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Journal Issue: Vol.8, No.3 - July 2009

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Editorial

Editorial: Regional Cooperative Activity of IAEA/RCA Program in Radiation Oncology

Cancer is a growing global issue in the 21st century. According to World Cancer Report, there were 12.4 million new cases and 7.6 million cancer deaths worldwide in 2008, and, in 2030, these numbers are projected to climb up to 26.4 million and 17.0 million, respectively.1 The burden of cancer will fall much more heavily on developing countries. The role of radiotherapy in the management of cancer, especially in the developing countries, is substantial not only because radiotherapy is indicated very widely to cancer patients ranging from as radical treatment to palliative treatment, but also because radiotherapy is one of the least expensive and the most effective cancer treatment modalities per patient.1, 2 However, the critical issue among the Asian and Pacific regions is the shortage of radiation oncology services. The availability of the radiotherapy equipment is related to the economic status of the countries in the Asian and Pacific region,3 and the personnel, infrastructures, and educational opportunities necessary for radiation oncology service are often in shortage among the countries in this region. Many efforts are made by many organizations, and the recent effort by the International Atomic Energy Agency (IAEA) to establish "Program of Action for Cancer Therapy" demonstrates the urging needs of actions for this emerging crisis. This article intends to introduce one of such activity of IAEA/RCA. What is IAEA/RCA? The RCA (the Regional Cooperative Agreement for Research, Development and Training Related to Nuclear Science and Technology) is an intergovernmental agreement among seventeen countries in the Asia and the Pacific Region. It was established in 1972 under the auspices of the IAEA to promote cooperation with each other and with the IAEA in the peaceful applications of nuclear science and technology, in which the Government Parties undertake, in co-operation with each other and with the IAEA to promote and co-ordinate co-operative research, development (R&D) and training projects in nuclear science and technology through their appropriate national institutions. Seventeen countries in the Asia and the Pacific Region (Australia, Bangladesh, Republic of China, India, Indonesia, Japan, Republic of Korea, Malaysia, Mongolia, Myanmar, New Zealand, Pakistan, the Philippines, Singapore, Sri Lanka, Thailand and Vietnam) are the current signatories to this agreement. The RCA program for 2009 comprises of 15 projects in the fields of Agriculture, Environment, Human Health, Industry, and Radiation Protection. Cancer care is undoubtedly an important focus in the field of Human Health. RCA activities in Human Health It had been a great honor for me to fulfill the position of IAEA/RCA Thematic Sector Lead Country Coordinator in Human Health until end of 2008. In 2008, there were 7 projects in the Human Health sector, and, among these, 3 projects described below were related to radiation oncology. RAS/6/038 "Strengthening Medical Physics through Education and Training" The objectives is to improve capability and capacity in medical physics in the region through the establishment of regional approaches on education and training of medical physicists; and to improve and upgrade safe operating practices and technical standards in the region through the establishment of a common quality assurance/quality control (QA/QC) program. This project is scheduled in 2003-2012. The project focuses on the development of a clinical training program for medical physicists in the RCA region and is currently in the effort to establish the training modules and the certification system for Radiation Oncology Medical Physicists (ROMP), who play an significant role in the daily practice of radiotherapy. This project plans to establish similar training modules for medical physicists in diagnostic medicine and nuclear medicine. RAS/6/040 "Improvement in Quality of Brachytherapy of Frequent Cancers in the Region" The objective was to improve the quality of the radiotherapy in the RCA Member States with a main focus on the use of brachytherapy in the cancer treatment. This project was conducted in 2003-2008. Regional training courses, mainly for radiation oncologists but also for medical physicists and radiotherapy technologists, were held under this project in order to improve the training of radiotherapy personnel in the region. A quality audit program of radiotherapy facility, QUATRO program developed by the IAEA, was conducted in the participating Member States to assess the status of their facility and improve the quality of their radiotherapy practice. RAS/6/048 "Application of High-Precision 3D Radiotherapy for Predominant Cancers in the RCA region" The objective is to improve the knowledge and skill of radiation oncologists and medical physicists in 3D conformal radiotherapy, which is a standard modality in developed countries, but may still be a rather new, laborious, and even currently unavailable procedure for developing countries. This project has held regional training courses on 3D conformal radiotherapy for radiation oncologists and medical physics to train representative trainers for national training projects and the national training courses are scheduled to be held by the national project coordinators of the participating Member States. Finally, the RCA programs aim to improve the quality of radiotherapy of the Member States in the Asian and Pacific region. While such efforts in the regional scale is necessary to improve the overall quality of cancer care for the patients in this region, the key to the success is whether such efforts will reach to the radiation oncologists, medical physicists, radiation technologists who provide the actual daily care of the cancer patients day by day in their communities. I would like to invite many enthusiastic radiation oncologists and other personnel to join IAEA/RCA activities. The dedication and collaboration among such enthusiasts will, without a doubt, lead to the improvement of cancer care among the Asian and Pacific people. 1) Boyle P, Levin B, editors. World Cancer Report 2008. Geneva: WHO Press; 2008. 2) Ploquin NP, Dunscombe PB. The cost of radiation therapy. Radiother Oncol 2008; 86:217-223. 3) Tatsuzaki H, Levin CV. Quantitative status of resources for radiation therapy in Asia and Pacific region. Radiother Oncol 2001;60:81-89. Takashi Nakano, MD, PhD Professor of Radiation Oncology, Graduate school of Medicine, Gunma University


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Profile: Prof. Constantinos Deltas

Prof. Constantinos Deltas Prof. Constantinos Deltas, an internationally reputed scientist and an expert in the field of Molecular Medicine as applied to Human Medical Genetics research and applied Molecular Diagnostics, is presently working as Professor of Genetics in the Department of Biological Sciences, University of Cyprus and the Head of the Laboratory of Molecular and Medical Genetics. Prof. Deltas is also holding the coveted post of the elected Chairman of the Department of Biological Sciences in the University of Cyprus. Prof. Deltas graduated in 1982 from the National and Kapodistrian University of Athens with a degree in Pharmaceutics. He then earned a PhD degree in Biochemistry, from Rutgers University, The State University of New Jersey in the United States in 1988, for work he performed in the biochemistry and molecular biology of connective tissue disorders with emphasis on Osteogenesis Imperfecta, a collagen type 1 disorder. Between 1988-1990 he worked as Instructor in Medicine, Jefferson Institute of Molecular Medicine, Thomas Jefferson University in Philadelphia, PA, USA. He then worked as a Visiting Research Associate in the Division of Neurology at Duke University Medical Center, at Durham, North Carolina, USA. In 1991, he returned to his home country, Cyprus, recruited at the newly established Cyprus Institute of Neurology and Genetics. He created and directed the Department of Molecular Genetics C' with emphasis on molecular diagnostics and genetics research, mostly engaged in inherited kidney disorders, among others. In 2002, Prof. Deltas was elected Professor of Genetics in the newly created Department of Biological Sciences of the University of Cyprus. He is Head of the Laboratory of Molecular and Medical Genetics and elected Chairman of the Department. He teaches undergraduate and graduate courses on human molecular and medical genetics and he continues research in Nephrogenetics while he is developing tools for better understanding of molecular pathomechanisms at cellular and animal level. He also has interest in molecular epidemiology and the genetic heritage of Cypriots, and he is preparing and maintaining the Genetic Map of Cyprus. His work has been reported in 74 original peer-reviewed publications in international journals and in additional review papers in local and international journals. As invited or distinguished speaker he lectured at international and local conferences as well as at Universities abroad while he served as a referee for many reputable peer-reviewed journals. His work was awarded first place awards seven times by the local Medical Associations in Cyprus. He is a member of the Cyprus National Bioethics Committee, a representative of Cyprus to the Standing Committee of the European Medical Research Council of the European Science Foundation and a Coordinator of the Committee of the Cyprus Council of the Recognition of Higher Education Qualifications (KY.S.A.T.S.), on the subject of Biology-Biochemistry. The highlights of his past research projects were concerned with the molecular and medical genetics of numerous inherited conditions including Cystic Fibrosis and Familial Mediterranean Fever. His work was instrumental in showing that these two diseases are not rare among the Cypriot population. On the contrary, work from his laboratory showed that Cystic Fibrosis was very frequent especially in a village where the common mutation DF508 had a carrier frequency of 1/14, perhaps the highest worldwide, while dehydration was a prominent feature at presentation of patients in childhood. Similarly, Familial Mediterranean Fever was proved to be a frequent condition with a carrier frequency of 1/9 and reduced penetrance, which was previously misdiagnosed. The introduction of molecular testing and awareness programs raised the quality of service to the community. In addition to the above, the main field of his research activities since 1991 has been the inherited kidney diseases. In collaboration with scientists in Cyprus and abroad, his laboratory was involved in the mapping and cloning of the PKD2 gene, which is mutated in Polycystic Kidney Disease type 2, with publications in Nature Genetics and Science. He was among the first to prove in human samples the two-hit hypothesis and the trans-heterozygous hypothesis for cyst formation in PKD2, reminiscent of the Knudson hypothesis and tumor formation process. He is presently involved with the development of cell and animal models for investigating the role of PKD2 gene in Autosomal Dominant Polycystic Kidney Disease using various approaches including miRNA technology. His team in Cyprus was the first to map the MCKD1 gene, mutations in which are responsible for the adult autosomal dominant form of Medullary Cystic Kidney Disease, by investigating families from an area at the south/west part of the island. More recent work in his laboratory, in collaboration with clinicians under the direction of Dr Alkis Pierides, a close friend and collaborator all these years, focused on the investigation of the genetics, primary genes involved and genetic modifiers in Thin Basement Membrane Nephropathy in conjunction with Familial Microscopic Hematuria and Focal Segmental Glomerulosclerosis. His work was instrumental in establishing a previously suspected link between Thin Basement Membrane Nephropathy and Focal Segmental Glomerulosclerosis, by studying a large number of Greek-Cypriot families among whom many patients satisfied a dual diagnosis, as a result of heterozygous collagen IV mutations. His future work aims at the development of cell and animal models for investigating the molecular pathomechanisms of renal impairment in glomerular basement membrane expressed collagen IV pathology. Among all these he has always been interested in developing and applying molecular diagnostics tools for inherited kidney diseases as well as other conditions such as inherited thrombophilia, Familial Mediterranean Fever, Alport Syndrome, Distal Renal Tubular Acidosis and Medullary Thyroid Carcinoma. His future dreams include the creation of a larger Research Unit with genomics and proteomics directions, with the use of human clinical material and animal models. In doing so, he maintains collaborations with major groups in Europe and the United States in order to transfer expertise and know how from larger groups and laboratories.


For the Time Being: Understanding the Temporality of Cancer Survival

Dr Jan Pascal, Ruth Endacott, Jennifer Lehmann

  1. Dr Jan Pascal
    Lecturer, School of Social Work and Social Policy, La Trobe University
  2. Ruth Endacott
  3. Jennifer Lehmann

This paper explores cancer survival experiences and offers the Heideggerian concept of temporality as a way of acknowledging and understanding the complex and pervasive nature of survivorhood. Firstly, despite demographic indicators, the process of cancer survival is under-reported in the research literature. Secondly, and embedded throughout this paper, is the notion that cancer survival is not an illness and requires its own analytic frameworks. Thirdly, this paper suggests temporality can assist to extend understanding of cancer survival beyond extant psychiatric diagnostic, disease trajectory, coping and adaptation, and illness narrative frameworks. This study explored the lived experience of cancer survival with participants who defined themselves as survivors of cancer. Fifteen participants were interviewed in rural Australian towns using an in-depth interviewing technique guided by phenomenological principles. Fourteen participants were interviewed on a second occasion, three to four months following the first interview. Temporality emerged as a key finding and, for the purposes of this paper, can be understood as the experiences of changes to self and relationships through time. This goes beyond chronicity, and is concerned with the meanings ascribed to one's past, present and future in light of a cancer diagnosis. Findings demonstrate that cancer problematised temporality for survivors through forcing an awareness of uncertainty and possible death. This raised existential questions about self, others and relationships of care. Extending the existing psychosocial literature, findings suggest that survivorhood is an on-going process of meaning-making, rather than a developmental trajectory. The findings have implications for health care and social work protocols for post-discharge planning and longer term care for cancer survivors, including personal and family casework, group work and community development practice.


Entrance and Exit Dose Measurements with MOSFET Detectors During Radiotherapy Treatments

Dr V Ramasubramanian, A Gopiraj

  1. Dr V Ramasubramanian
    Nuclear and Medical Physics Division, School of Science and Humanities, Vellore Institute of Technology University
  2. A Gopiraj

PURPOSE: To evaluate the feasibility of in vivo measurements with metal oxide semiconductor field effective transistor (MOSFET) dosimeter on patients during 6 MV x-ray irradiation of the pelvis and Head & Neck. MATERIALS AND METHODS: Entrance and exit dose was determined using MOSFET detectors placed on the entrance and exit detectors on the patients using appropriate buildup materials. The MOSFET detector were calibrated against the 0.6 cc ionization chamber. The expected entrance and exit doses for all fields were determined from the prowess panther treatment planning system. The expected and the measured entrance and exit dose values were compared. RESULTS: A total of 188 measurements were carried out for both entrance and exit points which includes 152 pelvic radiation fields and 36 Head and Neck radiation fields. For the entire 152 pelvic fields, the ratio of the measured entrance to the expected entrance dose was found to be 1.019 with a standard deviation (SD) of 0.055. Further the average of the ratio of measured exit dose to the expected exit dose was found to be 0.955 with a SD of 0.066. Head and neck (n = 36) cases showed an average value for the ratio between measured and expected doses for entrance and exit fields as 1.063 (SD=0.0545) and 0.984 (SD=0.0707). CONCLUSION: The accuracy and precision of in vivo dose determination using MOSFET system have been explored for patients treated in pelvic region and Head and Neck region. The MOSFET detector gives good estimation in the determination of entrance and exit doses of patients.


Is this Acute Lymphoblastic Leukaemia (ALL) or Juvenile Rheumatoid Arthritis (JRA)?

Dr Chellam Kirubakaran, Julius Xavier Scott, Sam Ebenezer

  1. Dr Chellam Kirubakaran
    Professor & Head, Dept. of Child Health- Unit II, Christian Medical College
  2. Julius Xavier Scott
  3. Sam Ebenezer

Aim: To identify any clinical or laboratory features to differentiate between the children with true JRA and ALL at the onset of disease. Methodology: 10 children with ALL who presented as JRA were compared with 10 other children with true JRA. The clinical features and the lab data at the onset of disease were compared. Results: Among the clinical features compared, only severity of pain as evidenced by inability to walk showed a statistical significance. Thrombocytopenia was noted in 70% of children with ALL whereas none with JRA had thrombocytopenia. Lymphocytosis was seen predominantly in children with ALL (70%) as compared to neutrophilia in 60% of children with JRA. Thus severity of pain, neutrophilia, lymphocytosis and thrombocytopenia were only statistically significant among the two groups. Conclusions: Hence it is important to have a high index of suspicion of malignancy in any children who presents with polyarthritis.


The Impact of Cancer Associated Inflammation on Cytotoxic Drug Metabolism and Nutritional Status: The Sydney Cancer Centre Experience

Dr Stephen Clarke, Christopher Liddle, Graham R. Robertson

  1. Dr Stephen Clarke
    Department of Medicine, Level 1, Clinical Sciences Building, Concord Hospital
  2. Christopher Liddle
  3. Graham R. Robertson

Cancer associated inflammation has long been recognised to be associated with worse cancer outcomes including survival. This process is driven by increased plasma cytokine concentrations, especially interleukin-6 (IL-6), derived either from the tumour or host immune cells. Research in the Clinical Pharmacology Unit at the Sydney Cancer Centre has focused on the impact of cancer-associated inflammation on hepatic cytotoxic drug metabolism and toxicity from chemotherapy. The majority of anti-cancer drugs are metabolised by the hepatic cytochrome P450 system of enzymes, in particular 3A4 (CYP3A4). This research has shown that an acute phase plasma protein reaction in cancer patients and murine tumour models is associated with reduced CYP3A4 metabolism. In addition, there is evidence of reduced hepatic expression of a range of drug transporters including Mdr2, Mrp2, Mrp3, Ntcp, Oatp2, Oatp-c and Bcrp. In combination, these changes lead to reduced plasma clearance and increased toxicity from chemotherapy. We have also shown that cancer associated inflammation is strongly correlated with nutritional status in cancer patients, creating a rationale for nutrition intervention strategies to reverse inflammation and improve cytotoxic drug metabolism. A range of anti-cytokine antibodies have been developed targeting IL-6, the IL-6 receptor and TNF-a, and these create the potential to reverse impaired drug metabolism prior to administration of chemotherapy, thereby improving toxicity.


The Anti-cancer Drug Arsenic Trioxide is an Important Neutrophil Agonist

Denis Girard, Francois Binet

  1. Denis Girard
    PhD
    INRS-Institut Armand-Frappier
  2. Francois Binet

In this review, we present our data obtained with the most recently identified neutrophil agonist we have investigated, arsenic trioxide. We found that this anticancer drug induces neutrophil apoptosis and cytoskeletal breakdown by a caspasedependent mechanism. In addition, we summarize what we know about its mode of action in neutrophils. The review ends with future perspectives dealing on the interaction between arsenic trioxide and neutrophils.


Epidemiologic Studies on Mobile Phone Use and the Risk of Brain Tumours: An Overview

Dr Joachim Sch?z

  1. Dr Joachim Sch?z
    Institute of Cancer Epidemiology

While there is convincing evidence that short-term use of mobile phones is not associated with an increased brain tumour risk, no firm conclusions can be drawn for long-term users of 10+ years. Even large studies included only patients diagnosed before 2004, hence the proportion of long-term users was small. However, evidence against a strong increase in risk is growing. A comprehensive prospective study offers the possibility to accompany the wider distribution and the newly emerging technologies of mobile telecommunication under health-relevant aspects. Considerations of applying precautionary measures need to be balanced against benefits of mobile telecommunication.


Elevated Pleural Fluid RCAS1 is a Diagnostic Marker and Outcome Predictor in Lung Cancer Patients

Dr Keisuke Aoe, Akio Hiraki, Yuichi Nakamura, Tomoyuki Murakami, Tadashi Maeda, Masaharu Nishimura, Kazuro Sugi, Hiroshi Ueoka

  1. Dr Keisuke Aoe
    MD, PhD
    Department of Respiratory Medicine and Clinical Research, NHO Sanyo National Hospital
  2. Akio Hiraki
  3. Yuichi Nakamura
  4. Tomoyuki Murakami
  5. Tadashi Maeda
  6. Masaharu Nishimura
  7. Kazuro Sugi
  8. Hiroshi Ueoka

RCAS1, a type II membrane protein also secreted in soluble form, may be important in tumor cell evasion of immune surveillance and contribute to aggressiveness of human tumors. We examined implications of elevated pleural fluid RCAS1 at onset of effusion in lung cancer patients. Of 102 patients presenting with pleural effusion, 59 proved to have a malignant effusion and 43, nonmalignant. Malignant effusions exhibited higher RCAS1 concentrations than nonmalignant effusions (mean 1 SD; 36.3 1 114 vs. 2.7 1 1.8 U/mL; p = 0.014). Lung cancer patients with pleural fluid RCAS1 concentrations below 15 U/mL had longer mean survival than those with higher concentrations (4.7 vs. 1.7 months; p < 0.05). By multivariate analysis, pleural fluid RCAS1 was an independent prognostic factor in lung cancer patients with effusion. In conclusion, RCAS1 determination at onset of pleural effusion is informative for both diagnosis and outcome prediction in lung cancer patients.


Cyclin D1 Genetic Polymorphism and Clinical Presentation of Childhood Acute Lymphoblastic Leukemia

Dr Samart Pakakasama, P Phaichitchinda, S Kajanachumpol, U Udomsubpayakul, S Apibal, S Hongeng

  1. Dr Samart Pakakasama
    M.D
    Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital
  2. P Phaichitchinda
  3. S Kajanachumpol
  4. U Udomsubpayakul
  5. S Apibal
  6. S Hongeng

CCND1 G870A polymorphism has been reported to be associated with risk, age of onset, and event-free survival in a variety of cancers. This study aimed to determine the association between CCND1 G870A polymorphism and age of onset, clinical presentations, and risk of childhood acute lymphoblastic leukemia (ALL). We enrolled 100 children with ALL and 300 healthy controls in the study. The CCND1 G870A polymorphism was analyzed by using PCR with specific restriction enzyme digestion. Our population had more frequent A allele (62%) than G allele (38%). There was no association between CCND1 G870A polymorphism and age of onset or any significant clinical presentations of children with ALL. The frequencies of CCND1 G870A genotypes in ALL were not different from controls. In conclusion, there was no association between CCND1 G870A polymorphism and age of onset, clinical presentations, or risk of ALL in Thai children.


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