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.

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.

Central3D: A Computer Tool to Help Clinicians Differentiate Central and Peripheral Lung Tumors.

PURPOSE: We present a concise description of an in-house decision aid software called "Central3D" that allows a quick and robust lung tumor classification between central and peripheral as defined by the Radiation Therapy Oncology Group (RTOG) 0813. METHODS AND MATERIALS: Twenty cases of lung tumors were selected for this study and four radiation oncologists blindly classified them as peripheral versus central without assistance of our software. All discordant cases were reviewed using Central3D and prompt consensus was obtained. RESULTS: Many authors have stressed the importance of adopting risk adaptive fractionation schedule with lower biological equivalent dose when treating centrally-located high risks lesions. Central3D addresses the limitation of current treatment planning systems to represent image data in fixed planes and can help radiation oncologists to fully characterize these pulmonary lesions.

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.

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.

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.

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.

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.