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Background: Long-term prospective patient-reported outcomes (PRO) after breast cancer adjuvant radiotherapy is scarce. TomoBreast compared conventional radiotherapy (CR) with tomotherapy (TT), on the hypothesis that TT might reduce lung-heart toxicity.Methods: Among 123 women consenting to participate, 64 were randomized to CR, 59 to TT. CR delivered 50 Gy in 25 fractions/5 weeks to breast/chest wall and regional nodes if node-positive, with a sequential boost (16 Gy/8 fractions/1.6 weeks) after lumpectomy. TT delivered 42 Gy/15 fractions/3 weeks to breast/chest wall and regional nodes if node-positive, 51 Gy simultaneous-integrated-boost in patients with lumpectomy. PRO were assessed using the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30. PRO scores were converted into a symptom-free scale, 100 indicating a fully symptom-free score, 0 indicating total loss of freedom from symptom. Changes of PRO over time were analyzed using the linear mixed-effect model. Survival analysis computed time to > 10% PRO-deterioration. A post-hoc cardiorespiratory outcome was defined as deterioration in any of dyspnea, fatigue, physical functioning, or pain.Results: At 10.4 years median follow-up, patients returned on average 9 questionnaires/patient, providing a total of 1139 PRO records. Item completeness was 96.6%. Missingness did not differ between the randomization arms. The PRO at baseline were below the nominal 100% symptom-free score, notably the mean fatigue-free score was 64.8% vs. 69.6%, pain-free was 75.4% vs. 75.3%, and dyspnea-free was 84.8% vs. 88.5%, in the TT vs. CR arm, respectively, although the differences were not significant. By mixed-effect modeling on early ≤2 years assessment, all three scores deteriorated, significantly for fatigue, P ≤ 0.01, without effect of randomization arm. By modeling on late assessment beyond 2 years, TT versus CR was not significantly associated with changes of fatigue-free or pain-free scores but was associated with a significant 8.9% improvement of freedom from dyspnea, P = 0.035. By survival analysis of the time to PRO deterioration, TT improved 10-year survival free of cardiorespiratory deterioration from 66.9% with CR to 84.5% with TT, P = 0.029.Conclusion: Modern radiation therapy can significantly improve long-term PRO.Trial Registration: Trial registration number ClinicalTrials.gov NCT00459628 , April 12, 2007 prospectively. [ABSTRACT FROM AUTHOR]

Background and purpose For tumor tracking, a correlation model is used to estimate internal tumor position based on external surrogate motion. When patients experience an internal/external surrogate drift, an update of the correlation model is required to continue tumor tracking. In this study, the accuracy of the internal tumor position estimation for both the clinical available update at discrete points in time (rebuild) and an in-house developed non-clinical online update approach was investigated. Methods A dynamic phantom with superimposed baseline drifts and 14 SBRT patients, treated with real-time tumor tracking (RTTT) on the Vero system, were retrospectively simulated for three update scenarios, respectively no update, clinical rebuild and 0.5 Hz automated online update of the correlation model. By comparing the target positions based on 0.5 Hz verification X-ray images with the estimated internal tumor positions regarding all three update scenarios, 95th percentile modeling errors (ME 95 ), incidences of full geometrical coverage of the CTV by a 5 mm extended PTV ( P 5mm ) and population-based PTV margins were calculated. Further, the treatment time reduction was estimated when switching from the clinical rebuild approach to the online correlation model update. Results For dynamic phantom motion with baseline drifts up to 0.4 mm/min, a 0.5 Hz intra-fraction update showed a similar accuracy in terms of ME 95 and P 5mm compared to clinical rebuild. For SBRT patients treated on Vero with RTTT, accuracy was improved by 0.5 Hz online update compared to the clinical rebuild protocol, yielding smaller PTV margins (from 3.2 mm to 2.7 mm), reduced ME 95,3D (from 4.1 mm to 3.4 mm) and an increased 5th percentile P 5mm (from 90.7% to 96.1%) for the entire patient group. Further, 80% of treatment sessions were reduced in time with on average 5.5 ± 4.1 (1 SD) min. Conclusion With a fast (0.5 Hz) automated online update of the correlation model, an efficient RTTT workflow with improved geometrical accuracy was obtained. [ABSTRACT FROM AUTHOR]

Purpose: Shoulder/arm morbidity is a known complication of breast cancer surgery and radiotherapy (RT), but the consequences of choosing one RT technology over another for shoulder/arm morbidity are not clearly defined. In this work, we examine early breast cancer patients to compare the incidence of shoulder/arm morbidity, including breast cancer related lymphedema (BCRL) of the arm, between conventional RT and short-course, image-guided RT (IGRT) treatments. Methods: We randomized patients between post-surgery IGRT over 3 weeks and conventional RT over 5 to 7 weeks, as part of the TomoBreast trial (whose primary endpoint was to assess pulmonary and cardiac toxicities). BCRL and shoulder/arm mobility were assessed prior to and between one and three months following RT, using physical function assessment and common terminology criteria for adverse events. Intention to treat analyses used the matched-pairs t-test for continuous measurements and the chi-squared test for categorical data. Results: Analysis of the first 91 evaluable patients found that >80% experienced an increase in the adverse event score in at least one shoulder/arm mobility measurement, and 18% had BCRL symptoms. Arm volume on both sides increased significantly and significant impairment of movement occurred in both limbs. However, there was no significant difference in BCRL incidence or shoulder/arm mobility impairment between the treatment groups. Conclusion: One to three months after treatment, short-course IGRT had not increased shoulder/arm morbidity compared with conventional RT. Although confirmation requires a longer follow-up, the results support the use of a short-course schedule. The incidental finding that morbidity affected the contralateral limb warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: TomoBreast is a unicenter, non-blinded randomized trial comparing conventional radiotherapy (CR) vs. hypofractionated Tomotherapy (TT) for post-operative treatment of breast cancer. The purpose of the trial is to compare whether TT can reduce heart and pulmonary toxicity. We evaluate early toxicities. Methods: The trial started inclusion in May 2007 and reached its recruitment in August 2011. Women with stage T1-3N0M0 or T1-2N1M0 breast cancer completely resected by tumorectomy (BCS) or by mastectomy (MA) who consented to participate were randomized, according to a prescribed computer-generated randomization schedule, between control arm of CR 25x2 Gy/5 weeks by tangential fields on breast/chest wall, plus supraclavicular-axillary field if node-positive, and sequential boost 8x2 Gy/2 weeks if BCS (cumulative dose 66 Gy/7 weeks), versus experimental TT arm of 15x2.8 Gy/3 weeks, including nodal areas if node-positive and simultaneous integrated boost of 0.6 Gy if BCS (cumulative dose 51 Gy/3 weeks). Outcomes evaluated were the pulmonary and heart function. Comparison of proportions used one-sided Fisher's exact test. Results: By May 2010, 70 patients were randomized and had more than 1 year of follow-up. Out of 69 evaluable cases, 32 were assigned to CR (21 BCS, 11 MA), 37 to TT (20 BCS, 17 MA). Skin toxicity of grade ≥1 at 2 years was 60% in CR, vs. 30% in TT arm. Heart function showed no significant difference for left ventricular ejection fraction at 2 years, CR 4.8% vs. TT 4.6%. Pulmonary function tests at 2 years showed grade ≥1 decline of FEV1 in 21% of CR, vs. 15% of TT and decline of DLco in 29% of CR, vs. 7% of TT (P = 0.05). Conclusions: There were no unexpected severe toxicities. Short course radiotherapy of the breast with simultaneous integrated boost over 3 weeks proved feasible without excess toxicities. Pulmonary tests showed a slight trend in favor of Tomotherapy, which will need confirmation with longer follow-up of patients. [ABSTRACT FROM AUTHOR]

Purpose: Validation of a prospective, risk-adapted strategy for early-stage non–small-cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). Methods and Materials: Patients with a T1–3N0M0 (American Joint Committee on Cancer 6th edition) NSCLC were accrued. Using the Radiation Therapy Oncology Group definition, patients were treated to a total dose of 60,Gy in three fractions for peripherally located lesions and four fractions for centrally located lesions. The primary endpoint was toxicity, graded according to the Radiation Therapy Oncology Group acute and late morbidity scoring system, and the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. Secondary endpoints were local control and survival. Results: A total of 40 patients were included, 17 with a centrally located lesion. The lung toxicity-free survival estimate at 2 years was 74% and was related to the location (central vs. peripheral) and the size of the target volume. No dose volumetric parameters could predict the occurrence of lung toxicity. One patient died because of treatment-related toxicity. The 1-year and 2-year local progression-free survival estimates were 97% and 84%, respectively, and were related to stage (T1 vs. T2) related (p = 0.006). Local failure was not more frequent for patients treated in four fractions. The 1-year local progression-free survival estimate dropped below 80% for lesions with a diameter of more than 4 cm. Conclusion: The proposed risk-adapted strategy for both centrally and peripherally located lesions showed an acceptable toxicity profile while maintaining excellent local control rates. The correlation between local control and tumor diameter calls for the inclusion of tumor stage as a variable in future study design. [ABSTRACT FROM AUTHOR]

Purpose: To investigate predictors for gastrointestinal (GI) and genitourinary (GU) acute toxicity after a short-course hypofractionated radiotherapy regimen for prostate cancer. Materials and Methods: Three institutions included 102 patients with T1-T3N0M0 prostate cancer in a Phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Acute toxicity was scored weekly during treatment and 1 and 2 months after treatment using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria extended with additional symptoms and the International Prostate Symptom Index (IPSS). Correlation with a number of clinical and dosimetric parameters was assessed by univariate and multivariate analyses. Results: No Grade 3 or 4 GI side effects were observed. Grades 1 and 2 rectal GI toxicity occurred in 36%, and 38%, respectively. Corresponding figures for Grades 1 and 2 GU toxicity were 42% and 39%, respectively. Grade 3 or higher GU toxicity was detected in 4% of patients. In multivariate analysis, percent rectal volumes higher than 8% receiving doses ≥53 Gy (V53) were statistically correlated to Grade 2 acute rectal reaction (p = 0.006). For GU morbidity, only the IPSS pretreatment score was independently associated (p = 0.0036) with an increase in GU acute effects. Conclusions: Acute GU and GI toxicity were comparable with other series. Our data show that increased incidence and intensity of acute toxicity is a transient effect related to shorter overall treatment time rather than a larger effect in biological equivalent dose with respect to a conventional fractionation regime. [Copyright &y& Elsevier]

Background: Modeling the relationship between age and mortality for breast cancer patients may have important prognostic and therapeutic implications. Methods: Data from 9 registries of the Surveillance, Epidemiology, and End Results Program (SEER) of the United States were used. This study employed proportional hazards to model mortality in women with T1-2 breast cancers. The residuals of the model were used to examine the effect of age on mortality. This procedure was applied to node-negative (N0) and node-positive (N+) patients. All causes mortality and breast cancer specific mortality were evaluated. Results: The relationship between age and mortality is biphasic. For both N0 and N+ patients among the T1-2 group, the analysis suggested two age components. One component is linear and corresponds to a natural increase of mortality with each year of age. The other component is quasiquadratic and is centered around age 50. This component contributes to an increased risk of mortality as age increases beyond 50. It suggests a hormonally related process: the farther from menopause in either direction, the more prognosis is adversely influenced by the quasi-quadratic component. There is a complex relationship between hormone receptor status and other prognostic factors, like age. Conclusion: The present analysis confirms the findings of many epidemiological and clinical trials that the relationship between age and mortality is biphasic. Compared with older patients, young women experience an abnormally high risk of death. Among elderly patients, the risk of death from breast cancer does not decrease with increasing age. These facts are important in the discussion of options for adjuvant treatment with breast cancer patients. [ABSTRACT FROM AUTHOR]

In order to target arteriovenous malformations (AVM) in a frameless approach, registration of two-dimensional (2D) digital-subtracted-angiographs (DSA) with three-dimensional (3D) computed tomography (CT) is required. Targeting accuracy and delineation of a frameless 2D-DSA and 3D-CT image registration tool based on bony anatomy of the skull was evaluated. This frameless approach assures accurate target localization and can be used in a clinical setting. [ABSTRACT FROM AUTHOR]