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Introduction: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT., Methods: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI method was used to question 24 national experts, with 115 questions regarding the following: (1) imaging techniques, (2) clinical target volume (CTV) and margins, (3) dose constraints to organs at risk, (4) dose and fractionation, and (5) follow-up and records. Consensus was defined when opinions reached more than or equal to 80% agreement., Results: We established the following recommendations: preoperative contrast-enhanced computed tomography (CT) scan is recommended (94% agreement); optimization of radiation delivery includes either a four-dimensional CT-based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT imaging (81% agreement); imaging fusion based on cardiovascular structures of preoperative and planning CT scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/volumetric modulated arc therapy is recommended (88% agreement); total dose is 50 Gy (81% agreement) with 1.8 to 2 Gy per fraction (94% agreement); cardiac evaluation and follow-up for patients with history of cardiovascular disease are recommended (88% agreement) with electrocardiogram and evaluation of left ventricular ejection fraction at 5 years and 10 years., Conclusion: This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices., Competing Interests: Disclosure The authors have no conflict of interest to disclose concerning the current work., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Ultracentral (UC) lung lesions are generally defined by the presence of the tumour or the Planning Target Volume (PTV) abutting proximal bronchial tree (PBT) or the esophagus. Initial reports rose awareness regarding the potential toxicity of stereotactic body radiotherapy (SBRT) when delivered to UC lesions. Major concerns include necrosis, stenosis, and bleeding of the PBT. Technological improvements now enable the delivery of more accurate treatments, possibly redefining the historical "no-fly zone". In this review, studies focusing on the treatment of UC lesions with SBRT are presented. The narrow therapeutic window requires a multidisciplinary approach., (Copyright © 2023. Published by Elsevier Masson SAS.)

Over the last decades, the refinement of radiation therapy techniques has been associated with an increasing interest for individualized radiation therapy with the aim of increasing or maintaining tumor control and reducing radiation toxicity. Developments in artificial intelligence (AI), particularly machine learning and deep learning, in imaging sciences, including nuclear medecine, have led to significant enthusiasm for the concept of "rapid learning health system". AI combined with radiomics applied to ( 18 F)-fluorodeoxyglucose positron emission tomography/computed tomography ([ 18 F]-FDG PET/CT) offers a unique opportunity for the development of predictive models that can help stratify each patient's risk and guide treatment decisions for optimal outcomes and quality of life of patients treated with radiation therapy. Here we present an overview of the current contribution of AI and radiomics-based machine learning models applied to ( 18 F)-FDG PET/CT in the management of cancer treated by radiation therapy., (Copyright © 2023 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Functional imaging allows the evaluation of numerous biological properties that could be considered at all steps of the therapeutic management of patients treated with brachytherapy. Indeed, it enables better initial staging of the disease, and some parameters may also be used as predictive biomarkers for treatment response, allowing better selection of patients eligible for brachytherapy. It may also improve the definition of target volumes with the aim of dose escalations by dose-painting. Finally, it could be useful during the follow-up to assess response to treatment. In this review, we report how functional imaging is integrated at the present time during the brachytherapy procedure, and what are its potential future contributions in the main tumour locations where brachytherapy is recommended. Functional imaging has great potential in the contact of brachytherapy, but still, several issues remain to be resolved before integrating it into clinical practice, especially as a biomarker or in dose painting strategies., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

We present the updated recommendations of the French Society for Radiation Oncology on benign intracranial tumours. Most of them are meningiomas, vestibular schwannomas, pituitary adenomas, craniopharyngiomas, and glomus tumours. Some grow very slowly, and can be observed without specific treatment, especially if they are asymptomatic. Symptomatic or growing tumours are treated by surgery, which is the reference treatment. When surgery is not possible, due to the location of the lesion, or general conditions, radiotherapy can be applied, as it is if there is a postoperative growing residual tumour, or a local relapse. Indications have to be discussed at a multidisciplinary panel, with precise evaluation of the benefit and risks of the treatments. The techniques to be used are the most modern ones, as multimodal imaging and image-guided radiation therapy. Stereotactic treatments, using fractionated or single doses depending on the size or the location of the tumours, are commonly realized, to avoid as much a possible the occurrence of late side effects., (Copyright © 2021. Published by Elsevier Masson SAS.)

Introduced in 2017, the reform of the 3rd cycle has modified the organization of the residency in all specialties, and in particular radiation oncology. The residency was thus divided into 3 phases with increasing knowledge and responsibilities. The latter, carried out under the status of "junior doctor", created and defined by decree n°2018-571 of July 3, 2018 and the decree of January 16, 2020, is a phase of supervised autonomy of the resident. Radiotherapy is a singular specialty, with multiple and complex activities, and requires multiple skills. A guide defining the status of the "Junior Doctor" in radiation oncology therefore appears necessary, defining each resident's role and obligations. This guide is of an advisory nature and must be adapted to the particularities of each department. This guide aims to help the implementation of the reform of the 3rd cycle in radiation oncology and especially the final year called the consolidation phase. It is destined to evolve, expanded by individual and collective feedback and the constant renewal of our speciality., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The French Higher Health Authority's (Haute Autorité de santé [HAS]) certification process is an important issue for a health care facility and in particular for a radiotherapy department. It is based on a quality-risk management methodology driven by the commitment and involvement of professionals. The radiotherapy department of the university hospital in Brest (France) has been engaged for many years in a demanding quality-risk management policy implementation, subjected to regular inspections by the French Nuclear Safety Authority (Autorité de sûreté nucléaire [ASN]). This implementation is driven by a strong commitment from department managers, who are determined to maintaining an efficient level for care quality and safety., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Radiomics is a field that has been growing rapidly for the past ten years in medical imaging and more particularly in oncology where the primary objective is to contribute to personalised and predictive medicine. This short review aimed at providing some insights regarding the potential value of radiomics for cancer patients treated with radiotherapy. Radiomics may contribute to each stage of the patients' management: diagnosis, planning, treatment monitoring and post-treatment follow-up (toxicity and response). However, its applicability in clinical routine is currently hindered by several factors, including lack of automation, standardisation and harmonisation. A major effort must be carried out to automate the workflow, standardise radiomics good practices and carry out large-scale studies before any transfer to daily clinical practice., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: During radiotherapy (RT) for prostate cancer (PCa), interfraction and intrafraction movements can lead to decreased target dose coverage and unnecessary over-exposure of organs at risk. New image-guided RT techniques accuracy allows planning target volume (PTV) margins reduction. We aim to assess the feasibility of a kilovoltage intrafraction monitoring (KIM) to track the prostate during RT., Methods and Materials: Between November 2017 and April 2018, 44 consecutive patients with PCa were included in an intrafraction prostate motion study using the Truebeam Auto Beam Hold® tracking system (Varian Medical Systems, United State) triggered by gold fiducials localization on kilovoltage (kV) imaging. A 5-mm PTV was considered. A significant gating event (SGE) was defined as the occurrence of an automatic beam interruption requiring patient repositioning following the detection of one fiducial outside a 5-mm target area around the marker during more than 45seconds., Results: Six patients could not benefit from the KIM because of technical issues (loss of one fiducial marker=1, hip prosthesis=4, morbid obesity causing table movements=1). The mean rate of SGE per patient was 14±19%, and the fraction average delivery time was increased by 146±86seconds. For a plan of 39 fractions of 2Gy, the additional radiation dose increased by 0.13±0.09Gy. The mean rates of SGE were 2% and 18% (P=0.002) in patients with planned fraction<90 and>90seconds respectively, showing that duration of the session strongly interfered with prostate intrafraction movements. No other significant clinical and technical parameter was correlated with the occurrence of SGE., Conclusion: Automated intrafraction kV imaging can effectively perform autobeam holds due to intrafraction movement of the prostate in the large majority of patients. The additional radiation dose and delivery time are acceptable. This technique may be a cost-effective alternative to electromagnetic transponder guidance., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Despite representing a 1% of diagnosed cancer cases in the USA and up to 5% in eastern Asia and Africa, oesophageal cancer still holds numerous questions concerning the best therapeutic management. For squamous cell carcinoma, while radiochemotherapy has proven itself to be the gold standard as part of the trimodality or alone as a definitive treatment, radiotherapy modalities are still debated especially regarding lymph node irradiation. Involved nodes irradiation was developed with the aim of maintaining clinical outcomes and enhancing quality of life but lacks grade 1 evidence. In this article, we aim to summarize the state of art regarding lymph node irradiation, discuss the impact of target definition, delivery techniques, concomitant treatment and the perspectives. Being highly connected to the lymph vessels, lymphatic metastases are frequent and can locate from the neck to the coeliac area with each node having a different prognostic significance. Regarding the comparison between elective nodal irradiation and involved nodes irradiation, evidence-based medicine mostly relies on retrospective studies. Pooled, it suggests similar clinical outcomes with lower acute toxicities in favour of involved nodes irradiation. However, delivery techniques, doses and concomitant treatment were not consensual. Studies are ongoing evaluating the impact of radiation delivery techniques and the choice of concomitant treatment, i.e. immunotherapy. Modern techniques of imaging, radiation therapy progressing each day and alternative treatment modalities being tested, the need of randomized controlled trials has never been so high. Elective nodal irradiation should remain the standard of care while phase 3 trials explore the safety of involved nodal irradiation., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Intensity-modulated radiation therapy reduces the dose to organs at risk in patients treated for gynecological malignancies. Given the steep dose gradients around the planning target volume, internal movement of organs during treatment may cause a planning target volume underdosage and organs at risk overdosage in case of systematic error. It is therefore important to take into account the movement of the pelvic organs and to investigate potential solutions provided by image-guided radiotherapy. A review of the literature was carried out using the following databases: Medline, Embase, Cochrane Library, Web of Science, Cinahl and Pubmed. Appropriate search strategies for each database were applied based upon the following terms "uterine neoplasms, image-guided radiotherapy, adaptive radiotherapy, organ motion and target volume". These studies show that uterine motion is mainly influenced by bladder filling and by cervix and vaginal vault motion due to rectal filling. Population-based clinical target volume-planning target volume margins are large resulting in unnecessary organs at risk inclusion within the planning target volume, reducing the benefits of intensity-modulated radiotherapy. As pelvic organ motion seems to be patient specific, individualised planning target volume margins and adaptive radiotherapy strategies could allow adequate coverage of the planning target volume and increase organs at risk savings. In this study, we review the different techniques of image-guided radiotherapy and the perspective of adaptive radiotherapy., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Therapeutic principles of radiation therapy in head and neck carcinomas will be discussed in this review. Intensity-modulated radiotherapy with concomitant cisplatin should be standard. In case of contraindication to chemotherapy, cetuximab is an option, while hyperfractionation should be considered in patients unfit for concomitant treatment. Concomitant chemotherapy should be administered in the presence of extracapsular extensions and positive margins in the postoperative setting. Current research areas such as desescalation in human papillomavirus-positive tumours, adaptive radiotherapy, radiomics and immunotherapy will also be addressed., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To study the impact on radiotherapy planning of an automatically segmented target volume delineation based on ( 18 F)-fluorodeoxy-D-glucose (FDG)-hybrid positron emission tomography-computed tomography (PET-CT) compared to a manually delineation based on computed tomography (CT) in oesophageal carcinoma patients., Methods and Materials: Fifty-eight patients diagnosed with oesophageal cancer between September 2009 and November 2014 were included. The majority had squamous cell carcinoma (84.5 %), and advanced stage (37.9 % were stade IIIA) and 44.8 % had middle oesophageal lesion. Gross tumour volumes were retrospectively defined based either manually on CT or automatically on coregistered PET/CT images using three different threshold methods: standard-uptake value (SUV) of 2.5, 40 % of maximum intensity and signal-to-background ratio. Target volumes were compared in length, volume and using the index of conformality. Radiotherapy plans to the dose of 50Gy and 66Gy using intensity-modulated radiotherapy were generated and compared for both data sets. Planification target volume coverage and doses delivered to organs at risk (heart, lung and spinal cord) were compared., Results: The gross tumour volume based manually on CT was significantly longer than that automatically based on signal-to-background ratio (6.4cm versus 5.3cm; P<0.008). Doses to the lungs (V20, D mean ), heart (V40), and spinal cord (D max ) were significantly lower on plans using the PTV SBR . The PTV SBR coverage was statistically better than the PTV CT coverage on both plans. (50Gy: P<0.0004 and 66Gy: P<0.0006)., Conclusion: The automatic PET segmentation algorithm based on the signal-to-background ratio method for the delineation of oesophageal tumours is interesting, and results in better target volume coverage and decreased dose to organs at risk. This may allow dose escalation up to 66Gy to the gross tumour volume., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

The benefit of postoperative radiotherapy for breast cancer both in terms of local control and overall survival is widely acknowledged. Today, technological advances in simulation imaging and positioning control enable the definition of new margins from CTV to PTV. Improvements in mathematical modeling of random and systematic errors impact the treatment plans. However, there is no universal absolute value to consistently determine the margins from CTV to PTV. It is down to each centre to assess and correct as much as possible uncertainties due to positioning and internal movements depending on techniques and methods used for the implementation of treatment and monitoring. IMRT and respiratory gating techniques for breast radiotherapy will be considered more systematically in the years to come., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: The purpose of this study was to compare free-breathing radiotherapy, end-expiration gating and end-inspiration gating for left breast cancer, with respect to the target volume coverage and dose to organs at risk., Patients and Methods: Sixteen patients underwent 3D and 4D simulation CT. For each patient, five dosimetric plans were compared: free breathing, end-inspiration gating, end-expiration gating, and two optimised plans with a 3mm reduction of the posterior field edge to create optimised end-inspiration and end-expiration plans. Dose-volume parameters, including planning target volume coverage and dose to lung, heart and left anterior descending coronary artery were analysed., Results: Planning target volume coverage was adequate and similar in the five dosimetric plans (P=0.49). Significant advantage was found for end-inspiration gating in sparing the ipsilateral lung, heart and left anterior descending coronary artery compared to free-breathing 3D radiotherapy. Optimised end-inspiration was even more favourable than end-inspiration gating (P<0.05), with less dose delivered to the ipsilateral lung, heart and left anterior descending coronary artery. When compared to end-expiration gating, end-inspiration gating dosimetric outcomes were similar regarding lung and left anterior descending coronary artery doses, but the heart dose was inferior on the end-inspiration gating compared to end-expiration gating., Conclusion: Breathing-adapted radiation therapy allowed for dose reduction to organs at risk (left lung, heart and left anterior descending coronary artery), while keeping the same planning target volume coverage. Therefore it can be considered as an interesting option for left breast cancer radiation treatment., (Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Cervical cancer, although less common in industrialized countries, is the fourth most common cancer affecting women worldwide and the fourth leading cause of cancer death. In developing countries, these cancers are often discovered at a later stage in the form of locally advanced tumour with a poor prognosis. Depending on the stage of the disease, treatment is mainly based on a chemoradiotherapy followed by uterovaginal brachytherapy ending by a potential remaining tumour surgery or in principle for some teams. The role of irradiation is crucial to ensure a better local control. It has been shown that the more the delivered dose is important, the better the local results are. In order to preserve the maximum of organs at risk and to allow this dose escalation, brachytherapy (intracavitary and/or interstitial) has been progressively introduced. Its evolution and its progressive improvement have led to the development of high dose rate brachytherapy, the advantages of which are especially based on the possibility of outpatient treatment while maintaining the effectiveness of other brachytherapy forms (i.e., low dose rate or pulsed dose rate). Numerous innovations have also been completed in the field of imaging, leading to a progress in treatment planning systems by switching from two-dimensional form to a three-dimensional one. Image-guided brachytherapy allows more precise target volume delineation as well as an optimized dosimetry permitting a better coverage of target volumes., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

The dense lymphatic network of the esophagus facilitates tumour spreading along the cephalo-caudal axis and to locoregional lymph nodes. A better understanding of microscopic invasion by tumour cells, based on histological analysis of surgical specimens and analysis of recurrence sites, has justified a reduction in radiotherapy target volumes. The delineation of the clinical target volume (CTV) depends on tumour characteristics (site, histology) and on its spread as assessed on endoscopic ultrasonography and ((18)F)-fluorodeoxyglucose positron-emission tomography (FDG-PET). We propose that positive and negative predictive values for FDG-PET should be used to adapt the CTV according to the risk of nodal involvement., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: For the last few years wafers of Gliadel have been inserted into the operation cavity in patients with glioblastoma multiforme. This is followed by concurrent radio-chemotherapy with temozolomide (TMZ) according to the Stupp protocol. Only a few studies have investigated this kind of treatment regimen and the impact in terms of survival and toxicity of the combination of Gliadel with TMZ and radiotherapy., Methods and Materials: From November 2006 to January 2010, 24 patients with a newly diagnosed glioblastoma have undergone a tumour resection which was considered to be macroscopically complete in 12 cases and with tumour residue in another 12 cases. The mean age at the moment of diagnosis was 60.25years and the median age 63. Twenty-three patients underwent subsequently concurrent radio-chemotherapy with TMZ followed by cycles of elevated doses of TMZ as an adjuvant treatment. One patient had adjuvant radiotherapy alone followed by adjuvant chemotherapy. Thirteen were able to receive 6 or more cycles of adjuvant TMZ. Seven patients had received less than 6 cycles of TMZ as an adjuvant therapy. Two patients did not receive adjuvant TMZ at all., Results: The median overall survival of our group was 19.2months and the median progression free survival was 12.3months. Overall survival for the macroscopically complete-resection patients was 14months, and 12.85months in subtotal-resection patients. The median OS was 14.25months for patients PS 0 - 1 at the moment of diagnosis and 12.65 for PS 2 patients. Chemotherapy with TMZ had to be stopped prematurely in 10 cases due to haematotoxicity, digestive toxicity or early relapse., Conclusions: The concomitant use of surgery with implantation of BCNU wafers and radio-chemotherapy seems to be well tolerated. Despite the small number of patients treated in our group, particular attention should be paid to the potential haematological consequences of this multimodal treatment regimen., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose: To describe the clinical results and tolerance of the combined treatment with radiotherapy and cetuximab for locally advanced head and neck cancer., Patients and Methods: From August 2006 and October 2010, 36 patients with advanced squamous cell head and neck carcinoma were treated with radiotherapy (70Gy/35 fractions) and cetuximab (400mg/m(2) one week before radiotherapy, following by 250mg/m(2) once weekly, until week 7 of radiotherapy). Tolerance was evaluated every week. All patients were examined every 3months the first 3years after therapy, and then every year., Results: The median follow-up was 14months. The majority of patients were male (31 out of 36). Mean age was 59years. The tumours sites were: oral cavity (n=8); oropharynx (n=15); hypopharynx (n=5); larynx (n=8). Ninety percent of tumors were T3 or T4, and 45% were N2 or N3. Complete response was seen in 74% of patients, partial response in 17% and no response in 9% of patients. The overall survival was 44.4%. Relapse occurred in six patients. Anaphylactic reaction during the first infusion of cetuximab was observed in one patient. One patient developed severe aplasia after 48Gy and 5weeks of cetuximab, and died of sepsis. Eighty percent of patients presented acne, 16 patients developed a mucositis grade 2-3 and 23 patients a grade 2 skin reaction., Conclusion: The concomitant use of cetuximab and radiotherapy in locally advanced head and neck carcinoma is well tolerated in this group of patients. The results seem comparable to those in the literature., (Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

PET imaging is now considered a gold standard tool in clinical oncology, especially for diagnosis purposes. More recent applications such as therapy follow-up or tumor targeting in radiotherapy require a fast, accurate and robust metabolically active tumor volumes delineation on emission images, which cannot be obtained through manual contouring. This clinical need has sprung a large number of methodological developments regarding automatic methods to define tumor volumes on PET images. This paper reviews most of the methodologies that have been recently proposed and discusses their framework and methodological and/or clinical validation. Perspectives regarding the future work to be done are also suggested., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Introduction: Curative therapy for patients with small-cell lung cancer (SCLC) is based on multidrug chemotherapy combinations and radiotherapy. After a long time follow-up, the aim of the study was to evaluate the efficacy and toxicity of sequential chemo-radiotherapy and the effect of prophylactic cranial irradiation (PCI)., Methods: From 1995-2005, 96 patients with SCLC (64 limited-disease [LD], 32 extensive-disease [ED]; median age 61 years [range 39-79]) were treated at our department with varying chemotherapy regimens and sequential mediastinal radiotherapy (50 Gy + 10 Gy boost in case of residual disease after chemotherapy). Afterwards, 15 patients with LD, good general condition and at least partial response after local treatment received PCI (30 Gy)., Results: After a median follow-up of 78.6 months, 20 patients remained alive (20.8%, median survival time 18.2 months). The 2-/5-year overall survival rates were 33.8% and 12.6%, the 2-/5-year loco-regional control rates were 30.3% and 24.5%, respectively. Distant metastases occurred in 43 patients (24 cerebral). Cerebral metastasis occurred in 6.7% and 27.2% of the patients with PCI and without PCI respectively. Only tumor stage showed a statistically significant impact on overall survival and loco-regional control in multivariate analysis. Radiotherapy was well tolerated. Grade 3/4 toxicity occurred in seven patients. Prognosis of patients with SCLC remains poor. Administration of PCI in selected patients bears a decrease in the incidence of cerebral metastases. Alternative chemotherapy schemes as well as irradiation schemes and techniques should be the substance of future randomized trials., (Copyright © 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Esophageal cancers are highly malignant tumours with often a poor prognostic, except for minimal lesions treated with surgery. Radiation therapy, or combined radiation and chemotherapy is the most used therapeutic modality, alone or before oesophagectomy. The delineation of target volumes is now more accurate owing the possibility to use routinely the new imaging techniques (mainly PET). The aim of this work is to precise the radio-anatomical particularities, the pattern of spread of esophageal cancer and the principles of 3D conformal radiotherapy illustrated with a clinical case., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Inverted papilloma (IP) is a rare nasosinusal benign tumour, with epithelium surface inversion to inside the stroma. Extension to intracranial temporal fossa and middle ear has been reported in few cases in the literature. This involvement may be derived from either direct extension from sinonasal cavity via the Eustachian tube or primary middle ear involvement secondary to metaplastic changes of the middle ear mucosa. Here, we report a case of inverted papilloma in a male patient, with multiple recurrences, middle ear and intracranial involvement into the temporal fossa with posterior development of malignancy. This patient had received multiple surgeries and radiotherapy but despite of that, his disease recurred several times. As a conclusion, inverted papilloma is a benign tumour with an aggressive course, tendency to recurrence and progression to malignancy. Intracranial and temporal fossa involvements are rare and the treatment depends of the symptoms and the severity of the disease., (2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Erythropoietin (EPO) is a glycoprotein hormone. This hormone is a growth factor for red blood cells precursors in the bone marrow. The decrease of oxygen partial pressure, a reduced number of erythrocytes caused by bleeding or excessive destruction, or increased tissues oxygen requirements lead to increased secretion of EPO. Its action takes place on bone marrow erythroblastic cells through specific receptors. EPO stimulates the proliferation of red cell precursors stem cells in the bone marrow, thus increasing their production in one to two weeks. The effectiveness of EPO at increasing haemoglobin and improving patients' quality of life has been demonstrated by several studies. However, its use in radiotherapy remains controversial. While tumour hypoxia caused by anaemia is a factor of radio resistance and thus a source of local failure, tumour expression of EPO receptors presents a significant risk for tumour progression and neo-angiogenesis, which would be increased during the administration of EPO. The purpose of this article is to answer the question: is there a place for EPO in combination with radiotherapy in the management of cancer?, (2009 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

A cohort of recipients of renal transplant after 2000 (N=310) was prospectively screened on the day of transplantation and 1 month later for a panel of 11 thrombophilic factors to assess their effect on posttransplant outcomes. All patients received prophylactic acetylsalicylic acid, started before transplantation. The rate of thromboembolic events or acute rejection episodes during the first posttransplant year (primary composite endpoint) was 16.7% among patients free of thrombophilic factor (N=60) and 17.2% in those with >or=1 thrombophilic factor (N=250) (p>0.99). The incidence of the primary endpoint was similar among patients free of thrombophilic factors and those with >or=2 (N=135), or >or=3 (N=53) factors (16.3% and 15.1% respectively; p=1) and in patients who remained thrombophilic at 1 month (15.7%; p=0.84). None of the individual thrombophilic factor present at the day of transplantation was associated with the primary endpoint. The incidence of cardiovascular events at 1-year, serum creatinine at 1-year, 4-year actuarial graft and patient survival were not influenced by the presence of >or=1 thrombophilic factor at baseline (p=NS). In conclusion, the presence of thrombophilic factors does not influence thromboembolic events, acute rejection, graft or patient survival in patients transplanted after 2000 and receiving prophylactic acetylsalicylic acid.

Tamoxifen is widely used in the breast cancer treatment. Its side effects on the endometrium are well-known, but more and more worse prognosis uterine sarcoma are described. Based on recent literature review, the cause and effect chain between tamoxifen and uterine sarcoma is argued, which confirms that a risk exists as from 2 years of treatment, a cumulative dose of 15 g, and that malignant mixed mesodermal tumours appear to be the most frequent.

Radiotherapy for bone metastases represents an important part of daily practice in our departments of radiotherapy. Majority of treatments deliver either one fraction (6 to 10 Gy) or multifractions mainly using 30 Gy in ten fractions. In the past decade, several randomized trials aimed to determine the optimal scheme of radiotherapy in this setting. In the present review, the efficacy of radiotherapy on bone metastases will be evaluated using the following parameters: the partial or complete responses on pain, the reduction of antalgic intake, bone recalcification, and need for reirradiation. Other parameters must also be considered, such as the primary site, number of metastasis, performance status, overall prognosis and side effects of radiotherapy.

Background: Recent studies give rise to the hypothesis, that adjuvant chemoradioimmunotherapy with 5-fluorouracil (5-FU), cisplatin and interferon-alpha (IFN-alpha) might be a possible new treatment of pancreatic cancer in resected patients. We report the up-to-now experience at our institution., Patients and Methods: Eleven patients with histological diagnosis of localized carcinoma of the pancreas (n=7) or periampullary (n=4) were prospectively analyzed. Four patients were deemed unresectable because of local invasion of adjacent organs (neoadjuvant setting) and seven patients underwent curative resection (adjuvant setting). Eight patients were classified as T3 carcinomas and three T4 carcinomas. Fifty-five per cent (6/11) of the patients presented with positive lymph node involvement. One histological Grade I, six Grade II and three Grade III were detected. External conformal irradiation to a total dose of 50.4 Gy with 1.8 Gy per day was delivered. All patients received a concomitant chemotherapy with continuous 5-FU 200 mg/m2 per day on 28 treatment days and intravenous bolus cisplatin 30 mg/m2 per week (Day 2, 9, 16, 23, 30). A recombinant r-IFN-alpha was administered on three days weekly during Week one to five of the radiotherapy course as subcutanous injections with 3*3 Mio. I.U. weekly., Results: The four-year overall survival rate for all patients was 55%. In the neoadjuvant group, three of four patients died due to progressive disease; in the adjuvant group, combined chemoradioimmunotherapy lead to controlled disease in five of seven patients. The overall toxicity was well-managed., Conclusion: Our data strengthens the hypothesis of concomitant chemoradioimmunotherapy with 5-FU, IFN-alpha and cisplatin as a possible new treatment of pancreatic cancer in resected patients.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

Oxaliplatin is integrated in treatment strategies against a variety of cancers including chemoradiation protocols against gastrointestinal, especially rectal cancers. Solid biological data with respect to radiosensitizing activity of oxaliplatin are still rare. This review is based on in vitro and experimental in vivo data concerning the combination of oxaliplatin and radiation published until July 2007. Taking either cell viability or clonogenic survival as an endpoint all reported on oxaliplatin-induced radiosensitization, and enhancement ratios ranged from 1.1 to 2.2. In vivo, enhanced tumor growth delay after combined oxaliplatin and radiation treatment was also reported. Therefore, oxaliplatin should be considered a potent radiosensitizer, although the mechanisms causing radiosensitizing properties of oxaliplatin have not been studied in detail. Herein, they are discussed with respect to apoptosis induction, p53-related signalling, cell cycle control, and DNA-repair.

Ovarian carcinosarcoma, also called malignant mixed mesodermal tumour, is a rare ovarian tumour representing less than two per cent of ovarian cancers. Carcinosarcoma is an aggressive tumour, which associates some epithelial elements (carcinoma) with a stromal component (sarcoma). This tumour can be found in the female genital tractus, mostly in the uterus. It can be found even more rarely on the ovaries. The initial stage of the disease at the diagnostic is considered as the only prognostic factor. There is no existing consensus concerning treatment. Nevertheless, surgical treatment is paramount for the survival of patients. Response rates to chemotherapy are about 20%.

Background: Coagulation abnormalities and thrombocytopenia are common in severe sepsis, but sepsis-related alterations in platelet function are ill-defined., Objectives: The purpose of this study was to elucidate the effect of sepsis on platelet aggregation, adhesiveness, and growth factor release., Patients and Methods: Agonist-induced platelet aggregation was measured in platelet-rich plasma separated from blood samples collected from 47 critically ill patients with sepsis of recent onset. Expression of platelet adhesion molecules was measured by flow cytometry and the release of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) was measured by ELISA in the supernatant of platelet aggregation., Results: Septic patients had consistently decreased platelet aggregation compared with controls, regardless of the platelet count, thrombin generation, or overt disseminated intravascular coagulation (DIC) status. The severity of sepsis correlated to the platelet aggregation defect. Adhesion molecules, receptor expression (CD42a, CD42b, CD36, CD29, PAR-1), and alpha-granule secretion detected by P-selectin expression remained unchanged but the release of growth factors was differentially regulated with increased VEGF and unchanged PDGF after agonist activation even in uncomplicated sepsis., Conclusions: Sepsis decreases circulating platelets' hemostatic function, maintains adhesion molecule expression and secretion capability, and modulates growth factor production. These results suggest that sepsis alters the hemostatic function of the platelets and increases VEGF release in a thrombin-independent manner.

We report on a squamous cell carcinoma of the tongue in a 20-year-old woman with co-infection of the tumor with human papilloma virus type 18 and Epstein-Barr virus. To our knowledge, this is the first case of co-infection in carcinoma of the tongue to be reported. We review the present data and theories concerning viral oncogenesis of oral carcinomas.

One of the main advantages of an aortic valve homograft in comparison with a mechanical prosthesis is the low incidence of thromboembolism without anticoagulation. Development of an obstructive thrombosis is virtually unknown. We report the case of a patient who twice was seen with hemodynamically significant thrombosis of an aortic valve homograft. The diagnosis was suspected on the basis of a subacute increase in the transvalvular gradient and was confirmed by transesophageal echocardiography. Lupus anticoagulant antibodies were detected. Oral anticoagulation proved to be effective in relieving the obstruction, but recurrence after discontinuation of acenocoumeral suggests that treatment should be long term, if not lifelong. To our knowledge, this complication of primary antiphospholipid syndrome is the first reported case of thrombotic obstruction of an aortic valve homograft.

Background: This study was designed to determine if a new point-of-care test (PFA-100) platelet function analyser) that assesses platelet function predicts blood loss after cardiac surgery., Methods: and results. Blood samples from 70 patients were drawn before and after cardiopulmonary bypass (CPB) for PFA-100 measurements. The system consists of a cartridge in which a membrane and an aperture are coated with either collagen/adenosine-5'-diphosphate or collagen/epinephrine. The instrument determines the time required for full occlusion of the aperture (closure time). We observed a weak correlation between pre-CPB collagen/epinephrine closure time and second-hour mediastinal blood loss (r=0.34, P=0.01). The sensitivity and positive predictive value of the PFA-100 measurements were comparable to platelet count for predicting excessive bleeding after CPB (75 and 27% vs 100 and 25%, respectively)., Conclusions: The PFA-100 is a logical test for detecting patients who could have excessive bleeding after CPB. However, the PFA-100 was not able to separate patients at low risk of subsequent bleeding from those who had substantial bleeding.

Purpose: Cyfra 21-1, measuring serum fragments of cytokeratin 19, has been found to be related to tumour stage and tumour size in patients with cervical cancer. It could be a promising marker in squamous lung cancer. We evaluated this new marker with carcinoembryonic antigen, (CEA) and squamous cell carcinoma antigen (SCC-Ag) in the monitoring of 27 patients with head and neck cancer., Patients and Methods: The retrospective study group consisted of 27 patients, 17 not suited for surgery and 10 after laser resection. Patients were clinically staged according to the TNM-classification. The mean age of the patients was 53 years (range 37-70 years). Serum levels of each marker were studied in relation to tumour stage and clinical status of the patients during radiotherapy and 6 weeks after the end of the treatment. The clinical performance of the various assays to separate those patients with complete remission from those patients with the presence of tumour was assessed., Results: Pre-treatment serum Cyfra 21-1, CEA, and SCC-Ag levels were not related to stage of disease and were not found to be predictive of tumour response. The clinical performance of post-treatment serum SCC-Ag levels in predicting the presence of tumour was not better than the Cyfra 21-1 assays., Conclusion: We could not conclude from this study that Cyfra 21-1 marker is an additional parameter in identifying patients at risk of residual tumour after treatment, recurrent or progressive disease. An elevation of cyfra 21-1 marker was not detectable in 70% of the cases with macroscopic tumour. Therefore, Cyfra 21-1 is not a reliable parameter for the monitoring of patients with head and neck cancer during radiotherapy.

Unlabelled: To directly compare the clinical efficacy of electronic to film portal images and the advantages of comparing directly on the monitor the simulation image and the portal image., Material and Methods: This study was designed to compare clinical efficacy of electronic to film portal images acquired using a liquid matrix ion-chamber electronic portal imaging device (EPID) and a conventional film system. Two radiation oncologists served as observers and evaluated a total of 30 sets of images for three different treatment sites: lung, pelvis, and head/neck. Each set of images included a simulation image, a portal film, a video paper print of electronic portal images, and a video prints of electronic portal images. Four to six anatomical landmarks were selected from each treatment site. Each observer was asked to rate each landmark in terms of its clinical visibility and to rate the ease of making the pertinent verification decision in the corresponding electronic and film portal images with the aid of the simulation image. The time needed to obtain and analyse a conventional portal image and an EPID would be analysed for the radiotherapist and the medical technicians., Results: Ratings for the visibility of landmarks and for the verification decision of treatment ports were similar for electronic and film images for most landmarks. However, vertebral bodies and several landmarks in the pelvis such as the acetabulum and pubic symphysis were more visible in the electronic portal images than in the portal film images. For the medical technicians, the EPID is more comfortable, and they do not need to develop any images., Conclusion: The visibility of landmarks in electronic portal images is comparable to that in film portal images. Verification of treatment ports based only on electronic portal images acquired using an electronic portal imaging device is generally achievable. Thus the integration of the EPID and simulation image in a network provides more flexibility in the daily work of a medical radiotherapy team.

Objective: To determine the nature of and to compare the inflammatory responses induced by (1) endovascular and (2) conventional abdominal aortic aneurysm (AAA) repair., Material and Methods: Twelve consecutive patients undergoing elective infrarenal AAA repair were prospectively studied. Seven patients were selected for endovascular procedures (the EAAA group); five patients underwent open surgery (the OAAA group). Three control patients undergoing carotid thromboendarterectomy were also included. Serial peripheral venous blood samples were collected preoperatively, immediately after declamping or placement of the endograft, and at hours 1, 3, 6, 12, 24, 48, and 72. Acute phase response expression of peripheral T lymphocyte and monocyte activation markers and adhesion molecules (flow cytometry), soluble levels of cell adhesion molecules (enzyme-linked immunosorbent assay), cytokine (tumor necrosis factor alpha, interleukin-6, and interleukin-8) release (enzyme-linked immunosorbent assay), and liberation of complement products (nephelometry) were measured., Results: Regarding acute phase response, the EAAA and OAAA groups showed significant increases in C-reactive protein (P <.001 and P =.001), body temperature (P =.035 and P =.048), and leukocyte count (P <.001 and P <.001). Similar time course patterns were observed with respect to body temperature (P =.372). Statistically significant different patterns were demonstrated for C-reactive protein (P =.032) and leukocyte count (P =.002). Regarding leukocyte activation, a significant upregulation of peripheral T lymphocyte CD38 expression was observed in the OAAA group only (P =.001). Analysis of markers such as CD69, CD40L, CD25, and CD54 revealed no perioperative fluctuations in any group. Regarding circulating cell adhesion molecules, the EAAA and OAAA groups displayed significant increases in soluble intercellular adhesion molecule-1 (P =.003 and P =.001); there was no intergroup difference (P =.193). All groups demonstrated high soluble von Willebrand factor levels (P =.018, P =. 007, and P =.027), there being no differences in the patterns (P =. 772). Otherwise, soluble vascular cell adhesion molecule-1, soluble E-selectin, and soluble P-selectin did not appear to vary in any group. Regarding cytokine release, although a tendency toward high tumor necrosis factor alpha and interleukin-8 levels was noticed in the EAAA group, global time course effects failed to reach statistical significance (P =.543 and P =.080). In contrast, interleukin-6 showed elevations in all groups (P =.058, P <.001, and P =.004). Time course patterns did not differ between the EAAA and OAAA groups (P =.840). Regarding complement activation, the C3d/C3 ratio disclosed significant postoperative elevations in the EAAA and OAAA groups (P =.013 and P =.009). This complement product release was reduced in the EAAA group (P <.001)., Conclusions: The current study indicated that both endovascular and coventional AAA repair induced significant inflammatory responses. Our findings showed that there were no large differences between the procedures with respect to circulating cell adhesion molecule and cytokine release. Moreover, the endoluminal approach produced a limited response in terms of acute phase reaction, T lymphocyte activation, and complement product liberation. This might support the concept that endovascular AAA repair represents an attractive alternative to open surgery. Given the relatively small sample size, further larger studies are required for confirmation of our observations.

Purpose: To analyse retrospectively the results of different treatment regimens of carcinomas of the floor of the mouth and tongue., Materials and Methods: Between 1982 and 1992, 61 patients with carcinoma of the floor of the mouth and 30 with tongue cancer (25 stage I, nine stage II, 28 stage III, 29 stage IV) were treated in the radiotherapy department of Poitiers. Nine patients with stage I tumours were treated with 70 Gy low-dose rate brachytherapy only, without nodal dissection. Stages II and III were treated with combined surgery with neck dissection; and radiotherapy of stage II with nodal metastasis and for all stage III cases. Stage IV cases were treated either surgically if possible, or with combined chemotherapy and radiation., Results: The five-year overall survival rate was 87.3% for stage I, 68.5% for stage II, 45.3% for stage III, and 0% for stage IV patients. Most relapses appeared in the first two years after treatment. Eight patients (32%) with stage I cancer developed nodal relapses, isolated in five cases. Complications of radiotherapy were acceptable. Four cases of osteonecrosis were observed after radiotherapy. All of these appeared simultaneously with a local relapse., Conclusion: These results are comparable with reports in the literature. The remarkable observation of our study is the high incidence of nodal recurrences after local treatment of stage I tumours. Therefore, local treatment is insufficient for early-stage tumours. The question of neck dissection for the early stage is discussed.

Background: Dendritic cell (DC)-based vaccine is a promising approach for cancer therapy. Pioneer trials have been conducted using DC generated in research conditions. There is now a need for generating DC in clinical grade conditions, including the use of closed systems, avoidance of FCS and respect of good manufacturing practices (GMP)., Methods: DC were generated from 84 leukapheresis products of 27 cancer patients enrolled in two Phase I/II trials of vaccination of either MAGE+tumors (n = 24) or prostate cancer (n = 3). Monocytes were seeded in culture bags in a serum-free medium supplemented with IL-4 and GM-CSF. After a 7 day culture, DC were collected and most were pulsed with various MAGE-derived peptides., Results: After a short leukapheresis (mean time: 66 min; mean processed blood: 5 L), a mean of 6 x 10(9) WBC were collected, from which 2.25 x 10(9) were seeded. The culture procedure yielded a large number of DC (mean: 62 x 10(6) DC) harboring the expected phenotype of immature DC (CD1a(+) CD14(-) HLA-DR(+) CD80(+) CD86(+) CD83(-)). This phenotype was not altered by peptide loading. These DC, either fresh or thawed, were functionally effective invitro. Their s.c. and i.v. injections were devoid of any short-term side effect and associated with the induction of immune responses in the patients., Discussion: Large numbers of functional immature clinical grade DC can be generated in a closed system from leukapheresis products in cancer patients. These results provide the basis for large-scale studies of cancer immunotherapy under improved safety conditions.

Purpose: Paclitaxel is an agent which stabilizes microtubules, and has been shown to block different cells in the G2/M phase of the cell cycle and thus to modulate their radioresponsiveness. We investigated the radiosensitizing potential of paclitaxel in human head and neck cancer cells., Materials and Methods: ZMK-1 cells were incubated with paclitaxel for 3, 9, or 24 h before or during 24 h after irradiation. Paclitaxel concentrations of 70 nM, 7 nM, and 0.7 nM were chosen to obtain equivalent toxicity at the different incubation times: 3 h, 9 h, and 24 h, respectively. Radiation doses ranged from 0 to 8 Gy using 60Co source. Cell survival was measured by a standard clonogenic assay after a 9-day incubation. Flow cytometry was used to measure the capacity of paclitaxel to accumulate cells in the G2/M phase., Results: Paclitaxel alone possessed cytotoxicity dependent on time and concentration. There was a total of 40% of cells accumulated in G2/M after 24-36 h. When combined with radiation, the 9 h preincubation resulted in a radiosensitization. The 3 h pre-incubation as well as the 24 h post-incubation resulted in an infra-additive effect., Conclusion: In our cells a radiosensitizing effect of paclitaxel could not be demonstrated unambiguously. The blockage of the cells in the G2/M phase is not the only mechanism to explain the potential radiosensitization of paclitaxel.

The pathogenesis of Kaposi's sarcoma (KS), a tumor of probable vascular origin, remains an enigma. It is still unclear whether KS is a true malignancy or whether it represents a reactive polyclonal process. Using both an immunohistochemical and an immunoblot approach, we found that cells derived from KS lesions express significant levels of Bcl-2, a protein known to prolong cellular viability and to antagonize apoptosis. Bcl-2 expression was found in AIDS-related KS-derived cells, as well as in cells derived from iatrogenic and sporadic KS, indicating that Bcl-2 upregulation may be important in the pathogenesis of KS regardless of its epidemiologic form. By contrast, fibroblasts and dermal microvascular endothelial, cells which are the probable vascular progenitors of KS cells, expressed low levels of Bcl-2. The expression of Bcl-2 in KS-derived cells was associated with a long-term survival in serum-deprived conditions, a situation that has been shown to induce apoptosis in various cell types. Incubation of fibroblasts or of dermal microvascular endothelial cells with KS cell-free supernatants did not enhance Bcl-2 expression, suggesting that Bcl-2 expression is not mediated by an agent released by KS cells. Analogously, KS supernatants failed to promote the viability of fibroblasts and of dermal microvascular endothelial cells cultured in serum-free conditions. Our findings suggest that the spindle cells derived from KS have a survival advantage and may adequately represent the tumor cells of KS.

Purpose: To evaluate a ionization chamber on-line portal imaging system in routine clinical radiotherapy of rectum cancers., Patients and Methods: Megavolt portal images were obtained using a fast electronic megavoltage radiotherapy imaging system in 13 cases of pelvic fields. A total of 208 portal images and 13 simulator films were used to determine the values of set-up deviations in the X-Z-directions of a fixed co-ordinate system, and of the rotation fields (R)., Results: Mean standard deviations of the difference between simulation and treatment images were 3.2 mm and 0.9 mm for X and Z, 3.6 mm for the rotation fault. The standard deviations were, respectively, 7.1 mm, 7.1 mm and 1.5 mm. The cumulative frequency distributions revealed that 80% and 95% of the absolute differences were less than 10 mm and 17.5 mm, respectively., Conclusion: These results indicate the difficulty of a reproducible daily set-up. A weekly control could be proposed in order to increase the quality of pelvic site treatment. The introduction of masks to improve the set-up is also discussed.

The first injection of OKT3 in kidney transplant recipients activates the common pathway of coagulation. This may result in early thrombosis of graft vessels. To this day, the cells involved in this phenomenon have not been identified. The aim of this study was to investigate whether circulating monocytes participated in this OKT3-induced coagulopathy. The procoagulant activity (PCA) of circulating monocytes rose from (mean +/- SEM) 0.15 +/- 0.02 mU/mL to 0.40 +/- 0.05 mU/mL at 3 hours (P = .002) and 0.56 +/- 0.21 at 5 hours (P = .045) after the initial OKT3 injection. These monocytes displayed increased tissue factor expression at the same moments (mean flourescence intensity: 14 +/- 2 before OKT3 injection versus 54 +/- 14 at 3 hours, P = .008 and 34 +/- 7 at 5 hours, P = .01). Tissue factor mRNA was detected in blood by reverse transcriptase-polymerase chain reaction as early as 2 hours after OKT3 administration. The circulating monocytes also displayed a steady increase in membrane expression upregulation of ICAM-1, CD29, CD11b, and CD11c. In vitro experiments showed that OKT3 as well as 2 mitogenic, humanized anti-CD3 antibodies potently induced monocytic PCA whereas the 4 nonmitogenic anti-CD3 antibodies tested were over 1,000-fold less potent than OKT3. We conclude that (1) OKT3 induces in vivo tissue factor gene upregulation and membrane expression resulting in increased PCA of circulating monocytes; and (2) nonmitogenic anti-CD3 antibodies seem devoid of significant procoagulant properties.

The use of OKT3 as prophylaxis in renal transplantation carries an increased risk of intragraft thrombosis, which is related to the systemic activation of the coagulation system that consistently occurs after the first dose of OKT3. As only a few patients develop thrombosis after OKT3 therapy, we searched for possible additional risk factor by comparing the demographic and clinical parameters of the 13 patients who developed thrombosis in our institution to those of 218 patients who did not. Multivariate analysis showed a relationship between the dose of methylprednisolone (mPDS) given before the first OKT3 injection and the risk of thrombosis: 6 out of 42 patients (14%) who received high (30 mg/kg) mPDS experienced a thrombotic event, as compared to 7 out of the 189 patients (3.7%) who received < or = 8 mg/kg of mPDS (P < 0.01). This led us to study the effects of mPDS on the procoagulant activity induced by OKT3 on peripheral blood mononuclear cells (PBMC) in vitro. The procoagulant activity of unstimulated PBMC (mean +/- SEM: 0.6 +/- 0.1 mU/ml) reached 3.0 +/- 0.7 mU/ml after OKT3 stimulation (P = 0.0062) and further increased to 7.4 +/- 2.0 mU/ml when PBMC were first preincubated overnight with mPDS before OKT3 stimulation (P = 0.018 as compared to OKT3 alone). This process involved the tissue factor/factor VII pathway, as shown by increased membrane expression of tissue factor on monocytes as well as by a marked reduction of the induced procoagulant activity when the clotting assay was performed with factor VII-deficient plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

We recently observed that the prophylactic administration of high doses of OKT3 monoclonal antibody (MoAb) in cadaveric renal transplantation favors the development of thromboses of the grafts' main vessels and of thrombotic microangiopathies. These clinical observations led us to perform sequential determinations of plasma levels of prothrombin fragment 1 and 2 (F 1 + 2) and fibrin degradation products (FDP) after the first injection of 5 or 10 mg OKT3 given as prophylaxis in kidney transplant recipients. The values observed have been compared with those of kidney transplant recipients not treated with OKT3. F 1 + 2 levels peaked four hours after the first injection of 5 mg OKT3 (mean +/- SEM: 4.82 +/- 0.73 vs. 1.75 +/- 0.37 nmol/liter in controls, P < 0.01), indicating activation of the common pathway of the coagulation cascade. FDP levels were already above baseline values at four hours and continued to increase until 24 hours (mean +/- SEM at 24 hr, 4729 +/- 879 vs. 1038 +/- 320 ng/ml in controls, P < 0.05), indicating a fibrinolytic process. The magnitude and the time course of the changes in F 1 + 2 and FDP plasma levels were similar whether the patients received 5 or 10 mg dose of OKT3. The levels of von Willebrand factor (VWF) antigen, a molecule released by activated or damaged endothelial cells, were also significantly increased after injection of OKT3 (mean +/- SEM at 24 hr, 3.67 +/- 0.18 vs. 2.17 +/- 0.11 U/ml in controls, P < 0.05). The procoagulant effects of OKT3 were further investigated in vitro on human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS)

Among 93 consecutive kidney-transplant patients who received prophylactic OKT3 10 mg/day for 2 weeks, 9 had intragraft thromboses within 2 weeks of transplantation. The thromboses were in graft artery in 1 patient and veins in 3. The other 5 had thromboses in glomerular capillaries and thrombotic microangiopathy similar to that of haemolytic-uraemic syndrome. All attempted treatments failed, and the 9 grafts had to be removed. The finding that plasma concentrations of prothrombin fragment 1 and 2 were higher 4 h after the first OKT3 dose in OKT3 recipients than in transplant patients who received other prophylaxis (mean 5.88 [SEM 0.76] vs 2.25 [0.59] nmol/l, p less than 0.01) confirms that OKT3 has procoagulant effects in vivo.

A micromethod of indirect immunofluorescence with monoclonal antibodies to study surface markers of leukocytes and precursors, is described. This method consists of attaching non specifically living cells on a slide, previously treated with a high molecular weight polymer (L-lysin). The advantage of this method consists of using only 1.10(4) cells by typage, and low amounts monoclonal antibodies (twenty to forty less). In addition, this common method can be used in most biology laboratories.

We describe a simple indirect immunofluorescence micromethod for cell typing. Cells are layered on 18-well immunofluorescence slides coated with high polymer poly-L-lysine. Expressed cell surface membrane markers are detected by indirect immunofluorescence using monoclonal antibodies and the cells are stained with Evans blue dye to permit easy morphological identification under fluorescence and light microscopy. We compared this method with a conventional method for lymphocyte typing in 16 blood samples and 10 bronchoalveolar lavage samples. The results of the two methods did not differ and correlated closely (r = 0.988 for blood samples; r = 0.995 for bronchoalveolar lavage samples). The principal advantages of this micromethod are: the small amounts of cells (10(4) cells) and reagents needed, the ease with which numerous antibodies can be tested and the convenience offered by fixation and staining of cell preparations for reading.