Mark Shaw

Impact of stereotactic radiotherapy on kidney function in primary renal cell carcinoma: Establishing a dose–response relationship

BACKGROUND AND PURPOSE To evaluate renal dysfunction after stereotactic ablative body radiotherapy (SABR) for inoperable primary renal cell carcinoma (RCC) using nuclear medicine assessments. MATERIALS AND METHODS In a prospective clinical trial, patients received single fraction renal SABR (26 Gy) for tumours <5 cm, or fractionated SABR (3 × 14 Gy) for tumours ⩾5 cm. Global and regional glomerular filtration rate (GFR) was calculated through (51)Cr-EDTA and (99m)Tc-DMSA SPECT/CT, respectively, at baseline and post-treatment (14, 90 days and at 1-year). Regional loss in function was correlated to the absolute and biologically effective doses (BED) delivered. RESULTS In 21 patients the mean (range) tumour size was 48 mm (21-75 mm). The mean ± SD GFR at baseline was 52 ± 24 ml/min. Net change in mean GFR was +0.6 ± 11.3, +3.2 ± 14.5 and -8.7 ± 13.4 ml/min (p=0.03) at 2 weeks, 3 months and 1 year, respectively. For every 10 Gy of physical dose delivered, an exponential decline in affected kidney GFR was observed at 39% for 26 Gy/1 fraction and 25% for 42 Gy/3 fractions. When normalised to BED3Gy, the dose-response relationship for each treatment prescription was similar with a plateau beyond 100 Gy. The R50% conformity index correlated with GFR loss (p=0.04). No patient required dialysis. CONCLUSIONS SABR results in clinically acceptable and dose-dependent renal dysfunction at 1-year. Sparing functional kidney from high-dose regions (>50% isodoses) may help reduce risk of functional loss.

Ventilation/Perfusion Positron Emission Tomography--Based Assessment of Radiation Injury to Lung.

PURPOSE To investigate (68)Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). METHODS AND MATERIALS In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). RESULTS A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r(2)=0.99, P<.01), with ventilation strongly negatively linear (r(2)=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. CONCLUSIONS Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT.

Ga-68 MAA Perfusion 4D-PET/CT Scanning Allows for Functional Lung Avoidance Using Conformal Radiation Therapy Planning

Background: Ga-68-macroaggregated albumin (68Ga-perfusion) positron emission tomography/computed tomography (PET/CT) is a novel imaging technique for the assessment of functional lung volumes. The purpose of this study was to use this imaging technique for functional adaptation of definitive radiotherapy plans in patients with non-small cell lung cancer (NSCLC). Methods: This was a prospective clinical trial of patients with NSCLC who received definitive 3-dimensional (3D) conformal radiotherapy to 60 Gy in 30 fx and underwent pretreatment respiratory-gated (4-dimensional [4D]) perfusion PET/CT. The “perfused” lung volume was defined as all lung parenchyma taking up radiotracer, and the “well-perfused” lung volume was contoured using a visually adapted threshold of 30% maximum standardized uptake value (SUVmax). Alternate 3D conformal plans were subsequently created and optimized to avoid perfused and well-perfused lung volumes. Functional dose volumetrics were compared using mean lung dose (MLD), V5 (volume receiving 5 Gy or more), V10, V20, V30, V40, V50, and V60 parameters. Results: Fourteen consecutive patients had alternate radiotherapy plans created based on functional lung volumes. When considering the original treatment plan, the dose to perfused and well-perfused functional lung volumes was similar to that of the conventional anatomical lung volumes with an average MLD of 12.15, 12.67, and 12.11 Gy, respectively. Plans optimized for well-perfused lung improved functional V30, V40, V50, and V60 metrics (all P values <.05). The functional MLD of well-perfused lung was improved by a median of 0.86 Gy, P < .01. However, plans optimized for perfused lung only showed significant improvement in the functional V60 dose parameter (median 1.00%, P = .04) but at a detriment of a worse functional V5 (median 3.33%, P = .05). Conclusions: This study demonstrates proof of principle that 4D-perfusion PET/CT may enable functional lung avoidance during treatment planning of patients with NSCLC. Radiotherapy plans adapted to well-perfused but not perfused functional lung volumes allow for reduction in dose to functional lung using 3D conformal radiotherapy.

Stereotactic Ablative Body Radiotherapy for Inoperable Primary Kidney Cancer: A Prospective Clinical Trial

To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess oncological and functional outcomes.

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial

BACKGROUND Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available. OBJECTIVE To determine the safety and feasibility of single fraction SABR for patients with oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response. DESIGN, SETTING, AND PARTICIPANTS In a prospective clinical trial, patients were screened with computed tomography, bone scan, and sodium fluoride positron emission tomography scan and had one to three oligometastases. Kaplan-Meier methods were used to determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo. INTERVENTION A single fraction of 20-Gy SABR to each lesion. RESULTS AND LIMITATIONS Between 2013 and 2014, 33 consecutive patients received SABR to a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The Gleason score was ≥8 in 15 patients (45%). Twenty patients had bone only, 12 had node only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97% (95% confidence interval [CI]: 91-100) and 93% (95% CI: 84-100), and DPFS was 58% (95% CI: 43-77) and 39% (95% CI: 25-60), respectively. In those not on androgen deprivation therapy (ADT; n=22), the 2-yr freedom from ADT was 48%. There was no significant difference from baseline QoL observed. Limitations include small sample size, limited duration of follow-up, and lack of a control arm. CONCLUSIONS A single SABR session was feasible and associated with low morbidity in this cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL measures were maintained with this treatment strategy. PATIENT SUMMARY This clinical trial investigated single treatment stereotactic radiotherapy for low volume advanced prostate cancer. The approach was found to be safe with avoidance of hormone therapy in almost half of the participants at 2 yr.

Analysis of the impact of chest wall constraints on eligibility for a randomized trial of stereotactic body radiotherapy of peripheral stage I non-small cell lung cancer.

Chest wall toxicities are recognized complications of stereotactic radiotherapy (SBRT) in non‐small cell lung cancer. To minimize toxicity, the Trans‐Tasman Radiation Oncology Group (TROG) 09.02 ‘CHISEL’ study protocol excluded patients with tumours within 1 cm of the chest wall. The purpose of this study is to evaluate the implication of chest wall proximity constraints on patient eligibility, toxicity and potential accrual.