Effect of Induction Chemotherapy With Paclitaxel, Cisplatin, and Capecitabine vs Cisplatin and Fluorouracil on Failure-Free Survival for Patients With Stage IVA to IVB Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial.

Importance: Induction chemotherapy added to concurrent chemoradiotherapy significantly improves survival for patients with locoregionally advanced nasopharyngeal carcinoma, but the optimal induction regimen remains unclear. Objective: To determine whether induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) improves survival vs cisplatin and fluorouracil (PF) prior to chemoradiotherapy for patients with stage IVA to IVB nasopharyngeal carcinoma. Design, Setting, and Participants: This randomized, open-label, phase 3 clinical trial recruited 238 patients at 4 hospitals in China from October 20, 2016, to August 29, 2019. Patients were 18 to 65 years of age with treatment-naive, nonkeratinizing stage IVA to IVB nasopharyngeal carcinoma and an Eastern Cooperative Oncology Group performance status of 0 to 1. Interventions: Patients were randomly assigned (1:1) to receive induction chemotherapy with two 21-day cycles of TPC (intravenous paclitaxel [150 mg/m2, day 1], intravenous cisplatin [60 mg/m2, day 1], and oral capecitabine [1000 mg/m2 orally twice daily, days 1-14]) or PF (intravenous cisplatin [100 mg/m2, day 1] and fluorouracil [800 mg/m2 daily, days 1-5]), followed by chemoradiotherapy. Main Outcomes and Measures: The primary end point was failure-free survival in the intention-to-treat population. Secondary end points included distant metastasis-free survival, locoregional relapse-free survival, overall survival, tumor response, and safety. Results: Overall, 238 eligible patients (187 men [78.6%]; median age, 45 years [range, 18-65 years]) were randomly assigned to receive TPC (n = 118) or PF (n = 120). The median follow-up duration was 48.4 months (IQR, 39.6-53.3 months). Failure-free survival at 3 years was 83.5% (95% CI, 77.0%-90.6%) in the TPC group and 68.9% (95% CI, 61.1%-77.8%) in the PF group (stratified hazard ratio [HR] for recurrence or death, 0.47; 95% CI, 0.28-0.79; P = .004). Induction with the TPC regimen resulted in a significant reduction in the risk of distant metastases (stratified HR, 0.49 [95% CI, 0.24-0.98]; P = .04) and locoregional recurrence (stratified HR, 0.40 [95% CI, 0.18-0.93]; P = .03) compared with the PF regimen. However, there was no effect on early overall survival (stratified HR, 0.45 [95% CI, 0.17-1.18]; P = .10). The incidences of grade 3 to 4 acute adverse events and late-onset toxicities were 57.6% (n = 68) and 13.6% (16 of 118), respectively, in the TPC group and 65.8% (n = 79) and 17.9% (21 of 117), respectively, in the PF group. One treatment-related death occurred in the PF group. Conclusions and Relevance: This randomized clinical trial found that induction chemotherapy with 2 cycles of TPC for patients with stage IVA to IVB nasopharyngeal carcinoma improved failure-free survival compared with 2 cycles of PF, with no increase in the toxicity profile. Trial Registration: ClinicalTrials.gov Identifier: NCT02940925.

Histological subtype remains a prognostic factor for survival in nasopharyngeal carcinoma patients.

OBJECTIVES: There is currently no consensus on the prognostic significance of the histological subtype of nasopharyngeal carcinoma (NPC). The aim of the current study was to evaluate the impact of histological subtype on survival in NPC patients based on the Surveillance, Epidemiology, and End Results (SEER) Program. METHODS: Patients with NPC were identified within the SEER database (2004-2015). The effects of histological subtype on cause-specific survival (CSS) in NPC patients were evaluated using univariate and multivariate Cox regression analyses. Subgroup analysis according to histological subtype in NPC patients was carried out by 1:1 propensity score matching (PSM). RESULTS: A total of 4085 NPC patients were selected from the SEER database, including 1929 with keratinizing squamous cell carcinoma (KSCC), 2203 with nonkeratinizing carcinoma (NKC), and 53 with basaloid squamous cell carcinoma (BSCC). The 3-year and 5-year CSS rates were 61.76% and 55.07% for KSCC patients, 79.57% and 72.09% for NKC patients, and 77.55% and 74.03% for BSCC patients, respectively. Multivariate analysis identified sex, age, marital status, race, T stage, N stage, M stage, radiotherapy, chemotherapy, and histological subtype as significant prognostic factors for CSS in NPC patients. KSCC was found to be associated with worse CSS than NKC on Kaplan-Meier analysis and subgroup analysis after 1:1 PSM. CONCLUSIONS: Histological subtype determines the long-term survival outcomes of patients with NPC. Moreover, the NKC subtype has the best prognosis, while the KSCC subtype has the worst prognosis. LEVEL OF EVIDENCE: NA Laryngoscope, 130:E83-E88, 2020.

A simplified T classification based on the 8th edition of the UICC/AJCC staging system for nasopharyngeal carcinoma.

Objective: This study aimed to establish a simplified T classification based on the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for nasopharyngeal carcinoma (NPC). Methods: In total, 325 patients with NPC were included in this study. All patients underwent magnetic resonance imaging, and the staging criteria were recorded. These patients were subjected to staging with the 8th edition of the UICC/AJCC staging system for NPC. Results:  Involvement of the oropharynx, nasal cavity, adjacent soft tissue (medial pterygoid, lateral pterygoid, and prevertebral muscles), cervical vertebra, orbit, and hypopharynx were always accompanied by other equivalently or more advanced T-stage classifications. All cases with involvement of the paranasal sinuses showed skull base erosion. The majority of cases with involvement of the pterygoid structure showed skull base erosion. Conclusion: According to the simplification principle, the following new T classification based on the 8th edition of the UICC/AJCC staging system was established: T1, tumor confined to nasopharynx, or beyond the nasopharynx without parapharyngeal involvement; T2, tumor with extension to the parapharyngeal space; T3, tumor with infiltration to bony structures at the skull base; T4, tumor with intracranial extension, involvement of the cranial nerves or parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle. Validation with a large series of patients is needed.

[Expression of HSP70 and P-glycoprotein (P-gp) in human hepatocarcinoma HepG2 cells induced by heat shock and inhibiting effect of quercetin on them].

BACKGROUND & OBJECTIVE: Heat shock protein 70 (HSP70) has been thought to inhibit apoptosis and reduce the effectiveness of hyperthermal therapy and chemotherapy on cancer. However, the relationship between HSP70 and the drug resistance to chemotherapy has not been definited. P-glycoprotein (P-gp) was a kind of protein that could decrease the effectiveness of chemotherapy. In order to explore the relationship between HSP70 and P-gp, the human hepatocarcinoma line HepG2 cells was induced by heat shock in vitro, and the inhibiting effect of quercetin on them was observed at the same time to seek the method increasing the effectiveness of hyperthermal therapy on hepatocarcinoma. METHODS: HepG2 cells were bathed in water at 42 degrees C stably for 90 minutes. The expression of HSP70 and P-gp were detected at 0, 2, 4, 8, 12, and 24 hours after 42 degrees C heat shock using immunocytochemistry and flow cytometry (FCM). Furthermore, at 4 hours later after heat shock, they were also detected in HepG2 cells which had been pretreated by quercetin in different concentrations within an hour before 42 degrees C heat shock. RESULTS: (1) Immunocytochemistry showed that HSP70 overexpressed in the cells and "moved" from cytoplasm to nucleus and nucleolus after heat shock. The percentage of HSP70 positive cells came to the climax (11.47%) at 4th hour and increased about 2 folds compared with that of the control group (6.64%) (P< 0.01). At the 24th hour after heat shock, it declined to a low level. The percentage of cells with P-gp positive went up following HSP70 after heat shock. It came to the climax(96.31%) at the 12th hour. And it increased about 3 folds compared with that of the control group(33.95%) (P< 0.01). (2) The overexpression of HSP70 and P-gp induced by heat shock could be inhibited effectively by quercetin in a dose-dependent manner, especially by quercetin at the concentrations of 100- 200 micromol/L(P< 0.01). CONCLUSION: (1) The overexpression of HSP70 and P-gp in HepG2 cells can be induced by heat shock and P-gp maybe has a correlation with HSP70. (2) The overexpression of HSP70 and P-gp in HepG2 cells induced by heat shock can be inhibited by quercetin.