Clinical and Dosimetric Impact of 2D kV Motion Monitoring and Intervention in Liver Stereotactic Body Radiation Therapy.

Purpose: Positional errors resulting from motion are a principal challenge across all disease sites in radiation therapy. This is particularly pertinent when treating lesions in the liver with stereotactic body radiation therapy (SBRT). To achieve dose escalation and margin reduction for liver SBRT, kV real-time imaging interventions may serve as a potential solution. In this study, we report results of a retrospective cohort of liver patients treated using real-time 2D kV-image guidance SBRT with emphasis on the impact of (1) clinical workflow, (2) treatment accuracy, and (3) tumor dose. Methods and Materials: Data from 33 patients treated with 41 courses of liver SBRT were analyzed. During treatment, planar kV images orthogonal to the treatment beam were acquired to determine treatment interventions, namely treatment pauses (ie, adequacy of gating thresholds) or treatment shifts. Patients were shifted if internal markers were >3 mm, corresponding to the PTV margin used, from the expected reference condition. The frequency, duration, and nature of treatment interventions (ie, pause vs shift) were recorded, and the dosimetric impact associated with treatment shifts was estimated using a machine learning dosimetric model. Results: Of all fractions delivered, 39% required intervention, which took on average 1.9 ± 1.6 minutes and occurred more frequently in treatments lasting longer than 7 minutes. The median realignment shift was 5.7 mm in size, and the effect of these shifts on minimum tumor dose in simulated clinical scenarios ranged from 0% to 50% of prescription dose per fraction. Conclusion: Real-time kV-based imaging interventions for liver SBRT minimally affect clinical workflow and dosimetrically benefit patients. This potential solution for addressing positional errors from motion addresses concerns about target accuracy and may enable safe dose escalation and margin reduction in the context of liver SBRT.

Evaluation of variables predicting PFT changes for lung cancer patients treated on a prospective 4DCT-ventilation functional avoidance clinical trial.

PURPOSE: Functional avoidance radiotherapy uses functional imaging to reduce pulmonary toxicity by designing radiotherapy plans that reduce doses to functional regions of the lung. A phase-II, multi-center, prospective study of 4DCT-ventilation functional avoidance was completed. Pre and post-treatment pulmonary function tests (PFTs) were acquired and assessed pulmonary function change. This study aims to evaluate which clinical, dose and dose-function factors predict PFT changes for patients treated with 4DCT-ventilation functional avoidance radiotherapy. MATERIALS AND METHODS: 56 patients with locally advanced lung cancer receiving radiotherapy were accrued. PFTs were obtained at baseline and three months following radiotherapy and included forced expiratory volume in 1-second (FEV1), forced vital capacity (FVC), and FEV1/FVC. The ability of patient, clinical, dose (lung and heart), and dose-function metrics (metrics that combine dose and 4DCT-ventilation-based function) to predict PFT changes were evaluated using univariate and multivariate linear regression. RESULTS: Univariate analysis showed that only dose-function metrics and the presence of chronic obstructive pulmonary disease (COPD) were significant (p<0.05) in predicting FEV1 decline. Multivariate analysis identified a combination of clinical (immunotherapy status, presence of thoracic comorbidities, smoking status, and age), along with lung dose, heart dose, and dose-function metrics in predicting FEV1 and FEV1/FVC changes. CONCLUSION: The current work evaluated factors predicting PFT changes for patients treated in a prospective functional avoidance radiotherapy study. The data revealed that lung dose- function metrics could predict PFT changes, validating the significance of reducing the dose to the functional lung to mitigate the decline in pulmonary function and providing guidance for future clinical trials.

Fiducial Markers Allow Accurate and Reproducible Delivery of Liver Stereotactic Body Radiation Therapy.

Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment and improvements in inter-observer reliability. Nineteen patients with 24 liver lesions were treated with SBRT. Target localization was performed using fiducial markers on cone-beam computed tomography (CBCT). Each CBCT procedure was retrospectively realigned to match both the liver edge and fiducial markers. The shifts were recorded by seven independent observers. Inter-observer variability was analyzed by calculating the mean error and uncertainty for the set-up. The mean absolute Cartesian error observed from fiducial and liver edge-based alignment was 1.5 mm and 5.3 mm, respectively. The mean uncertainty from fiducial and liver edge-based alignment was 1.8 mm and 4.5 mm, respectively. An error of 5 mm or greater was observed 50% of the time when aligning to the liver surface versus 5% of the time when aligning to fiducial markers. Aligning to the liver edge significantly increased the error, resulting in increased shifts when compared to alignment to fiducials. Tumors of 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials (4.8 cm vs. 4.4 cm, p = 0.003). Our data support the use of fiducial markers for safer and more accurate liver SBRT.

Characterizing Pulmonary Function Test Changes for Patients With Lung Cancer Treated on a 2-Institution, 4-Dimensional Computed Tomography-Ventilation Functional Avoidance Prospective Clinical Trial.

Purpose: Four-dimensional computed tomography (4DCT)-ventilation-based functional avoidance uses 4DCT images to generate plans that avoid functional regions of the lung with the goal of reducing pulmonary toxic effects. A phase 2, multicenter, prospective study was completed to evaluate 4DCT-ventilation functional avoidance radiation therapy. The purpose of this study was to report the results for pretreatment to posttreatment pulmonary function test (PFT) changes for patients treated with functional avoidance radiation therapy. Methods and Materials: Patients with locally advanced lung cancer receiving chemoradiation were accrued. Functional avoidance plans based on 4DCT-ventilation images were generated. PFTs were obtained at baseline and 3 months after chemoradiation. Differences for PFT metrics are reported, including diffusing capacity for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). PFT metrics were compared for patients who did and did not experience grade 2 or higher pneumonitis. Results: Fifty-six patients enrolled on the study had baseline and posttreatment PFTs evaluable for analysis. The mean change in DLCO, FEV1, and FVC was -11.6% ± 14.2%, -5.6% ± 16.9%, and -9.0% ± 20.1%, respectively. The mean change in DLCO was -15.4% ± 14.4% for patients with grade 2 or higher radiation pneumonitis and -10.8% ± 14.1% for patients with grade <2 radiation pneumonitis (P = .37). The mean change in FEV1 was -14.3% ± 22.1% for patients with grade 2 or higher radiation pneumonitis and -3.9% ± 15.4% for patients with grade <2 radiation pneumonitis (P = .09). Conclusions: The current work is the first to quantitatively characterize PFT changes for patients with lung cancer treated on a prospective functional avoidance radiation therapy study. In comparison with patients treated with standard thoracic radiation planning, the data qualitatively show that functional avoidance resulted in less of a decline in DLCO and FEV1. The presented data can help elucidate the potential pulmonary function improvement with functional avoidance radiation therapy.

Population-level and individual-level explainers for propensity score matching in observational studies.

Precis: The exclusion of unmatched observations in propensity score matching has implications for the generalizability of causal effects. Machine learning methods can help to identify how the study population differs from the unmatched subpopulation. Background: There has been widespread use of propensity scores in evaluating the effect of cancer treatments on survival, particularly in administrative databases and cancer registries. A byproduct of certain matching schemes is the exclusion of observations. Borrowing an analogy from clinical trials, one can view these exclusions as subjects that do not satisfy eligibility criteria. Methods: Developing identification rules for these "data-driven eligibility criteria" in observational studies on both population and individual levels helps to ascertain the population on which causal effects are being made. This article presents a machine learning method to determine the representativeness of causal effects in two different datasets from the National Cancer Database. Results: Decision trees reveal that groups with certain features have a higher probability of inclusion in the study population than older patients. In the first dataset, younger age categories had an inclusion probability of at least 0.90 in all models, while the probability for the older category ranged from 0.47 to 0.65. Most trees split once more on an even higher age at a lower node, suggesting that the oldest patients are the least likely to be matched. In the second set of data, both age and surgery status were associated with inclusion. Conclusion: The methodology presented in this paper underscores the need to consider exclusions in propensity score matching procedures as well as complementing matching with other propensity score adjustments.

Results of a Multi-Institutional Phase 2 Clinical Trial for 4DCT-Ventilation Functional Avoidance Thoracic Radiation Therapy.

PURPOSE: Radiation pneumonitis remains a major limitation in the radiation therapy treatment of patients with lung cancer. Functional avoidance radiation therapy uses functional imaging to reduce pulmonary toxic effects by designing radiation therapy plans that reduce doses to functional regions of the lung. Lung functional imaging has been developed that uses 4-dimensional computed tomography (4DCT) imaging to calculate 4DCT-based lung ventilation (4DCT-ventilation). A phase 2 multicenter study was initiated to evaluate 4DCT-ventilation functional avoidance radiation therapy. The study hypothesis was that functional avoidance radiation therapy could reduce the rate of grade ≥2 radiation pneumonitis to 12% compared with a 25% historical rate, with the trial being positive if ≤16.4% of patients experienced grade ≥2 pneumonitis. METHODS AND MATERIALS: Lung cancer patients receiving curative-intent radiation therapy (prescription doses of 45-75 Gy) and chemotherapy were accrued. Patient 4DCT scans were used to generate 4DCT-ventilation images. The 4DCT-ventilation images were used to generate functional avoidance plans that reduced doses to functional portions of the lung while delivering the prescribed tumor dose. Pneumonitis was evaluated by a clinician at 3, 6, and 12 months after radiation therapy. RESULTS: Sixty-seven evaluable patients were accrued between April 2015 and December 2019. The median prescription dose was 60 Gy (range, 45-66 Gy) delivered in 30 fractions (range, 15-33 fractions). The average reduction in the functional volume of lung receiving ≥20 Gy with functional avoidance was 3.5% (range, 0%-12.8%). The median follow-up was 312 days. The rate of grade ≥2 radiation pneumonitis was 10 of 67 patients (14.9%; 95% upper CI, 24.0%), meeting the phase 2 criteria. CONCLUSIONS: 4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra procedure necessary. This first report of a multicenter study of 4DCT-ventilation functional avoidance radiation therapy provided data showing that the trial met phase 2 criteria and that evaluation in a phase 3 study is warranted.

Optimizing Coded Aperture Imaging techniques to allow for online tracking of fiducial markers with high-energy scattered radiation from treatment beam.

PURPOSE: Real-time visualization of target motion using fiducial markers during radiation therapy treatment will allow for more accurate dose delivery. The purpose of this study was to optimize techniques for online fiducial marker tracking by detecting the scattered treatment beam through coded aperture imaging (CAI). Coded aperture imaging is a novel imaging technique that can allow target tracking in real time during treatment, and do so without adding any additional radiation dose, by making use of the scattered treatment beam radiation. METHODS: Radiotherapy beams of various energies, incident on phantoms containing gold fiducial markers were modeled using MCNP6.2 Monte Carlo transport code. Orthogonal scatter radiographs were collected through a CAI geometry. After decoding the simulated radiograph data, the centroid location and FWHM/SNR of the fiducial signals were analyzed. The effects of properties related to the CA (rank, pattern, and physical dimensions), detector (dimensions and pixel count), position (CA and phantom), and the incident beam (spectrum and direction) were investigated. These variables were evaluated by quantifying the positional accuracy, resolution, and SNR of the fiducials' signal. The effects of phantom scatter and decoding artifacts were reduced via Fourier filtering to avoid treatment interruption and physical interaction with the coded mask. RESULTS: The method was able to accurately localize the markers to within 1 pixel of a simulated radiograph. A 10 × 10 × 2 cm tungsten mask was chosen to attenuate >99 % of incident scatter through opaque elements, while minimizing collimation artifacts which arise from vignetting of the coded radiograph. Clear separation of centroids from fiducial signals with 2.5 mm separation was maintained, and initial optimization of parameters has produced an aperture which decodes the location of multiple fiducial markers inside a human phantom properly with a high SNR in the final radiograph image. CONCLUSION: Current results show a proof of concept for a novel real-time imaging method. Coded aperture imaging is a promising technique for extracting the fiducial scatter signal from a broader Compton-scatter background. These results can be used to further optimize the CAI parameter space and guide fabrication and testing of a clinical device.

Simulation of x-ray-induced acoustic imaging for absolute dosimetry: Accuracy of image reconstruction methods.

PURPOSE: Three-dimensional in-vivo dose verification is one of the standing challenges in radiation therapy. X-ray-induced acoustic tomography has recently been proposed as an imaging method for use in in-vivo dosimetry. The aim of this study was to investigate the accuracy of reconstructing three-dimensional (3D) absolute dose using x-ray-induced acoustic tomography. We performed this investigation using two different tomographic dose reconstruction techniques. METHODS: Two examples of 3D dose reconstruction techniques for x-ray acoustic imaging are investigated. Dose distributions are calculated for varying field sizes using a clinical treatment planning system. The induced acoustic pressure waves which are generated by the increase in temperature due to the absorption of pulsed MV x-rays are simulated using an advanced numerical modeling package for acoustic wave propagation in the time domain. Two imaging techniques, back projection and iterative time reversal, are used to reconstruct the 3D dose distribution in a water phantom with open fields. Image analysis is performed and reconstructed depth dose curves from x-ray acoustic imaging are compared to the depth dose curves calculated from the treatment planning system. Calculated field sizes from the reconstructed dose profiles by back projection and time reversal are compared to the planned field size to determine their accuracy. The iterative time reversal imaging technique is also used to reconstruct dose in an example clinical dose distribution. Image analysis of this clinical test case is performed using the gamma passing rate. In addition, gamma passing rates are used to validate the stopping criteria in the iterative time reversal method. RESULTS: Water phantom simulations showed that back projection does not adequately reconstruct the shape and intensity of the depth dose. When compared to the depth of maximum dose calculated by a treatment planning system, the maximum dose depth by back projection is shifted deeper by 55 and 75 mm for 4 × 4 cm and 10 × 10 cm field sizes, respectively. The reconstructed depth dose by iterative time reversal accurately agrees with the planned depth dose for a 4 × 4 cm field size and is shifted deeper by 12 mm for the 10 × 10 cm field size. When reconstructing field sizes, the back projection method leads to 18% and 35% larger sizes for the 4 × 4 cm and 10 × 10 cm fields, respectively, whereas the iterative time reversal method reconstructs both field sizes with < 2% error. For the clinical dose distribution, we were able to reconstruct the dose delivered by a 1 degree sub-arc with a good accuracy. The reconstructed and planned doses were compared using gamma analysis, with> 96% gamma passing rate at 3%/2 mm. CONCLUSIONS: Our results show that the 3D x-ray acoustic reconstructed dose by iterative time reversal is considerably more accurate than the dose reconstructed by back projection. Iterative time reversal imaging has a potential for use in 3D absolute dosimetry.

The Effect of Time to Postoperative Radiation Therapy on Survival in Resected Merkel Cell Carcinoma.

OBJECTIVES: Delays from surgery to adjuvant radiation therapy (aRT) are associated with poorer prognosis in multiple neoplasms. Presently, no data exist for Merkel cell carcinoma (MCC). The authors sought to assess the time interval from surgery to aRT and effect on outcomes in MCC. MATERIALS AND METHODS: The National Cancer Database was queried for histologically confirmed nonmetastatic MCC status post resection and aRT diagnosed between 2004 and 2015 who received aRT within 24 weeks of surgery. Kaplan-Meier analysis assessed univariate overall survival (OS); multivariable Cox proportional hazards modeling assessed multivariate OS; χ and logistic regression assessed differences in baseline characteristics and predictors of delayed aRT. RESULTS: Of 5952 patients meeting criteria, 13% commenced aRT within 4 weeks, 48% between 4 and 7 weeks, 23% between 8 and 11 weeks, 11% between 12 and 15 weeks, and 6% between 16 and 24 weeks. There were no differences in OS on the basis of the surgery-aRT interval (P=0.99). Predictors of worse OS on the multivariate analysis included advanced age, greater comorbidities, male sex, lower regional income, earlier year of diagnosis, more advanced tumor and nodal staging, positive margins, head and neck location, and treatment at community facilities (P<0.05 for all). Factors predictive of delayed aRT were identified. Subset analyses on these factors, such as receipt of chemotherapy or positive lymph nodes, did not demonstrate that the timing of aRT affected survival (P≥0.37). CONCLUSION: This study of a contemporary national database revealed that delays from resection to aRT were not associated with survival in MCC, somewhat discordant from other malignancies such as squamous cell carcinoma.

Objective assessment of the effects of tumor motion in radiation therapy.

PURPOSE: Internal organ motion reduces the accuracy and efficacy of radiation therapy. However, there is a lack of tools to objectively (based on a medical or scientific task) assess the dosimetric consequences of motion, especially on an individual basis. We propose to use therapy operating characteristic (TOC) analysis to quantify the effects of motion on treatment efficacy for individual patients. We demonstrate the application of this tool with pancreatic stereotactic body radiation therapy (SBRT) clinical data and explore the origin of motion sensitivity. METHODS: The technique is described as follows. (a) Use tumor-motion data measured from patients to calculate the motion-convolved dose of the gross tumor volume (GTV) and the organs at risk (OARs). (b) Calculate tumor control probability (TCP) and normal tissue complication probability (NTCP) from the motion-convolved dose-volume histograms. (c) Construct TOC curves from TCP and NTCP models. (d) Calculate the area under the TOC curve (AUTOC) and use it as a figure of merit for treatment efficacy. We used tumor motion data measured from patients to calculate the relation between AUTOC and motion magnitude for 25 pancreatic SBRT treatment plans. Furthermore, to explore the driving factor of motion sensitivity of a given plan, we compared the dose distribution of motion-sensitive plans and motion-robust plans and studied the dependence of motion sensitivity to motion directions. RESULTS: Our technique is able to recognize treatment plans that are sensitive to motion. Under the presence of motion, the treatment efficacy of some plans changes from providing high tumor control and low risks of complications to providing no tumor control and high risks of side effects. Several treatment plans experience falloffs in AUTOC at a smaller magnitude of motion than other plans. In our dataset, a potential indicator of a motion-sensitive treatment plan is that the duodenum is in proximity to the tumor in the SI direction. CONCLUSIONS: The TOC framework can serve as a tool to quantify the effects of internal organ motion in radiation therapy. With pancreatic SBRT clinical data, we applied this tool to study the change in treatment efficacy induced by motion for individual treatment plans. This framework could potentially be used clinically to understand the effects of motion in an individual patient and to design a patient-specific motion management plan. This framework could also be used in research to evaluate different components of the treatment process, such as motion-management techniques, treatment-planning algorithms, and treatment margins.

Quantifying Allowable Motion to Achieve Safe Dose Escalation in Pancreatic SBRT.

PURPOSE: Tumor motion plays a key role in the safe delivery of stereotactic body radiation therapy (SBRT) for pancreatic cancer. The purpose of this study was to use tumor motion measured in patients to establish limits on motion magnitude for safe delivery of pancreatic SBRT and to help guide motion-management decisions in potential dose-escalation scenarios. METHODS AND MATERIALS: Using 91 sets of pancreatic tumor motion data, we calculated the motion-convolved dose of the gross tumor volume, duodenum, and stomach for 25 patients with pancreatic cancer. We derived simple linear or quadratic models relating motion to changes in dose and used these models to establish the maximum amount of motion allowable while satisfying error thresholds on key dose metrics. In the same way, we studied the effects of dose escalation and tumor volume on allowable motion. RESULTS: In our patient cohort, the mean (range) allowable motion for 33, 40, and 50 Gy to the planning target volume was 11.9 (6.3-22.4), 10.4 (5.2-19.1), and 9.0 (4.2-16.0) mm, respectively. The maximum allowable motion decreased as the dose was escalated and was smaller in patients with larger tumors. We found significant differences in allowable motion between the different plans, suggesting a patient-specific approach to motion management is possible. CONCLUSIONS: The effects of motion on pancreatic SBRT are highly variable among patients, and there is potential to allow more motion in certain patients, even in dose-escalated scenarios. In our dataset, a conservative limit of 6.3 mm would ensure safe treatment of all patients treated to 33 Gy in 5 fractions.

Postoperative radiation performed at the same surgical facility associated with improved overall survival in oral cavity squamous cell carcinoma.

BACKGROUND: The purpose of this analysis is to evaluate whether postoperative radiotherapy (PORT) at the same facility as surgery portends to better survival outcomes compared to PORT given at a different facility. METHODS: Patients underwent upfront surgery at the National Cancer Database reporting facility followed by PORT. PORT was coded as performed at either the same facility or at a different facility as surgery. RESULTS: A total of 10 832 patients were selected. Five-year overall survival (OS) was higher in patients undergoing PORT at the same facility: 52.5% vs 48.4% (P < 0.001). PORT performed at the same facility was associated with improved OS under multivariate (HR, 0.92; P = 0.01) and propensity score matched (hazard ratio, 0.90; P = 0.004) analyses. CONCLUSIONS: OS was better among patients with head and neck cancer who received PORT at the same facility as surgery.

The Clinical and Dosimetric Impact of Real-Time Target Tracking in Pancreatic SBRT.

PURPOSE: Motion often hinders the safe delivery of ablative doses of radiation in the treatment of pancreatic tumors. Real-time tumor-tracking methods are an emerging technique to increase the accuracy of delivery. In this study, we report on a large, retrospective cohort of pancreatic patients treated with real-time, fiducial-based, kV-image guidance of stereotactic body radiation therapy (SBRT). The purpose of our study was to determine the impact of real-time tracking on treatment accuracy, tumor dose, and clinical workflow. METHODS AND MATERIALS: Real-time tracking data from 68 patients treated with pancreatic SBRT were analyzed. The kV images orthogonal to the treatment beam were acquired in real time during treatment to visualize the location of implanted fiducial markers. Positional corrections were made if the fiducial markers were observed >3 mm from the expected reference position. We recorded the frequency and nature of treatment interventions resulting from real-time tracking and derived a neural network-based dosimetric model to calculate the impact of these in-treatment interventions on target dose. RESULTS: Treatment pauses that required patient realignment because of real-time tumor tracking occurred during 32% of all fractions. The median magnitude of realignment shifts was 5.2 mm (range, 2.1-18.9 mm). Forty-five percent of shifts resulted in dosimetric differences to the tumor; of these, the median point dose difference was 23% ± 22% of prescription dose (maximum, 94%). The number of pauses per fraction was significantly higher in patients treated with respiratory gating (vs abdominal compression) and in patients with greater treatment time. CONCLUSION: Fiducial-based, real-time target tracking is clinically feasible for pancreatic SBRT treatment. Our data indicate that real-time tumor tracking leads to patient realignment in 32% of cases and results in significant benefits to target coverage. The increased accuracy of real-time target tracking may potentially enable safe dose escalation in pancreatic SBRT.

Comparing outcomes of concurrent chemotherapy regimens in patients 65 years old or older with locally advanced oropharyngeal carcinoma.

BACKGROUND: The comparative efficacy of cisplatin (CDDP), carboplatin, and cetuximab (CTX) delivered concurrently with radiation for locally advanced oropharyngeal squamous cell carcinoma continues to be evaluated. METHODS: The linked Surveillance, Epidemiology, and End Results-Medicare database was used to identify and compare patient and disease profiles, mortality, toxicity, and overall cost for patients with oropharynx cancer undergoing definitive concurrent chemoradiation with CDDP, carboplatin, or CTX between 2006 and 2011. The human papillomavirus status was unknown. The primary outcome was 2-year overall survival (OS). RESULTS: Four hundred nine patients receiving concurrent CDDP (n = 167), carboplatin (n = 69), or CTX (n = 173) were included. Those who were older, those who were nonwhite, and those with a Charlson Comorbidity Index ≥ 2 were less likely to receive CDDP. Two-year OS was inferior with CTX (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.08-2.60; P = .020) and no different with carboplatin (HR, 1.31; 95% CI, 0.73-2.35; P = .362) in a Cox proportional hazards model (reference CDDP). There was no statistically significant difference between carboplatin and CTX (HR, 1.28; 95% CI, 0.77-2.14; P = .891). Rates of antiemetic use and hospital visits for nausea/emesis/diarrhea or dehydration were statistically higher with CDDP. Pneumonia rates were higher with carboplatin. In the multivariate model, the corrected mean per-patient spending was significantly higher for CTX and carboplatin than CDDP ($61,133 and $65,721 vs $48,709). CONCLUSIONS: Patients who received CDDP had improved OS. CDDP was also associated with slightly lower overall costs and higher antiemetic usage and hospital visit rates, although a strong selection bias was observed because those receiving CTX and carboplatin were older and had higher comorbidity scores.

Nomogram for preoperative prediction of nodal extracapsular extension or positive surgical margins in oropharyngeal squamous cell carcinoma.

INTRODUCTION: Extracapsular extension (ECE) in regional lymph nodes and positive surgical margins (PSM) are considered high-risk adverse pathologic features in patients with oropharyngeal squamous cell carcinoma (OPSCC) that each constitute an indication for postoperative adjuvant chemoradiation. We identify pre-operative clinical factors that can predict post-operative ECE and/or PSM and create a nomogram to help clinical decision making. METHODS: Adult patients with non-metastatic OPSCC with initial surgical treatment and confirmed HPV status diagnosed between 2010 and 2014 were selected from the National Cancer Database. Clinical staging was modified to American Joint Committee on Cancer 8th edition parameters. Logistic regression was used for multivariate analysis to identify predictors of pathologic ECE and/or PSM. RESULTS: 5065 patients were included. 47.5% of the 3336 HPV-positive (HPV+) patients had ECE/PSM. 40.4% of the 1729 HPV-negative (HPV-) patients with had ECE/PSM. A model was built that included age, clinical ECE, tumor grade, and clinical T and N staging for HPV+ patients. Increasing N-classification was highly predictive of pathologic ECE and/or PSM (N1 OR = 3.6, N2 OR = 7.0, N3 OR = 11.2, p < 0.01). Clinical ECE (OR = 4.1, p < 0.01), tumor grade (ORs 2.2-4.4 with p < 0.05), and increasing clinical T-classification (ORs 1.2-1.8, p < 0.05) were also associated with ECE and/or PSM. A similar model was built for HPV- with similar predictive capability. Two internally validated nomograms were designed that demonstrated good discrimination (HPV+ AUC = 0.66, 95% CI: 0.64-0.68, and HPV- AUC = 0.70, 95% CI: 0.67-0.72) and good calibration (goodness-of-fit statistic of HPV+ 6.32, p = 0.61 and HPV- 11.66, p = 0.17). CONCLUSIONS: These are the first nomograms designed to help predict ECE or PSM for both HPV+ and HPV- OPSCC. The nomograms can facilitate shared decision-making between clinicians and patients as they consider upfront treatment selection for OPSCC.

Radiosurgery alone is associated with favorable outcomes for brain metastases from small-cell lung cancer.

INTRODUCTION: Whole-brain radiation therapy (WBRT) is the standard approach for brain metastases (BM) arising in patients with small-cell lung cancer (SCLC), but the neurocognitive toxicities of WBRT are well documented. For this reason, stereotactic radiosurgery (SRS) alone is the preferred modality for limited BM in most histologies, but in SCLC there are few data exploring this approach. METHODS: We queried the National Cancer Database (NCDB) for patients with SCLC with BM at diagnosis and stratified by upfront SRS compared with upfront WBRT ±â€¯SRS. We utilized multivariate Cox regression and propensity score matching (PSM) to determine the impact on overall survival (OS) of each approach. RESULTS: 5952 eligible patients (WBRT: 5752; SRS: 200) were identified from 2010 to 2014 with a median follow-up of 40.0 months. Upfront SRS was associated with superior OS (median 10.8 vs 7.1 months, HR 0.65, 95% CI 0.55-0.75, p < 0.001), which persisted on multivariate analysis controlling for comorbidities, extracranial metastases, age, race/ethnicity, and gender (HR 0.70, 95% CI 0.60-0.81, p < 0.001). These results were confirmed in PSM analysis. A subset analysis comparing outcomes after SRS vs SRS + WBRT showed no differences in OS (p = .601). CONCLUSIONS: To our knowledge, this is the largest dataset of patients treated with SRS alone for SCLC. The observation of favorable OS with SRS alone in this contemporary dataset suggests that SRS alone may be appropriate for some patients with SCLC. Prospective investigations of SRS in SCLC are warranted.

Post-Treatment Mortality After Surgery and Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer.

Purpose In early-stage non-small cell lung cancer (NSCLC), post-treatment mortality may influence the comparative effectiveness of surgery and stereotactic body radiotherapy (SBRT), with implications for shared decision making among high-risk surgical candidates. We analyzed early mortality after these interventions using the National Cancer Database. Patients and Methods We abstracted patients with cT1-T2a, N0, M0 NSCLC diagnosed between 2004 and 2013 undergoing either surgery or SBRT. Thirty-day and 90-day post-treatment mortality rates were calculated and compared using Cox regression and propensity score-matched analyses. Results We identified 76,623 patients who underwent surgery (78% lobectomy, 20% sublobar resection, 2% pneumonectomy) and 8,216 patients who received SBRT. In the unmatched cohort, mortality rates were moderately increased with surgery versus SBRT (30 days, 2.07% v 0.73% [absolute difference (Δ), 1.34%]; P < .001; 90 days, 3.59% v 2.93% [Δ, 0.66%]; P < .001). Among the 27,200 propensity score-matched patients, these differences increased (30 days, 2.41% v 0.79% [Δ, 1.62%]; P < .001; 90 days, 4.23% v 2.82% [Δ, 1.41%]; P < .001). Differences in mortality between surgery and SBRT increased with age, with interaction P < .001 at both 30 days and 90 days (71 to 75 years old: 30-day Δ, 1.87%; 90-day Δ, 2.02%; 76 to 80 years old: 30-day Δ, 2.80%; 90-day Δ, 2.59%; > 80 years old: 30-day Δ, 3.03%; 90-day Δ, 3.67%; all P ≤ .001). Compared with SBRT, surgical mortality rates were higher with increased extent of resection (30-day and 90-day multivariate hazard ratio for mortality: sublobar resection, 2.85 and 1.37; lobectomy, 3.65 and 1.60; pneumonectomy, 14.5 and 5.66; all P < 0.001). Conclusion Differences in 30- and 90-day post-treatment mortality between surgery and SBRT increased as a function of age, with the largest differences in favor of SBRT observed among patients older than 70 years. These representative mortality data may inform shared decision making among patients with early-stage NSCLC who are eligible for both interventions.

Perioperative Mortality in Nonelderly Adult Patients With Cancer: A Population-based Study Evaluating Health Care Disparities in the United States According to Insurance Status.

OBJECTIVES: The purpose of this study was to evaluate whether insurance status predicts for perioperative mortality (death within 30 d of cancer-directed surgery) for the 20 most common surgically treated cancers. METHODS: The SEER database was examined for the 20 most common surgically resected cancers and included nonelderly adults, aged 18 to 64 years. The database was queried from 2007 to 2011, with a total of 506,722 patients included in the analysis. RESULTS: Insurance status for all patients were the following: non-Medicaid insurance (83%), any Medicaid (10%), uninsured (4%), and unknown (3%). In univariate analyses, predictors for perioperative mortality included insurance status (P<0.001), age (P=0.015), race (P<0.001), marital status (P<0.001), residence (P=0.002), percent of county below the federal poverty level (P<0.001), and median county-level income (P<0.001). Perioperative mortality was also associated with advanced disease (P<0.001). Under multivariate analysis, patients with either Medicaid (Cochran-Mantel-Haenszel odds ratio [CMH OR], 1.21; 95% confidence interval [CI], 1.14-1.29; P<0.001) or uninsured status (CMH OR, 1.56; 95% CI, 1.44-1.70; P<0.001) were more likely to die within 30 days of surgery compared with patients with non-Medicaid insurance. When comparing Medicaid with the uninsured, Medicaid patients had significantly lower rates of perioperative mortality when compared with the uninsured (CMH OR, 0.80; 95% CI, 0.73-0.89, P<0.001). CONCLUSIONS AND RELEVANCE: In the largest reported analysis of perioperative mortality evaluating the 20 most common surgically treated malignancies, patients with Medicaid coverage or without health insurance were more likely to die within 30 days of surgery, with the uninsured having the worst outcomes.