ACHIEVEMENTS CUM PERFORMANCE REPORT 2003-2004 CANCER INSTITUTE (WIA) CHENNAI – 600 020 ACHIEVEMENTS CUM PERFORMANCE REPORT OVERVIEW The Cancer Institute (WIA) had an eventful year in 2003, with preparations being made for the Golden Jubilee in 2004. Our Chairman, Dr.V.Shanta, was honored with the Guild of service (Central) Award - in recognition of her contribution in the field of medicine; the Cosmo Award – for being an eminent and distinguished citizen of the country; the Kamaraj Centenary Award for contribution to fight against cancer; Alliance Francaise award for her meritorious service towards cancer patients and she delivered the Dr.M.Snehalatha Memorial Oration. After 2 years of struggle, the customs duty exemption for consumables and equipments for Research was received by the Institute. In connection with this, the Institute would like to thank Shri.S.Venkitaramanan I.A.S. (Retd), Shri C.S.Rao, Shri. V.Lakshmi Ratan, Shri. Vijay L.Kalker and others, who made this possible. Our sustained efforts, have benefited all the Regional Cancer Centers, as well, as the Regional Cancer Centers have been now included under Institutions eligible to claim customs duty exemption for Research consumables and equipments. The 20 varai 20 public donation scheme was inaugurated by Mr. Kamalahasan. The scheme aims to raise a contribution of Rs.20 crores through donation of Rs.20 or its multiples from the public. The funds are needed for replacing several aging equipments, including the Linear Accelerators, Cobalt tele-therapy unit and for purchase of newer equipments for patient treatment and Research. Subsequently several fund raising activities were initiated, including one on 16th August. The Annual No Tobacco Day was held on 7th June 2002, in the Madras University auditorium, with the Theme being "Tobacco free films and Fashions". The meeting was sponsored by the WHO and had more than 1000 participants. The meeting was inaugurated by Hon.Thiru A.Raja, Minister of State for Health, Govt. of India. Several Film and TV personalities spoke on the occasion and pledged not to use tobacco. The Annual Cancer Survivor’s Day was celebrated on 15th June 2002. There was an overwhelming response from our patients and relatives, who attended this function in large numbers. Mrs. Girija Vaidyanathan, Health Secretary, Govt. of Tamilnadu, was the Chief Guest. Mr.N.Ram, Editor, Frontline, and several TV personalities participated in the event. The Rotary club of Madras Metro, the Rotary Foundation of the Rotary International, the Rotary International Clubs of Malaysia and Indonesia, made a kind donation of Rs.20 lakhs towards the purchase of a new Mammography unit, to replace the old unit. The unit was inaugurated by His Excellency, the Governor of Tamilnadu, on 28th August, 2003. A kind donation of Rs.21 lakhs was made by the Chennai Willingdon Corporate Foundation towards the purchase of a Real time PCR unit. The unit was inaugurated by Hon. Minister for Health, Thiru Thalavai Sundaram on 23rd October, 2003. The Mahesh Memorial Trust held the foundation stone laying ceremony for the proposed New Pediatric ward at the Main Institute campus on 5th October, 2003. The ward will have a day care unit, ICU, dining hall, play area, mother's room etc. The Rotary Club of Madras Metro renovated the Dharamsala housing the Male General Ward. This has tremendously improved the ambience and has contributed to improving the psychological well being of the patients. They have also promised to renovate the Female General Ward section as well. The WHO has funded a Palliative care program which commenced operation from February 2003 and a Population screening programme in the Thiruvanmiyur area, which was launched in March 2003. Dr. B.Nagarajan, Prof and Head, Dept. of Tumour Microbiology, received the Indira Gandhi award for Outstanding contribution in the Chosen Profession. Dr. N.Mayilvahanan, Consultant Orthopaedic Oncologist at the Institute, was awarded the B.C.Roy award for the Limb salvage surgeries done predominantly at the Institute. Mrs. M.Gnanasundari, Nursing Staff in the post-operative ward received the Vocational Service award from Rotary Club of Madras Central. Dr. R.Priyadharshini was awarded a one year Fellowship under the Training and Research in Italian Laboratories (TRIL) programme, by the Abdus Salam International Center for Theoretical Physics and will spend a year in Italian Institutions, training in Nuclear Medicine, diagnostic radiology, MRI etc. Dr. A.Vasanthan, Chairman, Division of Radiation Oncology was appointed as a member of the ICMR (Indian Council of Medical Research) task force on management of cancers. Dr. R.Swaminathan was deputed to visit IARC, Lyon to analyze data on Cancer Survival for the 2nd Volume of the IARC Monograph on "Cancer Survival In Developing Countries". Dr. Nirmala Nancy was a visiting Scientist in King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, for training in newer techniques in Molecular Oncology. Dr. Vikas Mahajan underwent training in Hepatic Surgery under Prof. K.C.Tan and Prof. London Lucian Ooi, in Singapore. THE COLLEGE OF ONCOLOGICAL SCIENCES The College conducts super-specialty training in Medical Oncology, Surgical Oncology and Radiation Oncology; is recognized for Ph.D. training in its departments by the T.N.Dr.M.G.R.Medical University, Anna University of Technology and Madras University; conducts the M.Sc. Medical Physics course under the Anna University of Technology. Students who have completed their degrees / courses are Ph.D. Dr. B.Santhanaraj Dr. N.Vivekanandan Dr. P.Kumari Dr. R.Srivani D.M.(Medical Oncology) Dr.Devanand Dr.Subba Rao Dr.Sanjay Piplani M.Ch (Surgical Oncology) Dr.V.Sridevi Dr.Bargavi Dr.Praveen Garg M.Sc (Medical Physics) Anand, M.R. Arun Kumar, T. Balaji, N.Gaurav Sanyal Gypson Joe Anto Jisha Kumari, R. Kaviarasu, K. Kayalvizhi, L. Mahalakshmi, S. Merlin Praveena Kumari, A. Murugan, A. Sasikaladevi, T. Sellakumar, P Tamil Kumar, P Timothy Peace Balasingh, S. Ukash Ahamed Ibrahim Vikraman, S Vivekanandan, C. Yogesh Kumar, R. . Dr.Anita Chandra completed her M.Sc. Oncology course at Queen's Medical Center, Nottingham and was awarded with Diploma in Child Health from the Royal College of Pediatrics. The Institute also offers Radiotherapy Technician Training course, which is approved by the AERB. In 2002, the AERB approved the start of the Radio-Diagnosis Technician Training course. STUDENTS UNDER TRAINING Nine students are currently registered for M.Ch., and 9 for D.M.; 3 for M.D.(Radiation Oncology), 1 for D.M.R.T, 1 for Ph.D. in Biochemistry; 5 for Ph.D in Molecular Oncology; 19 students for M.Sc. (Medical Physics), 5 students for the Certificate Course in Radiotherapy Technology and 6 students for the Certificate course in Radio-diagnosis Technology. In addition, nearly hundred students from all over the country underwent Observership training in clinical and research departments. LECTURES, CONFERENCES, SEMINARS, WORKSHOPS AND CME PROGRAMMES 1. The Gynaec Oncology Workshop was held from 23rd - 25th, January 2003 and was attended by more than 100 delegates from all over the country. National and International faculty demonstrated operative procedures and conducted training sessions. 2. A “Cancer Registry Training Workshop” was organized for oncologists, physicist, statisticians and computer persons from four Regional Cancer Centres in Allahabad, Cuttack, Kolkata and Nagpur during March 17-21, 2003 and one other Regional Cancer Centre in Patna during 23-25 June 2003. The faculty for the workshops comprised Dr. R. Swaminathan, Dr. Nalini, Mrs. R. Rama, Mr. S. Devarajan, Ms. M. Kavitha, Mr. J.Murugaian and Mr. P.Thangavel. 3. CME on CML & Glivec in April, 2003. 4. A “Workshop on Cancer Registration” was organized for the personnel from Vital Statistics Division (Birth & Death Registrars), Corporation of Chennai on 14.6.2003 – about 60 delegates participated. 5. Medical Records and Registration departments of the Government and Private hospitals and other institutions in Chennai on 18.6.2003 – 125 delegates 6. CME on breast cancer on 21.06.2003 7. A National level workshop on “Cancer Registration: Principles & Methods” under the auspices of the National Cancer Registry Program of the Indian Council of Medical Research (ICMR), New Delhi, during November 11-12, 2003. – Attended by 100 delegates from cancer the registries all over India. 8. XIX Annual Review Meeting of Cancer Registries in India under the auspices of the National Cancer Registry Program of the Indian Council of Medical Research (ICMR), New Delhi, during November 13-14, 2003. INVITED LECTURES Dr. Srinivasa Madhavan, Consultant in Radiation Oncology, Dublin, Ireland, visited the Institute in November, 2003 and gave a lecture on radio-therapeutic management of prostate cancers, especially with conformal radiotherapy. In addition Tumour Boards and clinical audits were conducted every Friday. Clinical Demonstration, didactic lectures, Journal club sessions, Departmental seminars in the different disciplines were conducted Monday thro’ Saturday every week for 10 months in a year. CLINICAL STATISTICS FOR THE YEAR 2003 Total number of cases seen Total number of new cases registered Total numbers of cases seen on follow up Total number of subjects attended screening clinic Total number of new cancer cases registered Percentage of patients treated free 1,07,647 13,012 94,635 404 7,963 68% REGIONWISE DISTRIBUTION OF NEW CASES State Total No. Chennai Rest of Tamilnadu Andhra Pradesh Kerala Assam Other states Outside India Total 3664 5536 3007 209 193 394 9 13012 DIAGNOSTIC PROCEDURES Radiological studies 182295 Odelca camera studies 3725 Contrast radiography 44350 Mammography 7120 USGM 139989 CT scans 101260 Scintiscans 4076 Biochemical investigations 413295 Clinical Pathology 212802 Histopathology sections 416869 Specimen Dissections Done 2517 Cytology smears 47580 Bone marrow aspirations and biopsies 2785 Cytochemical studies 176 CSF Study 1083 Bacteriological studies 16186 Cytogenetic studies 600 Electron Microscopy studies 150 Immuno-histochemistry and cytochemistry 1107 Immunophenotyping & DNA study by FACSCAN 175 TREATMENT PROCEDURES Operative procedures 10198 Teleradiation treatment 170092 LDR Selectron cases 542 HDR Micro Selectron cases 733 (a) Intracavitary therapy 650 (b) Interstitial/Intraluminal therapy 83 Treatment Planning (a) 2D Plans 2603 (b) 3D Plans 103 Chemotherapy treatment 404982 Allogenic Bone-marrow transplant 3 Autologous Transplant & Cord blood Transplant 5 Metabolised Radio-active isotopes 2764mCi Blood Transfusions 2292 Blood component therapy 3699 Dental treatments 7056 % 28.2 42.5 23.1 1.6 1.5 3.0 0.1 100.0 RESEARCH PROJECTS INCLUDING CLINICAL RESEARCH 2003 DEPT. OF MOLECULAR ONCOLOGY ONGOING PROJECTS Detection and quantitation of minimal residual disease in Acute Lymphoblastic Leukemias (ALL) using Real Time PCR: a. Chromosomal Translocation: (E2A-PBX-1, MLL-AF4, mBCR-ABL and TEL-AML1) Fifty-five patients clinically diagnosed and immuno-phenotyped as ALL were studied for detection of fusion gene transcripts at presentation using Real Time PCR. All the 55 patients cDNA amplified for GAPDH gene (Taqman) confirming integrity of the RNA. Eleven of the 55 (20%) ALL revealed one of the 4 risk stratifying translocations by Real Time PCR. Five patients (45.5%) PCR amplified for the E2A-PBX1, 2 (18%) for ALL type mBCR-ABL, 3 (27%) for TEL-AML1 fusion gene transcripts and one for MLL-AF4 translocation in this series of patients. The specificity of the PCR products was confirmed by melting curve analysis. Sequencing of the translocations revealed no variations in the breakpoints. b. Gene Rearrangements DNA from BM/PB of 60 leukemia patients at presentation and 20 remission samples were isolated, quantitated by Real Time PCR using RNAse P standards and studied for gene rearrangements by PCRHeteroduplex analysis. DNA from BM/PB of 60 leukemia patients at presentation and 20 remission samples were isolated, quantitated by Real Time PCR and studied for gene rearrangements by PCR-Heteroduplex analysis. In T-ALL, TCR rearrangements were observed in 18/22 (81.9%) cases and TCR rearrangements are observed in 9/22 cases (40.9%). V1-J1 is the most common rearrangement. In the pediatric calla patients, 7 revealed V2-D3 rearrangement. Sequencing the Homoduplex, design of Allele specific oligonucleotides (ASO) specific for each patient and Taqman probes to J gamma-1, J delta-1, D delta-3 and IgH regions are being done to quantitate MRD in ALL. The DST funds the above studies. Hereditary cancer prevention and detection programme Population based Hereditary Cancer Registry This project funded by WHO, covers the Chennai Metropolitan area and is the first Population based Hereditary cancer registry in the country. A total of 206 cases have been collected. This includes 130 families where 2 members are affected with cancer and 47 families where more than two members are affected with cancer. There are 20 hereditary breast and ovarian families and 3 HNPCC families. Thirteen early onset colorectal cancer cases and 14 early onset breast cancer cases have been registered. There are two cases of early onset ovarian cancer. Hereditary cancer clinic So, far 358 cases have been registered in the clinic. This includes 151 families where 2 members are affected with cancer and 98 families where more than two members are affected with cancer. There are 44 hereditary breast and ovarian families and 11 HNPCC families. Sixty-one early onset colorectal cancer cases and 26 early onset breast cancer cases have been registered. There are three cases of early onset ovarian cancer. Hereditary breast and ovarian cancer study A total of 37 cases have been analyzed for mutations in the BRCA1 and BRCA2 genes and for CHEK2 1100 del C. Four pathogenic mutations have been identified in these cases. Two of these are novel and have been submitted to Gene Bank. Many known polymorphisms were identified both in BRCA1 and BRCA2 genes in all except one case. CHEK2 1100 del C was not seen in any of the cases so far analyzed. Hereditary colo-rectal cancer study. Under this study a total of 43 cases have been analyzed. First screen was done by microsatellite instability analysis (MSI), followed by mutational screen of hMLH1 and hMSH2 gene using d-HPLC. Five mutations have been identified and four of them are novel; Four are deleterious. Few polymorphisms were also identified. The novel mutations have been submitted to the Gene Bank. Both the above studies are funded by the DBT. Development of Diagnostics in Small round cell malignant tumours Small round cell malignant tumors can present diagnostic difficulty, as they may not be distinguishable by light microscopy. Cytogenetics studies have revealed specific chromosomal translocation in these tumors. The objective of the project was to develop a RT-PCR based assay for the diagnosis of small round cell malignant tumors mainly the Ewing's’ sarcoma and Rhabdomyosarcoma. Approximately 85% of Ewing's’ sarcoma harbor the translocation t(11: 22) which creates a functional EWS-FLI1 fusion gene. Most cases of Rhabdomyosarcoma have been found to have a t(2:13) or t(1:13) translocation which results in the formation of PAX3-FKHR or PAX5-FKHR fusion transcript respectively. Twelve biopsy samples were collected from patients whose clinical and radiological data were compatible with a diagnosis of Ewing's’ sarcoma or small round cell malignant tumor. Histo-pathological diagnosis of Ewing's’ sarcoma was made in seven cases and in four round cell tumors only a differential diagnosis was given and one sample was diagnosed as embryonal Rhabdomyosarcoma. Out of seven Ewing’s sarcoma cases, 6 (88 %) expressed EWS-FLI fusion transcript. Of the four diagnosed as round cell tumors, two showed EWS-FLI1 translocation. One of the histo-pathologically identified Ewing's’ sarcoma case, did not show either the t(11:22) or the t(21:22 translocations. PCR products were taken for direct sequencing. Sequence of amplified product revealed two different EWS-FLI 1 in-frame junctions (62% showed type 2 and 38% showed type 1). We have also standardized the RT-PCR assay for Rhabdomyosarcoma. The case diagnosed as Rhabdomyosarcoma showed the PAX3-FKHR fusion transcript, which was confirmed by sequencing. Identification of genes involved in radio-responsiveness in cervical cancer using Differential Display Our earlier studies involving gene expression analysis by differential display using tumor biopsy samples taken before radiation and after 10Gy of tele-radiation between a patient who responded to treatment and a patient who failed treatment identified CDC27 gene to be differentially expressed. Subsequent Immuno-histochemical analysis of pre- and post treatment tumour samples from 15 patients, showed that there was down-regulation of expression of CDC27 protein in seven patients in the post treatment samples compared to pre treatment sample. Down-regulation was associated with poorer response. In order to corroborate the in-vivo findings, cervical cancer cell lines SiHa and C33A, were studied for CDC27 expression. These cell lines had been earlier described to exhibit differential radio-sensitivity, with C33A being more sensitive than SiHa. Our studies on the dose survival patterns of the two cell lines also demonstrated similar effect. At 10 Gy dose, nearly 25% of the SiHa cells survived compared to less than 5% of C33A To study the expression levels of CDC27 before and after 10Gy of radiation The cells from the two cell lines were irradiated in duplicates, and independently to a dose of 10Gy delivered in five consecutive daily fractions of 2Gy. The nuclei from the un-irradiated cells and the irradiated cells were isolated and stained for CDC27 and analyzed for the expression. Using FACS, the nuclei of SiHa were found to show a marked down-regulation of CDC27 expression after treatment with 10 Gy radiation, with 6% of the nuclei expressing CDC27 compared to nearly 74% of the C33A nuclei expressing CDC27 after 10 Gy radiation. The present study has identified for the first time that CDC27 levels may be altered in response to radiation and down-regulation of the levels has been found to be associated with a poorer outcome to radiotherapy in patients with cancer of the cervix. The in vitro study using cell lines has also corroborated the in vivo data, in as much as the less radiosensitive cell line, SiHa, showing a marked down-regulation of CDC27 after exposure to 10 Gy radiation compared to the radio-sensitive cell line C33A. Differential displays performed on pre and post treatment samples (10 Gy) of SiHa cell line yielded a 318 bp fragment differentially expressed in the 10Gy sample. The differential expression was confirmed in northern blots using total RNA isolated from duplicate samples from an independent experiment. The fragment was cloned and sequenced. The sequence showed high similarity (e-139) to a EST clone. The characterization of the clones by sequencing is ongoing. This study was supported by the DAE. IDENTIFICATION OF PROGNOSTIC MARKERS AND GENES RELATED TO DRUG RESISTANCE MECHANISMS IN OSTEOSARCOMA Osteosarcomas are highly malignant bone tumors predominantly seen in pediatric age group and young adults. The crude incidence rate of osteosarcoma has been found to be 0.8/100,000 population (males) and 0.6/100,000 population (females) (Madras Metropolitan Tumor Registry). The etiology of osteosarcoma is not known. Even though, the intensive chemotherapeutic regimens has increased the cure rates to 60-70%, failure still occur due to the spread of the disease, outside of the site of origin, most commonly to lungs. Drug resistance is of major concern in the management of osteosarcoma. To further enhance osteosarcoma therapy, it would be very important to identify newer prognostic markers and also, to develop new therapeutic strategies based on most effective combination of cytotoxic drugs. A pilot study was done on the pattern of expression of FGFR1, FGFR2, FGFR3, BCL2, p53, MDM2 and MDR1 and assessment of its prognostic significance using immuno-histochemical approach in 47 highgrade non-metastatic osteosarcoma cases. Of the 47 osteosarcoma cases studied, FGFR1 and FGFR2 expression was found to be cytoplasmic (59.6% and 80.9% respectively) and nuclear (34% and 61.7% respectively). The FGFR3, BCL2 and MDR1 were expressed only in the cytoplasm (48.9%, 57.4% and 20% respectively) and in the case of p53 and MDM2 in the nucleus (34% and 27.7% respectively). The over expression of p53 (p<0.003) were found to correlate with poorer disease free survival. The 143B osteosarcoma cell line have been selected for resistance to adriamycin, cisplatin and ifosfamide by intermittent exposure to stepwise increasing concentration of the drug. Three drug resistant osteosarcoma 143B cell lines to cisplatin, adriamycin and ifosfamide have been established. The folds of resistance generated have been determined by the difference in percentage of viable cells between wild type and drug resistant cells through Micro culture Tetrazolium Test. The differential expressed genes between wild type and drug resistant 143B cells would be identified using differential display. Development and Clinical evaluation of Dendritic Cell Vaccine for HPV related cervix cancer. In the case of cervical cancer patients with HPV infection, the Immune system seems to play a significant role. The presence of high risk HPV alone is not sufficient though critical. The dysfunction is due to loss of effective presentation of antigenic peptide to the Immune cells and aberrations in effector systems. Dendritic cells are potent Antigen Presenting Cells hence this property can be exploited to increase the population of both specific CD4 and CD8 T cells. The aims of the project are to utilize monocytes derived from the peripheral blood of cervical cancer patients and convert them into dendritic cells. So far blood and biopsy samples have been collected from 13 patients, monocytes derived from these patients were converted to immature dendritic cells using IL4 and GM-CSF. The immature dendritic cells are to be primed with either the tumour cell lysate or total tumour RNA along with cytokines TNF alpha and IL1 beta to obtain mature dendritic cells that are potent antigen presenting cells. This is a DBT funded study. DEPT OF IMMUNOLOGY AND HEMATOLOGY ONGOING PROJECTS 1.Immunophenotyping of Acute lymphoblastic leukemia cases is being carried out since late 1989 with the objective of identifying the immuno-phenotypic subtype of ALL cases for its diagnostic, therapeutic and prognostic significance. A total of 671 newly diagnosed, untreated ALL cases have been studied till December 2003. Of this, 414 were paediatric cases and 257 were adult ALL cases. Study was conducted by flowcytometric immuno-fluorescent technique using a panel of 20 monoclonal antibodies. Analytical study of accrued data reveal that 36.4% of paediatric ALL cases were T subtype and 34.2% were C-ALL. Among adult ALL cases, 39.2% were T-ALL and 23.8% were CALL. 85% of paediatric T-ALL cases had their origin from the more mature thymic compartments 11 and 111. 15% of paediatric T-ALL cases had their origin from immature thymic compartment 1. Among total number of ALL cases studied, 65.7% were from lower socioeconomic group. Among TALL cases, 65% were from lower socioeconomic strata. Predominance of T-ALL, paucity of C-ALL and increased frequency of paediatric T-ALL from more mature thymic compartments are in variance with reported western data. Predominance of T-ALL cases among lower socioeconomic group is statistically significant. Over a period of 10 to 14 years, we notice a gradual reduction in paediatric T-ALL cases and a proportionate rise in paediatric C-ALL cases. This could be due to the fast development in the related environmental factors in our geographic setting. 2. DNA Analysis in Acute Lymphoblastic Leukemia Cases. Is being carried out since 1993 with the objective of determining the ploidy status and proliferative activity in ALL cases. A total of 368 new ALL cases have been studied till December 2003. Study was conducted by flowcytometric method using Propidium iodide as DNA dye. 58.4% of cases showed DNA diploidy, 41.6% of cases showed DNA aneuploidy and 24.2% of cases showed increased S-phase fraction. DNA diploidy indicates prognostically unfavorable category. S-phase fraction study has therapeutic significance. 3. Immunophenotypic characterization of Lymphoma cases. Is being carried out since 1990, with the objective of studying immuno-phenotypic characterization of Histo-pathologically problematic Lymphoma cases. A total of 782 Adult NHL cases were immunophenotyped till December 2003. 41.2% were found to be T-NHL and 58.8% were B-NHL. Study was conducted by immuno-histochemical method using appropriate monoclonal antibodies from a panel of 8 monoclonal antibodies, via LCA, UCHL 1, L26, Kappa, Lambda, CD68, CD15 and CD30. A total of 90 paediatric NHL cases were immuno-phenotyped till 2003. 78.2% were T-NHL and 16.9% were B-NHL. 85.3% of paediatric T-NHL and 44.6% of paediatric B-NHL were lymphoblastic in nature. 4. Immunophenotypic Characterisation of Solid Tumours. is being carried out since 1990 with the objective of identifying cell markers of diagnostic significance. A total of 4389 cases of neoplasm of uncertain histogenesis were studied till December 2003. Study was conducted on paraffin sections or fine needle aspiration smears by immuno-histochemical method. Appropriate monoclonal antibodies were selected from among 30 monoclonal antibodies available. Analysis of data reveals that in 80% of instances the study helped in arriving at a more precise diagnosis. In 20% of cases it was non-contributory mostly due to inadequate specimen or poor quality of tissue. 5. Prognostic Marker Study on Breast Carcinoma Cases. Is being carried out with the objective of evaluating its prognostic significance. A total of 2103 Breast carcinoma cases were subjected to ER and PR status study since 1996. 40.5% were ER positive and 28.9% were PR positive. Study of Cathepsin D, c-erbB2 and p53 was started since late 1998. So far a total of 986 cases were studied. Analysis on the accrued data reveal that 18.2% of cases were C-ErbB2 positive, 55.7% were Cathepsin D positive and 31.2% of cases were p53 positive. 6. Early detection of micro-metastasis in histologically node negative Ca Breast cases by Cytokeratin study on axillary lymph nodes. This study has been started during current year to evaluate presence of cytokeratin positive epithelial cells in axillary lymph nodes of histologically node negative breast cancer cases with the objective of detecting micro-metastasis. This study has considerable therapeutic significance. A total of 150 cases were studies so far. 6 (4%) of them showed micro-metastasis. 7. C-ErbB2 evaluation on ER and PR positive Breast Carcinoma cases with metastasis under Herceptin Trial. This study has been started since Nov.2002. A total of 6 cases have been studied so far. 8. Immuno-histochemical characterization of Gastrointestinal Stromal Tumours (GIST) with C-Kit. This has been started since Dec.2002. C-Kit proto-oncogene is supposed to have an important role in the development of tumour. This study has diagnostic and therapeutic significance. Study is under progress. 9. Demographic study of Immunophenotypic Characterisation of Acute Lymphoblastic Leukemia cases. A total of 19 cases were studied so far. Among paediatric ALL cases, 63% were TImmunophenotype and 27% were Calla positive. This data is in agreement with our reported and published data on hospital population. Study is continuing. 10. Oestrogen Receptor Evaluation for U.K. based Atlas Trial. This study is going on since 2000. More than 261 cases have been evaluated for ER status so far, for its therapeutic utility. 11. Project entitled “A comprehensive retrospective immuno-histochemical evaluation of axillary nodal status for micro-metastasis and prognostic marker status in primary tumour in breast cancer patients” is being funded by ICMR. During the year 2003, a total of 60 node negative breast cancer cases have been studied under this project. A total of 2 cases showed micro metastasis in axillary lymph nodes. 55 cases were subjected to ER study 16 (30%) showed ER positivity in primary breast tumour. PR study was done on 54 cases. 16 (30%) showed PR positivity 8 out of 48 cases studied for C-ErbB2 showed positivity (16.7%) 39 out of 49 cases showed for Cathepsin D showed positivity (80%). 13 out of 44 cases studied for p53 showed positivity (30%). Second year study is on progress. DEPT. OF TUMOUR MICROBIOLOGY Report on the completed Indo-French Collaboration "Prognostic Value of Cytokine in Cervical Cancer". Cancer Uterine Cervix in women is of high incidence as reported world over, especially in the AsiaPacific region. The prognosis of invasive cervical carcinoma is based exclusively on clinical staging, which is not always able to predict clinical outcome especially for early stage tumors. Different abnormalities in the level of cytokine production have been found in invasive cervical carcinomas such as an increase of IL6 production and a defect in IFNγ mRNA expression in cancer patients. By means of new biotechnologies such as quantitative Polymerase Chain Reaction (PCR) or In situ PCR, we have determined their concentrations and distribution directly at the tumor site. A comparison of these molecular diagnosis approaches with reference techniques such as immuno-cytochemistry were performed. A correlation between cytokine expression and different clinical parameters such as tumor stage, lymph node status, HPV expression, survival, disease free interval were studied. This will help to better define the role of cytokines as prognostic markers in cervical carcinoma and identify high risk cervical carcinoma patients for whom neoadjuvant chemotherapy or intensive therapy would be appropriate. Analysis of DNA adducts that index DNA damage and instability was also performed. These toxic biological endpoints are potential markers with implications in intermediate therapeutic management. 1 Development and validation of original techniques to detect and quantitate immune parameters in tumor tissue. a) In situ RT-PCR Up until now, immuno-cytochemistry remains the standard technique to analyze the expression of molecules in tissue. However, this technique is of low sensitivity and does not allow an accurate quantitation of markers in tumor tissue. In addition secreted molecules which do not concentrate in a cell compartment are not well characterized by this approach. In order to increase the threshold of sensitivity to detect immune parameters in situ, we have developed an original in situ RT-PCR method to analyze the expression of cytokine mRNA. We have identified the different fixative procedures and permeabilization steps which permit the accurate and specific detection of cytokines. The use of biotinylated primers, the introduction of recombinant Thermus thermophilus (rTth) DNA polymerase and a decreased duration of each cycle of PCR by combining the annealing and hybridization steps improved the reproducibility of the techniques and morphological preservation of the cells. Different cytokines such as IL-6, IFN and TNF were successfully analyzed by this method. We are trying to couple this high sensitive method to immunocytochemistry analysis to phenotype the cells responsible for the secretion of cytokines in cervical carcinoma patients. b) Comparison of different quantitative RT-PCR techniques. To ensure the reliability of the technique used to quantitate mRNA, we have compared a competitive PCR assay developed in our laboratory to the real time PCR (Taq Man). The sensitivity and the specificity of the two techniques appeared similar. The presence of an internal standard during the competitive RT-PCR allows absolute quantitation of mRNA. The presence of an external standard during the Taq Man technique may introduce a bias, which could be circumvented by performing several measures for a same point. Since the Taq Man technique has appeared easier and faster to perform, this technique has been selected to quantitate cytokine mRNA expression in cervical carcinoma biopsies. 2. Analysis of the role of Interleukin-17, a T cell derived cytokine in the control of human cervical tumor growth. IL-17 is produced by memory CD4-T cells. It is a pro-inflammatory cytokine, which induces the expression of IL-6, IL-8 and G-CSF. Using different cervical tumor cell lines we failed to demonstrate a direct in vitro effect of IL-17 on the growth rate of these cells. However, we have shown that IL-17 promotes the tumorigenicity of human cervical tumors transplanted in nude mice. Indeed two cervical cell lines transfected with a cDNA encoding IL-17 exhibited a significant increase in tumor size as compared to the parent tumor when transplanted in nude mice. This effect is mediated in part by the secondary induction of IL-6 and is associated with a macrophage infiltration. To assess the clinical relevance of this observation we have analyzed the expression of IL-17 in biopsies derived from cervical carcinoma patients. We found that IL-17 is expressed in most cases and as expected is associated with the infiltration of CD4+T cells. Recently in immunocompetent mice, we have shown that IL-17 inhibits the tumor growth of immunogenic tumor, whereas it exhibits either no activity or a pro-tumoral activity against non immunogenic murine tumors. IL-17 like other cytokines such as IL-6, IL- faces cytokine with potential pro or anti-tumor activity depending on the immunogenicity of the tumor. 3. Analysis of the expression of cytokines and other parameters in human invasive cervical carcinomas a) IL-6 and IL-8 as prognosis marker in invasive cervical carcinoma Two possible candidates with prognostic potential have been identified in this study – cytokines IL-6 and IL-8 secretion by tumor cells. IL-6 positivity was found both in tumor and stromal cells, suggesting the existence of both autocrine and paracrine loop. Significant correlation between the stromal positivity of IL-6 with macrophages in the stroma tends to confirm the macrophages as one of the chief sources of this cytokine. IL-8 positivity was also found to be present both in tumor and stromal cells. While tumor cell secretion of these cytokines showed a poor prognosis, stromal cell secretion did not. This clearly indicates their secretion by stromal cells as a normal function whose levels get elevated during the growth of tumor. Systematic evaluation of their levels in more number of patients with a longer follow-up is warranted for a definitive conclusion of their prognostic potential. b) Identification of a group of cervical carcinoma patients with decreased levels of both TH1 and TH2 cytokine mRNAs. We have selected the real time PCR (Taq-Man) to measure the expression of IFN (TH1 cytokine), IL-4 (TH2 cytokine) and IL-17 (TH0 cytokine) in biopsies derived from invasive cervical carcinoma patients belonging to different clinical stages. We identified a group of cervical carcinoma patients with undetectable intratumoral T cell-derived cytokine mRNAs, as IFN, IL-4 and IL-17 expression could not be detected in 5, 25 and 9 of the 52 biopsies analyzed, respectively. Global downregulation of type 1 and type 2 cytokines was observed in a subgroup of patients who more frequently presented advanced stage tumors. Biopsies of patients with no IFN gene expression did not appear to be less infiltrated by T cells than control biopsies with measurable IFN gene expression These results clearly demonstrate that, in some clinical situations, the decrease in intratumoral type 1 cytokines is not associated with a type 2 polarization, but rather reflects global deactivation of T cells at the tumor site. c) Macrophages and dendritic cells infiltration in invasive cervical carcinomas. By using DC Lamp a marker for mature dendritic cells (DC), it has been shown by immunocytochmistry (frozen and paraffin sections) that most tumors contained mature DC located around the tumor, whereas immature DC appeared inside the tumor as evidenced by the staining character with CD1a antibodies. As observed in other cancers, this suggests a maturation block of dendritic cells. We have may explain the presence of these cells in the stroma. We now are trying to explain mechanisms underlying the defect in the maturation of dendritic cells inside cytokines by the tumors) Expression of FC gamma receptors by tumor cells. In contrast to metastatic melanoma, cervical tumors were found to be negative for Fc gamma IIB expression. This was evidenced by immuno-cytochemistry on paraffin sections, using the polyclonal anti-Fc gamma RII B IgG. d) Analysis of DNA adducts in invasive cervical carcinomas. The levels of 8-oxodeoxyguanosine, which is implicated in several cancers, was high in chronically inflamed cervix as against invasive cancers. It is possible that this modification is an early event in carcinogenesis. The levels of bulky aromatic adducts of the PAH type were significantly higher in the invasive cancer group when compared to normal and dysplastic cervix. This suggests their possible role in cervical carcinogenesis. Since tobacco chewing is a common habit among Indian population, it is possible that tobacco constituents-related immuno-suppression is an important feature in the promotion of cervical carcinogenesis. DEPT OF BIOCHEMICAL ONCOLOGY COMPLETED PROJECTS: “Immunoscintigraphy of experimental tumor models using monoclonal antibody” –DAE project completed on 30th 99m Tc labeled human anti EGFR September,2003. Summary of the Project: The objective of this project was to evaluate the in vivo diagnostic potential of human anti-EGFR monoclonal antibody generated in this laboratory using animal tumor models. Tumor xenografts with overexpression of EGFR were induced in the flank region of BALB/c and Nude mice using carcinoma cell lines like A431, epidermoid carcinoma and MDAMB468, Breast carcinoma cell line. Tumors > 0.5 cm in diameter were used for gamma imaging. Scan pictures were taken at 2h and 24h time intervals after i.v administration of 50-100μCi of the 99mTc labeled MAb using Hitachi model 1500 Gamma camera. Highly discreet tumor images were visualized at the 24h scan due to specific uptake of the labeled MAb by the tumor. There was comparatively much less uptake in the liver and G.I. Tract. These results were comparable to those of Biodistribution studies performed at the end of each scan which revealed significantly high uptake of radiolabel by the tumor, with minimum concentration in normal tissues. The Bio-distribution of radio-labeled Ab has also been studied after administration to normal mice which revealed very low uptake by the G.I Tract. These results might indicate that this MAb has useful clinical application for early in vivo diagnosis of human cancers, which over-express EGFR. ONGOING PROJECTS: 1. DST- FIST Project: For Computational and Networking. The Central computing and Networking facility established under this project has been utilized for teaching trainee students, for Research data storage and Retrieval, Statistical analysis and Graphical representation of Research data, collection and survey of literature for research purposes, etc. 2. Epitope Mapping: To determine the nature of epitope recognized by the anti-EGFR MAb, the technique for Immunoprecipitation using 35S labeled EGFR has been standardized by incorporating 35S Methionine into MDA MB468 cells in culture and incubating an aliquot of the cell lysate with protein A Sepharose bound 4H3 antibody and subjecting the immunoprecipitate for SDS-PAGE analysis followed by Autoradiography which revealed the formation of a discreet band of 170kD. Further studies on Tunicamycin assay are in progress. 3. Mechanism of growth inhibition of EGFR over-expressing cell lines by MAb CIBCNSH3 at different phases of cell cycle Carcinoma cells of MDAMB468 cell line were seeded into petri plates and were treated with varying concentrations of Anti-EGFR MAb for 48h. The treated cells were collected and stained with propidium iodide and subjected to FACS scan analysis. The results showed the accumulation of cells in Go/G1 phase with higher concentrations of anti-EGFR MAb and very low % of accumulation of cells in control group i.e., without MAb. This preliminary study revealed that anti-EGFR MAb could arrest the carcinoma cells in Go phase and bring about apoptosis. 4) Anti-tumor activity of anti-EGFR MAb in comparison with chemotherapeutic agents like Cisplatin MAbs directed to the extra cellular domain of EGFR are known to inhibit the growth of carcinoma cells, thereby preventing tumor cell proliferation and tumor growth. In order to evaluate the antitumor activity of anti-EGFR MAb, in vitro studies have been performed using cell lines with high expression of EGFR. About 5X103 cells in 100μl of DMEM were seeded in to a 96-well falcon plate. After incubation for 4h at 370c, MAb was added at different concentrations in triplicates to the wells and Cisplatin at a concentration of 2.5μg, 5μg/ml to another set of wells. The cells were further incubated for a period of 4 days. After incubation, the cells were fixed in glutaraldehyde and stained with methylene blue. The O.D was measured using a BIOTEK ELISA reader. The results showed that the anti-EGFR MAb inhibited cell growth to a greater extent when compared to the conventional drug Cisplatin. Further studies are in progress. DEPT OF CYTOGENETICS ON GOING PROJECTS: Samples from different types of malignancies from patients are being evaluated for cytogenetic study and karyotype analysis as routine for diagnosis and primary study for FISH. Samples are being subjected to short-term culture of 24 hrs, 48 hrs, 72 hrs and 6 days based on the tissue type. Samples are being processed for fixed chromosomal preparations, G-banding pattern, micro-photography and karyotyping. Karyotypes are analyzed for numerical and structural chromosomal aberrations especially for reciprocal chromosomal translocations. Chromosomal translocations are specific for particular type of malignancy and even sub-types of leukemia. The findings are being correlated with clinical features, immuno-phenotyping, hematological and histopathological aspects. DEPT OF ELECTRON MICROSCOPY COMPLETED PROJECTS: ULTRASTRUCTURAL CHARACTERIZATION OF SPINDLE CELL TUMORS AND SMALL ROUND CELL TUMORS: 11 biopsy samples from various sites such as bone, soft tissue, kidney, bladder, etc., which were histopathologically classified as Malignant Spindle cell tumors and 16 samples reported a s Malignant Round cell tumors were processed for Transmission Electron microscopy. At electron microscopic magnifications, the spindle cell neoplasms could be further sub-classified. Two were in favor of MFH; one showed thick and thin filaments with aborted Z lines favoring RMS; one showed features of fibromatosis; one consistent with GIST where the spindle cells had nuclei with transverse folds and cytoplasmic filaments with focal densities. Among the round cell malignant tumors, a few dense core granules could be detected in 2 metastatic small cell carcinomas. In one lymph node biopsy presence of lymphocytes, macrophages and tumor cells with lipid granules was suggestive of Burkitt's lymphoma. ONGOING PROJECTS: FINE STRUCTURAL STUDIES ON FINE NEEDLE ASPIRATION BIOPSIES AND PARAFIIN EMBEDDED SECTIONS: Formalin fixed paraffin embedded tissue sections can be processed for Transmission electron microscopy in situations where fresh specimens are not available. Though ultra-structural features are not well preserved after formalin fixation, certain characteristic features, which could be identified on screening large number of sections, would help in confirming the light microscopic findings. A few cases have already been tried where EM has added to the diagnosis, while in 2 cases features were not definitive. Similarly, a few fine needle aspirates from soft tissue tumors have been processed for EM. The tumors could be characterized using these samples also. Studies on the above types of samples are still continuing. EPIDEMIOLOGY DIVISION AND CANCER REGISTRY COMPLETED PROJECTS ICMR project on “Development of an Atlas of Cancer in India” under MMTR, year 2002. The project envisaged collection of data from the MMTR data sources on invasive cancer cases who are non-residents of Chennai City. A total of 6256 cases registered during the year 2002 were sent to ICMR in the prescribed format as required ICMR project on “Development of an Atlas of Cancer in India” under HCR, Cancer Institute, year 2002. The project involved abstraction of data from the registry records on all patient attendances. A total of 6327 cancer cases were computerized and sent to ICMR as required. ICMR project on “Patterns of Care and Survival Studies on Cancer Cervix, Breast and Head & Neck: A hospital based study”. Data on 1060 cases of cancer cervix and 834 cases of female breast cancer, treated in 1997-98 at CI and followed through 1st January 2003 formed the study material. The complete follow up at 5 years from diagnosis was 76%. The overall survival at 1,3,5 years from diagnosis were 92%, 69% and 62% for cervix and 91%, 66% and 59% for breast cancers. A sample of 100 cases of head and neck cancers treated in 2002 were abstracted as part of a feasible study. The data on all the above has been sent to ICMR as required. ONGOING PROJECTS MMTR – partly funded by ICMR A continuing project since 1982 forming the basis of many research activity in the department including population based cancer survival and descriptive epidemiological studies. HCR – partly funded by ICMR. A continuing project since 1984 forming the basis of the Patterns of care and hospital based survival studies. ICMR project on “Development of an Atlas of Cancer in India” under MMTR, year 2003. A continuing activity since 2001. Data on invasive cancers among the non-residents of Chennai City are collected from the MMTR data sources. A total of 4436 cases have been registered so far. It is estimated that a total of 6500 cases will form the study material. ICMR project on “Development of an Atlas of Cancer in India” under HCR, Cancer Institute, year 2003. A continuing activity since 2001, Data on 2030 cases of invasive cancers attending the Cancer Institute (WIA), Chennai, in 2003 have been abstracted into the prescribed form so far. This project has enabled the timely availability of recent data and strengthened the existing HCR. IARC project on “Estimation of population based survival rates from Common Cancers in Chennai, India” A total of 20743 cases of invasive top ten ranking cancers registered in MMTR during 1990-99 formed the study material. The follow up is nearing completion. The data is to form a part of the second IARC Monograph on “Cancer survival in Developing Countries” expected to be released in the year 2004. WHO project on “Awareness and Early Detection of Cancer” A total of 14706 households have been covered so far and data on 64706 individuals collected so far from the Thiruvanmiyur area (Div 154 & 155). Apart from three medical camps conducted in the study area, ‘two’ clinics on ‘early detection of cancer’ manned by the personnel from the Cancer Institute (WIA) are regularly functioning in the Corporation Health Centres. A total of 2500 subjects have attended these clinics. Seven cancers have been identified: cervix (4), breast (1) and oral cavity (2). A total of 287 cases of pre-cancerous conditions of all of these cancers have been detected and are on follow up. Monograph on “Cancer Cervix: A Hospital Based Study” A total of 13,143 cases of invasive cervix cancers, which received treatment at the Cancer Institute (WIA) during 1960-94 and followed through 1st January 2003 formed the study material. An increasing trend in survival over calendar time was forthcoming. (This monograph is a CI Golden Jubilee publication and is scheduled to be released in June 2004). Monograph on “Cancer Breast: A Hospital Based Study” A total of 5688 cases of invasive breast cancers, which received treatment at the Cancer Institute (WIA) during 1960-97 and followed though 1st January 2003 formed the study material. An increasing trend in survival over calendar time was forthcoming. (This monograph is a CI Golden Jubilee publication and is scheduled to be released in June 2004). DEPT OF RADIATION ONCOLOGY COMPLETED PROJECTS HIGH DOSE RATE VERSUS LOW DOSE RATE BRACHYTHERAPY FOR CARCINOMA OF THE UTERINE CERVIX: A RANDOMIZED COMPARISON OF THE EFFICACY AND NORMAL TISSUE MORBIDITY The objectives of this trial were to compare the efficacy of HDR vs. LDR intracavitary brachytherapy in the treatment of stages II B and III B squamous cell carcinomas of the uterine cervix, and to compute the doses of irradiation delivered to specific volumes of bladder and rectum with dose volume histograms and to correlate them with the bladder and rectal morbidities. The eligible patients were stratified by stage and then randomized into the following two arms: External radiotherapy + LDR brachytherapy External radiotherapy + HDR brachytherapy Teleradiation was given with 6 MV x-rays delivering a total dose of 50 Gy in 5 weeks to the whole pelvis. LDR brachytherapy was done by a single intracavitary application, delivering a dose of 20 Gy to Point A, within a week after the completion of teletherapy, at a dose rate of 160 – 180 cGy / hour. In the HDR brachytherapy arm, three intracavitary applications, with an interval of one week in between, were done by remote afterloading technique, delivering a dose of 15 Gy to Point A, at a dose rate of 36 - 48 Gy / hour. The first application was done after 30 Gy of external therapy, so that the overall treatment time was equal in both arms. Dose volume histograms were obtained, with CT slices of the pelvis taken with the applicators loaded with dummy sources, and the mean dose values in the bladder and rectal volumes were worked out. The doses at specific reference points for the rectum and the bladder as defined by the ICRU Report 38 were also calculated. 400 patients were included in the study, 200 patients with stage II B disease and 200 with stage III B disease. 100 patients with stage II B disease and 100 with stage III B disease were randomized to the HDR arm and the rest to the LDR arm. In the LDR arm, out of the 168 patients who had completed the treatment and followed up for ≥ 6 months, 151 patients (89.9%) achieved CR. 136 out of 157 patients achieved CR in the HDR arm. The 2-year NED rate was 71.6% in the LDR arm and 75.5% in the HDR arm. The early morbidities were also comparable in both the arms. The patients are being followed up for assessing the long-term morbidity in both arms. REGIONAL HYPERTHERMIA COMBINED WITH RADIOTHERAPY FOR LOCALLY ADVANCED CERVICAL CANCERS The objective of this trial was to evaluate the role of hyperthermia in potentiating the local control achieved by radiotherapy in patients with stages II B, III A and III B squamous cell carcinomas of the uterine cervix, considered suitable for radical radiotherapy. The eligible patients were stratified by stage and then randomized into the following two arms: Radical Radiotherapy Radical Radiotherapy + Hyperthermia All patients were treated with 6 MV x-rays to a total dose of 50 Gy in 5 weeks to the whole pelvis, followed by LDR brachytherapy by remote afterloading technique, delivering a further dose of 20 Gy to Point A. If the patient was not suitable for intracavitary therapy, teletherapy was continued to a further dose of 15 Gy using reduced fields. Hyperthermia was delivered immediately following radiotherapy once a week, usually on Tuesdays, in the radiotherapy + hyperthermia group. Tumor temperature of more than 410 C but not more than 440 C was attempted and it was maintained for one hour. 100 patients were randomized, 50 in each arm. 92% of the patients in the Radiotherapy + Hyperthermia arm and 80% of the patients in the Radiotherapy only arm achieved CR. 2-year NED rates were 84.2% and 66.7% in the study and control arms respectively. The early reactions appeared to be a little more in the hyperthermia arm compared with the control arm (7 versus 3), but all the reactions were of grade I or II only, except in one patient who developed grade III blistering due to hyperthermia. The patients were being followed up for assessing the long-term effects in both arms. ONGOING PROJECTS ATLAS – Adjuvant Tamoxifen Longer Against Shorter This is a large simple randomized study to asses the efficacy and safety of prolonging the use of adjuvant tamoxifen in carcinoma breast patients, irrespective of the original histological type of the disease, nodal status, or whether the tumor was estrogen receptor positive or negative, who have received any type of curative surgery, with or without any adjuvant therapy, apparently to be free from disease, is receiving tamoxifen and where both the woman and her doctor are uncertain whether to continue tamoxifen or not. The women will be randomized either to stop tamoxifen or to continue tamoxifen for at least 5 extra years. Overall survival analysis will be complemented by subsidiary analyses of deaths from specific causes, such as breast cancer, myocardial infarction, endometrial cancer, etc. The incidence of second primary tumors, in particular, contra-lateral breast cancer, other female cancers and liver cancer, non-fatal myocardial infarctions and other vascular events requiring hospitalization will also be examined. The analyses will be stratified by the duration of tamoxifen given prior to randomization, age, ER status and by other prognostic factors recorded at randomization. Altogether 490 patients have been registered in the project. Among them 440 patients have been randomized, 220 are allotted to continue AE and 220 to stop AE. ER study has been conducted on 245 patients so far (72 are ER positive, 149 ER negative and ER study is not possible due to poor quality of slides in 24 patients). DEPT. OF MEDICAL ONCOLOGY ONGOING PROJECTS GIPAP (GLIVEC International Patient Assistance Programme). GLIVEC ® (Imatinib) is a new tyrosine kinase inhibitor which has been approved for use in CML and GIST. The major draw back logistically for its use is the cost which will be approximately Rs.1 Lakh/month. Novartis in association with Max foundation, U.S.A, has started the GIPAP programme to assist patients who cannot afford the medicine, by giving it free of cost. Cancer Institute (WIA) has been identified as one of the 10 centers in India for identifying and enrolling eligible patients. So far 180 patients have been enrolled from the Institute and are receiving GLIVEC free of cost. This also includes patients who have been referred from other places in South India like Coimbatore & Hyderabad. Late Effects Clinic Assessment of long term toxicities in survivors of paediatric cancer patients Influence of Cranial Radiation & Chemotherapy of Acute Lymphoblastic Leukaemia children – on cognitive functioning. Role of Astymin- 3 (Essential Amino acid preparation) Amino-acid infusion in patients on chemotherapy or in patients undergoing chemo-radiotherapy. It is planned to randomize 60 patients for this project. Forty patients enrollment has been completed so far. The aim of the study is to see whether weekly amino-acid infusion will mitigate the toxicities of treatment. Arimidex and Herceptin in metastatic breast cancer. Totally 7 patients were screened and 2 patients were enrolled for the trial. Both patients had progressive disease and they have succumbed to their illness. Randomized phase II trial comparing Paclitaxel + Carboplatin versus Paclitaxel + Carboplatin + Lactoferrin in unresectable advanced non small cell lung cancer. DEPT OF SURGICAL ONCOLOGY COMPLETED PROJECTS: 1. Intra-arterial chemotherapy - pilot study in non-metastatic Osteosarcoma: Accrual of 12 patients for the intra-arterial chemotherapy arm is completed. All these patients had nonmetastatic extremity osteosarcomas who were borderline for limb salvage surgery due to various reasons. Of these 12 patients, 2 patients defaulted treatment at various stages before surgery and the remaining 10 patients underwent surgery. Of these 10 patients, 7 patients (70%) underwent a limb salvage surgery (including one radical fibulectomy). 3 patients underwent amputation after neo-adjuvant chemo and one underwent amputation post limb salvage surgery for wound infection and secondary haemorrhage. Of the 10 patients who underwent surgery, 3 patients (30%) had good necrosis (> 90% necrosis). Four patients are alive without disease, four developed distant metastasis (3 in the lung and 1 in the spine) of whom one patient expired. Four patients are lost to follow up including the two who did not undergo surgery. 2. Conventional vs. Escalated Dose Chemotherapy Study:12 patients have been recruited into the escalated arm and 14 into the conventional arm so far. In the conventional arm, 9 patients underwent limb salvage surgery and none had an amputation. No patients had good necrosis following neo-adjuvant chemotherapy (0%). 8 out of 9 patients are alive. DEPT OF NUCLEAR MEDICINE COMPLETED PROJECTS: 1.Assessment of response of limb sarcoma to neo-adjuvant chemotherapy with Tc99m Sesta MIBI The advent of chemotherapy drugs (as neo adjuvant treatment) has facilitated conservative resection (Limb salvage Surgery) in limb tumors (Bone and soft tissue tumors) .In previous decades mutilating surgeries like amputation used to be the mode of treatment for these patients. In this context we have studied the uptake ratio of Tc99m Sesta MIBI in limb tumors before any treatment was given and again after the neo-adjuvant chemotherapy. Both Osteosarcoma and Ewing’s sarcoma were studied. It has been widely reported that Multi-drug Resistant gene (MDR1) expression in tumors can give rise to resistance to these drugs. We have correlated the response of these patients with the washout of MIBI from these tumors. Methods: 44 patients with limb tumors (34 Osteosarcoma and 10 Ewing’s Sarcoma) were studied. In Osteosarcoma (OS) patients, the 1st study was done before any chemotherapy and 2nd study after 3-4 courses of chemotherapy. In Ewing’s Sarcoma (ES) patients 1st study was done before any treatment was given, 2nd after 3 courses, 3rd after 6 courses and 4th after 12 courses of chemotherapy. The uptake ratio (UR) was calculated by dividing the number of counts in the involved tumor site by the number of counts in the contralateral symmetrical uninvolved site. Response ratio (RR) was calculated using uptake ratios in the first two studies in all patients. The wash out ratio of MIBI from the tumor site was also calculated in the first study. These ratios were correlated with clinical and histopathological responses. Results: 26 out of 34 OS patients had WR of more than 60 % over a period of 2 hours. Still 19 patients had responded clinically and had Limb salvage Surgery (LSS). Conclusion: There was no direct correlation between washout ratios and clinical responses in most of the patients. Those with high WR had responded clinically and had conservative surgery (LSS). 2.Role of Scinti-mammography in the evaluation of response to Neo-adjuvant chemo radiotherapy in Ca breast. Gene resistance is one of the major obstacles in the treatment of patients with chemotherapy. In this study we have tried to corroborate the wash out rates of Sesta MethoxyIsoButylIsonitrile(MIBI) from the tumour to the presence of Multi-Drug Resistant (MDR) gene in the tumour cells. Method: 51 patients were included in the study before they began any treatment. We did a baseline scintimammography before any biopsy was done. A second scan was done a month after the completion of Chemotherapy and Radiotherapy. The wash out rates have been calculated in the pre and post scintimammogram. Result: We found that all our patients had wash-out rates greater than 60% and yet had responded clinically to the treatment regime. Conclusion: Discrepancy could be ascribed to heterogeneity of the tumours, subsets of cells expressing varying and multiple resistant mechanisms may co-exist. Reduced blood flow to the tumour could be held accountable for poor penetration of MIBI in patients. DEPT OF RADIOLOGY AND IMAGING SCIENCES COMPLETED PROJECTS 1. Selective arteriography for intra-arterial chemotherapy in bone tumours prior to limb conservation procedures. 2. Selective arteriography with contrast radiography identifies feeding vessels in the region of tumors for effective intra-arterial chemotherapy and has a definite role when limb salvage procedure is contemplated. ONGOING PROJECTS 1. Value of selective arteriography for evaluation of status of internal carotid artery and collaterals in evaluation of its ligature in skull base surgeries. Pre-operative assessment of collateral circulation of ipsilateral internal carotid arterial system is essential for planning its division. Selective arteriography of contra-lateral internal carotid artery for assessing the collateral circulation in opposite side, intra-arterial balloon insuflation in ipsilateral internal carotid artery for 45 minutes and immediate R.N.I. of brain for perfusion have been done in five cases. These procedures are extremely informative in deciding the ligation of internal carotid artery in skull base surgeries. 2. Usefulness of mammo-sonography to evaluate dense breasts imaged with mammography. About 40-45% of patients screened by mammography have dense breasts. In these cases, mammosonography has been used and is found to differentiate the solid and the cystic lesions and identify and characterize the calcifications. This is also useful in guided FNAC procedures. 3. Role of Color Doppler mammo-sonography in solid breast lesions. The vascular color Doppler studies in 15 cases of solid breast mass lesions have yielded valuable information about blood flow patterns with reference to the characterization of nature of masses – benign and malignant. Study is continued for evaluation of diagnostic criteria. DEPT OF PATHOLOGY ONGOING PROJECTS 1. Role of routine applications of stain for mucin in cervical carcinomas. Categorization of Cervical Carcinomas based on only of their morphological appearance in Haematoxylin and Eosin stained sections yield incomplete and often erroneous diagnosis. Many mucinsecreting carcinomas show a higher incidence of lymph node metastasis and have poorer prognosis. Routine application of stains for mucin was carried out in 855 cases of cancer cervix and 744 cases were morphologically thought to be squamous cell carcinomas. After mucin stain 32 cases were diagnosed as adeno squamous carcinoma and 712 cases were diagnosed as squamous cell carcinomas. Without mucin stain 9.5% cases would have been diagnosed as squamous cell carcinomas erroneously. 2. Study of Helicobacter pylori in patients presenting with gastric symptoms and to evaluate any possible role with gastric cancer: H.pylori is a gram-negative spiral bacilli and is a causative agent in the development of chronic antral gastritis and leads to atrophic gastritis. This condition predisposes to pre cancerous changes in the stomach. The infection rarely resolves spontaneously and the bacteria remains in the gastric epithelium for years giving rise to gastritis and atrophy. Antibacterial therapy can eradicate H.pylori. In our Institute 186 cases of gastric biopsies were suitable for H.pylori study by Giemsa stain. Out of them 83 cases showed positive staining for H.pylori (44.6%). Most of the H.pylori positive cases showed antral gastritis. Seven adenocarcinoma patients out of 40, also showed associated H.pylori infection (17.5%). All these H.pylori positive patient will be followed up to see whether these cases will lead to any malignancy or not. Giemsa staining is an easy stain and can be carried out routinely for all gastric biopsies. Antral biopsy is ideal for H.pylori study and all gastric patients should have biopsy from gastric antrum along with biopsy from site of lesion. DEPT OF CYTOLOGY COMPLETED PROJECTS Cell Block Studies In Urine Cytology The aim of the study is to see whether cell block technique will improve the diagnostic accuracy of urine cytology where the material is hemorrhagic. Urine cytology is a very useful technique for the diagnosis of Carcinoma of the bladder. However in many cases where the urine specimen is mixed with blood the processing becomes difficult and the resultant smears may not be very representative. This study was initiated to see where the cell block technique using the centrifuged deposit from the urine samples will improve the pick up of malignant cells. 67 samples of blood mixed urine were studied . Pap stained smears and cell blocks of urine sediment were studied. 33 smears were positive for malignant cells. While the cell block showed positive in 35 cases. All cases which showed malignant cells by Pap stained smears were positive by cell block technique. In two cases where the smear did not show malignant cells the cell block sections show few groups of malignant cells. RESULT: Cell block techniques in hemorrhagic urine samples improved the pickup of malignant cells marginally. It is very likely that the pick up can be improved if RBCs are lysed before cell blocks preparation is done. DEPT OF CLINICAL MICROBIOLOGY ONGOING PROJECTS Increasing incidence of Coagulase Negative Methicillin resistant Staphylococcal infection. Coagulase negative staphylococci formerly regarded as harmless inhabitants of the skin and mucosal linings are now recognized as a major cause of nosocomial infections in wards and ICU’s We isolated about 18 strains of coagulase negative methicillin resistant staphylococci CONMAR from blood, pus and respiratory samples. Identification of staphylococci as coagulase negative was based on absence of coagulase enzyme, production of catalase and use of mannitol salt agar medium. These methicillin resistant isolates expressed resistance to multiple antibiotics, being sensitive only to Vancomycin, Teicoplanin, Linezolid, Imipenem and Clindamycin. Specimens/samples Blood Pus 11 3 Tracheal 2 Throat swab 2 Among the 11 CONMR staphylococcal blood isolates 9 (81%) were from pediatric patients causing bacteremia. Hence coagulase negative staphylococci should be kept in mind as the cause of nosocomial bacteremia in pediatric patients. DEPT OF MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING COMPLETED PROJECTS: 1. Study on the variation in implant catheter positions in interstitial HDR brachytherapy 2. Studies of lung, heart and brain using radio-nuclide imaging 3. Comparison of reconstruction methods and volume determination in SPECT imaging. 4. Development of a user friendly soft ward for simple dosimetric calculation in radiotherapy. 5. Clinical implementation of IAEA TRS 398 dosimetric protocols for high energy photon and electron beams. 6. Clinical implementation of AAPM TG 51 dosimetric protocols for high energy photon and electron beams. 7. Fabrication of indigenous Farmer type ionization chamber and TPR 20/10 water phantom. ONGOING PROJECTS 1. An analysis of TG21,TG51 ,TRS277 and TRS 398 protocols for calibration of high energy photon and electron beams using water proof chambers and in water. 2. QA Testing of RFA and Eclipse Treatment Planning Systems based on AAPM TG53 protocol. BLOOD BANK COMPLETED PROJECT Transfusion transmitted virus study. The incidence of hepatitis in immuno compromised patients (Medical Oncology cases) like AML/ALL/Lymphoma at the Institute was studied and the role of transfusion inducing hepatitis is found to be negligible. ONGOING PROJECT To study the benefits in the use of irradiated blood components. Transfusion associated GVHD (TA-GVHD) is an intensive immunologic reaction mediated by transfused immuno competent lymphocytes directed against an immuno compromised host. Prophylactic gamma irradiation of cellular blood components is currently the most efficient and reliable way to prevent TA-GVHD. PUBLICATIONS 1. Rajkumar T and Vijayalakshmi N. Is there a role for surrogate markers of pre-malignant lesions of cervix in India? Proc. Indian Natl Sci Acad. B69 (1), 73-82, 2003. 2. Rajkumar T, Sridhar H, Balaram P, Vaccarella S, Gajalakshmi V, Nanadakumar A, Ramdas K, Munoz N, Herrero R, Franceschi S and Weiderpass E. Oral cancer in Southern India: The influence of body size, diet, infections and sexual practices. Eur. J. Cancer Prevention, 12, 135-143, 2003. 3. Rajkumar T, Franceschi S, Vaccarella S, Gajalakshmi V, Sharmila A, Snijders PFJ, Munoz N, Meijer CJL, Herrero R. The role of paan chewing and dietary habits in cervical carcinoma in Chennai, India. Br J Cancer, 88: 1388-1393, 2003. 4. Franceschi S, Rajkumar T, Vaccarella S, Gajalakshmi V, Sharmila A, Snijders PFJ, Munoz N, Meijer CJL, Herrero R. Human papilloma virus and risk factors for cervical cancer in Chennai, India: A case control study. Int. J Cancer, 107: 127-133, 2003. 5. Rajkumar T, Soumittra N, Nirmala Nancy, Swaminathan R, Sridevi V, Shanta V BRCA1, BRCA2 and CHEK2 (1100 del C) germline mutations in hereditary breast and ovarian cancer families in South India. Asian Pac J Cancer Prevent. 4: 203-208, 2003. 6. Rajkumar T. Cancer in the next decade. Reach, 2003. 7. Nirmala Nancy and Rajkumar T Detection of minimal residual disease in ALL. Lalit Kumar ed., Progress in Haematologic Oncology. The Advanced Research Foundation, New York. 45-60, 2003. 8. Herrero R, Castellsague X, Pawlita M, Lissowska J, Kee F, Balaram P, Rajkumar T, Sridhar H, Rose B, Pintos J, Fernandez L, Idris A, Martinez C, Nieto A, Talamini R, Tavani A, Bosch FX, Snijders PJF, Viscidi R, Munoz N, Franceschi S. The viral etiology of oral cancer: evidence from the IARC multi-center study. JNCI, 95: 1772-1783, 2003. 9. Rajkumar T. Molecular mechanisms of cancer. Dr.V.Shanta, ed., Update in Oncology, Indian Journal of Clinical Practice (in press). 10. Rajkumar T. Hereditary cancers. Dr.V.Shanta, ed., Update in Oncology, Indian Journal of Clinical Practice (in press). 11. Rajkumar T. Molecular Biology of oesophageal cancer. S.Subash, ed., Principles and practical procedures in cancer oesophagus. Jaypee Brothers Medical Publishers (P) Ltd. (in press). 12. Rajkumar T, Soumittra N, Durgatosh Pandey, Karunakaran Nirmala Nancy, Vikas Mahajan and Urmila Majhi. Mutation analysis of hMSH2 and hMLH1 in colo-rectal cancer patients in India. Genetic Testing (in press). 13. Rajkumar T, Gopal G, Selvaluxmi G. CDC27 is involved in radiation response in squamous cell carcinoma of the cervix. Eur J Gynaecol Oncol. (Accepted). 14. Shanta V, Gajalakshmi V, Swaminathan R. India, Chennai (Madras). In: Cancer Incidence in Five Continents, Vol. VIII. (eds) Parkin DM, Whelan SL, Ferlay J, Teppo L and Thomas DB. (2002), IARC Scientific Publications No. 155, Lyon, IARC. pp 236-237. 15. Shanta V, Swaminathan R and Kavitha M. Population Based Cancer Registry, Chennai: Cancer Institute (W.I.A), Adyar, Chennai, In: Two year Report of the Population Based Cancer Registries, 1997-98. National Cancer Registry Program, Indian Council of Medical Research, New Delhi, 2003, pp 88-97. 16. Shanta V, Swaminathan R and Rama R. Hospital Based Cancer Registry, Cancer Institute (W.I.A), Adyar, Chennai (Madras). In: Five Year Consolidated Report of the Hospital Based Cancer Registries 1994-98- An assessment of the burden and care of cancer patients. National Cancer Registry Program, Indian Council of Medical Research, New Delhi, 2003, pp xxi-xxii. 17. Shanta V, Swaminathan R and Rama R. Cancer Institute (W.I.A), Chennai: A seat of hospital and population based cancer registries. SOUVENIR, XIX Annual Review Meeting of the National Cancer Registry Program, New Delhi 2003. 18. Swaminathan R, Rama R and Shanta V. An appraisal of active follow up system in the hospital cancer registry, Cancer Institute (W.I.A), Chennai. CRAB 2003; 10(1):23-29. 19. Swaminathan R. Theoretical concepts of logistic regression. In: Jayakumari s and Jayadevan S (eds) Proceedings of the “Workshop on Application of Logistic Regression in Medical Research, Academy of Medical Sciences, Kerala, 2003. 20. Shanta V, Swaminathan R, Nalini S, Rama R and Kavitha M. Hospital & Population Cancer Registries, Cancer Insititute (W.I.A), Chennai, 2001-2002. Consolidated report on “Development of an Atlas of Cancer in India”, World Health Organization, New Delhi and Indian Council of Medical Research, New Delhi, 2003. (In press) 21. Swaminathan R, Shanta V, Rama R. Cancer registration, pattern and trend in India in the last two decades. (In press) Indian Journal of Clinical Practices (Oncology Update). 22. Shanta V and Swaminathan R. Cancer incidence and mortality in Chennai: A Biennial Report, 19992000. Madras Metropolitan Tumor Registry, Indian Council of Medical Research, 2003. (In press) 23. Shanta V. Swaminathan R and Rama R. Biennial Report 1999-2000 of the Hospital Cancer Registry, Chennai, National Cancer Registry Program, Cancer Institute (W.I.A), Chennai, 2003. (In press). 24. R.Krishnakumar, R.Priyadarshini, K.Manivannan, B.Shanmugasundaram, Anuradha Quantification of Right to Left Shunt by Tc99m Macro aggregated Albumin - A case report. Indian Journal of Nuclear Medicine, September 2003. 25. R.Krishnakumar, R.Priyadarshini, B.Shanmugasundaram, Bulkis Begum, Anuradha. Assessment of response of limb sarcoma to neoadjuant chemotherapy with Tc99m Sesta MIBI. World Journal of Nuclear Medicine-supplement (in press). 26. R.Krishnakumar, R.Priyadarshini, Bulkis Begum. “Comparison of Ga 67 and Tc99m Tetrofosmin uptake in lymphoma. World Journal of Nuclear Medicine-supplement (in press). 27. R.Krishnakumar, R.Priyadarshini, Balkis Begum, B.Shanmugasundaram, K.Manivannan "Cerebral perfusion SPECT study in base of skull tumors - C.I. experience”. World Journal of Nuclear medicine (in press). 28. A.Meenakshi, R. Suresh Kumar, V. Ganesh and N. Sivakumar. Immunohistochemical assay (IHC) to study C-erbB-2 status of breast cancer using monoclonal antibody CIBCgp185”. Human Antibod, 2003. 29. Srivani R, Pritibha K, Selvaluxmy G, Nagarajan B, Molecular logistics of cytokines in cervical cancer. Current Science, Vol 84, No 3, 434-438, 2003. 30. Srivani R and Nagarajan B. (2003) A Prognostic Insight on in Vivo Expression of IL-6 in Uterine Cervical Cancer. Int. J. Gynecol Cancer 13: 331-339. 31. A Gey, P Kumari, A Sambandam, F. Lecuru, L. Cassard, C. Badoual, C Sautès- Fridman, B Nagarajan, WH Fridman, E Tartour. (2003) Identification and characterization of a group of cervical carcinoma patients with profound downregulation of intratumoral type 1 (IFN) and type 2 (IL-4) cytokine mRNA expression. Eur J. Cancer, 39: 595-603. 32. Nagarajan B (2003) Prognostic Markers in Human Epithelial Tumors. Proceedings Int. Congress Anti Cancer Treatment Paris. 33. Nagarajan B (2003) Molecular Characterization of Human Epithelial Tumors. Dr. V.R.Khanolkar Oration, National Academy of Medical Sciences. 34. Ravoori S., Vadhanam MV., Nagarajan B., Gupta RC (2003) Modulation of novel subgroups of DNA adducts during human cervical cancer development. Proc. Am. Assoc. Cancer Res., Vol. 44, pp. 111 35. Shirley Sunder Singh, Urmila Majhi, Anita Chandra. Adeno cortical Carcinoma in Children. Indian Journal of Medical and Paediatric Oncology, Vol 23 No.3 – 4. Sep – Dec 2002. 36. Shirley Sunder Singh, Urmila Majhi et al. Bilateral adrenal metastases from bilateral small cell neuroendocrine carcinoma of the ovary-Indian Journal of Surgery, Vol.65(4) Pages 378-380, 2003. 37. Shirley Sunder Singh, Urmila Majhi, et al. Sclerosing Hemangioma of the lung – A case Report- J Indian Medical Association (in press). 38. Shirley Sunder Singh, Urmila Majhi, et al. Gynandroblastoma of the ovary- Indian Journal of cancer (in press). 39. Shirley Sunder Singh, Urmila Majhi, et al. Infantile heamangioendothelioma of the liver- Annals of National Academy of Medical sciences (in press). 40. Sagar T G, Chandra A, Ramanan S G. Childhood Hodgkin’s disease treated with COPP/ABV hybrid chemotherapy. A progress report. Med Pediatr Oncol 2003; 40: 66-69. 41. Anita Chandra, T.G.Sagar, ShirleySunder Singh et.al. Primary fibrosarcoma of the Ovary. Indian Journal of Pathology and Microbiology (in press). 42. T.G.Sagar, Anita Chandra. “Hodgkin’s Disease” chapter in Postgraduate Oncology Update. (in press). 43. T.G.Sagar, S.G.Ramanan, P.S.Sreedharan. Ifosphamide based intensive MCP-842 protocol in diffuse intermediate and high grade NHL. Indian Journal of Medical & Paediatric Oncology 2003; 24(3). 44. Sreedharan P.S. Leukaemia & Lymphoma chapter in ‘Case book of haematology ‘ Jaypee brothers. 45. T.G.Sagar "How do I treat Childhood Hodgkin’s Lymphoma". Indian Journal of Medical & Paediatric Oncology (in press). PRESENTATIONS Dr. Shanta V, Chairman, Cancer Institute (W.I.A) & Principal Investigator, ICMR, was an invited speaker in the following: 1. “XII Annual Gynaec Oncology Meeting” (AIGCON) held at CMC Vellore on 27 th Nov 2003 – Chief Guest. 2. “Dr. M.Snehalatha Memorial Oration” at the Government Royapettah Hospital. Topic – “Contemporary issues in Ovarian Cancer” on 6th Nov 2003. 3. “International Network for Cancer Treatment and Research (INCTR) – Breast Cancer Strategy Group Meeting” held at Cairo, Egypt during 16-17 Oct 2003- Invited to attend the meeting. 4. “Workshop on Lymphoma” held at Cairo, Egypt during 16-17 Oct 2003- Invited to attend the workshop. 5. “Challenges are conquered – Update in Medical Oncology” at Continued Medical Education Programme organized by the Arignar Anna Memorial Cancer Hospital, Kancheepuram in September 2003 6. “Cancer-what one needs to know” - Invited speaker in “Science city-popular lecture series” in September 2003 7. “IV Annual Surgical Oncology Workshop -Gynaec Maligancy” held in January 2003 at Cancer Institute (W.I.A) Chennai – Invited speaker on “An overview of Gynaec malignancy in India” Dr.R.Swaminathan was an invited speaker in the following: 1. “WHO Workshop on community Based Research in Oncology” held at the Regional Cancer Centre, Patna, during Nov 29-30, 2003.- Invited speaker on the “System of active follow up at Cancer Institute (W.I.A), Chennai” and presented the results of the “Modified District Cancer Control Program conducted at Tiruchi & Perambalur districts in Tamil Nadu in 2001-2002 2. XIX Annual Review Meeting of Cancer Registries, National Cancer Registry Program of ICMR, November 11-14, 2003 - delivered lectures on (i) An overview of MMTR and operational strategies to other registries for improving the quality of registration (ii) Cancer incidence and mortality in Chennai, India: 1999-2000 and (iii) Results of the feasibility of conducting the study on Patterns of Care and Survival from cancers of the cervix and female breast, based on retrospective Hospital Cancer Registry data. 3. Workshop on “Current trends in Bio-Statistics” organized by the Madurai Kamaraj University, Madurai. - Lecture on “Recent Developments in Methods for Cancer Survival Analysis” on 1st Oct 2003. 4. Modified District Cancer Control Program - Review meetings held by the Ministry of Health, Government of India at New Delhi on March 20, 2003. Presented the analysis of data collected from more than 200,000 subjects in the districts of Trichy and Perambalur in Tamil Nadu. 5. “Workshop on Can Reg 4/ ICD-O-3” held at Bangalore, 4-7 March 2003, organized by the Indian Council of Medical Research in collaboration with International Agency for Research on Cancer, Lyon, France – an invited delegate. 6. “Training Workshop on Tobacco Cessation for the establishment of Tobacco Cessation SubCentres” held at Cancer Institute (W.I.A.) Chennai on 13th Feb 2003 – Talk on “Tobacco Related Cancers in Chennai– Incidence and Trend” 7. Workshop on “Application of Logistic Regression in Medical Research” held at Dept. of Community Medicine, Academy of Medical Sciences, Kannur, Kerala on 10th Jan 2003 – Lecture on “Theoretical concepts of logistic regression” and a faculty member. Dr. Nalini, Tutor was an invited speaker in XIX Annual Review Meeting of Cancer Registries National Cancer Registry Program of ICMR, November 11-14, 2003 handled the exercises on extent of disease and coding. Mrs R. Rama, Statistical Assistant, was an invited speaker in XIX Annual Review Meeting of Cancer Registries National Cancer Registry Program of ICMR, November 11-14, 2003 - delivered lecture on the Hospital Cancer Registry at Cancer Institute. Ms M Kavita, Statistical Assistant, was an invited speaker in XIX Annual Review Meeting of Cancer Registries National Cancer Registry Program of ICMR, November 11-14, 2003 – dealt with the statistical methods for cancer registry in cancer registration and exercises. Dr. B. Nagarajan has been awarded with the prestigious Dr. V.R. Khanolkar Oration from the Academy of Medical Sciences (India) and the oration was delivered in April 2003 at Indore. Dr. B. Nagarajan delivered a Guest lecture at the Association of Radiation Oncologists, Cochin November 2003. Dr. B. Nagarajan Guest lecture at the International Conference on Cancer Research, Silchar, Assam December 2003. Dr.T.G.Sagar delivered a lecture titled INCTR 02-04-protocol meeting at Tata Memorial Hospital, Mumbai, March 2003. Dr.T.G.Sagar gave a lecture titled “Metastatic Breast Cancer “ at Oncology 2003 at Tata Memorial Hospital, Mumbai, April 2003.. Dr.P.S.Sreedharan spoke on “Newer agents in CML and Cancer Institute experience with Glivec” – CME at Cancer Institute. April 2003Dr.S.G.Ramanan gave a lecture titled ‘Role of growth fractors in haematology’ in the symposium sponsored by Dr.Reddys Laboratory , Chennai. Dr.S.G.Ramanan delivered a lecture titled ‘Role of chemotherapy in Non-small cell lung cancer’ AROI TamilNadu Chapter meeting. Dr.S.G.Ramanan spoke on the ‘Role of pegylated liposomal anthracycline’ in the Kerala chapter of AROI meeting held at Calicut. Dr.S.G.Ramanan participated in the CME at Vadodara – He was a panelist on the discussion on gynaec malignancy and spoke on the role of chemotherapy in breast cancer. Dr.S.G.Ramanan gave a lecture titled "Role of chemotherapy in gynecologic Malignances" in the Oncology CME at Vijayawada. Dr.Ramachandran presented a Poster "Carcinoma Ovary – Neoadjuvant Chemotherapy, CI experience" in the Gynaec Oncology workshop at CI, Chennai, January 2003. Dr.Ramachandran presented a Poster on "Nasopharynx Carcinoma - Chemotherapy with radiotherapy". Extending Horizons meeting in February 2003, Mumbai. Dr.Pranoy presented a poster on "Lymphoma of orophaynx & nasopharynx" in the 2nd National meet on Head & Neck Oncology at Calcutta, January 2003. Dr.Parnoy presented a poster titled "Extranodal NHL" in the Extending horizons meeting held in February 2003, Mumbai. Dr. A. Vasanthan delivered Dr. Ida B. Scudder Memorial Oration titled, “Clinical trials in carcinomas of the buccal mucosa, uterine cervix and stomach and extremity soft tissue sarcomas” in the Nineteenth Annual Conference of the Association of Radiation Oncologists of India (Tamil Nadu & Pondicherry chapter) held at Chennai in November, 2003. Dr. A. Vasanthan delivered the Presidential Address during the inauguration of the 19 th Annual conference of the Association of Radiation Oncologists of India, Tamil Nadu and Pondicherry chapter, which was held in November, 2003 at Chennai. Dr. A. Vasanthan was the moderator of the panel discussion on the management of uterine cervical cancers during the Nineteenth Annual Conference of the Association of Radiation Oncologists of India (Tamil Nadu & Pondicherry chapter) held at Chennai in November, 2003. Dr. G. Selvaluxmy was one of the panelists and she discussed her experiences in Brachytherapy of uterine cervical cancers. Dr. G. Selvaluxmy presented a paper titled, “High dose rate versus low dose rate brachytherapy for carcinoma of the uterine cervix: A randomized comparison of the efficacy and normal tissue morbidity” in the 25th National Annual Conference of the Association of Radiation Oncologists of India, held at Kochi, in November, 2003. Dr.Puspha Viswanathan gave an invited talk on “ Fundamentals of Transmission Electron Microscopy" at Saveetha Dental College, Chennai on 21st Aug. 2003. Dr.Puspha Viswanathan gave a talk on “Heavy Metal Status in Food” at Madras Veterinary College, Chennai on 20th Nov. 2003 at the Seminar on “Occurrence, detection and control of pollutants and contaminants in dairy and food industry”. Shirley Sunder Singh made a Oral presentation titled "Pathological assessment of response to neoadjuvant chemoradiotherapy in locally advanced breast cancer and an evaluation of variables associated with complete response", in the IAPM Conference held in Orissa. Shirley Sunder Singh made a Poster presentation titled "Unusual sites of metastases from primary tumours involving the skin, ovary and eye" in the IAPM Conference held in Orissa. Dr.Ravi Kannan spoke on Oral Cancer and prevention at Carborundwin Universal Ltd. in Chennai on 26.02.2003. Dr.Ayyappan spoke on Skin cancer at the Annual Rapid Review Course 2002-2003 held at SRMC on 14.02.03. Dr.R.Ravi Kannan spoke on Oral Cancer at the Annual Rapid Review Course 2002-2003 held at SRMC on 19.02.03. Dr.Ravi Kannan went to Silchar to Cachar Cancer Centre for transfer of Surgical Technology in Oncologic Surgery and demonstrations of surgery in March 2003 and again in Nov. 2003. Dr.Ravi Kannan attended the Head and Neck Oncology Conference between 1st and 5th Oct. 2003 held at New Delhi and was a panellist in a discussion on (a) Thyroid Cancer, (b) Hypopharyngeal Cancer, (c) Salivary Gland, (d) Oral Cancer. He also gave a lecture on Management options in cancer of tongue. Dr.Ravi Kannan spoke on Reconstruction of Tongue Cancer in a symposium on Tongue Cancer on 10.10.2003, at the Asia Pacific Cancer Congress held at Bali, Indonesia. Dr.Ravi Kannan went to IMSACON 2003, Kochi on 26th - 28th Sept. and spoke on Advances in Management of oropharyngeal. Dr.Ravi Kannan attended a conference on malignancies in Cachar Cancer Hospital on 2nd - 4th Dec. 2003 and performed demo surgery. Dr.Vikash Mahajan went to Singapore and attended a workshop on Nutrition Franc Asia 2003. He also observed liver transplant and liver surgery with Dr.K.C.Tan and at Singapore General Hospital. Dr.Ayyappan attended a laparoscopic surgery workshop held at Coimbatore in Nov. 2003. Dr.Durgatosh Pandey went to Kanchipuram and presented a paper on Testicular Cancer. Dr.Ravi Kannan was a panellist in a discussion on Management of Papillary Carcinoma Thyroid organised on 21st June 2003 in Chennai City Br. of ASI. Dr.Sridevi went to Gem Hospital, Coimbatore for 2weeks from 3rd March 2004 to 15th March 2004, as a trainee in basic advanced laparoscopy. Dr.Sridevi attended CME organised by IMA at Vijayawada on Gynaecologic malignancies in December 2003. Dr.Sridevi attended II Annual Conference of Association of Gynaec Oncologist at CMC, Vellore between 27th Nov.2003 and 29th Nov. 2003. R.Krishnakumar presented two papers at the Asian Regional Cooperative Council for Nuclear Medicine, 68 February 2003, Dhaka, Bangladesh a. Assessment of response of limb sarcoma to neoadjuant chemotherapy with Tc99m Sesta MIBI (Oral) b. Comparison of Gallium-67 and Tc-99mTetrofosmin uptake in lymphoma (Poster) Dr.R.Krishnakumar presented a paper on the “Postoperative management of Differentiated Thyroid Cancer at the Institute with I 131 and subsequent follow up” at the National Consensus Conference on the management of Differentiated Thyroid Cancer, organized by the Amrita Institute of Medical Sciences & Research Centre, Kochi, April 12 & 13th, 2003 Dr.R.Krishnakumar presented a paper on “Cerebral Perfusion SPECT studies in Base of Skull Tumors management - C.I. experience” at the X Annual Conference of Medical Physics and Radiation Safety. 30th & 31st, Aug 03 held at Chennai. Dr.R.Krishnakumar presented a paper on “Tumor imaging with Isotopes” at the 9th annual Conference of SNM (I) Southern chapter held at Chennai, Sep13th, Sep.03. Dr.R.Krishnakumar presented a paper “SestaMIBI- is it a predictor of treatment response in tumors? ” at the 1st annual Conference of Association of Nuclear Medicine Physicians of India (ANMPI) held at Chennai, Sep., 03. Dr.R.Krishnakumar presented a paper “Sesta MIBI- Is it a predictor of treatment response in tumors? ” at the 19th annual Conference of the Association of Radiation Oncologists of India (TN and Pondicherry chapter) held at Chennai, 1st, 2nd, Nov.2003. Dr.R.Thendral presented a paper titled “Anesthetic management of esophagectomy – 7 years experience from teriary care center” – in the Indian Society of Anesthesiologist conference, held in Aug, 2003. Dr.T.Rajkumar gave a guest lecture in IBMS, Taramani on “Hereditary cancer”. Cancer Institute (WIA) on the National Technology Day on “Molecular revolution coming your way”. Janaki College for Women, on “ABC of Cancer” IIT, Madras on “ Molecular approaches to cancer prevention”. XVII APCC conference in Bali, on “Biological basis of CT+RT in nasopharyngeal cancer”. National AROI meeting in Kochi on i. “Molecular Biology of breast cancer”, ii. “Molecular markers of diagnostic and prognostic significance in cervical cancer”.