Biomedical subjects
Publications and source records attributed to V Shanta.
A 35 year old woman who was in clinical remission of acute lymphoblastic leukaemia on standard therapy presented with leukaemic involvement of both breasts. Local radiation therapy with concurrent systemic chemotherapy with vincristine, daunorubicin. L-asparaginase and prednisolone produced complete resolution of the breast lesions.
Granulocytic sarcoma is an uncommon tumour composed of granulocytic precursor cells. A rare presentation of granulocytic sarcoma of the ovary occurring in a patient with chronic granulocytic leukaemia in blastic crisis is reported.
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One thousand thirty-seven female breast cancers were treated at the Cancer Institute (WIA), Madras, between 1965 and 1978. Five hundred twenty-one of them (ie, just over 50%) were in stage III, with extensive local disease, unsuitable for surgery ab initio. Four hundred twelve of them (group A) received radiation therapy (RT) initially and 109 (group B) a combination of radiation and chemotherapy (CT). In 68% of the former and 77% of the latter the tumours became resectable after this preliminary treatment. Radical mastectomy in group A and Patey's mastectomy in group B were performed. The material in these two groups was similar. The five-year survival NED in group A was 45%, and in group B 64.61%. Adequate surgery following RT and CT seemed essential to improve survival. The impact of added chemotherapy (CT) was mainly felt in the node-positive cases.
Two-thirds of all cancers in South India are squamous cell carcinomas, of which 78% to 93% are late cases requiring radiotherapy. Oral cancers, which constitute the majority of these, provided an excellent clinical model for studies in radiotherapeutic biology. Their characteristics made them ideally suited for our clinical trials. The paper reviews the special biology of these lesions, the factors involved in their radiation non-response, the therapeutic postulations that suggested themselves, the implementation of these therapeutic protocols and the mixed story of failure and success that has marked the two decades of these studies. It discovers the fact that radiation response is not just a factor of tumor extent but involves several biological subtleties in both tumor and its host environment. It also discusses possible future approaches to bridge a gap of about 30% failure in these lesions, especially in the context of a poor economy.
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The present report is the sixth in a series of combination therapy trials in oral carcinoma in South India conducted since 1960. In the fifth trial a combination of bleomycin (BLM) and irradiation was compared with irradiation alone. The results gained and the subsequent experience in an unselected series demonstrated in buccal mucosal squamous cell carcinomas a highly superior effect with the irradiation-BLM combination, but still revealed a failure rate around 30 per cent. The present clinical trial--irradiation + BLM was compared with irradiation + BLM + hyperbaric oxygen (HbO) and irradiation + placebo + HbO--was undertaken in an attempt to eliminate or at least reduce these failures. The results were unexpectedly disappointing in that the irradiation combined with BLM + HbO proved to be inferior to irradiation + BLM. An attempt has been made to elucidate the possible reasons for this surprising outcome.
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A clinical trial comparing Bleomycin (BLM) plus radiation against radiation alone is reported. One hundred and fifty-seven previously untreated T3 and T4 and N0, N1 or N2 buccal squamous cell carcinomas were entered. Eighty-four of these received the combined therapy and 73 were controls. Cobalt-60 teletherapy using two opposing fields was employed. BLM was administered intra-arterially in 42 patients, intravenously in 22 patients and intramuscularly in 20 patients. The 73 controls received physiological saline as a placebo. Total clinical healing of the lesion within the volume of irradiation eight weeks after the end of radiotherapy was termed a favourable response. Anything else was a failure. Five-year recurrence-free rates and disease-free survival were also evaluated. The favourable response rate in the study group was 78.6% and in the control 19.1%. The corresponding recurrence-free rates and five-year survival rates were 71.8% and 17%, and 65.5 and 23.5% respectively. The main toxic features were acute mucositis, pneumonitis and dermatitis.
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We studied 145 cases of larynx cancer in relation to their etiology, methods of treatment, and results. It was found that better results were obtained with a combination of radiotherapy and surgery. Any postradiational edema of the larynx should subside within 3 months. If this edema persists or progresses, it always means residual disease in the submucosal plane. We have now improved our results by using intravenous Bleomycin concurrently.
A concurrent randomised controlled clinical trial to evaluate a combination of Bleomycin and radiation as against radiation only in the treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras, since 1971. All T3 and T4 previously untreated oral squamous cell carcinomas with N0, N1 and N2 regional nodes, or N3 nodes confined to the submandibular region, without systemic metastases or gross infiltration of the temporal and infratemporal fossa producing total trismus, and in decent general health were eligible for the trial. Patients with gross active pulmonary tuberculosis were excluded, as were recurrent carcinomas. Age, external fungation of growth or radiological bone invasion were no bar. Randomisation was done by the sealed envelope technique. The study group received concurrent fractionated cobalt 60 teletherapy using two opposing fields and 10-15 mg of Intra-arterial or Intravenous Bleomycin. The controls received fractionated cobalt teletherapy and i.v. or i.m. distilled water on the same protocol as the Bleomycin cases. All cases were evaluated double blind 8 weeks after the end of radiation therapy, and were classified as 'favourable response' or 'failure'. The criterion of 'favourable response' was 'total clinical healing of the tumour within the volume of irradiation with no subsequent recurrence within that volume, whatever the length of follow up'. Anything else was reported as a failure. A long term follow up of 3 years is also available. 136 cases have completed the trial. The favourable response in the study group was 77% as against 20.9% in the control group. The differential response is statistically significant. The present study is the fourth in the series of combined therapeutic trials conducted in advanced oral squamous cell carcinoma since 1958. (Krishnamurthi and Shanta, 1963, 1965, 1967 and 1971). A concurrent randomised controlled clinical trial to evaluate the combination of Bleomycin and radiation as against radiation only in treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras since 1971.
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