Frits van Coevorden

Surgical treatment of lung metastases: The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients.

Several reports have shown a prolonged survival after surgical treatment of pulmonary metastases from soft tissue sarcomas. However, it is still unclear which prognostic factors predict a favorable outcome. Series are not comparable and the data are conflicting. Therefore, a multi‐institutional study was undertaken to analyze prognostic factors in selecting patients for resection of pulmonary metastases from soft tissue sarcomas.

Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): A multicentre randomised controlled trial

BACKGROUND The effect of adjuvant chemotherapy on survival for resected soft-tissue sarcoma remains unknown. We investigated the effect of intensive adjuvant chemotherapy on survival in patients after resection of high-risk soft-tissue sarcomas. METHODS In this multicentre randomised trial, patients with macroscopically resected, Trojani grade II-III soft-tissue sarcomas at any site, no metastases, performance status lower than 2 and aged between 16 and 70 years were eligible within 4 weeks of definitive surgery. Patients were randomly assigned to receive adjuvant chemotherapy or no chemotherapy (control group). Randomisation was done with a minimisation technique, stratified by hospital, site of primary tumour, tumour size, planned radiotherapy, and isolated limb perfusion therapy. Chemotherapy consisted of five cycles of doxorubicin 75 mg/m(2), ifosfamide 5 g/m(2), and lenograstim every 3 weeks. Patients in both groups received radiotherapy if the resection was marginal or the tumour recurrent. The primary endpoint was overall survival and analyses were done by intention to treat. The final results are presented. This trial is registered with ClinicalTrials.gov, NCT00002641. FINDINGS Between February, 1995, and December, 2003, 351 patients were randomly assigned to the adjuvant chemotherapy group (175 patients) or to the control group (176). 258 (73%) of 351 patients received radiotherapy, 129 in each group. Overall survival did not differ significantly between groups (hazard ratio [HR] 0·94 [95% CI 0·68-1·31], p=0·72) nor did relapse-free survival (HR 0·91 [0·67-1·22], p=0·51). 5-year overall survival rate was 66·5% (58·8-73·0) in the chemotherapy group and 67·8% (60·3-74·2) in the control group. Chemotherapy was well tolerated, with 130 (80%) of 163 patients who started it completing all five cycles. 16 (10%) patients had grade 3 or 4 fever or infection, but no deaths due to toxic effects were recorded. INTERPRETATION Adjuvant chemotherapy with doxorubicin and ifosfamide in resected soft-tissue sarcoma showed no benefit in relapse-free survival or overall survival. Future studies should focus on patients with larger, grade III, and extremity sarcomas.

Factors Influencing the Local Failure Rate of Radiofrequency Ablation of Colorectal Liver Metastases

BackgroundThe prognosis of patients with colorectal cancer is poor, especially when there is distant metastatic disease. Local ablation of tumor by radiofrequency ablation (RFA) has emerged as a safe and effective new treatment modality, but its long-term efficacy may be hindered by renewed local tumor growth at the site of RFA. The objectives of this study were to identify risk factors for local RFA failure and to define exclusion criteria for RFA treatment of colorectal liver metastases.MethodsA total of 199 lesions in 87 patients were ablated with RFA. Factors influencing local failure rates were identified and compared with data from the literature.ResultsThe local failure rate was 47.2%, and the average time to local disease progression was 6.5 months. Factors that significantly correlated with increased failure rates were metachronous occurrence of liver metastases, large mean lesion size, and central tumor location.ConclusionsBecause accurate electrode placement is pivotal in achieving adequate tumor necrosis, RFA should not be performed percutaneously when electrode placement is impaired. We suggest that lesions >5 cm and lesions located near great vessels or adjacent organs should be treated with open RFA, thus allowing vascular inflow occlusion and complete mobilization of the liver. Lesions that are difficult to reach by electrodes should be approached by an open procedure.

Technical considerations in surgery for retroperitoneal sarcomas: Position paper from E-Surge, a master class in sarcoma surgery, and EORTC-STBSG

BackgroundSurgery is the principal treatment for retroperitoneal sarcoma. These tumors typically involve or abut multiple organs and therefore require multivisceral resections. Despite the complexity of such operations, a standardized approach has not been described. As a result, referral centers often see patients who have undergone suboptimal surgery, with gross disease left behind. This is one of the causes of the dismal prognosis of this disease.MethodsThese consensus statements came out from E-Surge, an educational symposium with live sarcoma surgery, performed by European and North American expert sarcoma surgeons illustrating an optimal technique to an international audience, held in 2010 and 2011. The content was then shared among members of the local subcommittee of European Organization for Research and Treatment of Cancer (EORTC)–Soft Tissue and Bone Sarcoma Group (STBSG).ResultsAn attempt to describe a reproducible and standardized approach to these tumors is illustrated. A detailed description of the different procedures according to the variety of different presentations is made.ConclusionsThe approach described herein should be used as the reference standard in clinical practice and serve to perform quality check of local treatment in future trials.

Resectable retroperitoneal soft tissue sarcomas : the effect of extent of resection and postoperative radiation therapy on local tumor control

Background. Soft tissue malignancies of the retro‐peritoneum are rare. Surgery is commonly considered the first choice of treatment. There is still no consensus concerning the precise value of the extent of surgery and the value of additional treatment modalities.

Isolated limb perfusion with tumor necrosis factor-α and melphalan for patients with unresectable soft tissue sarcoma of the extremities

Since 1992, isolated limb perfusion (ILP) with tumor necrosis factor‐α (TNFα) and melphalan has been used for the treatment of patients with unresectable soft tissue sarcomas of the extremities. The authors retrospectively studied the results of limb salvage surgery using TNFα‐ILP at their institution.

Desmoid tumors: need for an individualized approach.

Desmoid tumor, also known as aggressive fibromatosis or desmoid-type fibromatosis, is a rare monoclonal, fibroblastic proliferation arising in musculoaponeurotic structures. Although histologically benign, desmoids are often locally invasive and associated with a high local recurrence rate after resection. Since it is a heterogeneous disease, in particular regarding clinical presentation, anatomic location and biological behavior, treatment should be individualized to reduce local tumor control failure with concurrently acceptable morbidity and preservation of quality of life. Many issues regarding optimal treatment of desmoids remain controversial. However, wide surgical excision remains the treatment of choice, except when surgery is mutilating and is associated with considerable function loss or major morbidity. Involvement of surgical margins is probably associated with an increased risk of local recurrence. Postoperative radiotherapy results in a significant reduction of the local recurrence rate, but only in the case of involved surgical margins. Radiotherapy for gross disease is considerably effective, but is associated with a relatively high rate of complications, which are usually mild or moderate and radiation dose dependent. Radiotherapy should only be applied where anatomic constraints preclude complete resection and radiotherapy is not too toxic. Risk factors for local tumor control failure include young age, large size, presentation as recurrent disease, limb/girdle or intra-abdominal location, involved surgical margins, omission of radiotherapy, radiation dose less than 50 Gy and insufficient radiation field size. Increased comprehension of the pathogenesis and biological behavior of desmoids resulted in the emerging applicability of systemic therapies and a wait-and-see policy. Systemic treatment may be indicated in patients that have anatomic barriers to effective surgery or radiotherapy. Considering the significant morbidity of surgery and/or radiotherapy for certain locations, especially mutilation and loss of function, and the tumor’s natural history, which is often characterized by prolonged periods of stability or even regression, a period of watchful waiting may compose the most appropriate management in selected asymptomatic patients. Attempts to complete eradication of the disease may be worse than the disease itself.

Dynamic contrast-enhanced MR imaging in monitoring response to isolated limb perfusion in high-grade soft tissue sarcoma: initial results

The objective of this study was to evaluate whether dynamic contrast-enhanced MR imaging can determine tumor response and localize residual viable tumor after isolated limb perfusion (ILP) chemotherapy in soft tissue tumors. Twelve consecutive patients, with histologically proven high-grade soft tissue sarcoma, prospectively underwent non-enhanced MR and dynamic contrast-enhanced MR imaging before and after ILP. Tumor volume was measured on non-enhanced MR images. The temporal change of signal intensity in a region of interest on dynamic contrast-enhanced MR images was plotted against time. Start, pattern, and progression of enhancement were recorded. Histopathologic response was defined as complete response if no residual viable tumor was present, partial remission if <50% viable tumor was present, and no change if ≥50% viable tumor was present in the resection specimen. Resected specimens for correlation with histopathology were available for 10 patients; 5 patients had partial remission and 5 had no change. Volume measurements correctly predicted tumor response in 6 of 10 patients. Dynamic contrast-enhanced MR correctly predicted tumor response in 8 of 10 patients. Early rapidly progressive enhancement correlated histologically with residual viable tumor. Late and gradual, or absence of enhancement, was associated with necrosis, predominantly centrally located, or granulation tissue. These preliminary results show that dynamic contrast-enhanced MR imaging offers potential for non-invasive monitoring of response to isolated limb perfusion in soft tissue sarcomas due to identification of residual areas of viable tumor and subsequently may provide clinically useful information with regards to timing and planning of additional surgery. Further prospective studies in a larger patient population is warranted.

Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease: an immunohistochemical and molecular biological analysis

Almost all primary retroperitoneal liposarcomas can be classified as well-/dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence of myxoid areas and vascular crows feet pattern, which has resulted in a debate on the classification of liposarcoma in the retroperitoneum. Genetically, myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are different diseases. Myxoid/round cell liposarcoma is characterized by a translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well-/dedifferentiated liposarcoma is characterized by an amplification of the 12q13-15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is highly radio- and chemosensitive, differentiation between subtypes is important to optimize treatment. We studied whether primary retroperitoneal liposarcomas diagnosed as myxoid/round cell liposarcoma represent molecularly true myxoid/round cell liposarcoma or are histopathological mimics and represent well-/dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell liposarcoma (n=16) were compared to primary extremity myxoid/round cell liposarcoma (n=20). Histopathological and immunohistochemical features were studied. Amplification status of the 12q13-15 region was studied using a multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS-CHOP translocations were studied using RT-PCR. In primary retroperitoneal myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of 15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe amplification showed the amplification of 12q13-15 region in 16/16 primary retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary extremity myxoid/round cell liposarcomas, but absent in all primary retroperitoneal myxoid/round cell liposarcomas. On the basis of immunohistochemical and molecular characteristics, apparent primary retroperitoneal myxoid/round cell liposarcoma can be recognized as well-/dedifferentiated liposarcoma with morphological features mimicking myxoid/round cell liposarcoma. In these cases, treatment should probably be specifically designed as for well-/dedifferentiated liposarcoma. Moreover, finding of myxoid/round cell liposarcoma translocations in a retroperitoneal localization is highly suggestive of metastasis and should prompt search for a primary localization outside the retroperitoneum.

Prognostic factors and evaluation of surgical management of hepatic metastases from colorectal origin: A 10-year single-institute experience

The aim of this study was to determine prognostic factors and outcome after liver resection for colorectal metastases in 102 patients over a period of 10 years. A stepwise procedure using proportional hazard regression analysis was used to identify prognostic factors. Estimated survival at 2 years was 71%, and at 5 years, 29% (Kaplan-Meier). Of 19 patients with isolated liver recurrence, 6 had a second metastasectomy; 4 of the 6 are still alive.Wefound that the number of hepatic lesions on computed tomography (P = 0.012), the interval between resection of the primary colon tumor and the hepatic metastasectomy (P = 0.012), and synchronicity of the primary and the hepatic metastasis (P = 0.048) showed evidence of independent prognostic value regarding survival. Resection of hepatic colorectal metastases may result in long-term survival. Patients with recurrence after a first liver resection may benefit from a repeat metastasectomy. Our data suggest there is no strong predictor of survival. Survival seems to decrease with increasing number of metastases found on computed tomography.