Prognostic value of low skeletal muscle mass in patient treated by exclusive curative radiochemotherapy for a NSCLC.

Low skeletal muscle mass is a well-known prognostic factor for patients treated for a non-small-cell lung cancer by surgery or chemotherapy. However, its impact in patients treated by exclusive radiochemotherapy has never been explored. Our study tries to evaluate the prognostic value of low skeletal muscle mass and other antropometric parameters on this population. Clinical, nutritional and anthropometric date were collected for 93 patients treated by radiochemotherapy for a NSCLC. Anthropometric parameters were measured on the PET/CT by two methods. The first method was a manual segmentation at level L3, used to define Muscle Body Area (MBAL3), Visceral Fat Area (VFAL3) and Subcutaneous Fat Area (SCFAL3). The second method was an software (Anthropometer3D), allowing an automatic multislice measurement of Lean Body Mass (LBMAnthro3D), Fat Body Mass (FBMAnthro3D), Muscle Body Mass (MBMAnthro3D), Visceral Fat Mass (VFMAnthro3D), and Sub-Cutaneous Fat Mass (SCFMAnthro3D) on the PET/CT. All anthropometrics parameters were normalised by the patient's height. The primary end point was overall survival time. Univariate and then stepwise multivariate cox analysis were performed for significant parameters. Finally, Spearman's correlation between MBAL3 and MBMAnthro3D was assessed. Forty-one (44%) patients had low skeletal muscle mass. The median overall survival was 18 months for low skeletal muscle mass patients versus 36 months for non-low skeletal muscle mass patients (p = 0.019). Low skeletal muscle mass (HR = 1.806, IC95% [1.09-2.98]), serums albumin level < 35 g/l (HR = 2.203 [1.19-4.09]), Buzby Index < 97.5 (HR = 2.31 [1.23-4.33]), WHO score = 0 (HR = 0.59 [0.31-0.86] and MBMAnthro3D < 8.56 kg/m2 (HR = 2.36 [1.41-3.90]) were the only significant features in univariates analysis. In the stepwise multivariate Cox analysis, only MBMAnthro3D < 8.56 kg/m2 (HR = 2.16, p = 0.003) and WHO score = 0 (HR = 0.59, p = 0.04) were significant. Finally, muscle quantified by MBAL3 and MBMAnthro3D were found to be highly correlated (Spearman = 0.9). Low skeletal muscle mass, assessed on the pre-treatment PET/CT is a powerful prognostic factor in patient treated by radiochemotherapy for a NSCLC. The automatic software Anthropometer3D can easily identify patients a risk that could benefit an adapted therapy.

[Construction of radiobiological models as TCP (tumor control probability) and NTCP (normal tissue complication probability): from dose to clinical effects prediction]. / Construction des modèles radiobiologiques de type TCP (tumor control probability) et NTCP (normal tissue complication probability) : de la dose à la prédiction des effets cliniques.

In radiotherapy, the dose prescription is currently based on discretized dose-effects records that do not take into fully account for the complexity of the patient-dose-response relationship. Their predictive performance on both anti-tumour efficacy and toxicity can be optimized by integrating radiobiological models. It is with this in mind that the calculation models TCP (Tumor Control Probability) and NTCP (Normal Tissue Complication Probability) have been developed. Their construction involves several important steps that are necessary and important to understand. The first step is based on radiobiological models allowing to calculate according to more or less complexity the rate of surviving cells after irradiation. Two additional steps are required to convert the physical dose into an equivalent biological dose, in particular a 2Gy equivalent biological dose (EQD2): first to take into account the effect of the fractionation of the dose for both the target volume and the organs at risk; second to convert an heterogeneous dose to an organ into an homogeneous dose having the same effect (Niemierko generalized equivalent uniform dose (gEUD)). Finally, the process of predicting clinical effects based on radiobiological models transform doses into tumour control (TCP) or toxicity (NTCP) probabilities using parameters that reflect the radiobiological characteristics of the tissues in question. The use of these models in current practice is still limited, but since the radiotherapy softwares increasingly integrate them, it is important to know the principle and limits of application of these models.

Ileostomy After Intestinal Transplantation: The First in Depth Report on Techniques, Complications, and Outcomes.

BACKGROUND: Temporary ileostomy during intestinal transplantation (ITx) is the standard technique for allograft monitoring. A detailed analysis of the ITx ileostomy has never been reported. METHODS: A retrospective review of a single-center ITx database was performed. The analysis was divided into ileostomy formation and takedown episodes. RESULTS: One hundred thirty-five grafts underwent ileostomy formation, and 79 underwent ileostomy takedown. Median age at ITx was 7.7 years and weight was 23 kg. Allograft types were intestine (22%), liver/intestine (55%), multivisceral (16%), and modified multivisceral (7%). Sixty-four percent had 1-stage ITx, whereas 36% required 2-staged ITx. Final ileostomy types were end (20%), loop (10%), distal blowhole (59%), and proximal blowhole (11%). Ileostomy formation: Thirty-one grafts had complications (23%), including prolapse (26%), ischemia (16%), and parastomal hernia (19%). Twelve required surgical revision. There were no significant differences in graft type, ileostomy type, survival, and ileostomy takedown rate between grafts with and without complications. Colon inclusive grafts had higher complication rates (P = 0.002). Ileostomy takedown: Ileostomy takedown occurred at a median of 422 days post-ITx. Twenty-five complications occurred after 22 takedowns (28%), including small bowel obstruction (27%) and abscess (18%). Fifteen grafts required surgical correction. Recipients with complications had longer hospital stay (17 versus 9 d; P = 0.001) than those without complications. Graft type, ileostomy type, and survival were not different. CONCLUSIONS: The first of its kind analysis of the surgical ileostomy after ITx reveals that most recipients can undergo successful ileostomy formation/takedown, complication rates are significant but within an acceptable range, and complications do not affect survival. This study demonstrates that the routine use of transplant ostomies remains an acceptable practice after ITx. However, true analysis of risk and benefit will require a randomized control trial.

Comparison of Hypermetabolic and Hypoxic Volumes Delineated on [18F]FDG and [18F]Fluoromisonidazole PET/CT in Non-small-cell Lung Cancer Patients.

PURPOSE: The high rates of failure in the radiotherapy target volume suggest that patients with stage II or III non-small-cell lung cancer (NSCLC) should receive an increased total dose of radiotherapy. 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and [18F]fluoromisonidazole ([18F]FMISO) (hypoxia) uptake on pre-radiotherapy positron emission tomography (PET)/X-ray computed tomography (CT) have been independently reported to identify intratumor subvolumes at higher risk of relapse after radiotherapy. We have compared the [18F]FDG and [18F]FMISO volumes defined by PET/CT in NSCLC patients included in a prospective study. PROCEDURES: Thirty-four patients with non-resectable lung cancer underwent [18F]FDG and [18F]FMISO PET/CT before (pre-RT) and during radiotherapy (around 42 Gy, per-RT). The criteria were to delineate 40 % and 90 % SUVmax thresholds on [18F]FDG PET/CT (metabolic volumes), and SUV > 1.4 on pre-RT [18F]FMISO PET/CT (hypoxic volume). The functional volumes were delineated within the tumor volume as defined on co-registered CTs. RESULTS: The mean pre-RT and per-RT [18F]FDG volumes were not statistically different (30.4 cc vs 22.2; P = 0.12). The mean pre-RT SUVmax [18F]FDG was higher than per-RT SUVmax (12.7 vs 6.5; P < 0.0001). The mean [18F]FMISO SUVmax and volumes were 2.7 and 1.37 cc, respectively. Volume-based analysis showed good overlap between [18F]FDG and [18F]FMISO for all methods of segmentation but a poor correlation for Jaccard or Dice Indices (DI). The DI maximum was 0.45 for a threshold at 40 or 50 %. CONCLUSION: The correlation between [18F]FDG and [18F]FMISO uptake is low in NSCLC, making it possible to envisage different management strategies as the studies in progress show.

[Prophylactic nodal radiotherapy for breast cancer]. / Irradiation des aires ganglionnaires prophylactiques pour le cancer du sein.

Adjuvant radiotherapy is a key treatment in early-stage breast cancer. The meta-analysis by the Early Breast Cancer Trialist's Collaborative Group (EBCTCG) has demonstrated a decreased risk of locoregional relapse and death after whole-breast radiotherapy. Prophylactic lymph nodes irradiation in breast cancer has also proven to be beneficial in several therapeutic trials. At a time when three-dimensional conformal radiotherapy has become the standard procedure and with the development of intensity-modulated radiation therapy, defining nodal volumes is essential and practices should be harmonized to assess and compare the efficiency and toxicity of radiotherapy. Furthermore, the indication of lymph nodes irradiation has to take into account the risk/benefit balance as expanding the irradiated volume can increase radio-induced toxicity. Selection of patients receiving this treatment is essential. The aim of this update is to define nodal volumes, to precise the indications of their irradiation and to present the expected benefits as well as the potential side effects.

Prevalence of burnout, depression and job satisfaction among French senior and resident radiation oncologists.

PURPOSE: Cancer caregivers are at high risk of burn-out, with potential severe consequences on professionals' health and on patients' care. We have investigated the prevalence of burn-out and its impact in terms of psychological morbidity among French radiation oncologists. METHODS AND MATERIALS: An anonymous online questionnaire was advertised in all French senior radiation oncologists and residents, including demographical data, job-related stress factors, drug use, the Maslach Burn-out Inventory (MBI) and the General Health Questionnaire (GHQ-12). RESULTS: The response rates were 37% (76 out of 204) for radiation oncologists and 22% (166 out of 751) for residents. Sixty-four (84%) radiation oncology residents and 104 (63%) radiation oncologists met criteria for moderate/severe burn-out (odd ratio 2.1 [95% confidence interval 1.0-4.8], P=0.03). Radiation oncology residents were more prone to depersonalization (P<0.001) and lower personal accomplishment (P<0.001). Burn-out was more frequent in radiation oncologists working for public facilities. Symptoms of depression (GHQ-12≥4) were reported by 42% of residents and 36% of radiation oncologists (P=0.40). Psychological morbidity, suicidal ideation and anxiolytic consumption were more frequent in burnt out responders. CONCLUSION: Our figures are in the highest range of published data. Active screening and prevention of burn-out should be implemented and particularly aimed at radiation oncology residents.

SEGMENTATION OF ORGANS AT RISK IN THORACIC CT IMAGES USING A SHARPMASK ARCHITECTURE AND CONDITIONAL RANDOM FIELDS.

Cancer is one of the leading causes of death worldwide. Radiotherapy is a standard treatment for this condition and the first step of the radiotherapy process is to identify the target volumes to be targeted and the healthy organs at risk (OAR) to be protected. Unlike previous methods for automatic segmentation of OAR that typically use local information and individually segment each OAR, in this paper, we propose a deep learning framework for the joint segmentation of OAR in CT images of the thorax, specifically the heart, esophagus, trachea and the aorta. Making use of Fully Convolutional Networks (FCN), we present several extensions that improve the performance, including a new architecture that allows to use low level features with high level information, effectively combining local and global information for improving the localization accuracy. Finally, by using Conditional Random Fields (specifically the CRF as Recurrent Neural Network model), we are able to account for relationships between the organs to further improve the segmentation results. Experiments demonstrate competitive performance on a dataset of 30 CT scans.

[Usefulness of urethral endoprosthesis in the management of urinary retention after brachytherapy for localized prostate cancer]. / Intérêt de l'endoprothèse urétrale dans la prise en charge d'une rétention aiguë d'urine après curiethérapie pour cancer localisé de la prostate.

Brachytherapy is a possible treatment for localized low risk prostate cancer. Although this option is minimally invasive, some side effects may occur. Acute retention of urine (ARU) has been observed in 5% to 22% of cases and can be prevented in most cases by alpha-blocker treatment. Several alternatives have been reported in the literature for the management of ARU following brachytherapy: prolonged suprapubic catheterization, transurethral resection of the prostate and also intermittent self-catheterization. The authors report an original endoscopic approach, using urethral endoprosthesis, with a satisfactory voiding status.

Delegation of medical tasks in French radiation oncology departments: current situation and impact on residents' training.

OBJECTIVES: A national survey was conducted among the radiation oncology residents about their clinical activities and responsibilities. The aim was to evaluate the clinical workload and to assess how medical tasks are delegated and supervised. MATERIALS AND METHODS: A first questionnaire was administered to radiation oncology residents during a national course. A second questionnaire was mailed to 59 heads of departments. RESULTS: The response rate was 62% for radiation oncology residents (99 questionnaires) and 51% for heads of department (30). Eighteen heads of department (64%) declared having written specifications describing the residents' clinical tasks and roles, while only 31 radiation oncology residents (34%) knew about such a document (P=0.009). A majority of residents were satisfied with the amount of medical tasks that were delegated to them. Older residents complained about insufficient exposure to new patient's consultation, treatment planning and portal images validation. The variations observed between departments may induce heterogeneous trainings and should be addressed specifically. CONCLUSION: National specifications are necessary to reduce heterogeneities in training, and to insure that the residents' training covers all the professional skills required to practice radiation oncology. A frame endorsed by academic and professional societies would also clarify the responsibilities of both residents and seniors.

[Clinical target volume delineation for radiotherapy of the esophagus]. / Définition du volume cible anatomoclinique pour l'irradiation des cancers de l'œsophage.

The dense lymphatic network of the esophagus facilitates tumour spreading along the cephalo-caudal axis and to locoregional lymph nodes. A better understanding of microscopic invasion by tumour cells, based on histological analysis of surgical specimens and analysis of recurrence sites, has justified a reduction in radiotherapy target volumes. The delineation of the clinical target volume (CTV) depends on tumour characteristics (site, histology) and on its spread as assessed on endoscopic ultrasonography and ((18)F)-fluorodeoxyglucose positron-emission tomography (FDG-PET). We propose that positive and negative predictive values for FDG-PET should be used to adapt the CTV according to the risk of nodal involvement.

[Alpha/beta ratio revisited in the era of hypofractionation]. / Le rapport alpha/bêta revisité à l'heure de l'hypofractionnement.

Large doses per fraction are not recommended in daily radiotherapy due to a higher risk of late normal tissue injury. The technical refinements of modern radiotherapy and suggestions that some tumors could be sensitive to dose per fraction have renewed the interest in hypofractionated schedules. The estimation of α/ß ratio value requires large samples of carefully evaluated patients in whom total and fractional doses have varied independently. Tumor repopulation has to be considered when the treatment duration is altered. Without setting aside conflicting publication, the α/ß ratio values for prostate and breast (after lumpectomy) cancers could be as low as 2.5 Gy and 4 Gy, respectively. While it is too early to change our routine protocols, the time has come to conduct clinical trials comparing different fractionation schedules.

[Esophageal toxicity of radiation therapy: clinical risk factors and management]. / Toxicité œsophagienne de la radiothérapie : clinique, facteurs de risque et prise en charge.

Acute radiation-induced esophagitis includes all clinical symptoms (odynophagia, dysphagia) occurring within 90 days after thoracic irradiation start. Its severity can be graded using RTOG and CTCAE scales. The clinical risk factors are: age, female gender, initial performance status, pre-therapeutic body mass index, pre-therapeutic dysphagia, tumoral and nodal stage, delivered dose, accelerated hyperfractionned radiotherapy, concomitant association of chemotherapy to radiotherapy and response to the treatment. The dosimetric parameters predictive of esophagitis are: mean dose, V(20Gy), V(30Gy), V(40Gy), V(45Gy) and V(50Gy). Amifostine is the only drug to have a proven radioprotective efficacy (evidence level C, ESMO recommendation grade III). The medical management of esophagitis associates a diet excluding irritant food, medication against gastroesophageal reflux, analgesic treatment according to the WHO scale and management of dehydration and denutrition by enteral feeding.

[Interest of FDG-PET for lung cancer radiotherapy]. / Intérêt de la TEP au FDG pour la radiothérapie des cancers bronchiques.

The recent advances in medical imaging have profoundly altered the radiotherapy of non-small cell lung cancers (NSCLC). A meta-analysis has confirmed the superiority of FDG PET-CT over CT for initial staging. FDG PET-CT improves the reproducibility of target volume delineation, especially close to the mediastinum or in the presence of atelectasia. Although not formally validated by a randomized trial, the reduction of the mediastinal target volume, by restricting the irradiation to FDG-avid nodes, is widely accepted. The optimal method of delineation still remains to be defined. The role of FDG PET-CT in monitoring tumor response during radiotherapy is under investigation, potentially opening the way to adapting the treatment modalities to tumor radiation sensitivity. Other tracers, such as F-miso (hypoxia), are also under clinical investigation. To avoid excessive delays, the integration of PET-CT in routine practice requires quick access to the imaging equipment, technical support (fusion and image processing) and multidisciplinary delineation of target volumes.

[Dosimetric factors predictive of late toxicity in prostate cancer radiotherapy]. / Radiothérapie prostatique: prédiction de la toxicité tardive à partir des données dosimétriques.

Dose escalation in prostate cancer is made possible due to technological advances and to precise dose-volume constraints to limit normal tissue damage. This article is a literature review focusing on the correlations between exposure (doses and volumes) of organs at risk (OAR) and rectal, urinary, sexual and bone toxicity, as well as on mathematical models aiming at toxicity prediction. Dose-volume constraint recommendations are presented that have been shown to be associated with reduced rectal damage. Indeed, the clinical data is relatively strong for late rectal toxicity (bleeding), with constraints put on both the volume of the rectum receiving high doses (≥70 Gy) and the volume receiving intermediate doses (40 to 60 Gy). Predictive models of rectal toxicity (Normal Tissue Complication Probability) appear to accurately estimate toxicity risks. The correlations are much weaker for the bulb and the femoral heads, and nearly do not exist for the bladder. Further prospective studies are required, ideally taking into account patient-related risk factors (co-morbidities and their specific treatments), assays of normal tissue hypersensitivity to ionizing radiation and mathematical models applied on 3D images acquired under the treatment machine (e.g. Cone Beam CT).

[Probabilities of organs at risk damage: history and mathematical models]. / Probabilités de lésion des organes à risque: historique et principaux modèles mathématiques d'estimation.

The a priori evaluation of normal tissue complication probability is an important issue for the radiation oncologist looking for the best therapeutic index. The advances in radiobiological and technological knowledge provide a better understanding of the determinants of radiation effects. The amount of information required to optimize the treatment modalities justifies the use of mathematical models linking the treatment characteristics (dose, volume, treatment time...) to the likelihood of complications. The radiation oncologist needs a minimal understanding of the mathematical models and their limits to justify his prescriptions.

[Diagnosis and treatment of soft-tissue tumors]. / Prise en charge des tumeurs des parties molles de l'appareil locomoteur de l'adulte.

The diagnostic and therapeutic management of patients with soft-tissue tumors would be similar to the approach used for bone tumors if it were not for one crucial factor: the absolute necessity to recognize a sarcoma. The predominant features are the size of the tumor and its superficial or deep localization. If the tumor is small and superficial, biopsy can be associated with immediate resection without risk of dissemination to the deep tissues: this is the biopsy-resection approach. If the tumor is deep or superficial but large sized, search for locoregional spread with MRI is necessary before undertaking any surgical procedure. MRI can help guide the biopsy and plan resection if the tumor is a sarcoma. A first biopsy is necessary to establish the histological diagnosis and elaborate the therapeutic strategy. Samples should be sent immediately to the pathology lab which should examine sterile fresh tissue. Experience has demonstrated that proper rules for diagnosis and treatment are not necessarily applied initially in approximately one-fourth of all subjects with a malignant soft-tissue tumor. Besides the medical problems caused by this situation, the patient loses a chance for cure. When the tumor is a sarcoma, surgery is the basis of treatment. Complementary radiation therapy may be necessary, particularly for high-grade tumors or if the surgical margin was insufficient. Systemic or locoregional chemotherapy can also be used for high-grade or non-resectable tumors.

[Preliminary results of the assessment of intensity modulated radiotherapy (IMRT) for prostatic and head and neck tumors (STIC 2001)]. / Résultats préliminaires de l'évaluation de la radiothérapie conformationnelle avec modulation d'intensité (RCMI) pour le traitement des cancers prostatiques et ORL (STIC 2001).

INTRODUCTION: Between May 2002 and May 2004, eight French comprehensive cancer centres did a prospective nonrandomized study including 200 patients, 100 with cancer of the prostate and 100 with head and neck cancers. Half of each patient group was treated by IMRT and the others by RTC 3D. This clinical study was associated with an economic study and a physics study. We report here the first results. PATIENTS AND METHODS: For the clinical study, the analysis of the data of the first 88 patients irradiated for a prostatic cancer shows that 39 received RTC and 49 IMRT with a mean dose of 78 Gy at the ICRU point at 2 Gy per fraction. For H&N tumours, the preliminary analysis was done on the 87 first patients with a mean follow-up of 11.5 months (2 to 25 months) and a median of 8.4 months for the IMRT groups and 13.2 months for the RTC group. The economic study was done on the first 157 patients included during the first 18 months: 71 treated by RTC (35 for H&N and 36 for prostate) and 86 treated by IMRT (38 for H&N and 48 for prostate). The assessment of the direct costs was realized by a micro-costing technique. The physical study compared dose distributions for both techniques and has created quality control recommendations. RESULTS: Clinical studies of the acute reactions do not show any difference between groups, but we want to point out the short follow-up and the relatively high dose delivered to cancers of the prostate. The physics study demonstrates that IMRT is technically feasible in good clinical conditions with high quality assurance, a good reproducibility and precision. Dosimetric data show that IMRT could certainly spare organs at risk more than RTC for H&N tumours. The direct costs of "routine" treatments for H&N tumours were 4922 euros for IMRT versus 1899 euros for RTC and for the prostatic cancers 4911 euros for IMRT versus 2357 for RTC.

[Quality control during radiation therapy]. / Le contrôle de qualité en cours d'irradiation.

The aim of quality control procedures during radiation therapy is to check the consistency between actual and prescribed treatments. Given the technical complexity of modern radiotherapy, stricter policies are necessary to meet increasing requirements for quality and safety. Among the various tools available, electronic imaging systems play an increasing role in patient-beam position checking and in vivo dose measurements. Written procedures will have to be established in order to describe the control modalities and frequency, as well as the rules for error corrections according to the treatment intent. Non medical staff will be devoted to new tasks, under the radiation oncologist's responsibility. A special attention should be directed at electronic archives, since the present technology is unlikely to meet the legal requirement to keep medical records accessible for at least 30 years.