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Radiation therapy plays a potential curative role in the treatment of patients with non-small-cell lung cancer with locoregional disease who are not surgical candidates and a palliative role for patients with metastatic disease. Stereotactic body radiation therapy is a relatively new technique in patients with early-stage non-small-cell lung cancer. A trial from RTOG(®) reported >97% local control at 3 years. For patients with locally advanced disease, thoracic radiation to a dose of 60 Gy remains the standard of care. Sequential chemotherapy or radiation alone can be used for patients with poor performance status who cannot tolerate more aggressive approaches. Chemotherapy should be used for patients with metastatic disease. Radiation therapy is useful for palliation of symptomatic tumors, and a dose of approximately 30 Gy is commonly used. Endobronchial brachytherapy is useful for patients with symptomatic endobronchial tumors. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment., (Copyright © 2013 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: Controversy exists regarding whether or not amifostine might reduce the efficacy of cancer treatment. The aim of this meta-analysis was to evaluate the impact of amifostine on overall survival (OS) and progression-free survival (PFS) in patients treated with radiotherapy or chemoradiotherapy., Material and Methods: Updated data from individual patients with non-small-cell lung cancer, head and neck squamous cell carcinoma, and pelvic cancer treated with radiotherapy or chemoradiotherapy and randomly assigned to amifostine or not were included. The primary end point was OS., Results: Twenty-two randomized trials (2279 patients) were potentially eligible. Data were available for 16 trials (1554 patients), but four trials (435 patients) were excluded after data checking. Ultimately 12 trials and 1119 patients were analyzed. A total of 431 patients were treated with radiotherapy alone (three trials), and 688 patients were treated with chemoradiotherapy (nine trials). Thirty-three percent of patients had lung cancers, 65% had head and neck cancers, and 2% had pelvic carcinomas. Ninety-one percent of patients had locally advanced disease (early stage, 9%). Median follow-up was 5.2 years. The hazard ratio (HR) of death was 0.98 (95% CI, 0.84 to 1.14; P = .78). On the basis of 11 trials (1091 patients), the HR of progression, relapse, or death was 1.05 (95% CI, 0.90 to 1.22; P = .53). The tests for heterogeneity were not significant (P ≥ .73), and there was no significant variation of treatment effect according to sex, age, tumor site, stage, histology, locoregional treatment, or type of administration for either end point., Conclusion: Amifostine did not reduce OS and PFS in patients treated with radiotherapy or chemoradiotherapy.

Recently, many agents have been identified that target molecular pathways that can mitigate radiation toxicity. To date, no drugs have been approved as radiation injury mitigators, which are defined as agents administered after irradiation but before toxicity is manifest. In order to accelerate the application of potential mitigators for cancer patients, a meeting sponsored by the National Cancer Institute (NCI) and National Institute of Allergy and Infectious Diseases (NIAID) was held in January 2010. This article presents an algorithm to guide clinical trials for such agents in patients receiving radiotherapy or radiochemotherapy. It reviews the mechanisms of radiation injury, the clinical problem, the preclinical and clinical development of candidate agents, and the design and conduct of clinical trials. The central role of patient reported outcomes is outlined, as well as key lessons learned from prior clinical trials. Ultimately, the goal is to be able to apply such promising agents to improve the quality of life for patients receiving radiotherapy or chemoradiotherapy for cancer., (©2010 AACR.)

The purpose of this study was to evaluate the accuracy of a two-dimensional (2D) to three-dimensional (3D) image-fusion-guided target localization system and a mask based stereotactic system for fractionated stereotactic radiotherapy (FSRT) of cranial lesions. A commercial x-ray image guidance system originally developed for extracranial radiosurgery was used for FSRT of cranial lesions. The localization accuracy was quantitatively evaluated with an anthropomorphic head phantom implanted with eight small radiopaque markers (BBs) in different locations. The accuracy and its clinical reliability were also qualitatively evaluated for a total of 127 fractions in 12 patients with both kV x-ray images and MV portal films. The image-guided system was then used as a standard to evaluate the overall uncertainty and reproducibility of the head mask based stereotactic system in these patients. The phantom study demonstrated that the maximal random error of the image-guided target localization was +/-0.6 mm in each direction in terms of the 95% confidence interval (CI). The systematic error varied with measurement methods. It was approximately 0.4 mm, mainly in the longitudinal direction, for the kV x-ray method. There was a 0.5 mm systematic difference, primarily in the lateral direction, between the kV x-ray and the MV portal methods. The patient study suggested that the accuracy of the image-guided system in patients was comparable to that in the phantom. The overall uncertainty of the mask system was +/-4 mm, and the reproducibility was +/-2.9 mm in terms of 95% CI. The study demonstrated that the image guidance system provides accurate and precise target positioning.

Simple Summary: Elevated levels of the mitotic checkpoint kinase BUB1 are frequently observed in most solid cancers, including lung cancer. High BUB1 expression is linked to poorer patient survival. In the present study, we aimed to evaluate if a BUB1 targeting agent could enhance the effectiveness of chemotherapy and chemoradiation in lung cancer. Our findings suggest that BUB1 inhibitor sensitizes lung cancer cell lines to chemotherapy, radiotherapy, and chemoradiation and thus validate BUB1 as a novel molecular target. Background: Despite advances in targeted therapies and immunotherapies, traditional treatments like microtubule stabilizers (paclitaxel, docetaxel), DNA-intercalating platinum drugs (cisplatin), and radiation therapy remain essential for managing locally advanced and metastatic lung cancer. Identifying novel molecular targets could enhance the efficacy of these treatments. Hypothesis: We hypothesize that BUB1 (Ser/Thr kinase) is overexpressed in lung cancers and its inhibition will sensitize lung cancers to chemoradiation. Methods: BUB1 inhibitor (BAY1816032) was combined with cisplatin, paclitaxel, a PARP inhibitor olaparib, and radiation in cell proliferation and radiation-sensitization assays. Biochemical and molecular assays evaluated the impact on DNA damage signaling and cell death. Results: Immunostaining of lung tumor microarrays (TMAs) confirmed higher BUB1 expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) compared to normal tissues. In NSCLC, BUB1 overexpression correlated directly with the expression of TP53 mutations and poorer overall survival in NSCLC and SCLC patients. BAY1816032 synergistically sensitized lung cancer cell lines to paclitaxel and olaparib and enhanced cell killing by radiation in both NSCLC and SCLC. Molecular analysis indicated a shift towards pro-apoptotic and anti-proliferative states, evidenced by altered BAX, BCL2, PCNA, and Caspases-9 and -3 expressions. Conclusions: Elevated BUB1 expression is associated with poorer survival in lung cancer. Inhibiting BUB1 sensitizes NSCLC and SCLC to chemotherapies (cisplatin, paclitaxel), targeted therapy (olaparib), and radiation. Furthermore, we present the novel finding that BUB1 inhibition sensitized both NSCLC and SCLC to radiotherapy and chemoradiation. Our results demonstrate BUB1 inhibition as a promising strategy to sensitize lung cancers to radiation and chemoradiation therapies. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the impact of reducing Clinical Target Volume (CTV) to Planning Target Volume (PTV) margins on delivered radiation therapy (RT) dose and patient reported quality-of -life (QOL) for patients with localized prostate cancer. Methods: Twenty patients were included in a single institution IRB-approved prospective study. Nine were planned with reduced margins (4 mm at prostate/rectum interface, 5 mm elsewhere), and 11 with standard margins (6/10 mm). Cumulative delivered dose was calculated using deformable dose accumulation. Each daily CBCT dataset was deformed to the planning CT (pCT), dose was computed, and accumulated on the resampled pCT using a parameter-optimized, B-spline algorithm (Elastix, ITK/VTK). EPIC-26 patient reported QOL was prospectively collected pre-treatment, post-treatment, and at 2-, 6-, 12-, 18-, 24-, 36-, 48-, and 60-month follow-ups. Post -RT QOL scores were baseline corrected and standardized to a [0--100] scale using EPIC-26 methodology. Correlations between QOL scores and dosimetric parameters were investigated, and the overall QOL differences between the two groups (QOLMargin-reduced-QOLcontrol) were calculated. Results: The median QOL follow-up length for the 20 patients was 48 months. Difference between delivered dose and planned dose did not reach statistical significance (p > 0.1) for both targets and organs at risk between the two groups.At 4 years post-RT, standardized mean QOLMargin-reduced-QOLcontrol were improved for Urinary Incontinence, Urinary Irritative/Obstructive, Bowel, and Sexual EPIC domains by 3.5, 14.8, 10.2, and 16.1, respectively (higher values better). The control group showed larger PTV/rectum and PTV/bladder intersection volumes (7.2 ± 5.8, 18.2 ± 8.1 cc) than the margin-reduced group (2.6 ± 1.8, 12.5 ± 8.3 cc), though the dose to these intersection volumes did not reach statistical significance (p > 0.1) between the groups. PTV/rectum intersection volume showed a moderate correlation (r = -0.56, p < 0.05) to Bowel EPIC domain. Conclusions: Results of this prospective study showed that margin-reduced group exhibited clinically meaningful improvement of QOL without compromising the target dose coverage. [ABSTRACT FROM AUTHOR]

PURPOSE Historical racial disparities in lung cancer surgery rates resulted in lower survival in Black patients. Our objective was to examine racial differences in thoracic radiation treatments and toxicities in patients with non-small-cell lung cancer. METHODS AND MATERIALS A large institutional review board-approved statewide patient-level database of patients with stage II-III non-small-cell lung cancer who received definitive thoracic radiation from March 2012 to November 2019 was analyzed to assess associations between race and other variables. Race (White or Black) was defined by patient self-report. Provider-reported toxicity was defined by Common Terminology Criteria for Adverse Events version 4.0. Patient-reported toxicity was determined by the Functional Assessment of Cancer Therapy-Lung quality-of-life instrument. Univariable and multivariable regression models were fitted to assess relationships between race and variables of interest. Spearman rank-correlation coefficients were calculated between provider-reported toxicity and similar patient-reported outcomes. RESULTS One thousand four hundred forty-one patients from 24 institutions with mean age 68 years (range, 38-94 years) were evaluated. Race was not significantly associated with radiation or chemotherapy approach. There was significantly increased patient-reported general pain in Black patients at the preradiation and end-ofradiation time points. Black patients were significantly less likely to have provider-reported grade 21 pneumonitis (odds ratio 0.36, P 5 .03), even after controlling for known patient and treatment factors. Correlation coefficients between provider- and patient-reported toxicities were generally similar across race groups except for a stronger correlation between patient- and provider-reported esophagitis in White patients. CONCLUSION In this largemulti-institutional study, we found no evidence of racial differences in radiation treatment or chemotherapy approaches. We did, however, unexpectedly find that Black race was associated with lower odds of provider-reported grade 21 radiation pneumonitis. The stronger correlation between patient- and providerreported esophagitis and swallowing symptoms for White patients also suggests possible under-recognition of symptoms in Black patients. Further research is needed to study the implications for Black patients. [ABSTRACT FROM AUTHOR]

Purpose: To perform radiomic analysis of primary tumors extracted from pretreatment contrast‐enhanced computed tomography (CE‐CT) images for patients with oropharyngeal cancers to identify discriminant features and construct an optimal classifier for the characterization and prediction of human papilloma virus (HPV) status. Materials and methods: One hundred and eighty seven patients with oropharyngeal cancers with known HPV status (confirmed by immunohistochemistry—p16 protein testing) were retrospectively studied as follows: Group A: 95 patients (19HPV− and 76HPV+) from the MICAII grand challenge. Group B: 92 patients (52HPV− and 40HPV+) from our institution. Radiomic features (172) were extracted from pretreatment diagnostic CE‐CT images of the gross tumor volume (GTV). Levene and Kolmogorov–Smirnov's tests with absolute biserial correlation (>0.48) were used to identify the discriminant features between the HPV+ and HPV− groups. The discriminant features were used to train and test eight different classifiers. Area under receiver operating characteristic (AUC), positive predictive and negative predictive values (PPV and NPV, respectively) were used to evaluate the performance of the classifiers. Principal component analysis (PCA) was applied on the discriminant feature set and seven PCs were used to train and test a generalized linear model (GLM) classifier. Results: Among 172 radiomic features only 12 radiomic features (from 3 categories) were significantly different (P < 0.05, |BSC| > 0.48) between the HPV+ and HPV− groups. Among the eight classifiers trained and applied for prediction of HPV status, the GLM showed the highest performance for each discriminant feature and the combined 12 features: AUC/PPV/NPV = 0.878/0.834/0.811. The GLM high prediction power was AUC/PPV/NPV = 0.849/0.731/0.788 and AUC/PPV/NPV = 0.869/0.807/0.870 for unseen test datasets for groups A and B, respectively. After eliminating the correlation among discriminant features by applying PCA analysis, the performance of the GLM was improved by 3.3%, 2.2%, and 1.8% for AUC, PPV, and NPV, respectively. Conclusions: Results imply that GTV's for HPV+ patients exhibit higher intensities, smaller lesion size, greater sphericity/roundness, and higher spatial intensity‐variation/heterogeneity. Results are suggestive that radiomic features primarily associated with the spatial arrangement and morphological appearance of the tumor on contrast‐enhanced diagnostic CT datasets may be potentially used for classification of HPV status. [ABSTRACT FROM AUTHOR]

For nearly 40 years, the U.S. National Cancer Institute (NCI) has funded health-related quality-of-life (HRQOL) and symptom management in oncology clinical trials as a method for including a cancer patient's experience during and after treatment. The NCI's planned scope for HRQOL, symptom and patient-reported outcomes management research is explained as it pertains to radiopharmaceutical clinical development. An effort already underway to support protocol authoring via an NCI Cancer Therapy Evaluation Program (CTEP) Centralized Protocol Writing Service (CPWS) is described as this service aids incorporation of HRQOL, symptom and patient-reported outcomes management research into sponsored protocols. [ABSTRACT FROM AUTHOR]

Purpose: To model Head‐and‐Neck anatomy from daily Cone Beam‐CT (CBCT) images over the course of fractionated radiotherapy using principal component analysis (PCA). Methods and materials: Eighteen oropharyngeal Head‐and‐Neck cancer patients, treated with volumetric modulated arc therapy (VMAT), were included in this retrospective study. Normal organs, including the parotid and submandibular glands, mandible, pharyngeal constrictor muscles (PCMs), and spinal cord were contoured using daily CBCT image datasets. PCA models for each organ were developed for individual patients (IP) and the entire patient cohort/population (PP). The first 10 principal components (PCs) were extracted for all models. Analysis included cumulative and individual PCs for each organ and patient, as well as the aggregate organ/patient population; comparisons were made using the root‐mean‐square (RMS) of the percentage predicted spatial displacement for each PC. Results: Overall, spatial displacement prediction was achieved at the 95% confidence level (CL) for the first three to four PCs for all organs, based on IP models. For PP models, the first four PCs predicted spatial displacement at the 80%–89% CL. Differences in percentage predicted spatial displacement between mean IP models for each organ ranged from 2.8% ± 1.8% (1st PC) to 0.6% ± 0.4% (4th PC). Differences in percentage predicted spatial displacement between IP models vs the mean IP model for each organ based on the 1st PC were <12.9% ± 6.9% for all organs. Differences in percentage predicted spatial displacement between IP and PP models based on all organs and patients for the 1st and 2nd PC were <11.7% ± 2.2%. Conclusion: Tissue changes during fractionated radiotherapy observed on daily CBCT in patients with Head‐and‐Neck cancers, were modeled using PCA. In general, spatial displacement for organs‐at‐risk was predicted for the first 4 principal components at the 95% confidence levels (CL), for individual patient (IP) models, and at the 80%–89% CL for population‐based patient (PP) models. The IP and PP models were most predictive of changes in glandular organs and pharyngeal constrictor muscles, respectively. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) has been incorporated as an adjunct to CT to take advantage of its excellent soft tissue contrast for contouring. MR-only treatment planning approaches have been developed to avoid errors introduced during the MR-CT registration process. The purpose of this study is to evaluate calculated dose distributions after incorporating a novel synthetic CT (synCT) derived from magnetic resonance simulation images into prostate cancer treatment planning and to compare dose distributions calculated using three previously published MR-only treatment planning methodologies.Methods: An IRB-approved retrospective study evaluated 15 prostate cancer patients that underwent IMRT (n = 11) or arc therapy (n = 4) to a total dose of 70.2-79.2 Gy. Original treatment plans were derived from CT simulation images (CT-SIM). T1-weighted, T2-weighted, and balanced turbo field echo images were acquired on a 1.0 T high field open MR simulator with patients immobilized in treatment position. Four MR-derived images were studied: bulk density assignment (10 HU) to water (MRW), bulk density assignments to water and bone with pelvic bone values derived either from literature (491 HU, MRW+B491) or from CT-SIM population average bone values (300 HU, MRW+B300), and synCTs. Plans were recalculated using fixed monitor units, plan dosimetry was evaluated, and local dose differences were characterized using gamma analysis (1 %/1 mm dose difference/distance to agreement).Results: While synCT provided closest agreement to CT-SIM for D95, D99, and mean dose (<0.7 Gy (1 %)) compared to MRW, MRW+B491, and MRW+B300, pairwise comparisons showed differences were not significant (p < 0.05). Significant improvements were observed for synCT in the bladder, but not for rectum or penile bulb. SynCT gamma analysis pass rates (97.2 %) evaluated at 1 %/1 mm exceeded those from MRW (94.7 %), MRW+B300 (94.0 %), or MRW+B491 (90.4 %). One subject's synCT gamma (1 %/1 mm) results (89.9 %) were lower than MRW (98.7 %) and MRW+B300 (96.7 %) due to increased rectal gas during MR-simulation that did not affect bulk density assignment-based calculations but was reflected in higher rectal doses for synCT.Conclusions: SynCT values provided closest dosimetric and gamma analysis agreement to CT-SIM compared to bulk density assignment-based CT surrogates. SynCTs may provide additional clinical value in treatment sites with greater air-to-soft tissue ratio. [ABSTRACT FROM AUTHOR]

Image-guided adaptive radiotherapy requires deformable image registration to map radiation dose back and forth between images. The purpose of this study is to develop a novel method to improve the accuracy of an intensity-based image registration algorithm in low-contrast regions. A computational framework has been developed in this study to improve the quality of the 'demons' registration. For each voxel in the registration's target image, the standard deviation of image intensity in a neighborhood of this voxel was calculated. A mask for high-contrast regions was generated based on their standard deviations. In the masked regions, a tetrahedral mesh was refined recursively so that a sufficient number of tetrahedral nodes in these regions can be selected as driving nodes. An elastic system driven by the displacements of the selected nodes was formulated using a finite element method (FEM) and implemented on the refined mesh. The displacements of these driving nodes were generated with the 'demons' algorithm. The solution of the system was derived using a conjugated gradient method, and interpolated to generate a displacement vector field for the registered images. The FEM correction method was compared with the 'demons' algorithm on the computed tomography (CT) images of lung and prostate patients. The performance of the FEM correction relating to the 'demons' registration was analyzed based on the physical property of their deformation maps, and quantitatively evaluated through a benchmark model developed specifically for this study. Compared to the benchmark model, the 'demons' registration has themaximum error of 1.2 cm, which can be corrected by the FEM to 0.4 cm, and the average error of the 'demons' registration is reduced from 0.17 to 0.11 cm. For the CT images of lung and prostate patients, the deformation maps generated by the 'demons' algorithm were found unrealistic at several places. In these places, the displacement differences between the 'demons' registrations and their FEM corrections were found in the range of 0.4 and 1.1 cm. The mesh refinement and FEM simulation were implemented in a single thread application which requires about 45 min of computation time on a 2.6 GHz computer. This study has demonstrated that the FEM can be integrated with intensity-based image registration algorithms to improve their registration accuracy, especially in low-contrast regions. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies by our group and others have demonstrated the importance of sociodemographic factors in cancer-related outcomes. The identification of these factors has led to novel approaches to the care of the high-risk cancer patient, specifically in the adoption of clinical interventions that convey similar benefits as favorable sociodemographic characteristics. This study examined the importance of marital status and race as prognostic indicators in men with prostate cancer. Methods: This report is a meta-analysis of 3,570 patients with prostate cancer treated in three prospective RTOG clinical trials. The Kaplan-Meier method was used to estimate the survival rate and the cumulative incidence method was used to analyze biochemical failure rate. Hazard ratios were calculated for all covariates using either the Cox or Fine and Gray's proportional hazards model or logistic regression model with associated 95% confidence intervals and p values. Results: Hazard ratio (HR) for overall survival (OS) for single status compared to married status was 1.36 (95% CI, 1.2 to 1.53). OS HR for non-White compared to White patients was 1.05 (CI 0.92 to 1.21). In contrast, the disease-free survival (DFS) HR and biochemical failure (BF) HR were both not significantly different neither between single and married patients nor between White patients and non-White patients. Median time to death for married men was 5.68 years and for single men was 4.73 years. Median time for DFS for married men was 7.25 years and for single men was 6.56 years. Median time for BF for married men was 7.81 years and for single men was 7.05 years. Conclusions: Race was not associated with statistically significant differences in this analysis. Congruent with our previous work in other cancer sites, marital status predicted improved prostate cancer outcomes including overall survival. Implications for cancer survivors: Prostate cancer is the most common visceral cancer in men in the USA. The stratification of prostate cancer risk is currently modeled solely on pathologic prognostic factors including PSA and Gleason Score. Independent of these pathologic prognostic factors, our paper describes the central sociodemographic factor of being single as a negative prognostic indicator. Single men are at high risk of poorer outcomes after prostate cancer treatment. Intriguingly, in our group of patients, race was not a significant prognostic factor. The findings in this paper add to the body of work that describes important sociodemographic prognostic factors that are currently underappreciated in patients with cancer. Future steps will include the validation of these findings in prospective studies, and the incorporation of clinical strategies that identify and compensate for sociodemographic factors that predict for poorer cancer outcomes. [ABSTRACT FROM AUTHOR]

The article describes present knowledge on palliative thoracic radiotherapy and identifies potential areas for future research. A practice guideline and a consensus statement have demonstrated palliative thoracic radiotherapy as an effective modality in symptom palliation and cancer outcomes. Areas for future scientific inquiry include the roles of intensity-modulated radiation therapy and image-guided radiation therapy, and creation of common palliative endpoint for future clinical trials.

Purpose: During image-guided radiosurgery, it is common to account only for translational shifts while leaving rotational deviations uncorrected. The aim of this study is to investigate the rotational setup deviations and estimate the dosimetric impact in spinal radiosurgery. Materials and methods: Stereoscopic image registrations of 711 spine radiosurgery procedures (546 patients) were retrospectively reviewed and classified to cervical (C), thoracic (T), and lumbar (L) spines. The probability of rotational deviations were estimated in three orthogonal axis. In order to investigate the dosimetric impact, the original simulation CT images were rotated in the range of ±5 deg in each axis. Then, the dosimetric changes were recorded; including the coverage (V90) and minimum dose (Dmin) to the target, and the dose of 10% volume (D10) and maximum dose (Dmax) to the spinal cord. Results: Target rotations of >5 deg and >3 deg occurred respectively in 1% and 8% of cases. The mean rotations were small (|µ|<0.6 deg) with no axis and site dependent trends. The standard deviations (σ) of different sites and axes ranged from 1.4 to 2.0 deg (mean σ=1.7 deg). The overall dosimetric changes of the target coverage(V90) and cord D10 were small. Five degree rotation resulted in a target V90 decrease of 1±1%, 2±2% and 3±1%, respectively in the lateral, vertical, and longitudinal axes. The corresponding cord D10 increased by 3±6%, 2±2%, and 6±5%. The changes in cord Dmax ranged from 92% to 138% of the original reference spinal cord. Corresponding changes in target Dmin were 59~106%. Conclusion: Large target rotations occurred in a small percentage of patients. The overall dosimetric impact on target coverage and cord D10 was small. However larger effects were observed on the target Dmin and cord Dmax. Special care must be taken for targets of elongated shapes involving multiple vertebrae. [ABSTRACT FROM AUTHOR]

Background The combination of chemotherapy with thoracic radiotherapy (TRT) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non–small cell lung cancer. However, it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy. Methods A total of 610 patients were randomly assigned to two concurrent regimens and one sequential chemotherapy and TRT regimen in a three-arm phase III trial. The sequential arm included cisplatin at 100 mg/m2 on days 1 and 29 and vinblastine at 5 mg/m2 per week for 5 weeks with 60 Gy TRT beginning on day 50. Arm 2 used the same chemotherapy regimen as arm 1 with 60 Gy TRT once daily beginning on day 1. Arm 3 used cisplatin at 50 mg/m2 on days 1, 8, 29, and 36 with oral etoposide at 50 mg twice daily for 10 weeks on days 1, 2, 5, and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions beginning on day 1. The primary endpoint was overall survival, and secondary endpoints included tumor response and time to tumor progression. Kaplan–Meier analyses were used to assess survival, and toxic effects were examined using the Wilcoxon rank sum test. All statistical tests were two-sided. Results Median survival times were 14.6, 17.0, and 15.6 months for arms 1–3, respectively. Five-year survival was statistically significantly higher for patients treated with the concurrent regimen with once-daily TRT compared with the sequential treatment (5-year survival: sequential, arm 1, 10% [20 patients], 95% confidence interval [CI] = 7% to 15%; concurrent, arm 2, 16% [31 patients], 95% CI = 11% to 22%, P = .046; concurrent, arm 3, 13% [22 patients], 95% CI = 9% to 18%). With a median follow-up time of 11 years, the rates of acute grade 3–5 nonhematologic toxic effects were higher with concurrent than sequential therapy, but late toxic effects were similar. Conclusion Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies. [ABSTRACT FROM PUBLISHER]

Purpose: Radiation-induced damage, such as inflammation and fibrosis, can compromise ventilation capability of local functional units (alveoli) of the lung. Ventilation function as measured with ventilation images, however, is often complicated by the underlying mechanical variations. The purpose of this study is to present a 4DCT-based method to measure the regional ventilation capability, namely, regional compliance, for the evaluation of radiation-induced lung damage. Methods: Six 4DCT images were investigated in this study: One previously used in the generation of a POPI model and the other five acquired at Henry Ford Health System. A tetrahedral geometrical model was created and scaled to encompass each of the 4DCT image domains. Image registrations were performed on each of the 4DCT images using a multiresolution Demons algorithm. The images at the end of exhalation were selected as a reference. Images at other exhalation phases were registered to the reference phase. For the POPI-modeled patient, each of these registration instances was validated using 40 landmarks. The displacement vector fields (DVFs) were used first to calculate the volumetric variation of each tetrahedron, which represents the change in the air volume. The calculated results were interpolated to generate 3D ventilation images. With the computed DVF, a finite element method (FEM) framework was developed to compute the stress images of the lung tissue. The regional compliance was then defined as the ratio of the ventilation and stress values and was calculated for each phase. Based on iterative FEM simulations, the potential range of the mechanical parameters for the lung was determined by comparing the model-computed average stress to the clinical reference value of airway pressure. The effect of the parameter variations on the computed stress distributions was estimated using Pearson correlation coefficients. Results: For the POPI-modeled patient, five exhalation phases from the start to the end of exhalation were denoted by Pi, i=1,...,5, respectively. The average lung volume variation relative to the reference phase (P5) was reduced from 18% at P1 to 4.8% at P4. The average stress at phase Pi was 1.42, 1.34, 0.74, and 0.28 kPa, and the average regional compliance was 0.19, 0.20, 0.20, and 0.24 for i=1,...,4, respectively. For the other five patients, their average Rv value at the end-inhalation phase was 21.1%, 19.6%, 22.4%, 22.5%, and 18.8%, respectively, and the regional compliance averaged over all six patients is 0.2. For elasticity parameters chosen from the potential parameter range, the resultant stress distributions were found to be similar to each other with Pearson correlation coefficients greater than 0.81. Conclusions: A 4DCT-based mechanical model has been developed to calculate the ventilation and stress images of the lung. The resultant regional compliance represents the lung's elasticity property and is potentially useful in correlating regions of lung damage with radiation dose following a course of radiation therapy. [ABSTRACT FROM AUTHOR]

Purpose: Tumor control probability (TCP) models have been proposed to evaluate and guide treatment planning. However, they are usually based on the dose volume histograms (DVHs) of the planning target volume (PTV) and may not properly reflect the substantial variation in tumor burden from the gross tumor volume (GTV) to the microscopic extension (ME) and to the margin of PTV. In this study, the authors propose a TCP model that can account for the effects of setup uncertainties and tumor cell density decay in the ME region. Methods: The proposed TCP model is based on the total surviving clonogenic tumor cells (CTCs) after irradiation of a known dose distribution to a region with a CTC distribution. The CTC density was considered to be homogeneous within the GTV, while decreasing exponentially in the ME region. The effect of random setup uncertainty was modeled by convolving the dose distribution with a Gaussian probability density function, represented by a standard deviation, σ. The effect of systematic setup uncertainty was modeled by summing each calculated TCP for all potential offsets in a Gaussian probability, represented by Σ. The model was then applied to simplified cases to demonstrate the concept. TCP dose responses were calculated for various GTV volumes, DVH shapes, CTC density decay coefficients, probabilities of lymph node metastasis, and random and systematic errors. The slopes of the dose falloff to cover the CTC density decay in the ME region and the margins to compensate setup errors were also analyzed in generalized cases. Results: The sigmoid TCP dose response curve shifted to the right substantially for a larger GTV, while modestly for cold spots in DVH. A dose distribution with a uniform dose within the GTV, and a linear dose falloff in the ME region, tended to cause a minimal TCP deterioration if a proper dose falloff slope was used. When the dose falloff slope was less steep than a critical slope represented by kT, the D50, which is the prescription dose at TCP=50%, and Γ50, which is the TCP slope at TCP=50%, varied little with different dose falloff slopes. However, both D50 and Γ50 deteriorated fast when the slopes were steeper than kT. The random setup error tended to shift the TCP curve to the right, while the systematic error tended to compress the curve downward. For combined random and systematic errors, we demonstrated that based on the model, a margin of (0.75σ)2+(1.15Σ)2 added to the GTV was found to cause a TCP change corresponding to 2% drop at TCP=90%, or 0.5 Gy shift in D50. Conclusions: This study conceptually demonstrated that a TCP model incorporating the effects of tumor cell density variation and setup uncertainty may be used to guide radiation treatment planning. [ABSTRACT FROM AUTHOR]

Purpose: The authors propose a combined scatter reduction and correction method to improve image quality in cone-beam computed tomography (CBCT). Although using a beam-block approach similar to previous techniques to measure the scatter, this method differs in that the authors utilize partially blocked projection data obtained during scatter measurement for CBCT image reconstruction. This study aims to evaluate the feasibility of the proposed approach. Methods: A 1D grid, composed of lead septa, was placed between the radiation source and the imaging object for scatter measurement. Image data were collected from the grid interspace regions while the scatter distribution was measured in the blocked regions under the grid. Scatter correction was performed by subtracting the measured scatter from the imaging data. Image information in the penumbral regions of the grid was derived. Three imaging modes were developed to reconstruct full CBCT images from partial projection data. The single-rotation half-fan mode uses interpolation to fill the missing data. The dual-rotation half-fan mode uses two rotations, with the grid offset by half a grid cycle, to acquire two complementary sets of projections, which are then merged to form complete projections for reconstruction. The single-rotation full-fan mode was designed for imaging a small object or a region of interest. Full-fan projection images were acquired over a 360° scan angle with the grid shifting a distance during the scan. An enlarged Catphan phantom was used to evaluate potential improvement in image quality with the proposed technique. An anthropomorphic pelvis phantom was used to validate the feasibility of reconstructing a complete set of CBCT images from the partially blocked projections using three imaging modes. Rigid-body image registration was performed between the CBCT images from the single-rotation half-fan mode and the simulation CT and the results were compared to that for the CBCT images from dual-rotation mode and conventional CBCT images. Results: The proposed technique reduced the streak artifact index from 58% to 1% in comparison with the conventional CBCT. It also improved CT number linearity from 0.880 to 0.998 and the contrast-to-noise ratio (CNR) from 4.29 to 6.42. Complete sets of CBCT images with overall improved image quality were achieved for all three image modes. The longitudinal resolution was slightly compromised for the single-rotation half-fan mode. High resolution was retained for the dual-rotation half-fan and single-rotation full-fan modes in the longitudinal direction. The registration error for the CBCT images from the single-rotation half-fan mode was 0.8±0.3 mm in the longitudinal direction and negligible in the other directions. Conclusions: The proposed method provides combined scatter correction and direct scatter reduction. Scatter correction may eliminate scatter artifacts, while direct scatter reduction may improve the CNR to compensate the CNR degradation due to scatter correction. Complete sets of CBCT images are reconstructed in all three imaging modes. The single-rotation mode can be used for rigid-body patient alignment despite degradation in longitudinal resolution. The dual-rotation mode may be used to improve CBCT image quality for soft tissue delineation in adaptive radiation therapy. [ABSTRACT FROM AUTHOR]

Radiotherapy research and outcome analyses are essential for evaluating new methods of radiation delivery and for assessing the benefits of a given technology on locoregional control and overall survival. In this article, a computational platform is presented to facilitate radiotherapy research and outcome studies in radiation oncology. This computational platform consists of (1) an infrastructural database that stores patient diagnosis, IMRT treatment details, and follow-up information, (2) an interface tool that is used to import and export IMRT plans in DICOM RT and AAPM/RTOG formats from a wide range of planning systems to facilitate reproducible research, (3) a graphical data analysis and programming tool that visualizes all aspects of an IMRT plan including dose, contour, and image data to aid the analysis of treatment plans, and (4) a software package that calculates radiobiological models to evaluate IMRT treatment plans. Given the limited number of general-purpose computational environments for radiotherapy research and outcome studies, this computational platform represents a powerful and convenient tool that is well suited for analyzing dose distributions biologically and correlating them with the delivered radiation dose distributions and other patient-related clinical factors. In addition the database is web-based and accessible by multiple users, facilitating its convenient application and use. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) plays a major role in the definitive treatment of patients with non–small-cell lung cancer who are unable to tolerate surgery. Radiation therapy alone is used primarily for early-stage (stages I and II) patients. Higher doses of RT (>65 Gy) seem to improve outcomes, and modern techniques such as stereotactic body RT have been very promising. For patients with locally advanced disease (stages IIIA and IIIB), concurrent chemotherapy and RT remains the standard of care. However, many patients cannot tolerate the regimen because of its toxicity. Sequential chemotherapy followed by RT is used in these situations. Radiation therapy alone is used for the rare patient who cannot tolerate the use of any chemotherapy because of comorbid conditions. Palliative external-beam RT is useful for patients with metastatic disease, causing symptoms such as dyspnea, cough, hemoptysis, postobstructive pneumonia, and pain. Hypofractionation has been attempted as a means to provide more rapid and convenient symptom relief, but results from clinical trials are conflicting on whether it is an improvement over standard palliative fractionation. Endobronchial brachytherapy provides relief for patients with endobronchial lesions causing obstruction or hemoptysis. Palliative chemotherapy improves survival and quality of life in patients with metastatic disease compared with best supportive care. Chemotherapy also improves outcomes as a second-line and third-line treatment for patients in whom previous regimens have failed. Biologic therapies such as erlotinib and bevacizumab have been incorporated into every phase of chemotherapy with good results. [Copyright &y& Elsevier]

Purpose: To determine if physician prediction of survival duration (PSD) is accurate for patients with metastatic breast or prostate cancer. Methods: Radiation Therapy Oncology Group 9714 (RTOG 9714) was a randomized comparison of radiotherapy schedules for treatment of bone metastases. The treating physician assigned a baseline Karnofsky Performance Score (KPS) and predicted survival duration at study entry. Patients completed the Functional Assessment of Cancer Therapy (FACT). These three were compared to actual survival time. Results: Eight hundred ninety-eight patients were eligible and analyzable. Actual median survival was 9.3 months. The median PSD was 12 months. PSD, KPS, and FACT were all moderately correlated with actual survival. Patients with higher KPS had a longer survival time (882 patients, Spearman's ρ = 0.259, p < 0.0001). The median survival of the 618 expired patients is 6.5 months (PSD was 12 months). The PSD was within 1 month of actual survival in 61 (10%), with 177 (29%) patients surviving more than 1 month longer than predicted and 375 (61%) surviving more than 1 month less than predicted. A univariate analysis of actual overall survival was performed, dividing the PSD into 4 groups. For predicted survivals of 6 months or less, less than 6 to less than 12 months, 12 months, and more than 12 months, median actual survivals were 7.0, 7.2, 9.7. and 13.5 months ( p < 0.0001). Conclusions: KPS, FACT scores, and PSD all are correlated with actual survival. Physicians on this study were able to predict which patients would have longer survival times, although prediction of survival was optimistic compared to actual survival by an average of 3 months. [ABSTRACT FROM AUTHOR]

Purpose: The Novalis system has been demonstrated to achieve accurate target localization on anthropomorphic phantoms. However, other factors, such as rotational deviation, patient intrafraction motion, and image fusion uncertainty due to patient body deformation, could contribute additional position uncertainty for actual patients. This study evaluates such position uncertainty for spinal radiosurgery patients. Materials and Methods: Fifty-two consecutive spinal radiosurgery patients were included in the study. Rotational deviation was evaluated from 6-deg of freedom (6D) fusion results for all patients. The combined uncertainty of patient motion and image fusion was determined from fusion results of additional kV x-ray images acquired before, during, and after treatment for 25 of the 52 patients. The uncertainty of image fusion was also evaluated by performing 6D fusion ten different times with various regions of interest in the images selected for fusion. This was performed for two patients with L3 and T2 lesions, respectively, for comparison. Results: The mean rotational deviation was 0.7±1.8, 0.7±1.5, and 0.7±1.6 deg along the yaw, roll, and pitch directions, respectively. The combined uncertainty from patient motion and image fusion was 0.1±0.9, 0.2±1.2, and 0.2±1.0 mm in the anteroposterior (AP), longitudinal, and lateral directions, respectively. The uncertainty (standard deviation) due to image fusion was less than 0.28 mm in any direction for the L3 lesion and 0.8 mm in the AP direction for the T2 lesion. Conclusion: Overall position uncertainty for spinal radiosurgery patients has been evaluated. Rotational deviation and patient motion were the main factors contributed to position uncertainty for actual patient treatment. [ABSTRACT FROM AUTHOR]

The article discusses the surgical treatment of stage I and stage II non-small cell lung cancer. It is noted that the treatment of this disease continues to evolve in the areas of intraoperative lymph node staging, and the role of sublobar resections instead of lobectomy for treatment of smaller tumors. Extensive clinical experience indicates that the best chance of cure for these tumors comes with surgical resection.

Purpose: To identify factors significantly influencing accrual to clinical protocols by analyzing radiation Patterns of Care Study (PCS) surveys of 3,047 randomly selected radiotherapy (RT) patients. Methods and Materials: Patterns of Care Study surveys from disease sites studied for the periods 1992–1994 and 1996–1999 (breast cancer, n = 1,080; prostate cancer, n = 1,149; esophageal cancer, n = 818) were analyzed. The PCS is a National Cancer Institute–funded national survey of randomly selected RT institutions in the United States. Patients with nonmetastatic disease who received RT as definitive or adjuvant therapy were randomly selected from eligible patients at each institution. To determine national estimates, individual patient records were weighted by the relative contribution of each institution and patients within each institution. Data regarding participation in clinical trials were recorded. The factors age, gender, race, type of insurance, and practice type of treating institution (academic or not) were studied by univariate and multivariate analyses. Results: Overall, only 2.7% of all patients were accrued to clinical protocols. Of these, 57% were enrolled on institutional review board–approved institutional trials, and 43% on National Cancer Institute collaborative group studies. On multivariate analysis, patients treated at academic facilities (p = 0.0001) and white patients (vs. African Americans, p = 0.0002) were significantly more likely to participate in clinical oncology trials. Age, gender, type of cancer, and type of insurance were not predictive. Conclusions: Practice type and race significantly influence enrollment onto clinical oncology trials. This suggests that increased communication and education regarding protocols, particularly focusing on physicians in nonacademic settings and minority patients, will be essential to enhance accrual. [Copyright &y& Elsevier]

The purpose of this study was to develop a technique that could quantitatively monitor the nonrespiratory motion of a patient during stereotactic body radiotherapy (SBRT). Multiple infrared external markers were placed on the patient’s chest and abdominal surface to obtain patient motion signals. These motion signals contained both respiratory and nonrespiratory motion information. The respiratory motion usually has much larger amplitude on the abdominal surface than on the chest surface. Assuming that the nonrespiratory motion is a rigid body translation, we have developed a computer algorithm to derive both the respiratory and nonrespiratory motion signals instantly from two sets of motion signals. In first-order approximation, the respiratory motion was represented by the motion signal on the abdominal surface, and the nonrespiratory motion was represented by the motion signal on the chest surface subtracting its respiratory component. The algorithm was retrospectively tested on 24 patients whose motion signals were recorded during a gated-CT simulation procedure. The result showed that the respiratory noise in the nonrespiratory motion signal was reduced to less than 1 mm for almost all patients, demonstrating that the technique was able to detect nonrespiratory motion with a sensitivity of about 1 mm. It also showed that 50% of the patients had ≥2 mm, and 2 patients had ≥3 mm slow drift during the 15–25 min simulation procedure, suggesting that nonrespiratory motion could exist during prolonged treatment. This technique can potentially be used to control the nonrespiratory motion during SBRT. However, further validation is required for its clinical use. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy is effective in palliating pain from bone metastases. We investigated whether 8 Gy delivered in a single treatment fraction provides pain and narcotic relief that is equivalent to that ot the standard treatment course of 30 Gy delivered in 10 treatment fractions over 2 weeks. Methods: A prospective, phase III randomized study of palliative radiation therapy was conducted for patients with breast or prostate cancer who had one to three sites of painful bone metastases and mod!rate to severe pain. Patients were randomly assigned to 8 Gy in one treatment fraction (8-Gy arm) or to 30 Gy in 10 treatment fractions (30-Gy arm). Pain relief at 3 months after randomization was evaluated with the Brief Pain Inventory. The Wilcoxon-Mann-Whitney test was used to compare response to treatment in terms of pain and narcotic relief between the two arms and for each stratification variable. All statistical comparisons were two-sided. Results: There were 455 patients in the 8-Gy arm and 443 in the 30-Gy arm; pretreatment characteristics were equally balanced between arms. Grade 2-4 acute toxicity was more frequent in the 30-Gy arm (17%) than in the 8-Gy arm (10%) (difference = 7%! 95% CI = 3% to 12%; P .002). Late toxicity was rare (4%) in both arms. The over- all response rate was 66%. Complete and partial response rates were 15% and 50%, respectively, in the 8-Gy arm coma pared with 18% and 48% in the 40-Gy arm (P = .6). At 3 months, 33% of all patients no longer required narcotic medications. The incidence of subsequent pathologic fracture was 5% for the 8-Gy arm and 4% for the 30-Gy arm. The retreatment rate was statistically significantly higher in the 8-Gy arm (18%) than in the 30-Gy arm (9%)(P<.001). Conclusions: Both regimens were equivalent in forms of pain and narcotic relief at 3 months and were well tolerated with few adverse effects. The 8-Gy arm had a higher rate of re-treatment but had less acute toxicity than the 30-Gy arm. [ABSTRACT FROM AUTHOR]

: Background and purposeThe recently obtained low value of ∼1.5 for the α/β of prostate cancer has led us to reexamine the optimal prostate tumor biology parameters, while taking into account everything known about the radiation response of prostate clonogens for use in a predictive dose–response model.: Methods and materialsAverages of the literature values of the α- and β-inactivation coefficients for human prostate cancer cell lines were calculated. A robust tumor local control probability (TLCP) model was used that required average α and β, as well as σα, for the interpatient variation in single-hit killing (α). Median Po2 values ≤1 mm Hg in the prostates of Fox Chase Cancer Center brachytherapy patients had been found in 21% of 115 cases. The oxygen enhancement ratios of 1.75 and 3.25 for α- and β-inactivation, respectively, measured for tumor cells in vitro, were incorporated into the TLCP model, together with a clonogen density of ∼105 cells/cm3. Severe hypoxia and radioresistance were estimated for a proportion of tumors that was increased with PSA level.: ResultsFor asynchronous human prostate cell lines irradiated in air, αmean was 0.26 ± 0.07 (standard error) Gy−1, σα = 0.06 Gy−1, and βmean was 0.0312 Gy−2 ± 0.0064 (standard error) Gy−2. The TLCP data indicated that most tumors that contained aerobic cells would be cured, whereas most tumors that contained hypoxic cells would not be cured by total doses of 76 to 80 Gy. Clinical response data from the literature for external beam dose escalation, stratified by PSA value, and for low-dose-rate brachytherapy, were well predicted by the model, where the α/β ratio was 8.5 and 15.5 for well-oxygenated and hypoxic clonogens, respectively.: ConclusionsNeither α/β ratio nor clonogen number need be extremely low to explain the response of prostate cancer to brachytherapy and external beam therapy, contradicting other recent analyses. It is strongly suggested that severe hypoxia in the prostates of certain patients limits the overall cancer cure rate by conventional radiation therapy. [Copyright &y& Elsevier]

Based on clinical assessment alone, patients with stage II non-small cell lung cancer (NSCLC) comprise only 5% of all patients with NSCLC. In addition, patients with stage II NSCLC represent a heterogeneous group, since stage II consists of patients with T1-2N1 or T3N0 tumors. By definition, patients with tumor invading the chest wall apex, mediastinum, diaphragm, or even the mainstem bronchus may all have T3 tumors. The extent of the data available regarding treatment of each of these different groups is therefore limited. The quality of the data is limited as well, because information often comes from small series of patients. Studies of adjuvant therapy after complete resection of stage II NSCLC are an important exception to this generalization, since data from large, randomized studies of adjuvant radiation therapy, chemotherapy, or a combination of the two are available for analysis. Superior sulcus tumors are discussed elsewhere in these guidelines. [ABSTRACT FROM AUTHOR]

: ObjectivesTo investigate whether low partial pressure of oxygen (Po2) in prostate cancer (CaP) predicts for biochemical outcome after radiotherapy. We previously reported that hypoxic regions exist in human CaP.: MethodsCustom-made Eppendorf Po2 microelectrodes were used to obtain ∼100 Po2 readings from both pathologically involved regions of the prostate (as determined by sextant biopsies) and normal muscle (as an internal control). Fifty-seven patients with localized disease were prospectively studied; all received brachytherapy implants (48 low dose rate and 9 high dose rate) under spinal anesthesia. Nine patients had received prior hormonal therapy. Biochemical failure was defined as two consecutive rises in prostate-specific antigen level, without a return to baseline. Cox proportional hazards regression analysis was used to evaluate the influence of hypoxia on biochemical control, while adjusting for prostate-specific antigen, Gleason score, stage, implant type (low dose rate versus high dose rate), perineural invasion, hemoglobin level, use of hormonal therapy, average (mean) of the median prostate Po2, average median muscle Po2, and prostate/muscle Po2 (P/M) ratio.: ResultsWith a median follow-up of 19 months (range 4 to 31), 9 patients developed biochemical failure. A threshold analysis of the P/M ratio demonstrated that biochemical control at 2 years differed significantly at a ratio of less than 0.05 versus 0.05 or greater (31% versus 92%, P <0.0001). However, the classic prognosticators were similar in these two groups. On multivariate analysis, the P/M ratio was the only predictor of biochemical control (P = 0.0002).: ConclusionsTo our knowledge, this is the first study to correlate the degree of hypoxia in CaP with treatment outcome after radiotherapy. The P/M Po2 ratio was the strongest predictor for biochemical control on stepwise multivariate analysis. Longer follow up with more patients is planned to confirm this result. [Copyright &y& Elsevier]

We present a child diagnosed with glioblastoma multiforme during infancy and successfully treated with the ‘eight-in-one’ chemotherapy regimen, who developed an intracranial fibrosarcoma 5 years later. After resection of the fibrosarcoma, she received cranial radiation therapy and high dose chemotherapy with bone marrow transplant. She remains alive and recurrence-free 7 years following the diagnosis of her second intracranial malignancy.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Radiation therapy is part of the standard treatment regimen for non-small cell lung cancer (NSCLC). Although radiation therapy is an effective tool to manage NSCLC, it can be associated with significant dose-limiting toxicities. These toxicities can lead to treatment interruption or early termination and worsening clinical outcomes in addition to reductions in patient quality of life. Based on preclinical efficacy for radioprotection of normal tissues, we evaluated the clinical utility of BIO 300 Oral Suspension (BIO 300; synthetic genistein nanosuspension) in patients with NSCLC. In this multicenter, open-label, single-arm, ascending dose phase 1b/2a study, patients were enrolled with newly diagnosed stage II-IV NSCLC planned for 60 to 70/1.8-2.0 Gy radiation therapy and concurrent weekly paclitaxel/carboplatin. Oral BIO 300 (cohort 1, 500 mg/d; cohort 2, 1000 mg/d; cohort 3, 1500 mg/d) was self-administered once daily starting 2 to 7 days before initiating concurrent chemoradiotherapy and continued until the end of radiation therapy. The primary endpoint was acute dose-limiting toxicities attributable to BIO 300. Secondary outcomes included pharmacokinetics, pharmacodynamics, overall toxicity profile, quality of life, local response rate, and survival. Twenty-one participants were enrolled. No dose-limiting toxicities were reported. BIO 300 dosing did not alter chemotherapy pharmacokinetics. Adverse events were not dose-dependent, and those attributable to BIO 300 (n = 11) were all mild to moderate in severity (grade 1, n = 9; grade 2, n = 2) and predominantly gastrointestinal (n = 7). A dose-dependent decrease in serum transforming growth factor β1 levels was observed across cohorts. Based on safety analysis, the maximum tolerated dose of BIO 300 was not met. Patient-reported quality of life and weight were largely stable throughout the study period. No patient had progression as their best overall response, and a 65% tumor response rate was achieved (20% complete response rate). The low toxicity rates, along with the pharmacodynamic results and tumor response rates, support further investigation of BIO 300 as an effective radioprotector. [ABSTRACT FROM AUTHOR]

Purpose: Early clinical results on the application of magnetic resonance imaging (MRI) coupled with a linear accelerator to deliver Magnetic Resonance-guided Radiation Therapy (MRgRT) have demonstrated feasibility for safe delivery of stereotactic body radiation therapy in treatment of oligometastatic disease. Here, we set out to review the clinical evidence and challenges associated with MRgRT in this setting.Methods and Materials: We performed a systematic review of the literature pertaining to clinical experiences and trials on the use of MRgRT primarily for the treatment of oligometastatic cancers. We reviewed the opportunities and challenges associated with the use of MRgRT.Results: Benefits of MRgRT pertaining to superior soft-tissue contrast, real-time imaging and gating, and online adaptive radiation therapy facilitate safe and effective dose escalation to oligometastatic tumors while simultaneously sparing surrounding healthy tissues. Challenges concerning further need for clinical evidence and technical considerations related to planning, delivery, quality assurance of hypofractionated doses, and safety in the MRI environment must be considered.Conclusions: The promising early indications of safety and effectiveness of MRgRT for stereotactic body radiation therapy-based treatment of oligometastatic disease in multiple treatment locations should lead to further clinical evidence to demonstrate the benefit of this technology. [ABSTRACT FROM AUTHOR]

Purpose: Little data have been reported about the patient experience during curative radiation therapy (RT) for lung cancer in routine clinical practice or how this relates to treatment toxicity as reported by clinicians. The purpose of this study was to compare clinician-reported adverse events (AEs) with patient-reported outcomes (PROs), including both specific symptoms/side effects, as well as overall quality of life (QoL) during and after definitive RT for locally advanced lung cancer (LALC) in a large statewide cohort.Methods and Materials: PROs were prospectively collected from patients treated with definitive RT for LALC at 24 institutions within the Michigan Radiation Oncology Quality Consortium between 2012 and 2018 using the Functional Assessment of Cancer Therapy trial outcome index. Physicians prospectively recorded AEs using the Common Terminology Criteria for Adverse Events, version 4.0. Patient-reported QoL changes from baseline were assessed during and after RT using the Functional Assessment of Cancer Therapy trial outcome index. Spearman correlation coefficients were calculated for AEs and similar PROs, and a multivariable analysis was used to assess associations with QoL.Results: A total 1361 patients were included in the study, and 53% of respondents reported clinically meaningful declines in QoL at the end of RT. The correlation between clinician-reported esophagitis and patient-reported trouble swallowing was moderate (R = .67), but correlations between clinician-reported pneumonitis and patient-reported shortness of breath (R = .13) and cough (R = .09) were weak. Clinician-reported AEs were significantly associated with clinically meaningful declines in patient-reported QoL (R = - .46 for summary AE score). QoL was more strongly associated with fatigue (R = - .41) than lung-specific AEs.Conclusions: AEs are associated with clinically meaningful declines in QoL during and after RT for LALC, but associations between AEs and QoL are only modest. This highlights the importance of PRO data, and future research should assess whether earlier detection of PRO changes could allow for interventions that reduce the frequency of treatment-related clinically meaningful declines in QoL. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to determine whether prophylactic gabapentin usage in patients undergoing definitive concurrent chemotherapy and radiation therapy (chemoRT) for oropharyngeal cancer (OPC) improves treatment-related oral mucositis pain, opioid use, and feeding tube (FT) placement.Methods and Materials: This double-blind, randomized phase 3 study for patients with locally advanced OPC undergoing chemoRT randomly allocated patients to prophylactic gabapentin (600 mg thrice daily) or placebo. The primary endpoint was change in Patient-Reported Oral Mucositis Symptom (PROMS) scores over the entire treatment period (baseline to 6 weeks post-radiation therapy [RT] follow-up) with higher scores indicating worse outcomes. Opioid requirements, FT placement, and other patient-reported quality of life (QOL) metrics (Functional Assessment of Cancer Therapy-Head and Neck [FACT-HN] and Patient-Reported Outcomes version of the National Cancer Institute Common Terminology Criteria for Adverse Events [PRO-CTCAE]) were assessed. Lower scores suggested poorer QOL with the FACT-HN questionnaire, and higher scores suggested worse outcomes with the PRO-CTCAE questionnaire. Questionnaires were administered at baseline, weekly during RT, and at 6 weeks post-RT follow-up. Repeated measures analysis of variance was used to detect differences in PROMS scores and change in opioid use from baseline. Wilcoxon rank sum tests were used to compare averages for the other secondary endpoints. A P value less than .05 was considered statistically significant.Results: Treatment arms were well balanced overall, including T and N staging and dosimetric variables. There were 58 patients analyzed. No significant difference was found in PROMS scores (mean 29.1, standard deviation [SD] 22.5 vs 20.1, SD 16.8 for gabapentin vs placebo, respectively, P = .11). The FACT-HN functional well-being index had a significant decrease in scores from baseline to follow-up in the gabapentin arm (median -6, interquartile range [IQR] -10.0 to -0.5 vs -1, IQR -5.5 to 3.0, P = .03). PRO-CTCAE scores increased significantly at follow-up for gabapentin (median 6.5, IQR 3.5-11.8 vs 1, IQR -2.0 to 6.0, P = .01). There was no significant difference in average or change in opioid use. FT placement was significantly higher in the gabapentin arm (62.1% vs 20.7%, P < .01).Conclusions: This study suggests that prophylactic gabapentin is not effective in improving treatment-related oral mucositis symptoms in a select population of patients with OPC undergoing definitive chemoRT. [ABSTRACT FROM AUTHOR]

Purpose: Recent randomized studies have suggested improvements in progression-free and overall survival with the addition of stereotactic body radiation therapy (SBRT, also known as SABR) in patients with oligometastatic non-small cell lung cancer. Given the novelty and complexity of incorporating SBRT in the oligometastatic setting, the multidisciplinary American Radium Society Lung Cancer Panel was assigned to create appropriate use criteria on SBRT as part of consolidative local therapy for patients with oligometastatic and oligoprogressive non-small cell lung cancer.Methods and Materials: A review of the current literature was conducted from January 1, 2008, to December 25, 2020, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to systematically search the PubMed database to retrieve a comprehensive set of relevant articles.Results: Based on representation in existing randomized trials, the panel defined the term "oligometastasis" as ≤3 metastatic deposits (not including the primary tumor) in the previously untreated setting or after first-line systemic therapy after the initial diagnosis. "Oligoprogression" also referred to ≤3 discrete areas of progression in the setting of prior or ongoing receipt of systemic therapy. In all appropriate patients, the panel strongly recommends enrollment in a clinical trial whenever available. For oligometastatic disease, administering first-line systemic therapy followed by consolidative radiation therapy (to all sites plus the primary/nodal disease) is preferred over up-front radiation therapy. Owing to a dearth of data, the panel recommended that consolidative radiation therapy be considered on a case-by-case basis for 4 to 5 sites of oligometastatic disease, driver mutation-positive oligometastatic disease without progression on up-front targeted therapy, and oligoprogressive cases.Conclusions: Although SBRT/SABR appears to be both safe and effective in treating patients with limited metastatic sites of disease, many clinical circumstances require individualized management and strong multidisciplinary discussion on account of the limited existing data. [ABSTRACT FROM AUTHOR]

Purpose: Multiple factors influence the risk of developing pneumonitis after radiation therapy (RT) for lung cancer, but few resources exist to guide clinicians in predicting risk in an individual patient treated with modern techniques. We analyzed toxicity data from a state-wide consortium to develop an integrated pneumonitis risk model.Methods and Materials: All patients (N = 1302) received conventionally fractionated RT for stage II-III non-small cell lung cancer between April 2012 and July 2019. Pneumonitis occurring within 6 months of treatment was graded by local practitioners and collected prospectively from 27 academic and community clinics participating in a state-wide quality consortium. Pneumonitis was modeled as either grade ≥2 (G2+) or grade ≥3 (G3+). Logistic regression models were fit to quantify univariable associations with dose and clinical factors, and stepwise Akaike information criterion-based modeling was used to build multivariable prediction models.Results: The overall rate of pneumonitis of any grade in the 6 months following RT was 16% (208 cases). Seven percent of cases (n = 94) were G2+ and <1% (n = 11) were G3+. Adjusting for incomplete follow-up, estimated rates for G2+ and G3+ were 14% and 2%, respectively. In univariate analyses, gEUD, V5, V10, V20, V30, and mean lung dose (MLD) were positively associated with G2+ pneumonitis risk, whereas current smoking status was associated with lower odds of pneumonitis. G2+ pneumonitis risk of ≥22% was independently predicted by MLD of ≥20 Gy, V20 of ≥35%, and V5 of ≥75%. In multivariate analyses, the lung V5 metric remained a significant predictor of G2+ pneumonitis, even when controlling for MLD, despite their close correlation. For G3+ pneumonitis, MLD and V20 were statistically significant predictors. Number of patient comorbidities was an independent predictor of G3+, but not G2+ pneumonitis.Conclusions: We present an analysis of pneumonitis risk after definitive RT for lung cancer using a large, prospective dataset. We incorporate comorbidity burden, smoking status, and dosimetric parameters in an integrated risk model. These data may guide clinicians in assessing pneumonitis risk in individual patients. [ABSTRACT FROM AUTHOR]

: PurposeBiochemical failure (BF), defined by a rising prostate-specific antigen (PSA) profile, is an early surrogate of treatment failure. However, little evidence is available to show that BF is associated with death for patents with prostate cancer treated with radiotherapy. We examined the relationship between BF and death from prostate cancer.: Methods and materialsA total of 942 patients were treated between 1987 and 1998 with external beam radiotherapy who had sufficient PSA determinations in follow-up for the analyses described. The median radiation dose was 72 Gy, median PSA was 9.9 ng/mL, and median follow-up was 73 months. The American Society for Therapeutic Radiology and Oncology consensus definition was used to define BF. Kaplan-Meier calculations were from the start of radiotherapy. Cox proportional hazards regression multivariate analyses were used to investigate the association of BF (time-dependent variable) and other factors to distant metastasis (DM), cause-specific death (CSD), and overall death (OD). The year of treatment was included in some of the multivariate analyses to correct for potential unknown factors that may have occurred during the years of the study, such as stage migration.: ResultsBF was observed in 316 patients (34%), and 66 (7%) experienced DM, 32 (3%) died of prostate cancer, and 230 (24%) died overall during the study period. The Kaplan-Meier 5-year rate estimates from the start of treatment for BF, DM, CSD, and OD were 38%, 6%, 3%, and 13%, respectively. All patients with DM had BF. In multivariate analyses, BF was associated with DM and CSD, but not OD. The inclusion of the year of treatment did not alter these relationships.: ConclusionBF, as a time-dependent covariate, was the strongest determinant of DM and was also very significantly related to CSD. The inclusion of the year of treatment had little effect on these associations. Longer follow-up is needed to determine conclusively the relationship of BF to OD. [Copyright &y& Elsevier]

Purpose: We sought to develop a quality surveillance program for approximately 15,000 US veterans treated at the 40 radiation oncology facilities at the Veterans Affairs (VA) hospitals each year.Methods and Materials: State-of-the-art technologies were used with the goal to improve clinical outcomes while providing the best possible care to veterans. To measure quality of care and service rendered to veterans, the Veterans Health Administration established the VA Radiation Oncology Quality Surveillance program. The program carries forward the American College of Radiology Quality Research in Radiation Oncology project methodology of assessing the wide variation in practice pattern and quality of care in radiation therapy by developing clinical quality measures (QM) used as quality indices. These QM data provide feedback to physicians by identifying areas for improvement in the process of care and identifying the adoption of evidence-based recommendations for radiation therapy.Results: Disease-site expert panels organized by the American Society for Radiation Oncology (ASTRO) defined quality measures and established scoring criteria for prostate cancer (intermediate and high risk), non-small cell lung cancer (IIIA/B stage), and small cell lung cancer (limited stage) case presentations. Data elements for 1567 patients from the 40 VA radiation oncology practices were abstracted from the electronic medical records and treatment management and planning systems. Overall, the 1567 assessed cases passed 82.4% of all QM. Pass rates for QM for the 773 lung and 794 prostate cases were 78.0% and 87.2%, respectively. Marked variations, however, were noted in the pass rates for QM when tumor site, clinical pathway, or performing centers were separately examined.Conclusions: The peer-review protected VA-Radiation Oncology Surveillance program based on clinical quality measures allows providers to compare their clinical practice to peers and to make meaningful adjustments in their personal patterns of care unobtrusively. [ABSTRACT FROM AUTHOR]

Purpose: A lack of diversity has been observed in radiation oncology (RO), with women and certain racial/ethnic groups underrepresented as trainees, faculty, and practicing physicians. We sought to gain a nuanced understanding of how to best promote diversity, equity, and inclusion (DEI) based on the insights of RO department chairs, with particular attention given to the experiences of the few women and underrepresented minorities (URMs) in these influential positions.Methods and Materials: From March to June 2016, we conducted telephone interviews with 24 RO department chairs (of 27 invited). Purposive sampling was used to invite all chairs who were women (n = 13) or URMs (n = 3) and 11 male chairs who were not URMs. Multiple analysts coded the verbatim transcripts.Results: Five themes were identified: (1) commitment to DEI promotes quality health care and innovation; (2) gaps remain despite some progress with promoting diversity in RO; (3) women and URM faculty continue to experience challenges in various career domains; (4) solutions to DEI issues would be facilitated by acknowledging realities of gender and race; and (5) expansion of the career pipeline is needed.Conclusions: The chairs' insights had policy-relevant implications. Bias training should broach tokenism, blindness, and intersectionality. Efforts to recruit and support diverse talent should be deliberate and proactive. Bridge programs could engage students before their application to medical school. [ABSTRACT FROM AUTHOR]

The importance of emotional intelligence (EI) in physicians has attracted attention as researchers begin to focus on the relationship of EI to retention, promotion, and productivity among academic physicians. However, to date, no formal evaluation of EI has been conducted among current department chairs. The objectives of this study were to assess the EI of current chairs of academic radiation oncology departments and to correlate EI with a self-reported assessment of burnout. The authors invited 95 chairs of academic radiation oncology departments to participate in a survey, approved by an institutional review board, consisting of the Trait Emotional Intelligence Questionnaire Short Form (TEIQue-SF) and the abbreviated Maslach Burnout Inventory (a-MBI). TEIQue-SF scores were evaluated for correlation with respondents' demographics and self-reported burnout scores on the a-MBI. Sixty chairs responded to the survey, for a response rate of 63.2%. The median (interquartile range) TEIQue-SF for the responding cohort was 172 (155-182) out of a maximum possible score of 210. The a-MBI emotional exhaustion and depersonalization subscores were low, with median (interquartile range) scores of4 (2.25-6.75) and 1 (0-2.75) out of maximum possible scores of 18 and 30, respectively. Higher TEIQue-SF global scores were weakly correlated with decreased burnout. The study results show that academic radiation on- cology chairs had a high EI and low rates of self-reported burnout. EI may be of increasing importance with respect to recruitment and retention of academic medical leaders. [ABSTRACT FROM AUTHOR]

Purpose To provide updated American College of Radiology (ACR) appropriateness criteria for transrectal ultrasound-guided transperineal interstitial permanent source brachytherapy. Methods and Materials The ACR appropriateness criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Results Permanent prostate brachytherapy (PPB) is a treatment option for appropriately selected patients with localized prostate cancer with low to very high risk disease. PPB monotherapy remains an appropriate and effective curative treatment for low-risk prostate cancer patients demonstrating excellent long-term cancer control and acceptable morbidity. PPB monotherapy can be considered for select intermediate-risk patients with multiparametric MRI useful in evaluation of such patients. High-risk patients treated with PPB should receive supplemental external beam radiotherapy (EBRT) along with androgen deprivation. Similarly, patients with involved pelvic lymph nodes may also be considered for such combined treatment but reported long-term outcomes are limited. Computed tomography–based postimplant dosimetry completed within 60 days of PPB is essential for quality assurance. PPB may be considered for treatment of local recurrence after EBRT but is associated with an increased risk of toxicity. Conclusions Updated appropriateness criteria for patient evaluation, selection, treatment, and postimplant dosimetry are given. These criteria are intended to be advisory only with the final responsibility for patient care residing with the treating clinicians. [ABSTRACT FROM AUTHOR]

Radiotherapy is a standard cytotoxic therapy against solid cancers. It uses ionizing radiation to kill tumor cells through damage to DNA, either directly or indirectly. Radioresistance is often associated with dysregulated DNA damage repair processes. Most radiosensitizers enhance radiation-mediated DNA damage and reduce the rate of DNA repair ultimately leading to accumulation of DNA damages, cell-cycle arrest, and cell death. Recently, agents targeting key signals in DNA damage response such as DNA repair pathways and cell-cycle have been developed. This new class of molecularly targeted radiosensitizing agents is being evaluated in preclinical and clinical studies to monitor their activity in potentiating radiation cytotoxicity of tumors and reducing normal tissue toxicity. The molecular pathways of DNA damage response are reviewed with a focus on the repair mechanisms, therapeutic targets under current clinical evaluation including ATM, ATR, CDK1, CDK4/6, CHK1, DNA-PKcs, PARP-1, Wee1, & MPS1/TTK and potential new targets (BUB1, and DNA LIG4) for radiation sensitization. [Display omitted] [ABSTRACT FROM AUTHOR]