CBCT-to-CT Translation Using Registration-Based Generative Adversarial Networks in Patients with Head and Neck Cancer.

Recently, deep learning with generative adversarial networks (GANs) has been applied in multi-domain image-to-image translation. This study aims to improve the image quality of cone-beam computed tomography (CBCT) by generating synthetic CT (sCT) that maintains the patient's anatomy as in CBCT, while having the image quality of CT. As CBCT and CT are acquired at different time points, it is challenging to obtain paired images with aligned anatomy for supervised training. To address this limitation, the study incorporated a registration network (RegNet) into GAN during training. RegNet can dynamically estimate the correct labels, allowing supervised learning with noisy labels. The study developed and evaluated the approach using imaging data from 146 patients with head and neck cancer. The results showed that GAN trained with RegNet performed better than those trained without RegNet. Specifically, in the UNIT model trained with RegNet, the mean absolute error (MAE) was reduced from 40.46 to 37.21, the root mean-square error (RMSE) was reduced from 119.45 to 108.86, the peak signal-to-noise ratio (PSNR) was increased from 28.67 to 29.55, and the structural similarity index (SSIM) was increased from 0.8630 to 0.8791. The sCT generated from the model had fewer artifacts and retained the anatomical information as in CBCT.

A Meta-Analysis of Trials of Partial Breast Irradiation.

PURPOSE: Partial breast irradiation (PBI) is the delivery of radiation therapy (RT) limited to the tumor bed after breast conserving surgery. The results of recent trials of PBI compared with whole breast irradiation (WBI) have suggested conflicting results with respect to local control and toxicity. The purpose of this meta-analysis was to assess effectiveness of PBI and to compare the different techniques. METHODS AND MATERIALS: A meta-analysis of aggregate data from published randomized trials was performed to examine the effectiveness of PBI compared with WBI in patients with invasive breast cancer and ductal carcinoma in situ. Relevant data were extracted. The primary outcome was any ipsilateral breast event (invasive or noninvasive). Secondary outcomes included acute and late toxicity. The results of randomized trials were pooled using a fixed effects model and the inverse variance method. RESULTS: Fifteen trials involving 16,474 patients were identified. The majority of enrolled patients were >60 years of age and had T1N0 grade 1 to 2 disease treated with hormone therapy. The percent of ipsilateral breast events was higher in patients treated with PBI compared with WBI (5.0% vs 2.8%; risk ratio [RR], 1.72; 95% confidence interval [CI], 1.47-2.02). Heterogeneity (P = .0002) was observed between the 4 PBI techniques: external beam RT without computed tomography (CT) planning (RR, 2.06; 95% CI, 1.36-3.12); brachytherapy (RR, 1.21; 95% CI, 0.65-2.25); intraoperative RT (RR, 2.79; 95% CI, 2.08-3.73); and external beam RT with CT planning (RR, 1.25; 95% CI, 0.99-1.58). When external beam RT without CT planning and intraoperative RT trials were excluded, the percent of ipsilateral breast events was 3.3% versus 2.6%, respectively (RR, 1.25; 95% CI, 1.00-1.55; P = .05), and no heterogeneity was observed (P = .92). Overall, acute toxicity was less with PBI, and the effect on late toxicity varied by technique. CONCLUSIONS: Overall, WBI was more effective than PBI, but the effectiveness of PBI was technique related. PBI was less effective when given by external beam RT without CT planning or intraoperative therapy. Although PBI given by multicatheter brachytherapy or external beam RT with CT planning tended to be statistically less effective than WBI, the absolute difference between groups for ipsilateral breast events was very small (<1%), supporting these approaches for women considering PBI.

Evaluation and external validation of minor lymphatic pelvic pathway for distant metastases in cervical cancer patients treated with concurrent chemoradiotherapy.

To evaluate and validate the minor lymphatic pathway for distant metastases in cervical cancer. This is a retrospective cohort of cervical cancer patients underwent curative concurrent chemoradiotherapy. We used original dataset from 1 university hospital and validation dataset from 3 university hospitals. Lymphadenopathy status in CT imaging was reviewed by radiologist in either the obturator and external iliac nodes (major pathway) or the internal iliac and presacral nodes (minor pathway). We then used Cox regression to adjust for all potential confounders, including paraaortic nodes, T stage, histology, age, total treatment time, total number of nodes, total short axis of nodes. 397 and 384 patients were in the original and validation datasets (median follow-up period, 59.5 month's). The minor pathway was independent prognostic factor in multivariable analysis [HR=2.64; 95%CI=1.07-6.55; P = 0.036] and [HR=14.84; 95%CI=3.15-70.01; P= 0.001] in original and validation datasets, respectively. Whereas, the major pathway was statistically non-significant. Further validation showed that the minor pathway had the highest HR for distant metastases with both the EMBRACE (HR=6.05; 95% CI=1.30-28.08; P = 0.022) and the FIGO 2018 (HR=7.43; 95% CI=2.94-18.78; P<0.001) in the original dataset. A similar result was found with the validation dataset: EMBRACE, HR=30.91; 95% CI=2.78-343.62; P = 0.005; and FIGO 2018, HR=42.41; 95% CI=8.83-203.60; P<0.001.This is the first clinical study to validate that the minor lymphatic pathway was predominantly associated with distant metastases in cervical cancer. This finding should be validated in larger cohort to further integrate in standard staging for prediction of distant metastases.

Development and validation of a prognostic prediction model including the minor lymphatic pathway for distant metastases in cervical cancer patients.

To develop and validate a prognostic model, including the minor lymphatic pathway (internal iliac and presacral nodes). STUDY DESIGN: Retrospective cohort. PARTICIPANTS: Locally advanced cervical cancer underwent concurrent chemoradiotherapy. SAMPLE SIZE: 397 and 384 patients in the development and validation data set. PREDICTORS: Our new nodal staging system with the minor lymphatic pathway. OUTCOME: Distant metastases. STATISTICAL ANALYSIS: Cox regression; net reclassification improvement (NRI) and decision curve analysis (DCA). Our new nodal system was the strongest predictor. The predictors in the final model were new nodal system, tumor stage, adenocarcinoma, initial hemoglobin, tumor size and age. The nodal system and the pretreatment model had concordance indices of 0.661 and 0.708, respectively, with good calibration curves. Compared to the OUTBACK eligibility criteria, the nodal system showed NRI for both cases (22%) and controls (16%). The pretreatment model showed NRI for cases (31%) and controls (18%). DCA in both models showed threshold probability of 15% and 12%, respectively, when compared with 24% in OUTBACK eligibility criteria. Our new nodal staging system and the pretreatment model could differentiate between high-risk and low-risk patients, thus facilitating decisions to provide more aggressive treatment to prevent distant metastases.

Exploratory study of seed spots analysis to characterize dose and linear-energy-transfer effect in adverse event initialization of pencil-beam-scanning proton therapy.

BACKGROUND: Both dose and linear energy transfer (LET) could play a substantial role in adverse event (AE) initialization of cancer patients treated with pencil-beam-scanning (PBS) proton therapy. However, not all the voxels within the AE regions are directly induced from the dose and LET effect. It is important to study the synergistic effect of dose and LET in AE initialization by only including a subset of voxels that are dosimetrically important. PURPOSE: To perform exploratory investigation of the dose and LET effects upon AE initialization in PBS using seed spots analysis. METHODS: A total of 113 head-and-neck (H&N) cancer patients receiving curative PBS were included. Among them, 20 patients experienced unanticipated CTCAEv4.0 grade ≥3 AEs (AE group) and 93 patients did not (control group). Within the AE group, 13 AE patients were included in the seed spot analysis to derive the descriptive features of AE initialization and the remaining 7 mandible osteoradionecrosis patients and 93 control patients were used to derive the feature-based volume constraint of mandible osteoradionecrosis. The AE regions were contoured and the corresponding dose-LET volume histograms of AE regions were generated for all patients in the AE group. We selected high LET voxels (the highest 5% of each dose bin) with a range of moderate-to-high dose (≥∼40-Gy relative biological effectiveness) as critical voxels. Critical voxels that were contiguous with each other were grouped into clusters. Each cluster was considered a potential independent seed spot for AE initialization. Seed spots were displayed in a 2D dose-LET plane based on their mean dose and LET to derive the descriptive features of AE initialization. A volume constraint of mandible osteoradionecrosis was then established based on the extracted features using a receiver operating characteristic curve. RESULTS: The product of dose and LET (xBD) was found to be a descriptive feature of seed spots leading to AE initialization in this preliminary study. The derived xBD volume constraint for mandible osteoradionecrosis showed good performance with an area under curve of 0.87 (sensitivity of 0.714 and specificity of 0.807 in the leave-one-out cross-validation) for the very limited patient data included in this study. CONCLUSION: Our exploratory study showed that both dose and LET were observed to be important in AE initializations. The derived xBD volume constraint could predict mandible osteoradionecrosis reasonably well in the very limited H&N cancer patient data treated with PBS included in this study.

Oncologic Outcomes for Head and Neck Skin Malignancies Treated with Protons.

PURPOSE: Radiation therapy (RT) is the standard treatment for patients with inoperable skin malignancies of the head and neck region (H&N), and as adjuvant treatment post surgery in patients at high risk for local or regional recurrence. This study reports clinical outcomes of intensity-modulated proton therapy (IMPT) for these malignancies. MATERIALS AND METHODS: We retrospectively reviewed cases involving 47 patients with H&N malignancies of the skin (squamous cell, basal cell, melanoma, Merkel cell, angiosarcoma, other) who underwent IMPT for curative intent between July 2016 and July 2019. Overall survival was estimated via Kaplan-Meier analysis, and oncologic outcomes were reported as cumulative incidence with death as a competing risk. RESULTS: The 2-year estimated local recurrence rate, regional recurrence rate, local regional recurrence rate, distant metastasis rate, and overall survival were 11.1% (95% confidence interval [CI], 4.1%-30.3%), 4.4% (95% CI, 1.1%-17.4%), 15.5% (95% CI, 7%-34.3%), 23.4% (95% CI, 5.8%-95.5%), and 87.2% (95% CI, 75.7%-100%), respectively. No patient was reported to have a grade 3 or higher adverse event during the last week of treatment or at the 3-month follow-up visit. CONCLUSION: IMPT is safe and effective in the treatment of skin malignancies of the H&N.

Diagnostic performance of F-18 fluciclovine PET/CT in post-radical prostatectomy prostate cancer patients with rising prostate-specific antigen level ≤0.5 ng/mL.

PURPOSE: The aim of the study was to assess the diagnostic performance of fluciclovine positron emission tomography (PET)/computerized tomography (CT) in post-radical prostatectomy prostate cancer patients with rising prostate-specific antigen (PSA) ≤0.5 ng/mL, and identify the associated predictive factors of positive studies. PATIENTS AND METHODS: From 30 June 2017 to 9 August 2019, patients with post-radical prostatectomy prostate cancer who underwent F-18 fluciclovine PET/CT and had PSA level within 2-week interval (PSAPET) ≤0.5 ng/mL were enrolled into this single-institution retrospective study. Data on tumor characteristics, including Gleason scores, extra-prostatic extension, seminal vesicle invasion, surgical margin and nodal metastasis, PSA after radical prostatectomy, previous hormonal therapy, PSA doubling time (PSADT), scanner type, PSAPET and site of recurrence were collected. Comparison of these factors between groups of positive and negative fluciclovine PET/CT was done by using Mann-Whitney U-test and Fisher's exact test. RESULTS: Of 94 eligible patients with post-radical prostatectomy prostate cancer, 10 patients had positive studies (10.6%). Detection rate at PSAPET 0.1, 0.2, 0.3, 0.4 and 0.5 ng/mL were 0% (0/11), 0% (0/15), 20% (6/30), 4% (1/25) and 23.1% (3/13), respectively. Upon multivariate analysis of clinical factors, only a PSADT <3 months (P = 0.023) was shown to have a statistically significant correlation with a positive study. CONCLUSION: In post-radical prostatectomy prostate cancer patients with rising PSA 0.1-0.5 ng/mL, the sensitivity of F-18 fluciclovine PET/CT for identifying tumor recurrence/metastases is poor with an overall detection rate of 10.6%. Larger prospective studies are required to validate these findings.

Validation of the Functional Assessment of Cancer Therapy with Cervical Cancer Subscale (FACT-CX) for Quality of Life in Thai Patients Prior to Chemoradiotherapy.

OBJECTIVE: Cervical cancer is the second most common cancer in Thailand. For cervical cancer, there is no cancer specific quality of life questionnaire. This study aims to develop and validate Thai FACT-CX. METHODS: The cross-sectional study included all women aged ≥18 years with stage IB2-IIIB who planned to undergo chemoradiotherapy. Those who did not understand Thai language, had other cancers (except for skin cancer), were diagnosed with impaired cognition and/or overt psychosis, and major depression were excluded. The FACT-CX comprises 42 items with 5 domains and a score range of 0-168. The WHOQOL-BREF comprises 26 items with 4 domains and a score range of 26-130. The participants were interviewed about demographic and clinical data. Both questionnaires were self-completed.  Factor analysis was used to compare our data with the previous structure. The reliability used Cronbach's alpha. Spearman's correlation determined relationship between the domains of the modified FACT-CX and WHOQOL-BREF. Both questionnaires were compared with socioeconomic and clinical variables using the Ranksum test and Kruskal-Wallis test. P-value > 0.05 considered significant. RESULTS: The 245 participants included. Expletory factor analysis revealed an accumulative variance of 0.42 with 4 factors. The internal consistency was 0.84, 0.81, 0.78, 0.77 and 0.90 for perception of self, suffering symptoms, family support, life resilience and total questions. There was correlation between the domains of the modified FACT-CX and WHOQOL-BREF.  Both the modified FACT-CX and WHOQOL-BREF could identify differences between the groups of patients. CONCLUSION: Finally, the Thai modified FACT-CX was found to be reliable and valid for measuring quality of life among untreated cervical cancer patients.
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