Propensity-score matching method was used to match patients in both arms at equal ratio. Failure-free survival (FFS), overall survival (OS), distant metastasis–free survival (DMFS), and locoregional relapse–free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: In the original cohort of 396 patients, IC plus IMRT resulted in similar FFS (P = .565), OS (P = .334), DMFS (P = .854), and LRFS (P = .999) to IMRT plus CC. In the propensity-matched cohort of 188 patients, no significant survival differences were observed between the two treatment approaches (3-year FFS 80.3% vs 81.0%, P = .590; OS 93.4% vs 92.1%, P = .808; DMFS 85.9% vs 87.7%, P = .275; and LRFS 93.1% vs 92.0%, P = .763). Adjusting for the known prognostic factors in multivariate analysis, IC plus IMRT did not cause higher risk of treatment failure, death, distant metastasis, or locoregional relapse. CONCLUSIONS: IC plus IMRT appeared to achieve comparable survival to IMRT plus CC in locoregionally advanced nasopharyngeal carcinoma. Further investigations were warranted.     

Comparison of Long-Term Survival and Toxicity of Cisplatin Delivered Weekly versus Every Three Weeks Concurrently with Intensity-Modulated Radiotherapy in Nasopharyngeal Carcinoma

Background

We aimed to compare the long-term survival outcomes and acute toxicity of cisplatin administered weekly versus every three weeks concurrently with intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC).

Methods

This was a retrospective review of 154 patients with histologically proven, non-disseminated NPC who were treated using IMRT between January 2003 and December 2007. Seventy-three patients (47.4%) received 5–7 weeks of 30–40 mg/m² cisplatin weekly; 81 patients (52.6%) received two or three cycles of 80 mg/m² cisplatin every three weeks. IMRT was delivered at 68 Gy/30 fractions to the nasopharyngeal gross target volume and 60–66 Gy to the involved neck area.

Results

The clinical characteristics and treatment factors of the two groups were well-balanced. The median follow-up was 74 months (range, 6–123 months), and the 5-year overall survival, disease-free survival, locoregional relapse-free survival, and distant metastasis–free survival rates were 85.2% vs. 78.9% (P = 0.318), 71.6% vs. 71.0% (P = 0.847), 93.5% vs. 92.6% (P = 0.904), and 80.9% vs. 80.1% (P = 0.925) for the group treated every three weeks and weekly, respectively. Subgroup analyses indicated no significant differences in the survival rates of the two groups among patients with early- or advanced-stage disease. The incidence of acute toxicities was similar between groups.

Conclusion

IMRT with concurrent cisplatin administered weekly or every three weeks leads to similar long-term survival outcomes and acute toxicity in NPC regardless of whether patients have early- or advanced-stage disease.     

Long-term outcomes of induction chemotherapy followed by intensity-modulated radiotherapy and adjuvant chemotherapy in nasopharyngeal carcinoma patients with N3 disease

ObjectivesTo evaluate long-term outcomes of induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) and adjuvant chemotherapy (AC) in nasopharyngeal carcinoma (NPC) patients with N3 disease.Materials and methodsFrom September 2005 to August 2016, 143 patients confirmed NPC with the 8th AJCC/UICC staging criteria N3 were reviewed. All patients received IC followed by IMRT and AC.ResultsAfter a median follow-up of 67 months, the 5-year and 10-year overall survival (OS), progression-free survival (PFS), distant metastasis free survival (DMFS), local progression-free survival (LPFS) and regional progression-free survival (RPFS) were 75.7% and 61.6%, 61.2% and 53.4%, 73.1% and 72.1%, 92.4% and 87%, 88.9% and 81.8%, respectively. Multivariate analyses indicated that T stage (P = 0.001) appeared to be prognostic factors for OS. T stage (P = 0.001 and P = 0.002) and neck lymph node necrosis (P = 0.015 and P = 0.045) were independent predictors of PFS and DMFS. The acute toxicities were mainly grade 1/2 hematologic toxicities in patients treated with IC+IMRT+AC, and severe toxicities were uncommon.ConclusionsIC followed by IMRT and AC achieved satisfactory long-term survival outcomes in NPC patients with N3 disease. Neck lymph node necrosis and late T stage served as predictors of poor prognosis for patients.     

Long-term outcomes of induction chemotherapy followed by intensity-modulated radiotherapy and adjuvant chemotherapy in nasopharyngeal carcinoma patients with N3 disease

ObjectivesTo evaluate long-term outcomes of induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) and adjuvant chemotherapy (AC) in nasopharyngeal carcinoma (NPC) patients with N3 disease.Materials and methodsFrom September 2005 to August 2016, 143 patients confirmed NPC with the 8th AJCC/UICC staging criteria N3 were reviewed. All patients received IC followed by IMRT and AC.ResultsAfter a median follow-up of 67 months, the 5-year and 10-year overall survival (OS), progression-free survival (PFS), distant metastasis free survival (DMFS), local progression-free survival (LPFS) and regional progression-free survival (RPFS) were 75.7% and 61.6%, 61.2% and 53.4%, 73.1% and 72.1%, 92.4% and 87%, 88.9% and 81.8%, respectively. Multivariate analyses indicated that T stage (P = 0.001) appeared to be prognostic factors for OS. T stage (P = 0.001 and P = 0.002) and neck lymph node necrosis (P = 0.015 and P = 0.045) were independent predictors of PFS and DMFS. The acute toxicities were mainly grade 1/2 hematologic toxicities in patients treated with IC+IMRT+AC, and severe toxicities were uncommon.ConclusionsIC followed by IMRT and AC achieved satisfactory long-term survival outcomes in NPC patients with N3 disease. Neck lymph node necrosis and late T stage served as predictors of poor prognosis for patients.     

Treatment Outcomes of 257 Patients with Locoregionally Advanced Nasopharyngeal Carcinoma Treated with Nimotuzumab Plus Intensity-Modulated Radiotherapy with or without Chemotherapy: A Single-Institution Experience

OBJECTIVES: To report the long-term outcome and toxicity of locoregionally advanced nasopharyngeal carcinoma (LA NPC) treated with nimotuzumab (h-R3) plus intensity-modulated radiotherapy (IMRT) with or without chemotherapy. METHODS: From May 2008 to March 2014, 3022 newly histology-proven, nonmetastatic NPC patients were retrospectively reviewed; among them, 257 patients treated with h-R3 were enrolled in this study. The patients' age range was between 10 and 76 years. The distribution of patients by disease stage was 150 (58.4%) in stage III, 88 (34.2%) in stage IV A, and 19 (7.4%) in stage IV B. All the patients received the treatment of h-R3 plus IMRT, and from them, 239 cases were also treated with cisplatin-based chemotherapy. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. The accumulated survival was calculated according to the Kaplan-Meier method. Log-rank test was used to compare the survival difference. Multivariate analysis was performed using Cox's proportional-hazard model. RESULTS: All 257 patients had completed combined treatment; 231 patients received h-R3 plus IMRT with induction chemotherapy (IC), while 26 patients received only h-R3 plus IMRT. With a median follow-up of 48 months (range, 13-75 months), the estimated 5-year local recurrence-free survival, regional recurrence-free survival, distant metastases-free survival, progression-free survival, and overall survival (OS) rates were 94.3%, 94.8%, 91.9%, 83.4%, and 86.2%, respectively. Univariate analysis showed that age, T stage, clinical stage, and IC were related with OS. Multivariate analysis indicated that T stage and IC were independent prognostic factors for OS. The incidence of grade 3 to 4 acute mucositis and leukocytopenia was 10.9% and 19.8%, respectively, with no cases of skin rash and infusion reaction. Xerostomia was the most common late complication, and the degree of dry mouth in most survivors was mild to moderate at the last follow-up time. CONCLUSION: h-R3 plus IMRT with or without chemotherapy showed promising outcomes in terms of locoregional control and survival without increasing the incidence of radiation-related toxicities for patients.     

Induction Chemotherapy Has No Prognostic Value in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma and Chronic Hepatitis B Infection in the IMRT Era

BACKGROUND: The effectiveness of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) over CCRT alone in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and chronic hepatitis B infection in the intensity-modulated radiotherapy (IMRT) era is unknown. PATIENTS AND METHODS: A total of 249 patients with stage T1-2 N2-3 or T3-4 N1-3 NPC and chronic hepatitis B infection treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) was employed to balance covariates; 140 patients were propensity-matched (1:1 basis). Survival outcomes in the IC + CCRT and CCRT groups were compared using the Kaplan–Meier method, log-rank test and Cox proportional hazards model. RESULTS: No significant survival differences were observed between IC + CCRT and CCRT (5-year overall survival, 88.3% vs. 82.2%; P = .484; disease-free survival, 73.9% vs. 75.2%; P = .643; distant metastasis-free survival, 84.1% vs. 85.1%; P = .781; and locoregional failure-free survival, 87.9% vs. 85.1%; P = .834). After adjusting for known prognostic factors in multivariate analysis, IC was not an independent prognostic factor for any outcome (all P > .05); subgroup analysis based on T category (T1-2/T3-4), N category (N0-1/N2-3), and overall stage (III/IV) confirmed these results. The incidence of hepatic function damage in the IC + CCRT and CCRT groups was not significantly different. CONCLUSION: IC + CCRT leads to comparable survival outcomes and hepatic function damage compared to CCRT alone in patients with locoregionally advanced NPC with chronic hepatitis B infection in the IMRT era. Further investigations are warranted.     

Combination of Taxanes,Cisplatin and Fluorouracil as Induction Chemotherapy for Locally Advanced Head and Neck Cancer: A Meta-Analysis

Background

Some investigations have suggested that induction chemotherapy with a combination of taxanes, cisplatin and fluorouracil (TPF) is effective in locally advanced head and neck cancer. However, other trials have indicated that TPF does not improve outcomes. The objective of this study was to compare the efficacy and safety of TPF with a cisplatin and fluorouracil (PF) regimen through a meta-analysis.

Methods

Four randomized clinical trials were identified, which included 1,552 patients with locally advanced head and neck cancer who underwent induction chemotherapy with either a TPF or PF protocol. The outcomes included the 3-year survival rate, overall response rate and different types of adverse events. Risk ratios (RRs) and their 95% confidence intervals (CIs) were pooled using RevMan 5.1 software.

Results

The 3-year survival rate (51.0% vs. 42.4%; p = 0.002), 3-year progression-free survival rate (35.9% vs. 27.2%; p = 0.007) and overall response to chemotherapy (72.9% vs. 62.1%; p<0.00001) of the patients in the TPF group was statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia (7.0% vs. 3.2%; p = 0.001) and alopecia (10.8% vs. 1.1%; p<0.00001) was higher in the TPF group.

Conclusion

The TPF induction chemotherapy regimen leads to a significant survival advantage with acceptable toxicity rates for patients with locally advanced head and neck cancer compared with the PF regimen.     

The effect of adding concurrent chemotherapy to radiotherapy for stage II nasopharyngeal carcinoma with undetectable pretreatment Epstein-Barr virus DNA: Retrospective analysis with a large institutional-based cohort

Little is known about the value of adding concurrent chemotherapy (CC) to radiotherapy for stage II nasopharyngeal carcinoma (NPC) with undetectable (0 copies/mL) pretreatment Epstein-Barr Virus (EBV) DNA in the intensity-modulated radiotherapy (IMRT) era. To address this question, the present study retrospectively reviewed 514 patients with newly diagnosed stage II NPC and undetectable pretreatment EBV DNA from Sun Yat-sen University Cancer Center between March 2008 and October 2016. Clinical characteristics and survival outcomes between concurrent chemoradiotherapy (CCRT) and IMRT alone groups were compared. Propensity score matching analysis was conducted to control for confounding factors. Although CCRT group had significantly higher proportions of stage N1 disease than IMRT alone group before matching (85% vs. 61%, p < 0.001), no statistically significant differences were noted for OS (97.8% vs. 98.1%, p = 0.700), DFS (93.4% vs. 94.5%, p = 0.846), DMFS (96.0% vs. 96.9%, p = 0.762), and LRFS (97.3% vs. 98.1%, p = 0.701). After 1:1 propensity-score matching, 177 pairs were identified. Patients in each group were found to be well balanced in baseline characteristics and risk factors (all P > 0.05). The five-year OS (96.9% vs. 98.2%, p = 0.302), DFS (92.0% vs. 95.2%, p = 0.777), DMFS (95.2% vs. 97.6%, p = 0.896), and LRFS (97.3% vs. 97.6%, p = 0.328) rates remain comparable for both CCRT and RT alone groups. Additionally, subgroup analysis still failed to observe any significant survival benefit for the addition of CC to IMRT for N1 disease (P>0.05 for all). Our results indicated that IMRT alone appeared to achieve comparable survival to CCRT for stage II NPC with undetectable pretreatment EBV DNA.Keyword: Nasopharyngeal carcinoma, Epstein–Barr virus DNA, Survival, Intensity-modulated radiotherapy, Concurrent chemotherapy, Effect     

The Effect of Adding Neoadjuvant Chemotherapy to Concurrent Chemoradiotherapy in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma and Undetectable Pretreatment Epstein-Barr Virus DNA

PURPOSE: To assess the effect of adding neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and undetectable pretreatment Epstein-Barr virus (pEBV) DNA. MATERIALS AND METHODS: We enrolled 639 NPC patients with stage II to IVB and undetectable pEBV DNA to receive CCRT with or without NACT. Radiotherapy was 2.0 to 2.27 Gy per fraction with five daily fractions per week for 6 to 7 weeks to the primary tumor and 62 to 70 Gy to the involved neck area. NACT was cisplatin (80-100 mg/m² day 1) and 5-fluorouracil (800-1000 mg/m², 120-hour continuous intravenous infusion) every 3 weeks for two or three cycles. CCRT was cisplatin (80-100 mg/m² day 1) every 3 weeks for three cycles. RESULTS: For all patients, the 5-year overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates were 91.9%, 92.2%, 95.0%, and 86.4%, respectively. There was no significant difference in OS (5-year OS 90.8% [NACT + CCRT group] vs 92.7% [CCRT alone]; hazard ratio [HR] 1.24; P = .486), LRFS (HR 1.13, 95% confidence interval [CI] 0.59-2.14, P = .715), DMFS (HR 0.78, 95% CI 0.34-1.78, P = .554), or PFS (HR 1.21, 95% CI 0.75-1.95, P = .472). CONCLUSION: CCRT with or without NACT produced a good treatment outcome in patients with locoregionally advanced NPC and undetectable pEBV DNA, but NACT before CCRT did not significantly improve survival rates.     

Genetic Variations in Radiation and Chemotherapy Drug Action Pathways and Survival in locoregionally Advanced Nasopharyngeal Carcinoma Treated with Chemoradiotherapy

Background and Purpose

Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy.

Material and Methods

Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR) analysis was performed to detect potential gene-gene interaction.

Results

After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P<0.001). The ERCC1 rs3212986 CC (HR=1.711, 95% CI, 1.135-2.579, P=0.010), MDM2 rs2279744 GT/GG (HR=1.743, 95% CI, 1.086-2.798, P=0.021), MPO rs2243828 CT/CC (HR=3.184, 95% CI, 2.261-4.483, P<0.001) and ABCB1 rs2032582 AT/AA (HR=1.997, 95% CI, 1.086-3.670, P=0.026) genotypes were associated with poor progression-free survival. Prognostic score models based on independent prognostic factors successfully classified patients into low-, intermediate-, and high-risk groups. Furthermore, MDR analysis showed no significant interaction between polymorphisms.

Conclusions

Four single nucleotide polymorphisms were associated with survival in patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Combining clinical prognostic factors with genetic information was valuable in identifying patients with different risk.     

Prognoses and Long-Term Outcomes of Nasopharyngeal Carcinoma in Han and Uyghur Patients Treated with Intensity-Modulated Radiotherapy in the Xinjiang Autonomous Region of China

Objectives

The objective of this study was to investigate the long-term outcomes and prognostic factors for nasopharyngeal carcinoma (NPC) in Han and Uyghur patients treated with intensity-modulated radiotherapy (IMRT) in the Xinjiang region of China.

Materials and Methods

One hundred twenty-one Han and 60 Uyghur patients with newly diagnosed NPC without distant metastasis received IMRT at the Affiliated Tumor Hospital of Xinjiang Medical University between 2005 and 2008. The Kaplan-Meier method was used to estimate survival rates, and the log-rank test was used to evaluate differences in survival.

Results

Comparing Han and Uyghur patients, the 5-year overall survival (OS), disease-free survival (DFS), local control (LC), regional control (RC), and distant metastasis-free survival (DMFS) rates were 81.9% vs 77.6% (P = 0.297), 72.1% vs 65.6% (P = 0.493), 88.3% vs 86.5% (P = 0.759), 95.0% vs 94.6% (P = 0.929), and 79.1% vs 75.2% (P = 0.613), respectively. Multivariate Cox proportional hazards regression identified the following independent prognostic factors in Han patients: N stage (P = 0.007) and age (P = 0.028) for OS, and age (P = 0.028) for DFS. OS differed significantly between Han and Uyghur patients >60 years old group (P = 0.036). Among Uyghur patients, the independent prognostic factors were age for OS (P = 0.033), as well as N stage (P = 0.037) and age (P = 0.021) for DFS. Additionally, Uyghur patients were less likely to experience mucositis and dermatitis than Han patients.

Conclusion

Han and Uyghur patients with NPC had statistically significant differences in age, smoking history, and N staging. There was no significant difference in overall treatment outcomes with IMRT between these 2 ethnic populations in Xinjiang, China.     

Prognostic Value and Staging Classification of Retropharyngeal Lymph Node Metastasis in Nasopharyngeal Carcinoma Patients Treated with Intensity-modulated Radiotherapy

Background

The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the prognostic value and classification of TNM stage system for retropharyngeal lymph node (RLN) metastasis in NPC in the IMRT era.

Material and Methods

We retrospectively reviewed data from 749 patients with biopsy-proven, non-metastatic NPC. All patients received IMRT as the primary treatment. Chemotherapy was administered to 86.2% (424/492) of the patients with stage III or IV disease.

Results

The incidence of RLN metastasis was 64.2% (481/749). Significant differences were observed in the 5-year disease-free survival (DFS; 70.6% vs. 85.4%, P<0.001) and distant metastasis-free survival (DMFS; 79.2% vs. 90.1%, P<0.001) rates of patients with and without RLN metastasis. In multivariate analysis, RLN metastasis was an independent prognostic factor for disease failure and distant failure (P = 0.005 and P = 0.026, respectively), but not for locoregional recurrence. Necrotic RLN metastases have a negative effect on disease failure, distant failure and locoregional recurrence in NPC with RLN metastasis (P = 0.003, P = 0.018 and P = 0.005, respectively). Survival curves demonstrated a significant difference in DFS between patients with N0 disease and N1 disease with only RLN metastasis (P = 0.020), and marginally statistically significant differences in DMFS and DFS between N1 disease with only RLN metastasis and other N1 disease (P = 0.058 and P = 0.091, respectively). In N1 disease, no significant differences in DFS were observed between unilateral and bilateral RLN metastasis (P = 0.994).

Conclusions

In the IMRT era, RLN metastasis remains an independent prognostic factor for DFS and DMFS in NPC. It is still reasonable for RLN metastasis to be classified in the N1 disease, regardless of laterality. However, there is a need to investigate the feasibility of classifying RLN metastasis as N1a disease in future by a larger cohort study.     

Elevated High-Sensitivity C-Reactive Protein Levels Predict Decreased Survival for Nasopharyngeal Carcinoma Patients in the Intensity-Modulated Radiotherapy Era

Purpose

This study aimed to clarify the prognostic utility of high-sensitivity C-reactive protein (hs-CRP) in nasopharyngeal carcinoma (NPC) patients in the Intensity-Modulated Radiotherapy (IMRT) era.

Patients and Methods

In this observational study, 1,589 non-metastatic NPC patients treated with IMRT were recruited. Blood samples were collected before treatment for examination of hs-CRP levels. We evaluated the association of pretreatment hs-CRP levels with overall survival rate (OS), progression free survival rate (PFS), locoregional relapse free survival rate (LRFS) and distant metastasis free survival rate (DMFS).

Results

Baseline hs-CRP levels were correlated with sex, clinical stage, body mass index, smoking status, and EBV DNA level. Multivariate analysis showed that hs-CRP had significant association with OS (HR:1.723; 95%CI:1.238–2.398; p = 0.001), PFS (HR:1.621; 95%CI:1.273–2.064; p<0.001) and DMFS (HR:1.879; 95%CI:1.394–2.531; p<0.001). In subgroups such as advanced-stage group, low EBV DNA group and high EBV DNA group, elevated hs-CRP levels still predicted poor clinical outcomes. Furthermore, in patients with chronic HBV infection, decreased 4-year survival was observed in the cohort of high hs-CRP levels, with 87.4% vs. 94.9% (p = 0.023) for OS, 65.2% vs. 90.8% (p<0.001) for PFS, and 67.6% vs. 95.0% (p<0.001) for DMFS. A similar finding was observed for patients with cardiovascular disease, with 79.1% vs. 90.2% (p = 0.020) for PFS, and 71.4% vs. 97.6% (p = 0.002) for DMFS.

Conclusion

Elevated serum hs-CRP levels were correlated with poor survival for NPC patients in the IMRT era, playing a complementary role to TNM stage and EBV DNA. In addition, elevated hs-CRP level was still an effective indicator for patients with chronic HBV infection and cardiovascular disease.     

Comparison of a Concurrent Fluorouracil-Based Regimen and a Taxane-Based Regimen Combined with Radiotherapy in Elderly Patients with Esophageal Squamous Cell Carcinoma

Elderly patients with esophageal carcinoma may benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen has not been determined. The aim of our study was to assess the efficiency and tolerance of treatment with a concurrent 5-fluorouracil (5-Fu)–based regimen and a taxane-based regimen combined with radiotherapy in elderly patients with esophageal squamous cell carcinoma (ESCC). A total of 46 patients with ESCC aged older than 65 years were included in this study. The patient population was divided into two treatment groups: 24 patients who received CCRT with a 5-Fu–based regimen were allocated to the PF group, and 22 patients who received CCRT with a taxane-based regimen were allocated to the DP group. The median overall survival (OS), median progression-free survival (PFS), overall response rate, and treatment-related toxicity were assessed. For patients in the PF group, the median OS time was 27.8 ± 9.1 months, and the median PFS time was 12.5 ± 2.7 months. Patients in the DP group had comparable survival outcomes, with a median OS time of 34.4 ± 6.4 months and a median PFS time of 21.1 ± 6.4 months (P = .296 and P = .115, respectively). Grade ≥3 leukocytopenia and grade ≥2 anemia occurred in 63.6% and 59.1% of patients in the DP group, respectively, and in 25.0% and 16.7% of patients in the PF group, respectively. Our results suggest that CCRT with a taxane-based regimen results in a higher incidence of treatment-related toxicity than CCRT with a 5-Fu–based regimen but comparable survival outcomes.     

Prognostic Value of Cavernous Sinus Invasion in Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiotherapy

Purpose

To investigate the prognostic value of cavernoussinus invasion (CSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT).

Patients and Methods

Retrospective review of data from 1,087 patients with biopsy-proven, non-metastatic NPC. All patients were diagnosed using magnetic resonance imaging (MRI) scans and received IMRT as the primary treatment.

Results

The incidence of cavernoussinus invasion in this cohort was 12.1%. In univariate analysis, 5-year overall survival (OS) (70.6% vs. 88.5%, P < 0.001) and distant metastasis-free survival (DMFS) (71.4% vs. 87.7%, P < 0.001), but not locoregional relapse-free survival (LRFS) (93.9% vs. 93.7%, P = 0.341), were significantly different between patients with and without cavernoussinus invasion. In the T4 subgroup, the 5-year OS, DMFS, and LRFS of patients with and without cavernoussinus extension were 70.6% vs. 81.9% (P = 0.011), 71.4% vs. 84.1% (P = 0.011), and 91.2% vs. 89.7% (P = 0.501), respectively. In multivariate analysis, cavernoussinus invasion was an independent prognostic factor for poorer OS (HR = 1.782; P = 0.013) and DMFS (HR = 1.771; P = 0.016), but not LRFS (HR = 0.632; P = 0.294). In patients with lymph node metastasis, the DMFS rates of patients with and without cavernoussinus invasion were significantly different (P < 0.001). Preliminaryanalysis indicated that neoadjuvant chemotherapy led to better DMFS and OS in patients with cavernoussinus invasion than concurrent chemotherapy or radiotherapy alone; however, the differences were not significant.

Conclusions

In the IMRT era, cavernoussinus invasion remains a prognostic factor for poor DMFS and OS in NPC, even in patients with T4 disease.     

Radiochemotherapy in Anal Cancer: cCR,clinical outcomes and quality of life using two different treatment schedules

AimMain endpoint was a response rate to therapy; secondary endpoints were disease-free survival, overall survival, acute and late toxicities, specially in terms of anorectal and urinary continence.BackgroundRadiochemotherapy for anal cancer achieves a good clinical response, locoregional control, anal function preservation. However, oncologic outcomes can differ using radiotherapy plus fluorouracil and mytomicin vs. cisplatin and fluorouracil.MethodsBetween 2000 and 2012, 27 anal cancer patients receiving radiotherapy combined with two different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and cisplatin plus fluorouracil (group B). The Kaplan–Meier method was also used to estimate local control, overall survival and disease free survival. Statistical significance between curves was evaluated using the Log-rank test.ResultsComplete pathological response was found in 85.2% of patients, with higher rates of response in the group A (100% vs. 63.6%, p = 0.039). No significantly difference was found between the two groups for the other endpoints. Low rates of both acute and late toxicities were recorded.ConclusionRadiotherapy plus fluorouracil and mytomicin provide a better complete pathological response than radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter function preservation. Globally, radiochemotherapy of the anal cancer provides excellent clinical outcomes with a good profile of acute and late toxicity, without difference between the two groups studied.     

Concurrent Chemoradiotherapy With or Without Induction Chemotherapy for Patients with Stage II Nasopharyngeal Carcinoma: An Update

PURPOSE: In contrast to other studies, our previous study showed that adding induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) significantly worsened the prognosis of patients with stage II nasopharyngeal carcinoma (NPC). However, the population used was small; therefore, there is an urgent need to confirm the result in a larger population because IC is still widely used in certain sections of china for stage II NPC. METHODS AND MATERIALS: We retrospectively analyzed an additional 272 patients. Therefore, in total, we report the results for 445 patients with stage II NPC treated with IC + CCRT or CCRT between June 2003 to June 2016 at the Zhejiang Cancer Hospital and Sun Yat-Sen University Cancer Center. RESULTS: This study included 445 patients treated with IC + CCRT (n = 195) or CCRT (n = 250). By last analysis, 22 (11.3%) patients in the IC + CCRT group developed local-regional recurrence and 23 (11.8%) patients developed distant metastases. Twenty-four (9.6%) patients in the CCRT group developed local-regional recurrence and 12 (4.8%) patients developed distant metastases. Univariate analyses showed that adding IC to CCRT significantly decreased the 5-year disease-free survival (DFS) (80.6% vs. 88.5%, P = .043); however, there was no statistically significant difference in 5-year overall survival (OS) (90.5% vs. 95.0%, P = .375). CONCLUSION: Using a larger population, the present study showed that adding IC to CCRT had a negative effect on patients with stage II NPC, which warrants further investigation.     

The Effect of Adjuvant Chemotherapy on Survival in Patients with Residual Nasopharyngeal Carcinoma after Undergoing Concurrent Chemoradiotherapy

Background

Guidelines from the U.S. National Comprehensive Cancer Network have recommended use of concurrent chemoradiotherapy (CCRT), followed by a 3-cycles combination of platinum and 5-fluorouracil chemotherapy as standard treatment for nasopharyngeal carcinoma (NPC). The benefits of CCRT for treatment of locally advanced NPC have been established. Whether platinum and 5-fluorouracil chemotherapy should be routinely added to locally advanced NPC after CCRT is still open to debate. Whether adjuvant chemotherapy provides an additional survival benefit for the subgroup of patients with residual nasopharyngeal carcinoma who have undergone CCRT is also unclear. This retrospective study was initiated to determine the survival benefit of adjuvant chemotherapy (AC) in residual NPC patients who have undergone concurrent chemoradiotherapy.

Methods

The retrospective study included 155 nasopharyngeal carcinoma patients who had local residual lesions after the platinum-based CCRT without or with AC. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS).

Results

Median follow-up was 47 months. Adjuvant cisplatin or nedaplatin plus 5-fluorouracil chemotherapy did not significantly improve 3-year OS, LRFS, FFS, and DMFS for patients with residual nasopharyngeal carcinoma after undergoing CCRT. The 3-year OS rates for the no-AC group and AC group were 71.6% and 73.7%, respectively (P= 0.44). The 3-year FFS rates for no-AC group and AC group were 57.5% and 66.9%, respectively ((P= 0.19). The 3-year LRFS rates for no-AC group and AC group were 84.7% and 87.9%, respectively ((P= 0.51). The 3-year DMFS rates for no-AC group and AC group were 71.4% and 77.4%, respectively ((P= 0.23).

Conclusions

Since we did not find sufficient data to support significant survival in 3-year OS, LRFS, FFS, and DMFS, whether Adjuvant cisplatin or nedaplatin and 5-fluorouracil chemotherapy should be routinely added to residual nasopharyngeal carcinoma patients after undergoing CCRT remain uncertain.     

Sensorineural Hearing Loss after Combined Intensity Modulated Radiation Therapy and Cisplatin-Based Chemotherapy for Nasopharyngeal Carcinoma

PURPOSE: The incidence of sensorineural hearing loss (SNHL) after treatment with combination of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy in nasopharyngeal carcinoma (NPC) patients was evaluated, and relationships of SNHL with host factors, treatment-related factors, and radiation dosimetric parameters were investigated. METHODS: Fifty-one NPC patients treated with IMRT from 2004 to 2009 were analyzed. All patients received neoadjuvant, concurrent, or adjuvant use of cisplatin. Pure tone audiometry was performed during the follow-up period with a median time of 60 months, ranging from 28 to 84 months. Correlation of SNHL at low frequencies (pure tone average, 0.5-2 kHz) with a series of factors was analyzed. RESULTS: Among 102 ears, 12.7% had low-frequency SNHL and 42.2% had high-frequency (4 kHz) SNHL. The incidence of low-frequency SNHL was greater in patients with age > 40, with T-stage 4, or who received cumulative cisplatin dose (CCD) > 200 mg/m² (P = .034, .011, and .003, respectively) and in ears with secretory otitis media (SOM) (P = .002). Several dosimetric parameters were found to be correlated with SNHL. Univariate analysis showed that the minimum radiation dose to 0.1 ml highest dose volume (D0.1 ml) of the cochlea was the best radiation-related predictive parameter. Multivariate analysis indicated that CCD, SOM, and D0.1 ml of cochlea (P = .035, .012, and .022, respectively) were the factors associated with SNHL. CONCLUSION: For NPC patients treated with IMRT and chemotherapy, the incidence of treatment-related SNHL was associated with CCD, D0.1 ml of cochlea, and SOM.