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Objectives: Prostate cancer is one of the most common cancers worldwide in men, with a huge geographical variation both in incidence and mortality. Whereas, the incidence is higher in developed countries, mortality is higher in developing countries. The reasons for high mortality in these countries include variation in practice leading to early diagnosis. Artificial Intelligence (AI) and Machine learning (ML) are increasingly being used to improve the diagnostic accuracy of prostate cancer. We interrogated the published literature to review the usage of AI and ML in the diagnosis of prostate cancer. Methods: Research databases such as SCOPUS, Web of Science (WoS), and Google Scholar were searched to identify articles related to AI/ML in the diagnosis and management of prostate cancer. Key-words included (“prostate” AND “cancer”), (“machine” AND (“learn” OR “learning”)) OR (“artificial” AND (“intelligence” OR “intelligent”)). Results Using a screening criterion, 293 reviewed research papers were identified. The two most consistent themes were predictive modeling and application of AI/ ML tools for cancer grading and radiomics. AI and ML enhance the diagnostic accuracy by reducing the inter-individual variation in Gleason’s scoring, and complimenting the interpretation of multiparametric magnetic resonance imaging (mpMRI). A few publications reported the use of AI/ML tools by combining histopathology and MRI signals. Conclusions: AI and ML can improve the diagnostic accuracy of prostate cancer. Literature is beginning to emerge suggesting to use a combination of demographic features, clinical data, serological markers, pathological grading and radiological factors, and genomic data, to propose accurate non-invasive diagnosis of clinically significant prostate cancer.

Skin toxicity is a common adverse effect of breast radiotherapy. We investigated whether inverse-planned intensity-modulated radiotherapy (IMRT) would reduce the incidence of skin toxicity compared with forward field-in-field breast IMRT (FiF-IMRT) in early stage breast cancer.This phase III randomised controlled trial compared whole-breast irradiation with either FiF-IMRT or helical tomotherapy IMRT (HT-IMRT), with skin toxicity as the primary end point. Patients received 50 Gy in 25 fractions and were assessed to compare skin toxicity between treatment arms.In total, 177 patients were available for assessment and the median follow-up was 73.1 months. Inverse IMRT achieved more homogeneous coverage than FiF-IMRT; erythema and moist desquamation were higher with FiF-IMRT compared with HT-IMRT (61% versus 34%; P 0.001; 33% versus 11%; P 0.001, respectively). Multivariate analysis showed large breast volume, FiF-IMRT and chemotherapy were independent factors associated with worse acute toxicity. There was no difference between treatment arms in the incidence of late toxicities. The 5-year recurrence-free survival was 96.3% for both FiF-IMRT and HT-IMRT and the 5-year overall survival was 96.3% for FiF-IMRT and 97.4% for HT-IMRT.Our study showed significant reduction in acute skin toxicity using HT-IMRT compared with FiF-IMRT, without significant reduction in late skin toxicities. On the basis of these findings, inverse-planned IMRT could be used in routine practice for whole-breast irradiation with careful plan optimisation to achieve the required dose constraints for organs at risk.

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

In this study, we report the 24-month patient-reported outcomes of the randomized phase 2 CHIRP trial that compared conventional and hypofractionated radiation therapy (RT) in the treatment of high-risk prostate cancer.Men with high-risk localized prostate cancer were randomized to either conventional (78 Gy/39 fractions) or hypofractionated RT (68 Gy/25 fractions). All patients received pelvic nodal RT and adjuvant androgen deprivation therapy. Quality of life (QoL) data were collected through the expanded prostate cancer index composite and the short-form 12 (SF-12) health-related QoL questionnaire at baseline and at 3, 6, 12, 18, and 24 months posttreatment. We assessed change from baseline to account for differences in baseline comorbidities. Independent t test was used to identify differences between the 2 groups.Ninety-six participants were included in the QoL analysis, 49 in the hypofractionation arm and 47 in the standard fractionation arm. Urinary and sexual scores were similar between the 2 arms at all time points. Bowel bother scores exhibited a consistent trend favoring the standard arm from 3- to 18-months posttreatment and were statistically significant at 12 months (P = .016). SF-12 physical component scores showed a consistent trend favoring the hypofractionation arm from 6- to 18-months posttreatment and were statistically significant at 18 months (P = .017). At 24 months, there were no significant differences in QoL scores between the 2 groups.At 24 months post-RT, there were no major differences in patient-reported QoL between standard and hypofractionated RT. Early statistically significant differences in bowel bother and SF-12 physical component scores were no longer present at 24 months.

PURPOSE Radiotherapy (RT) plus long-term androgen suppression (AS) are a standard treatment option for patients with high-risk localized prostate cancer. We hypothesized that docetaxel chemotherapy (CT) could improve overall survival (OS) and clinical outcomes among patients with high-risk prostate cancer. PATIENTS AND METHODS The multicenter randomized NRG Oncology RTOG 0521 study enrolled patients with high-risk nonmetastatic disease between 2005 and 2009. Patients were randomly assigned to receive standard long-term AS plus RT with or without adjuvant CT. RESULTS A total of 612 patients were enrolled; 563 were evaluable. Median prostate-specific antigen was 15.1 ng/mL; 53% had a Gleason score 9 to 10 cancer; 27% had cT3 to cT4 disease. Median follow-up was 5.7 years. Treatment was well tolerated in both arms. Four-year OS rate was 89% (95% CI, 84% to 92%) for AS + RT and 93% (95% CI, 90% to 96%) for AS + RT + CT (hazard ratio [HR], 0.69; 90% CI, 0.49 to 0.97; one-sided P = .034). There were 59 deaths in the AS + RT arm and 43 in the AS + RT + CT arm, with fewer deaths resulting from prostate cancer in the AS + RT + CT arm versus AS + RT (23 v 16 deaths, respectively). Six-year rate of distant metastasis was 14% for AS + RT and 9.1% for AS + RT + CT, (HR, 0.60; 95% CI, 0.37 to 0.99; two-sided P = .044). Six-year disease-free survival rate was 55% for AS + RT and 65% for AS + RT + CT (HR, 0.77; 95% CI, 0.59 to 1.00; two-sided P = .053). CONCLUSION For patients with high-risk nonmetastatic prostate cancer, CT with docetaxel improved OS from 89% to 93% at 4 years, with improved disease-free survival and reduction in the rate of distant metastasis. The trial suggests that docetaxel CT may be an option to be discussed with selected men with high-risk prostate cancer.

PurposeOnly retrospective data are available for low-dose-rate (LDR) salvage prostate brachytherapy for local recurrence after external beam radiation therapy (EBRT). The primary objective of this prospective phase 2 trial (NCT00450411) was to evaluate late gastrointestinal and genitourinary adverse events (AEs) after salvage LDR brachytherapy.Methods and materialsEligible patients had low- or intermediate-risk prostate cancerbefore EBRT and biopsy-proven recurrence >30months after EBRT, with prostate-specific antigen levels

Purpose Hypofractionated radiation therapy (HFRT) may offer treatment advantages for patients with prostate cancer. However, HFRT may also increase the risk of gastrointestinal (GI) or genitourinary (GU) toxicity compared with conventionally fractionated radiation therapy (CFRT). Several large trials have found that HFRT is well tolerated in mixed risk population studies. Here, we report on a phase II, randomized controlled study conducted to evaluate these endpoints in exclusively high-risk patients with prostate cancer treated with prostate and pelvic nodal radiation. Methods and Materials After giving informed consent, patients with high-risk prostate cancer were randomly assigned to prostate plus pelvic nodal radiation therapy with either HFRT (68 Gy in 25 fractions) or CFRT (78 Gy in 39 fractions) and 18 months of androgen suppression therapy. Toxicity was scored using the Common Terminology Criteria for Adverse Events (version 4.0). Biochemical failure was determined by the Phoenix definition. Patients were analyzed on an intention-to-treat basis. Results From 2012 to 2018, 111 patients with high-risk prostate cancer were enrolled and 109 patients were treated. The cumulative incidence of grade 2 or higher acute GI toxicity was not significantly different between the arms (HFRT 18.9% vs CFRT 21.8%; P = .812). Similarly, acute GU (HFRT 30.2% vs CFRT 30.9%; P = 1.00), late GI (HFRT 16.0% vs CFRT 10.0%; P = .554), and late GU (HFRT 16.0% vs CFRT 6.0%; P = .200) were not significantly different between the arms. Median follow-up was 38.0 months (4.8-77.8 months). The 3-year biochemical recurrence-free survival was not significantly different between the 2 arms (97.3% for HFRT vs 91.0% for CFRT; P = .606). The 3-year overall survival was 94.8% in the HFRT arm and 100.0% in the CFRT arm (P = .116). Conclusions HFRT and CFRT using intensity modulated radiation therapy were both well tolerated for patients with high-risk prostate cancer and resulted in similar 3-year biochemical recurrence-free survival and overall survival.

Non-functioning pituitary adenomas (NFPAs) are benign pituitary tumours that constitute about one-third of all pituitary adenomas. They typically present with symptoms of mass effects resulting in hypopituitarism, visual symptoms, or headache. Most NFPAs are macroadenomas (>1 cm in diameter) at diagnosis that can occasionally grow quite large and invade the cavernous sinus causing acute nerve compression and some patients may develop acute haemorrhage due to pituitary apoplexy. The progression from benign to malignant pituitary tumours is not fully understood; however, genetic and epigenetic abnormalities may be involved. Non-functioning pituitary carcinoma is extremely rare accounting for only 0.1% to 0.5 % of all pituitary tumours and presents with cerebrospinal, meningeal, or distant metastasis along with the absence of features of hormonal hypersecretion. Pituitary surgery through trans-sphenoidal approach has been the treatment of choice for symptomatic NFPAs; however, total resection of large macroadenomas is not always possible. Recurrence of tumours is frequent and occurs in 51.5% during 10 years of follow-up and negatively affects the overall prognosis. Adjuvant radiotherapy can decrease and prevent tumour growth but at the cost of significant side effects. The presence of somatostatin receptor types 2 and 3 (SSTR3 and SSTR2) and D2-specific dopaminergic receptors (D2R) within NFPAs has opened a new perspective of medical treatment for such tumours. The effect of dopamine agonist from pooled results on patients with NFPAs has emerged as a very promising treatment modality as it has resulted in reduction of tumour size in 30% of patients and stabilization of the disease in about 58%. Despite the lack of long-term studies on the mortality, the available limited evidence indicates that patients with NFPA have higher standardized mortality ratios (SMR) than the general population, with women particularly having higher SMR than men. Older age at diagnosis and higher doses of glucocorticoid replacement therapy are the only known predictors for increased mortality.

333 Background: High-risk, localized prostate cancer has a poor prognosis. We hypothesized that adj docetaxel (D) and prednisone and long-term (24 mos) androgen suppression (AS) and radiation therapy (RT) would improve overall survival (OS) and tested this in NRG/RTOG 0521. Results with med follow-up of 5.7 yrs were reported (JCO 37:1159, 2019), showing a benefit of D (HR=0.69, 90% CI: 0.49-0.97, 1-sided p=0.034). Med follow-up is now 10.4 yrs and we report updated results for OS and metastasis (DM). Methods: NRG/RTOG 0521 opened 12/05 and closed 8/09 with targeted accrual of 600 and designed to detect a HR of 0.49, based on improvement in 4-yr OS from 86 to 93%. With 0.05 1-sided type I error and 90% power >78 deaths were required. Pts were stratified by predefined risk groups. Group 1: Gl 9-10, any T; Group 2: Gl 8, PSA

Purpose To report on the importance of cancer location from diagnostic prostate biopsies in predicting biochemical relapse for patients treated with 125 I seed implant brachytherapy as monotherapy for favorable risk disease; specifically, to assess the clinical significance of potentially underdosing the base region of the prostate gland. Methods and Materials Of 1145 consecutive patients, 846 had pretreatment biopsies allowing for sextant analysis and consequent evaluation of biochemical failure tendencies. Biochemical failure was defined as a posttreatment rise in the nadir prostate-specific antigen (PSA) by at least 2 ng/mL. Patient and tumor characteristics, dosimetry, the use of hormone therapy, source strength, and postimplant PSA kinetics were analyzed between sextant subgroups. Results Sixty-two patients (7.3%) with sextant pathology had biochemical failure. There was no significant difference between the failure locations. There were 528 patients (62.4%) with some element of base involvement (BI), and 318 patients (37.6%) with no evidence of BI. Of the 62 patients with biochemical failure, 42 (67.7%) showed BI on biopsy and 20 (32.3%) had no BI. The 10-year relapse-free survival rate is 88.2% (95% confidence interval: 84.3%, 92.2%) and 92.0% (95% confidence interval: 88.4%, 95.8%) for the BI and no BI groups, respectively ( p = 0.17). The mean D90 delivered to the base, midgland, and apex was 140.8 (±21.8) Gy, 170.8 (±22.5) Gy, and 177.9 (±29.5) Gy, respectively, for all patients. Conclusions There are no significantly worse outcomes for patients treated with an 125 I seed implant for favorable risk prostate cancer with some element of BI, despite lower doses of radiation delivered to the base region.

Dose-escalated hypofractionated radiotherapy (hfrt) using intensity-modulated radiotherapy (imrt), with inclusion of the pelvic lymph nodes (plns), plus androgen suppression therapy (ast) in high-risk prostate cancer patients should improve patient outcomes, but acute toxicity could limit its feasibility. Our single-centre phase ii prospective study enrolled 40 high-risk prostate cancer patients. All patients received hfrt using imrt with daily mega-voltage computed tomography imaging guidance, with 95% of planning target volumes (ptv68 and ptv50) receiving 68 Gy and 50 Gy (respectively) in 25 daily fractions. The boost volume was targeted to the involved plns and the prostate (minus the urethra plus 3 mm and minus 3 mm from adjacent rectal wall) and totalled up to 75 Gy in 25 fractions. Acute toxicity scores were recorded weekly during and 3 months after radiotherapy (rt) administration. For the 37 patients who completed rt and the 3-month follow-up, median age was 65.5 years (range: 50&ndash, 76 years). Disease was organ-confined (T1c&ndash, T2c) in 23 patients (62.1%), and node-positive in 5 patients (13.5%). All patients received long-term ast. Maximum acute genitourinary (gu) and gastrointestinal (gi) toxicity peaked at grade 2 in 6 of 36 evaluated patients (16.6%) and in 4 of 31 evaluated patients (12.9%) respectively. Diarrhea and urinary frequency were the chief complaints. Dose&ndash, volume parameters demonstrated no correlation with toxicity. The ptv treatment objectives were met in 36 of the 37 patients. This hfrt dose-escalation trial in high-risk prostate cancer has demonstrated the feasibility of administering 75 Gy in 25 fractions with minimal acute gi and gu toxicities. Further follow-up will report late toxicities and outcomes.

The objective of the study is to demonstrate the feasibility of using [11C]-choline positron-emission tomography (PET)/CT to deliver helical tomotherapy (HT) to the prostate with a simultaneous integrated boost to dominant intraprostatic lesions as a biological target volume for dose escalation. Eleven patients with intermediate-risk prostate cancer were included in this virtual planning study. Pretreatment baseline [11C]-choline PET/CT scans were acquired with a PET/CT scanner dynamically in 2-min frames from injection to 40 min post injection. PET data was reconstructed using the RAMLA 3D algorithm and analyzed to identify dominant intraprostatic lesion(s). Dominant lesions were defined as biological target volume(s) (BTV) including all voxels with a standardized uptake value of 75 % or above relative to the maximum standard uptake value (SUV) within the prostate gland. Three target volumes for optimization included the following: PTV78 (BTV + 5 mm margin), PTV68 (prostate + 5 mm posteriorly and 10 mm in all other dimensions), and PTV50 (prostate gland and proximal seminal vesicles + 7 mm margin posteriorly and 10 mm in all other dimensions). Dose constraints on organs at risk were implemented based on a published data using hypofractionated IMRT with long-term follow-up. Helical tomotherapy plans were generated to deliver hypofractionated radiation therapy to these volumes using simultaneous integrated boost in 25 fractions. Eight patients had one identifiable contiguous BTV, and the other three patients had two noncontiguous BTVs. The mean BTV ratio to prostate volume ratio was 6.03 % (minimum 0.80 %, maximum 13.44 %). Target volume and normal tissue constraints were met in seven of the 11 patients enrolled in the study. Targets and structures in the four patients that did not meet constraints were the bladder (3 patients), peritoneal cavity (2 patients), rectum (1 patient), PTV68 (1 patient), and PTV50 (1 patient). It is feasible in selected patients to use [11C]-choline PET/CT to deliver hypofractionated dose-escalated helical tomotherapy to dominant intraprostatic lesions with simultaneous integrated boost using clinically established normal tissue constraints.

Purpose: The purpose of this study was to characterize benign prostate-specific antigen (PSA) bounces of at least 2.0 ng/mL and biochemical failure as defined by the Phoenix definition after prostate brachytherapy at our institution, and to investigate distinguishing features between three outcome groups: patients experiencing a benign PSA bounce, biochemical failure, or neither. Material and methods: Five hundred and thirty consecutive men treated with low-dose-rate brachytherapy with follow-up of at least 3 years were divided into outcome groups experiencing bounce, failure, or neither. A benign bounce was defined as a rise of at least 2.0 ng/mL over the pre-rise nadir followed by a decline to 0.5 ng/mL or below, without intervention. Patient and tumor characteristics, treatment variables, and PSA kinetics were analyzed between groups. Results: Thirty-two (6.0%) men experienced benign bounces and 47 (8.9%) men experienced failure. Men experiencing a bounce were younger (p = 0.01), had a higher 6-month PSA level (p = 0.03), and took longer to reach a final nadir (p < 0.01). Compared to the failure group, men with bounce had a lower pre-treatment PSA level (p = 0.01) and experienced a rise of at least 2.0 ng/mL that occurred sooner after the implant (p < 0.01) with a faster PSA doubling time (p = 0.01). Only time to PSA rise independently differentiated between bounce and failure (p < 0.01), with a benign bounce not being seen after 36 months post-treatment. Prostate-specific antigen levels during a bounce reached levels as high as 12.6 ng/mL in this cohort, and in some cases took over 5 years to decline to below 0.5 ng/mL. Conclusions: Although there is substantial overlap between the features of benign PSA bounces and failure, physicians may find it useful to evaluate the timing, absolute PSA level, initial response to treatment, and rate of rise when contemplating management for a PSA rise after low-dose-rate brachytherapy. J Contemp Brachytherapy 2014; 6, 3: 247–253 DOI: 10.5114/jcb.2014.45093

Purpose To identify clinical, dosimetric, and genetic factors that are associated with late urinary toxicity after a 125 I prostate brachytherapy implant. Methods and Materials Genomic DNA from 296 men treated with 125 I prostate brachytherapy monotherapy was extracted from saliva samples for this study. A retrospective database was compiled including clinical, dosimetric, and toxicity data for this cohort of patients. Fourteen candidate single-nucleotide polymorphism (SNPs) from 13 genes ( TP53 , ERCC2 , GSTP1 , NOS , TGFβ1 , MSH6 , RAD51 , ATM , LIG4 , XRCC1 , XRCC3 , GSTA1 , and SOD2 ) were tested in this cohort for correlations with toxicity. Results This study identified 217 men with at least 2 years of followup. Of these, 39 patients developed Grade ≥2 late urinary complications with a transurethral resection of prostate, urethral stricture, gross hematuria, or a sustained increase in their International Prostate Symptom Score. The only clinical or dosimetric factor that was associated with late urinary toxicity was age ( p = 0.02). None of the 14 SNPs tested in this study were associated with late urinary toxicity in the univariate analysis. Conclusions This study identified age as the only variable being associated with late urinary toxicity. However, the small sample size and the candidate gene approach used in this study mean that further investigations are essential. Genome-wide association studies are emerging as the preferred approach for future radiogenomic studies to overcome the limitations from a candidate gene approach.

To compare the implant quality and clinical outcomes for patients treated with low and intermediate strength (125)I seeds in prostate brachytherapy implants.This retrospective review included 390 consecutive patients treated with prostate brachytherapy from 1999 to 2006. The first 142 patients were implanted with source strengths lower than 0.415U (0.327mCi), with the subsequent 248 patients implanted with source strengths higher than 0.493U (0.388mCi). Clinical, dosimetric, toxicity, and outcome data were compared between these two cohorts of patients.Despite having similar prostate volumes, fewer sources (median, 95 vs. 113; p0.0001) and fewer needles (median, 23 vs. 29; p0.0001) were implanted in the intermediate strength cohort. The postimplant dosimetry demonstrated better quality implants in patients treated with intermediate strength sources (median D90, 160.0Gy vs. 139.6Gy; p0.0001), with greater dose inhomogeneity identified in the intermediate strength cohort of patients. A higher incidence of late rectal toxicity was identified in patients treated with intermediate strength sources despite lower rectal doses in this cohort. The biochemical relapse-free survival, prostate cancer survival, and overall survival were not significantly different between the two cohorts.The transition from low to intermediate strength sources has led to fewer resources being used and improved postoperative dosimetry. Although there were more rectal complications identified in the intermediate strength cohort of patients in this analysis, there were no other significantly worse clinical or biochemical outcomes for patients implanted with intermediate strength sources.

The objective of the present study was to analyze, with relatively high sensitivity and specificity, uptake properties of [11C]-choline in prostate cancer patients by means of positron-emission tomography (pet)/computed tomography (ct) imaging using objectively defined pet parameters to test for statistically significant changes before, during, and after external-beam radiation therapy (ebrt) and to identify the time points at which the changes occur. The study enrolled 11 patients with intermediate-risk prostate cancer treated with ebrt, who were followed for up to 12 months after ebrt. The [11C]-choline pet scans were performed before treatment (baseline), at weeks 4 and 8 of ebrt, and at 1, 2, 3, 6, and 12 months after ebrt. Analysis of [11C]-choline uptake in prostate tissue before treatment resulted in a maximum standardized uptake value (suvmax) of 4.0 &plusmn, 0.4 (n = 11) at 40 minutes after injection. During week 8 of ebrt, the suvmax declined to 2.9 &plusmn, 0.1 (n = 10, p < 0.05). At 2 and 12 months after ebrt, suvmax values were 2.3 &plusmn, 0.3 (n = 10, p < 0.01) and 2.2 &plusmn, 0.2 (n = 11, p < 0.001) respectively, indicating that, after ebrt, maximum radiotracer uptake in the prostate was significantly reduced. Similar effects were observed when analyzing the tumour:muscle ratio (tmr). The tmr declined from 7.4 &plusmn, 0.6 (n = 11) before ebrt to 6.1 &plusmn, 0.4 (n = 11, nonsignificant) during week 8 of ebrt, to 5.6 &plusmn, 0.03 (n = 11, p < 0.05) at 2 months after ebrt, and to 4.4 &plusmn, 0.4 (n = 11, p < 0.001) at 12 months after ebrt. Our study demonstrated that intraprostatic [11C]-choline uptake in the 11 analyzed prostate cancer patients significantly declined during and after ebrt. The pet parameters SUVmax and tmr also declined significantly. These effects can be detected during radiation therapy and up to 1 year after therapy. The prognostic value of these early and statistically significant changes in intraprostatic [11C]-choline pet avidity during and after ebrt are not yet established. Future studies are indicated to correlate changes in [11C]-choline uptake parameters with long-term biochemical recurrence to further evaluate [11C]-choline pet changes as a possible, but currently unproven, biomarker of response.

We examined the impact of hypofractionated radiation therapy and androgen suppression therapy (ast) on quality of life (qol) in high-risk prostate cancer patients. Between March 2005 and March 2007, 60 patients with high-risk prostate cancer were enrolled in a prospective phase ii study. All patients received 68 Gy (2.72 Gy per fraction) to the prostate gland and 45 Gy (1.8 Gy per fraction) to the pelvic lymph nodes in 25 fractions over 5 weeks. Of the 60 patients, 58 received ast. The University of California&ndash, Los Angeles Prostate Cancer Index questionnaire was used to prospectively measure qol at baseline (month 0) and at 1, 6, 12, 18, 24, 30, and 36 months after radiation treatment. The generalized estimating equation approach was used to compare the qol scores at 1, 6, 12, 18, 24, 30, and 36 months with those at baseline. We observed a significant decrease in qol items related to bowel and sexual function. Several qol items related to bowel function were significantly adversely affected at both 1 and 6 months, with improvement toward 6 months. Although decreased qol scores persisted beyond the 6-month mark, they began to re-approach baseline at the 18- to 24-month mark. Most sexual function items were significantly adversely affected at both 1 and 6 months, but the effects were not considered to be a problem by most patients. A complete return to baseline was not observed for either bowel or sexual function. Urinary function items remained largely unaffected, with overall urinary function being the only item adversely affected at 6 months, but not at 1 month. Urinary function returned to baseline and remained unimpaired from 18 months onwards. In our study population, who received hypofractionated radiation delivered using dynamic intensity-modulated radiotherapy with inclusion of the pelvic lymph nodes, and 2&ndash, 3 years of ast prescription, qol with respect to bowel and sexual function was significantly affected, qol with respect to urinary function was largely unaffected. Our results are comparable to those in other published studies.

Purpose To perform a dosimetric comparison of three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and helical tomotherapy (HT) plans for pelvic and para-aortic RT in postoperative endometrial cancer patients; and to evaluate the integral dose (ID) received by critical structures within the radiation fields. Methods and Materials We selected 10 patients with Stage IIIC endometrial cancer. For each patient, three plans were created with 3D-CRT, IMRT, and HT. The IMRT and HT plans were both optimized to keep the mean dose to the planning target volume (PTV) the same as that with 3D-CRT. The dosimetry and ID for the critical structures were compared. A paired two-tailed Student t test was used for data analysis. Results Compared with the 3D-CRT plans, the IMRT plans resulted in lower IDs in the organs at risk (OARs), ranging from −3.49% to −17.59%. The HT plans showed a similar result except that the ID for the bowel increased 0.27%. The IMRT and HT plans both increased the IDs to normal tissue (see Table 1 and text for definition), pelvic bone, and spine (range, 3.31–19.7%). The IMRT and HT dosimetry showed superior PTV coverage and better OAR sparing than the 3D-CRT dosimetry. Compared directly with IMRT, HT showed similar PTV coverage, lower Ids, and a decreased dose to most OARs. Conclusion Intensity-modulated RT and HT appear to achieve excellent PTV coverage and better sparing of OARs, but at the expense of increased IDs to normal tissue and skeleton. HT allows for additional improvement in dosimetry and sparing of most OARs.

To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer.Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated.During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity).Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods.

56 Background: Since prostate cancer has intrinsic high radiation-fraction sensitivity, hypofractionated radiotherapy (HFRT) could offer treatment advantages. However, dose-escalated HFRT may increase risks of late genitourinary (GU) and gastrointestinal (GI) toxicity. Intensity-modulated radiotherapy (IMRT) can potentially deliver dose-escalated HFRT without increasing late toxicities. This study’s acute toxicity data was previously published. We now present five-year efficacy results and late toxicity data for prostate cancer patients treated with HFRT using IMRT. Methods: From 2005-2012, our Phase II prospective study enrolled one hundred patients with either high risk disease (one or more of: Stage ≥ T3, Gleason ≥ 8, or PSA ≥ 20 ng/mL) or high tier intermediate risk disease (Gleason 7 and PSA ≥ 15 ng/mL). All patients received HFRT using IMRT in 25 daily fractions. Sixty patients received 68 Gy to the prostate and proximal seminal vesicles, with simultaneous integrated boost (SIB) of 45 Gy to pelvic lymph nodes and distal seminal vesicles. Forty patients received 68 Gy to the prostate, and a SIB of 50 Gy to pelvic lymph nodes and seminal vesicles. Adjuvant hormonal therapy was given for two to three years. Biochemical failure was determined by the Phoenix definition. Late toxicity scores were recorded every 6 months after completing RT. Results: Median age of patients was 67 years. 33% had Stage ≥ T3, 52% had Gleason ≥ 8, and 44% had PSA ≥ 20 ng/mL. After a median follow-up of 5.4 years, median PSA at last follow-up was 0.10 ng/mL. Five-year biochemical control rate (BCR) was 91.8%, five-year progression-free survival (PFS) was 92.8%, and five-year overall survival (OS) was 88.7%. Five-year cumulative incidence of Grade ≥ 3 GU and GI toxicity were 13.0% and 16.7% respectively. At the five-year efficacy endpoint, ongoing Grade ≥ 3 GU and GI toxicity were 1.9% and 0% respectively. Conclusions: Dose-escalated HFRT using IMRT results in favourable five-year BCR, PFS, and OS for patients with localized high-risk prostate cancer, and is well-tolerated with acceptable late GU and GI toxicity. These findings support ongoing Phase III trials that are assessing the clinical use of IMRT-based HFRT. Clinical trial information: NCT00126802.

OBJECTIVE To assess late toxicity and outcomes in high-risk prostate cancer patients treated with hypofractionated radiation treatment with androgen suppression therapy. METHODS Sixty high-risk prostate cancer patients were enrolled. IMRT prescription was 68 Gy/25 fractions (2.7 Gy/fraction) to the prostate and proximal seminal vesicles (SV). The pelvic lymph nodes (PLN) and distal SV concurrently received 45 Gy/25 fractions (1.8 Gy/fraction). The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification before each treatment. RTOG Toxicity scores were recorded for a 5-year period. RESULTS Sixty patients completed RT with median follow-up of 63 months (range, 7 to 80 mo).At 5 years follow-up timepoint: Grade (G)2 and G3 late genitourinary toxicity was experienced in 7 (17.0%) and 1 (2.44%), respectively; gastrointestinal G2 as highest toxicity recorded in only 1 (2.44%) patient. There was no G3 gastrointestinal toxicity recorded at this timepoint.With 63-month median follow-up (mean of 65.41±1.72 mo), the 5-year overall survival was 86.67%; 5 years freedom from biochemical failure was 91.67% and freedom from clinical failure was 96.67%. CONCLUSIONS Dose escalation and hypofractionated radiation treatment with IMRT treating the prostate and proximal SV concurrently with the pelvic lymph nodes and distal SV and long-term androgen suppression therapy is well tolerated with respect to acute and late toxicity with 5-year actuarial overall survival 86.67%, freedom from biochemical failure 91.38%, and freedom from clinical failure 96.67%. Longer follow-up will provide more information on 10-year survival outcomes.

Importance Tadalafil is used to treat erectile dysfunction after prostate cancer treatment, but its role as a preventive agent is undefined. Objectives To determine primarily whether tadalafil preserved erectile function in men treated with radiotherapy for prostate cancer, and secondarily to determine whether participant- or partner-reported overall sexual function and sexual and marital satisfaction were affected. Design, Setting, and Participants Stratified, placebo-controlled, double-blind, parallel-group study with 1:1 randomization at 76 community-based and tertiary medical sites in the United States and Canada. Two hundred forty-two participants with intact erectile function scheduled to receive radiotherapy for prostate cancer were recruited between November 2009 and February 2012 with follow-up through March 2013. Interventions One hundred twenty-one participants were assigned 5 mg of tadalafil daily and 121 were assigned placebo for 24 weeks starting with external radiotherapy (63%) or brachytherapy (37%). Participant-reported International Index of Erectile Function response before radiotherapy and at weeks 2 and 4, between weeks 20 and 24, between weeks 28 and 30, and 1 year thereafter. Participants and partners could respond also to the Sexual Adjustment Questionnaire and to the Locke Marital Adjustment Test before radiotherapy, between weeks 20 and 24 and weeks 28 and 30, and at 1 year. Main Outcomes and Measures Primary outcome was off-drug spontaneous erectile function 28 to 30 weeks after radiotherapy started. Secondary end points were spontaneous erection at 1 year; overall sexual function and satisfaction; marital adjustment; and partner-reported satisfaction and marital adjustment at 28 to 30 weeks and 1 year, predictors of tadalafil response; and adverse events. Results Among 221 evaluable participants, 80 (79%; 95% CI, 70%-88%) assigned to receive tadalafil retained erectile function between weeks 28 and 30 compared with 61 (74%; 95% CI, 63%-85%) assigned to receive placebo ( P = .49); an absolute difference of 5% (95% CI, −9% to 19%). A significant difference was also not observed at 1 year (72%; 95% CI, 60%-84% vs 71%; 95% CI, 59%-84%; P = .93). Tadalafil was not associated with significantly improved overall sexual function or satisfaction; a significant difference was not observed in any domain subscale. Partners of men assigned tadalafil noted no significant effect on sexual satisfaction, and marital adjustment was not significantly improved in participants or partners. Conclusions and Relevance Among men undergoing radiotherapy for prostate cancer, daily use of tadalafil compared with placebo did not result in improved erectile function. These findings do not support daily use of tadalafil to prevent erectile dysfunction in these patients. Trial Registration clinicaltrials.gov Identifier:NCT00931528

Small-cell carcinomas (sccs) of the genitourinary (gu) tract are rare systemic diseases, and there is no standard treatment strategy for patients with this malignancy. The objectives of the present study were to report the management and outcome of patients with scc of the gu tract treated at a tertiary-care institution from 1982 to 2009. In a chart review of all patients diagnosed with scc of the gu tract between 1982 and 2009, data on demographics, clinical and pathologic characteristics, treatment, and patient outcomes were collected. The 58 patients identified had scc in the following primary sites: urinary bladder (n = 35), prostate (n = 17), and upper urinary tract (n = 6). In 38 patients (66%), the scc was of pure histology, in the remainder, histology was mixed. Overall, 28 patients had limited-stage disease, 24 had extensive-stage disease, and staging was unknown in 6 patients. Median survival for the entire cohort was 7.5 months, with extensive-stage disease being identified as a poor prognostic factor (survival was 22.0 months for limited-stage patients and 4.1 months for extensive-stage patients, p < 0.001). Based on site, prostate patients fared worst, with a median survival of only 5.1 months. Compared with best supportive care, treatment was associated with better outcomes (median survival: 12.3 months vs. 2.3 months, p < 0.0001). Small-cell cancer of the gu tract is an aggressive cancer, with a poor prognosis overall. Although there is no standard of care, patients should be treated using a multimodality approach analogous to that used in the treatment of small-cell lung cancer.

Purpose To determine the safety and efficacy of hypofractionated intensity modulated radiation therapy (Hypo-IMRT) using helical tomotherapy (HT) with concurrent low dose temozolomide (TMZ) followed by adjuvant TMZ in patients with glioblastoma multiforme (GBM). Methods and materials Adult patients with GBM and KPS > 70 were prospectively enrolled between 2005 and 2007 in this phase I study. The Fibonacci dose escalation protocol was implemented to establish a safe radiation fractionation regimen. The protocol defined radiation therapy (RT) dose level I as 54.4 Gy in 20 fractions over 4 weeks and dose level II as 60 Gy in 22 fractions over 4.5 weeks. Concurrent TMZ followed by adjuvant TMZ was given according to the Stupp regimen. The primary endpoints were feasibility and safety of Hypo-IMRT with concurrent TMZ. Secondary endpoints included progression free survival (PFS), pattern of failure, overall survival (OS) and incidence of pseudoprogression. The latter was defined as clinical or radiological suggestion of tumour progression within three months of radiation completion followed by spontaneous recovery of the patient. Results A total of 25 patients were prospectively enrolled with a median follow-up of 12.4 months. The median age at diagnosis was 53 years. Based on recursive partitioning analysis (RPA) criteria, 16%, 52% and 32% of the patients were RPA class III, class IV and class V, respectively. All patients completed concurrent RT and TMZ, and 19 patients (76.0%) received adjuvant TMZ. The median OS was 15.67 months (95% CI 11.56 - 20.04) and the median PFS was 6.7 months (95% CI 4.0 – 14.0). The median time between surgery and start of RT was 44 days (range of 28 to 77 days). Delaying radiation therapy by more than 6 weeks after surgery was an independent prognostic factor associated with a worse OS (4.0 vs. 16.1 months, P = 0.027). All recurrences occurred within 2 cm of the original gross tumour volume (GTV). No cases of pseudoprogression were identified in our cohort of patients. Three patients tolerated dose level I with no dose limiting toxicity and hence the remainder of the patients were treated with dose level II according to the dose escalation protocol. Grade 3–4 hematological toxicity was limited to two patients and one patient developed Grade 4 Pneumocystis jiroveci pneumonia. Conclusion Hypo-IMRT using HT given with concurrent TMZ is feasible and safe. The median OS and PFS are comparable to those observed with conventional fractionation. Hypofractionated radiation therapy offers the advantage of a shorter treatment period which is imperative in this group of patients with limited life expectancy.

Purpose This study quantified the treatment margin (TM) around the prostate that received 100% of the prescribed dose and analyzed postimplant dosimetry in different regions of the prostate for 125I seed implants. Methods and Materials An average target volume (ATV) was created from postoperative MRI scan contours drawn independently by five radiation oncologists in 40 patients. The MRI was fused with the postoperative CT for dosimetry purposes. The TM, defined as the radial distance between the ATV and the 100% isodose line, was measured at 16 points at the base, midgland, and apex. The ATV was divided into four quadrants: anterior–superior, posterior–superior, anterior–inferior, and posterior–inferior quadrants. The values of the dose that covers 90% of the ATV (D90) and the percentage of the ATV receiving the prescribed dose (V100) received by the whole prostate and its four quadrants were documented. Results The range of the mean TM, in millimeter, was −8.88 to 3.68, 1.12 to 10.42, and 6.27 to 18.25 at the base, midgland, and apex, respectively. The mean D90 was 135.8, 162.8, 191.0, and 194.6 Gy for the anterior–superior, posterior–superior, anterior–inferior, and posterior–inferior quadrants, respectively. Conclusions Despite having a relatively uniform preoperative planning target volume, this study identified variable TMs postoperatively in different regions of the prostate. In particular, the anterior base is most underdosed, whereas the lateral regions of the midgland and apex have generous TMs. Postimplant dosimetric parameters were lowest in the anterior–inferior quadrant.

The Editor Current Oncology 23 April 2016 I thank Dr. Nabil Ismaili for reading our article1 and giving his valuable comments with regard to the management of genitourinary small-cell carcinoma (scc). Dr. Ismaili agrees with us about the essential role of chemotherapy in the management of genitourinary scc. However, he does not agree with our suggestion of treatment being analogous to that in small-cell lung cancer. We suggested a platinum-containing chemotherapy regimen for scc of the urinary bladder because the chemotherapy used in either scc or transitional-cell carcinoma of the bladder is platinum-based. Also, pure scc behavior is thought to be similar in its various anatomic sites, and no randomized trial has established a specific chemotherapy regimen in this malignancy. We mentioned in our article that scc of the urinary bladder can be managed by various combinations of chemotherapy, surgery, and radiotherapy. Our study demonstrated that approximately 37% of the cases of scc of the urinary bladder were associated with transitional-cell carcinoma of the bladder1. In my opinion, those cases can be treated with neoadjuvant chemotherapy followed by surgery, if feasible. On the other hand, neoadjuvant chemotherapy followed by concurrent chemoradiation can be used when organ preservation is preferred, especially in cases with pure scc histology. In our cohort, only 1 patient was treated with prophylactic cranial irradiation, and 1 who was untreated with prophylactic cranial irradiation developed brain metastasis at a later stage1. We therefore did not recommend routine use of prophylactic cranial irradiation in genitourinary scc. Any related decisions should be made on an individual case basis. I noted a 50% rate of brain metastasis reported by the MD Anderson group2 in stage iii and iv patients. That rate of brain metastasis is higher than the rate observed in our report and in other published retrospective studies1,3. I concur with Dr. Ismaili that the optimal management of small-cell carcinoma of the prostate is not well defined. However, we suggest limiting the use of androgen deprivation therapy in a mixed histology of scc and adenocarcinoma.

To compare preimplant prostate contours and contouring variability between magnetic resonance (MR) and transrectal ultrasound images.Twenty-three patients were imaged using ultrasound (US) and MR before permanent brachytherapy treatment. Images were anonymized, randomized, and duplicated, and the prostate was independently delineated by five radiation oncologists. Contours were compared in terms of volume, dimensions, posterior rectal indentation, and observer variability. The Jaccard index quantified spatial overlap between contours from duplicated images.The mean US/MR volume ratio was 0.99±0.08 (p=0.5). The width, height, and length ratios for the prostate were 0.98±0.06 (p=0.09), 0.99±0.08 (p=0.4), and 1.05±0.14 (p=0.1). Rectal indentation was larger on US by 0.18mL (p=0.01) and correlated with prostate volume (p0.01). MR and US interobserver variability in volume were similar at 3.5±1.7 and 3.3±1.9mL (p=0.6). Intraobserver variability was smaller on US at 1.4±1.1mL compared with MR at 2.4±2.2mL (p=0.01). Local intraobserver variability was lower on US at the midgland slice (p0.01) but lower on MR at the base (p0.01) and apex (p0.01) slices.US is comparable to MR for preimplant prostate delineation, with no significant difference in volume and dimensions. Rectal indentation because of the transrectal ultrasound probe was measurable, although the effects were small. Intraobserver variability was lower on US for the prostate volume but was lower on MR locally at the base and apex. However, the difference was not observed for the interobserver variability, which was similar between MR and US.

Purpose To estimate the late morbidity of a novel, hypofractionated external beam radiotherapy schedule of 55Gy in 16 fractions (4 fractions/week, 3.4Gy per fraction) for localized prostate cancer. Methods and materials A multi-center phase 2 study enrolled seventy-three patients between September 2004 and June 2006. After insertion of fiducial gold markers, they were treated with image-guidance (IGRT) using conformal techniques with intensity-modulation, if necessary, and then followed every 6months for toxicity rating and PSA. Patient reported outcomes were collected yearly. Median follow up was 4.6years. Results At 4years post-radiotherapy, the cumulative incidence of combined urinary and bowel grade 3 toxicity was 7% (95% CI 3–16%) and grade 2+ was 33% (95% CI 24–46%). All except two patients recovered from their grade 3 events. Patient-reported reduction of function was most pronounced at year two for urinary function (mean −7, SD 16), and at year one for bowel function (mean −7, SD 21). The cumulative incidence of biochemical (PSA nadir+2) or biopsy-proven relapse at 4years was 9% (95% CI 4–18%). Conclusions Hypofractionated radiotherapy is clinically feasible and more convenient than conventional schedules for patients with localized prostate cancer. Phase 3 multicenter studies are on-going (NCT00126165).

The objective of this study is to determine whether there is less contouring variability of the prostate using higher-strength magnetic resonance images (MRI) compared with standard MRI and computed tomography (CT).Forty patients treated with prostate brachytherapy were accrued to a prospective study that included the acquisition of 1.5-T MR and CT images at specified time points. A subset of 10 patients had additional 3.0-T MR images acquired at the same time as their 1.5-T MR scans. Images from each of these patients were contoured by 5 radiation oncologists, with a random subset of patients repeated to quantify intraobserver contouring variability. To minimize bias in contouring the prostate, the image sets were placed in folders in a random order with all identifiers removed from the images.Although there was less interobserver contouring variability in the overall prostate volumes in 1.5-T MRI compared with 3.0-T MRI (p0.01), there was no significant differences in contouring variability in the different regions of the prostate between 1.5-T MRI and 3.0-T MRI. MRI demonstrated significantly less interobserver contouring variability in both 1.5-T and 3.0-T compared with CT in overall prostate volumes (p0.01, p = 0.01), with the greatest benefits being appreciated in the base of the prostate. Overall, there was less intraobserver contouring variability than interobserver contouring variability for all of the measurements analyzed.Use of 3.0-T MRI does not demonstrate a significant improvement in contouring variability compared with 1.5-T MRI, although both magnetic strengths demonstrated less contouring variability compared with CT.

Purpose To quantify the time course of postimplant prostatic edema magnitude and spatial isotropy using serial magnetic resonance imaging (MRI). Methods and Materials Forty patients with histologic diagnosis of prostate cancer received an iodine-125 seed implant (Day 0) and consented to 1.5-T MRI on Days −1, 0, 14, and 28. Seeds of strength 0.39 mCi were placed in a modified peripheral loading pattern to deliver 145 Gy to the target volume. MR images consisted of 3–4 mm thick axial slices with no gap. The image sets were anonymized and randomized to minimize contouring bias, then contoured by a single radiation oncologist. Contours were reoriented about their center of mass to align the prostate long axis with the superior–inferior (S−I) direction; prostate volumes and dimensions in the left–right (L−R), anterior–posterior (A−P), and S−I directions through the center of mass were calculated. Results The average relative edema volume was 1.18 ± 0.14 (1 standard deviation) on Day 0 and 1.01 ± 0.15 on Day 30. Between Days 0 and 30, the edema resolved linearly with time on average. Average relative edema dimensions on Day 0 in the L−R, A−P, and S−I directions were 1.01 ± 0.07, 1.11 ± 0.09, and 1.08 ± 0.13, respectively. Conclusions As measured using MRI, the average edema magnitude for our study population was ∼20% on Day 0 and resolved linearly with time to ∼0% on Day 30. The edema exhibited spatial anisotropy, the prostate expanding on Day 0 by ∼10% in each of the A−P and S−I directions and by ∼0% in the L−R direction.

Purpose A planning study to compare helical tomotherapy (HT) and intensity-modulated radiotherapy (IMRT) for the treatment of anal canal cancer. Materials and methods Sixteen (8 males and 8 females) patients with anal cancer previously treated radically were identified. HT and IMRT plans were generated and dosimetric comparisons of the plans were performed. The planning goals were to deliver 54Gy to the tumor (PTV 54Gy ) and 48Gy to the nodes at risk (PTV Node ) in 30 fractions. Results PTVs: HT plans were more homogeneous for both men and women. Male patients: HT vs. IMRT: D max : 55.87±0.58 vs. 59.17±3.24 ( p =0.036); D min : 52.91±0.36 vs. 44.09±6.84 ( p =0.012); female patients: HT vs. IMRT: D max : 56.14±0.71 vs. 59.47±0.81 ( p =0.012); D min : 52.36±0.87 vs. 50.97±1.42 ( p =0.028). OARs: In general, HT plans delivered a lower dose to the peritoneal cavity, external genitalia and the bladder and IMRT plans resulted in greater sparing of the pelvic bones (iliac crest/femur) for both men and women. Iliac crest/femur: the difference was significant only for the mean V10Gy of iliac crest in women ( p ⩽0.012). External genitalia: HT plans achieved better sparing in women compared to men ( p ⩽0.046). For men, the mean doses were 18.96±3.17 and 15.72±3.21 for the HT and IMRT plan, respectively ( p ⩽0.017). Skin: both techniques achieved comparable sparing of the non-target skin ( p =NS). Conclusions HT and IMRT techniques achieved comparable target dose coverage and organ sparing, whereas HT plans were more homogeneous for both men and women.

Purpose To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients. Methods and Materials Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of ≥T3a or an initial prostate-specific antigen [PSA] level of ≥20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales. Results All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity. Conclusion Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.

Purpose The objective of this study was to survey the use of reirradiation (Re-RT) for in-field failures after previous radical radiation treatment (RT) among Canadian radiation oncologists (ROs). Methods and Materials An electronic survey was sent to 271 ROs in Canada. The completed surveys were received electronically via e-mail and the data were analyzed using SAS 9.1.3 software. Results A total of 183 ROs (67.5%) completed and returned the survey. The majority of the respondents were involved in the practice of either breast (48%) or genitourinary (43%) tumor sites. A total of 49% of the participants were interested in using Re-RT for the management of in-field recurrences. The goals of the therapy would be improvement of quality of life (99%), locoregional control (80%), or cure (32%). Most of the physicians believed that patients should have a minimum Karnofsky performance status of 50 or Eastern Cooperative Oncology Group performance status of 3, a minimum life expectancy of 3 months, and a minimum interval from initial treatment of 3 months if Re-RT were to be given with curative intent. Conclusions This survey showed that a wide variation existed among ROs in their approach to Re-RT. Newer technologies in RT planning and delivery would be employed to facilitate normal tissue avoidance. The results of this study suggested that a consensus meeting was needed to establish guidelines for the practice and prospective evaluation of Re-RT.

LBA5002 Background: High-risk, localized prostate cancer (PCa) patients have a relatively poor prognosis. We hypothesized that the addition of adjuvant docetaxel and prednisone to long-term (24 month) AS and radiation therapy (RT) would improve overall survival (OS). Methods: RTOG 0521 opened December 2005 and closed August 2009 with targeted accrual of 600 cases. It was designed to detect improvement in 4-year OS from 86% to 93% with a 51% hazard reduction (HR = 0.49). Under a 0.05 1-sided type I error and 90% power, at least 78 deaths were required to analyze the OS endpoint. Patients had 1) Gleason (Gl) 7-8, any T-stage, and PSA > 20, or 2) Gl 8, ≥ T2, any PSA, or 3) Gl 9-10, any T-stage, any PSA. All had PSA ≤ 150. RT dose was 75.6 Gy. CT consisted of 6, 21-day cycles of docetaxel + prednisone starting 28 days after RT. Results: Of 612 enrolled, 50 were excluded for eligibility issues, leaving 562 evaluable. Median age = 66, median PSA = 15.1, 53% had Gl 9-10, 27% had cT3-4. Median follow-up = 5.5 yrs. 4-yr OS rates were 89% [95% CI: 84-92%] for the AS+RT arm and 93% [95% CI: 90-96%] for the AS+RT+CT arm (1-sided p = 0.03, HR = 0.68 [95% CI: 0.44, 1.03]). There were 52 centrally-reviewed deaths in the AS+RT arm and 36 in the AS+RT+CT arm, with fewer deaths both due to PCa/treatment (20 vs 16) and due to other causes/unknown (32 vs 20) in the AS+RT+CT arm. 5-yr disease-free survival rates were 66% for AS+RT and 73% for AS+RT+CT (2-sided p = 0.05, HR = 0.76 [95% CI: 0.57, 1.00]). There was 1, Gr 5 unlikely-related adverse event (AE) in the AS+RT arm and 2, Gr 5 possibly/probably-related AEs with AS+RT+CT. Conclusions: For high-risk, localized PCa, adjuvant CT improved the OS from 89% to 93% at 4 years. Toxicity was acceptable. This trial was designed with a short OS assessment period and additional follow-up is warranted to determine the long-term benefit of CT to the current standard of care of long-term AS+RT. This project was supported by grants U10CA21661, U10CA180868, U10CA180822, from the National Cancer Institute and Sanofi with additional support from AstraZeneca for Australian site participation. Clinical trial information: NCT00288080.

Introduction: Active surveillance (AS) is an increasingly popular management strategy for men diagnosed with low-risk indolent prostate cancer. Current tests (prostate-specific antigen [PSA], clinical staging, and prostate biopsies) to monitor indolent disease lack accuracy. 11 C-choline positron emission tomography (PET) has excellent detection rates in local and distant recurrence of prostate cancer. We examine 11 C-choline PET for identifying aggressive prostate cancer warranting treatment in the AS setting. Methods: In total, 24 patients on AS had clinical assessment and PSA testing every 6 months and 11 C-choline PET and prostate biopsies annually. The sensitivity and specificity to identify prostate cancer and progressive disease (PD) were calculated for each 11C-choline PET scan. Results: In total, 62 biopsy-paired, serial 11 C-choline PET scans were analyzed using a series of standard uptake value-maximum (SUVmax) cut-off thresholds. During follow-up (mean 25.3 months), 11 of the 24 low-risk prostate cancer patients developed PD and received definitive treatment. The prostate cancer detection rate with 11 C-choline PET had moderate sensitivity (72.1%), but low specificity (45.0%). PD prediction from baseline 11 C-choline PET had satisfactory sensitivity (81.8%), but low specificity (38.5%). The addition of clinical parameters to the baseline 11 C-choline PET improved specificity (69.2%), with a slight reduction in sensitivity (72.7%) for PD prediction. Conclusions: Addition of 11 C-choline PET imaging during AS may help to identify aggressive disease earlier than traditional methods. However, 11C-choline PET alone has low specificity due to overlap of SUV values with benign pathologies. Triaging low-risk prostate cancer patients into AS versus therapy will require further optimization of PET protocols or consideration of alternative strategies (i.e., magnetic resonance imaging, biomarkers).