ABSTRACT
BACKGROUND: A current recommendation for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy (RT) with concurrent cisplatin followed by adjuvant cisplatin and 5-fluorouracil (PF). This randomized NPC-0501 trial evaluated the therapeutic effect of changing to an induction-concurrent sequence or accelerated-fractionation sequence, and/or replacing 5-fluorouracil with capecitabine (X). METHODS: Patients with American Joint Committee on Cancer/International Union Against Cancer stage III to stage IVB NPC initially were randomly allocated to 1 of 6 treatment arms (6-arm full-randomization cohort). The protocol was amended in 2009 to permit centers to opt out of randomization regarding fractionation (3-arm chemotherapy cohort). RESULTS: A total of 803 patients were accrued (1 of whom was nonevaluable) from 2006 to 2012. Based on the overall comparisons, neither changing the chemotherapy sequence nor accelerated fractionation improved treatment outcome. However, secondary analyses demonstrated that when adjusted for RT parameters and other significant factors, the induction-concurrent sequence, especially the induction-PX regimen, achieved significant improvements in progression-free survival (PFS) and overall survival. Efficacy varied among different RT groups: although no impact was observed in the accelerated-fractionation group and the 3-arm chemotherapy cohort, a comparison of the induction-concurrent versus concurrent-adjuvant sequence in the conventional-fractionation group demonstrated a significant benefit in PFS (78% vs 62% at 5 years; P = .015) and a marginal benefit in overall survival (84% vs 72%; P = .042) after adjusting for multiple comparisons. Comparison of the induction-PX versus the adjuvant-PF regimen demonstrated better PFS (78% vs 62%; P = .027) without an increase in overall late toxicity. CONCLUSIONS: For patients irradiated using conventional fractionation, changing the chemotherapy sequence from a concurrent-adjuvant to an induction-concurrent sequence, particularly using induction cisplatin and capecitabine, potentially could improve efficacy without an adverse impact on late toxicity. However, further validation is needed for confirmation of these findings.
Subject(s)
Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/radiotherapy , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/radiotherapy , Adolescent , Adult , Aged , Capecitabine/administration & dosage , Capecitabine/adverse effects , Chemoradiotherapy/adverse effects , Disease-Free Survival , Dose Fractionation, Radiation , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Progression-Free Survival , Treatment Outcome , Young AdultABSTRACT
Background: Given the distinct biological characteristics and regional distribution of nasopharyngeal carcinoma (NPC) compared with other head and neck cancers, and uncertainties regarding therapeutic strategies, physicians require high-quality clinical practice guidelines (CPGs) to provide transparent recommendations for NPC treatment. This study aimed to critically appraise the quality of NPC CPGs and assess the consistency of their recommendations. Methods: We identified CPGs that provided recommendations on the diagnosis and management of NPC published up to December 2015. Four investigators independently appraised CPG quality using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Key recommendations by CPGs were also evaluated. Results: A total of 7 CPGs were eligible for this study: 5 produced by professional organizations or governmental agencies and 2 were developed based on expert consensus. Of the 6 AGREE II domains, the applicability domain scored consistently low across CPGs (range, 13.5%-30.2%); no CPG achieved a score of >50% in all 6 domains. The scope and purpose domain (≥73.6% for 4 CPGs) and editorial independence domain (≥75.0% for 6 CPGs) scored highest. Of the 23 AGREE II items, 9 scored less than half of the points available in all 7 CPGs. The recommendations by CPGs were consistent in general; heterogeneity mainly existed among recommended therapeutic strategies. Conclusions: Variation exists in NPC CPG development processes and recommendations. Increased efforts are required to make comprehensive resources available to guide healthcare providers and enhance delivery of high-quality, evidence-based care for NPC. International collaboration is necessary to enable the development of high-quality and regionally relevant CPGs for NPC.
Subject(s)
Carcinoma/diagnosis , Carcinoma/therapy , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/therapy , Quality of Health Care , Disease Management , Humans , Nasopharyngeal Carcinoma , Neoplasm Metastasis , Neoplasm Staging , Practice Guidelines as Topic , RecurrenceABSTRACT
BACKGROUND: A previous individual patient data meta-analysis by the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess the addition of chemotherapy to radiotherapy showed that it improves overall survival in nasopharyngeal carcinoma. This benefit was restricted to patients receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy. METHODS: We searched PubMed, Web of Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov, and meeting proceedings to identify published or unpublished randomised trials assessing radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma and obtained updated data for previously analysed studies. The primary endpoint of interest was overall survival. All trial results were combined and analysed using a fixed-effects model. The statistical analysis plan was pre-specified in a protocol. All data were analysed on an intention-to-treat basis. FINDINGS: We analysed data from 19 trials and 4806 patients. Median follow-up was 7·7 years (IQR 6·2-11·9). We found that the addition of chemotherapy to radiotherapy significantly improved overall survival (hazard ratio [HR] 0·79, 95% CI 0·73-0·86, p<0·0001; absolute benefit at 5 years 6·3%, 95% CI 3·5-9·1). The interaction between treatment effect (benefit of chemotherapy) on overall survival and the timing of chemotherapy was significant (p=0·01) in favour of concomitant plus adjuvant chemotherapy (HR 0·65, 0·56-0·76) and concomitant without adjuvant chemotherapy (0·80, 0·70-0·93) but not adjuvant chemotherapy alone (0·87, 0·68-1·12) or induction chemotherapy alone (0·96, 0·80-1·16). The benefit of the addition of chemotherapy was consistent for all endpoints analysed (all p<0·0001): progression-free survival (HR 0·75, 95% CI 0·69-0·81), locoregional control (0·73, 0·64-0·83), distant control (0·67, 0·59-0·75), and cancer mortality (0·76, 0·69-0·84). INTERPRETATION: Our results confirm that the addition of concomitant chemotherapy to radiotherapy significantly improves survival in patients with locoregionally advanced nasopharyngeal carcinoma. To our knowledge, this is the first analysis that examines the effect of concomitant chemotherapy with and without adjuvant chemotherapy as distinct groups. Further studies on the specific benefits of adjuvant chemotherapy after concomitant chemoradiotherapy are needed. FUNDING: French Ministry of Health (Programme d'actions intégrées de recherche VADS), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.
Subject(s)
Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/epidemiology , Nasopharyngeal Neoplasms/radiotherapy , Carcinoma , Chemotherapy, Adjuvant , Clinical Trials as Topic , Combined Modality Therapy , Disease-Free Survival , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/pathology , Treatment OutcomeABSTRACT
BACKGROUND: A current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy with concurrent cisplatin plus adjuvant cisplatin and fluorouracil (PF). In this randomized trial, the authors evaluated the potential therapeutic benefit from changing to an induction-concurrent chemotherapy sequence, replacing fluorouracil with oral capecitabine, and/or using accelerated rather than conventional radiotherapy fractionation. METHODS: Patients with stage III through IVB, nonkeratinizing NPC were randomly allocated to 1 of 6 treatment arms. The protocol was amended in 2009 to permit confining randomization to the conventional fractionation arms. The primary endpoint was progression-free survival. Secondary endpoints included overall survival and safety. RESULTS: In total, 803 patients were accrued, and 706 patients were randomly allocated to all 6 treatment arms. Comparisons of induction PF versus adjuvant PF did not indicate a significant improvement. Unadjusted comparisons of induction cisplatin and capecitabine (PX) versus adjuvant PF indicated a favorable trend in progression-free survival for the conventional fractionation arm (P = .045); analyses that were adjusted for other significant factors and fractionation reflected a significant reduction in the hazards of disease progression (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.36-0.80) and death (HR, 0.42; 95% CI, 0.25-0.70). Unadjusted comparisons of induction sequences versus adjuvant sequences did not reach statistical significance, but adjusted comparisons indicated favorable improvements by induction sequence. Comparisons of induction PX versus induction PF revealed fewer toxicities (neutropenia and electrolyte disturbance), unadjusted comparisons of efficacy were statistically insignificant, but adjusted analyses indicated that induction PX had a lower hazard of death (HR, 0.57; 95% CI, 0.34-0.97). Changing the fractionation from conventional to accelerated did not achieve any benefit but incurred higher toxicities (acute mucositis and dehydration). CONCLUSIONS: Preliminary results indicate that the benefit of changing to an induction-concurrent sequence remains uncertain; replacing fluorouracil with oral capecitabine warrants further validation in view of its convenience, favorable toxicity profile, and favorable trends in efficacy; and accelerated fractionation is not recommended for patients with locoregionally advanced NPC who receive chemoradiotherapy.
Subject(s)
Chemoradiotherapy, Adjuvant/methods , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Fluorouracil/administration & dosage , Nasopharyngeal Neoplasms/therapy , Neoplasm Recurrence, Local/therapy , Adult , Aged , Capecitabine , Carcinoma , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Dose Fractionation, Radiation , Fluorouracil/adverse effects , Humans , Induction Chemotherapy , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
PURPOSE: To identify predictors for the development of temporal lobe injury (TLI) after intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma. MATERIALS AND METHODS: Data in 351 patients with nasopharyngeal carcinoma treated with IMRT were reviewed retrospectively according to institutional ethics committee approval. Clinical factors associated with TLI were analyzed. Dose-volume histograms for 550 evaluable temporal lobes were analyzed, and the predictive value of therapy-associated and patient-associated factors for the occurrence of TLI was evaluated. Survival curves were depicted by using the Kaplan-Meier method and compared by using the log-rank test. Logistic regression analysis was used for multivariate analyses. RESULTS: Median follow-up was 76 months (range, 6-100 months). Twenty-nine of 351 patients (8.3%) developed TLI; 21 patients had unilateral TLI, and eight had bilateral TLI. Median latency from IMRT until first TLI was 33 months (range, 12-83 months) among patients with TLI. The actuarial TLI-free survival rates were 94.4% and 91.3% at 3 and 5 years after radiation therapy, respectively. Logistic regression analysis demonstrated that dose delivered to a 1-cm(3) volume of the temporal lobe (D1cc) was the only independent predictor for TLI. The biologically equivalent tolerance doses at 2 Gy for a 5% and 50% probability of developing TLI were 62.83-Gy equivalents (95% confidence interval: 59.68, 65.97) and 77.58-Gy equivalents (95% confidence interval: 74.85, 80.32), respectively. CONCLUSION: D1cc is predictive for radiation-induced TLI, suggesting that delivery of a high dose of radiation to a small volume of the temporal lobe is unsafe. A D1cc of 62.83 Gy by using a correction formula for varying fraction size may be the dose tolerance of the temporal lobe.
Subject(s)
Nasopharyngeal Neoplasms/radiotherapy , Radiation Injuries/etiology , Radiotherapy, Intensity-Modulated/adverse effects , Temporal Lobe/injuries , Adult , Carcinoma , Dose-Response Relationship, Radiation , Female , Humans , Male , Middle Aged , Models, Statistical , Nasopharyngeal Carcinoma , Retrospective StudiesABSTRACT
PURPOSE: To evaluate the prognostic value of cervical nodal necrosis (CNN) in patients with nasopharyngeal carcinoma (NPC) with magnetic resonance (MR) imaging. MATERIALS AND METHODS: This was an institutional review board-approved retrospective study of 1800 patients with newly diagnosed stage T1, 4N1, 3M0 NPC who were treated with definitive radiation therapy, with or without chemotherapy, between January 2007 and December 2009; the requirement to obtain informed consent was waived. MR images were reviewed to assess lymph node status, and patients were divided into CNN and non-CNN groups. The overall survival, disease-free survival, regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared by using the log-rank test. RESULTS: The incidence of CNN was 44.0% (792 of 1800). After the median follow-up period of 53 months, the 5-year overall survival, disease-free survival, RRFS, and DMFS rates of the CNN and non-CNN groups were 78.8% and 91.8%, 78.2% and 91.2%, 78.6% and 91.8%, and 78.4% and 91.6%, respectively (for all rates, P < .001). The distant metastasis rate was 18.7% (148 of 792) for the CNN group versus 4.6% (46 of 1008) for the non-CNN group (P < .01). Subgroup analysis revealed similar survival outcomes between stage N1 disease with CNN and stage N2 disease without CNN, stage N2 disease with CNN, and stage N3 disease regardless of CNN. CNN, T stage, N stage, age older than 44 years, and male sex were significant independent negative prognostic factors for overall survival, disease-free survival, RRFS, and DMFS. CONCLUSION: CNN is an independent negative prognostic factor in patients with NPC, and it may be appropriate to investigate whether N stage should be upgraded by one level in patients with CNN.
Subject(s)
Lymph Nodes/pathology , Magnetic Resonance Imaging , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma , Child , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/secondary , Neck , Necrosis , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Rate , Young AdultABSTRACT
INTRODUCTION: The properties of a tumor itself were considered the main factors determining the survival of patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). However, recurrent tumors were mainly evaluated by using the American Joint Committee on Cancer staging system, which was modeled on primary tumors and did not incorporate the tumor volume. This study aimed to investigate the prognostic values of the primary tumor location and tumor volume, and to determine whether evaluating these parameters could improve the current staging system. METHODS: Magnetic resonance (MR) images for 229 patients with locally recurrent NPC who underwent IMRT were analyzed retrospectively. RESULTS: The skull base, parapharyngeal space, and intracranial cavity were the most common sites of tumors. There was a difference in the survival between patients with T1 and T2 diseases (77.6% vs. 50.0%, P<0.01) and those with T3 and T4 diseases (33.0% vs. 18.0%, P=0.04) but no difference between patients with T2 and T3 diseases (50.0% vs. 33.0%, P=0.18). Patients with a tumor volume≤38 cm3 had a significantly higher survival rate compared with those with a tumor volume>38 cm3 (48.7% vs. 15.2%, P<0.01). CONCLUSIONS: A new staging system has been proposed, with T3 tumors being down-staged to T2 and with the tumor volume being incorporated into the staging, which may lead to an improved evaluation of these tumors. This new system can be used to guide the treatment strategy for different risk groups of recurrent NPC.
Subject(s)
Nasopharyngeal Neoplasms , Neoplasm Staging , Prognosis , Radiotherapy, Intensity-Modulated , Tumor Burden , Carcinoma , Humans , Nasopharyngeal Carcinoma , Recurrence , Retrospective Studies , Survival RateABSTRACT
BACKGROUND: The optimal model of total dose and fraction size for patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) remains unclear. The authors designed a randomized phase 2 clinical trial to investigate the efficacy of 2 different models, with the objective of determining an optimal model. METHODS: Between January 2003 and December 2007, a total of 117 patients with locally recurrent nonmetastatic nasopharyngeal carcinoma were randomized to 2 different models of total dose and fraction size: group A (59 patients) received 60 gray in 27 fractions and group B (58 patients) received 68 gray in 34 fractions. Both groups received 5 daily fractions per week. All patients received IMRT alone. RESULTS: The median follow-up was 25.0 months. The 5-year overall survival in group A was higher than that in group B (44.2% vs 30.3%; P =.06), and the local failure-free survival in group A was slightly lower than that in group B (63.7% vs 71.0%; P =.41). Severe late complications were the main cause of death. The incidences of mucosal necrosis and massive hemorrhage in patients in group B were significantly higher than those among patients in group A at 50.8% versus 28.8% (P =.02) and 31.0% versus 18.6% (P =.12), respectively. Tumor volume (P<.01) and model of total dose and fraction size (P =.03) were found to be significant factors for mucosal necrosis and massive hemorrhage. CONCLUSIONS: Appropriately decreasing the total dose and increasing the fraction size can achieve local control similar to that achieved with a higher dose after IMRT; furthermore, it can improve overall survival by significantly reducing the incidence of severe late complications including mucosal necrosis and massive hemorrhage.
Subject(s)
Nasopharyngeal Neoplasms/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Radiotherapy, Intensity-Modulated , Adult , Aged , Carcinoma , Cause of Death , Female , Humans , Male , Middle Aged , Multivariate Analysis , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local/mortality , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Treatment Failure , Tumor BurdenABSTRACT
PURPOSE: The purpose of this study was to analyze the mode of relapse patterns and survival of 209 patients with stage IVA and IVB nasopharyngeal carcinoma (NPC). PATIENTS AND MATERIALS: A total of 209 patients who underwent magnetic resonance imaging (MRI) and were subsequently histologically diagnosed with nondisseminated stage IV NPC received intensity-modulated radiotherapy (IMRT) as their primary treatment and were included in this retrospective study. RESULTS: Median follow-up time was 65 months (range, 3-108 months). The 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates for patients with stage IVA and stage IVB NPC were 72.7 vs. 60.0 % (p = 0.319), 62.9 vs. 51.3 % (p = 0.070), 82.9 vs. 93.1 % (p = 0.070), 82.9 vs. 82.9 % (p = 0.897), 76.4 vs. 58.5 % (p = 0.003), respectively. Age older than 44 years was found to be a statistically significant adverse independent prognostic factor for OS. Patients with advanced N status had worse OS, DFS, and DMFS rates. Patients with a primary gross tumor volume (GTV-P) ≥ 55.11 ml had worse OS, DFS, and LRRFS rates. CONCLUSION: The results of treating stage IVA NPC with IMRT were excellent. Distant metastasis remains the most difficult treatment challenge for patients with stage IVA and IVB NPC, and more effective systemic chemotherapy should be explored.
Subject(s)
Endemic Diseases/prevention & control , Endemic Diseases/statistics & numerical data , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/radiotherapy , Neoplasm Recurrence, Local/mortality , Radiotherapy, Conformal/mortality , Adolescent , Adult , Age Distribution , Aged , Carcinoma , China/epidemiology , Disease-Free Survival , Female , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Prevalence , Retrospective Studies , Risk Factors , Sex Distribution , Survival Rate , Treatment Failure , Young AdultABSTRACT
Background: Detectable Epstein-Barr virus (EBV) DNA levels and unsatisfactory tumor response to induction chemotherapy (IC) could be used to guide the risk-adapted treatment strategy of locoregionally advanced nasopharyngeal carcinoma (LANPC) before concurrent chemoradiotherapy. We aim to compare the efficacy and safety of concurrent chemotherapy using taxane plus cisplatin [double-agent concurrent chemotherapy (DACC) group] with those of cisplatin alone [single-agent concurrent chemotherapy (SACC) group] in high-risk LANPC. Methods: Overall, 197 LANPC patients with detectable EBV DNA or stable disease (SD) after IC were retrospectively included. Potential confounders between the DACC and SACC groups were adjusted by propensity score matching. Short-term efficacy and long-term survival were assessed in the two groups. Results: Although the objective response rate of the DACC group was marginally higher than that of the SACC group, the difference was not significant (92.7% versus 85.3%, p = 0.38). Concerning long-term survival, DACC did not show superiority to SACC after patient matching: 3-year progression-free survival: 87.8% versus 81.7%, p = 0.80; overall survival: 97.6% versus 97.3%, p = 0.48; distant metastasis-free survival: 87.8% versus 90.5%, p = 0.64, and; locoregional relapse-free survival: 92.3% versus 86.9%, p = 0.77. The incidence of grade 1-4 hematological toxicities was significantly higher in the DACC group. Conclusion: Due to the small sample size, we do not have sufficient evidence that concurrent chemotherapy using taxane plus cisplatin provides additional survival benefits in LANPC patients with an unfavorable response (detectable EBV DNA levels or SD) after IC. But concurrent taxane and cisplatin chemotherapy is associated with a higher rate of hematologic adverse events. Further clinical trials will be required to establish evidence and identify more effective treatment modalities for high-risk LANPC patients.
ABSTRACT
BACKGROUND: To describe the clinical characteristics of the patients who suffered from relapse after conventional irradiation for nasopharyngeal carcinoma (NPC). METHODS: Three hundred and fifty-one consecutive patients with first-time recurrent NPC between January 1999 and July 2005 were included. The patients' clinical data were reviewed, including recurrent interval time, symptoms, signs, imaging characteristics, pathologic features, and restaging. RESULTS: The median interval of relapse was 26.0 months. The most common symptoms in symptomatic patients were nasal bloody discharge (37.9%) and headache (31.1%). Local recurrence alone accounted for 73.5%. Most patients were restaged as stage III (23.1%) and stage IV (51.1%). Subgroup analysis suggested a significantly higher proportion of the long-latent relapses originated from early primary. A series of postreirradiation complications were more frequent in patients with longer latency at reception. CONCLUSIONS: Most recurrent nasopharyngeal carcinoma is advanced disease. Patients with different recurrent interval time show different nature behavior.
Subject(s)
Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local , Adult , Aged , China/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Nasopharyngeal Neoplasms/epidemiology , Retrospective StudiesABSTRACT
PURPOSE: The current recommendation for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is cisplatin-based induction chemotherapy (IC) or adjuvant chemotherapy (AC) plus concurrent chemoradiotherapy (CRT). However, data on the optimal platinum doses for each phase of combined regimens are lacking. EXPERIMENTAL DESIGN: 742 patients with NPC in the NPC-0501 trial treated with CRT plus IC/AC and irradiated with intensity-modulated radiotherapy (IMRT) were analyzed. The optimal platinum dose to achieve the best overall survival (OS) in the concurrent and induction/adjuvant phases was studied. RESULTS: Evaluation of the whole series shows the optimal platinum dose was 160 mg/m2 in the concurrent and 260 mg/m2 in the induction/adjuvant phase. Repeating the analyses on 591 patients treated with cisplatin throughout (no replacement by carboplatin) confirmed the same results. The cohort with optimal platinum doses in both phases had better OS than the cohort suboptimal in both phases (stage III: 90% vs. 75%; stage IVA-B: 80% vs. 56%, at 5-year). Multivariable analyses confirmed optimal platinum doses in both phases versus suboptimal dose in each phase are significant independent factors for OS, with HR of 0.61 [95% confidence interval (CI), 0.41-0.91] and 0.67 (95% CI, 0.48-0.94), respectively. Treatment sequence was statistically insignificant after adjusting for platinum doses. CONCLUSIONS: Both concurrent and IC/AC are needed for locoregionally advanced NPC, even for patients irradiated by IMRT; the concurrent platinum dosage could be set at ≥160 mg/m2 when coupled with adequate induction/adjuvant dosage at ≥260 mg/m2 (or at least ≥240 mg/m2). To achieve these optimal dosages, IC-CRT at conventional fractionation is favored.
Subject(s)
Nasopharyngeal Neoplasms , Radiotherapy, Intensity-Modulated , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemoradiotherapy/methods , Chemotherapy, Adjuvant , Cisplatin , Fluorouracil , Humans , Induction Chemotherapy/methods , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/etiology , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/radiotherapy , Platinum/therapeutic useABSTRACT
PURPOSE: To evaluate the long-term local control, failure patterns, and toxicities after individualized clinical target volume (CTV) delineation in unilateral nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). METHODS: Unilateral NPC was defined as a nasopharyngeal mass confined to one side of the nasopharynx and did not exceed the midline. From November 2003 to December 2017, 95 patients were retrospectively included. All patients received IMRT. The CTVs were determined based on the distance from the gross tumor. The contralateral para-pharyngeal space and skull base orifices were spared from irradiation. RESULTS: There were three local recurrences and eight regional recurrences in 10 patients during an 84-month follow-up. All local recurrences were within PGTVnx, and all in-field recurrences. No recurrences were found in traditional high-risk areas including contralateral the para-pharyngeal space and skull base orifices. The 10-year local-recurrence-free survival, regional-recurrence-free survival and overall survival were 96.2%, 90.5% and 84.7%, respectively. The dosimetry parameters of the tumor-contralateral organs were all lower than the values of the tumor-ipsilateral side (P < 0.05). The late toxicities occurred mainly in the tumor-ipsilateral organs, including radiation-induced temporal lobe injury, impaired visuality, hearing loss and subcutaneous fibrosis. CONCLUSION: Individualized CTV delineation in unilateral NPC could yield excellent long-term local control with limited out-of-field recurrences, reduced dose to tumor- contralateral organs and mild late toxicities, which is worthy of further exploration.
Subject(s)
Nasopharyngeal Neoplasms , Radiation Injuries , Radiotherapy, Intensity-Modulated , Follow-Up Studies , Humans , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Staging , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective StudiesABSTRACT
Although many studies have investigated intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), sample sizes in the reported studies are usually small and different in outcomes in different T and N subgroups are seldom analyzed. Herein, we evaluated the outcomes of NPC patients treated with IMRT and further explored treatment strategy to improve such outcome. We collected clinical data of 865 NPC patients treated with IMRT alone or in combination with chemotherapy, and classified all cases into the following prognostic categories according to different TNM stages: early stage group (T1-2N0-1M0), advanced local disease group (T3-4N0-1M0), advanced nodal disease group (T1-2N2-3M0), and advanced locoregional disease group (T3-4N2-3M0). The 5-year overall survival (OS), local relapse-free survival (LRFS), and distant metastases-free survival (DMFS) were 83.0%, 90.4%, and 84.0%, respectively. The early disease group had the lowest treatment failure rate, with a 5-year OS of 95.6%. The advanced local disease group and advanced nodal disease group had similar failure pattern and treatment outcomes as well as similar hazard ratios for death (4.230 and 4.625, respectively). The advanced locoregional disease group had the highest incidence of relapse and death, with a 5-year DMFS and OS of 62.3% and 62.2%, respectively, and a hazard ratio for death of 10.402. Comparing with IMRT alone, IMRT in combination with chemotherapy provided no significant benefit to locoregionally advanced NPC. Our results suggest that the decision of treatment strategy for NPC patients should consider combinations of T and N stages, and that IMRT alone for early stage NPC patients can produce satisfactory results. However, for advanced local, nodal, and locoregional disease groups, a combination of chemotherapy and radiotherapy is recommended.
Subject(s)
Nasopharyngeal Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated , Adolescent , Adult , Aged , Carcinoma , Chemoradiotherapy , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local , Neoplasm Staging , Radiotherapy Dosage , Survival Rate , Young AdultABSTRACT
OBJECTIVE: At present, the clinical data about the effect of overall treatment time (OTT) on local control for nasopharyngeal carcinomas (NPC) patients mainly derived from conventional radiotherapy (CRT). The effect of OTT on local control for NPC patients treated with IMRT is still unclear. This study was to explore the effect of OTT on local control in IMRT for NPC patients. METHODS: Clinical data of 850 NPC (T1-4N0-3M0) patients that had undergone radical radiotherapy with IMRT from May 2001 to January 2008 in Sun Yat-sen University Cancer Center were analyzed retrospectively. All patients were divided into two groups, which were group with OTT ≤ 42 and group with OTT > 42 days respectively. Survival was calculated using the Kaplan-Meier method. The log-rank test was used to compare survival curves. The effect of clinical factors and treatment related factors on LCR were studied with univariate and multivariate analyses using logistic regression. RESULTS: The 5-years local recurrence-free survival (LRFS) rate of group with OTT ≤ 42 were 90.7%, and 90.9% in group with OTT > 42, no significant differences were found between these two groups (χ² = 0.028, P = 0.866). Further stratified analysis found that the LRFS rate for early T-stage patients was no significant difference between group with OTT ≤ 42 and group with > 42 days, they were 97.2% and 97.9% (χ² = 0.672, P = 0.412). For advanced T-stage patients, the LRFS rate of OTT ≤ 42 and > 42 days were 86.5% and 87.2% respectively (χ² = 0.151, P = 0.698). The 5-year LRFS rate were 94.4% vs 93.0% (χ² = 0.090, P = 0.764) at OTT > 42 vs ≤ 42 days for patients treated with IMRT alone, and 89.7% vs 87.6% (χ² = 0.060, P = 0.807) for patients in combination chemotherapy with IMRT. We divided all patients into three groups: OTT ≤ 42 d, 43 - 49 d and ≥ 50 d, the 5-years LRFS rate of the three group was 90.7%, 91.7% and 88.4%, respectively, there was no significant difference of LRFS among those three groups (χ² = 0.136, P = 0.934). Univariate analysis showed that T-stage and GTV volume were correlation with local control. In multivariate analysis, GTV volume was confirmed as independent prognostic factors for local control. CONCLUSIONS: Within the range of the OTT observed in our study, prolonged OTT did not have adverse effect on local control. GTV volume was independent prognostic factors in local control for NPC patients treated with IMRT.
Subject(s)
Nasopharyngeal Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated , Adolescent , Adult , Aged , Carcinoma , Female , Humans , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Multivariate Analysis , Nasopharyngeal Carcinoma , Retrospective Studies , Time Factors , Treatment Outcome , Young AdultABSTRACT
PURPOSE: Reirradiation for locally recurrent nasopharyngeal carcinoma (NPC) is challenging because prior radiation dose delivered in the first course is often close to the tolerance limit of surrounding normal structures. A delicate balance between achieving local salvage and minimizing treatment toxicities is needed. However, high-level evidence is lacking because available reports are mostly retrospective studies on small series of patients. Pragmatic consensus guidelines, based on an extensive literature search and the pooling of opinions by leading specialists, will provide a useful reference to assist decision-making for these difficult decisions. METHODS AND MATERIALS: A thorough review of available literature on recurrent NPC was conducted. A set of questions and preliminary draft guideline was circulated to a panel of international specialists with extensive experience in this field for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the whole panel for review and reconsideration. The current guideline was based on majority voting after repeated iteration for final agreement. RESULTS: The initial round of questions showed variations in clinical practice even among the specialists, reflecting the lack of high-quality supporting data and the difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of reirradiation (including patient selection, targets contouring, dose prescription, and constraints). CONCLUSION: This paper provides useful reference on radical salvage treatment strategies for recurrent NPC and optimization of reirradiation through review of published evidence and consensus building. However, the final decision by the attending clinician must include full consideration of an individual patient's condition, understanding of the delicate balance between risk and benefits, and acceptance of risk of complications.
Subject(s)
Internationality , Nasopharyngeal Carcinoma/radiotherapy , Practice Guidelines as Topic , Radiotherapy, Intensity-Modulated , Re-Irradiation , Disease-Free Survival , Humans , Radiotherapy Dosage , Recurrence , Salvage TherapyABSTRACT
BACKGROUND AND OBJECTIVE: At present, although appropriate radiotherapy and combined treatments are widely used for the patients with primary nasopharyngeal carcinoma (NPC), local or regional recurrence rates are still high. According to clinical performance, pathology, and diagnostic imaging of the patients with the first recurrence of NPC, this study analyzed the clinical features of recurrent NPC to provide a reference for tracking the rules of recurrence after the treatment of patients with NPC. METHODS: Clinical data of 337 patients diagnosed with recurrent NPC for the first time were collected. The diagnoses were based on pathology and/or imaging and the patients were treated at the Sun Yat-sen University Cancer Center between January 1999 and December 2004. Data used for statistical analysis included clinical performance during the patient visit, the extension of the invasion as shown on imaging, pathologic features, Epstein-Barr virus (EBV) serology, restaging, etc. RESULTS: Patients were staged according to the system developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) in 2002. Patients with diseases at stages I/II accounted for 25.2%, while those with stage III/IV accounted for 74.8%. The median interval of relapse was 25 months. Patients had local recurrence (69.4%), regional recurrence (4.5%), or both (26.1%). Epistaxis and headache were the most common symptoms. Abduct dysfunction and facial numbness induced by cranial nerve damage were the most common signs. The probability of invasion of structures adjacent to the nasopharynx, such as the oropharynx, the prestyloid space, and the carotid sheath area, was low in patients with recurrent NPC. By contrast, the probability of invasion of structures far from the nasopharynx, such as the base of the skull, the paranasal sinuses, cranial nerves, the cavernous sinus, the brain, the pterygopalatine fossa, the infratemporal fossa, the orbital apex, and the soft palate, was higher in recurrent NPC. CONCLUSIONS: The most common interval of relapse is about 2 years. The relapsed disease is usually more widespread and located deeper. Most recurrent NPC is advanced disease.
Subject(s)
Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Adult , Aged , Antigens, Viral/blood , Bone Neoplasms/secondary , Capsid Proteins/blood , Female , Humans , Immunoglobulin A/blood , Lung Neoplasms/secondary , Lymphatic Metastasis , Male , Middle Aged , Nasopharyngeal Neoplasms/blood , Nasopharyngeal Neoplasms/virology , Neoplasm Invasiveness , Neoplasm Staging , Retrospective Studies , Young AdultABSTRACT
BACKGROUND AND OBJECTIVE: The primary submucous type of nasopharyngeal carcinoma (NPC) or the recurrent NPC in the parapharyngeal space is difficult to be diagnosed histologically by conventional biopsy because of the obstruction of the surrounding structures. This study was performed to evaluate the needle biopsy approach through the madibular area into the parapharyngeal space under the guidance of computed tomography (CT) for NPC. METHODS: Between July 6, 2005 and October 23, 2009, a total of 6 patients were enrolled into the study. Two patients with cervical lymph node metastasis were clinically suspicious of NPC according to their clinical manifestations. However, no cancer cell could be found by repeated nasopharyngeal biopsies followed by histologic examinations. The other 4 patients were diagnosed with recurrent NPCs by magnetic resonance imaging (MRI) or/and positron emission tomography (PET)-CT scan, showing tumors in the parapharyngeal spaces in 3 patients and enlarged retropharyngeal lymph node in 1 patient. The CT-guided puncture was performed through the mandibular skin and the cutting needle biopsy was taken at the parapharyngeal space focus. RESULTS: All the cutting needle biopsies of projected locations have been performed safely. Finally, all the 7 specimens met the requirement of pathologic diagnosis and the cases were all confirmed histologically to be NPCs. The main complication was mild ache at the puncture point. No blood vessel or nerve was injured and no patient needed special treatment. CONCLUSIONS: The CT-guided puncture biopsy of the parapharyngeal space through the mandibular area is simple and feasible. It can be an additional option for routine nasopharyngeal biopsy.
Subject(s)
Biopsy, Needle/methods , Lymph Nodes/pathology , Nasopharyngeal Neoplasms/diagnosis , Pharynx/pathology , Adult , Aged , Female , Humans , Lymphatic Metastasis , Magnetic Resonance Imaging , Male , Mandible , Middle Aged , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local , Positron-Emission Tomography , Tomography, X-Ray ComputedABSTRACT
PURPOSE: To define the clinical characteristics and prognostic value of pre-retreatment plasma Epstein-Barr virus (EBV) DNA, we investigated EBV status in locoregional recurrent nasopharyngeal carcinoma (lrNPC) patients. METHODS: Between April 2008 and August 2016, the data of patients with nonmetastatic lrNPC were retrospectively reviewed. The survival indexes of patients between different pre-retreatment EBV status groups were compared. RESULTS: A total of 401 patients with nonmetastatic lrNPC were enrolled, and 197 (49.1%) patients had detectable pre-retreatment plasma EBV DNA. Treatment included radiotherapy alone (n = 37 patients), surgery alone (n = 105), radiotherapy (n = 208), surgery combined with radiotherapy (n = 20), chemotherapy and targeted therapy (n = 31). Median follow-up was 32 months. The 3-year locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates for the entire cohort were 64.8%, 89.4%, and 58.8%, respectively. The estimated 3-year LRRFS, DMFS, and OS rates for the pre EBV-positive group vs the pre EBV-negative group were 54.2% vs 75.0% (P < 0.001), 86.6% vs 91.9% (P = 0.05), 51.6% vs 65.9% (P = 0.01), respectively. Among patients in the clinical stage rI/II, there were 17 patients in the radiotherapy alone group and 49 patients in the surgery alone group. And there was no significant difference in overall survival between radiotherapy and surgery, even among the different pre-EBV statuses (P > 0.05). In terms of long-term toxic and side effects, the incidence of radioactive temporal lobe injury in the radiotherapy group was higher than that in the surgery group (35.3% vs 8.2%, P < 0.001), and no statistically significant difference was found in other long-term toxic and side effects. CONCLUSIONS: The positive rate of pre-retreatment plasma EBV DNA in lrNPC is lower than primary NPC. The prognosis of EBV DNA negative group is better than positive group. For locally early-stage lrNPC, regardless of EBV DNA status, radiotherapy and surgery are available options and both can achieve better long-term survival.