A deep learning method for generating pseudo-CT by cone beam CT in radiotherapy / 中华放射肿瘤学杂志

Objective:To investigate the pseudo-CT generation from cone beam CT (CBCT) by a deep learning method for the clinical need of adaptive radiotherapy.Methods:CBCT data from 74 prostate cancer patients collected by Varian On-Board Imager and their simulated positioning CT images were used for this study. The deformable registration was implemented by MIM software. And the data were randomly divided into the training set ( n=59) and test set ( n=15). U-net, Pix2PixGAN and CycleGAN were employed to learn the mapping from CBCT to simulated positioning CT. The evaluation indexes included mean absolute error (MAE), structural similarity index (SSIM) and peak signal to noise ratio (PSNR), with the deformed CT chosen as the reference. In addition, the quality of image was analyzed separately, including soft tissue resolution, image noise and artifacts, etc. Results:The MAE of images generated by U-net, Pix2PixGAN and CycleGAN were (29.4±16.1) HU, (37.1±14.4) HU and (34.3±17.3) HU, respectively. In terms of image quality, the images generated by U-net and Pix2PixGAN had excessive blur, resulting in image distortion; while the images generated by CycleGAN retained the CBCT image structure and improved the image quality.Conclusion:CycleGAN is able to effectively improve the quality of CBCT images, and has potential to be used in adaptive radiotherapy.

Establishment and validation of a multigene model to predict the risk of relapse in hormone receptor-positive early-stage Chinese breast cancer patients / 中华医学杂志(英文版)

BACKGROUND@#Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery.@*METHODS@#In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC).@*RESULTS@#A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model.@*CONCLUSIONS@#A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.

Long-term outcomes of watch&wait (W&W) after neoadjuvant treatment in patients with rectal cancer / 中华放射肿瘤学杂志

Objective:To compare the outcomes of watch&wait (W&W) strategy in patients with locally advanced rectal cancer who achieved complete clinical response (cCR) after neoadjuvant therapy, with those who obtained pathological complete response (pCR) after total mesorectal excision (TME).Methods:This is a retrospective cohort analysis study. Patients histologically proven with locally advanced rectal adenocarcinoma (stage Ⅱ-Ⅲ) who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing neoadjuvant therapy and follow-up ≥1 year (W&W group), and patients who did not have cCR but pCR after TME (pCR group). The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (NR-DFS), and organ preservation rate. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM).Results:A total of 118 patients were enrolled, 49 of whom had cCR and managed by W&W, 69 had pCR, with a median follow-up period of 49.5 months (12.1-79.9 months). No difference was observed in the 3-year OS (97.1% vs. 96.7%) and 5-year OS (93.8% vs. 90.9%, P=0.696) between the W&W and pCR groups. Patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs. 43.5%, P<0.001), better 3-year DFS (83.6% vs. 97.0%) and 5-year DFS (83.6% vs. 91.2%, P=0.047) compared with those achieving pCR. The 3-year NR-DFS (95.9% vs. 97.0%) and 5-year NR-DFS (92.8% vs. 97.0%, P=0.407) did not significantly differ between the W&W and pCR groups. Local regeneration occurred in six cases, and 87.7% of patients had successful rectum preservation in the W&W group. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs. 26.5%, P<0.001) was noted in the W&W group. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19.0 vs. 9.8 weeks, P<0.001). Conclusions:The oncological outcomes of W&W strategy in patients with locally advanced rectal cancer are safe and effective, significantly improving the quality of life. Longer interval for cCR evaluation may improve rectal organ preservation rate.

Preliminary application of MR-Linac in breast cancer radiotherapy in a single academic center / 中华放射肿瘤学杂志

Objective:To describe a prospective study of pre-operative tumor-bed boost performed at the 1.5 T MR-Linac in combination with adjuvant whole breast irradiation, and a first case, with an accentuation on clinical feasibility and safety.Methods:A phase II, single arm study recruiting early stage patients follows a paradigm that first boosts the tumor bed and then undergoes breast conservative surgery in 2 weeks, and last irradiates the whole breast in 6 weeks. The primary endpoint is ≥ grade 2 acute breast toxicity. A 43 years old patient affected by a breast carcinoma, not special type of the right-sided lateral quadrant, staged cT 2N 0M 0, was planned and treated. The dose, 8 Gy for one time, was calculated by Monaco on CT simulation images. Both the air electron stream effect (ESE) and the electron return effect (ERE) at the presence of 1.5 T magnetic field were evaluated. During the pre-treatment evaluation, we carried out adaptation-to-position adjustment. Results:The normal organ dosimetry is within toleration. The Dmax to the skin, the chin and the right upper arm was 8.44 Gy, 28.5 cGy and 17.8 cGy, respectively. There was no increased toxicity from ERE and ESE, and the treatment was well tolerated without > grade 1 acute toxicity. The patient received breast conservative surgery on day 7 without delayed wound healing.Conclusions:This is the first case successfully treated within a clinical trial by pre-operative tumor-bed boost under 1.5 T MR-Linac in our institution. More participants are needed to validate and optimize the paradigm.

Preliminary study of clinical application of magnetic resonance linear accelerator in liver malignancies / 中华放射肿瘤学杂志

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.

Impact of status determined by comprehensive geriatric assessment on setup error during rectal cancer radiotherapy for elderly patients / 中华放射医学与防护杂志

Objective:To explore the impacts of comprehensive geriatric assessment (CGA) on setup errors during the radiotherapy of elderly patients with rectal cancer.Methods:A total of 45 patients over 70 years of age and receiving radiotherapy were enrolled in the study. A comprehensive geriatric assessment was conducted before the radiotherapy. The enrolled patients had a median age of 77 years, including 28 male and 17 female cases. Meanwhile, 31 patients were determined to be in a good CGA status and 14 were determined to be in a poor CGA status, and 35 patients received radiotherapy in the prone position and 10 in the supine position. Cone beam CT (CBCT) was used for setup correction during radiotherapy. CBCT was performed daily in the first week and once a week from the second week. By fusing and aligning the CBCT images with simulation CT images according to the lumbar vertebra, setup errors in the left-right ( x axis), cranio-caudal ( y axis), and anterior-posterior ( z axis) directions were obtained. A total of 338 CBCT images were obtained. A generalized linear model was used to evaluate the effects of multiple factors on the setup errors. Results:During the radiotherapy, setup errors of all patients were (0.24±0.19) cm in the left-right direction, (0.33±0.25) cm in the cranio-caudal direction, and (0.19±0.15) cm in the anterior-posterior direction. The setup error in the cranio-caudal direction was more than that in the left-right direction and that in the anterior-posterior direction ( Z=-4.86, -7.72, P< 0.001). The setup error in the left-right direction was greater than that in the anterior-posterior direction ( Z=-2.79, P=0.005). The mean setup errors of the good and poor status groups in the left-right direction were (0.21 ± 0.17) and (0.30 ± 0.22) cm, respectively ( Z=2.16, P=0.031). There was no statistically significant difference in the setup errors between cranio-caudal direction and anterior-posterior direction ( P>0.05). The setup errors in the anterior-posterior direction were (0.17 ± 0.13) and (0.27 ± 0.19) cm, respectively for the prone and supine positions during the radiotherapy ( Z=2.85, P=0.004). There was no statistically significant difference in the setup errors between the left-right direction and the cranio-caudal direction ( P>0.05). Conclusion:The status of CGA elderly patients with rectal cancer affects the setup error in the left-right direction. It may be necessary to clinically adjust the PTV margin.

Clinical application of laparoscopic sentinel lymph node mapping in early staged cervical cancer / 中华妇产科杂志

Objective:To investigate the application of sentinel lymph node biopsy (SLNB) in early-staged cervical cancer by laparoscopy.Methods:It was a prospective, single-arm, single-center clinical study. Seventy-eight cases of cervical cancer patients were collected from July 2015 to December 2018 at the Fourth Hospital of Hebei Medical University. All the patients were injected with tracer into the disease-free block of cervical tissue after anesthesia by the same surgeon who learned sentinel lymph node (SLN) mapping technique in Memorial Sloan-Kettering Cancer Center, and underwent SLN mapping followed by complete pelvic lymphadenectomy. Moreover, all the dissected lymph nodes were stained with hematoxylin eosin staining (HE) pathological examination. Besides, the negative SLN on hematoxylin-eosin staining were detected by immunohistochemistry cytokeratin staining micro-metastasis. To analyze the distribution, detection rate, false negative rate the sensitivity and negative predictive value of the SLN in early-staged cervical cancer by laparoscopy, and explore the value of SLN mapping in predicting the lymph nodes metastasis in early-staged cervical cancer.Results:The overall detection rate of SLN in cervical cancer was 99% (77/78), bilateral detection rate was 87% (68/78). The average of 12.4 lymph node (LN) and 3.6 SLN were dissected for each patients each side. SLN of cervical cancer were mainly distributed in the obturator space (61.5%, 343/558), followed by external iliac (23.5%, 131/558), common iliac (7.3%, 41/558), para-uterine (3.8%, 21/558), internal iliac (2.2%, 12/558), para abdominal aorta (1.1%, 6/558), and anterior sacral lymphatic drainage area (0.7%, 4/558). Fourteen cases of LN metastasis were found among all 78 cases. There were a total of 38 positive LN, including 26 SLN metastasis and 12 none sentinel LN metastasis. Through immunohistochemical staining and pathological ultra-staging, 1 SLN was found to be isolated tumor cells (ITC), and 5 SLNs were found to be micro-metastases (MIC), accounting for 23% (6/26) of positive SLN. SLN mapping with pathological ultra-staging improved the prediction of LN metastasis in cervical cancer (2/14). Metastatic SLN mainly distributed in the obturator space (65%, 17/26), peri-uterine region (12%, 3/26), common iliac region (15%, 4/26), and external iliac region (8%, 2/26). The consistency of the diagnosis of lymph node metastasis by SLN biopsy and postoperative retroperitoneal lymph node metastasis showed that the Kappa value was 1.000 ( P<0.001), indicated that the metastasis status of SLN and retroperitoneal lymph node were completely consistent. The sensitivity, specificity, accuracy, false-negative rate, and negative predictive value of SLN biopsy in the diagnosis of lymph node metastasis were 100%, 100%, 100%, 0, and 100%, respectively. Conclusions:SLN in early-staged cervical cancer patients were mainly distributed in the obturator and external iliac space, pathalogical ultra-staging of SLN could improve the prediction of LN metastasis. Intraoperative SLN mapping is safe, feasible and could predict the state of retroperitoneal LN metastasis in early-staged cervical cancer. SLNB may replace systemic pelvic lymphadenectomy.

Expression of FGL1, Distribution of Tumor-Infiltrating Lymphocytes, and Their Clinical Significance in Esophageal Squamous-Cell Carcinoma / 肿瘤防治研究

Objective To explore the expression of fibrinogen-like protein 1 (FGL1), the distribution of tumor-infiltrating lymphocytes (TILs), and their relationship with the prognosis of esophageal squamous-cell carcinoma (ESCC) patients. Methods We analyzed retrospectively the clinical data of 120 ESCC patients. The expression of FGL1 was detected through immunohistochemistry. The distributions of intratumoral TILs (iTILs) and stromal TILs (sTILs) were evaluated under a microscope. Survival analysis was used to evaluate the patient outcomes. Results The positive rate of FGL1 in ESCC was 18.3% (22/120), and it was connected to the TNM stage, lymph node status, and TILs. A total of 73 cases (60.8%) showed low levels of iTILs (iTILs≤10%), and 47 cases (39.2%) exhibited high iTIL levels (iTILs > 10%). Similarly, 82 cases (68.3%) presented low levels of sTILs (sTILs≤10%), and 38 cases (31.7%) manifested high sTIL levels (sTILs > 10%). The distribution of iTILs was associated with FGL1, tumor differentiation, and TNM stage, whereas the distribution of sTILs was associated with FGL1, tumor location, and TNM stage. The Kaplan–Meier survival analysis showed that tumor diameter, TNM stage, lymph node status, FGL1, and TILs were associated with the prognosis of patients with ESCC (P < 0.05). Multivariate Cox regression revealed that FGL1, TILs and TNM stage were the influencing factors of prognosis. Conclusion FGL1 expression is associated with the poor prognosis and may be a prognostic biomarker of ESCC. FGL1 combined with TILs can be used as a biomarker to predict ESCC.

Bladder-sparing treatment following noninvasive down-staging after transurethral resection of bladder tumor plus systemic chemotherapy for muscle-invasive bladder cancer / 中华泌尿外科杂志

Objective:To investigate the long-term survival and safety in patients with muscle-invasive bladder cancer (MIBC) who experienced a noninvasive down-staging (≤pT 1)after transurethral resection of bladder tumor (TURBT) plus systemic chemotherapy and received bladder-sparing treatment. Methods:The records of patients with MIBC who underwent maximal TURBT plus systemic chemotherapy-guided bladder-sparing treatment were reviewed retrospectively from Dec 2013 to Dec 2020. Eventually, 22 patients who achieved noninvasive down-staging underwent conservative management. The total patient cohort contained 10 males and 12 females. A majority of patients had single lesion and stage T2 disease. The median age of the patients was 66 years and the median tumor size was 3.0 cm. All patients underwent maximal TURBT to resect all visible diseases and followed by 3-4 cycles platinum-based systemic chemotherapy. After achieving noninvasive down-staging, 14 patients received concurrent chemoradiotherapy, and the other 8 patients underwent surveillance. Overactive bladder symptom score (OABSS) was used to assess the bladder function after treatment.Results:Twelve patients achieved pT 0 and 10 patients were down-staged to cT a-T 1. At a median follow-up of 36.7 months, 90.9%(20/22) patients retained their bladder function successfully. Among the 14 patients who received concurrent chemoradiotherapy, 4 had grade 3 or 4 adverse events. Among the 8 patients who underwent surveillance, 3 had grade 3 or 4 adverse events after systemic chemotherapy.Nine patients experienced tumor recurrence in the bladder, and 2 patients died of bladder cancer. Seven (31.8%) patients experienced Ⅲ/Ⅳ grade complications. The 5-year recurrence-free survival (RFS) and overall survival (OS) in patients achieved pT0 were 66.7% and 100.0%, respectively. The 5-year RFS and OS in patients achieved cTa-T1 were 40% and 72%, respectively. The OABSS score of 20 patients who retained their bladder successfully was (1.00±1.03). Conclusions:MIBC patients who achieved noninvasive down-staging might be candidates for the bladder-sparing treatment with maximum TURBT followed by systemic chemotherapy.The patients who achieved pT 0 might have better prognosis with functional bladder.

Neoadjuvant Chemotherapy–Guided Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer: Results of a Pilot Phase II Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. @*Materials and Methods@#Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. @*Results@#Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. @*Conclusion@#After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Primary carcinoid of testis: a case report / 中华泌尿外科杂志

Carcinoid is a rare clinical disease, especially primary carcinoid of testis. On December 11, 2019, a patient with primary testicular carcinoid was admitted to the Fourth Hospital of Hebei Medical University. The physical examination, color Doppler ultrasound and scrotal CT showed that left testicular tumor. The patient underwent radical orchiectomy and sent for pathology examination on December 14, 2019. Gastroscopy, enteroscopy and CT examination of pelvic and abdominal cavity showed no obvious abnormalities. Postoperative pathology combined with immunohistochemistry was diagnosed as primary carcinoid of testis. The patient was followed up for 23 months with no recurrence.

Four-dimensional computed tomography scan analysis of liver tumor motion treated with abdominal compression during stereotactic treatment / 中华放射肿瘤学杂志

Objective:To explore the motion and influencing factors of implanted gold markers in guiding liver stereotactic body radiation therapy (SBRT) using abdominal compression.Methods:Twenty patients with oligometastatic colorectal cancer or primary hepatocellular carcinoma from January 2016 to December 2019 were included. All patients were treated with SBRT under abdominal compression, with 1-3 gold markers were implanted within 2 cm from the lesion before positioning. Four-dimensional computed tomography (4DCT) scan was used for treatment planning. The respiratory cycle was divided into 0-90% respiratory phase images based on the respiratory signal, which were reconstructed by the system (Pinnacle 3 version 9.1; Philips Medical System, Madison, WI, USA), and cone beam CT validation images before radiation exposure were obtained. The liver volume was divided into 3 parts: within 2 cm from the main hepatic portal vein, 2-5 cm from the main hepatic portal vein, and>5 cm from the main hepatic portal vein. The motion of different tumor locations was evaluated. Results:The average intrafractional motion amplitude was (2.63±2.81) mm in the cranial-caudal (CC) direction, (1.35±1.23) mm in the anterior-posterior (AP) direction, and (0.76±0.88) mm in the left-right (LR) direction, respectively. The average interfractional motion amplitude was (3.45±3.06) mm, (2.64±2.60) mm, and (2.23±2.07) mm, respectively. Both the intra-or inter-fractional motion amplitudes in the CC direction were the highest, followed by those in the AP and LR direction (all P<0.001). The motion varied at different tumor locations. The longer distance from the main hepatic portal vein, the larger the intrafractional motion (all P<0.05). To cover the 95% population-based confidence interval, the internal target volume (ITV) was suggested to include the expansion of 3.9 mm, 5.2 mm and 7.9 mm in the LR, AP and CC direction. The expansion of 4.3 mm, 4.4 mm and 6.1 mm was delivered within 2 cm from the main hepatic portal vein, and 3.5 mm, 7.3 mm and 9.7 mm>5 cm from the main hepatic portal vein, respectively. The expansion varied significantly depending on the tumor location, whereas the motion in the CC direction was the largest regardless of the tumor location. The longer distance of the tumor from the main portal vein, the larger expansion in the CC direction. The expansion of tumor > 5 cm from the main portal vein in the AP direction was larger than that of inner parts. Conclusion:Liver tumors at different locations require individual external expansion of ITV.

Dosimetric evaluation, acute toxicity and short-term efficacy of postmastectomy hypofractionated internal mammary chain irradiation with electrons / 中华放射肿瘤学杂志

Objective:To investigate the dosimetric characteristics, acute toxicity and short-term efficacy of postmastectomy hypofractionated internal mammary (IM) chain irradiation with electrons in patients with high-risk breast cancer.Methods:A total of 155 patients with breast cancer who underwent modified mastectomy between November 2018 and January 2020 were selected. Among them, 137(88.4%) patients were classified as stage Ⅲ and 18(11.6%) as stage Ⅱ. All patients received standard chemotherapy, endocrine therapy and anti-Her2 targeted therapy. CTV im was divided into three subregions: CTV im1, CTV im2 and CTV im3, which represented the first, second and third intercostal IM, respectively. The planning target volume of subraclavicular region (PTV sc) was delineated. CTV cw and CTV im were irradiated with 6-15 MeV electron at 43.5 Gy in 15 fractions over 3 weeks. Moreover, PTV sc was irradiated with 6 MV X-ray at 43.5 Gy in 15 fractions over 3 weeks using two-dimensional radiotherapy (2DRT) or three-dimensional radiotherapy (3DRT). The dosimetric characteristics of CTV im, PTV sc, lung, heart, left anterior descending coronary artery (LAD) and right coronary artery (RA) were evaluated, and the acute toxicity and short-term efficacy were analyzed. Results:The mean dose (D mean) of CTV im was (43.3±2.6) Gy, D 95% was (30.5±8.3) Gy, V 90% was (85.0±10.5)% and V 80% was (91.0±7.4)%, respectively. The corresponding parameters of CTV im1 were significantly lower than those of CTV im2 and CTV im3(all P<0.001). Body mass index exerted no significant effect on IM dose ( P>0.05). Compared with 2DRT, 3DRT for SC significantly increased theD mean of CTV im[(43.4±2.6) Gy vs.(41.4±2.3) Gy, P=0.021], and the hot spot within PTV sc[V 110%: (26.7±17.5) cm 3vs.(12.5±8.4) cm 3, P=0.018; V 120%: (6.1±5.3) cm 3vs.(2.0±2.6) cm 3, P=0.023]. TheD mean of the ipsilateral lung was (9.8±1.9) Gy, and V 20Gy was (19.7±4.7)%. TheD mean of heart was (3.3±1.7) Gy in the whole group, (4.7±1.4) Gy for the left-sided breast cancer and (2.6±1.2) Gy for the right-sided breast cancer, respectively. TheD mean of LAD for the left-sided breast cancer was (13.9±4.9) Gy. TheD mean of RA for the right-sided breast cancer was (7.5±3.7) Gy. The incidence rates of ≥ grade 2 acute radiation dermatitis, esophagitis and pneumonitis were 19.3%, 4.5% and 2.6%, respectively. With a median follow-up time of 20.5 months (range: 9.9-41.8 months), 2 cases of chest wall recurrence, 2 regional lymph node recurrence, 6 distant metastases and 1 death were reported. Conclusions:When hypofractionated internal mammary chain is irradiated by electrons after mastectomy, the doses to the lung, heart and coronary artery are low, and the acute toxicities are mild. However, the dose to CTV im1 is inadequate. Although short-term efficacy is high, long-term follow-up is warranted.

Radiotherapy and prognostic analysis of breast cancer patients with isolated regional recurrence after mastectomy / 中华放射肿瘤学杂志

Objective:To analyze the prognosis of patients with isolated regional recurrence (RR) after mastectomy, and evaluate the efficacy of radiotherapy and identify the optimal radiation target volumes.Methods:Clinical data of 144 patients with first isolated RR after mastectomy between 2001 and 2018 were retrospectively analyzed. All patients had not received post-mastectomy radiotherapy. The primary endpoints consisted of the subsequent locoregional recurrence (sLRR), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS).Results:With a median follow-up of 82.5 months after RR, the 5-year sLRR, DM, PFS and OS rates for the entire group were 42.1%, 71.9%, 22.9% and 62.6%, respectively. Local plus systemic therapy was an independent favorable prognostic factor for sLRR ( P<0.001) and PFS ( P=0.013). The sLRR rate in the surgery plus radiotherapy group was the lowest ( P<0.001). Surgery plus radiotherapy significantly reduced the 5-year risk of recurrence within the initially involved nodal regions ( P<0.001). Patients with chest wall irradiation obtained the 5-year subsequent chest wall recurrence rate of 12.1% compared to 14.8%( P=0.873) for those without chest wall irradiation. The subsequent supraclavicular recurrence rate was lower in patients with prophylactic supraclavicular irradiation than that without prophylactic supraclavicular irradiation (9.9% vs. 23.8%, P=0.206). The incidence rates of initially uninvolved axillary and internal mammary nodal recurrence were below 10% regardless of prophylactic irradiation or not. Conclusions:Patients with RR alone have an optimistic 5-year OS in the contemporary era. Comprehensive locoregional treatment including surgery and radiotherapy combined with systemic therapy is recommended. The chest wall, axillary and internal mammary nodal prophylactic irradiation should not be routinely performed for all patients with RR. The value of supraclavicular prophylactic irradiation remains to be evaluated.

Total neoadjuvant therapy for locally advanced gastric cancer: an interim study of phase Ⅱ clinical trial / 中华放射肿瘤学杂志

Objective:To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) model of" neoadjuvant chemoradiotherapy plus consolidation neoadjuvant chemotherapy (CNCT) followed by surgery" for locally advanced gastric cancer.Methods:From 2018 to 2020, 28 patients clinically diagnosed with locally advanced gastric adenocarcinoma or Siewert Ⅱ/Ⅲ adenocarcinoma gastroesophageal junction cancer were prospectively enrolled. The neoadjuvant chemoradiotherapy (NCRT) was delivered with a total dose of 45 Gy, 1.8 Gy/f. Concurrent chemotherapy was S-1 at a dose of 40-60 mg twice daily. Then, patients received four to six cycles of CNCT of SOX regimen at three weeks after neoadjuvant chemoradiotherapy. D 2 lymphadenectomy was performed at 4-6 weeks after CNCT. Results:A total of 28 patients completed the whole therapy. Grade 3 or above adverse events occurred in 3 cases (11%) during CCRT, including thrombocytopenia, leukopenia and anorexia; 2 cases (7%) developed leukopenia and 3 cases (11%) of thrombocytopenia during CNCT. Twenty patients (71%) completed the surgery. The proportion of patients with pathological complete remission (pCR) was 50%. Three patients experienced surgical complications including anastomotic leak, anastomotic stenosis and intra-abdominal sepsis. All were recovered after symptomatic treatment.Conclusion:Interim analysis results demonstrate that TNT can yield significant down-staging for patients with locally advanced gastric cancer, which causes tolerable adverse events and postoperative complications.

Radiotherapy for and prognosis of breast cancer patients with isolated chest wall recurrence after mastectomy / 中华放射肿瘤学杂志

Objective:To investigate the radiation field and dose selection of patients with isolated chest wall recurrence (ICWR) after modified radical mastectomy, and analyze the prognostic factors related to subsequent chest wall recurrence.Methods:Clinical data of 201 patients with ICWR after mastectomy admitted to the Fifth Medical Center, Chinese PLA General Hospital from 1998 to 2018 were retrospectively analyzed. None of the patients received postoperative adjuvant radiotherapy. After ICWR, 48 patients (73.6%) underwent surgery and 155 patients (77.1%) received radiotherapy. Kaplan-Meier method was used to calculate the post-recurrence progression-free survival (PFS) rates and the difference was compared by log-rank test. Multivariate analysis was performed using Cox regression model. Competing risk model was adopted to estimate the subsequent local recurrence (sLR) rates after ICWR and the difference was compared with Gray test. Multivariate analysis was conducted using F&G analysis. Results:With a median follow up of 92.8 months after ICWR, the 5-year PFS rate was 23.2%, and the 5-year sLR rate was 35.7%. Multivariate analysis showed that patients with surgery plus radiotherapy and recurrence interval o F>12 months had a lower sLR rate. Patients with recurrence interval o F>48 months, local plus systemic treatment and surgery plus radiotherapy had a higher PFS rate. Among the 155 patients who received chest wall radiotherapy after ICWR, total chest wall irradiation plus local boost could improve the 5-year PFS rate compared with total chest wall irradiation alone (34.0% vs. 15.4%, P=0.004). Chest wall radiation dose (≤60 Gy vs.>60 Gy) exerted no significant effect upon the sLR and PFS rates (both P>0.05). In the 53 patients without surgery, the 5-year PFS rates were 9.1% and 20.5%( P=0.061) with tumor bed dose ≤60 Gy and>60 Gy, respectively. Conclusions:Local radiotherapy is recommended for patients with ICWR after modified radical mastectomy of breast cancer, including total chest wall radiation plus local boost. The radiation dose for recurrence should be increased to 60 Gy, and it should be above 60 Gy for those who have not undergone surgical resection. In addition, patients with ICWR still have a high risk of sLR, and more effective treatments need to be explored.

Relationship between gastric filling status and intra-or inter-fractional displacement of tumor in the preoperative radiotherapy of adenocarcinoma of the esophagogastric junction / 中华放射肿瘤学杂志

Objective:To investigate the relationship between gastric filling status and intra-or inter-fractional tumor displacement in patients with adenocarcinoma of the esophagogastric junction (AEG) undergoing preoperative radiotherapy.Methods:From October 2018 to June 2019, 10 patients with locally advanced AEG who received totally neoadjuvant therapy were enrolled in this prospective study. Patients received two markers implanted at the cranial and caudal borders of the tumors under gastroscope and a total of 20 fiducial markers were implanted finally. All patients underwent 4DCT scan under the gastric fasting and filling status. Ten images of 0% to 90% respiratory phase were automatically reconstructed by the system (Pinnacle 3, version 9.1, Philips Medical Systems, Eindhoven, The Netherland). Each patient obtained one hundred sets of images. Results:In the tumors proximal to the chest, gastric filling did not significantly affect intrafractional or interfractional tumor displacements. Nevertheless, in the tumors distal to the chest, the interfractional displacement in the cranio-caudal (CC) direction under the gastric fasting status was significantly larger compared with that under the gastric filling status (6.22±4.67 mm vs. 4.13±3.68 mm, P=0.013). To ensure 95% of the prescribed dose irradiated to at least 90% of the tumor volume during the radiotherapy, the margins of tumors proximal to the chest in the left-right (LR), antero-posterior (AP) and CC directions were 9 mm, 8.5 mm, 12.1 mm under gastric filling status with 300 ml semi-fluid. Six patients diagnosed with gastric cancer with proximal thoracic fiducial markers treated by preoperative radiotherapy were included in the validation group, revealing that the fiducial markers of 93% patients were covered in this margin. Conclusion:During the preoperative radiotherapy in AEG patient, the approach of quantitative gastric filling can be considered.

Clinical efficacy and prognosis of 85 patients with extracranial metastatic breast cancer receiving radiotherapy / 中华放射肿瘤学杂志

Objective:To evaluate the clinical efficacy of radiotherapy in the treatment of extracranial metastatic breast cancer, and to investigate the significance and prognostic factors of whole-lesion radiotherapy (WLRT).Methods:Clinical data of 85 patients with extracranial metastatic breast cancer treated with radiotherapy between 2014 and 2019 were retrospectively analyzed. Thirty-six patients were assigned into the WLRT group and 49 in the non-WLRT group. The local control (LC), progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan- Meier method, log-rank test and univariate prognostic analysis. Cox proportional hazards model was used for multivariate prognostic analysis. Results:The median follow-up time was 26.7 months. The 2-year LC, PFS, OS rates were 77%, 26%, 77%, respectively. The 2-year LC (91% vs. 67%, P=0.001), PFS (47% vs. 8%, P<0.001), OS rates (84% vs. 71%, P=0.010) in the WLRT group were significantly higher than those in the non-WLRT group, respectively. Multivariate analysis demonstrated that WLRT was an independent favorable prognostic factor for the LC, PFS and OS. Furthermore, bone metastasis alone was associated with improved LC and positive hormone receptor status was correlated with improved OS. Conclusions:WLRT has the potential to prolong the survival of patients with extracranial metastatic breast cancer. The patients with bone metastases alone obtain better LC, whereas those with negative hormone receptor status has worse OS.

Comparison of the value of two scores for predicting prognosis in patients with locally advanced rectal cancer undergoing concurrent chemoradiotherapy plus surgery / 中华放射肿瘤学杂志

Objective:To evaluate the prognostic significance of neoadjuvant rectal (NAR) score and downstaging depth score (DDS) after neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC).Methods:Retrospective analysis was performed for 200 patients with LARC (T 3-T 4 and/or N 1-N 2, M 0), who were initially treated in the Cancer Hospital of Chinese Academy of Medical Sciences from 2015 to 2018. All patients had baseline MRI data and received preoperative nCRT and radical resection. All patients received preoperative radiotherapy with a dose of 45-50Gy combined with concurrent capecitabine. The effect of NAR and DDS scores on clinical prognosis was statistically compared. The 3-year disease-free survival (DFS) was calculated using the Kaplan- Meier method and compared by the log- rank test. Cox proportional hazards model was used to perform multivariate survival analysis. The predictive performance for 3-year DFS was calculated using the receiver operating characteristic (ROC) curve. Results:The median follow-up time was 30.5(10.6-54.0) months. In terms of DDS, the 3-year DFS rate was 56.4% in the DDS ≤0 group, significantly lower than 83.0% in the DDS >0 group ( P=0.002). In terms of NAR score, the 3-year DFS rates were 90.1%, 73.8% and 53.6% in NAR score ≤8, 8-16 and>16 groups, respectively ( P<0.001). In the whole cohort, the area under the ROC curve (AUC) of DDS and NAR scores for predicting 3-year DFS were 0.683 and 0.756( P=0.037). In yp0-I stage patients ( n=72), the AUC of DDS and NAR scores for predicting 3-year DFS were 0.762 and 0.569( P=0.032). Conclusions:High DDS and low NAR scores after nCRT indicate good prognosis for patients with LARC. NAR score yields better accuracy than DDS in predicting clinical prognosis, but DDS is significantly better than NAR score in yp0-I stage population.

Comparison of MRI and CT for target volume delineation and dose coverage for partial breast irradiation in patients with breast cancer / 中华放射肿瘤学杂志

Objective:To compare magnetic resonance imaging (MRI)-based and computed tomography (CT)-based target volume delineation and dose coverage in partial breast irradiation (PBI) for patients with breast cancer, aiming to explore the application value of MRI localization in PBI after breast-conserving surgery.Methods:Twenty-nine patients with early breast cancer underwent simulating CT and MRI scans in a supine position. The cavity visualization score (CVS) of tumor bed (TB) was evaluated. The TB, clinical target volume (CTV), planning target volume (PTV) were delineated on CT and MRI images, and then statistically compared. Conformity indices (CI) between CT- and MRI-defined target volumes were calculated. PBI treatment plan of 40 Gy in 10 fractions was designed based on PTV-CT, and the dose coverage for PTV-MRI was evaluated.Results:The CVS on CT and MRI images was 2.97±1.40 vs. 3.10±1.40( P=0.408). The volumes of TB, CTV, PTV on MRI were significantly larger than those on CT, (24.48±16.60) cm 3vs. (38.00±19.77) cm 3, (126.76±56.81) cm 3vs. (168.42±70.54) cm 3, (216.63±81.99) cm 3vs. (279.24±101.55) cm 3, respectively, whereas the increasing percentage of CTV and PTV were significantly smaller than those of TB. The CI between CT-based and MRI-based TB, CTV, PTV were 0.43±0.13, 0.66±0.11, 0.70±0.09( P<0.001), respectively. The median percentage of PTV-MRI receiving 40 Gy dose was 81.9%(62.3% to 92.4%), significantly lower than 95.6%(95.0%~97.5%) of PTV-CT. Conclusions:The CVS between CT and MRI is not significantly different, but the MRI-based TB, CTV, PTV are significantly larger than CT-based values. The PTV-MRI is of underdose if PBI treatment plan is designed for PTV-CT. As a supplement of CT scan, MRI can enhance the accuracy of TB delineation after breast-onserving surgery.