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Journal Issue: Vol.6, No.2 - April 2007

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Editorial

Editorial: The Current Status and Advancement of Radiation Oncology in China

In 1998 WHO?s data showed that 45% malignant tumors can be cured. This includes 22% cured by surgery, 18% by radiotherapy, 5% is by chemotherapy. Radiotherapy has been one of the essential treatment modalities in oncotherapy. Approximately 70% of patients receive radiotherapy during the whole treatment procedure. The radiotherapy cure rate has reached 37%~53% in oral pharynx carcinoma, lingual root carcinoma, amygdale carcinoma. In other cancers, such as antrum high nori carcinoma, antrum ethmoidale carcinoma, early stage carcinoma of tongue, carcinoma of rhino pharynx and cervical cancer the cure rate can reach 38%~40%. The cure rate can even get to 80% in early stage esophageal carcinoma. Up to now, while there have been certain advances with chemicals and biotherapy technique, radiotherapy is still one of the main treatments for malignant tumor. Radiotherapy oncology started in China in the 1930s, in only a few hospitals in Shanghai, Beijing, Guangzhou. After 1949, with the great development of medical treatment and health services, radiotherapy made great progress assisting in dramatic improvement in patient care. But in comparison with the developed countries, radiation oncology in China still has a great distance to cover including equipment items, personnel, therapy frequency, treatment technique etc. Until 2001, investigation data from the Chinese Medical Society of Radiation Oncology showed about 800 Chinese hospitals applied radiation to cancer patients. The whole Chinese personnel engaged in radiation oncology is more than ten thousand and whole radiotherapy equipment is more than 2000 units. In the whole nation, the departments which are able to apply x-knife therapy have approached have the ability to use Y-knife. The annual irradiated patients is now more than 500 000. Three-dimensional conformal radiation therapy could be applied in more than 200 departments. Compared with the 1990s, the number of radiotherapy departments, equipment and the number of staff has increased three times, four times and twice respectively. This speed of development is the fastest in the world. The market for China-made radiotherapy equipments is increasingly rapidly. At present, China can produce high numbers of low-energy medical linear accelerator, ten thousand curie active series cobalt therapeutic machine, simulation machine, after loading machine, low-energy X-ray beam machine, Y-knife as well as radiotherapy treatment planning system. Among the total, 60Co therapeutic machine and after loading machines made in our country take up more portions in the domestic market. Although the number of radiotherapy equipment increased fast, the capacity per capita is still lower than the average world level. WHO suggest that there would be 2~3 tele-radiotherapy treatment facilities per million people. The number is currently 3.4 in British, 8.2 in America, in France it is 4. However the possession of accelerators is 0.43 per million population in China, and merely 0.79 when 60Co therapeutic machines are included. This means Chins still is short 2000 radiotherapy units. The per capita possession is similar to East-Asian and Middle American countries, but it is better than African, Southeast-Asian countries, India and Eastern Europe. Furthermore, these limited facilities are mostly located in eastern China. The major index in western China such as radiotherapy organization, radiotherapy equipment and radiotherapy organization, radiotherapy equipment and radiotherapy applicable level are greatly lower than the country average. The lack of auxiliary equipment is also a present character of China. Radiotherapy equipment (accelerator, cobalt machine, after loading machine) should educe therapeutically effect thoroughly to achieve invariably high-quality medical treatment level, the major equipment still need the assistance of simulation machine, dose meter, radiotherapy treatment planning system and check system etc. At present in China, only the provincial cancer hospital can some big hospitals in large cities possess the above-mentioned conditions. Some radiation oncology departments in middle-small cities administer treatment using only one therapeutic machine and a few hospitals only have after loading machine or Y-knife without any auxiliary equipment. However most provincial cancer centers have now developed a high-level technique of radiotherapy, such as intensity modulated radiotherapy technique, 3-dimensional conformal radiotherapy, total body radiation technique, ant symmetry campus irradiation technique, stereo tactic radiotherapy, radio surgery and Y-knife. The cobalt machine only is still used in western China. There are also some regions which us Y-knife but neglecting technique development, which is also a recent Chinese phenomenon. These disproportion phenomena result in mass deviation of medical treatment. Radiation oncology is a general medical system, the optimal tumor radiotherapy depends on the cooperation and technique applied by the members of a multidisciplinary team consisting of physicians, radiotherapy technicians, radiotherapy engineers and so on. The role of the radiotherapy engineer in our country is not optimal. Because our technicians still stay in a low-grade educational level, they cannot fully participate in planning and administering treatment. Most radiotherapy technicians in radiation oncology departments are transferred from nursing or technologists from different fields. The radiation oncologist should not only master clinical knowledge, pharmaceutical sciences, oncology, diagnostic imagelogy, radio-physics, radio-biology, but also biochemistry of cancer, computer technique, and information medical knowledge etc.. Confronting the radiotherapy technique reform guided by precise radiotherapy, only a few cancer hospitals or college hospitals posses such high quality of personnel. For example, the ratio in most developed countries has achieved 3:1 (doctor:physicist), and the rate reached to 2:1 in Hong Kong, but in China it is only 8:1. Further, most physicists have not received special training. In fact, the ratio is only 6:1 excluding the untrained physicists. Most radiation oncologists are clinically trained as oncologists without specialized radiotherapy knowledge unlike the qualifications of 8 years training in America, Europe and Japan. We can see from the report of the plenary lecture and exhibition of ASTRO and ESTRO, that tumor radiotherapy is changing from 3D to 4D, which raises higher demands again on the radiation oncologists, but also provides a good opportunity for China to improve the status of radiotherapy technician and catch up with the advances technology of the world. In China, the incidence of cancer is rising. According to the estimation of the national cancer treatment and prevention department, newly diagnosed patients are about 2 million while people succumbing to malignant tumor are about 1.4 million every year. According to the statistics of cancer hospitals in Beijing, Shanghai, Guangzhou and Hangzhou, about 65%~75% cancer patients undergo radiation therapy as part of their whole treatment procedure, while the data is 60% in the United States. It is therefore estimated about 1.3 million persons should be treated with radiation in China every year but currently only 0.283 million patients receive treatment, so it is a long way from guaranteeing 70% of 2 million cancer patients can obtain radiation therapy every year in China. Radiation oncology comes now with just one hundred years history, but it is developing very fast. In the past decade, traditional and common radiotherapy has changed greatly with the development of computer technology, network technology, medical imaging technology and biotechnology. Tumors targeting is becoming much more reasonable and precise. With the help of PET/CT or functional MR, the biological targeting radiation will be finally realized. The calculating mode of physical dosage is changing gradually to biology-physical dosage mode. With the help of network technology, it is now possible to integrate radiotherapy information. The commercialization of IGRT, has helped the integration of radiotherapy come true. In the coming 10 years, ART and BCRT will be on the agenda. Modern radiation oncology tends to be multi-subject integrated and continuing high technology application. In China, radiation oncology while facing a big challenge also has a chance to improve the level of radiotherapy. Chinese hospitals should improve the quality of the radiotherapy team, maintain continuous education, support the national production research and manufacturing in radiotherapy auxiliary equipment while introducing advanced equipment and technology. Meanwhile, we should reinforce the research-on-research about modern radiotherapy, promote communication with developed countries, establish nation-wide consistent quality management and manipulation network system as soon as possible. We believe that the whole level of radiotherapy and quality of China will move to a new stage in the future.


Profile

Profile: Dr. Jingcheng Zheng

Dr. Jingcheng Zheng, an expert in the field of cancer research and hospital administration is currently deputy president of General Hospital of Chinese People?s Armed Police Forces (GHCAPE), Professor in the Department of Oncology, Chief Medical Officer of the Chinese International Medical Rescue Team. Dr. Zheng graduated from Xinjiang Medical University of China in 1983 and he focused on the subject of Hospital Administration and obtained his master degree at the Logistics Command College. In 1997, he founded the cancer center of the General Hospital of Chinese People?s Armed Police Forces which was one of the biggest cancer center in military medical institution of China and the cancer center could treat more than 1000 patients every year. From 1992 to 2006, Dr. Zheng visited some countries for academic exchanges or attend international oncology conference. He had published four books which introduced the advance of medical oncology and experience of his practice on cancer treatment. He also concentrates on other medical science such as emergency medicine, hospital administration and so on. Dr. Zheng published more than 50 scientific research papers on international and Chinese medical journal. Because of Dr.Zheng?s excellent work, the Cancer Center of General Hospital of Chinese People?s Armed Police Forces has established good relationships with many institutions from USA, India, France, Japan, Pakistan, Australia and so on. In addition to his research and academic responsibilities, Dr. Zheng currently serves as the member of information administration of Chinese Administrative Committee, of the First Aid and Resuscitation Committee of Chinese Physician Association of the CAPF?s Science Technology Committee. Furthermore, he also was the reviewer of several military publications. Now he holds the post of vice chief editor of Chinese Medical Teaching and Clinic, and as the member of CAPF Medical journal. He also devotes himself to teach and to train medical post-graduate students. Now Dr. Zheng is leading a vigorous medical team consisting of radiation oncologists and medical oncologists to offer the best treatment for cancer patients. Most patients are from China, but some foreign patients come to receive treatment become Dr. Zheng could apply Chinese medicine to these patients. Dr. Zheng received many medical science research awards and honor due to his great scientific achievements in the field of oncology and hospital administration. He was awarded the Outstanding Hospital Administrators Official of Beijing. He also made great contributions to Chinese International Medical Rescue Team and health service, so Chinese State Council awarded him the First Prize in 2006. Dr. Zheng?s specialty include radiation induced disease and the integrated traditional and western medicine for carcinoma.


Manuscript

Mechanisms Modifying DNA Methylation in Differentiated Cells

Dr B.C Richardson

  1. Dr B.C Richardson
    MD, PhD
    Department of Medicine, 5310 Cancer Centre and Geriatrics center building, University of Michigan

DNA methylation plays an essential role in mammalian development through its effects on chromation structure and gene expression. However, acquired abnormalities can modify DNA methylation patterns in differentiated cells, with detrimental effects on gene expression and cellular function. Recent studies have implicated these changes in several pathologic process including carcinogenesis, autoimmunity, and immune senescence. The mechanism modifying DNA methylation patterns have only recently begun to be analyzed, but include exogenous agents such as diet, medications, chemicals, and ultraviolet light. These can exert their effect by altering intracellular pools of precursors necessary for transmethylation reactions, by modifying the activity of the enzymes and proteins mediating DNA methylation, and by modifying pathways regulating expressions of the DNA methylation machinery. Compensatory mechanisms have been identified which may help maintain DNA methylation patterns, but how these are regulated, and whether abnormalities in these mechanisms can also contribute to altered patterns of DNA methylation is unknown. The homeostasis of DNA methylation is a developing and important area of study, and has important implications for our understanding of the pathogenesis and prevention of multiple pathologic conditions. Further studies are needed to identify these mechanisms in order to prevent the development of the resulting diseases.


Psychological and Psychiatric Sequelae of Steroid Use in Hematology Treatments: A Review of the Literature

Dr Pam McGrath, Sarah James, Paul Pun, Hamish Holewa

  1. Dr Pam McGrath
    B.Soc.Wk; MA; PhD
  2. Sarah James
  3. Paul Pun
  4. Hamish Holewa

There is considerable evidence that corticosteroid treatments are frequently associated with severe emotional and even psychiatric disturbances. Since their introduction as therapeutic agents, corticosteroids have been associated with symptoms ranging from mood disturbances to (florid) psychosis. In consideration of the centrality of steroid use in hematology, the expectation is that there should be extensive literature on the psychological and psychiatric interface with steroids in the treatment of these diagnostic groups. To date, however, although the emotional impact of corticosteroid use is reported in a wide range of diagnostic disorders there has been scant attention to this phenomenon in relation to treatment for hematological malignancies. The lack of research insights into this area has left a vacuum for clinical care and psychosocial support. More research needs to be done to address this imbalance, to achieve the optimum outcome for hematology patients and their families. This review provides a starting point by outlining the present literature on the psychological and psychiatric impact of steroid use.


Neoplastic Diseases: Biological Statement and Clinical Relevance

Dr Jean Paul Bureau, Thierry Lavabre-Betrand, Laurent Henry, Serge Carillo, Isabelle Guiraud, Jean Francois Rossi

  1. Dr Jean Paul Bureau
    Laboratorie d'Histologie, Faculte de Medecine de Montpellier-Nimes
  2. Thierry Lavabre-Betrand
  3. Laurent Henry
  4. Serge Carillo
  5. Isabelle Guiraud
  6. Jean Francois Rossi

We measured the plasma proteasome level using an ELISA test in 73 normal donors, 20 patients with solid tumor, 318 patients with various haemopoietic malignancies (myeloproliferative syndrome, myelodysplastic syndrome, chronic lymphatic leukaemia, and Non-Hodgkin's lymphoma) and 25 patients with auto-immune disease, in order to assess the interpretation rules and the clinical relevance of this test. The result obtained were highly reproducible. In normal individuals, mean plams proteasome levels ranged was 4712-254 ng/ml. High values were found in auto-immune disorders as compared to normal individuals. In solid tumors, plasma proteasome level was generally elevated as well as in myeloproliferative and myelodysplastic syndromes. In contrast, all lymphoproliferative disorders tested inhibited a significantly lower level than normal donors, irrespectively of clinical status or histologic type, except during an aggressive stage, where proteasome levels were found increased. Based on these data, we propose guidelines for interpretation of pathologic plasma proteasome levels in apparently normal individuals, and in patients with solid tumor, myeloid or lymphoid disorders, which emphasize the interest of the test in the diagnosis and follow-up of these pathologies.


Peripheral Blood CD25+CD4+T Cells in Childhood Patients Treated with Allogeneic Stem Cell Transplantation

Dr Kenichi Sugita, Tatsuo Tsuboi, Yuya Sato, Hidemitsu Kurosawa, Osamu Arisaka

  1. Dr Kenichi Sugita
    Department of Pediatrics, Dokkyo Medical University
  2. Tatsuo Tsuboi
  3. Yuya Sato
  4. Hidemitsu Kurosawa
  5. Osamu Arisaka

We here studied regulatory T cells (CD25+CD4+T cells) post-allogeneic stem cell transplantation (SCT) as an important marker in the understanding of immune reconstitution post-SCT. 22 patients with SCT were enrolled. Peripheral blood was obtained and surface antigen was examined by flow cytometry. The percentage and absolute count of CD4+T cells were low at three and six months post-SCT. The percentage of CD25 expression on CD4+T cells at any stage post-SCT was within normal value, whereas the absolute count of CD25+CD4+T cells was low. In contrast, the percentage of HLA-DR expression, an active marker, on CD4+T cells was high at three and six months post-SCT, and the absolute count of HLA-DR+CD4+T cells increased at six and 18 months post-SCT. As a result we found that the difference between CD25 and HLA-DR expression was important as a marker for a development of GVHD. The percentage in subtracting HLA-DR from CD25 expression clearly tends to become positive on periods post-SCT and in fact that in every patient with PSL-therapy for GVHD was negative. We concluded that it took a long period for CD25+CD4+T cell count to normalize and GVHD strongly depended on the difference between CD25 and HLA-DR expression on CD4+T cells.


An Analysis of the Survival Benefits of Biophosphonate Therapy to Patients with Bone Metastases Treated with Radiation

Maria Mazurkiewicz, Anna Brzozowska, Tomasz Mazurkiewicz

  1. Maria Mazurkiewicz
    Katedra l Zakad Onkologi AM w Lublinie, UL K Jaczewskiego 7
  2. Anna Brzozowska
  3. Tomasz Mazurkiewicz

One of the methods of dealing with malignant bone metastases (mbm) involves therapy with bisphosphonates, whose action reduces hypercalcemia, alleviates pain, abates skeletal complications and decreases the incidence of future mbm. The purpose of the study was to analyse how bisphosphonates affect the mean survival time of patients irradiated for mbm. The retrospective study involved 305 patients irradiated for mbm. 94 of the patients were given bisphosphonates. We analysed the mean survival time beginning from the completion of the radiotherapy until death. The effects of bisphosponates on the survival rate were gauged by means of U Mann-Whitney non-parametric test. The mean survival time in the group that had received radiation treatment alone was 5,24 months, whereas in the group that had undergone a course of radiation and had additionally received bisphosphonate treatment had the mean survival time was 8,1 months. Also, the mean survival rate after the combination treatment differed depending on the location of the primary tumor and was significantly longer for breast cancer patients (p=0,001) as well as for those with an unknown primary site (p=0,016). Bisphosphonates increased the survival time of all mbm patients treated with radiation independent of the primary tumor location. Bisphosphonate therapy was particularly beneficial to breast cancer patients irradiated for mbm and those with an unknown primary tumor location. Their mean survival time was increased by 5 and 3,5 months respectively.


Congenital Mesoblastic Nephroma in a Child above Three Years of Age: A Case Report

Dr Rakesh Mittal, Aaron Olaolu Adesina, Shafika Al Awadi

  1. Dr Rakesh Mittal
    Department of Medical Oncology, Hussain Maki Al Juma Centre for Specialized Surgeries (KCCC)
  2. Aaron Olaolu Adesina
  3. Shafika Al Awadi

Since CMN is usually a disease of the neonatal period and early infancy we wished to report the first case of congenital mesoblastic nephroma (CMN) in a patient older than three years of age at presentation. Clinical Presentation: A 3 years and 8 month old child presented with a left renal tumor. He was clinically and radiologically diagnosed as a case of Wilm's tumor and was treated with preoperative chemotherapy. There was no response to chemotherapy. He underwent a nephrectomy, and histopathology revealed a diagnosis of CMN. He was not given any further treatment, and is well 2.5 years after the surgery.


Surgical Management of Chronis Pancreatitis

Dr George Sakorafas, George Peros

  1. Dr George Sakorafas
    MD, PhD
  2. George Peros

Although initial management of patients with chronic pancreatitis is always conservative, a selected subgroup of them will require surgical treatment at some time during the natural history of the disease.1,2 Despite recent progress in our understanding of the pathophysiology of pain in chronic pancreatitis, the wide availability of modern imaging methods and the increasing safety of pancreatic surgery (including major pancreatic resections, such as pancreatoduodenectomy), the management of these patients remains a challenging problem for the surgeon. This is not only due to the inability of surgery to achieve complete pain relief in all these patients, but also to the metabolic consequences of both pancreatic surgery and the underlying chronic pancreatitis, as well as to the chronic alcoholism, which represents one of the commonest etiologies of the disease. The combination of these factors may result in significant long-term morbidity and even mortality, especially among the non-compliant, medically unreliable alcoholic patients.3 To achieve the best results while at the same time minimizing both early and late morbidity and mortality, careful patient selection should be performed.4-6 This patient selection should be based mainly on the structural changes of the pancreas and adjacent organs, as demonstrated on imaging methods and verified at surgery. This review summarizes our current diagnostic and therapeutic approach in patients with chronic pancreatitis.


Pancreatic Resections: A Five Year Analysis

C Ramachandra, Suraj Manjunath, P Prabhakaran, Geethashree Mukherjee, Venkata Satya Suresh Attili

  1. C Ramachandra
  2. Suraj Manjunath
  3. P Prabhakaran
  4. Geethashree Mukherjee
  5. Venkata Satya Suresh Attili

BACKGROUND: Pancreaticoduodenectomy remains a daunting procedure with considerable morbidity and mortality even today. We describe our experience with pancreaticoduodenectomy for malignancy over a five year period. METHODS: Between October 1999 to September 2004, 144 patients with carcinoma of the pancreas or duodenum underwent surgery out of which 57 were submitted to pancreaticoduodenectomy. The surgical outcomes are reviewed. RESULTS: The mortality was 5.3% (three patients) and morbidity 35.1% (20 patients). Two of our patients have survived for more than five years and another three patients have survived for more than three years. CONCLUSION: In spite of poor overall survival rates, surgery remains the only hope for cure in patients with pancreatic cancer, and can be performed with acceptable risk.


Small-angle Solution Scattering of Proteins

Ruth Prassl, Michal Hammel, Peter Laggner

  1. Ruth Prassl
    Institute of Biophysics and X-Ray Structure Research, Austrian Academy of Sciences
  2. Michal Hammel
  3. Peter Laggner

In structural proteomics it has become increasingly evident that the structure of proteins in solution and under the influence of different, specific or non-specific additives, is often different from the crystal structure. This feature might exert fundamental functional influence on e.g. membrane association, ligand or receptor binding, enzyme activity or immune response. At the same time, the methods of small angle scattering have reached a state of development, both in hard- and software, where the routine application in the proteomics laboratory has become feasible. Hence, questions such as oligomerization or conformational changes induced by different environmental conditions can be answered. The impact of small molecules, ligands, lipids or drugs on the overall conformation of the protein can be visualized. Moreover, a rational combination of small angle scattering data with X-ray crystallographic data, molecular dynamics and bioinformatics offers to structural biologists the opportunity to assemble individual protein modules in a bottom-up strategy to get information on complex macromolecular structures. Thus, most recent advances in instrumentation and methodology of small angle scattering have opened important new ways for molecular structure determination. In this mini-review we report on the rapid increasing progress achieved in the field of small angle scattering techniques and outline some problems which can be addressed by solution scattering. We briefly review the strengths and limitations of the methodology and finally discuss some of our recent results showing how small angle scattering can be used to obtain essential information on protein structure in solution and how conclusions on the functional behavior of a protein can be drawn based on solution structural data.


Epidermal Growth Factor Targeted Therapy: Are we ready for these Magic Bullets?

Dr Bindhu Joseph, Venkata Satya Suresh Attili

  1. Dr Bindhu Joseph
    Department of Radiation Oncology ad Medical Oncology, KIDWAI Memorial Institute of Oncology
  2. Venkata Satya Suresh Attili

Targeted therapies are emerging as an innovative, high potential new trend in cancer therapy. Epidermal growth factor receptor (EGFR) represents one of the earliest and most widely investigated molecules. Preclinical and clinical data now support the role of integrating EGFR targeting in the multidisciplinary approach of cancer treatment for a number of malignancies including carcinoma lung (NSCL), Breast, Head & Neck, Colorectal and Malignant Glioma. The EGFR is a member of the family of membrane receptors with tyrosine kinase activity and is abnormally activated in a number of epithelial malignancies. The aberrant activation of this receptor can lead to multiple tumor promoting activities viz. enhanced proliferation, escape from apoptosis, cell transformation and angiogenesis. The anti-EGFR ammunition currently available includes monoclonal antibodies that target the extracellular domain, tyrosine kinase inhibitors and cancer vaccines. Early clinical data has strongly supported the rationality of EGFR targeting with benefits in local control & survival. However several grey areas still exist as to predicting the quantum of benefit, the optimal dose and schedule. Current research is directed at improving strategies to integrate anti-EGFR agents with current conventional treatment regimens and also evaluating its synergy with other molecular targeted approaches. This brief review attempts to give a clinical perspective of this emerging new wave in cancer treatment.


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