Prerequisites for the clinical implementation of a markerless SGRT-only workflow for the treatment of breast cancer patients.

PURPOSE: A markerless workflow for the treatment of breast cancer patients has been introduced and evaluated retrospectively. It includes surface-guided radiation therapy (SGRT)-only positioning for patients with small cone beam CT (CBCT) position corrections during the first five fractions. Prerequisites and the frequency of its clinical application were evaluated, as well as potential benefits in terms of treatment time and dose savings, the frequency of CBCT scans, and the accuracy of the positioning. METHODS: A group of 100 patients treated with the new workflow on two Versa HD linacs has been compared to a matched control group of patients treated with the former workflow, which included prepositioning with skin markings and lasers, SGRT and daily CBCT. The comparison was based on the evaluation of logfiles. RESULTS: Of the patients treated with the new workflow, 40% did not receive daily CBCT scans. This resulted in mean time savings of 97 s, 166 s and 239 s per fraction for the new workflow, for patients treated without daily CBCT and for SGRT-only fractions, respectively, when compared to the old workflow. Dose savings amounted to a weighted computed tomography dose index reduction of CTDIW = 2.56 cGy on average for normofractionated treatment and weekly CBCTs, while for patients not treated with daily CBCT, SGRT-based positioning accuracy was 5.2 mm for the mean translational magnitude, as evaluated by CBCT. CONCLUSION: For 40% of the patients, after five fractions with small CBCT corrections, the workflow could be changed to SGRT-only positioning with weekly CBCT. This leads to imaging dose and time savings and thus also reduced intrafraction motion, potentially increased patient throughput and patient comfort, while assuring appropriate positioning accuracy.

Region of interest optimization for radiation therapy of breast cancer.

PURPOSE: The goal of this study was to investigate how the choice of the region of interest (ROI) affects the registration results of surface imaging for daily positioning of breast cancer patients. METHODS: The AlignRT system (VisionRT, London) and the XVI Cone beam CT (CBCT; Elekta, Stockholm) installed on two Versa HD linacs (Elekta) were used in this study, which included 28 patients (160 fractions). In the clinical workflow, patients were prepositioned with AlignRT and then shifted in 6 degrees of freedom (DOF) according to the CBCT. A new reference capture was taken immediately afterward. Retrospectively, the surface capture resulting from prepositioning was registered to the latest reference capture. By varying the ROI used for registration, the surface-based results were optimized in terms of minimizing the deviation to the clinically applied CBCT shifts. Two sets of ROIs were used: one obtained by applying a variable margin to the breast surface, another by combining ROIs of anatomical structures, including the sternum and contralateral breast. RESULTS: Registration results showed significant differences from one ROI to another. Generally, the results improved with increasing ROI size, especially for rotational DOFs. ROIs, including the axilla or supraclavicular lymph drainage region, did not yield an improved registration result. On the other hand, an ROI comprising the breast surface, sternum, and a belt caudal to the breasts decreased the average magnitude of the translational and rotational deviations by 6.6% and 30.8% (p < 0.01), respectively, compared to the breast surface only results. CONCLUSION: The influence of the ROI choice on surface imaging registration results was analyzed and the surface-based shifts were compared to clinically applied CBCT shifts. An optimal ROI for the treatment of breast cancer patients, consisting of the breast surface, sternum, and a belt, was identified.

Recurrent glioblastoma: who receives tumor specific treatment and how often?

The recurrence of glioblastoma (rGBM) is inevitable and often short-term. Therefore, information on the prognosis and effectiveness of tumor-specific versus purely palliative approaches should be more in-depth than a mere list of available treatment options for patients in this situation. However, follow-up data on the course of the disease in unselected patient populations after completion of primary treatment are scarce. This single-center analysis investigated the rate and number of glioblastoma recurrences after initial radiotherapy in 189 consecutive GM patients, focusing on the incidence of early death and the frequency of tumor-specific treatment (TST) versus best-supportive care (BSC) as well as the outcomes for the different approaches. In 61 % of initial population first recurrence (rGBM) could be determined by histology or imaging. 47 % received TST. 58 % of the patients with rGBM and TST were diagnosed with a second recurrence. Up to five recurrences were treated. 35-45 % of patients died before undergoing imaging studies to confirm the next recurrence. Multivariate analysis identified male sex and KPS score as independent factors (p < 0.01) for the choice of TST over BSC. Median overall survival from the diagnosis of first recurrence was 267 days in the TST group versus 65 days in patients receiving BSC (p < 0.0001). Nearly half of all rGBM patients received second-line TST, but a remarkably high proportion died early. Gender and KPS played a role in the choice of TST over BSC for recurrence treatment.

Effects of Hippocampal Sparing Radiotherapy on Brain Microstructure-A Diffusion Tensor Imaging Analysis.

Hippocampal-sparing radiotherapy (HSR) is a promising approach to alleviate cognitive side effects following cranial radiotherapy. Microstructural brain changes after irradiation have been demonstrated using Diffusion Tensor Imaging (DTI). However, evidence is conflicting for certain parameters and anatomic structures. This study examines the effects of radiation on white matter and hippocampal microstructure using DTI and evaluates whether these may be mitigated using HSR. A total of 35 tumor patients undergoing a prospective randomized controlled trial receiving either conventional or HSR underwent DTI before as well as 6, 12, 18, 24, and 30 (±3) months after radiotherapy. Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD), and Radial Diffusivity (RD) were measured in the hippocampus (CA), temporal, and frontal lobe white matter (TL, FL), and corpus callosum (CC). Longitudinal analysis was performed using linear mixed models. Analysis of the entire patient collective demonstrated an overall FACC decrease and RDCC increase compared to baseline in all follow-ups; ADCC decreased after 6 months, and MDCC increased after 12 months (p ≤ 0.001, 0.001, 0.007, 0.018). ADTL decreased after 24 and 30 months (p ≤ 0.004, 0.009). Hippocampal FA increased after 6 and 12 months, driven by a distinct increase in ADCA and MDCA, with RDCA not increasing until 30 months after radiotherapy (p ≤ 0.011, 0.039, 0.005, 0.040, 0.019). Mean radiation dose correlated positively with hippocampal FA (p < 0.001). These findings may indicate complex pathophysiological changes in cerebral microstructures after radiation, insufficiently explained by conventional DTI models. Hippocampal microstructure differed between patients undergoing HSR and conventional cranial radiotherapy after 6 months with a higher ADCA in the HSR subgroup (p ≤ 0.034).

Tumor-infiltrating cytotoxic T cells but not regulatory T cells predict outcome in anal squamous cell carcinoma.

PURPOSE: Tumor-infiltrating lymphocytes (TIL) are a possible prognostic factor in solid tumors. Cytotoxic TILs are generally considered as prognostically favorable, whereas regulatory T cells (Treg) may have adverse effects by virtue of their ability to inhibit effector cells. We have evaluated the effect of T-cell subsets on survival in patients with anal squamous cell carcinoma following radiochemotherapy. METHODS: Biopsy specimens from 38 patients with anal carcinomas were evaluated using tissue microarrays and immunohistochemistry for the presence of tumor-infiltrating immune cells using CD3, CD4, CD8, and CD68 antibodies. Treg were identified using an antibody directed against the transcription factor FoxP3, and granzyme B served as a marker for cytotoxic cells. Intratumoral immune cells were enumerated using a semiautomatic image analysis program. Prognostic effect of TIL subsets was evaluated by the log-rank test comparing no evidence of disease survival for groups with high and low numbers using median values as cutoff. RESULTS: CD3+ and CD4+ TILs influenced no evidence of disease survival: 3-year rates for patients with low numbers were 89% and 95%, respectively, and 54% (P = 0.02) and 48%, (P = 0.01), respectively, in cases with high numbers. Large numbers of tumor-infiltrating granzyme B+ cytotoxic cells had a significant negative prognostic effect (P = 0.008), whereas no effect was observed for Treg. CONCLUSIONS: TILs were identified as negative prognostic indicators in anal squamous cell carcinomas with granzyme B+ cytotoxic cells showing highest effect on outcome. This is possibly explained by the selection of therapy-resistant tumor cell clones. No prognostic influence of Treg was found. Knowledge of local immune responses is important for the development of immunotherapeutic strategies.

A Model to Predict the Feasibility of Concurrent Chemoradiotherapy With Temozolomide in Glioblastoma Multiforme Patients Over Age 65.

OBJECTIVES: It is controversial whether concurrent chemoradiotherapy (CRT) with temozolomide is feasible and beneficial in elderly patients with glioblastoma. MATERIALS AND METHODS: Retrospective analysis of 74 elderly glioblastoma patients (65 y and above) treated with concurrent CRT with temozolomide. Factors influencing prognosis and feasibility of CRT were investigated. RESULTS: The median overall survival was 11.3 months. Univariate analysis showed a significant difference in median overall survival for cumulative dose of concurrent temozolomide (optimal cutoff, 2655 mg/m; 13.9 mo for >2655 mg/m vs. 4.9 mo for ≤2655 mg/m; P=0.0216, adjusted for multiple testing). Furthermore, cumulative dose of concurrent temozolomide >2655 mg/m was a significant independent prognostic parameter in multivariate analysis (hazard ratio, 0.33; P=0.002). Hematotoxicity was the most common cause of treatment interruption or discontinuation in patients with an insufficient cumulative temozolomide dose. Prognostic factors for successful performance of CRT with a cumulative dose of concurrent temozolomide >2655 mg/m were female sex (odds ratio [OR], 0.174; P=0.006), age (OR, 0.826 per year; P=0.017), and pretreatment platelet count (OR, 1.013 per 1000 platelets/µL; P=0.001). For easy clinical application of the model an online calculator was developed, which is available at http://www.OldTMZ.com. CONCLUSIONS: The probability of successful performance of concurrent CRT with temozolomide can be estimated based on the patient's age, sex, and pretreatment platelet count using the model developed in this study. Thus, a subgroup of elderly glioblastoma patients suitable for chemoradiation with temozolomide can be identified.