Christian Marchal

Bio: Christian Marchal is an academic researcher from Centre national de la recherche scientifique. The author has contributed to research in topics: Brachytherapy & Radiation therapy. The author has an hindex of 15, co-authored 38 publications receiving 798 citations.

Nine breast angiosarcomas after conservative treatment for breast carcinoma: a survey from French comprehensive Cancer Centers.

Abstract: Objectives: To conduct a survey of the angiosarcomas developing after breast conservation for carcinoma in the French Cancer Centers, to study the evolution of these cases in detail, and to review literature in an attempt to propose an optimal treatment scheme. Material and Methods: Eleven of the 20 French Cancer Centers agreed to research and retrospectively analyze all angiosarcomas discovered in patients previously treated by conservative treatment. The majority of the patients were node negative, T1N0M0. The mean age of the patients at the time of primary breast cancer treatment was 62.5 years, and 69 years at the diagnosis of the angiosarcoma. Results: During the last two decades, nearly 20,000 patients have been treated conservatively in these 11 centers, and only 9 cases of angiosarcoma were found. The median latency period between the treatment of the breast carcinoma and the diagnosis of the breast angiosarcoma was approximately 74 months, with a range of 57–108 months. Mastectomy was performed as the main treatment of this angiosarcoma. All recurrences after mastectomy for the angiosarcoma appeared within 16 months after the mastectomy. A median time of recurrence was found to be 7.5 months, regardless of the treatment. The angiosarcomas appeared to be very aggressive, and chemotherapy, radiotherapy, and sometimes hyperthermia could only palliate the condition for a short time. After the diagnosis of angiosarcoma, the median survival was 15.5 months, showing a particularly poor prognosis. Only 1 patient of 9 is alive without progressive disease at 32 months after salvage mastectomy for the recurrence of the angiosarcoma. Precise data obtained from 11 centers show that, of 18115 breast carcinomas treated conservatively, only 9 breast angiosarcomas are reported, which represents a prevalence of 5 cases of angiosarcoma per 10,000, which is the same prevalence for primary breast angiosarcomas occurring in healthy breasts. Conclusion: Angiosarcoma developing after breast conserving therapy for carcinoma is a rare event, and induction of it by treatment is controversial. However, early diagnosis is essential and it appears that radical mastectomy gives the highest chance of cure and the best long-term survival.

Spheroids in radiobiology and photodynamic therapy.

Abstract: Spheroids are tridimensional aggregates of tumor cells coming from one or several cell clones. This model, which mimics the micro-tumors structure and some of their properties, shows oxygen, pH and nutrient gradients inducing a necrotic area in the center of the spheroid. Analysis of spheroids, cultured under static or stirred conditions, can be performed on whole spheroids or dissociated spheroids. The spheroids sensitivity to ionizing radiation and photodynamic therapy can be altered by oxygen status, damage repair, intercellular commmunications and apoptosis induction, as in experimental tumor models. In radiobiology, the similarity of radiation response between spheroids and tumor xenograft bearing mice makes the spheroids to be a good alternative model to in vivo irradiation studies. In photodynamic therapy, spheroids lead to a better understanding of the own tumor response without interactions with vascular system. Finally, despite the quality of spheroid model, only the use of new technology for analysis of spheroid populations will help to increase their experimental use, particularly in preclinical oncology.

Radiotherapy for solitary extramedullary plasmacytoma in the head-and-neck region: A dose greater than 45 Gy to the target volume improves the local control

Abstract: Purpose: Our aim was to determine the dose to the clinical target volume (CTV) required for solitary extramedullary plasmacytoma (EMP) in the head and neck (HN). Methods and Materials: Seventeen patients (15 Stage I and 2 Stage II) were treated for HN EMP at our institution between 1979 and 2003. The mean International Commission on Radiation Units (ICRU) dose prescribed to the CTV was 52.6 Gy (range, 40–65 Gy) over 24 fractions (range: 20–30). The Stage II patients received neck irradiation doses of 40 and 60 Gy. A mean dose of 36.4 Gy was used for 5 Stage I patients who received elective neck irradiation. Dose administrated to the CTV was evaluated from dosimetric data or from planning films when dosimetric data were not available. Two groups of patients were distinguished: CTV covered with a dose greater than 40 Gy and CTV covered with a dose greater than 45 Gy. Results: The 5-year local control was 72.8%. It was 100% for patients who received dose to the CTV ≤ 45 Gy vs. 50% for dose to the CTV p = 0.034). The prognostic factor for 5-year disease-specific survival (81.6%) was local control ( p = 0.058). The prognostic factors for disease-free survival (64.1%) were monoclonal immunoglobulin secretion ( p = 0.008) and a CTV dose ≤ 45 Gy ( p = 0.056) Conclusions: Local control of EMP in the HN seems to be improved when the dose to the CTV is ≤ 45 Gy. A minimum dose of 45 Gy should be recommended to the CTV.

Breast carcinoma located in ectopic breast tissue: a case report and review of the literature.

Abstract: Ectopic breast tissue usually develops along the mammary ridge. The incidence of this anomaly has been reported as high as 6%. Malignant development is rare. A case of carcinoma of aberrant breast tissue, located in the axilla is described. Mammographies of the ectopic breast performed few years before the diagnosis of carcinoma are presented and also those done for the diagnosis of the tumor. A literature study was performed on carcinoma and ectopic breast tissue. Considering high frequence of node involvements for these cases, the optimal therapeutic strategies are discussed.

Conservative treatment by irradiation of epidermoid carcinomas of the anal margin.

Abstract: Purpose: Few series have described treatment results of anal margin tumors as defined in the UICC 87 classification. The purpose of this article is to describe experience with an uncommon condition in a single cancer center. Methods and Materials: From 1971 to 1995, 32 patients with carcinoma of the anal margin were irradiated with a curative intent, and 31 were followed-up for more than 6 months (mean = 4.5 years). There were 9 T1, 15 T2, 7 T3, and 1 T4 (vulvar), with 26 N0 and 6 N1. There was a minor invasion of the lower canal in 17 patients. The histological types were 24 squamous cell and 7 basocellular carcinomas, and 1 Paget's disease. The treatment was a combined External Beam Irradiation (EBI) and Brachytherapy (BT) in 16 patients, an exclusive BT in12 patients, and an exclusive EBI in 4 patients. No prophylactic inguinal irradiation was delivered. Results: The 5-year actuarial restults are as follows: overall survival=67%, specific survival=89%. The only prognostic factor was nodal involvement ( p Conclusion: Results are similar to other series, and seem better than for anal canal cancer. We recommended exclusive irradiation. There is no data recommending concomitant chemotherapy. Depending on the tumor size and localization, the tumor boost can be applied by EBI or BT. Surgery is reserved for small tumors far from the canal or for salvage. An inguinal prophylactic bilateral irradiation should be recommended for N0, with tumors over 4 cm.

Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies

Abstract: The median-effect equation derived from the mass-action law principle at equilibrium-steady state via mathematical induction and deduction for different reaction sequences and mechanisms and different types of inhibition has been shown to be the unified theory for the Michaelis-Menten equation, Hill equation, Henderson-Hasselbalch equation, and Scatchard equation. It is shown that dose and effect are interchangeable via defined parameters. This general equation for the single drug effect has been extended to the multiple drug effect equation for n drugs. These equations provide the theoretical basis for the combination index (CI)-isobologram equation that allows quantitative determination of drug interactions, where CI 1 indicate synergism, additive effect, and antagonism, respectively. Based on these algorithms, computer software has been developed to allow automated simulation of synergism and antagonism at all dose or effect levels. It displays the dose-effect curve, median-effect plot, combination index plot, isobologram, dose-reduction index plot, and polygonogram for in vitro or in vivo studies. This theoretical development, experimental design, and computerized data analysis have facilitated dose-effect analysis for single drug evaluation or carcinogen and radiation risk assessment, as well as for drug or other entity combinations in a vast field of disciplines of biomedical sciences. In this review, selected examples of applications are given, and step-by-step examples of experimental designs and real data analysis are also illustrated. The merging of the mass-action law principle with mathematical induction-deduction has been proven to be a unique and effective scientific method for general theory development. The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.

Sulforhodamine B colorimetric assay for cytotoxicity screening

Abstract: The sulforhodamine B (SRB) assay is used for cell density determination, based on the measurement of cellular protein content. The method described here has been optimized for the toxicity screening of compounds to adherent cells in a 96-well format. After an incubation period, cell monolayers are fixed with 10% (wt/vol) trichloroacetic acid and stained for 30 min, after which the excess dye is removed by washing repeatedly with 1% (vol/vol) acetic acid. The protein-bound dye is dissolved in 10 mM Tris base solution for OD determination at 510 nm using a microplate reader. The results are linear over a 20-fold range of cell numbers and the sensitivity is comparable to those of fluorometric methods. The method not only allows a large number of samples to be tested within a few days, but also requires only simple equipment and inexpensive reagents. The SRB assay is therefore an efficient and highly cost-effective method for screening.

Spheroid-based drug screen: considerations and practical approach

Abstract: Although used in academic research for several decades, 3D culture models have long been regarded expensive, cumbersome and unnecessary in drug development processes. Technical advances, coupled with recent observations showing that gene expression in 3D is much closer to clinical expression profiles than those seen in 2D, have renewed attention and generated hope in the feasibility of maturing organotypic 3D systems to therapy test platforms with greater power to predict clinical efficacies. Here we describe a standardized setup for reproducible, easy-handling culture, treatment and routine analysis of multicellular spheroids, the classical 3D culture system resembling many aspects of the pathophysiological situation in human tumor tissue. We discuss essential conceptual and practical considerations for an adequate establishment and use of spheroid-based drug screening platforms and also provide a list of human carcinoma cell lines, partly on the basis of the NCI-DTP 60-cell line screen, that produce treatable spheroids under identical culture conditions. In contrast to many other settings with which to achieve similar results, the protocol is particularly useful to be integrated into standardized large-scale drug test routines as it requires a minimum number of defined spheroids and a limited amount of drug. The estimated time to run the complete screening protocol described herein--including spheroid initiation, drug treatment and determination of the analytical end points (spheroid integrity, and cell survival through the acid phosphatase assay)--is about 170 h. Monitoring of spheroid growth kinetics to determine growth delay and regrowth, respectively, after drug treatment requires long-term culturing (> or =14 d).