Radiomics and dosiomics for predicting radiation-induced hypothyroidism and guiding intensity-modulated radiotherapy.

To guide individualized intensity-modulated radiotherapy (IMRT), we developed and prospectively validated a multiview radiomics risk model for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma. And simulated radiotherapy plans with same dose-volume-histogram (DVH) but different dose distributions were redesigned to explore the clinical application of the multiview radiomics risk model. The radiomics and dosiomics were built based on selected radiomics and dosiomics features from planning computed tomography and dose distribution, respectively. The multiview radiomics risk model that integrated radiomics, dosiomics, DVH parameters, and clinical factors had better performance than traditional normal tissue complication probability models. And multiview radiomics risk model could identify differences of patient hypothyroidism-free survival that cannot be stratified by traditional models. Besides, two redesigned simulated plans further verified the clinical application and advantage of the multiview radiomics risk model. The multiview radiomics risk model was a promising method to predict radiation-induced hypothyroidism and guide individualized IMRT.

Immunochemotherapy alone or immunochemotherapy plus subsequent locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma.

BACKGROUND: To demonstrate whether the benefit of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma remains in the immunotherapy era and which patients can benefit from radiotherapy. MATERIALS AND METHODS: A total of 273 histopathology-confirmed de novo metastatic nasopharyngeal carcinoma was enrolled between May 2017 and October 2021 if receiving immunochemotherapy with or without subsequent intensity-modulated radiotherapy to the nasopharynx and neck. We compared the progression-free survival, overall survival, and safety between the two groups. Additionally, subgroup analysis was conducted and a scoring model was developed to identify suitable patients for radiation. RESULTS: There were 95 (34.8 %) patients with immunochemotherapy alone, and 178 (65.2 %) with immunochemotherapy plus subsequent locoregional radiotherapy. With a median follow-up time of 18 months, patients with immunochemotherapy plus subsequent radiotherapy had higher 1-year progression-free survival (80.6 % vs. 65.1 %, P < 0.001) and overall survival (98.3 % vs. 89.5 %, P = 0.001) than those with immunochemotherapy alone. The benefit was retained in multivariate analysis and propensity score-matched analysis. Mainly, it was more significant in patients with oligometastases, EBV DNA below 20,200 copies/mL, and complete or partial relapse after immunochemotherapy. The combined treatment added grade 3 or 4 anemia and radiotherapy-related toxicities. CONCLUSION: Immunochemotherapy plus subsequent locoregional radiotherapy prolonged the survival of de novo metastatic nasopharyngeal carcinoma with tolerable toxicities. A scoring model based on oligometastases, EBV DNA level, and response after immunochemotherapy could facilitate individualized management.

Deep learning-based precise prediction and early detection of radiation-induced temporal lobe injury for nasopharyngeal carcinoma.

Background: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. Methods: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3-5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. Findings: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P < 0.001). The temporal lobes in all the cohorts were stratified into three groups with discrepant TLI-free survival. Personalized follow-up schedules developed for each risk group could detect TLI 1.9 months earlier than the RTOG recommendation. According to a higher median predicted 3-year TLI-free survival (99.25% vs. 99.15%, P < 0.001), the model identified a better plan than previous models. Interpretation: The deep learning model predicted TLI more precisely. The model-determined risk-based follow-up schedule detected the TLI earlier. The planning evaluation was refined because the model identified a better plan with a lower risk of TLI. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), Medical Scientific Research Foundation of Guangdong Province (A2022367), and Guangzhou Science and Technology Program (2023A04J1788).

Benefit of [18F] FDG PET/CT in the diagnosis and salvage treatment of recurrent nasopharyngeal carcinoma.

PURPOSE: To compare PET/CT, MRI and ultrasonography in detecting recurrence of nasopharyngeal carcinoma and identify their benefit in staging, contouring and overall survival (OS). METHODS: Cohort A included 1453 patients with or without histopathology-confirmed local recurrence, while cohort B consisted of 316 patients with 606 histopathology-confirmed lymph nodes to compare the sensitivities and specificities of PET/CT, MRI and ultrasonography using McNemar test. Cohorts C and D consisted of 273 patients from cohort A and 267 patients from cohort B, respectively, to compare the distribution of PET/CT-based and MRI-based rT-stage and rN-stage and the accuracy of rN-stage using McNemar test. Cohort E included 30 random patients from cohort A to evaluate the changes in contouring with or without PET/CT by related-samples T test or Wilcoxon rank test. The OS of 61 rT3-4N0M0 patients staged by PET/CT plus MRI (cohort F) and 67 MRI-staged rT3-4N0M0 patients (cohort G) who underwent similar salvage treatment were compared by log-rank test and Cox regression. RESULTS: PET/CT had similar specificity to MRI but higher sensitivity (93.9% vs. 79.3%, P < 0.001) in detecting local recurrence. PET/CT, MRI and ultrasonography had comparable specificities, but PET/CT had greater sensitivity than MRI (90.9% vs. 67.6%, P < 0.001) and similar sensitivity to ultrasonography in diagnosing lymph nodes. According to PET/CT, more patients were staged rT3-4 (82.8% vs. 68.1%, P < 0.001) or rN + (89.9% vs. 69.3%, P < 0.001), and the rN-stage was more accurate (90.6% vs. 73.8%, P < 0.001). Accordingly, the contours of local recurrence were more precise (median Dice similarity coefficient 0.41 vs. 0.62, P < 0.001) when aided by PET/CT plus MRI. Patients staged by PET/CT plus MRI had a higher 3-year OS than patients staged by MRI alone (85.5% vs. 60.4%, P = 0.006; adjusted HR = 0.34, P = 0.005). CONCLUSION: PET/CT more accurately detected and staged recurrence of nasopharyngeal carcinoma and accordingly complemented MRI, providing benefit in contouring and OS.

Dosiomics Risk Model for Predicting Radiation Induced Temporal Lobe Injury and Guiding Individual Intensity-Modulated Radiation Therapy.

PURPOSE: We aimed to assess the value of dose distribution-based dosiomics and planning computed tomography-based radiomics to predict radiation-induced temporal lobe injury (TLI) and guide individualized intensity modulated radiation therapy. METHODS AND MATERIALS: A total of 5599 nasopharyngeal carcinoma patients were enrolled, including 2503, 1072, 988, and 1036 patients in the training, validation, prospective test, and external test cohorts, respectively. The concordance index (C-index) was used to compare the performance of the radiomics and dosiomics models with that of the quantitative analyses of normal tissue effects in the clinic and Wen's models. The predicted TLI-free survival rates of redesigned simulated plans with the same dose-volume histogram but different dose distributions for same patient in a cohort of 30 randomly selected patients were compared by the Wilcoxon matched-pairs signed-rank test. RESULTS: The radiomics and dosiomics signatures were constructed based on 30 selected computed tomography features and 10 selected dose distribution features, respectively, which were important predictors of TLI-free survival (all P <.001). However, the radiomics signature had a low C-index. The dosiomics risk model combining the dosiomics signature, D1cc, and age had favorable performance, with C-index values of 0.776, 0.811, 0.805, and 0.794 in the training, validation, prospective test, and external test cohorts, respectively, which were better than those of the quantitative analyses of normal tissue effects in the clinic model and Wen's model (all P <.001). The dosiomics risk model can further distinguish patients in a same risk category divided by other models (all P <.05). Conversely, the other models were unable to separate populations classified by the dosiomics risk model (all P > .05). Two simulated plans with the same dose-volume histogram but different dose distributions had different TLI-free survival rates predicted by dosiomics risk model (all P ≤ .002). CONCLUSIONS: The dosiomics risk model was superior to traditional models in predicting the risk of TLI. This is a promising approach to precisely predict radiation-induced toxicities and guide individualized intensity modulated radiation therapy.

Analysis of Treatment Outcomes and Prognosis After Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer.

The aims of this study were to investigate the short-term and long-term efficacies and chronic radiotoxicity of concurrent chemoradiotherapy (CCRT) combined with image-guided adaptive brachytherapy (IGABT) in patients with locally advanced cervical cancer (LACC) and identify prognostic factors in this patient population. The clinical data of 204 patients with cervical cancer who completed CCRT and subsequent brachytherapy in our hospital between February 2015 and March 2017 were retrospectively analyzed. Short-term and long-term outcomes, chronic radiotoxicity, and prognostic factors were assessed. The median follow-up was 61.1 months. The short-term objective response (OR) rate was 85%. Lymph node metastasis before treatment was an independent predictor of OR (HR = 6.290, 95% CI: 2.211-17.897, p = 0.001). Fifty-two patients developed recurrence, with a median recurrence-free survival of 9.9 months (range, 2.4-52.2 months) and a post-recurrence survival of 12.1 months (range, 2.9-58.1 months). At 3 years, the cumulative incidence of overall recurrence was 26% (95% CI: 17-36). Multivariate analysis showed that Stage IIIB (HR = 2.332, 95% CI: 1.195-4.551, p = 0.013; reference, Stage IIB) and lymph node metastasis (HR = 4.462, 95% CI: 2.365-8.419, p < 0.001) were significant independent predictors of recurrence. Fifty-three patients developed chronic radiation proctitis (CRP). The incidence of severe CRP was approximately 5%, and the average rectal D 2 c m 3 accumulation in patients with severe CRP was 73.4 Gy which is 3.9 Gy higher than that in patients without CRP (p = 0.013). At 4 years, the overall survival (OS) and disease-free survival rates were 65% and 62%, respectively, and lymph node metastasis before treatment was an independent prognostic risk factor for OS. The short-term and long-term efficacies of CCRT combined with IGABT for the treatment of LACC patients were relatively satisfactory. However, the short-term and long-term efficacies of patients with lymph node metastasis before treatment were poor. For patients with lymph node metastasis before treatment, more active individualized treatment strategies should be adopted. When designing a radiotherapy plan, it is necessary to strictly limit the rectal D 2 c m 3 accumulation to prevent serious CRP.

Prognostic value of serum bilirubin in southern Chinese patients with advanced nasopharyngeal carcinoma.

BACKGROUND: We evaluated the prognostic value of serum bilirubin in advanced nasopharyngeal carcinoma (NPC) patients. METHODS: Seven-hundred fifty-nine advanced NPC patients treated with definitive chemoradiotherapy were retrospectively analyzed. Serum indirect bilirubin (IBIL) and direct bilirubin (DBIL) were measured before treatment. To evaluate different cutoff points for serum bilirubin, we utilized ROC curves. The Kaplan-Meier method and log-rank test were adopted to calculate and compare survival outcomes. Cox proportional hazard models were used to perform univariate and multivariate analyses. RESULTS: At 5 y, IBIL >7.15 µmol/l were significantly associated with superior progression-free survival (PFS, 83.6% vs 70.3%; P < .001), overall survival (OS, 88.6% vs 80.5%; P = .012), distant metastasis-free survival (DMFS, 90.3% vs 82.8%; P = .006), and locoregional relapse-free survival (LRFS, 92.1% vs 86.4%; P = .048) than IBIL ≤7.15 µmol/l. Similarly, patients with DBIL >2.65 µmol/l had better prognosis across all outcomes than those of patients with DBIL ≤2.65 µmol/l (all P < .05), except no difference was observed in LRFS (90.5% vs. 87.3%, P = .195). Multivariate analyses showed that IBIL >7.15 µmol/l was an independent protective prognostic factor for PFS (HR, 0.57; 95% CI, 0.40-0.81; P = .002), OS (HR, 0.67; 95% CI, 0.43-0.92; P = .041), and DMFS (HR, 0.63; 95% CI, 0.40-0.98; P = .034); while serum DBIL only remained significant for PFS (HR, 0.63; 95% CI, 0.44-0.89; P = .009). CONCLUSIONS: Pretreatment IBIL and DBIL are potentially independent prognostic factors for patients with advanced NPC.

[Effect of Qibai Pingfei capsule medicated serum on protein expressions of KATP channel in pulmonary arterial smooth muscle cells via nitric oxide].

To investigate the ATP-sensitive potassium channel (KATP channel) protein expressions during different periods under hypoxia condition and explore the effect of Qibai Pingfei capsule medicated serum (hereinafter referred to as QBPF) on the correlation between the protein expressions of KATP channel and nitric oxide in rat pulmonary arterial smooth muscle cells(PASMCs). Qibai Pingfei capsules were given to SD rats via continuous gavage for 10 days to obtain QBPF. Primary rats PASMCs were cultured by the direct adherent culture method. Western blot was applied to detect the protein expression levels of KATP channel (Kir6.1 and SUR2B) in PASMCs. Then the noncompetitive inhibitor of NO synthase--Nω-nitro-L-arginine methyl ester(L-NAME) and KATP channel inhibitor--glyburide(GLYB) were applied respectively to evaluate the effect of QBPF on the protein expressions of KATP channel. The protein expressions of Kir6.1 and SUR2B were increased after 6-hour hypoxia treament, peaked at the 24-hour hypoxia treament, and decreased in both 48-hour and 72-hour hypoxia groups. Especially, QBPF could further up-regulate the Kir6.1 and SUR2B protein expressions under 24-hour hypoxia condition; however, such up-regulation effect could be blocked by KATP channel inhibitor GLYB and NO specific inhibitor L-NAME, indicating that QBPF played the role of opening KATP channel. The regulatory mechanism was probably associated with up-regulating KATP channel protein expression via NO relative pathway, involving pulmonary vasodilation, and thus relieving the occurence and development of COPD.

Research on frequency of application with modern Chinese herbal medicine.

OBJECTIVE: To study the relationship between 500 kinds of commonly used Chinese herbal medicine and the classification of their efficacies in Chinese Materia Medica in relation to the common diseases listed in Internal Medicine. METHODS: Database retrieval frequency of the quantitative statistical method was adopted. First, the 8 980 kinds of Chinese herbal medicine recorded in Chinese Materia Medica were used as the original search objects, and 4 493 kinds which were cited in more than five articles were picked out and then rechecked for further title citations. Second, as judged based on the Criterion, the numbers of articles which included the medicines in the line of standards were examined. As a result, 500 species of Chinese herbal medicine were singled out based on their retrieval frequency and were then used for compilation of the classification statistics according to their efficacy and the common diseases in Internal Medicine. RESULTS: From the classification of Chinese medicines, herbs with wide efficiency and a meek nature had higher frequencies, but those which were not appropriate as decoctions had relatively lower frequencies. However, according to the average frequency, the Chinese herbal medicine for nourishing qi and tonifying blood, at 36,346 times and 34,544 times, respectively, were the most commonly used. Analyzed from the frequency of application of the Chinese medicine in the treatment of common diseases, most of the top 10 kinds of Chinese herbal medicine with the highest frequencies generally coincided with the 500 selected medicines. In addition, the Chinese medicines with clear pharmacological efficiency were easily isolated and purified to be made into injections, although other forms are more commonly used. CONCLUSION: The results of the research objectively reflected the current applications of Chinese herbal medicine, and could be used as references in teaching, research, clinical applications, and in compiling and increasing the drugs in textbooks and Pharmacopoeia.