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The history of cancer care of Kerala spread back to colonial era, where the first hospitals with cancer care facilities were started and run by the London Missionary Society. Later, many government hospitals started cancer care and establishment of the Regional Cancer Centre in 1981 elevated the status of Kerala in the cancer care map of India. The history of modern cancer care in Kerala dates back to the nineteenth century. In Travancore, where the capital of Kerala was later located, modern medicine was first made available in 1811 to the royal family followed by their officials, prisoners and the general public respectively.

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BACKGROUND: Chemo-radiotherapy has become the standard of care for loco-regionally advanced head and neck cancers. Platinum based regimens are the most effective. Although benefits are proven with chemo-radiation, acute toxicities are markedly increased. The dose and delivery schedules of Cisplatin have ranged from intermittent higher dose [100 mg/m2] every 3 weeks to low dose [6 mg/m2] daily administration. At present there is no data indicating which regimen is superior. PURPOSE: To compare acute toxicities of two chemotherapy schedules for head and neck cancers. MATERIALS AND METHODS: A total of 83 head and neck cancer patients treated with two schedules of concurrent chemo RT were analyzed, retrospectively, for treatment toxicity. In group A [51 patients], chemotherapy [CT] was administered on week 1, 4 and 7 [cisplatin 100 mg/m2] over a period of 2-3 days. In group B [32 patients], CT was delivered weekly [cisplatin 40 mg/m2]. Radiotherapy dose was 7000 cGy in 35 fractions for definitive concurrent chemo-radiation and 6600 cGy in 33 fractions for adjuvant treatment. RESULTS: Group B patients had increased grade III skin and hematological toxicity, where as patients in group A had more pharyngeal toxicity. Treatment interruptions and percentage of weight loss were higher in group B. Weekly CT schedule had higher rate of severe mucositis, which was statistically significant on both univariate [P = 0.005] and multivariate [P = 0.007] analysis. CONCLUSIONS: Three weekly CT is less toxic than weekly. Weekly CT can be made more acceptable by reducing the dose and using feeding tubes for nutrition.

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Successful management of large AVMs is difficult. Traditionally they are considered less responsive and even unsuitable for radiosurgery. This case report demonstrates total angiographic obliteration in a complex, large corpus callosum AVM (volume 36.52 cc) in a 39-year-old male. Stereotactic radiation was delivered with a Linear Accelerator using ultra conformal treatment planning. Large volume AVMs can be subjected to stereotactic radiosurgery if the shape and location makes it possible to deliver an adequate radiation dose.

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The survival experience of 452 cervical cancer patients registered during 1984 by the hospital registry of the Regional Cancer Centre, Trivandrum, Kerala, India, is described in this paper. Eighty per cent of the patients completed the prescribed treatment, which was predominantly radiotherapy. The vital status of each patient was established by scrutiny of case records and by reply-paid postal enquiries. The observed survival rates were estimated by the Kaplan-Meier method and prognostic factors were assessed using Cox's proportional hazards regression analysis. The overall 5 year observed survival rate was 47.4% (95% CI, 41.6-52.9%). Socioeconomic status, performance status and the clinical stage of disease emerged as independent predictors of survival. Low survival was associated with advanced stages of disease, low socioeconomic status and poor performance status. The problems in studying survival from cancer in developing countries and the strategies used to improve follow-up rates in India are discussed. It is stressed that trends in survival rates may be used to evaluate cancer control programmes in developing countries in the absence of reliable mortality statistics and, even when mortality data are available, survival rates are valuable comparative statistics. Earlier detection by improving the awareness of the population and the physicians will improve survival rates, but a more effective and prudent approach would be to prevent invasive cervical cancer, and thereby reduce mortality, by implementing feasible and effective screening programmes in India.

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BACKGROUND: Hodgkin's disease seen in the developing countries differs from that seen in developed countries. There are only a few reports from India regarding the epidemiologic and clinicopathologic features of Hodgkin's disease. METHODS: The records of 159 evaluable patients with Hodgkin's disease seen at the Regional Cancer Centre, Trivandrum, India, during the period 1983-1989 were reviewed for clinicoepidemiologic profile and survival analysis. The Kaplan-Meier product limit method was used to compute survival, and Cox proportional hazard regression analysis was used to study the factors affecting survival. RESULTS: The male-to-female ratio was 3.1:1. The mean age at presentation was 38 years in adults. Supradiaphragmatic presentation (44.7%) was more common, and mixed cellularity (50.3%) was the predominant histologic subtype. There were 9.4% patients with Stage I disease, 37.1% with Stage II, 33.4% with Stage III, and 20.1% with Stage IV disease. Of the patients, 57.9% were treated with chemotherapy, whereas 23.3% had radiation therapy alone, and 18.8% had a combination of radiation therapy and chemotherapy. Complete response was noted in 77.4% (n = 123) of patients, of whom 20.3% (n = 25) later experienced disease relapse. Second remission could be achieved in 8 of 25 patients with disease relapse. The overall 5-year survival rate was 55%. The stage-related survival rates were 89%, 69%, 53%, and 27% in Stage I-IV, respectively. On multivariate regression analysis, patient age and disease stage emerged as significant predictors of survival. CONCLUSION: Mixed cellularity was the most common histologic subtype. The inferior survival rate observed could be attributable to advanced stage of presentation, compromise on the drug and dose, and the lack of proper supportive measures. Patient age and disease stage were the important predictors of survival.

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Sera from 93 patients with carcinoma of the buccal mucosa were analysed for its regulatory effect on CD2 antigen expression using anti CD2 monoclonal antibodies and sheep erythrocyte rosetting assay. The sera from 55.5% of the patients showed an inhibitory effect (blocker sera) while sera from 44.5% showed an enhancing effect (enhancer sera) on the CD2 antigen expression. An interesting feature observed was the dominance of enhancer sera in the early stages of the cancer, well differentiated squamous cell carcinoma and verrucous carcinoma. The regulatory effect of the sera had no correlation to the concentration of circulating immune complexes (CIC), ferritin, and serum immunoglobulins on an individual basis. Taken as a whole, the concentration of CIC was higher in the enhancer sera while the concentration of IgG and IgM were higher in the blocker sera. The dominance of enhancer sera in groups with better prognosis in clinical practice suggest a correlation with the presence of serum enhancing factors to a good prognosis. The correlation of regulatory status to the prognosis of the patient is examined as the second phase of the study.

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There have been no reports concerning the independent predictors of response and disease-free survival (DFS) in oral cancer in India, where the highest incidence is reported. The authors analyzed the outcome of radical radiation therapy of 378 patients with oral cancer and found that the complete response rate within 6 months of completion of treatment was 45% and the 5-year DFS was 34% (95% confidence interval 29% to 39%). Regional lymph node involvement (P less than 0.001), histologic type (P less than 0.01), and the intraoral site of lesion (P less than 0.025) were identified as independent predictors of response when adjusted in a forward stepwise logistic regression analysis. The Cox proportional hazards regression analysis revealed that regional lymph node involvement (P less than 0.001) and histologic type (P less than 0.05) were independent prognostic factors for DFS. Patients with fixed regional lymph node involvement demonstrated a relative risk (RR) of 2.4 compared with those with N0 disease. Patients with well-differentiated squamous carcinoma had an RR of 2, and those with other histologic types (other than verrucous carcinoma) had an RR of 1.5.

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A case-control study of oesophageal cancer was carried out in Trivandrum, Kerala, involving 267 cases and 895 controls. Risk factors studied in males were pan (betel)-tobacco chewing, bidi and cigarette smoking, drinking alcohol and taking snuff. Only pan-tobacco chewing was investigated in females as very few indulged in the other habits. Among males significant associations with higher risk were observed for bidi smoking (p less than 0.001), bidi plus cigarette smoking (p greater than 0.05) and drinking alcohol (p less than 0.001). While a significant effect of duration of pan-tobacco chewing (p less than 0.005) was observed in males, there was no significant trend, the risk first falling then rising as duration of use increased. This was partly due to confounding with smoking. No effect of pan-tobacco use was observed in females. A step-wise model was fitted, retaining only those risk factors which were significant when adjusted for other factors; the risk factors included were duration of pan-tobacco chewing, duration of bidi smoking, daily frequency of bidi and cigarette smoking and alcohol use (yes or no). An adjusted relative risk of 2.03 was observed for a pan-tobacco habit of more than 40 years' duration, of 4.70 for more than 20 years of bidi smoking, of 4.80 for more than 20 bidis/cigarettes per day, and of 2.33 for regular alcohol use (in each category relative to a baseline of those never indulging in the relevant habit).

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An analysis of lymphocyte subpopulations was done in patients with cancer of the uterine cervix before and at different intervals after the commencement of radiation therapy. A common feature was a duration of T-cell and B-cell lymphopenia after therapy. The findings relating to the T-cell subsets were interesting. Although the CD4/CD8 ratio remained unchanged in Stages I/IIA for 24 months after treatment, patients with Stages IIB and III showed a lowering of the ratio immediately after treatment. Distinctive patterns of lymphocyte subset distribution were seen in a comparison between patients who were disease-free and those with recurrent disease. The CD4+ cell counts and CD4/CD8 ratio differed between the two groups, with consistent lowered values during the follow-up associated with recurrent disease. This study demonstrates the effects of radiation therapy in altering lymphocyte subset distribution, resulting in characteristic patterns which could be used as clinical and prognostic indicators.

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A multiparameter analysis of immune function was done on patients with squamous cell carcinoma of the uterine cervix to look for any variable(s) that could be correlated with the clinical stage of the disease. Five immunological variables, viz., CD4+ lymphocytes, CD4/CD8 ratio, natural killer cells, concanavalin A-induced suppressor index, and circulating immune complexes, were found to consistently vary with tumor load. When these variables were subjected to a multiple regression and multivariate analysis, an equation for a diagnostic index curve was derived. Application of this equation led to an immunological staging system which could be used as an excellent prognostic indicator. The immunological staging system showed that patients classified into a particular clinical (FIGO) stage behaved in a heterogeneous way immunologically and that patients developing recurrent disease could easily be identified from those remaining disease free, even before treatment. Subsequent follow-up of these patients further confirmed this observation, with the recurrent disease group easily identifiable. These results point out the immense potential of such a staging system and the importance of immunological evaluation in the preliminary management of patients with malignant cervical neoplasia.

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Peripheral blood lymphocytes from patients with different stages of cancer of the uterine cervix were analysed for concanavalin-A-induced suppressor cell activity. All cancer patients had high levels of suppressor activity, the increase corresponding to tumour load. Radiotherapy resulted in further increase of suppressor activity. About six months after radiotherapy, patients who remained disease free returned to pretreatment levels of suppressor cell activity and later showed even lewer levels of suppression. On the other hand, patients who developed recurrent disease maintained sustained high levels of suppression and for all stages they always had higher suppressor activity than the patients who remained disease free in the corresponding stage. These results stress the importance of a possible deranged immune system in these patients and also shows the clinical and prognostic significance of the assay.

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Clinical and prognostic significance of radiation associated eosinophilia (RAE) and radiation associated monocytosis (RAM) was evaluated in 176 patients with squamous cell carcinoma of the uterine cervix followed up after radiotherapy. Significant RAE was noticed in patients with Stages I/IIA and IIB who remained disease-free after treatment. On the contrary, patients belonging to these two stages but who developed recurrent disease showed absence of RAE. These patients as well as those belonging to Stage III showed considerably higher levels of RAM as compared to those patients remaining disease-free. These observations showed the usefulness of these two simple inexpensively carried out parameters in prognosticating disease course in malignant cervical neoplasia.

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105 patients with cancer of the tongue were treated with radical radiotherapy in 1982 at the Regional Cancer Centre, Trivandrum, India. The overall local control rate was 55% and the 3-year actuarial disease-free survival was 36% with radiotherapy. The analysis revealed a close correlation between stage of the disease and local control as well as survival. 45% of the patients with clinically positive cervical nodes had their disease controlled by radiotherapy. Since the best results were obtained with early disease, the need for clinical downstaging by early detection is stressed.

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In vitro assays of immunocompetence were done in 60 patients with differing extents of tumor load and various histologic types of lung cancer and were compared to values obtained for 60 normal controls. Profound alterations in monoclonal antibody-defined T-lymphocytes and circulating B-cells were seen. All patients showed impaired blastogenic response to the mitogens used with the exception of a normal response to pokeweed mitogen (PWM) in patients with localized disease. Increase levels of serum IgG were seen in patients with localized disease whereas high levels of IgA was seen in patients with more advanced disease. Distant metastases were associated with low IgM levels. All patients studied regardless of stage and histologic type had elevated levels of circulating immunocomplexes. These findings indicate gross immunologic abnormalities in these patients.

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Peripheral blood lymphocytes of patients with malignant cervical neoplasia were studied for their capacity to produce interleukin-2 (IL-2) upon in vitro mitogen stimulation. Patients with early disease (Stage I/IIA) showed levels comparable to normal controls but those with advanced disease showed reduced levels, the reduction increasing with tumour load. These findings excellently correlated with our previous observations on a depressed cellular immunity in these patients. On follow up of the patients it was noticed that those who developed recurrent disease showed sustained lower levels of IL-2 production compared to those who remained disease free. These results stress the importance of a deranged immune system in these patients and also shows the clinical and prognostic value of such an assay.

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A case-control study of cancer of the gingiva was carried out in Kerala, Southern India, using 187 cases and 895 hospital-based controls. We investigated the effects on risk in males of pan (betel)-tobacco chewing, bidi and cigarette smoking, drinking alcohol and taking snuff. In females only pan-tobacco chewing was investigated as very few females indulged in the other habits. Among males, significant positive associations with risk were observed for pan-tobacco chewing (P less than 0.001), bidi smoking (P less than 0.001) alcohol drinking (P less than 0.001) and snuff use (P less than 0.05). In females, pan-tobacco chewing had a similar predisposing effect (P less than 0.001). Daily frequency of pan-tobacco chewing was the strongest predictor of risk in males, with a relative risk of 15.07 associated with chewing ten or more quids per day. The corresponding relative risk among females was 13.69. In males a relative risk of 3.20 was associated with smoking more than 20 bidis per day, and relative risks of 2.62 and 3.90 were associated with regular use of alcohol and snuff respectively. Surprisingly high relative risks were observed in association with occasional use of pan-tobacco, bidi, cigarettes, alcohol and snuff. A stepwise logistic regression analysis yielded four predictors: pan-tobacco daily frequency, duration of bidi use, and alcohol and snuff use (regular versus never). There were also significantly elevated risks associated with occasional indulgence in these four habits. Total lifetime exposure was no better at predicting risk than daily frequency or duration of habits.

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In vitro modulation of spontaneous cell mediated cytotoxicity by interferon and interleukin 2 was carried out using peripheral blood lymphocytes from patients with cancer of the uterine cervix before and at different intervals after commencement of radiation treatment. A total of 150 patients with various stages of the disease were included and cytotoxicity was measured using the single cell cytotoxic assay. These results indicate a beneficial effect in vitro of interleukin 2 and interferon in augmenting spontaneous cell mediated cytotoxicity, a possibly vital antitumour immune mechanism in patients with relatively early cervix cancer. Natural killer cell, lymphokine activated killer cell and interferon activated killer cell activity was depressed immediately following radiotherapy. The activity of these cell types later on increased above pretreatment levels in patients with stages I, IIA and IIB. A similar rebound above pretreatment levels was not observed in patients with stages III and IV.

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The significance of immune reactive proteins in malignant cervical neoplasia, with particular reference to its prognostic and clinical relevance, was studied in 229 patients. All stages of the disease showed elevated levels of circulating immune complexes (CIC). Patients with stages I/IIA showed elevated levels of IgG, whereas those with stages III and IV showed depressed IgM levels. In the case of IgA, the situation was reversed: patients with advanced disease showed increased levels. Radiotherapy resulted in highly elevated levels of CIC, IgG, and IgA. However, in patients who remained disease-free after radiation treatment, levels of these proteins came down, often falling below pretreatment levels. On the other hand, patients developing recurrent disease showed sustained, high levels of CIC and IgA, with IgG as an isolated case in stage I/IIA. The present study therefore shows that although these increases were non-tumour-specific, patients with persistent elevation of CIC and IgA levels were at much greater risk of developing recurrent disease, thereby proving the merit of these substances as markers in prognosticating the course of disease in malignant cervical neoplasia.

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