Nuclear ß-catenin positivity as a predictive marker of long-term survival in advanced epithelial ovarian cancer.

BACKGROUND: Classical features as histomorphology, grade, FIGO stage, and residual tumour mass have strong prognostic value in advanced epithelial ovarian carcinomas (AEOC). Most AEOCs are associated with early recurrence and poor overall survival (OS). Despite of early recurrence, general poor outcome, both high grade tumours or tumours with advanced FIGO stage at the time of diagnosis, in some of such cases, long-term survival (LTS) has been recorded . The aim of this study was to compare the utility of "classical" prognostic factors to molecular factors such as ß-catenin- E-cadherin-, mutated TP53-, and MiB-1 (Ki-67) labelling index determination in predicting long-term survival. METHODS: The expression of ß-catenin, E-cadherin, Ki-67, and p53 was determined by immunohistochemistry (IHC) in AEOC. Correlation was sought for between expression of these proteins and the status of classical features vis-á-vis overall survival of patients. Statistical evaluation of the data included Kaplan-Meier analysis, the log-rank test and Cox proportional hazards model. RESULTS: As expected, residual tumour size was an independent adverse prognostic factor for OS (univariate analysis: p=0.003, multivariate analysis: p=0.005). Nuclear expression of ß-catenin in advanced ovarian cancer of LTS patients proved to be not only an independent favourable predictor of OS (univariate analysis: p=0.025, multivariate analysis: p=0.041) but also showed strong correlation with platinum sensitivity and platinum re-induction. CONCLUSIONS: Translocation of stabilized ß-catenin from cytoplasm to the nucleus plays an important role in predicting platinum sensitivity. It also seems to support the chance for platinum re-induction in AEOC and thus enhances long-term survival.

Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: Cilengitide is a selective αvß3 and αvß5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. METHODS: In this multicentre, open-label, phase 3 study, we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries. Eligible patients (newly diagnosed, histologically proven supratentorial glioblastoma, methylated MGMT promoter, and age ≥18 years) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and centrally randomised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy with cilengitide 2000 mg intravenously twice weekly (cilengitide group) or temozolomide chemoradiotherapy alone (control group). Patients and investigators were unmasked to treatment allocation. Maintenance temozolomide was given for up to six cycles, and cilengitide was given for up to 18 months or until disease progression or unacceptable toxic effects. The primary endpoint was overall survival. We analysed survival outcomes by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00689221. FINDINGS: Overall, 3471 patients were screened. Of these patients, 3060 had tumour MGMT status tested; 926 patients had a methylated MGMT promoter, and 545 were randomly assigned to the cilengitide (n=272) or control groups (n=273) between Oct 31, 2008, and May 12, 2011. Median overall survival was 26·3 months (95% CI 23·8-28·8) in the cilengitide group and 26·3 months (23·9-34·7) in the control group (hazard ratio 1·02, 95% CI 0·81-1·29, p=0·86). None of the predefined clinical subgroups showed a benefit from cilengitide. We noted no overall additional toxic effects with cilengitide treatment. The most commonly reported adverse events of grade 3 or worse in the safety population were lymphopenia (31 [12%] in the cilengitide group vs 26 [10%] in the control group), thrombocytopenia (28 [11%] vs 46 [18%]), neutropenia (19 [7%] vs 24 [9%]), leucopenia (18 [7%] vs 20 [8%]), and convulsion (14 [5%] vs 15 [6%]). INTERPRETATION: The addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes; cilengitide will not be further developed as an anticancer drug. Nevertheless, integrins remain a potential treatment target for glioblastoma. FUNDING: Merck KGaA, Darmstadt, Germany.

A prospective study of supine versus prone positioning and whole-body thermoplastic mask fixation for craniospinal radiotherapy in adult patients.

PURPOSE: To evaluate neuroaxis irradiation for adults in the supine position using head body thermoplastic mask fixation, from the aspects of dose distribution, patient comfort and set-up accuracy. METHODS AND MATERIALS: Nine of the 12 adult patients were positioned for craniospinal axis irradiation in both prone and supine positions. After mask fixation and planning CTs in both positions, a questionnaire relating to the comfort was completed. The doses to the target and to the organs at risk of the 3D conformal plans in the supine and prone positions were compared. Portal images of all 12 patients irradiated in the supine position were evaluated, the van Herk formulas being used to calculate the systemic and random errors. RESULTS: No significant difference was found between the prone and supine positions target coverage, the dose homogeneity and the dose to the organs at risk. The supine position was considered more comfortable by the patients (scores of 2.8 versus 4.29), with a vector random error of 3.27 mm, and a systematic error of 0.32 mm. The largest random set-up error was observed in the lateral direction: 4.83 mm. CONCLUSIONS: The more comfortable supine position is recommended for craniospinal irradiation in adult patients. Whole-body thermoplastic mask immobilization provides excellent repositioning accuracy.

Cosmetic outcome 1-5 years after breast conservative surgery, irradiation and systemic therapy.

The late side-effects of the local therapy of early breast cancer depend on many patient- and therapy-related parameters. We aimed at investigating the factors that influence the cosmetic and functional outcomes among our breast cancer patients after breast-conserving surgery and conformal radiotherapy, with or without adjuvant systemic therapy. A study was made of the association of the cosmetic outcome after a median follow-up time of 2.4 years and the clinical data on 198 patients extracted from a prospectively compiled database. Breast tenderness occurred more frequently among patients ≤50 years old (p < 0.05). Long-term side effects were related to radiotherapy-related factors the most, while no effect of the systemic therapy could be detected. The risk of hyperpigmentation, breast edema and breast fibrosis increased by 18%, 23% and 7%, respectively for every 100 cm(3) increase in the irradiated breast volume, while that of breast edema and breast fibrosis increased by 21% and 12%, respectively for every 10 cm(3) increase in the boost volume. Patients who received a photon boost were significantly more likely to develop breast edema and fibrosis than those who received electrons (p < 0.005). Dose inhomogeneity was related to the volume of the irradiated breast (p = 0.037). Dyspigmentation developed more often among patients older than 50 years, while smoking favoured both dyspigmentation and teleangiectasia. Breast edema was related to dyspigmentation (p = 0.003), fibrosis (p < 0.001) and breast asymmetry (p = 0.032), whereas none of these abnormalities were associated with teleangiectasia. Body image changes were more frequent at a younger age (p < 0.005), while the need to change clothing habits occurred more often at an older age (p < 0.05). Radiotherapy-related parameters appear to exert the greatest effect on the overall cosmetic outcome after breast-conserving surgery and postoperative radiotherapy.

Tumour topoisomerase II alpha protein expression and outcome after adjuvant dose-dense anthracycline-based chemotherapy.

There is a need for the selection of those breast cancers where benefit may be attained from the addition of an anthracycline to the adjuvant chemotherapy. The expression of topoisomerase II alpha (TOP2A) protein in 3 cohorts of breast cancers treated with adjuvant dose-dense anthracycline-based chemotherapy was determined retrospectively. The TOP2A status was analysed in relation with the other standard tumour features and the outcome. TOP2A IHC results were assessable in 106 patients: with a cut-off value of 15%, 48% of the tumours were classified as TOP2A-positive. The expression of TOP2A correlated with that of Ki67 (R = 0.532, p < 0.001) and a high grade (p = 0.04), but did not correlate with the proportion of ER- or PR-positive cells in the tumour. More tumors were TOP2A-negative among the ER- or PR-positive cancers than among the ER/PR-negative cancers (p = 0.021 and p = 0.002, respectively). After a median follow-up time of 64.5 months, 31 relapses (23.5%) and 23 deaths (17.4%) had occurred in 131 patients. The overall survival was longer in the TOP2A-positive cases than in the TOP2A-negative cases. The recurrence-free survival and the overall survival were significantly more favourable in the ER/PR-negative and TOP2A-positive tumours than in other subgroups. In a Cox proportional hazards model, the grade and TOP2A remained significant determinants in the ER/PR-negative subgroup. TOP2A positivity and grade 3 indicated a decrease in the risk of death with HR = 0.211 (95% CI: 0.042-1.05, p = 0.056) and HR = 0.216 (95% CI: 0.047-0.990, p = 0.048), respectively. A higher sensitivity to anthracycline-containing regimens is suggested in ER/PR-negative and TOP2A-positive cancers.

Tumor topoisomerase II alpha status and response to anthracycline-based neoadjuvant chemotherapy in breast cancer.

OBJECTIVES: Individualized chemotherapy for breast cancer improves the outcome. Anthracyclines target the enzyme topoisomerase IIα (TOP2A). We set out to perform a retrospective study of the presence of gene abnormalities and the expression of TOP2A in a cohort of breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. METHODS: Forty-three patients with 45 breast cancers were treated with neoadjuvant docetaxel-epirubicin with/without capecitabine chemotherapy. The TOP2A status of the cancers, determined retrospectively by fluorescent in situ hybridization and immunohistochemistry, was analyzed in relation to the standard clinical and pathological data. RESULTS: Clinically and pathologically complete remission (pCR) was achieved in 15 (33.3%) and 9 (20%) cases, respectively. The TOP2A gene was amplified in 2 human epidermal growth factor receptor 2 (HER2)-positive cancers (8%), and 32 (84.2%) overall exhibited TOP2A expression in >15% of the cells. The expression of TOP2A exhibited a strong correlation with the expression of Ki67 (R = 0.743, p < 0.001), and was negatively correlated with estrogen receptors (ER; R = 0.404, p = 0.012) and progesterone receptors (R = 0.430, p = 0.007). The expression of TOP2A was not related to the amplification of the TOP2A gene or the HER2 status of the tumor. The proportions of Ki67- and TOP2A-positive tumor cells were significantly reduced after chemotherapy (56.1 ± 23.6 vs. 19.0 ± 27.7%, p = 0.004, and 41.0 ± 27.9 vs. 12.7 ± 24.8%, p < 0.001, respectively). The development of pCR was related to a high grade (p = 0.054), ER negativity (p = 0.027) and high TOP2A expression (p = 0.037). The expression of TOP2A was an independent predictor of pCR (OR = 1.460, for every 10% increase, 95% CI: 1.016-2.096, p = 0.041). After a median follow-up time of 31.0 months, neither relapse-free survival nor overall survival was related to the tumor response. CONCLUSIONS: TOP2A expression is a marker of the tumor's proliferation rate and sensitivity to anthracycline-based chemotherapy, and does not depend on the amplification of its gene.

Role of systemic therapy in the development of lung sequelae after conformal radiotherapy in breast cancer patients.

PURPOSE: To analyze the risk of radiogenic lung damage in breast cancer patients after conformal radiotherapy and different forms of systemic treatment. METHODS AND MATERIALS: In 328 patients receiving sequential taxane-based chemotherapy, concomitant hormone therapy (tamoxifen or aromatase inhibitors), or no adjuvant systemic therapy, symptomatic and asymptomatic lung sequelae were prospectively evaluated via the detection of visible CT abnormalities, 3 months or 1 year after the completion of the radiotherapy. RESULTS: Significant positive associations were detected between the development of both pneumonitis and fibrosis of Grade 1 and patient age, ipsilateral mean lung dose, volume of the ipsilateral lung receiving 20 Gy, and irradiation of the regional lymph nodes. In multivariate analysis, age and mean lung dose proved to be independent predictors of early (odds ratio [OR] = 1.035, 95% confidence interval [CI] 1.011-1.061 and OR = 1.113, 95% CI 1.049-1.181, respectively) and late (OR = 1.074, 95% CI 1.042-1.107 and OR = 1.207, 95% CI 1.124-1.295, respectively) radiogenic lung damage, whereas the role of systemic therapy was significant in the development of Grade 1 lung fibrosis (p = 0.01). Among the various forms of systemic therapy, tamoxifen increased the risk of late lung sequelae (OR = 2.442, 95% CI 1.120-5.326, p = 0.025). No interaction was demonstrated between the administration of systemic therapy and the other above-mentioned parameters as regards the risk of radiogenic lung damage. CONCLUSIONS: Our analyses demonstrate the independent role of concomitant tamoxifen therapy in the development of radiogenic lung fibrosis but do not suggest such an effect for the other modes of systemic treatment.

Roles of BCL-2 and MDR1 expression in the efficacy of paclitaxel-based lung cancer chemoradiation.

BACKGROUND: The associations between B-cell lymphoma 2 (BCL-2) and multi-drug resistance associated P-glycoprotein (MDR1) expressions and chemoradiotherapy outcome of patients with non-small cell lung cancer (NSCLC) were analysed. PATIENTS AND METHODS: Thirty-two NSCLC patients were treated with paclitaxel-based chemoradiotherapy. The tumour expressions of BCL-2 and MDR1 were analysed by means of immunohistochemistry with regard to the clinical response and survival data. RESULTS: Partial remission and stable disease were achieved in 19 (59%) and 10 (31%) cases, respectively. Significant differences in progression-free survival were observed between responders and non-responders (13.7 vs. 6.0 months, p=0.028), and between patients with or without a gross tumour volume (GTV) shrinkage (GTV(>50) 13.7 vs. 6.0 months, p=0.009). Overexpression of BCL-2 and of MDR1 was observed in 6 (21.4%) cases each. Overexpression of both markers together was associated with poor response (GTV reduction: p=0.005; RECIST: p=0.023) and lower progression-free survival (overexpression of both, low expression of both, mixed: 3.1, 13.4, 4.1 months, respectively, p<0.001). CONCLUSION: BCL-2 and MDR1 overexpression may predict the inefficacy of paclitaxel-based chemoradiotherapy.

Breast cancer under 40 years of age: increasing number and worse prognosis.

Breast cancer at a relatively young age with a poor prognosis is currently exhibiting an increasing incidence. In a retrospective cohort analysis of early breast cancer cases after surgery from our institutional patient registry, 141 patients aged ≤ 40 years constituted the younger group, with 300 randomly selected patients aged >40 years as controls. A significant and steady increase was found in the relative number of younger cases during the years 2004-2009. The histological type and grade and the lymph node status of the cancers differed significantly between the two groups, with more aggressive biological behaviour, a more advanced stage and a worse prognosis in the younger group. Half of the cancers in the younger cohort were ER-negative, while two-thirds in the control group were ER-positive. Comparatively more tumours were PR-positive and HER2-negative in the control group than in the younger group. The rates of triple-negative cases were 25% and 13% in the younger age and the control group, respectively (p = 0.026). Significantly higher mastectomy and axillary block dissection rates were observed in the younger age group, and more chemotherapy was administered than in the control group. Our findings demonstrate the significance of breast cancer in cases aged <40 years, and draw attention to the need for appropriate care in these cases.

Long-term efficiency and toxicity of adjuvant dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy in high-risk breast cancer.

OBJECTIVES: To perform a protocol-specified analysis of the dose-dense adriamycin-paclitaxel-cyclophosphamide (ddATC) study. METHODS: Survival and late toxicity were analyzed in 55 patients enrolled to receive 4 x adriamycin 60 mg/m(2), 4 x paclitaxel 200 mg/m(2), 4 x cyclophosphamide 800 mg/m(2), every 2 weeks, with cardioxane and filgrastim support. Kaplan-Meier curves were used to analyze relapse-free survival (RFS), distant disease-free survival (DDFS), and overall survival (OS). Survival analyses were performed according to the presence of casting-type calcifications on the mammogram. RESULTS: After a median follow-up time of 78.5 (64.3-100.0) months, 29 (52.7%) patients were free of relapse (local, regional, distant or contralateral breast cancer), 34 (61.8%) patients were free of distant metastases, and 36 patients (65.5%) survived. The median times of RFS, DDFS and OS were not yet reached at 100.0 months. The median RFS, DDFS and OS times among breast cancer patients with tumors not associated with casting-type calcifications were >100.0 months, the corresponding parameters among patients with tumors accompanied by casting calcifications were 11.5 (p < 0.001), 11.5 (p < 0.001) and 29.6 months (p = 0.035), respectively. None of the patients developed myelodysplastic syndrome or leukemia. No cardiac failure occurred during the follow-up period. CONCLUSIONS: Our results indicate that adjuvant sequential ddATC is an efficient and less toxic chemotherapy regimen in high-risk breast cancer. The presence of casting-type calcifications on the mammogram points to a special biologic nature with very poor prognosis.

[Effect of lifestyle counseling given by health personnel on the changes in dietary habits of Hungarian women treated for cancer]. / Az egészségügyi személyzet életmód-tanácsadó tevékenységének szerepe daganatos betegséggel kezelt nôk táplálkozási szokásainak megváltoztatásában.

The aim of this study was to investigate the changes in dietary habits in women with gynecological or breast cancer, and to analyze the role of some demographic factors, type of the malignant tumor, and the role of medical staff's advice in dietary behavior change of these women, after the diagnosis of cancer. A self-administered questionnaire-based retrospective study was performed, and 155 randomly selected patients, treated for gynecological or breast cancer, were involved. A self-developed questionnaire was used to measure the socio-demographic characteristics, the circumstances of visiting the physician, therapy, present health status and lifestyle before and after the diagnosis of neoplasm. More than three-fourths of the women reported changes in nutrition after the diagnosis of cancer. The consumption of fruits and vegetables increased in the highest proportion (70.3%). Women with higher education changed their diet in higher proportion (p=0.031) compared to women with lower education. Women who were advised to change their lifestyle by their therapists were about four times more likely (OR: 3.87; CI: 1.40-10.69 ) to change their nutrition. Patients with breast cancer changed three times more likely (OR: 3.21; CI: 1.05-9.84) their dietary habits than patients with gynecological cancer. The most influential proven factor to make cancer patients alter their diet was being advised for this by physicians. Thus, our study proved that physicians and nurses have a very important role in changing their cancer patients' nutritional habits into a healthier one.

Individual positioning: a comparative study of adjuvant breast radiotherapy in the prone versus supine position.

PURPOSE: To study breast radiotherapy in the prone vs. supine positions through dosimetry and clinical implementation. METHODS AND MATERIALS: Conformal radiotherapy plans in 61 patients requiring only breast irradiation were developed for both the prone and supine positions. After evaluation of the of the first 20 plan pairs, the patients were irradiated in the prone or supine position in a randomized fashion. These cases were analyzed for repositioning accuracy and skin reactions related to treatment position and patient characteristics. RESULTS: The planning target volume covered with 47.5-53.5 Gy in the prone vs. the supine position was 85.1% +/- 4.2% vs. 89.2 +/- 2.2%, respectively (p < 0.0001). Radiation exposure of the ipsilateral lung, expressed in terms of the mean lung dose and the V(20Gy), was dramatically lower in the prone vs. supine position (p < 0.0001), but the doses to the heart did not differ. There was no difference in the need to correct positioning during radiotherapy, but the extent of displacement was significantly higher in the prone vs. supine position (p = 0.021). The repositioning accuracy in the prone position exhibited an improvement over time and did not depend on any patient-related parameters. Significantly more radiodermatitis of Grade 1-2 developed following prone vs. supine irradiation (p = 0.025). CONCLUSIONS: Conformal breast radiotherapy is feasible in the prone position. Its primary advantage is the substantially lower radiation dose to the ipsilateral lung. The higher dose inhomogeneity and increased rate of Grade 1-2 skin toxicity, however, may be of concern.

[Neoadjuvant systemic therapy in breast cancer]. / Neoadjuváns szisztémás terápia emlorákban.

Neoadjuvant (preoperative) systemic therapy is a good possibility for the treatment of symptomatic breast cancers of the locoregional stage. Chemotherapy or hormone therapy chosen according to the characteristics of the primary tumor, result in the regression of the tumor in the majority of the cases, favoring breast conserving surgery thereafter. The long-term effects of neoadjuvant systemic therapy are equivalent to that of adjuvant therapy, and the in vivo observed efficiency of the treatment reflects prognosis. Finally, systemic therapy introduced prior to surgery is not delayed by the possible adverse effects of the surgery. Detailed examination of the tumor and the patient is mandatory before starting systemic therapy. Besides breast imaging and histological examinations, staging is necessary. Pathological characterization of the tumor will enhance treatment choice based on the features of chemo- or hormone-sensitivity. For the treatment of chemosensitive tumors, taxane- and anthracycline-based polychemotherapy is the most efficacious. Data on neoadjuvant hormone therapy have been provided by studies on postmenopausal patients. Since the aromatase inhibitors are more efficient than tamoxifen, their use is the first option in this patient population. Among the molecular targeted agents, trastuzumab combined with chemotherapy produces extending therapeutic response rate. Following the completion of the neoadjuvant systemic therapy, breast imaging is required once more before performing breast and lymph node surgery. Postoperative radiotherapy is generally needed. The use of a common language and professional guidelines by the members of the multidisciplinary breast team is a condition for neoadjuvant systemic therapy.

Seasonal variation of childhood acute lymphoblastic leukaemia is different between girls and boys.

The aim of this study was to investigate seasonal trends in the incidence of acute lymphoblastic leukaemia (ALL) around the times of birth and diagnosis in children aged 0-4 years and also to examine gender specific effects. Children born in South Hungary during 1981-1997 were analysed. Registrations of first malignancies for children, diagnosed under age 5 years before the end of 2002 were obtained from the Hungarian Paediatric Oncology Group providing a representative sample of Hungarian children over a 17 year period of time. Data were available on the corresponding numbers of births for each month of the study period were obtained. Statistical analyses were performed using logistic regression with harmonic components. The study analysed 121 cases of children, aged under 5 years, who were diagnosed with ALL. We found no seasonal effect related to date of diagnosis. However, there was seasonal variability for ALL related to date of birth. Maximal rates were seen in children born in February and August in the simple harmonic regression model for all children diagnosed with ALL. Analysis by gender found evidence of seasonality related to month of birth with peaks in February and August in boys, but different seasonal effects were seen for girls (peak in November, nadir in May). Our study provides some evidence that male specific immune responses to infections around the time of birth could explain the male predominance in the incidence of ALL.

Tumor characteristics in screen-detected and symptomatic breast cancers.

The natural course of early breast cancer has changed as a result of the introduction of mammographic screening. The present aim was a prospective analysis of screen-detected and symptomatic operable breast cancers in the era of mammographic service screening. The mode of detection (screen-detected, symptomatic or interval cancer), the type of mammographic image and other characteristics (the invasive tumor size, histological tumor type, grade, nodal, hormone receptor and HER2 status and the presence of lymphovascular invasion) of 569 invasive breast cancers were studied. Screen-detected cancers were significantly more frequently of grade I, < 10 mm of size and node-negative (p < 0.001, respectively). Symptomatic/interval cancers were significantly more frequently of grade 3, >20 mm of size (p < 0.001), and exhibited lymphovascular invasion (p = 0.001). Screening-detection of the tumor favored breast-conserving surgery, sentinel lymph node biopsy and the avoidance of chemotherapy (p < 0.001). Cancers associated with casting-type calcifications on the mammogram were typically of ductal type (p = 0.043), of grade 2-3, estrogen receptor and progesterone receptor-negative and HER2-positive (p < 0.001). Interval cancers occurred significantly more often at a younger age and remained mammographically occult as compared with other cancers. Mammographic screen-detected cancers demonstrate more favorable prognostic features, and need less extensive treatment than symptomatic or interval cancers. The mammographic appearance of the tumor reflects its biological behavior, and this should be considered in the management optimization.

Controlled study of lactoperoxidase gel on oral flora and saliva in irradiated patients with oral cancer.

The aim of this study was to determine if radiotherapy induces hyposalivation altering oral microbial flora. The purpose of this placebo-controlled, single-blind study was to determine beneficial effects of a saliva substitute and an oral hygiene product on irradiated patients with oropharyngeal cancer. Eighteen patients were assigned to the test group (Biotène Oral Balance gel [Lacléde Incorporated Healthcare Products, Gardena, CA] and toothpaste used daily), and another 18 were put on a conventional daily regimen (carboxymethylcellulose gel and Oral-B toothpaste [Laclede Pharmaceuticals, Gardena, CA]). Cultures for identifying and quantitating microorganisms, whole unstimulated saliva, and visual analog measurements for comfort were obtained before mucositis occurred and after treatment. Daily use of Biotène products enhanced control of microbial flora, improved salivary flow, and increased oral comfort as compared with control subjects. Four weeks after mucositis, some aerobic isolates disappeared in the test group; periodontal-associated bacteria were markedly decreased in the test group; and candidal species were significantly lowered in the test group. Although baseline saliva was lower in the test group (P = 0.001), after 4 weeks, no difference between groups existed; comfort was greater in the test group (P = 0.007). Use of enzyme-engineered Biotène products that assist in control of the oral microbial flora as well as supporting oral comfort through lubrication appear to be useful aids for irradiated patients with oropharyngeal cancer.

[Approaches to individual radiotherapy in breast cancer: individual risk estimation and individualized techniques]. / Törekvés a sugárterápia individualizálására emlorákban: egyéni rizikóbecslés és egyénileg alkalmazott technikák.

INTRODUCTION: Radiotherapy comprises an integral part of the curative therapy of breast cancer by improving the locoregional control and survival when given on an individualized basis. Conformal radiotherapy and three-dimensional radiation treatment planning enhance the safety of radiotherapy by adjusting the irradiated volume to the shape of the target volume, and providing control of the radiation dose to the organs at risk (OARs). PATIENTS AND METHODS: The methods introduced at the authors' institute in 2002 are demonstrated. The breast/chest wall and lymph node areas were irradiated provided that there was a minimum risk of local or locoregional relapse of 10%. CT-based 3D radiotherapy treatment planning and individual patient-positioning were applied, with thermoplastic mask-fixation in the second part of the study. The dose constraints of the OARs were given in accordance with the literature recommendations. In the first group of patients, individually shaped blocks, in the second group, multileaf collimator, and in the third group, with the aim of a more homogenous dose-distribution in the target volume, intensity-modulated beams were applied. RESULTS: During the study, 737 breast cancer patients received conformal radiotherapy based on individual risk estimation. In 372 cases only local, while in 365 cases locoregional radiotherapy was delivered. The dose-homogeneity in the target volume was significantly improved in the second period of the study, when segments were superposed on the radiotherapy fields. The proportions of the target volumes irradiated with +/-10% of the planned dose in the breast/chest wall, axillary and supraclavicular lymph nodes and internal mammary lymph nodes varied between 90.5-94.2%, 84.1-93.8% and 86.7-91.6%, respectively, depending on the radiation technique used. The parameters indicating the dose to the ipsilateral lung or to the heart were significantly higher when locoregional radiotherapy was applied compared to that in case of local radiotherapy. Radiation dose to the ipsilateral lung and the heart was significantly reduced in the second part of the study when locoregional, but not when local radiotherapy was delivered. The introduction of individual immobilization by means of thermoplastic mask-fixation resulted in a relevant decrease in the uncertainty due to breathing motion and daily positioning errors, and also in a significant reduction of the dose to the contralateral breast. CONCLUSIONS: Adjuvant radiotherapy should be based on individual risk-benefit features. The need of the introduction of special techniques may be decided after the dose-volume analysis of the conformal radiotherapy plan based on 3D radiation treatment planning.

The risk of early and late lung sequelae after conformal radiotherapy in breast cancer patients.

PURPOSE: To study the risks of early and late radiogenic lung damage in breast cancer patients after conformal radiotherapy. METHODS AND MATERIALS: Radiogenic lung sequelae were assessed prospectively in 119 patients by means of clinical signs, radiologic abnormalities, and the mean density change (MDC) of the irradiated lung on CT. RESULTS: Significant positive associations were detected between the development of lung abnormalities 3 months or 1 year after the radiotherapy and the age of the patient, the ipsilateral mean lung dose (MLD), the radiation dose to 25% of the ipsilateral lung (D(25%)) and the volume of the ipsilateral lung receiving 20 Gy (V(20 Gy)). The irradiation of the axillary and supraclavicular lymph nodes favored the development of pneumonitis but not that of fibrosis. No relation was found between the preradiotherapy plasma TGF-beta level and the presence of radiogenic lung damage. At both time points, MDC was strongly related to age. Significant positive associations were demonstrated between the risks of pneumonitis or fibrosis and the age of the patient, MLD, D(25%), and V(20 Gy). A synergistic effect of MLD, D(25%), and V(20 Gy) with age in patients older than 59 years is suggested. CONCLUSION: Our analyses indicate that the risks of early and late radiogenic lung sequelae are strongly related to the age of the patient, the volume of the irradiated lung, and the dose to it.

Elevated levels of circulating insulin-like growth factor-I, IGF-binding globulin-3 and testosterone predict hormone-dependent breast cancer in postmenopausal women: a case-control study.

There is increasing evidence that different types of breast cancers are related to distinct risk factors. We analyzed the risk of breast cancer with respect to circulating insulin-like growth factor (IGF)-I, IGF-binding protein (IGFBP)-3, 17beta-estradiol, estrone, testosterone, androstenedione and sex hormone-binding globulin (SHBG), taking into consideration the characteristics of the tumors. Plasma hormone levels of 102 postmenopausal patients with breast cancer detected by mammography screening, and 102 matched controls were analyzed in relation to the histological type, the status of the estrogen receptor (ER), the progesterone receptor (PR) and the HER2 in the tumors. Significant positive associations were revealed between the IGF-I concentration and the overall risk of breast cancer (OR=3.1, 95% CI: 1.5-6.2), ER+PR+ breast cancer (OR=2.4, 95% CI: 1.1-5.4) and ER+PR- breast cancer (OR=4.3, 95% CI: 1.2-14.3) when the highest and the lowest ranges of IGF-I were compared. Significant associations were also found between the highest and the lowest quartiles of testosterone, resulting in OR=4.1 (95% CI: 1.8-9.4) for the risks of breast cancer and OR=5.8 (96% CI: 2.1-16.2) of ER+PR+ breast cancer. A synergy was seen between IGF-I and testosterone levels. When both plasma IGF-I and testosterone were in the highest quartile ranges, an OR=26.4 (95% CI: 1.6-426.5, p=0.021) was computed for breast cancer overall. No significant synergistic effects could be demonstrated with other parameters. There were significant, 2.5-fold (95% CI: 1.2-5.6), and 16-fold (95% CI: 2.0-133.5) increases in the overall risks of breast cancer and of ER+PR- breast cancer, respectively, when the highest and the lowest quartiles of IGFBP-3 were compared. No associations were found between any of the hormones and the risk of ER-PR- tumors. The increased prevalence of ER+ breast cancers in patients with higher levels of IGF-I, IGFBP-3 or testosterone implicate these hormones in the etiology of hormone-dependent breast cancer. Additional analyses specific for breast cancer subtypes may shed light on the value of hormone determinations for tailored chemoprevention.

Collaborative/active participation per se does not decrease anxiety in breast cancer.

The information needs of breast cancer patients on their disease, its treatment, the prognosis, and their attitude to decision-making concerning treatment were assessed. One hundred and fifty early and 45 metastatic breast cancer patients were recruited into the study. The amount of information and role in the treatment decision-making process preferred by the patient were independently estimated by the patient and the oncologist, using questionnaires. Information was provided in accordance with the wishes of the patient as perceived by the physician. Test of anxiety was performed before, and one week after the consultation. Most of the patients claimed to anticipate the provision of extensive information and an active role in the decision-making, but real interest during the consultation was found less frequently. The post-consultation anxiety test revealed a significant decrease in situational anxiety; this was not related to the patient's information needs or her attitude to the decision-making concerning treatment. Our study demonstrates that a significant decrease in anxiety may be achieved via a consultation tailored to the needs of the patient. Loading the patient with information and involvement in the decision regarding therapy as much as the patient seems comfortable with lowers distress.