MRI radiomics for predicting intracranial progression in non-small-cell lung cancer patients with brain metastases treated with epidermal growth factor receptor tyrosine kinase inhibitors.

To identify clinical and magnetic resonance imaging (MRI) radiomics predictors specialised for intracranial progression (IP) after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in non-small-cell lung cancer (NSCLC) patients with brain metastases (BMs). Seventy EGFR-mutated NSCLC patients with a total of 212 BMs who received first-line EGFR-TKI therapy were enrolled. Radiomics features were extracted from the BM regions on the pretreatment contrast-enhanced T1-weighted images, and the radiomics score (rad-score) of each BM was established based on the selected features. Furthermore, the mean rad-score derived from the average rad-score of all included BMs in each patient was calculated. Univariate and multivariate logistic regression analyses were performed to identify potential predictors of IP. Prediction models based on different predictors and their combinations were constructed, and nomogram based on the optimal prediction model was evaluated. Thirty-three (47.1 %) patients developed IP, and the remaining 37 (52.9 %) patients were IP-free. EGFR-19del mutation (OR 0.19, 95 % CI 0.05-0.69), third-generation TKI treatment (OR 0.33, 95 % CI 0.16-0.67) and mean rad-score (OR 5.71, 95 % CI 1.65-19.68) were found to be independent predictive factors. Models based on these three predictors alone and in combination (combined model) achieved AUCs of 0.64, 0.64, 0.74, and 0.86 and 0.64, 0.64, 0.75, and 0.84 in the training and validation sets, respectively, and the combined model demonstrated optimal performance for predicting IP. The model integrating EGFR-19del mutation, third-generation TKI treatment and mean rad-score had good predictive value for IP after EGFR-TKI treatment in NSCLC patients with BM.

Qu J ，Zhang T ，Zhang X ，Zhang W ，Li Y ，Gong Q ，Yao L ，Lui S ... -  《-》

MRI radiomics predicts the efficacy of EGFR-TKI in EGFR-mutant non-small-cell lung cancer with brain metastasis.

To develop and validate models based on magnetic resonance imaging (MRI) radiomics for predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in EGFR-mutant non-small-cell lung cancer (NSCLC) patients with brain metastases. 117 EGFR-mutant NSCLC patients with brain metastases who received EGFR-TKI treatment were included in this study from January 1, 2014 to December 31, 2021. Patients were randomly divided into training and validation cohorts in a ratio of 2:1. Radiomics features extracted from brain MRI were screened by least absolute shrinkage and selection operator (LASSO) algorithm. Logistic regression analysis and Cox proportional hazard regression analysis were used to screen clinical risk factors. Clinical (C), radiomics (R), and combined (C + R) nomograms were constructed in models predicting short-term efficacy and intracranial progression-free survival (iPFS), respectively. Calibration curves, Harrell's concordance index (C-index), and decision curve analysis (DCA) were used to evaluate the performance of models. Overall response rate (ORR) was 57.3% and median iPFS was 12.67 months. The C + R nomograms were more effective. In the short-term efficacy model, the C-indexes of C + R nomograms in training cohort and validation cohort were 0.860 (0.820-0.901, 95%CI) and 0.843 (0.783-0.904, 95%CI). In iPFS model, the C-indexes of C + R nomograms in training cohort and validation cohort were 0.837 (0.751-0.923, 95%CI) and 0.850 (0.763-0.937, 95%CI). The C + R nomograms were more effective in predicting EGFR-TKI efficacy of EGFR-mutant NSCLC patients with brain metastases than single clinical or radiomics nomograms.

Qi H ，Hou Y ，Zheng Z ，Zheng M ，Sun X ，Xing L ... -  《-》

Multiphases DCE-MRI Radiomics Nomogram for Preoperative Prediction of Lymphovascular Invasion in Invasive Breast Cancer.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) radiomics had been used to evaluate lymphovascular invasion (LVI) in patients with breast cancer. However, no studies had explored the associations between features from delayed phase as well as multiphases DCE-MRI and the LVI status. Thus, we aimed to develop an efficient nomogram based on multiphases DCE-MRI to predict the LVI status in invasive (IBC) breast cancer patients. A retrospective analysis was conducted on preoperative clinical, pathological, and DCE-MRI data of 173 breast cancer patients. All patients were randomly assigned into training set (n=121) and validation set (n=52) in 7:3 ratio. The clinical, pathologic, and conventional MRI characteristics were then subjected to univariate and multivariate logistic regression analysis, and the clinical risk factors with P < 0.05 in the multivariate logistic regression were used to build clinical models. Different single-phase models (early phase, peak phase, and terminal phase), as well as a multiphases model integrating radiomics features from multiple phases, were established. Furthermore, a preoperative radiomics nomogram model was constructed by combining the rad-score of the multiphases model with clinicopathologic independent risk factors. Finally, the performance of the multiphases model, clinical model, and rad-score was compared using receiver operating characteristic (ROC) curves, area under the curve (AUC) values, and decision curve analysis (DCA). The clinical utility of the rad-score was evaluated using calibration curves, and Delong test was used to compare the differences in AUC values among the different models. The axillary lymph nodes (ALN) status and Ki-67 had been identified as clinicopathologic independent predictors and a clinical model had been constructed. Image features that were extracted from the terminal phase of the DCE-MRI exhibited notably superior predictive performances compared to features from the other single phases. Particularly, in the multiphases model, terminal phase features were identified as potentially providing more predictive information. Among the nine features that were found to be associated with LVI in the multiphase model, one was derived from the early phase, two from the peak phase, and six from the terminal phase, indicating that terminal phase features contributed significantly more information towards predicting LVI. Evaluation of the nomogram performance revealed promising results in both the training set (AUCs: clinical model vs. multiphase model vs. nomogram=0.734 vs. 0.840 vs. 0.876) and the validation set (AUCs: clinical model vs. multiphase model vs. nomogram=0.765 vs. 0.753 vs. 0.832). The DCE-MRI-based radiomics model demonstrated utility in predicting LVI status, features of the terminal phase offered more valuable information particularly. The preoperative radiomics nomogram enhanced the diagnostic capability of identifying LVI status in IBC patients, and might aid clinicians in making personalized treatment decisions.

Ma Q ，Lu X ，Chen Q ，Gong H ，Lei J ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

Favorable survival outcomes in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer sequentially treated with a tyrosine kinase inhibitor and osimertinib in a real-world setting.

EGFR tyrosine kinase inhibitor (TKI) therapy in EGFR-mutated lung cancer is limited by acquired resistance. In half of the patients treated with first/second-generation (1st/2nd gen) TKI, resistance is associated with EGFR p.T790M mutation. Sequential treatment with osimertinib is highly active in such patients. Currently, there is no approved targeted second-line option for patients receiving first-line osimertinib, which thus may not be the best choice for all patients. The present study aimed to evaluate the feasibility and efficacy of a sequential TKI treatment with 1st/2nd gen TKI, followed by osimertinib in a real-world setting. Patients with EGFR-mutated lung cancer treated at two major comprehensive cancer centers were retrospectively analyzed by the Kaplan-Meier method and log rank test. A cohort of 150 patients, of which 133 received first-line treatment with a first/second gen EGFR TKI, and 17 received first-line osimertinib, was included. Median age was 63.9 years, 55% had ECOG performance score of ≥ 1. First-line osimertinib was associated with prolonged progression-free survival (P = 0.038). Since the approval of osimertinib (February 2016), 91 patients were under treatment with a 1st/2nd gen TKI. Median overall survival (OS) of this cohort was 39.3 months. At data cutoff, 87% had progressed. Of those, 92% underwent new biomarker analyses, revealing EGFR p.T790M in 51%. Overall, 91% of progressing patients received second-line therapy, which was osimertinib in 46%. Median OS with sequenced osimertinib was 50 months. Median OS of patients with p.T790M-negative progression was 23.4 months. Real-world survival outcomes of patients with EGFR-mutated lung cancer may be superior with a sequenced TKI strategy. Predictors of p.T790M-associated resistance are needed to personalize first-line treatment decisions.

Kraskowski O ，Stratmann JA ，Wiesweg M ，Eberhardt W ，Metzenmacher M ，Schmid KW ，Herold T ，Schildhaus HU ，Darwiche K ，Aigner C ，Stuschke M ，Laue K ，Zaun G ，Kasper S ，Hense J ，Sebastian M ，Schuler M ，Pogorzelski M ... -  《-》