Anne Dagnault

Treatment with α-helical-CRF(9–41) prevents the anorectic effect of 17-β-estradiol

The role of corticotropin-releasing factor (CRF) in the anorexia induced by 17-β-estradiol (E2) has been assessed in castrated female rats that were trained to eat their daily food ration in three separate meals. Each rat was implanted with a permanent guide cannula that was aimed at the right lateral ventricle of the brain. Seven days after the brain surgery each rat was also subcutaneously implanted with an osmotic minipump containing Buserelin, a potent GnRH agonist that induces reversible castration in rats. Eight rats were used in the study, and each of them underwent four experimental treatments that consisted of a) a subcutaneous (SC) injection of oil combined with an intracerebroventricular (ICV) infusion of saline, b) a SC injection of E2 combined with an ICV infusion of saline c) a SC injection of oil combined with an ICV infusion of a-helical CRF(9–41), and d) a SC injection of E2 combined with an ICV injection of α-helical CRF(9–41). Subcutaneous injections of E2 or oil were carried out the day before the ICV infusions of α-helical CRF(9–41) or saline. Intracerebroventricular infusions were performed 30 min before the meal for which the interaction effect of E2 and a-helical CRF(9–41) on food intake was determined. E2 and a-helical CRF(9–41) interacted on food intake; E2 brought about a 33% reduction in food intake in rats when infused with saline, whereas it was without effect when infused with a-helical-CRF(9–41)-treated rats. The present results provide evidence that CRF is involved in the anorectic effect of E2.

Use of axillary deodorant and effect on acute skin toxicity during radiotherapy for breast cancer: a prospective randomized noninferiority trial.

PURPOSE To prospectively determine the effect of deodorant use on acute skin toxicity and quality of life during breast radiotherapy (RT). METHODS AND MATERIALS Before breast RT, 84 patients were randomly assigned to the deodorant group (n = 40) or the no-deodorant group (n = 44). The patients were stratified by axillary RT and previous chemotherapy. Toxicity evaluations were always performed by the principal investigator, who was unaware of the group assignment, at the end of RT and 2 weeks after completion using the Radiation Therapy Oncology Group acute skin toxicity criteria. Symptoms of acute skin toxicity (i.e., discomfort, pain, pruritus, sweating) and quality of life were self-evaluated. For each criterion, the point estimate of rate difference with the 95% one-sided upper confidence limit was computed. To claim noninferiority owing to deodorant use, the 95% one-sided upper confidence limit had to be lower than the noninferiority margin, fixed to 12.8%. RESULTS In the deodorant vs. no-deodorant groups, Grade 2 axillary radiodermatitis occurred in 23% vs. 30%, respectively, satisfying the statistical criteria for noninferiority (p = .019). Grade 2 breast radiodermatitis occurred in 30% vs. 34% of the deodorant vs. no-deodorant groups, respectively, also satisfying the statistical criteria for noninferiority (p = .049). Similar results were observed for the self-reported evaluations. The deodorant group reported less sweating (18% vs. 39%, p = .032). No Grade 3 or 4 radiodermatitis was observed. CONCLUSION According to our noninferiority margin definition, the occurrence of skin toxicity and its related symptoms were statistically equivalent in both groups. No evidence was found to prohibit deodorant use (notwithstanding the use of an antiperspirant with aluminum) during RT for breast cancer.

Functional avoidance of lung in plan optimization with an aperture-based inverse planning system.

PURPOSE To implement SPECT-based optimization in an anatomy-based aperture inverse planning system for the functional avoidance of lung in thoracic irradiation. MATERIAL AND METHODS SPECT information has been introduced as a voxel-by-voxel modulation of lung importance factors proportionally to the local perfusion count. Fifteen cases of lung cancer have been retrospectively analyzed by generating angle-optimized non-coplanar plans, comparing a purely anatomical approach and our functional approach. Planning target volume coverage and lung sparing have been compared. Statistical significance was assessed by a Wilcoxon matched pairs test. RESULTS For similar target coverage, perfusion-weighted volume receiving 10 Gy was reduced by a median of 2.2% (p=0.022) and mean perfusion-weighted lung dose, by a median of 0.9 Gy (p=0.001). A separate analysis of patients with localized or non-uniform hypoperfusion could not show which would benefit more from SPECT-based treatment planning. Redirection of dose sometimes created overdosage regions in the target volume. Plans consisted of a similar number of segments and monitor units. CONCLUSIONS Angle optimization and SPECT-based modulation of importance factors allowed for functional avoidance of the lung while preserving target coverage. The technique could be also applied to implement PET-based modulation inside the target volume, leading to a safer dose escalation.

Impact of locoregional radiotherapy in node-positive patients treated by breast-conservative treatment.

PURPOSE The aim of this study is to evaluate the impact of locoregional radiation in node-positive patients treated by tumorectomy and radiation therapy. METHODS A retrospective study including all our 1368 T1-2 node-positive patients was conducted. Conservative surgery was followed by breast irradiation. Axillary and supraclavicular irradiation was left to the discretion of the treating radiation oncologist. RESULTS In the group receiving locoregional radiation (472 patients), the 10-year regional control was 97% vs. 91% for the group receiving radiation to the breast only (896 patients) (p = 0.004). In a Cox model analysis, locoregional radiation is associated with a better regional control rate (hazard ratio: 0.27; 95% confidence interval: 0.13-0.54, p = 0.0001). Locoregional radiotherapy is associated with a better rate of locoregional control (hazard ratio: 0.56; 95% confidence interval: 0.38-0.8, p = 0.002). In particular, for the N>3 group, the substantial 10-year locoregional failure rate (26% with breast irradiation only) is cut by 50%. Locoregional radiotherapy, however, is not associated with a lower rate of distant metastases. CONCLUSION Locoregional radiation decreases the rate of locoregional failure by nearly 50%. Locoregional radiotherapy should be considered for node-positive patients, especially if they have more than 3 positive nodes.

Influence of smoking status on treatment outcomes after post-operative radiation therapy for non-small-cell lung cancer

BACKGROUND AND PURPOSE The role of post-operative radiotherapy in patients with resected non-small-cell lung cancer (NSCLC) is unclear. Modifiable factors, like smoking, may help guide therapy. We retrospectively evaluated the impact of smoking on control in patients undergoing post-operative radiation therapy (PORT) for NSCLC. MATERIALS AND METHODS Between 1995 and 2007, 152 patients who underwent surgery for NSCLC were analyzed (median follow-up 26 months). Non-smokers were defined as patients who never smoked or who had stopped smoking at the time of initial consultation. Sixty seven percent were non-smokers; 5% never smoked, 40% of the non-smokers had ceased smoking for a year or less, while 55% had stopped for more than a year. RESULTS On univariate analysis, smokers had worse 5-year local control than non-smokers (70% versus 90%, p=0.001) and locoregional control (52% versus 77%, p=0.002). The 5-year survival rate was 21% for smokers and 31% for non-smokers (p=0.2). On multivariate analysis, smokers maintained a detrimental effect on locoregional control (HR 3.6, p=0.0006). CONCLUSIONS Smokers at initial consultation have poorer local and locoregional control after PORT than non-smokers. In patients being considered for PORT for NSCLC, quitting smoking before treatment confers additional treatment advantage.

Postoperative Radiotherapy for Lung Cancer: Improvement in Locoregional Control Using Three-Dimensional Compared With Two-Dimensional Technique

PURPOSE To determine whether lung cancer patients treated with three-dimensional (3D) postoperative radiotherapy (PORT) have more favorable outcomes than those treated with two-dimensional (2D) PORT. PATIENTS AND METHODS We retrospectively analyzed the charts of 153 lung cancer patients who underwent PORT with curative intent at our center between 1995 and 2007. The patients were grouped according to the RT technique; 66 patients were in the 2D group and 87 in the 3D group. The outcomes included locoregional control, survival, and secondary effects. All patients were treated using a linear accelerator at a total dose of approximately 50 Gy and 2 Gy/fraction. A few patients (21%) also received chemotherapy. Most tumors were in the advanced stage, either Stage II (30%) or Stage III (65%). The main clinical indications for PORT were positive resection margins (23%) and Stage pN2 (52%) and pN1 (22%). The patient characteristics were comparable in both groups. RESULTS Kaplan-Meier analysis showed that the 3D technique significantly improved the locoregional control rate at 5 years compared with the 2D technique (81% vs. 56%, p = .007 [Cox]). The 2D technique was associated with a more than twofold increased risk of locoregional recurrence (hazard ratio, 2.7; 95% confidence interval, 1.3-5.5; p = .006). The overall survival rate did not differ at 5 years (38% vs. 20%, p = .3 [Cox]). The toxicities were also similar and acceptable in both groups. CONCLUSION The 3D technique for conformal PORT for lung cancer improved the locoregional control rates of patients compared with the 2D technique.

Dose escalation in the radiotherapy of non-small-cell lung cancer with aperture-based intensity modulation and photon beam energy optimization for non-preselected patients.

PURPOSE To verify the potential of aperture-based intensity-modulated radiotherapy (AB-IMRT) to realize dose escalation plans for non-preselected non-small-cell lung cancer (NSCLC) patients, using photon beam energy optimization. METHODS AND MATERIALS Seven cases of NSCLC were retrospectively studied. Clinical reference plans were made at 60 Gy by an experienced dosimetrist. Dose escalation was applied to PTV2, a subvolume within the main PTV1. Escalation plans were optimized by considering beam angles (table and gantry), energy (6 and 23 MV) and weights, for an increasing dose to the PTV2, starting from 66 Gy and keeping 30 fractions. RESULTS In five cases, doses over 78 Gy could be achieved before exceeding organs at risk (OARs) standard tolerance. Peripheral overdosages, as well as lung and spinal cord tolerance doses, limited escalation. Means+/-SD V(95%) parameters were (97.3+/-0.9)% for PTV1s and (96.7+/-2.2)% for PTV2s. Doses to OARs were also maintained at acceptable levels. Optimized plans made use of both low- and high-energy beams and had a similar number of monitor units compared to the 60 Gy clinical plans. CONCLUSIONS The AB-IMRT system can successfully realize dose escalation for a sizeable number of cases. Plans produced contained few large segments, and are applicable to a wide range of tumor volumes and locations.

Prophylactic irradiation of intervention sites in malignant pleural mesothelioma

BACKGROUND AND PURPOSE To assess the effectiveness of prophylactic irradiation of intervention track (PIT) to prevent tumor seeding in patients with malignant pleural mesothelioma. MATERIALS AND METHODS A retrospective review was conducted of 171 patients with a histological diagnosis of pleural mesothelioma with some undergoing prophylactic irradiation of intervention sites. RESULTS Forty-eight patients (28%) received PIT. A majority of patients were followed until death. Thoracoscopy (88%) was the procedure most often performed. Thirty-three percent of patients received chemotherapy. The median dose of PIT was 21 Gy in 3 fractions with electrons or 6 MV photons. The local progression free survival (LPFS) at the intervention site was significantly higher in the PIT group and was not influenced by chemotherapy. At 6 months, LPFS for the intervention sites was 91% with PIT and 74% without PIT (p=0.002). During the follow-up, 6 patients (13%) in the PIT group had tumor invasion of the subcutaneous tissue compared to 40 patients (33%) in the group without PIT (p=0.008). CONCLUSIONS This study suggests that PIT in mesothelioma reduces the incidence of procedure tract metastasis. Finally, chemotherapy does not seem to have an influence on the incidence of tract metastasis.

Retrospective study of 81 patients treated with brachytherapy for endobronchial primary tumor or metastasis

PURPOSE The purpose of this retrospective study is to evaluate the role of endobronchial brachytherapy in the palliation of lung cancer (or metastasis) symptoms and its potential impact on overall survival. METHODS AND MATERIALS Eighty-one patients were included in this study. Endobronchial brachytherapy catheter was placed under conscious sedation. The projection of the tumor was drawn by the bronchoscopist to help the radiation oncology team to perform the dosimetry. Patients were treated with iridium-192 high-dose rate afterloading unit. Patients were planned to receive 5 Gy in four fractions weekly for a total of 20 Gy. RESULTS Seventy-three percent of the patients were treated for primary lung cancer. The remaining patients were treated for lung metastasis of other primary. Most patients presented dyspnea, cough, or hemoptysis. These three main symptoms were relieved in 85%, 77%, and 100%, respectively. The median survival was 14.7 months and local progression-free survival at 12 months was 77% and at 24 months 64%, respectively. CONCLUSION Endobronchial brachytherapy is a very effective palliative treatment for endobronchial lesions.

Patient-specific Monte Carlo-based dose-kernel approach for inverse planning in afterloading brachytherapy.

PURPOSE Brachytherapy planning software relies on the Task Group report 43 dosimetry formalism. This formalism, based on a water approximation, neglects various heterogeneous materials present during treatment. Various studies have suggested that these heterogeneities should be taken into account to improve the treatment quality. The present study sought to demonstrate the feasibility of incorporating Monte Carlo (MC) dosimetry within an inverse planning algorithm to improve the dose conformity and increase the treatment quality. METHODS AND MATERIALS The method was based on precalculated dose kernels in full patient geometries, representing the dose distribution of a brachytherapy source at a single dwell position using MC simulations and the Geant4 toolkit. These dose kernels are used by the inverse planning by simulated annealing tool to produce a fast MC-based plan. A test was performed for an interstitial brachytherapy breast treatment using two different high-dose-rate brachytherapy sources: the microSelectron iridium-192 source and the electronic brachytherapy source Axxent operating at 50 kVp. RESULTS A research version of the inverse planning by simulated annealing algorithm was combined with MC to provide a method to fully account for the heterogeneities in dose optimization, using the MC method. The effect of the water approximation was found to depend on photon energy, with greater dose attenuation for the lower energies of the Axxent source compared with iridium-192. For the latter, an underdosage of 5.1% for the dose received by 90% of the clinical target volume was found. CONCLUSION A new method to optimize afterloading brachytherapy plans that uses MC dosimetric information was developed. Including computed tomography-based information in MC dosimetry in the inverse planning process was shown to take into account the full range of scatter and heterogeneity conditions. This led to significant dose differences compared with the Task Group report 43 approach for the Axxent source.