To develop and compare delta-radiomics signatures from 2- (2D) and 3-dimensional (3D) features that predict treatment outcomes following preoperative chemoradiotherapy (CCRT) and surgery for locally advanced rectal cancer. In total, 101 patients (training cohort, n = 67; validation cohort, n = 34) with locally advanced rectal adenocarcinoma between 2008 and 2015 were included. We extracted 55 features from T2-weighted magnetic resonance imaging (MRI) scans. Delta-radiomics feature was defined as the difference in radiomics feature before and after CCRT. Signatures were developed to predict local recurrence (LR), distant metastasis (DM), and disease-free survival (DFS) from 2D and 3D features. The least absolute shrinkage and selection operator regression was used to select features and build signatures. The delta-radiomics signatures and clinical factors were integrated into Cox regression analysis to determine if the signatures were independent prognostic factors. The radiomics signatures for LR, DM, and DFS were developed and validated using both 2D and 3D features. Outcomes were significantly different in the low- and high-risk patients dichotomized by optimal cutoff in both the training and validation cohorts. In multivariate analysis, the signatures were independent prognostic factors even when considering the clinical parameters. There were no significant differences in C-index from 2D vs. 3D signatures. This is the first study to develop delta-radiomics signatures for rectal cancer. The signatures successfully predicted the outcomes and were independent prognostic factors. External validation is warranted to ensure their performance.

There is ongoing debate regarding the significance of complete or near-complete response after neoadjuvant chemoradiotherapy (CRT) for rectal cancer. This study assessed the prognostic value of the Dworak tumor regression grade (TRG) following neoadjuvant CRT and surgery primarily in patients with pathological stage (ypStage) II and III rectal cancer. The records of 331 patients who underwent neoadjuvant CRT followed by total mesorectal excision between 2004 and 2015 were retrospectively reviewed. Patients were categorized as having a good response (GR, TRG 3/4, n = 122) or a poor response (PR, TRG 1/2, n = 209). At a median follow-up of 65 months, five-year disease-free survival (DFS) was higher in the GR group than in the PR group (91.3% vs. 66.6%, p < 0.001). Patients with a GR and ypStage II disease had a five-year DFS that was indistinguishable from that of patients with ypStage 0–I disease (92.3% vs. 90.7%, p = 0.885). Likewise, patients with a GR and ypStage III disease had a five-year DFS similar to those with ypStage II disease (76.0% vs. 75.9%, p = 0.789). A new modified staging system that incorporates grouped TRG (GR vs. PR) was developed. The prognostic performance of this modified stage and the ypStage was compared with the Harrell C statistic. C statistic of the modified stage was higher than that of the ypStage (0.784 vs. 0.757, p = 0.012). The results remained robust after multivariate Cox regression analyses. In conclusion, a GR to neoadjuvant CRT is an independent predictor of good DFS and overall survival and further stratifies patients so as to estimate the risk of recurrence and survival among patients with ypStage II and III rectal cancer.

Objective: To analyze the effect of intra- and interfractional motion during breast intensity modulated radiation therapy (IMRT) by calculating dose distribution based on four-dimensional computed tomography (4DCT). Methods: 20 patients diagnosed with left breast cancer were enrolled. Three-dimensional CT (3DCT) along with 10 phases of 4DCT were collected for each patient, with target volumes independently delineated on both 3DCT and all phases of 4DCT. IMRT plans were generated based on 3DCT (43.2 Gy in 16 fractions). The plan parameters for each segment were split into phases based on time duration estimates for each respiratory phase, with phase-specific dose distributions calculated and summated (4D-calculated dose). The procedure is repeated for 16 fractionations by randomly allocating starting phase using random-number generation to simulate interfractional discrepancy caused by different starting phase. Comparisons of plan quality between the original and 4D-calculated doses were analyzed. Results: There was a significant distortion in 4D-calculated dose induced by respiratory motion in terms of conformity and homogeneity index compared to those of the original 3D plan. Mean doses of the heart and the ipsilateral lung were significantly higher in the 4D-calculated doses compared to those of the original 3D plan (0.34 Gy, p = 0.010 and 0.59 Gy, p < 0.001), respectively). The mean internal mammary lymph node (IMN) dose was significantly greater in the 4D-calculated plan, compared to the original 3D plan (1.42 Gy, p < 0.001). Conclusions: IMN doses should be optimized during the dose-calculation for the free-breathing left breast IMRT. Advances in knowledge: The interplay effect between respiratory motion and multileaf collimator modulation caused discrepancies in dose distribution, particularly in IMN.