Background: This study determined the reliability of topographic motor cortical maps and MEP characteristics in the extensor digitorum communis (EDC) evoked by single-pulse TMS among patients with chronic stroke. Methods: Each of ten patients was studied on three occasions. Measures included location of the EDC hotspot and center of gravity (COG), threshold of activation and average amplitude of the hotspot, number of active sites, map volume, and recruitment curve (RC) slope. Results: Consistent intrahemispheric measurements were obtained for the three TMS mapping sessions for all measured variables. No statistically significant difference was observed between hemispheres for the number of active sites, COG distance or the RC slope. The magnitude and range of COG movement between sessions were similar to those reported previously with this muscle in able-bodied individuals. The average COG movement over three sessions in both hemispheres was 0.90 cm. The average COG movement in the affected hemisphere was 1.13 (± 0.08) cm, and 0.68 (± 0.04) cm) for the less affected hemisphere. However, significant interhemispheric variability was seen for the average MEP amplitude, normalized map volume, and resting motor threshold. Conclusion: The physiologic variability in some TMS measurements of EDC suggest that interpretation of TMS mapping data derived from hemiparetic patients in the chronic stage following stroke should be undertaken cautiously. Irrespective of the muscle, potential causes of variability should be resolved to accurately assess the impact of pharmacological or physical interventions on cortical organization as measured by TMS among patients with stroke.
Background:
We previously reported a prospective study showing axillary lymph node dissection (ALND) is associated with increased breast skin thickening during and 6 weeks post-radiation therapy (RT), and now report ALND’s long-term impact at 1 year.
Methods:
Among 66 women who received whole breast RT after lumpectomy, objective ultrasound measurements of epidermal thickness over four quadrants of the treated breast were measured at five time points: before RT, week 6 of RT, and 6 weeks, 6 months, and 1 year post-RT. Skin thickness ratio (STRA) was generated by normalizing for corresponding measurements of the contralateral breast.
Results:
A total of 2,436 ultrasound images were obtained. Among 63 women with evaluable data at 1 year, mean STRA significantly increased at 6 months (absolute mean increase of 65%, SD 0.054), and remained elevated at 1 year post-RT (absolute mean increase of 44%, SD 0.048). In multivariable analysis, ALND compared to sentinel lymph node biopsy, longer interval between surgery and RT, increased baseline STRA, and Caucasian race predicted for more severe changes in STRA at 1 year compared to baseline (all P < .05).
Conclusions:
In the setting of whole breast RT, our findings suggest that ALND has long-term repercussions on breast skin thickening.
Purpose: Radical treatment of metastases with stereotactic body radiation therapy (SBRT) is commonly implemented in patients receiving concurrent immune checkpoint inhibition (ICI), despite limited safety and toxicity data. The purpose of this study was to evaluate the safety and tolerability of lung SBRT with concurrent ICI. Methods and Materials: Records from a single academic institution were reviewed to identify patients treated with lung SBRT and concurrent (within 30 days) ICI; a contemporaneous cohort receiving lung SBRT alone was included for reference. Treatment-related adverse effects occurring within 30 days (acute) and 180 days (subacute) of SBRT were evaluated. Results: Our study included 117 patients; 54 received SBRT with concurrent ICI (56 courses, 69 target lesions), and 63 received SBRT alone (68 courses, 79 lesions). Median follow-up was 9.2 months in the SBRT + ICI cohort. Among the patients, 67.9% received ICI monotherapy, 17.9% ICI/chemotherapy, and 14.3% ICI/ICI combinations; 25% received ICI between SBRT fractions, and 42.9% received ICI both before and after SBRT. The risk of grade 3 pneumonitis was higher in the SBRT + ICI versus SBRT alone cohort (10.7% vs 0%, P <.01) and any-grade pneumonitis was similar (33.9% vs 27.9%, SBRT + ICI vs SBRT, P =.47). The risk of any-grade pneumonitis appeared elevated with ICI/ICI combinations (62.5% vs 29.2%). Receipt of ICI, planning treatment volume, and lobes involved in SBRT were linked to high-grade pneumonitis. Subacute grade 3+ adverse effects occurred in 26.8% of SBRT + ICI and 2.9% of SBRT-alone patients. Conclusions: Overall, concurrent lung SBRT + ICI is safe. Given the clinically meaningful risk of pneumonitis, closer monitoring should be considered for SBRT + ICI patients, especially those receiving radiation therapy with ICI/ICI combinations.
Background
The discovery of molecular markers associated with various breast cancer subtypes has greatly improved the treatment and outcome of breast cancer patients. Unfortunately, breast cancer cells acquire resistance to various therapies. Mounting evidence suggests that resistance is rooted in the deregulation of the G1 phase regulatory machinery.
Methods
To address whether deregulation of the G1 phase regulatory machinery contributes to radiotherapy resistance, the MCF10A immortalized human mammary epithelial cell line, ER-PR-Her2+ and ER-PR-Her2- breast cancer cell lines were irradiated. Colony formation assays measured radioresistance, while immunocytochemistry, Western blots, and flow cytometry measured the cell cycle, DNA replication, mitosis, apoptosis, and DNA breaks.
Results
Molecular markers common to all cell lines were overexpressed, including cyclin A1 and cyclin D1, which impinge on CDK2 and CDK4 activities, respectively. We addressed their potential role in radioresistance by generating cell lines stably expressing small hairpin RNAs (shRNA) against CDK2 and CDK4. None of the cell lines knocked down for CDK2 displayed radiosensitization. In contrast, all cell lines knocked down for CDK4 were significantly radiosensitized, and a CDK4/CDK6 inhibitor sensitized MDA-MB-468 to radiation induced apoptosis. Our data showed that silencing CDK4 significantly increases radiation induced cell apoptosis in cell lines without significantly altering cell cycle progression, or DNA repair after irradiation. Our results indicate lower levels of phospho-Bad at ser136 upon CDK4 silencing and ionizing radiation, which has been shown to signal apoptosis.
Conclusion
Based on our data we conclude that knockdown of CDK4 activity sensitizes breast cancer cells to radiation by activating apoptosis pathways.
Background
This study determined the reliability of topographic motor cortical maps and MEP characteristics in the extensor digitorum communis (EDC) evoked by single-pulse TMS among patients with chronic stroke.
Methods
Each of ten patients was studied on three occasions. Measures included location of the EDC hotspot and center of gravity (COG), threshold of activation and average amplitude of the hotspot, number of active sites, map volume, and recruitment curve (RC) slope.
Results
Consistent intrahemispheric measurements were obtained for the three TMS mapping sessions for all measured variables. No statistically significant difference was observed between hemispheres for the number of active sites, COG distance or the RC slope. The magnitude and range of COG movement between sessions were similar to those reported previously with this muscle in able-bodied individuals. The average COG movement over three sessions in both hemispheres was 0.90 cm. The average COG movement in the affected hemisphere was 1.13 (± 0.08) cm, and 0.68 (± 0.04) cm) for the less affected hemisphere. However, significant interhemispheric variability was seen for the average MEP amplitude, normalized map volume, and resting motor threshold.
Conclusion
The physiologic variability in some TMS measurements of EDC suggest that interpretation of TMS mapping data derived from hemiparetic patients in the chronic stage following stroke should be undertaken cautiously. Irrespective of the muscle, potential causes of variability should be resolved to accurately assess the impact of pharmacological or physical interventions on cortical organization as measured by TMS among patients with stroke.
Purpose: Stereotactic radiosurgery (SRS) is increasingly used in the management of patients with resected brain metastases (rBMs). A significant complication of this therapy can be radiation necrosis (RN). Despite radiation therapy dose de-escalation and the delivery of several rather than a single dose fraction, rates of RN after SRS for rBMs remain high. We evaluated the dosimetric parameters associated with radiographic RN for rBMs.
Methods and Materials: From 2008 to 2016, 55 rBMs at a single institution that were treated postoperatively with 5-fraction linear accelerator–based SRS (25-35 Gy) with minimum 3 months follow-up were evaluated. For each lesion, variables recorded included radiation therapy dose to normal brain, location and magnitude of hotspots, clinical target volume (CTV), and margin size. Hotspot location was stratified as within the tumor bed alone (CTV) or within the planning target volume (PTV) expansion margin volume (PTV minus CTV). Cumulative incidence with competing risks was used to estimate rates of RN and local recurrence. Optimal cut-points predicting for RN for hotspot magnitude based on location were identified via maximization of the log-rank test statistic.
Results: Median age for all patients was 58.5 years. For all targets, the median CTV was 17.53 cm3, the median expansion margin to PTV was 2 mm, and the median max hotspot was 111%. At 1 year, cumulative incidence of radiographic RN was 18.2%. Univariate analysis showed that max hotspots with a hazard ratio of 3.28 (P = .045), hotspots within the PTV expansion margin with relative magnitudes of 105%, 110%, and 111%, and an absolute dose of 33.5 Gy predicted for RN (P = .029, P = .04, P = .038, and P = .0488, respectively), but hotspots within the CTV did not.
Conclusions: To our knowledge, this is the first study that investigated dosimetric factors that predict for RN after 5-fraction hypofractionated SRS for rBM. Hotspot location and magnitude appear important for predicting RN risk, thus these parameters should be carefully considered during treatment planning.
BACKGROUND: The purpose of the current study was to evaluate the impact of radiotherapy (RT) among women aged≥70 years with T1-2N0 estrogen receptor (ER)-negative breast cancer using Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data.
METHODS: The study included 3432 women, 2850 of whom received and 582 of whom did not receive RT after breast-conserving surgery. Outcomes were estimated by the cumulative incidence method and compared with the Gray test. The Fine and Gray subdistribution hazard regression models were used to assess the impact of RT and other variables.
RESULTS: Women who received RT were more commonly aged < 75 years (42% vs 16%), had T1 tumors (78% vs 65%), ductal carcinoma histology (91% vs 88%), a Charlson-Deyo Comorbidity Index of 0 (41% vs 25%), and had received chemotherapy (29% vs 12%). The 5-year cumulative incidence of mastectomy and breast cancer-specific death for patients who received versus those did not receive adjuvant RT was 4.9% and 8.3% versus 10.8% and 24.1%, respectively (P < .001). On multivariable analysis, the omission of RT was found to be an independent predictor of an increased risk of mastectomy (hazard ratio, 2.33; 95% confidence interval, 1.56-3.49). Among women aged≥80 years or with T1N0 tumors, the mastectomy incidence with or without receipt of RT was 3.4% vs. 6.9%, and 5.3% vs 7.7%, respectively.
CONCLUSIONS: The use of adjuvant RT after breast-conserving surgery in older women with T1-2N0 estrogen receptor-negative breast cancer is associated with a reduced incidence of future mastectomy and breast cancer death. The magnitude of benefit may be small for women aged ≥80 years or those with T1 tumors.