A competing risk analysis of the patterns and risk factors of recurrence in early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

INTRODUCTION: To assess patterns of recurrence after stereotactic ablative radiotherapy (SABR) in patient ineligible to surgery with early-stage non-small cell lung cancer (ES-NSCLC), report survival and treatment after first recurrence. METHODS: We performed a retrospective analysis on 1068 patients with ES-NSCLC and 1143 lesions. Between group differences were estimated using competing risk analysis and cause-specific hazard ratios were calculated. Overall survival (OS) after first recurrence was calculated. RESULTS: Median follow-up was 37.6 months. Univariate analysis demonstrated that ultra-central location was associated with higher risk of regional recurrence (RR) and distant metastasis (DM) (p = 0.004 and 0.01). Central lesions were associated with higher risk of local recurrence (LR) and RR (p < 0.001). Ultra-central lesions were associated with shorter OS (p = 0.002) compared to peripheral lesions. In multivariate analysis, central location was the only factor associated with increased LR and RR risks (p = 0.016 and 0.005). Median OS after first recurrence was 14.8 months. There was no difference in OS after first recurrence between ultra-central, central, and peripheral lesions (p = 0.83). Patients who received a second SABR course had an OS of 51.3 months, compared to 19.5 months with systemic therapy and 8.1 months with supportive care (p < 0.0001). DISCUSSION: The main prognostic factor for LR and RR risks was central location. Ultra-central and central tumors might benefit from treatment intensification strategies such as dose escalation and/or addition of systemic therapy to improve radiotherapy outcomes. After a first recurrence post SABR, patients with contralateral lung recurrences and those who were eligible to receive a second course of SABR had improved OS.

Stereotactic Ablative Radiotherapy for oligo-progressive disease refractory to systemic therapy in Non-Small Cell Lung Cancer: A registry-based phase II randomized trial (SUPPRESS-NSCLC).

BACKGROUND: Management of Non-Small Cell Lung Cancer (NSCLC) patients with oligoprogression remains controversial. There is limited data to support the strategy of Stereotactic Ablative Radiotherapy (SABR) targeting the oligoprogressive disease in combination with ongoing systemic treatment. We aim to assess the benefit of this approach compared to standard of care in the treatment of oligoprogressive NSCLC. METHODS: This phase II study will enroll 68 patients with oligoprogressive NSCLC, defined as 1-5 progressive extracranial lesions ≤5 cm involving ≤3 organs. Patients on active systemic therapy (chemotherapy, immunotherapy, targeted therapy or a combination) will be randomized 1:1 to either continue their current systemic therapy in combination with SABR to all lesions or the standard of care (switch to the next line of treatment, continue same treatment or observation). The co-primary endpoints are progression-free survival (PFS) and overall survival (OS). Secondary endpoints include time to next systemic treatment, patient-reported quality of life, cost effectiveness as well as translational analysis to characterize both adaptive immunity and immunogenic cell death markers in the peripheral blood. DISCUSSION: There is an unmet need to carefully examine the efficacy, safety and quality of life impact of SABR in the context of oligoprogressive disease. The present study will provide higher level randomized evidence on the role of SABR in oligoprogressive NSCLC.

Cardiac Sparing with Personalized Treatment Planning for Early-stage Left Breast Cancer.

Purpose To compare cardiac doses of different whole-breast optimization schemes including free-breathing (FB) tangential radiotherapy (TRT), deep-inspiration breath-hold (DIBH) TRT, and FB helical tomotherapy (HT). Methods Early-stage left-sided breast cancer patients who underwent breast-conserving surgery followed by adjuvant radiotherapy were included in the study. Planning images included FB and DIBH CT scans acquired in the same supine treatment position with both arms abducted. A hypofractionated regimen of 42.5 Gy in 16 fractions was used. Clinical target volume delineation was aided through the use of a radio-opaque wire. A 7-mm margin was used in generating the planning target volumes. TRT plans were generated both in FB and DIBH. For the FB tomotherapy technique, a first plan (Tomo 1) was optimized limiting the maximum contralateral breast dose to 3.1 Gy. A second tomotherapy plan (Tomo 2) focused on the reduction of the mean heart dose without controlling the contralateral breast dose. All plans were optimized to obtain an equivalent planning target volume (PTV) coverage of ≥95% of the prescribed dose while minimizing the dose to organs at risk. Results Twenty-three patients treated between October 2012 and March 2016 were included in this retrospective study. Eleven patients (48%) had at least one major cardiovascular risk factors including one patient (4%) with a history of myocardial infarction. Six patients (26%) had been exposed to cardiotoxic chemotherapy agents. The average mean dose to the heart was 3.1 Gy with FB TRT, 1.1 with DIBH TRT, 2.4 Gy for Tomo 1, and 1.5 Gy for Tomo 2. The mean dose to the left anterior descending artery was 27.0 Gy, 8.0 Gy, 13.7 Gy and 6.6 Gy for FB TRT, DIBH TRT, Tomo 1 and Tomo 2 plans respectively. Conclusion Different cardiac-sparing optimization schemes are possible when treating left breast cancer. Although DIBH offers clear mean heart dose reductions, tomotherapy can be an interesting alternative treatment modality to spare the heart and coronary vessels, notably in patients who cannot comply with DIBH.

To Biopsy or Not to Biopsy?: A Matched Cohort Analysis of Early-Stage Lung Cancer Treated with Stereotactic Radiation with or Without Histologic Confirmation.

PURPOSE: For nonoperable stage I non-small cell lung cancer, stereotactic body radiation therapy (SBRT) has emerged as a standard treatment option. We aimed to compare the clinical outcomes of lung SBRT between patients with versus without pathologic cancer diagnosis. METHODS AND MATERIALS: We included patients treated by SBRT for a single pulmonary lesion between July 2009 and July 2017. Patients in the clinical diagnosis group had a positron emission tomography/computed tomography scan showing hypermetabolism, growth of the mass on sequential computed tomography, and were not eligible for biopsy, refused biopsy, or had an inconclusive biopsy. For each of those patients, a matched pair in the pathologic diagnosis group was identified by matching for patient, treatment, and tumoral characteristics. We performed a power calculation to estimate the sample size required to detect a difference arising from a 5% or 15% rate of benign processes in the group without pathology. RESULTS: A total of 924 lung SBRT treatments were performed among 878 patients from 2009 to 2017. Within this population, 131 patients were treated based on clinical findings. They were matched with 131 patients with a pathologic diagnosis who received treatment. At 3 years, no significant differences were observed in overall survival (hazard ratio [HR], 1.2; 95% confidence interval [CI], 0.7-2.1), local control (HR, 0.9; 95% CI, 0.4-2), or regional (HR, 0.5; 95% CI, 0.2-1.4) or distant recurrence (HR, 0.6; 95% CI, 0.3-1.1). CONCLUSIONS: In our population, we found no clinically significant difference in patterns of recurrence or survival after lung SBRT for patients who had received clinical versus pathological diagnoses. There was, however, a trend toward more distant recurrences in the pathologic diagnosis group. Our power calculation suggests that data from multiple institutions would be required to rule out a difference in outcomes due to 5% to 15% of clinically diagnosed cases being treated for benign processes.

Risk-adapted stereotactic ablative radiotherapy for central and ultra-central lung tumours.

BACKGROUND: SABR is a widely accepted treatment for early-stage lung cancer but there are safety concerns for central and ultra-central tumours. Herein we report our experience using risk-adapted fractionation (prescribed doses: 40-60 Gy in 3-8 fractions) with prioritization of dose to organs at risk. METHODS: Patient declining or unsuitable for surgery with primitive or recurrent lung cancer were included. Tumours inside a 2 cm area around proximal bronchial tree (PBT) were classified as central while tumours with PTV overlapping PBT, oesophagus, great vessels and pericardial pleura were classified as ultra-central. We assessed overall survival (OS), disease-free survival (DFS), local control (LC) and toxicities. RESULTS: From 2009 to 2016, 137 patients were treated (median age: 75 years), with 60 central and 77 ultra-central tumours. Median follow-up was 36 months. Median tumour size, GTV and PTV were 2.5 cm (0.9-7), 7.8 cm3 (0.7-94.2) and 30.6 cm3 (6.5-274.3), respectively. For the whole population, median OS and DFS were 46 months and 33 months. One- and 2-years LC rates were 95% and 81%. Median OS between central and ultra-central tumours was statistically different with 57 vs 37 months (HR 0.48, p = 0.017), but LC was not different among them. We observed 4 Grade 3 and 6 Grade 5 toxicities (no grade 4). CONCLUSIONS: SABR for central and ultra-central tumours is associated with good OS, DFS and LC rates, with 7.3% grade 3-5 toxicities. Central tumours had a better prognosis in our cohort.

In a Heartbeat: An Assessment of Dynamic Dose Variation to Cardiac Structures Using Dual Source Computed Tomography.

PURPOSE: To assess radiation dose variation to the left anterior descending artery (LAD), left main coronary artery (LMCA), left ventricle (LV), and whole heart (WH) during the cardiac cycle using dual source computed tomography (DSCT). METHODS AND MATERIALS: The present prospective study included patients with left-side breast cancer planned to undergo tangential radiation therapy. An electrocardiogram-synchronized contrast-injected DSCT scan was obtained with the patient in the treatment position, in deep-inspiration breath-hold, using retrospective sequential acquisition. The WH, LV, LMCA, and proximal, middle, and distal LAD segments were contoured on each phase of the cardiac cycle. The maximum, minimum, and mean Hausdorff distance between each structure and the tangential fields was assessed in ventricular systole and diastole. Four-dimensional dose-volume histograms were used to compare the systolic and diastolic dosimetric data. RESULTS: Ten patients were enrolled. The average maximum, minimum, and mean Hausdorff distance variation from systole to diastole was ≤4 mm for the LV and LMCA and ≤3 mm for the WH and LAD segments. WH maximum dose and volume receiving 5 Gy were decreased in systole compared with diastole (42.9 Gy versus 44.5 Gy, P = .03, and 21.7 cm3 versus 27.7 cm3, P = .01), but the mean dose remained similar throughout the cycle. The maximum and mean dose to the distal LAD was 21.2 Gy versus 26.6 Gy (P = .005) and 8.6 Gy versus 13.2 Gy (P = .006) in systole versus diastole, respectively. The maximum and mean dose to the middle LAD was 18.4 Gy versus 25.1 Gy (P = .005) and 8.5 Gy versus 10.2 Gy in systole versus diastole (P = .005). The maximum dose to the LV was lower in systole than in diastole (21.5 Gy vs 26.7 Gy; P = .005). CONCLUSIONS: In addition to deep-inspiration breath-hold, systolic irradiation is associated with a reduction in dose to the LAD, LV, and WH. In addition to its potential use in radiation planning for cardiac gating, DSCT imaging can be used to help define a planning organ at risk volume for clinically important cardiac substructures.

Helical Tomotherapy for Postmastectomy Radiotherapy after Immediate Left Breast Reconstruction: A Case Study.

A 43-year-old premenopausal female presented with a multicentric infiltrating lobular carcinoma of the left breast with axillary nodes metastasis. She underwent modified radical mastectomy with axillary lymph node dissection (level I and II) followed by a mixed autologous latissimus dorsi flap reconstruction with the addition of prosthesis. The final pathological analysis revealed a 6 cm invasive lobular carcinoma pT3N2aM0, grade III/III, estrogen and progesterone positive, human epidermal growth factor receptor 2 (HER2) negative, with 5/16 positive lymph nodes. She received neoadjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel. Post-mastectomy radiotherapy with axillary, supraclavicular and internal mammary lymph nodes (IMLN) irradiation was delivered to a dose of 50 Gy/25 fx. In this case with multiple risk factors for radiation-induced cardiac toxicity (left-sided lesion, internal mammary lymph nodes (IMLN) irradiation), we discuss the role of helical tomotherapy as a treatment alternative to conventional tangential radiotherapy.

Phase 1-2 Study of Dual-Energy Computed Tomography for Assessment of Pulmonary Function in Radiation Therapy Planning.

PURPOSE: To quantify lung function according to a dual-energy computed tomography (DECT)-derived iodine map in patients treated with radiation therapy for lung cancer, and to assess the dosimetric impact of its integration in radiation therapy planning. METHODS AND MATERIALS: Patients treated with stereotactic ablative radiation therapy for early-stage or intensity modulated radiation therapy for locally advanced lung cancer were prospectively enrolled in this study. A DECT in treatment position was obtained at time of treatment planning. The relative contribution of each voxel to the total lung function was based on iodine distribution. The composition of each voxel was determined on the basis of a 2-material decomposition. The DECT-derived lobar function was compared with single photon emission computed tomography/computed tomography (SPECT/CT). A functional map was integrated in the treatment planning system using 6 subvolumes of increasing iodine distribution levels. Percent lung volume receiving 5 Gy (V5), V20, and mean dose (MLD) to whole lungs (anatomic) versus functional lungs were compared. RESULTS: Twenty-five patients with lung cancer, including 18 patients treated with stereotactic ablative radiation therapy and 7 patients with intensity modulated radiation therapy (locally advanced), were included. Eighty-four percent had chronic obstructive pulmonary disease. Median (range) forced expiratory volume in 1 second was 62% of predicted (29%-113%), and median diffusing capacity of the lung for carbon monoxide was 56% (39%-91%). There was a strong linear correlation between DECT- and SPECT/CT-derived lobar function (Pearson coefficient correlation r=0.89, P<.00001). Mean (range) differences in V5, V20, and MLD between anatomic and functional lung volumes were 16% (0%-48%, P=.03), 5% (1%-15%, P=.12), and 15% (1%-43%, P=.047), respectively. CONCLUSIONS: Lobar function derived from a DECT iodine map correlates well with SPECT/CT, and its integration in lung treatment planning is associated with significant differences in V5 and MLD to functional lungs. Future work will involve integration of the weighted functional volume in the treatment planning system, along with integration of an iodine map for functional lung-sparing IMRT.

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.

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.

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

INTRODUCTION: 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. METHOD: This analysis included lung tumours treated with VMAT to 50-60 Gy in 3-5 fractions. Treatment planning was based on four-dimensional CT scans from which internal tumour volumes (ITV) were derived. An isotropic 5 mm margin was added to obtain the final planning target volume (PTV). Patients were treated supine with a customized dual vacuum immobilization device (BodyFIX, Elekta, Sweden). All patients underwent pre and mid-treatment CBCTs. Following each CBCT, a rigid registration was performed by a radiation oncologist. IFM was defined as the target displacement from pre to mid-treatment CBCT. For patients with an IFM vector ≥5 mm, a post hoc dose calculation analysis was performed to assess the dosimetric impact of CBCT-guided repositioning. RESULTS: Ninety-seven patients (367 fractions) were included. Mean (±SD) overall treatment time was 53:02 ± 13:08 min. Mean time for mid-treatment CBCT scan acquisition and patient repositioning was 15:49 ± 4:14 min. Mean IFM vector was 1.5 ± 1.4 mm (max = 8.1 mm) and was <5 mm in 354/367 (96%) of fractions. For all 13 fractions with an IFM vector ≥5 mm, dose calculation analysis of worst-case scenario indicates that ITV coverage would have remained ≥95% without mid-treatment repositioning. CONCLUSION: For 96% of fractions, the IFM vector was within the 5 mm PTV margin. Mid-treatment CBCT-guided couch repositioning did not significantly impact ITV coverage and prolonged treatment duration.

Analysis of Pulmonary Vein Antrums Motion with Cardiac Contraction Using Dual-Source Computed Tomography.

PURPOSE: The purpose of the study was to determine the extent of displacement of the pulmonary vein antrums resulting from the intrinsic motion of the heart using 4D cardiac dual-source computed tomography (DSCT). METHODS: Ten consecutive female patients were enrolled in this prospective planning study. In breath-hold, a contrast-injected cardiac 4-dimensional (4D) computed tomography (CT) synchronized to the electrocardiogram was obtained using a prospective sequential acquisition method including the extreme phases of systole and diastole. Right and left atrial fibrillation target volumes (CTVR and CTVL) were defined, with each target volume containing the antral regions of the superior and inferior pulmonary veins. Four points of interest were used as surrogates for the right superior and inferior pulmonary vein antrum (RSPVA and RIPVA) and the left superior and inferior pulmonary vein antrum (LSPVA and LIPVA). On our 4D post-processing workstation (MIM Maestro™, MIM Software Inc.), maximum displacement of each point of interest from diastole to systole was measured in the mediolateral (ML), anteroposterior (AP), and superoinferior (SI) directions. RESULTS: Median age of the enrolled patients was 60 years (range, 56-71 years). Within the CTVR, the mean displacements of the superior and inferior surrogates were 3 mm vs. 1 mm (p=0.002), 2 mm vs. 0 mm (p= 0.001), and 3 mm vs. 0 mm (p=0.00001), in the ML, AP, and SI directions, respectively. On the left, mean absolute displacements of the LSPVA vs. LIPVA were similar at 4 mm vs. 1 mm (p=0.0008), 2 mm vs. 0 mm (p= 0.001), and 3 mm vs. 1 mm (p=0.00001) in the ML, AP, and SI directions. CONCLUSION: When isolated from breathing, cardiac contraction is associated with minimal inferior pulmonary veins motion and modest (1-6 mm) motion of the superior veins. Target deformation was thus of a magnitude similar or greater than target motion, limiting the potential gains of cardiac tracking. Optimal strategies for cardiac radiosurgery should thus either incorporate the generation of an internal target or cardiac gating. In either case, cardiac 4D DSCT would allow for personalized margin definition.

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.

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.

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.

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.

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.

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, patient's 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.

A phase II comparative study of gross tumor volume definition with or without PET/CT fusion in dosimetric planning for non-small-cell lung cancer (NSCLC): primary analysis of Radiation Therapy Oncology Group (RTOG) 0515.

BACKGROUND: Radiation Therapy Oncology Group (RTOG) 0515 is a Phase II prospective trial designed to quantify the impact of positron emission tomography (PET)/computed tomography (CT) compared with CT alone on radiation treatment plans (RTPs) and to determine the rate of elective nodal failure for PET/CT-derived volumes. METHODS: Each enrolled patient underwent definitive radiation therapy for non-small-cell lung cancer (≥ 60 Gy) and had two RTP datasets generated: gross tumor volume (GTV) derived with CT alone and with PET/CT. Patients received treatment using the PET/CT-derived plan. The primary end point, the impact of PET/CT fusion on treatment plans was measured by differences of the following variables for each patient: GTV, number of involved nodes, nodal station, mean lung dose (MLD), volume of lung exceeding 20 Gy (V20), and mean esophageal dose (MED). Regional failure rate was a secondary end point. The nonparametric Wilcoxon matched-pairs signed-ranks test was used with Bonferroni adjustment for an overall significance level of 0.05. RESULTS: RTOG 0515 accrued 52 patients, 47 of whom are evaluable. The follow-up time for all patients is 12.9 months (2.7-22.2). Tumor staging was as follows: II = 6%; IIIA = 40%; and IIIB = 54%. The GTV was statistically significantly smaller for PET/CT-derived volumes (98.7 vs. 86.2 mL; p < 0.0001). MLDs for PET/CT plans were slightly lower (19 vs. 17.8 Gy; p = 0.06). There was no significant difference in the number of involved nodes (2.1 vs. 2.4), V20 (32% vs. 30.8%), or MED (28.7 vs. 27.1 Gy). Nodal contours were altered by PET/CT for 51% of patients. One patient (2%) has developed an elective nodal failure. CONCLUSIONS: PET/CT-derived tumor volumes were smaller than those derived by CT alone. PET/CT changed nodal GTV contours in 51% of patients. The elective nodal failure rate for GTVs derived by PET/CT is quite low, supporting the RTOG standard of limiting the target volume to the primary tumor and involved nodes.