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1.
J Clin Oncol ; : JCO2101467, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34990291

RESUMO

PURPOSE: Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS: Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS: Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, -4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION: Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

2.
BMC Cancer ; 21(1): 1320, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34886807

RESUMO

BACKGROUND: To evaluate the prognostic value of the apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) and monitor the early treatment response to induction chemotherapy (IC) with plasma EBV DNA in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). RESULTS: A total of 307 stage III-IVb NPC patients were prospectively enrolled. All patients underwent MRI examinations to calculate ADC and plasma EBV DNA measurements pretreatment and post-IC. The participants' ADC value of 92.5% (284/307) increased post-IC. A higher percent change in ADC value (ΔADC%high group) post-IC was associated with a higher 5-year OS rate (90.7% vs 74.9%, p < 0.001) than those in the ΔADC%low group. Interestingly, ΔADC% was closely related to the response measured by RECIST 1.1 (p < 0.001) and plasma EBV DNA level (p = 0.037). The AUC significantly increased when post-IC plasma EBV DNA was added to ΔADC% to predict treatment failure. Thus, based on ΔADC% and plasma EBV DNA, we further divided the participants into three new prognostic response phenotypes (early response, intermediate response, and no response) that correlated with disparate risks of death (p = 0.001), disease progression (p < 0.001), distant metastasis (p < 0.001), and locoregional relapse (p < 0.001). CONCLUSION: The percentage change in ADC post-IC is indicative of treatment response and clinical outcome. ΔADC% and plasma EBV DNA-based response phenotypes may provide potential utility for early termination of treatment and allow guiding risk-adapted therapeutic strategies for LA-NPC.

3.
JAMA Netw Open ; 4(12): e2138470, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34928359

RESUMO

Importance: Nedaplatin-based concurrent chemoradiotherapy (CCRT) regimen at 2 years was noninferior to cisplatin-based regimen in patients with locoregional, stage II to IVB nasopharyngeal carcinoma (NPC) and was associated with fewer late adverse events, but longer-term outcomes and toxicity are unclear. Objective: To evaluate the 5-year outcomes and late toxicity profile of nedaplatin-based CCRT in patients with locoregional, stage II to IVB NPC. Design, Settings, and Participants: This 5-year follow-up secondary analysis of an open-label, noninferiority, multicenter randomized clinical trial enrolled patients with nonkeratinizing stage II to IVB NPC between January 16, 2012, and July 16, 2014, with a median follow-up duration of 78 months (IQR, 3-99 months). Data analysis was conducted from November 10, 2020, to July 8, 2021. Interventions: Patients were randomly assigned (1:1) to receive nedaplatin (100 mg/m2)- or cisplatin (100 mg/m2)-based chemotherapy every 3 weeks for 3 cycles concurrently with intensity-modulated radiotherapy. Main Outcomes and Measures: The primary end point was progression-free survival (PFS). Secondary end points were overall survival, distant metastasis-free survival, and locoregional relapse-free survival. Results: A total of 402 eligible participants were enrolled (median [IQR] age, 45 [18-65] years; 302 [75.1%] male). Patients were randomly assigned to receive nedaplatin- or cisplatin-based CCRT (n = 201 for each): 196 patients (97.5%) started nedaplatin-based CCRT and 197 patients (98.0%) started cisplatin-based CCRT. Intention-to-treat analysis demonstrated a 5-year progression-free survival rate of 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for nedaplatin group, with a difference of 1.6% (95% CI, -6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs 88.8%, P = .63), distant metastasis-free survival (85.9% vs 90.4%, P = .17), and locoregional relapse-free survival (92.6% vs 89.6%, P = .17) rates. The cisplatin group had a higher incidence of grade 3 and 4 auditory toxic effects than the nedaplatin group (35 [17.7%] vs 21 [10.5%], P = .04). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, long-term analysis confirmed that nedaplatin-based CCRT could be regarded as an alternative doublet treatment strategy to cisplatin-based CCRT in stage II to IVB NPC. Trial Registration: ClinicalTrials.gov Identifier: NCT01540136.


Assuntos
Quimiorradioterapia/efeitos adversos , Cisplatino/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Compostos Organoplatínicos/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Quimiorradioterapia/métodos , Cisplatino/toxicidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/toxicidade , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
4.
Eur J Cancer ; 159: 133-143, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34743068

RESUMO

PURPOSE: To compare the prognosis and adverse effects of induction or adjuvant chemotherapy (IC or AC) plus concurrent chemoradiotherapy (CCRT) versus CCRT alone in paediatric nasopharyngeal carcinoma (NPC) patients in the intensity-modulated radiotherapy (IMRT) era. METHODS AND MATERIALS: 549 patients diagnosed from 2005 to 2021 were enrolled. Our primary endpoint was progression-free survival (PFS). The recursive partitioning analysis (RPA) was applied to derive a risk stratification system. Kaplan-Meier survival curves were used to assess the cumulative survival rates, and cox analysis was applied to evaluate the relationship between variables and endpoints. RESULTS: The RPA-based risk stratification identified three different risk groups. In the intermediate-risk (stage IVa and EBV<4000 copies/ml) group, patients who received IC followed by CCRT achieved a significantly better 3-year PFS rate than those treated with CCRT alone (87.35% versus 75.89%; P = 0.04). But survival benefit was not obtained from the additional IC or AC in the low-risk (stage II-III and EBV<4000 copies/ml) or high-risk (stage II-IVa and EBV≥4000 copies/ml) group. The most common grade 3 or 4 adverse events in patients treated with CCRT, IC + CCRT, and CCRT + AC were neutropenia (8.1%, 33.0% versus 36.9%, respectively) and leukopenia (14.1%, 26.8% versus 32.3%, respectively) with statistically significant difference. CONCLUSIONS: Paediatric NPC patients in the intermediate-risk group treated with IC followed by CCRT had significantly better PFS compared with patients treated with CCRT alone. And the overall incidence of acute adverse events in patients treated with IC or AC plus CCRT was higher than in patients treated with CCRT alone.

5.
SAGE Open Med Case Rep ; 9: 2050313X211057704, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777811

RESUMO

Alpha-fetoprotein hardly increased due to nasopharyngeal cancer. In this article, we reported a 57-year-old male nasopharyngeal carcinoma patient who had posttreatment subscapular metastasis with high serum alpha-fetoprotein but negative plasma Epstein-Barr virus DNA. Pathology results indicated that the scapular mass was undifferentiated non-keratinizing carcinoma originated in the nasopharynx. Moreover, no liver lesion was detected by imaging examination. In view of the positive alpha-fetoprotein and alpha-fetoprotein messenger RNA staining result in the right scapular mass fine needle aspiration biopsy sample, we considered the diagnosis of alpha-fetoprotein-producing nasopharyngeal carcinoma that had never been reported before.

6.
Head Neck ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636116

RESUMO

BACKGROUND: To evaluate the prognostic value of the dynamic change in absolute lymphocyte counts (ALCs) and absolute monocyte counts (AMCs) and identify patients with N stage and plasma Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) who are at risk of treatment failure. METHODS: A total of 1124 eligible patients with Stage II-IVb NPC treated with concurrent chemoradiotherapy (CCRT) were enrolled. Percentage changes in the ALC (ΔALC%) and AMC (ΔAMC%) were calculated. RESULTS: Patients with high ΔALC% were correlated with poorer 5-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) rates than those with low ΔALC%. Likewise, high ΔAMC% was significantly associated with worse outcome than low ΔAMC% (OS, p = 0.001; PFS, p = 0.001; DMFS, p = 0.034). Multivariate analyses revealed that ΔALC% (p = 0.046), ΔAMC% (p = 0.019), and EBV DNA level (p < 0.001) were independent prognostic factors for OS. With respect to PFS, ΔALC% (p = 0.036), ΔAMC% (p = 0.011), N classification (p = 0.016), and EBV DNA level (p < 0.001) were also independent prognosticators. Based on the aforementioned independent risk factors (ΔALC% ≥ 83.33%, ΔAMC% ≥ 40.00%, Stage N2-3, EBV DNA ≥ 4000 copies/ml), patients were divided into three different risk groups (low-risk group [with <1 risk factor], intermediate risk group [with 1-3 risk factors], and high-risk group [with 4 risk factors]) that correlated with disparate risks of death (p < 0.001), disease progression (p < 0.001), and distant metastasis (p < 0.001). CONCLUSIONS: High ΔALC% and ΔAMC% were correlated with poor prognosis in patients with NPC. Risk stratification based on ΔALC%, ΔAMC%, N classification, and plasma EBV DNA levels could provide potential utility for risk-adapted therapeutic strategies for NPC.

7.
Front Pharmacol ; 12: 627935, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512316

RESUMO

Background: Despite the development of such multiple therapeutic approaches, approximately 20% patients experience recurrence. Identification of molecular markers for stratifying the different risks of tumour recurrence and progression is considered imperative. Methods: We used a RayBio Human Cytokine Antibody Array that simultaneously detected the levels of 297 proteins and profiled the conditioned medium of HONE1 cells and the radioresistant NPC cells HONE1-IR. We found Angiogenin(ANG) expression to be significantly increased in HONE1-IR and HONE1-IR cells exposed to 4-Gy X-ray radiation. Results: We investigated the expression of ANG in NPC tissues and explored its prognostic significance in patients with NPC. We found that ANG expression was increased in recurrent NPC tissues. Elevated expression of ANG induced radio-resistance in NPC cells, in addition to being significantly associated with shorter PFS, OS, and LRFS in patients with NPC. Multivariate analysis results revealed that ANG was an independent prognostic factor that predicted PFS, OS, and LRFS. Furthermore, a nomogram model was generated to predict OS in terms of ANG expression. Conclusion: Our results found the radioresistant function of ANG and proved the clinical prognostic significance of ANG, and the results could help predict radio-sensitivity and stratify high-risk patients or tumour recurrence.

8.
Radiother Oncol ; 163: 185-191, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34453953

RESUMO

BACKGROUND: Unsatisfactory tumor response to induction chemotherapy (IC) is an adverse prognostic factor of locoregionally advanced nasopharyngeal carcinoma (LANPC). A re-induction strategy which applies additional cycles of an alternative IC regimen prior to radiotherapy (RT) has been adopted. METHODS: A total of 419 LANPC patients who attained suboptimal response (stable disease or disease progression) according to the Response Evaluation in Solid Tumors (RECIST) guideline after initial IC were retrospectively included. They were divided into those who received additional cycles of re-induction regimen prior to RT (re-induction group, n = 87) and those who had no additional chemotherapy (direct to RT group, n = 332). Propensity score matching (PSM) was used to adjust for potential confounders. Tumor response and long-term survival were compared between two groups. RESULTS: After receiving a second IC regimen, 39.1% of the patients in re-induction group attained partial response; however, the tumor control of subsequent RT was not significantly improved when compared with direct to RT group (patients attaining complete response after RT 55.2% vs. 52.5%, P = 0.757). Patients who received re-induction therapy showed worse locoregional relapse-free survival (LRFS) and progression-free survival (PFS) than those proceeded directly to RT (3-year LRFS 75.7% vs. 83.1%, P = 0.005; 3-year PFS 62.4% vs. 68.3%, P = 0.037). The increased hematological toxicities were observed in re-induction group that included grade 3-4 anemia, thrombocytopenia and liver enzyme increase. CONCLUSION: Re-induction therapy decreased LRFS and PFS and increased toxicities among patients who attain suboptimal response to initial IC regimen, as compared with direct to RT strategy.

9.
Ann Transl Med ; 9(7): 532, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33987230

RESUMO

Background: Nutritional status is a key factor influencing the prognosis of patients with cancer. The Geriatric Nutritional Risk Index (GNRI) has been used to predict mortality risk and long-term outcomes. In this study, we aimed to evaluate the predictive value of pretreatment GNRI in patients with nasopharyngeal carcinoma (NPC). Methods: A total of 1,065 patients with biopsy-proven non-disseminated nasopharyngeal carcinoma were included. Based on a cutoff value of pretreatment GNRI, patients were divided into two groups (low ≤107.7 and high >107.7). Combining GNRI and baseline Epstein-Barr virus (EBV) DNA, all patients were further stratified into three risk groups, namely, high-risk (high EBV DNA and low GNRI), low-risk (low EBV DNA and high GNRI), and medium-risk (except the above) groups. Multivariate analyses were performed using the Cox proportional hazards model to assess the predictive value of the GNRI. Results: Among the 1,065 patients, 527 (49.5%) and 538 (50.5%) were divided into low and high GNRI groups, respectively. Within a median follow-up of 83 months, patients with a high GNRI score exhibited significantly higher overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) compared to those with low GNRI scores (P<0.05). Multivariate analyses revealed that high GNRI is an independent prognostic factor for OS and PFS (hazard ratio, HR, 0.471, 95% CI, 0.270-0.822, P=0.008; HR 0.638, 95% CI, 0.433-0.941, P=0.023, respectively). Using a combination of baseline GNRI and EBV DNA, a satisfying separation of survival curves between different risk groups for OS, PFS, DMFS was observed. The survival rates of patients in the high-risk group were significantly lower than those in the low- and medium-risk groups (all P<0.001). The combined classification was demonstrated to be an independent prognostic factor for OS and PFS after adjustment using multivariate analysis. Conclusions: Pretreatment GNRI is an independent prognostic factor for NPC patients. The combination of baseline GNRI score and EBV DNA level improved the prognostic stratification of NPC patients.

10.
Radiother Oncol ; 160: 9-17, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33839205

RESUMO

PURPOSE: Curative radiotherapy for nasopharyngeal carcinoma (NPC) can lead to acquired nasal cavity stenosis and atresia (ANCSA). As the first study to investigate risk factors of ANCSA in a large cohort of NPC patients, this article aims to develop and validate a multivariate normal tissue complication probability (NTCP) model to predict the development of ANCSA and to establish a nomogram for clinical use. METHODS AND MATERIALS: The retrospective cohort was comprised of 548 NPC patients treated with radical radiotherapy. The cohort was randomly divided into training and validation groups. Least absolute shrinkage and selection operator regression was performed for variable selection from the clinical and dosimetric characteristics in the training group. A multivariate NTCP model and a nomogram were established for the prediction of ANCSA development. Discrimination and calibration were tested using receiver operating characteristic (ROC) curves and calibration tests, respectively, for both groups. RESULTS: ANCSA was observed in 132 (24.1%) of 548 patients with NPC who underwent radical radiotherapy. The median time to ANCSA detection after treatment was 2.8 months (range, 0.0-57.7 months). Five potential predictors, including choanal invasion, low white blood cell count, high C-reactive protein level, high serum amyloid A level, and high V70Gy of the nasal cavity, were selected to develop the NTCP model based on 365 patients in the training group. The model had a fairly good discriminative power according to the ROC analysis in both the training (area under ROC curve = 0.79, 95%CI: 0.73-0.84) and validation (0.73, 0.64-0.82) groups. The calibration power was tested using the calibration test in the training (E-max = 0.069, E-avg = 0.015, p = 0.977) and validation (E-max = 0.057, E-avg = 0.032, p = 0.747) groups. CONCLUSIONS: We developed and successfully validated an NTCP model for early prediction of ANCSA in patients with NPC after radical radiotherapy. This could help clinicians assess the risk of ANCSA before the initiation of follow-ups and ensure appropriate and timely management of this complication.


Assuntos
Cavidade Nasal , Neoplasias Nasofaríngeas , Constrição Patológica , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Nomogramas , Estudos Retrospectivos , Fatores de Risco
11.
Eur Radiol ; 31(7): 5222-5233, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33416977

RESUMO

OBJECTIVES: The value of using PET/CT for staging of stage I-II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. METHODS: A total of 1003 patients with pathologically confirmed NPC of stages I-II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. RESULTS: Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3-82.1] vs. 91.1% [84.8-97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8-100.0] vs. 76.4% [67.6-85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. CONCLUSIONS: This study showed PET/CT is of little value for staging of stage I-II NPC patients at initial imaging. KEY POINTS: • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I-II NPC patients.


Assuntos
Neoplasias Nasofaríngeas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos de Casos e Controles , Fluordesoxiglucose F18 , Humanos , Linfonodos/patologia , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X
12.
Eur J Nucl Med Mol Imaging ; 48(8): 2586-2598, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33420610

RESUMO

PURPOSE: This study aimed to establish an effective nomogram to predict primary distant metastasis (DM) in patients with nasopharyngeal carcinoma (NPC) to guide the application of PET/CT. METHODS: In total, 3591 patients with pathologically confirmed NPC were consecutively enrolled. The nomogram was constructed based on 1922 patients treated between 2007 and 2014. Multivariate logistical regression was applied to identify the independent risk factors of DM. The predictive value of the nomogram was evaluated using the concordance index (C-index), calibration curve, probability density functions (PDFs), and clinical utility curve (CUC). The results were validated in 1669 patients enrolled from 2015 to 2016. Net reclassification improvement (NRI) was applied to compare performances of the nomogram with other clinical factors. The best cut-off value of the nomogram chosen for clinical application was analyzed. RESULTS: A total of 355 patients showed primary DM among 3591 patients, yielding an incidence rate of 9.9%. Sex, N stage, EBV DNA level, lactate dehydrogenase level, and hemoglobin level were independent predictive factors for primary DM. C-indices in the training and validation cohort were 0.796 (95% CI, 0.76-0.83) and 0.779 (95% CI, 0.74-0.81), respectively. The NRI indices demonstrated that this model had better predictive performance than plasma EBV DNA level and N stage. We advocate for a threshold probability of 3.5% for guiding the application of PET/CT depending on the clinical utility analyses. CONCLUSION: This nomogram is a useful tool to predict primary DM of NPC and guide the clinical application of PET/CT individually at the initial staging.


Assuntos
Neoplasias Nasofaríngeas , Nomogramas , Fluordesoxiglucose F18 , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico
13.
Front Oncol ; 10: 543646, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194602

RESUMO

Objectives: To investigate the optimal treatment pattern in patients with de novo metastatic nasopharyngeal carcinoma (NPC). Methods: We assessed 502 consecutive and unselected de novo metastatic NPC patients in Sun Yat-sen University Cancer Center (SYSUCC) from November 2006 to October 2016 in our study. All patients were treated with palliative chemotherapy (PCT) and 308 patients received locoregional radiotherapy (LRRT) subsequently. Our primary study endpoint was overall survival (OS). Results: The patients treated with LRRT were associated with improved survival on univariate analysis (3-year OS rate 63.7% vs. 31.8%, P < 0.001) and multivariate analysis (HR 0.52, 95%CI 0.40-0.68, P < 0.001). The overall survival benefit of more than 4 PCT cycles was significant in female (HR 0.45, 95% CI 0.24-0.86, P = 0.016) and patients with multiple metastatic sites (HR 0.42, 95% CI 0.26-0.66, P < 0.001). The application of concurrent chemotherapy (CCT) was not associated with better survival among patients receiving LRRT (HR 1.31, 95% CI 0.92-1.86, P = 0.141). Conclusion: LRRT prolonged survival in de novo metastatic NPC. For patients treated with multiple metastatic sites, more than 4 cycles of PCT is necessary. CCT does not improve survival in de novo metastatic NPC patients.

14.
Ther Adv Med Oncol ; 12: 1758835920928214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536983

RESUMO

Background: This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 1814 eligible patients with stage II-IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method, and the differences were compared using the log-rank test. Results: Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups (p = 0.040). Conclusion: IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

15.
Oral Oncol ; 106: 104711, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32298996

RESUMO

OBJECTIVE: Thus far, there is no final conclusion on the treatment of local recurrent nasopharyngeal carcinoma (lrNPC) patients. Herein, we developed a nomogram which combined prognostic biomarkers to predict clinical outcome and guide individual treatment. MATERIALS AND METHODS: From 2006 to 2016, 303 patients with lrNPC were retrospectively reviewed. Overall survival (OS) was the primary endpoint. The nomogram was established with the significant prognostic factors (P < 0.05) selected by multivariate analysis using Cox regression model. Harrell Concordance Index (C-index), calibration curves, and decision curve analysis (DCA) were applied to evaluate this model. RESULTS: Four independent prognostic factors (age, hypertension, relapsed T (rT) stage, and Epstein-Barr virus DNA) identified from multivariable analysis were included into the nomogram. The C-index of the nomogram was 0.687. The calibration curves for 1-, 3-, and 5-year OS rate showed satisfactory agreements between the predicted and actual values. The decision curve analysis also exhibited a preferable net benefit of this model. All patients were subdivided into three risk groups based on the nomogram. Local treatment was associated with higher OS than palliative chemotherapy alone in the low (P < 0.001) and intermediate-risk groups (P = 0.001). However, no significant difference was observed between different treatment methods in the high-risk group (P = 0.176). CONCLUSION: We established the nomogram for patients with lrNPC to predict OS and guide individual treatment, which showed satisfactory performance in accuracy, discrimination capability, and clinical utility.


Assuntos
Neoplasias Nasofaríngeas/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Nomogramas , Prognóstico
16.
Cancer Commun (Lond) ; 40(1): 32-42, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32112522

RESUMO

BACKGROUND: Capecitabine was previously used as a second-line or salvage therapy for metastatic nasopharyngeal carcinoma (NPC) and has shown satisfactory curative effect as maintenance therapy in other metastatic cancers. This study aimed to explore the role of capecitabine as maintenance therapy in de novo metastatic NPC patients with different plasma Epstein-Barr virus (EBV) DNA levels before treatment. METHODS: We selected de novo metastatic NPC patients treated with locoregional radiotherapy (LRRT) for this retrospective study. The propensity score matching (PSM) was applied to balance potential confounders between patients who underwent capecitabine maintenance therapy and those who did not with a ratio of 1:3. Overall survival (OS) was the primary endpoint. The association between capecitabine maintenance therapy and survival was assessed using the log-rank test and a Cox proportional hazard model. RESULTS: Among all patients eligible for this study, 64 received capecitabine maintenance therapy after LRRT. After PSM, 192 patients were identified in the non-maintenance group. In the matched cohort, patients treated with capecitabine achieved a higher 3-year OS rate compared with patients in the non-maintenance group (68.5% vs. 61.8%, P = 0.037). Multivariate analysis demonstrated that capecitabine maintenance therapy was an independent prognostic factor. In subgroup analysis, 3-year OS rate was comparable between the maintenance and non-maintenance groups in patients with high pretreatment EBV DNA levels (˃30,000 copies/mL) (54.8% vs. 45.8%, P = 0.835), whereas patients with low pretreatment EBV DNA levels (≤30,000 copies/mL) could benefit from capecitabine maintenance therapy in OS (90.0% vs. 68.1%, P = 0.003). CONCLUSION: Capecitabine maintenance therapy may be superior to non-maintenance therapy in prolonging OS for de novo metastatic NPC patients with pretreatment EBV DNA ≤ 30,000 copies/mL.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Capecitabina/administração & dosagem , Infecções por Vírus Epstein-Barr/virologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/virologia , Adolescente , Adulto , Idoso , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/patologia , Feminino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
17.
BMC Cancer ; 20(1): 89, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013967

RESUMO

BACKGROUND: We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC. METHODS: The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA < 1500 copies) and high-risk group (pre-EBV DNA ≥ 1500 copies). Progression free survival (PFS), overall survival (OS), locoregional relapse free survival (LRFS), distant metastasis free survival (DMFS) and grade 3-4 toxicities were compared among different IC regimens. The survival rates were compared using log-rank test and a Cox proportional hazards model was used to perform multivariate analyses. RESULTS: A multivariate analysis revealed TPF to be more effective than TP. Among stage III patients, no significant difference in clinical outcome between the different IC regimens was showed, while TPF was associated with significantly better survival conditions in the stage IV patients. A further subgroup analysis revealed that only patients with pre-EBV DNA ≥ 1500 copies could benefit from the application of TPF among stage IV NPC. In terms of acute toxicities, PF was associated with fewer grade 3/4 acute toxicities. CONCLUSIONS: In low-risk NPC patients, PF-based IC showed similar efficacy as TPF and TP but was associated with fewer grade 3/4 acute toxicities. In high-risk patients, however, the TPF regimen was superior to PF and TP, although grade 3/4 toxicities were more common with the TPF regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , DNA Viral/genética , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/virologia , Estudos Retrospectivos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento , Adulto Jovem
18.
J Cancer ; 10(23): 5614-5621, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737097

RESUMO

Objectives: To evaluate the prognostic significance of Adult Comorbidity Evaluation-27 (ACE-27) for elderly patients (age ≥70 years) with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with Intensity-Modulated Radiotherapy (IMRT), with or without chemotherapy. Methods: 206 elderly patients with locoregionally advanced NPC treated from December 2006 to December 2016 were involved into analysis as the training cohort. Besides, a separate cohort of 72 patients from the same cancer center collected between January 2003 and October 2006 served as the validation cohort. By using propensity score matching (PSM), we created a balanced cohort by matching patients who received chemoradiotherapy with patients who received IMRT alone. Treatment toxicities were calculated between CRT and RT groups using the χ2 test. The primary endpoint was cancer-specific survival (CSS). Multivariate analysis was performed to assess the relative risk for each factor by using a Cox's proportional hazards regression model. Results: The median follow-up was 39.0 months (range = 3-137 months). In the PSM cohort, patients in the CRT group achieved comparable survival compared with patients in the RT group. The 3-year CSS rate was 64.3% and 65.2%, respectively (P =0.764). In multivariate analysis, the addition of chemotherapy to IMRT was not an independent prognostic factor for CSS, whereas a high ACE-27 score was an independent risk factor. In subgroup analysis with ACE-27 score ≥ 2, the 3-year CSS rate was worse in patients from the CRT group (63.5% vs. 46.3%, P = 0.041). Conclusions: CRT is comparable to IMRT alone for elderly patients with locoregionally advanced NPC. The ACE-27 tool may help to identify high-risk subgroup for poor disease outcome and tailor individualized treatment.

19.
Drug Des Devel Ther ; 13: 3207-3216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686783

RESUMO

Objective: We aimed to investigate the efficacy and safety of cetuximab (CTX) or nimotuzumab (NTZ) on the addition of palliative chemotherapy (PCT) in patients with de novo metastatic nasopharyngeal carcinoma (NPC). Materials and methods: From 2007 to 2016, 451 eligible patients with de novo metastatic NPC were enrolled in the study. With propensity score matching technique, we created a well-balanced cohort by matching patients who received CTX/NTZ plus PCT (62 patients) with those receiving PCT alone (248 patients) in a ratio of 1:4. The primary endpoint was overall survival (OS). All potential prognostic factors were involved in the multivariate analysis with the Cox regression hazards model. Kaplan-Meier curves were used to compare the survival status, and log-rank test to measure the significance. Results: The median follow-up time was 27.7 months (range, 1-126 months). No significant difference in survival was observed between the CTX/NTZ plus PCT group and PCT group. (3-year OS: 63.0% vs 58.1%; P=0.485). The administration of CTX/NTZ was not found to be an independent prognostic factor in multivariate analysis. With regard to toxicity, the development of a G3-4 skin reaction and mucositis was more common in patients receiving CTX plus PCT. Interaction effects analysis did not show any significant interaction effects on OS between the treatment regimen and prognostic factors (P>0.05). Conclusion: The efficacy of CTX/NTZ and PCT is comparable to single PCT treatment in terms of survival outcomes among de novo metastatic NPC patients. Moreover, the application of CTX exacerbated skin reactions and mucositis.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cetuximab/farmacologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Pontuação de Propensão , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Estudos de Coortes , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/metabolismo , Estudos Retrospectivos , Análise de Sobrevida
20.
BMC Cancer ; 19(1): 908, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511059

RESUMO

BACKGROUND: This study aimed to evaluate the prognostic value of maximal standard uptake values (SUVmax) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) comparing with Epstein-Barr virus (EBV) DNA levels in de novo metastatic nasopharyngeal carcinoma (NPC) patients. METHODS: From December 2006 to December 2016, 253 de novo metastatic NPC patients assessed by PET/ computed tomography were involved in current study. SUVmax-T, SUVmax-N, and SUVmax-M referred to the SUVmax at the primary tumor, cervical lymph nodes, and metastatic lesions respectively. Overall survival (OS) was the primary endpoint. RESULT: Patients who died during the follow-up had significantly higher SUVmax-N, SUVmax-M, and EBV DNA level than those in the patients who were alive. SUVmax-N and SUVmax-M were positively correlated with EBV DNA level. The cut-off values of SUVmax-T, SUVmax-N, SUVmax-M, and EBV DNA were 17.0, 12.7, and 6.9, and 13,800 copies/mL respectively, which were determined by receiver operating characteristic (ROC) curve analysis. Patients with elevated SUVmax-N, SUVmax-M, and EBV DNA levels had a lower 3-year OS rate. In multivariate analysis, the independent prognostic factors of OS included EBV DNA, metastatic site, and locoregional radiotherapy application, while SUVmax was not an independent prognostic factor. CONCLUSION: In de novo metastatic NPC patients, higher SUVmax-N and SUVmax-M were associated with worse prognosis. However, the predictive ability of SUVmax-N and SUVmax-M was poorer than that of EBV DNA.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Fluordesoxiglucose F18 , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/etiologia , Tomografia por Emissão de Pósitrons , Adulto , Idoso , DNA Viral , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/etiologia , Neoplasias Nasofaríngeas/mortalidade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Curva ROC
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