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 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.     

Friend Leukemia Virus Integration 1 Expression Has Prognostic Significance in Nasopharyngeal Carcinoma

This study aimed to investigate the expression pattern and prognostic value of friend leukemia virus integration 1 (FLI-1) in nasopharyngeal carcinoma (NPC). Immunohistochemistry (IHC) staining of FLI-1 was performed in specimens from 198 untreated NPC patients. Ninety-nine patients were randomly assigned to the training set to analyze the prognostic value of FLI-1 and other clinicopathological characteristics, while the others were assigned to the testing set for validation. Clinicopathological data were compared using the Pearson chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards model to test independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI). Cytoplasmic FLI-1 expression positively correlated with N stage, distant metastasis and death (P< 0.05) and also predicted poorer overall survival (OS) (P= 0.014), distant metastasis-free survival (DMFS) (P= 0.010), progression-free survival (PFS) (P= 0.031). In multivariate analysis, FLI-1 expression and clinical stage were both independent prognostic factors of poor OS and DMFS. Prognoses of patients in the training set, the testing set, and the entire set were clearly divided into four risk subgroups by supplementing FLI-1 with clinical stage. These results indicate that FLI-1 expression is an independent prognostic factor for NPC patients and suggest that supplementing FLI-1 with clinical stage could be helpful for more accurate risk definition.     

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.     

Efficacy of cascade-primed cell infusion as an adjuvant immunotherapy with concurrent chemotherapy for patients with non–small-cell lung cancer: A retrospective observational study with a 5-year follow-up

BackgroundClinical studies have shown the efficacy of combination therapy for various malignancies. In this study, the characteristics, safety and feasibility of use of cascade-primed (CAPRI) cells for the combination treatment of non–small-cell lung cancer (NSCLC) were evaluated both in vitro and in vivo.MethodsSixty-five patients with stage II–IV NSCLC were recruited. Of these patients, 31 patients received CAPRI cell therapy combined with chemotherapy (CAPRI group), and the other 34 patients constituted the control group and received chemotherapy alone. This study primarily aimed to evaluate the overall survival (OS), progression-free survival (PFS), short-term responses and treatment efficacy.ResultsCD83, CD1a, CD80 and CD86 marker levels were significantly upregulated in CAPRI cells. Interferon-γ expression levels were highest in CD3⁺CD8⁺ cells (33.77% ± 4.40%). Furthermore, interleukin-2 levels were highest in CD3⁺CD56⁺ cells (26.73% ± 6.63%), whereas perforin expression levels were similar in CD3⁺CD8⁺ and CD3⁺CD56⁺ cells. Furthermore, CAPRI cells had a better anti-tumor potential in CD3⁺CD56⁺ cells and displayed the highest expression levels of CD107a to H460 and A549 cell lines. The 5-year OS was significantly greater in the CAPRI group than in the control group (P = 0.008), and the PFS of two groups exhibited a significant difference (P = 0.007). Median OS (48 versus 31.6 months; P = 0.004) and PFS (48 versus 36.4 months; P = 0.016) differed between these two groups. Moreover, treatment-associated toxicities were mild and well-tolerated by patients with NSCLC.ConclusionCAPRI cell therapy potentially prolongs the survival of patients with NSCLC when combined with chemotherapy.     

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     

Prognostic value of Ki-67 in nasopharyngeal carcinoma: a meta-analysis

The prognostic value of Ki-67 in nasopharyngeal carcinoma (NPC) was controversial according to previous studies. We aimed to clarify the association between K-67 expression and survival in NPC through meta-analysis. We conducted a meta-analysis to explore the potential prognostic effect of Ki-67 on overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) in NPC. A total of 13 studies comprising 1314 NPC patients were included. High Ki-67 expression was associated with poor OS (hazard ratio [HR]= 2.70, 95% confidence interval [CI]= 1.97–3.71, P<0.001), DFS (HR = 1.93, 95% CI = 1.49–2.50, P<0.001), and LRFS (HR = 1.86, 95% CI = 1.11–3.12, P=0.019). However, there was no significant association between Ki-67 and DMFS (HR = 1.37, 95% CI = 0.78–2.38, P=0.270). Furthermore, the prognostic role of Ki-67 was maintained throughout different sample sizes, analyses of HR, and study designs for OS and DFS in various subgroups. Elevated Ki-67 expression is a reliable prognostic factor for poorer survival outcomes in NPC.     

Anti-PD1 checkpoint inhibitor with or without chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma

PurposeTo compare the efficacy and safety of anti-PD1 checkpoint inhibitor plus chemotherapy with anti-PD1 checkpoint inhibitor alone in recurrent and metastatic nasopharyngeal carcinoma (R/M NPC) progressing after first or subsequent-line therapy.Methods and materialsA total of 67 patients with recurrent and metastatic nasopharyngeal carcinoma from our hospital were included. All patients were sorted into two arms: anti-PD1 checkpoint inhibitor+ chemotherapy arm and anti-PD1 checkpoint inhibitor arm. We retrospectively estimated objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in patients of both arms. Chi-square test and Kaplan–Meier methodology were used to analyze.ResultsFrom September 2018 to March 2020, this research included 67 patients. For anti-PD1 checkpoint inhibitor+ chemotherapy arm, partial response and stable disease were observed in fourteen and 11 patients, respectively, for an ORR of 53.8%. For anti-PD1 checkpoint inhibitor arm, complete response and partial response were observed in one and 5 patients, respectively, for an ORR of 14.6%. The incidence of hyperprogressive disease was higher in the anti-PD1 checkpoint inhibitor group compared with anti-PD1 checkpoint inhibitor+ chemotherapy group (39.0% vs 3.8%, p<0.05). Univariable analyses discovered that 6-month PFS and OS benefits were observed for anti-PD1 checkpoint inhibitor+ chemotherapy arm compared to anti-PD1 checkpoint inhibitor arm (65.4% vs. 28.6%, P = 0.001; 100.0% vs. 73.5%, P = 0.014).ConclusionIn present study, we revealed that adding chemotherapy to anti-PD1 checkpoint inhibitor significantly improved 6-month PFS and OS for patients with R/M NPC progressing after first-line therapy. It warrants further study.     

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.     

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.     

The predictive efficacy of tumor mutation burden in immunotherapy across multiple cancer types: A meta-analysis and bioinformatics analysis

PurposeTo explore the predictive efficacy of tumor mutation burden (TMB) as a potential biomarker for cancer patients treated with Immune checkpoint inhibitors (ICIs).MethodsWe systematically searched PubMed, Cochrane Library, Embase and Web of Science for clinical studies (published between Jan 1, 2014 and Aug 30, 2021) comparing immunotherapy patients with high TMB to patients with low TMB. Our main endpoints were objective response rate (ORR), durable clinical benefit (DCB), overall survival (OS) and progress-free Survival (PFS). Moreover, we downloaded simple nucleotide variation (SNV) data of 33 major cancer types from the TCGA database as non-ICIs group, and compared the high TMB patients’ OS between the non-ICIs group and meta-analysis results.ResultsOf 10,450 identified studies, 41 were eligible and were included in our analysis (7713 participants). Compared with low TMB patients receiving ICIs, high TMB yielded a better ORR (RR = 2.73; 95% CI: 2.31–3.22; P = 0.043) and DCB (RR = 1.93; 95% CI: 1.64–2.28; P = 0.356), and a significantly increased OS (HR =0.24; 95% CI: 0.21–0.28; P < 0.001) and PFS (HR = 0.38; 95% CI: 0.34–0.42; P < 0.001). Furthermore, compared with non-ICIs group from the TCGA database, immunotherapy can improve OS in some cancer types with high TMB and better prognosis, including colorectal cancer, gastric cancer, lung cancer, melanoma and pan-cancer.ConclusionTMB is a promising therapeutic and prognostic biomarker for immunotherapy, which indicates a better ORR, DCB, OS and PFS. If there is a standard for TMB assessment and cut-off, it could improve the management of different cancers.     

The prognostic value of circulating tumor DNA in patients with melanoma: A systematic review and meta-analysis

BackgroundCirculating tumor DNA (ctDNA) has been investigated as a potential prognostic biomarker to evaluate the therapeutic efficacy and disease progression in melanoma patients, yet results remain inconclusive. The purpose of this study was to illustrate the prognostic value of ctDNA in melanoma.ObjectivesTo describe the clinical prognostic value of ctDNA for melanoma patients.MethodsSearched for eligible articles from Pubmed, Web of Science and Embase. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ctDNA at baseline or during treatment and overall survival (OS) and progression-free survival (PFS).ResultsA total of 9 articles were obtained, involving 617 melanoma patients. The pooled HRs revealed that compared with baseline undetectable ctDNA patients, detectable ctDNA was highly correlated with poor OS (HR 2.91, 95% CI: 2.22–3.82; p < 0.001) and PFS (HR 2.75, 95% CI: 1.98–3.83; p < 0.001). A meta-analysis of these adjusted HRs was performed and confirmed that ctDNA collected at baseline was associated with poorer OS/PFS (OS: HR 3.00, 95% CI 2.19–4.11, p < 0.001/PFS: HR 2.68, 95% CI 1.77–4.06, p < 0.001). During treatment, a significant association was shown between ctDNA and poorer OS/PFS (OS: HR 6.26, 95% CI 2.48–15.80, p < 0.001; PFS: HR 4.93, 95% CI 2.36–10.33, p < 0.001).ConclusionInvestigation and application of ctDNA will improve "liquid biopsy" and play a role in early prediction, monitoring disease progression and precise adjusting treatment strategies in melanoma patients.     

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.     

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.     

Effects of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma: A real-world study

BackgroundTo evaluate the value of locoregional radiotherapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (dmNPC) and identify predictive factors for additional LRRT after palliative chemotherapy (PCT).MethodsOverall survival (OS) was the primary endpoint. Patients who underwent PCT and LRRT were categorized as the PCT+LRRT group; patients who only received palliative chemotherapy were categorized as the PCT group. Oligometastatic diseases (OMD) was defined as ≤5 metastatic lesions and ≤2 metastatic organs.ResultsA total of 168 patients were included for this study. The median OS of patients in the PCT+LRRT group was significantly higher than those in the PCT group (57 months vs. 22 months, P<0.001). Multivariate analyses (MVA) showed that LRRT (HR=0.533, 95% CI: 0.319–0.889, P = 0.016) and OMD (HR=0.548, 95% CI: 0.331–0.907, P = 0.019) were independent prognostic factors for dmNPC. Furthermore, Kaplan–Meier analyses showed that the 3-year OS of patients who received LRRT was significantly better than those who did not receive LRRT in the OMD subgroup (66.3% vs. 25.2%, P<0.001). While, the 3-year OS of patients who received LRRT and without LRRT was no different in the polymetastatic disease (PMD) subgroup (38.9% vs.11.5%, P = 0.115). MVA showed that LRRT was a favorable prognosticator in the OMD subgroup (HR=0.308, 95% CI: 0.159–0.598; P<0.001), and not a favorable prognosticator in the PMD subgroup (HR=0.510, 95% CI: 0.256–1.014, P = 0.055).ConclusionsLRRT has the potential to prolong OS in NPC patients with de novo OMD. These results suggest that OMD is a potential indicator for filtering beneficiaries from LRRT.     

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.     

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.     

Evaluation of the prognostic value of lymphadenectomy for low-grade serous ovarian cancer: A case-control multicenter retrospective study

BackgroundThe prognostic value of lymphadenectomy in low-grade serous ovarian cancer (LGSOC) remains uncertain.Materials and methodsA retrospective analysis of 155 patients with LGSOC who underwent surgery over a ten-year period (2011–2020) was performed. The propensity score matching (PSM) algorithm was performed between the lymphadenectomy and no lymphadenectomy groups, and Kaplan-Meier analyses were conducted to evaluate clinical prognosis. Finally, univariate and multivariate Cox proportional hazards regression analyses were performed to analyze high-risk factors associated with clinical prognosis.ResultsIn the pre-PSM cohort, 110 (71.0%) patients underwent lymphadenectomy. Of these, 54 (34.8%) experienced recurrence, and 27 (17.4%) died. There were statistical differences in disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016) in the post-PSM cohort. In the subgroup analysis, there were no statistically significant differences in DFS (P = 0.449) or OS (P = 0.167) in the FIGO I/II cohort. However, in the FIGO III/IV cohort, DFS (P = 0.011) and OS (P = 0.046) were statistically different between the two groups. Age > 50 years, FIGO stage III/IV, and suboptimal cytoreductive surgery were risk factors associated with prognosis. In the lymphadenectomy group, the histological status of pelvic lymph nodes had no significant effect on DFS (P = 0.205) or OS (P = 0.114).ConclusionLymphadenectomy was associated with DFS and OS, particularly in patients with advanced LGSOC patients. Age > 50 years, advanced FIGO stage III/IV, and suboptimal cytoreductive surgery were high-risk factors associated with clinical prognosis in patients with LGSOC.     

Early risk-assessment of patients with nasopharyngeal carcinoma: the added prognostic value of MR-based radiomics

ObjectivesTo assess the additive prognostic value of MR-based radiomics in predicting progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC)MethodsPatients newly diagnosed with non-metastatic NPC between June 2006 and October 2019 were retrospectively included and randomly grouped into training and test cohorts (7:3 ratio). Radiomic features (n=213) were extracted from T2-weighted and contrast-enhanced T1-weighted MRI. The patients were staged according to the 8^th edition of American Joint Committee on Cancer Staging Manual. The least absolute shrinkage and selection operator was used to select the relevant radiomic features. Univariate and multivariate Cox proportional hazards analyses were conducted for PFS, yielding three different survival models (clinical, stage, and radiomic). The integrated time-dependent area under the curve (iAUC) for PFS was calculated and compared among different combinations of survival models, and the analysis of variance was used to compare the survival models. The prognostic performance of all models was validated using a test set with integrated Brier scores.ResultsThis study included 81 patients (training cohort=57; test cohort=24), and the mean PFS was 57.5 ± 43.6 months. In the training cohort, the prognostic performances of survival models improved significantly with the addition of radiomics to the clinical (iAUC, 0.72–0.80; p=0.04), stage (iAUC, 0.70–0.79; p=0.001), and combined models (iAUC, 0.76–0.81; p<0.001). In the test cohort, the radiomics and combined survival models were robustly validated for their ability to predict PFS.ConclusionIntegration of MR-based radiomic features with clinical and stage variables improved the prediction PFS in patients diagnosed with NPC.     

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.