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Salvage regimens for pediatric patients with relapsed nasopharyngeal carcinoma.

ABSTRACT: There is no established salvage regimen for pediatric patients with relapsed nasopharyngeal carcinoma (NPC) and outcomes are dismal. We performed a multicenter retrospective review to determine outcomes after first salvage therapy for pediatric patients with relapsed NPC. Fourteen patients were treated with varied regimens. Two of the 14 patients received oxaliplatin-containing regimens and achieved a long-term complete response. Although definitive recommendations cannot be made based on outcomes for 14 patients who received varied regimens, we discuss justification for an oxaliplatin-containing regimen in combination with gemcitabine as a reasonable choice for first-line salvage therapy for pediatric patients with relapsed NPC.

SUBMITTER: DeRenzo C

PROVIDER: S-EPMC6249063 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Salvage regimens for pediatric patients with relapsed nasopharyngeal carcinoma.

DeRenzo Christopher C Lam Catherine C Rodriguez-Galindo Carlos C Rapkin Louis L Gottschalk Stephen S Venkatramani Rajkumar R

Pediatric blood & cancer 20181014 1

There is no established salvage regimen for pediatric patients with relapsed nasopharyngeal carcinoma (NPC) and outcomes are dismal. We performed a multicenter retrospective review to determine outcomes after first salvage therapy for pediatric patients with relapsed NPC. Fourteen patients were treated with varied regimens. Two of the 14 patients received oxaliplatin-containing regimens and achieved a long-term complete response. Although definitive recommendations cannot be made based on outcom ...[more]

PMID: 30318742

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Project description:Importance:The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial. Objectives:To update meta-analyses on the association of survival outcomes with IC and AC regimens in patients with locoregionally advanced NPC and assess whether the current evidence is conclusive by a trial sequential analysis (TSA) approach. Data Sources:PubMed, Embase, and Web of Science were searched for articles published from inception until June 1, 2019. Study Selection:Randomized clinical trials that assessed the efficacy of radiotherapy with or without chemotherapy among previously untreated patients and patients with nondistant metastatic NPC. Data Extraction and Synthesis:Data were extracted by 2 investigators from each trial independently and synthesized by the 2 investigators. All trial results were combined and analyzed by a fixed- or random-effects model. Main Outcomes and Measures:Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS). Results:A total of 8036 patients (median age, 46.5 years; 5872 [73.1%] male) from 28 randomized clinical trials were included in the analysis. Pooled analyses revealed that concurrent chemoradiotherapy (CCRT) was significantly associated with improved OS, PFS, DMFS, and LRFS compared with radiotherapy across all subgroups. The TSA confirmed the treatment outcomes of CCRT compared with radiotherapy. The additional IC regimen was associated with an improvement in OS (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), PFS (HR, 0.73; 95% CI, 0.64-0.84), DMFS (HR, 0.67; 95% CI, 0.59-0.78), and LRFS (HR, 0.74; 95% CI, 0.64-0.85). These findings were consistent in subgroup analyses of multicenter trials with sample sizes greater than 250, years of survival rate of 5 or greater, median follow-up longer than 5 years, or low risk of bias. However, the additional AC regimen was not associated with a survival benefit in OS (HR, 0.98; 95% CI, 0.78-1.23), PFS (HR, 0.86; 95% CI, 0.70-1.07), DMFS (HR, 0.84; 95% CI, 0.64-1.10), or LRFS (HR, 0.80, 95% CI, 0.59-1.09). The TSA provided sound evidence on the additional benefit of IC but not AC. Conclusions and Relevance:These data suggest a significant association of survival outcomes with CCRT in patients with locoregionally advanced NPC. The addition of IC instead of AC could achieve survival benefits. The potential therapeutic gain of AC should be explored in the future.

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

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Salvage regimens for pediatric patients with relapsed nasopharyngeal carcinoma.

Publications

Salvage regimens for pediatric patients with relapsed nasopharyngeal carcinoma.

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