[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.

Videodermoscopy and doppler-ultrasound in spider naevi: towards a new classification?

INTRODUCTION: Spider naevi (SN) are considered a subtype of telangiectasias, currently classified as low-flow vascular malformations. OBJECTIVE: To describe the videodermoscopy and Doppler-ultrasound (US) features of a large group of SN. MATERIAL AND METHODS: A retrospective study of cases of SN collected at our Dermatology department during the period between June 2015 and June 2017 was performed. Clinical images, dermoscopic, videodermoscopic and Doppler-US files were reviewed. For each case, the age of the patient, time since onset, size and dermoscopic pattern of the lesions were recorded. The presence of pulsatility was also evaluated visually on the videodermoscopy. RESULTS: Two hundred and thirty-three SN in 189 patients were included. The mean age was 39.5 years (range: 10-76 years). Mean size of the lesions was 4.1 ± 2.0 mm. We described three dermoscopic patterns: network, star and looping. Older age, longer time since onset and larger size were found associated with higher frequency of the looping and star patterns compared to that of network pattern (P < 0.01). Pulsatility during videodermoscopy was found in 88 patients (37%). This pulsatility phenomenon was more commonly associated with the looping pattern (64.7%) than star- (40.3%) or network-like patterns (29.9%) (P < 0.001). In Doppler-US studies, a high-flow with arterial biphasic waveform was found. CONCLUSIONS: In the light of the results, we support that SN could be reconsidered in upcoming classifications as lesions closer to the group of high-flow arteriovenous malformations.

Cutaneous collagenous vasculopathy: a new case series with clinicopathologic and ultrastructural correlation, literature review, and insight into the pathogenesis.

Cutaneous collagenous vasculopathy (CCV) is a rare distinct idiopathic microangiopathy of the superficial cutaneous vasculature. Seven new cases are reported (6 females and 1 male) ranging in age from 42 to 85 years, with some showing unusual clinical and histopathological findings. All presented with macular telangiectases starting on the lower extremities and spreading progressively in 5 cases and were suspected to have generalized essential telangiectasia. Two cases had a history of over 20 years. One case had lesions in the abdominal striae, and 1 was markedly ecchymotic. All skin biopsies showed the characteristic features of CCV with dilatation and marked thickening of the walls of superficial dermal blood vessels displaying reduplication of the basement membrane on periodic acid-Schiff-diastase stain and deposition of hyaline collagenous material immunostaining as collagen type IV, and showing decreased or absent actin staining. However, the changes were subtle and only seen focally in some biopsies. Few lymphoid cells were present around occasional vessels. Electron microscopy showed increased basement membrane lamellae with marked deposition of normal and some abnormal collagen (Luse-like bodies) and focal endothelial damage, suggesting reparative perivascular fibrosis resulting from repeated endothelial injury. These cases (and all 18 previously reported ones) are of a wide age range and no gender predilection. This disorder is underdiagnosed, and it is likely that some cases clinically suspected to be generalized essential telangiectasia may actually represent CCV. Better recognition by dermatologists may lead to more biopsies from patients with generalized telangiectasia and a further understanding of the pathogenesis of CCV and its relationship to other cutaneous vascular disorders.

A Delphi exercise and cluster analysis to aid in the development of potential classification criteria for systemic sclerosis using SSc experts and databases.

OBJECTIVES: Since the 1980 ACR classification criteria for systemic sclerosis (SSc) do not identify 20% with SSc, revised criteria are necessary. METHODS: Suggested new criteria from the literature were sent in random order to 96 SSc experts. A 3-round Delphi Consensus eliminated criteria. Then cluster analysis reduced items. The Canadian Scleroderma Research Group (CSRG) database was used to determine the prevalence of each item. RESULTS: Seventy-one of 96 (71%) completed all 3 rounds; 47 items were expanded to 76 in round 2. Thirty items had at least 50% consensus and 18 had >75% agreement to include (a priori cut point). Clustering occurred for 4 categories: proximal to MCP skin involvement, vascular abnormalities, autoantibodies and tissue damage. Proximal to MCPs skin involvement identified 80% of patients. Adding one item from each of the other 3 categories or 1 or more items from 2 of 3 remaining categories increased the proportion of patients classified to 94% in CSRG patients. Categories included (1) Vascular (dilated capillaries, telangiectasia, Raynaud's phenomenon [RP]), (2) Autoantibodies (anticentromere [ACA] or antitopoisomeraseI [Topo1]) and (3) Fibrosis/damage (esophogeal dysmotility dysphagia, sclerodactyly, digital ulcers). In the CSRG, 98% were identified if using proximal skin involvement; or sclerodactyly plus one of: RP, ACA or Topo1. CONCLUSIONS: This is a first step toward developing new SSc classification criteria. A Delphi exercise alone cannot suffice for item reduction. Also, validation prospectively in SSc patients and diseases that mimic SSc is needed in order to calculate sensitivity and specificity of future criteria.

Treating telangiectasias: my method.

AIM: The authors propose a new classification of telangiectasias: conditions involving demonstrated reflux are classified as type A telangiectasias; clustered, spider telangiectasias not related to reflux and with vein diameters of >0.2 mm are classified as type B, while isolated telangiectatic veins of ≤0.2 mm diameter are classed as type C. This histological and pathophysiological approach is the basis for the Authors' Multi-Therapy Treatment Protocol (MTT). METHODS: The treatment regimen provides for initial treatment of type A telangiectasias with just conventional reflux sclerotherapy, followed three weeks later by treatment of type B telangiectasias with 0.25-0.5% polidocanol foam, associated with both external compression and tumescent vasoconstriction (START technique). This is then followed after a further three months by dermal stimulation with mesoglycan (LIDS technique) to reinforce the district underlying the type C telangiectasias. The MTT Protocol was used on 63 patients (125 limbs). A 12-month follow-up showed the treatment regimen to provide better aesthetic and functional results than classical sclerotherapy, with few adverse effects and greater patient satisfaction.

Acquired poikiloderma: proposed classification and diagnostic approach.

"Poikiloderma" is a morphologic and descriptive term referring to a combination of cutaneous atrophy, telangiectasia, and varied macular pigmentary changes that result in a mottled skin appearance. Its etiology includes both congenital and acquired causes. Many studies have reported different causes of acquired poikiloderma; however, no single well-defined classification has been explored to date. Herein, we analyze all the possible causes of acquired poikiloderma and propose an etiological classification that, hopefully, will lead to better characterization for this ill-defined condition. Moreover, this study presents a step-by-step approach to the management of patients with acquired poikiloderma and summarizes the key differentiating features for each individual cause, which may help in easy and precise diagnosis of different causes of acquired poikiloderma.

The continuum of primary retinal telangiectasia.

BACKGROUND: Primary retinal telangiectasia is characterized by abnormalities in the retinal vasculature. Any alteration of the normal retinal vasculature may result in variable degrees of retinal leakage, hemorrhages, and exudates. The retinal telangiectatic conditions of Coats' disease, Leber's miliary aneurysms, and idiopathic macular telangiectasia (IMT), although historically considered separate entities, may in fact be variants of the same pathophysiologic vascular process. This is based on observations noting that they share similarities in pathogenesis, histology, and clinical presentation. These observations are controversial and are contested in the literature. Conversely, others have documented Coats' disease, Leber's miliary aneurysms, and IMT as unique and separate retinal conditions, each with specific features. METHODS: Three cases are presented spanning the spectrum of primary retinal telangiectasia. Clinical evaluation, dilated fundus examination, and auxiliary testing document both the similar characteristics that the entities share as well as the distinct features, which define each disease's nomenclature and categorization. CONCLUSION: Coats' disease, Leber's miliary aneurysms, and IMT may be part of a singular clinical spectrum sharing pathophysiologic and histopathologic features and similarities in clinical presentation.

Macular telangiectasia: patterns of distribution of macular pigment and response to supplementation.

PURPOSE: By analyzing the patterns of macular pigment (MP) in type 2 idiopathic telangiectasia eyes, different stages in the changes reflecting the extent of disease can be observed. The purpose of this study was to determine whether the amount and the pattern of MP can be influenced by supplementation. METHOD: Eleven patients with type 2 idiopathic telangiectasia received 12 mg lutein and 0.6 mg zeaxanthin (Ocuvite Lutein AMD) daily for 9 months. For a period of 12 months, MP concentration was determined every 3 months by autofluorescence (2 excitation wavelengths: 488 and 514 nm). RESULTS: When central accumulation of MP was similar to that in healthy subjects (with segment of reduced MP in the temporal fovea: MP Class I), supplementation enriched the MP at 0.5 degrees, 2 degrees, and 5 degrees to 6 degrees. In MP Class II (reduced concentration of MP centrally), accumulation could be detected at 2 degrees and 5 degrees to 6 degrees but not centrally. In MP Class III (oval-shaped effacement of MP centrally, surrounding oval-shaped ring of MP at 5 degrees-7 degrees eccentricity), supplementation promoted MP accumulation only at 5 degrees to 6 degrees. CONCLUSION: After oral supplementation with lutein/zeaxanthin, an increase in the MP was detected only in areas where the MP was present at baseline. Supplementation did not produce an increase in the area where the MP was absent. Degenerative processes causing an impairment in transport and storage of lutein and zeaxanthin may play a leading role in the pathogenesis of type 2 idiopathic telangiectasia.

The prevalence of macular telangiectasia type 2 in the Beaver Dam eye study.

PURPOSE: To examine the prevalence of macular telangiectasia type 2 and lesions characterizing it. DESIGN: Population-based cohort study. METHODS: setting: City and township of Beaver Dam, 1988-1990. study population: A total of 4790 people 43-86 years of age. observation procedure(s): Grading from stereoscopic fundus photographs to measure macular telangiectasia type 2. main outcome measure: Prevalent macular telangiectasia type 2. RESULTS: Macular telangiectasia type 2 was present at baseline in 0.1% of the population (95% confidence interval [CI] 0.09, 0.1). The frequencies of loss of retinal transparency, crystals in the inner retinal layers, blunted retinal vessels, localized intraretinal pigment migration in the juxtafoveolar region, and presence of yellow deposits and lamellar holes in the foveal area in those without macular telangiectasia type 2 varied from 0.06% for retinal telangiectatic vessels to 1.2% for lamellar holes. Smoking was associated with pigment clumping (odds ratio [OR] per pack year 1.02; 95% CI 1.00, 1.03; P = .02), retinal pigment epithelial (RPE) depigmentation (OR 1.02 per pack year; 95%CI 1.00, 1.04; P = .02), loss of transparency (OR 1.02 per pack year; 95% CI 1.00, 1.03; P = .008), and the presence of a yellow spot in the fovea (OR 2.24 current vs past or never smoker; 95% CI 1.29, 3.89; P = .004), but not with presence of macular telangiectasia type 2 (OR 2.72; 95% CI 0.45, 16.28; P = .27). CONCLUSIONS: The prevalence of macular telangiectasia type 2 (0.1%) is higher than previously thought. These data are useful in estimating the burden of this condition in the population. The role of smoking in the development of macular telangiectasia type 2 requires further study.

Idiopathic macular telangiectasia type 2: distribution of macular pigment and functional investigations.

PURPOSE: Analysis and categorization of macular pigment (MP) distribution in type 2 idiopathic macular telangiectasia (IMT2) with regard to a possible grading scale for the severity of the disease. METHODS: Nineteen IMT2 patients were examined including visual acuity (VA), fundus biomicroscopy, fluorescein angiography (FLA), microperimetry and optical coherence tomography (OCT). Distribution of MP was analyzed and categorized in MP density maps calculated from autofluorescence images obtained at 488 and 514 nm excitation wavelengths. RESULTS: Typical features in MP density maps are in class I (n=8), a triangular segment of reduced MP in the temporal fovea and central accumulation of MP, class II (n=12), further expansion of the segment and vanishing of central accumulation, and class III (n=18), oval effacement of MP centrally, surrounding halo of MP at 5-7 degrees eccentricity. These classes were associated with the stages of the disease and increasing restrictions in visual function. CONCLUSION: Association between changes in MP distribution, stages of IMT2 and restrictions in visual functions suggests that the classification of MP patterns reflects a severity scale for IMT2. Degenerative processes causing impairments in transport and storage of lutein (L) and zeaxanthin (Z) leading to secondary vascular changes may play a causative role in the disease.

Baseline characteristics of participants in the natural history study of macular telangiectasia (MacTel) MacTel Project Report No. 2.

PURPOSE: To describe the baseline characteristics of a large international cohort of patients with macular telangiectasia type 2 (MacTel Type 2) in anticipation of a longitudinal natural history study to evaluate structural and functional changes, identify potential risk factors and related outcomes. METHODS: Images including fundus photographs, fluorescein angiograms, optical coherence tomography and fundus autofluorescence were collected. A grading system for MacTel type 2 was developed by the central reading center to evaluate lesion characteristics. Relationships between lesion characteristics and visual acuity were evaluated. RESULTS: A total of 310 participants have been enrolled in the study. The mean time since diagnosis was 3 years (range 0 to 25 years). The mean age at the baseline examination was 61 +/- 9 years. The mean visual acuity in the better eye was approximately 20/32 Snellen equivalents and approximately 20/50 in the worse eye. The visual acuity in the better eye of half of the participants was 20/32 or better. We found some relationships between visual acuity and lesions characteristic of MacTel Type 2. CONCLUSIONS: This is the first large-scale study of patients with MacTel Type 2. More than half of the patients had 20/32 or better vision in their better eye, which is a sign that decreased function in these participants may not be reflected in central visual acuity. These findings highlight the limitation of using visual acuity measurements as a measure of function and as an outcome measure in potential clinical trials in patients with MacTel Type 2.

The prevalence estimates of macular telangiectasia type 2: the Melbourne Collaborative Cohort Study.

PURPOSE: The purpose of this study was to determine the prevalence estimates of macular telangiectasia type 2 in an Australian population based on nonmydriatic digital fundus photography. METHODS: Participants of the Melbourne Collaborative Cohort Study, initiated to investigate risk factors for common aging diseases, had nonmydriatic digital macular images taken from both eyes and graded for any macular abnormalities. Prevalence of the features suggestive of macular telangiectasia type 2 was assessed. RESULTS: Macular images from the 22,062 subjects with a mean age of 64.96 years (range, 47-85 years) were assessed. Of these images, 43,234 images were gradable (21,708 images of the right eye and 21,526 images of the left eye). Using only the grading features of the macular images taken by the nonmydriatic digital fundus photography, 5 subjects with signs consistent with bilateral macular telangiectasia type 2 in this population were found by the authors. Based on the Gass-Blodi staging of this disease, all (5) were determined to be in stages 2 and 3. CONCLUSION: In an Australian population, the prevalence estimates of macular telangiectasia type 2 were found to be 1 of 22,062 to 5 of 22,062 or 5 to 23 cases per 100,000 people in which disease was at least at stages 2 and 3.

Integrated clinical evaluation of Type 2A idiopathic juxtafoveolar retinal telangiectasis.

PURPOSE: To describe spectral high-resolution optical coherence tomography (OCT) findings correlated with fundus autofluorescence (FAF), confocal blue reflectance (CBR), and fluorescein angiography (FA) patterns in patients affected by Type 2A idiopathic juxtafoveolar retinal telangiectasis. METHODS: We reviewed OCT, FA, CBR, and FAF images of both eyes from 11 patients affected by Type 2A idiopathic juxtafoveolar retinal telangiectasis. One eye had Stage 2 disease, 13 eyes had Stage 3 disease, 5 eyes had Stage 4 disease, and 3 eyes had Stage 5 disease. All the imaging modalities were obtained with a combined instrument for confocal scanning laser ophthalmoscopy and Spectral-domain OCT. Simultaneous acquisition of OCT images with FA, CBR, and FAF images was achieved with perfect point-to-point correspondence. RESULTS: Increased parafoveal CBR was observed in all but 2 eyes that had Stage 5 disease. A correspondence of hyperautofluorescence on FAF and anatomical localization of the intraretinal cyst was observed in the 16 eyes where the cyst was visible by OCT. All eyes showed some alterations of the plexiform layers. A correspondence between increased CBR and late-phase FA hyperfluorescence occurred in the 4 eyes with focal and oval CBR pattern, whereas none of the 10 eyes with ring-pattern lesions had this correspondence. Patterns of increased CBR corresponded to areas of increased FAF in 94% of eligible eyes. CONCLUSION: The simultaneous acquisition of Spectral-domain OCT and reference images (FA, FAF, and CBR) with point-to-point correlation may further add to the understanding of morphologic alterations in Type 2A idiopathic juxtafoveolar retinal telangiectasis.

Spectral domain optical coherence tomography in type 2 idiopathic perifoveal telangiectasia.

BACKGROUND AND OBJECTIVE: To compare images acquired by Stratus time domain optical coherence tomography (OCT) (Carl Zeiss Meditec, Dublin, CA) and Cirrus spectral domain OCT (Carl Zeiss Meditec) in cases of bilateral type 2 idiopathic perifoveal telangiectasia. PATIENTS AND METHODS: Twenty-three eyes of 12 patients with type 2 idiopathic perifoveal telangiectasia were examined on the same day with both OCT systems. RESULTS: Foveal cystoid spaces were detected in more eyes by Cirrus than Stratus OCT (19 of 23 vs 13 of 23). Disruptions of the inner segment/outer segment photoreceptor line were detected with both systems but were only quantified on Cirrus images. Thinning of central foveal thickness was established by both, but only Cirrus OCT measured outer retinal thinning on the temporal compared to the nasal side of the fovea. CONCLUSIONS: Spectral domain OCT could become a new noninvasive tool for facilitating early diagnosis of type 2 idiopathic perifoveal telangiectasia and for following its evolution and the effects of any treatments.

Retinal vascular caliber and macular telangiectasia type 2.

OBJECTIVE: To examine the relationship of retinal vascular caliber to macular telangiectasia (MT) type 2. DESIGN: Case-control study. PARTICIPANTS: Patients with MT aged 18 years and older were identified from Australian sites of the multicenter Macular Telangiectasia Project. Three controls per case were selected from participants of the Australian Diabetes, Obesity and Lifestyle study, matched according to age and diabetes status. METHODS: Baseline ophthalmic examinations of cases included assessment of best corrected visual acuity, fluorescein angiography, autofluorescence imaging, optical coherence tomography, and retinal photography. Retinal vascular caliber of cases and controls were measured from optic disc-centered digital retinal images by a computer-assisted method. MAIN OUTCOME MEASURES: MT, central retinal arteriolar, and venular caliber. RESULTS: There were 55 cases and 170 controls. After controlling for diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, triglycerides, hypertension, fasting plasma glucose, and glycosylated hemoglobin, each standard deviation (SD) increase in retinal arteriolar caliber was associated with a 2-fold higher odds of MT (odds ratio [OR] 2.18; 95% confidence interval [CI], 1.50-3.18). Similarly, each SD increase in retinal venular caliber was associated with increased odds of having MT (OR 1.87; 95% CI, 1.31-2.67). CONCLUSIONS: This study shows that MT is associated with wider arteriolar and venular caliber, measured outside of the foveal area. Generalized changes in retinal vascular caliber may reflect underlying dysfunction in retinal pericytes or glial cells, and may provide a means to monitor progression of disease. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.