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      Radiation-induced temporal lobe injury after intensity modulated radiotherapy in nasopharyngeal carcinoma patients: a dose-volume-outcome analysis

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          Abstract

          Background

          To identify the radiation volume effect and significant dosimetric parameters for temporal lobe injury (TLI) and determine the radiation dose tolerance of the temporal lobe (TL) in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT).

          Methods

          Twenty NPC patients with magnetic resonance imaging (MRI)-diagnosed unilateral TLI were reviewed. Dose-volume data was retrospectively analyzed.

          Results

          Paired samples t-tests showed all dosimetric parameters significantly correlated with TLI, except the TL volume (TLV) and V 75 (the TLV that received ≥75 Gy, P = 0.73 and 0.22, respectively). Receiver operating characteristic (ROC) curves showed V 10 and V 20 ( P = 0.552 and 0.11, respectively) were the only non-significant predictors from V 10 to V 70 for TLI. D 0.5cc (dose to 0.5 ml of the TLV) was an independent predictor for TLI ( P < 0.001) in multivariate analysis; the area under the ROC curve for D 0.5cc was 0.843 ( P < 0.001), and the cutoff point 69 Gy was deemed as the radiation dose limit. The distribution of high dose ‘hot spot’ regions and the location of TLI were consistent.

          Conclusions

          A D 0.5cc of 69 Gy may be the dose tolerance of the TL. The risk of TLI was highly dependent on high dose ‘hot spots’ in the TL; physicians should be cautious of such ‘hot spots’ in the TL during IMRT treatment plan optimization, review and approval.

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          Most cited references12

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          Tolerance of normal tissue to therapeutic irradiation

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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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              Locoregional extension patterns of nasopharyngeal carcinoma and suggestions for clinical target volume delineation

              Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection. This study aimed to define the locoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV delineation. Magnetic resonance imaging scans of 2366 newly diagnosed NPC patients were reviewed. According to incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were classified into high-risk (>30%), medium-risk (5%–30%), and low-risk (<5%) groups. The lymph node (LN) level was determined according to the Radiation Therapy Oncology Group guidelines, which were further categorized into the upper neck (retropharyngeal region and level II), middle neck (levels III and Va), and lower neck (levels IV and Vb and the supraclavicular fossa). The high-risk anatomic sites were adjacent to the nasopharynx, whereas those at medium- or low-risk were separated from the nasopharynx. If the high-risk anatomic sites were involved, the rates of tumor invasion into the adjacent medium-risk sites increased; if not, the rates were significantly lower (P < 0.01). Among the 1920 (81.1%) patients with positive LN, the incidence rates of LN metastasis in the upper, middle, and lower neck were 99.6%, 30.2%, and 7.2%, respectively, and skip metastasis happened in only 1.2% of patients. In the 929 patients who had unilateral upper neck involvement, the rates of contralateral middle neck and lower neck involvement were 1.8% and 0.4%, respectively. Thus, local disease spreads stepwise from proximal sites to distal sites, and LN metastasis spreads from the upper neck to the lower neck. Individualized CTV delineation for NPC may be feasible.
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                Author and article information

                Contributors
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central
                1471-2407
                2013
                27 August 2013
                : 13
                : 397
                Affiliations
                [1 ]State Key Laboratory of Oncology in Southern China, Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou 510060, People’s Republic of China
                [2 ]State Key Laboratory of Oncology in Southern China, Imaging Diagnosis and Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou 510060, People’s Republic of China
                [3 ]Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510060, People’s Republic of China
                Article
                1471-2407-13-397
                10.1186/1471-2407-13-397
                3851326
                23978128
                2d7eed07-e720-4ecc-9b99-06f787d077c2
                Copyright © 2013 Sun 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
                : 21 January 2013
                : 22 August 2013
                Categories
                Research Article

                Oncology & Radiotherapy
                nasopharyngeal carcinoma,temporal lobe injury,intensity modulated radiotherapy,radiation volume effect,dose tolerance

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