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.

Outcomes and toxicities in oligometastatic patients treated with stereotactic body radiotherapy for adrenal gland metastases: A multi-institutional retrospective study.

BACKGROUND: Studies reporting SBRT outcomes in oligometastatic patients with adrenal gland metastases (AGM) are limited. Herein, we present a multi-institutional analysis of oligometastatic patients treated with SBRT for AGM. MATERIAL/METHODS: The Consortium for Oligometastases Research (CORE) is among the largest retrospective series of patients with oligometastases. Among CORE patients, those treated with SBRT for AGM were included. Clinical and dosimetric data were collected. Adrenal metastatic burden (AMB) was defined as the sum of all adrenal GTV if more than one oligometastases is present.Competing risk analysis was used to estimate actuarial cumulative local recurrence (LR) and widespread progression (WP). Kaplan-Meier method was used to report overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). Treatment related toxicities were also reported. RESULTS: The analysis included 47 patients with 57 adrenal lesions. Median follow-up was 18.2 months. Median LRFS, PFS, and OS were 15.3, 5.3, and 19.1 months, respectively. A minimum PTV dose BED10 > 46 Gy was associated with an improved OS and LRFS. A prescribed BED10 > 70 Gy was an independent predictor of a lower LR probability. AMB>10 cc was an independent predictor of a lower risk for WP. Only one patient developed an acute Grade 3 toxicity consisting of abdominal pain. CONCLUSION: SBRT to AGM achieved a satisfactory local control and OS in oligometastatic patients. High minimum PTV dose and BED10 prescription doses were predictive of improved LR and OS, respectively. Prospective studies are needed to determine comprehensive criteria for patients SBRT eligibility and dosimetric planning.

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.

Production of N2 and N2 O from nitrate ingested by sheep.

Supplementing ruminants with nitrate (NO3-) reduces their enteric methane (CH4 ) emissions; however, the greenhouse gas (GHG) mitigation achieved can be partially offset by small emissions of nitrous oxide (N2 O), a more potent GHG. Sheep were dosed intraruminally with 15 NO3- to investigate whether dietary NO3- is a precursor of N2 O and/or di-nitrogen gas (N2 ), and to quantify the amounts of NO3- recovered as N2 O and N2 in gas emissions from sheep adapted or not adapted to dietary NO3-. Ruminally cannulated sheep were adapted to a hay diet supplemented with NO3- (n = 3; 10 g NO3-/kg DM) or urea (n = 3; 5.3 g urea/kg DM). On the day of the experiment all sheep were dosed intraruminally with 15 NO3- and quickly moved into gas-tight chambers to enable recovery of 15 N in N2 O and N2 to be measured. Measurements of gases accumulating in the chambers were made over 10 successive 50 min periods; this enabled the amount of N2 O produced, and the recovery of 15 NO3--N in N2 O and N2 to be determined over a total of 10 hr. Only 0.04% of labelled NO3--N was recovered as N2 O, and this was not dependent (p > .05) on whether or not the animals had been adapted to dietary NO3-. Approximatively 3% of 15 NO3--N was recovered as 15 N2 , which was also not dependent (p > .05) on whether sheep had been adapted to NO3-. Because the kinetics of rumen ammonia (NH3 ) were uncertain, the recovery of 15 N from NO3- in rumen NH3 could not accurately be quantified, but our results suggest that approximately 76% of dietary NO3- was converted to NH3 in the rumen. We conclude that the small amount of NO3- recovered in N2 was evidence of denitrification, previously thought not to occur in the rumen.

Quantifying Health Utilities in Patients Undergoing Stereotactic Body Radiation Treatment for Liver Metastases for Use in Future Economic Evaluations.

AIM: Stereotactic body radiation therapy (SBRT) is increasingly used as an option for those with liver metastases. In order to facilitate future economic impact of health technologies, health utility scores may be used. The EuroQOL-5D-3L (EQ-5D) preference-based healthy utility instrument was used to evaluate the impact of treatment with SBRT on health utility scores. MATERIALS AND METHODS: Between August 2013 and October 2014, 31 patients treated with 3-5 fractions of SBRT for liver metastases were enrolled in this study. The EQ-5D instrument was administered at baseline, during and up to 6 months post-SBRT. RESULTS: Mean EQ-5D score at baseline was 0.857, which remained stable across the entire study time period. Transient increases in difficulties with mobility (9.7% reported at baseline to 16.1% on the last day of treatment) and usual activities (3.2% reported at baseline to 34.5% on day two) were found during the course of treatment; these returned to baseline levels subsequently. The mean visual analogue score at baseline was 65.8 and remained unchanged throughout treatment and follow-up. CONCLUSIONS: The stability of health utility scores and problems reported by patients undergoing treatment indicate that SBRT for liver metastases does not impart a significant adverse effect on quality of life. These results may be used for future economic evaluation of SBRT.

Stereotactic Ablative Body Radiotherapy for Primary Renal Cell Carcinoma in Non-surgical Candidates: Initial Clinical Experience.

AIMS: To report the outcomes of a cohort of patients with renal cell carcinoma (RCC) treated using stereotactic ablative body radiotherapy (SABR). MATERIALS AND METHODS: Patients treated with SABR for primary RCC from 1 January 2012 to 1 April 2015 were retrospectively reviewed. Patients were non-surgical candidates treated with doses ranging from 30 to 40 Gy in five fractions. The tumour sizes and serum creatinine were compared between the pre-treatment assessment and subsequent follow-up assessments. The worst acute and late grade ≥2 toxicity rates were recorded. RESULTS: In total, 16 patients were included in this study. The median follow-up was 19 months (range 7-30). Eleven patients had stable disease, four had partial responses and none had progressive disease, indicating a local control rate of 100%. One patient had grade 2 acute nausea and two patients had grade 4 renal toxicities (two patients with pre-existing stage 4-5 chronic kidney disease required dialysis following SABR). Four of four patients with pre-SABR symptoms (pain and/or haematuria) had symptomatic relief after SABR. CONCLUSION: SABR for RCC is safe, the toxicities are minimal, and the local control is excellent at early follow-up. This technique should be further evaluated in prospective clinical trials.

Predictors of Chest Wall Toxicity after Lung Stereotactic Ablative Radiotherapy.

AIMS: To determine the incidence and predictive factors of rib fracture and chest wall pain after lung stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: Patients were treated with lung SABR of 48-60 Gy in four to five fractions. The treatment plan and follow-up computed tomography scans of 289 tumours in 239 patients were reviewed. Dose-volume histogram (DVH) metrics and clinical factors were evaluated as potential predictors of chest wall toxicity. RESULTS: The median follow-up was 21.0 months (range 6.2-52.1). Seventeen per cent (50/289) developed a rib fracture, 44% (22/50) were symptomatic; the median time to fracture was 16.4 months. On univariate analysis, female gender, osteoporosis, tumours adjacent (within 5 mm) to the chest wall and all of the chest wall DVH metrics predicted for rib fracture, but only tumour location adjacent to the chest wall remained significant on the multivariate model (P < 0.01). The 2 year fracture-free probability for those adjacent to the chest wall was 65.6%. Among those tumours adjacent to the chest wall, only osteoporosis (P = 0.02) predicted for fracture, whereas none of the chest wall DVH metrics were predictive. Eight per cent (24/289) experienced chest wall pain without fracture. CONCLUSIONS: None of the chest wall DVH metrics independently predicted for SABR-induced rib fracture when tumour location is taken into account. Patients with tumours adjacent (within 5 mm) to the chest wall are at greater risk of rib fracture after lung SABR, and among these, an additional risk was observed in osteoporotic patients.

Predictive factors for local control in primary and metastatic lung tumours after four to five fraction stereotactic ablative body radiotherapy: a single institution's comprehensive experience.

AIMS: We report the outcomes of a large lung stereotactic ablative body radiotherapy (SABR) programme for primary non-small cell lung cancer (NSCLC) and pulmonary metastases. The primary study aim was to identify factors predictive for local control. MATERIALS AND METHODS: In total, 311 pulmonary tumours in 254 patients were treated between 2008 and 2011 with SABR using 48-60 Gy in four to five fractions. Local, regional and distant failure data were collected prospectively, whereas other end points were collected retrospectively. Potential clinical and dosimetric predictors of local control were evaluated using univariate and multivariate analyses. RESULTS: Of the 311 tumours, 240 were NSCLC and 71 were other histologies. The 2 year local control rate was 96% in stage I NSCLC, 76% in colorectal cancer (CRC) metastases and 91% in non-lung/non-CRC metastases. Predictors of better local control on multivariate analysis were non-CRC tumours and a larger proportion of the planning target volume (PTV) receiving ≥100% of the prescribed dose (higher PTV V100). Among the 45 CRC metastases, a higher PTV V100 and previous chemotherapy predicted for better local control. CONCLUSIONS: Lung SABR of 48-60 Gy/four to five fractions resulted in high local control rates for all tumours except CRC metastases. Covering more of the PTV with the prescription dose (a higher PTV V100) also resulted in superior local control.