Stereotactic Body Radiotherapy for Renal Cell Carcinoma: Oncological and Renal Function Outcomes.

AIMS: To evaluate oncological and renal function outcomes of stereotactic body radiotherapy (SBRT) for medically inoperable patients with localised renal cell carcinoma. MATERIALS AND METHODS: Consecutive patients treated with curative intent SBRT (30-45 Gy in five fractions or 42 Gy in three fractions) were included. Data on local control (Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), distant metastasis, impact on estimated glomerular filtration rate (eGFR) and proportional ipsilateral and contralateral renal functions (measured through renal scans) were collected. Univariate and multivariable analyses were conducted to determine association of variables with oncological and renal function outcomes. RESULTS: Seventy-four patients were analysed. The median follow-up was 27.8 months (interquartile range 17.6-41.7). Fifty-seven per cent had tumours ≥ T1b. One-, 2- and 4-year cumulative incidence of local failure was 5.85, 7.77 and 7.77%, respectively. The cumulative incidence of distant metastasis at 2 years was 4.24%. On multivariable analysis, a lower planning target volume (PTV) mean dose (P = 0.019) and a larger PTV (P = 0.005) were significantly associated with the risk of developing local failure. A lower PTV maximum dose (P = 0.039) was significantly associated with the risk of developing distant metastasis. The median change in global eGFR (ml/min) from pre-SBRT levels was -7.0 (interquartile range -14.5 to -1.0) at 1 year and -11.5 (interquartile range -19.5 to -4.0) at 2 years. The proportion of ipsilateral (differential) renal function decreased over time from 47% of overall renal function pre-SBRT to 36% at 2 years, whereas the proportion of contralateral renal function correspondingly improved. On multivariable analysis, a higher volume of uninvolved renal cortex (P < 0.0001) was significantly associated with a smaller decrease in eGFR over time. CONCLUSION: In this large institutional cohort, oncological outcomes of renal cell carcinoma treated with SBRT were favourable and a longitudinal decline in renal function in the ipsilateral kidney and compensatory increase in the contralateral kidney were observed. Clinical and dosimetric factors were significantly associated with oncological and renal function outcomes.

Cardiac Morbidity Following Chemoradiation in Stage III Non-small Cell Lung Cancer Patients: A Population-Based Cohort Study.

AIMS: To assess the risk of cardiac toxicity following radical radiotherapy in advanced lung cancer patients. MATERIALS AND METHODS: Patients with a diagnosis of stage III non-small cell lung cancer (NSCLC) receiving chemoradiotherapy were extracted from a population-based cohort in Ontario, Canada. The primary outcome of cardiac toxicity, defined as cardiac events or congestive heart failure, was assessed at 1 and 5 years following chemoradiotherapy. Secondary outcomes included overall survival, survival in relationship to post-treatment cardiac events and the effect of radiotherapy technique on cardiac toxicity. RESULTS: In total, 2031 NSCLC patients were included. The cumulative incidence of cardiac toxicity at 5 years was 20.3% (18.4-22.3). The median survival was 13.7 months in NSCLC patients who had a cardiac event post-chemoradiotherapy compared with 23.4 months in those who did not (P = 0.012). There was a trend towards increased cumulative cardiac toxicity (hazard ratio 3.37, P = 0.14) with three-dimensional conformal radiotherapy compared with intensity-modulated or volumetric arc radiotherapy techniques. CONCLUSION: The risk of cardiac events and congestive heart failure 5 years after radical thoracic radiotherapy appears high and survival is inferior at 1 year in those patients who experience a cardiac event post-treatment. More conformal radiotherapy techniques may help reduce cardiac toxicity. Further studies should investigate adaptive treatment planning and close monitoring and intervention in this high-risk group after chemoradiotherapy.

Patient-reported Quality of Life following Stereotactic Body Radiation Therapy for Primary Kidney Cancer - Results from a Prospective Cohort Study.

AIMS: We report on the first prospective series of patient-reported quality of life (QoL) following stereotactic body radiation therapy (SBRT) for primary kidney cancer. MATERIALS AND METHODS: Patients were treated on a multi-institutional prospective cohort study with 30-42 Gy SBRT in three or five fractions. QoL assessments were carried out using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-15 Palliative (EORTC-QLQ-C15-PAL), the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FACT FKSI-19) and the EuroQol-5D-3L tools at baseline, 1 week, and 1, 3 and 6 months post-treatment. QoL over time was analysed using linear mixed modelling, pairwise and anchor-based analyses. RESULTS: Twenty-eight patients were included. No significant reduction in any QoL metric was observed on repeated measures. However, a trend to reduced EORTC global QoL and fatigue was observed at 1 week, with improvement over time in other symptom scores such as pain, appetite and nausea. On pairwise analysis, there were statistically significant reductions in global QoL at 1 week (with subsequent recovery) and dyspnoea at 6 months post-SBRT. Trends to improved pain, appetite and nausea were observed following SBRT. Less than half of patients reported stable or better EORTC global QoL at 1 week. For all other QoL and symptom scales, most patients had reported stable or better scores at all times, with a slight proportional improvement in emotional functioning, nausea, fatigue, pain and appetite, and a slight worsening of physical functioning and dyspnoea over time. CONCLUSIONS: SBRT results in well-preserved QoL in the weeks to months following treatment for primary kidney cancer.

Chest wall toxicity after stereotactic radiation in early lung cancer: a systematic review.

Background: Radiation-induced chest wall pain (cwp) and rib fracture (rf) are late adverse effects after stereotactic body radiation therapy (sbrt) for stage i non-small-cell lung cancer (nsclc); however, the literature about their incidence and risk factors shows variability. We performed a systematic review to determine the pooled incidence of cwp and rf in the relevant population. Methods: A literature search using the prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines considered English publications in medline and embase from January 1996 to August 2017. Abstracts were screened, followed by full-text review and data extraction. Results: The database searches identified 547 records. Twenty-eight publications comprising 3892 patients met the inclusion criteria. Median reported ages and follow-up durations fell into the ranges 67-82 years and 12-84 months. Prescriptions fell into the range of 40-70 Gy in 3-10 fractions. Despite study heterogeneity, the pooled incidences of cwp and rf were estimated to be 8.94% and 5.27% respectively. Nineteen studies reported cwp grade: 58 of 308 patients (18.8%) experienced grades 3-4 cwp (no grade 5 events reported). Thirteen studies reported rf grade: grades 3-4 rf were observed in 9 of 113 patients (7.96%). A high chest wall V30 was an important predictor of cwp and rf. Conclusions: In patients with stage i nsclc, rates of cwp and rf after sbrt are low; however, tumour location, accurate toxicity reporting, and dose-fractionation schemes might alter those rates. Prospective correlation with dosimetry and quality of life assessment will further improve the understanding of cwp and rf after sbrt.

Surgery after chemoradiotherapy in patients with stage III (N2 or N3, excluding T4) non-small-cell lung cancer: a systematic review.

Background: Chemoradiation with curative intent is considered the standard of care in patients with locally advanced, stage iii non-small-cell lung cancer (nsclc). However, some patients with stage iii (N2 or N3, excluding T4) nsclc might be eligible for surgery. The objective of the present systematic review was to investigate the efficacy of surgery after chemoradiotherapy compared with chemoradiotherapy alone in patients with potentially resectable locally advanced nsclc. Methods: A search of the medline, embase, and PubMed databases sought randomized controlled trials (rcts) comparing surgery after chemoradiotherapy with chemoradiotherapy alone in patients with stage iii (N2 or N3, excluding T4) nsclc. Results: Three included rcts consistently found no statistically significant difference in overall survival between patients with locally advanced nsclc who received surgery and chemoradiotherapy or chemoradiotherapy alone. Only one rct found that progression-free survival was significantly longer in patients treated with chemoradiation and surgery (hazard ratio: 0.77; 95% confidence interval: 0.62 to 0.96). In a post hoc analysis of the same trial, the overall survival rate was higher in the surgical group than in matched patients in a chemoradiation-only group if a lobectomy was performed (p = 0.002), but not if a pneumonectomy was performed. Furthermore, fewer treatment-related deaths occurred in patients who underwent lobectomy than in those who underwent pneumonectomy. Conclusions: For patients with locally advanced nsclc, the benefits of surgery after chemoradiation are uncertain. Surgery after chemoradiation for patients who do not require a pneumonectomy might be an option.

MEDiastinal Irradiation and CArdio-Toxic Effects (MEDICATE): Exploring the Relationship between Cardiac Irradiation and High Sensitivity Troponins.

AIMS: Radiation-induced heart disease is a late effect of cardiac irradiation and has been shown in patients with lymphoma and thoracic cancers. There is no established measurement tool to detect acute cardiac damage. However, high sensitivity troponin I and T (HsTnI and HsTnT) and echocardiograms have shown promise in some studies. A pilot trial was conducted to characterise whether these instruments may detect subclinical radiotherapy-induced cardiac damage. MATERIALS AND METHODS: Eligible patients received high cardiac doses defined by either at least 30 Gy to 5% of cardiac volume or a mean dose of 4 Gy. HsTnI and HsTnT were measured before radiotherapy and after 2 and 4 weeks of radiotherapy; three-dimensional echocardiograms were completed before and 1 year after radiotherapy. RESULTS: Of 19 patients, the median 'mean left ventricular dose' was 3.1 Gy and the 'mean cardiac dose' was 8.6 Gy. Significant positive associations between HsTnI and HsTnT were observed at all time points, but there was no significant association with cardiac dose. The mean left ventricular dose and the maximum left ventricular dose were, however, associated with a decrease in ejection fraction (P = 0.054, 0.043) as well as an increase in left ventricular strain (P = 0.058). CONCLUSION: This study suggests that HsTnI and HsTnT are intimately related, but detection of acute cardiac damage was not shown, potentially due to limitations of these markers or low radiotherapy doses using conformal techniques. Our results also suggest subacute damage at 1 year may depend on the dose to the left ventricle. Further studies are needed, as identification of early damage could facilitate the ability to closely monitor and intervene in patients at risk for radiation-induced heart disease.

Identifying barriers to accrual in radiation oncology randomized trials.

BACKGROUND: Data about factors driving accrual to radiation oncology trials are limited. In oncology, 30%-40% of trials are considered unsuccessful, many because of poor accrual. The goal of the present study was to inform the design of future trials by evaluating the effects of institutional, clinician, and patient factors on accrual rates to a randomized radiation oncology trial. METHODS: Investigators participating in sabr-comet (NCT01446744), a randomized phase ii trial open in Canada, Europe, and Australia that is evaluating the role of stereotactic ablative radiotherapy (sabr) in oligometastatic disease, were invited to complete a survey about factors affecting accrual. Institutional ethics approval was obtained. The primary endpoint was the annual accrual rate per institution. Univariable and multivariable linear regression analyses were used to identify factors predictive of annual accrual rates. RESULTS: On univariable linear regression analysis, off-trial availability of sabr (p = 0.014) and equipoise of the referring physician (p = 0.014) were found to be predictive of annual accrual rates. The annual accrual rates were lower when centres offered sabr for oligometastases off-trial (median: 3.7 patients vs. 8.4 patients enrolled) and when referring physicians felt that, compared with having equipoise, sabr was beneficial (median: 4.8 patients vs. 8.4 patients enrolled). Multivariable analysis identified perceived level of equipoise of the referring physician to be predictive of the annual accrual rate (p = 0.023). CONCLUSIONS: The level of equipoise of referring physicians might play a key role in accrual to radiation oncology randomized controlled trials. Efforts to communicate with and educate referring physicians might therefore be beneficial for improving trial accrual rates.

Systematic review with meta-analysis: enteral nutrition therapy for the induction of remission in paediatric Crohn's disease.

BACKGROUND: Despite potential adverse-events in a paediatric population, corticosteroids are used to induce remission in paediatric Crohn's disease. Exclusive enteral nutrition also induces remission, but is infrequently used in the USA because corticosteroids are considered the superior therapy. New data have become available since the publication of the most recent meta-analysis in 2007. AIM: To see if current literature supports the use of EEN versus CS in paediatric populations. METHODS: All studies with comparator arms of exclusive enteral nutrition and an exclusive corticosteroids, with remission clearly defined were identified by searching eight online databases. RESULTS: Of 2795 identified sources, nine studies met our inclusion criteria. Eight of these (n = 451), had data that could be abstracted into our meta-analysis. Exclusive enteral nutrition was as effective as corticosteroids in inducing remission (OR = 1.26 [95% CI 0.77, 2.05]) in paediatric Crohn's disease. There was no difference between Exclusive enteral nutrition and corticosteroids efficacy when comparing newly diagnosed Crohn's (OR = 1.61 [95% CI .87, 2.98]) or relapsed (OR = 0.76 [95% CI .29-1.98]). Intestinal healing was significantly more likely among patients receiving Exclusive enteral nutrition compared to corticosteroids (OR = 4.5 [95% CI 1.64, 12.32]). There was no difference in the frequency of biomarker normalisation including CRP (OR = 0.85 [95% CI .44, 1.67]) and faecal calprotectin (OR 2.79 [95% CI .79-10.90]). CONCLUSIONS: There is no difference in efficacy between exclusive enteral nutrition and corticosteroids in induction of remission in Crohn's disease in a paediatric population. Exploratory analyses suggest that a greater proportion of patients treated with exclusive enteral nutrition achieved mucosal healing.

Comparative survival in patients with brain metastases from non-small-cell lung cancer treated before and after implementation of radiosurgery.

INTRODUCTION: Survival after a diagnosis of brain metastasis in non-small-cell lung cancer (nsclc) is generally poor. We previously reported a median survival of approximately 4 months in a cohort of patients treated with whole-brain radiotherapy (wbrt). Since that time, we implemented a program of stereotactic radiosurgery (srs). In the present study, we examined survival and prognostic factors in a consecutive cohort of patients after the introduction of the srs program. METHODS: Data from a retrospective review of 167 nsclc patients with brain metastasis referred to a tertiary cancer centre during 2010-2012 were compared with data from a prior cohort of 91 patients treated during 2005-2007 ("pre-srs cohort"). RESULTS: Median overall survival from the date of diagnosis of brain metastasis (4.3 months in the srs cohort vs. 3.9 months in the pre-srs cohort, p = 0.74) was not significantly different in the cohorts. The result was similar when the no-treatment group was excluded from the srs cohort. Within the srs cohort only, significant differences is overall survival were observed between treatment groups (srs, wbrt plus srs, wbrt, and no treatment), with improved survival being observed on univariate and multivariate analysis for patients receiving srs compared with patients receiving wbrt alone (p < 0.001). CONCLUSIONS: No improvement in survival was observed for nsclc patients with brain metastases after the implementation of srs. Selected patients (younger age, female sex, good performance status, fewer brain metastases) treated with srs appeared to demonstrate improved survival. However, those observations might also reflect better patient selection for srs or a greater tendency to offer those patients systemic therapy in addition to srs.

Management of small-cell lung cancer with radiotherapy-a pan-Canadian survey of radiation oncologists.

BACKGROUND: The management of small-cell lung cancer (sclc) with radiotherapy (rt) varies, with many treatment regimens having been described in the literature. We created a survey to assess patterns of practice and clinical decision-making in the management of sclc by Canadian radiation oncologists (ros). METHODS: A 35-item survey was sent by e-mail to Canadian ros. The questions investigated the role of rt, the dose and timing of rt, target delineation, and use of prophylactic cranial irradiation (pci) in limited-stage (ls) and extensive-stage (es) sclc. RESULTS: Responses were received from 52 eligible ros. For ls-sclc, staging (98%) and simulation or dosimetric (96%) computed tomography imaging were key determinants of rt suitability. The most common dose and fractionation schedule was 40-45 Gy in 15 once-daily fractions (40%), with elective nodal irradiation performed by 31% of ros. Preferred management of clinical T1/2aN0 sclc favoured primary chemoradiotherapy (64%). For es-sclc, consolidative thoracic rt was frequently offered (88%), with a preferred dose and fractionation schedule of 30 Gy in 10 once-daily fractions (70%). Extrathoracic consolidative rt would not be offered by 23 ros (44%). Prophylactic cranial irradiation was generally offered in ls-sclc (100%) and es-sclc (98%) after response to initial treatment. Performance status, baseline cognition, and pre-pci brain imaging were important patient factors assessed before an offer of pci. CONCLUSIONS: Canadian ros show practice variation in sclc management. Future clinical trials and national treatment guidelines might reduce variability in the treatment of early-stage disease, optimization of dose and targeting in ls-sclc, and definition of suitability for pci or consolidative rt.

The Canadian Association of Radiation Oncology scope of practice guidelines for lung, liver and spine stereotactic body radiotherapy.

AIMS: The Canadian Association of Radiation Oncology-Stereotactic Body Radiotherapy (CARO-SBRT) Task Force was established in 2010. The aim was to define the scope of practice guidelines for the profession to ensure safe practice specific for the most common sites of lung, liver and spine SBRT. MATERIALS AND METHODS: A group of Canadian SBRT experts were charged by our national radiation oncology organisation (CARO) to define the basic principles and technologies for SBRT practice, to propose the minimum technological requirements for safe practice with a focus on simulation and image guidance and to outline procedural considerations for radiation oncology departments to consider when establishing an SBRT programme. RESULTS: We recognised that SBRT should be considered as a specific programme within a radiation department, and we provide a definition of SBRT according to a Canadian consensus. We outlined the basic requirements for safe simulation as they pertain to spine, lung and liver tumours, and the fundamentals of image guidance. The roles of the radiation oncologist, medical physicist and dosimetrist have been detailed such that we strongly recommend the development of SBRT-specific teams. Quality assurance is a key programmatic aspect for safe SBRT practice, and we outline the basic principles of appropriate quality assurance specific to SBRT. CONCLUSION: This CARO scope of practice guideline for SBRT is specific to liver, lung and spine tumours. The task force recommendations are designed to assist departments in establishing safe and robust SBRT programmes.

Sci-Thur AM: Planning - 06: Planning target volume margin suitability in lung stereotactic body radiation therapy: A preliminary evaluation using cone-beam computed tomography.

Stereotactic body radiation therapy (SBRT) requires precise delivery of radiation to the target; intra- and inter-fraction lung tumour motion may adversely impact local tumour control. The purpose of this study was to retrospectively evaluate the impact of planning target volume (PTV) margin size on the coverage of the internal target volume (ITV) as localized in pre- and post-treatment cone-beam computed tomography (CBCT) images. Data from two patients undergoing SBRT were evaluated. For planning, free-breathing and 4DCT scans were performed, and used to contour the ITV. A 5mm margin was added to create the PTV. During treatment, 14 CBCTs were collected pre- and post-beam delivery. A data set comprising the average 4DCT intensities where available and treatment planning CT intensities for voxels that were beyond the field of view of the 4DCT was constructed. Registration of the combined planning image to each CBCT was performed using a deformable image registration algorithm. The transformations aligning the combined planning image with the CBCTs were applied to the planning ITV to obtain the treatment ITVs. For each CBCT, the fraction of treatment ITV within the PTV was determined using Boolean logic. This was repeated for various PTV margins ranging from 0 to 10 mm at 1mm intervals. The 3 and 5 mm PTV margins covered 95.1 ± 5.9% and 99.0 ± 2.0% of the ITV, respectively. Analysis of additional patients will be performed to confirm these preliminary results, which reinforce the use of a 5mm PTV margin for lung SBRT.

Use of video capsule endoscopy in Crohn's disease.

Capsule endoscopy has been available since 2001 to image the small intestine, a boon to practitioners managing patients with inflammatory bowel disease. During the last ten years, new technologies have been developed, including computed tomographic enterography, magnetic resonance enterography, in addition to our standard small bowel follow through, all of which image the small bowel. This has created a situation in which multiple options are available to the gastroenterologist to image the small bowel, each with strengths. This review focuses on capsule endoscopy as it pertains to the imaging of the small bowel in patients with known or suspected Crohn's disease. We will focus on comparative imaging data, how capsule endoscopy may aid in the prediction of disease type and course, the avoidance and meaning of capsule retention, along with cost considerations, and directions for the future.

Radiotherapy for oncologic emergencies on weekends: examining reasons for treatment and patterns of practice at a Canadian cancer centre.

PURPOSE: Radiotherapy for oncologic emergencies is an important aspect of the management of cancer patients. These emergencies-which include malignant spinal cord compression, brain metastases, superior vena cava obstruction, and uncontrolled tumour hemorrhage -may require treatment outside of hospital hours, particularly on weekends and hospital holidays. To date, there remains no consensus among radiation oncologists regarding the indications and appropriateness of radiotherapy treatment on weekends, and treatment decisions remain largely subjective. The main aim of the present study was to document the incidence and indications for patients receiving emergency treatment on weekends or scheduled hospital holidays at a single institution. The secondary aim was to investigate the compliance of such treatment with the institution's quality assurance policies, both local and provincial. METHODS: From September 1, 2002, to September 30, 2004, patients being treated over weekends (defined as commencing at 6 pm on a Friday and concluding at 8 am of the next scheduled workday) and hospital holidays were retrospectively identified using the Oncology Patient Information System scheduling module. Relevant patient data-including patient age, sex, primary cancer site, specific radiation field, rationale for treatment, referring hospital, total treatment dose, radiation dose fractionation, inpatient or outpatient status, and duration of treatment-were collected and subsequently analyzed. Comparison to local policy was performed subjectively. RESULTS: Over the 2-year period, 161 patients were prescribed urgent radiotherapy over a weekend or on a hospital holiday. Of this cohort, 68% were treated on both Saturday and Sunday, 22% on Saturday alone, and 10% on Sunday alone. Most patients presented with lung (31%), prostate (18%), and breast cancer (17%). The top reasons for referral for emergency weekend treatment included spinal cord compression (56%), brain metastases (15%), and superior vena cava obstruction (6%). Most of the indications for treatment generally followed the quality assurance policies implemented both locally and provincially. CONCLUSIONS: Patients treated over a weekend or on a hospital holiday were generally found to be treated with appropriate intent. Most treatment indications within this study both complied with provincial policy and showed a pattern of care similar to that seen in other studies in the literature. Local policy appears to be robust; however, policy improvements may allow for more cohesiveness across radiation oncologists in patterns of care in this important group of patients. Comparisons with practice at other institutions would be valuable and also a key step in developing sound guidelines for all members of the radiotherapy community to follow.