Biomedical subjects
Publications and source records attributed to C L Harmer.
A new treatment for post-radiotherapy telangiectasia is reported. Five patients were successfully treated by injection of a dilute solution of sodium tetradecyl sulphate. Several (4-7) half hour sessions of injection sclerotherapy at 5-weekly intervals were necessary.
Twenty patients with soft-tissue sarcomas arising within previously irradiated fields have been analysed. The initial radiation dose ranged from 8.8 to 70 Gy, comprising either orthovoltage or megavoltage treatment. The latent interval following radiotherapy ranged from 7 to 45 years (mean 16.8 years). The commonest histological subtype was malignant fibrous histiocytoma. Four patients required forequarter amputation. The 5-year survival was only 14 per cent. The high morbidity and mortality accompanying post-radiation sarcomas must be borne in mind when the choice between therapeutic options for potentially curable cancers is finely balanced.
This study analyzes the results of 46 cases of biopsy-proven primary lymphoma of the thyroid, localized at diagnosis and treated at the Royal Marsden Hospital between 1948-1980. In all cases, disease was limited to the thyroid and cervical lymph nodes. There were 43 females and 3 males, with a mean age of 64.4 years (median 66 years; range 17-86). A short history (less than 3 months) of a neck mass and local compressive symptoms was the typical presentation. The majority of patients (91%) had adverse histologies, with diffuse histiocytic lymphomas being most common (78%). The overall crude 5-year survival rate was 40%, with 30% of patients surviving beyond 10 years. Disease-free and overall survival were virtually identical, indicating the ineffectiveness of salvage therapy. The important prognostic factors were: size of tumor, fixation, extra-capsular extension, and retrosternal involvement. Survival was not correlated with age, sex, histology, thyroid status, or stage of disease, as defined by the Ann Arbor classification. Patients who had total macroscopic removal of tumor had the highest rate of local control and long survival (p less than 0.005). No significant difference was seen between lobectomy, subtotal or total thyroidectomy, but 7 of 9 long-term survivors (58-129 months) have had total thyroidectomy. A radiotherapy dose to the tumor, of at least 40 Gy, was required to produce consistent local control in patients with unresected disease. The majority of patients who died had generalized disease. Only 52% of these patients were free of local recurrence. In view of the frequency of occult disseminated disease, adjuvant chemotherapy is one recommendation for patients with poor prognostic factors. For optimal local control, complete surgical eradication is recommended followed by high-dose local radiotherapy. The use of aggressive cytoreductive chemotherapy prior to radiotherapy is a possible alternative option which needs to be explored.
In an effort to improve local control in the radiation treatment of sarcomas, up to 7 weekly fractions of 6.6 Gy each were administered to 64 patients. They were divided into two groups: Group A consisted of 37 patients with measurable disease who achieved a partial response rate of 22%, with no complete responses. Group B consisted of 27 postoperative patients with varying degrees of completeness of surgical excision, two have relapsed locally to date. Early radiation damage was documented in 26%, but was not a dose-limiting or incapacitating event in any case. Late normal tissue damage occurred in 23 out of 32 evaluable patients (72% of those at risk), and was a cause of serious morbidity in 6 patients. Response rates were low in Group A compared with other series, but in Group B the local recurrence rate is comparable with other centers using "conventional" fractionation. No apparent improvement in therapeutic gain was demonstrated for large weekly fractions.
A case of infiltrative fibromatosis in a 25-year-old man is described. This is a rare, recurring tumour most commonly seen in the shoulder and pelvic girdles, whose behaviour seems to justify the opinion that it is a non-metastasizing, low-grade fibrosarcoma.
Between 1979 and 1984, 34 patients with advanced lymphoma or leukemia resistant to other treatments have been treated with single or sequential hemibody irradiation (HBI). Good symptomatic relief was obtained in the majority of patients, with minimal acute toxicity. Disease regression occurred in the majority of patients and was maintained in those achieving a complete remission. Stage III disease and 'good risk' histology predicted a good outcome. Marrow toxicity was marked only in those patients with marrow involvement. HBI is recommended as a worthwhile palliative treatment particularly in nodal nodular disease.
One hundred and sixty-four patients with Graves' disease were treated with low-dose radioiodine (2 mCi), with a mean follow up of 4 1/2 years. At this time 74 (45%) were euthyroid having had a single dose, with a total of 131 (80%) being controlled with one or more doses. Three (2%) were still toxic but their mean follow up was only 3 years. Thirty (18%) were rendered hypothyroid, two-thirds of these after a single dose of 2 mCi 131I. The one-year incidence of hypothyroidism was 6%, with an incidence at 6 years of 20%. Previous surgery, medical treatment and thyroid antibody status appeared to have no influence on the outcome.
Experience using low-dose radioiodine given six-monthly instead of yearly in hyperthyroid patients with Graves' disease is reported. One hundred and thirty-five patients have been treated over a three-year period with 74 MBq (2 mCi) doses of 131I. Thirty-eight percent were controlled with a single dose. Those patients requiring more than one dose were treated with a further 74 MBq (2 mCi) 131I at six-monthly intervals until euthyroid. Using this approach, 46% were euthyroid one year after starting treatment, and 75% were euthyroid at two years. The incidence of hypothyroidism following treatment was 2.2% at one year, with a yearly incidence thereafter of 4-6%. Six-monthly scheduling of low-dose radioiodine in Graves' disease can reduce the time taken to become euthyroid, compared with conventional yearly low-dose treatments. Further follow up is required to confirm the present low incidence of hypothyroidism following treatment.
Two hundred sixty-three patients with unilateral primary breast cancer, treated by local excision of the primary tumor and radical radiation therapy between 1954 and 1969, were followed up for a minimum of 10 years and a maximum of 20 years. The treatment plan delivered 4500 rad in fractions of orthovoltage irradiation to five fields: tangential breast fields, axilla with posterior axillary field, parasternal and supraclavicular, with a subsequent boost of 1000 rad to the primary tumor site, axilla, and supraclavicular fossa. Patients were clinically staged using the TNM (UICC) system; 115 patients had tumors less than 2 cm in diameter and a clinically negative axilla (T1N0N1a), 96 had tumors 2 to 5 cm in diameter with a clinically negative axilla (T2N0N1a), and 52 had tumors less than 5 cm in diameter and clinical axillary lymph node metastases (T1T2N1b). The actuarial relapse-free survival of patients with T1N0N1a tumors was 72% at 5 years, 59% at 10 years, and 47% at both 15 and 20 years. The relapse-free survival of patients with T2N0N1a tumors was not statistically different (P greater than 0.05). A significantly worse survival was observed in patients with clinical axillary lymph node metastases (T1T2N1b), with a survival of 37% at 5 years, 29% at 10 years, 23% at 15 years, and 22% at 20 years, when compared with patients with clinically negative lymph nodes (P less than 0.01). Locoregional relapse occurred in 22%, at 10 years, of those patients with T1 or T2N0N1a tumors and 52% of the patients with T1T2N1b tumors. The pattern of locoregional relapses indicated that approximately 50% occur at least 5 years after treatment; this contrasts with the pattern of early locoregional relapse after mastectomy. The commonest sites of relapse were in the breast in 19% and axilla in 6% of patients with T1 or T2N0N1a tumors. There was no attenuation of the radiation dose administered at the site of a subsequent relapse. Surgery for radiation failure produced a 42% crude relapse-free survival at 5 years after salvage mastectomy in those patients originally treated for T1 or T1N0N1a tumors. The results of this study suggest that a significant proportion of patients relapse locally over a prolonged period after breast conservation. The evolution of new radiation techniques may provide better locoregional control and early salvage surgery may result in improved long-term survival.
Nineteen patients who have had medullary carcinomas of the thyroid have been followed up at the Royal Marsden Hospital. All had nodal involvement. Postoperative unprovoked serum calcitonin assays have been performed. Four patients had incomplete excisions of their tumours and these had the highest postoperative levels. Two died within 3 years, one has stable disease 8 years later and one remains well 13 years later. Four patients had postoperative calcitonin assays of over 100 ng/ml but had no clinical evidence of remaining disease. Only one has died (7 years later), the others remaining well 10, 10 and 3 years later. Four patients died of their disease and all had assays of over 200 ng/ml, before death. Slightly raised postoperative assays were found in all the other patients, but these have not significantly altered. These patients had good prognoses. Three patients also had regular carcino-embryonic antigen (CEA) assays and the value of this is discussed.
The case records of 235 patients who were treated for differentiated thyroid cancer between 1949 and 1981 were reviewed. Forty-two (18%) had distant metastatic spread outside the neck and received radioiodine (131I) therapy. In cases where the distant spread was confined to the lungs, 54% of patients were alive, free of disease, 10 years after 131I treatment was started. By contrast, no patient with skeletal involvement has survived for 10 years and only one for five years after treatment. A variety of cytotoxic drugs has been tried on an ad hoc basis with no notable success. One patient developed preleukaemia three months after completion of 131I treatment, but no other serious side effects were observed. Factors that influence the behaviour of metastatic thyroid carcinoma are discussed and a possible revised approach to 131I therapy is suggested in the light of these findings.
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Two hundred and thirteen unselected postmenopausal women with advanced breast cancer were treated with aminoglutethimide and hydrocortisone. There were 6 complete responses (CR), 47 partial responses (PR), 25 stable disease (SD) and 3 mixed response. Overall objective response rate was 28%, and with SD 41%. Median duration of objective response was 14 months. Years after menopause, age and tumour-free interval did not affect response rates. Main side-effects were drowsiness and lethargy (33%), rash (23%) and nausea (15%). Eleven patients (5%) stopped treatment because of toxicity. Median survival from start of treatment was 28 months and was the same for CRs, PRs and SD, compared with 10 months for progressive disease (P less than 0.001). Median survival from first metastasis was 43 months for PR/CR, 40 months for SD (not significantly different) and 22 months for progressive disease (P less than 0.001). Aminoglutethimide is an effective endocrine therapy in advanced postmenopausal breast cancer, particularly for bone deposits. Disease stabilization is associated with symptomatic and survival benefit similar to CR/PR.
A 44-year-old woman presented with a systemic illness characterized by a rash, polyarthritis and hypothyroidism. She later developed angioimmunoblastic lymphadenopathy (AIL) which became progressively resistant to chemotherapy. Pulmonary features were prominent throughout her illness and included pleural effusions, hilar adenopathy and parenchymal infiltrates. Lung histology showed a transition from nonspecific chronic inflammation with fibrosis to a polymorphic cellular infiltrate typical of AIL. Immunological features included a low C3 level, hypogammaglobulinaemia and depressed cell-mediated immunity.
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Altogether 117 patients with advanced breast cancer were treated with either tamoxifen 10 mg by mouth twice daily or aminoglutethimide 250 mg by mouth four times daily with hydrocortisone 20 mg twice daily in a randomised cross-over trial in which patients who failed to respond to the first treatment or relapsed while receiving it were switched to the other. Eighteen (30%) out of 60 patients initially treated with tamoxifen achieved an objective response and 11 (18%) showed stable disease. Seventeen (30%) out of 57 patients treated initially with aminoglutethimide achieved an objective response and 13 (23%) achieved stable disease. Objective responses in bone metastases were achieved more commonly with aminoglutethimide (11 patients (35%)) than with tamoxifen (five (17%)). The predicted median duration of response for tamoxifen was 15 months and for aminoglutethimide over 15 months (no significant difference). Five (15%) out of 34 patients who failed to respond to tamoxifen and four out of six patients who relapsed after responding to tamoxifen subsequently responded to aminoglutethimide. In contrast, only two (6%) out of 31 patients who failed to respond to aminoglutethimide and none out of four patients who relapsed while receiving aminoglutethimide subsequently responded to tamoxifen. The main side effects occurring in the 97 patients who received aminoglutethimide as first- or second-line treatment were lethargy and drowsiness (36 patients) and rash (29); seven patients had to stop treatment because of side effects. In contrast, side effects were rare and mild with tamoxifen and no patient had to stop treatment because of them. Both tamoxifen and aminoglutethimide appeared from this study to be equally effective in the medical endocrine treatment of advanced breast cancer.
Serum thyroglobulin (Tg) was measured in 274 patients with differentiated thyroid cancer; 266 had previous thyroidectomy, which had been followed by ablative iodine-131 in 183 cases. Neither the presence nor the titre of anti-Tg antibodies appeared to affect Tg assays. Serum Tg reflected the presence or absence of cancer in 83% of 164 patients not receiving thyroxine (T4). This concordance improved to 97.5% in 158 patients tested while receiving T4. 34 patients in remission were tested both on and off T4 therapy; in all these patients the Tg level when receiving T4 was less than 5 micrograms/l. In 19 of 21 patients with cancer T4 treatment did not suppress Tg. Serum Tg thus provides an excellent marker for the presence or absence of thyroid cancer in patients taking T4, even if anti-Tg antibodies are present. It is proposed that monitoring of patients by assay of serum Tg should supplant routine assessment by radioactive-iodine scans of the neck or whole body.