Head and neck cancers volume reduction: should we reduce our prophylactic node radiation to spare the antitumor immune response?

Radiotherapy for locally advanced head and neck cancer classically include large prophylactic node volume. However, the use of these large volumes can be responsible for significant toxicity. Furthermore, the disappointing results of radioimmunotherapy combinations in head and neck tumors raise concerns about radiotherapy's potential negative impact on the immune response when large lymph node volumes are treated. Besides, in other tumor locations, such as lung cancers, the volumes of elective irradiation have been considerably reduced, with the same local control as before. This opinion piece reviews the current state of radiation volumes in head and neck cancers, the rationale for these volumes, the potential impact of radiotherapy on immune response, and the volume changes that would improve the efficacy of radioimmunotherapy combinations.

Outcomes Following Hypofractionated Stereotactic Radiotherapy to the Cavity After Surgery for Melanoma Brain Metastases.

AIMS: Hypofractionated stereotactic radiotherapy (HSRT) to the cavity after surgical resection of brain metastases improves local control. Most reported cohorts include few patients with melanoma, a population known to have high rates of recurrence and neurological death. We aimed to assess outcomes in patients with melanoma brain metastases who received HSRT after surgery at two Australian institutions. MATERIALS AND METHODS: A retrospective analysis was carried out including patients treated between January 2012 and May 2020. HSRT was recommended for patients with melanoma brain metastases at high risk of local recurrence after surgery. Treatment was delivered using appropriately commissioned linear accelerators. Routine follow-up included surveillance magnetic resonance imaging brain every 3 months for at least 2 years. Primary outcomes were overall survival, local control, incidence of radiological radionecrosis and symptomatic radionecrosis. RESULTS: There were 63 cavities identified in 57 patients. The most common HSRT dose prescriptions were 24 Gy in three fractions and 27.5 Gy in five fractions. The median follow-up was 32 months in survivors. Local control was 90% at 1 year, 83% at 2 years and 76% at 3 years. Subtotal brain metastases resection (hazard ratio 12.5; 95% confidence interval 1.4-111; P = 0.0238) was associated with more local recurrence. Overall survival was 64% at 1 year, 45% at 2 years and 40% at 3 years. There were 10 radiological radionecrosis events (16% of cavities) during the study period, with 5% at 1 year and 8% at 2 years after HSRT. The median time to onset of radiological radionecrosis was 21 months (range 6-56). Of these events, three became symptomatic (5%) during the study period at a median time to onset of 26 months (range 21-32). CONCLUSION: Cavity HSRT is associated with high rates of local control in patients with melanoma brain metastases. Subtotal resection strongly predicts for local recurrence after HSRT. Symptomatic radionecrosis occurred in 5% of cavities but increased to 8% of longer-term survivors.

Age, Blasts, Performance Status and Lenalidomide Therapy Influence the Outcome of Myelodysplastic Syndrome With Isolated Del(5q): A Study of 58 South American Patients.

BACKGROUND: Myelodysplastic Syndrome (MDS) with isolated deletion 5q is associated with a low risk to leukemic evolution and long overall survival (OS); it comprises 3%-4.5% of MDS cases in Latin America classified according to the World Health Organization 2008. This study aims to describe clinical, laboratory and the outcome of patients according to the newest World Health Organization 2016 proposal. METHODS: We retrospectively reviewed patients from four Brazilian (BR) and four Argentinean (AR) centers diagnosed between 1999 and 2019. RESULTS: The 58 patients (16-AR and 42-BR) presented a median age of 67 (IQR 61-75) years old, women predominance (70.7%) and transfusion dependency (62.5%) at diagnosis. Median hemoglobin level was 8.1g/dL, 27.5% and 44.4% presented thrombocytosis and neutropenia, respectively. Bone marrow (BM) was predominantly hypercellular (43.1%) with 66% showing dysplasia >1 lineage and 37.9% with >2% of blasts. Deletion 5q was mostly isolated (79.3%) and a variety of abnormalities were observed in remaining cases. Most patients were treated with erythropoietin-stimulating agents (ESA), 18 with lenalidomide and 15 with thalidomide. Median follow-up was 7.6 years, with a median OS of 3.5 years and an 8-years leukemic evolution rate of 18.4%. Multivariate analysis showed that age >75 years (HR 2.19), ECOG ≥2 (HR 5.76), BM blasts >2% (HR 2.92) and lenalidomide treatment (HR 0.25) independently influenced the OS. CONCLUSION: Older age, worse performance status and higher percentage of blasts, that can be easily assessed, were associated to a worse prognosis. Also, our results corroborate the protective influence of lenalidomide in terms of OS in this South American series.

A priori quality assurance using a benchmark case of the randomized phase 2 GORTEC 2014-14 in oligometastatic head and neck cancer patients.

PURPOSE: A Benchmark Case (BC) was performed as part of the quality assurance process of the randomized phase 2 GORTEC 2014-14 OMET study, testing the possibility of multisite stereotactic radiation therapy (SBRT) alone in oligometastatic head and neck squamous cell carcinoma (HNSCC) as an alternative to systemic treatment and SBRT. MATERIAL AND METHODS: Compliance of the investigating centers with the prescription, delineation, planning and evaluation recommendations available in the research protocol was assessed. In addition, classical dosimetric analysis was supplemented by quantitative geometric analysis using conformation indices. RESULTS: Twenty centers participated in the BC analysis. Among them, four major deviations (MaD) were reported in two centers. Two (10%) centers in MaD had omitted the satellite tumor nodule and secondarily validated after revision. Their respective DICE indexes were 0.37 and 0 and use of extracranial SBRT devices suboptimal There were significant residual heterogeneities between participating centers, including those with a similar SBRT equipment, with impact of plan quality using standard indicators and geometric indices. CONCLUSION: A priori QA using a BC conditioning the participation of the clinical investigation centers showed deviations from good SBRT practice and led to the exclusion of one out of the twenty participating centers. The majority of centers have demonstrated rigorous compliance with the research protocol. The use of quality indexes adds a complementary approach to improve assessment of plan quality.

Discontinuous stereotactic body radiotherapy schedule increases overall survival in early-stage non-small cell lung cancer.

OBJECTIVES: The duration of stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) may affect patient outcomes. We aimed to determine the impact of a continuous versus discontinuous SBRT schedule on local control (LC) and overall survival (OS) in NSCLC patients. MATERIALS AND METHODS: Consecutive NSCLC stage I patients (475) treated with SBRT in four centers were retrospectively analyzed. The delivered dose ranged from 48 to 75 Gy in 3-10 fractions. Based on the ratio between the treatment duration (TD) and number of fractions (n), patients were divided into two groups: continuous schedule (CS) (TD ≤ 1.6n; 239 patients) and discontinuous schedule (DS) (TD > 1.6n; 236 patients). LC and OS were compared using Cox regression analyses after propensity score matching (216 pairs). RESULTS: The median follow-up period was 41 months. Multivariate analysis showed that the DS (hazard ratio (HR): 0.42; 95 % confidence interval (CI): 0.22-0.78) and number of fractions (HR: 1.24; 95 % CI: 1.07-1.43) were significantly associated with LC. The DS (HR: 0.67; 95 % CI: 0.51-0.89), age (HR: 1.02; 95 % CI: 1-1.03), WHO performance status (HR: 2.27; 95 % CI: 1.39-3.7), and T stage (HR: 1.4; 95 % CI: 1.03-1.87) were significantly associated with OS. The 3-year LC and OS were 92 % and 64 % and 81 % and 53 % for DS and CS treatments, respectively (p < 0.01). Cox analysis confirmed that the discontinuous SBRT schedule significantly increased LC and OS. CONCLUSION: DS is associated with significantly improved LC and OS in early-stage NSCLC patients treated with SBRT.

PET and MRI guided adaptive radiotherapy: Rational, feasibility and benefit.

Adaptive radiotherapy (ART) corresponds to various replanning strategies aiming to correct for anatomical variations occurring during the course of radiotherapy. The goal of the article was to report the rational, feasibility and benefit of using PET and/or MRI to guide this ART strategy in various tumor localizations. The anatomical modifications defined by scanner taking into account tumour mobility and volume variation are not always sufficient to optimise treatment. The contribution of functional imaging by PET or the precision of soft tissue by MRI makes it possible to consider optimized ART. Today, the most important data for both PET and MRI are for lung, head and neck, cervical and prostate cancers. PET and MRI guided ART appears feasible and safe, however in a very limited clinical experience. Phase I/II studies should be therefore performed, before proposing cost-effectiveness comparisons in randomized trials and before using the approach in routine practice.

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.

ITV versus mid-ventilation for treatment planning in lung SBRT: a comparison of target coverage and PTV adequacy by using in-treatment 4D cone beam CT.

BACKGROUND: The internal target volume (ITV) approach and the mid-ventilation (MidV) concept are the two main respiratory motion-management strategies under free breathing. The purpose of this work was to compare the actual in-treatment target coverage during volumetric modulated arctherapy (VMAT) delivered through both ITV-based and MidV-based planning target volume (PTV) and to provide knowledge in choosing the optimal PTV for stereotactic body radiotherapy (SBRT) for lung lesions. METHODS AND MATERIALS: Thirty-two lung cancer patients treated by a VMAT technique were included in the study. For each fraction, the mean time-weighted position of the target was localized by using a 4-dimensional cone-beam CT (4D-CBCT)-based image guidance procedure. The respiratory-correlated location of the gross tumor volume (GTV) during treatment delivery was determined for each fraction by using in-treatment 4D-CBCT images acquired concurrently with VMAT delivery (4D-CBCTin-treat). The GTV was delineated from each of the ten respiratory phase-sorted 4D-CBCTin-treat datasets for each fraction. We defined target coverage as the average percentage of the GTV included within the PTV during the patient's breathing cycle averaged over the treatment course. Target coverage and PTVs were reported for a MidV-based PTV (PTVMidV) using dose-probabilistic margins and three ITV-based PTVs using isotropic margins of 5 mm (PTVITV + 5mm), 4 mm (PTVITV + 4mm) and 3 mm (PTVITV + 3mm). The in-treatment baseline displacements and target motion amplitudes were reported to evaluate the impact of both parameters on target coverage. RESULTS: Overall, 100 4D-CBCTin-treat images were analyzed. The mean target coverage was 98.6, 99.6, 98.9 and 97.2% for PTVMidV, PTVITV + 5mm, PTVITV + 4mm and PTVITV + 3mm, respectively. All the PTV margins led to a target coverage per treatment higher than 95% in at least 90% of the evaluated cases. Compared to PTVITV + 5mm, PTVMidV, PTVITV + 4mm and PTVITV + 3mm had mean PTV reductions of 16, 19 and 33%, respectively. CONCLUSION: When implementing VMAT with 4D-CBCT-based image guidance, an ITV-based approach with a tighter margin than the commonly used 5 mm margin remains an alternative to the MidV-based approach for reducing healthy tissue exposure in lung SBRT. Compared to PTVMidV, PTVITV + 3mm significantly reduced the PTV while still maintaining an adequate in-treatment target coverage.

Head-and-Neck MRI-only radiotherapy treatment planning: From acquisition in treatment position to pseudo-CT generation.

PURPOSE: In context of head-and-neck radiotherapy, this study aims to compare MR image quality according to diagnostic (DIAG) and radiotherapy (RT) setups; and to optimise an MRI-protocol (including 3D T1 and T2-weighted sequences) for dose-planning (based on pseudo-CT generation). MATERIALS AND METHODS: To compare DIAG and RT setups, signal-to-noise-ratio (SNR) and percentage-image-uniformity (PIU) were computed on T1 images of phantoms and volunteers. Influence of the sample conductivity on SNR was quantified using homemade phantoms. To obtain reliable T1 and T2 images for RT-planning, an experimental design was performed on volunteers by using SNR, contrast-to-noise-ratio (CNR) and mean-opinion-score (MOS). Further, pseudo-CTs were generated from 8 patients T2 images with a state-of-art deep-learning method. These pseudo-CTs were evaluated by mean-absolute-error (MAE) and mean-error (ME). RESULTS: SNR was higher for DIAG-setup compared to RT-setup (SNR-ratio=1.3). A clear influence of the conductivity on SNR was observed. PIU was higher for DIAG-setup (38.8%) compared to RT-setup (33.5%). Regarding the protocol optimisation, SNR, CNR, and MOS were 20.6, 6.16, and 3.91 for the optimal T1 sequence. For the optimal T2 sequence, SNR, CNR and MOS were 25.6, 44.46 and 4.0. In the whole head-and-neck area, the mean MAE and ME of the pseudo-CTs were 82.8 and -3.9 HU. CONCLUSION: We quantified the image quality decrease induces by using an RT-setup for head-and-neck radiotherapy. To compensate this decrease, an MRI protocol was optimised by using an experimental design. This protocol of 15minutes provides accurate images which could be used for MRI-dose-planning in clinical practice.

Implementation of an optimization method for parotid gland sparing during inverse planning for head and neck cancer radiotherapy.

PURPOSE: To guide parotid gland (PG) sparing at the dose planning step, a specific model based on overlap between PTV and organ at risk (Moore et al.) was developed and evaluated for VMAT in head-and-neck (H&N) cancer radiotherapy. MATERIALS AND METHODS: One hundred and sixty patients treated for locally advanced H&N cancer were included. A model optimization was first performed (20 patients) before a model evaluation (110 patients). Thirty cases were planned with and without the model to quantify the PG dose sparing. The inter-operator variability was evaluated on one case, planned by 12 operators with and without the model. The endpoints were PG mean dose (Dmean), PTV homogeneity and number of monitor units (MU). RESULTS: The PG Dmean predicted by the model was reached in 89% of cases. Using the model significantly reduced the PG Dmean: -6.1±4.3Gy. Plans with the model showed lower PTV dose homogeneity and more MUs (+10.5% on average). For the inter-operator variability, PG dose volume histograms without the optimized model were significantly different compared to those with the model; the Dmean standard deviation for the ipsilateral PG decreased from 2.2Gy to 1.2Gy. For the contralateral PG, this value decreased from 2.9Gy to 0.8Gy. CONCLUSION: During the H&N inverse planning, the optimized model guides to the lowest PG achievable mean dose, allowing a significant PG mean dose reduction of -6.1Gy. Integrating this method at the treatment-planning step significantly reduced the inter-patient and inter-operator variabilities.

Voxel-based identification of local recurrence sub-regions from pre-treatment PET/CT for locally advanced head and neck cancers.

BACKGROUND: Overall, 40% of patients with a locally advanced head and neck cancer (LAHNC) treated by chemoradiotherapy (CRT) present local recurrence within 2 years after the treatment. The aims of this study were to characterize voxel-wise the sub-regions where tumor recurrence appear and to predict their location from pre-treatment 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images. MATERIALS AND METHODS: Twenty-six patients with local failure after treatment were included in this study. Local recurrence volume was identified by co-registering pre-treatment and recurrent PET/CT images using a customized rigid registration algorithm. A large set of voxel-wise features were extracted from pre-treatment PET to train a random forest model allowing to predict local recurrence at the voxel level. RESULTS: Out of 26 expert-assessed registrations, 15 provided enough accuracy to identify recurrence volumes and were included for further analysis. Recurrence volume represented on average 23% of the initial tumor volume. The MTV with a threshold of 50% of SUVmax plus a 3D margin of 10 mm covered on average 89.8% of the recurrence and 96.9% of the initial tumor. SUV and MTV alone were not sufficient to identify the area of recurrence. Using a random forest model, 15 parameters, combining radiomics and spatial location, were identified, allowing to predict the recurrence sub-regions with a median area under the receiver operating curve of 0.71 (range 0.14-0.91). CONCLUSION: As opposed to regional comparisons which do not bring enough evidence for accurate prediction of recurrence volume, a voxel-wise analysis of FDG-uptake features suggested a potential to predict recurrence with enough accuracy to consider tailoring CRT by dose escalation within likely radioresistant regions.

[Adaptive radiotherapy: Strategies and benefits depending on tumor localization]. / Radiothérapie adaptative : stratégies et bénéfices selon les localisations tumorales.

Adaptive radiotherapy (ART) is a complexe image-guided radiotherapy modality that comprises multiple planning to account for anatomical variations occurring during irradiation. Schematically, two strategies of RTA can be distinguished and combined according to tumor locations. One or more replanning can be proposed to correct systematic variations such as tumor shrinkage. A library of treatment plans with day-to-day plan selection from cone-beam CT imaging can also be proposed to correct random variations such as uterine motion or bladder/rectum volume changes. Because of strong anatomical variations occurring during irradiation, RTA appears therefore particularly justified in head and neck, lung, bladder, cervical and rectum and pancreas tumors, and to a lesser extent for prostate tumors and other digestive tumors. For these tumor locations, ART provides a fairly clear dosimetric benefit but a clinical benefit not yet formally demonstrated. ART cannot be proposed in a routine practice but must be evaluated medico-economically in the context of prospective trials. A rigorous quality control must be associated.

[Individualization of dose and fractionation of radiotherapy for head and neck cancers]. / Personnalisation de la dose et du fractionnement de la radiothérapie des cancers de la tête et du cou.

Head and neck cancers comprise a variety of tumours depending on the sub-site, for which target volumes and the prescribed doses need to be individualized according to each patient's history and presentation. This article aims at describing the main factors involved in decision-making regarding dose and volume, as well as ongoing research. Contouring and treatment guidelines, use of altered fractionation, major prognostic factors, the role of Human papillomavirus and of functional imaging will be presented and discussed.

Salvage reirradiation for local prostate cancer recurrence after radiation therapy. For who? When? How?

PURPOSE: Literature review reporting results of salvage brachytherapy and stereotactic body radiotherapy for prostate recurrence only after radiotherapy for prostate cancer. MATERIALS AND METHODS: A total of 38 studies (including at least 15 patients per study) were analysed: 19 using low-dose-rate brachytherapy, nine high-dose-rate brachytherapy and ten stereotactic body radiotherapy. Only five studies were prospective. The median numbers of patients were 30 for low-dose-rate brachytherapy, 34 for high-dose-rate brachytherapy, and 30 for stereotactic body radiotherapy. The median follow-up were 47months for low-dose-rate brachytherapy, 36months for high-dose-rate brachytherapy and 21months for stereotactic body radiotherapy. RESULTS: Late genitourinary toxicity rates ranged, for grade 2: from 4 to 42% for low-dose-rate brachytherapy, from 7 to 54% for high-dose-rate brachytherapy and from 3 to 20% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 24% for low-dose-rate brachytherapy, from 0 to 13% for high-dose-rate brachytherapy and from 0 to 3% for grade 3 or above (except 12% in one study) for stereotactic body radiotherapy. Late gastrointestinal toxicity rates ranged, for grade 2: from 0 to 6% for low-dose-rate brachytherapy, from 0 to 14% for high-dose-rate brachytherapy and from 0 to 11% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 6% for low-dose-rate brachytherapy, and from 0 to 1% for high-dose-rate brachytherapy and stereotactic body radiotherapy. The 5-year biochemical disease-free survival rates ranged from 20 to 77% for low-dose-rate brachytherapy and from 51 to 68% for high-dose-rate brachytherapy. The 2- and 3-year disease-free survival rates ranged from 40 to 82% for stereotactic body radiotherapy. Prognostic factors of biochemical recurrence have been identified. CONCLUSION: Despite a lack of prospective data, salvage reirradiation for prostate cancer recurrence can be proposed to highly selected patients and tumours. Prospective comparative studies are needed.

A density assignment method for dose monitoring in head-and-neck radiotherapy.

BACKGROUND AND PURPOSE: During head-and-neck (H&N) radiotherapy, the parotid glands (PGs) may be overdosed; thus, a tool is required to monitor the delivered dose. This study aimed to assess the dose accuracy of a patient-specific density assignment method (DAM) for dose calculation to monitor the dose to PGs during treatment. PATIENTS AND METHODS: Forty patients with H&N cancer received an intensity modulated radiation therapy (IMRT), among whom 15 had weekly CTs. Dose distributions were calculated either on the CTs (CTref), on one-class CTs (1C-CT, water), or on three-class CTs (3C-CT, water-air-bone). The inter- and intra-patient DAM uncertainties were evaluated by the difference between doses calculated on CTref and 1C-CTs or 3C-CTs. PG mean dose (Dmean) and spinal cord maximum dose (D2%) were considered. The cumulated dose to the PGs was estimated by the mean Dmean of the weekly CTs. RESULTS: The mean (maximum) inter-patient DAM dose uncertainties for the PGs (in cGy) were 23 (75) using 1C-CTs and 12 (50) using 3C-CTs (p ≤ 0.001). For the spinal cord, these uncertainties were 118 (245) and 15 (67; p ≤ 0.001). The mean (maximum) DAM dose uncertainty between cumulated doses calculated on CTs and 3C-CTs was 7 cGy (45 cGy) for the PGs. Considering the difference between the planned and cumulated doses, 53% of the ipsilateral and 80% of the contralateral PGs were overdosed by +3.6 Gy (up to 8.2 Gy) and +1.9 Gy (up to 5.2 Gy), respectively. CONCLUSION: The uncertainty of the three-class DAM appears to be clinically non-significant (<0.5 Gy) compared with the PG overdose (up to 8.2 Gy). This DAM could therefore be used to monitor PG doses and trigger replanning.

Adaptive radiotherapy for head and neck cancer.

INTRODUCTION: Large anatomical variations can be observed during the treatment course intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), leading to potential dose variations. Adaptive radiotherapy (ART) uses one or several replanning sessions to correct these variations and thus optimize the delivered dose distribution to the daily anatomy of the patient. This review, which is focused on ART in the HNC, aims to identify the various strategies of ART and to estimate the dosimetric and clinical benefits of these strategies. MATERIAL AND METHODS: We performed an electronic search of articles published in PubMed/MEDLINE and Science Direct from January 2005 to December 2016. Among a total of 134 articles assessed for eligibility, 29 articles were ultimately retained for the review. Eighteen studies evaluated dosimetric variations without ART, and 11 studies reported the benefits of ART. RESULTS: Eight in silico studies tested a number of replanning sessions, ranging from 1 to 6, aiming primarily to reduce the dose to the parotid glands. The optimal timing for replanning appears to be early during the first two weeks of treatment. Compared to standard IMRT, ART decreases the mean dose to the parotid gland from 0.6 to 6 Gy and the maximum dose to the spinal cord from 0.1 to 4 Gy while improving target coverage and homogeneity in most studies. Only five studies reported the clinical results of ART, and three of those studies included a non-randomized comparison with standard IMRT. These studies suggest a benefit of ART in regard to decreasing xerostomia, increasing quality of life, and increasing local control. Patients with the largest early anatomical and dose variations are the best candidates for ART. CONCLUSION: ART may decrease toxicity and improve local control for locally advanced HNC. However, randomized trials are necessary to demonstrate the benefit of ART before using the technique in routine practice.

[Circulating tumour DNA: Current detection methods, use in radiotherapy and future development]. / ADN tumoral circulant : principes, applications actuelles en radiothérapie et développement futur.

Recent technological developments enable the detection and quantification of circulating tumour DNA in the blood, with potentially major clinical implications, particularly for cancers treated with curative intent. Circulating tumour DNA has a potential impact before, during and after treatment. If limitations of this approach remain, requiring further development, it is important to know the principles and applications in view of the potential impact on the clinical practice. In this review, we will discuss the current detection methods, then the place of circulating tumour DNA in oncology and more particularly in radiotherapy.

(18F)-FDG PET/CT parameters to predict survival and recurrence in patients with locally advanced cervical cancer treated with chemoradiotherapy.

PURPOSE: To identify predictive (18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)-based parameters for locoregional control, disease-free survival and overall survival, by testing different thresholds of metabolic tumor volume and total lesion glycolysis in patients with locally-advanced cervical cancer. PATIENTS AND METHODS: Thirty-seven patients treated with standard chemoirradiation underwent a pretreatment (18F)-FDG-PET/CT. Using different thresholds of maximum standardized uptake value, the following PET parameters were computed: maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume and total lesion glycolysis for primary tumor and lymph nodes and a new parameter combining the metabolic tumor volume and the distance between lymph nodes and the primary tumor, namely metabolic node distance. Correlation between PET and clinical parameters with clinical outcome (overall survival, disease-free survival, and locoregional control) was assessed using univariate and multivariate analyses (Cox model). RESULTS: In univariate analyses, PET/CT parameters associated with overall survival and disease-free survival were: metabolic tumor volume and total lesion glycolysis of the primary tumor, total lesion glycolysis of lymph nodes and metabolic node distance. The most predictive threshold segmentation for metabolic tumor volume and total lesion glycolysis was 48% of maximum standardized uptake value for the primary tumor and 30% for the lymph nodes. In multivariate Cox analysis, the total lesion glycolysis of primary tumor 48% and metabolic node distance were the two independent risk factors for overall survival (P<0.01), disease-free survival (P<0.01) and locoregional control (P=0.046). CONCLUSION: Total lesion glycolysis of primary tumor and distance between the invaded positive lymph node and the primary tumor seem to have the highest predictive value when compared to classical clinical prognostic parameters and may be useful to identify high risk groups at time of diagnosis and to tailor the therapeutic approach in locally-advanced cervical cancer.

Mortality Analysis of Acute Liver Failure in Uruguay.

BACKGROUND: Acute liver failure (ALF) is a syndrome with high mortality. OBJECTIVE: Describe characteristics and outcomes of patients with ALF in Uruguay, and identify factors associated with mortality. METHODS: A retrospective analysis of 33 patients with ALF was performed between 2009 and 2017. RESULTS: The patients' median age was 43 years, and 64% were women. Average Model for End-Stage Liver Disease (MELD) score at admission was 33. The median referral time to the liver transplant (LT) center was 7 days. The most common etiologies were viral hepatitis (27%), indeterminate (21%), autoimmune (18%), and Wilson disease (15%). Overall mortality was 52% (71% of transplanted and 46% of nontransplanted patients). Dead patients had higher referral time (10 vs 4 days, P = .008), higher MELD scores at admission (37 vs 28) and highest achieved MELD scores (42 vs 29; P < .001), and higher encephalopathy grade III to IV (94% vs 25%, P < .001) than survivors. Patients without LT criteria (n = 4) had lower MELD score at admission (25 vs 34, P = .001) and highest achieved MELD score (27 vs 37, P = .008) compared with the others. Patients with LT criteria but contraindications (n = 7) had higher MELD scores at admission (38 vs 31, P = .02), highest achieved MELD scores (41 vs 34, P = .03), and longer referral time (10 days) than those without contraindications (3.5 days) or those without LT criteria (7.5 days, P = .02). Twenty-two patients were listed; LT was performed in 7, with a median time on waiting list of 6 days. CONCLUSIONS: ALF in Uruguay has high mortality associated with delayed referral to the LT center, MELD score, and encephalopathy. The long waiting times to transplantation might influence mortality.