Acute and Late Genitourinary Toxicity after 72 Gy of Conventionally Fractionated Conformal Radiotherapy for Localised Prostate Cancer: Impact of Individual and Clinical Parameters.

AIM: Our aim was to estimate the incidence of acute and late genitourinary toxicity in patients treated with three-dimensional conformal radiotherapy (3DCRT) for localised prostate cancer and to estimate the possible influence of individual and clinical characteristics. MATERIALS AND METHODS: Between September 2009 and September 2013, 225 patients with localised prostate cancer were treated with 3DCRT. Ninety-four patients with an estimated risk of lymph node involvement ≤15%, according to the Roach formula, were evaluated in this study. All patients received a total dose of 72 Gy in 36 fractions. Acute and late genitourinary toxicity were graded according to the European Organization for Research and Treatment of Cancer radiation morbidity scoring scale. Characteristics such as age, smoking status, previous abdominal or pelvic surgery (PAPS), diabetes mellitus and the use of diuretics were analysed as possible predictive factors of toxicity. The median follow-up was 27 months. RESULTS: Grade ≥2 acute toxicity during 3DCRT developed in 25 of 94 patients (26.5%). Predictive factors of acute genitourinary toxicity grade ≥2 in the multivariate logistic regression analysis (MVA) were current smoking status (P = 0.003), PAPS (P = 0.012) and the use of diuretics (P = 0.017). The 2 and 3 year cumulative risk of late genitourinary toxicity grade ≥1 was 25.3% and 30.2%, respectively. In the MVA, acute genitourinary toxicity was significantly associated with late genitourinary toxicity (P = 0.024). CONCLUSION: Current smoking status, PAPS and the use of diuretics have a significant effect on the occurrence of acute genitourinary toxicity grade ≥2. The occurrence of any grade of acute genitourinary toxicity has a significant influence on the development of any grade of late genitourinary toxicity.

Health technologies for the improvement of chronic disease management: a review of the Medical Advisory Secretariat evidence-based analyses between 2006 and 2011.

BACKGROUND: As part of ongoing efforts to improve the Ontario health care system, a mega-analysis examining the optimization of chronic disease management in the community was conducted by Evidence Development and Standards, Health Quality Ontario (previously known as the Medical Advisory Secretariat [MAS]). OBJECTIVE: The purpose of this report was to identify health technologies previously evaluated by MAS that may be leveraged in efforts to optimize chronic disease management in the community. DATA SOURCES: The Ontario Health Technology Assessment Series and field evaluations conducted by MAS and its partners between January 1, 2006, and December 31, 2011. REVIEW METHODS: Technologies related to at least 1 of 7 disease areas of interest (type 2 diabetes, coronary artery disease, atrial fibrillation, chronic obstructive pulmonary disease, congestive heart failure, stroke, and chronic wounds) or that may greatly impact health services utilization were reviewed. Only technologies with a moderate to high quality of evidence and associated with a clinically or statistically significant improvement in disease management were included. Technologies related to other topics in the mega-analysis on chronic disease management were excluded. Evidence-based analyses were reviewed, and outcomes of interest were extracted. Outcomes of interest included hospital utilization, mortality, health-related quality of life, disease-specific measures, and economic analysis measures. RESULTS: Eleven analyses were included and summarized. Technologies fell into 3 categories: those with evidence for the cure of chronic disease, those with evidence for the prevention of chronic disease, and those with evidence for the management of chronic disease. CONCLUSIONS: The impact on patient outcomes and hospitalization rates of new health technologies in chronic disease management is often overlooked. This analysis demonstrates that health technologies can reduce the burden of illness; improve patient outcomes; reduce resource utilization intensity; be cost-effective; and be a viable contributing factor to chronic disease management in the community. PLAIN LANGUAGE SUMMARY: People with chronic diseases rely on the health care system to help manage their illness. Hospital use can be costly, so community-based alternatives are often preferred. Research published in the Ontario Health Technology Assessment Series between 2006 and 2011 was reviewed to identify health technologies that have been effective or cost-effective in helping to manage chronic disease in the community. All technologies identified led to better patient outcomes and less use of health services. Most were also cost-effective. Two technologies that can cure chronic disease and 1 that can prevent chronic disease were found. Eight technologies that can help manage chronic disease were also found. Health technologies should be considered an important part of chronic disease management in the community.

Direct health-care costs attributed to hip fractures among seniors: a matched cohort study.

SUMMARY: Using a matched cohort design, we estimated the mean direct attributable cost in the first year after hip fracture in Ontario to be $36,929 among women and $39,479 among men. These estimates translate into an annual $282 million in direct attributable health-care costs in Ontario and $1.1 billion in Canada. INTRODUCTION: Osteoporosis is a major public health concern that results in substantial fracture-related morbidity and mortality. It is well established that hip fractures are the most devastating consequence of osteoporosis, yet the health-care costs attributed to hip fractures in Canada have not been thoroughly evaluated. METHODS: We determined the 1- and 2-year direct attributable costs and cost drivers associated with hip fractures among seniors in comparison to a matched non-hip fracture cohort using health-care administrative data from Ontario (2004-2008). Entry into long-term care and deaths attributable to hip fracture were also determined. RESULTS: We successfully matched 22,418 female (mean age = 83.3 years) and 7,611 male (mean age = 81.3 years) hip fracture patients. The mean attributable cost in the first year after fracture was $36,929 (95 % CI $36,380-37,466) among women and $39,479 (95 % CI $38,311-$40,677) among men. These estimates translate into an annual $282 million in direct attributable health-care costs in Ontario and $1.1 billion in Canada. Primary cost drivers were acute and post-acute institutional care. Approximately 24 % of women and 19 % of men living in the community at the time of fracture entered a long-term care facility, and 22 % of women and 33 % of men died within the first year following hip fracture. Attributable costs remained elevated into the second year ($9,017 among women, $10,347 among men) for patients who survived the first year. CONCLUSIONS: We identified significant health-care costs, entry into long-term care, and mortality attributed to hip fractures. Results may inform health economic analyses and policy decision-making in Canada.

The significance of HER-2 amplification and the size and type of pathological unicentric, initially operable clinical stage I and IIA/IIB breast cancer, in determining the treatment strategy.

PURPOSE: In order to determine the initial treatment strategies for primary operable unicentric breast cancer, the possible relationships of the amplification of human epidermal growth-factor receptor-2 (HER-2), with age, menstrual status, tumor pathological size (pT), histopathological tumor type (HP) and kind of surgical treatment were studied. METHODS: Analysed were 301 patients treated initially by surgery in the period 2006-2009. HP tumor type, pT and HER-2 status (using firstly immunohistochemistry and then chromogenic in situ hybridization/CISH) were determined. The patients were divided into 2 subgroups according to the presence (CISH+)/absence (CISH-) of HER-2 amplification. RESULTS: Data on pT and HER-2 analyses were available for 293/301 (98.3%) patients with ductal (DC) and lobular carcinoma (LC). Amplification of HER-2 was found in 66 (21.9%) patients. No significant difference between the two subgroups regarding age (p=0.08), menstrual status (p>0.05) and kind of operation (p>0.05) was found. HP showed statistically significant difference between DC (55; 83.3%) and LC (11; 16.7%) patients with HER-2 amplification (p<0.01). Further HP analysis of the type of cancer within the pT category as a subgroup showed significantly higher frequency of HER-2 amplification in DC patients for pT1 (p<0.01) and in pT2 + pT3pN0 (p<0.05) compared with patients with LC. CONCLUSION: This study showed a significantly higher incidence of HER-2 amplification in DC tumors, especially in pT1 and pT2, than in LC, which may influence the options in treatment strategies in primary unicentric operable DC type of breast cancer.

Local control of glomus tumors of the head & neck by radiation therapy and surgery.

PURPOSE: Glomus tumors are rare tumors, highly vascular and typically radiosensitive. Therapeutic options include surgery, radiation therapy (RT), embolisation or any combination of them, but the appropriate treatment still remains a challenge. The purpose of this study was to report the results of local control of 7 patients with glomus tumors treated with surgery and external beam RT (EBRT). METHODS: All of the patients underwent primary surgery and then postoperative EBRT. Follow-up was calculated from the date of initiation of EBRT and ranged from 3 to 15 years (mean 7.14, median 6.2). The likelihood of local control was analysed using the Kaplan-Meier product limit method. We also analysed the average duration of response between two groups of patients with different doses of EBRT as well as the presence of acute and late EBRT complications. RESULTS: Local control was obtained in 6/7 (85.7%) patients. Moreover, local control was achieved in 3/4 (75%) patients with recurrent glomus tumors, while in patients with postoperative residual disease local control was obtained in 3/3 (100%) of them. Patients who received <50 Gy (n=2) had shorter average duration of response compared to patients who received >50 Gy (n=5; p=0.248). There were no severe treatment complications. CONCLUSION: Surgery and RT represent an appropriate treatment approach for advanced glomus tumors with acceptable complications.

The role of the psychologist in the preparation of young children for radiotherapy: short review.

Psychooncology is now recognized as an important part of the holistic approach to therapy of very young cancer patients. When the psychologist is included in a multidisciplinary team, his/her duty is to prepare the child for several procedures he/she is scheduled for. If the very young child has to be treated by radiotherapy, adequate preparation of the child before the start of radiotherapy may enable the child to undergo the whole procedure without sedation or repeated anesthesia. Such practice has started in Serbia in 2002, at the Department of Pediatric Oncology of the Institute for Radiology and Oncology of Serbia, Belgrade. In this article, we discuss the model we currently use, and we present how this approach has been successfully applied in a 5-year-old girl treated by radiotherapy.

Outcome of childhood brain tumors in Serbia.

PURPOSE: To present the results of treatment for childhood brain tumors in Serbia. METHODS: The medical records of patients with brain tumors diagnosed and operated at the Institute of Neurosurgery, Clinical Center of Serbia and treated with postoperative radiotherapy and chemotherapy at the Institute of Oncology and Radiology of Serbia, Belgrade, between January 1995 and December 2004, were reviewed. Of the 247 patients who were identified, 212 formed the basis of this study. Overall survival (OS) was determined by the Kaplan-Maier method, using log-rank test for comparisons. RESULTS: With a mean follow up of 46.9-33.6 months (range 7-120), the 5-and 8-year OS rates were 70.0% and 61.5%, respectively. At the time of evaluation 119 (60.1%) patients had no evidence of disease. Among 79 patients who failed therapy, most of them (n=61; 77.2%) had local failure only. According to histologic tumor type most of them (n=27; 34.2%) were in the group of malignant medulloblastoma. Girls had better survival than boys, but without statistical significance (p=0.185). Also, no significant difference in survival in relation to age was seen (p=0.291). Patients with supratentorial tumors had significantly better survival than those with infratentorial localizations (p=0.036). Patients with low grade astrocytomas had significantly better survival than malignant gliomas, ependymomas and primitive neuroectodermal tumors (PNETs) (p=0.0001). CONCLUSION: OS rates were concordant with the results of other modern series. Although the survival rates were encouraging, there is still significant room for improvement in the management of childhood brain tumors.

[Pediatric brain tumors--diagnostic and treatment].

During the period 1995-2004 we treated 212 patients (pts) with brain tumors. There were 133 boys and 79 girls, aged from 2,5 yrs up to 18 yrs (Me = 9, 7 yrs). The majority of pts were in age group (4-16) yrs-179 pts. Supratentorial tumors were diagnosed in 118 pts vs. infratentorial 94 pts. Therapy involved surgery, postoperative radiotherapy with or without chemotherapy. Survival rates were calculated using Caplan-Meier method and differences between curves with log-rank test. During the follow-up period from 1 to 9 year (Me = 3 yrs) 5-year disease free survival rate was 55.7%. 79 pts failed to therapy. There was no statistically significant difference in survival according to sex (p = 0.123) and age (p = 0.367). Pts with supratentorial tumors had statistically significant better survival (p = 0.036). Pts with histologic type low grade astrocitomas had statistically significant better survival than malignant gliomas, ependymomas and PNET (p = 0.0001). Surgery, postoperative radiotherapy and chemotherapy in selected cases are efficient therapeutic approach for pediatric brain tumors.

[Postoperative radiotherapy of cervival carcinoma: treatment results and analysis of prognostic factors].

The purpose of the study was to evaluate the efficacy of postoperative radiotherapy (RT) and to investigate prognostic factors for early-stage cervical cancer patients. We reviewed the medical records of 162 cervical cancer patients treated by RT during 2003 year. RT included 30-45 Gy of external photons to pelvis in 12-25 fractions. Brachytherapy with 192Ir was delivered in 3-5 fractions to a dose of 27-32 Gy. The mean age was 49 years (range 27-71). Majority of patients 130 had Stage Ib. Radical hysterectomy with lymphadenectomy was performed in 122 pts. and simple hysterectomy in 40 pts. The 5-year actuarial overall survival (OS) for all patients was 92.6% and disease-free survival (DFS) was 90.9%.There was statistically significant differences in OS and DFS in pat. with positive vs. negative pelvic lymph nodes; tumor 4 cm vs. tumor < or = 4 cm; positive vs. negative surgical margin/residual tumor (p < 0.05). Late GIT complications were determined in 35.8% and UT in 12.3%. In conclusion, postoperative radiotherapy has achieved high-satisfactory survival with acceptable complications. The survival benefit was less evident among patients with positive lymph nodes, tumor > 4 cm and positive surgical margin/residual tumor.

[Role of radiotherapy in combined therapy of soft tissue sarcoma in children and adolescents]. / Uloga radioterapije u kombinovanom lecenju sarkoma meki tkiva kod dece i omladine.

Over last decades with modern approach to combined treatment of soft tissue sarcoma in children and adolescents, with effective systemic chemotherapy and adequate local control most frequently with conservative surgery and radiotherapy, or radiotherapy alone, results of treatment from 20% of a three-year overall survival to 75% were improved significantly. Nevertheless, combined treatment involves risk of acute radiation reactions and late side effects, so there is a need for precise radiotherapy planning with optimal schedule of fractionating, adequate radiation volume and optimal tumour dose. The purpose of our study was to evaluate the results of combined treatment of soft tissue sarcoma, role of radiotherapy in local control use of the optimal tumour dose and assessment of acute radiation reactions in an examined group of patients. A retrospective clinical study involved 47 patients treated with radiotherapy at the Institute of Oncology and Radiology of Serbia over the period from 1990 to 1997. The most frequent tumour sites were the head and neck and the extremities. According to the IRS classification most patients were in CS III (21 patients). Forty patients had histological type--Rhabdomyosarcoma (Table 1). All patients were treated with chemotherapy, and local therapy were surgery and radiotherapy or radiotherapy alone. Thirty one patients were operated on. All 47 patients were treated with radiotherapy; in 37 patients as primary treatment and in 10 patients as therapy for local relapse. Radiotherapy was planned according to tumour size, tumour site, age of the patient and type of surgery. Tumour dose from 45 Gy to 60 Gy was given in cases with a residual tumour. Lower tumour doses were used in cases of postoperative microscopic disease, in certain cases of local relapse treatment or when the size of residual tumour and patient's age allowed no delivery of higher tumour doses. Standard fractionating regimen was given to all patients, with daily fractions from 150 cGy to 214 cGy, five times per week. The majority of patients (24) were treated on Linear Accelerator machine with X photons of 10 MeV energy and with X photons of 6 MeV energy (13 patients) (Table 2). Statistical data processing was made by the following methods: Kaplan-Meier for survival rate and Long-rang and Wilcox test for assessment of the statistical significance in survival difference. In our group of patients treated over the period from 1990 to 1997 a three-year overall survival was 59.15%, and disease free survival was 46.68% (Figure 1). There were 21 patients (44.7%) without signs of the disease, 12 patients had a local disease (25.5%), 9 patients had both local and metastatic disease (19.1%) and 5 patients had only metastatic disease (10.50%). In the group of 47 patients who received radiotherapy, 24 patients received a tumour dose from 45 Gy to 60 Gy and 23 patients a tumour dose from 32 Gy to 45 Gy. The group of patients treated without tumour dose more than 45 Gy had a significantly better overall survival rate (p = 0.002) (Figure 2). Although the obtained results are in agreement with data from literature, a critical analysis is necessary. Namely, in addition to the group irradiated with a tumour dose from 32 Gy to 45 Gy, because of the postoperative microscopic disease, certain number of patients was irradiated with a "lower" dose because of an objective impossibility to administer a "higher" dose or this dose was planned for palliative reasons. The tumour dose of 45 Gy was delivered to 6 of 10 patients treated for local relapse. The tumour dose of 45 Gy was also used in four patients in CS IV, in two subjects for local control and in two as a palliative treatment. Seven patients in CS III received a tumour dose of 45 Gy, because the age of children, tumour site and tumour size permitted no higher tumour doses. That is when planning an adequate local therapy one must have in mind the initial tumour size, type of administered systematic chemo

Growth hormone secretagogues in pathological states: diagnostic implications.

The identification and cloning of the receptor for synthetic growth hormone (GH) secretagogues, even before the endogenous ligand has been identified or its precise physiological role established, suggests that there is a novel target of action for this class of drug. In an attempt to select patients who will benefit from GH treatment, GH secretagogues are being evaluated for their usefulness in diagnosing GH deficiency. The effects of GH-releasing peptides (GHRPs) on GH release as a function of age and metabolic status, and in different neuroendocrine pathologies, are described, as are the different mechanisms of action, potency and reproducibility of the response to GHRPs compared with GH-releasing hormone (GHRH). GHRPs offer the advantage over GHRH in natural models of deranged GH secretion in that, in various metabolic states (e.g. obesity, anorexia nervosa and non-insulin-dependent diabetes mellitus), the GH response to GHRH is more impaired than it is to GHRPs. However, in some neuroendocrine pathologies, the reverse is true. Thus, both secretagogues provide separate information on the physiological status of somatotrophs.