Radiation induced lymphopenia - a possible critical factor in current oncological treatment.

BACKGROUND: The effect of ionizing radiation on the immune system during the treatment of malignant tumors has long remained a point of great interest. This issue is currently gaining importance, especially in connection with the advancing development and availability of immunotherapeutic treatment. During cancer treatment, radiotherapy has the ability to influence the immunogenicity of the tumor by increasing the expression of certain tumor-specific antigens. These antigens can be processed by the immune system, stimulating the transformation of naïve lymphocytes into tumor-specific lymphocytes. However, at the same time, the lymphocyte population is extremely sensitive to even low doses of ionizing radiation, and radiotherapy often induces severe lymphopenia. Severe lymphopenia is a negative prognostic factor for numerous cancer dia-gnoses and negatively impacts the effectiveness of immunotherapeutic treatment. AIM: In this article, we summarize the possible influence of radiotherapy on the immune system, with a particular emphasis on the impact of radiation on circulating immune cells and the subsequent consequences of this influence on the development of cancer. CONCLUSION: Lymphopenia is an important factor influencing the results of oncological treatment, with a com-mon occurrence during radiotherapy. Strategies to reduce the risk of lymphopenia consist of accelerating treatment regimens, reducing target volumes, shortening the beam-on time of irradiators, optimizing radiotherapy for new critical organs, using particle radiotherapy, and other procedures that reduce the integral dose of radiation.

How and why to monitor Pseudomonas aeruginosa infections in the long term at a cystic fibrosis centre.

BACKGROUND: Pseudomonas aeruginosa is a major cystic fibrosis (CF) pathogen causing chronic respiratory infections and posing a risk for cross-infection between patients with CF. AIM: To propose an algorithm for long-term surveillance of P. aeruginosa and assess its suitability for monitoring the epidemiological situation at a CF centre with approximately 300 patients. METHODS: Over a nine-year period, over 300 P. aeruginosa isolates from 131 infected patients were tested by multi-locus sequence typing (MLST) and/or random amplified polymorphic DNA (RAPD) assay. FINDINGS: MLST analysis led to the identification of 97 different sequence types which were distributed among 17 RAPD-generated (pseudo)clusters. This indicates that the easy-to-perform RAPD assay is only suitable for intra-individual, not interindividual, strain analyses. No epidemic strains were observed. Longitudinal analysis revealed that 110 of the 131 patients were infected with the same strain over the observation period, whereas 21 patients had a strain replacement or a new infection. Chronic infection was found in 99 of the 131 patients, and the remaining 32 patients met the criteria for intermittent infection (as defined by the Leeds criteria). Eighteen of the 32 patients (56%) with intermittent infection were infected with the same strain for up to nine years. CONCLUSION: The strain type only changed in 16% of 131 patients with chronic or intermittent infection. As many as 56% of patients considered to have intermittent infection were actually chronically infected with the same strain for many years.

[Very late effects of radiotherapy -  limiting factor of current radiotherapy techniques]. / Velmi pozdní následky radioterapie -  limitující faktor soucasných radioterapeutických technik.

BACKGROUND: Very late effects of radiotherapy occur within decades after the initial exposure. Their development is induced by low doses of ionizing radiation (from 4 Gy per radiation series) and their clinical manifestations are difficult to distinguish from other independent diseases diagnosed in individuals not formerly treated with radiation. A long time period from the exposure confounds any causal relationships between radiation and adverse events. Still, these side effects not only reduce the patients quality of life but also lead to an early morbidity and mortality, hence generating significant costs in health care and social systems. PURPOSE: This article summarizes findings about the most common very late consequences of radiotherapy, which include cardiotoxicity, CNS toxicity, pneumotoxicity, renal toxicity and secondary malignancies. This issue is crucial in the group of children cancer patients, malignant lymphomas, testicular tumors and CNS tumors. Generally, the risk of very late effects of radiotherapy (RT) should be considered in all patients irradiated at a relatively early age with a high chance of long term survival. The risk of very late effects of RT is also one of the key limiting factors in the use of RT in the treatment of patients with benign lesions with longterm survival expectation, e. g. in patients with glomus tumors, neurofibromas, desmoid tumors or hemangiomas or other benign lesions (arterio venous malformations). Currently, the only known prevention of these very late adverse effects is to minimize the dose to critical structures to the lowest achievable level.

Treatment of high risk prostate cancer with combined radiotherapy and hormonal treatment- results and identification of factors influencing outcome.

PURPOSE: The aim of this work was to prospectively analyze the outcome of combined hormonal treatment and radical radiotherapy in high risk non metastatic prostate cancer patients (T1=4, N0-1, M0). METHODS: Between April 2003 and December 2007 196 patients with high risk prostate cancer were treated with curative intent. The treatment consisted of 2-month neoadjuvant hormonal treatment (LHRH analog), radical radiotherapy (68-78 Gy, conformal technique) and an optional 2-year adjuvant hormonal treatment. RESULTS: The median follow up time was 59 months. Fiveyear overall survival was 86% and 5-year biochemical disease free survival (DFS) 70%. Factors found to be statistically significant relative to outcomes were Gleason score (p=0.017), initial PSA value (p=0.039) and adjuvant hormonal treatment (p=0.035). There was no significant association between radiotherapy dose or volume and biochemical DFS (bDFS). Late genitourinary and gastrointestinal toxicity was acceptable. CONCLUSION: Treatment combining hormonal therapy and radical radiotherapy can be recommended for this subgroup of prostate cancer patients. Adjuvant hormonal treatment should also be used.

[The role of radiotherapy in the treatment of malignant lymphomas - recommendations of the Czech Lymphoma Study Group]. / Postavení radioterapie v lécbe maligních lymfomu - doporucení Kooperativní lymfomové skupiny.

BACKGROUND: Indication of radiotherapy in lymphoma treatment is an important strategic decision requiring comprehensive expertise. It also calls for a better definition of the position of radiotherapy in clinical practice. DESIGN: This position paper represents a consensus between hematooncologists and radiation oncologists on the role of RT in treatment of different histological types and stages of malignant lymphomas. The discussion was underway within professional societies of both specializations (Czech Lymphoma Study Group for the hematooncologists and the Society of Radiation Oncology, Biology and Physics for the radiation oncologists). RESULTS: The consensus presented here was reached in early 2012 and draws on evidence-based medicine and clinical practice. Besides defining the role of radiotherapy in lymphoma treatment, this paper also gives specific recommendations on total doses of radiotherapy in lymphoma treatment. CONCLUSION: These recommendations will supplement 7th edition of "Diagnostic and treatment guidelines in patients with malignant lymphoma" scheduled for publication in 2013.

FDG-PET for assessment of early treatment response after four cycles of chemotherapy in patients with advanced-stage Hodgkin's lymphoma has a high negative predictive value.

BACKGROUND: As positron emission tomography (PET) seems to be a powerful prognostic marker in the treatment of Hodgkin's lymphoma (HL), we analysed the prognostic value of PET after four cycles of combination therapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) in patients with advanced-stage HL. PATIENTS AND METHODS: From January 2004 to March 2007, 50 patients with newly diagnosed HL in clinical stages IIB with large mediastinal mass or extranodal disease, III and IV were treated according to the HD15 protocol of the German Hodgkin Study Group. All patients received a PET scan after four cycles of BEACOPP (PET-4). RESULTS: Of the overall group, 14 of 50 patients had a positive PET-4 while 36 had a negative PET-4. At a median observation time of 25 months, 2 of the 14 patients with a positive PET-4 had progressed or relapsed, while there was no progression or relapse in PET-4-negative patients. CONCLUSION: Our results indicate a very good negative predictive value of PET-4 in advanced-stage HL patients treated with BEACOPP.

Prognostic impact of bone involvement in Hodgkin lymphoma.

The purpose of the study is to determine incidence and prognostic impact of osseous Hodgkin lymphoma (HL). Between 1997 and 2004, 198 patients with HL were treated at our institution. Advanced stages and nodular sclerosis histology prevailed. All patients were treated according to protocols of the German Hodgkin Study Group (GHSG). After minimum follow-up of 24 months, we retrospectively analyzed the incidence of osseous HL, treatment response and parameters of survival. We recorded 14 cases of osseous HL (7 %), always with concurrent nodal disease. Axial skeleton was most frequently involved. Eleven patients (78,5 %) achieved complete remission and three (21,5 %) progressed primarily. The patients with osseous HL had significantly lower 2-year freedom from treatment failure than the patients without bone involvement (71,4 and 92,7 %, respectively, p=0,004), with no significant difference in 2-year overall survival (85,7 and 95 %, respectively, p=0,14). On multivariate analysis, advanced stage was the only independent adverse prognostic factor. In conclusion, bone involvement is a relatively common finding in HL and is not an independent adverse prognostic factor.