Isotropic reconstruction of a 4-D MRI thoracic sequence using super-resolution.

PURPOSE: Four-dimensional (4D) thoracic magnetic resonance imaging (MRI) sequences have been shown to successfully monitor both tumor and lungs anatomy. However, a high temporal resolution is required to avoid motion artifacts, which leads to volumes with poor spatial resolution. This article proposes to reconstruct an isotropic 4D MRI thoracic sequence with minimum modifications to the acquisition protocols. This could be an important step toward the use of 4D MRI for thoracic radiotherapy applications. METHODS: In a postacquisition step, three orthogonal 4D anisotropic acquisitions are combined using super-resolution to reconstruct a series of isotropic volumes. A new phantom that simulates lung tumor motion is developed to evaluate the performance of the algorithm. The proposed framework is also applied to real data of a lung cancer patient. RESULTS: Subjective and objective evaluations show clear resolution enhancement and partial volume effect diminution. The isotropic reconstruction of patient data significantly improves both the visualization and segmentation of thoracic structures. CONCLUSIONS: The results presented here are encouraging and suggest that super-resolution can be regarded as an efficient method to improve the resolution of 4D MRI sequences. It produces an isotropic 4D sequence that would be impossible to acquire in practice. Further investigations will be required to evaluate its reproducibility in various clinical applications.

Neoadjuvant chemotherapy followed by concurrent chemoradiation for locoregionally advanced nasopharyngeal carcinoma: interim results from 2 prospective phase 2 clinical trials.

BACKGROUND: The authors studied the efficacy of neoadjuvant chemotherapy, consisting of a taxane, cisplatin, and 5-fluorouracil (5-FU) (the TPF regimen) followed by concurrent chemoradiation, in 2 separately designed and synchronously executed phase 2 trials for stage III and IVA/IVB nasopharyngeal cancer (NPC). METHODS: Patients with newly diagnosed NPC were accrued to 2 trials, 1 for patients with stage III disease and the other for patients with IVA/IVB disease. All patients received TPF (docetaxel 75 mg/m(2), cisplatin 75 mg/m(2), and 5-FU 2500 mg/m(2) every 3 weeks for 3 cycles) followed by cisplatin 40 mg/m(2) per week concurrently with either 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy. RESULTS: From January 2007 to July 2011, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued. With a median follow-up of 32.9 months, the 3-year overall survival rates were 94.8% (95% confidence interval [CI], 87.6%-100%) and 90.2% (95% CI, 81.8%-98.6%) for the stage III NPC group and the IVA/IVB NPC group, respectively. The 3-year progression-free survival, distant metastasis-free survival, and local progression-free survival rates were 78.2% (95% CI, 64.6%-91.8%), 90.5% (95% CI, 79.7%-100%), and 93.9%(87.1%-100%), respectively, for patients with stage III NPC and 85.1% (95% CI, 75.1%-95.1%), 88% (95% CI, 78.6%-97.4%), and 100%, respectively, for patients with stage IVA/IVB NPC. The most common severe (grade 3/4) hematologic and nonhematologic adverse events were neutropenia (64 patients; 55.2%) and nausea/vomiting (23 patients; 19.8%). CONCLUSIONS: Neoadjuvant TPF followed by concurrent chemoradiation was well tolerated and produced encouraging outcomes in patients with locally advanced NPC in this hypothesis-generating study. The authors concluded that randomized controlled trials are warranted to definitively confirm this aggressive and potentially efficacious strategy.

Recombinant adenovirus-p53 (Gendicine) sensitizes a pancreatic carcinoma cell line to radiation.

OBJECTIVE: In this study, we examine the effects of recombinant adenovirus-p53 (rAd-p53) on the pancreatic carcinoma cell line SW1990. Specifically, we determine if expression of rAd-p53 sensitizes these cells to radiation. METHODS: Following transfection of SW1990 cells with rAd-p53, we measured expression of P53, P21 and Bax by immunocytochemistry. Both transfected and control cell lines were irradiated with a range of doses, and the survival fractions (SF) were calculated. Dose survival curves were constructed and modeled for comparison. RESULTS: Transfection of SW1990 cells with rAd-p53 resulted in increased expression of P53, P21 and Bax in a time-dependent manner. At 96 h after transfection, 89.92% of cells expressed P53, 56.8% expressed P21, and 76.50% expressed Bax. The SF following radiation was lower in the rAd-p53 transfected cells compared to the control cells, suggesting that rAd-p53 sensitizes SW1990 cells to radiation (D0 for the experimental and control groups was 2.199 and 2.462, respectively). CONCLUSIONS: Use of the adenoviral vector is an effective means of transfecting SW1990 cells with wild-type P53, and this sensitizes the cell line to irradiation. This work suggests that combining rAd-p53 with radiation therapy in pancreatic cancer may be therapeutically beneficial.

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

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.

Investigation of small lung lesion detection for lung cancer screening in low dose FDG PET imaging by deep neural networks.

Purpose: FDG PET imaging is often recommended for the diagnosis of pulmonary nodules after indeterminate low dose CT lung cancer screening. Lowering FDG injecting is desirable for PET imaging. In this work, we aimed to investigate the performance of a deep learning framework in the automatic diagnoses of pulmonary nodules at different count levels of PET imaging. Materials and methods: Twenty patients with 18F-FDG-avid pulmonary nodules were included and divided into independent training (60%), validation (20%), and test (20%) subsets. We trained a convolutional neural network (ResNet-50) on original DICOM images and used ImageNet pre-trained weight to fine-tune the model. Simulated low-dose PET images at the 9 count levels (20 × 106, 15 × 106, 10 × 106, 7.5 × 106, 5 × 106, 2 × 106, 1 × 106, 0.5 × 106, and 0.25 × 106 counts) were obtained by randomly discarding events in the PET list mode data for each subject. For the test dataset with 4 patients at the 9 count levels, 3,307 and 3,384 image patches were produced for lesion and background, respectively. The receiver-operator characteristic (ROC) curve of the proposed model under the different count levels with different lesion size groups were assessed and the areas under the ROC curve (AUC) were compared. Results: The AUC values were >0.98 for all count levels except for 0.5 and 0.25 million true counts (0.975 (CL 95%, 0.953-0.992) and 0.963 (CL 95%, 0.941-0.982), respectively). The AUC values were 0.941(CL 95%, 0.923-0.956), 0.993(CL 95%, 0.990-0.996) and 0.998(CL 95%, 0.996-0.999) for different groups of lesion size with effective diameter (R) <10 mm, 10-20 mm, and >20 mm, respectively. The count limit for achieving high AUC (≥0.96) for lesions with size R < 10 mm and R > 10 mm were 2 million (equivalent to an effective dose of 0.08 mSv) and 0.25 million true counts (equivalent to an effective dose of 0.01 mSv), respectively. Conclusion: All of the above results suggest that the proposed deep learning based method may detect small lesions <10 mm at an effective radiation dose <0.1 mSv. Advances in knowledge: We investigated the advantages and limitations of a fully automated lung cancer detection method based on deep learning models for data with different lesion sizes and different count levels, and gave guidance for clinical application.

Quantitative accuracy of radiomic features of low-dose 18F-FDG PET imaging.

BACKGROUND: 18F-FDG PET based radiomics is promising for precision oncology imaging. This work aims to explore quantitative accuracies of radiomic features (RFs) for low-dose 18F-FDG PET imaging. METHODS: Twenty lung cancer patients were prospectively enrolled and underwent 18F-FDG PET/CT scans. Low-dose PET situations (true counts: 20×106, 15×106, 10×106, 7.5×106, 5×106, 2×106, 1×106, 0.5×106, 0.25×106) were simulated by randomly discarding counts from the acquired list-mode data. Each PET image was created using the scanner default reconstruction parameters. Each lesion volume of interest (VOI) was obtained via an adaptive contouring method with a threshold of 50% peak standardized uptake value (SUVpeak) in the PET images with full count data and VOIs were copied to the PET images at the reduced count level. Conventional SUV measures, features calculated from first-order statistics (FOS) and texture features (TFs) were calculated. Texture based RF include features calculated from gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), gray-level size zone matrix (GLSZM), neighboring gray-level dependence matrix (NGLDM) and neighbor gray-tone difference matrix (NGTDM). Bias percentage (BP) at different count levels for each RF was calculated. RESULTS: Fifty-seven lesions with a volume greater than 1.5 cm3 were found (mean volume, 25.7 cm3, volume range, 1.5-245.4 cm3). In comparison with normal total counts, mean SUV (SUVmean) in the lesions, normal lungs and livers, Entropy and sum entropy from GLCM, busyness from NGTDM and run-length non-uniformity from GLRLM were the most robust features, with a BP of 5% at the count level of 1×106 (equivalent to an effective dose of 0.04 mSv) RF including cluster shade from GLCM, long-run low grey-level emphasis, high grey-level run emphasis and short-run low grey-level emphasis from GLRM exhibited the worst performance with 50% of bias with 20×106 counts (equivalent to an effective dose of 0.8 mSv). CONCLUSIONS: In terms of the lesions included in this study, SUVmean, entropy and sum entropy from GLCM, busyness from NGTDM and run-length non-uniformity from GLRLM were the least sensitive features to lowering count.

Supervised learning with cyclegan for low-dose FDG PET image denoising.

PET imaging involves radiotracer injections, raising concerns about the risk of radiation exposure. To minimize the potential risk, one way is to reduce the injected tracer. However, this will lead to poor image quality with conventional image reconstruction and processing. In this paper, we proposed a supervised deep learning model, CycleWGANs, to boost low-dose PET image quality. Validations were performed on a low dose dataset simulated from a real dataset with biopsy-proven primary lung cancer or suspicious radiological abnormalities. Low dose PET images were reconstructed on reduced PET raw data by randomly discarding events in the PET list mode data towards the count level of 1 million. Traditional image denoising methods (Non-Local Mean (NLM) and block-matching 3D(BM3D)) and two recently-published deep learning methods (RED-CNN and 3D-cGAN) were included for comparisons. At the count level of 1 million (true counts), the proposed model can accurately estimate full-dose PET image from low-dose input image, which is superior to the other four methods in terms of the mean and maximum standardized uptake value (SUVmean and SUVmax) bias for lesions and normal tissues. The bias of SUV (SUVmean, SUVmax) for lesions and normal tissues are (-2.06±3.50%,-0.84±6.94%) and (-0.45±5.59%, N/A) in the estimated PET images, respectively. However, the RED-CNN achieved the best score in traditional metrics, such as structure similarity (SSIM), peak signal to noise ratio (PSNR) and normalized root mean square error (NRMSE). Correlation and profile analyses have successfully explained this phenomenon and further suggested that our method could effectively preserve edge and also SUV values than RED-CNN, 3D-cGAN and NLM with a slightly higher noise.

Palliative radiotherapy in symptomatic locally advanced gastric cancer: A phase II trial.

To evaluate the response and quality of life of palliative gastric radiotherapy in patients with symptomatic locally advanced gastric cancer. Patients with bleeding, pain or obstruction and were treated with palliative gastric radiotherapy to a dose of 36 Gy in 12 daily fractions. The primary outcomes were symptom response rates. Secondary outcomes included overall survival, adverse events and proportion of patients with ≥10-point absolute improvement in the fatigue, nausea/vomiting and pain subscales in the EORTC Qualify of Life Questionnaire C30 (EORTC QLQ-C30) and dysphagia/pain subscales in the gastric specific module (STO22) at the end of RT and 1 month after the completion of radiotherapy. Fifty patients were accrued. Median survival duration was 85 days. 40/50 patients (80%) with bleeding, 2/2 (100%) patients with obstruction and 1/1 (100%) patient with pain responded to radiotherapy. Improvements fatigue, nausea/vomiting and pain subscales of the EORTC QLQ-C30 was seen in 50%, 28% and 44% of patients at the end of RT and in 63%, 31% and 50% of patients 1 month after RT. Improvements in dysphagia/pain subscales of the STO22 was seen in 42% and 28% of patients at then end of RT and 44% and 19% of patients 1 month after RT. Two patients (5%) had grade 3 anorexia and gastritis. Palliative gastric radiotherapy was effective, well tolerated and resulted in improvement in fatigue, dysphagia and pain at the end of radiotherapy and 1 month after the completion of radiotherapy in a significant proportion of patients.

Induction chemotherapy for locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiation: A systematic review and meta-analysis.

PURPOSE: To determine if the addition of induction chemotherapy (IC) to concurrent chemoradiation (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC) can improve survival. METHODS: We performed a meta-analysis of both randomized controlled trials (RCTs) and observational studies (OBS) to compare the effects of addition of IC to CCRT versus (vs) CCRT alone on overall survival (OS), progression free survival (PFS), distant metastasis-free survival (DMFS) and adverse events (AE) in LA-NPC. We searched MEDLINE for eligible studies comparing IC plus CCRT vs CCRT for LA-NPC from Jan 1996 to May 2017. We selected RCTs and OBS that included patients with non-metastatic, LA-NPC who received IC followed by CCRT or CCRT alone. Three reviewers independently assessed the abstracts for eligibility. We assessed the methodological quality of the included studies using the MERGE criteria. We performed the meta-analysis with random effects model. We used the GRADE approach to appraise the quality of evidence from RCTs. The primary outcome was OS; secondary outcomes included PFS, DMFS and AE. RESULTS: We found six RCTs and five OBS including 2802 patients with low to moderate risk of bias in their methodological quality. There was high quality evidence from the RCTs that IC improved PFS (HR 0.69, 95% CI 0.57-0.84, P = 0.0003, I2 = 0%) and OS (HR 0.77, 95% CI 0.60-0.98, P = 0.03, I2 = 0%) significantly and was associated with more frequent AE. The estimates of IC effects from RCTs and OBS were similar (PFS HR 0.69 vs 0.71, interaction P (IP) = 0.92; OS HR 0.77 vs 0.58, IP = 0.27). CONCLUSIONS: IC delays disease progression and improves survival significantly for LA-NPC treated with CCRT, and was associated with more toxicity. There were no divergent results between RCTs and OBS. IC followed by CCRT can be considered one of the standard treatment options for LA-NPC.

Impact of Image Reconstruction Settings on Texture Features in 18F-FDG PET.

UNLABELLED: Evaluation of tumor heterogeneity based on texture parameters has recently attracted much interest in the PET imaging community. However, the impact of reconstruction settings on texture parameters is unclear, especially relating to time-of-flight and point-spread function modeling. Their effects on 55 texture features (TFs) and 6 features based on first-order statistics (FOS) were investigated. Standardized uptake value (SUV) measures were also evaluated as peak SUV (SUVpeak), maximum SUV, and mean SUV (SUVmean). METHODS: This study retrospectively recruited 20 patients with lesions in the lung who underwent whole-body (18)F-FDG PET/CT. The coefficient of variation (COV) of each feature across different reconstructions was calculated. RESULTS: SUVpeak, SUVmean, 18 TFs, and 1 FOS were the most robust (COV ≤ 5%) whereas skewness, cluster shade, and zone percentage were the least robust (COV > 20%) with respect to reconstruction algorithms using default settings. Heterogeneity parameters had different sensitivities to iteration number. Twenty-four parameters including SUVpeak and SUVmean exhibited variation with a COV less than 5%; 28 parameters, including maximum SUV, showed variation with a COV in the range of 5%-10%. In addition, skewness, cluster shade, and zone percentage were the most sensitive to iteration number. In terms of sensitivity to full width at half maximum (FWHM), 15 TFs and 1 FOS had the best performance with a COV less than 5%, whereas SUVpeak and SUVmean had a COV between 5% and 10%. Grid size had the largest impact on image features, which was demonstrated by only 11 features, including SUVpeak and SUVmean, having a COV less than 10%. CONCLUSION: Different image features have different sensitivities to reconstruction settings. Iteration number and FWHM of the gaussian filter have a similar impact on the image features. Grid size has a larger impact on the features than iteration number and FWHM. The features that exhibited large variations such as skewness in FOS, cluster shade, and zone percentage should be used with caution. The entropy in FOS, difference entropy, inverse difference normalized, inverse difference moment normalized, low gray-level run emphasis, high gray-level run emphasis, and low gray-level zone emphasis are the most robust features.

Addition of intracavitary brachytherapy to external beam radiation therapy for T1-T2 nasopharyngeal carcinoma.

PURPOSE: We compared efficacy and toxicity outcomes of patients with T1-T2 nasopharyngeal carcinoma (NPC) treated with external beam radiation therapy (EBRT) in combination with intracavitary brachytherapy (BT) vs. a historical cohort treated with EBRT alone. METHODS AND MATERIALS: Of the 348 NPC patients diagnosed with T1-2N0-3M0 disease, 175 received EBRT + BT and 173 received EBRT alone. For the EBRT + BT group, median dose of EBRT was 58 Gy and median dose of BT was 20 Gy; for the EBRT group, median dose was 72 Gy (range, 60-82.4 Gy). Measured outcomes included 5- and 10-year local control (LC), regional failure-free survival, distant metastasis-free survival, disease-free survival, overall survival (OS), and late toxicity. RESULTS: Median followup duration was 120 months (range, 5-190). Ten-year OS and LC rates for the EBRT + BT and EBRT-alone groups were 71.7% vs. 49.9% and 94.0% vs. 85.2%, respectively (χ(2) = 21.273, p = 0.000 for OS and χ(2) = 4.684, p = 0.030 for LC). Late complication rates for EBRT + BT were generally lower compared with the EBRT-alone group except for nasopharyngeal ulceration or necrosis, where the rate was higher but not statistically significant. Both stage of disease at diagnosis and treatment techniques (i.e., the use of BT) were significant predictive factors for OS and LC. CONCLUSION: Intracavitary BT in combination with EBRT may improve the therapeutic ratio for T1-T2 NPC.

Combined high-dose radiation therapy and systemic chemotherapy improves survival in patients with newly diagnosed metastatic nasopharyngeal cancer.

OBJECTIVES: To investigate the efficacy of high-dose radiation therapy (RT) to the primary and regional disease in combination with systemic chemotherapy and local treatment to metastatic foci in patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC). METHODS: One hundred and five consecutive patients with pathologically confirmed NPC with distant metastasis at diagnosis seen between 1995 and 2002 were reviewed. All were offered cisplatin-based chemotherapy, high-dose RT (>30 Gy) to the head and neck region, and active treatment to the metastatic foci. RESULTS: Patients' median age was 46 years, and all had a Karnofsky Performance Score of ≥70. Eighty-nine patients (85%) had metastases confined to 1 organ. Ninety-six patients (91%) received at least 1 cycle of chemotherapy and 71 (68%) received greater than 65 Gy of radiation to the head and neck region. With a median follow-up time of 22 months (range: 2 to 142 mo), 90 patients had deceased, and the median survival time of the entire group was 25 months. The 2 and 5-year estimated overall survival rates were 50% and 17%, respectively. Radiation dose of greater than 65 Gy to the primary region (P = 0.05) and number of organs with metastases (single vs. multiple) (P = 0.002) were independent predictive factors for overall survival on log-rank tests. Only moderately severe acute toxicities, such as Radiation Therapy Oncology Group grade 3 mucositis, skin desquamation, and leukocytopenia were observed. No patient experienced grade 4 acute toxicities. CONCLUSIONS: High-dose RT is indicated for local disease control in patients with metastatic NPC, and may improve survival when actively used with systemic chemotherapy and local treatment for metastatic foci. Patients with single-organ metastases have a better prognosis as compared with those with more widespread metastases.

Intensity-modulated radiation therapy in the salvage of locally recurrent nasopharyngeal carcinoma.

PURPOSE: Local recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC. METHODS AND MATERIALS: Between August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percent of the tumors were classified asrT3-4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy. RESULTS: The median dose to the recurrent tumor was 70 Gy (range, 50-77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors. CONCLUSION: Reirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.

Preoperative concomitant boost intensity-modulated radiotherapy with oral capecitabine in locally advanced mid-low rectal cancer: a phase II trial.

PURPOSE: We aimed to assess the safety and efficacy of preoperative intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced mid-low rectal cancer using a concomitant boost technique. MATERIALS AND METHODS: Patients with resectable locally advanced mid-low rectal cancer (node-negative ≥T3 or any node-positive tumor) were eligible. The eligible patients received IMRT to 2 dose levels simultaneously (50.6 and 41.8 Gy in 22 fractions) with concurrent capecitabine 825 mg/m(2) twice daily 5 days/week. The primary end point included toxicity, postoperative complication, and pathological complete response rate (ypCR). The secondary endpoints included local recurrence rate, progression-free survival (PFS), and overall survival (OS). RESULTS: Sixty-three eligible patients were enrolled; five patients did not undergo surgery. Of the 58 patients evaluable for pathologic response, the ypCR rate was 31.0% (95% CI 19.1-42.9). Grade 3 toxicities included diarrhea (9.5%), radiation dermatitis (3.2%), and neutropenia (1.6%). There was no Grade 4 toxicity reported. Four (6.9%) patients developed postoperative complications. Two-year local recurrence rate, PFS, and OS were 5.7%, 90.5%, and 96.0%, respectively. CONCLUSIONS: The design of preoperative concurrent boost IMRT with oral capecitabine could achieve high rate of ypCR with an acceptable toxicity profile.