Sarcomas of the bone and soft tissue: general observations

The term sarcomas regroups a large variety of malignant tumors originating from the mesenchymal tissues, which represent only 1% of cancers, with a higher relative frequency in children. Whether bone or soft tissue tumors, their preeminent general evolutive characteristics are a high local aggressiveness and a high frequency of hematogenic metastatic diffusion, with a predilection for pulmonary involvement. An improved knowledge of the natural history of sarcomas has led to a better definition of multidisciplinary therapeutical protocols for each particular disease.     

Sarcomas of soft tissue in the adult. Therapeutical indications

Treatment of soft-tissue sarcomas has to deal simultaneously with three goals: 1) to obtain the control of the primary tumor, 2) to preserve the function, and 3) to treat the micrometastatic disease. For local control, surgery remains the most efficient treatment, but the extent of the resection of macroscopically non-involved tissue, and as consequence, resulting dysfunction, can be reduced by properly planned postoperative radiotherapy and chemotherapy. Moreover, surgery may be easier, following preoperative radiotherapy or chemotherapy, which may also allow secondary excision of a primarily inoperable tumor. For the treatment of the micrometastatic disease, the efficacy of adjuvant chemotherapy has to be confirmed by further studies; some results published to date are encouraging. Thus, treatment of soft-tissue sarcomas remains difficult, but important advances are to be expected in the next few years. A multidisciplinary approach is necessary, involving not only surgeons, radiotherapists and medical oncologists, but also radiologists and pathologists.     

Solitary plasmacytoma of bone and soft tissue

Between 1962 and 1978, 15 patients presenting with a solitary plasmacytoma were treated with curative intent by radiotherapy alone at the University of Florida. Criteria for admission to this study were: 1) a biopsy-proven, apparently solitary focus of plasmacytoma; 2) bone marrow biopsy showing less than 10% plasma cells; and 3) no evidence of disseminated disease. In 9 patients the primary site was osseous and in 6 patients extramedullary; 5 of the 6 extramedullary lesions were located in the upper respiratory passages. Two of the 6 extramedullary plasmacytomas progressed to multiple myeloma at 2 and 7 months. The remaining 4 patients have been disease free for periods ranging from $\text{2}\text{2}\text{3}$ years to over 16 years. Of the 9 patients with osseous lesions, 3 developed multiple myeloma in 3–23 months and one developed a solitary second bone lesion at 9 years. One patient with a large sacral lesion developed a local recurrence following an initial radiation dose of 3000 rad. The recurrence was re-treated with radiation, and local control was obtained. No other local failures occurred. This study presents a detailed analysis of the time-dose relationship required for local control, based on a study of our own patients and a review of the literature.     

Epidemiology of bone and soft tissue sarcomas

Although bone and soft tissue sarcomas are not common, a significant number of patients who develop these tumors will die with metastatic disease. Part of the reason is that many of the patients have advanced disease at diagnosis. Identification of an etiologic agent should allow for diagnosis at an earlier stage. This is particularly true of radiation-induced sarcomas because patients who develop this malignancy seem to have a poor prognosis. As more patients survive their malignancies, we may see an increase in the incidence of postradiation sarcomas. Therefore, patients who receive radiation should be monitored closely, and a high index of suspicion should be maintained for complaints referable to the irradiated site. The role of various chemical agents in the development of sarcomas needs further definition, as the literature is replete with conflicting reports. Problems exist in that we are dealing with a variety of agents with different levels of exposure, possibly resulting in different types of neoplasms. Additionally, many of the agents in question are not pure substances, but frequently are contaminated with other potentially carcinogenic agents. Finally, the majority of studies reported are from different countries. Thus, there may be unidentified operative genetic and environmental factors. The recent advances in cytogenetics and molecular biology have already resulted in a significant increase in information related to bone and soft tissue sarcomas. Many chromosomal abnormalities identified will have diagnostic, prognostic, and therapeutic implications. Even more exciting is the fact that the identification of chromosomal abnormalities directs us to investigate abnormal areas of the genome that may identify the changes responsible for malignant degeneration on a molecular basis.     

Xeroradiography of bone and soft tissue tumors.

Xeroradiography was used for the study of 233 cases of bone and soft tissue tumors, both benign and malignant, 177 of which were histologically proven. In 150 cases, comparative x-ray films were also available. In bone tumors, xeroradiography was more effective than film radiography in 33 cases (44%), less effective in 16 cases (22%) and the 2 techniques were substantially equivalent in 25 cases (34%). In soft tissue tumors, xeroradiography was more effective than film radiography in 59 cases (78%), less effective in 2 cases (3%) and equivalent in 15 cases (19%). Xeroradiography is held to be a useful second-line technique in selected bone tumors, in particular for the study of trabecular structure, periosteal calcifications and cortical bone. In the field of soft tissue tumors, xeroradiography can be a promising first-choice examination in the presence of a mass or when a recurrence is suspected. The advantages and drawbacks of this technique in both types of tumors are reviewed and discussed.     

Chemotherapy of advanced bone and soft tissue sarcoma

The primary site of metastasis of bone and soft tissue sarcoma is the lung. Control of these sarcomas depends upon the prevention and treatment of their pulmonary metastasis. The introduction of a chemotherapy consisting mainly of Adriamycin and high-dose methotrexate dramatically improved the prognosis of osteosarcoma. However the effectiveness of chemotherapy has not yet been duplicated in soft tissue sarcomas except some childhood sarcomas. We analyzed the clinical data for pulmonary metastasis of osteosarcomas and soft tissue sarcomas. Based on these analyses, we tried to clarify the nature of pulmonary metastasis of these sarcomas and to evaluate its response to treatment, that this would yield clues to future treatment of these sarcomas.     

Prognostic factors of bone and soft tissue sarcomas

Prognostic factors of bone and soft tissue sarcomas were analyzed and common factors observed were the size of tumor, histological malignancy and metastasis. When these factors were viewed in advance of treatment, however, the prognosis of the sarcomas has definitely improved with chemotherapy and radical surgery of primary and metastatic lesions, combined and not combined with radiotherapy. Preoperative adjuvant chemotherapy now plays an important role in the whole strategic regimen of cancer treatment. Of various prognostic factors, the dominance of the sensitivity of each patient to preoperative adjuvant chemotherapy was indicated.     

Historical note on bone and soft tissue sarcoma

Since antiquity, the large bony and fleshy tumors have been called sarcomas. It was not until after the development of cellular pathology during the middle of the 19th century that sarcomas were separated from carcinomas on the basis of their tissues of origin. This paper traces the growth of these ideas as well as the introduction of effective methods of treatment of the sarcomas.     

Surgical treatment for bone and soft tissue sarcoma

There are many kinds of wide excision or wide resection, which are methods to remove the tumor with surrounding tissues. The curability of wide resection depends on the range and characteristics of the normal surrounding tissues. The fascia, periosteum and perivascular sheath act as barriers against invasion of tumors. Therefore, evaluation of the surgical margin is essential in surgery for malignancy. Some sarcomas characteristically show invasive growth patterns while others have a discrete border. Causes of the local recurrence are 1) insufficient surgical margin, 2) skip metastasis, 3) tumor thrombus, and 4) lymph node metastasis. The so-called "Safety surgical margin" is the margin that prevents local recurrence due to insufficient surgical treatment. Local recurrence due to other causes can not be treated by surgery alone as chemotherapy is also required. For example, the infiltrative type of malignant fibrous histiocytoma requires a curative procedure. On the other hand, non-infiltrative types of sarcoma or high-grade sarcoma, which are good responders to preoperative treatment, are locally controlled by an adequate wide margin procedure. When the tumor is close to the bone, main vessels and/or nerves, it is sometimes very difficult to preoperatively decide whether or not to sacrifice these important organs. A new surgical method, "In Situ Preparation (ISP)," is a useful method to solve such problems. ISP makes it possible to evaluate the surgical margin without contamination. And additional procedures including alcohol soaking or pasteurization can be achieved according to the surgical margin. Because ISP can prevent overtreatment, the number of our cases that require resection of the nerves or vessels have decreased. After a wide resection, there have been many possible complications, including infection, deep venous thrombosis, loosening of prosthesis, skin necrosis, and arterial occlusion. Once postoperative complications occur, patients must remain in the hospital for a long time. To prevent this, the preservation of normal tissue, meaning reduction of surgical margin, is important.     

骨与软组织肿瘤穿刺活检技术

目的探讨穿刺活检的技术及方法。方法自1994年1月至2004年12月共有1304例骨与软组织肿瘤患者在我院接受治疗,通过分析术前穿刺活检病理与术后病理的相关性,研究穿刺活检的技术特点及影响穿刺活检准确性的因素及改进方法。结果将术前穿刺病理及术后病理的相关性分为三种:正确、支持、阴性。1304例穿刺活检,正确918例(69.4%),支持346例(26.2%),阴性57例(4.4%)。结论穿刺活检是损伤小、操作简便的获取病理诊断的方法,在影像学检查的指导下可完成复杂部位的活检,具有很高的准确率。     

术中置管近距离放疗在骨与软组织肉瘤治疗中的应用

目的分析术中置管近距离放疗在骨与软组织肉瘤综合治疗中应用的疗效和毒性。方法163例骨与软组织肉瘤的病例，其中59例采用手术＋化疗＋外照射，另外104例采用手术＋化疗＋近距离放疗＋夕h照射的综合治疗方法。结果采用近距离放疗的一组患者有较好的疗效和较低的毒性。结论术中置管近距离放疗在骨与软组织肉瘤的综合治疗中有较好临床应用价值．．     

Chemotherapy using cisplatin in bone and soft tissue sarcoma

Cisplatin was used in 14 bone and soft tissue sarcomas. Severe vomiting developed in all cases, but the duration was relatively short. Renal function was disturbed in cases with a higher total dose. This side effect was considered to be the dose-limiting factor of cisplatin. Seven cases showed high-frequency deafness but they did not complain of disturbance during conversation. In seven metastatic osteosarcomas, one was evaluated as a partial response and one as a minor response. No response was observed among three soft tissue sarcomas. Three cases of osteosarcoma receiving cisplatin in adjuvant chemotherapy have been disease-free for 4 and 46 months after resection of pulmonary metastases and for 50 months after resection of the primary tumor. We consider cisplatin to be the first-choice drug in cases resistant to adriamycin or methotrexate, but there are some problems when cisplatin is used in adjuvant chemotherapy, because of its side effects.     

Hypofractionated radiotherapy for non-metastatic bone and soft tissue sarcomas

PurposeTo evaluate the efficacy and toxicity of hypofractionated radiotherapy in non-metastatic soft tissue and bone sarcomas.Patients and methodsThirty patients underwent hypofractionated radiotherapy between 2007 and 2015. Overall, 17 patients underwent primary hypofractionated radiotherapy, nine underwent hypofractionated radiotherapy for reirradiation, and four received a boost dose via hypofractionated radiotherapy after external beam radiotherapy. Most common disease sites were head and neck and retroperitoneum. Hypofractionated radiotherapy was administered with a definitive, adjuvant, or neoadjuvant intent.ResultsMedian age was 37 years (range: 11–82 years). Median hypofractionated radiotherapy dose was 35 Gy (range: 20–50 Gy) in three to five fractions. Median follow-up was 21 months (range: 1–108 months). One- and 2-year overall survival rate was 75% and 52%, respectively. One- and 2-year local recurrence-free survival rate was 59% and 48%, with local recurrence rates of 16% and 33% in 1 and 2 years, respectively. Univariate analysis revealed tumour size (P = 0.04), hypofractionated radiotherapy intent (P = 0.016) and reirradiation (P = 0.001) as prognostic factors for local recurrence-free survival. Severe late toxicity was observed in one patient as grade 3 trismus.ConclusionHypofractionated radiotherapy as the primary treatment or for reirradiation has been shown to be safe in the treatment of bone and soft tissue sarcomas. It can provide relatively good local control and survival rates.     

骨与软组织肉瘤化疗的耐药性

化疗在抗癌治疗中,占有不可取代的重要地位。由于近年来使用了更为有效的化疗药物,同时制定了更完善的化疗方案,抗癌药物的疗效得到了稳定的提高。但肿瘤细胞耐药性而导致的化疗失效(drug treatment failure)仍然是大多数癌症患者治疗上的一个主要难题。据统计,癌症死亡中90％以上存在着耐药性这一问题。 化疗药物的疗效与下列因素是紧密关联的:(1)肿瘤的大小及其所在的位置直接决定了肿瘤的血运,也影响到药物经血到达肿瘤组织的量和深度。(2)细胞周期的长短与化疗疗效及G0期耐药性有关:如细胞周期太长不能保证每个周期的细胞都能接触药物。而周期太短则肿瘤细胞的增殖快于被杀灭的速度。(3)癌基因的表达。(4)肿瘤的细胞耐药性:无论是内在耐药性或是获得性耐药性均直接影响化疗效果。     

Radioisotopic exploration of sarcomas of the bone and soft tissue

Radioisotopic methods are widely applied to investigations of bone sarcoma and soft tissue neoplasms. We have at our disposal molecules with osseous, tumoral or vascular tropism. Their use, as single agents or combination, is helpful in positive and differential diagnosis and provides nosological informations. They are also useful in treatment monitoring and in long-term follow-up.     

Pathological anatomy of sarcomas of the bone and soft tissue

The different pathologic aspects of bone and soft-tissue sarcomas are discussed: usefulness of special techniques, particularly immunohistochemistry, histologic classification and grading, diagnosis of frozen sections and assessment of treatment effects, particularly of postoperative chemotherapy.     

Cytogenetic data on sarcomas of the bone and soft tissue

Cytogenetic data are now available in most bone and soft tissue sarcomas. The characteristic chromosomal rearrangements observed are of great importance for the diagnosis, the classification and the comprehension of these cancers at the molecular level.     

Intra-arterial infusion of cisplatinum in bone and soft tissue tumors

Cisplatin was administered by intravenous injection, intra-arterial injection, and balloon-occluded arterial infusion. The total Pt, ultrafiltrated Pt, and free Pt levels were measured. Intra-arterial injection, in which ultra-filtrated Pt level on the normal side is the same as in intravenous injection, acts to increase the ultrafiltrated Pt level on the affected side. Thus, intra-arterial injection is as effective as preoperative chemotherapy. In two-route chemotherapy, free Pt level on the affected side is extremely high, so for only local control of tumors, two-route chemotherapy is very effective.