Prognosis and predictors of site of first metastasis after definitive radiation therapy for non-small cell lung cancer.

Background and purpose Evidence suggests that distinct biologic phenomenon produce different patterns of distant metastatic (DM) failures. We attempted to identify prognostically poor sites of first DM and to define factors predictive of their development. Methods and materials A total of 1074 patients treated with ≥60 Gy definitive radiation for initially non-metastatic non-small cell lung cancer (NSCLC) were analyzed. Uni- and multivariate Cox regression was utilized to associate clinical factors with DM site, and metastatic site with overall survival (OS). To account for competing events, multivariate Fine and Gray regression was utilized to identify treatment and disease factors predictive of site-specific metastases. Results Sites of first DM associated with worse survival were liver (median OS: 5 months after DM) and bone (median OS: 6.7 months after DM). Multivariate regression identified non-squamous histology to be associated with first DM within the liver (HR = 2.04, 95% CI 1.16-3.60, p = 0.01), while delay between diagnosis and RT (third vs. first tertile: HR = 2.3, 95% CI 1.26-4.21, p = 0.007) in addition to advanced stage (stage III vs. II/I: HR = 2.37, 95% CI 1.11-5.06, p = 0.03) were associated with first DM within bone. Conclusions Liver and bone as site of first DM is associated with worse prognosis and are predicted by different disease and treatment factors.

Smartphone-based augmented reality patient education in radiation oncology.

We built an augmented reality (AR) patient education application for portable iOS and Android devices that allows patients to view a virtual simulation of themselves receiving radiation treatment. We created software that reads data from the clinical treatment planning system and renders the patient's actual radiotherapy plan in AR on a tablet or smartphone. The patient's CT simulation data are converted into a 3D translucent virtual human shown being treated with visible radiation beams from a virtual linear accelerator. We conducted a patient study to determine if showing patients this AR simulation improves patient understanding of radiotherapy and/or reduces anxiety about treatment. A total of 75 patients completed this study. The most common plans were 3D breast tangents and intensity modulated radiotherapy lung plans. Patients were administered questionnaires both before and after their AR viewing experience. After their AR viewing, 95% of patients indicated that they had a better understanding of how radiotherapy will be used to treat their cancer. Of the 35 patients who expressed anxiety about radiotherapy beforehand, 21 (60%) indicated that they had decreased anxiety after the AR session. In our single-arm prospective patient study, we found that this simplified low-cost tablet-based personalized AR simulation can be a helpful educational tool for cancer patients undergoing radiotherapy.

Stereotactic ablative radiation therapy for pulmonary metastases: Improving overall survival and identifying subgroups at high risk of local failure.

BACKGROUND & PURPOSE: Stereotactic ablative radiation therapy (SABR) is an emerging treatment option for patients with pulmonary metastases; identifying patients who would benefit from SABR can improve outcomes. MATERIALS & METHODS: We retrospectively analyzed local failure (LF), distant failure (DF), overall survival (OS), and toxicity in 317 patients with 406 pulmonary metastases treated with SABR in January 2006-September 2017 at a tertiary cancer center. RESULTS: Median follow-up time was 23 months. Primary adrenal, colorectal, sarcoma, or pancreatic ("less responsive") tumors led to high rates of LF. LF rates for patients with less responsive vs. responsive tumors were 4.6% vs. 1.6% at 12 months and 12.8% vs. 3.9% at 24 months (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.11-0.73; Log-Rank P = 0.0087). A nomogram for 24-month local control was created using Cox multivariate factors (surgical history, planning target volume, primary disease site, lung lobe location). Treating patients with ≤3 pulmonary metastases vs. >3 pulmonary metastases was associated with improved 24-month (74.2% vs. 59.3%) and 48-month (47.7% vs. 35.1%) OS (HR 0.66, 95% CI 0.47-0.95; Log-Rank P = 0.043), and reduced 12-month (22.5% vs. 50.8%) and 24-month (31.8% vs. 61.4%) intrathoracic DF (HR 0.53, 95% CI 0.38-0.74; Log-Rank P < 0.0001). The most common toxicity was asymptomatic pneumonitis (14.8%). Six patients had grade 3 events (5 pneumonitis, 1 brachial plexus). CONCLUSIONS: SABR for pulmonary metastases was effective and well tolerated. Irradiating limited intrathoracic sites of disease led to improved OS and intrathoracic DM. Higher SABR doses or surgery could be considered for less radio-responsive primary tumors.

Underuse of Radiation Therapy After Breast Conservation Surgery in Puerto Rico: A Puerto Rico Central Cancer Registry-Health Insurance Linkage Database Study.

PURPOSE: To identify rates of postoperative radiation therapy (RT) after breast conservation surgery (BCS) in women with stage I or II invasive breast cancer treated in Puerto Rico and to examine the sociodemographic and health services characteristics associated with variations in receipt of RT. METHODS: The Puerto Rico Central Cancer Registry-Health Insurance Linkage Database was used to identify patients diagnosed with invasive breast cancer between 2008 and 2012 in Puerto Rico. Claims codes identified the type of surgery and the use of RT. Logistic regression models were used to examine the independent association between sociodemographic and clinical covariates. RESULTS: Among women who received BCS as their primary definitive treatment, 64% received adjuvant RT. Significant predictors of RT after BCS included enrollment in Medicare (odds ratio [OR], 2.14; 95% CI, 1.46 to 3.13; P ≤ .01) and dual eligibility for Medicare and Medicaid (OR, 1.61; 95% CI, 1.14 to 2.27; P < .01). In addition, it was found that RT was more likely to have been received in certain geographic locations, including the Metro-North (OR, 2.20; 95% CI, 1.48 to 3.28; P < .01), North (OR, 1.78; 95% CI, 1.20 to 2.64; P < .01), West (OR, 4.04; 95% CI, 2.61 to 6.25; P < .01), and Southwest (OR, 2.79; 95% CI, 1.70 to 4.59; P < .01). Furthermore, patients with tumor size > 2.0 cm and ≤ 5.0 cm (OR, 0.61; 95% CI, 0.40 to 0.93; P = .02) and those with tumor size > 5.0 cm (OR, 0.37; 95% CI, 0.15 to 0.92; P = .03) were found to be significantly less likely to receive RT. CONCLUSION: Underuse of RT after BCS was identified in Puerto Rico. Patients enrolled in Medicare and those who were dually eligible for Medicaid and Medicare were more likely to receive RT after BCS compared with patients with Medicaid alone. There were geographic variations in the receipt of RT on the island.

Stereotactic ablative radiotherapy for adrenal gland metastases: Factors influencing outcomes, patterns of failure, and dosimetric thresholds for toxicity.

PURPOSE: We report our single-institution experience with stereotactic ablative radiotherapy (SABR) for adrenal metastasis and identify factors influencing outcomes, patterns of failure, and dosimetric thresholds for toxicity. METHODS AND MATERIALS: We identified patients with adrenal metastases treated with SABR from 2009 to 2015. Toxicity was evaluated with Common Terminology Criteria for Adverse Events v4.0. Local failures were categorized as in-field, marginal, or out-of-field. New or progressive disease outside the treated adrenal gland was considered distant failure. Survival and time to local and distant failure were estimated by the Kaplan-Meier method. Prognostic factors were evaluated with a Cox proportional hazards model. Fisher's exact tests were used to compare toxicity between dosimetric thresholds. RESULTS: Forty-three patients with 49 adrenal metastases (84% from lung) were treated with SABR to a median prescribed dose of 60 Gy in 10 fractions. Median overall survival time was 19 months, and 1- and 2-year rates were 65% and 42%, respectively. Bilateral adrenal metastases were associated with worse overall survival (P = .01). Median progression-free survival (PFS) time was 6 months, with most progressions being distant failure (most often to brain or bone). PFS was better in patients with a solitary adrenal metastasis (P = .03). Median time to local failure was not reached; the 1-year freedom from local failure rate was 74%. Nine failures were in field and 1 was marginal; no local failures occurred in lesions treated with biologically equivalent doses of >100 Gy. No patient experienced grade 3-5 toxicity. Low-grade gastrointestinal toxicity was common, but grade 2 toxicity was avoided in patients with a maximum stomach-bowel point dose of ≤50 Gy (P = .03). Low-grade adrenal insufficiency was common with bilateral treatment. CONCLUSION: SABR was well tolerated and resulted in good 1-year local control; PFS was promising for patients with solitary metastases. Low-grade toxicity was common, but can be minimized with strict dosimetric constraints.

Early experience with intensity modulated proton therapy for lung-intact mesothelioma: A case series.

PURPOSE: The purpose of this study was to describe our experience implementing intensity modulated proton therapy (IMPT) for lung-intact malignant pleural mesothelioma (MPM), including patient selection, treatment planning, dose verification, and process optimization. METHODS AND MATERIALS: Seven patients with epithelioid MPM were reviewed; 6 underwent pleurectomy, whereas 1 had biopsy alone. Four patients received IMPT and 3 received intensity modulated radiation therapy. Treatment plans for the other modality were created for dosimetric comparisons. Quality assurance processes included dose verification and robustness analysis. Image-guided setup was performed with the first isocenter, and couch shifts were applied to reposition to the second isocenter. RESULTS: Treatment with IMPT was well tolerated and completed without breaks. IMPT plans were designed with 2 isocenters, 4 beams, and ≤64 energy layers per beam. Dose verification processes were completed in 3 hours. Total daily treatment time was approximately 45 minutes (20 minutes for setup and 25 minutes for delivery). IMPT produced lower mean doses to the contralateral lung, heart, esophagus, liver, and ipsilateral kidney, with increased contralateral lung sparing when mediastinal boost was required for nodal disease. CONCLUSIONS: Our initial experience showed that IMPT was feasible for routine care of patients with lung-intact MPM.

Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma: toxicity, patterns of failure, and a matched survival analysis.

PURPOSE: To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). METHODS AND MATERIALS: In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or out of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. RESULTS: Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). CONCLUSIONS: Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but led to progressive declines in pulmonary function; OS and PFS were better in PD-IMRT compared with EPP-IMRT.

Simulation system for a rebreathing technique to measure multiple cardiopulmonary function parameters.

BACKGROUND: We developed a simple method for simulating a rebreathing maneuver to test the accuracy of the apparatus for simultaneous measurement of lung volume, diffusing capacity of the lung for carbon monoxide (Dlco), diffusing capacity of the lung for nitric oxide (Dlno), and pulmonary blood flow (Qc). METHODS: A test gas mixture containing 0.3% methane, 0.3% CO, 0.8% acetylene, 30% O(2), and 40 ppm nitric oxide in balance of nitrogen was sequentially diluted with a rebreathing gas mixture containing 0.3% acetylene, 0.3% methane, and 21% O(2) in balance of nitrogen in order to simulate the in vivo end-tidal disappearance of the test gas mixture. Simulation of one rebreathing maneuver consisted of at least four serial dilution steps with a performance time of < 5 min. Using this technique, we estimated functional residual capacity, Qc, Dlco, and Dlno at various flow rates and dilution ratios (0.95 to 4.04 L, 3.54 to 6.83 L/min, 7.27 to 15.12 mL/min/mm Hg, and 6.51 to 12.00 mL/min/mm Hg, respectively) and verified simulation results against nominal values. The same apparatus also could simulate a single-breath procedure. RESULTS: Compared to nominal values, errors in measured values by rebreathing and single-breath Dlco simulation remained < 5% and 7%, respectively. Slopes of the correlations were close to 1.0 (within +/- 5% and +/- 6.4% in rebreathing and single-breath Dlco simulation studies, respectively). CONCLUSION: The results demonstrate the feasibility of this simulation method for standardizing the experimental measurements obtained by rebreathing and single-breath techniques. Incorporation of these simulation steps enhances the noninvasive assessment of cardiopulmonary function.

Diminished alveolar microvascular reserves in type 2 diabetes reflect systemic microangiopathy.

OBJECTIVE: Alveolar microvascular function is moderately impaired in type 1 diabetes, as manifested by restriction of lung volume and diffusing capacity (DL(CO)). We examined whether similar impairment develops in type 2 diabetes and defined the physiologic sources of impairment as well as the relationships to glycemia and systemic microangiopathy. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted at a university-affiliated diabetes treatment center and outpatient diabetes clinic, involving 69 nonsmoking type 2 diabetic patients without overt cardiopulmonary disease. Lung volume, pulmonary blood flow (Q), DL(CO), membrane diffusing capacity (measured from nitric oxide uptake [DL(NO)]), and pulmonary capillary blood volume (V(C)) were determined at rest and exercise for comparison with those in 45 healthy nonsmokers as well as with normal reference values. RESULTS: In type 2 diabetic patients, peak levels of oxygen uptake, Q and DL(CO), DL(NO), and V(C) at exercise were 10-25% lower compared with those in control subjects. In nonobese patients (BMI <30 kg/m(2)), reductions in DL(CO), DL(NO), and V(C) were fully explained by the lower lung volume and peak Q, but these factors did not fully explain the impairment in obese patients (BMI >30 kg/m(2)). The slope of the increase in V(C) with respect to Q was reduced approximately 20% in patients regardless of BMI, consistent with impaired alveolar-capillary recruitment. Functional impairment was directly related to A1C level, retinopathy, neuropathy, and microalbuminuria in a sex-specific manner. CONCLUSIONS: Alveolar microvascular reserves are reduced in type 2 diabetes, reflecting restriction of lung volume, alveolar perfusion, and capillary recruitment. This reduction correlates with glycemic control and extrapulmonary microangiopathy and is aggravated by obesity.