Multiple primary malignancies in association with soft tissue sarcomas

BACKGROUND: Modern cancer treatment has increased the survival of patients with various malignancies substantially. One of the late sequelae of successful treatment is the development of a second malignant tumor. However, in many cases of second primary tumors, exposure to chemotherapy or radiation therapy is not evident, and it should be postulated that the putative mechanism for the development of the second tumor is different. In the current series, the association between soft tissue sarcoma (STS) in adults and the development of other primary malignancies was studied. METHODS: A retrospective search of the data files of 610 patients with STS or bone sarcomas who were treated at the study institution between January 1995 and December 1999 was performed. All files regarding patients with STS who developed a second malignant tumor were retrieved for analysis. RESULTS: Of 375 patients with STS, 28 (7.5%) developed other malignant neoplasms either before or after the diagnosis of STS. STS as the first tumor occurred in 14 patients (ages 16-72 years). Only three patients were treated with chemotherapy for their sarcoma. Radiation therapy was administered to five patients as an adjuvant to surgery for the first tumor. The second tumor types mainly included STS and renal cell carcinoma. The time interval between the diagnosis of the STS and the second malignancy was 0 (for synchronous tumors) to 21 years. Three patients developed a third primary tumor within 3 years after the diagnosis of the second tumor. The median overall survival was > 78 months. Fourteen patients (ages 35-87 years) had a first primary tumor other than STS (mainly breast carcinoma and genitourinary malignancies). The second tumors (mainly STS) appeared within 0 (for synchronous tumors) to 27 years. The median overall survival for the 14 patients in this group from the time of diagnosis of the first tumor was > 102 months. CONCLUSIONS: The phenomenon of two or three primary neoplasms developing in patients in whom one of the tumors was STS occurs at a rate of 7.5%, a significantly higher rate than that reported for the occurrence of STS among the general cancer population (1%). The majority of cases occur incidentally. The clinical implication includes the need to search for an occult second primary tumor in patients with STS as an integral part of their follow-up. This is especially true in patients with primary malignant fibrous histiocytoma who demonstrate a risk for developing a renal cell carcinoma.     

Pediatric soft tissue sarcomas

Many of the soft tissue sarcomas that occur in children are of the same histology as those in adults; however, the relative prevalence of these sarcomas is different between children and adults. In some cases, the biologic behavior of pediatric sarcomas is more benign than that in adults. Treatment for sarcomas in children is also different. Pediatric sarcomas are more commonly responsive to chemotherapy. Furthermore, in children who are still growing, surgery and radiation are associated with higher morbidity than in adults. This article discusses the diagnosis and treatment of rhabdomyosarcoma and undifferentiated sarcomas, with an emphasis on surgical considerations, and the diagnosis and treatment of nonrhabdomyosarcomatous soft tissue sarcomas in children.     

Pelvic soft tissue sarcomas

Pelvic soft tissue sarcomas (PSTS) are a rare, heterogeneous group of tumors. They have been usually analyzed with retroperitoneal sarcomas (RPS), but actually have key differences. Due to their unique anatomic location, symptomatic presentation of PSTS may be more common than RPS. Adequate imaging approach is paramount for guiding differential diagnosis, while preoperative biopsy is mandatory, especially when preoperative treatment may be considered as initial approach. The most frequent histologic subtype is leiomyosarcoma, which is different as expected in the retroperitoneum where liposarcoma is the commonest histology. Also solitary fibrous tumor is commonly diagnosed in the pelvis. Surgical approach for PSTS differs from that for RPS mainly due to anatomic relations. Similarly, in the lack of definite evidence from specific trials about neoadjuvant and adjuvant treatments, the anatomic constraints to obtain wide margins in the pelvis as well as the expected functional outcome in case of organ resections should be factored into decision for individualized treatment offer. Vascular and genitourinary involvement are frequent, as well as herniation through pelvic foramina. For these reasons a multidisciplinary surgical team should always be considered. Early referral of these patients to high-volume centers is critical and may impact on survival, given that optimal initial resection is a major predictor of curative treatment. International consensus on PSTS treatment is advocated, similarly to the recent efforts realized for RPS.     

Follow-up in soft tissue sarcomas

The strategy for the follow-up of soft tissue sarcomas (STS) after therapy is tailored to the individual risk of recurrence and based on efficient rather than sophisticated methods of observation. Along with advances in the treatment of sarcomas, earlier detection of a less advanced and resectable recurrent disease (local or metastasis—especially to the lungs) can prolong patient survival. Since the majority of STS relapses occur within 5 years after treatment (approximately 80?% of metastases to the lung and close to 70?% of local recurrences within the first 2–3 years), in the period between 2 and 3 years after treatment, it is mandatory to follow-up patients every 3 months and perform careful history and physical examination (especially scars after surgery of the primary site) and a chest X-ray. There is no reason to perform other studies in asymptomatic patients (unless the patient reports symptoms). In case of retroperitoneal or intraperitoneal STS (including gastrointestinal stromal tumor), contrast-enhanced computed tomography of the abdomen and pelvis is recommended as the follow-up modality of choice. In this paper we outline the current recommendations for the follow-up strategy.     

Update on soft tissue sarcomas

Important refinements have taken place in the diagnosis of soft tissue sarcoma with extensive use of immuno-histochemistry. New entities have been described, while malignant histiocytofibroma, the most diagnosed sarcoma type during the last two decades, has been dismembered. As for prognosis, the new UICC classification is effectively more discriminating in the definition of prognostic groups; but the usefullness of new biological or genetic markers remains to be assessed. Several breakthrough have taken place in the last years in the treatment of soft tissue sarcoma. Isolated limb perfusion with TNF, hyperthermia and melphalan have proven its efficacy, and is now an alternative to preoperative chemotherapy and/or radiotherapy for limb sparing treatment of the primary tumor site or to amputation. For systemic treatments, novel cytostatic drugs have been shown to be active in sarcomas, including ecteinascidine (ET743) and Glivec (STI571). This last drug has been shown to be remarkably active in c-kit+ stromal sarcoma of the gastro-intestinal tract. It can hopefully regarded as an example for targeted therapies, which may come with a better understanding of the molecular mechanisms triggered by the fundamental, specific genetic alterations shown in sarcoma.     

Pediatric nonrhabdomyosarcoma soft tissue sarcomas

The nonrhabdomyosarcoma soft tissue sarcomas (NRSTSs) are a heterogeneous group of mesenchymal cell neoplasms that account for about 4% of childhood cancers. Because each histologic subtype of NRSTS is rare, they have been poorly studied and little is known about their biology, natural history, or optimal treatment. Data from adults with soft tissue sarcomas provide some helpful insight, but adult and childhood NRSTSs differ considerably in the distribution of their histologic subtypes, and certain entities are known to behave differently in young children. The greater risks posed to children by treatment, particularly by radiotherapy, also must be considered in treatment planning for children. This article summarizes what is known to date about childhood NRSTS, including the epidemiology, pathogenesis, and clinical approach to diagnosis and treatment of these tumors.     

Treatment and local control of primary extremity soft tissue sarcomas.

BACKGROUND AND OBJECTIVES: Modern series of adult extremity soft tissue sarcomas utilize combinations of modalities in all patients. Remaining questions: 1) is it necessary to strive for wide margins in the multimodality era; 2) to use adjuvant therapy in every high-grade sarcoma? 3) Does previous partial or marginal resection seriously interfere with the definitive resection? METHODS: In a retrospective review of 194 extremity soft tissue sarcomas (1977-1994), limb preservation was possible in 181/194 (93%) of cases. Patients with narrow margins received adjuvant radiation. Some patients were referred after partial (n = 39) or "complete" (n = 63) excision. RESULTS: Local recurrence was observed in 181/141 (13%) of patients treated with wide or compartmental resection, and in 10 of 42 (24%) of those treated with conservative resection plus radiation (P = 0.14). The 5-year survival rate for grade III, >/=5-cm sarcomas was not significantly different (P = 0.82) with adjuvant (46%) or without (48%) adjuvant systemic chemotherapy. Five-year survival varied (P = 0.0001) according to grade. Patients referred with partial, or "complete" (63%, 38/63, had residual tumor at reoperation) excision had a local recurrence rate of 8% and 6%, and 5-year survival rates of 75% and 84%, respectively. CONCLUSIONS: 1) It is important to strive for wide margins even when adjuvant radiation is intended. 2) When a wide margin is possible, adjuvant radiation may not be necessary. 3) Adjuvant systemic chemotherapy may be considered for high-grade tumors, preferably within a prospective protocol. 4) A partial or "complete" excision of the tumor before referral to a tertiary center does not appear to compromise the limb preservation, local control, or survival rates of these patients.     

Liver metastases from soft tissue sarcomas

Twenty-three patients with liver metastases from soft tissue sarcoma were reviewed. Patients with metastases to the liver first had poorer survival than those who developed spread to other sites first (P=.0035). The median time from diagnosis of the primary tumor to diagnosis of liver metastases was 14 months; the median time from diagnosis of liver metastases to death was 7 months. The median survival from diagnosis for four patients who underwent liver resection was 54 months compared to 20 months for those who did not undergo resection (NS). Soft tissue sarcomas rarely metastasize to the liver; when this occurs it is usually late in the course of the disease and after it has spread to other sites. The opportunity for successful liver resection is infrequent but may prolong survival. © 1995 Wiley-Liss, Inc.     

Chemotherapy in soft tissue sarcomas]

Despite they represent an heterogeneous entity, the same protocols were applied to all subtypes of soft-tissue sarcomas until recently. Although doxorubicin and ifosfamide remain the cornerstone of therapy, their association yields enhanced response rates but has no obvious effect on survival. The benefit of adjuvant therapy is still matter of debate; however, it seems to improve relapse-free survival and might of particular interest for patients with high-grade tumours of the extremities. Yet, the major change occurring over the past few years is probably the development of subtype-specific regimens. Whether targeted therapies could provide additional benefit is a major concern but further studies are needed.     

软组织肉瘤的非计划切除

虽然软组织肿瘤的发病率较高,但其中以良性肿瘤居多[1],而软组织肉瘤的发病率较低,仅占所有恶性肿瘤的0.8%～1.0%[2-3]。在我国,目前尚没有有效的转诊制度。骨与软组织肿瘤的患者,特别是软组织肿瘤的患者的治疗既有在骨科进行的,也有在普通外科进行的,甚至于在其他的一些外科专业科室接受治疗[4]。即便是在骨科进行治疗,也多不是经由专业的骨与软组织肿瘤专业医师。另一方面,我国的骨与软组织肿瘤专科培训工作尚不普及,地区差别较大。甚至于发达地区的大型综合医院,其骨与软组织肿瘤的治疗理念也与专科医师存在巨大的差异。临床上,特别是那些发生在深筋膜浅层的肿物,经常会见到在没有术前影像学检查的情况下,或仅凭一个B超报告就进行了草率的切除而术后病理证实为软组织肉瘤的病例。有时甚至是直到复发再次就诊时都没有第一次手术后病理诊断的病例。因此,治疗方法参差不齐,效果难以保障。一旦患者术后诊断为肉瘤,就会给患者造成不必要的损失。     

Targeted therapy of soft tissue sarcomas

Soft tissue sarcomas (STS) are rare mesenchymal cancers with a heterogeneous histology. In terms of oncogenesis, sarcomas may be differentiated into diseases with defined molecular events and sarcomas presenting with complex karyotypes lacking identifiable specific genetic changes or expression profile signatures. The former subtype is amenable to therapy with targeted drugs, especially if the tumor carries a consistent causal mutation occurring early in the disease development. While targeted therapy based on tyrosine kinase inhibition such as imatinib and second generation tyrosine kinase inhibitors plays an important role in the treatment of gastrointestinal stromal tumors (GIST), some progress was also achieved in non-GIST sarcomas. Targeting the PI3 kinase/Akt pathway has been shown to be clinically promising in a diversity of different sarcoma subtypes, and inhibition of the vascular endothelial growth factor (VEGF)/VEGF receptor pathway is of special interest in vascular sarcoma subtypes. MDM2 and p53 seem to be interesting targets for STS, but their role has yet to be defined in further clinical trials. Modification of epigenetic mechanisms, especially deacetylation, might be crucial in other STS subtypes such as translocation-associated entities, but its role has yet to be clinically confirmed. Inclusion of patients in controlled clinical trials combined with a translational research platform is critical for further progress.     

Adjuvant chemotherapy for soft tissue sarcomas

Soft tissue sarcomas are rare mesenchymal neoplasms with considerable heterogeneity in biologic behavior and response to systemic therapy. Most patients present with localized disease and are potentially curable with multidisciplinary treatment. In patients with a high risk of developing metastatic disease, optimal use of neoadjuvant/adjuvant therapy has a definite role in improving patient outcomes by decreasing local and distant recurrences. Histology-specific clinical trials enrolling a homogenous high-risk population have been more successful in demonstrating benefit than larger trials with unselected heterogeneous patient populations. In specific histologic subtypes responsive to chemotherapy, neoadjuvant chemotherapy with close monitoring of response is recommended.     

Clinical trials and soft tissue sarcomas

Soft tissue sarcomas are a challenging disease entity with a variety of histologic subtypes that can arise anywhere on the body. Much effort has been put forward to advance the care of patients with soft tissue sarcomas. Radical amputations have largely given way to limb-sparing procedures. With multimodality treatment, there has been progress in local control rates as well. As knowledge of the basic biology of this disease grows, there likely will be new strategies to treat soft tissue sarcomas. The development of STI-571, and its demonstrated effectiveness in GIST, represents an important advance in the treatment of these tumors and potentially a new paradigm for the development of therapeutic intervention in other sarcomas. Developing collaboration among ACOSOG other cooperative groups in the United States, Canada, and Europe may provide physicians with new venues for asking important clinical questions about these low-incidence tumors. The importance of collaboration in enrolling patients in clinical trials to evaluate these future therapies cannot be overstated.     

Imaging of sarcomas of soft tissue

Modern imaging of soft tissue sarcomas now includes ultrasounds, CT and MRI. These new techniques allow a better evaluation of initial local extension, of the response to treatment and are able to detect local recurrences early.     

Brachytherapy in soft tissue sarcomas]

Soft tissue sarcomas are rare tumors with a high risk or local recurrence and a risk of distant metastases. Standard treatment advocated is the combination of conservative resection and external radiotherapy. Brachytherapy is an integrated part of the multidisciplinary treatment. Brachytherapy can increase local control with good functional results. Primary exclusive brachytherapy has been used and is effective and safe in high grade sarcomas (randomized trial of MSKCC). Brachytherapy seems to be important as part of the treatment of central localization (shoulder, groin) and sarcomas with positive resection margins, but its relation with external radiotherapy has to be defined. Brachytherapy used with special guidelines allows to obtain an improved local control with an acceptable level of complication.     

Multidisciplinary management of soft tissue sarcomas

Musculoskeletal sarcomas are a heterogeneous group of malignant neoplasms derived from connective tissue. Sarcomas represent about 1% of cancer in adults. The annual incidence in adults in Europe is around 14,000 new cases of soft tissue sarcomas (STS) and 4,800 new cases of bone sarcomas. Musculoskeletal tumours arise anywhere in the body, although lower extremities are the most common site of appearance, followed by upper extremities, trunk, retroperitoneum and head and neck area. Adequate management of STS is a stimulating challenge for oncologists. The aim of treatment should be focused on four main aspects: improving survival, avoiding local recurrence, maximising organ function and, finally, minimising morbidity. Surgery, radiotherapy and, sometimes though increasingly, chemotherapy are the pillars on which rests the modern treatment of sarcomas. The optimal management of musculoskeletal tumour requires a multidisciplinary integration of these different approaches in treatment planning right from the initial diagnoses. Referring patients to qualified centres should be desirable to achieve the maximum probability of control and even cure for STS.