Toni Vu

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.

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 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.

Limitations of Personalized Medicine and Gene Assays for Breast Cancer

Adjuvant systemic treatments reduce the risk of breast cancer recurrence following the local treatment of primary stage I-III breast cancers. For patients with hormone-positive breast cancers receiving hormonal therapy, the risk of distant recurrence is under 20% and therefore, many patients may potentially be spared of chemotherapy. Consequently, several molecular signatures based on gene expression were developed to better determine which breast cancer patients would benefit from chemotherapy. We present the case of a 62-year-old woman diagnosed with an early stage hormone receptor-positive breast cancer that was treated with a partial mastectomy. Oncotype DX (Genomic Health, Redwood City, CA) molecular testing was performed on the surgical specimen, which reported a recurrence score of 0. The patient commenced adjuvant radiotherapy during which she developed symptoms suggestive of bone metastasis and was subsequently diagnosed with a spinal cord compression that required neurosurgery and radiotherapy. Pathology review of the specimen from the spine surgery revealed a metastatic breast carcinoma with neuroendocrine differentiation. Molecular assays such as Oncotype DX are increasingly used to prognosticate patient outcomes and help determine who may avoid chemotherapy. This case report seeks to illustrate that such assays should not be used in the presence of rare histological subtypes like neuroendocrine breast cancers, which are often under-reported. The current status of personalized medicine and gene assays in breast cancer is reviewed and potential strategies are suggested to identify these rare cases to better orient diagnostic and treatment decisions.

A dosimetric parameter to limit chest wall toxicity in SABR of NSCLC

OBJECTIVE Chest wall (CW) toxicity (rib fracture and/or pain) is a recognized complication of stereotactic ablative radiotherapy (SABR) for non-small-cell lung cancer. The aim of this study was to evaluate the frequency of CW toxicity following SABR and to propose a new dosimetric parameter. METHODS We reviewed the charts and SABR plans from patients treated for T1-T2N0 peripheral non-small-cell lung cancer between 2009 and 2015. The CW structure was created through a 3-cm expansion of the lung. The median dose delivered to the planning target volume was 60 Gy. SABR was delivered in three fractions for patients with CW V30 < 30 cm3. If the CW V30 exceeded 30 cm3, five fractions were used, and the plan was optimized based on CW V37 (biologically equivalent to the V30 of three-fraction plans). RESULTS In 6 years, 361 lesions from 356 patients were treated (3 fractions: 297; 5 fractions: 64). The median follow-up was 16 months. 23 patients (6.5%) developed CW toxicity after a median time of 10 months following treatment. The mean CW V30/V37 was 21 cm3 for patients with CW toxicity and 17 cm3 for patients without toxicity (p < 0.05). The 2-year local control and the CW toxicity rates were similar, whether patients received three or five fractions (97% vs 96% and 7% vs 5%). CONCLUSION When the CW V30 is >30 cm3, altered fractionation combined with V37 optimization can limit CW toxicity. Advances in knowledge: The CW V37 is a suggested dosimetric parameter adapted to fractionation that may potentially limit CW toxicity after lung SABR.

Accuracy of Breath-hold CT in Treatment Planning for Lung Stereotactic Ablative Radiotherapy

PURPOSE The objectives of this study are (1) to measure concordance of tumor position on breath-hold (BH) computed tomography (CT) scans relative to the natural tumor path during free breathing (FB) and (2) to evaluate the benefits of the breathing monitoring device Abches (Apex Medical, Tokyo) for stereotactic ablative radiotherapy (SABR) treatment planning. METHODS In 53 lung cancer patients treated with CyberKnife™ robotic radiosurgery system, FB four-dimensional computerized tomography (4DCT) and end-expiration (EE) BH CT images were obtained. Extent of natural tumor motion was assessed with rigid registration derived from end-inspiration (EI) and EE phases of the 4DCT. Tumor displacement in BH scans relative to the natural tumor path was measured relative to the EE 4DCT phase. RESULTS Mean tumor motion (+/- 1 SD) during natural FB was 1 ± 1 mm, 2 ± 2 mm, and 6 ± 6 mm in medio-lateral, anterior-posterior, and cranio-caudal directions, respectively. Tumor position on BH CT scan was closer to EE than EI 4DCT phase for 35/53 patients (66%). Difference of BH tumor position vs. EE state was 4 ± 3 mm. Gross tumor displacements perpendicular to natural tumor path were as great as 11 mm (anterior-posterior) and were seen with or without the breathing monitoring device. CONCLUSION Tumor position during BH CT may not accurately correspond to positions observed on FB 4DCT. Hence, accurate and custom 4D analysis for each individual patient is recommended for treatment planning, especially those involving BH acquisitions.

The impacts of mid‐treatment CBCT‐guided patient repositioning on target coverage during lung VMAT

The purpose of this study is quantify intrafraction motion (IFM) during lung volumetric‐modulated arc therapy (VMAT) and evaluate the impact of mid‐treatment cone beam computed tomography (CBCT)‐guided patient repositioning on target coverage.