Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To investigate the long-term efficacy, safety and prognostic factors of intraoperative radiotherapy (IORT) for narrow-margin (resection margin < 1 cm) hepatectomy in patients with hepatocellular carcinoma (HCC) during radical surgery.Methods:A retrospective cohort study was conducted. The data of primary HCC patients undergoing radical surgery and narrow-margin hepatectomy IORT in the Cancer Hospital of the Chinese Academy of Medical Sciences from November 2009 to February 2019 were collected. IORT applied 6 MeV or 9 MeV electron beams and a single irradiation was given to the margin. Kaplan-Meier method was used for the overall survival (OS) and disease-free survival (DFS) analysis; log-rank test was used for survival comparison among subgroups. The recurrence patterns and adverse reactions were recorded. Univariate and multivariate Cox proportional hazards models were used to analyze the factors influencing the OS and DFS.Results:A total of 64 patients were enrolled, with the median age [ M ( Q1, Q3)] of 57 years (49, 63) years. All patients included 55 males (85.9%) and 9 females (14.1%). The median dose of IORT was 15 Gy (range: 12-17 Gy). The median follow-up time was 83.3 (64.4, 91.9) months. The 1-year, 3-year, 5-year, 7-year, 10-year OS rates were 90.4%, 80.6%, 75.5%, 71.4% and 47.6%, respectively; the 1-year, 3-year, 5-year, 7-year,10-year DFS rates were 77.8%, 68.1%, 59.6%, 57.6% and 38.4%, respectively. Univariate Cox regression analysis indicated that preoperative serum alpha-fetoprotein (AFP) > 400 ng/ml was an independent risk factor for poor OS (> 400 ng/ml vs. ≤ 400 ng/ml: HR = 6.57, 95% CI: 2.16-19.96, P < 0.001), while not the independent influencing factor of poor DFS ( HR = 1.71, 95% CI: 0.65-4.52, P = 0.277). The age ≤ 60 years or not, gender, viral hepatitis or not, American Joint Committee on Cancer stage, tumor diameter (> 5 cm or not), tumor number, degree of tumor differentiation, microvascular invasion or not, microsatellite nodules or not, anatomical liver resection or not, and the dose of IORT ≤15 Gy or not were not the independent influencing factors of poor OS and DFS (all P > 0.05). Kaplan-Meier method analysis showed that patients with preoperative serum AFP ≤ 400 ng/ml (48 cases) had better OS compared with those with preoperative serum AFP>400 ng/ml (16 cases) (5-year OS rate: 84.8% vs. 44.9%; 7-year OS rate: 79.9% vs.37.4%), and the difference was statistically significant ( P = 0.002). There was no statistically significant difference in the DFS between the 2 groups ( P = 0.134). During the follow-up, 28 patients (43.8%) relapsed, including 17 cases (26.6%) of early recurrence and 11 cases (17.2%) of late recurrence. No marginal recurrence was observed. There were 22 cases (34.4%) of intrahepatic recurrence alone, 2 cases (3.1%) of extrahepatic recurrence and 4 cases (6.3%) of stimutaneous recurrence inside and outside the liver. The 1-, 3-, 5- and 7-year cumulative recurrence rates inside the liver were 19.0%, 27.2%, 37.4% and 39.3% respectively, and the cumulative recurrence rates outside the liver were 6.4%, 8.0%, 9.6% and 9.6% respectively. There were no adverse reactions above grade 3 in the entire group. There were no surgery-related deaths within 30 d after the operation, and no radiation-induced liver disease occurred. Conclusions:Narrow-margin IORT helps HCC patients receiving hepatectomy to achieve favorable long-term survival and adverse reactions are tolerable. It can be used as a safe and effective adjuvant therapy alternative.

Objective:To investigate the difference of MRI and clinicopathological characteristics between patients with breast cancer susceptibility gene (BRCA)-positive and BRCA-negative breast cancer.Methods:The study was a cross-sectional study. MRI images and clinicopathological data of breast cancer patients with postoperative pathologically confirmed and determined BRCA gene status in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 2012 to April 2021 were retrospectively analyzed. A total of 120 BRCA-positive patients with 122 lesions and 120 BRCA-negative patients with 126 lesions were enrolled. All patients underwent MRI examinations, including pre-contrast and post-contrast scans. The breast MRI features of the patients were analyzed, including internal necrosis, lesion depth, degree of background parenchymal enhancement (BPE), type of lesion, shape and margin of the mass lesion, internal enhancement, and edema. Clinicopathological analysis included family history, molecular subtype, nuclear grade, and the status of human epidermal growth factor 2 (HER-2), estrogen receptor (ER), and progesterone receptor (PR). The χ2 test and Fisher exact test were performed to determine the differences in MRI features and clinicopathological manifestations of BRCA-positive and BRCA-negative breast cancers. Significant features obtained by univariate analysis were included in the multivariate logistic regression analyses to select independent influencing factors for predicting BRCA mutation in breast cancer. Results:Statistically significant differences were observed between patients with BRCA-positive and BRCA-negative breast cancers in the following features: family history, molecular subtype, ER or PR-positive status, HER-2-negative status, nuclear grade, BPE, internal necrosis, edema, and the shape and margin of the mass lesion( P?0.05). The multivariate logistic regression analyses showed that HER-2 negativity ( OR=3.277, 95% CI 1.087-9.875, P=0.035), round or oval shape ( OR=2.688,95% CI 1.143-6.320, P=0.023), circumscribed margin ( OR=3.001,95% CI 1.374-6.554, P=0.006), edema ( OR=4.407,95% CI 2.100-9.244, P<0.001), and the minimal or mild degree of BPE ( OR=2.520,95% CI 1.328-4.782, P=0.005) were significant independent factors in predicting BRCA gene mutations. Conclusions:There are differences in MRI features and clinicopathological manifestations of BRCA-positive and BRCA-negative breast cancers. HER-2 status, the shape and margin of lesions, edema and the degree of BPE could independently predict the BRCA status of breast cancer.

Precision management of breast cancer is essential for improving patient outcomes.Radiomics enables high-throughput extraction of quantitative imaging features that reflect tumor biological behavior and heterogeneity from medical imaging data.With the rapid advancement of artificial intelligence(AI),particularly deep learning,feature extraction capability and model performance in radiomics have been significantly enhanced.Based on multimodal imaging modalities such as MRI,ultrasound and mammography,AI-and radiomics-based models can address key clinical challenges including tumor diagnosis,staging,molecular subtype prediction and therapeutic response assessment,thereby facilitating precision breast cancer care.This review summarizes recent advances in AI-driven radiomics for breast cancer diagnosis and treatment and discusses future application prospects and challenges toward clinical translation.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Precision management of breast cancer is essential for improving patient outcomes.Radiomics enables high-throughput extraction of quantitative imaging features that reflect tumor biological behavior and heterogeneity from medical imaging data.With the rapid advancement of artificial intelligence(AI),particularly deep learning,feature extraction capability and model performance in radiomics have been significantly enhanced.Based on multimodal imaging modalities such as MRI,ultrasound and mammography,AI-and radiomics-based models can address key clinical challenges including tumor diagnosis,staging,molecular subtype prediction and therapeutic response assessment,thereby facilitating precision breast cancer care.This review summarizes recent advances in AI-driven radiomics for breast cancer diagnosis and treatment and discusses future application prospects and challenges toward clinical translation.

Objective:To investigate the long-term efficacy, safety and prognostic factors of intraoperative radiotherapy (IORT) for narrow-margin (resection margin < 1 cm) hepatectomy in patients with hepatocellular carcinoma (HCC) during radical surgery.Methods:A retrospective cohort study was conducted. The data of primary HCC patients undergoing radical surgery and narrow-margin hepatectomy IORT in the Cancer Hospital of the Chinese Academy of Medical Sciences from November 2009 to February 2019 were collected. IORT applied 6 MeV or 9 MeV electron beams and a single irradiation was given to the margin. Kaplan-Meier method was used for the overall survival (OS) and disease-free survival (DFS) analysis; log-rank test was used for survival comparison among subgroups. The recurrence patterns and adverse reactions were recorded. Univariate and multivariate Cox proportional hazards models were used to analyze the factors influencing the OS and DFS.Results:A total of 64 patients were enrolled, with the median age [ M ( Q1, Q3)] of 57 years (49, 63) years. All patients included 55 males (85.9%) and 9 females (14.1%). The median dose of IORT was 15 Gy (range: 12-17 Gy). The median follow-up time was 83.3 (64.4, 91.9) months. The 1-year, 3-year, 5-year, 7-year, 10-year OS rates were 90.4%, 80.6%, 75.5%, 71.4% and 47.6%, respectively; the 1-year, 3-year, 5-year, 7-year,10-year DFS rates were 77.8%, 68.1%, 59.6%, 57.6% and 38.4%, respectively. Univariate Cox regression analysis indicated that preoperative serum alpha-fetoprotein (AFP) > 400 ng/ml was an independent risk factor for poor OS (> 400 ng/ml vs. ≤ 400 ng/ml: HR = 6.57, 95% CI: 2.16-19.96, P < 0.001), while not the independent influencing factor of poor DFS ( HR = 1.71, 95% CI: 0.65-4.52, P = 0.277). The age ≤ 60 years or not, gender, viral hepatitis or not, American Joint Committee on Cancer stage, tumor diameter (> 5 cm or not), tumor number, degree of tumor differentiation, microvascular invasion or not, microsatellite nodules or not, anatomical liver resection or not, and the dose of IORT ≤15 Gy or not were not the independent influencing factors of poor OS and DFS (all P > 0.05). Kaplan-Meier method analysis showed that patients with preoperative serum AFP ≤ 400 ng/ml (48 cases) had better OS compared with those with preoperative serum AFP>400 ng/ml (16 cases) (5-year OS rate: 84.8% vs. 44.9%; 7-year OS rate: 79.9% vs.37.4%), and the difference was statistically significant ( P = 0.002). There was no statistically significant difference in the DFS between the 2 groups ( P = 0.134). During the follow-up, 28 patients (43.8%) relapsed, including 17 cases (26.6%) of early recurrence and 11 cases (17.2%) of late recurrence. No marginal recurrence was observed. There were 22 cases (34.4%) of intrahepatic recurrence alone, 2 cases (3.1%) of extrahepatic recurrence and 4 cases (6.3%) of stimutaneous recurrence inside and outside the liver. The 1-, 3-, 5- and 7-year cumulative recurrence rates inside the liver were 19.0%, 27.2%, 37.4% and 39.3% respectively, and the cumulative recurrence rates outside the liver were 6.4%, 8.0%, 9.6% and 9.6% respectively. There were no adverse reactions above grade 3 in the entire group. There were no surgery-related deaths within 30 d after the operation, and no radiation-induced liver disease occurred. Conclusions:Narrow-margin IORT helps HCC patients receiving hepatectomy to achieve favorable long-term survival and adverse reactions are tolerable. It can be used as a safe and effective adjuvant therapy alternative.

Objective:To investigate the difference of MRI and clinicopathological characteristics between patients with breast cancer susceptibility gene (BRCA)-positive and BRCA-negative breast cancer.Methods:The study was a cross-sectional study. MRI images and clinicopathological data of breast cancer patients with postoperative pathologically confirmed and determined BRCA gene status in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 2012 to April 2021 were retrospectively analyzed. A total of 120 BRCA-positive patients with 122 lesions and 120 BRCA-negative patients with 126 lesions were enrolled. All patients underwent MRI examinations, including pre-contrast and post-contrast scans. The breast MRI features of the patients were analyzed, including internal necrosis, lesion depth, degree of background parenchymal enhancement (BPE), type of lesion, shape and margin of the mass lesion, internal enhancement, and edema. Clinicopathological analysis included family history, molecular subtype, nuclear grade, and the status of human epidermal growth factor 2 (HER-2), estrogen receptor (ER), and progesterone receptor (PR). The χ2 test and Fisher exact test were performed to determine the differences in MRI features and clinicopathological manifestations of BRCA-positive and BRCA-negative breast cancers. Significant features obtained by univariate analysis were included in the multivariate logistic regression analyses to select independent influencing factors for predicting BRCA mutation in breast cancer. Results:Statistically significant differences were observed between patients with BRCA-positive and BRCA-negative breast cancers in the following features: family history, molecular subtype, ER or PR-positive status, HER-2-negative status, nuclear grade, BPE, internal necrosis, edema, and the shape and margin of the mass lesion( P?0.05). The multivariate logistic regression analyses showed that HER-2 negativity ( OR=3.277, 95% CI 1.087-9.875, P=0.035), round or oval shape ( OR=2.688,95% CI 1.143-6.320, P=0.023), circumscribed margin ( OR=3.001,95% CI 1.374-6.554, P=0.006), edema ( OR=4.407,95% CI 2.100-9.244, P<0.001), and the minimal or mild degree of BPE ( OR=2.520,95% CI 1.328-4.782, P=0.005) were significant independent factors in predicting BRCA gene mutations. Conclusions:There are differences in MRI features and clinicopathological manifestations of BRCA-positive and BRCA-negative breast cancers. HER-2 status, the shape and margin of lesions, edema and the degree of BPE could independently predict the BRCA status of breast cancer.

Objective To evaluate the predictive value of T2-fluid attenuated inversion recovery (FLAIR)signal suppression rate for the short arm of chromosome 1 and long arm of chromosome 19 (1p/19q)molecular features in lower-grade gliomas (LGG),and to construct and verify the predictive model based on magnetic resonance imaging (MRI)tumor features and T2-FLAIR signal suppression rate.Methods Clincal and imaging data of the patients with pathologically confirmed supratentorial LGG (WHO grade 2～3)in our medical center from 2017 to 2021 were collected and retrospectively analyzed.According to the results of postoperative molecular pathology,they were divided into 1 p/19q-codeleted (1 p/19q-Codel)and 1 p/19q-noncodeleted (1 p/19q-Noncodel)groups.MRI tumor features were blindly assessed by 2 neuroradiologists.Five circular regions of interest were respectively delineated in the tumor area and the normal-appearing white matter in contralateral semioval center using the hot-spot method in order to calculate the T2-FLAIR signal suppression rate.The differences of clinical features,MRI tumor features and T2-FLAIR signal suppression rate were analyzed between the 2 groups.Univariate and multivariate logistic regression analyses were used to screen independent predictors and constructa predictive model and nomogram.Receiver operating characteristic (ROC)curve,calibration curve and Hosmer-Lemeshow test were applied to assess the model performance,and the model was internally validated by bootstrap method.Results A total of 146 supratentorial LGG patients were enrolled,including 68 being assigned into the 1 p/19q-Codel group and 78 into the 1 p/19q-Noncodel group.The T2-FLAIR signal suppression rate was 0.43 (0.28,0.62)in the 1 p/19q-Noncodel group,which was significantly higher than that in the 1 p/19q-Codel group[0.29 (0.24,0.35),P<0.001].Multivariate logistic regression analysis showed that T2-FLAIR signal suppression rate>0.374 (P<0.001),cortex infiltration (P=0.001) and calcification (P=0.004) were independent predictors for 1 p/19q status.The AUC value of T2-FLAIR signal suppression rate>0.374 in predicting 1 p/19q-Noncodel was 0.720,the sensitivity was 60.26％ and the specificity was 83.82％.DeLong test indicated that T2-FLAIR signal suppression rate>0.374 was more effective than T2-FLAIR mismatch sign in predicting 1 p/19q molecular features (P<0.001).ROC curve analysis suggested that the predictive model established by T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification had good performance,with an AUC value of 0.808,and the AUC value verified internally by bootstrap method was 0.807.At the same time,the calibration and goodness of fit of the model were good.Conclusion T2-FLAIR signal suppression rate can be used as a quantitative imaging marker to predict 1 p/19q-Noncodel LGG.The predictive model with T2-FLAIR signal suppression rate>0.374 combined with cortex infiltration and calcification can effectively predict 1 p/19q molecular features.

Objective:To explore the patterns of failure after postoperative intensity-modulated radiotherapy for gastric cancer.Methods:Clinical data of patients diagnosed with gastric cancer or gastroesophageal junction carcinoma with pathological stages T 3-4N 0 or T xN 1-3 admitted to Cancer Hospital of Chinese Academy of Medical Sciences from May 2009 to December 2018 were retrospectively analyzed. All patients received postoperative radiotherapy. During the follow-up, tumor recurrence was confirmed by imaging or endoscopic or pathological data, etc. According to the location of tumor recurrence, recurrence patterns were divided into local, regional and distant recurrence. Differences in recurrence patterns among different groups were compared using t-test and Chi-square test. Patient survival was assessed through Kaplan-Meier method. Results:A total of 76 patients were enrolled, with a median age of 49 years old (27-67 years old), 34 cases (45%) were classified as T 3 stage, 40 cases (53%) of T 4 stage, and 75 cases (99%) of N 1-3 stage, respectively. Seventy-three patients (92%) were classified as stage Ⅲ, and 38 patients (50%) underwent D2 dissection. The median follow-up time was 32.8 months (7.1-138.5 months). The median time of recurrence was 17.6 months (2.9-113.6 months). The median survival time after recurrence was 8.19 months (0.6-91.9 months). There were 13 cases (17%) of local recurrence, 6 cases (8%) of regional recurrence, and 72 cases (95%) of distant metastasis in patients. Peritoneal metastasis (33 cases, 43%) and distant lymph node metastasis (12 cases, 16%) were the main patterns of distant recurrence. Conclusions:By intensity-modulated radiotherapy technology, adjuvant radiotherapy yields favorable local and regional control for gastric cancer. Distant metastasis is still the main pattern of recurrence.