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BackgroundCancer patients’ treatment is often dispersed across multiple physician communities that may not exchange information. We measured the association between this type of discoordinated care and healthcare utilization, cost, and mortality in stage IV non-small cell lung cancer (NSCLC).MethodsStage IV NSCLC patients ≥65 years were identified from the Surveillance, Epidemiology, and End Results database attached to Medicare claims. A discoordinated care subgroup was selected using a novel index that approximated how many physician communities each patient encountered. Communities were defined by (1) using claims data to create a nationwide social network of healthcare providers and then (2) dividing that network into communities using cluster label propagation. Associations between discoordinated care and overall survival (OS), cancer-specific survival (CSS), hospitalizations, the burden of diagnostic imaging, and cost were assessed.ResultsOf the 11,417 patients in our cohort, 5,855 received discoordinated care. Discoordination was associated with younger age, higher socioeconomic status, higher physician density, and lack of a home health aide. Discoordinated care was associated with improved OS and CSS (HR = 0.92, 95% CI 0.88 - 0.95 for OS). However, discoordinated patients also received 32% more MRIs (p = 0.007) and paid $494.02 more for imaging (p = 0.004). There was no association with other kinds of imaging, rates of hospitalization, or other healthcare costs, including total cost.ConclusionsDiscoordinated care was associated with additional MRIs, but also improved survival. The reason is unclear, but discoordinated patients may be seeking the best care at the expense of continuity.Key PointsQuestionHow does dispersing healthcare across multiple physician communities impact healthcare utilization and survival in patients with advanced stage non-small cell lung cancer?FindingsIn this retrospective cohort study, we found that discoordinated care was associated with increased utilization of MRIs and total cost of imaging. Surprisingly, it was also associated with improved survival.MeaningCancer patients with dispersed healthcare may be seeking care through a tertiary care center or clinical trial. This may lead to increased healthcare utilization but also improved survival.

Background High-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC). Methods We selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods. Results Of the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86–1.09), ETFS (HR 1.05; 95% CI 0.93–1.18), CSS (HR 0.94; 95% CI 0.84–1.04), or OS (HR 0.95; 95% CI 0.87–1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively. Conclusion hfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost. hfIGRT deserves further scrutiny through a randomized controlled trial.

Purpose Stereotactic ablative radiation therapy (SABR) is an established treatment for selected lung tumors. Sinoatrial node (SAN) toxicity after thoracic SABR has not been reported in the literature. We sought to understand the risk of SAN toxicity owing to incidental dose to the SAN from SABR. Methods and materials We conducted a retrospective review of patients with early-stage lung cancer or limited pulmonary metastases who underwent thoracic SABR to a right-sided central lung tumor (within 2 cm of the mainstem bronchus or other mediastinal structures) between January 2008 and December 2014, analyzed a subset whose treatment imparted dose to the SAN exceeding 10% of the prescription dose, and examined patient and treatment dosimetric characteristics. Mean follow-up interval was 28 months. Time to toxicity was defined from start of SABR. Results Of 47 patients with central tumors in the right lung treated with SABR reviewed, 13 met our study criteria. A contouring atlas of regional cardiac anatomy was created. One patient treated with SABR for non-small cell lung cancer at the right hilum developed symptomatic sick sinus syndrome, requiring pacemaker placement 6 months after treatment. Her acute presentation and short interval between SABR and onset of symptoms suggest that SAN toxicity was likely due to radiation-induced injury. Both her age and mean dose to her SAN were the third highest in our cohort. She remained free from cancer progression at 24 months' follow-up. Twelve additional patients who received significant dose to the SAN from SABR did not develop toxicity. Conclusion While uncommon, SAN toxicity from SABR to right-sided central thoracic tumors should be recognized and followed in future studies.

Background The addition of procarbazine, lomustine, vincristine (PCV) chemotherapy to radiotherapy (RT) for patients with high-risk (≥40 y old or subtotally resected) low-grade glioma (LGG) results in an absolute median survival benefit of over 5 years. We evaluated the cost-effectiveness of this treatment strategy. Methods A decision tree with an integrated 3-state Markov model was created to follow patients with high-risk LGG after surgery treated with RT versus RT+PCV. Patients existed in one of 3 health states: stable, progressive, or dead. Survival and freedom from progression were modeled to reflect the results of RTOG 9802 using time-dependent transition probabilities. Health utility values and costs of care were derived from the literature and national registry databases. Analysis was conducted from the health care perspective. Deterministic and probabilistic sensitivity analysis explored uncertainty in model parameters. Results Modeled outcomes demonstrated agreement with clinical data in expected benefit of addition of PCV to RT. The addition of PCV to RT yielded an incremental benefit of 4.77 quality-adjusted life-years (QALYs) (9.94 for RT+PCV vs 5.17 for RT alone) at an incremental cost of $48635 ($188234 for RT+PCV vs $139598 for RT alone), resulting in an incremental cost-effectiveness ratio of $10186 per QALY gained. Probabilistic sensitivity analysis demonstrates that within modeled distributions of parameters, RT+PCV has 99.96% probability of being cost-effectiveness at a willingness-to-pay threshold of $100000 per QALY. Conclusion The addition of PCV to RT is a cost-effective treatment strategy for patients with high-risk LGG.

Purpose: For brain metastases, surgical resection with postoperative stereotactic radiosurgery is an emerging standard of care. Postoperative cavity stereotactic radiosurgery is associated with a specific, underrecognized pattern of intracranial recurrence, herein termed nodular leptomeningeal disease (nLMD), which is distinct from classical leptomeningeal disease. We hypothesized that there is poor consensus regarding the definition of LMD, and that a formal, self-guided training module will improve interrater reliability (IRR) and validity in diagnosing LMD. Methods and Materials: Twenty-two physicians at 16 institutions, including 15 physicians with central nervous system expertise, completed a 2-phase survey that included magnetic resonance imaging and treatment information for 30 patients. In the ``pretraining{''} phase, physicians labeled cases using 3 patterns of recurrence commonly reported in prospective studies: local recurrence (LR), distant parenchymal recurrence (DR), and LMD. After a self-directed training module, participating physicians completed the ``posttraining{''} phase and relabeled the 30 cases using the 4 following labels: LR, DR, classical leptomeningeal disease, and nLMD. Results: IRR increased 34\% after training (Fleiss' Kappa K = 0.41 to K = 0.55, P < .001). IRR increased most among non-central nervous system specialists (+58\%, P < .001). Before training, IRR was lowest for LMD (K = 0.33). After training, IRR increased across all recurrence subgroups and increased most for LMD (+67\%). After training, >= 27\% of cases initially labeled LR or DR were later recognized as nLMD. Conclusions: This study highlights the large degree of inconsistency among clinicians in recognizing nLMD. Our findings demonstrate that a brief self-guided training module distinguishing nLMD can significantly improve IRR across all patterns of recurrence, and particularly in nLMD. To optimize outcomes reporting, prospective trials in brain metastases should incorporate central imaging review and investigator training. (C) 2019 Elsevier Inc. All rights reserved.

Purpose The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) –overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab. Patient and Methods We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions. Results Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained. Conclusion THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States.

Medulloblastoma patients are treated with surgery, radiation and chemotherapy. Radiation dose to the temporal lobe may be associated with neurocognitive sequelae. Longitudinal changes of temporal lobe cortical thickness may result from neurodevelopmental processes such as synaptic pruning. This study applies longitudinal image analysis to compare developmental change in cortical thickness in medulloblastoma (MB) patients who were treated by combined modality therapy to that of cerebellar juvenile pilocytic astrocytoma (JPA) patients who were treated by surgery alone. We hypothesized that the rates of developmental change in cortical thickness would differ between these two groups. This retrospective cohort study assessed changes in cortical thickness over time between MB and JPA patients. High-resolution magnetic resonance (MR) images of 14 MB and 7 JPA subjects were processed to measure cortical thickness of bilateral temporal lobe substructures. A linear mixed effects model was used to identify differences in substructure longitudinal changes in cortical thickness. The left temporal lobe exhibited overall increased cortical thickness in MB patients relative to JPA patients who showed overall cortical thinning (mean annual cortical thickness change: MB 0.14 mm/year versus JPA -0.018 mm/year across all substructures), particularly in the inferior temporal lobe substructures (p

Background Alternative treatment regimens are needed for patients with non-small cell lung cancer (NSCLC) who cannot receive definitive treatment with concurrent chemoradiotherapy, surgery, or stereotactic ablative radiotherapy (SABR). Patients and Methods We report survival, patterns of failure and toxicity outcomes for patients with NSCLC who were not eligible for surgical resection, concurrent chemoradiotherapy, or SABR and underwent hypofractionated intensity-modulated radiotherapy (IMRT). Kaplan-Meier survival analysis was used to evaluate the progression-free and overall survival. Competing risk analysis was used to evaluate in-field, locoregional, and distant failure. Results A total of 42 patients treated to 52.5 to 60 Gy in 15 fractions were included. Most of the patients had metastatic or recurrent disease (64%) and a relatively large, centrally located tumor burden (74%). The median follow-up period was 13 months (interquartile range, 6-18 months). All patients received the total prescribed dose. The median survival was 15.1 months. The overall and progression-free survival rates at 1 year were 63% and 22.5%, respectively. The pattern of failure was predominantly distant, with only 2% of patients experiencing isolated in-field recurrence. The cumulative incidence of in-field failure at 6 and 12 months was 2.5% (95% confidence interval, 0.4%-15.6%) and 16.1% (95% confidence interval, 7.5%-34.7%), respectively. The risk of esophageal toxicity was associated with the esophageal mean dose, maximal point dose, and dose to the 5 cm3 volume. The risk of pneumonitis was associated with the lung mean dose and volume receiving 18 Gy. Conclusion Hypofractionated IMRT without concurrent chemotherapy provides favorable rates of local control and survival for well-selected patients with NSCLC who cannot tolerate standard definitive therapy.

This study was initiated to evaluate the efficacy of negative contrast-enhanced microcomputed tomography (microCT) colonography for the noninvasive detection of colonic tumors in living mice. After colonic preparation, 20 anesthetized congenic mice were scanned with high-resolution microCT. Images were displayed by using commercial visualization software and interpreted by two gastrointestinal radiologists, who were unaware of tumor prevalence and findings at gross pathology. Two-dimensional multiplanar images were assessed by using a five-point scale to distinguish colonic tumors (polyps) from fecal pellets (5 = definitely a tumor, 4 = probably a tumor, 3 = indeterminate, 2 = probably not a tumor, 1 = definitely not a tumor). Gross pathologic evaluation of excised mouse colons served as the reference standard. Data analysis included dichotomizing results, with 1–2 indicating no tumor and 3–5 indicating tumor and also receiver operator characteristic curve analysis with area under the curve for threshold-independent assessment. A total of 41 colonic polyps in 18 of the 20 mice were identified at gross examination on necropsy, of which 30 measured 2–5 mm and 11 measured 2 mm was 93.3% (56/60). The pooled per-mouse sensitivity for polyps >2 mm was 97.1% (33/34). Pooled specificity for distinguishing fecal pellets from tumor was 98.5% (65/66). The combined area under the curve from receiver operator characteristic curve analysis was 0.810 ± 0.038 (95% confidence interval, 0.730–0.890). These findings indicate that accurate noninvasive longitudinal monitoring of colon tumor progression or response to various therapies is now technically feasible in live mice by using this microCT colonography method.

132 Background: Sinoatrial node (SAN) injury following stereotactic ablative radiation therapy (SABR) in the chest has not been reported in the literature. We report SAN dysfunction as a potential toxicity of SABR in the chest. Methods: We examined the clinical courses and SABR plans of 47 patients treated for T1 or T2 non-small cell lung cancer of the right upper lobe, middle lobe, lower lobe, or hilum. After developing a contouring atlas for the SAN, based upon the junction between the superior vena cava and the right atrium, dose to the SAN was retrospectively determined for each patient. We identified 13 patients whose treatment imparted significant dose to the SAN, as defined by the SAN encompassed within the 10% prescription isodose (IDL) line. Biologically effective doses (BED), acute and chronic, were correlated with SAN toxicity. Results: Patients underwent SABR to the right lung to a dose of 40-50 Gy in 4 or 5 fractions, with mean acute BED (alpha/beta ratio = 10) of 100.2 Gy and late BED (alpha/beta ratio = 3) of 222.7 Gy. Mean volume of the GTV and PTV were 26.1 and 75.1 mL, respectively. Mean follow-up was 25.5 months. The mean volume of the SAN was 0.37 mL. Average max dose and mean dose to the SAN were 24.7 and 70.7 Gy, respectively. Of the 13 patients whose treatment imparted significant dose to the SAN, one patient without prior arrhythmia developed symptomatic SAN dysfunction requiring pacemaker placement at 6 months after completion of treatment. The sinoatrial node of the patient received a maximum dose of 44.8 Gy in 4 fractions, correlated with an acute BED (alpha/beta ratio = 10) of 90 Gy and late BED (alpha/beta ratio = 3) of 194.1 Gy, and a mean dose of 35.5 Gy in 4 fractions, correlated with an acute BED (alpha/beta ratio = 10) of 71 Gy and late BED (alpha/beta ratio = 3) of 153.8 Gy. This was the third highest max dose and second highest mean dose to SAN in the cohort. Conclusions: We report sinoatrial node dysfunction as a potential toxicity of SABR in the chest for non-small cell lung cancer. Caution is advised when treatment imparts significant dose to the sinoatrial node.

To compare liver lesion volume measurement on multiple 3D software platforms using a liver phantom. An anthropomorphic phantom constructed with ten liver lesions of varying size, attenuation, and shape with known volume and long axis measurement was scanned (120 kVp, 80–440 smart mA, NI 12). DICOM data were uploaded to five commercially available 3D visualization systems and manual tumor volume was obtained by three-independent readers. Accuracy and reproducibility of linear and volume measurements were compared. The two most promising systems were then compared with an additional prototype system by two readers using both manual and semi-automated measurement with similar comparison between linear and volume measures. Measurements were performed on 5- and 1.25-mm data sets. Inter- and intra-observer variability was also assessed. Overall mean % volume error on the five commercially available software systems (averaging all ten liver lesions among all three readers) was 8.0% ± 7.5%, 13.7% ± 11.2%, 14.2% ± 15.2%, 16.4% ± 14.8 %, and 16.9% ± 13.8%, varying almost twofold across vendor. Moderate inter-observer variability was present. Volume measurement was slightly more accurate than linear measurement, but linear measurement was more reproducible across readers and systems. On the two “best” systems, the manual measurement method was more accurate than the automated method (p = 0.001). The prototype system demonstrated superior semi-automated assessment, with a mean % volume error of 5.3% ± 4.1% (vs. 17.8% ± 11.1% and 31.5% ± 19.7%, p

Purpose: To predict response to radiation treatment using computational FDG-PET and CT images in locally advanced head and neck cancer (HNC). Methods: 68 patients with State III-IVB HNC treated with chemoradiation were included in this retrospective study. For each patient, we analyzed primary tumor and lymph nodes on PET and CT scans acquired both prior to and during radiation treatment, which led to 8 combinations of image datasets. From each image set, we extracted high-throughput, radiomic features of the following types: statistical, morphological, textural, histogram, and wavelet, resulting in a total of 437 features. We then performed unsupervised redundancy removal and stability test on these features. To avoid over-fitting, we trained a logistic regression model with simultaneous feature selection based on least absolute shrinkage and selection operator (LASSO). To objectively evaluate the prediction ability, we performed 5-fold cross validation (CV) with 50 random repeats of stratified bootstrapping. Feature selection and model training was solely conducted on the training set and independently validated on the holdout test set. Receiver operating characteristic (ROC) curve of the pooled Result and the area under the ROC curve (AUC) was calculated as figure of merit. Results: For predicting local-regional recurrence, our model built on pre-treatment PET of lymph nodes achieved the best performance (AUC=0.762) on 5-fold CV, which compared favorably with node volume and SUVmax (AUC=0.704 and 0.449, p

This paper outlines the first attempt to segment the boundary of preclinical subcutaneous tumours, which are frequently used in cancer research, from micro-computed tomography (microCT) image data. MicroCT images provide low tissue contrast, and the tumour-to-muscle interface is hard to determine, however faint features exist which enable the boundary to be located. These are used as the basis of our semi-automatic segmentation algorithm. Local phase feature detection is used to highlight the faint boundary features, and a level set-based active contour is used to generate smooth contours that fit the sparse boundary features. The algorithm is validated against manually drawn contours and micro-positron emission tomography (microPET) images. When compared against manual expert segmentations, it was consistently able to segment at least 70% of the tumour region (n = 39) in both easy and difficult cases, and over a broad range of tumour volumes. When compared against tumour microPET data, it was able to capture over 80% of the functional microPET volume. Based on these results, we demonstrate the feasibility of subcutaneous tumour segmentation from microCT image data without the assistance of exogenous contrast agents. Our approach is a proof-of-concept that can be used as the foundation for further research, and to facilitate this, the code is open-source and available from www.setuvo.com. © 2013 Institute of Physics and Engineering in Medicine.

e18082Background: Studies have shown that socioeconomic (SE) disparities contribute to differences in cancer survival, with patients in lower SE classes consistently having poorer survival compared...

201 Background: Various schedules of palliative radiotherapy (pRT) are prescribed for metastatic breast cancer (MBC) patients. Length of treatment can vary from a single day to three weeks. Single fraction pRT provides similar pain relief vs. multi-fraction pRT for bone metastases, but retreatment rates are higher. In the era of targeted and hormonal therapy, patients with MBC can survive many years after their initial diagnosis. We investigated whether patients with MBC who were prescribed single fraction pRT had poorer prognoses and experienced shorter survival than patients who were prescribed multi-fraction pRT. Methods: Patients at a single institution with MBC underwent pRT, with fractionation schedules including 8 Gy in 1 fraction (fx), 20 Gy in 5 fx, 30 Gy in 10 fx, 37.5 Gy in 15 fx between 2001-2015. 392 treatments were prescribed (109/241/29/13 in each regimen as above). Date of death was obtained from medical records, Social Security Death Index, or published obituaries. Patients who were alive or whose date of death could not be determined were censored at the date of their last encounter. Survival was calculated from the start of treatment to the date of death or censorship. Results: Patients treated with 37.5 Gy in 15 fx (MS 20 months, p = 0.002) or 30 Gy in 10 fx (MS 22 months, p = 0.03) experienced longer survival than patients treated with 8 Gy in 1 fx (MS 8 months). There was no significant survival difference between patients treated with 20 Gy in 5 fx (MS 18 months, p = 0.49) and patients treated with 8 Gy in 1 fx. There was no significant survival difference between patients treated by the three multi-fractionation schedules. Conclusions: MBC patients who were prescribed 37.5 Gy and 30 Gy lived longer than patients who were prescribed 8 Gy of pRT. No statistically significant difference was found between patients who were prescribed 20 Gy compared to 8 Gy, possibly due to the lower number of patients who received these regimens. Single fraction pRT was more likely to be prescribed to patients who would ultimately have shorter survival. More research is needed, ideally across multiple institutions, to explore the correlation between physician estimation of patient survival and selection of pRT regimen for patients with MBC.

6047 Background: To determine whether total lesion glycolysis (TLG) measured during radiation for locally advanced oropharyngeal cancer (OPC) correlates with outcomes. Methods: Patients with Stage ...