The aim of this work was to quantify the ability to predict intrafraction diaphragm motion from an external respiration signal during a course of radiotherapy. The data obtained included diaphragm motion traces from 63 fluoroscopic lung procedures for 5 patients, acquired simultaneously with respiratory motion signals (an infrared camera-based system was used to track abdominal wall motion). During these sessions, the patients were asked to breathe either (i) without instruction, (ii) with audio prompting, or (iii) using visual feedback. A statistical general linear model was formulated to describe the relationship between the respiration signal and diaphragm motion over all sessions and for all breathing training types. The model parameters derived from the first session for each patient were then used to predict the diaphragm motion for subsequent sessions based on the respiration signal. Quantification of the difference between the predicted and actual motion during each session determined our ability to predict diaphragm motion during a course of radiotherapy. This measure of diaphragm motion was also used to estimate clinical target volume (CTV) to planning target volume (PTV) margins for conventional, gated, and proposed four-dimensional (4D) radiotherapy. Results from statistical analysis indicated a strong linear relationship between the respiration signal and diaphragm motion (p<0.001) over all sessions, irrespective of session number (p=0.98) and breathing training type (p=0.19). Using model parameters obtained from the first session, diaphragm motion was predicted in subsequent sessions to within 0.1 cm (1 sigma) for gated and 4D radiotherapy. Assuming a 0.4 cm setup error, superior-inferior CTV-PTV margins of 1.1 cm for conventional radiotherapy could be reduced to 0.8 cm for gated and 4D radiotherapy. The diaphragm motion is strongly correlated with the respiration signal obtained from the abdominal wall. This correlation can be used to predict diaphragm motion, based on the respiration signal, to within 0.1 cm (1 sigma) over a course of radiotherapy.

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The clinical significance of tumor-infiltrating immune cells has been reported in a variety of human carcinomas including breast cancer. However, molecular signature of tumor-infiltrating immune cells and their prognostic value in breast cancer patients remain elusive. We hypothesized that a distinct network of immune function genes at the tumor site can predict a low risk versus high risk of distant relapse in breast cancer patients regardless of the status of ER, PR, or HER-2/neu in their tumors. We conducted retrospective studies in a diverse cohort of breast cancer patients with a 1–5 year tumor relapse versus those with up to 7 years relapse-free survival. The RNAs were extracted from the frozen tumor specimens at the time of diagnosis and subjected to microarray analysis and real-time RT-PCR. Paraffin-embedded tissues were also subjected to immunohistochemistry staining. We determined that a network of immune function genes involved in B cell development, interferon signaling associated with allograft rejection and autoimmune reaction, antigen presentation pathway, and cross talk between adaptive and innate immune responses were exclusively upregulated in patients with relapse-free survival. Among the 299 genes, five genes which included B cell response genes were found to predict with >85% accuracy relapse-free survival. Real-time RT-PCR confirmed the 5-gene prognostic signature that was distinct from an FDA-cleared 70-gene signature of MammaPrint panel and from the Oncotype DX recurrence score assay panel. These data suggest that neoadjuvant immunotherapy in patients with high risk of relapse may reduce tumor recurrence by inducing the immune function genes.

A B S T R A C T PurposeMany seriously ill patients with cancer do not discuss prognosis or advance directives (ADs), which may lead to inappropriate and/or unwanted aggressive care at the end of life. Ten years ago, patients with cancer said they would not like to discuss ADs with their oncologist but would be willing to discuss them with an admitting physician. We assessed whether this point of view still held. Patients and MethodsSemi-structured interviews were conducted with 75 consecutively admitted patients with cancer in the cancer inpatient service. ResultsOf those enrolled, 41% (31 of 75) had an AD. Nearly all (87%, 65 of 75) thought it acceptable to discuss ADs with the admitting physician with whom they had no prior relationship, and 95% (62 of 65) thought that discussing AD issues was very or somewhat important. Only 7% (5 of 75) had discussed ADs with their oncologist, and only 23% (16 of 70) would like to discuss ADs with their oncologist. When specifically asked which physician they would choose, 48% (36 of 75) of patients would prefer their oncologist, and 35% (26 of 75) would prefer their primary care physician. ConclusionFewer than half of seriously ill patients with cancer admitted to an oncology service have an AD. Only 23% (16 of 70) would like to discuss their ADs with their oncologist but nearly all supported a policy of discussing ADs with their admitting physician. However, fully 48% (36 of 75) actually preferred to discuss advance directives with their oncologist if AD discussion was necessary. We must educate patients on why communicating their ADs is beneficial and train primary care physicians, house staff, hospitalists, and oncologists to initiate these difficult discussions.

The accuracy of the frame-based and frameless systems was not statistically significantly different (p = 0.22). Note, however, that frameless techniques offer advantages in patient comfort, separation of imaging from surgery, and decreased operating time.

Accurate modeling of the respiratory cycle is important to account for the effect of organ motion on dose calculation for lung cancer patients. The aim of this study is to evaluate the accuracy of a respiratory model for lung cancer patients. Lujan et al. [Med. Phys. 26(5), 715-720 (1999)] proposed a model, which became widely used, to describe organ motion due to respiration. This model assumes that the parameters do not vary between and within breathing cycles. In this study, first, the correlation of respiratory motion traces with the model f(t) as a function of the parameter n (n = 1, 2, 3) was undertaken for each breathing cycle from 331 four-minute respiratory traces acquired from 24 lung cancer patients using three breathing types: free breathing, audio instruction, and audio-visual biofeedback. Because cos2 and cos4 had similar correlation coefficients, and cos2 and cos1 have a trigonometric relationship, for simplicity, the cos1 value was consequently used for further analysis in which the variations in mean position (z0), amplitude of motion (b) and period (tau) with and without biofeedback or instructions were investigated. For all breathing types, the parameter values, mean position (z0), amplitude of motion (b), and period (tau) exhibited significant cycle-to-cycle variations. Audio-visual biofeedback showed the least variations for all three parameters (z0, b, and tau). It was found that mean position (z0) could be approximated with a normal distribution, and the amplitude of motion (b) and period (tau) could be approximated with log normal distributions. The overall probability density function (pdf) of f(t) for each of the three breathing types was fitted with three models: normal, bimodal, and the pdf of a simple harmonic oscillator. It was found that the normal and the bimodal models represented the overall respiratory motion pdfs with correlation values from 0.95 to 0.99, whereas the range of the simple harmonic oscillator pdf correlation values was 0.71 to 0.81. This study demonstrates that the pdfs of mean position (z0), amplitude of motion (b), and period (tau) can be used for sampling to obtain more realistic respiratory traces. The overall standard deviations of respiratory motion were 0.48, 0.57, and 0.55 cm for free breathing, audio instruction, and audio-visual biofeedback, respectively.

Background and purpose Transcranial direct current stimulation (tDCS) has shown mixed results in post-stroke motor recovery, possibly because of tDCS dose differences. The purpose of this meta-analysis was to explore whether the outcome has a dose–response relationship with various dose-related parameters. Methods The literature was searched for double-blind, randomized, sham-controlled clinical trials investigating the role of tDCS (≥5 sessions) in post-stroke motor recovery as measured by the Fugl-Meyer Upper Extremity (FM-UE) scale. Improvements in FM-UE scores were compared between active and sham groups by calculating standardized mean differences (Hedge’s g) to derive a summary effect size. Inverse-variance-weighted linear meta-regression across individual studies was performed between various tDCS parameters and Hedge’s g to test for dose–response relationships. Results Eight studies with total of 213 stroke subjects were included. Summary Hedge’s g was statistically significant in favor of the active group (Hedge’s g = 0.61, p = 0.02) suggesting moderate effect. Specifically, studies that used bihemispheric tDCS montage (Hedge’s g = 1.30, p = 0.08) or that recruited chronic stroke patients (Hedge’s g = 1.23, p = 0.02) showed large improvements in the active group. A positive dose–response relationship was found with current density (p = 0.017) and charge density (p = 0.004), but not with current amplitude. Moreover, a negative dose–response relationship was found with electrode size (p < 0.001, smaller electrodes were more effective). Conclusions Our meta-analysis and meta-regression results suggest superior motor recovery in the active group when compared to the sham group and dose–response relationships relating to electrode size, charge density and current density. These results need to be confirmed in future dedicated studies.

Context Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and persistent consequence of numerous classes of antineoplastic agents, affecting up to 30%–40% of patients. To date, there is no effective prevention or therapy. An evolving hypothesis for reducing CIPN pain involves direct nerve stimulation to reduce the pain impulse. Objectives To evaluate the impact on CIPN associated with the MC5-A Calmare® therapy device. Methods The MC5-A Calmare® therapy device is designed to generate a patient-specific cutaneous electrostimulation to reduce the abnormal pain intensity. Sixteen patients from one center received one-hour interventions daily over 10 working days. Results Of 18 patients, 16 were evaluable. The mean age of the patients was 58.6 years—four men and 14 women—and the duration of CIPN was three months to eight years. The most common drugs were taxanes, platinums, and bortezomib (Velcade, Millenium Pharmaceuticals, Cambridge MA). At the end of the study (Day 10), a 20% reduction in numeric pain scores was achieved in 15 of 16 patients. The pain score fell 59% from 5.81 ± 1.11 before treatment to 2.38 ± 1.82 at the end of 10 days (P < 0.0001 by paired t-test). A daily treatment benefit was seen with a strong statistically significant difference between the preand post-daily pain scores (P < 0.001). Four patients had their CIPN reduced to zero. A repeated-measures analysis using the scores from all 10 days confirmed these results. No toxicity was seen. Some responses have been durable without maintenance. Conclusion Patient-specific cutaneous electrostimulation with the MC5-A Calmare® device appears to dramatically reduce pain in refractory CIPN patients with no toxicity. Further studies are underway to define the benefit, mechanisms of action, and optimal schedule.