Daniel Vanel

Soft tissue and visceral sarcomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up

Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy; Instituto Portugues de Oncologia de Lisboa Francisco Gentil, EPE, Lisbon, Portugal; University Hospital Essen, Essen, Germany; Department of Oncological Orthopedics, Musculoskeletal Tissue Bank, IFO, Regina Elena National Cancer Institute, Rome, Italy; Klinikum Stuttgart-Olgahospital, Stuttgart, Germany; Institut Curie, Paris, France; NORDIX, Athens, Greece; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands; Vienna General Hospital (AKH), Medizinische Universität Wien, Vienna, Austria; Hospital Universitario Virgen del Rocio-CIBERONC, Seville, Spain; Centro di Riferimento Oncologico di Aviano, Aviano; Ospedale Regionale di Treviso “S.Maria di Cà Foncello”, Treviso, Italy; Integrated Unit ICO Hospitalet, HUB, Barcelona, Spain; Sarcoma Unit, University College London Hospitals, London, UK; Skane University Hospital-Lund, Lund, Sweden; N. N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation; Institute of Scientific Hospital Care (IRCCS), Regina Elena National Cancer Institute, Rome; Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; Istituto Ortopedico Rizzoli, Bologna; Azienda Ospedaliera Universitaria Careggi Firenze, Florence, Italy; Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands; Institut Jules Bordet, Brussels, Belgium; Candiolo Cancer Institute, FPO IRCCS, Candiolo, Italy; Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam and Department of Radiotherapy, Leiden University Medical Centre, Leiden, The Netherlands; Turku University Hospital (Turun Yliopistollinen Keskussairaala), Turlu, Finland; Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Mannheim University Medical Center, Mannheim; Department of Medicine III, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany; Helsinki University Central Hospital (HUCH), Helsinki, Finland; Royal Marsden Hospital, London; The Institute of Cancer Research, London, UK; University Medical Center Groningen, Groningen; Radboud University Medical Center, Nijmegen, The Netherlands; University Hospital Motol, Prague; Masaryk Memorial Cancer Institute, Brno, Czech Republic; Gustave Roussy Cancer Campus, Villejuif, France; Maria Skłodowska Curie Institute, Oncology Centre, Warsaw, Poland; Tel Aviv Sourasky Medical Center (Ichilov), Tel Aviv, Israel; Medical Oncology, University Hospital of Lausanne, Lausanne, Switzerland; Azienda Ospedaliera, Universitaria, Policlinico S Orsola-Malpighi Università di Bologna, Bologna; Azienda Ospedaliero, Universitaria Cita della Salute e della Scienza di Torino, Turin, Italy; Fundacio de Gestio Sanitaria de L’hospital de la SANTA CREU I Sant Pau, Barcelona, Spain; Helios Klinikum Berlin Buch, Berlin, Germany; YCRC Department of Clinical Oncology, Weston Park Hospital NHS Trust, Sheffield, UK; Aarhus University Hospital, Aarhus, Finland; Leuven Cancer Institute, Leuven, Belgium; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy; Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway; Institute of Oncology of Ljubljana, Ljubljana, Slovenia; Netherlands Cancer Institute Antoni van Leeuwenhoek, Amsterdam, The Netherlands; University College Hospital, London, UK; Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Münster, Germany; Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway; Centre Leon Bernard and UCBL1, Lyon, France

Electropotential measurements as a new diagnostic modality for breast cancer

BACKGROUND Proliferative changes in breast epithelium are an intrinsic aspect in the development of breast cancer, and result in regions of epithelial electrical depolarisation within the breast parenchyma, which can extend to the skin surface. Diagnostic information might be obtained from a non-imaging and non-invasive test based on skin-surface electropotentials. METHODS In 661 women, scheduled for open biopsy at eight European centres, we studied whether measurements of breast electrical activity with surface sensors could distinguish benign from malignant breast disease. A depolarisation index was developed. RESULTS We found a highly significant trend of progressive electrical changes according to the proliferative characteristics of the biopsied tissue. Discriminatory information was obtained in both premenopausal and postmenopausal women, and the index was not related to age. The best test performances were for women with palpable lesions. The median index was 0.398 for non-proliferative benign lesions, 0.531 for proliferative benign lesions, and 0.644 for cancer (ductal carcinoma-in-situ and invasive). A specificity of 55% was obtained at 90% sensitivity for women with palpable lesions when a discriminant based on age and the depolarisation index was used. INTERPRETATION This new modality may have diagnostic value, especially in reducing the number of unnecessary diagnostic tests among women with inconclusive findings on physical examination. Understanding and control of the biological variability of these electrical phenomena will be important in the improvement of this test. Studies in populations with a lower cancer prevalence are needed to assess further the diagnostic value of this approach.

Malignant histiocytosis in childhood. Clinical study and therapeutic results in 22 cases

Twenty‐two children with malignant histiocytosis ranging in age from 2 to 13 1/2 years are described. In 10 cases, the correct diagnosis was only made retrospectively. The most salient pathologic features were found in lymph node biopsy specimens. Fever and wasting were the most prominent symptoms in 21 cases, and abdominal pains were striking in 9. Peripheral lymphadenopathy, mostly of the cervicoaxillary type, was present in 21 patients, with marked tenderness in 14. Abnormal mediastinal and/or paraaortic lymph nodes were detected radiographically in two‐thirds of the patients. Other prominent features included subcutaneous inflammatory infiltration in 12 patients and skin nodules in 8. Pleural effusions were seen in 8 children. The haematologic findings are described. Only 5 of 19 children had bonemarrow involvement. Fifteen patients died, one to 45 months from onset of their illness (median survival time, five months). Nine patients are alive with no evidence of disease 21 to 46+ months (median, 40 months) after the time of diagnosis and 8 have currently been off treatment for periods ranging from three to 29 months; they all have been treated with vincristine, prednisone, cyclophosphamide, and adriamycin and 4 have achieved remission after treatment with vinblastine, bleomycin, and CCNU or cytosine‐arabinoside. It is concluded from this study that clearly delineated clinical features of malignant histiocytosis in childhood should allow more rapid determination of the proper diagnosis and should result in early treatment by means of intensive systemic combination chemotherapy, which has dramatically improved the prognosis.

MRI of bone metastases

Abstract. Some knowledge of MR theory is required to be able to achieve high contrast between bone metastases and normal marrow. Three factors are used in MR to diagnose bone metastases: fat–water distribution, artifacts induced by bone trabeculae, and uptake of contrast medium. Using MR-histological correlations based on specimens of the lumbar spine, and studies of patients, we explain the advantages and limitations of sequences studying fat and water (spin-echo T1, STIR, in- and out-of-phase gradient echo, fat presaturation), bone trabeculae (gradient echo with long TE), and the injection of contrast medium.

MR imaging of clear cell sarcoma (malignant melanoma of the soft parts): A multicenter correlative MRI-pathology study of 21 cases and literature review

Abstract Objective. To evaluate MR imaging and pathology findings in order to define the characteristic features of clear cell sarcoma of the soft tissues (malignant melanoma of the soft parts). Design and patients. MR examinations of 21 patients with histologically proven clear cell sarcoma of the musculoskeletal system were retrospectively reviewed and assessed for shape, homogeneity, delineation, signal intensities on T1- and T2-weighted images, contrast enhancement, relationship with adjacent fascia or tendon, secondary bone involvement, and intratumoral necrosis. In 19 cases the pathology findings were available for review and for a comparative MR-pathology study. Results. On T1-weighted images, lesions were isointense (n=3), hypointense (n=7) or slightly hyperintense to muscle (n=11). Immunohistochemical examination was performed in 17 patients. All 17 specimens showed positivity for HMB-45 antibody. In nine of 11 lesions with slightly increased signal intensity on T1-weighted images, a correlative MR imaging-pathology study was possible. All nine were positive to HMB-45 antibody. Conclusions. Clear cell sarcoma of the musculoskeletal system often has a benign-looking appearance on MR images. In up to 52% of patients, this lesion with melanocytic differentiation has slightly increased signal intensity on T1-weighted images compared with muscle. As the presence of this relative higher signal intensity on T1-weighted images is rather specific for tumors displaying melanocytic differentiation, radiologists should familiarize themselves with this rare entity and include it in their differential diagnosis when confronted with a well-defined, homogeneous, strongly enhancing mass with slightly higher signal intensity compared with muscle on native T1-weighted images.

Does adjuvant radiation therapy increase loco-regional control after optimal resection of soft-tissue sarcoma of the extremities?

Adjuvant radiotherapy (RT) is routinely recommended for most soft-tissue sarcomas (STS) of the extremities. However, its impact on local control is not clearly established after wide complete excision. We performed a retrospective analysis of patients who underwent wide resection in our institution (first or second resection in cases of incomplete surgery) and either did or did not receive adjuvant RT. All histological specimens of patients operated upon between 1975 and 1996 were carefully analysed and only patients with free tumour margins (ftm) were retained for the analysis. The histopathological classification was as follows: minimal resection (mR) (ftm<10 mm) and optimal resection (oR) (ftm >/=10 mm). There were 133 patients with a median age of 44 years (range 16-88 years). The median tumour size was 6 cm (range 1-20 cm) with 28, 44 and 28% of stage I, II and III lesions, respectively. 93 patients (70%) were reoperated upon and residual tumour was found in 55% of the patients (51/93). 69 patients (17 oR and 52 mR) received adjuvant RT and 64 patients did not (54 oR and 10 mR). Other patient characteristics (age, tumour size, stage, deep-seated lesion, histoprognostic grade, adjuvant chemotherapy) were similar in both the RT and no-RT groups. Median follow-up was 10 years (3-25 years). The 5- and 10-year local relapse-free survival rates were 78 and 71%, respectively. 33 patients relapsed locally: 11 in the RT group and 22 patients in the control group (P=0.01). In the univariate analysis, adjuvant RT was correlated with relapse-free survival, while tumour grade and tumour margin status were correlated with overall survival. The multivariate analysis demonstrated a favourable impact of RT and negative influence of malignant fibrous histiocytoma (MFH) on local relapse-free survival; the tumour grade was correlated with overall survival. RT had a positive influence on local control exclusively in patients with mR resection (P=0.005) and in patients with residual tumour cells after re-excision (P=0.001). RT had no influence on 5- and 10-year overall survival. The 5- and 10-year overall survival for the entire population were 77 and 67%, respectively. Optimal resection seems to be the best predictive parameter for a favourable outcome in localised STS. Adjuvant RT is indicated after mR resection and for residual tumour after definitive surgery, but its role after oR resection (primary resection or no residual tumour after re-excision) should be evaluated in a prospective randomised trial.

Dynamic contrast-enhanced MRI with subtraction of aggressive soft tissue tumors after resection

Abstract Objective. To report the application of dynamic contrast-enhanced subtraction MRI for detecting recurrences in aggressive or malignant soft tissue tumors. Design. The imaging studies consisted of static (T1- and T2-weighted spin-echo) acquisitions, followed by dynamic conventional spin-echo short TR/TE images (at 45 s, 1 min 30 s and 5 min) after a bolus of intravenous contrast medium. Contrast images were subtracted from the precontrast scan on the console. Patients. Ninety-eight patients were studied who had had aggressive or malignant soft tissue tumors treated by surgery, and were followed up to assess recurrences. Results. Subtraction MRI characterized recurrences better than routine sequences in 10 patients (1 lesion was seen only with this technique, 6 were better delineated, and 3 inflammatory pseudotumors were identified), and less well in 4 cases. Conclusion. As the number of levels studied on dynamic images is limited, and all but one recurrence were detected on T2-weighted images, it remains logical to start the examination with T2-weighted spin-echo images, and to use the dynamic study only if contrast injection is required.

MRI of bone marrow disorders.

Abstract. Four factors can be used in MR of bone marrow: fat–water distribution, artifacts induced by bone trabeculae, diffusion, and uptake of contrast media. Fat–water is imaged using T1-weighted spin-echo, short tau inversion recovery (STIR), and fast STIR, in- and out-of-phase gradient echo, and fat pre-saturation sequences; bone trabeculae by gradient echo with long TE; diffusion by single-shot spin-echo. The injection of contrast media is a more easy and efficient way to improve the specificity. The value and limitations of those sequences are discussed in marrow replacements (metastases, lymphoma, leukemia) and in myeloid hyperplasia or depletion.

Fast magnetic resonance imaging with contrast for soft tissue sarcoma viability.

Because dynamic (fast) contrast-enhanced magnetic resonance imaging with its temporal resolution allows evaluation of contrast kinetics of soft tissue sarcomas, its efficacy for defining viable tumor in these neoplasms was studied for three applications: biopsy localization, chemotherapeutic response, and differentiation between recurrence and inflammation after treatment. After conventional T1-weighted and T2-weighted magnetic resonance sequences to localize the lesion, patients had dynamic contrast-enhanced magnetic resonance imaging with fast and ultrafast sequences and postprocessing techniques (subtraction, time-intensity curves, and parametric color-encoding). In 10 of 40 patients, dynamic imaging more precisely defined the most malignant foci of tumor for biopsy than conventional magnetic resonance imaging. After chemotherapy, dynamic imaging distinguished 11 good responders from 21 poor responders. In followup of 196 patients, dynamic imaging detected 42 early enhancing recurrences and excluded recurrent tumor in six late enhancing pseudotumors. Dynamic imaging can differentiate viable tumor from nonviable tumor and inflammation by showing two temporally different phases of contrast enhancement: an early phase correlative with viable tumor at histologic examination, and a late phase when all tissues enhance simultaneously and may be indistinguishable. By showing tumor viability, dynamic contrast-enhanced magnetic resonance imaging can help define biopsy sites, chemotherapeutic response, and presence or absence of recurrences and therefore affect the initial evaluation, treatment, and followup of patients with soft tissue sarcomas.

The role of magnetic resonance imaging in the evaluation of Ewing sarcoma. A report of 27 cases

The experience with magnetic resonance imaging (MRI) in 27 patients with Ewing sarcoma is reported and compared with computed tomography (CT) and plain films. Plain radiography proved to be the best imaging method to asses probable histological diagnosis in all cases (n=6). For the evaluation of chemotherapeutic response (n=4), CT and MRI gave the same information about the variation in size of the tumor. In this small series, the high signal in T2 weighted images was not altered significantly by therapy. In preoperative evaluation (n=14), MRI gave better information than CT of soft tissue involvement and extension within the bone marrow in two cases each. The ability of MRI to accurately define extension through the epiphyseal plate in two cases permitted limb salvage which otherwise would not have been possible. In the long-term follow-up (n=12), three patients without recurrence one year after therapy showed a low signal in the surgical area in T2 weighted images. Nine patients had a high signal in T2 weighted images: four were reactive lesions, two had obvious recurrence, and one was a hematoma. In the two remaining cases plain films and CT were normal, in the presence of both active tumor and reactive lesions. It was not possible with MRI to differentiate active tumor from reactive change, even after Gd-DTPA infusion.