Predicting response to radiotherapy of head and neck squamous cell carcinoma using radiomics from cone-beam CT images.

INTRODUCTION: Radiotherapy (RT) for head and neck cancer is now guided by cone-beam computed tomography (CBCT). We aim to identify a CBCT radiomic signature predictive of progression to RT. MATERIAL AND METHODS: A cohort of 93 patients was split into training (n = 60) and testing (n = 33) sets. A total of 88 features were extracted from the gross tumor volume (GTV) on each CBCT. Receiver operating characteristic (ROC) curves were used to determine the power of each feature at each week of treatment to predict progression to radio(chemo)therapy. Only features with AUC > 0.65 at each week were pre-selected. Absolute differences were calculated between features from each weekly CBCT and baseline CBCT1 images. The smallest detectable change (C = 1.96 × SD, SD being the standard deviation of differences between feature values calculated on CBCT1 and CBCTn) with its confidence interval (95% confidence interval [CI]) was determined for each feature. The features for which the change was larger than C for at least 5% of patients were then selected. A radiomics-based model was built at the time-point that showed the highest AUC and compared with models relying on clinical variables. RESULTS: Seven features had an AUC > 0.65 at each week, and six exhibited a change larger than the predefined CI 95%. After exclusion of inter-correlated features, only one parameter remains, Coarseness. Among clinical variable, only hemoglobin value was significant. AUC for predicting the treatment response were 0.78 (p = .006), 0.85 (p < .001), and 0.99 (p < .001) for clinical, CBCT4-radiomics (Coarseness) and clinical + radiomics based models respectively. The mean AUC of this last model on a 5-fold cross-validation was 0.80 (±0.09). On the testing cohort, the best prediction was given by the combined model (balanced accuracy [BAcc] 0.67 , p < .001). CONCLUSIONS: We described a feature selection methodology for delta-radiomics that is able to select reproducible features which are informative due to their change during treatment. A selected delta radiomics feature may improve clinical-based prediction models.

[Erectile dysfunction evaluation after brachytherapy for low risk prostate adenocarcinoma: prospective study of patients with a baseline IIEF5>16]. / Évolution de la fonction érectile après curiethérapie prostatique : étude prospective chez des patients ayant un score IIEF5 initial>16.

PURPOSE: To evaluate erectile function (EF) prospectively from 1 to 2 years post-brachytherapy in patients with a baseline IIEF5 score>16. METHODS: Between 2007 and 2012, 179 patients underwent an exclusive brachytherapy for localised low risk prostate adenocarcinoma. Neo-adjuvant hormotherapy (15.6%) and post-brachytherapy intake phosphodiesterase inhibitors (PDE5i) were not considered as exclusion criteria. EF was evaluated via a scoring questionnaire IIEF5 before the surgical implantation, at month 12 and 24 post-operation. Only patients with an initial IIEF5 score>16 were included. RESULTS: Of the 179 patients, 102 (57%) had a baseline IIEF5>16. At 12 months, 51.1% maintained an IIEF5>16 and 24.5% had a mild to moderate erectile dysfunction (ED), so that a total of 75.6% with IIEF5≥12. About 18% of patients had used PDE5i. At 24 months, 53.2% had an IIEF5>16 and 80.6% had an IIEF5≥12. Severe ED was reported in only 14.5% of the patients. The mean IIEF5 was 16.2 with an average decline of 5 points from the initial stage. All patients who were treated with PDE5i (27%) could have sexual intercourse. EF at baseline was reported as the only predictive factor of ED in multivariate analysis, 70% of patient without ED initially, had an IIEF5>16 at 1 and 2 years. CONCLUSION: Severe ED was quite rare (14%) during the first 2 years post-brachytherapy and more than half of patients maintained an IIEF5>16. The main predictive factor was the erectile function at baseline. LEVEL OF EVIDENCE: 4.

Influence of partial volume correction in staging of head and neck squamous cell carcinoma using PET/CT.

Aim: PET/CT is widely used for the detection of lymph node involvement in head and neck squamous cell carcinoma (HNSCC). However, PET qualitative and quantitative capabilities are hindered by partial volume effects (PVE). Therefore, a retrospective study on 32 patients (57 lymph nodes) was carried out to evaluate the potential improvement of PVE correction (PVEC) in FDG PET/CT imaging for the diagnosis of HNSCC. Histopathological analysis of lymph nodes following neck dissection was used as the gold standard. Methods: A previously proposed deconvolution based PVEC approach was used to derive improved quantitative accuracy PET images, while the anatomical lymph node volumes were determined on the CT images. Different parameters including SUVmax and SUVmean were derived from both original and PVEC PET images for each patient. Results: Histopathology confirmed that SUVmax and SUVmean after PVEC allows a statistically significant differentiation of malignant and benign lymph nodes (p<0.05). The sensitivity of SUVmax and SUVmean was 64% and 57% respectively with or without PVEC. PVEC increased specificity from 71% to 76% for SUVmax and 57% to 66% for SUVmean. Corresponding accuracy increased from 66% to 71% for SUVmax and from 59% to 66% for SUVmean. However, the most accurate differentiation between benign and malignant nodes was obtained while using the magnitude of SUVmax increase after PVEC with a corresponding sensitivity, specificity and accuracy of 77%, 82% and 80% respectively. Conclusion: Our work shows that the use of partial volume effects correction allows a more accurate nodal staging using FDG PET imaging in HNSCC.

Stereotactic radiotherapy for ultracentral lung tumours.

Ultracentral (UC) lung lesions are generally defined by the presence of the tumour or the Planning Target Volume (PTV) abutting proximal bronchial tree (PBT) or the esophagus. Initial reports rose awareness regarding the potential toxicity of stereotactic body radiotherapy (SBRT) when delivered to UC lesions. Major concerns include necrosis, stenosis, and bleeding of the PBT. Technological improvements now enable the delivery of more accurate treatments, possibly redefining the historical "no-fly zone". In this review, studies focusing on the treatment of UC lesions with SBRT are presented. The narrow therapeutic window requires a multidisciplinary approach.

Radiotherapy modification based on artificial intelligence and radiomics applied to (18F)-fluorodeoxyglucose positron emission tomography/computed tomography.

Over the last decades, the refinement of radiation therapy techniques has been associated with an increasing interest for individualized radiation therapy with the aim of increasing or maintaining tumor control and reducing radiation toxicity. Developments in artificial intelligence (AI), particularly machine learning and deep learning, in imaging sciences, including nuclear medecine, have led to significant enthusiasm for the concept of "rapid learning health system". AI combined with radiomics applied to (18F)-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) offers a unique opportunity for the development of predictive models that can help stratify each patient's risk and guide treatment decisions for optimal outcomes and quality of life of patients treated with radiation therapy. Here we present an overview of the current contribution of AI and radiomics-based machine learning models applied to (18F)-FDG PET/CT in the management of cancer treated by radiation therapy.

Impact of learning curve and technical changes on dosimetry in low-dose brachytherapy for prostate cancer.

PURPOSE: To assess the impact of experience and technical changes on peri- and postimplantation (1 month later) dosimetry for permanent prostate brachytherapy (PPB). PATIENTS AND METHODS: From July 2003 to May 2010, 150 prostate cancer patients underwent low-dose, loose-seed I(125) PPB as monotherapy with intraoperative planning. Patients were divided into three groups-P1 (n = 64), P2 (n = 45), P3 (n = 41)-according to the technical changes that occurred during the study period: use of an automatic stepper at the beginning of P2 and a high-frequency ultrasound probe in P3. Peri- and postimplantation dosimetric parameters (on day 30) were reported: D90 (dose received by 90% of prostate volume), V100 and V150 (prostate volume receiving, respectively, 100% and 150% of the prescribed dose), D2 cc and D0.1 cc (doses received by 2 cc and 0.1 cc of the rectum), R100 (rectum volume that received 100% of the prescribed dose), and D10 and D30 (doses received by 10% and 30% of the urethra, only during peri-implantation). RESULTS: We observed a decrease in the number of needles and seeds used over time. The mean peri-implantation D90 was 187.52 Gy without a significant difference between the three periods (p = 0.48). The postimplantation D90, V100, and V150 parameters were, respectively, 168.3 Gy, 91.9%, and 55% with no significant difference between the three periods. The peri-implantation and postimplantation D0.1 cc and R100 significantly decreased over time; on day 30: D0.1 cc P1 = 223.1 Gy vs. D0.1 cc P3 = 190.4 Gy (p = 8.10(-5)) and R100 P1 = 1.06 cc vs. R100 P3 = 0.53 cc (p = 0.0008). CONCLUSION: We observed a learning curve for the implantation parameters, which led to a significant decrease in the rectal doses without having any impact on the prostate dosimetric parameters.

Integration of functional imaging in brachytherapy.

Functional imaging allows the evaluation of numerous biological properties that could be considered at all steps of the therapeutic management of patients treated with brachytherapy. Indeed, it enables better initial staging of the disease, and some parameters may also be used as predictive biomarkers for treatment response, allowing better selection of patients eligible for brachytherapy. It may also improve the definition of target volumes with the aim of dose escalations by dose-painting. Finally, it could be useful during the follow-up to assess response to treatment. In this review, we report how functional imaging is integrated at the present time during the brachytherapy procedure, and what are its potential future contributions in the main tumour locations where brachytherapy is recommended. Functional imaging has great potential in the contact of brachytherapy, but still, several issues remain to be resolved before integrating it into clinical practice, especially as a biomarker or in dose painting strategies.

Radiotherapy of benign intracranial tumours.

We present the updated recommendations of the French Society for Radiation Oncology on benign intracranial tumours. Most of them are meningiomas, vestibular schwannomas, pituitary adenomas, craniopharyngiomas, and glomus tumours. Some grow very slowly, and can be observed without specific treatment, especially if they are asymptomatic. Symptomatic or growing tumours are treated by surgery, which is the reference treatment. When surgery is not possible, due to the location of the lesion, or general conditions, radiotherapy can be applied, as it is if there is a postoperative growing residual tumour, or a local relapse. Indications have to be discussed at a multidisciplinary panel, with precise evaluation of the benefit and risks of the treatments. The techniques to be used are the most modern ones, as multimodal imaging and image-guided radiation therapy. Stereotactic treatments, using fractionated or single doses depending on the size or the location of the tumours, are commonly realized, to avoid as much a possible the occurrence of late side effects.

[Application of the « Junior Doctor ¼ status in Radiation Oncology]. / Guide du Docteur Junior en oncologie-radiothérapie.

Introduced in 2017, the reform of the 3rd cycle has modified the organization of the residency in all specialties, and in particular radiation oncology. The residency was thus divided into 3 phases with increasing knowledge and responsibilities. The latter, carried out under the status of "junior doctor", created and defined by decree n°2018-571 of July 3, 2018 and the decree of January 16, 2020, is a phase of supervised autonomy of the resident. Radiotherapy is a singular specialty, with multiple and complex activities, and requires multiple skills. A guide defining the status of the "Junior Doctor" in radiation oncology therefore appears necessary, defining each resident's role and obligations. This guide is of an advisory nature and must be adapted to the particularities of each department. This guide aims to help the implementation of the reform of the 3rd cycle in radiation oncology and especially the final year called the consolidation phase. It is destined to evolve, expanded by individual and collective feedback and the constant renewal of our speciality.

Radiomics analysis of 3D dose distributions to predict toxicity of radiotherapy for lung cancer.

PURPOSE: (Chemo)-radiotherapy (RT) is the gold standard treatment for patients with locally advanced lung cancer non accessible for surgery. However, current toxicity prediction models rely on clinical and dose volume histograms (DVHs) and remain unsufficient. The goal of this work is to investigate the added predictive value of the radiomics approach applied to dose maps regarding acute and late toxicities in both the lungs and esophagus. METHODS: Acute and late toxicities scored using the CTCAE v4.0 were retrospectively collected on patients treated with RT in our institution. Radiomic features were extracted from 3D dose maps considering Gy values as grey-levels in images. DVH and usual clinical factors were also considered. Three toxicity prediction models (clinical only, clinical + DVH and combined, i.e., including clinical + DVH + radiomics) were incrementally trained using a neural network on 70% of the patients for prediction of grade ≥2 acute and late pulmonary toxicities (APT/LPT) and grade ≥2 acute esophageal toxicities (AET). After bootstrapping (n = 1000), optimal cut-off values were determined based on the Youden Index. The trained models were then evaluated in the remaining 30% of patients using balanced accuracy (BAcc). RESULTS: 167 patients were treated from 2015 to 2018: 78% non small-cell lung cancers, 14% small-cell lung cancers and 8% other histology with a median age at treatment of 66 years. Respectively, 22.2%, 16.8% and 30.0% experienced APT, LPT and AET. In the training set (n = 117), the corresponding BAcc for clinical only/clinical + DVH/combined were 0.68/0.79/0.92, 0.66/0.77/0.87 and 0.68/0.73/0.84. In the testing evaluation (n = 50), these trained models obtained a corresponding BAcc of 0.69/0.69/0.92, 0.76/0.80/0.89 and 0.58/0.73/0.72. CONCLUSION: In patients with a lung cancer treated with RT, radiomic features extracted from 3D dose maps seem to surpass usual models based on clinical factors and DVHs for the prediction of APT and LPT.

Thrombophilic factors do not predict outcomes in renal transplant recipients under prophylactic acetylsalicylic acid.

A cohort of recipients of renal transplant after 2000 (N=310) was prospectively screened on the day of transplantation and 1 month later for a panel of 11 thrombophilic factors to assess their effect on posttransplant outcomes. All patients received prophylactic acetylsalicylic acid, started before transplantation. The rate of thromboembolic events or acute rejection episodes during the first posttransplant year (primary composite endpoint) was 16.7% among patients free of thrombophilic factor (N=60) and 17.2% in those with >or=1 thrombophilic factor (N=250) (p>0.99). The incidence of the primary endpoint was similar among patients free of thrombophilic factors and those with >or=2 (N=135), or >or=3 (N=53) factors (16.3% and 15.1% respectively; p=1) and in patients who remained thrombophilic at 1 month (15.7%; p=0.84). None of the individual thrombophilic factor present at the day of transplantation was associated with the primary endpoint. The incidence of cardiovascular events at 1-year, serum creatinine at 1-year, 4-year actuarial graft and patient survival were not influenced by the presence of >or=1 thrombophilic factor at baseline (p=NS). In conclusion, the presence of thrombophilic factors does not influence thromboembolic events, acute rejection, graft or patient survival in patients transplanted after 2000 and receiving prophylactic acetylsalicylic acid.

[French Health Authority certification visit in a radiotherapy department]. / Conduite d'une visite de certification par la Haute Autorité de santé dans un service de radiothérapie.

The French Higher Health Authority's (Haute Autorité de santé [HAS]) certification process is an important issue for a health care facility and in particular for a radiotherapy department. It is based on a quality-risk management methodology driven by the commitment and involvement of professionals. The radiotherapy department of the university hospital in Brest (France) has been engaged for many years in a demanding quality-risk management policy implementation, subjected to regular inspections by the French Nuclear Safety Authority (Autorité de sûreté nucléaire [ASN]). This implementation is driven by a strong commitment from department managers, who are determined to maintaining an efficient level for care quality and safety.

Use of radiomics in the radiation oncology setting: Where do we stand and what do we need?

Radiomics is a field that has been growing rapidly for the past ten years in medical imaging and more particularly in oncology where the primary objective is to contribute to personalised and predictive medicine. This short review aimed at providing some insights regarding the potential value of radiomics for cancer patients treated with radiotherapy. Radiomics may contribute to each stage of the patients' management: diagnosis, planning, treatment monitoring and post-treatment follow-up (toxicity and response). However, its applicability in clinical routine is currently hindered by several factors, including lack of automation, standardisation and harmonisation. A major effort must be carried out to automate the workflow, standardise radiomics good practices and carry out large-scale studies before any transfer to daily clinical practice.

Kilovoltage intrafraction monitoring during normofractionated prostate cancer radiotherapy.

PURPOSE: During radiotherapy (RT) for prostate cancer (PCa), interfraction and intrafraction movements can lead to decreased target dose coverage and unnecessary over-exposure of organs at risk. New image-guided RT techniques accuracy allows planning target volume (PTV) margins reduction. We aim to assess the feasibility of a kilovoltage intrafraction monitoring (KIM) to track the prostate during RT. METHODS AND MATERIALS: Between November 2017 and April 2018, 44 consecutive patients with PCa were included in an intrafraction prostate motion study using the Truebeam Auto Beam Hold® tracking system (Varian Medical Systems, United State) triggered by gold fiducials localization on kilovoltage (kV) imaging. A 5-mm PTV was considered. A significant gating event (SGE) was defined as the occurrence of an automatic beam interruption requiring patient repositioning following the detection of one fiducial outside a 5-mm target area around the marker during more than 45seconds. RESULTS: Six patients could not benefit from the KIM because of technical issues (loss of one fiducial marker=1, hip prosthesis=4, morbid obesity causing table movements=1). The mean rate of SGE per patient was 14±19%, and the fraction average delivery time was increased by 146±86seconds. For a plan of 39 fractions of 2Gy, the additional radiation dose increased by 0.13±0.09Gy. The mean rates of SGE were 2% and 18% (P=0.002) in patients with planned fraction<90 and>90seconds respectively, showing that duration of the session strongly interfered with prostate intrafraction movements. No other significant clinical and technical parameter was correlated with the occurrence of SGE. CONCLUSION: Automated intrafraction kV imaging can effectively perform autobeam holds due to intrafraction movement of the prostate in the large majority of patients. The additional radiation dose and delivery time are acceptable. This technique may be a cost-effective alternative to electromagnetic transponder guidance.

Performance comparison of modified ComBat for harmonization of radiomic features for multicenter studies.

Multicenter studies are needed to demonstrate the clinical potential value of radiomics as a prognostic tool. However, variability in scanner models, acquisition protocols and reconstruction settings are unavoidable and radiomic features are notoriously sensitive to these factors, which hinders pooling them in a statistical analysis. A statistical harmonization method called ComBat was developed to deal with the "batch effect" in gene expression microarray data and was used in radiomics studies to deal with the "center-effect". Our goal was to evaluate modifications in ComBat allowing for more flexibility in choosing a reference and improving robustness of the estimation. Two modified ComBat versions were evaluated: M-ComBat allows to transform all features distributions to a chosen reference, instead of the overall mean, providing more flexibility. B-ComBat adds bootstrap and Monte Carlo for improved robustness in the estimation. BM-ComBat combines both modifications. The four versions were compared regarding their ability to harmonize features in a multicenter context in two different clinical datasets. The first contains 119 locally advanced cervical cancer patients from 3 centers, with magnetic resonance imaging and positron emission tomography imaging. In that case ComBat was applied with 3 labels corresponding to each center. The second one contains 98 locally advanced laryngeal cancer patients from 5 centers with contrast-enhanced computed tomography. In that specific case, because imaging settings were highly heterogeneous even within each of the five centers, unsupervised clustering was used to determine two labels for applying ComBat. The impact of each harmonization was evaluated through three different machine learning pipelines for the modelling step in predicting the clinical outcomes, across two performance metrics (balanced accuracy and Matthews correlation coefficient). Before harmonization, almost all radiomic features had significantly different distributions between labels. These differences were successfully removed with all ComBat versions. The predictive ability of the radiomic models was always improved with harmonization and the improved ComBat provided the best results. This was observed consistently in both datasets, through all machine learning pipelines and performance metrics. The proposed modifications allow for more flexibility and robustness in the estimation. They also slightly but consistently improve the predictive power of resulting radiomic models.

Cancer of the oesophagus and lymph nodes management in the neoadjuvant or definitive radiochemotherapy setting.

Despite representing a 1% of diagnosed cancer cases in the USA and up to 5% in eastern Asia and Africa, oesophageal cancer still holds numerous questions concerning the best therapeutic management. For squamous cell carcinoma, while radiochemotherapy has proven itself to be the gold standard as part of the trimodality or alone as a definitive treatment, radiotherapy modalities are still debated especially regarding lymph node irradiation. Involved nodes irradiation was developed with the aim of maintaining clinical outcomes and enhancing quality of life but lacks grade 1 evidence. In this article, we aim to summarize the state of art regarding lymph node irradiation, discuss the impact of target definition, delivery techniques, concomitant treatment and the perspectives. Being highly connected to the lymph vessels, lymphatic metastases are frequent and can locate from the neck to the coeliac area with each node having a different prognostic significance. Regarding the comparison between elective nodal irradiation and involved nodes irradiation, evidence-based medicine mostly relies on retrospective studies. Pooled, it suggests similar clinical outcomes with lower acute toxicities in favour of involved nodes irradiation. However, delivery techniques, doses and concomitant treatment were not consensual. Studies are ongoing evaluating the impact of radiation delivery techniques and the choice of concomitant treatment, i.e. immunotherapy. Modern techniques of imaging, radiation therapy progressing each day and alternative treatment modalities being tested, the need of randomized controlled trials has never been so high. Elective nodal irradiation should remain the standard of care while phase 3 trials explore the safety of involved nodal irradiation.

Combining radiation with oxaliplatin: a review of experimental results.

Oxaliplatin is integrated in treatment strategies against a variety of cancers including chemoradiation protocols against gastrointestinal, especially rectal cancers. Solid biological data with respect to radiosensitizing activity of oxaliplatin are still rare. This review is based on in vitro and experimental in vivo data concerning the combination of oxaliplatin and radiation published until July 2007. Taking either cell viability or clonogenic survival as an endpoint all reported on oxaliplatin-induced radiosensitization, and enhancement ratios ranged from 1.1 to 2.2. In vivo, enhanced tumor growth delay after combined oxaliplatin and radiation treatment was also reported. Therefore, oxaliplatin should be considered a potent radiosensitizer, although the mechanisms causing radiosensitizing properties of oxaliplatin have not been studied in detail. Herein, they are discussed with respect to apoptosis induction, p53-related signalling, cell cycle control, and DNA-repair.