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Objective: The management of cervical artery dissections (CADs) is poorly standardized given the scarce number of prospective studies comparing medical and interventional approach to CAD. The aim of the present study is to perform a systematic review and meta-analysis of studies on the treatments of CAD., Methods: Systematic review and meta-analysis (pre-registered on PROSPERO [CRD42022297512] are performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses [PRISMA] guidelines searching in three different databases [PubMed, Embase and Cochrane Database]) of studies on medical or interventional approach to CAD. Only prospective studies were selected to reduce the risk of bias for the primary meta-analysis. Secondarily, retrospective studies were also included. The aim was to assess the rate of stroke and of stroke/death/bleeding (major or intracranial) by Der Simonian-Laird weights of random effects model., Results: After screening 456 articles, 6 prospective and 22 retrospective studies were identified. Two randomized controlled trials and five retrospective studies comparing antiplatelet (APT) vs oral anticoagulant therapy (OAC) for CAD were identified, as well as four prospective and 17 retrospective single-arm studies evaluating stenting for CAD. In the meta-analysis of randomized controlled trials comparing APT vs OAC, 444 patients were considered, and a borderline significant association was identified in terms of stroke/death in the APT vs OAC groups (odds ratio [OR], 5.6; 95% confidence interval [CI], 0.94-33.38; P = .06; I 2  = 0%). No differences were found for the stroke/death/bleeding outcome (OR, 1.25; 95% CI, 0.19-8.18; P = .81; I 2  = 0%) between the two treatments. In the meta-analysis including also retrospective studies, overall risk of bias was considered "serious," and 4104 patients were included with no differences in APT vs OAC for stroke (OR, 1.06; 95% CI, 0.53-2.11; P = .29; I 2  = 18%); no other comparisons were possible. The pooled meta-analysis of prospective studies on stenting for CAD included four series, for a total of 68 patients, in whom stenting was adopted primarily after failed medical therapy or after traumatic dissection. The pooled rate of stroke/death was 7% (95% CI, 3%-17%; I 2  = 0%). The analysis of moderators identified a significant inverse association between the percentage of traumatic dissection and a reduction in postoperative stroke (Y = -1.60-2.02X; P = .03). The pooled rate of the composite endpoint of stroke/death/ or major bleeding was 8% (95% CI, 3%-18%; I 2  = 0%). Secondarily, the meta-analysis also included 17 retrospective studies with overall 457 patients and showed a 2.1% pooled rate of stroke/death (95% CI, 1.0%-3.3%; I 2  = 0%) and 3.2% stroke/death/bleeding (95% CI, 1.8%-4.7%; I 2  = 0%)., Conclusions: Few prospective studies on CAD treatment are present in literature. APT and OAC seem to have similar efficacy in reducing the recurrence of stroke after CAD. No definitive conclusion can be drawn for stenting, due to the low number of studies available. More prospective studies are necessary to evaluate its potential additional value over medical therapy alone in the early phase after CAD., Competing Interests: Disclosures None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Persistent type II endoleaks (pEL2s) are not uncommon after endovascular aneurysm repair and their impact on long-term outcomes is well-documented. However, their occurrence and natural history after fenestrated/branched endografting (F/B-EVAR) for juxtarenal and pararenal aneurysms (J/P-AAAs) have been scarcely investigated. Aim of this study was to report incidence, risk factors, and natural history of pEL2 after F/B-EVAR in J/P-AAAs., Methods: Between 2016 and 2022, all J/P-AAAs undergoing F/B-EVAR were prospectively collected and retrospectively analyzed. EL2 were assessed at the completion angiography, at 30 days and after 6 months as primary outcomes. Preoperative risk factors for pEL2, follow-up survival, freedom from reinterventions (FFR) and aneurysm shrinkage (≥5 mm) were considered as secondary outcomes., Results: Of 132 patients, there were 88 (67%) JAAAs and 44 (33%) PAAAs. Seventeen EL2 (13%) were detected at the completion angiography and 36 (27%) at 30-day computed tomography angiography. The mean follow-up was 28 ± 23 months. Eleven (31%) EL2 sealed spontaneously within 6 months and three new cases were detected, for an overall of 28 pEL2/107 patients (26%) with available radiological follow-up of ≥6 months. Preoperative antiplatelet therapy (odds ratio, 4.7; 95% confidence interval [CI[, 1-22.1; P = .05), aneurysm thrombus volume of ≤40% and six or more patent aneurysm afferent vessels (odds ratio, 7.2; 95% CI, 1.8-29.1; P = .005) were independent risk factors for pEL2. The estimated 3-year survival was 80%, with no difference between cases with and without pEL2 (78% vs 85%; P = .08). The estimated 3-year FFR was 86%, with no difference between cases with and without pEL2 (81% vs 87%; P = .41). Four cases (3%) of EL2-related reinterventions were performed. In 65 cases (49%), aneurysm shrinkage was detected. pEL2 was an independent risk factor for absence of aneurysm shrinkage during follow-up (hazard ratio, 3.2; 95% CI, 1.2-8.3; P = .014). Patients without shrinkage had lower follow-up survival (64% vs 86% at 3-year; P = .009) and FFR (74% vs 90% at 3 years; P = .014) than patients with shrinkage., Conclusions: PEL2 is not infrequent (26%) after F/B-EVAR for J/P-AAAs and is correlated with preoperative antiplatelet therapy, aneurysm thrombus volume of ≤40%, and six or more patent sac afferent vessels. Patients with pEL2 have a diminished aneurysm shrinkage, which is correlated with lower follow-up survival and FFR compared with patients with aneurysm shrinkage., Competing Interests: Disclosures E.G., G.L.F., and M.G. are clinical proctors for Cook Medical fenestrated and branched endografting., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Fenestrated and branched thoracic endovascular aortic repair (F/B-TEVAR) of the aortic arch is a viable approach in patients unsuitable for open repair. The aim was to summarise the published results of manufactured F/B-TEVAR devices for partial and total repair of the aortic arch, and to compare fenestrated with branched configurations., Data Sources: PubMed, Scopus and The Cochrane Library were searched for articles (2018 - 2021) about patients with elective, urgent, or emergency aortic requiring a proximal landing zone in the aortic arch (zone 0 - 1 - 2) and treated by F/B-TEVAR., Review Methods: The systematic review and meta-analysis were performed according to the PRISMA guidelines. Open repair, supra-aortic trunk (SAT) debranching + standard TEVAR, and in situ physician modified and parallel grafts were excluded. Primary outcomes were technical success and 30 day mortality rate. Secondary outcomes were 30 day major adverse events, and overall survival and procedure related endpoints during follow up., Results: Of 458 articles screened, 18 articles involving 571 patients were selected. Indications for intervention were chronic dissections (50.1%), degenerative aneurysms (39.6%), penetrating aortic ulcers (7.4%), and pseudoaneurysms (2%). F-TEVAR, B-TEVAR, and F+B-TEVAR were used in 38.4%, 54.1%, and 7.5% of patients, respectively. Overall, technical success was 95.9% (95% confidence interval [CI] 0.93 - 0.97; I 2  = 0%; p for heterogeneity (Het) = .77) and the 30 day mortality rate was 6.7% (95% CI 0.05 - 0.09; I 2  = 0%; p Het = .66). No statistical differences were found comparing fenestrated with branched endografts, except for a higher rate of type I - III endoleaks in F-TEVAR (9.8% vs. 2.6%; p = .034). The overall survival rate and freedom from aortic related death at the one year follow up ranged between 82 - 96.4% and 94 - 94.7%, respectively. Thirteen and five studies were considered at moderate and high risk of bias, respectively., Conclusion: F/B-TEVAR for the treatment of the aortic arch, according to experience in dedicated centres, now enjoys a satisfactory level of technical success together with a progressively reduced early mortality rate. There are several limitations, and further studies are needed to reach clearer conclusions., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Radiation-induced acute and late toxicity depends on several parameters. The type, severity and duration of morbidity are mainly related to irradiated volume, total dose and its fractionation and the intrinsic radiosensitivity of the patients. The follow-up of these toxicities is essential. However, unlike many specialties, morbidity and mortality reviews procedures are not developed as part of quality governance programs in radiation therapy departments for the monitoring of toxicity which sometimes hinder the patients' quality of life. One French survey published within the framework of the project entitled Prospective Registration of Morbidity and Mortality, Individual Radiosensitivity and Radiation Technique (Proust), conclude that there was a lack of knowledge of morbidity and mortality reviews and considerable confusion between these reviews and other quality processes without perspective for the local morbidity and mortality reviews development in a large number of the participated centers. In this article, we will discuss the procedure of the "ideal morbidity and mortality reviews" and its implementation through a monocentric experience started in 2015. Thus, the Proust project is a unique opportunity to implement and standardize a national morbidity and mortality reviews implementation in radiation therapy departments by involving the French regions., (Copyright © 2023 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: In the pivotal phase III, randomized, multicenter ICARIA-MM study (NCT02990338), isatuximab plus pomalidomide and dexamethasone (Isa-Pd) improved progression-free survival and overall response rate versus pomalidomide and dexamethasone (Pd) in the overall population of patients with relapsed/refractory multiple myeloma., Patients and Methods: In this predefined subgroup analysis, efficacy, and safety between East Asian patients and the overall population were assessed., Results: In total, 36 East Asian patients were included (Japanese, n = 13; Korean, n = 9; Taiwanese, n = 14). At a median follow-up of 11.6 months, median progression-free survival was not reached (95% confidence interval [CI] 5.80-not calculable) in the Isa-Pd arm and was 7.9 months (95% CI 2.90-not calculable) in the Pd arm. The hazard ratio for the between-group difference was 0.52 (95% CI 0.19-1.39), which was similar to the overall population (hazard ratio, 0.60; 95% CI 0.44-0.82). No new safety signals were observed, except that a higher proportion of patients in the East Asian population experienced Grade ≥ 3 neutropenia compared with the overall population., Conclusion: These results confirm the efficacy of Isa-Pd in East Asian patients with relapsed/refractory multiple myeloma, and the related safety data are consistent with those observed in the overall population and are manageable., (Copyright © 2022. Published by Elsevier Inc.)

Background: Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma., Methods: We did a randomised, multicentre, open-label, phase 3 study at 102 hospitals in 24 countries in Europe, North America, and the Asia-Pacific regions. Eligible participants were adult patients with relapsed and refractory multiple myeloma who had received at least two previous lines of treatment, including lenalidomide and a proteasome inhibitor. Patients were excluded if they were refractory to previous treatment with an anti-CD38 monoclonal antibody. We randomly assigned patients (1:1) to either isatuximab 10 mg/kg plus pomalidomide 4 mg plus dexamethasone 40 mg (20 mg for patients aged ≥75 years), or pomalidomide 4 mg plus dexamethasone 40 mg. Randomisation was done using interactive response technology and stratified according to the number of previous lines of treatment (2-3 vs >3) and age (<75 years vs ≥75 years). Treatments were assigned based on a permuted blocked randomisation scheme with a block size of four. The isatuximab-pomalidomide-dexamethasone group received isatuximab intravenously on days 1, 8, 15, and 22 in the first 28-day cycle, then on days 1 and 15 in subsequent cycles. Both groups received oral pomalidomide on days 1 to 21 in each cycle, and oral or intravenous dexamethasone on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal. Dose reductions for adverse reactions were permitted for pomalidomide and dexamethasone, but not for isatuximab. The primary endpoint was progression-free survival, determined by an independent response committee and assessed in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. This study is registered at ClinicalTrials.gov, number NCT02990338., Findings: Between Jan 10, 2017, and Feb 2, 2018, we randomly assigned 307 patients to treatment: 154 to isatuximab-pomalidomide-dexamethasone, and 153 to pomalidomide-dexamethasone. At a median follow-up of 11·6 months (IQR 10·1-13·9), median progression-free survival was 11·5 months (95% CI 8·9-13·9) in the isatuximab-pomalidomide-dexamethasone group versus 6·5 months (4·5-8·3) in the pomalidomide-dexamethasone group; hazard ratio 0·596, 95% CI 0·44-0·81; p=0·001 by stratified log-rank test. The most frequent treatment-emergent adverse events (any grade; isatuximab-pomalidomide-dexamethasone vs pomalidomide-dexamethasone) were infusion reactions (56 [38%] vs 0), upper respiratory tract infections (43 [28%] vs 26 [17%]), and diarrhoea (39 [26%] vs 29 [20%]). Adverse events with a fatal outcome were reported in 12 patients (8%) in the isatuximab-pomalidomide-dexamethasone group and 14 (9%) in the pomalidomide-dexamethasone group. Deaths due to treatment-related adverse events were reported for one patient (<1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection)., Interpretation: The addition of isatuximab to pomalidomide-dexamethasone significantly improves progression-free survival in patients with relapsed and refractory multiple myeloma. Isatuximab is an important new treatment option for the management of relapsed and refractory myeloma, particularly for patients who become refractory to lenalidomide and a proteasome inhibitor., Funding: Sanofi. VIDEO ABSTRACT., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This phase 1b dose-escalation study evaluated isatuximab plus pomalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor (PI), were enrolled and received isatuximab at 5, 10, or 20 mg/kg (weekly for 4 weeks, followed by every 2 weeks), pomalidomide 4 mg (days 1-21), and dexamethasone 40 mg (weekly) in 28-day cycles until progression/intolerable toxicity. The primary objective was to determine the safety and recommended dose of isatuximab with this combination. Secondary objectives included evaluation of pharmacokinetics, immunogenicity, and efficacy. Forty-five patients received isatuximab (5 [n = 8], 10 [n = 31], or 20 [n = 6] mg/kg). Patients received a median of 3 (range, 1-10) prior lines; most were refractory to their last regimen (91%), with 82% lenalidomide-refractory and 84% PI-refractory. Median treatment duration was 9.6 months; 19 patients (42%) remain on treatment. Most common adverse events included fatigue (62%), and upper respiratory tract infection (42%), infusion reactions (42%), and dyspnea (40%). The most common grade ≥3 treatment-emergent adverse event was pneumonia, which occurred in 8 patients (17.8%). Hematologic laboratory abnormalities were common (lymphopenia, leukopenia, anemia, 98% each; neutropenia, 93%; and thrombocytopenia, 84%). Overall response rate was 62%; median duration of response was 18.7 months; median progression-free survival was 17.6 months. These results demonstrate potential meaningful clinical activity and a manageable safety profile of isatuximab plus pomalidomide/dexamethasone in heavily pretreated patients with RRMM. The 10 mg/kg weekly/every 2 weeks isatuximab dose was selected for future studies. This trial was registered at www.clinicaltrials.gov as #NCT02283775., (© 2019 by The American Society of Hematology.)

Objectives: This was a prospective observational study to assess the short- to mid-term efficacy and safety of catheter foam sclerotherapy (CFS) of the great saphenous vein (GSV), including peri-saphenous tumescence infiltration (PST) and intra-saphenous saline irrigation (ISI), in combination with phlebectomy of the varicose tributaries., Methods: Eighty-eight limbs in 82 patients (19 male, 63 female, mean age 55.7 years) affected by varices related to GSV incompetence were submitted to CFS of the refluxing GSV segment after PST and ISI, combined with phlebectomy of the varicose tributaries. Sodium tetradecylsulfate (STS) 3% + CO 2 /O 2 sclerosant foam (SF) (median 7 mL) was injected in the GSV trunk (median caliber 7.1 mm) by means of a 4F catheter. Clinical and colour duplex ultrasound (CDU) investigation was performed pre-operatively, and 40 days, 6, 12, and 36 months post-operatively. A visual analogue scale (VAS) was used to assess procedure related symptoms and venous symptoms before and 40 days after the treatment., Results: Clinical recurrence (visible varices) at 40 days, 6 and 12 months was 0%, whereas at 36 months it was 4.7%; VAS pre-operative score of heaviness, pain, and cramps/paraesthesiae decreased from 6 (IQR 6-8) to 1 (IQR 0-3), from 3 (IQR 0-7) to 0 (IQR 0-1), and from 3 (IQR 0-7) to 0 (IQR 0-1) respectively at 40 days. The CDU based occlusion rate at 40 days, 6, 12, and 36 months was 100% (88/88), 100% (88/88), 94.3% (83/88), and 89.4% (76/85) respectively. Six of the nine patent saphenous veins (average diameter 1.4 mm) had anterograde flow (overall 96.5% reflux free GSVs). One superficial venous thrombosis was recorded without any further relevant complication., Conclusions: GSV treatment by means of CFS and adjuvant PST + ISI, combined with phlebectomy of varicose tributaries, proved to be safe and effective in terms of clinical and duplex based outcomes at short/mid-term follow-up., (Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

This phase 1b, open-label, dose-escalation study assessed the safety, efficacy, and pharmacokinetics of anti-CD38 monoclonal antibody isatuximab given in 2 schedules (3, 5, or 10 mg/kg every other week [Q2W] or 10 or 20 mg/kg weekly [QW] for 4 weeks and then Q2W thereafter [QW/Q2W]), in combination with lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (QW), in patients with relapsed/refractory multiple myeloma (RRMM). Patients received 28-day treatment cycles; the primary objective was to determine the maximum tolerated dose (MTD) of isatuximab with lenalidomide and dexamethasone. Fifty-seven patients (median 5 [range 1-12] prior regimens; 83% refractory to previous lenalidomide therapy) were treated. Median duration of dosing was 36.4 weeks; 15 patients remained on treatment at data cutoff. Isatuximab-lenalidomide-dexamethasone was generally well tolerated with only 1 dose-limiting toxicity reported (grade 3 pneumonia at 20 mg/kg QW/Q2W); the MTD was not reached. The most common isatuximab-related adverse events were infusion-associated reactions (IARs) (56%), which were grade 1/2 in 84% of patients who had an IAR and predominantly occurred during the first infusion. In the efficacy-evaluable population, the overall response rate (ORR) was 56% (29/52) and was similar between the 10 mg/kg Q2W and 10 and 20 mg/kg QW/Q2W cohorts. The ORR was 52% in 42 evaluable lenalidomide-refractory patients. Overall median progression-free survival was 8.5 months. Isatuximab exposure increased in a greater than dose-proportional manner; isatuximab and lenalidomide pharmacokinetic parameters appeared independent. These data suggest that isatuximab combined with lenalidomide and dexamethasone is active and tolerated in heavily pretreated patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT01749969., (© 2017 by The American Society of Hematology.)

Background and Purposes: We evaluate the early toxicity of concurrent use of radiotherapy, pertuzumab and trastuzumab in patients with HER2-positive metastatic or locally recurrent unresectable breast cancer., Patients and Methods: A retrospective study was performed in a population of 23 consecutive patients between 2013 and 2015. Radiotherapy was performed on the chest area or metastatic sites during maintenance with pertuzumab and trastuzumab after six cycles of pertuzumab, trastuzumab and docetaxel. Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria version 4., Results: Irradiation volumes were whole breast (8 patients) and chest wall (9 patients) at 50Gy in 25 fractions, the supraclavicular nodes (16 patients), the axillary area (nine patients) and the internal mammary nodes (9 patients) at 46Gy in 23 fractions. For five patients, radiotherapy was palliative: bone irradiation (4 patients), whole brain radiotherapy (one patient). Median follow-up was 12.6 months (range: 6.1-21.6 months) since the start of pertuzumab and trastuzumab. One patient presented an asymptomatic decrease of left ventricular ejection fraction below 50%. No symptomatic cardiac events were reported. Two patients presented asymptomatic grade I radiation pneumonitis. Acute skin toxicity was grade III (one patient), grade II (6 patients), and grade I (5 patients). There were two grade II esophagitis., Conclusion: Combination of pertuzumab, trastuzumab and radiotherapy was well tolerated, which should be confirmed by the results of larger studies., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Whole-breast normofractionated irradiation following breast-conserving surgery is the reference treatment. It delivers a dose of 50Gy in 25 fractions of 2Gy to the reference point, and, in some patients, an additional dose of 16Gy in 8 fractions of 2Gy in the tumor bed. Long-term results and toxicity of this irradiation scheme was prospectively evaluated in several randomised trials and meta-analyses, in invasive cancers as well as in ductal carcinoma in situ. The average 10-year rate of in breast recurrences was 6 % in these trials, with limited cardiac and pulmonary toxicity and limited rate of severe fibrosis. Identification of risk factors of recurrences may help to design new irradiation schemes adapted to tumor biology. The new irradiation schemes must be rigorously evaluated in the long-term in the frame of prospective clinical trials, in order to validate them as new standards of treatment., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Objective/background: The objective of this study was to compare the efficacy and comfort of inelastic bandages (IBs) and adjustable Velcro compression devices (AVCDs) in reducing venous leg edema in the initial treatment phase., Methods: Forty legs from 36 patients with untreated venous edema (C3EpsAsdPr) were randomized to two groups. Patients in the first group received IBs (n = 20) and those in the second AVCDs (n = 20). Both compression devices were left on the leg day and night, and were renewed after 1 day. Patients in the AVCD group were asked to re-adjust the device as needed when it felt loose. Leg volume was calculated using the truncated cone formula at baseline (T0), after 1 day (T1) and after 7 days (T7). The interface pressure of the two compression devices was measured by an air filled probe, and the static stiffness index calculated after applying compression at T0 and T1, and just before removal of compression on T1 and T7. Patient comfort with regard to the two compression systems was assessed by grading signs and symptoms using a visual analog scale., Results: At T1, the median percent volume reduction was 13% for the IB group versus 19% for the AVCD group; at T7 it was 19% versus 26%, respectively (p < .001). The pressure of the IBs was significantly higher compared with the AVCDs at T0 (63 vs. 43 mmHg) but dropped by > 50% over time, while it remained unchanged with AVCDs owing to the periodic readjustment by the patient. Comfort was reported to be similar with the two compression devices., Conclusion: Re-adjustable AVCDs with a resting pressure of around 40 mmHg are more effective in reducing chronic venous edema than IBs with a resting pressure of around 60 mmHg. AVCDs are effective and well tolerated, not only during maintenance therapy, but also in the initial decongestive treatment phase of patients with venous leg edema., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Introduction: Sinus aspergillosis is a potential complication after root canal therapy of antral teeth. Indeed, zinc oxide-eugenol cement overfilling in the sinus may promote fungal infection. Moreover, if sinus aspergillosis triggers chronic sinusitis with aspergilloma, it may also lead to invasive phenomena, especially for immunocompromised patients., Methods: We reported a sinus aspergillosis case of a patient treated with infliximab (Remicade; Janssen Biologics BV, Leiden, Netherlands). The purpose of this article was to explore the mechanisms of this pathosis, especially the impact of the root canal sealer overextension, which is a contributing factor for fungal infection. The surgical management and the follow-up are also described., Results: Six months after surgery, the patient showed no clinical signs and presented with a healthy and airy right maxillary sinus on the computed tomography scan., Conclusions: In conclusion, prevention and screening of aspergillosis of maxillary sinus may be considered before starting an anti-tumor necrosis factor alpha therapy., (Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Brain metastases (BMs) are associated with a poor prognosis. Standard treatment comprises whole-brain radiation therapy (WBRT). As neo-angiogenesis is crucial in BM growth, combining angiogenesis inhibitors such as bevacizumab with radiotherapy is of interest. We aimed to identify the optimal regimen of bevacizumab combined with WBRT for BM for phase II evaluation and provide preliminary efficacy data., Patients and Methods: In this multicentre single-arm phase I study with a 3 + 3 dose-escalation design, patients with unresectable BM from solid tumours received three cycles of bevacizumab at escalating doses [5, 10 and 15 mg/kg every 2 weeks at dose levels (DL) 0, 1 and 2, respectively] and WBRT (30 Gy/15 fractions/3 weeks) administered from day 15. DL3 consisted of bevacizumab 15 mg/kg with WBRT from day 15 in 30 Gy/10 fractions/2 weeks. Safety was evaluated using NCI-CTCAE version 3. BM response (RECIST 1.1) was assessed by magnetic resonance imaging at 6 weeks and 3 months after WBRT., Results: Nineteen patients were treated, of whom 13 had breast cancer. There were no DLTs. Grade 1-2 in-field and out-field toxicities occurred for five and nine patients across all DLs, respectively, including three and six patients (including one patient with both, so eight patients overall) of nine patients in DL3. One patient experienced BM progression during treatment (DL0). At the 3-month post-treatment assessment, 10 patients showed a BM response: one of three treated at DL0, one of three at DL1, two of three at DL2 and six of seven at DL3, including one complete response. BM progression occurred in five patients, resulting in two deaths. The remaining patient died from extracranial disease progression., Conclusion: Bevacizumab combined with WBRT appears to be a tolerable treatment of BM. DL3 warrants further efficacy evaluation based on the favourable safety/efficacy balance. ClinicalTrials.gov Identifier: NCT01332929., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The purpose of this multicenter prospective and descriptive study was to determine late toxicities and outcomes among patients with non-metastatic breast cancer receiving concurrent bevacizumab (BV) and radiation therapy (RT) in the clinical trials. Early and late toxicities were assessed and evaluation was available for 63 patients (pts) at 12 months. Acute radiation dermatitis was observed in 48 (76%): grade 1 for 27, grade 2 for 17 and grade 3 for 4 pts. Grade 2 acute oesophagitis was observed in one patient (2%). Little toxicity was described 1 year after the completion of RT: 7 pts (12%): grade 1-2 pain, 3 (5%) presented grade 1 fibrosis, and 2 pts (4%) - telangiectasia. One patient (2%) experienced grade 1 dyspnoea. Five grade 1-2 lymphoedema occurred. Only one patient experienced a LEVF value less than 50% one year after the end of RT. In conclusion, the concurrent BV with locoregional RT provides acceptable toxicities., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We report the first case report indicating that locoregional radiotherapy provide acceptable early and late toxicities in patient with erythrokeratodermia variabilis after 2 years of follow-up. However, preclinical data showing radiation-induced tumor genesis in case of deficiency of some connexins point out the need of a careful surveillance of these patients., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To evaluate the dosimetry and acute toxicity of helical tomotherapy for locoregional irradiation of patients after breast-conserving surgery., Patients and Methods: Twenty breast cancer patients with breast-conserving surgery treated by helical tomotherapy have been studied. The median age was 49 (min: 25, max: 69). The whole breast, tumour bed and lymph nodes were prescribed 52.2 Gy, 63.8 Gy and 50.4 Gy, all in 29 fractions. The dose per fraction was 2.2 Gy to the boost, 1.8 Gy to the breast and 1.74 Gy to the lymph node volumes. The reproducibility was analysed by recording the daily shifts in x, y and z directions and roll rotation. All toxicities were described using the Common Terminology Criteria for Adverse Effects v3.0., Results: Twenty-two tumours were irradiated. Six-eight percent were located in the inner quadrant. In 90 % of patients supraclavicular and internal mammary nodes were treated. The coverage of planning target volumes (PTV) was as follows: PTV boost: V107 = 0.3 % ± 0.5 SD, V95 = 98.4 % ± 1.9 SD; PTV breast: -V107 = 7.8 % ± 17.3 SD, V95 = 96.8 % ± 2.2 SD; PTV LN: V107 = 2.5 % ± 4.2 SD, V95 = 92.7 % ± 13.2 SD. The mean V20 of the homolateral lung was 18.9 % ± 3.5 SD. For left side lesion, the mean V30 of the heart was 0.9 % ± 0.8 SD. The mean V5 was: V5 homolateral lung: 73.1 % ± 11.8 ET, controlateral lung: 38.9 % ± 21, heart (left side breast): 57.3 % ± 21, controlateral breast: 15.5 % ± 9.6. Median shifts were as follow: x-axis -0.04 mm (IC 95: -0.4 +0.38), y-axis -0.37 mm ± 5.51 (IC 95: -0.88 +0.14), z-axis 2.90 mm ± 5.42 (IC 95:+2.4+3.4) and roll rotation 0.22 ± 1.10 (IC 95: -0.1+0.32). The treatment tolerance was acceptable with 1 definitive interruption couple of fractions before the end and 3 temporal interruptions for skin toxicity. No grade 3 or 4 toxicity. Ninety-five percent of patients experienced skin toxicity: 45 % grade 2. There were 3 cases of oesophagitis. The median follow-up of presented series is 9.7 months and all of the patients are free of disease without any residual early or late toxicity., Conclusions: Helical tomotherapy can achieve full target coverage while protected to the heart and ipsilateral lung. This treatment was well tolerated and reproducible. However, the low doses to normal tissue volumes need to be reduced in future studies., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: Prospective monocentric study of the toxicities related to concurrent administration of trastuzumab to breast radiotherapy., Patients and Methods: One hundred and seventy-three patients were treated between June 2003 and March 2009 by concurrent trastuzumab with normofractionated radiotherapy. Trastuzumab was delivered every 3 weeks (8mg/kg in the first infusion then 6mg/kg) during a median time of 12 months (2-62). Left ventricular ejection fraction was assessed by echocardiography or cardiac scintigraphy at baseline, before and after radiotherapy, every 3 months for 1 year and annually. A left ventricular ejection fraction strictly lower than 55% was considered as altered. All toxicities were evaluated using Common Terminology Criteria for Adverse Effects version 3.0., Results: Median follow-up was 52 months (17-88). Median age was 52 years (25-83). One hundred and thirty-four patients (77.5%) received radiotherapy to the internal mammary chain. Acute grade 1, 2 and 3 epithelitis was described in 132 (76.3%), 32 (18.5%) and six patients (3.4%), respectively. At 23 months, grade 1 and 2 fibrosis was observed in 31 and eight patients, respectively (18.8 and 4.6%). Left ventricular ejection fraction remained normal for 159 patients (91.9%) before radiotherapy. Among them, 18 (11.3%) experienced a left ventricular ejection fraction alteration, eight (5.0%) at the completion of radiotherapy. Congestive heart failure occurred in one patient (0.6%)., Conclusions: Toxicities related to the association of trastuzumab to breast radiotherapy were mild. Further follow-up is warranted., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Chronically ill patients are complex health care cases that require the coordinated interaction of multiple professionals. A correct intervention of these sort of patients entails the accurate analysis of the conditions of each concrete patient and the adaptation of evidence-based standard intervention plans to these conditions. There are some other clinical circumstances such as wrong diagnoses, unobserved comorbidities, missing information, unobserved related diseases or prevention, whose detection depends on the capacities of deduction of the professionals involved. In this paper, we introduce an ontology for the care of chronically ill patients and implement two personalization processes and a decision support tool. The first personalization process adapts the contents of the ontology to the particularities observed in the health-care record of a given concrete patient, automatically providing a personalized ontology containing only the clinical information that is relevant for health-care professionals to manage that patient. The second personalization process uses the personalized ontology of a patient to automatically transform intervention plans describing health-care general treatments into individual intervention plans. For comorbid patients, this process concludes with the semi-automatic integration of several individual plans into a single personalized plan. Finally, the ontology is also used as the knowledge base of a decision support tool that helps health-care professionals to detect anomalous circumstances such as wrong diagnoses, unobserved comorbidities, missing information, unobserved related diseases, or preventive actions. Seven health-care centers participating in the K4CARE project, together with the group SAGESA and the Local Health System in the town of Pollenza have served as the validation platform for these two processes and tool. Health-care professionals participating in the evaluation agree about the average quality 84% (5.9/7.0) and utility 90% (6.3/7.0) of the tools and also about the correct reasoning of the decision support tool, according to clinical standards., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery., Patients and Methods: Medical records of 72 women who developed either ductal carcinoma in situ or stage I-III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed., Results: Median age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40 Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%)., Conclusions: Breast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position., (Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To assess the benefits of using cardiac gated images for treatment planning of breast and internal mammary nodes., Patients and Methods: Inspiration breath hold computed tomography (CT) series acquired at prospectively gated diastolic phase were used for planning. Three different techniques were compared. Technique A used tangents and an internal mammary nodes field covering the three first inter-rib spaces; technique B used an extended internal mammary nodes including part of the medial breast in junction with tangential fields; the 3(rd) technique used helical tomotherapy. For each technique, two treatment plans were performed: one plan (plan-01) where mean dose and V(25) to the heart were considered for plan evaluation and a second plan (plan-02) where the irradiation of the left anterior descending artery was minimized., Results: V(25) to the heart was found to be less than 5% for all six plans. Mean doses to the heart were within 4.8 to 7.2 Gy. By attempting to lower the dose to the left anterior descending artery, heart D(mean) was decreased by 20-30% for the two techniques A and B while being unchanged for tomotherapy. Regarding target coverage, there was no marked difference between plans where only heart dose was considered (plans-01) and plans where the left anterior descending artery dose was minimized (plans-02). When the left anterior descending artery dose was part of plan evaluation, D(mean) to the left anterior descending artery could be decreased by 24, 19 and 9% for techniques A, B and tomotherapy respectively. The three techniques exposed segments of the left coronary to different levels of dose., Conclusion: This study showed that evaluation of the dose to the left anterior descending artery coronary may change the treatment strategy. Cardiac gated images without IV contrast permitted a good visualization of the coronaries in order to optimize the dose on these structures. In addition to heart V(25,) the dose to the coronaries should be included in prospective studies on radiotherapy related heart toxicity in association with all additional risk factors., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To assess the benefit of breast surgery for inflammatory breast cancer., Patients and Methods: This retrospective series was based on 232 patients treated for inflammatory breast cancer. All patients received primary chemotherapy followed by either exclusive radiotherapy (118 patients, 51%) or surgery with or without radiotherapy (114 patients, 49%). The median follow-up was 11 years., Results: The two groups were comparable apart from fewer tumors smaller than 70 mm (43% vs 33%, P=0.003), a higher rate of clinical stage N2 (15% vs 5%, P=0.04) and fewer histopathological grade 3 tumors (46% vs 61%, P<0.05) in the no-surgery group. The addition of surgery was associated with a significant improvement in locoregional disease control (P=0.04) but with no significant difference in overall survival rates or disease-free intervals. Late toxicities were not significantly different between the two treatment groups except for a higher rate of fibrosis in the no-surgery group (P<0.0001), and more lymphedema in the surgery group (P=0.002)., Conclusion: Our data suggest an improvement in locoregional control in patients treated by surgery, in conjunction with chemotherapy and radiotherapy, for inflammatory breast cancer., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: Patients with permanent cardiac pacemakers occasionally require radiotherapy. Therapeutic irradiation may cause pacemakers to malfunction due to the effects of ionizing radiation or electromagnetic interference. We studied the breast cancer patients who needed breast and/or chest wall and lymph node irradiation to assess the feasibility and tolerance in this population of patients., Patients and Methods: From November 2008 to December 2009, more than 900 patients received radiotherapy for their breast cancer in our department using megavoltage linear accelerator (X 4-6 MV and electrons). Among them, seven patients were with permanent pacemaker. All patients have been treated to the breast and chest wall and/or lymph nodes. Total dose to breast and/or chest wall was 50 Gy/25 fractions and 46 Gy/23 fractions to lymph nodes. Patients who underwent conserving surgery followed by breast irradiation were boosted when indicated to tumour bed with 16 Gy/8 fractions. All patients were monitored everyday in presence of radiation oncologist to follow the function of their pacemaker. All pacemakers were controlled before and after radiotherapy by the patients' cardiologist., Results: Seven patients were referred in our department for postoperative breast cancer radiotherapy. Among them, only one patient was declined for radiotherapy and underwent mastectomy without radiotherapy. In four cases the pacemaker was repositioned before the beginning of radiotherapy. Six patients, aged between 48 and 84 years underwent irradiation for their breast cancer. Four patients were treated with conserving surgery followed by breast radiotherapy and two with mastectomy followed by chest wall and internal mammary chain, supra- and infra-clavicular lymph node irradiation. The dose to the pacemaker generator was kept below 2 Gy. There was no pacemaker dysfunction observed during the radiotherapy., Conclusion: The multidisciplinary work with position change of the pacemaker before radiotherapy and everyday monitoring permitted the safe treatment of our patients. Updated guidelines are definitely needed with more details about acceptable doses at the different parts of the pacemaker., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To determine whether exclusive radiotherapy could be a therapeutic option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancers (EBC)., Patients and Methods: Between 1985 and 1999, 1477 patients received néoadjuvante chemotherapy for early breast cancer considered to be too large for primary conservative surgery. Of 165 patients with complete clinical response, 65 were treated by breast surgery (with radiotherapy) and 100 by exclusive radiotherapy., Results: The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the exclusive radiotherapy group. There were no significant differences in overall, disease-free and metastasis-free survivals. Five-year and 10-year overall survivals were 91 and 77% in the no surgery group and 82 and 79% in the surgery group, respectively (P = 0.9). However, a non-significant trend towards higher locoregional recurrence rates (LRR) was observed in the no surgery group (31 vs. 17% at 10 years; P = 0.06). In patients with complete responses on mammography and/or ultrasound, LRR were not significantly different (P=0.45, 10-year LRR: 21 in surgery vs. 26% in exclusive radiotherapy). No significant differences were observed in terms of the rate of cutaneous, cardiac or pulmonary toxicities., Conclusion: Surgery is a key component of locoregional treatment for breast cancers that achieved complete clinical response to neoadjuvant chemotherapy., (Copyright © 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: We retrospectively assessed the use of trastuzumab concurrently with whole-brain radiotherapy (WBRT) for brain metastases., Patients and Methods: From April 2001 to April 2007, 31 patients with brain metastases from HER2-positive breast cancer were referred for WBRT with concurrent trastuzumab. In most cases, concurrent WBRT delivered 30 Gy in 10 daily fractions. In six patients, other fractionations were chosen because of either poor performance status or patients’ convenience., Results: At time of brain progression, median age was 55 years (range: 38 to 73 years) and all patients had a performance status of 0 to 2. Median time to brain progression was 10.5 months. Following WBRT, radiological responses were observed in 23 patients (74.2%), including six patients (19.4%) with complete radiological responses and 17 patients (54.8%) with partial radiological response. Clinical responses were observed in 27 patients (87.1%). Median survival from the start of WBRT was 18 months (range: two to 65 months). No grade 2 or more acute toxicity was observed., Conclusion: Our results suggest that trastuzumab concurrently with WBRT may have a potential clinical impact with low toxicity. Although promising, these preliminary data warrant further validation of trastuzumab as radio sensitizer for WBRT in brain metastases from breast cancer in the setting of a clinical trial. Larger prospective studies are needed to confirm these results.

Purpose: To assess the efficacy of exclusive hypo-fractionated radiotherapy (HFRT) without previous breast-conserving surgery (BCS) in elderly women., Materials and Methods: From 1995 to 1999, we have treated with breast-conserving treatment 396 patients older than 70 years with early-stage breast cancer (T1,T2 tumours) at the Institut Curie, Paris, France. Seventy-nine consecutive elderly non-metastatic patients treated for early breast cancer have been treated with HFRT. Of them, 50 underwent BCS followed by HFRT of 32.5 Gy/5 fractions/5 weeks, and 29 patients (presented with different co-morbidities, inoperable or patients' refusal, and/or transportation problems) received the same HFRT schedule followed by a 13 Gy boost (two fractions of 6.5 Gy) as exclusive radiotherapy treatment. This population of 29 patients has been studied. In case of hormonal positive status, hormonal therapy was also proposed to the patients., Results: There was a median follow-up of 93 months (9-140 months). At 7-year follow-up, the cause-specific survival was 96.4% (confidence interval (CI) 95: 89.8.6-100%), the metastasis-free survival rate was 92.4% (CI 95: 82.8-100%) and the loco-regional control rate was 95.8% (CI 95: 88.2-100%)., Conclusions: This long-term follow-up retrospective study demonstrated acceptable local control and good outcome in elderly patients treated by exclusive HFRT for early breast cancer. However, large-scale prospective randomised trials are needed to confirm these results., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

From March 2003 to April 2004, were prospectively collected in France 1,289 ductal carcinoma in situ (DCIS) with data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). DCIS was diagnosed by mammography in 87.6% of patients. Mastectomy (M), conservative surgery alone (CS) and conservative surgery with radiotherapy (CS + RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients. Nuclear grade was low in 21% of patients, intermediate in 38.5% and high in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS + RT) of patients. Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin, grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

Purpose: Given the scarcity of malignant phyllode tumours of the breast and the absence of consensus regarding their management justify the need for institutional retrospective evaluations of clinical practices., Patients and Methods: Retrospective study with central pathology review of the 25 consecutive patients treated at the Institut Curie (Paris, France) between 1969 and 2006 for non metastatic malignant phyllodes tumors of the breast. The median follow-up was 65 months (7-257 months)., Results: Median age at diagnosis was 52 years (20-64 years). Breast surgery was conservative in five patients (20%). Surgical margins were wide (> 10mm), narrow, involved or unknown in respectively 17 (68%), three (12%), three (12%) and two (8%) patients. Median tumour size was 65 mm (12-250 mm). Adjuvant radiotherapy was delivered in seven (28%) patients (two patients, post-tumorectomy; five patients, post-mastectomy) and 13 patients (52%) received anthracycline-based adjuvant chemotherapy. Five-year overall survival rate was 91% (95% CI, 80-100%). Five patients (20%) developed distant metastases (one after chemotherapy) and three (12%) locoregional relapse (one after tumorectomy and unknown margin without radiotherapy, two after mastectomy and involved margins with radiotherapy)., Conclusion: Wide breast surgery (that can be conservative in selected patients) is the mainstay of the treatment of non metastatic malignant phyllodes tumors of the breast. To better determine the respective roles of adjuvant systemic treatment and radiotherapy, further clinical studies and the search for new prognostic and predictive factors remain necessary.

Purpose: Prospective monocentric study of the skin and heart tolerance of a concurrent administration of trastuzumab (T) and radiotherapy (RT) for breast cancer (BC)., Patients and Methods: From February 2004 to January 2007, 57 patients (pts), were treated by a concomitant administration of T and normo-fractionated RT of either whole breast (+/-boost) or chest. The perfusion of T started either with or after chemotherapy (CT). Left ventricular ejection fractions (LEVF), assessed at baseline, before start of RT, after completion of RT and then every four to six months with either echocardiography or multiple gated acquisition scanning, were considered normal if greater or equal to 50% or stated so by the cardiologist. Inclusion criteria included a normal LVEF at baseline. Skin toxicity was evaluated using CTCAEV3. Median age was 49 years (25-80). CT with anthracycline was administered in 84% (total dose 300 mg/m(2)). All but one patient (treated weekly) received T every three weeks (8 mg/kg followed by 6 mg/kg) for a median duration of 12 months (6-33). The internal mammary chain was irradiated in 88% of cases. Median follow-up for LVEF assessment was 13 months (2-33)., Results: LVEF at pre-RT were normal in 54 pts (100%, three Missing Data [MD]), at post-RT in 56 pts (98%, no MD) and at last follow-up in 53 pts (95%, one MD). There were two grade 0, 44 grade I and 11 grade II skin reactions. For the 27 patients with a skin toxicity assessment after six months, late skin toxicity was grade 0 in 22 pts, grade 1 in four, grade 2 in one., Conclusion: Provided that the technique is adapted, the acute skin and heart toxicities of the concomitant administration of T-RT appeared satisfactory. More patients and longer follow-up are still mandatory.

Dysfunction of the ataxia telangiectasia mutated (ATM) gene has been related to defective cell cycle control and genomic instability due to the impaired repair of DNA double strand breaks. Although increased radiosensitivity in ATM heterozygous patients has been suggested in preclinical data, clinical implication of ATM variant remains debated. Despite frequent in vitro hypersensitivity in patients with severe radiation-induced delayed toxicity, heterozygoty for ATM gene does not represent the major cause of unexpected complications after radiation therapy. This might be partially due to potential coexistence of alterations in additional genes that would play a role in development of late radiation-induced adverse response. Although several data suggest that some ATM polymorphisms would increase grade 3 subcutaneous fibrosis at lower doses compared with patients who did not possess these genetic alterations, the relationship between the presence of ATM mutations or sequence variants and radiation-induced toxicity remains controversial in part because of their biological and functional significance. Considering the lack of prospective data, patients with ATM mutation should be considered as candidates for both dose volume and dose reduction clinical trials.

Purpose: To assess the skin toxicity of this scheme and the time to its appearance., Patients and Methods: Eighty-one prospectively recorded patients (pts), treated in Radiotherapy Department for Breast Cancer (BC) with radiotherapy (RT) to the whole breast at the dose of 42.9Gy per 13 fractions (F) per 5 weeks have been studied. Skin reactions were monitored weekly using the National Cancer Institute-Common Toxicity Criteria scoring system, version 3. All risk factors as tobacco smoking, diabetes, obesity were also recorded., Results: All 81 pts, aged from 40 to 83 years (median: 70 years) received whole breast RT 42.9Gy per 13 F without lymph node irradiation after breast conserving surgery. There were no pts with concurrent chemo- and/or hormonal therapy. Seventeen patients (21%) have been treated using decubitus dorsal (DD) technique and 64 (79%) using the previously described isocentric decubitus lateral (IDL) technique. During the RT, only 34 pts (42%) experienced grade I skin reactions and 47 pts (58%) were without. At the last day of the breast irradiation, there were 66 (81%) grade I (N=59) and II (N=7) skin reactions and 15 pts (19%) without. The early skin tolerance of this scheme was considered to be excellent. But in the 2 weeks after the RT, 20 pts (25%) asked for new clinics with their radiation oncologist as a matter of urgency due to worsening of their skin condition. All of them have been seen by their physician and/or the nurse. Of them, nine presented grade I and 11 presented grade II skin reactions, with necessity of special skin care. The analysis of these results was realized and delayed clinics were organized for all pts treated with this scheme 10-14 days after the end of the radiation treatment., Conclusions: The breast RT 42.9Gy/13 F have been previously described as an efficacious and well tolerated scheme. This prospective homogeneous group of patients showed that delayed early skin reactions could appear in some cases. Therefore complementary clinics are needed to detect and treat these reactions.

Routine follow-up of breast cancer patients in specialist clinics is standard practice. This follow-up involves regularly scheduled breast cancer check-ups during the disease-free period, in order to detect recurrence. However, demands on specialist resources rise with the increase in the prevalence of diagnosed breast cancer. Since September 2004, it was proposed in our Institut an alternative routine follow-up schedule. Some patients who are in remission for more than 5 years will be deferred to their general practitioner or gynaecologist for follow-up schedule, alternatively with their referent practitioner from the institut (oncologist, radiation oncologist, or surgeon). We herein present the preliminary results of this strategy, and demonstrate that partially transferring primary responsibility for follow-up does not compromise its quality.

Several meta-analyses of the effects of radiotherapy in breast cancer were published. Methodological quality varied largely in these studies, from simply gathering data from published studies or even published abstracts, to more rigorous studies gathering individual data from each patient having participated in the trials analysed. A model of the latter is represented by the successive meta-analyses from the Early Breast Cancer Trialists' Cooperative Group (EBCTCG). These studies have had a strong impact on the clinical practice of radiotherapy in breast cancer, by demonstrating its long-term potential toxic effects, but also its ability to decrease the long-term breast-cancer mortality, regardless of the effects of other breast-cancer treatments. Therefore, it has contributed to the continuous improvement in the techniques of radiotherapy, as well as to its use in the multidisciplinary management of breast-cancer patients.

Adjuvant radiotherapy to the breast plays a significant role in preventing local failure in women treated for early stage breast cancer. This fact is supported by multiple clinical trials demonstrating that adjuvant radiotherapy decreases the risk of local recurrence and increases the rate of breast preservation, and actually the rules of adjuvant breast irradiation are clearly established. Sarcomas are a rare but recognized complication of radiation therapy for breast carcinoma, and are associated with poor prognosis. The first case of a bone sarcoma after radiation therapy of breast cancer was described by Beck in 1922. In 1948, Cahan et al. defined the criteria for diagnosis of radiation-induced sarcoma. Since then, some studies have reported the incidence of radiation-induced sarcoma after radiotherapy for different cancers. This article reports and discusses the incidence, management and treatment outcome of radiation-induced sarcomas occurring after radiotherapy for breast cancer in our institute. The incidence, histology, latency of appearance, genesis, their treatment and the prognostic factors of these rare tumors are discussed and the literature is reviewed.

Purpose: To compare conventional 2D simulation and virtual simulation on 14 patients with breast cancer., Patients and Methods: Patients were simulated for treatment using standard procedure. They subsequently underwent CT scan in the treatment position. The CTV was defined as breast tissue. The PTV was obtained by adding a 3D margin of 1 cm around CTV. Organs at risk (lungs and heart) were outlined. Ballistics and dose distribution obtained with the two planning methods were compared., Results: With conventional simulation, 95% of CTV received 95% of the dose prescribed. Virtual simulation significantly improved dosimetric coverage of PTV without increasing irradiation volume of lung and heart. In 2D simulation, using three slices allowed optimisation by adjusting wedge angle. The five-slice plan was a much better predictor of the maximum dose regions when compared to the three-slice plan. Using entire CT data didn't give any benefit., Conclusion: Variations in CTV delineation and PTV definition limit interest of virtual simulation. In classic simulation, a 5 CT slice-plan can be used to optimise dose distribution.

Aims: Tamoxifen is widely used as adjuvant therapy in receptor positive post menopausal breast cancer. Little is known about its efficacy as neo adjuvant therapy in terms of breast conservation and improved survival., Methods: We analyzed the tumour response to 20-30 mg Tamoxifen for 6 months in post menopausal patients with oestrogen receptor positive tumours. Treatment included Tamoxifen for 6 months, surgical resection, and irradiation for post menopausal patients refusing initial mastectomy; aged > or =70 years; or with other factors delaying surgery., Results: Between April 1994 and June 1998, 102 patients, age 73+/-87 (54-90) were studied. There were 24 T1, 56 T2, 14 T3, and 8 T4 tumours. Clinical response to Tamoxifen was observed in all patients, with a median size reduction from 31+/-15 (9-70) to 16+/-9 mm (0-50), 15 clinical and 6 complete responses. 88/102 patients were treated conservatively. Radiotherapy was given to 80 and a flash technique to 8 patients. All patients but one are still alive., Conclusion: Neo adjuvant Tamoxifen in operable post menopausal ER positive breast cancer is associated with a good clinical response rate and facilitates conservative surgery. Tamoxifen has a valuable role as neo-adjuvant treatment in terms of breast conservation and survival.

Respiration-gated radiotherapy offers a significant potential for improvement in the irradiation of tumor sites affected by respiratory motion such as lung, breast and liver tumors. An increased conformality of irradiation fields leading to decreased complications rates of organs at risk (lung, heart...) is expected. Respiratory gating is in line with the need for improved precision required by radiotherapy techniques such as 3D conformal radiotherapy or intensity modulated radiotherapy. Reduction of respiratory motion can be achieved by using either breath hold techniques or respiration synchronized gating techniques. Breathhold techniques can be achieved with active, in which airflow of the patient is temporarily blocked by a valve, or passive techniques, in which the patient voluntarily breath-hold. Synchronized gating techniques use external devices to predict the phase of the respiration cycle while the patient breaths freely. These techniques presently investigated in several medical centers worldwide. Although promising, the first results obtained in lung and liver cancer patients require confirmation. Physical, technical and physiological questions still remain to be answered. This paper describes the most frequently used gated techniques and the main published clinical reports on the use of respiration-gated radiotherapy in order to evaluate the impact of these techniques.

The authors report the occurrence of papillary carcinoma of the thyroid in nine first-degree relatives of four families among a consecutive series of 97 patients with papillary carcinoma of the thyroid who were operated on from 1991 to 1998. Total thyroidectomy was performed in all cases. All patients are alive without evidence of disease after a mean follow-up period of 43 months. Since in our series familial papillary carcinoma of the thyroid was found in 9.3% of patients, we suggest an adequate screening among first-degree relatives of all patients with papillary thyroid carcinoma. Because of reported aggressive behaviour of familial papillary carcinoma of the thyroid, aggressive surgical treatment plus post-operative thyroid remnant ablation with radio-iodine should be warranted in all patients., (Copyright 2000 Harcourt Publishers Ltd.)

Technical problems often arise during irradiation to the breast, chest wall, and regional lymph nodes. The following are among the most frequently encountered problems: avoidance of normal tissues (heart and lungs) during chest wall, internal mammary nodes, and large breast irradiations; dose heterogeneity in large breasts; under- or overdosage at field junctions (breast medial tangent and internal mammary fields in particular). Various technical solutions have been offered: modified treatment positions, field inclinations, and conformal irradiation. Many are currently under evaluation. These new technical approaches in breast cancer irradiation require modern facilities for imaging, simulation, and dosimetry, which help to individually design treatment planning.

Conservative treatment of multifocal breast cancer is still very controversial. This retrospective study concerns 56 patients with stage I or II multifocal breast cancer who underwent conservative treatment at the Institut Curie from January 1983 to December 1989. These patients (group 1) were matched with 132 patients with multifocal lesions treated by mastectomy (group 2). Surgical treatment consisted of a single wide lumpectomy followed by external radiotherapy. Adjuvant systemic therapy and regional nodal irradiation were administered as indicated by current protocols. The actuarial 5-year overall survival rate was 94% 6 in group 1, and 90% 6 in group 2 (NS). The actuarial 5-year ipsilateral breast recurrence rate was 11% 8 in group 1, and 11% 5 in group 2 (NS). In group 1 patients, the ipsilateral breast recurrence rate was related neither to type of multifocality nor to presence of intra ductal breast carcinoma, nodal status, tumor margins, radiotherapy boost, or distance between tumors. Consequently, conservative treatment of multifocal breast cancers which can be completely removed by a single lumpectomy seems, when technically feasible, an alternative to mastectomy.

The aim of the paper consists to select criterias of the therapeutic effect of superoxide-dismutase (PEG-SOD) administrated as an ointment twice a day for 3 months. An original scoring method including qualitative and quantitative data was set up in order to appreciate the importance of the fibrosis and its variations when under local administration of PEG-SOD. Clinical and paraclinical controls were made as T0, T1 (6 weeks), T2 (3 months), T3 (6 months). After 6 months, results enabled us to show PEG-SOD in its galenic form was efficient on radiofibrosis with a 41% score reduction compared to pretreatment score T0, thus an improvement of nearly half of the potential theoretical recovery. The therapeutic efficiency was greater on the most recent fibrosis and there was a chronological order to the different recovery stages. After 6 weeks of administration pains were reduced or stopped; then after 3 months of treatment fibrous texture broke up and softened. An effective reduction of the surface as well as lightened of the pigmentation would not usually start until the 4th month after the start of treatment. PEG-SOD is thus an enzyme the therapeutic interest of which offers interesting prospects. The score which was set up enable a fair evaluation of the intensity and the variations of the treated fibrosis. A prospective study is currently on going in order to research the biological conditions in which the enzyme reacts.

From December 1991 to September 1992, 20 patients due to receive total body irradiation (TBI) prior to allogenic or autologus bone marrow transplantation were given granisetron (Kytril) in order to prevent intestinal (nausea and vomiting) early intolerance. TBI regimen was delivered on a fractional basis of six fractions, over 3 days. Twelve grays were delivered with a lung protection decreasing the pulmonary dose to 9 Gy. Granisetron (3 mg) was administered by a 5-min intravenous infusion, 1 h before TBI. Up to two further infusions were given if nausea or vomiting occurred. The pretreatment perfusion was sufficient to prevent nausea and vomiting in 10/20 patients, one additional post-treatment perfusion was necessary in 7/20 patients, and two in 1/20 patients. In 2/20 cases, nausea and vomiting persisted in spite of three perfusions. Excellent or good efficacy was noted in 15/20 patients and a minor (or no) efficacy in five. Granisetron appears to be superior to the conventional anti emetic schemes to prevent nausea and vomiting in patients receiving TBI for bone marrow transplantation.

Whether or not young age at diagnosis is an adverse prognostic factor in breast cancer has long been controversial, in part because much previous work has not taken due account of menopausal status and confounding factors. We have analysed the influence of age on prognosis in a consecutive series of 1703 patients with stage I-III breast cancer. All were premenopausal and all were treated in one centre (Institut Curie, Paris) between 1981 and 1985. Mean age was 44 years (range 23-55) and median follow-up was 82 months. Younger patients had significantly lower survival rates and higher local and distant relapse rates than older patients. The hazard rate of relapse decreased over time in the youngest age group (< or = 33) to reach that of older patients after 5 years. The relation between the hazard of recurrence and age was a continuous one, best fitted by a log-linear function and indicating a 4% decrease in recurrence for every year of age. Multivariate analysis of both survival and disease-free interval demonstrated that the worse prognosis of young age was independent of other factors such as clinical tumour size, clinical node status, histological grade, hormone receptor status, locoregional treatment procedure, and adjuvant systemic therapy. This difference in outlook has yet to be explained biologically but it does suggest the need for a closer look at the natural history of breast cancer in young women.

Ductal carcinoma in situ of the breast is very rare in men, representing 0-7% of all male breast cancers. We analysed 15 cases from a retrospective multicentric series of 404 patients (3.7%). It occurs earlier than infiltrating carcinoma (mean age: 55 years), sometimes before 40 years of age. The main symptoms are bloody nipple discharge or retro areolar mass. Modified radical mastectomy constitutes the basic treatment. Lower axillary dissection can eventually be indicated in comedocarcinoma or in tumors larger than 25 mm. The main histologic subgroup is papillary carcinoma, pure or intracystic. As is the case in women, local recurrence, invasive or not, rarely occurs. Theoretically, the cure rate approaches 100%. However, as in all cases of breast cancer in men, an important number of deaths due to secondary cancer or intercurrent disease have been noted. Until now, no clear etiologic factors have been found.