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      Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: A meta-analysis of clinical evidence

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          Abstract

          Background

          The characteristics of cervical lymphatic metastasis in nasopharyngeal carcinoma (NPC) are not completely understood. As such, radiotherapy to the entire lymphatic of the neck bilaterally has been empirically practiced even in early stage disease, although not supported by clinical evidence. We studied the pattern and probability of nodal metastasis through a meta-analysis of published evidences, with an aim to establish an evidence-based guideline for selecting and delineation of clinical target volume of neck lymphatics for conformation radiation for NPC.

          Methods

          A literature search yielded an initial 411 original articles, and 13 studies with 2920 NPC cases staged via MRI were included in this analysis. The occurrence of nodal metastasis was calculated and analyzed according to the respective regional nodal levels.

          Results

          85% of NPC cases presented with lymphadenopathy. The most commonly involved regions include retropharyngeal (69%) and level II lymph nodes (70%). The overall probability of levels III, IV, and V nodal involvement are 45%, 11%, and 27%, respectively. Low-risk node groups included the supraclavicular, levels IA/IB and VI nodes, and parotid nodes with involvement rates at 3%, 0%, 3%, 0%, and 1%, respectively. Nodal metastases followed an orderly pattern and the probability of "skip" metastasis between levels varied between 0.5-7.9%.

          Conclusions

          Lymph node metastasis in NPC follows a predictable and orderly pattern. The rarity of metastasis in certain nodal groups and "skip" metastasis suggest that reduced treatment volume is feasible in conformal radiotherapy for NPC.

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          Most cited references20

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          Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy: the Hong Kong experience.

          To evaluate the efficacy of using intensity-modulated radiotherapy (IMRT) in the primary treatment of nasopharyngeal carcinoma (NPC), including the role of dose escalation above 66 Gy level. Between July 2000 and September 2002, 63 newly diagnosed NPC patients were treated with IMRT. The disease was Stage I in 9 (14%), Stage II in 18 (29%), Stage III in 22 (35%), and Stage IV in 14 (22%). The prescribed dose was 66 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the planning target volume (PTV), and 54-60 Gy to the clinically negative neck. All 20 (100%) patients with T1-2a tumors received intracavitary brachytherapy (ICB) boost, and 15/42 (36%) patients with T2b-T4 tumors received conformal boost (8 Gy/4 fractions). Nineteen patients with advanced stage disease also received either neoadjuvant or concurrent chemotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. With a median follow-up of 29 months (range 8-45 months), 4 patients developed local in-field failure, 1 patient developed regional relapse, and 13 patients developed distant metastases. All 4 patients with local failure had either T3 or T4 disease before primary treatment and did not have ICB or conformal boost. The 3-year actuarial LRFS, NRFS, DMFS, and OS were 92%, 98%, 79%, and 90%, respectively. Multivariate analysis showed that dose escalation above 66 Gy was significantly associated with better PFS and DMFS, whereas GTV size was a significant adverse factor for OS. The worst acute mucositis was Grade 1 or 2 in 36 (59%), and Grade 3 in 25 (41%) patients. Acute dysphagia requiring tube feeding occurred in 5 (8%) patients. The proportion of patients with Grade 2-3 xerostomia was 57% at 3 months, and 23% at 2 years after IMRT. Within the subset of patients with a mean parotid dose of <31 Gy, the proportions with Grade 2-3 xerostomia were 30% and 17% at 3 months and 2 years, respectively. Our experience of using IMRT in the primary treatment of NPC showed a very high rate of locoregional control and favorable toxicity profile. Furthermore, we found that dose escalation above 66 Gy of IMRT-based therapy was a significant determinant of progression-free survival and distant metastasis-free survival for advanced T-stage tumors. Distant metastases represent the predominant mode of treatment failure.
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            Sequential chemotherapy and intensity-modulated radiation therapy in the management of locoregionally advanced nasopharyngeal carcinoma: Experience of 370 consecutive cases

            Introduction To investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) after induction chemotherapy, with or without concomitant chemotherapy. Methods Between August 2003 and March 2007, 370 patients with locoregionally advanced NPC were treated with IMRT. Presenting stages were stage IIB in 62, stage III in 197, and stage IVA/B in 111 patients. All patients except for 36 patients with cervical lymphadenopathy of 4 cm or less in diameter received 2 cycles of cisplatin-based neoadjuvant chemotherapy. Forty-eight patients received cisplatin-based concurrent chemotherapy as well. Results With a median follow-up time of 31 months (range 5 to 61 months), the 3-year local control, regional control, metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) rates were 95%, 97%, 86%, 81% and 89%, respectively. Multivariate analyses revealed that both age (≤ 60 vs. >60) and N-classification are significant prognosticators for OS (P = 0.001, hazard ratio [HR] 2.395, 95% confidence interval [CI] 1.432-4.003; P = 0.012, hazard ratio [HR] 2.614, 95% confidence interval [CI] 1.235-5.533); And N-classification is the only significant predicative factor for MFS (P = 0.002, [HR] 1.99, 95% CI 1.279-3.098). T-classification and concurrent chemotherapy were not significant prognostic factors for local/regional control, MFS, DFS, or OS. Subgroup analysis revealed that concurrent chemotherapy provided no significant benefit to IMRT in locoregionally advanced NPC, but was responsible for higher rates of grade 3 or 4 acute toxicities (50% vs. 29.8%, P < 0.005). No grade 3 or 4 late toxicity including xerostomia was observed. However, two patients treated with IMRT and neoadjuvant but without concurrent and adjuvant chemotherapy died of treatment related complications. Conclusion IMRT following neoadjuvant chemotherapy produced a superb outcome in terms of local control, regional control, MFS, DFS, and OS rates in patients with stage IIB to IVB NPC. Effective treatment strategy is urgently needed for distant control in patients diagnosed with locoregionally advanced NPC.
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              Neck node metastases from nasopharyngeal carcinoma: MR imaging of patterns of disease.

              The purpose was to use MR imaging to document the patterns of nodal involvement in the upper neck in nasopharyngeal carcinoma (NPC). The MR images of 150 patients with newly diagnosed NPC were reviewed retrospectively. Nodes were considered abnormal on MR criteria of size, necrosis, and extracapsular spread. Retropharyngeal nodes (RN) were more frequently involved than nonretropharyngeal nodes (NRNs) (94% vs 76% in 115 patients with nodal metastases). NRN involvement without RN was seen in only 7 of 115 patients (6%). Involvement of RN at the level of the oropharynx (82%) was as common as at the nasopharynx (83%) level. Internal jugular nodes were the most frequently involved NRN nodes (72%). Spinal accessory nodal involvement was also common (57%) but seldom in isolation (8%). Submandibular (3%) and parotid (2%) nodal metastases were uncommon and were always associated with advanced nodal metastases in the ipsilateral RN, internal jugular, and spinal accessory regions. Retropharyngeal nodes are the first echelons of nodal metastases. Direct lymphatic spread to the neck without involvement of the RN nodes is uncommon. RN metastases at the level of the oropharynx are more common than previously suspected, and this should influence radiotherapy planning. NRN outside the internal jugular and spinal accessory chains are rare and only occur when the usual routes of lymphatic spread have already been blocked by tumor.
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                Author and article information

                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central
                1471-2407
                2012
                21 March 2012
                : 12
                : 98
                Affiliations
                [1 ]Department of Radiation Oncology, National University Cancer Institute, National University Health System, 5 Lower Kent Ridge Road, Singapore 119074, Republic of Singapore
                [2 ]Centre for Quantitative Medicine, Duke-NUS Graduate Medical School, 8 College Road, Singapore, Singapore 169857
                Article
                1471-2407-12-98
                10.1186/1471-2407-12-98
                3353248
                22433671
                3386723a-8d3e-4d35-a14d-3ccfc7036ff0
                Copyright ©2012 Ho et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 September 2011
                : 21 March 2012
                Categories
                Research Article

                Oncology & Radiotherapy
                lymphatic metastasis,meta-analysis,lymph nodes,nasopharyngeal cancer
                Oncology & Radiotherapy
                lymphatic metastasis, meta-analysis, lymph nodes, nasopharyngeal cancer

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