Prediction of Neoadjuvant Chemoradiotherapy Response in Rectal Cancer Patients Using Harmonized Radiomics of Multcenter 18F-FDG-PET Image.

We developed machine and deep learning models to predict chemoradiotherapy in rectal cancer using 18F-FDG PET images and harmonized image features extracted from 18F-FDG PET/CT images. Patients diagnosed with pathologic T-stage III rectal cancer with a tumor size > 2 cm were treated with neoadjuvant chemoradiotherapy. Patients with rectal cancer were divided into an internal dataset (n = 116) and an external dataset obtained from a separate institution (n = 40), which were used in the model. AUC was calculated to select image features associated with radiochemotherapy response. In the external test, the machine-learning signature extracted from 18F-FDG PET image features achieved the highest accuracy and AUC value of 0.875 and 0.896. The harmonized first-order radiomics model had a higher efficiency with accuracy and an AUC of 0.771 than the second-order model in the external test. The deep learning model using the balanced dataset showed an accuracy of 0.867 in the internal test but an accuracy of 0.557 in the external test. Deep-learning models using 18F-FDG PET images must be harmonized to demonstrate reproducibility with external data. Harmonized 18F-FDG PET image features as an element of machine learning could help predict chemoradiotherapy responses in external tests with reproducibility.

Gene Expression Profiles Associated with Radio-Responsiveness in Locally Advanced Rectal Cancer.

LARC patients were sorted according to their radio-responsiveness and patient-derived organoids were established from the respective cancer tissues. Expression profiles for each group were obtained using RNA-seq. Biological and bioinformatic analysis approaches were used in deciphering genes and pathways that participate in the radio-resistance of LARC. Thirty candidate genes encoding proteins involved in radio-responsiveness-related pathways, including the immune system, DNA repair and cell-cycle control, were identified. Interestingly, one of the candidate genes, cathepsin E (CTSE), exhibited differential methylation at the promoter region that was inversely correlated with the radio-resistance of patient-derived organoids, suggesting that methylation status could contribute to radio-responsiveness. On the basis of these results, we plan to pursue development of a gene chip for diagnosing the radio-responsiveness of LARC patients, with the hope that our efforts will ultimately improve the prognosis of LARC patients.

High dose stereotactic body radiotherapy using three fractions for colorectal oligometastases.

BACKGROUND AND OBJECTIVES: This study evaluated the treatment result of high dose stereotactic body radiation therapy (SBRT) for colorectal oligometastases. METHODS: Between 2003 and 2009, 41 patients with 50 lesions confined to one organ from colorectal cancer (CRC) and treated with high dose SBRT ≥45 Gy were retrospectively reviewed. Lymph nodes (LNs) (18 patients) were the most frequent sites followed in order by lung (12) and liver (11). SBRT doses ranged from 45 to 60 Gy in three fractions (median 48 Gy). The cumulative gross tumor volume (GTV) ranged from 2 to 123 ml (median 13 ml). RESULTS: The median follow-up period from the SBRT date was 28 months (range, 6-65 months). The 3-year local control and overall survival rates were 64 and 60%, and the respective 5-year rates were 57 and 38%. Cumulative GTV and SBRT dose were statistically significant prognostic factors for local control. The grade 3 or 4 complications occurred in three patients (7%). CONCLUSIONS: High dose SBRT for colorectal oligometastases was found to produce results comparable with surgical series. To improve local control, dose higher than 48 Gy are recommend when possible, but further study will be required to define the optimal normal tissue constraints and acceptable toxicity.

Oligometastases confined one organ from colorectal cancer treated by SBRT.

To determine the feasibility and efficacy of stereotactic body radiotherapy (SBRT) for oligometastases from colorectal cancer (CRC). Total of 59 patients with 78 lesions confined to one organ and treated from 2001 to 2006 were involved in this retrospective review. These patients presented with 1-4 metastatic lesions of largest diameter of <7 cm, progressed after chemotherapy, and were amenable to local treatment. The median radiation dose administered was 42 Gy, which was delivered in 3 fractions. Lymph node lesions were most frequent, followed in order by the lung and liver. Five-year overall survival and local control rates were 29 and 19%, respectively. Cumulative gross tumor volume, site of metastasis, and SBRT dose were found to be significantly associated with overall survival. In terms of local control, a cumulative GTV below 23 ml was found to be a significantly favorable prognostic factor. Acute grade 1-2 toxicities occurred in 24 of the 59 patients, and a late grade 4 complication occurred in 2 (3%), and these were relieved by bypass surgery. CRC patients with oligometastases generally fare well after SBRT. In particular, the survival rates of patients with a pelvic LN or a small tumor are promising.