Oxaliplatin-related dysphagia: Mixed-methods study.

OBJECTIVES: To evaluate participant-reported atypical dysphagia symptoms and their association with oxaliplatin treatment. METHODS: This observational study recruited 73 adults with solid tumours outside the head, neck or upper gastrointestinal tract. All had dysphagia, were in hospital or hospice and were treated by Medical Oncology, Radiation Oncology or Palliative Care. Participants reported their experiences of swallowing difficulties by semistructured interview. Oral Health Assessment Tool was used to ensure swallow difficulties were not due to mucositis. Responses were transcribed and analysed by content analysis. Atypical difficulties were examined for association with oxaliplatin treatment by Fischer's Exact. RESULTS: Oxaliplatin treatment was associated with three unusual dysphagia symptoms: problems with cold or hot bolus (p=0.01), pins and needles (p=0.001) and throat spasm (p=0.035). Carbonation was problematic for one participant. Chemotherapy commencement coincided with swallow problem onset for 67%. Dysphagia symptoms were unrelated to mucositis (p=0.165). CONCLUSIONS: Swallowing difficulties in oxaliplatin-treated patients are atypical and attributable to chemotherapy commencement. Previous research suggests that dysphagia is triggered by cold exposure, but hot and carbonated boluses also caused problems here. Dysphagia symptoms and triggers should be studied more fully to help patients safely enjoy their meals and prevent food avoidance, which could exacerbate malnutrition.

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma.

PURPOSE: The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. PATIENTS AND METHODS: All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). RESULTS: IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively). CONCLUSION: Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.

A strategy to reduce fraction number in peripheral lung stereotactic ablative body radiotherapy.

Background and purpose: Hypo-fractionated lung Stereotactic Ablative Body Radiotherapy (SABR) has often been avoided when tumours are close to the chest wall. Our strategic objective was the reduction of fraction number, while maintaining target biological effective dose coverage without increasing chest wall toxicity (CWT) predictors. Materials and methods: Twenty previously treated lung SABR patients were stratified into four cohorts according to distance from PTV to the chest wall, <1 cm, <0.5 cm, overlapping up to 0.5 cm and 1.0 cm. For each patient, four plans were created; a chest wall optimised plan for 54 Gy in 3 fractions, the clinical plan re-prescribed for 55 Gy in 5, 48 Gy in 3 and 45 Gy in 3 fractions. Results: For a PTV distance of 0.5-0.0 cm, a reduction of the median (range) Dmax from 55.7 (57.5-54.1) Gy to 40.0 (37.1-42.0 Gy) Gy was observed for the chest wall optimised plans. The median V30Gy decreased from 18.9 (9.7-25.6) cm3 to 3.1 (1.8-4.5) cm3. For a PTV overlap of up to 0.5 cm, the Dmax reduced from 66.5 (64.1-70) Gy to 53.2 (50.6-55.1) Gy. The V30Gy decreased from 21.5 (16.5-29.5) cm3 to 14.9 (11.3-20.2) cm3. For the cohort with up to 1.0 cm overlap, there was a reduction in Dmax values of 9.9 Gy. The V30Gy for clinical plans, at 66.8 (18.7-188.8) cm3, decreased to 55.3 (15.5-149) cm3. Conclusion: When PTVs are within 0.5 cm of chest wall, lung SABR dose heterogeneity can be used to reduce fraction number without increasing CWT predictors.

Efficacy and toxicity of primary re-irradiation for malignant spinal cord compression based on radiobiological modelling: a phase II clinical trial.

BACKGROUND: The efficacy and safety of primary re-irradiation for MSCC are not known. Our aim was to establish the efficacy and safety of biologically effective dose-based re-irradiation. METHODS: Patients presenting with MSCC at a previously irradiated spine segment, and not proceeding with surgical decompression, were eligible. A 3 Gray per fraction experimental schedule (minimum 18 Gy/6 fractions, maximum 30 Gy/10 fractions) was used, delivering a maximum cumulative spinal dose of 100 Gy2 if the interval since the last radiotherapy was within 6 months, or 130 Gy2 if longer. The primary outcome was a change in mobility from week 1 to week 5 post-treatment, as assessed by the Tomita score. The RTOG SOMA score was used to screen for spinal toxicity, and an MRI performed to assess for radiation-induced myelopathy (RIM). RESULTS: Twenty-two patients were enroled, of whom eleven were evaluable for the primary outcome. Nine of eleven (81.8%) had stable or improved Tomita scores at 5 weeks. One of eight (12.5%) evaluable for late toxicity developed RIM. CONCLUSIONS: Re-irradiation is an efficacious treatment for MSCC. There is a risk of RIM with a cumulative dose of 120 Gy2. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland (ICORG 07-11); NCT00974168.

Interobserver Variability of Gross Tumor Volume Delineation for Colorectal Liver Metastases Using Computed Tomography and Magnetic Resonance Imaging.

Purpose: The purpose of this study was to evaluate the interobserver variability in the contouring of the gross tumor volume (GTV) on magnetic resonance (MR) imaging and computed tomography (CT) for colorectal liver metastases in the setting of SABR. Methods and Materials: Three expert radiation oncologists contoured 10 GTV volumes on 3 MR imaging sequences and on the CT image data set. Three metrics were chosen to evaluate the interobserver variability: the conformity index, the DICE coefficient, and the maximum Hausdorff distance (HDmax). Statistical analysis of the results was performed using a 1-sided permutation test. Results: For all 3 metrics, the MR liver acquisition volume acquisition (MR LAVA) showed the lowest interobserver variability. Analysis showed a significant difference (P < .01) in the mean DICE, an overlap metric, for MR LAVA (0.82) and CT (0.74). The HDmax that highlights boundary errors also showed a significant difference (P = .04) with MR LAVA having a lower mean HDmax (7.2 mm) compared with CT (5.7 mm). The mean HDmax for both MR single shot fast spin echo (SSFSE) (19.3 mm) and diffusion weighted image (9.5 mm) showed large interobserver variability with MR SSFSE having a mean HDmax of 19.3 mm. A volume comparison between MR LAVA and CT showed a significantly higher volume for small GTVs (<5 cm3) when using MR LAVA for contouring in comparison to CT. Conclusions: This study reported the lowest interobserver variability for the MR LAVA, thus indicating the benefit of using MR to complement CT when contouring GTV for colorectal liver metastases.

Dysphagia in Solid Tumors Outside the Head, Neck or Upper GI Tract: Clinical Characteristics.

CONTEXT: Dysphagia is common in cancer, but underlying pathophysiology and manifestations within patients are unknown. OBJECTIVES: To examine dysphagia characteristics in those with solid malignancies outside the head, neck and upper gastrointestinal tract. METHODS: Seventy-three individuals with dysphagia (46 male, 27 female, aged 37-91) were recruited from a parent trial conducted in two acute hospitals and one hospice. Cranial nerve function, Oral Health Assessment Tool (OHAT), Mann Assessment of Swallowing Ability (MASA) and Functional Oral Intake Scale (FOIS) evaluated swallow profile. RESULTS: Only 9/73 (12%) had documented dysphagia prior to study enrollment. MASA risk ratings found n=61/73 (84%) with dysphagia risk and n=22/73 (30%) with aspiration risk. Food texture modification was required for n=34/73 (47%), fluid texture modification for n=1/73 (1%). Compensatory strategies for food were needed by n=13/73 (18%) and for fluids by n=24/73 (33%). Cranial nerve deficits were present in n=43/73 (59%). Oral health problems were common, with xerostomia in two-thirds. Worse dysphagia on MASA was associated with disease progression, affecting hospice, and palliative care the most. Worse performance status was indicative of poorer MASA raw score (P<0.001, OR 2.2, 95% CI 1.5-3.4), greater risk of aspiration (P=0.005, OR 2.1, 95% CI 1.3-3.6) and lower FOIS (P=0.004, OR 2.0, 95% CI 1.2-3.2). CONCLUSION: Dysphagia management in those with cancer requires robust assessment to uncover clinically important needs like food texture modification and safe swallowing advice. Better assessment tools should be developed for this purpose. Oral health problems should be routinely screened in this population since they exacerbate dysphagia.

Radium-223 in combination with enzalutamide in metastatic castration-resistant prostate cancer: a multi-centre, phase II open-label study.

BACKGROUND: Radium-223 and enzalutamide are approved agents for patients with metastatic castration-resistant prostate cancer (mCRPC). Combining radium-223 and enzalutamide to improve outcomes is of clinical interest due to their differing modes of action and non-overlapping toxicity profiles. METHODS: This phase II study enrolled patients with mCRPC and bone metastases. Patients received six cycles of radium-223 in combination with enzalutamide, followed by enzalutamide alone. The primary endpoint was safety for the combination; secondary endpoints included radiographic/clinical progression-free survival (PFS), PSA PFS, overall survival (OS), change in alkaline phosphatase, patient-reported pain outcomes and skeletal related events. RESULTS: Forty-five patients received the combination treatment: 42 patients (93.3%) received all six cycles. Fourteen patients (31.1%) developed grade 3 or 4 toxicities, most commonly fatigue and neutropaenia. Fractures during the combination period occurred in four patients (8.9%). A further 13 patients (28.9%) developed fractures after completing combination treatment, giving a total of 17 patients (37.8%) who developed a fracture at any time on study. The median time to fracture was greater than 17.2 months [95% confidence interval (CI), 17.2-not estimable]. The median time to PSA progression was 18.1 months (95% CI, 12.68-22.60) and the median time to radiological/clinical progression was 28.0 months (95% CI, 22.54-not reached). At the primary analysis, 19 (42.2%) out of 45 patients had died with a median OS not reached (mean 34.8 months, standard error 1.4). CONCLUSION: In men with progressive mCRPC and bone metastases, the combination of radium-223 and enzalutamide was tolerable with the majority of patients completing the combination treatment. Bone fractures during the combination period were uncommon; however, we did identify a higher incidence of fractures occurring in patients after completing combination treatment. Bone health agents should be administered and bone health should be closely monitored following treatment with radium-223 and enzalutamide.

Individual patient data meta-analysis of neoadjuvant chemotherapy followed by surgery versus upfront surgery for carcinoma of the oesophagus or the gastro-oesophageal junction.

INTRODUCTION: Which neoadjuvant treatment for locally advanced thoracic oesophagus (TE) or gastro-oesophageal junction carcinoma is best remains an open question. Randomised controlled trials variously accrued patients with adenocarcinoma and squamous cell carcinoma, making strong conclusions hard to obtain. The primary objective of this individual participant data meta-analysis was to investigate the effect of neoadjuvant chemotherapy on overall survival (OS). PATIENTS AND METHODS: Eligible trials should have closed to accrual before 2016 and compared neoadjuvant chemotherapy and surgery (CS) to surgery alone. All relevant published and unpublished trials were identified via searches of electronic databases, conference proceedings and clinical trial registers. The main end-point was OS. Investigators were contacted to obtain the individual patient data, which was recorded, harmonised and checked. A random-effects Cox model, stratified by trial, was used for meta-analysis and subgroup analyses were preplanned. RESULTS: 16 trials were identified as eligible. Individual patient data were obtained from 12 trial and 2478 patients. CS was associated with an improved OS versus surgery, hazard ratio (HR) = 0.83 [0.72-0.96], p < 0.0001, translating to an absolute benefit of 5.7% at 5-years from 16.8% to 22.5%. Treatment effects did not vary substantially between adenocarcinoma (HR = 0.73 [0.62-0.87]) and squamous cell carcinoma (HR = 0.91 [0.76-1.08], interaction p = 0.26). A somewhat more pronounced effect was observed in gastro-oesophageal junction (HR = 0.68 [0.50-0.93]) versus TE (HR = 0.87 [0.75-1.00], interaction p = 0.07). CS was also associated with a greater disease-free survival (HR = 0.74 [0.64-0.85], p < 0.001). CONCLUSIONS: Neoadjuvant chemotherapy conferred a better OS than surgery alone and should be considered in all anatomical location and histological subtypes.

Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression.

BACKGROUND: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome. METHODS: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = 'Walk unaided', 2 = 'With walking aid' and 3 = 'Bed-bound'. The margin used to establish non-inferiority was a detrimental change of -0.4 in the mean difference between arms. RESULTS: One-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30-87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was -0.12 to 0.6. Since -0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2-3 AE compared with six (11%) patients in the SF arm (p = 0.093). CONCLUSION: For mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.

Dosimetric impact of uncorrected systematic yaw rotation in VMAT for peripheral lung SABR.

AIM: This study aimed to evaluate the dosimetric impact of uncorrected yaw rotational error on both target coverage and OAR dose metrics in this patient population. BACKGROUND: Rotational set up errors can be difficult to correct in lung VMAT SABR treatments, and may lead to a change in planned dose distributions. MATERIALS AND METHODS: We retrospectively applied systematic yaw rotational errors in 1° degree increments up to -5° and +5° degrees in 16 VMAT SABR plans. The impact on PTV and OARs (oesophagus, spinal canal, heart, airway, chest wall, brachial plexus, lung) was evaluated using a variety of dose metrics. Changes were assessed in relation to percentage deviation from approved planned dose at 0 degrees. RESULTS: Target coverage was largely unaffected with the largest mean and maximum percentage difference being 1.4% and 6% respectively to PTV D98% at +5 degrees yaw.Impact on OARs was varied. Minimal impact was observed in oesophagus, spinal canal, chest wall or lung dose metrics. Larger variations were observed in the heart, airway and brachial plexus. The largest mean and maximum percentage differences being 20.77% and 311% respectively at -5 degrees yaw to airway D0.1cc, however, the clinical impact was negligible as these variations were observed in metrics with minimal initial doses. CONCLUSIONS: No clinically unacceptable changes to dose metrics were observed in this patient cohort but large percentage deviations from approved dose metrics in OARs were noted. OARs with associated PRV structures appear more robust to uncorrected rotational error.

Dysphagia Prevalence and Predictors in Cancers Outside the Head, Neck, and Upper Gastrointestinal Tract.

CONTEXT: Dysphagia is usually associated with malignancies of the head, neck, and upper gastrointestinal tract but also occurs in those with tumors outside anatomic swallow regions. It can lead to aspiration pneumonia, malnutrition, reduced quality of life, and psychosocial distress. No studies have yet reliably described dysphagia prevalence in those with malignancies outside anatomic swallow regions. OBJECTIVE: The objective of this study was to establish the prevalence and predictors of dysphagia in adults with solid malignancies outside the head, neck, and upper gastrointestinal tract. METHODS: A cross-sectional, observational study using consecutive sampling was conducted. There were 385 participants (mean age 66 ± 12 years) with 21 different primary cancer sites from two acute hospitals and one hospice. Locoregional disease was present in 33%, metastatic in 67%. Dysphagia was screened by empirical questionnaire and confirmed through swallow evaluation. Demographic and clinical predictors were determined by univariate and multivariate binary regression. RESULTS: Dysphagia occurred in 19% of those with malignancies outside anatomic swallow regions. Prevalence was 30% in palliative care and 32% in hospice care. Dysphagia was most strongly associated with cough, nausea, and worse performance status. It was also associated with lower quality of life and nutritional difficulties. CONCLUSION: Dysphagia was common and usually undiagnosed before study participation. It occurred at all disease stages but coincided with functional decline. It may therefore represent a cancer frailty marker. Oncology and palliative care services should routinely screen for this symptom. Timely dysphagia identification and management may improve patient well-being and prevent adverse effects like aspiration pneumonia and weight loss.

Linac-Based Radiosurgery for Patients With Brain Oligometastases From a Breast Primary, in the Trastuzumab Era-Impact of Tumor Phenotype and Prescribed SRS Dose.

Background: The role of stereotactic radiosurgery (SRS) in the treatment of limited numbers of brain metastases in selected breast cancer patients is well-established. Aims: To analyse outcome from a single institutional experience with SRS, to identify any significant prognostic factors and to assess the influence of Her-2, estrogen receptor status, and prescribed dose on outcome. Methods: The medical records of 56 patients treated at in a single institution between 2009 and 2014 were reviewed. Demographic, treatment related and outcome data were analyzed to identify prognostic factors in this patient population. The primary endpoints were overall survival and local control. Secondary endpoint was distant intra-cranial progression-free survival. Results: The median follow- up time for the entire cohort was 10.33 months (1.25-97.28). The overall median survival was 12.5months (95%CI = 5.8-19.2), with 53.3%, and 35.8% surviving at 1- and 2- years post-SRS. After adjustment for the effect of Her 2 status, uncontrolled extra-cranial disease at the time of SRS predicted for shorter survival (HR for death = 3.1, 95% CI = 1.4-6.9, p = 0.006). At the time of death, 75% of the patients had active, uncontrolled intra-cranial disease, with 56% these patients presenting intra-cranial disease only. Sustained local control was observed in 56 (59.6%) of 94 treated metastases. In univariate analysis, Her2 status, ERHer2 group status?, and prescribed SRS dose were highly significant for local progression free-survival (LPFS). After adjustment for the effect of Her 2 status, patients receiving 12-16 Gy can expect shorter LPFS than those receiving 18-20 Gy (HR = 1.7, 95% CI = 1.0-2.8, p = 0.043). After adjustment for the effect of dose group, patients with Her 2 negative cancer can expect shorter LPFS than those with Her 2 positive cancer (HR = 2.6, 95% CI = 1.5-4.4, p < 0.0005). Use of prior WBRT did not impact survival, local or distant intra-cranial progression-free survival. Conclusions: Survival outcome is similar to the published literature. Improved outcomes are observed in patients with Her 2-positive, controlled extracranial disease at the time of SRS and higher SRS dose delivered. Achieving intra-cranial control appears to be an important factor for the survival of the breast cancer patients in the era of targeted therapies.

ICORG 06-35: a prospective evaluation of PET-CT scan in patients with non-operable or non-resectable non-small cell lung cancer treated by radical 3-dimensional conformal radiation therapy: a phase II study.

BACKGROUND: Radiotherapy (RT) is a key treatment modality in the curative treatment of patients with non-small cell lung cancer (NSCLC). Incorrect definition of the gross, or clinical, target volume is a common source of error which can lead to a reduced probability of tumour control. OBJECTIVE: This was a pilot and a phase II study. The pilot evaluated the technical feasibility of integrating positron emission tomography-computed tomography (PET-CT) fusion. The primary outcome of the phase II study was to evaluate the safety of PET-CT scan-based RT by evaluating the rate of loco-regional recurrence outside the PET-CT planning target volume (PTV) but within conventional 3-D PTV. METHODS: Patients underwent standard post-treatment follow-up, including repeated three monthly CT scans of the thorax. In case of loco-regional recurrence, three categories were considered, with only extra-PET scan PTV and intra-CT scan PTV recurrences considered as a failure. Our hypothesis was that the rate of these events would be < 10%. RESULTS: Twelve patients were recruited; the study closed early due to poor recruitment. The primary endpoint of the pilot was met; it was feasible to deliver a PET-CT-based plan to ≥ 60% of patients. Two patients had intra-PET scan PTV recurrences, six had extra-PET scan PTV and extra-CT, and three patients had both. Another patient had extra-PET scan PTV and extra-CT as well as extra-PET scan PTV and intra-CT scan PTV recurrence. CONCLUSION/ADVANCES IN KNOWLEDGE: PET-based planning has the potential to reduce radiation treatment volumes because of the avoidance of mediastinal lymph nodes that are PET negative.

Treatment completion, treatment compliance and outcomes of old and very old patients treated by dose adapted stereotactic ablative radiotherapy (SABR) for T1-T3N0M0 non-small cell lung cancer.

AIM: This is a retrospective single-institution review of the treatment completion and clinical outcomes of patients aged 75 and older, treated with stereotactic ablative body radiotherapy (SABR) for T1-T3 N0 M0 non-small cell lung cancer (NSCLC). METHODS: From April 2008 to September 2015, 200 patients, aged 75-93, received respiratory-managed, intensity-modulated-based SABR. Dose fractionation was risk-adapted and delivered in 2-3 weekly treatments. Treatment completion, local control, overall survival and treatment-related toxicities were evaluated. RESULTS: All patients completed the prescribed SABR course. However, 29 patients required interruption of at least one fraction of SABR and optimization of pain control before continuation of the fraction. Median follow-up was 20.9 months. The median OS was 31.6 months with 1-,3-year survival rates of 80.7%, and 44.4% respectively. Local control at 1- and 3- years were 97.6%, 83.5% respectively. Treatment was well-tolerated. However, there were two (1%) G5 (fatal) toxicities: one acute sudden dyspnoea of unknown cause and one late SABR-related haemoptysis. No statistically significant differences in outcomes/toxicities were observed between old (75-84 years old) and very old patients (>85 years old). CONCLUSIONS: Old and very old patients can successfully complete SABR for NSCLC, with good local control, survival and acceptable toxicity. Old patients might require increased supportive care for successful treatment delivery.

A comparison of bladder volumes based on treatment planning CT and BladderScan® BVI 6100 ultrasound device in a prostate radiation therapy population.

OBJECTIVE:: The aim of this study is to investigate if a handheld ultrasound device (BladderScan® BVI 6100) can accurately measure bladder volumes in prostate radiotherapy (RT) patients. METHODS:: A comparison was made of contoured bladder volumes based on treatment planning CT (TPCT) and BladderScan® BVI 6100 ultrasound device in a large prostate RT population. Three bladder volume (BV) measurements were taken using the bladder volume instrument (BVI) device on prostate RT patients immediately prior to TPCT (n = 190). The CT delineation bladder volumes were also recorded. The mean of the three BVI readings (BVImean) and the maximum (BVImax) of the readings were considered for a comparative analysis. RESULTS:: There was a strong positive correlation between the BVI and CT delineated bladder volumes (BVImean r = 0.825; BVImax r = 0.830). The mean difference [± standard deviation (SD)] was an underestimation of BV for both BVImean and BVImax (44.8 ± 88.2 ml and 32.9 ± 87.5 ml, respectively). CONCLUSION:: This is the largest study to date (n = 190), assessing the accuracy of the BladderScan® BVI 6100 in the prostate RT population. The BVI 6100 provides an acceptable indication of BV for use in prostate RT patients for the purposes of monitoring BV. ADVANCES IN KNOWLEDGE:: The BladderScan® BVI 6100 provides a convenient and non-irradiating method of indicating BV for use in prostate RT patients.

Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer.

TITLE: Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer. NCT01176487. BACKGROUND & PURPOSE: Trials of radiation therapy for the palliation of intra-thoracic symptoms from locally advanced non-small cell lung cancer (NSCLC) have concentrated on optimising fractionation and dose schedules. In these trials, the rates of oesophagitis induced by this "palliative" therapy have been unacceptably high. In contrast, this non-randomised, single-arm trial was designed to assess if more technically advanced treatment techniques would result in equivalent symptom relief and reduce the side-effect of symptomatic oesophagitis. MATERIALS & METHODS: Thirty-five evaluable patients with symptomatic locally advanced or metastatic NSCLC were treated using a three-dimensional conformal technique (3-DCRT) and standardised dose regimens of 39 Gy in 13 fractions, 20 Gy in 5 fractions or 17 Gy in 2 fractions. Treatment plans sought to minimise oesophageal dose. Oesophagitis was recorded during treatment, at two weeks, one month and three months following radiation therapy and 3-6 monthly thereafter. Mean dose to the irradiated oesophagus was calculated for all treatment plans. RESULTS: Five patients (14%) had experienced grade 2 oesophagitis or dysphagia or both during treatment and 2 other patients had these side effects at the 2-week follow-up. At follow-up of one month after therapy, there was no grade two or higher oesophagitis or dysphagia reported. 22 patients were eligible for assessment of late toxicity. Five of these patients reported oesophagitis or dysphagia (one had grade 3 dysphagia, two had grade 2 oesophagitis, one of whom also had grade 2 dysphagia). Quality of Life (QoL) data at baseline and at 1-month follow up were available for 20 patients. At 1-month post radiation therapy, these patients had slightly less trouble taking a short walk, less shortness of breath, did not feel as weak, had better appetite and generally had a better overall quality of life than they did at baseline. They did report being slightly more tired. CONCLUSIONS: This trial is the first of its kind showing that 3-DCRT provides patients with lower rates of oesophageal toxicity whilst yielding acceptable rates of symptom control. (Sponsored by Cancer Trials Ireland (ICORG) Study number 06-34, the Friends of St. Luke's and the St. Luke's Institute of Cancer Research.).

Heterogeneity in high-risk prostate cancer treated with high-dose radiation therapy and androgen deprivation therapy.

BACKGROUND: Our aim was to assess the heterogeneity of high-risk (HR) prostate cancer managed with high-dose external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT). METHODS: We identified 547 patients who were treated with modern EBRT from 1997 to 2013, of whom 98% received ADT. We analyzed biochemical relapse-free survival (bRFS) and distant metastases-free survival (DMFS). RESULTS: Median EBRT dose was 74 Gy, and median ADT duration was 8 months. At 5 years, the DMFS was 85%. On multivariate analysis, significant predictors of shorter bRFS were biopsy Gleason score (bGS) of 8 to 10, higher prostate-specific antigen (PSA) level, shorter duration of ADT and lower radiation dose while predictors of shorter DMFS were bGS of 8 to 10, higher PSA level, and lower radiation dose. We identified an unfavorable high-risk (UHR) group of with 2-3 HR factors based on 2015 National Comprehensive Cancer Network (NCCN) criteria and a favorable high-risk (FHR) group, with 1 HR feature. Comparing very-HR prostate cancer, UHR & FHR, 5 year bRFS rates were 58.2%, 66.2%, and 69.2%, and 5 year DMFS rates were 78.4%, 81.2%, and 88.0%. CONCLUSION: Patients with multiple HR factors have worse outcome than patients with 1 HR factor. Future studies should account for this heterogeneity in HR prostate cancer.

Patients with colorectal lung oligometastases (L-OMD) treated by dose adapted SABR at diagnosis of oligometastatic disease have better outcomes than patients previously treated for their metastatic disease.

AIM: To evaluate the clinical outcomes of patients with OMD from a CRC primary, who underwent SABR either as first treatment at diagnosis of metachronous oligometastatic disease to lung or at progression in lung after prior treatments for metastatic disease. METHODS: This is a retrospective review of 60 patients with 85 lung oligometastases treated by SABR at two institutions, between May 2009 and September 2014. Local control (LC), overall survival (OS), progression - free survival (PFS), and toxicity were evaluated. RESULTS: Median follow-up was 22.9±15.5 months (range: 2.6-68.6). For the entire cohort, LC was observed for 76.6% of the target lesions; the 2- year OS and PFS were 77% and 28 % respectively. After a median of 7.9 months from SABR, 39 patients presented a first progression. In univariate analysis, patients with multiple recurrences prior to SABR (p=0.001) and those who received chemotherapy for metastatic progression (p=0.014) had poorer PFS from time of SABR. Median PFS for patients with no prior treatment for L-OMD vs. prior chemotherapy +/- local treatment vs. local treatment only was: not reached vs. 8.83 (± 2) vs. 32.5 (±2.75) months. The main pattern of first progression was out of field progression: in-field progression alone occurred in 7 patients (12%) and with synchronous regional/distant progression in 10 patients (17%. In all patients, chemotherapy was withheld until progression post-SABR. Treatment was well tolerated; only one patient experienced grade 3 bronchial toxicity, three months after completion of SABR. CONCLUSIONS: SABR achieves high rates of local control with limited toxicities in patients with lung oligometastatic disease from a colorectal primary. This retrospective data indicates that patients with newly diagnosed lung oligometastatic disease may be safely treated with SABR as first treatment, with chemotherapy held in reserve. In heavily pretreated patients, SABR may allow patients a treatment break from systemic therapy, which may be beneficial both psychologically and physically. Future randomized SABR studies should evaluate sequencing of chemotherapy, the role of immunotherapies, and the quality of life of patients undergoing SABR.

A randomized trial comparing bladder volume consistency during fractionated prostate radiation therapy.

PURPOSE: Organ motion is a contributory factor to the variation in location of the prostate and organs at risk during a course of fractionated prostate radiation therapy (RT). A prospective randomized controlled trial was designed with the primary endpoint to provide evidence-based bladder-filling instructions to achieve a consistent bladder volume (BV) and thus reduce the bladder-related organ motion. The secondary endpoints were to assess the incidence of acute and late genitourinary (GU) and gastrointestinal (GI) toxicity for patients and patients' satisfaction with the bladder-filling instructions. METHODS AND MATERIALS: One hundred ten patients were randomly assigned to 1 of 2 bladder-filling protocols; 540 mL (3 cups) of water or 1080 mL (6 cups) of water, in a single institution trial. A portable ultrasound device, BladderScan BVI 6400 (Verathon Inc, Bothell, WA), measured BVs at treatment planning computed tomography (TPCT) scan and 3 times per week during RT. Maximum bladder dose and BV receiving ≥ 50, 60, and 70 Gy were recorded. Acute and late GU and GI toxicity were evaluated, as were patients' comfort, perception of urinary symptoms, and quality of life (QoL). RESULTS: There was significantly less BV variation in the 540 mL arm when compared with 1080 mL (median: 76 mL vs 105 mL, P = .003). Larger BVs on initial TPCT correlated with larger BV variations during RT (P < .0005). There were no statistically significant associations between arm and GU/GI toxicity, dose median comfort scores, or median QoL scores. CONCLUSIONS: The 540 mL bladder-filling arm resulted in reproducible BVs throughout a course of RT, without any deterioration in QoL or increase in toxicities for prostate patients.

Temporal patterns of late bowel and bladder radiotherapy toxicity in a randomised controlled trial assessing duration of neo-adjuvant hormones in prostate cancer.

BACKGROUND: To assess the temporal patterns of late gastrointestinal (GI) and genitourinary (GU) radiotherapy toxicity and resolution rates in a randomised controlled trial (All-Ireland Cooperative Oncology Research Group 97-01) assessing duration of neo-adjuvant (NA) hormone therapy for localised prostate cancer. MATERIAL AND METHODS: Node negative patients with > 1 of: PSA > 20 ng/mL, Gleason score ≥ 7, and stage T3 or more, were included. Follow-up, including toxicity assessment, was three-monthly in the early stages and yearly thereafter. RESULTS: Median follow-up from the end of RT was 6.8 years. In the interval between 90 days following the end of RT and the last toxicity assessment, GI and GU toxicity (any grade) was found in 50% and 51% of 240 and 241 patients, respectively. For those who did develop toxicity, the median time from end of RT until the first development of any grade GI or GU toxicity was 1.2 years and 1.6 years, respectively, whilst median time to final resolution was 1.6 years and 2.2 years, respectively. Grade 2 (G2) or greater GI and GU toxicity occurred in 29 (12.1%) and 40 (16.6%) patients, respectively. The proportion with unresolved G2 + GI and GU toxicity was 89% and 79%, respectively, in year 1, 69% and 65% in year 2, 59% and 52% in year 3 and 27% and 32% in year 5. CONCLUSION: Long-term toxicities continue to occur many years after NA hormone therapy and RT. The rate of occurrence does not appear to reduce within the time frame during which our patients were followed. The percentage of patients suffering from G2 + toxicity at any time is however low. Resolution of these toxicities continues for the duration of the follow-up.