[Concurrent radiation therapy and dual HER2 blockade in breast cancer: Assessment of toxicity]. / Association du double blocage de HER2 et radiothérapie dans la prise en charge du cancer du sein exprimant HER2.

PURPOSE: The tolerance of the concurrent use of radiotherapy, pertuzumab and trastuzumab is unknown. The purpose of this study was to evaluate the toxicity of this association in patients treated for HER2 positive metastatic and/or locally recurrent unrespectable breast cancer. MATERIAL AND METHODS: A retrospective study was performed in our institution for all consecutive patients treated with concurrent irradiation, pertuzumab and trastuzumab. The radiotherapy was performed while pertuzumab and trastuzumab were administrated as a maintenance treatment at the dose of 420mg (total dose) and 6mg/kg respectively every 3 weeks without chemotherapy. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Left ventricular ejection fraction (LVEF) was measured at baseline and then every 3-4 months. RESULTS: We studied 77 patients. treated in between 2013 and 2019 with median follow-up of 38 months (range 0-264 months). Median age was 53 years (33-86). There were 50 patients (64.9%) with metastatic and 27 patients (35.1%) with recurrent disease. All patients received docetaxel followed by P-T as first line treatment and they received 34 cycles (10-85) of pertuzumab and trastuzumab. All patients experienced partial or complete response according to RECIST criteria. Irradiation volumes were whole breast (41 patients, 53.2%) and chest wall (29 patients, 37.7%) at a dose of 50Gy with a median duration of 39 days. Radiotherapy of lymph nodes was performed in 53 patients (68.8%) as following: supraclavicular-infraclavicular and axillary lymph nodes in 52 patients (67.5%), and internal mammary nodes in 31 patients (40.3%). For 20 patients. (26.0%) radiotherapy was palliative: bone irradiation (12 patients, 15.6%), whole-brain radiotherapy (2 patients, 2.6%), cerebral metastasis irradiation (6 patients). As early toxicity we observed: radio dermatitis as following: 36 patients (46.8%) presented grade I, 17 patients (22.1%) presented grade II, and 3 patients (3.9%) presented grade III. One patient (1.3%) presented grade II esophagitis. One patient (1.3%) presented asymptomatic decrease of LVEF during treatment and 6 patients (7.7%) presented a decrease of LVEF. There was no radiation-induced pneumonitis. As late toxicity, we observed 1 (1.3%) case of grade I and 1 (1.3%) with grade II telangiectasia. There was 1 case (1.3%) of grade III cardiac toxicity, 8 months after the concurrent treatment. CONCLUSION: The concurrent use of radiotherapy, pertuzumab and trastuzumab is feasible with good tolerance. Larger prospective data with longer follow-up is needed to confirm these results.

Evaluation of the scars' vascularization using computer processing of the digital images.

BACKGROUND: The application of new techniques of the scars' correction requires the objective evaluation of their vascularization. OBJECTIVE: To evaluate the effectiveness of digital program ImageJ in assessing neovascularization of pathologic scars. MATERIAL AND METHODS: In this cross-sectional study, a total of 25 patients with pathologic scars were enrolled. Vessel selection in the first set of digital images of their scars was performed by computer processing started from thresholding with subsequent manual correction. In the second set of the same pictures, Vessel Analysis plugin was used. Comparison of both approaches was performed by three independent investigators. The time required for images processing was measured. RESULTS: The average time that image processing and calculation have taken in the first group (753.3 ± 88.02 seconds) was statistically longer (P < 0.0001) than in the second one (358.1 ± 105.91 seconds). Independent investigators scored the precision of vessel selection in the first group as 80.4 ± 9.82, in the second group as 72.6 ± 10.53 (P < 0.0001). Kolmogorov-Smirnov test demonstrated higher precision of vessel selection by method that involves manual correction (P < 0.001). The results of Vascular Density measurements were obviously overestimated in the second group. More expedient looks calculation of the Vascular Length Density: ratio of skeletonized vasculature area to total area. Skeletonization avoids overestimation of Vascular Density, but the density of the vessel mesh can be determined. CONCLUSIONS: Computer processing of the scars' digital photographs using ImageJ software gives cheap, technically easy and not cumbersome way of superficial scars' vascularization objectifying. Vessel selection with subsequent manual correction has advantage of higher precision.

Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel.

BACKGROUND: Rosacea is currently diagnosed by consensus-defined primary and secondary features and managed by subtype. However, individual features (phenotypes) can span multiple subtypes, which has implications for clinical practice and research. Adopting a phenotype-led approach may facilitate patient-centred management. OBJECTIVES: To advance clinical practice by obtaining international consensus to establish a phenotype-led rosacea diagnosis and classification scheme with global representation. METHODS: Seventeen dermatologists and three ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and severity evaluation. All voting was electronic and blinded. RESULTS: Consensus was achieved for transitioning to a phenotype-based approach to rosacea diagnosis and classification. The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes. Flushing, telangiectasia, inflammatory lesions and ocular manifestations were not considered to be individually diagnostic. The panel reached agreement on dimensions for phenotype severity measures and established the importance of assessing the patient burden of rosacea. CONCLUSIONS: The panel recommended an approach for diagnosis and classification of rosacea based on disease phenotype.

The relationship between nailfold capillaroscopic assessment and telangiectasia score with severity of peripheral vascular involvement in systemic sclerosis.

OBJECTIVES: To determine the association of nailfold video-capillaroscopy (NVC) findings and telangiectasia score with digital ulcer (DU) history and severity of peripheral vascular involvement (PVI) in systemic sclerosis (SSc). METHODS: Fifty-nine SSc patients fulfilling Leroy & Medsger criteria were evaluated including telangiectasia score, disease activity and severity scores. NVC was performed according to qualitative (early, active and late patterns) and semi-quantitative assessments. RESULTS: When DU+ and DU- groups were compared; the mean score of capillary number (CN) was 2.0±0.5 vs. 1.4±0.7 (p<0.001), irregularly enlarged capillaries (IEC) was 1.8±0.6 vs. 1.4±0.7 (p<0.05), microangiopathy evolution score (MES) was 2.5±1.5 vs. 1.8±1.0 (p<0.05) and 'early' pattern was significantly less frequent in DU+ patients (1 vs. 9, p=0.016). The frequency of severe-PVI (Medsger severity score of 2-4) was 22% in females (12/54) and 80% in males (4/5). When severe and non-severe groups were compared; the mean score of CN was 2.1±0.4 vs. 1.5±0.7 (p<0.001), MES was 2.8±1.6 vs. 1.8±1.1 (p<0.05) and 'early' pattern was significantly less frequent in patients with severe PVI (0 vs. 9, p=0.049). The mean values of telangiectasia score were similar between groups. CONCLUSIONS: DU history and severe PVI in SSc were associated with capillary loss and microangiopathy. 'Early' NVC pattern was very rare in patients with DU history and was not found in severe PVI. Severe PVI in males was more frequent than females. Telangiectasia scores were not found to be related to PVI. NVC may be a helpful method in the assessment of SSc patients for PVI prognosis, warranting prospective studies.

Repair halftimes estimated from observations of treatment-related morbidity after CHART or conventional radiotherapy in head and neck cancer.

BACKGROUND AND PURPOSE: The CHART (Continuous Hyperfractionated Accelerated Radiotherapy) head and neck cancer fractionation schedule delivered 54 Gy in 36 fractions on 12 consecutive days and this was compared in a randomised controlled trial with conventional fractionation delivering 66 Gy in 33 fractions over 6-7 weeks. Patients receiving CHART experienced statistically significantly less treatment-related morbidity after 6 months than patients receiving conventional fractionation. However, this improved tolerance was much less than anticipated from existing knowledge of dose-fractionation effects on late-responding normal tissues. Here, the experience from the CHART study is analysed and repair halftimes for three types of late treatment-related morbidity of human tissues are estimated. PATIENTS AND METHODS: The CHART trial was open for patient accrual from March 1990 to April 1995 and a total of 918 patients in 11 participating centres were randomised. All patients were followed at regular intervals for a minimum of 5 years or until the time of death. At each follow-up, a number of treatment-related morbidity items were evaluated and scored prospectively. Data for three late endpoints are analysed here: laryngeal oedema, skin telangiectasia and subcutaneous fibrosis. Differences in the incidence of these endpoints in the two trial arms were quantified by means of the ratio of hazard rates in a Cox proportional hazards model. Monte Carlo sampling was performed from distributions of fractionation sensitivity (quantified by the alpha/beta-ratio) and steepness of the dose-response curve (quantified by the normalised dose-response gradient, gamma50) with means and standard deviations derived from the literature. Each pair of values were used to convert a Monte Carlo sampled estimate of the difference in biological effect into an estimate of the repair halftime. From the distribution of 1000 Monte Carlo samples, the mean repair halftime and its 95% confidence interval were estimated. RESULTS: The estimated repair halftimes, with 95% confidence intervals in parentheses, were 4.9 h (3.2, 6.4) for laryngeal oedema, 3.8 h (2.5, 4.6) for skin telangiectasia and 4.4 h (3.8, 4.9) for subcutaneous fibrosis. Calculations show that these repair halftimes are consistent with the observations from two published randomised controlled trials of altered fractionation in head and neck cancer, the EORTC 22791 and 22851 trials. CONCLUSIONS: These long repair halftimes for late effects in human normal tissues have to be considered in order to gain the full benefit from fractionation schedules employing multiple fractions per day.

Factors affecting cosmetic outcome in breast-conserving cancer treatment--objective quantitative assessment.

A battery of objective measurements of cosmetic outcome was performed on 114 patients who had been treated by breast-preservation techniques for breast cancer. Cosmetic breast retraction, as determined by Breast Retraction Assessment (BRA) measurements, was significantly greater in patients who underwent extensive primary tumor resection, were more than 60 years old, weighed more than 150 lbs, or had a primary tumor in an upper breast quadrant. While use of a local RT boost, per se, was not a significant factor, those patients with high dose and/or large volume local boosts more frequently had marked retraction. Breast telangiectasia and depigmentation (T/D) was related to use of a local RT boost, patient age greater than 60 years, and use of separate nodal RT fields. Breast T/D was significantly more frequent with use of electron beam local RT boost which delivered a boost skin dose exceeding 1600 cGy. Objective quantitative assessments, such as BRA and T/D area measurements, provide data to determine factors related to each type of cosmetic change and thus provide guidelines for optimizing cosmetic outcome. Limiting the extent of primary tumor resection may minimize the amount of breast retraction. Omitting the local RT boost, particularly large volume, high dose boosts, may reduce the frequency of marked cosmetic retraction and skin T/D.