Prognostic value of local relapse for patients with endometrial cancer.

BACKGROUND: The objective of our study was to determine survival and prognostic factors associated with isolated local recurrence of endometrial cancer. METHODS: Data of 1229 patients with endometrial carcinoma treated between 2000 and 2012 were extracted from maintained databases of nine French University Hospitals as well as from the Senti-Endo trial. Patients with isolated central pelvic and vaginal recurrence were selected for further analysis. RESULTS: Two hundreds and twenty five patients recurred during the inclusion period, 20 with isolated central pelvic recurrence and 23 with vaginal recurrence. Patients without recurrence had initially significantly less lymphovascular space invasion (p = 0.01), less advanced diseases (>stage II) (p < 0.001) and more often low or intermediate risk tumours than patients with local recurrence. Local recurrence was statistically associated with better overall survival than non-local recurrence (p = 0.028) but dramatically decreased overall survival when compared to patients without any recurrence (p < 0.001). The site of recurrence, i.e. vaginal or central pelvic, was significantly associated with overall survival (p = 0.015). Patients without brachytherapy at initial management were more likely to have local recurrence of their disease when compared to those without recurrence (p = 0.03). None of the prognostics factors for survival in patients with local recurrence was statistically significant in multivariate analysis. CONCLUSIONS: Local recurrence is a key event in endometrial cancer evolution severely impacting overall survival. Better understanding of the factors associated with prolonged survival is mandatory to improve our management of these patients.

Twenty Fraction Prostate Radiotherapy with Intra-prostatic Boost: Results of a Pilot Study.

AIMS: For patients with high-risk, locally bulky prostate cancer, an intra-prostatic boost to tumour volumes (dose-painting) offers a risk-adapted dose escalation. We evaluated the feasibility of hypofractionated dose-painting radiotherapy and the associated toxicity. The possibility to streamline a radiobiologically optimised planning protocol was also investigated. MATERIALS AND METHODS: Twenty-eight patients were treated using a dose-painting approach; boost volumes were identified with functional magnetic resonance imaging scans. The prostate dose outside the boost volume was 60 Gy in 20 fractions, and the maximum integrated boost dose was set to 68 Gy, provided that the dose constraints to the organs at risk could be fulfilled. Rotational intensity-modulated radiotherapy was used with daily image guidance and fiducial markers. RESULTS: The boost dose was escalated to 68 Gy for 25 patients (median dose 69 Gy, range 68-70 Gy); for three patients the boost dose was 67 Gy, due to the proximity of the urethra and/or the rectum. The mean normal tissue complication probability for rectal bleeding was 4.7% (range 3.4-5.8%) and was 3.5% for faecal incontinence (range 2.3-5.0%). At a median follow-up of 38 months (range 32-45) there was no grade 3 toxicity. Two patients developed grade 2 genitourinary toxicity (7.1%) and none developed grade 2 gastrointestinal toxicity. The mean prostate-specific antigen (PSA) for 23 patients who had stopped the adjuvant hormone therapy with a normal testosterone was 0.27 ng/ml (0.02-0.72) at follow-up; two patients have suppressed PSA and testosterone after stopping 3 year adjuvant hormone and three patients have relapsed (one pelvic node, two PSA only) at 36, 12 and 42 months, respectively. CONCLUSIONS: A hypofractionated radiotherapy schedule, 60 Gy in 20 fractions with intra-prostatic boost dose of 68 Gy, can be achieved without exceeding dose constraints for organs at risk. Hypofractionated dose-painting escalated radiotherapy has an acceptable safety profile. The same planning protocol was used in a phase II single-arm trial (BIOPROP20: ClinicalTrials.gov identifier NCT02125175) and will further be used in a large phase III randomised trial (PIVOTALboost): patients will be randomised standard radiotherapy (60 Gy in 20 fractions) with or without lymph node radiotherapy versus dose-painting radiotherapy with or without lymph node radiotherapy; the trial will be opened for recruitment in summer 2017.

Prostate Dose-painting Radiotherapy and Radiobiological Guided Optimisation Enhances the Therapeutic Ratio.

AIMS: To describe the treatment of 11 patients with radiobiologically guided dose-painting radiotherapy and report on toxicity. MATERIALS AND METHODS: Boost volumes were identified with functional magnetic resonance imaging scans in 11 patients with high-risk prostate cancer. Patients were treated using a dose-painting approach; the boost dose was limited to 86 Gy in 37 fractions, while keeping the rectal normal tissue complication probability to 5-6%. Rotational intensity-modulated radiotherapy was used with daily image guidance and fiducial markers. RESULTS: The median dose to the prostate (outside the boost volume) and urethra was 75.4 Gy/37 fractions (range 75.1-75.8 Gy), whereas the median boost dose was 83.4 Gy (range 79.0-87.4 Gy). The tumour control probability (TCP) (Marsden model) increased from 71% for the standard plans to 83.6% [76.6-86.8%] for the dose-painting boost plans. The mean (Lyman-Kutcher-Burman) normal tissue complication probability for rectal bleeding was 5.2% (range 3.3-6.2%) and 5.2% for faecal incontinence (range 3.6-7.8%). All patients tolerated the treatment well, with a low acute toxicity profile. At a median follow-up of 36 months (range 24-50) there was no grade 3 late toxicity. Two patients had grade 2 late urinary toxicity (urethral stricture, urinary frequency and urgency), one patient had grade 1 and one grade 2 late rectal toxicity. The mean prostate-specific antigen at follow-up was 0.81 ng/ml after stopping hormone therapy; one patient relapsed biochemically at 32 months (2.70 ng/ml). CONCLUSIONS: The toxicity for this radiobiological guided dose-painting protocol was low, but we have only treated a small cohort with limited follow-up time. The advantages of this treatment approach should be established in a clinical trial.

4D radiobiological modelling of the interplay effect in conventionally and hypofractionated lung tumour IMRT.

OBJECTIVE: To study the impact of the interplay between respiration-induced tumour motion and multileaf collimator leaf movements in intensity-modulated radiotherapy (IMRT) as a function of number of fractions, dose rate on population mean tumour control probability ([Formula: see text]) using an in-house developed dose model. METHODS: Delivered dose was accumulated in a voxel-by-voxel basis inclusive of tumour motion over the course of treatment. The effect of interplay on dose and [Formula: see text] was studied for conventionally and hypofractionated treatments using digital imaging and communications in medicine data sets. Moreover, the effect of dose rate on interplay was also studied for single-fraction treatments. Simulations were repeated several times to obtain [Formula: see text] for each plan. RESULTS: The average variation observed in mean dose to the target volumes were -0.76% ± 0.36% for the 20-fraction treatment and -0.26% ± 0.68% and -1.05% ± 0.98% for the three- and single-fraction treatments, respectively. For the 20-fraction treatment, the drop in [Formula: see text] was -1.05% ± 0.39%, whereas for the three- and single-fraction treatments, it was -2.80% ± 1.68% and -4.00% ± 2.84%, respectively. By reducing the dose rate from 600 to 300 MU min(-1) for the single-fraction treatments, the drop in [Formula: see text] was reduced by approximately 1.5%. CONCLUSION: The effect of interplay on [Formula: see text] is negligible for conventionally fractionated treatments, whereas considerable drop in [Formula: see text] is observed for the three- and single-fraction treatments. Reduced dose rate could be used in hypofractionated treatments to reduce the interplay effect. ADVANCES IN KNOWLEDGE: A novel in silico dose model is presented to determine the impact of interplay effect in IMRT treatments on [Formula: see text].

Radiobiologically guided optimisation of the prescription dose and fractionation scheme in radiotherapy using BioSuite.

OBJECTIVE: Radiobiological models provide a means of evaluating treatment plans. Keeping in mind their inherent limitations, they can also be used prospectively to design new treatment strategies which maximise therapeutic ratio. We propose here a new method to customise fractionation and prescription dose. METHODS: To illustrate our new approach, two non-small cell lung cancer treatment plans and one prostate plan from our archive are analysed using the in-house software tool BioSuite. BioSuite computes normal tissue complication probability and tumour control probability using various radiobiological models and can suggest radiobiologically optimal prescription doses and fractionation schemes with limited toxicity. RESULTS: Dose-response curves present varied aspects depending on the nature of each case. The optimisation process suggests doses and fractionation schemes differing from the original ones. Patterns of optimisation depend on the degree of conformality, the behaviour of the normal tissue (i.e. "serial" or "parallel"), the volume of the tumour and the parameters of clonogen proliferation. CONCLUSION: Individualising the prescription dose and number of fractions with the help of BioSuite results in improved therapeutic ratios as evaluated by radiobiological models.

Thrombotic stroke following snake bites by the "Fer-de-Lance"Bothrops lanceolatus in Martinique despite antivenom treatment: a report of three recent cases.

BACKGROUND: The severity of envenoming from Bothrops lanceolatus is determined by the development of cerebral, myocardial or pulmonary infarctions, and occasionnaly by serious local envenoming. Introduction of specific antivenom has resulted in a dramatic improvement in the prognosis of this envenoming. Against this background, we report 3 recent cases of patients bitten by B. lanceolatus who developed cerebral infarctions despite early administration of antivenom. METHODS: In 1991 a protocol was designed to apply the same evaluation and treatment to all envenomed patients. The clinical results have been continuously monitored. RESULTS: Between April 1993 and July 2003, 128 envenomed patients (age 6-83 (mean 45) years) were treated. No coagulopathy, thrombotic complication or death occurred in patients who were given early antivenom therapy--up to 6h following the bite--and 126 patients recovered. Between August 2003 and October 2004, 10 additional patients (18-66 (mean 46) years) were given antivenom at the time of admission at hospital. Of these, 3 developed cerebral infarctions within 24h. Effectiveness of antivenom was tested on mouse, and found to be lower than specified by the manufacturer. DISCUSSION: Our data shows that recently the antivenom may have lost some of its efficacy. Possible mechanisms include variability in venom composition or loss of activity of the antibodies produced more than 15 years ago. The question is whether we should attempt to produce improved antivenom. This could include activity against the venom of Bothrops caribbaeus from the neighbouring island of St Lucia, which shares a monophyletic group with B. lanceolatus and whose venom produces a similar thrombotic syndrome. CONCLUSION: Prevention of systemic vessels thrombosis remains the main therapeutic challenge of B. lanceolatus envenoming in Martinique.

[Primary mucinous carcinoma of the female ureter]. / Le carcinome mucineux primitif de l'urètre féminin.

The authors report a new case of primary mucinous carcinoma of the urethral meatus in a 66-year-old patient, treated by simple excision. The patient is in very good general health one year after the diagnosis. Although primary mucinous carcinoma of the female urethra is very rare, this diagnosis should be considered in any case of macroscopically suspicious urethral polyp, after having eliminated a gastrointestinal, vesical or gynaecological origin. Only seventeen cases have been published in the literature. Unlike our case, most of the reported lesions involved all of the urethra at the time of diagnosis and frequently presented extension to periurethral tissues or adjacent organs. A very poor prognosis is reported in the literature, even despite treatment, based on surgery and/or radiotherapy.