Dosimetric evaluation of VMAT and helical tomotherapy techniques comparing conventional volumes with clinical target volumes based on new ESTRO ACROP post-mastectomy with immediate implant reconstruction contouring guidelines.

BACKGROUND: The ESTRO-ACROP Consensus Guideline (EACG) recommends implant excluded clinical target volume (CTVp) definitions for post-mastectomy radiation therapy after implant-based immediate breast reconstruction (IBR). The purpose of this study is to investigate the effectiveness of Helical Tomotherapy (HTp) and Volumetric Modulated Arc Therapy (VMATp) treatment techniques in terms of CTVp coverage and reduced organ at risk (OAR), normal tissue and implant doses when CTVp was used for treatment planning as the target structure instead of conventional CTV. METHODS: Eight left-sided and eight right-sided breast cancer patients who underwent IBR after mastectomy were included in this study. Planning CT data sets were acquired during free breathing and patients were treated with HT technique targeted to conventional CTV. Retrospectively, CTVp was delineated based on EACG by the same radiation oncologist, and treatment plans with HTp and VMATp techniques were generated based on CTVp. For each patient, relevant dosimetric parameters were obtained from three different treatment plans. RESULTS: There was no statistically significant difference on target coverage in terms of, PTVp-D95, PTVp-Vpres, homogeneity index (p > 0.05) between HTp and VMATp plans. But, the conformity numbers were significantly higher (HTp vs VMATp, 0.69 ± 0.15 vs 0.79 ± 0.12) for VMATp (Z = - 2.17, p = 0.030). While HTp significantly lowered Dmax and Dmean for LAD (LAD-Dmax: χ2 = 12.25, p = 0.002 and LAD-Dmean: χ2 = 12.30, p = 0.002), neither HTp nor VMATp could reduce maximum and mean dose to heart (p > 0.05). Furthermore, heart volume receiving 5 Gy was significantly higher for VMATp when compared to HTp (21.2 ± 9.8 vs 42.7 ± 24.8, p: 0.004). Both techniques succeeded in reducing the mean dose to implant (HTp vs HT, p < 0.001; VMATp vs HT, p < 0.001; VMATp vs HTp, p = 0.005). CONCLUSION: Both HTp and VMATp techniques succeeded to obtain conformal and homogeneous dose distributions within CTVp while reducing the mean implant dose. HTp was found to be superior to VMATp with regards to lowering all OAR doses except for CB.

Complete labial fusion causing urinary retention in a postmenopausal woman.

Labial fusion or labial adhesion can rarely be encountered postmenopausal and may be diagnosed in advanced stages especially in sexually inactive women. It may be a rare cause of voiding dysfunction or urinary retention. We present a case of a postmenopausal woman presenting with urinary retention due to complete labial fusion. The patient was treated both with topical estrogen and surgical separation of labial fusion. No recurrences developed after the procedure. Topical estrogen treatment may not resolve adhesions in postmenopausal women and invasive procedures may be necessary to resolve urinary retention.

Impact of Superoxide Dismutase-Gliadin on Radiation-induced Fibrosis: An Experimental Study.

AIM: Radiation-induced fibrosis (RIF) has since long been considered as irreversible. Further understanding of its mechanisms has led to trials investigating RIF treatment and prevention. The effect of superoxide dismutase (SOD)-gliadin, an oral form of SOD that resists gastrointestinal inactivation, on RIF treatment was evaluated in this experimental study. MATERIALS AND METHODS: A total of 36 Wistar albino mice were randomly distributed into four groups. According to group, 25 Gy radiation or sham-radiation were performed on day 0. Acute and late reactions were recorded. After 6 months, mice were treated with SOD-gliadin, 10,000 units per kg per day, or placebo. SOD-gliadin and placebo treatments were administered daily for 8 days by oral gavage. Later the mice were sacrificed, dissected and histopathologically analyzed. Accumulated hyaline and collagen at the dermis is an indicator of fibrosis. Therefore measurements of the dermal thickness were used to quantify the degree of RIF. Additionally, the morphological changes were analyzed, and the differences reported. RESULTS: The mean and standard deviation for dermal thickness were 0.45±0.09 mm in the sham-irradiated placebo-treated group, 0.51 mm±0.16 mm in the sham-irradiated SOD-gliadin-treated group, 0.92 mm±0.23 mm in the irradiated placebo-treated group and 0.71 mm±0.17 mm in the irradiated SOD-gliadin-treated group. The difference in mean dermal thickness between irradiated placebo-treated and irradiated SOD-gliadin-treated mice was statistically significant (p=0.002). CONCLUSION: Quality of life while prolonging survival has an increasing importance in patients with cancer. RIF can be a crucial problem after all radiotherapy modalities. SOD-gliadin has advantageous effects on conditions that call for an increased expression of antioxidant enzymes. The results of our study suggest that oral SOD-gliadin may prevent or ameliorate RIF and patients can benefit from the positive effects of SOD.

A cross-sectional survey of the diagnosis and management of bone metastasis in breast cancer patients in Turkey.

PURPOSE: This study aimed to report the practice of managing breast cancer with bone metastasis in Turkey and to determine the adherence to the British Association of Surgical Oncology (BASO) guidelines. METHODS: This multicenter, cross-sectional epidemiological survey was conducted in 38 centers across Turkey. Data from 1,026 breast cancer patients with bone metastases (mean age 54.0 ± 11.9 years) were analyzed. RESULTS: Over 30 % of patients had a diagnosis of metastatic breast cancer (stage IV) at the time of primary diagnosis. The imaging modalities used for diagnosing bone metastases were bone scintigraphy (57.8 %), radiography (22.8 %), and bone survey (4.4 %). Tumor markers were detected in 94.9 %, and markers of bone metabolism were measured in 90.4 % of patients. A total of 3.5 % of patients underwent surgery for bone metastasis, 26.4 % underwent palliative chemotherapy (most commonly docetaxel + capecitabine), and 56.5 % endured radiotherapy. Most patients (96 %) also received bisphosphonate. Radiography, bone scintigraphy, and CT were the main imaging tools used for postoperative follow-up of bone metastasis. Our results were >95 % in line with the BASO guidelines for the management of bone metastasis, except that interventional procedures, such as biopsy, were applied less frequently in our survey. CONCLUSIONS: The diagnosis and management practices of breast cancer with bone metastasis in Turkey were generally compatible with international guidelines. However, the awareness and knowledge of physicians on the current guidelines should be increased, and equipment for the appropriate interventional procedures should be provided in every clinic to obtain optimal and standard management of bone metastases.

Association of coping style, cognitive errors and cancer-related variables with depression in women treated for breast cancer.

OBJECTIVE: The purpose of this study was to examine the correlation between depression levels with coping styles and cognitive errors in women treated for breast cancer. METHODS: A total of 110 breast cancer outpatients who had had surgery at least 6 months previously, had completed adjuvant cancer treatment and had not experienced metastasis or recurrent lesions were evaluated. The Automatic Thoughts Questionnaire, Cognitive Errors Questionnaire, Mental Adjustment to Cancer Scale and Beck Depression Inventory were administered to all patients. Semi-structured interview forms were used to obtain medical and demographic data. All patients were categorized into depression and non-depression groups according to their Beck Depression Inventory scores. The study protocol was approved by the Medical Ethics Committee of Istanbul University Oncology Institute. RESULTS: Higher cognitive errors and automatic thought scores were found in the depression group. Fighting spirit was found to be the primary coping style used in the non-depression group, while helplessness/hopelessness, anxious/preoccupation and fatalism were the coping styles used the most in the depression group. No association between depression and socio-demographic (except for educational level) and cancer-related variables was detected. However, it was found that automatic thoughts, cognitive errors, education level, fighting spirit and anxious/preoccupation are important indicators of depression in our sample. CONCLUSIONS: A causal relationship exists between depression and a patient's cognitive patterns and accompanying anxiety. The degree of depression is inversely related to both fighting spirit coping type and educational level. If clinicians take this into consideration, diagnosing and treating depression will be more effective.

Does partial expander deflation exacerbate the adverse effects of radiotherapy in two-stage breast reconstruction?

BACKGROUND: The optimum protocol for expander volume adjustment with respect to the timing and application of radiotherapy remains controversial. METHODS: Eighteen New Zealand rabbits were divided into three groups. Metallic port integrated anatomic breast expanders of 250 cc were implanted on the back of each animal and controlled expansion was performed. Group I underwent radiotherapy with full expanders while in Group II, expanders were partially deflated immediately prior to radiotherapy. Control group did not receive radiotherapy.The changes in blood flow at different volume adjustments were investigated in Group II by laser Doppler flowmetry. Variations in the histopathologic properties of the irradiated tissues including the skin, capsule and the pocket floor, were compared in the biopsy specimens taken from different locations in each group. RESULTS: A significant increase in skin blood flow was detected in Group II with partial expander deflation. Overall, histopathologic exam revealed aggravated findings of chronic radiodermatitis (epidermal atrophy, dermal inflammation and fibrosis, neovascularisation and vascular changes as well as increased capsule thickness) especially around the lower expander pole, in Group II. CONCLUSIONS: Expander deflation immediately prior to radiotherapy, may augment the adverse effects, especially in the lower expander pole, possibly via enhanced radiosensitization due to a relative increase in the blood flow and tissue oxygenation.

Does radiotherapy planning without breath control compensate intra-fraction heart and its compartments' movement?

This prospective study investigated radiation dose and volume changes during breathing cycle. Ten patients with left breast carcinoma receiving radiotherapy were included. Treatment planning images were obtained as three different sets of series taken: without breath control (F), deep inspiration (I), and end of expiration (E), with 3-mm intervals. As such, whole breath cycle was simulated. CT images taken during I and E were registered to F, according to DICOM coordinates. Each patient's target and organ at risk volumes were contoured by the primary radiation oncologist except heart components which were contoured by radiologist on F, I and E series. Radiotherapy planning was done on F series, then planning and beam data were transferred from F to I and E image series. Target and organs at risk (OAR) dose distributions for E and I image series were obtained. Dose changes between F, E, and I phases for whole heart and components, namely, left ventricle (LV), right ventricle (RV), left auricle (LA), right auricle (RA), and left anterior descendent artery (LAD) were examined. Furthermore, the issue of any compartment representing the maximum heart dose was investigated. Volume and dose variations for heart, LV, RV, LA, RA, and LAD were observed during breath cycle. Exposured dose was more than defined tolerance level for LV, RV, and LAD in some patients. However, dose differences between F-I and F-E were not statistically significant. Radiotherapy planning without breath control is not capable of compensating for whole intra-fraction heart and its components' volumes and dose changes.

Correlation of clinical and MRI staging in cervical carcinoma treated with radiation therapy: a single-center experience.

PURPOSE: To correlate clinical and MRI findings in patients with cervical carcinoma treated with radiation therapy (RT). MATERIALS AND METHODS: Forty-two patients with pretreatment IB-IVA cervical carcinoma were included in this retrospective study. Pre- and post-treatment MRI findings of the patients were reevaluated and compared with clinical staging. Six-month, one-year, and two-year follow-up imaging by MR was performed for 36, 20, and 7 patients, respectively. The correlation between clinical and MRI findings was assessed by a Spearman's rho (rank correlation) test. Univariate analyses were performed to identify the prognostic significance of the tumor volume and lymph node status. RESULTS: Pre-treatment correlations between MRI and clinical findings for diagnoses without parametrial invasion, with parametrial invasion, and with pelvic sidewall invasion were 71.0%, 64.7%, and 15.8%, respectively. According to the Spearman's rho (rank correlation) test, the parametrial invasion correlation was poor (r = 0.410, P < 0.01). The correlation of clinical and MRI findings at 6 months was 88.9% (r = 0.674, P < 0.0001). CONCLUSION: In advanced cervical cancer, the correlation of clinical and MRI staging prior to neoadjuvant RT was low despite a high correspondence in the assessment of local response after RT.

Lower level of MAPK expression is associated with anthracycline resistance and decreased survival in patients with hormone receptor negative breast cancer.

INTRODUCTION: Hormone receptor negative breast cancer is encountered in about 30% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular markers in patients with receptor negative breast cancer. METHODS: Tumor specimens from 140 patients with receptor negative (ER, PR) breast cancer were analyzed for MAPK, Her-2/neu, EGFR and PI3K expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables were determined with respect to disease-free and overall survival. RESULTS: Nineteen (13.6%), 45 (32.1%), 16 (11.4%) and 47 (33.5%) patients had positive staining for EGFR, PI3K, Her-2/neu and MAPK, respectively. Twenty-three patients with positive MAPK (16.4%) had a high level of expression (score 4-7) and 24 (17.1%) had a low score (1-3). A lower percentage of MAPK expression was significantly associated with a poorer OS (p = 0.03) and a tendency for shorter DFS (p = 0.08) among those who were positive for MAPK. Anthracycline resistance remained the only independent significant variable for OS by Cox regression analysis (p = 0.001, HR:26.1). In patients with recurrent disease, median survival after initial relapse was 16.8 months. MAPK was determined as the only prognostic factor for this endpoint. Patients with higher level of MAPK staining showed significantly shorter survival following initial recurrence (p = 0.04). CONCLUSION: MAPK expression is a significant prognostic factor for non-metastatic patients with hormone receptor breast cancer. A lower level of staining is shown to be associated with with antracycline resistance and oveall survival, whereas a higher expression level is correlated with shorter survival following initial relapse, suggesting possible role of different molecular mechanisms pertaining to tumor progression once recurrence occurs. Further translational research is required to elucidate molecular mechanisms of the cross-talk between intracellular signaling and molecular pathways leading to drug resistance in patients with receptor negative breast cancer.

Factors affecting the prognosis of breast cancer patients with brain metastases.

The aim of this retrospective analysis was to investigate the factors affecting the prognosis of brain metastases in breast cancer patients to identify subgroups which might benefit from prophylactic treatments in future. Seventy-three early and 13 advanced stage patients with known Erb-2 status were included. In 14% of the early stage patients, the first recurrence site was isolated brain metastasis. None of the anthracycline resistant patients had brain metastases as their first recurrence site. The median interval between diagnosis and brain metastasis was 41.5 months (95% CI, 35.79-47.20) in early stage patients. The median interval between the first extracerebral metastases to the brain metastases was 15.5 months (95% CI, 12.24-18.76) in all patients. High histologic and nuclear grade, large tumor, anthracycline resistance were the factors which significantly affected the early appearance of brain metastases but only advanced age (> or =55 years, P=.035) correlated with isolated brain metastasis. Progression with isolated brain metastases was significantly higher in responsive ErbB-2 positive population (P=.036) and none of other pathological factors was associated with isolated brain metastasis in advanced stage. The median survival after brain metastasis in patients with brain metastasis as first recurrence was longer than the patients with brain metastasis after other organ metastasis (13 months vs 2 months P=.003). The median survival following brain metastases in complete responsive patients was higher than the others (24 months vs 6 months, P=.002). Therefore, response to systemic treatment was more determinative in the development of isolated brain metastases than clinical and pathologic features. ErbB-2 should be emphasized in prophylactic treatment strategies. Prophylactic cranial radiotherapy may be an effective treatment option for metastatic patients with complete responsive disease and with controlled ErbB-2 positive disease.

Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) of the penis.

Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) of the penis has been very rarely defined. We report a case of a 19-year-old patient with a tumor, localized in the dorsal side of penis, composed of small round cells with diffuse membranous mic-2 (CD99) immunopositivity. The patient was treated with multiagent chemotherapy and radiotherapy.