Assessment of genetic referrals and outcomes for women with triple negative breast cancer in regional cancer centres in Australia.

BACKGROUND: Guidelines for referral to cancer genetics service for women diagnosed with triple negative breast cancer have changed over time. This study was conducted to assess the changing referral patterns and outcomes for women diagnosed with triple negative breast cancer across three regional cancer centres during the years 2014-2018. METHODS: Following ethical approval, a retrospective electronic medical record review was performed to identify those women diagnosed with triple negative breast cancer, and whether they were referred to a genetics service and if so, the outcome of that genetics assessment and/or genetic testing. RESULTS: There were 2441 women with newly diagnosed breast cancer seen at our cancer services during the years 2014-2018, of whom 237 women were diagnosed with triple negative breast cancer. Based on age of diagnosis criteria alone, 13% (31/237) of our cohort fulfilled criteria for genetic testing, with 81% (25/31) being referred to a cancer genetics service. Of this group 68% (21/31) were referred to genetics services within our regions and went on to have genetic testing with 10 pathogenic variants identified; 5x BRCA1, 4x BRCA2 and × 1 ATM:c.7271 T > G. CONCLUSIONS: Referral pathways for women diagnosed with TNBC to cancer genetics services are performing well across our cancer centres. We identified a group of women who did not meet eligibility criteria for referral at their time of diagnosis, but would now be eligible, as guidelines have changed. The use of cross-discipline retrospective data reviews is a useful tool to identify patients who could benefit from being re-contacted over time for an updated cancer genetics assessment.

A critical literature review on the use of bellyboard devices to control small bowel dose for pelvic radiotherapy.

Delivering curative radiotherapy doses for rectal and gynaecological tumours has historically been complicated by the dose tolerance of the small bowel. Acute radiation-induced small bowel toxicity includes side effects such as abdominal pain, nausea and diarrhoea. With the advent of new treatment delivery modalities, such as IMRT (Intensity modulated radiotherapy) and VMAT (Volumetric modulated Arc radiotherapy), there has been an expectation that small bowel doses can be better controlled with the use of these technologies. These capabilities enable the creation of treatment plans that can better avoid critical radiosensitive organs. The purpose of this review is to look beyond advances in linear accelerator technology in seeking improvements to small bowel dose and toxicity. This review examines whether an alternative prone patient positioning approach using a bellyboard device in conjunction with IMRT and VMAT treatment delivery can reduce small bowel doses further than using these technologies with the patient in a traditional supine position.

Application of an incident taxonomy for radiation therapy: Analysis of five years of data from three integrated cancer centres.

AIM: To develop and apply a clinical incident taxonomy for radiation therapy. BACKGROUND: Capturing clinical incident information that focuses on near-miss events is critical for achieving higher levels of safety and reliability. METHODS AND MATERIALS: A clinical incident taxonomy for radiation therapy was established; coding categories were prescription, consent, simulation, voluming, dosimetry, treatment, bolus, shielding, imaging, quality assurance and coordination of care. The taxonomy was applied to all clinical incidents occurring at three integrated cancer centres for the years 2011-2015. Incidents were managed locally, audited and feedback disseminated to all centres. RESULTS: Across the five years the total incident rate (per 100 courses) was 8.54; the radiotherapy-specific coded rate was 6.71. The rate of true adverse events (unintended treatment and potential patient harm) was 1.06. Adverse events, where no harm was identified, occurred at a rate of 2.76 per 100 courses. Despite workload increases, overall and actual rates both exhibited downward trends over the 5-year period. The taxonomy captured previously unidentified quality assurance failures; centre-specific issues that contributed to variations in incident trends were also identified. CONCLUSIONS: The application of a taxonomy developed for radiation therapy enhances incident investigation and facilitates strategic interventions. The practice appears to be effective in our institution and contributes to the safety culture. The ratio of near miss to actual incidents could serve as a possible measure of incident reporting culture and could be incorporated into large scale incident reporting systems.

Women's Preferences for Hypofractionated Radiation Therapy for Treatment of Early-Stage Breast Cancer: A Discrete Choice Experiment.

PURPOSE: The primary treatment recommended for early-stage breast cancer is breast conserving surgery followed by external beam radiation therapy of the whole breast. Previously, radiation therapy for early-stage breast cancer was given using more fractions over longer durations. Guidelines support treatments with fewer fractions over a shorter time (hypofractionated radiation therapy). This study aimed to understand women's preferences for different features of treatments for early-stage breast cancer. METHODS AND MATERIALS: A discrete choice experiment with 12 choice tasks was conducted, describing the treatments by extent of surgery, duration of radiation treatment, need to relocate for treatment, local side effects, changes in breast appearance, costs, and difficulty with daily activities during and after treatment. Participants were women with breast cancer and from the general population. Mixed logit analyses were conducted and trade-offs between attributes estimated. RESULTS: Four hundred twenty respondents completed the discrete choice experiment. The relative importance of attributes varied by respondent characteristics; the most influential attribute for younger women was type of surgery (breast conserving surgery). Type of surgery did not influence older women's preferences. Shorter treatment duration, avoiding relocation, fewer local side effects, and less difficulty with daily activities all positively influenced treatment preference. Younger women were willing to accept 32 to 40 days of radiation treatment before a treatment that included mastectomy was potentially acceptable. CONCLUSIONS: Attributes of treatment such as duration, need for relocation, side effects, and effects on normal daily activities during and after treatment significantly influenced women's preference for treatment, including surgery. Our findings have the potential for real impact for patients and services including supporting one-on-one clinical discussions, supporting program and patient resource development, and informing service funding, organization, and delivery.

Clinical evaluation of deep learning and atlas-based auto-segmentation for critical organs at risk in radiation therapy.

INTRODUCTION: Contouring organs at risk (OARs) is a time-intensive task that is a critical part of radiation therapy. Atlas-based automatic segmentation has shown some success at reducing this time burden on practitioners; however, this method often requires significant manual editing to reach a clinically accurate standard. Deep learning (DL) auto-segmentation has recently emerged as a promising solution. This study compares the accuracy of DL and atlas-based auto-segmentation in relation to clinical 'gold standard' reference contours. METHODS: Ninety CT datasets (30 head and neck, 30 thoracic, 30 pelvic) were automatically contoured using both atlas and DL segmentation techniques. Sixteen critical OARs were then quantitatively measured for accuracy using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). Qualitative analysis was performed to visually classify the accuracy of each structure into one of four explicitly defined categories. Additionally, the time to edit atlas and DL contours to a clinically acceptable level was recorded for a subset of 9 OARs. RESULTS: Of the 16 OARs analysed, DL delivered statistically significant improvements over atlas segmentation in 13 OARs measured with DSC, 12 OARs measured with HD, and 12 OARs measured qualitatively. The mean editing time for the subset of DL contours was 50%, 23% and 61% faster (all P < 0.05) than that of atlas segmentation for the head and neck, thorax, and pelvis respectively. CONCLUSIONS: Deep learning segmentation comprehensively outperformed atlas-based contouring for the majority of evaluated OARs. Improvements were observed in geometric accuracy and visual acceptability, while editing time was reduced leading to increased workflow efficiency.

SABR for Early Non-Small Cell Lung Cancer: Changes in Pulmonary Function, Dyspnea, and Quality of Life.

PURPOSE: The aim of this study was to report pulmonary function tests (PFTs) and clinician-reported and patient-reported quality-of-life (QoL) outcomes on a cohort of patients with non-small cell lung cancer (NSCLC) treated with SABR. METHODS AND MATERIALS: A total of 119 patients with NSCLC were treated with SABR in the prospective cohort SSBROC study of patients with T1-T2N0M0 NSCLC. PFTs and QoL measures were obtained at baseline pretreatment and at 6-month intervals. Here we report on the 6- to 18-month time points. Analysis of covariance (ANCOVA) methods adjusting for baseline analyzed potential predictors on outcomes of PFTs and patient-reported dyspnea at 18 months. RESULTS: The only statistically significant decline in PFTs was seen in forced expiratory volume in 1 second (FEV1) at 18 months post-SABR, with a decline of -0.11 L (P = .0087; 95% CI, -0.18 to -0.02). Of potential predictors of decline, only a 1-unit increase in smoking pack-years resulted in a -0.12 change in diffusing capacity for carbon monoxide (P = .026; 95% CI, -0.02 to -0.23) and a 0.003 decrease in FEV1 (P = .026; 95% CI, -0.006 to -0.0004). For patient-reported outcomes, statistically significant worsening in both the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (QLQ-C30 Version 3) and the lung module (QLQ-LC13) dyspnea scores occurred at the 18-month time point, but not earlier. No potential predictors of worsening dyspnea were statistically significant. There was no statistically significant decline in clinician-reported outcomes or global QoL scores. CONCLUSIONS: We found a statistically significant decline in FEV1 at 18 months posttreatment. Smoking pack-years was a predictor for decline in diffusing capacity for carbon monoxide and FEV1 at 18 months. Worsening of patient-reported dyspnea scores was observed, consistent with the expected progression of lung comorbid disease.

Metaplastic carcinoma of the breast: Clinicopathological features and treatment outcomes with long-term follow up.

Metaplastic breast carcinoma is an uncommon subtype of invasive ductal carcinoma with a tendency towards poorer clinical outcomes. Following ethical approval, the current study reviewed the institutional records of ~2,500 women with breast cancer. A total of 14 cases of metaplastic breast cancer were reviewed for management and treatment outcomes. The results demonstrated that patients had median follow up of 30 months, a 5-year disease-free survival of 57.1% and 5-year overall survival of 57.1%. The majority of patients had at least T2 disease and all tumours were high grade. Additionally, most patients were triple negative and nodal metastases were uncommon. Metaplastic breast cancer is an aggressive variant of invasive breast cancer. Most patients can be treated with breast conservation and survival parameters tend to be worse than more common breast cancer subtypes.

Long-term outcomes of patients with conserved breast cancer treated with adjuvant hypofractionated prone breast intensity-modulated radiation therapy.

INTRODUCTION: New techniques for adjuvant radiation therapy after breast conservation include prone positioning, hypofractionation and intensity-modulated radiation therapy (IMRT). Long-term evaluations of this combination are lacking, and we report our own experience. METHODS: Patients with invasive breast cancer followed for a minimum 36 months post-IMRT were eligible. Dose used was 40 Gray in 15 fractions over 3 weeks to the whole breast via forward-planned prone, whole breast IMRT. A 10 Gy in 5 fraction supine boost was offered. RESULTS: Between January 2012 and January 2020, 2199 patients had breast conservation and adjuvant radiation: 489 received hypofractionated prone breast IMRT, with 155 eligible for our evaluation. Median follow-up was 52 months. Median age was 62 (range 36-80), 78.7% were T1, 20.6% were T2, and 12.3% were node-positive. Grade was 1 in 26.5%, 2 in 43.9% and 3 in 29.7%; 87.1% were oestrogen receptor positive, 3.2% were HER2 positive, and 11.0% were triple negative. 58.6% received a boost, 74.8% endocrine therapy and 32.3% chemotherapy. No patient developed local recurrence. One regional recurrence was successfully salvaged. Six patients (3.9%) developed metastases, and 1.9% died. Five-year actuarial local recurrence-free, regional recurrence-free and breast cancer-specific survival rates were 100.0%, 98.2% and 94.8%. Late grade 1 and 2 breast pain occurred in 20.0% and 1.3% of patients. Only 11.0% had new pain compared to pre-radiation. No patient developed radiation-induced pneumonitis, pulmonary fibrosis, rib fracture or cardiac toxicity. All patients scored cosmesis as 'good' or better. CONCLUSION: Adjuvant hypofractionated prone breast IMRT has excellent locoregional control and minimal toxicity.

Collaborative implementation of stereotactic ablative body radiotherapy: A model for the safe implementation of complex radiotherapy techniques in Australia.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) for lung cancer is a modality of treatment that has improved outcomes for lung cancer patients. However, radiotherapy for lung cancer is underutilized and fewer than half of elderly patients with non-small cell lung cancer (NSCLC) receive active treatment. The purpose of this study is to report on a collaboration in implementing an NSCLC SABR (stereotactic ablative body radiation) program safely, efficiently, and uniformly across several centers, including regional sites. The first aim of this paper is to detail the collaboration and implementation that started in 2013 and is ongoing. The second aim of this paper is to document early toxicities and quality of life outcomes. METHOD: A tripartite approach was used to develop the protocol and networks required for the implementation of SABR across multiple sites in NSW. Departments starting the programmes were supported and physics credentialing with central site submission was required before commencing the treatment. Additional ongoing support was available via an email discussion group involving all members of the collaboration. RESULTS: Between July 22, 2013 and February 22, 2016, 41 patients were enrolled with 34 patients in active follow up. The toxicity profile so far is similar to those of published studies with no appreciable effect on quality of life outcomes. CONCLUSION: The collaboration formed an effective framework in facilitating the implementation of SABR across several sites in NSW and could be used as a model for the safe and uniform implementation of new technologies in Australia.

Toxicity after post-prostatectomy image-guided intensity-modulated radiotherapy using Australian guidelines.

INTRODUCTION: We evaluated single institution toxicity outcomes after post-prostatectomy radiotherapy (PPRT) via image-guided intensity-modulated radiation therapy (IG-IMRT) with implanted fiducial markers following national eviQ guidelines, for which late toxicity outcomes have not been published. METHODS: Prospectively collected toxicity data were retrospectively reviewed for 293 men who underwent 64-66 Gy IG-IMRT to the prostate bed between 2007 and 2015. RESULTS: Median follow-up after PPRT was 39 months. Baseline grade ≥2 genitourinary (GU), gastrointestinal (GI) and sexual toxicities were 20.5%, 2.7% and 43.7%, respectively, reflecting ongoing toxicity after radical prostatectomy. Incidence of new (compared to baseline) acute grade ≥2 GU and GI toxicity was 5.8% and 10.6%, respectively. New late grade ≥2 GU, GI and sexual toxicity occurred in 19.1%, 4.7% and 20.2%, respectively. However, many patients also experienced improvements in toxicities. For this reason, prevalence of grade ≥2 GU, GI and sexual toxicities 4 years after PPRT was similar to or lower than baseline (21.7%, 2.6% and 17.4%, respectively). There were no grade ≥4 toxicities. CONCLUSIONS: Post-prostatectomy IG-IMRT using Australian contouring guidelines appears to have tolerable acute and late toxicity. The 4-year prevalence of grade ≥2 GU and GI toxicity was virtually unchanged compared to baseline, and sexual toxicity improved over baseline. This should reassure radiation oncologists following these guidelines. Late toxicity rates of surgery and PPRT are higher than following definitive IG-IMRT, and this should be taken into account if patients are considering surgery and likely to require PPRT.

Tangential intensity modulated radiation therapy (IMRT) to the intact breast.

INTRODUCTION: Inverse-planned intensity modulated radiation therapy (IP-IMRT) has potential benefits over other techniques for tangential intact breast radiotherapy. Possible benefits include increased homogeneity, faster planning time, less inter-planner variability and lower doses to organs at risk (OAR). We therefore conducted a pilot study of previously treated intact breast patients to compare the current forward-planned 'field-in-field' technique (FP-IMRT) with an IP-IMRT alternative. METHODS: The IP-IMRT plans of 20 patients were generated from a template created for the planning system. All patients were prescribed adjuvant whole breast radiotherapy using a hypofractionated regimen of 40.05 Gy in 15 fractions over 3 weeks. Plans were assessed based on visual inspection of coverage as well as statistical analysis and compared to the clinically acceptable FP-IMRT plans. Patients were planned retrospectively in Monaco 3.2® using a laterality-specific, tangential planning template. Minor adjustments were made as necessary to meet the planning criteria in the protocol. Dose coverage, maximums, homogeneity indices and doses to OAR were recorded. RESULTS: The IP-IMRT plans provided more consistent coverage (38.18 Gy vs. 36.08 Gy of D95; P = 0.005), a comparable though higher average maximum (D2 = 42.52 Gy vs. 42.08 Gy; P = 0.0001), more homogeneous plans (homogeneity index = 0.908 vs. 0.861; P = 0.01) and somewhat lower V20 heart and lung doses (0.11% vs. 0.89% for heart; 5.4% vs. 7.52% for lung) than FP-IMRT (P > 0.05). CONCLUSION: Clinically acceptable plans have been generated using the IP-IMRT templates in Monaco. Improvements in consistency and quality were seen when compared to the FP-IMRT plans. The template-based process is an efficient method to inversely plan IMRT for breast patients.

Toxicity and dosimetric analysis of non-small cell lung cancer patients undergoing radiotherapy with 4DCT and image-guided intensity modulated radiotherapy: a regional centre's experience.

INTRODUCTION: For patients receiving radiotherapy for locally advance non-small cell lung cancer (NSCLC), the probability of experiencing severe radiation pneumonitis (RP) appears to rise with an increase in radiation received by the lungs. Intensity modulated radiotherapy (IMRT) provides the ability to reduce planned doses to healthy organs at risk (OAR) and can potentially reduce treatment-related side effects. This study reports toxicity outcomes and provides a dosimetric comparison with three-dimensional conformal radiotherapy (3DCRT). METHODS: Thirty curative NSCLC patients received radiotherapy using four-dimensional computed tomography and five-field IMRT. All were assessed for early and late toxicity using common terminology criteria for adverse events. All plans were subsequently re-planned using 3DCRT to the same standard as the clinical plans. Dosimetric parameters for lungs, oesophagus, heart and conformity were recorded for comparison between the two techniques. RESULTS: IMRT plans achieved improved high-dose conformity and reduced OAR doses including lung volumes irradiated to 5-20 Gy. One case each of oesophagitis and erythema (3%) were the only Grade 3 toxicities. Rates of Grade 2 oesophagitis were 40%. No cases of Grade 3 RP were recorded and Grade 2 RP rates were as low as 3%. CONCLUSION: IMRT provides a dosimetric benefit when compared to 3DCRT. While the clinical benefit appears to increase with increasing target size and increasing complexity, IMRT appears preferential to 3DCRT in the treatment of NSCLC.

Definitive intensity-modulated radiotherapy concurrent with systemic therapy for oropharyngeal squamous cell carcinoma: Outcomes from an integrated regional Australian cancer centre.

INTRODUCTION: Oropharyngeal squamous cell carcinoma (OPSCC) incidence has increased over the past two decades largely because of an increase in human papilloma virus (HPV)-related OPSCC. We report here outcomes of definitive radiation therapy for OPSCC with simultaneous integrated boost intensity-modulated radiotherapy (IMRT) in a regional Australian cancer centre. METHODS: We retrospectively reviewed electronic medical records (EMR) of all patients treated with IMRT for head and neck cancer. We included patients who received a curative intent IMRT for OPSCC (2010-2014). RESULTS: Of 61 patients, 80% were men, and the median age was 57 years. Ninety percent of our patients received concurrent systemic therapy, and 68% were p16 positive. The median radiotherapy dose received was 70 Gy in 35 fractions. The median follow up for surviving patients was 22 months. Twenty-four month actuarial data show that the loco-regional recurrence free, metastasis-free MFS, cancer-specific (CaSS) and overall survival percentages were 98.3%, 92.6%, 91% and 90.3%, respectively. We did not observe grades 4 or 5 acute or late toxicities, and 10 patients (16.2%) exhibited persistent grade 3 toxicity 6 months after completing the treatment. CONCLUSION: The results from curative IMRTs for OPSCC delivered in a regional cancer centre are comparable with results published by tertiary referral centres. A long-term follow up of this patient cohort will continue for further analyses and comparisons with tertiary centres.

Use of hypofractionated post-mastectomy radiotherapy reduces health costs by over $2000 per patient: An Australian perspective.

INTRODUCTION: The most recent clinical practice guidelines released by Cancer Australia draw attention to unanswered questions concerning the health economic considerations associated with hypofractionated radiotherapy. This study aimed to quantify and compare the healthcare costs at a regional Australian radiotherapy institute with respect to conventionally fractionated post-mastectomy radiotherapy (Cf-PMRT) versus hypofractionated post-mastectomy radiotherapy (Hf-PMRT) administration. METHODS: Medical records of 196 patients treated with post-mastectomy radiotherapy at the NSW North Coast Cancer Institute from February 2008 to June 2014 were retrospectively reviewed. Australian Medicare item numbers billed for patients receiving either Cf-PMRT of 50 Gy in 25 daily fractions or Hf-PMRT of 40.05 Gy in 15 daily fractions were calculated. Decision tree analysis was used to model costs. Independent-samples t-tests and Mann-Whitney U-tests were used to compare crude average costs for Cf-PMRT and Hf-PMRT and determine which treatment components accounted for any differences. RESULTS: Hf-PMRT, with or without irradiation to the regional lymph nodes, was associated with significantly reduced Medicare costs ($5613 AUD per patient for Hf-PMRT vs $8272 AUD per patient for Cf-PMRT; P < 0.001). Savings associated with Hf-PMRT ranged from $1353 (22.1%) for patients receiving no regional irradiation to $2898 (32.0%) for patients receiving both axillary and supraclavicular therapy. CONCLUSIONS: Hf-PMRT results in a significant reduction in the financial costs associated with treating breast cancer patients in a regional Australian setting when compared with Cf-PMRT.

Regional cancer centre demonstrates voluntary conformity with the national Radiation Oncology Practice Standards.

Radiation Oncology Practice Standards have been developed over the last 10 years and were published for use in Australia in 2011. Although the majority of the radiation oncology community supports the implementation of the standards, there has been no mechanism for uniform assessment or governance. North Coast Cancer Institute's public radiation oncology service is provided across three main service centres on the north coast of NSW. With a strong focus on quality management, we embraced the opportunity to demonstrate conformity with the Radiation Oncology Practice Standards. The Local Health District's Clinical Governance units were engaged to perform assessments of our conformity with the standards and this was signed off as complete on 16 December 2013. The process of demonstrating conformity with the Radiation Oncology Practice Standards has enhanced the culture of quality in our centres. We have demonstrated that self-assessment utilising trained auditors is a viable method for centres to demonstrate conformity. National implementation of the Radiation Oncology Practice Standards will benefit individual centres and the broader radiation oncology community to improve the service delivered to our patients.

Is modern external beam radiotherapy with androgen deprivation therapy still a viable alternative for prostate cancer in an era of robotic surgery and brachytherapy: a comparison of Australian series.

INTRODUCTION: We compare the results of modern external-beam radiotherapy (EBRT), using combined androgen deprivation and dose-escalated intensity-modulated radiotherapy with MRI-CT fusion and daily image guidance with fiducial markers (DE-IG-IMRT), with recently published Australian series of brachytherapy and surgery. METHODS: Five-year actuarial biochemical disease-free survival (bDFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCaSS) were calculated for 675 patients treated with DE-IG-IMRT and androgen deprivation therapy (ADT). Patients had intermediate-risk (IR) and high-risk (HR) disease. A search was conducted identifying Australian reports from 2005 onwards of IR and HR patients treated with surgery or brachytherapy, reporting actuarial outcomes at 3 years or later. RESULTS: With a median follow-up of 59 months, our 5-year bDFS was 93.3% overall: 95.5% for IR and 91.3% for HR disease. MFS was 96.9% overall (99.0% IR, 94.9% HR), and PCaSS was 98.8% overall (100% IR, 97.7% HR). Prevalence of Grade 2 genitourinary and gastrointestinal toxicity at 5 years was 1.3% and 1.6%, with 0.3% Grade 3 genitourinary toxicity and no Grade 3 gastrointestinal toxicity. Eight reports of brachytherapy and surgery were identified. The HDR brachytherapy series' median 5-year bDFS was 82.5%, MFS 90.0% and PCaSS 97.9%. One surgical series reported 5-year bDFS of 65.5% for HR patients. One LDR series reported 5-year bDFS of 85% for IR patients. CONCLUSIONS: Modern EBRT is at least as effective as modern Australian surgical and brachytherapy techniques. All patients considering treatment for localised prostate cancer should be referred to a radiation oncologist to discuss EBRT as an equivalent option.

Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer.

PURPOSE: Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. METHODS AND MATERIALS: Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. RESULTS: Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. CONCLUSION: There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses and compares favorably with published series for the treatment of prostate cancer.

Improved outcomes with intensity modulated radiation therapy combined with temozolomide for newly diagnosed glioblastoma multiforme.

Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

Statin use and asthma control in patients with severe asthma.

OBJECTIVES: We hypothesised that severe asthmatics taking a statin drug, in addition to inhaled corticosteroids/long-acting ß-agonist inhaler therapy, would have better asthma symptom control and improved lung function compared to their controls. STUDY DESIGN: A retrospective, cross-sectional study of 165 patients with severe asthma seen from 2001-2008. Hierarchical linear and logistic regression models were used for modelling fitting. SETTING: University of California, Davis Medical Center (Sacramento, California, USA). Academic, single-centre, severe asthma subspecialty clinic. PARTICIPANTS: 612 screened, 223 eligible and 165 adult patients were included in the final study (N=165; 31 statin users and 134 non-users). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was asthma control as measured by the Asthma Control Test (ACT). The secondary endpoints included lung function, symptoms and the need for corticosteroid burst and peripheral eosinophil count. RESULTS: At baseline, statin users compared to non-users were older, had lower lung function (FEV1% predicted, FEV1, forced vital capacity and FEF25-75%) and had a higher prevalence of comorbid conditions. Statin use was associated with more aspirin and ipratropium inhaler use than in non-users. Patients in both groups were obese (body mass index ≥ 30). Statin users had better asthma symptom control compared to non-users (higher adjusted mean ACT score by 2.2±0.94 points, p<0.02). Median statin use was for 1 year. There were no statistically significant differences in lung function, corticosteroid or rescue bronchodilator use or peripheral eosinophilia between the two groups. CONCLUSIONS: In our severe asthma referral population, statin users already taking inhaled controller therapy achieved better asthma control compared to non-users. The implications of this study is that patients with severe asthma could potentially benefit from added statin treatment. Because our study population was on average obese, the obese severe asthmatic may be a viable asthma subphenotype for further studies. Prospective randomised clinical trials evaluating the safety and efficacy of statins in severe asthma are warranted.

Decision regret in men undergoing dose-escalated radiation therapy for prostate cancer.

PURPOSE: Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. METHODS AND MATERIALS: We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. RESULTS: There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). CONCLUSION: Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery.