[en] Purpose/Objective(s): The aim of this study is to build the estimator of toxicity using artificial neural network (ANN) for head and neck cancer patients Materials/Methods: An ANN can combine variables into a predictive model during training and considered all possible correlations of variables. We constructed an ANN based on the data from 73 patients with advanced H and N cancer treated with external beam radiotherapy and/or chemotherapy at our institution. For the toxicity estimator we defined input data including age, sex, site, stage, pathology, status of chemo, technique of external beam radiation therapy (EBRT), length of treatment, dose of EBRT, status of post operation, length of follow-up, the status of local recurrences and distant metastasis. These data were digitized based on the significance and fed to the ANN as input nodes. We used 20 hidden nodes (for the 13 input nodes) to take care of the correlations of input nodes. For training ANN, we divided data into three subsets such as training set, validation set and test set. Finally, we built the estimator for the toxicity from ANN output. Results: We used 13 input variables including the status of local recurrences and distant metastasis and 20 hidden nodes for correlations. 59 patients for training set, 7 patients for validation set and 7 patients for test set and fed the inputs to Matlab neural network fitting tool. We trained the data within 15% of errors of outcome. In the end we have the toxicity estimation with 74% of accuracy. Conclusion: We proved in principle that ANN can be a very useful tool for predicting the RT outcomes for high risk H and N patients. Currently we are improving the results using cross validation

[en] Purpose: Accurate detection of radiation-induced fibrosis (RIF) is crucial in management of breast cancer survivors. Tissue compliance meter (TCM) has been validated in musculature. We validate TCM in healthy breast tissue with respect to interobserver and intraobserver variability before applying it in RIF. Methods and Materials: Three medical professionals obtained three consecutive TCM measurements in each of the four quadrants of the right and left breasts of 40 women with no breast disease or surgical intervention. The intraclass correlation coefficient (ICC) assessed interobserver variability. The paired t test and Pearson correlation coefficient (r) were used to assess intraobserver variability within each rater. Results: The median age was 45 years (range, 24-68 years). The median bra size was 35C (range, 32A-40DD). Of the participants, 27 were white (67%), 4 black (10%), 5 Asian (13%), and 4 Hispanic (10%). ICCs indicated excellent interrater reliability (low interobserver variability) among the three raters, by breast and quadrant (all ICC ≥0.99). The paired t test and Pearson correlation coefficient both indicated low intraobserver variability within each rater (right vs. left breast), stratified by quadrant (all r≥ 0.94, p < 0.0001). Conclusions: The interobserver and intraobserver variability is small using TCM in healthy mammary tissue. We are now embarking on a prospective study using TCM in women with breast cancer at risk of developing RIF that may guide early detection, timely therapeutic intervention, and assessment of success of therapy for RIF.

[en] Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen

[en] Purpose/objective: In this study, we evaluated in a serial manner whether radiation dose to the bulb of the penis is predictive of erectile dysfunction, ejaculatory difficulty (EJ), and overall satisfaction with sex life (quality of life) by using serial validated self-administered questionnaires. Methods and materials: Twenty-nine potent men with AJCC Stage II prostate cancer treated with three-dimensional conformal radiation therapy alone to a median dose 72.0 Gy (range: 66.6-79.2 Gy) were evaluated by determining the doses received by the penile bulb. The penile bulb was delineated volumetrically, and the dose-volume histogram was obtained on each patient. Results: The median follow-up time was 35 months (range, 16-43 months). We found that for D₃₀, D₄₅, D₆₀, and D₇₅ (doses to a percent volume of PB: 30%, 45%, 60%, and 75%), higher than the corresponding median dose (defined as high-dose group) correlated with an increased risk of impotence (erectile dysfunction firmness score = 0) (odds ratio [OR] = 7.5, p = 0.02; OR = 7.5, p = 0.02; OR = 8.6, p = 0.008; and OR = 6.9, p = 0.015, respectively). Similarly, for EJD D₃₀, D₄₅, D₆₀, and D₇₅, doses higher than the corresponding median ones correlated with worsening ejaculatory function score (EJ = 0 or 1) (OR = 8, p = 0.013; OR = 8, p 0.013; OR = 9.2, p = 0.015; and OR = 8, p = 0.026, respectively). For quality of life, low (≤median dose) dose groups of patients improve over time, whereas high-dose groups of patients worsen. Conclusions: This study supports the existence of a penile bulb dose-volume relationship underlying the development of radiation-induced erectile dysfunction. Our data may guide the use of inverse treatment planning to maximize the probability of maintaining sexual potency after radiation therapy

[en] Purpose: To examine a relationship between serum transforming growth factor β -1 (TGF-β1) values and radiation-induced fibrosis (RIF). Methods and Materials: We conducted a prospective analysis of the development of RIF in 39 women with American Joint Committee on Cancer stage 0-I breast cancer treated with lumpectomy and accelerated partial breast irradiation via intracavitary brachytherapy (IBAPBI). An enzyme-linked immunoassay (Quantikine, R and D, Minneapolis, MN) was used to measure serum TGF-β1 before surgery, before IBAPBI, and during IBAPBI. Blood samples for TGF-β1 were also collected from 15 healthy, nontreated women (controls). The previously validated tissue compliance meter (TCM) was used to objectively assess RIF. Results: The median time to follow-up for 39 patients was 44 months (range, 5-59 months). RIF was graded by the TCM scale as 0, 1, 2, and 3 in 5 of 20 patients (25%), 6 of 20 patients (30%), 5 of 20 patients (25%), and 4 of 20 patients (20%), respectively. The mean serum TGF-β1 values were significantly higher in patients before surgery than in disease-free controls, as follows: all cancer patients (30,201 ± 5889 pg/mL, P=.02); patients with any type of RIF (32,273 ± 5016 pg/mL, P<.0001); and women with moderate to severe RIF (34,462 ± 4713 pg/mL, P<0.0001). Patients with moderate to severe RIF had significantly elevated TGF-β1 levels when compared with those with none to mild RIF before surgery (P=.0014) during IBAPBI (P≤0001), and the elevation persisted at 6 months (P≤.001), 12 months (P≤.001), 18 months (P≤.001), and 24 months (P=.12). A receiver operating characteristic (ROC) curve of TGF-β1 values predicting moderate to severe RIF was generated with an area under the curve (AUC)_ROC of 0.867 (95% confidence interval 0.700-1.000). The TGF-β1 threshold cutoff was determined to be 31,000 pg/mL, with associated sensitivity and specificity of 77.8% and 90.0%, respectively. Conclusions: TGF-β1 levels correlate with the development of moderate to severe RIF. The pre-IBAPBI mean TGF-β1 levels can serve as an early biomarker for the development of moderate to severe RIF after IBAPBI

[en] This study explores whether meningioma expresses epidermal growth factor receptor (EGFR) and determines if there is a correlation between the WHO grade of this tumor and the degree of EGFR expression. Following institutional review board approval, 113 meningioma specimens from 89 patients were chosen. Of these, 85 were used for final analysis. After a blinded review, immunohistochemical stains for EGFR were performed. Staining intensity (SI) was scored on a scale 0-3 (from no staining to strong staining). Staining percentage of immunoreactive cells (SP) was scored 1-5 (from the least to the maximum percent of the specimen staining). Immunohistochemical score (IHS) was calculated as the product of SI and SP. Eighty-five samples of meningioma were classified in accordance with World Health Organization (WHO) criteria: benign 57/85 (67%), atypical 23/85 (27%), and malignant 5/85 (6%). The majority of samples demonstrated a moderate SI for EGFR. IHS for EGFR demonstrated a significant association between SI and histopathologic subtype. Also, there was a correlation between the SP and histopathologic subtype (p = 0.029). A significant association was determined when the benign and the atypical samples were compared to the malignant with respect to the SP (p = 0.009). While there was a range of the IHS for the benign and the atypical histologic subtypes, malignant tumors exhibited the lowest score and were statistically different from the benign and the atypical specimens (p < 0.001). To our knowledge, this represents the largest series of meningioma samples analyzed for EGFR expression reported in the literature. EGFR expression is greatest in benign meningiomas and may serve a potential target for therapeutic intervention with selective EGFR inhibitors