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The relations of dosimetric parameters with long-term outcomes and late toxicities in advanced T-stage nasopharyngeal carcinoma with IMRT.

ABSTRACT: BACKGROUND:Balancing the dose requirements between targets and normal tissue is a challenge in radiation of nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the dosimetric parameters and clinical outcomes in NPC. METHODS:We presented a retrospective review of patients with T3-4 NPC treated by intensity-modulated radiation therapy (IMRT). Patient characteristics, dosimetric parameters, and the follow-up data for survival and late toxicities were analyzed. RESULTS:The 5-year overall survival, local relapse-free survival, and distant metastasis-free survival were 83.0%, 90.1%, and 82.4%, respectively. Multivariate analysis revealed that the volume of involved lymph node was an independent prognostic factor. The volume of primary tumor and the maximal dose were significant factors affecting temporal lobe injury. CONCLUSIONS:IMRT provided satisfactory local control for advanced T-stage NPC, with acceptable late toxicities. The dose constraint criteria of selected critical structures can be appropriately loosen.

SUBMITTER: Gou X

PROVIDER: S-EPMC6973082 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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The relations of dosimetric parameters with long-term outcomes and late toxicities in advanced T-stage nasopharyngeal carcinoma with IMRT.

Gou Xiaoxia X Duan Baofeng B Shi Huashan H Qin Lei L Xiao Jianghong J Chen Nianyong N

Head & neck 20191024 1

<h4>Background</h4>Balancing the dose requirements between targets and normal tissue is a challenge in radiation of nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the dosimetric parameters and clinical outcomes in NPC.<h4>Methods</h4>We presented a retrospective review of patients with T3-4 NPC treated by intensity-modulated radiation therapy (IMRT). Patient characteristics, dosimetric parameters, and the follow-up data for survival and late toxicities were analyzed.<h4 ...[more]

PMID: 31650657

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Project description:BackgroundNeoadjuvant chemotherapy (NACT) treatment in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) can lead to considerable toxicity. Loss of skeletal muscle mass showed relevance with increased chemotherapy-related toxicity and poor survival in various cancer types, but its significance in NPC remains unclear. This study aimed to investigate the relationship between body composition parameters and the incidence of NACT toxicity in LA-NPC patients.MethodsNinety-six LA-NPC patients were retrospectively enrolled. All patients had pre-treatment abdominal computed tomography (CT) images to exclude distant metastasis. Lean body mass (LBM, kg) was estimated based on cross-sectional muscle area at the third lumbar vertebra (L3) level on CT, and skeletal muscle index (SMI, cm2/m2) was calculated. Doses of chemotherapeutics were normalized as dose/LBM (mg/kg). Grade 3-4 toxicity was defined as severe. The associations between body composition parameters and severe toxicities were assessed using univariate and multivariate logistic regression analyses. Optimal cutoff points were obtained with a receiver operating characteristic (ROC) curve.ResultsOf the 96 patients, 81.2% received the docetaxel + cisplatin (TP) regimen, and the rest received the gemcitabine + cisplatin (GP) regimen. Males had more LBM and a higher SMI at baseline, and females received a markedly higher dose of docetaxel and gemcitabine per kg LBM (P<0.001). With a cutoff value of 52.7 cm2/m2, patients with higher SMI showed lower risk of severe toxicity. For TP regimen group, those presented with grade 3-4 neutropenia had a higher dose per kg LBM. Univariate and multivariate analyses showed that the LBM-adjusted dose was significantly associated with severe neutropenia in the TP regimen group (P<0.001). The LBM-normalized docetaxel cutoff value of 2.64 mg/kg was a prominent predictor of ≥ grade 3 neutropenia (P=0.003), but a higher dose of docetaxel per kg LBM did not provide a better objective response rate.ConclusionsLA-NPC patients with lower SMI and higher dose of docetaxel per kg LBM are more likely to suffer from severe treatment-related toxicity. Higher docetaxel dose per kg LBM is a prominent predictor for severe neutropenia, but not for NACT response. LBM showed good potential in toxicity risk prediction and dose determination.

Project description:Purpose: We aimed to determine whether adding induction chemotherapy (IC) to concurrent chemoradiation (CCRT) improved outcomes in each stage of locally advanced nasopharyngeal carcinoma (LANPC). Methods: From 2007 to 2013, we retrospectively collected 259 histopathologically identified adult LANPC patients from two campuses in south Taiwan. Among the 238 eligibly treated cases, 156 patients received CCRT (CCRT group) upfront and 82 received IC followed by CCRT (IC group). Of these patients, 130 were stage III (92 patients that received CCRT and 38 that received IC adding CCRT) and 108 were stage IV (76 CCRT and 32 IC adding CCRT). Most chemotherapy regimens for IC are composed of cisplatin (P), 5-fluorouracil (F), and ifosfamide (I), while concurrent chemotherapy (CC) was essentially cisplatin-based. For CCRT as the upfront treatment, a P or PF regimen was usually used in CC. Survival outcomes were accessed with a Kaplan-Meier estimate and a p-value by log-rank test to compare the survival distributions of IC added to CCRT or CCRT as the upfront treatment in all LANPC stage III and LANPC IV patients. The failure free survival (FFS), overall survival (OS), local relapse free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), first failure site, and other prognostic factors were analyzed. Results: The median follow-up time of all treated LANPC patients was 59 months. For all LANPC patients, there was a significant difference only in the DMFS favoring IC group (91.5% vs 79.4%, p=0.013). In the subgroup study, for the stage III group, there was no significant difference between the groups for overall OS (IC group 71.3% vs CCRT group 78.7%), FFS (71.5% vs 62.4%) and RRFS (91.9% vs 90.9%). However, inferior LRLS (71.7% vs 91.5%; p = 0.03) was noted for the IC group. In contrast, for stage IV, there were significantly longer OS (75.8% vs 52.6%), FFS (66.8% vs 46.8%), and DMFS (86.0% vs 69.6%; p = 0.02, p = 0.04, and p = 0.03, respectively) rates in the IC group. Conclusion: Adding PIF-based IC to CCRT for the LANPC patients resulted in better outcomes for stage IV patients, but not for stage III patients. A future properly designed study should stratify enough LANPC cases under the structure of the AJCC stage grouping system to determine which subgroups truly benefit from adding IC to CCRT.

Project description:BackgroundN-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 methodsBetween 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.ResultsWith 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: ?2 = 3.935, P = 0.047; anemia: ?2 = 9.760, P = 0.002; thrombocytopenia: ?2 = 8.821, P = 0.003), and both liver and renal dysfunction (?2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups.ConclusionIMRT 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.

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The relations of dosimetric parameters with long-term outcomes and late toxicities in advanced T-stage nasopharyngeal carcinoma with IMRT.

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The relations of dosimetric parameters with long-term outcomes and late toxicities in advanced T-stage nasopharyngeal carcinoma with IMRT.

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