Dosimetric assessment of patient-specific breath-hold reproducibility on liver motion for SBRT planning.

PURPOSE: To investigate the impact of breath-hold reproducibility on liver motion using a respiratory motion management device. METHODS: Forty-four patients with hepatic tumors, treated with SBRT with breath-hold, were randomly selected for this study. All patients underwent three consecutive computed tomography (CT) scans using active breath-hold coordinator (ABC) with three repeated single breath-hold during simulation. The three CT scans were labeled as ABC1-CT, ABC2-CT, and ABC3-CT. Displacements of centroids of the entire livers among the three ABC-CTs were measured as a surrogate for intrafractional motion. For each patient, two different treatment plans were prepared: (a) a clinical plan using a 5-mm expansion of an ITV that encompassed all three GTVs from each of the three ABC-CTs, and (b) a research plan using a 5-mm expansion of the GTV from only ABC1-CT to create PTV. The clinical plan acceptance criteria were that 95% of the PTV and 99% of the GTV received 100% of the prescription dose. Dosimetric endpoints were analyzed and compared for the two plans. RESULTS: All shifts in the medial-lateral direction (range: -3.9 to 2.0 mm) were within 5 mm while 7% of shifts in the anterior-posterior direction (range: -10.5 to 16.7 mm) and 11% of shifts in the superior-inferior direction (range: -17.0 to 8.7 mm) exceeded 5 mm. Six patients (14%) had an intrafraction motion greater than 5 mm in any direction. For these six patients, if a plan was created based on a PTV from a single CT (ex. ABC1-CT), 5 of 12 GTVs captured from other ABC-CTs would fail to meet the clinical acceptance criteria due to poor breath-hold reproducibility. CONCLUSIONS: Non-negligible intrafractional motion occurs in patients with poor breath-hold reproducibility. To identify this subgroup of patients, acquiring three CTs with active breath-hold during simulation is a feasible practical method.

Assessment of Setup Accuracy Using Anatomical Landmarks for Breast and Chest Wall Irradiation With Surface Guided Radiation Therapy.

PURPOSE: This study aimed to determine setup accuracy using anatomic landmarks for breast irradiation with and without surface guided radiation therapy (SGRT) and assess setup time with SGRT. METHODS AND MATERIALS: This study included 115 patients with 1945 treatment fractions. Patients were treated with 4 techniques: tangents, tangents using deep-inspiration breath hold, and tangents with regional nodal irradiation with and without deep-inspiration breath hold. A total of 915 portal verification images were analyzed to determine setup errors for the skin, chest wall (CW), and heart. Setup error at each landmark was defined as the mean and maximum distances between the projected planning structure and the delineated structure on the portal image. Setup time for each fraction was determined using 2 recorded time outs: one upon the patient entering the treatment room and another before radiation beam on. RESULTS: Setup errors for the skin were significantly reduced with SGRT for all 4 treatment techniques (P < .001). On average, the mean and maximum errors for the skin decreased from 3.5 mm to 2.3 mm (P < .001) and from 7.6 mm to 5.6 mm (P < .001), respectively. Setup errors for the CW were not significantly different for tangent treatments, but significantly different for locoregional treatments. For all patients, the average mean and maximum errors for the CW were reduced from 3.1 mm to 3.0 mm (P = .21) and from 6.1 mm to 5.5 mm (P = .001), respectively. No significant change in setup errors for the heart was observed. Setup times with SGRT were slightly longer (P < .01), and the average setup time increased from 5.4 to 6.3 minutes. CONCLUSIONS: Using anatomic landmarks, we confirm that SGRT improved patient setup accuracy with a slight, but clinically nonsignificant increase in setup time.

NCTN Assessment on Current Applications of Radiomics in Oncology.

Radiomics is a fast-growing research area based on converting standard-of-care imaging into quantitative minable data and building subsequent predictive models to personalize treatment. Radiomics has been proposed as a study objective in clinical trial concepts and a potential biomarker for stratifying patients across interventional treatment arms. In recognizing the growing importance of radiomics in oncology, a group of medical physicists and clinicians from NRG Oncology reviewed the current status of the field and identified critical issues, providing a general assessment and early recommendations for incorporation in oncology studies.

Dosimetric differences between local failure and local controlled non-small cell lung cancer patients treated with stereotactic body radiotherapy: A matched-pair study.

INTRODUCTION: Concerns were raised about the accuracy of pencil beam (PB) calculation and potential underdosing of medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). From our institutional series, we designed a matched-pair study where each local failure and controlled patient was matched based upon several clinical factors, to investigate the dose difference between the matched-pair. METHODS: Eighteen pairs of NSCLC patients, treated with 50 Gy in five fractions, were selected. These patients were matched based on treatment intent, tumour size, histology and clinical follow-up. All PB calculated clinical plans were retrospectively recalculated with a MC algorithm. The D99 and DMean of the gross tumour volume (GTV) and D95 and DMean of the planning tumour volume (PTV) from PB and Monte Carlo (MC) calculation were compared between local failures and controls using the Mann-Whitney test. RESULTS: The mean PB calculated D95 of PTV was 50.4 Gy for both failures and controls (P = 0.85), indicating no planning differences between the groups. From MC calculations, the mean (±SD) of GTV D99 , GTV DMean , PTV D95 , PTV DMean were 47.6 ± 2.6/46.3 ± 2.4, 50.4 ± 2.1/49.8 ± 1.6, 44.4 ± 2.7/43.6 ± 3.1, 48.7 ± 2.4/48.2 ± 2.4 Gy for failure/controlled groups, respectively, and there was no significant difference between two groups (all P > 0.1). The dose differences between MC and PB calculations were in agreement with other literatures and there was no significant difference between two groups. CONCLUSIONS: While PB algorithms may overestimate tumour doses relative to MC algorithms, our matched-pair study did not find dose differences between local failure and local controlled cases.

Weight-based dosing in medication use: what should we know?

BACKGROUND: Weight-based dosing strategy is still challenging due to poor awareness and adherence. It is necessary to let clinicians know of the latest developments in this respect and the correct circumstances in which weight-based dosing is of clinical relevance. METHODS: A literature search was conducted using PubMed. RESULTS: Clinical indications, physiological factors, and types of medication may determine the applicability of weight-based dosing. In some cases, the weight effect may be minimal or the proper dosage can only be determined when weight is combined with other factors. Medications within similar therapeutic or structural class (eg, anticoagulants, antitumor necrosis factor medications, P2Y12-receptor antagonists, and anti-epidermal growth factor receptor antibodies) may exhibit differences in requirements on weight-based dosing. In some cases, weight-based dosing is superior to currently recommended fixed-dose regimen in adult patients (eg, hydrocortisone, vancomycin, linezolid, and aprotinin). On the contrary, fixed dosing is noninferior to or even better than currently recommended weight-based regimen in adult patients in some cases (eg, cyclosporine microemulsion, recombinant activated Factor VII, and epoetin α). Ideal body-weight-based dosing may be superior to the currently recommended total body-weight-based regimen (eg, atracurium and rocuronium). For dosing in pediatrics, whether weight-based dosing is better than body surface-area-based dosing is dependent on the particular medication (eg, methotrexate, prednisone, prednisolone, zidovudine, didanosine, growth hormone, and 13-cis-retinoic acid). Age-based dosing strategy is better than weight-based dosing in some cases (eg, intravenous busulfan and dalteparin). Dosing guided by pharmacogenetic testing did not show pharmacoeconomic advantage over weight-adjusted dosing of 6-mercaptopurine. The common viewpoint (ie, pediatric patients should be dosed on the basis of body weight) is not always correct. Effective weight-based dosing interventions include standardization of weight estimation, documentation and dosing determination, dosing chart, dosing protocol, order set, pharmacist participation, technological information, and educational measures. CONCLUSION: Although dosing methods are specified in prescribing information for each drug and there are no principal pros and cons to be elaborated, this review of weight-based dosing strategy will enrich the knowledge of medication administration from the perspectives of safety, efficacy, and pharmacoeconomics, and will also provide research opportunities in clinical practice. Clinicians should be familiar with dosage and administration of the medication to be prescribed as well as the latest developments.

Dose differences in intensity-modulated radiotherapy plans calculated with pencil beam and Monte Carlo for lung SBRT.

For patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy, early treatment plans were based on a simpler dose calculation algorithm, the pencil beam (PB) calculation. Because these patients had the longest treatment follow-up, identifying dose differences between the PB calculated dose and Monte Carlo calculated dose is clinically important for understanding of treatment outcomes. Previous studies found significant dose differences between the PB dose calculation and more accurate dose calculation algorithms, such as convolution-based or Monte Carlo (MC), mostly for three-dimensional conformal radiotherapy (3D CRT) plans. The aim of this study is to investigate whether these observed dose differences also exist for intensity-modulated radiotherapy (IMRT) plans for both centrally and peripherally located tumors. Seventy patients (35 central and 35 peripheral) were retrospectively selected for this study. The clinical IMRT plans that were initially calculated with the PB algorithm were recalculated with the MC algorithm. Among these paired plans, dosimetric parameters were compared for the targets and critical organs. When compared to MC calculation, PB calculation overestimated doses to the planning target volumes (PTVs) of central and peripheral tumors with different magnitudes. The doses to 95% of the central and peripheral PTVs were overestimated by 9.7% ± 5.6% and 12.0% ± 7.3%, respectively. This dose overestimation did not affect doses to the critical organs, such as the spinal cord and lung. In conclusion, for NSCLC treated with IMRT, dose differences between the PB and MC calculations were different from that of 3D CRT. No significant dose differences in critical organs were observed between the two calculations.

Flattening filter-free accelerators: a report from the AAPM Therapy Emerging Technology Assessment Work Group.

This report describes the current state of flattening filter-free (FFF) radiotherapy beams implemented on conventional linear accelerators, and is aimed primarily at practicing medical physicists. The Therapy Emerging Technology Assessment Work Group of the American Association of Physicists in Medicine (AAPM) formed a writing group to assess FFF technology. The published literature on FFF technology was reviewed, along with technical specifications provided by vendors. Based on this information, supplemented by the clinical experience of the group members, consensus guidelines and recommendations for implementation of FFF technology were developed. Areas in need of further investigation were identified. Removing the flattening filter increases beam intensity, especially near the central axis. Increased intensity reduces treatment time, especially for high-dose stereotactic radiotherapy/radiosurgery (SRT/SRS). Furthermore, removing the flattening filter reduces out-of-field dose and improves beam modeling accuracy. FFF beams are advantageous for small field (e.g., SRS) treatments and are appropriate for intensity-modulated radiotherapy (IMRT). For conventional 3D radiotherapy of large targets, FFF beams may be disadvantageous compared to flattened beams because of the heterogeneity of FFF beam across the target (unless modulation is employed). For any application, the nonflat beam characteristics and substantially higher dose rates require consideration during the commissioning and quality assurance processes relative to flattened beams, and the appropriate clinical use of the technology needs to be identified. Consideration also needs to be given to these unique characteristics when undertaking facility planning. Several areas still warrant further research and development. Recommendations pertinent to FFF technology, including acceptance testing, commissioning, quality assurance, radiation safety, and facility planning, are presented. Examples of clinical applications are provided. Several of the areas in which future research and development are needed are also indicated.

Dose calculation differences between Monte Carlo and pencil beam depend on the tumor locations and volumes for lung stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) has been increasingly used as an efficacious treatment modality for early-stage non-small cell lung cancer. The accuracy of dose calculations is compromised due to the presence of inhomogeneity. For the purpose of a consistent prescription, radiation doses were calculated without heterogeneity correction in several RTOG trials. For patients participating in these trials, recalculations of the planned doses with more accurate dose methods could provide better correlations between the treatment outcomes and the planned doses. Using a Monte Carlo (MC) dose calculation algorithm as a gold standard, we compared the recalculated doses with the MC algorithm to the original pencil beam (PB) calculations for our institutional clinical lung SBRT plans. The focus of this comparison is to investigate the volume and location dependence on the differences between the two dose calculations. Thirty-one clinical plans that followed RTOG and other protocol guidelines were retrospectively investigated in this study. Dosimetric parameters, such as D1, D95, and D99 for the PTV and D1 for organs at risk, were compared between two calculations. Correlations of mean lung dose and V20 of lungs between two calculations were investigated. Significant dependence on tumor size and location was observed from the comparisons between the two dose calculation methods. When comparing the PB calculations without heterogeneity correction to the MC calculations with heterogeneity correction, we found that in terms of D95 of PTV: (1) the two calculations resulted in similar D95 for edge tumors with volumes greater than 25.1 cc; (2) an average overestimation of 5% in PB calculations for edge tumors with volumes less than 25.1 cc; and (3) an average overestimation of 9% or underestimation of 3% in PB calculations for island tumors with volumes smaller or greater than 22.6 cc, respectively. With heterogeneity correction, the PB calculations resulted in an average reduction of 23.8% and 15.3% in the D95 for the PTV for island and edge lesions, respectively, when compared to the MC calculations. For organs at risks, very small differences were found among all the comparisons. Excellent correlations for mean dose and V20 of lungs were observed between the two calculations. This study demonstrated that using a single scaling factor may be overly simplified when accounting for the effects of heterogeneity correction. Accurate dose calculations, such as the Monte Carlo algorithms, are highly recommended to understand dose responses in lung SBRT.

[Culture and quality of life assessment in Chinese populations].

OBJECTIVE: To investigate the impact of cultural factors on quality of life (QOL) and to identify appropriate ways of dividing sub-populations for population norm-based quality of life assessment. METHODS: The WHOQOL-BREF was used as a QOL instrument. Another questionnaire was developed to assess cultural values. A cross-sectional survey was undertaken in 1090 Guangzhou residents, which included 635 respondents from communities and 455 patients who visited outpatient departments of hospitals. Cronbach's a coefficients and item-domain correlation coefficients were calculated to test the reliability and validity of the WHOQOL-BREF, respectively. Student t test, ANOVA and stepwise multiple linear regression analysis were performed to identify the variables that might have an impact on the QOL. Two regression models with and without including cultural variables were constructed, and the extent of impact exerted by the cultural factors was assessed through a comparison of the change of adjusted R square values. RESULTS: A total of 1052 (96%) valid questionnaire were returned. The Cronbach's alpha coefficients of the WHOQOL-BREF ranged from 0.67 to 0.78. Age, education, occupation and family income were correlated with all of the domains of the WHOQOL-BREF. Chronic condition was correlated with physical, psychological, and social relationship domains of the WHOQOL-BREF. Gender was correlated with physical and psychological domains of the WHOQOL-BREF. The multiple regression analysis showed that social and demographic factors contributed to 6.3%, 13.6%, 10.4% and 8.7% of the predicted variances for the physical, psychological, social relationship, and environment domains, respectively. Social support, horizontal collectivism, vertical individualism, escape acceptance, fear of death, health value, supernatural belief had a significant impact on QOL. However, social support was the only one factor that had an impact on all of the four QOL domains. CONCLUSION: It is necessary to divide sub-cultural populations for population norm-based QOL assessment. Further research is needed to develop a practical approach to the sub-cultural population division.

Assessment of carotid artery dose in the treatment of nasopharyngeal cancer with IMRT versus conventional radiotherapy.

PURPOSE: To determine the radiation dose to the carotid artery in nasopharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT) and to compare it to the dose delivered by a conventional three-field (3F) technique. MATERIALS AND METHODS: Sixteen patients with nasopharyngeal cancer who were treated at UCSF with IMRT were selected for this analysis. 3F plans were reconstructed for comparison. The carotid arteries were retrospectively contoured, and the dose received by each of the 32 carotid arteries was determined for both IMRT and 3F plans. A subset of 8 patients with N0/N1 nodal disease was selected for IMRT replanning using additional constraints to reduce the dose to the arteries. RESULTS: Using the standard prescription doses for IMRT and 3F plans, the dose delivered to 95% of the tumor volume was significantly higher in the IMRT plans, reflecting the greater conformality of this technique. The median mean dose to the carotid arteries was 65.7Gy with IMRT vs. 58.4Gy with 3F (p<0.001). After the application of dose constraints to the carotid arteries, it was possible to reduce the mean carotid dose to 54Gy in the IMRT replans. CONCLUSIONS: IMRT achieves a higher tumoricidal dose and superior clinical target volume coverage, but results in an increase in the carotid artery dose as compared to conventional 3F technique. With careful IMRT planning, it is possible to constrain the carotid dose for a subset of patients with low-risk neck disease. Further study is necessary to quantify the long-term clinical impact of this intervention.

Investigation of using a power function as a cost function in inverse planning optimization.

The purpose of this paper is to investigate the use of a power function as a cost function in inverse planning optimization. The cost function for each structure is implemented as an exponential power function of the deviation between the resultant dose and prescribed or constrained dose. The total cost function for all structures is a summation of the cost function of every structure. When the exponents of all terms in the cost function are set to 2, the cost function becomes a classical quadratic cost function. An independent optimization module was developed and interfaced with a research treatment planning system from the University of North Carolina for dose calculation and display of results. Three clinical cases were tested for this study with various exponents set for tumor targets and sensitive structures. Treatment plans with these exponent settings were compared, using dose volume histograms. The results of our study demonstrated that using an exponent higher than 2 in the cost function for the target achieved better dose homogeneity than using an exponent of 2. An exponent higher than 2 for serial sensitive structures can effectively reduce the maximum dose. Varying the exponent from 2 to 4 resulted in the most effective changes in dose volume histograms while the change from 4 to 8 is less drastic, indicating a situation of saturation. In conclusion, using a power function with exponent greater than 2 as a cost function can effectively achieve homogeneous dose inside the target and/or minimize maximum dose to the critical structures.

Assessment of intra- and interobserver variability of pulmonary vein measurements from CT angiography.

RATIONALE AND OBJECTIVES: Pulmonary vein (PV) stenosis is a common complication after radiofrequency ablation for atrial fibrillation. This study investigated the intra- and interobserver variability and precision of PV ostial measurements from three-dimensional computed tomography angiography. MATERIALS AND METHODS: Four observers measured the maximum and minimum diameters, as well as area, of the four PVs of seven patients who underwent a three-dimensional computed tomography scan before radiofrequency ablation. Each observer performed two sets of measurements. The intra- and interobserver variability of the measurements was calculated using analysis of variance. RESULTS: Intraobserver variability was approximately two times lower than interobserver variability in measurements of diameter and area. The standard error of the measurement (SEM), SEM(intra) and SEM(inter), were lower for the mean diameter than the maximum diameter. The minimum detectable changes in diameters, DeltaD(intra) and DeltaD(inter), and area, DeltaA(intra) and DeltaA(inter), demonstrated the same statistical trend as the corresponding SEM for each of the four veins. Both DeltaD(intra) and DeltaD(inter) and DeltaA(intra) and DeltaA(inter) were smaller than the corresponding lower bounds of the 95% confidence interval for 50% diameter reduction and 75% area reduction. The direct results of DeltaA(intra) and DeltaA(inter) for each of the four veins were consistently less than DeltaA's calculated from the corresponding DeltaD(intra) and DeltaD(inter). CONCLUSION: PV ostial measurements are less variable when made by a single observer than by multiple observers, and mean diameter measurements are more precise than a single, maximum diameter measurement. Both diameter and area measurements are capable of quantifying the mild PV stenosis. Furthermore, area can be measured with greater precision than mean diameter and should be used in PV ostium caliber determination.