Interstitial brachytherapy for lip carcinomas: Comparison between Ir-192 low-dose-rate and high-dose-rate treatment.

PURPOSE: Low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy are known to be effective in the treatment of lip carcinomas. The aim of this study was to retrospectively compare oncologic and toxicity outcomes between the two techniques. PATIENTS AND METHODS: From 2007 to 2018, patients at the Institut de cancérologie de Lorraine (France) who received exclusive or adjuvant interstitial brachytherapy for lip squamous carcinomas were studied. Two groups were defined: the LDR/PDR group, including patients treated with iridium-192 wires, or pulsed-dose rate technique, and the high-dose-rate group, with patients treated by high-dose-rate technique. The dose ranged between 50Gy and 65Gy (depending on previous surgery) for low-dose-/pulsed-dose rate treatments, and 39Gy for high-dose-rate (twice a day). Early, late toxicity events and oncologic control were reported. RESULTS: Among the 61 patients whose data were analyzed retrospectively, 36 received the low-dose-/pulsed-dose rate treatment (59%) and 25 the high-dose-rate brachytherapy (41%). The median follow-up time was 44 months. At 36 months, the local control rates were 96.3% for LDR/PDR group and 100% for HDR (P=0.180). The regional control rates were 85.9% and 92% without any difference according to the two groups (P=0.179). The specific overall survival rate was 95.5% with no difference between groups. There were more grade 2 or higher mucositis in the HDR group than in LDR/PDR group (40% versus 16.7%, P=0.042). One case of grade 3 mucositis was recorded in each group. No grade 3 late complications were recorded. High-dose-rate brachytherapy reduced the length of hospitalization by 2 days (P<0.001). CONCLUSION: High-dose- or low-dose-/pulsed-dose rate brachytherapy seemed to be as effective and well tolerated in our experience of 61 patients.

Place of radiotherapy for treatment of metastatic cervical, vaginal and endometrial uterine cancer.

Beyond classical palliative-intent irradiation schemes, there are increasing data suggesting a benefit for intensive locoregional treatments in metastatic gynecological cancers. Such approach aims at avoiding local symptoms related to tumor progression, but may also improve survival outcome by shrinking tumor burden to a microscopic state. This strategy is rarely considered upfront (in highly selected patients with very limited oligometastatic disease), but rather after systemic treatment. In case of tumor response (especially if complete response) of the metastatic sites, pelvic±para-aortic radiotherapy can be considered in combination with a brachytherapy boost to obtain long-term local control, in particular in cervical or vaginal cancer patients. Such approach seems particularly relevant when there is isolated persistence or progression of macroscopic disease within the pelvis. In parallel, there is also an increasing place for radiotherapy of oligo-metastatic sites. We review the literature on the place of radiotherapy in the management of cancers of the cervix and metastatic endometrial cancer.

Hypofractionated radiotherapy for invasive squamous cell carcinoma of the scalp in the elderly: Efficacy and tolerance, preliminary results.

PURPOSE: Skin squamous cells carcinomas (SCC) are frequently tumor, especially in the elderly population. Surgical excision is the standard treatment. But for patients suffering large tumor or/with comorbidity, a conservative approach with irradiation can be proposed. The hypofractionated schedule is used to shorten the overall treatment time with same results and without compromising therapeutic outcomes. The aim of this study is to assess the efficacy and tolerance of hypofractionated radiotherapy for invasive SCC of the scalp in elderly. PATIENTS AND METHODS: We included patients suffering from SCC of the scalp and treated by hypofractionated radiotherapy at the Institut de cancérologie de Lorraine or centre Émile-Durkeim d'Épinal, from January 2019 to December 2021. Characteristics of patients, size of the lesion and side effects were collected retrospectively. Tumor size at 6 months corresponded to the primary endpoint. Toxicity was collected for the secondary endpoint. RESULTS: Twelve patients with a median age of 85 years old were included. The mean size was 4,5cm with a bone invasion in 2/3 of cases. Radiotherapy was delivered after surgical excision for half of the patient. The dose delivered was 54Gy in 18 daily fractions size. Six months after irradiation: 6/11 patients had no residual lesion, 2/11 had a partial response with a residual lesion of about 1cm. 3 patients presented local recurrence. One patient died within 6 months of radiotherapy because of another comorbidity. In total, 25% had presented a grade 3 acute radiation dermatitis, no grade 4 toxicity. CONCLUSION: Short term of moderately hypofractionated schedule radiotherapy was a success with complete or partial response for more than 70% of the patients in squamous cell carcinomas. There is no major side effect.

Impact of external beam pelvic radiotherapy of endometrial carcinoma: A focus on chronic digestive toxicity.

PURPOSE: The standard treatment for endometrial cancer is surgery, although depending on the risk factors, adjuvant radiation therapy may also be given. It is proposed for high-risk carcinomas for which an improvement in progression-free survival though not overall survival has been shown. However, despite the development of radiotherapy treatments with intensity modulation and image guidance, adjuvant radiation therapy remains toxic to the digestive system. We aimed to investigate the incidence of digestive toxicity and the presence of any predictive factors. MATERIALS AND METHODS: Data were retrospectively collected from patients treated with adjuvant radiotherapy for endometrial carcinoma at the Institut de cancérologie de Lorraine and centre hospitalier Émile-Durkheim between January 2010 and October 2016 and analyzed to identify factors associated with chronic digestive toxicity. RESULTS: One hundred and thirty-nine patients received a total dose of 50Gy fractionated into 25 sessions, five per week for five weeks. The median follow-up after irradiation completion was 38 months. The incidence of gastrointestinal and rectal toxicity in all patients treated with pelvic irradiation for endometrial carcinoma was 11.1% (95% confidence interval [95%CI]: 5.4-19%) for grade 3-4 and 25.6% (95%CI: 17.0-34.9%) for grade 2-4. No factor was found to be significantly predictive of chronic digestive toxicity. At five years, the overall survival was 74.3%, (95%CI: 65.3-81.4%), progression-free survival was 69.6% (95%CI: 60.1-77.3%) and incidence of pelvic recurrence was 7.9% (95%CI: 3.8-13.9%). CONCLUSION: Our results confirmed that pelvic radiotherapy can induce a relatively high rate of digestive toxicity but failed to identify relevant factors able to predict it.

Radiotherapy of cervical cancer.

External beam radiotherapy and brachytherapy are major treatments in the management of cervical cancer. For early-stage tumours with local risk factors, brachytherapy is a preoperative option. Postoperative radiotherapy is indicated according to histopathological criteria. For advanced local tumours, chemoradiation is the standard treatment, followed by brachytherapy boost, which is not optional. We present the update of the recommendations of the French Society of Oncological Radiotherapy on the indications and techniques for external beam radiotherapy and brachytherapy for cervical cancer.

Radiotherapy for endometrial cancer.

The first intent upfront treatment of endometrial cancer is surgery. External radiotherapy and brachytherapy; however, are important tools in adjuvant setting, according to histopathological risk factors for locoregional recurrence or in the event of an inoperable tumor. We present the update of the recommendations of the French society of oncological radiotherapy on the indications and technical methods of performing radiotherapy and brachytherapy for endometrial cancer.

Interstitial multi-catheter breast brachytherapy: Technical aspects and experience feedback in a comprehensive cancer center.

PURPOSE: To focus on technical aspects of the implementation of interstitial high dose rate brachytherapy, with a step-by-step approach. MATERIALS AND METHODS: Patients were selected during multidisciplinary tumor boards, according to inclusion criteria adapted from GEC-ESTRO guidelines. A CT scan was performed a few days before implantation. On pre-implant CT, using surgical scar and clips, surgical and pathological reports, and preoperative images, we delineated the tumor bed to be included in the Clinical Target Volume (CTV), according to GEC ESTRO Recommendations. A 3D virtual implant simulation of the best catheter positions was performed in order to cover the target volume. Implantation was then carried out under local anaesthetic using 3D projections of the catheter inlets and outlets. Dosimetry was performed on post-implantation CT scan. A dose of 34Gy was delivered in 10 fractions. Acute and late side effects, and local control were evaluated 2 and 8 months after treatment. RESULTS: Between July 2017 and January 2020, 20 patients were treated with accelerated partial breast irradiation. Dose constraints regarding target volume coverage, overdose, dose homogeneity, conformation index and organs at risk were met in 94.7%, 100%, 63.2%, 0% and 89.5% of the treatment plans, respectively. Grade 1-2 acute adverse events were observed in 21% of patients, with no grade 3-4 events. CONCLUSION: The first dosimetric results and early clinical tolerance and efficacy achieved by the implementation of breast interstitial multicatheter brachytherapy in routine clinical practice are very encouraging, and confirm the interest of extending this practice.

[Dose optimization in 3D pulsed dose rate brachytherapy for patients with locally advanced cervical cancer: A French multicenter phase II trial]. / Optimisation de la curiethérapie utérovaginale de débit pulsé des cancers du col utérin localement évolués : résultats finaux du PHRC Tridicol.

PURPOSE: We present the results of the PHRC Tridicol, a prospective French phase II study whose objective was to increase the dose delivered to the target volume during brachytherapy for locally advanced cervical cancers. MATERIAL AND METHODS: Eight centers included 48 patients, treated with concomitant radiochemotherapy, then uterovaginal brachytherapy. RESULTS: The median follow-up was 63 months. The dose of brachytherapy delivered in biological equivalent dose (EQD2) to 90% of the High Risk CTV (D90 CTV HR) was 80Gy in median dose. The 5-year local control rate (LC) was 84%, close to the hypothesis of 86.7%. The rate of severe complications (grade 3-4) was 23% at 5 years. The rectal dose was correlated with the risk of severe complications. CONCLUSION: HR CTV dose was below the target (85Gy) due to low use of parametrial interstitial needles, as the centers did not always have an adequate applicator, or were at the time at the beginning of their learning curve. The 5-year LC rate was improved compared to that of the comparable STIC PDR group (78%) but lower than the retroEMBRACE cohort of GEC ESTRO (89%). The complication rate was higher than in the comparable group of STIC PDR but close to that of retroEMBRACE. Training brachytherapy teams in interstitial implantation or referring patients to referral centers should help improve the therapeutic index of cervical cancer.

Radiotherapy for oral cavity cancers.

Intensity modulated radiation therapy and brachytherapy are standard techniques of irradiation for the treatment of oral cavity cancers. These techniques are detailed in terms of indication, planning, delineation and selection of the volumes of interest, dosimetry and patients positioning control. This is an update of the guidelines of the French Society of Radiotherapy Correspondence.

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.

[Can stereotactic body radiotherapy replace brachytherapy for locally advanced cervical cancer? French society for radiation oncology statement]. / La radiothérapie stéréotaxique peut-elle remplacer la curiethérapie pour les cancers du col utérin localement évolués ? Positionnement de la Société française de radiothérapie oncologique.

Brachytherapy is part of the treatment of locally advanced cervical cancers, accounting for about half of the total delivered dose. The benefit of dose escalation is the most important in advanced cases or if the tumor has responded poorly. The use of interstitial implantations makes it possible to reach doses of the order of 85 to 90Gy (including external beam radiotherapy contribution) in most patients, through image-guided approaches. Brachytherapy delivery is one of the quality criteria for patient care. To date, no data allow us to consider as an alternative the use of external boost through intensity-modulated or stereotactic body radiotherapy. Indeed, the doses delivered to the tumor and the capacity to spare normal tissues remains lower, as compared to what is permitted by brachytherapy. It is therefore appropriate for centers that do not have access to the technique to establish networks with centers where brachytherapy is performed, to allow each patient to have access to the technique. It is also necessary to promote brachytherapy teaching. The issue of reimbursement will be crucial in the coming years to maintain expertise that is today insufficiently valued in its financial aspects, but has a very high added value for patients.

Quantification of right ventricular extracellular volume in pulmonary hypertension using cardiac magnetic resonance imaging.

PURPOSE: The purpose of this prospective study was to assess the value of biventricular extracellular volume (ECV) in pre-capillary pulmonary hypertension (PH) obtained using cardiac magnetic resonance imaging (CMR) and to correlate ECV with markers of prognosis such as strain echocardiography and blood biomarkers of fibrosis. MATERIALS AND METHODS: Twelve patients with PH (6 men, 6 women; mean age=50±16 [SD] years; age range: 22-73 years) underwent the same day: (i), transthoracic echocardiography including measurement of right ventricular (RV) fractional shortening (RVfs), tricuspid annular plane systolic excursion (TAPSE), maximal tricuspid annular velocity, RV global and segmental deformation; (ii), right heart catheterization measuring pulmonary arterial pressures (inmmHg) and cardiac output (inL/min); (iii), CMR at 1.5-T measuring RV volumes and ejection fraction; (iv), native and 15min post-contrast T1 mapping using modified look-locker inversion-recovery sequence; and (v), serum quantification of two biomarkers of collagen turnover and hematocrit. Non-parametric Mann-Whitney tests were used to search for differences between categorical variables. Spearman correlation test was used for search for correlation between quantitative values. RESULTS: Global RV ECV was 34%±4.2 (SD) for our entire population. A significant correlation was found between RV ECV and RVfs (r=0.6; P=0.026), S wave velocity (r=0.7; P=0.009), TAPSE (r=0.6; P=0.040) and RV systolic ejection fraction on CMR (r=0.6; P=0.04). There were no correlations between the ECV values in the lateral wall of the RV and in the septum (r=0.4; P=0.206). A significant correlation was found between septal ECV and 2D septal strain (r=0.7; P=0.013). CONCLUSION: ECV in PH as obtained using CMR appears to correlate with known echocardiographic prognostic markers and more specifically with the markers, which assess RV systolic function.

Inducing dissociation and schizotypal experiences through "vision-deforming" glasses.

Derealization, depersonalization and schizotypal experiences are described as separate concepts but they can be hard to distinguish. One way to show the uniqueness of these concepts is by showing a dissociation between these experiences. The aim of this study was to experimentally induce derealization without inducing depersonalization or schizotypal experiences. Healthy participants watched a neutral video in one of four conditions: (1) with stroboscopic light, (2) while wearing deforming glasses, (3) with stroboscopic light and while wearing "vision deforming glasses" or (4) without any manipulation. The results show that the "vision deforming" glasses induced derealization without inducing depersonalization but not without inducing schizotypal experiences. The stroboscopic light showed no significant effect, nor was there a significant interaction between the stroboscopic light and the deforming glasses. The results indicate that using "vision deforming" glasses as a manipulation method can show a single dissociation between derealization and depersonalization but cannot dissociate derealization from state schizotypy. This association between derealization and schizotypal experiences might be helpful in understanding the high comorbidity rate between dissociative disorders and schizophrenia spectrum disorders.

[Brachytherapy for head and neck cancers]. / Curiethérapie des cancers de la tête et du cou : synthèse des recommandations européennes et principales indications.

The main indications of the brachytherapy of head and neck cancers are the limited tumours of the lip, the nose, the oral cavity and the oropharynx. Nasopharynx tumours are nowadays treated by intensity-modulated radiotherapy. This technique can be exclusive, associated with external radiotherapy or postoperative. It can also be a salvage treatment for the second primaries in previously irradiated areas. If the low dose rate brachytherapy rules remain the reference, the pulse dose rate technique allows the prescription of the dose rate and the optimisation of the dose distribution. Results of high dose rate brachytherapy are now published. This paper reports the recommendations of the Gec-ESTRO, published in 2017, and takes into account the data of the historical low dose rate series, and is upgraded with the pulsed-dose rate and high dose rate series.

Approach-avoidance of facial affect is moderated by the presence of an observer-irrelevant trigger.

This study examined whether approach-avoidance related behaviour elicited by facial affect is moderated by the presence of an observer-irrelevant trigger that may influence the observer's attributions of the actor's emotion. Participants were shown happy, disgusted, and neutral facial expressions. Half of these were presented with a plausible trigger of the expression (a drink). Approach-avoidance related behaviour was indexed explicitly through a questionnaire (measuring intentions) and implicitly through a manikin version of the affective Simon task (measuring automatic behavioural tendencies). In the absence of an observer-irrelevant trigger, participants expressed the intention to avoid disgusted and approach happy facial expressions. Participants also showed a stronger approach tendency towards happy than towards disgusted facial expressions. The presence of the observer-irrelevant trigger had a moderating effect, decreasing the intention to approach happy and to avoid disgusted expressions. The trigger had no moderating effect on the approach-avoidance tendencies. Thus the influence of an observer-irrelevant trigger appears to reflect more of a controlled than automatic process.

The influence of adjunctive treatment and metacognitive deficits in schizophrenia on the experience of work.

Enhancing work function is now widely considered a core element of comprehensive schizophrenia treatment. While research efforts have illuminated factors that influence how well patients perform at work, less is known about the factors influencing the subjective experience of work. It is not known how, and to what extent, symptoms, cognitive deficits or metacognitive capacities impact job satisfaction and whether treatment can have an effect on job satisfaction. To explore this issue, data from a trial in which participants in a six-month vocational program were assigned to either a standard support group or a cognitive behavioral group therapy, and asked to fill in weekly self-reports of job satisfaction was analyzed. Work satisfaction and the consistency of these ratings were compared between the two groups and the moderating influence of metacognitive capacity was analyzed. A significant interaction effect revealed that higher metacognitive capacity predicted higher average job satisfaction only in the CBT group. Additionally, higher metacognitive capacity led to a more varied appraisal of work satisfaction only in the support group.

[Giant renal angiomyolipoma with right heart failure]. / Angiomyolipome rénal géant compliqué d'insuffisance cardiaque droite.

We report the case of a 63-year-old woman presenting a 26cm right renal angiomyolipoma with intratumoral arteriovenous fistula responsible for a high-output right heart failure. A radical surgical treatment after preoperative embolization allowed rapid improvement of cardiac symptoms with an uneventful postoperative course.

[Mitochondrial cardiomyopathy in an adult: a case history]. / Cardiomyopathie mitochondriale de l'adulte: à propos d'un cas.

We report an original case of mitochondrial cardiomyopathy discovered in a young woman during an episode of cardiac decompensation. The diagnosis was suspected from the echocardiographic appearances of granite-like heterogeneous hypertrophic cardiomyopathy. It was confirmed by endomyocardial biopsies. The clinical evolution was favourable with classical treatment. Mitochondrial cardiomyopathy is a rare cause of cardiomyopathy, generally observed in children, with multisystemic localisation. The pathophysiology and genetics are complex. Cardiac involvement is observed in 25% of cases, with the principal manifestation being hypertrophic cardiomyopathy. In the absence of any specific clinical or paraclinical signs, echocardiography and MRI are the techniques of choice for morphological evaluation. Diagnosis relies upon myocardial biopsy, which should be readily advocated in every unexplained case of cardiomyopathy in a young subject. The prognosis is poor and no specific treatment is available.

[Torsades de pointes caused by cetirizine overdose]. / Torsades de pointes induites par surdosage en cétirizine: à propos d'un cas.

Several therapeutic substances can cause torsades de pointes, especially if they prolong the QT interval and/or if there is an associated hypokalaemia. Certain second generation H1 antihistamines have been incriminated in the occurrence of such ventricular arrhythmias, such as terfenadine and astezimole, which have been withdrawn. Cetirizine, widely used in the treatment of allergic reactions, is a second generation H1 antihistamine with as yet no precautions of use regarding rhythm disturbances. No documented case of arrhythmia attributable to this drug has been reported. We report the case of a dialysed patient with chronic renal failure who had symptomatic episodes of torsades de pointes in the context of hypokalaemia and cetirizine overdose. In the light of this observation it would appear that the prescription of cetirizine is contra-indicated under such conditions.