M. Kind

A critical analysis of treatment strategies in desmoid tumours: a review of a series of 106 cases

BACKGROUND The management of desmoid tumours, previously based on strategies employed for sarcomas, should be reassessed, given the morbidity of interventions used in their treatment. METHODS Long-term follow-up (median 123 months) of a series of 106 treated patients with 69 primary and 37 recurrent desmoids, in order to study natural history and outcome. RESULTS Desmoids typically evolved actively over a median period of 3 years, and stabilised thereafter. Recurrences or progression most commonly occurred between 14 and 17 months. Risk factors for recurrence were presentation (primary vs. recurrent), gender, tumour location and resection margins. However, survival was independent from these factors, with equivalent survival whether resection had been performed or not. Tumour control and functional outcome depended on location and presentation. Functional impairment was proportional to number of operations and whether patients had received radiotherapy. Recurrences were observed in 12/23 patients after radiotherapy. CONCLUSION Desmoids are relatively indolent tumours needing different approaches than sarcomas. Direct surgery is advisable only in primary lower trunk wall/girdle locations. Wait-and-see and medical treatment is preferable in other types of presentations.

Surgical resection and radiotherapy for primary retroperitoneal soft tissue sarcoma

METHODS AND MATERIALS Forty-five patients were consecutively treated for primary retroperitoneal soft tissue sarcoma with surgery in combination with radiation therapy in the same institution. The median follow-up time was 53 months (7-108). RESULTS Seventeen (38%) patients had clear microscopic margins (R0 resection), 26 patients (58%) had gross complete surgical excision (R1 resection) and two patients (4%) had a macroscopic residual disease (R2 resection). External radiotherapy doses ranged from 40.8 to 59.4 Gy (mean and median: 49 Gy). Seventeen patients underwent intraoperative radiation therapy (IORT). Moreover, 11 patients received chemotherapy. The overall 1-, 2-, and 5-year survival for all 45 patients were 93, 85 and 60%, respectively. The 1-, 2-, and 5-year locoregional relapse-free rate for the whole group was 91, 70 and 40%, respectively. In univariate analysis, quality of surgery was the only variable to show a significant effect for overall survival (P=0.0386) and for local control (P=0.0059). Tumor size and tumor grade had no statistically significant effect. For the patients receiving IORT+external beam radiation therapy, no difference was observed for survival or locoregional control. The most frequent acute side effects treatment complications were radiation-induced nausea or vomiting (42%) and moderate enteritis (30%). Significant late morbidity was observed for two patients. CONCLUSIONS This study confirms the feasibility of external postoperative radiotherapy with an acceptable level of toxicity. However, the high rate of local relapses (especially in field of radiation) does not demonstrate the usefulness of radiotherapy at the level of dose used and further preferably randomized studies should be planned.

MAGNETIC RESONANCE IMAGING IN THE TREATMENT PLANNING OF RADIATION THERAPY IN CARCINOMA OF THE CERVIX TREATED WITH THE FOUR-FIELD PELVIC TECHNIQUE

PURPOSE To evaluate magnetic resonance imaging (MRI) in the planning of radiation therapy for patients with carcinoma of the cervix treated with a four-field technique. METHODS AND MATERIALS Between May 1994 and February 1995, 18 patients with carcinoma of the cervix were entered in the study (1 T1 N-; 2 T2a N-; 1 T2b NO; 10 T2b N-; 2 T2b N+; 2 T3b N+). Node status was assessed by a laparoscopic pelvic lymphadenectomy. During the first step, all the patients were simulated with an isocentric four-field pelvic technique. In one group (11 patients) simulation was done based on clinical examination, computed tomography (CT), and standard guidelines. In the second group (seven patients) simulation was based on clinical examination, CT, and with the help of diagnostic MRI, which was available at that time. During the second step, MRI in treatment position with skin markings of the isocenter of the radiation fields was then performed in every patient. During the third step, in each patient, the simulated radiation fields were correlated with the MRI defined target volume by superimposing them on midsagittal and midcoronal MR images. The adequacy of the margins was arbitrarly defined as 1 cm around the MRI defined target volume (tumor of the cervix and its extension, and uterus). RESULTS In the first group (11 patients), MRI in treatment position led to a change in 7 patients: six inadequate margins in the lateral fields and one in the anterior and lateral field. In almost all the cases, the adjustments were of an increase of 10 mm, equally matched between the anterior and posterior borders of the lateral fields. In the second group (seven patients), MRI in treatment position has led to a change in lateral fields in five patients. The mean adjustment was 10 mm: four increases (two anterior border, one posterior border, one anterior and posterior border), and one decrease of the posterior border. In the two groups, modifications of the anterior border of the lateral fields have allowed adequate margins around the uterine fundus and modifications of the posterior border have allowed adequate coverage of the cervical tumor. CONCLUSION When treating carcinoma of the cervix with a four-field radiation technique, standard portals do not exist. The design of lateral fields has to be based on individual morbid anatomy, which is given accurately by diagnostic MRI. Magnetic resonance imaging in treatment position assesses the design of simulated lateral fields.

Retroperitoneal soft tissue sarcomas: A pilot study of intraoperative radiation therapy

This pilot study was conducted to evaluate the feasibility and tolerance of a multimodal therapy of retroperitoneal soft tissue sarcoma (STS), including intraoperative radiation therapy (IORT). Nineteen patients (14 primarily treated patients and 5 treated for a recurrent tumor) were included. Surgery included a complete resection (14), a partial resection (2), and no resection (2). The median IORT dose was 17 Gy. Thirteen patients also received an external radiation therapy (ERT). Nine patients received chemotherapy. There was no postoperative mortality. Immediate postoperative complications occurred in four patients (21%). Delayed complications occurred in six patients, including one lethal iliac artery disruption. With a median follow‐up of 17 months, the 2‐year disease‐free survival rate was 60%, and the 2‐year actuarial local control rate was 76%. A multimodality approach of treatment, including IORT and ERT and eventually chemotherapy, appears feasible in patients with retroperitoneal STS. However, the treatment‐related morbidity appeared relatively high in this study.

Clinical outcome of leiomyosarcomas of vascular origin: comparison with leiomyosarcomas of other origin

BACKGROUND There are no data about the natural history of leiomyosarcoma of vascular origin (vLMS) in comparison with leiomyosarcoma (LMS) of other origin and about the management of advanced disease. METHODS Among 1472 patients diagnosed with sarcoma from January 1980 to December 2008 at our institution, 195 patients (13%) had LMS. LMS had a vascular origin in 14 cases (7%). RESULTS Patients with vLMS had a significantly worse median metastasis-free survival (MFS) (0.25 versus 9.6 years, P = 0.001) and overall survival (OS; 2.1 versus 7 years, P < 0.0001) than patients with LMS of other origin. On multivariate analysis, grade and vascular origin were the sole independent adverse prognostic factors for OS. Eight metastatic patients with vLMS received a first-line anthracycline chemotherapy regimen. Two patients had partial response, four had stable disease and two had progressive disease. OS of patients with metastatic vLMS was not significantly different from that observed in patients with metastatic LMS of other origin (22.1 versus 16.5 months, P = 0.84). CONCLUSIONS Vascular origin is an independent adverse prognostic factor for MFS and OS in patients with LMS. Patients with metastatic vLMS had a similar outcome than patients with metastatic LMS of other origin.

Histology and imaging of soft tissue sarcomas

Imaging and histology are two complementary morphological techniques which play a fundamental role in the diagnosis and management of soft tissue sarcomas. Imaging allows to identify some pseudosarcomatous benign lesions such as myositis ossificans, intramuscular hemangioma, angiomyolipoma, intramuscular lipoma, giant cell tumour of tendon sheath, desmoid tumour and elastofibroma. There is no formal criterion for diagnosing a sarcoma on magnetic resonance imaging (MRI) but malignancy is strongly suspected with the presence of necrosis and vascular, bone or joint invasion. Imaging may also suggest some histological types of sarcoma such as well-differentiated liposarcoma, dedifferentiated liposarcoma, synovial sarcoma or extraskeletal osteosarcoma. Imaging is also extremely helpful in determining the appropriate kind of sampling to carry out and in guiding the performance of a microbiopsy. The appearance observed on imaging should always be taken into consideration for the interpretation of the microbiopsy by the pathologist.

Clinical activity of sunitinib in patients with advanced desmoplastic round cell tumor: a case series

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy with poor outcome occurring in adolescents and young adults. Therapeutic options for patients with advanced disease are limited. Preclinical studies have shown that VEGFR-2 and VEGFA are overexpressed in DSRCT and that DSRCT xenografts were highly responsive to anti-VEGF agents such as bevacizumab. We report here the clinical activity of sunitinib in eight patients with DSCRT. Our data suggest that sunitinib may be associated with clinical benefit even in heavily pretreated patients.

Temsirolimus in advanced leiomyosarcomas: patterns of response and correlation with the activation of the mammalian target of rapamycin pathway

Preclinical data have indicated that alteration of PTEN and activation of the mammalian target of rapamycin (mTOR) pathway play a crucial role in the oncogenesis of leiomyosarcoma. The objective of this exploratory study was to assess the clinical role of mTOR inhibition in patients with advanced leiomyosarcoma refractory to standard chemotherapy. Patients with advanced leiomyosarcoma were treated with temsirolimus and consented to retrospective collection of data from their medical records and analysis of archival tumor specimens. Tumor response was determined according to the response evaluation criteria in solid tumor (RECIST) and Choi criteria. Tumors were assessed for immunohistochemical evidence of PTEN loss of expression and mTOR activation. Six patients participated in the study. According to the RECIST, three patients had stable disease and three patients had progressive disease. The three patients with RECIST stable disease had partial response according to the Choi criteria. Partial response according to the Choi criteria was associated with clinical improvement and biological signs of temsirolimus antitumor activity. The immunohistochemical status of PTEN and phosphorylated S6 ribosomal protein was not predictive of the outcome. This exploratory study indicates antitumor activity of temsirolimus in leiomyosarcoma, possibly through a mechanism involving aberration of the PTEN gene. Further investigations of the phosphoinositide 3-kinases/PTEN/Akt/mTOR pathway are needed to explore the role of mTOR inhibitors, either alone or in combination, in patients with advanced sarcoma.

Evaluating surgery quality in soft tissue sarcoma.

To identify pertinent indicators for oncologic outcomes in assessing surgery in soft tissue sarcomas, only local recurrences are considered here. Functional outcomes and treatment morbidity, equally important end-points for evaluating surgery quality, are less frequently reported and are not taken into account in this review. Herein, we review recent publications reporting indicators of surgery quality in soft tissue sarcoma treatment. Local recurrence-free interval is the major end-point in evaluating the quality of surgery. Disease-free survival should not be used because the risk factors for metastases are different from those for local recurrence. Five-year local recurrence-free estimations for limb and trunk wall sarcoma should be below 20%, and best approach 10%. The risk of local recurrence depends on tumour biology (i.e. grade) and quality of surgery as defined by the quality of margins. Better than margin width as measured on the tumour specimen, margin quality determined consensually between surgeons and pathologists is the best indicator for local outcome. Quality of margin should be expressed according the UICC residual disease definitions (R0: in sano, R1: microscopic residual disease, R2: macroscopic residual disease). Other important indicators for surgery quality are treatment in specialised centres, a planned, organised surgery, and treatment within a multidisciplinary team. Soft tissue sarcoma should also be treated in specialised centres. Surgery quality depends on obtained margins that are determined best by close collaboration between the surgeon and the pathologist.

Chronic lymphedema due to morbid obesity: an exceptional cause of abdominal wall angiosarcoma.

Sir, Angiosarcomas are rare malignant soft tissue tumors that show differentiation toward endothelial cells occurring in various clinical settings, including lymphedema-associated angiosarcoma, idiopathic angiosarcoma on the head and neck in elderly people, angiosarcoma arising on chronically sundamaged skin and post-irradiation angiosarcoma [4]. Chronic lymphedema secondary to mastectomy and axillary lymphadenectomy for breast cancer, and more rarely to infectious disease, congenital disease and traumatism, is a known predisposing condition for cutaneous and superficial soft tissue angiosarcoma. We report a new case of high-grade abdominal wall angiosarcoma in a chronically lymphedematous abdominal panniculus due to morbid obesity. A 44-year-old morbidly obese man presented with a skin lesion in the periumbilical region. Clinical examination revealed a 10-cm papular lesion on a post-operative abdominal wall hernia. There was a clinical history of Crohns disease diagnosed 34 years previously. Treatment included many abdominal operations. A contrast-enhanced computed tomography scan of the abdomen revealed extensive heterogeneous thickening of the skin and subcutaneous fat, with infiltration of the abdominal musculature (Fig. 1). In October 2006, a dermolipectomy was performed. Histologically, the tumor involved the whole dermis, subcutaneous fat with an infiltrative pattern and margins. Beside the tumor, many ectatic vessels lined by a normal appearing endothelium were noted (Fig. 2a). Cell proliferation consisted of solid sheets of fusiform cells with Virchows Arch (2008) 453:217–219 DOI 10.1007/s00428-008-0623-8