The management of retroperitoneal soft tissue sarcoma: a single institution experience with a review of the literature.

AIM: Ten percent of soft tissue sarcomas (STS) arise in the retroperitoneal tissues. The prognosis for patients with retroperitoneal sarcoma is poor with a 5-year survival rate between 12% and 70%. Stage at presentation, high histological grade, unresectable primary tumour and incomplete resection are associated with a less favourable outcome. METHODS: Complete follow-up data were available on 22 patients who underwent surgery for retroperitoneal STS in our institution between 1990 and 2000. Patient, tumour and treatment variables were analysed including use of adjuvant therapy and survival status. RESULTS: Eighteen patients underwent surgery for primary disease, four patients were treated for recurrent disease or metastases. Ten patients presented with pain, seven with an abdominal mass, other presentation included weight loss and haematuria. Thirteen patients presented with tumours larger than 10 cm. The tumours were seven liposarcomas, six leiomyosarcomas, three malignant fibrous histiocytomas, two rhabdomyosarcomas, two malignant schwannomas and two undifferentiated sarcomas. Six primary tumours were completely excised, five patients received radiotherapy and five received chemotherapy. Local recurrence rate was 45% and recurrence-free interval for 10 patients with recurrence was 11 months. Five patients received radiotherapy and five received chemotherapy. The median survival for patients with primary tumours was 36 months, and 5-year survival was 44%. Adjuvant therapy was not associated with higher survival rates. CONCLUSION: This study re-emphasizes the poor outcome of patients with retroperitoneal STS. Adjuvant radiotherapy and chemotherapy do not appear to be any proven benefit and the single most important prognostic factor is aggressive successful en bloc resection of the primary tumour. Our resection rate and 5-year survival rates are comparable with previous reported UK series although lower than large reports from North American centres. This might partly be explained by difficulty in data collection in a retrospective analysis, but may reflect inadequate subspecialization in UK centres. Copyright Harcourt Publishers Limited.     

Identification of low-risk tumours in histological high-grade soft tissue sarcomas

In more than one-third of patients with a histological high-grade malignant soft tissue sarcoma metastasis develops despite local control of the primary tumour. Hence, adjuvant chemotherapy is increasingly used for these relatively chemoresistant tumours which requires improved prognostication to exclude low-risk patients from overtreatment. We assessed the value of stepwise prognostication in a series of 434 histological high-grade STS of the extremity and trunk wall. Vascular invasion was used as the first discriminator whereafter the risk factors tumour necrosis, size (>8cm) and infiltrating growth pattern were used to discriminate high- and low-risk tumours. We identified a high-risk group with a cumulative incidence of metastasis >0.4 at 5 years, and a low-risk group, comprising half of the tumours, with a cumulative incidence of metastasis <0.15. The model was validated in an independent material of 175 patients. This model improved prognostication in STS and is of value for identifying patients who probably should not receive adjuvant chemotherapy.     

Long-term prognosis of primary retroperitoneal soft tissue sarcoma.

AIMS: To evaluate the result of treatment and long-term outcome of a population-based cohort of patients with retroperitoneal soft tissue sarcoma (RSTS). METHODS: Between 1 January 1989 and 1 January 1994, 143 patients diagnosed as having primary RSTS were selected from a national pathology database (PALGA) in the Netherlands. In this population-based group of patients, the result of surgery, overall survival (OS) and disease-free survival (DFS) were analysed as well as factors affecting OS and DFS. Median follow-up was 10.2 years. RESULTS: Operative treatment resulted in a complete tumour resection in 55% of the patients (n=78), low- and intermediate-grade tumours were more often completely resected than high-grade tumours (P=0.016). Five- and 10-year cumulative OS was 39% and 21%, respectively, while DFS was 22% and 17%, respectively. In a multivariate analysis low malignancy grade (P=0.017) and a complete tumour resection (P<0.001) were associated with better OS. CONCLUSIONS: Complete tumour resection and low malignancy grade were independent favourable prognosticators. However, these factors were related too, since surgical success was influenced by malignancy grade.     

Disease incidence and results of extremity lesion treatment: mersey region soft tissue sarcomas (1975-1985)

Purpose. The incidence and treatment results of extremity soft tissue sarcoma (STS) in the Mersey Region, in the absence of a Multi-Disciplinary Unit, for the period 1975-1985, have been analysed.Subjects and methods. Data from cases presenting with STS within the Mersey region, from 1 January 1975 until 31 December 1985, were reviewed. Only patients with sarcoma of head and neck, thoracic wall, abdominal wall, retroperitoneum, limb girdle or extremity were included. Extremity lesions were staged according to the MTS system. Pathological data also were assigned a grade according to tumour differentiation, mitosis count and tumour necrosis. Data from patients with a minimum follow-up of 5 years were collated, and patterns of treatment failure were investigated. Finally, time to first occurrence was analysed.Results and Discussion. The incidence of STS in this study was identical to that reported by the US Department of Health in 1976. Five year survival rate for Stage I tumours was only 51.7% which compares very unfavourably with contemporary series from Multi-Disciplinary Units. Five year survival rate following wide local excision +/- adjuvant therapy is 52.4%, while that following amputation +/- adjuvant therapy is 45.5%. While not attaining the results reported by other centres, limb-sparing surgery does not appear to appreciably prejudice long-term survival.Conclusions. STS are rare in the UK, leading to poor classification and suboptimal treatment of lesions. It is important to establish multidisciplinary teams of surgeons, radiologists, radiotherapists and oncologists to plan and organise multimodality therapy for STS.     

Prognostic factors predicting survival in the treatment of retroperitoneal sarcoma.

METHODS: Retroperitoneal soft tissue sarcomas are rare tumours. The management of these tumours has been difficult because of low resectability and a high recurrence rate. A retrospective review of a prospectively compiled database of 32 consecutive patients with retroperitoneal sarcomas treated at Oulu University Hospital between 1977 and 1996 was performed. RESULTS: The resectability rate of primary tumours was 75%, and 44% of the patients underwent radical resection. The recurrence rate after radical resection was 57% and the resectability rate for recurrent tumours after radical primary operation, 50%. The actuarial overall 5-year survival rate was 31%, 10-year survival rate 19% and median survival 36 months. In univariate analysis the principal factors associated with prognosis were radical resection, recurrent disease, pre-operative loss of weight and histological tumour grade. Complete excision of the primary tumour was the only significant predictor of survival in multivariate analysis. CONCLUSIONS: Complete resection of retroperitoneal sarcoma continues to be the most important prognostic factor. The inefficiency of adjuvant therapy, the high recurrence rate and the very low chance of curing the patient after recurrence make the prognosis of these patients poor.     

Primary breast synovial sarcoma: a rare primary breast neoplasm

A primary synovial sarcoma based on the breast is rare. The usual tumours on the breast are carcinomas. Synovial sarcomas account for about 6–9% of soft tissue sarcomas and most commonly develop in the extremity of young adults (80%). The other 20% of synovial sarcomas can arise in non-extremity sites (trunk 8%, retroperitoneal/abdominal 7%, head and neck 5%) but synovial sarcomas can develop in almost any other anatomical location. We report a case of a young woman who presented with a suspected common breast tumour and started treatment of this tumour with carcinoma neoadjuvant chemotherapy. We were surprised when the pathologist identified a synovial sarcoma in the histopathology study.     

Incidence and survival of soft tissue sarcoma in England between 2013 and 2017, an analysis from the National Cancer Registration and Analysis Service

There is a paucity of population-based data detailing the incidence and survival of patients with soft tissue sarcoma (STS), in part due to the heterogeneity of disease and changes to classification. Here, the incidence and survival of all STS subtypes registered in England between 2013 and 2017 were analysed using cancer registry data held by the National Cancer Registration and Analysis Service. Age-standardised incidence rates were calculated per 1 000 000 using the 2013 European Standard Population. Net survival was computed using Brenner's alternative method, with the Ederer II estimator. Age-specific overall survival was assessed using Kaplan-Meier. The influence of age, sex, socioeconomic deprivation and diagnostic routes on survival was assessed using Cox proportional hazards modelling. In total, 19 717 patients were diagnosed with STS, an average of 3943 patients per year and representing approximately 0.8% of malignancies. The most common histological diagnoses were Gastrointestinal Stromal Tumours (GIST), leiomyosarcoma and undifferentiated sarcoma, accounting for 20.2%, 13.3% and 12.7% of all sarcomas, respectively. Five-year net survival for all malignant STS was 65.0%; and was lowest for patients with vascular tumours at 39%. Patients from most deprived cohorts had 23% greater chance of dying within 5 years than patients in least deprived areas. This population-based study has allowed us for the first time to define the incidence and survival rates of prevalent STS subtypes in England such as GIST, liposarcoma and leiomyosarcoma, as well as rare entities and groups with inferior outcome. This data is invaluable for service provision, benchmarking and addressing inequality.     

Extraosseous retroperitoneal Ewing’s sarcoma

Ewing's sarcoma/primitive neuroectodermal tumour (ES/PNET) belongs to the group of paediatric small round blue-cell tumours. ES/PNET is classically a tumour of the soft tissue or bone in children and young adults. The case of a 21-year-old woman with a retroperitoneal localisation of Ewing's sarcoma is described.     

Structural alterations of the RB1 gene in human soft tissue tumours

Sixty-nine primary soft tissue tumours were examined for alterations of the RB1 gene which has previously been implicated in the genesis of retinoblastoma. In three tumours loss of both alleles of this gene (homozygous deletion) was detected. Two of these, both leiomyosarcomas, contained a chromosomal breakpoint within the RB1 gene, while in the third tumour, a radiation induced sarcoma, complete deletion was observed. Using a probe that detects a polymorphic locus within the RB1 gene we found loss of only one allele (heterozygous deletion) in 33% of soft tissue sarcomas examined, including two leiomyosarcomas, a malignant peripheral nerve sheath tumour, a rhabdomyosarcoma and a chondrosarcoma. When taken together our results suggest that alterations of the RB1 locus may play an important part in the pathogenesis of soft tissue tumours and particularly in leiomyosarcomas which accounted for four of the eight RB1 alterations observed in this study.     

Tumour oxygenation assessed by 18F-fluoromisonidazole PET and polarographic needle electrodes in human soft tissue tumours.

BACKGROUND AND PURPOSE: The aim of the study was to identify hypoxia in human soft tissue sarcomas (STS) by PET scanning using the hypoxia marker [18F]-fluoromisonidazole ([18F]FMISO) and invasive oxygen sensitive probes (Eppendorf pO2 Histograph, Germany). MATERIALS AND METHODS: Thirteen patients with tumours suspected to be STS were examined by [18F]FMISO PET scanning, and eleven of these patients completed a set of Eppendorf pO2 Histograph measurements following the scanning. RESULTS AND DISCUSSION: By histopathological diagnosis, seven tumours were shown to be STS and six tumours were benign. Ratios between tumour and muscle radioactivity and time activity curves for tumours and muscle tissue were examined in defined regions of interest. Only two malignant tumours showed [18F]FMISO uptake in higher amounts than muscle tissue over time. Hypoxia was present in both benign and malignant tumours as measured by the oxygen electrode method. CONCLUSIONS: [18F]FMISO PET in our setting seemed not to be feasible for the detection of tumour hypoxia in human soft tissue tumours. Neither did it reflect the extent of hypoxia as determined with the oxygen electrode measurements.     

Significance of intraoperative radiation therapy and high cumulative radiation doses in retroperitoneal soft tissue sarcoma

IntroductionIn retroperitoneal soft tissue sarcoma (STS) local recurrence (LR) rates remain high despite more aggressive surgical approaches. Since wide resection margins cannot be achieved in all patients, application of intraoperative radiation therapy (IORT) has been frequently discussed. Still, the significance of IORT in multimodal treatment of retroperitoneal STS remains unclear.Material and methodsPatients undergoing resection of primary or recurrent retroperitoneal STS at the University of Heidelberg Department of General, Visceral and Transplantation Surgery were retrospectively analyzed. Univariate Kaplan-Meyer and multivariate Cox regression analyses were performed to identify predictors of LR-free survival and to investigate the impact of IORT and high cumulative radiation doses. Analyses with propensity-score matched subgroups for IORT and cumulative radiation dose were performed to control for selection bias. Subgroup analyses for patients with retroperitoneal liposarcoma were likewise performed.Results272 patients were identified. Recurrent tumors, histology of dedifferentiated liposarcoma or unclassified sarcoma and microscopically incomplete resection were associated with decreased LR-free survival. In liposarcoma, only recurrent and dedifferentiated tumors were confirmed as poor prognostic factors concerning LR. IORT and cumulative radiation doses exceeding 60 Gy did not influence LR rates (estimated 5-year LR-free survival: IORT: 39%, non-IORT: 46%; p = 0.79).ConclusionIn this retrospective evaluation, additional application of IORT does not significantly influence oncological outcome in retroperitoneal soft tissue sarcoma. Randomized trials are needed to clarify the benefit of IORT.     

Increased risk of malignancies in a population-based study of 818 soft-tissue sarcoma patients

Soft-tissue sarcomas (STS) have been associated with various rare cancer syndromes and occur at increased frequencies in survivors of childhood cancer. Also adult patients with STS have been suggested to be at an increased risk of additional malignancies. After exclusion of syndrome-associated and radiation-induced sarcomas, we studied multiple primary malignancies in a population-based cohort of 818 patients with primary STS of the extremities and the trunk wall. In total, 203 other malignancies developed in 164 (20%) patients median 10 (0-32) years before and median 4 (0-35) years after the sarcoma diagnosis. Standardised morbidity ratios (SMRs) were determined for primary malignancies following a STS. Hereby individuals who had developed a STS were identified to be at increased risk of second primary malignancies (SMR for all malignant tumours=1.3; 95% CI=1.0-1.5; P=0.02) with STS being the only specific tumour type that occurred at an increased risk (SMR=17.6; 95% CI=8.1-33.5; P<0.001). Hence, this population-based series demonstrates a high frequency of second primary tumours among STS patients and indicates a particularly increased risk of developing a new STS.     

Soft tissue tumours of the retroperitoneum

Purpose. This review summarizes the more prevalent soft tissue tumours arising in the retroperitoneum and highlights some recent fundamental and diagnostic developments relevant to mesenchymal tumours.Discussion. The retroperitoneum is an underestimated site for benign and malignant neoplastic disease, and represents the second most common site of origin of primary malignant soft tissue tumours (sarcomas) after the deep tissues of the lower extremity. In contrast to the predominance of benign soft tissue lesions over malignant sarcomas elsewhere, retroperitoneal mesenchymal lesions are far more likely to be malignant. The differential diagnosis is primarily with the more common lymphoproliferative and parenchymatous epithelial lesions arising in this area, and with metastatic disease from known or unknown primary sites elsewhere.The most prevalent mesenchymal tumours at this site are of a lipomatous, myogenic or neural nature.Their generally late clinical presentation and poorly accessible location provides numerous clinical challenges; optimal radiological imaging and a properly performed biopsy are essential cogs in the management route. Histopathological diagnosis may be complicated, but has been aided by developments in the fields of immunohistochemistry and tumour (cyto)genetics. Despite significant advances in oncological management protocols, the prognosis remains generally less favourable than for similar tumours at more accessible sites.     

Surgical management of soft tissue sarcoma in patients over 80 years

AIMS: To report outcome on patients over 80years of age with soft tissue sarcoma (STS), with respect to surgical treatment, co-morbidity, complications and survival. METHODS: From a prospective database of 3400 patients with STS presenting over a 13-year period, all patients over 80years of age were identified and reviewed, with respect to tumour characteristics morbidity, mortality and outcome. RESULTS: 128 patients over 80years were treated for STS with 63 referred for treatment of primary disease, of whom 50 underwent resectional surgery. The remaining 65 patients were treated for recurrent or incompletely excised disease. Of the 50 patients treated primarily with surgery, 56% of tumours where high grade and 56% were greater than 10cm in diameter. The overall complication rate was 34%, with a 30-day mortality of 4%. Two- and 5-year survival rates were 56% and 46%, with a local recurrence rate of 22% at a mean follow-up of 22months. CONCLUSION: This patient group presented with poor prognosis tumours that were associated with poor outcomes in the medium to long term. Age need not be considered a contra-indication to radical surgery with curative intent.     

The management of retroperitoneal liposarcoma with synchronous intra-duodenal sarcoma.

Intra-abdominal (as opposed to extremity or limb and limb-girdle) soft tissue sarcomas (STS) are rare and account for less than 1% of all diagnosed neoplasms. These tumours are usually associated with a poor prognosis and are often locally invasive and metastatic at the time of presentation. Retroperitoneal sarcomas with synchronous or metachronous different histological types are rare and intra-duodenal sarcomas extremely unusual. A case of a giant retroperitoneal STS weighing approximately 15 kg consisting of two histologically different types is presented. Intra-duodenal involvement with sarcoma was found intra-operatively. We discuss the management of this condition in the context of an illustrative case in our recent experience.     

The adhesion molecule CD44v6 is associated with a high risk for local recurrence in adult soft tissue sarcomas

In many malignant diseases the expression levels of CD44 and its splice variant v6 (CD44v6) have been associated with the prognosis. The purpose of this study was to investigate the clinical significance of CD44 in adult soft tissue sarcomas (STS). 133 STS patients with a limb or superficial trunk tumour treated at the Helsinki University Central Hospital in 1987-1993 with a median follow-up time of 68 months were included in this study. The expression of CD44 and CD44v6 was determined immunohistochemically on paraffin-embedded tumour samples. 95% of the tumours expressed CD44 and CD44v6 was detected in 57%. Strong CD44 expression was associated with low grade (P = 0.04) and small tumour size (P = 0.02). In diploid tumours the CD44 expression was correlated with low S-phase fraction (P = 0.001). High expression of both, CD44 in general as well as that of CD44v6, predicted a higher risk for local recurrence (CD44: P = 0.01 and CD44v6: P = 0.05). Low CD44v6 content of the primary tumour correlated with poor survival (P = 0.02). Determining the expression of CD44 or CD44v6 in a primary STS could be a valuable tool for selecting the group of patients who might benefit from intensified local tumour treatment.     

Prognostic information in soft tissue sarcoma using tumour size,vascular invasion and microscopic tumour necrosis-the SIN-system

We have earlier devised a system for soft tissue sarcoma (STS), based on three negative prognostic features: large tumour size, vascular invasion, and microscopic tumour necrosis, the SIN-system. Tumours which exhibit 2 or 3 of these features are categorised as high-risk, the others as low-risk. We have now tested this system for reproducibility both as regards recognition of its components, and as regards prognostic strength in patients from another institution. We have also compared it with the American Joint Committee on Cancer (AJCC) system. 200 patients with STS were analysed, all had been treated by surgery, in 97 patients combined with radiotherapy. The median follow-up for the 117 survivors was 10 (1.5-27) years. Without knowledge of the clinical data, three groups of pathologists independently reviewed original slides from all of the tumours. Based on the factors, the tumours were classified as high-risk or low-risk. The prognostic strength was compared using the results obtained by the different observers. Concordance in recognition of vascular invasion, tumour necrosis, and overall grading was seen in 156 (78%), 154 (77%), and 167 (84%) of the 200 tumours, respectively. Based on the different observers' grading, the cumulative 5-year metastasis-free survival rate (MFSR) varied for patients with low-risk tumours between 0.85 and 0.80, and for patients with high-risk tumours between 0.48 and 0.43. The Kappa-value for grading between all three groups of observers was 0.77. The SIN-system gave more clinically useful prognostic information than the AJCC system. Useful prognostic information in STS can be obtained by using tumour size, vascular invasion and microscopic tumour necrosis. This system provides two distinct prognostic groups, and has a high reproducibility.     

The significance of size change of soft tissue sarcoma during preoperative radiotherapy

Aim

To assess the significance of change in tumour size during preoperative radiotherapy in patients with soft tissue sarcoma (STS).

Methods

A retrospective review of 91 cases with STS was performed. Inclusion criteria were localised extremity and truncal STS with measurable disease, older than 18 years, treated with preoperative radiotherapy and wide local excision, in the period between January 1966 and December 2005. Patients with head and neck STS, or who received neoadjuvant chemotherapy were excluded. A difference in excess of 10% of the greatest tumour diameter of the pre-radiotherapy and the post-radiotherapy MRI scans was considered as change in tumour size.

Results

Increase in tumour size was noted in 28 patients (31%) (Group 1). No change or decrease in size was observed in 63 patients (Group 2). There were no significance differences in local control or overall survival rates between the 2 groups. The estimated overall actuarial local recurrence free, event-free and overall survival rates were 90.5%, 64.4%, 62.9% in Group 1, and 85.7%, 60.8%, 68.9% in Group 2 respectively.

Conclusion

Increase in tumour size during preoperative radiotherapy for soft tissue sarcoma does not seem to associate with inferior local tumour control or compromise survival. Lack of reduction in tumour size is not necessarily a sign of lack of response to preoperative radiotherapy.     

Extraskeletal Ewing's sarcoma presenting with pulmonary embolism

Small round cell tumours with the morphologic characteristics of Ewing's sarcoma arise rarely in soft tissues of the extremities, retroperitoneum, chest and orbit. Patients usually present with symptoms arising from the swelling at the primary site. We report on a patient with a retroperitoneal extraskeletal Ewing's sarcoma who presented with massive tumour embolism to the pulmonary vasculature. To our knowledge, this is the first report of extraskeletal Ewing's sarcoma presenting with pulmonary tumour embolism.     

Outcome and toxicity of an Ifosfamide-based soft tissue sarcoma treatment protocol in children. The importance of local therapy

Background. Although the survival of children with soft tissue sarcoma (STS) has improved considerably, the outcome of patients with metastatic disease, and those with primary tumours of the extremities or parameningeal sites remains disappointing. We describe the clinical outcome of an ifosfamide-based regimen with local therapy directed only to children who failed to achieve a complete response to initial chemotherapy.Patients and Methods. Twenty-one children with STS (16 rhabdomyosarcoma) who presented with unresectable tumours were treated with five courses of ifosfamide (9 g/m(2)) and etoposide (600 mgm(2)). Patients who did not achieve a complete response then received local therapy. Chemotherapy with ifosfamide combined with etoposide, vincristine (1.5 mg/m(2) and doxorubicin (60 mg/m(2)) or vincristine and actinomycin D (1.5 mg/m(2)) was continued for one year.Results and Discussion. Objective responses to five courses of ifosfamide and etoposide were seen in all patients. Disease free survival (DFS) at a median follow up of 59 months was 57% (95% CI 29-75%). The DFS of children who received local therapy was 89% compared with 33% in those who received chemotherapy alone (p=0.027). Locoregional recurrences did not occur in children who received radiotherapy to the site of the primary tumour. Ifosfamide-based chemotherapy does not reduce the incidence of loco-regional recurrence in children who do not receive local therapy.