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The study objective was to validate the National Surgical Quality Improvement Program (NSQIP) Risk Calculator in stratifying risk estimates for patients who received surgery or stereotactic body radiation therapy for clinical stage I non-small cell lung cancer.A retrospective analysis of patients with clinical stage I non-small cell lung cancer undergoing surgery (N = 279) or stereotactic body radiation therapy (N = 206) from 2009 to 2012 was performed. NSQIP complication risk estimates were calculated for both surgical and stereotactic body radiation therapy cases using the NSQIP Surgical Risk Calculator. NSQIP complication risk estimates were compared as continuous variables and by quartile ranges.Compared with patients undergoing video-assisted thoracoscopic surgery wedge resection, patients receiving stereotactic body radiation therapy were older, had larger tumors, had lower forced expiratory volume (FEV1) in 1 second and diffusing capacity of the lungs (DLCO) for carbon monoxide values, had higher American Society of Anesthesiologists scores, had higher rates of dyspnea, and had higher NSQIP serious complication risk estimates (all P.05). Compared with patients undergoing video-assisted thoracoscopic surgery lobectomy, patients receiving stereotactic body radiation therapy had similar disparities, along with higher Adult Comorbidity Evaluation-27 (ACE) scores comorbidity scores, higher rates of cardiac comorbidities, and worse functional status (all P.05). Variables associated with receiving stereotactic body radiation therapy treatment, rather than wedge resection, included increasing age, higher Adult Comorbidity Evaluation (ACE)-27 comorbidity score, dyspnea status, and decreasing FEV1 in 1 second and DLCO for carbon monoxide, but NSQIP serious complication risk score. In addition, surgical patients' actual serious complication rate (16.6% vs 8.8%) and pneumonia rate (6.0% vs 3.2%) were significantly higher than the NSQIP risk calculator predicted (all P.05).The National Surgical Quality Improvement Program risk calculator does not effectively classify or stratify risk in patients with stage I non-small cell lung cancer. Continued efforts are needed to assess risk in this population and develop more tailored treatment decision aids.

Purpose To demonstrate the feasibility of online adaptive magnetic resonance (MR) image guided radiation therapy (MR-IGRT) through reporting of our initial clinical experience and workflow considerations. Methods and Materials The first clinically deployed online adaptive MR-IGRT system consisted of a split 0.35T MR scanner straddling a ring gantry with 3 multileaf collimator-equipped 60 Co heads. The unit is supported by a Monte Carlo–based treatment planning system that allows real-time adaptive planning with the patient on the table. All patients undergo computed tomography and MR imaging (MRI) simulation for initial treatment planning. A volumetric MRI scan is acquired for each patient at the daily treatment setup. Deformable registration is performed using the planning computed tomography data set, which allows for the transfer of the initial contours and the electron density map to the daily MRI scan. The deformed electron density map is then used to recalculate the original plan on the daily MRI scan for physician evaluation. Recontouring and plan reoptimization are performed when required, and patient-specific quality assurance (QA) is performed using an independent in-house software system. Results The first online adaptive MR-IGRT treatments consisted of 5 patients with abdominopelvic malignancies. The clinical setting included neoadjuvant colorectal (n=3), unresectable gastric (n=1), and unresectable pheochromocytoma (n=1). Recontouring and reoptimization were deemed necessary for 3 of 5 patients, and the initial plan was deemed sufficient for 2 of the 5 patients. The reasons for plan adaptation included tumor progression or regression and a change in small bowel anatomy. In a subsequently expanded cohort of 170 fractions (20 patients), 52 fractions (30.6%) were reoptimized online, and 92 fractions (54.1%) were treated with an online-adapted or previously adapted plan. The median time for recontouring, reoptimization, and QA was 26 minutes. Conclusion Online adaptive MR-IGRT has been successfully implemented with planning and QA workflow suitable for routine clinical application. Clinical trials are in development to formally evaluate adaptive treatments for a variety of disease sites.

For patients with non-small cell lung cancer (NSCLC) metastatic to hilar lymph nodes (N1), guidelines recommend surgery and adjuvant chemotherapy in operable patients and chemoradiation (CRT) for those deemed inoperable. It is unclear how these recommendations are applied nationally, however.The National Cancer Database was queried to identify patients with a tumor7 cm (T1/T2) with clinically positive N1 nodes. Patients undergoing CRT (comprising chemotherapy and radiation45 Gy) or surgical resection were considered adequately treated. Remaining patients were classified as receiving inadequate or no treatment.Of the 20,366 patients who met the study criteria, 63% underwent adequate treatment (48% surgical resection, 15% CRT). The remainder received inadequate treatment (23%) or no treatment (14%). In univariate analysis, the patients receiving inadequate or no treatment were older, tended to be non-Caucasian, had a lower income, and had a higher comorbidity score. Patients undergoing adequate treatment had improved overall survival (OS) compared with those receiving inadequate or no treatment (median OS, 34.0 months vs 11.7 months; P .001). Of those receiving adequate treatment, logistic regression identified several variables associated with surgical resection, including treatment at an academic facility, Caucasian race, and annual income$35,000. Increasing age and T2 stage were associated with nonoperative management. Following propensity score matching of 2308 patient pairs undergoing surgery or CRT, resection was associated with longer median OS (34.1 months vs 22.0 months; P .001).Despite the established guidelines, many patients with T1-2N1 NSCLC do not receive adequate treatment. Surgery is associated with prolonged survival in selected patients. Surgical input in the multidisciplinary evaluation of these patients should be mandatory.

Stereotactic radiosurgery and percutaneous radiofrequency ablation are emerging therapies for pain palliation and local control of spinal metastases. However, the post-treatment imaging findings are not well characterized and the risk of long-term complications is unknown. We present the case of a 46-year-old woman with delayed vertebral body collapse after stereotactic radiosurgery and radiofrequency ablation of a painful lumbar metastasis. Histopathologic-MRI correlation confirmed osteonecrosis as the underlying etiology and demonstrated that treatment-induced vascular fibrosis and tumor progression can have identical imaging appearances.

BACKGROUND Because of their rarity, outcomes regarding spinal atypical meningiomas (AMs) remain unclear. OBJECTIVE To describe the recurrence rate and postoperative outcomes after resection of spinal AMs, and to discuss an appropriate resection strategy and adjuvant therapy for spinal AMs. METHODS Data from all patients who presented with spinal AMs to 2 tertiary referral centers between 1998 and 2013 were obtained by chart review. RESULTS From 102 patients with spinal meningioma, 20 AM tumors (7 cervical, 11 thoracic, 2 thoracolumbar) were identified in 18 patients (median age, 50 years [range, 19-75] at time of resection; 11% male; median follow-up, 32 months [range, 1-179] after resection). Before resection, patients had sensory deficits (70%), pain (70%), weakness (60%), ataxia (50%), spasticity (65%), and incontinence (35%). One tumor presented asymptomatically. Simpson grade I, II, III, and IV resection were achieved in 3 (15%), 13 (65%), 2 (10%), and 2 (10%) tumors, respectively. One patient that underwent Simpson grade III resection received adjuvant radiation therapy. After Simpson grade I-III or gross total resection, no tumors recurred (0%; confidence interval, 0%-17.6%). After Simpson grade IV resection, 1 tumor recurred (50%; confidence interval, 1.3%-98.7%). With the exception of 1 patient who had bilateral paraplegia perioperatively, all other patients experienced improvement of preoperative symptoms after surgery (median time, 3.6 months [range, 1-13] after resection). CONCLUSION Despite published cases suggesting an aggressive clinical course for spinal AMs, this series of spinal AMs reports that gross total resection without adjuvant radiation therapy resulted in symptom resolution and low recurrence.

BACKGROUND: Acute severe lymphopenia (ASL) frequently develops during radiotherapy and temozolomide (RT + TMZ) for high-grade glioma (HGG) and has been shown to be correlated with survival. This study is designed to identify potential predictors of ASL, especially RT-specific parameters that can be modified. METHODS: From January 2007 to December 2012, 194 patients with HGG were treated RT + TMZ and had available data including lymphocyte count and radiation dose-volume histogram (DVH) parameters. RT was delivered to 2 planning target volumes (PTV1) over a median of 43 days (range 19-75): 60Gy (40.05-66) to PTV 1 and 51Gy (30-54) to PTV2. Concurrent TMZ was given daily at a dose of 75 mg/m2 for the duration of RT. ASL was defined as less than 500/ul (Common Toxicity Criteria version 4.0, grade 3-4) within the first two months from the start of RT. Peripheral blood including lymphocyte count was typically assessed weekly during RT and then monthly thereafter. DVH parameters were determined for brain, brainstem and PTV from the original RT plan. The stepwise logistic regression analysis (SLRA) was used to determine the most important predictors of ASL. RESULTS: Forty-five patients (23%) developed ASL. Patients with ASL had significantly worse OS than those without (median 11.2 vs 18.3 months, respectively, p < 0.001). The SLRA showed that female gender (odd ratio [OR], 5.21; 95% confidence interval [CI], 2.34-11.63), elder age (1.05; 1.01-1.08), higher V25Gy (volume receiving 25Gy) of brain (1.04; 1.01-1.06), lower pretreatment lymphocyte count (1.001; 1.00-1.002) were the most significant predictors for ASL. ASL rate was 40% for patients with V25Gy ≥ 66% and 15% for V25Gy < 66%. CONCLUSIONS: Female gender, elder age, increased V25Gy of brain, and low pretreatment lymphocyte count are significant predictors of ASL during treatment of HGG. Maintaining V25Gy of brain below 66% may reduce the rate of ASL.

INTRODUCTION: Pseudoprogression (PsP) is a radiologic phenomenon in which treatment results in disruption of the blood brain barrier resulting in areas of contrast enhancement that is indistinguishable from true tumor progression. In glioblastoma, PsP occurs more frequently in tumors with MGMT promoter methylation and is associated with a better prognosis. We investigated whether the two recurrent genetic alterations, 1p/19q codeletions and IDH1 R132H mutation, which have prognostic significance in oligodendrogliomas (OG) and oligoastrocytomas (OA), are associated with PsP. METHODS: Institutional review board approval was granted to query a pathologic database for grade II and III OG/OA and to perform IDH1 R132H immunohistochemistry on archival material. 139 patient cases were identified, in which serial imaging was performed, records were available for review, and the tumors were treated with fractionated radiotherapy. IDH1 R132H immunohistochemistry was performed on archival material from these cases when available and their charts were reviewed for clinical data. RESULTS: PsP occurred less frequently in OG/OAs with 1p/19q codeletions (8% of tumors) than tumors without 1p/19q codeletions (27% of tumors) with an odds ratio of 0.168 and 95% CI of 0.050-0.562 when adjusting for covariables by multivariate modeling. Within the cohort without 1p/19q codeletions, the development of PsP in OG/OA was independently associated with worse survival when compared to tumors without early contrast enhancement following treatment (p = 0.0059). Additionally, within this cohort without 1p/19q codeletions, 50% of the tumors with PsP were negative for IDH1 R132H mutation by immunohistochemistry, compared to 26% negativity among tumors without early contrast enhancement. CONCLUSIONS: In this study, we are the first to show that PsP occurs more frequently in OG/OA with a worse prognosis and that PsP may have an inverse association with 1p/19q codeletions and IDH1 R132H mutation.

BACKGROUND: The efficacies of adjuvant stereotactic radiosurgery (SRS) and external beam radiation therapy (EBRT) for atypical meningiomas (AMs) after subtotal resection (STR) remain unclear. OBJECTIVE: To analyze the clinical, histopathological, and radiographic features associated with progression in AM patients after STR. METHODS: Fifty-nine primary AMs after STR were examined for predictors of progression, including the impact of SRS and EBRT, in a retrospective cohort study. RESULTS: Twenty-seven patients (46%) progressed after STR (median, 30 months). On univariate analysis, spontaneous necrosis positively (hazard ratio = 5.2; P = .006) and adjuvant radiation negatively (hazard ratio = 0.3; P = .009) correlated with progression; on multivariate analysis, only adjuvant radiation remained independently significant (hazard ratio = 0.3; P = .006). SRS and EBRT were associated with greater local control (LC; P = .02) and progression-free survival (P = .007). The 2-, 5-, and 10-year actuarial LC rates after STR vs STR/EBRT were 60%, 34%, and 34% vs 96%, 65%, and 45%. The 2-, 5-, and 10-year actuarial progression-free survival rates after STR vs STR/EBRT were 60%, 30%, and 26% vs 96%, 65%, and 45%. Compared with STR alone, adjuvant radiation therapy significantly improved LC in AMs that lack spontaneous necrosis (P = .003) but did not improve LC in AMs with spontaneous necrosis (P = .6). CONCLUSION: Adjuvant SRS or EBRT improved LC of AMs after STR but only for tumors without spontaneous necrosis. Spontaneous necrosis may aid in decisions to administer adjuvant SRS or EBRT after STR of AMs.

BACKGROUND Indications for external beam radiation therapy (EBRT) for atypical meningiomas (AMs) remain unclear. OBJECTIVE To analyze features associated with recurrence in AM patients after gross total resection (GTR) and to assess the relative benefit of EBRT in a retrospective cohort study. METHODS One hundred fifty-one primary AMs after GTR (88 female patients; median follow-up, 45.0 months) were examined for possible predictors of recurrence (age, sex, location, volume, bone involvement, brain invasion). The Fisher exact and Wilcoxon rank-sum tests were used to analyze the association between these predictors and use of EBRT. The impact on recurrence for these predictors and EBRT was analyzed with Kaplan-Meier and Cox regression. RESULTS Of 151 patients, 13 (8.6%) experienced recurrence after GTR (median, 47.0 months). Multivariate analysis identified elevated mitotic index (P = .007) and brain invasion (P = .002) as predictors of recurrence. Larger volume (P = .96) was not associated with recurrence but was more likely to prompt EBRT (P = .001). Recurrences occurred in 11 of 112 with GTR (9.8%; median, 44 months) and 2 of 39 with GTR/EBRT (5.1%; median, 133 months). The 2-, 5-, and 10-year progression-free survival rates after GTR vs GTR/EBRT were 97%, 86%, and 68% vs 100%, 100%, and 78%. Kaplan-Meier analysis demonstrated no difference in progression-free survival or overall survival after GTR vs GTR/EBRT (P = .8, P > .99). CONCLUSION Brain invasion and high mitotic rates may predict recurrence. After GTR of AMs, EBRT appears not to affect progression-free survival and overall survival, suggesting that observation rather than EBRT may be indicated after GTR.

To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT).Adult patients aged70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM.Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P.0001), GTR/NTR (P.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged50 years or those who had GTR/NTR.Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.

To investigate the impact of exclusively using intravenous (IV) contrast x-ray computed tomography (CT) scans on lung cancer intensity-modulated radiation therapy (IMRT) treatment planning.Eight patients with lung cancer (one small cell, seven nonsmall cell) scheduled to receive IMRT consented to acquisition of simulation CT scans with and without IV contrast. Clinical treatment plans optimized on the noncontrast scans were recomputed on contrast scans and dose coverage was compared, along with the γ passing rates.IV contrast enhanced scans provided better target and critical structure conspicuity than the noncontrast scans. Using noncontrast scan as a reference, the median absolute/relative differences in mean, maximum, and minimum doses to the planning target volume (PTV) were -4.5 cGy/-0.09%, 41.1 cGy/0.62%, and -19.7 cGy/-0.50%, respectively. Regarding organs-at-risk (OARs), the median absolute/relative differences of maximum dose to heart was -13.3 cGy/-0.32%, to esophagus was -63.4 cGy/-0.89%, and to spinal cord was -16.3 cGy/-0.46%. The median heart region of interest CT Hounsfield Unit (HU) number difference between noncontrast and contrast scans was 136.4 HU (range, 94.2-161.8 HU). Subjectively, the regions with absolute dose differences greater than 3% of the prescription dose were small and typically located at the patient periphery and/or at the beam edges. The median γ passing rate was 0.9981 (range, 0.9654-0.9999) using 3% absolute dose difference/3 mm distance-to-agreement criteria. Overall, all evaluated cases were found to be clinically equivalent.PTV and OARs dose differences between noncontrast and contrast scans appear to be minimal for lung cancer patients undergoing IMRT. Using IV contrast scans as the primary simulation dataset could increase treatment planning efficiency and accuracy by avoiding unnecessary scans, manually region overriding, and planning errors caused by nonperfect image registrations.

To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS).Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value.05 was considered statistically significant.Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥ 1.75 was 84% versus 69% for conformality index1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index.Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.

Lung cancer is a highly incident disease, and the major cause of cancer death worldwide. Trends in lung cancer incidence and mortality follow an epidemiological link to the history of tobacco consumption, although a recent increase of cases in never smokers has been observed. Throughout this chapter, readers will have the chance to appreciate the major changes and advances that took place in the presentation, diagnosis, and treatment of lung cancer in the past decades. The pathology and staging classification of lung cancer has evolved over time, as has the knowledge on its genomic landscape. The discovery of driver mutations such as EGFR and ALK has revolutionized the field of targeted therapy. Molecular testing has become a standard in non-squamous NSCLC, and results are now essential to link patients to better-suited therapies. The greater understanding of cancer immunology also impacted lung cancer therapy. Immune checkpoint inhibitors are now a routine in most lung cancer cases, including metastatic and locally advanced NSCLC. The advance in imaging diagnostics and intervention allowed better detection (including screening programs), staging (mainly due to PET-CT), and treatment. Minimally invasive techniques are commonly used to help diagnose and stage lung cancer. Daily examples include CT-guided biopsies, EBUS, EUS, video-assisted and robotic surgery. Modern radiation devices have enabled the application of highly precise doses to localized nodules, adding new treatment opportunities to different disease stages. Altogether, lung cancer control requires multidisciplinary care and continuous research effort.

Four-dimensional (4D) dose calculations for lung cancer radiotherapy have been technically feasible for a number of years but have not become standard clinical practice. The purpose of this study was to determine if clinically significant differences in tumor control probability (TCP) exist between 3D and 4D dose calculations so as to inform the decision whether 4D dose calculations should be used routinely for treatment planning. Radiotherapy plans for Stage I-II lung cancer were created for 8 patients. Clinically acceptable treatment plans were created with dose calculated on the end-exhale 4D computed tomography (CT) phase using a Monte Carlo algorithm. Dose was then projected onto the remaining 9 phases of 4D-CT using the Monte Carlo algorithm and accumulated onto the end-exhale phase using commercially available deformable registration software. The resulting dose-volume histograms (DVH) of the gross tumor volume (GTV), planning tumor volume (PTV), and PTVsetup were compared according to target coverage and dose. The PTVsetup was defined as a volume including the GTV and a margin for setup uncertainties but not for respiratory motion. TCPs resulting from these DVHs were estimated using a wide range of alphas, betas, and tumor cell densities. Differences of up to 5Gy were observed between 3D and 4D calculations for a PTV with highly irregular shape. When the TCP was calculated using the resulting DVHs for fractionation schedules typically used in stereotactic body radiation therapy (SBRT), the TCP differed at most by 5% between 4D and 3D cases, and in most cases, it was by less than 1%. We conclude that 4D dose calculations are not necessary for most cases treated with SBRT, but they might be valuable for irregularly shaped target volumes. If 4D calculations are used, 4D DVHs should be evaluated on volumes that include margin for setup uncertainty but not respiratory motion.

This study tested the hypothesis that time of day of treatment with stereotactic radiosurgery (SRS) has an effect on local control (LC) and overall survival (OS) in a large cohort of patients with non-small cell lung cancer (NSCLC) brain metastases.At Washington University in St. Louis, 437 patients with NSCLC were treated with SRS for NSCLC brain metastases. Receiver operating characteristics analysis was used to identify an optimal cut-point for OS relative to time of day. Kaplan-Meier log-rank statistics, and Cox regression univariate and multivariate analysis were employed to isolate any independent effect of treatment time on OS and LC. Matched-pair analysis was performed to isolate any independent effect of time on OS and LC of day while controlling for confounding variables.Receiver operating characteristics analysis identified a cut-point of 11:41 AM as providing the highest predictive value for OS. On univariate analysis, late SRS was associated with decreased OS, as was age, Karnofsky performance status, risk-stratification schemes, extracranial disease status, and overall burden of brain metastases. On univariate analysis for LC, late SRS was associated with decreased LC, as was burden of brain metastases. On multivariate analysis, only Graded Prognostic Assessment remained predictive of OS, and total number of targets and total tumor volume remained predictive of LC. Matched-pair analysis demonstrated no significant effect of time of day on LC or OS.Although earlier treatment appears to be associated with improved LC and OS, treatment time fails to remain significant when accounting for confounding variables.

Introduction Ongoing prospective trials exploring stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) often exclude minimally invasive adenocarcinoma or adenocarcnioma in situ, formerly bronchioloalveolar carcinoma (BAC), due to concerns for accurate target delineation on CT. We performed a patterns of failure analysis to compare outcomes between BAC and other NSCLC subtypes. Methods One hundred twenty patients with early stage NSCLC were treated with SBRT from 2004–2009. Pathologic confirmation of NSCLC was obtained in 97 patients. Radiotherapy was delivered according to RTOG guidelines. The log-rank test was used to compare outcomes between BAC and other NSCLC. Results Median follow-up was 29 months. The median SBRT dose was 5400 cGy. Thirteen patients had radiographically diagnosed BAC and five patients had biopsy confirmed BAC, of which two had both. The three-year local control was 100% for biopsy-proven or radiographically diagnosed BAC (n = 18) and 86% for all other NSCLC subtypes (n = 102) (p = 0.13). Likewise, no significant difference was detected between BAC and other NSCLC for 3-year regional failure (12% vs. 20%, p = 0.45), progression-free survival (57.6% vs. 53.5%, p = 0.84) or overall survival (35% vs. 47%, p = 0.66). There was a trend towards lower three-year rates of freedom from distant failure in patients with any diagnosis of BAC compared to those without (26% vs. 38%, p = 0.053). Conclusions Compared to other NSCLC subtypes, BAC appears to have similar patterns of failure and survival after treatment with SBRT, however there may be an increased risk of distant metastases with BAC. RTOG guideline-based target delineation provides encouraging local control rates for patients with BAC.

Objective We sought to compare the relative cost-effectiveness of surgical intervention and stereotactic body radiation therapy in high risk patients with clinical stage I lung cancer (non–small cell lung cancer). Methods We compared patients chosen for surgical intervention or SBRT for clinical stage I non–small cell lung cancer. Propensity score matching was used to adjust estimated treatment hazard ratios for the confounding effects of age, comorbidity index, and clinical stage. We assumed that Medicare-allowable charges were $15,034 for surgical intervention and $13,964 for stereotactic body radiation therapy. The incremental cost-effectiveness ratio was estimated as the cost per life year gained over the patient's remaining lifetime by using a decision model. Results Fifty-seven patients in each arm were selected by means of propensity score matching. Median survival with surgical intervention was 4.1 years, and 4-year survival was 51.4%. With stereotactic body radiation therapy, median survival was 2.9 years, and 4-year survival was 30.1%. Cause-specific survival was identical between the 2 groups, and the difference in overall survival was not statistically significant. For decision modeling, stereotactic body radiation therapy was estimated to have a mean expected survival of 2.94 years at a cost of $14,153 and mean expected survival with surgical intervention was 3.39 years at a cost of $17,629, for an incremental cost-effectiveness ratio of $7753. Conclusions In our analysis stereotactic body radiation therapy appears to be less costly than surgical intervention in high-risk patients with early stage non–small cell lung cancer. However, surgical intervention appears to meet the standards for cost-effectiveness because of a longer expected overall survival. Should this advantage not be confirmed in other studies, the cost-effectiveness decision would be likely to change. Prospective randomized studies are necessary to strengthen confidence in these results.

Background and purpose Patients with multiple primary lung cancers (MPLC) present a therapeutic dilemma, particularly when they are at high risk for surgical resection. We evaluated the role of stereotactic body radiation therapy (SBRT) in the treatment of MPLC. Materials and methods A prospective thoracic SBRT registry was explored for patients with either synchronous or metachronous MPLC treated with SBRT for one or both of their tumors. Sixty-three patients were identified and clinical data were analyzed. Results Fifteen patients had synchronous lesions and 48 patients had metachronous lesions. Seventy-six lesions were treated with SBRT. Median follow-up was 24months for living patients. Median progression-free survival (PFS) and overall survival (OS) for the entire cohort was 15.5 and 20months, respectively. Patients with metachronous MPLC had a significantly higher 2year PFS (53.3% vs. 0%, p =0.0466) compared to patients with synchronous MPLC. Likewise, 2year OS was also superior for patients with metachronous versus synchronous MPLC (68.1% vs. 27.5%, p =0.0014). Six tumors (7.9%) recurred within the radiation field. There were no grade ⩾3 toxicities. Conclusions SBRT for patients with MPLC appears to be a safe and effective local treatment alternative to surgery, particularly for medically inoperable patients. Patients with metachronous MPLC have encouraging survival rates, and thus local therapy appears justified. However, patients with synchronous MPLC have poor OS and PFS despite having excellent local control, and thus the utility of local therapy in this population requires further study.

Purpose: To compare the efficacy of three lung stereotactic body radiotherapy (SBRT) regimens in a large institutional cohort. Methods:Between2004and2009,130patientsunderwentdefinitivelungcancerSBRTtoasinglelesionattheMallinckrodt Institute of Radiology. We delivered 18 Gy � 3 fractions for peripheral tumors (n = 111) and either 9 Gy � 5 fractions (n =8 ) or 10 Gy� 5 fractions (n = 11) for tumors that were central or near critical structures. Univariate and multivariate analysis of prognostic factors was performed using the Cox proportional hazard model. Results: Median follow-up was 11, 16, and 13 months for the 9 Gy � 5, 10 Gy � 5, and 18 Gy � 3 groups, respectively. Local control statistics for Years 1 and 2 were, respectively, 75% and 50% for 9 Gy � 5, 100% and 100% for 10 Gy � 5, and 99% and 91% for 18 Gy � 3. Median overall survival was 14 months, not reached, and 34 months for the 9 Gy � 5, 10 Gy � 5, and 18 Gy � 3 treatments, respectively. No difference in local control or overall survival was found between the 10 Gy � 5 and 18 Gy � 3 groups on log–rank test, but both groups had improved local control and overall survival compared with 9 Gy � 5. Treatment with 9 Gy � 5 was the only independent prognostic factor for reduced local control on multivariate analysis, and increasing age, increasing tumor volume, and poor performance status predicted independently for reduced overall survival. Conclusion: Treatment regimens of 10 Gy � 5 and 18 Gy � 3 seem to be efficacious for lung cancer SBRT and provide superior local control and overall survival compared with 9 Gy � 5. 2011 Elsevier Inc. Lung, Cancer, NSCLC, SBRT, Stereotactic.

Purpose: To determine survival and changes in neurologic function and Karnofsky performance status (KPS) in a series of patients treated for low-grade astrocytoma of the spinal cord during the past two decades. Methods: This study consisted of 14 patients with pathologically confirmed low-grade astrocytoma of the spinal cord who were treated between 1980 and 2003. All patients underwent decompressive laminectomy followed by biopsy ( n = 7), subtotal resection ( n = 6), or gross total resection ( n = 1). Ten patients underwent postoperative radiotherapy (median total dose 50 Gy in 28 fractions). The overall survival, progression-free survival, and changes in neurologic function and KPS were measured. Results: The overall survival rate at 5, 10, and 20 years was 100%, 75%, and 60%, respectively. The progression-free survival rate at 5, 10, and 20 years was 93%, 80%, and 60%, respectively. Neither overall survival nor progression-free survival was clearly correlated with any patient, tumor, or treatment factors. Neurologic function and KPS worsened after surgery in 8 (57%) of 14 and 9 (69%) of 13 patients, respectively. At a mean follow-up of 10.2 years, neurologic function had stabilized or improved in 8 (73%) of 11 remaining patients, but the KPS had worsened in 5 (50%) of 10. Most patients who were employed before surgery were working at last follow-up. Conclusion: Patients who undergo gross total resection of their tumor may be followed closely. Patients who undergo limited resection should continue to receive postoperative RT (50.4 Gy in 1.8-Gy fractions). The functional measures should be routinely evaluated to appreciate the treatment outcomes.

BACKGROUND: Structural and biologic tissue characteristics prior to and following radiosurgery (SRS) can be quantified by analyzing physiologic imaging sequences including diffusion and perfusion weighted imaging (DWI, PWI) and considering their derived parameters including apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV). Increasingly in neuro-oncology, these types of imaging sequences are being considered as prognostic and diagnostic markers. Patients' primary tumor type may impact these imaging values, and an understanding of how baseline DWI and PWI measures depend upon primary tumor type is necessary in order to consider how these markers may impact therapeutic response or when considering diagnostic possibilities such as radiation necrosis. METHODS: 78 patients with 187 brain metastases were identified retrospectively from a cohort of patients who underwent SRS between August, 2011 and March 2014 at two institutions. Included subjects had undergone MRI with physiologic (DWI and PWI) imaging prior to SRS. The physiologic sequences were processed and co-registered to anatomic sequences acquired on the day of treatment. Lesions were segmented and ROIs were generated for image analysis using the T1 + Gd sequence. Quantitative measures included rCBV, rCBF, ADC and tumor volume for each lesion. Tumor subtypes included breast, lung, colon, melanoma, renal cell, ovarian, and “other”. RESULTS AND CONCLUSIONS: There was no significant difference in tumor volume based upon tumor type, although there was a trend toward larger tumors at diagnosis for colon and ovarian primaries. There was no significant difference in ADC between tumor type; a significant elevation in rCBV was seen for renal cell and ovarian primary tumors (2.51 and 2.46) when compared with breast, colon, melanoma and lung primary tumors (1.18, 1.24, 1.38, 1.27, respectively). When considering questions of diagnostic specificity, it is important to recognize the relatively low rCBV in many active brain metastases, particularly as compared with primary brain tumors.

ObjectivesComparative studies of survival between stereotactic body radiation therapy (SBRT) and surgery have been limited by lack of comparisons of recurrence patterns between matched cohorts in non−small cell lung cancer (NSCLC).MethodsAll patients undergoing treatment with surgery or SBRT for clinical stage I NSCLC between June 2004 and December 2010 were reviewed. Age, tumor characteristics, comorbidity score, pulmonary function, overall survival (OS), disease-free survival (DFS), and recurrence data were collected and propensity matching performed.ResultsThe mean age for surgery (n = 458) was 65.8 ± 10.5 versus 74.4 ± 9.4 for SBRT (n = 151) (P

Purpose: To investigate the impact of exclusively using intravenous (IV) contrast x-ray computed tomography (CT) scans on lung cancer intensity-modulated radiation therapy (IMRT) treatment planning. Methods: Eight patients with lung cancer (one small cell, seven nonsmall cell) scheduled to receive IMRT consented to acquisition of simulation CT scans with and without IV contrast. Clinical treatment plans optimized on the noncontrast scans were recomputed on contrast scans and dose coverage was compared, along with the γ passing rates. Results: IV contrast enhanced scans provided better target and critical structure conspicuity than the noncontrast scans. Using noncontrast scan as a reference, the median absolute/relative differences in mean, maximum, and minimum doses to the planning target volume (PTV) were −4.5 cGy/−0.09%, 41.1 cGy/0.62%, and −19.7 cGy/−0.50%, respectively. Regarding organs-at-risk (OARs), the median absolute/relative differences of maximum dose to heart was −13.3 cGy/−0.32%, to esophagus was −63.4 cGy/−0.89%, and to spinal cord was −16.3 cGy/−0.46%. The median heart region of interest CT Hounsfield Unit (HU) number difference between noncontrast and contrast scans was 136.4 HU (range, 94.2–161.8 HU). Subjectively, the regions with absolute dose differences greater than 3% of the prescription dose were small and typically located at the patient periphery and/or at the beam edges. The median γ passing rate was 0.9981 (range, 0.9654–0.9999) using 3% absolute dose difference/3 mm distance-to-agreement criteria. Overall, all evaluated cases were found to be clinically equivalent. Conclusions: PTV and OARs dose differences between noncontrast and contrast scans appear to be minimal for lung cancer patients undergoing IMRT. Using IV contrast scans as the primary simulation dataset could increase treatment planning efficiency and accuracy by avoiding unnecessary scans, manually region overriding, and planning errors caused by nonperfect image registrations.

The SV40 T antigen database (http://www.pitt.edu/pipaslab/) lists viruses and plasmids expressing mutant forms of large T antigen. Each entry contains information regarding the mutant designation, mutant type, virus strain, nucleotide change, amino acid change and pertinent references. The database is now available as an internet searchable index.

Purpose: Investigate the potential of magnetic resonance elastography (MRE) to differentiate and delineate tissues with different viscoelastic properties, with the purpose of applying MRE to differentiate and delineate recurrent brain tumor and radiation necrosis. Methods: To simulate tumor or radiation necrosis inside normal brain tissue, a 10 mm radius cylindrical inclusion was modeled inside a 150×150 mm2 rectangular prismatic domain. Typical storage modulus (2.5 kPa) and loss modulus (0.5 kPa) of brain tissue were assigned to the prismatic region. Varying tissue properties were assigned to the cylindrical region (storage modulus 0.5–5 kPa, with loss factor 0.2), mimicking the shear modulus difference between recurrent tumor and radiation necrosis. Wave propagation (30–100 Hz) was simulated in this domain, using the frequency‐domain analysis in the structural mechanics module in COMSOL Multiphysics software (COMSOL, Burlington, MA). A 3D inversion method was used to estimate tissue properties. Results: In all the simulation results, the cylindrical lesion can be identified based on the modulus difference between the region and its surroundings. The lesion boundary can be delineated based on the normalized residual error (NRE) map of the fitting procedure used for modulus estimation. The estimated complex shear modulus is close to the true value when the applied frequency is or above 60 Hz. The estimate of the storage modulus is more accurate than the loss modulus. NRE is typically maximal at the boundary of the inclusion (lesion). Conclusion: This study demonstrates the potential of MRE to differentiate lesions with different shear moduli. The results show the possibility of using MRE to differentiate recurrent tumor from radiation necrosis, based on the difference between their moduli, and the potential of lesion delineation based on NRE at boundaries. Physical phantom studies and ex vivo mechanical testing of the tissue will be used in the future for further verification.