Correlation of Ktrans derived from dynamic contrast-enhanced MRI with treatment response and survival in locally advanced NSCLC patients undergoing induction immunochemotherapy and concurrent chemoradiotherapy.

PURPOSE: This study aimed to investigate the prognostic significance of pretreatment dynamic contrast-enhanced (DCE)-MRI parameters concerning tumor response following induction immunochemotherapy and survival outcomes in patients with locally advanced non-small cell lung cancer (NSCLC) who underwent immunotherapy-based multimodal treatments. MATERIAL AND METHODS: Unresectable stage III NSCLC patients treated by induction immunochemotherapy, concurrent chemoradiotherapy (CCRT) with or without consolidative immunotherapy from two prospective clinical trials were screened. Using the two-compartment Extend Tofts model, the parameters including Ktrans, Kep, Ve, and Vp were calculated from DCE-MRI data. The apparent diffusion coefficient was calculated from diffusion-weighted-MRI data. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to assess the predictive performance of MRI parameters. The Cox regression model was used for univariate and multivariate analysis. RESULTS: 111 unresectable stage III NSCLC patients were enrolled. Patients received two cycles of induction immunochemotherapy and CCRT, with or without consolidative immunotherapy. With the median follow-up of 22.3 months, the median progression-free survival (PFS) and overall survival (OS) were 16.3 and 23.8 months. The multivariate analysis suggested that Eastern Cooperative Oncology Group score, TNM stage and the response to induction immunochemotherapy were significantly related to both PFS and OS. After induction immunochemotherapy, 67 patients (59.8%) achieved complete response or partial response and 44 patients (40.2%) had stable disease or progressive disease. The Ktrans of primary lung tumor before induction immunochemotherapy yielded the best performance in predicting the treatment response, with an AUC of 0.800. Patients were categorized into two groups: high-Ktrans group (n=67, Ktrans＞164.3×10-3/min) and low-Ktrans group (n=44, Ktrans≤164.3×10-3/min) based on the ROC analysis. The high-Ktrans group had a significantly higher objective response rate than the low-Ktrans group (85.1% (57/67) vs 22.7% (10/44), p<0.001). The high-Ktrans group also presented better PFS (median: 21.1 vs 11.3 months, p=0.002) and OS (median: 34.3 vs 15.6 months, p=0.035) than the low-Ktrans group. CONCLUSIONS: Pretreatment Ktrans value emerged as a significant predictor of the early response to induction immunochemotherapy and survival outcomes in unresectable stage III NSCLC patients who underwent immunotherapy-based multimodal treatments. Elevated Ktrans values correlated positively with enhanced treatment response, leading to extended PFS and OS durations.

CT radiomics-based long-term survival prediction for locally advanced non-small cell lung cancer patients treated with concurrent chemoradiotherapy using features from tumor and tumor organismal environment.

BACKGROUND: Definitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LANSCLC) patients, but the treatment response and survival outcomes varied among these patients. We aimed to identify pretreatment computed tomography-based radiomics features extracted from tumor and tumor organismal environment (TOE) for long-term survival prediction in these patients treated with CCRT. METHODS: A total of 298 eligible patients were randomly assigned into the training cohort and validation cohort with a ratio 2:1. An integrated feature selection and model training approach using support vector machine combined with genetic algorithm was performed to predict 3-year overall survival (OS). Patients were stratified into the high-risk and low-risk group based on the predicted survival status. Pulmonary function test and blood gas analysis indicators were associated with radiomic features. Dynamic changes of peripheral blood lymphocytes counts before and after CCRT had been documented. RESULTS: Nine features including 5 tumor-related features and 4 pulmonary features were selected in the predictive model. The areas under the receiver operating characteristic curve for the training and validation cohort were 0.965 and 0.869, and were reduced by 0.179 and 0.223 when all pulmonary features were excluded. Based on radiomics-derived stratification, the low-risk group yielded better 3-year OS (68.4% vs. 3.3%, p < 0.001) than the high-risk group. Patients in the low-risk group had better baseline FEV1/FVC% (96.3% vs. 85.9%, p = 0.046), less Grade ≥ 3 lymphopenia during CCRT (63.2% vs. 83.3%, p = 0.031), better recovery of lymphopenia from CCRT (71.4% vs. 27.8%, p < 0.001), lower incidence of Grade ≥ 2 radiation-induced pneumonitis (31.6% vs. 53.3%, p = 0.040), superior tumor remission (84.2% vs. 66.7%, p = 0.003). CONCLUSION: Pretreatment radiomics features from tumor and TOE could boost the long-term survival forecast accuracy in LANSCLC patients, and the predictive results could be utilized as an effective indicator for survival risk stratification. Low-risk patients might benefit more from radical CCRT and further adjuvant immunotherapy. TRIAL REGISTRATION: retrospectively registered.

Comparison and quantification of different concurrent chemotherapy regimens with radiotherapy in locally advanced non-small cell lung cancer: Clinical outcomes and theoretical results from an extended LQ and TCP model.

PURPOSE: To develop a new radiobiological model and compare the efficacy of four concurrent chemotherapy regimens administered with radiotherapy in locally advanced non-small-cell lung cancer (LANSCLC) by in-field locoregional progression-free survival (LPFS). MATERIALS AND METHODS: 151 LANSCLC patients were reviewed and divided into 5 groups according to their concurrent chemotherapy regimens, including 24 patients treated with radiotherapy alone, 30 treated with concurrent 4-week etoposide-cisplatin (EP), 26 with 3-week pemetrexed-cisplatin (AP), 37 with weekly paclitaxel-cisplatin (TP) and 34 with weekly docetaxel-cisplatin (DP). In-field LPFS and toxicities were compared among groups. A novel tumor control probability (TCP) model, LQRGC, incorporating four "R"s of radiobiology, Gompertzian tumor growth and chemotherapeutic effect, was related to in-field LPFS. Chemo-induced biologically effective doses (BEDs) in LQRGC/TCP model were used to quantify the concurrent chemotherapeutic efficacy. RESULTS: The median follow-up time was 54.5 months. The weekly DP and 4-week EP groups had favorable median in-field LPFS (EP:46.2 months, AP:30.3 months, TP:12.2 months, DP: not reached, radiotherapy alone: 12.2 months, p = 0.001). The 4-week EP group had a higher incidence of ≥grade 3 leukopenia (EP:76.7%, AP:15.4%, TP:24.3%, DP:14.7%, radiotherapy alone: 12.5%, p < 0.001) than the other four. The LQRGC/TCP model fitted well with the in-field LPFS with the average absolute and relative fitting errors of 6.36% and 12.12%. The chemo-induced BEDs of EP, AP, TP and DP were 5.17, 0.63, 1.89 and 2.52 Gy, respectively. CONCLUSION: The LQRGC/TCP model achieved promising fitting accuracy for in-field LPFS. As quantified by the model, the 4-week EP and weekly DP showed higher chemo-induced BEDs when concurrently administered with radiotherapy in LANSCLC.

Quantifying the Interfractional motion of Esophagus Using Daily Cone Beam Computed Tomography with Oral Contrast During Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer.

PURPOSE: To quantify the interfractional motion of the esophagus during fractionated radiation therapy for locally advanced non-small cell lung cancer. METHODS AND MATERIALS: We registered simulation 4-dimensional computed tomography (CT) and daily cone beam CT (CBCT) and documented the motion of the esophagus centroid at 5-mm interval slices in right-left (RL) and anterior-posterior (AP) directions. Oral barium sulfate was administrated during CBCT to help localize the esophagus. Thirty-five patients were enrolled. Thirty-five 4-dimensional CT scans, 595 CBCT scans, and 25,970 slices were analyzed. The slice-derived motion values for all patients were presented as 2.5 to 97.5 percentiles and ranges stratified by segments. The magnitude of motion for each individual patient was defined as the standard deviation (SD) of daily motion values stratified by segments. Correlations between the magnitude of motion and clinical variables were explored. RESULTS: The 2.5 to 97.5 percentiles of RL and AP motion were -4.2 to 7.1 and -4.4 to 5.1; -10.3 to 6.0 and -4.3 to 3.8; -8.7 to 5.5 and -6.4 to 2.8; and -9.1 to 4.7 and -5.8 to 3.3 mm for cervical, proximal, middle, and distal thoracic esophagus, respectively. The interfractional motion was direction- and location-dependent. The magnitude of RL motion was greater than that of AP motion for the 4 segments (P < .05). In the RL direction, the magnitude of motion was greater for the middle thoracic esophagus than for the cervical (median SD 2.7 vs 2.0 mm, P = .001) and proximal thoracic esophagus (median SD 2.7 vs 2.1 mm, P = .002). Patients with right lung tumor and bulky lymph nodes tended to display greater RL esophageal motion. CONCLUSIONS: The interfractional motion of the esophagus can be considerable during radiation therapy in locally advanced non-small cell lung cancer, especially for middle thoracic esophagus in RL direction. Strategies to minimize the effect of interfractional esophageal motion on dosimetry should be considered.