A retrospective study of the role of radiotherapy in the treatment of soft-tissue sarcoma

One hundred and forty patients with soft-tissue sarcoma were seen between 1965 and 1974 and the pathology has been reviewed in 93 cases. One hundred and eight patients were treated radically. Their overall survival rate was 53% at 5 years and 41% at 10 years. Overall local control was 63% but primary local control varied considerably with treatment, being highest for those receiving surgery and post-operative radiotherapy. The poor prognosis of patients with paravertebral tumours is confirmed.     

Radioisotope therapy in bone and joint disease

The short range tissue destruction of beta-emitting radioisotopes can be utilized in painful metastatic disease of the skeleton by employing a radionuclide that is specifically metabolized in or adjacent to these lesions. Sodium phosphate P 32 has been used for this purpose for the past 25 yr. It uptake in skeletal tumor and in osteoblastic new bone adjacent to tumor can be markedly increased by pharmacologic stimulation using androgenic steroids, or during rebound deposition after a course of parathyroid hormone. Although efficacy in terms of subjective pain relief is high, more objective signs of success are often lacking, and survival, while more confortable, is not prolonged. Marrow depression is the most significant side effect. A beta-emitting, bone-seeking isotope, 89Sr, may have a better therapeutic/toxic ratio, and should receive further trial. Radiation-induced necrosis has also been applied, though more hesitantly, to the proliferative, destructive, but nonmalignant synovium in rheumatoid disease. Here, a number of colloidal preparations, most commonly 198Au, have been employed. Again, relief of symptoms, particularly recurrent joint effusions, is quite high, although the basic disease process is not reversed. The major hazard here appears to be leakage of material to regional lymph nodes, resulting in irradiation of circulating lymphocytes. Although chromosomal damage can be detected when such cells are then cultured, the actual consequences of this, if any, are not presently known. Both shorter-lived (165Dy) and longer-lived (32P) larger-size colloids are being evaluated, which may prove safer in this regard than 198Au.     

The bone scan in inflammatory osseous disease

The 99mTc-phosphate bone scan has become a sensitive, reliable, and safe method for evaluating the patient with suspected inflammatory disease of bone. The scan may become positive as early as the first 24 hr after the symptoms and 10-14 days before roentgenographic changes occur. It can be used to differentiate successfully a variety of diseases from osteomyelitis, and in conjunction with 67Ga-citrate scan has become a mainstay in the work-up of the patient with infectious disease. Applications of the bone scan to infectious diseases in pediatric practice are especially helpful, since these diseases are common problems in this age group. Increased experience with the 99mTc-phosphate bone scan has already defined several areas of "limitations" in evaluating inflammatory disease. "Cold" defects, negative scans in early stages of osteomyelitis, and "extended uptake" may all pose problems in interpretation, but careful correlation of the bone scan results with clinical history and physical findings, blood cultures, and roentgenography will significantly reduce these problems.     

Rationale for the use of bone scans in selected metastatic and primary bone tumors

Since the introduction of bone scans in 1951, there have been many studies comparing biologic and physical characteristics of new bone-imaging agents and the results of scintigraphy and radiology in large numbers of patients. Relatively speaking, there have been fewer studies detailing the health benefits and financial cost associated with the use of skeletal scintigraphy. This review concerns these aspects in patients with malignancies of various sites and stages. About 2% of patients with stage I or II breast cancer have bone metastases at the time they first present, whereas nearly 28% of patients with stage III disease have bone metastases. A large percentage of patients with initially negative scans develop bone metastases during the first 3--4 yr; many of them develop them within the first 12--18 mo after initial diagnosis. For patients with lung cancer, the use of bone scans in staging their disease is somewhat controversial. Several studies indicate that the yield of positive bone scans may range from as low as 2% to as high as 35%. Data on the use of bone scans in staging prostatic cancer initially are similar to those in patients with breast cancer, that is, yields of 7% in patients with stage I or II disease and a yield of about 20% with stage III disease. Children with osteosarcoma or Ewing's sarcoma rarely have bone disease distant from the site of their primary bone lesion at presentation. However, a large percentage of them (30%--40% or so) develop bone metastases during the follow-up period. As in the case with patients with breast cancer, about half of these bone metastases are evident by 12--18 mo.     

Value of bone scanning in neoplastic disease

This article reviews recent literature on a variety of primary and secondary bone tumors in an attempt to indicate the use of bone scans in the peri- and posttreatment phases. The data indicate that the yields and value of bone scans are tumor specific and that for some tumors (particularly breast and prostate) interpretation of studies on patients undergoing hormonal or chemotherapy can be complicated by the "flare phenomenon." Data are still needed on the rate of development of bone metastases in the follow-up period on a stage-specific and therapy-specific basis.     

Paget''s disease of bone

Nuclear medicine techniques are currently playing an important complementary role in the evaluation, management, and follow-up of the patient who is suspected of having Paget's disease of bone. The earlier diagnoses made possible by some of the described techniques should lead to a better understanding of the basic pathophysiology and, in addition, result in improved therapeutic modalities.     

Bone trauma and related benign disease: Assessment by bone scanning

The radionuclide investigation of skeletal trauma in the past was confined generally to scintimetry and an occasional bone scan. The development of improved radiopharmaceuticals, including 99mTc-labeled compounds with their enhanced sensitivity, and the refinement of imaging devices offering superior resolution and speed have allowed a more detailed assessment of conditions resulting from trauma. Practical approaches to the diagnosis of subtle bone injury resulting in stress fracture, the differentiation between delayed healing and nonunion, and early recognition of avascular necrosis and osteomyelitis are now available. The changing pattern of radionuclide uptake in bone following damage by radiation and other abnormalities as a consequence of trauma also can be easily studied.     

Pinhole imaging in legg-perthes disease: Further observations

Fifty-nine patients with Legg-Perthes disease and 12 others were studied using 99mTc-polyphosphate and the pinhole collimator imaging technique. Radiographs of both hips were correlated with images in each patient. In the Legg-Perthes patients, a radionuclide uptake deficiency of variable size was observed in the proximal femoral epiphysis (EOC), which we believe is related to varying degrees of impaired blood supply. During later disease stages, adjacent zones of increased radionuclide activity of revascularization were observed that would replace the uptake defect eventually. Unless radiographic evidence of new bone formation was observed in the EOC, it was impossible to predict either the presence or extent of revascularization until bone imaging was done. Those patients with revascularization activity in the EOC exhibited a relatively short time interval (average, 3.2 months) before evidence of new bone formation radiographically. Others with increased radionuclide concentration limited to the growth plate and/or metaphysis averaged a much longer 7.8 months. In two patients there was a reversal of the initially increased activity in the growth plate, suggesting another vascular insult. There were no false-negative bone-image findings in the 12 cases that clinically and/or radiologically simulated Legg-Perthes disease. Our image studies correlate well with published histopathologic investigations, indicating to us that assessment of extent of pathologic involvement and of the disease course is facilitated by this technique. Subsequently, this could influence treatment selection and provide a more objective baseline from which to judge treatment results. Continued experience suggests pinhole bone imaging has useful clinical application in Legg-Perthes disease and other childhood hip disorders.     

The scintigraphic findings in Paget's disease of bone.

Bone scans and radiographic skeletal surveys have been done in 41 patients who had Paget's disease. The scintigraphic findings are consistent with what is known of the pathophysiology of Paget's disease. Diseased bone demonstrates increased vascularity, an increased degree of uptake of bone-seeking radiotracers and, in appropriate bones, evidence of marrow replacement. The bone scintiscan is a more sensitive indicator of the extent of polyostotic Paget's disease than conventional radiograph, demonstrating 34% more lesions. Because it reflects shorter term changes in osteoblastic activity the bone scan is of some value in providing immediate objective evidence of the therapeutic effectiveness of Mithramycin which has been used in this study in the treatment of the minority of patients with pain in Pagetoid bone. A technique for documenting alterations in uptake by diseased bone numerically is presented. Upon treatment with Mithramycin the ratio of abnormal uptake in relation to normal bone fell from 8.7 to 3.9.     

Observations on the mechanism of 99mTc-labeled phosphate complex uptake in metabolic bone disease.

This communication describes a series of clinical and animal in vivo and in vitro investigations designed to elucidate the mechanism of 99mTc-Sn-phosphate complex concentration in metabolic bone disease. Rachitic and lathyritic animals were used as experimental models. Based on these studies it is concluded that 99mTc alters the pharmacology of the phosphate complexes, in particular pyrophosphate, which was the test agent most extensively employed, so that the usual affinity for mineral is for the greater part replaced by organic matrix binding. There is also evidence to suggest the immature collagen moiety of the organic matrix is the prime target of 99mTc-Sn-phosphate complex binding. Specifically, the aldehyde groups of the collagen molecule are suspected as being the major site of interaction.