A Prospective Study of Magnetic Resonance Imaging Assessment of Post-radiation Changes Following Stereotactic Body Radiation Therapy for Non-small Cell Lung Cancer.

AIMS: Follow-up computed tomography scans after lung stereotactic body radiation therapy (SBRT) are difficult to interpret due to the presence of benign fibrosis, which can make the detection of local recurrence difficult. The objective of this study was to determine the feasibility of a novel thoracic magnetic resonance imaging (MRI) protocol incorporating diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging for the assessment of the treated lung parenchyma after SBRT. MATERIALS AND METHODS: On a prospective trial, post-treatment MR images were acquired in 30 patients treated with SBRT (divided into three different cohorts according to the likelihood of local recurrence as per an expert panel). These images were assessed by an expert thoracic radiologist blind to clinical data, who indicated local recurrence in a dichotomous manner. Local recurrence was confirmed by biopsy or subsequent growth on follow-up computed tomography scans. RESULTS: Thirty patients underwent MRI as part of this study; 27/30 patients were analysable for local recurrence. MRI was conducted at a median of 27.3 months (range 6.5-71 months) from SBRT. No side-effects resulted from either MRI or contrast administration. At a median follow-up time of 45 months after treatment, three local recurrence episodes have occurred. MRI assessment diagnosed seven patients as having a local recurrence, which was later confirmed in three and did not miss any of the true local recurrences. When comparing apparent diffusion coefficient (ADC) values according to local recurrence, the mean ADC value for the local recurrence-free group was 1770 × 10-3 mm/s2 (range 1038-3105 × 10-3 mm/s2) versus 981 × 10-3 mm/s2 (range 926.6-1065 × 10-3 mm/s2) for the local recurrence group (P = 0.0014). CONCLUSIONS: A novel 3.0 T MRI protocol incorporating DWI and DCE was feasible and confirmed the suspicion of local recurrence in patients with highly suspicious computed tomography scans. This imaging tool could potentially aid in selecting patients for salvage treatment after local SBRT failure. Future work should be pursued to validate these findings.

Prognostic value of pretreatment circulating neutrophils, monocytes, and lymphocytes on outcomes in lung stereotactic body radiotherapy.

PURPOSE: In the present study, we determined the association of pretreatment circulating neutrophils, monocytes, and lymphocytes with clinical outcomes after lung stereotactic body radiotherapy (sbrt). METHODS: All patients with primary lung cancer and with a complete blood count within 3 months of lung sbrt from 2005 to 2012 were included. Overall survival (os) was calculated using the Kaplan-Meier method. Factors associated with os were investigated using univariable and multivariable Cox proportional hazards regression. Fine-Gray competing risk regression was performed to test the association of the neutrophil:lymphocyte (nlr) and monocyte:lymphocyte (mlr) ratios with two types of failure: disease-related failure and death, and death unrelated to disease. RESULTS: Of the 299 sbrt patients identified, 122 were eligible for analysis. The median and range of the nlr and mlr were 3.0 (0.3-22.0) and 0.4 (0.1-1.9) respectively. On multivariable analysis, sex (p = 0.02), T stage (p = 0.04), and nlr (p < 0.01) were associated with os. On multivariable analysis, T stage (p < 0.01) and mlr (p < 0.01) were associated with disease-related failure; mlr (p = 0.03), nlr (p < 0.01), and sbrt dose of 48 Gy in 4 fractions (p = 0.03) and 54 Gy or 60 Gy in 3 fractions (p = 0.02) were associated with disease-unrelated death. Median survival was 4.3 years in the nlr≤3 group (95% confidence interval: 3.5 to not reached) and 2.5 years in the nlr>3 group (95% confidence interval: 1.7 to 4.8; p < 0.01). CONCLUSIONS: In lung sbrt patients, nlr and mlr are independently associated with os and disease-unrelated death. If validated, nlr and mlr could help to identify patients who would benefit most from sbrt.

Outcomes of accelerated hypofractionated radiotherapy in stage i non-small-cell lung cancer.

PURPOSE: Outcomes after treatment with accelerated hypofractionated radiotherapy in stage i medically inoperable non-small-cell lung cancer (nsclc) patients were determined. METHODS: Our single-institution retrospective review looked at medically inoperable patients with T1-2N0M0 nsclc treated with accelerated hypofractionated curative-intent radiotherapy between 1999 and 2009. Patients were staged mainly by computed tomography imaging of chest and abdomen, bone scan, and computed tomography/magnetic resonance imaging of brain. Positron-emission tomography (pet) staging was performed in 6 patients. Medical charts were reviewed to determine demographics, radiotherapy details, sites of failure, toxicity (as defined by the Common Terminology Criteria for Adverse Events, version 3.0) and vital status. The cumulative incidence of local and distant failure was calculated. Overall (os) and cause-specific (css) survival were estimated by the Kaplan-Meier method. RESULT: In the 60 patients treated during the study period, the dose regimens were 50 Gy in 20 fractions (n = 6), 55 Gy in 20 fractions (n = 8), 60 Gy in 20 fractions (n = 42), and 60 Gy in 25 fractions (n = 4). All patients were treated once daily. The median follow-up was 27 months (range: 4-94 months). The os rates at 2 and 5 years were 61% [95% confidence interval (ci): 50% to 75%] and 19% (95% ci: 10% to 34%) respectively. The css rates at 2 and 5 years were 79% (95% ci: 68% to 91%) and 39% (95% ci: 24% to 63%) respectively. The cumulative incidence of local failure was 20% at 5 years. The cumulative incidence of distant failure was 28% at 5 years. No patients experienced grade 3 or greater pneumonitis or esophagitis. CONCLUSIONS: Accelerated hypofractionated regimens are well tolerated and provide good local control in medically inoperable patients with stage i nsclc. Such regimens may be a reasonable treatment alternative when stereotactic body radiation therapy is not feasible.

Improving superficial target delineation in radiation therapy with endoscopic tracking and registration.

PURPOSE: Target delineation within volumetric imaging is a critical step in the planning process of intensity modulated radiation therapy. In endoluminal cancers, endoscopy often reveals superficial areas of visible disease beyond what is seen on volumetric imaging. Quantitatively relating these findings to the volumetric imaging is prone to human error during the recall and contouring of the target. We have developed a method to improve target delineation in the radiation therapy planning process by quantitatively registering endoscopic findings contours traced on endoscopic images to volumetric imaging. METHODS: Using electromagnetic sensors embedded in an endoscope, 2D endoscopic images were registered to computed tomography (CT) volumetric images by tracking the position and orientation of the endoscope relative to a CT image set. Regions-of-interest (ROI) in the 2D endoscopic view were delineated. A mesh created within the boundary of the ROI was projected onto the 3D image data, registering the ROI with the volumetric image. This 3D ROI was exported to clinical radiation treatment planning software. The precision and accuracy of the procedure was tested on two solid phantoms with superficial markings visible on both endoscopy and CT images. The first phantom was T-shaped tube with X-marks etched on the interior. The second phantom was an anatomically correct skull phantom with a phantom superficial lesion placed on the pharyngeal surface. Markings were contoured on the endoscope images and compared with contours delineated in the treatment planning system based on the CT images. Clinical feasibility was tested on three patients with early stage glottic cancer. Image-based rendering using manually identified landmarks was used to improve the registration. RESULTS: Using the T-shaped phantom with X-markings, the 2D to 3D registration accuracy was 1.5-3.5 mm, depending on the endoscope position relative to the markings. Intraobserver standard variation was 0.5 mm. Rotational accuracy was within 2°. Using the skull phantom, registration accuracy was assessed by calculating the average surface minimum distance between the endoscopy and treatment planning contours. The average surface distance was 0.92 mm with 93% of all points in the 2D-endoscopy ROI within 1.5 mm of any point within the ROI contoured in the treatment planning software. This accuracy is limited by the CT imaging resolution and the electromagnetic (EM) sensor accuracy. The clinical testing demonstrated that endoscopic contouring is feasible. With registration based on em tracking only, accuracy was 5.6-8.4 mm. Image-based registration reduced this error to less than 3.5 mm and enabled endoscopic contouring in all cases. CONCLUSIONS: Registration of contours generated on 2D endoscopic images to 3D planning space is feasible, with accuracy smaller than typical set-up margins. Used in addition to standard 3D contouring methods in radiation planning, the technology may improve gross tumour volume (GTV) delineation for superficial tumors in luminal sites that are only visible in endoscopy.

Early metabolic response evaluation after stereotactic radiotherapy for lung cancer: pilot experience with 18F-fluorodeoxyglucose positron emission tomography-computed tomography.

The early response of lung tumours to stereotactic radiotherapy was prospectively evaluated with 18F-fluorodeoxyglucose positron emission tomography-computed tomography. Three months after treatment, the maximum standardised uptake value and the tumour diameter fell by 64 and 30%, respectively. This imaging strategy therefore remains under ongoing evaluation with the aim of identifying predictive and prognostic factors.

Factors associated with negative margins of lumpectomy specimen: potential use in selecting patients for intraoperative radiotherapy.

BACKGROUND: Lumpectomy followed by radiation is standard treatment for early breast cancer. Recently, the use of partial breast intraoperative radiation (IORT) has been developed, and patients selected for IORT should not have positive margins. This study's purpose was to identify factors predicting negative margins after lumpectomy. METHODS: Patient age, preoperative investigations, surgery, final pathology, and margin status were examined using a prospective database between 1999 and 2005. Univariate and multivariate logistic regression analysis were performed to identify patient and tumor factors predicting an increased rate of negative margins. The results were used to generate a patient selection algorithm. RESULTS: The rate of positive margins at first resection was 17% in 730 lumpectomies (708 patients). Multivariate analysis revealed that older age (P = .0006), smaller tumor size (P < .0025), type of surgery (OR = 3.4 for ultrasound vs mammogram-guided wire localization, P = .003), and having a core needle biopsy (CNB) with preoperative cancer diagnosis (P < .0001) were predictive for having a negative margin. Patients older than age 50 with a preoperative CNB showing invasive cancer less that 3 cm that can be localized under ultrasound had a negative margin rate of 98% (n = 178). These patients would be ideal for consideration of IORT. CONCLUSIONS: Negative margin rates after lumpectomy are predicted by age, tumor size, preoperative investigations, and localization technique. These variables can be used to select patients for IORT with a 2.2% chance of positive margins.