Dataset Information

Stage-dependent conditional survival and failure hazard of non-metastatic nasopharyngeal carcinoma after intensity-modulated radiation therapy: Clinical implications for treatment strategies and surveillance.

ABSTRACT:

Purpose

Conditional survival (CS) and failure hazard estimations can provide important dynamic prognostic information for clinical decision-making and surveillance counseling. The current study aimed to investigate the CS and dynamic failure hazard in non-metastatic nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT).

Methods

Conditional overall survival (COS) and progression-free survival (CPFS) estimates adjusted for age and gender against each AJCC 8th stage were calculated. Multivariable Cox regression (MCR) models were fitted in the entire population at baseline and subsequently separate MCR models were fitted in patients who have maintained event-free time of 1 to 10 years to generate respective hazard ratio (HR). Annual hazard rates of death and progression over 10 years for each stage were also estimated.

Results

A total of 1993 patients were eligible for analysis. The estimated 5-year OS and PFS for entire cohort were 79.0% and 70.7% at initial diagnosis. After 5 years of event-free follow-up, additional 5-year COS and CPFS increased to 85.9% and 85.5%, respectively. Stage I/II maintained dramatically favorable CS and low hazard (< 5%) of death and progression over time. Relative to stage I/II, stage III manifested non-significantly higher failure hazard for the first 3 years of survivorship and approached to similar level of stage I/II afterwards. Stage IVA presented most impressive improvement in terms of both COS (∆=9.8%) and CPFS (∆ = 16.8%) whereas still drastically inferior to that of stage I-III across all conditional time points. After 4 years of follow-up, progression hazard of stage IVA became relatively steady of approximate 6%.

Conclusions

Survival prospect of non-metastatic NPC improves over years with distinct dynamic patterns across stages, providing important implications for personalized decision-making in terms of both clinical management and surveillance counseling. Stage-dependent and hazard-adapted clinical management and surveillance are warranted.

SUBMITTER: Wang J

PROVIDER: S-EPMC8178506 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportancePatients with nonmetastatic nasopharyngeal carcinoma (NPC) are primarily treated by radiotherapy with curative intent with or without chemotherapy and often experience substantial treatment-related toxic effects even with modern radiation techniques, such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) may improve the toxicity profile; however, there is a paucity of data given the limited availability of IMPT in regions with endemic NPC.ObjectiveTo compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic NPC when treated with IMPT vs IMRT with or without chemotherapy.Design, setting, and participantsThis retrospective cohort study included 77 patients with newly diagnosed nonmetastatic NPC who received curative-intent radiotherapy with IMPT or IMRT at a tertiary academic cancer center from January 1, 2016, to December 31, 2019. Forty-eight patients with Epstein-Barr virus (EBV)-positive tumors were included in a 1:1 propensity score-matched analysis for survival outcomes. The end of the follow-up period was March 31, 2021.ExposuresIMPT vs IMRT with or without chemotherapy.Main outcomes and measuresThe main outcomes were the incidence of acute and chronic treatment-related adverse events (AEs) and oncologic outcomes, including locoregional failure-free survival (LRFS), progression-free survival (PFS), and overall survival (OS).ResultsWe identified 77 patients (25 [32.5%] women; 52 [67.5%] men; median [interquartile range] age, 48.7 [42.2-60.3] years), among whom 28 (36.4%) were treated with IMPT and 49 (63.6%) were treated with IMRT. Median (interquartile range) follow-up was 30.3 (17.9-41.5) months. On multivariable logistic regression analyses, IMPT was associated with lower likelihood of developing grade 2 or higher acute AEs compared with IMRT (odds ratio [OR], 0.15; 95% CI, 0.03-0.60; P = .01). Only 1 case (3.8%) of a chronic grade 3 or higher AE occurred in the IMPT group compared with 8 cases (16.3%) in the IMRT group (OR, 0.21; 95% CI, 0.01-1.21; P = .15). Propensity score matching generated a balanced cohort of 48 patients (24 IMPT vs 24 IMRT) and found similar PFS in the IMPT and IMRT groups (2-year PFS, 95.7% [95% CI, 87.7%-100%] vs 76.7% [95% CI, 60.7%-97.0%]; hazard ratio [HR], 0.31; 95% CI, 0.07-1.47; P = .14). No locoregional recurrence or death was observed in the IMPT group from the matched cohort. Two-year LRFS was 100% (95% CI, 100%-100%) in the IMPT group and 86.2% (95% CI, 72.8%-100%) in the IMRT group (P = .08). Three-year OS was 100% (95% CI, 100%-100%) in the IMPT group and 94.1% (95% CI, 83.6%-100%) in the IMRT group (P = .42). Smoking history was the only clinical factor significantly associated with both poor LRFS (HR, 63.37; 95% CI, 3.25-1236.13; P = .006) and poor PFS (HR, 6.33; 95% CI, 1.16-34.57; P = .03) on multivariable analyses.Conclusions and relevanceIn this study, curative-intent radiotherapy with IMPT for nonmetastatic NPC was associated with significantly reduced acute toxicity burden in comparison with IMRT, with rare late complications and excellent oncologic outcomes, including 100% locoregional control at 2 years. Prospective trials are warranted to direct the optimal patient selection for IMPT as the primary radiotherapy modality for nonmetastatic NPC.

Project description:Introduction: The prognostic role of plasma Epstein-Barr virus (EBV) DNA clearance when intensity-modulated radiotherapy (IMRT) and the 8th edition of American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM Staging Classification are fully implemented remains undeciphered. We investigated if its half-life clearance during radical treatment for non-metastatic nasopharyngeal carcinoma (NPC) was an early prognosticator. Patients and methods: Patients with previously untreated non-metastatic NPC were prospectively treated with radical IMRT and concurrent chemotherapy +/- induction/adjuvant chemotherapy from 2014 to 2018. Their plasma EBV DNA was measured immediately before treatment followed by weekly schedules until 0 copy/ml in two consecutive measurements. Cox regression models were employed to identify prognostic factors. Results: Forty-five patients were prospectively recruited and analyzed. After a median follow-up of 30.3 months, 2 (4.5%), 1 (2.3%), and 6 (13.6%) patients experienced local, regional, and distant relapses, respectively. The median half-life clearance of plasma EBV DNA was 7.92 days. Those with half-life clearance of >15 days had a worse 3-years progression-free survival (PFS) (79.5 vs. 25.0%, p = 0.005), distant metastasis-free survival (DMFS) (85.0 vs. 31.3%, p = 0.009), and overall survival (OS) (91.3 vs. 75.0%, p = 0.024) when compared to those with a shorter half-life. Multivariable analyses demonstrated that only half-life (>15 days) was prognostic of DMFS [HR (95% CI): 4.91 (1.31; 18.39), p = 0.01] and OS [HR (95% CI): 5.24 (1.06; 26.05)] while half-life (>15 days) [HR (95% CI): 5.14 (1.28; 22.73), p = 0.02] and sum of pretreatment gross tumor volumes of the primary nasopharyngeal tumor and the radiologically positive neck nodes (GTV_P+N) [HR (95% CI): 1.01 (1.00; 1.03), p = 0.02] were prognostic of PFS. Conclusion: The half-life clearance of plasma EBV DNA was prognostic in non-metastatic NPC staged and treated in the contemporary era. Earlier biomarker surveillance during treatment should be considered. Clinical Trial Registration: This study has been registered with ClinicalTrials.gov (Identifier: NCT03830996).

Project description:BACKGROUND:The National Comprehensive Cancer Network guidelines recommend intensity-modulated radiotherapy (IMRT) as the primary curative treatment for newly diagnosed nasopharyngeal carcinoma (NPC), but the radiation-related complications and relatively high medical costs remain a consequential burden for the patients. Endoscopic nasopharyngectomy (ENPG) was successfully applied in recurrent NPC with radiation free and relatively low medical costs. In this study, we examined whether ENPG could be an effective treatment for localized stage I NPC. METHODS:Ten newly diagnosed localized stage I NPC patients voluntarily received ENPG alone from June 2007 to September 2017 in Sun Yat-sen University Cancer Center. Simultaneously, the data of 329 stage I NPC patients treated with IMRT were collected and used as a reference cohort. The survival outcomes, quality of life (QOL), and medical costs between two groups were compared. RESULTS:After a median follow-up of 59.0 months (95% CI 53.4-64.6), no death, locoregional recurrence, or distant metastasis was observed in the 10 patients treated with ENPG. The 5-year overall survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival among the ENPG-treated patients was similar to that among the IMRT-treated patients (100% vs. 99.1%, 100% vs. 97.7%, 100% vs. 99.0%, 100% vs. 97.4%, respectively, P?>?0.05). In addition, compared with IMRT, ENPG was associated with decreased total medical costs ($ 4090.42?±?1502.65 vs. $ 12620.88?±?4242.65, P?<?0.001) and improved QOL scores including dry mouth (3.3?±?10.5 vs. 34.4?±?25.8, P?<?0.001) and sticky saliva (3.3?±?10.5 vs. 32.6?±?23.3, P?<?0.001). CONCLUSIONS:ENPG alone was associated with promising long-term survival outcomes, low medical costs, and satisfactory QOL and might therefore be an alternative strategy for treating newly diagnosed localized stage I NPC patients who refused radiotherapy. However, the application of ENPG should be prudent, and prospective clinical trials were needed to further verify the results.

Project description:BackgroundTo investigate the feasibility of a knowledge-based automated intensity-modulated radiation therapy (IMRT) planning technique for locally advanced nasopharyngeal carcinoma (NPC) radiotherapy.MethodsOne hundred forty NPC patients treated with definitive radiation therapy with the step-and-shoot IMRT techniques were retrospectively selected and separated into a knowledge library (n = 115) and a test library (n = 25). For each patient in the knowledge library, the overlap volume histogram (OVH), target volume histogram (TVH) and dose objectives were extracted from the manually generated plan. 5-fold cross validation was performed to divide the patients in the knowledge library into 5 groups before validating one group by using the other 4 groups to train each neural network (NN) machine learning models. For patients in the test library, their OVH and TVH were then used by the trained models to predict a corresponding set of mean dose objectives, which were subsequently used to generate automated plans (APs) in Pinnacle planning system via an in-house developed automated scripting system. All APs were obtained after a single step of optimization. Manual plans (MPs) for the test patients were generated by an experienced medical physicist strictly following the established clinical protocols. The qualities of the APs and MPs were evaluated by an attending radiation oncologist. The dosimetric parameters for planning target volume (PTV) coverage and the organs-at-risk (OAR) sparing were also quantitatively measured and compared using Mann-Whitney U test and Bonferroni correction.ResultsAPs and MPs had the same rating for more than 80% of the patients (19 out of 25) in the test group. Both AP and MP achieved PTV coverage criteria for no less than 80% of the patients. For each OAR, the number of APs achieving its criterion was similar to that in the MPs. The AP approach improved planning efficiency by greatly reducing the planning duration to about 17% of the MP (9.85 ± 1.13 min vs. 57.10 ± 6.35 min).ConclusionA robust and effective knowledge-based IMRT treatment planning technique for locally advanced NPC is developed. Patient specific dose objectives can be predicted by trained NN models based on the individual's OVH and clinical TVH goals. The automated planning scripts can use these dose objectives to efficiently generate APs with largely shortened planning time. These APs had comparable dosimetric qualities when compared to our clinic's manual plans.