Thomas Mulliez

Hypofractionated whole breast irradiation for patients with large breasts: A randomized trial comparing prone and supine positions

BACKGROUND AND PURPOSE Comparison of acute toxicity of whole-breast irradiation (WBI) in prone and supine positions. MATERIALS AND METHODS This non-blinded, randomized, prospective, mono-centric trial was undertaken between December 29, 2010, and December 12, 2012. One hundred patients with large breasts were randomized between supine multi beam (MB) and prone tangential field (TF) intensity modulated radiotherapy (IMRT). Dose-volume parameters were assessed for the breast, heart, left anterior descending coronary artery (LAD), ipsilateral lung and contralateral breast. The primary endpoint was acute moist skin desquamation. Secondary endpoints were dermatitis, edema, pruritus and pain. RESULTS Prone treatment resulted in: improved dose coverage (p<0.001); better homogeneity (p<0.001); less volumes of over-dosage (p=0.001); reduced acute skin desquamation (p<0.001); a 3-fold decrease of moist desquamation p=0.04 (chi-square), p=0.07 (Fishers exact test)); lower incidence of dermatitis (p<0.001), edema (p=0.005), pruritus (p=0.06) and pain (p=0.06); 2- to 4-fold reduction of grades 2-3 toxicity; lower ipsilateral lung (p<0.001) and mean LAD (p=0.007) dose; lower, though statistically non-significant heart and maximum LAD. CONCLUSIONS This study provides level I evidence for replacing the supine standard treatment by prone IMRT for whole-breast irradiation in patients with large breasts. A confirmatory trial in a multi-institutional setting is warranted.

Neuroanatomy and neurophysiology related to sexual dysfunction in male neurogenic patients with lesions to the spinal cord or peripheral nerves.

Study design:Review article.Objectives:The neuroanatomy and physiology of psychogenic erection, cholinergic versus adrenergic innervation of emission and the predictability of outcome of vibration and electroejaculation require a review and synthesis.Setting:University Hospital Belgium.Methods:We reviewed the literature with PubMed 1973–2008.Results:Erection, emission and ejaculation are separate phenomena and have different innervations. It is important to realize, which are the afferents and efferents and where the motor neuron of the end organ is located. When interpreting a specific lesion it is important to understand if postsynaptic fibres are intact or not. Afferents of erection, emission and ejaculation are the pudendal nerve and descending pathways from the brain. Erection is cholinergic and NO-mediated. Emission starts cholinergically (as a secretion) and ends sympathetically (as a contraction). Ejaculation is mainly adrenergic and somatic. For vibratory-evoked ejaculation, the reflex arch must be complete; for electroejaculation, the postsynaptic neurons (paravertebral ganglia) must be intact.Conclusion:Afferents of erection, emission and ejaculation are the pudendal nerve and descending pathways from the brain. Erection is cholinergic and NO-mediated. Emission starts cholinergically (as a secretion) and ends sympathetically (as a contraction). Ejaculation is mainly adrenergic and somatic. In neurogenic disease, a good knowledge of neuroanatomy and physiology makes understanding of sexual dysfunction possible and predictable. The minimal requirement for the success of penile vibration is a preserved reflex arch and the minimal requirement for the success of electroejaculation is the existence of intact post-ganglionic fibres.

Whole breast radiotherapy in prone and supine position: is there a place for multi-beam IMRT?

BackgroundEarly stage breast cancer patients are long-term survivors and finding techniques that may lower acute and late radiotherapy-induced toxicity is crucial. We compared dosimetry of wedged tangential fields (W-TF), tangential field intensity-modulated radiotherapy (TF-IMRT) and multi-beam IMRT (MB-IMRT) in prone and supine positions for whole-breast irradiation (WBI).MethodsMB-IMRT, TF-IMRT and W-TF treatment plans in prone and supine positions were generated for 18 unselected breast cancer patients. The median prescription dose to the optimized planning target volume (PTVoptim) was 50 Gy in 25 fractions. Dose-volume parameters and indices of conformity were calculated for the PTVoptim and organs-at-risk.ResultsProne MB-IMRT achieved (p<0.01) the best dose homogeneity compared to WTF in the prone position and WTF and MB-IMRT in the supine position. Prone IMRT scored better for all dose indices. MB-IMRT lowered lung and heart dose (p<0.05) in supine position, however the lowest ipsilateral lung doses (p<0.001) were in prone position. In left-sided breast cancer patients population averages for heart sparing by radiation dose was better in prone position; though non-significant. For patients with a PTVoptim volume ≥600 cc heart dose was consistently lower in prone position; while for patients with smaller breasts heart dose metrics were comparable or worse compared to supine MB-IMRT. Doses to the contralateral breast were similar regardless of position or technique. Dosimetry of prone MB-IMRT and prone TF-IMRT differed slightly.ConclusionsMB-IMRT is the treatment of choice in supine position. Prone IMRT is superior to any supine treatment for right-sided breast cancer patients and left-sided breast cancer patients with larger breasts by obtaining better conformity indices, target dose distribution and sparing of the organs-at-risk. The influence of treatment techniques in prone position is less pronounced; moreover dosimetric differences between TF-IMRT and MB-IMRT are rather small.

Heart dose reduction by prone deep inspiration breath hold in left-sided breast irradiation

BACKGROUND AND PURPOSE Cardiac disease has been related to heart dose after left-sided breast radiotherapy. This trial evaluates the heart sparing ability and feasibility of deep inspiration breath hold (DIBH) in the prone position for left-sided whole breast irradiation (WBI). MATERIALS AND METHODS Twelve patients underwent CT-simulation in supine shallow breathing (SB), supine DIBH, prone SB and prone DIBH. A validation cohort of 38 patients received prone SB and prone DIBH CT-scans; the last 30 patients were accepted for prone DIBH treatment. WBI was planned with a prescription dose of 40.05 Gy. RESULTS DIBH was able to reduce (p<0.001) heart dose in both positions, with results for prone DIBH at least as favorable as for supine DIBH. Mean heart dose was lowered from 2.2 Gy for prone SB to 1.3 Gy for prone DIBH (p<0.001), while preserving the lung sparing ability of prone positioning. Moreover prone DIBH nearly consistently reduced mean heart dose to less then 2 Gy, regardless of breast volume. All patients were able to perform the simulation procedure, 28/30 patients were treated with prone DIBH. CONCLUSIONS This trial demonstrates the ability and feasibility of prone DIBH to acquire optimal heart and lung sparing for left-sided WBI.

Prone left-sided whole-breast irradiation: Significant heart dose reduction using end-inspiratory versus end-expiratory gating

PURPOSE To quantify the influence on heart dose metrics of prone left-sided whole-breast irradiation in an end-inspiratory phase (PrIN) versus an end-expiratory phase (PrEX). PATIENTS AND METHODS Twenty patients underwent CT-simulation in PrIN and PrEX. Dynamic intensity-modulated radiotherapy was planned for whole-breast irradiation with a median prescription dose of 40.05Gy in 15 fractions and maximal sparing of the organs at risk. Dose-volume parameters were analyzed for heart, left anterior descending coronary artery, ipsilateral lung and both breasts. RESULTS PrIN consistently reduced (P<0.001) heart and left anterior descending coronary artery dose metrics compared to PrEX. Population averages for maximum and mean heart dose were 6.2Gy and 1.3Gy for PrIN versus 21.4Gy and 2.5Gy for PrEX, respectively. Moreover, a maximum heart dose less than 10Gy was achieved in 80% of patients for PrIN. Target dose distribution, ipsilateral lung and contralateral breast sparing by radiation dose were similar for both procedures. CONCLUSIONS Inspiratory gating consistently reduced heart dose metrics pointing to a possible benefit of breathing-adapted radiotherapy for prone left-sided whole-breast irradiation.

Deep inspiration breath hold in the prone position retracts the heart from the breast and internal mammary lymph node region

Deep inspiration breath hold in the prone position causes a caudal shift of the heart away from the nearly unmodified breast and internal mammary lymph node region, suggesting better heart protection for left-sided whole breast irradiation with or without regional nodal radiotherapy.

Does an integrated boost increase acute toxicity in prone hypofractionated breast irradiation? A randomized controlled trial

BACKGROUND AND PURPOSE The safety of a simultaneous integrated boost (SIB) in combination with prone hypofractionated whole-breast irradiation (WBI) was investigated. MATERIALS AND METHODS 167 patients were randomized between WBI with a sequential boost (SeB) or SIB. All patients were treated in prone position to 40.05Gy in 15 fractions to the whole breast. In the control arm, a SeB of 10Gy in 4 fractions (negative surgical margins) or 14.88Gy in 6 fractions (transsection) was prescribed. In the experimental arm a SIB of 46.8 or 49.95Gy (negative and positive surgical margins, respectively) was prescribed. RESULTS Patient age was the only significantly different parameter between treatment arms with patients in the SIB arm being slightly older. In both arms, 6/83 patients developed moist desquamation. Grade 2/3 dermatitis was significantly more frequent in the SeB arm (38/83vs 24/83 patients, p=0.037). In the SIB and SeB arm, respectively, 36 patients (43%) and 51 patients (61%) developed pruritus (p=0.015). The incidence of oedema was lower in the SIB arm (59vs 68 patients), but not statistically significant (p=0.071). CONCLUSIONS The primary endpoint, moist desquamation, was not significantly different between treatment arms.

294PHYPOFRACTIONATED RADIOTHERAPY REDUCES ACUTE SKIN TOXICITY IN SMALL AND LARGE BREASTED PATIENTS RECEIVING WHOLE-BREAST IRRADIATION

ABSTRACT Aim: Despite the results of large randomized trials in the UK and Canada showing that hypofractionation (HF) radiotherapy is at least as favorable as normofractionation (NF) schemes for whole-breast irradiation (WBI) in terms of loco-regional control and cosmetic outcome, some radiation oncologists are reluctant to use HF WBI fearing increased toxicity, especially in large breasted patients. In this study the effect of the fractionation schedule on acute toxicity was investigated in a cohort of 229 breast cancer patients with various cup sizes treated with WBI in 2 different radiotherapy centers. Methods: From May 2010 till December 2012, 150 patients from Ghent University Hospital (GUH) and 79 patients from Clinique et Maternite Sainte-Elisabeth Namur (CMSE) were included in a prospective study aiming at developing a prediction model for radiation-related breast toxicity using clinical, dosimetric and genetic parameters. All patients at GUH were treated with a HF scheme of 40,05 Gy in 15 fractions. At CMSE patients with a cup size D or more were treated with NF WBI (50 Gy in 25 fractions), while patients with a cup size Results: Patients with a cup size Conclusions: HF whole-breast radiotherapy results in significantly less moist desquamation compared to NF regardless of cup size. Disclosure: All authors have declared no conflicts of interest.