Karl H. Proppe

Preoperative, intraoperative, and postoperative radiation in the treatment of primary soft tissue sarcoma.

The rationale for combining radiation with conservative surgery in the treatment of sarcoma of soft tissue is discussed, as well as the advantages for performing the radiation preoperatively on the one hand and postoperatively on the other. The results of treatment of soft tissue sarcoma by radical resectional surgery or amputation in 464 patients at four centers and by conservative surgery, and postoperative radiation in 416 patients at three centers, have been reviewed. The local failure rates were 18.1% and 18.3%, respectively. The results obtained by radiation administered postoperatively (110 patients) or preoperatively (60 patients) at the Massachusetts General Hospital during the period September 1971 to August 1982 are analyzed and discussed with reference to 5‐year actuarial local control and survival results as well as causes of failure with respect to AJC stage, histologic type, anatomic site, and size of tumor. The results which have been obtained by the preoperative approach are judged to be superior, particularly for the larger lesions and higher grades that predominated in that group. Of a total of 170 patients, there were 19 local failures; 13 of these were diagnosed at the time when metastatic disease was not evident. Of those 13, 12 have been subjected to salvage surgery and 7 remain with no evidence of disease at 1 to 3.5 years after the salvage procedure. A major problem in the management of these patients remains the occult metastatic disease.

Postoperative spindle cell nodules of genitourinary tract resembling sarcomas. A report of eight cases

Eight cases of proliferative spindle cell nodules that developed 5 weeks to 3 months after operations on the lower genital tract of four women, and the lower urinary tract of four men, are described. The lesions ranged up to 4 cm in diameter, resembled spindle cell sarcomas on microscopical examination, and were initially interpreted as such in most of the cases. Six of the lesions were treated by local excision alone, and two by a radical surgical procedure, followed by radiation therapy in one case. The six patients whose lesions were treated inadequately on the assumption that they were sarcomas were free of disease 9–60 months (average, 28 months) postoperatively, and the two men who were treated by radical procedures were well 18 and 60 months later. The microscopic features, the unusual clinical setting, and the favorable prognosis of these lesions suggest that they were examples of a hitherto undescribed form of benign reactive lesion resembling a sarcoma.

Selection bias in clinical trials.

Of 90 patients with intermediate or high-grade sarcoma eligible for a randomized trial of adjuvant doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), 48 were not entered: 24 (27%) by physicians choice and 24 refused randomization. Sixty-five percent of lower stage patients were randomized compared with 37% of those with higher stage (P = .02). Patients with extremity lesions were more frequently offered participation in the study (P = .07). Patients with lower stage lesions accepted randomization more readily than those with higher stage lesions (P = .01). As predicted by the higher stage and percentage of central lesions, the disease-free survival of nonrandomized patients was inferior to that of randomized patients (P = .15). Thus, patients at high risk appeared to avoid randomization and adjuvant doxorubicin in this trial, resulting in an inferior disease-free survival for the nonrandomized control group. Important questions generally require randomized trials that reliably determine relative treatment differences. If, however, the patients in a clinical trial are not representative of the entire patient population because of patient and physician selection biases, the generalizability of the results to the entire patient population may be compromised. For example, the prognosis of the general population cannot necessarily be inferred from the selected group in the study. In this study, the randomized and nonrandomized series yielded differing conclusions regarding treatment efficacy, even when an adjustment was made for known prognostic facts.

Preoperative radiation therapy for sarcoma of soft tissue

Experience at the Massachusetts General Hospital in the management of 36 patients with sarcoma of soft tissue who were accepted for treatment by radiation followed by surgery is described. The tumors in these patients were extensive: greater than 5 cm in 33. Actual radiation doses covered a broad range for a variety of technical and medical reasons. The general dose aim has been 5000–6000 rad (200 rad 5 times a week) followed in approximately three weeks by conservative resection; a boost dose to the tumor bed has been given intraoperatively (interstitial or electron beam technique) or postoperatively (small field external beam, fractionated dose technique). Histologic change in the operative specimen increased with histologic grade of tumor, viz. more severe change in the less well‐differentiated tumor. There was a trend toward more marked change with increasing dose for levels of 4000 rad and more. Local control has been achieved in 31 of 33 patients (follow‐up of three months to eight years) treated by radiation followed by surgery. For three patients, the planned resection proved not to be technically feasible and treatment was completed by further radiation; of these, two had a local failure. Wound healing was delayed in six of the 33 treated by radiation followed by resection.

Radiation therapy of retroperitoneal soft tissue sarcomas

Between 1971 and 1982, 23 patients have been treated with radiation therapy at the Massachusetts General Hospital (MGH) for retroperitoneal soft tissue sarcomas. Seventeen patients were treated with curative intent and six with palliative intent. Of the patients treated with curative intent, the 5 year actuarial survival rate was 54% and the 5 year actuarial local control rate was also 54%. With a complete surgical resection local tumor control was obtained in 5 of 7 patients (71%), 4 of 7 (57%) with incomplete resection and 1/3 (33%) with no resection having local control. The radiation dose appeared to influence tumor control with 2 of 6 patients (33%) having local control with less than 5,000 cGy compared to 0 of 5 patients with doses of 5,000 to 6,000 cGy and 5 of 6 (83%) with doses greater than 6,000 cGy. An effect of tumor grade on either local control or on rate of metastasis formation could not be demonstrated in this series. Long-term local control and survival appears to be associated with maximal surgical resection and high dose radiation therapy.

Treatment of Malignant Tumors of the Spermatic Cord: A Study of 10 Cases and a Review of the Literature

Ten patients with sarcoma of the spermatic cord were treated at our hospital between 1940 and 1977. Although there are 191 reported cases in the literature controversy remains concerning optimal treatment. In our series of 10 patients 5 of 7 (71 per cent) followed for more than 5 years postoperatively have suffered local recurrence. Thus, we believe that this treatment is inadequate and recommend postoperative radiation therapy to the scrotum and pelvis. Of our patients 2 suffered recurrence in the retroperitoneal lymphatics and we favor dissection of these nodes as part of the initial treatment.

Malignant tumors of nerve sheath origin

A clinicopathologic study of malignant nerve sheath tumors diagnosed between 1962 and 1979 at the Massachusetts General Hospital was undertaken. During this 17‐year period, 24 patients with such a neoplasm were seen while 607 patients were treated for schwannoma or neurofibroma. Criteria were developed for establishing the nerve sheath origin and malignancy of a given neoplasm which allowed a secure diagnosis of malignant nerve sheath tumor to be made in 11 of the 24 cases. In 7 of the remaining cases, the malignant tumors were of uncertain histogenesis and in 6 cases, a new diagnosis was made. The malignant tumors constituted 2% of all neoplasms of nerve sheath origin diagnosed during this period. An attempt was made to grade these neoplasms, but clinical and histologic parameters were only approximately predictive of their behavior. The treatment and survival of the 11 patients with malignant nerve sheath tumors and the 7 with malignant neoplasms of uncertain histogenesis are detailed and compared. In the former group, 4 patients died within four and a half years and there were eight recurrences in 4 patients. In the latter group, 4 died within three and a half years and there were five recurrences in 3 patients.

Evaluation of Prostate Specific Acid Phosphatase and Prostate Specific Antigen in Identification of Prostatic Cancer

The peroxidase-anti-peroxidase technique was used to stain for prostate specific acid phosphatase and prostate specific antigen in 12 patients with primary tumors and in 12 patients with metastases in whom the nature of the tumor was in doubt after routine histopathological studies. Nine of the primary tumors were positive for both markers and an additional 2 tumors stained for prostate specific antigen only. Six metastatic lesions stained for both markers and a seventh for prostate specific antigen alone. Thus, 11 of 12 primary tumors and 7 of 12 metastases studied were proved to be of prostatic orgin. While the peroxidase staining was sometimes weak and uneven this method, using prostate specific antigen and prostate specific acid phosphatase, allowed for ready identification of metastases. The heterogeneity of the tumors in regard to these 2 prostate markers is demonstrated, and the value of staining for prostate specific acid phosphatase and prostate specific antigen is emphasized.

Invasive Bladder Cancer: Tumor Configuration, Lymphatic Invasion and Survival

The pathologic slides of 86 patients who underwent radical cystectomy for invasive (stage T2 plus) bladder carcinoma were reviewed. The tumors were classified according to the demonstration or absence of small vessel invasion and the papillary or solid configuration. Of the 86 patients regional nodal metastases were noted in 24. Eighteen of 48 patients (38 per cent) with small vessel invasion also had nodal metastases compared to 6 of 38 (16 per cent) without small vessel invasion. Of the 62 patients without nodal metastases the crude 5-year survival was 52 per cent for 32 without small vessel involvement compared to 30 per cent for 30 with small vessel involvement.

Malignant fibrous histiocytoma and pleomorphic sarcoma in association with medullary bone infarcts

A malignant fibrous histiocytoma arose in the proximal tibia of a 40‐year‐old man who had multiple, symmetrically distributed, medullary bone infarcts of unknown etiology, involving the distal femora and the tibiae. Despite amputation and chemotherapy, widespread metastases developed and death occurred 19 months after surgery. A pleomorphic sarcoma, probably representing an anaplastic malignant fibrous histiocytoma, arose in association with a single medullary infarct in the proximal humerus of a 33‐year‐old woman. She remains well without evidence of disease five years after treatment by radical radiotherapy followed by shoulder disarticulation. Sarcoma arising in association with bone infarction is a rare entity. Sixteen cases reported in the medical literature, including our own, are reviewed. The sarcomas arose in the tibia in nine cases, the femur in six cases and the humerus in one case. The patients were usually older individuals and 13 of the 16 were male. All but two had multiple bone infarctions. Four of the patients had caisson disease, three had what is probably an hereditary bone dysplasia, one had sickle cell disease and eight had infarcts of unknown etiology. Most patients have had a rapidly fatal outcome. Thirteen of the sarcomas have been fibrosarcomas or malignant fibrous histiocytomas, both of which are rare primary bone tumors. Analysis of the published cases of bone infarction‐related sarcomas suggests that the risk of developing a sarcoma is greatest in infarcts with large medullary components.