Left-sided Treatment Research Articles

Dosimetric comparison between intensity-modulated radiotherapy and standard wedged tangential technique for whole-breast radiotherapy in Asian women with relatively small breast volumes

We sought to investigate whether intensity-modulated radiotherapy (IMRT) has a dosimetric advantage compared to the standard wedged tangential technique (SWT) for whole-breast radiotherapy (WBRT) in Asian women with relatively small breast volume. Computed tomography images of 25 Asian patients with early-stage breast cancer (right 15, left 10) used for WBRT planning were examined. After contouring the target volumes and bilateral lungs and, for left-side treatment, the heart, 4 plans were made for each patient: namely, SWT, tangential-field IMRT (T-IMRT), 3-field IMRT (3F-IMRT), and 4-field IMRT (4F-IMRT). The prescribed dose was 5000 cGy. The median planning target volume (PTV) for WBRT was 552.6 cc (range 288.8-1518.4 cc). Compared to SWT, (1) T-IMRT achieved significant improvement for dose homogeneity in the PTV (p < 0.001) and the dose received by 2% (D2) of the PTV (p < 0.001). T-IMRT also reduced the bilateral lung mean dose (p < 0.001) and the ipsilateral lung volume which received more than 20 Gy (V20) (p = 0.01). (2) 3F-IMRT resulted in a significant increase in the mean dose to the ipsilateral lung (p < 0.001) and to the contralateral lung (p < 0.001). (3) 4F-IMRT also resulted in a significant increase in the mean dose to the ipsilateral lung (p < 0.001) and to the contralateral lung (p < 0.001). Tangential-field IMRT provided an improved dose distribution compared with SWT for WBRT in Asian women with a relatively small breast volume.

Quantifying dose to the reconstructed breast: Can we adequately treat?

To evaluate how immediate reconstruction (IR) impacts postmastectomy radiotherapy (PMRT) dose distributions to the reconstructed breast (RB), internal mammary nodes (IMN), heart, and lungs using quantifiable dosimetric end points. 3D conformal plans were developed for 20 IR patients, 10 autologous reconstruction (AR), and 10 expander-implant (EI) reconstruction. For each reconstruction type, 5 right- and 5 left-sided reconstructions were selected. Two plans were created for each patient, 1 with RB coverage alone and 1 with RB + IMN coverage. Left-sided EI plans without IMN coverage had higher heart Dmean than left-sided AR plans (2.97 and 0.84 Gy, p = 0.03). Otherwise, results did not vary by reconstruction type and all remaining metrics were evaluated using a combined AR and EI dataset. RB coverage was adequate regardless of laterality or IMN coverage (Dmean 50.61 Gy, D95 45.76 Gy). When included, IMN Dmean and D95 were 49.57 and 40.96 Gy, respectively. Mean heart doses increased with left-sided treatment plans and IMN inclusion. Right-sided treatment plans and IMN inclusion increased mean lung V20. Using standard field arrangements and 3D planning, we observed excellent coverage of the RB and IMN, regardless of laterality or reconstruction type. Our results demonstrate that adequate doses can be delivered to the RB with or without IMN coverage.

Automating RTOG-defined target volumes for postmastectomy radiation therapy

PurposeConsistency in defining and contouring target structures in radiation therapy (RT) is critical for highly conformal RT, for evaluating treatment plans, and for quality assurance in multi-institutional RT trials. The Radiation Therapy Oncology Group (RTOG) has published consensus guidelines for contouring targets for postmastectomy RT. To aid in contouring such structures, we evaluated the potential use of an automated contouring technique, known as deformable image registration-based breast segmentation (DEF-SEG). Methods and MaterialsThe RTOG definitions were used to contour the chest wall (CW); levels I, II, and III axillary nodes (Ax1, Ax2, Ax3); supraclavicular (SCV) nodes; internal mammary (IM) nodes; and the heart. Left-sided and right-sided templates were created. The DEF-SEG was then used to generate auto-segmented contours from the appropriate template to computed tomographic scans of 20 test cases (10 left, 10 right). To assess the accuracy of this method, those contours were manually modified as necessary to match the RTOG definitions, and the extent of the overlap was compared. The dosimetric impact of the difference in contours was then evaluated by comparing dose-volume histograms for modified and unmodified contours. ResultsMean volume–overlap ratios between the unmodified DEF-SEG–generated contours and modified contours were as follows: CW, 0.91; Ax1, 0.68; Ax2, 0.64; Ax3, 0.68; SCV node, 0.66; IM node, 0.32, and the heart, 0.93. Mean differences in volume receiving 45 Gy (V45) for the modified versus unmodified contours were as follows: CW, 2.1%; SCV node, 4.8%; Ax1, 5.1%; Ax2, 5.6%; Ax3, 3.0%; and IM node, 10.1%. Mean differences in V10 between the modified heart and the unmodified heart were 0.4% for right-sided treatment and 0.5% for left-sided treatment. ConclusionsThe DEF-SEG can be helpful for delineating structures according to the RTOG consensus guidelines, particularly for the CW and the heart. No clinically significant dosimetric differences were found between the modified and unmodified contours. The DEF-SEG may be useful for evaluating treatment plans for postmastectomy RT in multi-institutional trials.

Evaluation of Acute Locoregional Toxicity in Patients With Breast Cancer Treated With Adjuvant Radiotherapy in Combination With Bevacizumab

Preclinical studies have shown that bevacizumab combined with radiotherapy (RT) induces a radiosensitizing effect. Published reports regarding the safety of combination therapy involving bevacizumab and RT are lacking. The purpose of this study was to analyze acute locoregional toxicity in patients with breast cancer receiving concurrent bevacizumab plus RT. After institutional review board approval was obtained, patients with breast cancer who received bevacizumab were identified; these patients were then cross-referenced with patients receiving RT. Toxicity was scored by the Common Terminology Criteria for Adverse Events. Patients were matched 1:1 with those who did not receive bevacizumab. Statistical analysis was performed to analyze toxicity between the two groups. Fourteen patients were identified to have received bevacizumab plus RT. All patients received bevacizumab during RT without delay or treatment breaks; there were no RT treatment breaks in all patients. No patient receiving bevacizumab plus RT experienced ≥Grade 3 toxicity; 3 matched control patients experienced a Grade 3 skin reaction. There was no difference in fatigue, radiation fibrosis, pneumonitis, or lymphedema between the two groups. Five patients (35%) developed reduction in ejection fraction; 2 with right-sided and 3 with left-sided treatment. Patients with left-sided treatment experienced a persistent reduction in ejection fraction compared with those receiving right-sided treatment. Concurrent bevacizumab and RT did not increase acute locoregional toxicity in comparison with matched control patients who did not receive RT alone. The addition of concurrent RT when treating the intact breast, chest wall, and associated nodal regions in breast cancer seems to be safe and well tolerated.

Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder: A Review

Several studies demonstrated that repetitive transcranial magnetic stimulation (rTMS) is an efficacious treatment for treatment-resistant major depressive disorder (TRD). Recent metaanalyses and more recent large multicentre studies provided evidence suggesting that rTMS is indeed a promising treatment; however, its efficacy has often been shown to be modest, compared with sham stimulation. We review these lines of evidence and discuss several reasons that may explain the modest therapeutic efficacy in most of these studies, including: most involved left-sided treatment alone to the dorsolateral prefrontal cortex (DLPFC) only, which may be less optimal than applying bilateral stimulation; suboptimal methods were used to target the DLPFC (that is, the 5-cm anterior method), limiting the treatment potential of inherently a targeted form of treatment; some treatment durations were short (that is, 2 to 4 weeks); and stimulation intensity might have been insufficient by not considering coil-to-cortex distance, which has been linked to rTMS-induced antidepressant response. Future studies attempting to address the above-mentioned limitations are necessary to potentially optimize the efficacy of this already promising treatment option in TRD. Finally, it is also essential that research investigate the mechanisms of therapeutic efficacy, thus increases in understanding can be translated into enhanced treatment. For several reasons that will be reviewed, cortical excitability may represent an important mechanism, linked to the therapeutic efficacy of this disorder.

Neuropsychological performance following staged bilateral pallidal or subthalamic nucleus deep brain stimulation for Parkinson's disease

Deep brain stimulation (DBS) has the potential to significantly reduce motor symptoms in advanced Parkinson's disease (PD). Controversy remains about non-motor effects of DBS and the relative advantages of treatment at two brain targets, the globus pallidus internus (GPi) and the subthalamic nucleus (STN). We investigated effects of DBS on neuropsychological functioning in 42 patients with advanced PD randomly assigned to receive staged bilateral DBS surgery of either the GPi or STN. Patients underwent neuropsychological assessment prior to and 6 months after unilateral surgery. Twenty-nine subsequently underwent surgery to the contralateral side and completed a second follow-up neuropsychological evaluation 15 months later. Unilateral treatment resulted in small but statistically significant reductions in performance on several measures, including verbal fluency and working memory. A similar pattern was observed after bilateral treatment. Reductions in verbal associative fluency were significant only after left-sided treatment. There were few significant differences related to treatment at the two surgical targets. Supplementary analyses suggested that decrements in select neuropsychological domains following DBS are unrelated to age or post-surgical reduction in dopaminergic medication dose. Findings are discussed with reference to possible causes of neuropsychological decline and the need for further controlled studies of specific neuropsychological effects of DBS.

A randomized trial of low-frequency right-prefrontal-cortex transcranial magnetic stimulation as augmentation in treatment-resistant major depression

Low-frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) appears to have antidepressant properties although the effectiveness of this treatment in clinical practice has not been assessed nor have the optimal stimulation parameters been adequately defined. A total of 130 patients with treatment-resistant depression were randomized to either 1- or 2-Hz rTMS over the right prefrontal cortex (PFC) for 2 wk with a possible further 2 wk extension. Non-responders were randomized to either 5- or 10-Hz left PFC rTMS. Overall, 66 patients (51%) achieved response and 35 (27%) remission criteria. For right-sided treatment, depression significantly improved but there was no between-group difference. Twenty-eight (42%) patients in the 1-Hz group and 33 (53%) patients in the 2-Hz group achieved response criteria (chi2=1.40, p>0.05). Depression symptom scores also improved for patients who crossed over to left-sided treatment but there was no significant difference in response between 5- and 10-Hz rTMS. Despite a heterogeneous sample, a significant proportion of patients met clinical response criteria following treatment but response to 1 and 2 Hz did not differ. 2-Hz right PFC rTMS has antidepressant properties but offers no advantage over 1 Hz despite doubling pulse number.

Evoked potentials following unilateral ECT. II. The flash evoked potential

The flash evoked potential (VEP) was recorded in 16 depressed patients before, during and for 0.5 h following administration of unilateral ECT. In 14 the recordings were made following right ECT and in 3 following left ECT. One patient was recorded after right- and left-sided treatments administered on separate occasions. While the patients were conscious, responses were averaged with eyes open and eyes closed. During anaesthesia, ictus and post-ictal coma the response to repetitive stimulation through closed eyes was recorded continuously in sequential runs. Consistent latency differences between VEPs with eyes open and closed were established in the runs prior to treatment. In post-ictal coma there was a marked asymmetry in the response from the two sides. Component P140 , in particular, was significantly smaller and later over the side which received ECT. On average, these symmetries lasted less than 15 min following the treatment. A significant latency increase, common to both hemispheres, was found at the end of the recording session.

EEG immediately after unilateral ECT

EEG was continuously recorded in 15 patients for a period extending from just before to 1/2 hour after unilateral ECT. Fourier analysis was performed on the EEG following 15 right-sided treatments and five left-sided treatments. During the induced seizure, epileptic slow-wave activity had significantly greater power on the treated side. Immediately after the seizure, there was significantly more delta activity and less alpha and beta activity on the treated side. This asymmetry, though becoming less marked, was usually still present at the end of the recording period. Analysis of other variables associated with the treatment showed that there was a significant correlation between the time to eye-opening after ECT and both the duration of the seizure and the amount of anaesthetic administered. The similarity between these induced unilateral seizures and unilateral seizures occurring spontaneously in some epileptics is discussed.