Summary Background Definitive chemoradiotherapy is a curative treatment option for oesophageal carcinoma, especially in patients unsuitable for surgery. The PRODIGE5/ACCORD17 trial aimed to assess ...the efficacy and safety of the FOLFOX treatment regimen (fluorouracil plus leucovorin and oxaliplatin) versus fluorouracil and cisplatin as part of chemoradiotherapy in patients with localised oesophageal cancer. Methods We did a multicentre, randomised, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 24 centres in France between Oct 15, 2004, and Aug 25, 2011. Eligible participants had confirmed stage I–IVA oesophageal carcinoma (adenocarcinoma, squamous-cell, or adenosquamous), Eastern Cooperative Oncology Group (ECOG) status 0–2, sufficient caloric intake, adequate haematological, renal, and hepatic function, and had been selected to receive definitive chemoradiotherapy. Patients were randomly assigned (1:1) to receive either six cycles (three concomitant to radiotherapy) of oxaliplatin 85 mg/m2 , leucovorin 200 mg/m2 , bolus fluorouracil 400 mg/m2 , and infusional fluorouracil 1600 mg/m2 (FOLFOX) over 46 h, or four cycles (two concomitant to radiotherapy) of fluorouracil 1000 mg/m2 per day for 4 days and cisplatin 75 mg/m2 on day 1. Both groups also received 50 Gy radiotherapy in 25 fractions (five fractions per week). Random allocation to treatment groups was done by a central computerised randomisation procedure by minimisation, stratified by centre, histology, weight loss, and ECOG status, and was achieved independently from the study investigators. The primary endpoint was progression-free survival. Data analysis was primarily done by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00861094. Findings 134 participants were randomly allocated to the FOLFOX group and 133 to the fluorouracil and cisplatin group (intention-to-treat population), and 131 patients in the FOLFOX group and 128 in the fluorouracil and cisplatin group actually received the study drugs (safety population). Median follow-up was 25·3 months (IQR 15·9–36·4). Median progression-free survival was 9·7 months (95% CI 8·1–14·5) in the FOLFOX group and 9·4 months (8·1–10·6) in the fluorouracil and cisplatin group (HR 0·93, 95% CI 0·70–1·24; p=0·64). One toxic death occurred in the FOLFOX group and six in the fluorouracil–cisplatin group (p=0·066). No significant differences were recorded in the rates of most frequent grade 3 or 4 adverse events between the treatment groups. Of all-grade adverse events that occurred in 5% or more of patients, paraesthesia (61 47% events in 131 patients in the FOLFOX group vs three 2% in 128 patients in the cisplatin–fluorouracil group, p<0·0001), sensory neuropathy (24 18% vs one 1%, p<0·0001), increases in aspartate aminotransferase concentrations (14 11% vs two 2%, p=0·002), and increases in alanine aminotransferase concentrations (11 8% vs two 2%, p=0·012) were more common in the FOLFOX group, whereas serum creatinine increases (four 3% vs 15 12%, p=0·007), mucositis (35 27% vs 41 32%, p=0·011), and alopecia (two 2% vs 12 9%, p=0·005) were more common in the fluorouracil and cisplatin group. Interpretation Although chemoradiotherapy with FOLFOX did not increase progression-free survival compared with chemoradiotherapy with fluorouracil and cisplatin, FOLFOX might be a more convenient option for patients with localised oesophageal cancer unsuitable for surgery. Funding UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer.
Abstract
We aimed to evaluate the impact of prostate-specific membrane antigen ligand labelled with gallium-68 (PSMA-11) PET/CT in restaging patients with castration-resistant nonmetastatic prostate ...cancer (PCa). Thirty patients were included. At least one malignant focus was found in 27/30 patients (90%). The PSMA-11 PET/CT positivity rate in patients whose prostate-specific antigen serum level (PSA) was greater than 2 ng/ml was 100% (20/20), significantly superior to that of patients whose PSA was less than 2 ng/ml (7/10 = 70%). Six patients (20%) were categorized as oligometastatic (≤3 metastatic foci). Based on the 17 patients for whom a standard of truth was feasible, the overall sensitivity and specificity of PSMA-11 PET/CT in detecting residual disease in castration-resistant PCa patients were 87% and 100% respectively. PSMA-11 PET/CT impacted patients’ disease management in 70% of cases, 60% of case when PSA was less than 2 ng/ml. This management was considered as adequate in 91% of patients. PSMA-11 PET/CT appeared to be effective in restaging patients with castration-resistant nonmetastatic PCa. PSMA-11 PET/CT should be considered as a replacement for bone scans under these conditions.
Purpose
To achieve accurate image segmentation, which is the first critical step in medical image analysis and interventions, using deep neural networks seems a promising approach provided ...sufficiently large and diverse annotated data from experts. However, annotated datasets are often limited because it is prone to variations in acquisition parameters and require high-level expert’s knowledge, and manually labeling targets by tracing their contour is often laborious. Developing fast, interactive, and weakly supervised deep learning methods is thus highly desirable.
Methods
We propose a new efficient deep learning method to accurately segment targets from images while generating an annotated dataset for deep learning methods. It involves a generative neural network-based prior-knowledge prediction from pseudo-contour landmarks. The predicted prior knowledge (i.e., contour proposal) is then refined using a convolutional neural network that leverages the information from the predicted prior knowledge and the raw input image. Our method was evaluated on a clinical database of 145 intraoperative ultrasound and 78 postoperative CT images of image-guided prostate brachytherapy. It was also evaluated on a cardiac multi-structure segmentation from 450 2D echocardiographic images.
Results
Experimental results show that our model can segment the prostate clinical target volume in 0.499 s (i.e., 7.79 milliseconds per image) with an average Dice coefficient of 96.9 ± 0.9% and 95.4 ± 0.9%, 3D Hausdorff distance of 4.25 ± 4.58 and 5.17 ± 1.41 mm, and volumetric overlap ratio of 93.9 ± 1.80% and 91.3 ± 1.70 from TRUS and CT images, respectively. It also yielded an average Dice coefficient of 96.3 ± 1.3% on echocardiographic images.
Conclusions
We proposed and evaluated a fast, interactive deep learning method for accurate medical image segmentation. Moreover, our approach has the potential to solve the bottleneck of deep learning methods in adapting to inter-clinical variations and speed up the annotation processes.
Purpose
This paper addresses the detection of the clinical target volume (CTV) in transrectal ultrasound (TRUS) image-guided intraoperative for permanent prostate brachytherapy. Developing a robust ...and automatic method to detect the CTV on intraoperative TRUS images is clinically important to have faster and reproducible interventions that can benefit both the clinical workflow and patient health.
Methods
We present a multi-task deep learning method for an automatic prostate CTV boundary detection in intraoperative TRUS images by leveraging both the low-level and high-level (prior shape) information. Our method includes a channel-wise feature calibration strategy for low-level feature extraction and learning-based prior knowledge modeling for prostate CTV shape reconstruction. It employs CTV shape reconstruction from automatically sampled boundary surface coordinates (pseudo-landmarks) to detect the low-contrast and noisy regions across the prostate boundary, while being less biased from shadowing, inherent speckles, and artifact signals from the needle and implanted radioactive seeds.
Results
The proposed method was evaluated on a clinical database of 145 patients who underwent permanent prostate brachytherapy under TRUS guidance. Our method achieved a mean accuracy of
0.96
±
0.01
and a mean surface distance error of
0.10
±
0.06
mm
. Extensive ablation and comparison studies show that our method outperformed previous deep learning-based methods by more than 7% for the Dice similarity coefficient and 6.9 mm reduced 3D Hausdorff distance error.
Conclusion
Our study demonstrates the potential of shape model-based deep learning methods for an efficient and accurate CTV segmentation in an ultrasound-guided intervention. Moreover, learning both low-level features and prior shape knowledge with channel-wise feature calibration can significantly improve the performance of deep learning methods in medical image segmentation.
The development of innovative approaches that would reduce the sensitivity of healthy tissues to irradiation while maintaining the efficacy of the treatment on the tumor is of crucial importance for ...the progress of the efficacy of radiotherapy. Recent methodological developments and innovations, such as scanned beams, ultra-high dose rates, and very high-energy electrons, which may be simultaneously available on new accelerators, would allow for possible radiobiological advantages of very short pulses of ultra-high dose rate (FLASH) therapy for radiation therapy to be considered. In particular, very high-energy electron (VHEE) radiotherapy, in the energy range of 100 to 250 MeV, first proposed in the 2000s, would be particularly interesting both from a ballistic and biological point of view for the establishment of this new type of irradiation technique. In this review, we examine and summarize the current knowledge on VHEE radiotherapy and provide a synthesis of the studies that have been published on various experimental and simulation works. We will also consider the potential for VHEE therapy to be translated into clinical contexts.
Immunological tolerance is maintained by specialized subsets of T cells including CD4(+)CD25(+)FOXP3(+) regulatory cells (Treg). Previous studies established that Treg thymic differentiation or ...peripheral conversion depend on CD28 and Lck signaling. Moreover, foxp3 gene transfer in murine CD4(+)CD25(-) T lymphocytes results in the acquisition of suppressive functions. However, molecular pathways leading to FOXP3 expression remain to be described. In this study, we investigated the molecular events driving FOXP3 expression. We demonstrated that CD28 activation in CD4(+)CD25(-) T lymphocytes leads to STAT3 Tyr(705) phosphorylation in an Lck-dependent manner. STAT3 neutralization during naive peripheral CD4(+)CD25(-) T cell conversion into Treg through costimulation with TCR/CD28 and TGF-beta1, decreased FOXP3 expression, prevented the acquisition of suppressive functions and restored the ability of the converted lymphocytes to produce IL-2 and IFN-gamma. Furthermore, we observed that STAT3 ablation using small interfering RNA strategies inhibited FOXP3 expression and suppressive functions among naturally differentiated CD4(+)CD25(+) T lymphocytes, suggesting a direct role of STAT3 in Treg phenotype and function maintenance. CD4(+)CD25(+) T lymphocytes transduced with specific STAT3 small interfering RNA were devoid of suppressive functions and failed to control the occurrence of acute graft-vs-host disease. Finally, STAT3 inhibition in CD4(+) lymphocytes enhanced the anti-tumor immunity conferred by a lymphocyte adoptive transfer. In summary, our findings determine that STAT3 is critical in the molecular pathway required for FOXP3 expression. STAT3 modulation should be taken into account when assessing how regulatory T cells contribute to inflammatory diseases and tumor immunosurveillance.
Stereotactic body radiation therapy (SBRT) has become a valid option for the treatment of low- and intermediate-risk prostate cancer. In randomized trials, it was found not inferior to conventionally ...fractionated external beam radiation therapy (EBRT). It also compares favorably to brachytherapy (BT) even if level 1 evidence is lacking. However, BT remains a strong competitor, especially for young patients, as series with 10-15 years of median follow-up have proven its efficacy over time. SBRT will thus have to confirm its effectiveness over the long-term as well. SBRT has the advantage over BT of less acute urinary toxicity and, more hypothetically, less sexual impairment. Data are limited regarding SBRT for high-risk disease while BT, as a boost after EBRT, has demonstrated superiority against EBRT alone in randomized trials. However, patients should be informed of significant urinary toxicity. SBRT is under investigation in strategies of treatment intensification such as combination of EBRT plus SBRT boost or focal dose escalation to the tumor site within the prostate. Our goal was to examine respective levels of evidence of SBRT and BT for the treatment of localized prostate cancer in terms of oncologic outcomes, toxicity and quality of life, and to discuss strategies of treatment intensification.
Purpose
To evaluate whether radiomics from 18F-FDG PET and/or MRI before re-irradiation (reRT) of recurrent head and neck cancer (HNC) could predict the occurrence and the location “in-field” or ...“outside” of a second locoregional recurrence (LR).
Methods
Among the 55 patients re-irradiated at curative intend for HNC from 2012 to 2019, 48 had an MRI and/or PET before the start of the reRT. Thirty-nine radiomic features (RF) were extracted from the re-irradiated GTV (rGTV) using LIFEx software. Student
t
tests and Spearman correlation coefficient were used to select the RF that best separate patients who recurred from those who did not, and “in-field” from “outside” recurrences. Principal component analysis involving these features only was used to create a prediction model. Leave-one-out cross-validation was performed to evaluate the models.
Results
After a median follow-up of 17 months, 40/55 patients had developed a second LR, including 18 “in-field” and 22 “outside” recurrences. From pre-reRT MRI, a model based on three RF (GLSZM_SZHGLE, GLSZM_LGLZE, and skewness) predicted whether patients would recur with a balanced accuracy (BA) of 83.5%. Another model from pre-reRT MRI based on three other RF (GLSZM_ LZHGE, NGLDM_Busyness, and GLZLM_SZE) predicted whether patients would recur “in-field” or “outside” with a BA of 78.5%. From pre-reRT PET, a model based on four RF (Kurtosis, SUVbwmin, GLCM_Correlation, and GLCM_Contrast) predicted the LR location with a BA of 84.5%.
Conclusion
RF characterizing tumor heterogeneity extracted from pre-reRT PET and MRI predicted whether patients would recur, and whether they would recur “in-field” or “outside”.
Abstract Background and purpose To identify rectal subregions at risks (SRR) highly predictive of 3-year rectal bleeding (RB) in prostate cancer IMRT. Materials and methods Overall, 173 prostate ...cancer patients treated with IMRT/IGRT were prospectively analyzed, divided into “training” ( n = 118) and “validation” cohorts ( n = 53). Dose–volume histograms (DVHs) were calculated in three types of rectal subregions: “geometric”, intuitively defined (hemi-rectum,…); “personalized”, obtained by non-rigid registration followed by voxel-wise statistical analysis (SRRp); “generic”, mapped from SRRps, located within 8 × 8 rectal subsections (SRRg). DVHs from patients with and without RB were compared and used for toxicity prediction. Results Training cohort SRRps were primarily within the inferior anterior hemi-rectum and upper anal canal, with 3.8 Gy mean dose increase for Grade ⩾ 1 RB patients. The SRRg, representing 15% of the absolute rectal volume, was located in 10 inferior–anterior rectal subsections. V18–V70 for SRRps and V58–V65 for SRRg were significantly higher for RB patients than non-RB. Maximum areas under the curve (AUCs) for SRRp and SRRg RB prediction were 71% and 64%, respectively. The validation cohort confirmed the predictive value of SRRg for Grade ⩾ 1 RB. The total cohort confirmed the predictive value of SRRg for Grade ⩾ 2 RB. Geometrical subregions were not RB predictors. Conclusion The inferior–anterior hemi anorectum was highly predictive of RB.
PDF
![[18F]-FDG PET and MRI radio...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1619-7070/small "[18F]-FDG PET and MRI radiomic signatures to predict the risk and the location of tumor recurrence after re-irradiation in head and neck cancer")
