Variability of clinical target volume delineation for rectal cancer patients planned for neoadjuvant radiotherapy with the aid of the platform Anatom-e.

OBJECTIVE: Delineation of treatment volumes is a major source of uncertainties in radiotherapy (RT). This is also true for rectal cancer patients undergoing neoadjuvant RT, with a potential impact on treatment quality. We investigated the role of the digital platform Anatom-e (Anatom-e Information Sytems Ltd., Houston, Texas) in increasing the compliance to follow a specific treatment protocol in a multicentric setting. MATERIALS AND METHODS: Two clinical cases of locally advanced rectal cancer were chosen. Participants were instructed to follow the 2009 Radiation Therapy Oncology Group consensus atlas and asked to manually segment clinical target volumes (CTVs), for both patient 1 and 2, on day 1 with and without the use of Anatom-e. After one week (day 2), the same radiation oncologist contoured again, with and without Anatom-e, the same CT series. Intraobserver (Intra-OV) and interobserver (Inter-OV) variability were evaluated with the Dice similarity coefficient (DSC), the Hausdorff distance (HD) and mean distance to agreement (MDA). RESULTS: For clinical case 1, no significant difference was found for Intra-OV and Inter-OV. For clinical case 2, no significant difference was found for Intra-OV but a statistically significant difference was found for Inter-OV in DSC when using or not the platform. Mean DCS was 0.65 (SD: ±0.64; range: 0.58-0.79) for day 1 vs reference volume without Anatom-e and 0.72 (SD: ±0.39; range: 0.67-0.77) (p = 0.03) with it. Mean MDA was lower with Anatom-e (3.61; SD: ±1.33; range: 2.85-4.78) than without (4.14; SD: ±2.97; range: 2.18-5.21), with no statistical significance (p = 0.21) The use of Anatom-e decreased the SD from 2.97 to 1.33. Mean HD was lower with Anatom-e (26.06; SD: ±2.05; range: 24.08-32.62), with no statistical significance (p = 0.14) compared to that without (31.39; SD: ±1.31; range: 26.14-48.72). CONCLUSIONS: The use of Anatom-e decreased the Inter-OV in the CTV delineation process for locally advanced rectal cancer with complex disease presentation planned for neoadjuvant RT. This system may be potentially helpful in increasing the compliance to follow shared guidelines and protocols.

Induction Chemotherapy and Sequential Concomitant Chemo-radiation in Locally Advanced Head and Neck Cancers: How Induction-phase Intensity and Treatment Breaks May Impact on Clinical Outcomes.

AIM: The purpose of the study was to assess outcomes of locally advanced head and neck (LAHNC) treated with induction chemotherapy (ICT) and subsequent concurrent chemo-radiation. PATIENTS AND METHODS: A total of 71 LAHNC patients were treated with 2-3 cycles of docetaxel, cisplatin and 5-fluorouracil as induction chemotherapy and subsequent concurrent chemoradiation with weekly cisplatin or carboplatin. Definitive radiotherapy was delivered with intensity-modulated radiation and a simultaneous integrated boost approach up to a total dose of 70 Gy in 35 fractions to the macroscopic primary and nodal disease. RESULTS: Actuarial 2-year OS, CSS, DFS, MFS, LC were 55.3% (95%CI=39.3-68.6), 58.6% (95%CI=41.9-72), 60.5% (95%CI=47.3-71.4), 87.3% (95%CI=76.2-93.5) and 74.7% (95%CI=61.5-83.9), respectively. On multivariate analysis undergoing to 3 vs. 2 cycles of TPF (HR=22.31; 95%CI=2.68-185.66; p=0.004) and radiotherapy treatment break >4 days (HR=1.28; 95%CI=1.06-1.55; p=0.01) negatively affected cancer-specific survival (CSS) with statistical significance. Achieving complete remission after ICT had a statistically significant impact on CSS (HR=0.9; 95%CI=0.01-0.54; p=0.009). Patients undergoing ICT with 3 cycles had more frequently treatment breaks compared to those submitted to 2 cycles (HR=1.36; 95%CI=1.06-1.73; p=0.01), and had statistically significant longer treatment break time (5.9+1.8 vs. 3+0.36; p=0.02). CONCLUSION: A shorter ICT phase may be a better option enhancing patients' tolerance during concurrent chemoradiation and affecting clinical outcomes.

Exclusive Radiotherapy for Early-stage Glottic Cancer: A Single-institution Retrospective Analysis with a Focus on Voice Quality.

AIM: To report on clinical outcomes of patients with early-stage glottic cancer treated with exclusive radiotherapy with specific analysis of voice quality. PATIENTS AND METHODS: A consecutive cohort of 55 patients with early glottic cancer was retrospectively analyzed. Patients were treated with exclusive radiation up to a conventionally fractionated total dose of 66-70 Gy with a 3-dimensional conformal technique. Oncological outcomes and toxicity profiles were investigated. A sub-sample of this cohort was also analyzed in terms of voice quality employing subjective and objective tools such as the Voice Handicap Index-10 (VHI-10) and the Multidimensional Voice Program (MDVP™) software and was compared to a group of similar patients treated with CO2 laser cordectomy. RESULTS: after a median observation time of 74.5 months, 5- and 10-year local control was 89% [95% confidence interval (CI)=70.7-93.1%] and 86% (95% CI=68.7-89.6%), respectively. Larynx-preservation rate was 91.8% (95% CI=82.4%-94.9%) at 10 years. Five- and 10-year actuarial overall survival was 72% (95% CI=50.4-79.2%) and 56% (95% CI=48.7-64.3%). Maximum detected acute toxicity included G3 dermatitis (5.4%) and G4 dyspnea (1.8%). Late toxicity profile was mild. VHI-10 scores showed a mild voice disability in both groups, with no statistically significant difference (p=0.12), even when investigating different domains. Patients treated with radiation had a lower deterioration rate in all parameters excluding low voice, interruptions of sound and diplophony. CONCLUSION: Exclusive radiation proved an effective treatment for patients with early glottic cancer in terms of both oncological outcome and voice quality.

Pulmonary function and quality of life after VMAT-based stereotactic ablative radiotherapy for early stage inoperable NSCLC: a prospective study.

OBJECTIVES: To analyze changes in pulmonary function and quality of life (QoL) at different time points after Stereotactic Ablative Radiotherapy (SABR) for early stage inoperable lung cancer, and potential correlations between radiation dose-volume parameters and pulmonary toxicity or changes in pulmonary function tests (PFT) and QoL. MATERIALS AND METHODS: From July 2012 to October 2013, 30 patients were enrolled in this prospective observational study. Complete PFT were performed and Lung Cancer Symptoms Scale (LCSS) questionnaire administered prior to SABR; all patients then underwent Computed Tomography (CT) scan and PFT at 45, 135, 225 and 315 days after SABR, together with LCSS questionnaire. Clinical lung toxicity and radiological toxicity (acute and late) were prospectively recorded by using the Radiation Therapy Oncology Group (RTOG) scoring system. RESULTS: A decline in Slow Vital Capacity (SVC), Forced Expiratory Volume in 1s (FEV1), Single-breath lung diffusing capacity (DLCO) and blood partial pressure of oxygen (PaO2) was seen at 135 days post-SABR. PaO2 values rescued to normal levels at 315 days. None of the baseline PFT parameters resulted to be associated with the occurrence of pulmonary toxicity or with late radiological changes. Mean V5, V10, and V20 and MLD2Gy were higher in patients who developed radiation pneumonitis, even if not significantly associated at Cox regression analysis. LCSS QoL showed a significant worsening of the single item fatigue at 135 days after SABR. CONCLUSIONS: A small (mean 10%) but significant decline in lung volumes and DLCO was recorded after SABR, with clinical impact of such change difficult to estimate in individual patients. Global QoL was not significantly impaired. Dose-volume parameters did not emerge as significantly predictive of any clinical, radiological or functional toxicity.

Acute skin toxicity management in head and neck cancer patients treated with radiotherapy and chemotherapy or EGFR inhibitors: Literature review and consensus.

The adverse effects of radiation therapy, often integrated with chemotherapy and/or targeted therapies, on the skin include severe acute and chronic dermatitis associated with pain, discomfort, itching, and burning, and may heavily affect patients' quality of life. The management of these skin adverse effects in head and neck cancer patients (HNCPs) are very heterogeneous due to the lack of shared rigorous classification systems and evidence based treatments. A multidisciplinary group of head and neck cancer specialists from Italy met with the aim of reaching a consensus on a clinical definition and management of dermatitis in HNCPs treated with radiotherapy with or without systemic therapies in order to improve skin toxicity management. The Delphi Appropriateness Method was used. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. This paper offers contains seven clusters of statements about the management of dermatitis in HNCPs and a review of recent literature on these topics.

Sepsis in head and neck cancer patients treated with chemotherapy and radiation: Literature review and consensus.

The reporting of infection/sepsis in chemo/radiation-treated head and neck cancer patients is sparse and the problem is underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met with the aim of reaching a consensus on a clinical definition and management of infections and sepsis. The Delphi appropriateness method was used for this consensus. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. The paper contains seven clusters of statements about the clinical definition and management of infections and sepsis in head and neck cancer patients, which had a consensus. Furthermore, it offers a review of recent literature in these topics.

Late sensorial alterations in different radiotherapy techniques for nasopharyngeal cancer.

Intensity-modulated radiation therapy (IMRT) for nasopharyngeal cancer (NPC) allowed a better distribution of the dose to the tumor volume, sparing surrounding structures. Aim of the study is the objective evaluation of olfactory and gustatory impairments in patients who underwent chemo-radiotherapy for NPC. Correlation between smell and taste alterations, xerostomy, and radiation technique was investigated. Thirty healthy subjects and 30 patients treated with chemo-radiation therapy for NPC, with at least a 2-years follow-up period, were evaluated. All subjects underwent symptoms evaluation, endoscopic fiber optic nasal examination, taste strips, Sniffin' sticks tests, Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring system. Patients were divided in 2 groups: 2-dimensional radiotherapy/conformal 3-dimensional radiotherapy and IMRT. A higher percentage of rhinorrhea, nasal obstruction, xerostomy, hyposmia, hypogeusia, mucosal hyperemia, and presence of nasopharyngeal secretions was found in irradiated subjects (P < 0.05). Concerning olfactory and gustatory scores, we demonstrated a statistically significant difference between healthy subjects and irradiated patients (P < 0.05), with lower gustatory total score in IMRT group (P < 0.01). In conclusion, chemo-radiotherapy for NPC induces long-term smell and taste impairments, which can compromise quality of life. Although based on small samples, it is also important to consider that IMRT can induce higher taste dysfunction compared with traditional techniques.

Nasal cytological changes as late effects of radiotherapy for nasopharyngeal cancer.

BACKGROUND: Radiation therapy is a cornerstone in nasopharyngeal cancer treatment. However, it can induce acute and long-term adverse effects, such as acute mucositis and late submucosal fibrosis. Late toxicities could not only affect submucosa but also mucosal cells, determining long-term cytological changes. OBJECTIVE: Evaluation of delayed nasal cytological alterations in patients who underwent radiation therapy for nasopharyngeal carcinoma (NPC). METHODS: In this case-control study, we analyzed 30 healthy subjects and 30 patients treated with chemotherapy and radiotherapy for NPC between 2003 and 2011, with a median follow-up of 59 months. All subjects underwent symptoms anamnestic evaluation (rhinorrea, nasal obstruction), endoscopic fiber optic nasal examination, skin-prick tests, and nasal scraping for cytological exam. RESULTS: A higher percentage of rhinorrhea, nasal obstruction, mucosal hyperemia, and presence of nasopharyngeal secretions at fiber optic endoscopic exam was found in radiated subjects (p < 0.05). Nasal cytology analysis demonstrated a higher percentage of neutrophilic inflammation and squamous cell metaplasia and mucous cell metaplasia in treated patients (p < 0.05). No cytological atypia was seen. No statistically significant correlation between nasal cytological changes and objective findings, patients' age, tobacco smoking, and gastroesophageal reflux has been found in the radiotherapy group (p > 0.05). CONCLUSION: Radiation therapy induces late nasal mucosal changes, which may be related to clinical consequences, such as abundant mucus production and its consequent endonasal stagnation. In the future, detailed knowledge of cytological changes in patients' nasal mucosa could represent a key prerequisite for the choice of effective interventions for late radiation-induced rhinitis.

Three-dimensional ultrasound-based image-guided hypofractionated radiotherapy for intermediate-risk prostate cancer: results of a consecutive case series.

External beam radiotherapy (EBRT) is a standard of care in the treatment of prostate cancer. Hypofractionation is a valid option either radiobiologically and logistically in this context. Image-guidance procedures are strongly needed to provide ballistic precision to radiation delivery. The Clarity platform allows for the acquisition of three-dimensional ultrasound scans (3D-US) to perform image-guided radiotherapy. We treated a consecutive series of intermediate-risk prostate cancer patients (according to NCCN stratification) with a hypofractionated schedule (70.2 Gy/26 fractions at 2.7 Gy/daily to the prostate gland excluding the seminal vesicles at 62.1 Gy) under 3D-US guidance with the Clarity platform. The 3-year biochemical-relapse-free survival, distant-metastases-free, cancer-specific and overall survival were 98.6% (CI: 91.1-99.6%), 98.6% (CI: 91.1-99.6%), 97.5% (CI: 94.5-99.1%), and 94.3% (CI: 90.4-96.7%), respectively. Maximum detected acute GU toxicity was G0 in 22 patients (29.7%), G1 in 30 (22.7%), G2 in 19 (25.6%), G3 in 3 (4%). Maximum detected acute GI toxicity at the end of EBRT was G0 in 42 patients (56.8%), G1 in 22 (29.7%), G2 in 9 (12.1%), G3 in 1 (1.4%). The 3-year actuarial rates of ≥ G2 late toxicities were 6.1% for genito-urinary and 8.9% for gastrointestinal. The whole image-guidance workflow resulted in being robust and reliable. EBRT delivered employing a hypofractionated schedule under 3D-US-based image guidance proved to be a safe and effective treatment approach with consistent biochemical control and a mild toxicity profile. Hence, it has been transferred into daily clinical practice in our Department.

Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study.

BACKGROUND: Radiation dermatitis is common in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and global quality of life. We prospectively evaluated the role of hypericum perforatum and neem oil (Holoil®; RIMOS srl, Mirandola, Italy) in the treatment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer. METHODS: A consecutive series of 28 head and neck cancer patients submitted to radiotherapy (RT) was enrolled onto this mono-institutional single-arm prospective observational study. Patients undergoing both definitive or post-operative radiotherapy were allowed, either as exclusive modality or combined with (concomitant or induction) chemotherapy. We started Holoil treatment whenever bright erythema, moderate oedema or patchy moist desquamation were observed. Holoil® was used during all RT course and during follow up time, until acute skin toxicity recovery. RESULTS: The maximum detected acute skin toxicity was Grade 1 in 7% of patients, Grade 2 in 68%, Grade 3 in 25%, while at the end of RT was Grade 0 in 3.5%, Grade 1 in 32%, Grade 2 in 61%, Grade 3 in 3.5%. For patients having G2 acute skin toxicity, it mainly started at weeks 4-5; for those having G3, it began during weeks 5-6. Median times spent with G2 or G3 toxicity were 17.5 and 11 days. Patients having G2 acute skin toxicity had a dermatitis worsening in 27% of case (median occurrence time: 7 days). G3 events were reconverted to a G2 profile in all patients (median time: 7 days). Those experiencing a G2 skin event were converted to a G1 score in 23% of cases (median time: 14 days). Time between maximum acute skin toxicity and complete skin recovery after RT was 27 days. CONCLUSIONS: Holoil® proved to be a safe and active option in the management of acute skin toxicity in head and neck cancer patients submitted to RT or chemo-radiotherapy. A prophylactic effect in the prevention of moist desquamation may be hypothesized for hypericum and neem oil and need to be tested within a prospective controlled study.

Impact of the observers' experience on daily prostate localization accuracy in ultrasound-based IGRT with the Clarity platform.

The aim of this study is to evaluate the accuracy of daily prostate localization with ultrasound imaging of various radiation oncologists with nonhomogeneous expertise. For ten patients who underwent radical radiotherapy for localized prostate cancer, 11 radiation oncologists reviewed daily ultrasound scans acquired during three different treatment sessions. The average values of two senior radiation oncologists, considered to be expert observers, were selected as reference. The remaining nine observers were divided into two groups, Group 1 and Group 2, with more and less than one year of experience, respectively. The recorded shifts in prostate position were divided in three classes: <3 mm, 3-5 mm, and > 5 mm. Deviations from reference were less than 3 mm in all directions in 91% and 81% of measurements in Groups 1 and 2, respectively. The maximum difference in terms of root mean square error (RMSE) was reported for superior-inferior (SI) direction, in particular a mean difference of 3.24 mm was observed for Group 2 in respect to the reference; moreover RMSE was 1 and 1.3 mm higher for Group 2 for anterior-posterior (AP) and left-right (LR) directions, respectively. The difference between Groups 1 and 2 was significant (p < 0.01) for all directions. The mean values for the shifts in all three directions between Group 1 and the references were 0.235 mm, 0.385 mm, and 0.009 mm for the LR, SI, and AP directions, respectively. The position of the prostate gland is more easily detectable (p = 0.956) in the AP direction, while the visibility is lower for LR (p = 0.105) and SI boundaries (p < 0.05). The observers' experience is essential for positioning the target correctly; therefore, a training period is recommended before putting the system into clinical practice.

Conventional 2D (2DRT) and 3D conformal radiotherapy (3DCRT) versus intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer treatment.

PURPOSE: Nasopharyngeal carcinoma represents a distinct entity as compared to other head and neck tumours. Radio-chemotherapy is the treatment of first choice in non-metastatic disease. Intensity-modulated radiation therapy (IMRT) allows the sparing of parotid glands, improving the toxicity profile. The aim of this study was to compare the results obtained with IMRT with those obtained with conventional 2D (2DRT) and 3D conformal radiation therapy (3DCRT) in terms of tumour control, survival, acute and late toxicity. MATERIALS AND METHODS: We reviewed the clinical records of 52 patients with histologically proven carcinoma of the nasopharynx (stage I-IVB according to the 2002 American Joint Committee on Cancer staging system) treated with curative intent between January 2003 and August 2011: 26 patients were treated with 2D or 3D technique (arm A) and 26 with IMRT technique (arm B) with simultaneous integrated boost. Fifty patients (96 %) received chemotherapy. Local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), acute and late toxicity were retrospectively evaluated. RESULTS: After a median follow-up of 37.6 months (69 months in arm A and 23 months in arm B), 69 % of patients were alive and disease-free, 10 % were alive with disease and 21 % died of disease, with an OS of 81 % at 2 years and 79 % at 5 years, a LC rate of 88 % at 2 years and 78 % at 5 years, a LRC rate of 80 % at 2 years and 73 % at 5 years and a DFS of 74 % at 2 years and 65 % at 5 years, with no statistically significant differences between IMRT and 2DRT/3DCRT. In multivariate analysis, the TNM stage and the volume treated at high dose correlated with DFS. No factor was found to be related to OS. Chronic toxicity was not statistically different in the two study groups and in particular ≥ G2 xerostomia rates were 67 and 41 % in arm A and B, respectively (p = 0.10). CONCLUSIONS: The findings of this study confirm that IMRT associated with chemotherapy, even with moderately hypofractionated regimens, allows good disease control with better results in terms of late xerostomia, although without statistically significant differences compared to 2DRT and 3DCRT. The hypothesis of an impact of IMRT on survival has yet to be confirmed.

Environmental influences on mate preferences as assessed by a scenario manipulation experiment.

Many evolutionary psychology studies have addressed the topic of mate preferences, focusing particularly on gender and cultural differences. However, the extent to which situational and environmental variables might affect mate preferences has been comparatively neglected. We tested 288 participants in order to investigate the perceived relative importance of six traits of an ideal partner (wealth, dominance, intelligence, height, kindness, attractiveness) under four different hypothetical scenarios (status quo/nowadays, violence/post-nuclear, poverty/resource exhaustion, prosperity/global well-being). An equal number of participants (36 women, 36 men) was allotted to each scenario; each was asked to allocate 120 points across the six traits according to their perceived value. Overall, intelligence was the trait to which participants assigned most importance, followed by kindness and attractiveness, and then by wealth, dominance and height. Men appraised attractiveness as more valuable than women. Scenario strongly influenced the relative importance attributed to traits, the main finding being that wealth and dominance were more valued in the poverty and post-nuclear scenarios, respectively, compared to the other scenarios. Scenario manipulation generally had similar effects in both sexes, but women appeared particularly prone to trade off other traits for dominance in the violence scenario, and men particularly prone to trade off other traits for wealth in the poverty scenario. Our results are in line with other correlational studies of situational variables and mate preferences, and represent strong evidence of a causal relationship of environmental factors on specific mate preferences, corroborating the notion of an evolved plasticity to current ecological conditions. A control experiment seems to suggest that our scenarios can be considered as realistic descriptions of the intended ecological conditions.

Salvage external beam radiotherapy for recurrent prostate adenocarcinoma after high-intensity focused ultrasound as primary treatment.

INTRODUCTION: The main objective was to evaluate feasibility, toxicity and biochemical control rates of salvage external beam radiotherapy (EBRT) in recurrent localized prostate cancer after high-intensity focused ultrasound (HIFU) as primary therapy. PATIENTS AND METHODS: A total of 24 patients who underwent salvage EBRT after 1 or 2 HIFU sessions and with a minimum post-treatment follow-up of 24 months were retrospectively evaluated. Primary endpoints were toxicity and biochemical disease-free survival (bDFS, defined according to the ASTRO Phoenix definition). RESULTS: Median follow-up was 40.3 months. Gastrointestinal toxicity was low. Acute genitourinary (GU) toxicity grade ≤II rate was 45.8%, with only few patients presenting grade III (8.3%) and grade IV (4.2%) toxicity. Late grade ≥III GU toxicity was registered in 16.7% of patients. The 3-year bDFS rate was 77.8%. Patients achieving a nadir prostate-specific antigen (nPSA) of ≤0.35 ng/ml after EBRT had significantly higher bDFS (3-year bDFS: 87.7 vs. 50%, respectively; p = 0.001). Achieving nPSA ≤0.35 ng/ml was the only factor independently associated to long-term bDFS both on univariate (p = 0.01) and multivariate analysis (HR 7.06, p = 0.039). CONCLUSIONS: Salvage EBRT after HIFU failure is feasible and allows to obtain satisfactory biochemical control rates, especially in patients attaining a nPSA ≤0.35 ng/ml after EBRT.

The handedness of imagined bodies in action and the role of perspective taking.

Past research at the nexus of motor control and perception investigated the role of perspective taking in many behavioral and neuroimaging studies. Some investigators addressed the issue of one's own vs. others' action imagination, but the possible effects of a front or a back view in imagining others' actions have so far been neglected. We report two 'single trial' experiments in which a total of 640 participants were asked to imagine a person performing a manual action - either in a front or in a back view - and then to indicate the hand used by the imagined person during movement execution. In such a task, we assume the existence of two distinct biases: a perceptual-mnemonic bias due to subjects' visual experience of others' actions, encouraging them to imagine right-handed movements, and a motor bias due to subjects' experience of self-made actions, encouraging them to imagine movements performed with the same hand as their dominant hand. We hypothesized that a greater involvement of motor representations in the back view compared to the front view could result in an increased correspondence between one's own manual preference and the hand used by the imagined agent in the former condition. The results of both experiments were consistent with this hypothesis, suggesting that while imagining others' actions we employ motor simulations in different degrees according to the perspective adopted.

Efficacy and safety of tadalafil 20 mg on demand vs. tadalafil 5 mg once-a-day in the treatment of post-radiotherapy erectile dysfunction in prostate cancer men: a randomized phase II trial.

INTRODUCTION: The role of phosphodiesterase type 5 inhibitors in the treatment of post-radiotherapy erectile dysfunction (ED) has not been extensively investigated. AIM: To compare the efficacy and safety of on-demand 20-mg tadalafil (arm A) with the newly released tadalafil 5-mg once-a-day dosing (arm B) in patients with ED following radiotherapy for prostate cancer (PC). METHODS: Randomized study to receive on-demand 20-mg or once-a-day 5-mg tadalafil for 12 weeks. Main Outcome Measures. Changes in the International Index of Erectile Function (IIEF) domain scores and Sexual Encounter Profile (SEP) question 2 and 3 positive response rates. RESULTS: Fifty-two out of 86 screened patients were randomized. Forty-four patients were evaluable for efficacy. A significant improvement in all domains of the IIEF was observed in both arms (P = 0.0001) with mean erectile function domain scores values of 25 and 27.1 for the 20-mg and 5-mg tadalafil, respectively (P = 0.19). SEP 2 and 3 positive response rates increased from 0% in both arms at baseline to 81% and 70% in the 20-mg arm and 90% and 73% in the 5-mg arm, respectively, at the end of treatment (P = 0.27). End of treatment global efficacy question positive answers were 86% in the 20-mg arm and 95% in the 5-mg arm (P = 0.27). Higher treatment compliance was shown in arm B (100%) as compared with arm A (86%). There was a nonstatistically significant trend toward fewer side effects in favor of the 5-mg daily dose arm. CONCLUSIONS: In the study population, both tadalafil formulations generated significantly high response rates according to the outcome measures and were well tolerated. The once-a-day 5-mg dosing showed higher compliance and marginally reduced side effects, thus making it an attractive alternative to on-demand therapy for ED in post-radiotherapy PC patients.