Andrew R. Harwood

Kaposi's sarcoma in recipients of renal transplants.

Abstract The purpose of this study was threefold; to ascertain if immunosuppression may be a factor in the causation of Kaposis sarcoma, to find out if there is a correlation between abnormalities in in vitro studies of cellular immune function and the extent of the disease, and to analyze the literature on Kaposis sarcoma arising in renal transplant recipients to determine a management policy for these patients. The charts of 44 patients with Kaposis sarcoma seen in a 20 year period at The Princess Margaret Hospital were reviewed in a search for evidence of immunosuppression as a possible risk factor. Such evidence was found in seven patients. Four of these seven patients were renal transplant recipients, two had generalized lymphomas and were receiving chemotherapy whereas one had a glioblastoma multiforme and was receiving chemotherapy. Studies of cellular immunity using phytohemagglutinin, conconavalin A, pokeweed mitogen, the mixed leukocyte reaction and dinitrochlorobenzene skin testing, in eight patients with Kaposis sarcoma, three of whom had previous renal transplants, indicate that a correlation exists between the degree of immunologic deficiency and the extent of the Kaposis sarcoma. Our seven patients were all of Jewish or Mediterranean ancestry. The four cases of Kaposis sarcoma arising in renal transplant recipients developed in a population of 100 renal transplant recipients of similar ethnic background (4 per cent). This incidence, when compared with our experience of 40 cases arising in 500,000 people of similar ancestry in the Toronto area, represents a 400 to 500 fold greater incidence in renal transplant recipients than in the control population. A literature review has yielded 12 additional cases of Kaposis sarcoma developing in renal transplant recipients. On the basis of this review and our own experience we have proposed a management policy for these patients. It is proposed that the etiology of Kaposis sarcoma is multifactorial and that a combination of immunosuppression and/or immunologic stimulation combined with a hereditary predisposition to the disease are responsible for the major increase in its incidence.

Radiotherapy of chondrosarcoma of bone

A retrospective analysis of 31 cases of chondrosarcoma of bone treated by radiotherapy at the Princess Margaret Hospital between 1958 and 1976 is presented. In comparison with other large series, our group of patients were found to have been unfavourably selected with respect to the known prognostic factors: histology (39% mesenchymal and dedifferentiated), site (75% arising in the trunk and head and neck), adequacy of operative treatment (none having had a complete surgical excision), and presenting symptoms (two‐thirds presenting with pain). Twelve patients with primary (good, moderate, and unknown differentiation) chondrosarcoma were radically irradiated; 6 of these 12 have been alive and well without tumor for periods ranging from three and a half to 16 years and 3 of these are alive and well for 15 years or more following radiotherapy. The other 6 patients responded or disease stabilized following radiotherapy for periods ranging from 16 months to eight years. One poorly differentiated tumor was radically irradiated and did not respond. Eleven patients were irradiated palliatively (5 dedifferentiated and mesenchymal, 4 secondary, and 2 primary chondrosarcomas), generally with low doses of irradiation, and only 4 responded transiently for periods ranging from three to 12 months. Seven patients with mesenchymal and dedifferentiated tumors were radically irradiated. Four responded or disease stabilized, and 1 of these patients was alive and well at 3 years; 3 did not respond. Six died with distant metastasis. It is concluded that chondrosarcoma of bone is a radioresponsive tumor and the place of radiotherapy in the treatment of this disease and the reason for its being labelled a radioresistant tumor are discussed. The problems of assessing response of chondrosarcoma to therapy are also discussed. It is suggested that chemotherapy may have a role in the management of mesenchymal and dedifferentiated chondrosarcoma.

Second primary respiratory tract malignancies in glottic carcinoma

Of 740 cases of glottic cancer, a second respiratory tract tumor developed in 48. Only 14 cases would have been expected in a sample of the same age and sex distribution drawn from the general population of Ontario. Of 25 patients with second tumors in the lung, 23 are dead. Of these 23, 17 had been cured of Stage T1 glottic cancer. An actuarial method for calculating the risk of developing a second respiratory tract tumor amongst the survivors of glottic cancer is described. Of the survivors, 12% will have a second respiratory tract tumor within ten years following initial diagnosis of glottic cancer. Of patients with Stage T1 glottic cancer, 7% will die of a second respiratory tract tumor within ten years. This rate is slightly more than that for those who die of laryngeal cancer in this stage grouping. Late recurrences and/or second primary tumors in the larynx following radiotherapy are rare. Methods for reducing the risk of death from a second respiratory tract tumor are discussed.

Postirradiation sarcoma of bone. A perspective

Ten cases of irradiation induced sarcoma of bone which fulfilled Cahans criteria were seen in a twenty year period at the Princess Margaret Hospital. The overall incidence of this complication is 0.035% of all irradiated five year survivors. Combining our data with three other large series presented in the literature, a dose complication curve could be deduced. On the basis of the human and animal data reviewed, it was concluded that the risk of radiation induced sarcoma is so low in the dose range of modern radiotherapeutic practise that it does not represent a contraindication to the use of radiation therapy.

Radiotherapy of Kaposi's sarcoma.

Between 1958 and 1976, 34 patients with Kaposis sarcoma were seen. Two patients were kidney transplant recipients. Co‐existing malignancies were seen in 22% of patients. From 1958 to 1965, cutaneous lesions were treated solely with local radiotherapy techniques, single doses of 800 rads being found adequate to produce a complete response. In 1965, because of the multicentric occurrence of the disease and frequent recurrences after local radiotherapy techniques, extended field radiotherapy was begun. Ten of twelve patients thus treated responded completely. It is concluded that extended field radiotherapy using a single dose of 800 rads offers complete relief of symptoms and better control of the disease when compared to local radiotherapy. There was very little morbidity, with the extended field technique.

Prognostic factors in T2 glottic cancer

During a ten‐year period from 1965 through 1974, 164 patients with T2N0M0 glottic cancer were seen at the Princess Margaret Hospital. These patients were treated by radiotherapy reserving surgery for salvage of recurrent or persistent disease. One hundred and fifty‐four cases have been analyzed in detail with respect to two variables: impairment of mobility and surface extension of disease. Two end‐points of analysis were used: actuarial local recurrence‐free rates and corrected actuarial survival. The five‐year corrected actuarial survival rate was 12% less in the T2N0M0 patients with impaired vocal cord mobility (75.2%) when compared to those cases with normal vocal cord mobility (86.8%) (P = 0.068). No difference in survival was seen with increasing degrees of surface extension of disease when correction for the effects of impairment of mobility was performed. There was a highly significant difference in local control rates with radiotherapy when comparing cases with normal vocal cord mobility (76.7% locally controlled) vs. impaired vocal cord mobility (51.1% locally controlled) (P = 0.015). Again, no significant trend in local control rates could be ascertained with increasing surface extension of disease. The number of patients with nodal disease was insufficient to permit meaningful analysis of the effects of the presence or absence of nodal disease on survival. On the basis of this analysis, we suggest that the Stage T2 grouping in glottic cancer be subdivided into Stage T2a for those tumors with normal vocal cord mobility and T2b for those with impaired vocal cord mobility.

The radiotherapy of lentigo maligna and lentigo maligna melanoma of the head and neck

Between 1958 and 1977, 8 cases of lentigo maligna (LM) and 15 cases of lentigo maligna melanoma (LMM) were treated with radiotherapy at the Princess Margaret Hospital. Only 1 of the 8 cases of LM recurred following irradiation and this recurrence was controlled with further radiotherapy. Of 15 cases of LMM, 14 were controlled by irradiation for periods ranging from two months to six years postradiotherapy; the 1 recurrence was salvaged with local excision. Conventional orthovoltage irradiation using doses of 4500–5000 rad in ten to 15 fractions has been found to be highly effective in controlling this disease. The lesion may take up to 24 months to completely regress following irradiation. The benefits of this modality of treatment for a disease process which predominantly occurs in the head and neck region of elderly people is discussed in detail. The results are compared with other methods of irradiation (Mieschers technique) and other modalities of treatment.

Whole abdominal radiation in the management of metastatic gastrointestinal carcinoid tumor

Abstract Twenty-eight patients with metastatic gastrointestinal carcinoid tumor were treated with whole abdominal radiation. Twenty-one of these patients had the carcinoid syndrome. The prescribed mid-line tumor dose was 2000 to 2500 rad. in 20 to 25 fractions in 4 to 5 weeks. The overall 5 year survival was 35% (median survival 2.5 years). A marked survival difference was noted in those patients with carcinoid syndrome compared to the non-functioning group. None of the syndrome patients survived five years (median survival 1.7 years) whereas six of the seven non-syndrome patients are five year survivors.

Prognostic factors in T3 glottic cancer

A detailed statistical analysis of prognostic factors influencing the local control rate by irradiation in T3 glottic cancer is presented. This has been done to identify favorable and unfavorable prognostic factors in order to precisely identify areas where new treatment strategies are needed. Between 1963 and 1977, 110 patients with T3NOMO glottic cancer were treated with radical radiotherapy with surgery for salvage. Only one of 12 women recurred following irradiation compared with 50 recurrences so far among the 98 men (P = 0.006). The recurrence rate among men using an NSD of less than 1700 rets was significantly higher than when an NSD of greater than 1700 rets was used (P = 0.022). This difference remained significant even after correction for other possible confounding variables. The recurrence rate among men over the age of 60 years was significantly lower than in men under 60 (P = 0.022). This difference in local control is due to a high proportion of patients with residual disease following irradiation. Factors not found to be of significance included radiation field size, superficial extent of disease, and tracheostomy before or during treatment. No difference in surgical salvage between the residual and recurrent disease cases has been seen. The cause of failure to respond to irradiation is discussed and possible ways to improve the local control by irradiation, particularly in young males, are suggested.

Radiotherapy in nonlentiginous melanoma of the head and neck.

Thirty‐seven patients with superficial spreading or nodular melanoma of the head and neck treated with irradiation are reviewed. Twenty‐one patients were referred within three months of surgery. Six had an incisional biopsy followed by postoperative irradiation, 4 were locally controlled (1 dying of metastatic melanoma, 2 dying of intercurrent disease and 1 is alive and well), and 2 were not (both dead of melanoma). Fifteen patients had a local excisional biopsy (11 having tumor to the limits of the excision) followed by postoperative irradiation. Fourteen of the 15 had local control (3 had lymph node metastases and died, 3 died of distant metastases from melanoma, 7 are alive and well from 1‐14 years following treatment, and one is dead of intercurrent disease), and 1 had a local recurrence and subsequently died of metastatic melanoma.