OBJECTIVES:To develop and validate a deep learning model for whole breast clinical target volume (CTV) contouring and evaluate clinical features affecting its performance. METHODS:Five datasets with 857 patients from a single center were used. Dataset 1 (n = 300) trained and tested the model. Dataset 2 (n = 10) evaluated contouring time and dosimetric parameters. Datasets 3 (n = 20) and 4 (n = 10) were for clinical evaluation. Dataset 5 (n = 517) identified clinical factors influencing auto-contouring accuracy. Model performance was assessed using Dice Similarity Coefficient (DSC) and 95th percentile Hausdorff Distance (HD95). RESULTS:The median DSC and HD95 for left- and right-sided models in Dataset 1 were 0.941, 1.75 mm and 0.937, 2.47 mm, respectively. In Dataset 2, both auto-contouring and auto-contouring with manual corrections were significantly faster than manual contouring (P = .005 for both), while still achieving clinically acceptable dosimetric results. In Dataset 3, two physicians rated automatic and manual contours as equivalent (P = .214, P = .075), while the other rated auto-contouring higher (P < .001). In Dataset 4, the auto-contouring model outperformed 1/5 physicians by DSC (P = .009) and 3/5 by HD95 (P = .015, P = .007, P = .017). In Dataset 5, peripheral tumor-bed and low-density breast tissue were associated with lower DSC (P < .001 for both) and higher HD95 (P < .001 for both). Cases without unfavorable factors performed better than those with (P < .001 for both). CONCLUSIONS:The proposed model demonstrated acceptable accuracy, consistency, and efficiency in breast CTV contouring. Peripheral tumor-bed and low-density breast tissue reduced auto-contouring performance. ADVANCES IN KNOWLEDGE:The characteristics of challenging cases in whole breast CTV auto-contouring should be identified.

Background: To report the early toxicity and quality assurance of the HARVEST study which was to investigate whether hypofractionated radiotherapy (HF-RT) with regional nodal irradiation (RNI, including internal mammary nodes) is non-inferior to conventional fractionated radiotherapy (CF-RT) for breast cancer. Methods: Breast cancer patients after breast surgery were randomized into the HF-RT group (40.05 Gy/15Fx) or CF-RT group (50 Gy/25Fx). Acute toxicity was assessed with the Common Terminology Criteria for Adverse Events (CTCAE) V.3.0 scale. Cosmetic outcome was assessed using the Harvard scale. Findings: There were 400 and 401 patients enrolled in HF-RT and CF-RT group, respectively. No significant differences were observed in clinical pathological factors between two groups. Protocol compliances were above 90% for targets coverage and OARs constraints in both groups. No significant difference between the two groups in proportion of ≥ grade 2 any acute toxicity (p=0.34). Dermatitis was the most common acute toxicity with a significantly higher incidence in the CF-RT group than the HF-RT group (≥ grade 2: 6.7% vs. 3.3%, p=0.02). There were no significant differences in the incidence of other acute toxicities, including radiation-induced fatigue, radiation pneumonitis, breast pain, dysphagia and breast edema, and the proportion of good or excellent cosmesis in breast conservative patients between the two groups. Interpretation: This early analysis demonstrated that HF-RT with RNI is associated with comparable acute toxicities and cosmesis results compared with CF-RT. Additional follow-up is needed to assess the long-term safety and efficacy.

PURPOSE:The multicenter, single-arm, phase 2 SHIFT trial evaluated an ultra-hypofractionated radiation therapy regimen that completes both whole breast irradiation and a sequential tumor bed boost within 1.5 weeks, with the primary endpoint of acute toxicity. METHODS AND MATERIALS:Patients at 4 tertiary hospitals in China aged 18 years or above with invasive breast carcinoma (pT1-3, N0-1mic, M0) or ductal carcinoma in situ after BCS were eligible. All enrolled patients underwent whole breast irradiation of 26 Gy in 5 fractions over 5 days. A sequential tumor bed boost of 10.4 Gy in 2 fractions over 2 days was at the discretion of the radiation oncologist. The primary endpoint was the incidence of grade ≥2 acute radiation-induced toxicity within 6 months after RT, including fatigue, dermatitis, and breast pain. This trial is registered at ClinicalTrials.gov (NCT04926766). RESULTS:Between January 2021 and July 2023, recruitment of 217 patients has been completed, of whom 209 received tumor bed boost. Within 6 months after RT, 157 (72.4%) patients experienced G1 acute toxicity only, 16 (7.4%) patients experienced G2 acute toxicity, with no G3 events observed. No toxicity event was reported in 44 (20.3%) patients. At a median follow-up of 28.3 months, no severe toxicities were found in any patient at any time during follow-up. No locoregional recurrence, distant metastasis, or death occurred. Dosimetric analysis demonstrated high protocol compliance across all centers. CONCLUSIONS:The integrated ultra-hypofractionated radiation therapy regimen is well-tolerated, with acute toxicity profiles confirming its favorable safety profile. Long-term follow-up is ongoing to assess late effects and efficacy.

Background and purpose:Pelvic radiotherapy-induced bone marrow (BM) damage adversely affects patient prognosis. Progress in BM-sparing radiotherapy is limited by the lack of standardized BM quantification and the inherent constraints of magnetic resonance spectroscopy (MRS), the current gold standard for BM magnetic resonance imaging (MRI). Proton density fat fraction (PDFF), derived from DIXON-based MRI, has emerged as an imaging biomarker for detecting BM changes. This study evaluated the potential of DIXON-based MRI in pelvic BM for radiotherapy. Materials and methods:Three existing DIXON-based techniques were optimized and compared to establish clinical protocols. In vitro measurements were performed using fat phantoms calibrated against thermogravimetric analysis, while in vivo measurements were based on data from 30 volunteers with MRS serving as the reference standard. Quantitative accuracy was assessed using mean absolute error (MAE), repeatability via intra-class correlation coefficients (ICCs), and image quality using an ACR phantom. Results:Comprehensive evaluation identified optimal parameters for each DIXON-based sequence. For in vitro measurements, the MAE for MRS was 3.5 % and the highest MAE across three optimized DIXON-based sequences was 5.9 %. For in vivo measurements, linear regressions between MRS and each of the optimized DIXON-based sequence resulted in R2 ≥ 0.93 and MAE ≤ 7.6 %. All three optimized DIXON-based sequences demonstrated high repeatability (ICCs ≥ 0.97) and clearly visualized BM with varying fat fractions, with no consistently outperforming in image quality. Conclusion:For BM assessment, this study demonstrated DIXON-based PDFF quantification achieved high accuracy, repeatability, and image quality, supporting its potential for radiotherapy.

Osteosarcoma (OS) is the most frequent primary bone sarcomas with high recurrence and poor prognosis. Emerging evidence indicates that membraneless organelles stress granules (SGs), whose assemblies are driven by scaffold protein G3BP1, are extensively involved in tumor, especially in OS. However, how SGs behave and communicate with organelles, particularly nucleoli and mitochondria, during drug challenges remain unknown. This study revealed that chemotherapeutic drugs activated the cysteine protease asparagine endopeptidase (AEP) to specifically cleave the SG core protein G3BP1 at N258/N309 in OS and malignant glioma. tG3BP1-Ns modulated SG dynamics by competitively binding to full-length G3BP1. Strikingly, tG3BP1-Cs, containing a conserved RNA recognition motif CCUBSCUS, sequestered mRNAs of ribosomal proteins and oxidative phosphorylation genes in the nucleoli and mitochondria to repress translation and oxidative stress. Moreover, the inhibition of AEP promoted the tumor-suppressing effect of chemotherapeutic drugs, whereas AEP-cleaved G3BP1 rescue reversed the effect in both OS and glioma models. Cancerous tissues exhibited high levels of AEP and G3BP1 truncations, which were strongly associated with poor prognosis. Accordingly, this study proposed a new paradigm and potential therapeutic targets to address chemotherapy sensitivity conferred by AEP-cleaved G3BP1-mediated SGs/nucleoli/mitochondria coordination.

INTRODUCTION:Shortening the duration of postoperative radiotherapy (RT) for breast cancer while maintaining efficacy and safety has become a significant trend. The 3-week regimen of 40-42.5 Gy in 15-16 fractions is now a preferred option in clinical practice. Following the publication of the 5-year outcomes from the Fast-Forward trial, interest in 1-week regimens has surged, prompting the initiation of multiple studies. However, trials exploring the 1-week regimen for regional nodal irradiation (RNI), especially involving internal mammary nodes (IMN), remain scarce. Additionally, the optimal fractionation scheme for tumour bed boost in the era of ultra-hypofractionated regimens is still debated. To address these gaps, we initiated the adjuvant regional nodal radiation therapy for one week in breast cancer (ARROW) trial to evaluate the feasibility of a 1-week regimen for RNI of 26 Gy in five fractions, with optional sequential tumour bed boost of 10.4 Gy in two fractions. The findings from our trial are expected to extend the application of ultra-hypofractionated regimens to include sequential tumour bed boosts and RNI, pioneering its use in IMN irradiation. METHODS AND ANALYSIS:The ARROW trial is an open-label, single-arm, multicentre phase II trial, encompassing four teaching hospitals in China. Enrolled patients will receive a total of 26 Gy in five fractions to ipsilateral whole breast/chest wall and regional regions, including supraclavicular/infraclavicular nodes, IMN and any portion of the undissected axilla deemed at risk. A sequential tumour bed boost of 10.4 Gy in two fractions is delivered in patients at high risk for recurrence, which is at the discretion of the radiation oncologist. The sample size for the ARROW trial was 197 patients. Both intensity-modulated radiation therapy and proton therapy are permitted. The primary endpoint is acute radiation-induced toxicity, graded according to Radiation Therapy Oncology Group (RTOG) criteria and CTCAE V.3.0. Secondary endpoints include cosmetic outcomes for breast-conserving surgery, late radiation-induced toxicity, local regional recurrence, distant metastasis, invasive tumour-free survival, overall survival and quality-of-life assessment. ETHICS AND DISSEMINATION:The trial has been approved by the Ethical Committee of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, as well as approvals from the ethical committees of each participating centre have also been obtained. Research findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER:ARROW trial: NCT04509648.

To investigate the early predictive value of dynamic magnetic resonance imaging (MRI)-based radiomics for progression and prognosis in locally advanced cervical cancer (LACC) patients treated with concurrent chemoradiotherapy (CCRT). A total of 111 LACC patients (training set: 88; test set: 23) were retrospectively enrolled. Dynamic MR images were acquired at baseline (MRIpre), before brachytherapy delivery (MRImid) and at each follow-up visit. Clinical characteristics, 2-year progression-free survival (PFS), and 2-year overall survival (OS) were evaluated. The least absolute shrinkage and selection operator (LASSO) method was applied to extract features from MR images as well as from clinical characteristics. The support vector machine (SVM) model was trained on the training set and then evaluated on the test set. Compared with single-sequence models, multisequence models exhibited superior performance. MRImid-based radiomics models performed better in predicting the prognosis of LACC patients than the post-treatment did. The MRIpre-, MRImid- and the ΔMRImid (variations in radiomics features from MRIpre and MRImid) -based radiomics models achieve AUC scores of 0.723, 0.750 and 0.759 for 2-year PFS and 0.711, 0.737 and 0.789 for 2-year OS in the test set. When combined with the clinical characteristics, the ΔMRImid-based predictive model also performed better than the other models did, with an AUC of 0.812 for progression and 0.868 for survival. We built machine learning models from dynamic features in longitudinal images and found that the ΔMRImid-based model can serve as a non-invasive indicator for the early prediction of prognosis in LACC patients receiving CCRT. The integrated models with clinical characteristics further enhanced the predictive performance.

To evaluate the advantage of the manual adaptive plans comparing to the scheduled plans, and explored clinical factors predicting patients suitable for adaptive strategy. Eighty two patients with weekly online cone-beam computed tomography (CBCT) were enrolled. The re-CT simulation was performed after 15 fractions and a manual adaptive plan was developed if a significant deviation of the planning target volume (PTV) was found. To evaluate the dosimetric benefit, D98, homogeneity index (HI) and conformity index (CI) for the planning target volume (PTV), as well as D2cc of the bowel, bladder, sigmoid and rectum were compared between manual adaptive plans and scheduled ones. The clinical factors influencing target motion during radiotherapy were analyzed by chi-square test and logistic regression analysis. The CI and HI of the manual adaptive plans were significantly superior to the scheduled ones (P = 0.0002, 0.003, respectively), demonstrating a better dose coverage of the target volume. Compared to the scheduled plans, D98 of the manual adaptive plans increased by 3.3

This phase I/II trial (ChiCTR2000032879) assessed the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma. Twenty-two patients, regardless of their programmed death ligand-1 (PD-L1) status, received toripalimab combined with concurrent chemoradiotherapy (CCRT). CCRT included cisplatin (40 mg/m2, once weekly for 5 weeks), radiotherapy (45–50.4 Gy/25–28 Fx, 5 fractions weekly), followed by brachytherapy (24–30 Gy/3–5 Fx) and toripalimab (240 mg, intravenous) on days 1, 22 and 43 during CCRT. The primary endpoints were safety and 2-year progression-free survival (PFS). The secondary endpoints included 2-year local control (LC), local regional control and overall survival (OS). All patients successfully completed CCRT and toripalimab treatment. Grade III and higher adverse events (AEs) were observed in 11 patients (11/22, 50

Oxygen and nutrient deprivation are common features of solid tumors. Although abnormal alternative splicing (AS) has been found to be an important driving force in tumor pathogenesis and progression, the regulatory mechanisms of AS that underly the adaptation of cancer cells to harsh microenvironments remain unclear. Here, we found that hypoxia- and nutrient deprivation-induced asparagine endopeptidase (AEP) specifically cleaved DDX3X in a HIF1A-dependent manner. This cleavage yields truncated carboxyl-terminal DDX3X (tDDX3X-C), which translocates and aggregates in the nucleus. Unlike intact DDX3X, nuclear tDDX3X-C complexes with an array of splicing factors and induces AS events of many pre-mRNAs; for example, enhanced exon skipping (ES) in exon 2 of the classic tumor suppressor PRDM2 leads to a frameshift mutation of PRDM2. Intriguingly, the isoform ARRB1-Δexon 13 binds to glycolytic enzymes and regulates glycolysis. By utilizing in vitro assays, glioblastoma organoids, and animal models, we revealed that AEP/tDDX3X-C promoted tumor malignancy via these isoforms. More importantly, high AEP/tDDX3X-C/ARRB1-Δexon 13 in cancerous tissues was tightly associated with poor patient prognosis. Overall, our discovery of the effect of AEP-cleaved DDX3X switching on alternative RNA splicing events identifies a mechanism in which cancer cells adapt to oxygen and nutrient shortages and provides potential diagnostic and/or therapeutic targets.

BackgroundThe purpose of this real-world study was to investigate the risk factors for developing recurrence among patients with pathological T1-3N0 breast cancer (BC) treated with breast-conserving surgery (BCS) followed by whole breast irradiation alone (WBI) and identify those clinically high-risk BCs who could benefit from regional nodal irradiation (RNI).Materials and methodsFemale BC patients treated at Shanghai Ruijin hospital from 2009 to 2016 were retrospectively reviewed. The disease-free survival (DFS), breast cancer specific survival (BCSS) and overall survival (OS) were estimated by the Kaplan-Meier method, and survival differences were compared with the log-rank test. Univariate and multivariate analysis was performed using Cox proportional hazards regression analysis. An external validation was conducted by using SEER database.ResultsA total of 622 BC patients treated with BCS+WBI alone were included. With a median follow-up of 82 months, the 7-year OS, BCSS and DFS for the entire cohort was 97%, 99% and 91%, respectively. Multivariable Cox analysis indicated that tumor size (p=0.006), tumor location (p=0.033), lymphovascular invasion (LVI) status (p=0.0028) and Ki-67 index (p=0.051) were independent risk factors for DFS. A scoring system was developed using these four factors and the 7-year DFS and OS were 97% and 96% for patients with 0-1 risk factors, 95% and 82% for patients with ≥2 risk factors (p<0.0001 for DFS, and p=0.0063 for OS). Based on tumor size and tumor location, an external validation by demonstrated that the 7-year OS was 90% and 88% for patients with 0-1 risk factor, which was significantly better than those defined as high-risk BC patients (82%, p<0.0001).ConclusionBy using our institute database, we establish a risk stratification system for identifying sub-group of pN0 BC patients, who are at high risk for developing recurrence. The results of our study support tailored RT decision-making according to individual risks, which needed to be confirmed in further studies.

BACKGROUND:The immune milieu of colorectal cancer is a complex phenomenon. It is imperative to investigate the crucial immune factors that promote the progression of colorectal cancer. Immune suppressor cells are granulocytic myeloid-derived suppressor cells (G-MDSCs). However, they also increased cancer growth in other ways that need to be investigated further. METHODS:Using flow cytometry, we isolated G-MDSCs from colorectal cancer tissues. Ultracentrifugation was used to separate exosomes from the supernatant of G-MDSCs, and western blotting, transmission electron microscopy (TEM), and flow cytometry were used to confirm their presence. RNA sequencing was used to identify unique miRNAs and transcripts, which were subsequently confirmed by RT-qPCR (real-time quantitative real-time PCR). The CCK-8 test was used to determine the rate of proliferation. Lentiviral vectors were employed to manipulate the expression of miRNAs and genes in order to investigate their role in the development of colorectal cancer. RESULTS:Colorectal cancer tissues have been found to contain granulocyte-myeloid-derived suppressor cells (G-MDSCs) that secrete exosomes. These exosomes have been shown to accelerate cancer progression by promoting cell proliferation. Further research has identified microRNA-166-5p as a target from G-MDSC-derived exosomes. This downregulation leads to the inhibition of integral membrane protein 2B (ITM3E) transcription, which in turn activates the PI3K/Akt signaling pathway. This pathway promotes cell proliferation and can be inhibited using deguelin. The accelerated development of colorectal cancer has been further confirmed in mice models. CONCLUSION:The primary results of this work show that exosomes produced from G-MDSCs and the miR-166-5p/ITM3E axis have therapeutic and diagnostic promise in colorectal cancer.

Abstract Background Currently, the standard treatment for locally advanced cervical cancer is concurrent chemoradiation (CCRT). Forty percent of patients present with disease recurrence. This study aims to investigate the feasibility, safety and efficacy of neoadjuvant chemotherapy (NACT) with weekly cisplatin and paclitaxel (TP) followed by CCRT. Methods We are conducting a phase III trial comparing the efficacy and side effects of patients with cervical cancer (FIGO 2018 stage IIB to IVA) who were assigned to four cycles of NACT with cisplatin (40 mg/m2) and paclitaxel (60 mg/m2) weekly followed by CCRT or CCRT alone. In this report, we studied the medium-term effect of 50 patients enrolled in the NACT + CCRT arm. The primary endpoints were the response rate post-NACT and 12 weeks post-CCRT evaluated by MR/CT based on RECIST v 1.1. The secondary endpoints were 3-year OS (overall survival) and PFS (progression-free survival) measured by the Kaplan–Meier method. Results Among 50 patients enrolled in the NACT + CCRT arm, the complete and partial response rates were 10.4% and 68.8%, post-NACT. Twelve weeks after treatment completion, the complete response rate was 72.0%, whereas the total response rate (complete and partial response) was 90.0%. After a median follow-up of 28 months, the 3-year OS rate was 83.9%, and the 3-year PFS rate was 73.6%. NACT response was related to superior PFS and OS compared with NACT nonresponse (P < 0.01). Late AEs were exiguous, while early AEs mainly included myelosuppression and gastrointestinal AEs. Conclusions This study showed a good response rate achieved by dose-dense weekly cisplatin and paclitaxel followed by standard CCRT. The treatment regimen is feasible, as evidenced by the acceptable toxicity of NACT and by the high compliance with radiotherapy. Trial registration Protocol version number and date. Chinese clinical trial registry, ChiCTR1900025327; http://www.chictr.org.cn . Registered 24 August 2019. Retrospectively registered, medresman.org.cn/ChiCTR1900025326. The date recruitment began 01–01-2019.

Introduction:Pancreatic cancer is one of the most common malignant tumors and is characterized by high malignancy, occult incidence and poor prognosis. Traditional chemotherapy drugs have limited efficacy and strong side effects. Therefore, there is an urgent need for a better treatment of the malignancy.Methods:The prepared arginine glycine peptide (RGD)-human serum albumin (HSA)-Gemcitabine (GEM)/Curcumin (CUR) nanoparticles (NPs) were characterized for physicochemical properties, stability and in vitro release. Comparisons of HSA-GEM/CUR NPs and RGD-HSA-GEM/CUR NPs regarding tissue distributions and pharmacodynamics were also carried out using mice as the animal models.Results:Transmission electron micrographs showed that RGD peptide-conjugated HSA-NPs had an irregular surface, good dispersion (PDI=0.139±0.03) and a uniform size distribution (Mean PS=115.6±5.7 nm). The ζ-potential was -17.3 mV. As regards in vitro release, non RGD modified NPs showed a faster release rate in 24 hours, yielding a release amount of 75% for GEM and 72% for CUR. RGD-HSA-GEM/CUR NPs exhibited 67% of accumulated release of GEM (63% for CUR) in 24 hours. This may be due to the HSA chain covering the surface of NPs, which hindered the drug release. The cytotoxicity of GEM/CUR co-loaded NPs was significantly higher than that of single-drug NPs (P < 0.05). In vivo study results indicated that RGD-HSA-GEM/CUR NPs had notable targeting effect on subcutaneous tumors, with a potential to actively deliver drugs to tumor tissues.Conclusion:In this study, we prepared RGD-HSA-GEM/CUR NPs that had both good water solubility and tumor-targeting property. The results also showed that the RGD modified NPs had advantages in increasing GEM/CUR concentration at tumor sites and reducing its distribution in peripheral organs.

Introduction Short course regimen has become the major trend in the field of adjuvant radiotherapy for patients with breast cancer. Hypofractionated radiotherapy (HF-RT) regimen of 40–42.5 Gy in 15–16 fractions has been established as a preferred option for whole breast irradiation. However, few evidences of hypofractionated regional nodal irradiation (RNI), especially involving internal mammary nodes (IMNs), could be available during the era of intensity-modulated radiation therapy (IMRT). Against this background, we design this trial to explore the hypothesis that HF-RT regimen involving RNI (including infraclavicular, supraclavicular nodes and IMNs) will be non-inferior to a standard schedule by using IMRT technique.Methods and analysis This is an open-label randomised, non-inferior, multicentre phase III trial. Patients with breast cancer with an indication for RNI after breast conserving surgery or mastectomy are randomised at a ratio of 1:1 into the following two groups: hypofractionated regimen of 2.67 Gy for 16 fractions or conventional regimen of 2 Gy for 25 fractions. The dose was prescribed to ipsilateral chest wall or whole breast and RNI (including infraclavicular, supraclavicular nodes and IMNs, lower axilla if indicated). The trial plans to enrol a total of 801 patients and all patients will be treated using IMRT technique. The primary endpoint is 5-year locoregional recurrence. The secondary endpoints include 5-year distant metastasis free survival, invasive recurrence-free survival, overall survival, accumulative acute radiation-induced toxicity and accumulative late radiation-induced toxicity, cosmetic outcomes and quality of life.Ethics and dissemination The study has been approved by the Ethical Committee of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine (version 2018-95-3) and approvals from ethical committee of each participating centre have also been obtained. Research findings will be submitted for publication in peer-reviewed journals.Trial registration number NCT03829553.

Background Since the publication of MA-20 and EORTC-22922 trials, chest wall (CW)/ whole breast (WB) irradiation + comprehensive regional nodal irradiation (RNI) with internal mammary node irradiation (IMNI) has been the standard adjuvant treatment for early-stage breast cancer (BC). However, one size does not fit all BC, and the risk of recurrence significantly varies among this patient population. In addition, whether all BC patients presented with one to three positive lymph nodes (pN1) could benefit from IMNI remains controversial. Thus, the optimal adjuvant RNI volume for early-stage BC with T1-2N1 remains undetermined. Methods The IMNI PRECISION trial is a single institute, open-labeled, non-inferior, randomized controlled trial. A total of 214 clinically “high risk” BC patients which is characterized as having at least two of the five clinically adverse factors (age ≤ 40, three positive LN, T2 stage, grade 3 and Ki-67 index ≥ 14%), but genomic score “low risk” (the genomic score ≤ 44) N1 breast cancers are randomly assigned to omitting IMNI group (experimental group) or with IMNI (control group) with a 1:1 ratio. The primary endpoint of this trial is event-free survival, and secondary endpoints include overall survival and locoregional recurrence-free survival. Discussion The IMNI PRECISION design allows promising clinical-genomic model to stratify the individualized risk of developing recurrence and guides the optimal RNI treatment for early-stage (pT1-2N1) BC patients. We anticipate that our results would provide high-level evidence to tailor IMNI according to individualized recurrence risk of BC. Trial registration ClinicalTrials.gov Identifier NCT04517266 . Date of registration: August 18, 2020. Status: Recruiting.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a type of rare and distinct entity of non-Hodgkin lymphoma with poor prognosis. It is important to evaluate the early treatment response accurately to decide further treatment strategy. 18F-FDG PET/CT plays an important role in response evaluation and prognostic prediction in some kinds of lymphomas. However, data available regarding patients with ENKTL are limited. Thus, in this prospective study, we analyzed the prognostic value of 18F-FDG PET/CT in ENKTL. Thirty-four patients with newly diagnosed ENKTL were enrolled in this phase 2 study (NCT02825147, July 7, 2016). The patients received pre-, mid-, and end-treatment 18F-FDG PET/CT scans. Deauville score (DS), maximal standardized uptake values (SUVmax), and the change in SUVmax (ΔSUVmax) were recorded for response assessment. The median follow-up period was 42.2 months. The 2-year overall survival (OS) and progression-free survival (PFS) were 82.4% and 73.5%, respectively. Univariate analysis revealed that Ann Arbor stage (P < 0.002), mid-treatment DS (P = 0.005), mid-SUVmax (P = 0.001), mid-∆SUVmax (P = 0.004), end-treatment DS (P < 0.001), and end-SUVmax (P = 0.014) were prognostic factors for OS. Ann Arbor stage (P = 0.001), mid-treatment DS (P = 0.008), mid-SUVmax (P = 0.029), mid-∆SUVmax (P < 0.001), and end-treatment DS (P =0.021) were of prognostic significance for PFS. Multivariate analysis showed that mid-SUVmax (P = 0.042) and DS at the middle (P = 0.050) and end (P = 0.044) of treatment were significant independent predictors of PFS. 18F-FDG PET/CT is useful for predicting the prognosis of ENKTL.

ObjectiveTo explore the suitable cases for vaginal cuff brachytherapy (VCB) combined with external beam radiation therapy (EBRT) in the postoperative treatment of cervical cancer.MethodsWe retrospectively analyzed the clinical data of 214 postoperative cervical cancer patients who received radiotherapy from January 2008 to December 2015. Among them, 146 patients received postoperative EBRT, 68 received EBRT plus VCB. There was no statistical difference in clinical and pathological characteristics between these two groups. Those who with negative vaginal cuff underwent supplemented 12–18 Gy/2–3 Fx VCB. Survival analyses were performed using Kaplan–Meier method, and Cox model was used to analyze prognostic factors.ResultsThe median follow-up was 52 months (9–136 months), and 4-year RFS (recurrence-free survival) was 77%. Among them, 58 patients (27.10%) had local or distant recurrences, 29 (13.55%) in pelvis, six (2.80%) with metastases to para-aortic, 19 (8.88%) with distant metastases (including inguinal lymph nodes) and four (1.87%) with both local and distant recurrences. The postoperative brachytherapy boost did not improve RFS or OS (overall survival) among the investigated subjects, P = 0.77, P = 0.99, respectively. Neither it decreased the local relapse in the pelvis or vaginal cuff, P = 0.56, P = 0.59. Subgroup analyses showed that brachytherapy boost improved RFS in patients who had bulky mass (>4 cm) as well as 1) with deep stromal invasion (>50% stromal invasion), P = 0.012 or 2) received low EBRT dose (≤45 Gy), P = 0.033, and in patients with deep stromal invasion as well as received low EBRT dose (P = 0.018).ConclusionsWe first proposed the case selection model for postoperative EBRT plus VCB. Brachytherapy boost were considered in the setting of postoperative radiotherapy if the patients had at least two out of these following factors: bulky mass, deep stromal invasion and low EBRT dose.

The presence of hypoxia in solid tumors is considered one of the major factors that contribute to radiation resistance. The aim of the present study was to establish a therapeutic system, which can be controlled by radiation itself, to enhance radiosensitivity. For this purpose, a lentiviral gene therapy vector containing the human inhibitor of growth 4 (ING4) and its upstream promoter, human early growth response factor-1 (EGR1), which possesses the radiation-inducible characteristics to activate the transcription of its downstream genes, was constructed. Downstream fluorescence proteins were investigated to ensure that the EGR1 promoter was induced by irradiation. Furthermore, ING4 open reading frame (ORF) expression was detected by western blotting. The cell cycle was analyzed by fluorescence-activated cell sorting analysis 48 h after the cells were exposed to X-rays ranging between 0 and 8 Gy. In cells stably and transiently transfected with reporter plasmids, the EGR1-driver gene was sensitive to ionizing irradiation. Furthermore, irradiation-induced ING4 gene expression was observed. The enhanced ING4 expression increased the number of cells in the G2/M phase and decreased the proportion of cells in the G1/S phase. Therefore, ING4 expression inhibited cell proliferation and was associated with less colonies being formed. Furthermore, ING4 suppressed hypoxia-inducible factor 1α expression under hypoxic conditions and promoted cell apoptosis. Overall, these results revealed that combining the EGR1 promoter and ING4 ORF using a lentivirus system may be a promising therapeutic strategy with which to enhance radiosensitivity controlled by radiation. However, further studies using in vivo models are required to confirm these findings.