Houda Bahig

Predictive Parameters of CyberKnife Fiducial-less (XSight Lung) Applicability for Treatment of Early Non-Small Cell Lung Cancer: A Single-Center Experience

PURPOSE To determine which parameters allow for CyberKnife fiducial-less tumor tracking in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. METHODS AND MATERIALS A total of 133 lung SBRT patients were preselected for direct soft-tissue tracking based on manufacturer recommendations (peripherally located tumors ≥1.5 cm with a dense appearance) and staff experience. Patients underwent a tumor visualization test to verify adequate detection by the tracking system (orthogonal radiographs). An analysis of potential predictors of successful tumor tracking was conducted looking at: tumor stage, size, histology, tumor projection on the vertebral column or mediastinum, distance to the diaphragm, lung-to-soft tissue ratio, and patient body mass index. RESULTS Tumor visualization was satisfactory for 88 patients (66%) and unsatisfactory for 45 patients (34%). Median time to treatment start was 6 days in the success group (range, 2-18 days) and 15 days (range, 3-63 days) in the failure group. A stage T2 (P=.04), larger tumor size (volume of 15.3 cm(3) vs 6.5 cm(3) in success and failure group, respectively) (P<.0001), and higher tumor density (0.86 g/cm(3) vs 0.79 g/cm(3)) were predictive of adequate detection. There was a 63% decrease in failure risk with every 1-cm increase in maximum tumor dimension (relative risk for failure = 0.37, CI=0.23-0.60, P=.001). A diameter of 3.6 cm predicted a success probability of 80%. Histology, lung-to-soft tissue ratio, distance to diaphragm, patients body mass index, and tumor projection on vertebral column and mediastinum were not found to be predictive of success. CONCLUSIONS Tumor size, volume, and density were the most predictive factors of a successful XSight Lung tumor tracking. Tumors >3.5 cm have ≥80% chance of being adequately visualized and therefore should all be considered for direct tumor tracking.

Hypofractionated Radiation Therapy for Breast Ductal Carcinoma In Situ

PURPOSE Conventional radiation therapy (RT) administered in 25 fractions after breast-conserving surgery (BCS) is the standard treatment for ductal carcinoma in situ (DCIS) of the breast. Although accelerated hypofractionated regimens in 16 fractions have been shown to be equivalent to conventional RT for invasive breast cancer, few studies have reported results of using hypofractionated RT in DCIS. METHODS AND MATERIALS In this multicenter collaborative effort, we retrospectively reviewed the records of all women with DCIS at 3 institutions treated with BCS followed by hypofractionated whole-breast RT (WBRT) delivered in 16 fractions. RESULTS Between 2003 and 2010, 440 patients with DCIS underwent BCS followed by hypofractionated WBRT in 16 fractions for a total dose of 42.5 Gy (2.66 Gy per fraction). Boost RT to the surgical bed was given to 125 patients (28%) at a median dose of 10 Gy in 4 fractions (2.5 Gy per fraction). After a median follow-up time of 4.4 years, 14 patients had an ipsilateral local relapse, resulting in a local recurrence-free survival of 97% at 5 years. Positive surgical margins, high nuclear grade, age less than 50 years, and a premenopausal status were all statistically associated with an increased occurrence of local recurrence. Tumor hormone receptor status, use of adjuvant hormonal therapy, and administration of additional boost RT did not have an impact on local control in our cohort. On multivariate analysis, positive margins, premenopausal status, and nuclear grade 3 tumors had a statistically significant worse local control rate. CONCLUSIONS Hypofractionated RT using 42.5 Gy in 16 fractions provides excellent local control for patients with DCIS undergoing BCS.

Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft Tissue Sarcoma of the Extremity

PURPOSE Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). METHODS AND MATERIALS Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. RESULTS The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm(3) (7-413 cm(3)), 280 cm(3) and 360 cm(3). The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm(3) (24-565 cm(3)) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm(3) (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm(3), respectively. There were 3 large tumors with >30 cm(3) of SE not included in the CTV3cm volume. CONCLUSION Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE.

Predictive factors of survival and treatment tolerance in older patients treated with chemotherapy and radiotherapy for locally advanced head and neck cancer

PURPOSE To report outcomes and predictive factors of overall survival, hospitalization and treatment completion rates in elderly patients with locally advanced head and neck cancer treated with concurrent chemoradiotherapy (CRT). MATERIAL AND METHODS A retrospective analysis of patients aged 70years or older treated with concurrent CRT for locally advanced head and neck cancer was conducted. Univariate and multivariate analysis as well as competing risk survival analysis were used to determine predictors of mortality. Logistic regression was used to predict for hospitalization and treatment completion rates. RESULTS In total, 129 patients were included. Median follow-up was 27months (range: 1.7-125months). Completion rate of combined CRT was 84%. Actuarial OS and DSS at 4years were 56% and 75%. Hospitalization rate was 36%. On multivariate analysis, a Karnofsky performance status (KPS) ⩽80 was predictive of mortality. Using competing risks, KPS ⩽80 and weight loss >5% were predictive of cancer mortality whereas Charlson score ⩾3 was predictive of mortality due to other causes. On logistic regression, patients with abnormal renal function and lower body mass index were more likely to be hospitalized during their treatment course. Charlson score and chemotherapy regimen were predictive of treatment completion. CONCLUSION Concurrent CRT may be a feasible treatment option for healthier older patients at the cost of high hospitalization rates. Pre-treatment factors linked to physiological age such as KPS ⩽80, Charlson score ⩾3, abnormal renal function should be considered at the time of treatment decision.

Severe radiation pneumonitis after lung stereotactic ablative radiation therapy in patients with interstitial lung disease

PURPOSE To investigate the incidence and predictive factors of severe radiation pneumonitis (RP) after stereotactic ablative radiation therapy (SABR) in early-stage lung cancer patients with preexisting radiological interstitial lung disease (ILD). METHODS AND MATERIALS A retrospective analysis of patients with stage I lung cancer treated with SABR from 2009 to 2014 was conducted. Interstitial lung disease diagnosis and grading was based on pretreatment high-resolution computed tomography imaging. A central review of pretreatment computed tomography by a single experienced thoracic radiologist was conducted. Univariate and multivariate analyses were conducted to determine potential predictors of severe RP in patients with ILD. RESULTS Among 504 patients treated with SABR in this period, 6% were identified as having preexisting ILD. There was a 4% rate of ≥ grade 3 RP in the entire cohort. Interstitial lung disease was associated with increased risk of ≥ grade 3 RP (32% in ILD+ vs 2% in ILD-, P < .001). Five patients (21%) with ILD developed grade 5 RP. Lower forced expiratory volume in 1 second and forced vital capacity, higher V5Gy and mean lung dose, presence of severe radiological ILD, and combined emphysema were significant predictors of ≥ grade 3 RP on univariate analysis; only forced expiratory volume in 1 second remained on multivariate analysis. CONCLUSION Interstitial lung disease is associated with an increased risk of severe RP after SABR. Chest imaging should be reviewed for ILD before SABR, and the risk of fatal RP should be carefully weighed against the benefits of SABR in this subgroup.

Excellent Cancer Outcomes Following Patient-adapted Robotic Lung SBRT But a Case for Caution in Idiopathic Pulmonary Fibrosis

The aim of this study is to report outcomes and prognostic factors for early stage non-small cell lung cancer treated with patient-adapted Cyberknife stereotactic body radiotherapy. A retrospective analysis of 150 patients with T1-2N0 non-small cell lung cancer treated with stereotactic body radiotherapy was conducted. An algorithm based on tumor and patient’s characteristics was used to orient patients towards soft tissue (Xsight Lung), fiducials or adjacent bone (Xsight Spine) tracking. Median biological effective dose without correction for tissue inhomogeneities was 180 Gy10 for peripheral tumors and 113 Gy10 for central tumors. Median follow-up was 22 months. Actuarial 2 years local control, overall survival and disease-specific survival were respectively 96%, 87% and 95%. Every 1 cm increase in tumor diameter was associated with a relative risk for regional or distant relapse of 2 (95%CI = 1.2-3.6, p = 0.009). With doses ≥132 Gy10 and <132 Gy10, local control was 98% vs. 82% (p = 0.07), disease-specific survival 97% vs. 78% (p = 0.02) and overall survival 93% vs. 76% (p = 0.01), respectively. Better disease-specific survival and a trend for better overall survival was observed for peripheral vs. central tumors (96% vs. 79%, p = 0.05 and 92% vs. 74%, p = 0.08, respectively). A higher Charlson comordibity score (≥4) predicted lower overall survival (79% vs. 98%, p = 0.01). Toxicities included 3 patients with idiopathic pulmonary fibrosis who developed grade 5 pneumonitis and 2 patients with grade 3 pneumonitis. We therefore report excellent local control and disease-specific survival following patient-adapted Cyberknife lung stereotactic body radiotherapy. Although toxicities were in general minimal, patients with pulmonary fibrosis might be at greater risk of severe complications. Small size, peripheral location, dose ≥ 132 Gy10 and a low Charlson co-morbidity score seem to be associated with better outcomes.

Long-term quality of life in early-stage non-small cell lung cancer patients treated with robotic stereotactic ablative radiation therapy

PURPOSE The purpose of this study was to prospectively evaluate the quality of life (QoL) and pulmonary function of patients with early-stage non-small cell lung cancer treated with robotic stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS Eligible patients all had histologically confirmed stage I non-small cell lung cancer and were not surgical candidates because of poor pulmonary function, comorbidities, or refusal of surgery. SABR was delivered at a median dose of 60 Gy in 3 fractions for peripheral tumors and 50 Gy in 4 or 5 fractions for central tumors. QoL was scored using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (QLQ-C30) and Lung Cancer-13 questionnaires. Pulmonary function tests (PFTs) included forced expiratory volume in 1 second (FEV1) and lung diffusion capacity. Changes over time in QoL scores and PFTs were tested with nonparametric tests for longitudinal data. Local control, survival, and toxicities are also presented. RESULTS From January 2010 to May 2013, 45 patients were enrolled. Median follow-up was 41 months. QLQ-C30 mean baseline scores for global QoL and physical functioning were 66 ± 20% and 73 ± 22%. Multilevel analyses showed no statistically and clinically significant (10-point change) deterioration in any of the QoL scores after SABR. Mean baseline FEV1 was 1.39 ± 0.51 L, and mean lung diffusion capacity was 63 ± 25% of predicted. We saw no significant change in PFTs at any time point. At 3 years, local control, disease-free survival, and overall survival were, respectively, 94%, 67%, and 75%. CONCLUSIONS In nonsurgical patients with multiple comorbidities, lung SABR achieves long-term local control while maintaining QoL and pulmonary function.

Assessing lung function using contrast‐enhanced dual‐energy computed tomography for potential applications in radiation therapy

Purpose: There is an increasing interest in the evaluation of lung function from physiological images in radiation therapy treatment planning to reduce the extent of postradiation toxicities. The purpose of this work was to retrieve reliable functional information from contrast‐enhanced dual‐energy computed tomography (DECT) for new applications in radiation therapy. The functional information obtained by DECT is also compared with other methods using single‐energy CT (SECT) and single‐photon emission computed tomography (SPECT) with CT. The differential function between left and right lung, as well as between lobes is computed for all methods. Methods: Five lung cancer patients were retrospectively selected for this study; each underwent a SPECT/CT scan and a contrast‐injected DECT scan, using 100 and 140 Sn kVp. The DECT images are postprocessed into iodine concentration maps, which are further used to determine the perfused blood volume. These maps are calculated in two steps: (a) a DECT stoichiometric calibration adapted to the presence of iodine and followed by (b) a two‐material decomposition technique. The functional information from SECT is assumed proportional to the HU numbers from a mixed CT image. The functional data from SPECT/CT are considered proportional to the number of counts. A radiation oncologist segmented the entire lung volume into five lobes on both mixed CT images and low‐dose CT images from SPECT/CT to allow a regional comparison. The differential function for each subvolume is computed relative to the entire lung volume. Results: The differential function per lobe derived from SPECT/CT correlates strongly with DECT (Pearsons coefficient r = 0.91) and moderately with SECT (r = 0.46). The differential function for the left lung shows a mean difference of 7% between SPECT/CT and DECT; and 17% between SPECT/CT and SECT. The presence of nonfunctional areas, such as localized emphysema or a lung tumor, is reflected by an intensity drop in the iodine concentration maps. Functional dose volume histograms (fDVH) are also generated for two patients as a proof of concept. Conclusion: The extraction of iodine concentration maps from a contrast‐enhanced DECT scan is achieved to compute the differential function for each lung subvolume and good agreement is found in respect to SPECT/CT. One promising avenue in radiation therapy is to include such functional information during treatment planning dose optimization to spare functional lung tissues.

Robust quantitative contrast‐enhanced dual‐energy CT for radiotherapy applications

Purpose The purpose of this study was to develop and validate accurate methods for determining iodine content and virtual noncontrast maps of physical parameters, such as electron density, in the context of radiotherapy. Methods A simulation environment is developed to compare three methods allowing extracting iodine content and virtual noncontrast composition: (a) two‐material decomposition, (b) three‐material decomposition with the conservation of volume constraint, and (c) eigentissue decomposition. The simulation allows comparing the performance of the methods using iodine‐based contrast agent contents in tissues from a reference dataset with variable density and elemental composition. The comparison is performed in two ways: (a) with a priori knowledge on the composition of the targeted tissue, and (b) without a priori knowledge on the base tissue. The three methods are tested with patient images scanned with dual‐energy CT and iodine‐based contrast agent. An experimental calibration adapted to the presence of iodine is performed by imaging tissue equivalent materials and diluted contrast agent solutions with known atomic composition. Results Results show that in the case of known a priori on the composition of the targeted tissue, the two‐material decomposition is robust to variable densities and atomic compositions without biasing the results. In the absence of a priori knowledge on the target tissue composition, the eigentissue decomposition method yields minimal bias and higher robustness to variations. Results from the experimental calibration and the images of two patients show that the extracted quantities are accurate and the bias is negligible for both methods with respect to clinical applications in their respective scope of use. For the patient imaged with a contrast agent, virtual noncontrast electron densities are found in good agreement with values extracted from the scan without contrast agent. Conclusion This study identifies two accurate methods to quantify iodine‐based contrast agents and virtual noncontrast composition images with dual‐energy CT. One is the two‐material decomposition with a priori knowledge of the constituent components focused on organ‐specific applications, such as kidney or lung function assessment. The other method is the eigentissue decomposition and is useful for general radiotherapy applications, such as treatment planning where accurate dose calculations are needed in the absence of contrast agent.

Assessing the Need for Adjuvant Chemotherapy After Stereotactic Body Radiation Therapy in Early-stage Non-small Cell Lung Carcinoma

Purpose Surgery remains the standard treatment for medically operable patients with early-stage non-small cell lung carcinoma (NSCLC). Following surgical resection, adjuvant chemotherapy is recommended for large tumors >4 cm. For unfit patients, stereotactic body radiation therapy (SBRT) has emerged as an excellent alternative to surgery. This study aims to assess patterns of recurrence and discuss the role of chemotherapy after SBRT for NSCLC. Methods We reviewed patients treated with SBRT for primary early-stage NSCLC between 2009 and 2015. Total target doses were between 50 and 60 Gy administered in three to eight fractions. All patients had a staging fluorodeoxyglucose (FDG) positron emission tomography (PET) integrated with computed tomography (CT) scan, and histologic confirmation was obtained whenever possible. Mediastinal staging was performed if lymph node involvement was suspected on CT or PET/CT. Survival outcomes were estimated using the Kaplan-Meier method. Results Among the 559 early-stage NSCLC patients treated with SBRT, 121 patients were stage T2N0. The one-year and three-year overall survival rates were 88% and 70%, respectively, for patients with T2 disease, compared to 95% and 81%, respectively, for the T1 patients (p<0.05). The one-year and three-year local control rates were equal in both groups (98% and 91%, respectively). In T2 patients, 25 (21%) presented a relapse, among which 21 (84%) were nodal or distant. The median survival of T2N0 patients following a relapse was 11 months. Conclusion Lung SBRT provides high local control rates, even for larger tumors. When patients relapse, the majority of them do so at regional or distant sites. These results raise the question as to whether adjuvant treatment should be considered following SBRT for larger tumors.