Rapid Standardized CT-Based Method to Determine Lean Body Mass SUV for PET-A Significant Improvement Over Prediction Equations.

In 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) studies, maximum standardized uptake value (SUVmax) is the parameter commonly used to provide a measurement of the metabolic activity of a tumor. SUV normalized by body mass is affected by the proportions of body fat and lean tissue, which present high variability in patients with cancer. SUV corrected by lean body mass (LBM), denoted as SUL, is recommended to provide more accurate, consistent, and reproducible SUV results; however, LBM is frequently estimated rather than measured. Given the increasing importance of a quantitative PET parameter, especially when comparing PET studies over time to evaluate disease response clinically, and its use in oncological clinical trials, we set out to evaluate the commonly used equations originally derived by James (1976) and Janmahasatian et al. (2005) against computerized tomography (CT)-derived measures of LBM. Methods: Whole-body 18F-FDG PET images of 195 adult patients with cancer were analyzed retrospectively. Representative liver SUVmean was normalized by total body mass. SUL was calculated using a quantitative determination of LBM based on the CT component of the PET/CT study (LBMCT) and compared against the equation-estimated SUL. Bland and Altman plots were generated for SUV-SUL differences. Results: This consecutive sample of patients undergoing usual care (men, n = 96; women, n = 99) varied in body mass (38-127 kg) and in Body Mass Index (BMI) (14.7-47.2 kg/m2). LBMCT weakly correlated with body mass (men, r2 = 0.32; women, r2 = 0.22), and thus SUV and SULCT were also weakly correlated (men, r2 = 0.24; women, r2 = 0.11). Equations proved inadequate for the assessment of LBM. LBM estimated by James' equation showed a mean bias (overestimation of LBM compared with LBMCT) in men (+6.13 kg; 95% CI 4.61-7.65) and in women (+6.32 kg; 95% CI 5.26-7.39). Janmahasatian's equation provided similarly poor performance. Conclusions: CT-based LBM determinations incorporate the patient's current body composition at the time of a PET/CT study, and the information garnered can provide care teams with information with which to more accurately determine FDG uptake values, allowing comparability over multiple scans and treatment courses and will provide a robust basis for the use of PET Response Criteria in Solid Tumors (PERCIST) in clinical trials.

Determination of Ir-192 micrselectron-V2 HDR/PDR dwell position reproducibility using a slit camera.

PURPOSE: To examine the limits of dwell position reproducibility of an ELEKTA microSelectron-V2 HDR/PDR remote afterloader. METHODS AND MATERIALS: The variability in source dwell position of an ELEKTA Microselectron mHDR - V2 HDR/PDR Microselectron was assessed using a slit camera. 100 consecutive extensions each of the source were made to positions of 1200 mm and 1470 mm and the variations in dwell position were observed. RESULTS: Maximum deviations of 0.4 mm from the median dwell position were observed. 72% of all deviations from median dwell position were 0.15 mm or less while 96% were no greater than 0.3 mm. CONCLUSION: Guide wire flexibility makes buckling over the length of source extension an unavoidable reality which, in turn, produces variability in the dwell position achieved. Fortunately these deviations in source dwell position are small and may be compensated for using margins along the dose distribution length.

Bortezomib retreatment for relapsed and refractory multiple myeloma in real-world clinical practice.

AIMS: Studies have shown that bortezomib retreatment is effective in relapsed/refractory multiple myeloma (MM). The observational, prospective electronic VELCADE® OBservational Study (eVOBS) study assessed bortezomib-based therapies for patients with MM in everyday practice. Here, we report on those patients receiving retreatment with bortezomib. METHODS: Consenting adults scheduled to receive bortezomib for MM were enrolled at 162 sites across Europe, Canada, Brazil, Russia, and Turkey between 2006 and 2010. Retrospective data on prior therapies and prospective observational data after bortezomib initiation were captured electronically at baseline, after every bortezomib cycle, and every 12 weeks after discontinuation or progression. Investigator-assessed responses and adverse events (AEs) were evaluated. RESULTS: Ninety-six of 873 patients enrolled to eVOBS received bortezomib as first retreatment for progressive disease during the prospective observation period. Median age was 62 years, 53% were male, and median number of prior therapies at retreatment was 4. Overall, 41% of patients initiated bortezomib retreatment in combination with dexamethasone, 16% in combination with lenalidomide, and 21% received monotherapy. Rate of partial response or better (≥PR) was 75% at initial bortezomib therapy, including 44% complete response (CR)/near CR (nCR); at retreatment, ≥PR rate was 46%, including 15% CR/nCR. Median progression-free survival was 11.4 months (95% confidence interval [CI]: 9.1-12.7) from start of initial bortezomib treatment and 6.4 months (95% CI: 4.4-7.2) from start of retreatment. Median overall survival from start of retreatment was 17.6 months (95% CI: 14.4-23.5). Of the 96 patients retreated with bortezomib, 77% reported an AE. Peripheral neuropathy during bortezomib retreatment occurred in 49% of patients, including 10% grade 3/4. CONCLUSION: These data suggest that retreatment with bortezomib is a feasible option for patients with relapsed/refractory MM.

Bortezomib-based therapy for relapsed/refractory multiple myeloma in real-world medical practice.

OBJECTIVE: The efficacy and safety of bortezomib-based therapy for relapsed/refractory multiple myeloma (RRMM) in clinical trials may differ from the oncology practice experience. The electronic VELCADE® OBservational Study was designed to prospectively evaluate bortezomib for multiple myeloma (MM) in real-world medical practice. METHOD: Patients scheduled to receive intravenous bortezomib for MM were eligible. The primary objective was to evaluate clinical outcomes, including response, time to response, time to next therapy, treatment-free interval, progression-free survival (PFS), and overall survival (OS). Secondary objectives included safety and healthcare resource utilization. RESULTS: In total, 873 patients with a median of two therapy lines prior to initiating bortezomib were included. The overall response rate (≥partial response) was 69%, including 37% complete response/near-complete response. Median time to response was 1.8 months, median time to next therapy was 9.7 months, and median treatment-free interval was 7.9 months. After 22.6 months' median follow-up, median PFS was 12.0 months and median OS was 36.1 months. The most common adverse events (AEs) were neuropathy not otherwise specified (19%), diarrhea NOS, and thrombocytopenia (each 17%); 230 (26%) patients discontinued bortezomib due to AEs. Of 689 (79%) patients without baseline peripheral neuropathy (PN), the rate of new-onset any-grade PN increased to 51% (12% grade 3/4) by cycle 8. Overall, 244 (28%) patients were hospitalized, 372 (43%) attended an outpatient visit, and 341 (39%) underwent a diagnostic/therapeutic procedure during bortezomib treatment. CONCLUSION: These prospective real-world data demonstrate the effectiveness and safety of bortezomib-based therapy for RRMM and confirm high response rates and long OS for this population.

Economic burden of relapsed or refractory multiple myeloma: Results from an international trial.

OBJECTIVE: The direct cost of relapsed or refractory multiple myeloma (RRMM) is documented; indirect costs are being explored. Healthcare payers seek cost-offsets from therapies that improve clinical outcomes but challenge budgets; employers seek lower absenteeism and better productivity. Study goals were to: (i) identify direct and indirect economic factors of RRMM, and (ii) explore longitudinal relationships between clinical, economic, and health-related quality of life (HRQoL) assessments. METHODS: Economic questionnaire, clinical, and HRQoL data from a multisite, international, randomized, controlled study in RRMM were analyzed. RESULTS: Patients (n=263) were 53.6% male, 91.6% Caucasian; mean age of 62.9 years, median Eastern Cooperative Oncology Group status of 1 (56.3%). Moderate to severe pain or fatigue was reported by 30.4% and 70.6%, respectively. At baseline, ≥1 hospitalization was reported by 107 (41.8%); 182 (71.1%) and 86 (33.6%) reported specialist and family physician visits, respectively. A total of 28 (10.8%) were working: 10 (37.0%) of which reported RRMM-driven absenteeism ≥1 day. Of those who were not working, 110 (48.2%) indicated that it was due to RRMM. Multivariate modeling showed lower hospitalization with a major tumor response (ß=-1.44, CI: -2.89 to 0.01, P=.05). CONCLUSIONS: Substantial RRMM indirect, social costs were observed. Better major tumor response may reduce hospital visits.

The influence of baseline characteristics and disease stage on health-related quality of life in multiple myeloma: findings from six randomized controlled trials.

This descriptive, cross-sectional analysis evaluated the impact of baseline characteristics on health-related quality of life (HR-QoL) at different stages of multiple myeloma (MM). The bortezomib clinical-trial programme evaluated HR-QoL early and consistently, producing a large multi-study dataset. Baseline data, captured using the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-C30), were pooled from six bortezomib randomized trials conducted in different disease-stage categories: 'New' (previously untreated; n = 753), 'Early' (1-3 prior therapies; n = 1569) and 'Late' (≥4 prior therapies; n = 239) disease. Mean EORTC global health scores were similar across the three stages. Unexpectedly, emotional, physical and role functioning were higher in the later stages, indicating better perceived health. Symptom scores, including pain, were largely similar or lower in the later versus earlier stages, signifying a lower symptom burden/better symptom control with more advanced disease. Notable variation in HR-QoL was observed by age and clinical parameters within and across stages. Multivariate modelling indicated that opioid use and performance status were key factors driving overall HR-QoL across stages. Using an age-restricted analysis, transplant eligibility had little impact on HR-QoL in New disease patients. Thus, changes in HR-QoL over the treatment course of MM are complex and impacted by baseline factors. A prospective observational international inception cohort study that captures key clinical, HR-QoL and demographic characteristics, along with safety and supportive care information, is needed.

Deriving health utility values from a randomized, double-blind, placebo-controlled trial of siltuximab in subjects with multicentric Castleman's disease.

PURPOSE: To estimate health utility values, explore predictors of utility values, and estimate the quality-adjusted life years (Q.A.L.Y.s) gained by treatment in multicentric Castleman's disease (M.C.D.). METHODS: The SF-36 was administered to 79 patients enrolled in a randomized, double-blind, placebo-controlled, multi-national study to determine the safety and efficacy of siltuximab plus best supportive care (B.S.C.) compared with B.S.C., in subjects with symptomatic M.C.D. Utility (SF-6D) scores were derived from the SF-36. Sensitivity analyses using utilities obtained by mapping the SF-36 to the EQ-5D were also conducted. Repeated measures, mixed effects models were conducted to estimate effects of treatment, responder status and ≥ Grade 3 adverse events (A.E.s) on changes in utility values over time, controlling for baseline utility value. Additionally, differential Q.A.L.Y. gain was assessed in the trial using multiple regression. RESULTS: Patients on siltuximab and those who experienced a complete or partial response had higher mean utility values over time than those on placebo or those with stable disease. After an initial response to treatment, the mean utility remained relatively stable for patients on siltuximab and those who experienced a complete or partial response during the period when most patients were on study. A significantly different Q.A.L.Y. gain was found for patients on siltuximab (versus placebo) as calculated by SF-6D (0.070 Q.A.L.Y.s, p < .05) scores at 6 months (EQ-5D 0.096 Q.A.L.Y.s, p < 0.05). CONCLUSIONS: Siltuximab demonstrated improved, durable health utility gains in this rare disease over B.S.C. The main SF-6D results were supported by EQ-5D sensitivity analysis. These findings are limited by the small study sample size and substantial missing data caused predominantly by crossover. A longitudinal, multisite international observational study capturing clinical, safety and health-related quality of life (H.R.Q.L.) endpoints are needed to confirm these findings.

Chest X-ray Artifact Caused by Bilateral 99mTc-Antimony Trisulfite Injection for Sentinel Node Imaging in a Patient With Breast Cancer.

A 52-year-old woman diagnosed with invasive ductal carcinoma of both breasts had a chest x-ray for preoperative assessment. A striking artifact was noted by the x-ray technologist, who, as a result, became very concerned about radiation exposure from the patient. The patient had undergone bilateral sentinel lymph node injections in the nuclear medicine department with Tc-antimony trisulfite colloid just 2 hours before the chest x-ray. Radiation exposure to the x-ray technologist was determined to be similar to 8 hours of naturally occurring background radiation (∼2.96 µSv).

Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma: 5-year follow-up.

This follow-up extension of a randomised phase II study assessed differences in long-term outcomes between bortezomib-thalidomide-dexamethasone (VTD) and VTD-cyclophosphamide (VTDC) induction therapy in multiple myeloma. Newly diagnosed patients (n = 98) were randomised 1:1 to intravenous bortezomib (1·3 mg/m(2); days 1, 4, 8, 11), thalidomide (100 mg; days 1-21), and dexamethasone (40 mg; days 1-4, 9-12), with/without cyclophosphamide (400 mg/m(2); days 1, 8), for four 21-day cycles before stem-cell mobilisation/transplantation. After a median follow-up of 64·8 months, median time-to-next therapy was 51·8 and 47·9 months with VTD and VTDC, respectively. Type of subsequent therapy was similar in both arms. After adjusting for asymmetric censoring, median time to progression was not significantly different between VTD and VTDC [35·7 vs. 34·5 months; Hazard ratio (HR) 1·26, 95% confidence interval: 0·76-2·09; P = 0·370]. Five-year survival was 69·1% and 65·3% with VTD and VTDC, respectively. When analysed by minimal residual disease (MRD) status, overall survival was longer in MRD-negative versus MRD-positive patients with bone marrow-confirmed complete response (HR 3·66, P = 0·0318). VTD induction followed by transplantation provides long-term disease control and, consistent with the primary analysis, there is no additional benefit from adding cyclophosphamide. This study was registered at ClinicalTrials.gov (NCT00531453).

Clinical characteristics and healthcare utilization of patients with multicentric Castleman disease.

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disease. Little is known about how patient clinical features and healthcare utilization varies by human immunodeficiency virus (HIV) status and disease subtype. Data of MCD patients identified between 2000 and 2009 were collected from medical records at two United States treatment centres. Clinical, demographic, and biochemical characteristics, drug therapies and medical utilization were descriptively reported by HIV status and cell histology, and statistically compared with the Fisher's Exact and Kruskal-Wallis tests. Patients (n = 59) had a pathologically and clinically confirmed MCD diagnosis: plasmacytic (42%), hyaline vascular (29%) and mixed (15%); 10% had HIV infection. In the first year after diagnosis, MCD patients on average saw a healthcare provider more than six times, were hospitalized at least once and underwent frequent radiological and laboratory testing. Rituximab was the most commonly used drug therapy, followed by corticosteroids and conventional chemotherapy. One- and 2-year survival was excellent in HIV-negative patients (100% and 97%, respectively) but inferior for HIV-positive cases (67% and 67%, respectively). Heterogeneous treatment decisions were observed in this MCD study; HIV status was the only distinguishing clinical criteria associated with pharmacotherapies. Additional research is necessary to guide treatment of this rare lymphoproliferative disorder.

Clinical epidemiology and treatment patterns of patients with multicentric Castleman disease: results from two US treatment centres.

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disease with little known about its epidemiology or treatment modalities. Clinical and demographic data of MCD patients identified between 2000 and 2009 were collected from medical records at two United States (US) MCD referral centres. ZIP codes identified patient residences; prevalence and incidence were estimated based on catchment areas. Patient clinical, demographic, and biochemical characteristics, drug therapies and medical utilization were descriptively reported. MCD patients (n = 59) were 61% male, mean age of 53 years (median = 55 years) and 68% Caucasian. Of those with known human immunodeficiency virus (HIV) status (n = 41), 85% (n = 35) were negative, 15% (n = 6) were positive. Most frequent physician-reported symptoms (n = 33) were fatigue (49%, n = 16), fever (39%, n = 13), and night sweats (30%, n = 10). The estimated US 10-year prevalence was 2·4 per million. During first year of follow-up after study entry, the top two systemic therapies (n = 27) were monotherapies: prednisone (33%, n = 9) and rituximab (19%, n = 5). After a follow-up of 2 years, 92% of patients were alive. This study provides new information on MCD population demographics, treatment patterns, and medical utilization; a minimal US period prevalence rate is proposed. Study replication is needed to improve external validity.

First demonstration of intrafractional tumor-tracked irradiation using 2D phantom MR images on a prototype linac-MR.

PURPOSE: To demonstrate intrafractional MR tumor tracking using a prototype linac-MR by delivering radiation to a moving target undergoing simulated tumor motions. METHODS: A prototype linac-MR at the Cross Cancer Institute was used for intrafractional MR imaging and simultaneous beam delivery. A Varian 52-leaf MK-II multileaf collimator (MLC) was used for beam collimation. The authors used an inhouse built MR compatible motion phantom to simulate tumor motions during tracking with two different motion patterns (sine and modified cosine). Gafchromic film was inserted in the phantom to measure radiation exposure, and this film measurement was converted to dose (cGy) for further analysis. The authors demonstrated intrafractional tracking in various scenarios: [Scenario 0 (S0)] no phantom motion + no beam margin, (S1) no phantom motion + maximum beam margin, (S2) phantom motion + no beam margin, (S3) S2 + MLC tracking, and (S4) S3 + motion prediction. S0 emulates a perfect tumor tracking scenario, and its result was used as a "gold-standard" to evaluate tracking accuracy from other scenarios. The authors compared (1) time difference in phantom and MLC motion curves in S3 and S4, and (2) dose profiles (50% beam width, 80%-20% penumbra width) from scenarios S1-S4 to S0. RESULTS: In S4, no observable time difference exists between the phantom and MLC motion curves, indicating that MLC tracks phantom motion accurately. Comparing S4 to S0, 50% beam width reveals minimal differences of < 0.5 mm, while the increase in 80%-20% penumbra width is limited to 0.4 and 1.7 mm in the sine and modified cosine patterns, respectively. CONCLUSIONS: The authors report the first demonstration of intrafractional tumor tracking using 2D MR images. During 2 min of tracking, the authors delivered highly conformal dose to a moving target that simulates tumor motions. Compared to static target irradiation, the 50% beam width remains essentially the same (within 0.5 mm), with an increase in 80%-20% penumbra width of less than 1.7 mm in moving target irradiation. These results illustrate potential dosimetric advantages of intrafractional MR tumor tracking in treating mobile tumors as shown for the phantom case.

Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma.

PURPOSE: Bortezomib-thalidomide-dexamethasone (VTD) is an effective induction therapy in multiple myeloma (MM). This phase II, noncomparative study sought to determine whether addition of cyclophosphamide to this regimen (VTDC) could further increase efficacy without compromising safety. PATIENTS AND METHODS: Patients age 18 to 70 years with previously untreated, measurable MM, who were eligible for high-dose chemotherapy-autologous stem-cell transplantation (HDCT-ASCT), were randomly assigned to bortezomib 1.3 mg/m(2), thalidomide 100 mg, and dexamethasone 40 mg, with (n = 49) or without (n = 49) cyclophosphamide 400 mg/m(2) for four 21-day cycles, followed by HDCT-ASCT. The primary end point was postinduction combined rate of near-complete response (nCR) or better (including complete response [CR] with normalized serum κ:λ free light chain ratio, CR, and nCR). RESULTS: Postinduction, 51% (VTD) and 44% (VTDC) of patients achieved combined CR/nCR, with bone marrow-confirmed CR in 29% and 31%, overall response rates of 100% and 96%, respectively, and very good partial response or better rates of 69% per arm. Post-HDCT-ASCT, combined CR/nCR rates were 85% (VTD) and 77% (VTDC). In all, 35% (VTD) and 27% (VTDC) of patients were negative for minimal residual disease (MRD) during induction and postinduction. Three-year overall survival was 80% (both arms). Grade 3 to 4 adverse events (AEs) and serious AEs were observed in 47% and 22% (VTD) and 57% and 41% (VTDC) of patients, respectively. The primary health-related quality of life end point (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [EORTC QLQ-C30] Global Health score) steadily increased with VTD during induction and reached a clinically relevant difference post-transplantation versus baseline. CONCLUSION: Both VTD and VTDC are highly active induction regimens producing high combined CR/nCR and MRD-negative rates; however, VTDC was associated with increased toxicity and suggestion of transient decreases in Global Health score, without an increase in activity.

An artificial neural network (ANN)-based lung-tumor motion predictor for intrafractional MR tumor tracking.

PURPOSE: To address practical issues of implementing artificial neural networks (ANN) for lung-tumor motion prediction in MRI-based intrafractional lung-tumor tracking. METHODS: A feedforward four-layered ANN structure is used to predict future tumor positions. A back-propagation algorithm is used for ANN learning. Adaptive learning is incorporated by continuously updating weights and learning rate during prediction. An ANN training scheme specific for MRI-based tracking is developed. A multiple-ANN structure is developed to reduce tracking failures caused by the lower imaging rates of MRI. We used particle swarm optimization to optimize the ANN structure and initial weights (IW) for each patient and treatment fraction. Prediction accuracy is evaluated using the 1D superior-inferior lung-tumor motions of 29 lung cancer patients for system delays of 120-520 ms, in increments of 80 ms. The result is compared with four different scenarios: (1), (2) ANN structure optimization + with∕without IW optimization, and (3), (4) no ANN structure optimization + with∕without IW optimization, respectively. An additional simulation is performed to assess the value of optimizing the ANN structure for each treatment fraction. RESULTS: For 120-520 ms system delays, mean RMSE values (ranges 0.0-2.8 mm from 29 patients) of 0.5-0.9 mm are observed, respectively. Using patient specific ANN structures, a 30%-60% decrease in mean RMSE values is observed as a result of IW optimization, alone. No significant advantages in prediction performance are observed, however, by optimizing for each fraction. CONCLUSIONS: A new ANN-based lung-tumor motion predictor is developed for MRI-based intrafractional tumor tracking. The prediction accuracy of our predictor is evaluated using a realistic simulated MR imaging rate and system delays. For 120-520 ms system delays, mean RMSE values of 0.5-0.9 mm (ranges 0.0-2.8 mm from 29 patients) are achieved. Further, the advantage of patient specific ANN structure and IW in lung-tumor motion prediction is demonstrated by a 30%-60% decrease in mean RMSE values.

An evaluation of the Clarity 3D ultrasound system for prostate localization.

The purpose of this study is to evaluate the accuracy and precision of the Clarity 3D ultrasound system to track prostate gland positional variations due to setup error and organ motion. Seventeen patients (n = 17) undergoing radical external beam radiation therapy for localized prostate cancer were studied. Subsequent to initial reference ultrasound and planning CT scans, each patient underwent seven repeat weekly tracking CT and ultrasound (US) scans during the course of treatment. Variations in the location of the prostate between reference and tracking scans were measured. Differences reported by CT and ultrasound scans are compared. Ultrasound tracking was initially performed clinically by a group of trained general users. Retrospective prostate localization was then performed by a trained dedicated user upon the original raw data set and also a reduced data set derived from the original by an expert user from Resonant Medical. Correlation accuracy between ultrasound and CT shifts acquired and delineated by a pool of trained general users was deemed unacceptable for radiotherapy purposes. A mean discrepancy between CT and US localizations of greater than 10 mm, with a 5 mm or greater discrepancy rate of nearly 90%, was observed. Retrospective analysis by a dedicated user of both the original and Resonant Medical reduced data sets yielded mean CT-Us discrepancies of 8.7 mm and 7.4 mm, respectively. Unfortunately, the 5 mm or greater CT-US discord rate for these retrospective analyses failed to drop below 80%. The greatest disparity between CT and ultrasound was consistently observed in the superior-inferior direction, while greatest agreement was achieved in the lateral dimension. Despite an expert reanalysis of the original data, the Clarity ultrasound system failed to deliver an acceptable level of geometric accuracy required for modern radiotherapy purposes.

Content development for the Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM): use of qualitative and quantitative methods for scale construction.

CONTEXT: Multiple myeloma (MM) is a common hematologic malignancy and is associated with symptom burden and impairments in health-related quality of life (HRQL). OBJECTIVES: To develop a disease-specific, patient-reported outcome (PRO) measure for the assessment of HRQL among patients with MM as part of the Functional Assessment of Cancer Therapy (FACT) measurement system. METHODS: HRQL concerns and symptoms associated with MM were tabulated based on a literature review, and 52 candidate PRO items were identified. Expert clinicians (n=13) rated 52 items on relevance to HRQL for MM patients (0-3 scale). Experts added 11 items for comprehensive PRO assessment in MM. A list of 63 candidate items was rated (0-3 scale) by 13 MM patients enrolled through the International Myeloma Foundation website. Qualitative data and quantitative item ratings were reviewed to select FACT-MM scale items. RESULTS: Expert clinicians provided the highest HRQL relevance ratings for bone pain, bodily pain, difficulty walking (2.9), tiring easily (2.6), feeling discouraged (2.5), interference with activities and difficulty with self-care as a result of bone pain (2.5), and fatigue (2.5). Mean age of patients was 57 years; Eastern Cooperative Oncology Group performance status was 0 (38%), 1 (31%), or 2 (31%). Quantitative ratings by patients identified sexual function (1.3), uncertainty about health (1.2), fatigue (1.0), weight gain (1.0), and emotional concerns, such as worry about new symptoms and difficulty planning for the future (1.0) as most relevant to HRQL. CONCLUSION: The 14-item FACT-MM PRO measure was developed based on expert clinician and patient data, ensuring relevance to HRQL for MM patients.

Health-related quality of life in elderly, newly diagnosed multiple myeloma patients treated with VMP vs. MP: results from the VISTA trial.

OBJECTIVES: The phase 3 VISTA study (ClinicalTrials.gov NCT00111319) in transplant-ineligible myeloma patients demonstrated superior efficacy with bortezomib-melphalan-prednisone (VMP; nine 6-wk cycles) vs. melphalan-prednisone (MP) but also increased toxicity. Health-related quality of life (HRQoL; exploratory endpoint) was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). The phase 3 VISTA study (ClinicalTrials.gov NCT00111319) in transplant-ineligible myeloma patients demonstrated superior efficacy with bortezomib-melphalan-prednisone (VMP; nine 6-wk cycles) vs. melphalan-prednisone (MP) but also increased toxicity. Health-related quality of life (HRQoL; exploratory endpoint) was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). METHODS: EORTC QLQ-C30 was administered at screening, on day 1 of each cycle, at the end-of-treatment visit, and every 8 wk until progression. EORTC QLQ-C30 scores were evaluated among patients with a valid baseline and at least one post-baseline HRQoL assessment. RESULTS: At baseline, domain scores were similar between arms. By cycle 4, mean differences were clinically meaningful for most domains, indicating poorer health status with VMP. From cycle 5 onwards, improvements relative to baseline/MP were observed for all domains with VMP. Mean scores were generally improved by the end-of-treatment assessment vs. baseline in both arms. Among responding patients, mean scores generally improved from time of response to end-of-treatment assessment, substantially driven by patients achieving complete response (CR). Multivariate analysis showed a significant impact of duration of response/CR on improving global health status, pain, and appetite loss scores. Analyses by bortezomib dose intensity indicated better HRQoL in patients receiving lower dose intensity. CONCLUSIONS: These findings demonstrate clinically meaningful, transitory HRQoL decrements with VMP and relatively lower HRQoL vs. MP during early treatment cycles, associated with the expected additional toxicities. However, HRQoL is not compromised in the long term, recovering by the end-of-treatment visit to be comparable vs. MP.

Evaluation of a lung tumor autocontouring algorithm for intrafractional tumor tracking using low-field MRI: a phantom study.

PURPOSE: The first aim of this study is to investigate the feasibility of online autocontouring of tumor in low field MR images (0.2 and 0.5 T) by means of a phantom and simulation study for tumor-tracking in linac-MR systems. The second aim of this study is to develop an MR compatible, lung tumor motion phantom. METHODS: An autocontouring algorithm was developed to determine both the position and shape of a lung tumor from each intra fractional MR image. To initiate the algorithm, an expert user contours the tumor and its maximum anticipated range of motion (herein termed the Background) using pretreatment scan data. During treatment, the algorithm processes each intrafractional MR image and automatically contours the tumor. To evaluate this algorithm, the authors built a phantom that replicates the low field contrast parameters (proton density, T(1), T(2)) of lung tumors and healthy lung parenchyma. This phantom allows simulation of MR images with the expected lung tumor CNR at 0.2 and 0.5 T by using a single 3 T scanner. Dynamic bSSFP images (approximately 4 images per second) are acquired while the phantom undergoes a series of preprogrammed motions based on patient lung tumor motion data. These images are autocontoured off-line using our algorithm. The fidelity of autocontouring is assessed by comparing autocontoured tumor shape and its centroid position to the actual tumor shape and its position. RESULTS: The algorithm successfully contoured the shape of a moving tumor model from dynamic MR images acquired every 275 ms. Dice's coefficients of > 0.96 and > 0.93 are achieved in 0.5 and 0.2 T equivalent images, respectively. Also, the algorithm tracked tumor position during dynamic studies, with root mean squared error (RMSE) values of < 0.55 and < 0.92 mm for 0.5 and 0.2 T equivalent images, respectively. Autocontouring speed is approximately 5 ms for each image. CONCLUSIONS: Dice's coefficients of > 0.96 and > 0.93 are achieved between autocontoured and real tumor shapes, and the position of a tumor can be tracked with RMSE values of < 0.55 and < 0.92 mm in 0.5 and 0.2 T equivalent images, respectively. These results demonstrate the feasibility of lung tumor autocontouring in low field MR images, and, by extension, intrafractional lung tumor tracking with our laboratory's linac-MR system.

Temporal lung tumor volume changes in small-cell lung cancer patients undergoing chemoradiotherapy.

PURPOSE: Small-cell lung cancer is considered to be relatively chemosensitive and radiosensitive. Small-cell tumor volume changes during concurrent chemoradiotherapy have not been quantified. The purpose of this work is to quantify small-cell lung tumor volume variations in limited-stage patients undergoing chemoradiotherapy. METHODS AND MATERIALS: Eligible patients had pathologically confirmed limited-stage small-cell lung cancer, underwent concurrent chemoradiotherapy, and signed study-specific consent forms. Patients underwent serial chest computed tomography (CT) scans on a CT simulator with images acquired at the same phase of patients' respiratory cycle. Computed tomography scans were obtained at the time of planning CT scan and 3 times a week during radiotherapy (RT). Gross tumor volumes (GTVs) were contoured on each CT scan. Gross tumor volumes defined on each CT scan were analyzed for volume changes relative to pre-RT scans. RESULTS: We obtained 104 CT scans (median, 11.5 scans per patient). The median tumor dose was 50 Gy. The median pre-RT GTV was 98.9 cm(3) (range, 57.8-412.4 cm(3)). The median GTV at the final serial CT scan was 10.0 cm(3) (range, 4.2-81.6 cm(3)). The mean GTV relative to pre-RT volume at the end of each RT week was 53.0% for Week 1, 29.8% for Week 2, 22.9% for Week 3, 19.5% for Week 4, and 12.4% for Week 5. CONCLUSIONS: Dramatic shrinkage of small-cell lung tumors occurred in patients undergoing chemoradiotherapy in this trial. Most of the observed GTV shrinkage occurred during the first week of RT.

Association between patient unconscious or not alert conditions and cardiac arrest or high-acuity outcomes within the Medical Priority Dispatch System "Falls" protocol.

INTRODUCTION: Falls are one of the most common types of complaints received by 9-1-1 emergency medical dispatch centers. They can be accidental or may be caused by underlying medical problems. Though "not alert" falls patients with severe outcomes mostly are "hot" transported to the hospital, some of these cases may be due to other acute medical events (cardiac, respiratory, circulatory, or neurological), which may not always be apparent to the emergency medical dispatcher (EMD) during call processing. OBJECTIVES: The objective of this study was to characterize the risk of cardiac arrest and "hot-transport" outcomes in patients with "not alert" condition, within the Medical Priority Dispatch System (MPDS®) Falls protocol descriptors. METHODS: This retrospective study used 129 months of de-identified, aggregate, dispatch datasets from three US emergency communication centers. The communication centers used the Medical Priority Dispatch System version 11.3-OMEGA type (released in 2006) to interrogate Emergency Medical System callers, select dispatch codes assigned to various response configurations, and provide pre-arrival instructions. The distribution of cases and percentages of cardiac arrest and hot-transport outcomes, categorized by MPDS® code, was profiled. Assessment of the association between MPDS® Delta-level 3 (D-3) "not alert" condition and cardiac arrest and hot-transport outcomes then followed. RESULTS: Overall, patients within the D-3 and D-2 "long fall" conditions had the highest proportions (compared to the other determinants in the "falls" protocol) of cardiac arrest and hot-transport outcomes, respectively. "Not alert" condition was associated significantly with cardiac arrest and hot-transport outcomes (p<0.001). CONCLUSIONS: The "not alert" determinant within the MPDS® "fall" protocol was associated significantly with severe outcomes for short falls (<6 feet; 2 meters) and ground-level falls. As reported to 9-1-1, the complaint of a "fall" may include the presence of underlying conditions that go beyond the obvious traumatic injuries caused by the fall itself.