Jun-lin Yi

Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for T4 nasopharyngeal carcinoma.

The goal of this study is to study and report the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for T4 nasopharyngeal carcinoma (NPC). A total of 70 patients treated with IMRT between 2004 and 2009 were eligible for study inclusion. According to the staging system of 2010 AJCC, all the primary tumors were attributed to T4 stage, while the distribution of disease by N stage was N0 in 2, N1 in 23, N2 in 39, N3a in 1, and N3b in 5. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. The median follow-up period was 26.8 (range, 4-78) months. The overall 2-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 82.1%, 92.3%, 73.8%, and 82.5%, respectively. Thirty-three patients had developed treatment failure. Of the 33 patients, 11, 2, and 15 had developed local failure, regional failure, and distant metastasis, respectively, 2 had developed locoregional failure, 1 had developed distant metastasis and failure at the primary, and 2 had developed distant metastasis and failure at the primary and nodal site. Eight of the locoregional failures were marginal. The results of treating T4 NPC with IMRT were excellent. Advanced T4 disease remained difficult to treat. One possible strategy is to lessen the dose constraint criteria of selected neurologic structures. Distant metastasis remains the most difficult treatment challenge for patients with T4 NPC at present, and more effective systemic chemotherapy should be explored.

Hypofractionated stereotactic radiotherapy for brain metastases larger than three centimeters

BackgroundTo evaluate the efficacy and outcomes of hypofractionated stereotactic radiotherapy (HSRT) for brain metastases > 3 cm.MethodsFrom March 2003 to October 2009, 40 patients with brain metastases larger than 3 cm were treated by HSRT. HSRT was applied in 29 patients for primary treatment and in 11 patients for rescue. Single brain metastasis was detected in 21 patients. Whole brain radiotherapy was incorporated into HSRT in 10 patients for primary treatment. HSRT boosts were applied in 23 patients. The diameters of the brain metastases ranged from 3.1 to 5.5 cm (median, 4.1 cm). The median prescribed dose (not including HSRT boosts) was 40 Gy (range, 20-53 Gy) with a median of 10 fractions (range, 4-15 fractions) to the 90% isodose line. The median dose of the boost was 20 Gy (range, 10-35 Gy) in 4 fractions (range, 2-10 fractions).ResultThe median overall survival time was 15 months. The overall survival and local control rate at 12 months was 55.3% and 94.2%, respectively. Four patients experienced local progression of large brain metastases. Nine patients died of intracranial disease progression. One patient died of radiation necrosis with brain edema.ConclusionHSRT was a safe and effective treatment for patients with brain metastases ranged from 3.1 to 5.5 cm. Dose escalation of HSRT boost may improve local control with an acceptable toxicity.

Definitive radiotherapy for cervical esophageal cancer.

The role of contemporary radiotherapy (RT) has not yet been elucidated, mainly because of the low incidence of cervical esophageal cancer. The purpose of this study was to analyze the outcome in patients with cervical esophageal cancer treated with definitive RT.

USEFULNESS OF HIF-1 IMAGING FOR DETERMINING OPTIMAL TIMING OF COMBINING BEVACIZUMAB AND RADIOTHERAPY

PURPOSE To study the relationship between the hypoxia-inducible factor-1 (HIF-1) activity level after bevacizumab treatment and the antitumor effects of radiation to determine the optimal combination schedule of bevacizumab with radiotherapy. METHODS AND MATERIALS The tumor hypoxia changes induced after bevacizumab treatment were evaluated using optical imaging with a HIF-1-dependent reporter gene using the NCI-H441 human lung adenocarcinoma xenograft model. The combined effects of bevacizumab with radiation were evaluated according to the timing of combination. RESULTS In vivo imaging experiments revealed that bevacizumab treatment had little effect on intratumoral HIF-1 activity 1 day after bevacizumab treatment, but it dramatically upregulated it thereafter through increases in the hypoxic fractions of the tumors. When bevacizumab treatment was combined with 14 Gy of radiation at 24 h or 72 h after bevacizumab treatment, the former combination delayed, but the latter combination accelerated, tumor growth compared with irradiation alone. CONCLUSION These data suggest that an optimal window exists for combining bevacizumab with radiotherapy that determines whether the combination will be beneficial and that the imaging of HIF-1 activity would be useful in determining this window.

Inherently poor survival of elderly patients with nasopharyngeal carcinoma

The purpose of this study was to determine the features of the elderly patient with nasopharyngeal carcinoma (NPC).

Update report of T4 classification nasopharyngeal carcinoma after intensity-modulated radiotherapy: An analysis of survival and treatment toxicities

OBJECTIVE To evaluate the long-term survival outcomes and toxicity of a larger series of patients with non-metastatic T4 classification nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS From March 2004 to June 2011, 335 non-metastatic T4 classification NPC patients treated by IMRT were analyzed retrospectively. Treatment induced toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0. RESULTS With a median follow-up time of 53.6 months (range, 2.8-114.9 months), the 5-year local failure-free survival (LFFS), regional failure free survival (RFFS), distant failure-free survival (DFFS), and overall survival (OS) were 84.1%, 92.2%, 74.1%, and 63.0%, respectively. At their last follow-up visit, 118 patients (35.2%) had developed treatment failure. Distant metastasis was the major failure pattern after treatment. The most common toxicities were mainly in grade 1 or 2. Concurrent chemotherapy failed to improve survival rates for patients with T4 classification NPC. CONCLUSION The results of T4 classification NPC treated by IMRT were excellent, and distant metastasis was the most commonly failure pattern. Treatment-related toxicities were well tolerable. The role of concurrent chemotherapy for T4 classification NPC needs to be further investigated in the era of IMRT.

Spread patterns of lymph nodes and the value of elective neck irradiation for esthesioneuroblastoma

OBJECTIVES This study was aimed to characterize patterns of lymphatic spread and assess the value of prophylactic elective neck irradiation (ENI) for esthesioneuroblastoma (ENB). METHODS A retrospectively analysis of 116 patients with newly diagnosed ENB at our institution over 35-year period was undertaken. RESULTS 32 patients (28%) presented lymph node metastasis at initial diagnosis, the common sites involved were level II, Ib, level III and VIIa. Among 80 N-negative patients staged in Modified Kadish B/C, 50 patients were delivered with ENI, 30 patients were not. The 5-year regional failure-free survival was 98% in patients treated with ENI and 75% in patients without ENI (p=0.005), regional failure rate decreased significantly from 23% (7/30) to 2% (1/50) after ENI (p=0.002). Multivariate analysis also suggested that ENI was an independent favorable predictor for regional controlling (HR, 0.102; 95% CI: 0.012-0.848; p=0.035). CONCLUSIONS This is the largest cohort of ENB so far in a single institute, and also the first detailed description of nodal spread patterns of N-positive ENB. Elective neck irradiation reduced the regional failure significantly and should be recommended as a part of initial treatment strategy for patients staged with Modified Kadish B/C.

Deep Deconvolutional Neural Network for Target Segmentation of Nasopharyngeal Cancer in Planning Computed Tomography Images

Background Radiotherapy is one of the main treatment methods for nasopharyngeal carcinoma (NPC). It requires exact delineation of the nasopharynx gross tumor volume (GTVnx), the metastatic lymph node gross tumor volume (GTVnd), the clinical target volume (CTV), and organs at risk in the planning computed tomography images. However, this task is time-consuming and operator dependent. In the present study, we developed an end-to-end deep deconvolutional neural network (DDNN) for segmentation of these targets. Methods The proposed DDNN is an end-to-end architecture enabling fast training and testing. It consists of two important components: an encoder network and a decoder network. The encoder network was used to extract the visual features of a medical image and the decoder network was used to recover the original resolution by deploying deconvolution. A total of 230 patients diagnosed with NPC stage I or stage II were included in this study. Data from 184 patients were chosen randomly as a training set to adjust the parameters of DDNN, and the remaining 46 patients were the test set to assess the performance of the model. The Dice similarity coefficient (DSC) was used to quantify the segmentation results of the GTVnx, GTVnd, and CTV. In addition, the performance of DDNN was compared with the VGG-16 model. Results The proposed DDNN method outperformed the VGG-16 in all the segmentation. The mean DSC values of DDNN were 80.9% for GTVnx, 62.3% for the GTVnd, and 82.6% for CTV, whereas VGG-16 obtained 72.3, 33.7, and 73.7% for the DSC values, respectively. Conclusion DDNN can be used to segment the GTVnx and CTV accurately. The accuracy for the GTVnd segmentation was relatively low due to the considerable differences in its shape, volume, and location among patients. The accuracy is expected to increase with more training data and combination of MR images. In conclusion, DDNN has the potential to improve the consistency of contouring and streamline radiotherapy workflows, but careful human review and a considerable amount of editing will be required.

Fractionated stereotactic radiotherapy for 136 patients with locally residual nasopharyngeal carcinoma

BackgroundTo evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) in patients with residual nasopharyngeal carcinoma (NPC).MethodsFrom January 2000 to December 2009, 136 NPC patients with residual lesions after primary radiotherapy (RT) were treated by FSRT. The total dose of primary RT was 68.0-78.0 Gy (median, 70.0 Gy). The median time from the primary RT to FSRT was 24.5 days. Tumor volumes for FSRT ranged from 0.60 to 77.13 cm3 (median, 13.45 cm3). The total FSRT doses were 8.0-32.0Gy (median, 19.5 Gy) with 2.0-10.0 Gy per fraction.ResultsFive-year local failure-free survival (LFFS), freedom from distant metastasis (FFDM), overall survival (OS), and disease free survival (DFS) rates for all patients were 92.5%, 77.0%, 76.2%, and 73.6%, respectively. No statistical significant differences were found in LFFS, DFS and OS in patients with stage I/II versus stage III/ IV diseases. Nineteen patients exhibited late toxicity. T stage at diagnosis was a significant prognostic factor for OS and DFS. Age was a prognostic factor for OS.ConclusionFSRT after external beam radiotherapy provides excellent local control for patients with residual NPC. The incidence of severe late toxicity is low and acceptable. Further investigation of optimal fractionation regimens will facilitate reduction of long-term complications.

Clinical characteristics and patterns of failure in the parotid region after intensity-modulated radiotherapy for nasopharyngeal carcinoma

OBJECTIVE To discuss the clinical characteristics and patterns of failure in the parotid region after intensity-modulated radiotherapy for nasopharygeal carcinoma. MATERIALS AND METHODS We retrospectively reviewed the charts of 716 patients with nasopharygeal carcinoma who underwent intensity-modulated radiotherapy in our centre from January 2005 to December 2010. Disease recurred in a spared parotid gland in 10 patients (1.4%). There were 2 females and 8 males with a median age of 38.5 (34-53) years. The most common presenting symptom was a swelling in pre-auricular region (7/10). Parotid glands were spared bilaterally in these patients. None of these patients had undergone previous radiotherapy or surgical treatment of the head and neck. The location of periparotid failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. RESULTS The median time from day 1 of radiotherapy to periparoid recurrence was 17.4 (4.4-40.5) months. The median survivial after periparoid recurrence was 25.1 (5.0-74.5) months. There were 9 (90%) patients with lateral retropharyngeal lymphadenopathy. Seven of the periparotid failures were marginal. Of the 7 marginal failures, 6 occurred at the ipslateral parotid of the primary tumor centre. The average mean dose of the ipslateral parotid was 38.1 (32.3-44.1) Gy. CONCLUSION Periparotid recurrence is an uncommon pattern of failure after definitive intensity-modulated radiotherapy for nasopharygeal carcinoma. To reduce the risk of periparotid recurrence,one possible strategy is to lessen the dose constraint criteria to ipslateral parotid of the primary tumor centre especially for nasopharygeal carcinoma with lateral retropharyngeal lymphadenopathy.