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Radiation therapy is an integral component of adjuvant therapy in women who undergo breast conservative surgery, decreasing the likelihood of tumor recurrence and extending survival. The likelihood of tumor recurrence is highest within a proximity of the lumpectomy cavity, which prompted the idea of partial breast irradiation in place of the usual standard-of-care treatment with external beam whole breast radiation therapy. Targeted intraoperative radiation therapy (TARGIT-A) is a multicenter trial initially developed in 1999 and designed as a randomized clinical trial comparing whole breast radiation therapy to risk-adapted intraoperative radiation therapy (IORT). TARGIT-A recruited its first patient in March 2000, with the study concluding in 2012. At a median follow-up of 8.6 years, the prepathology TARGIT-A trial noted results to be noninferior to external beam radiation therapy, with no statistically significant difference in ipsilateral breast tumor recurrence, mastectomy-free survival, distant disease-free survival, or breast cancer-specific mortality. These results are consistent with the majority of retrospective and prospective trials. Risk-adapted IORT, as performed in the prospective randomized TARGIT-A trial, gives level 1 evidence that this approach is a standard option in the treatment of breast cancer., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

We evaluated how race, insurance status, and other sociodemographic, tumor, and treatment variables influenced the response to neoadjuvant chemotherapy (NAC) in breast cancer. We performed an IRB-approved retrospective review of 298 breast cancer patients treated with NAC from 2006-2018 at our institution. Univariable and multivariable binary logistic regression analyses were performed to estimate the effects of race, insurance status, and other variables on outcomes. Outcomes of interest included pathologic complete response (pCR), partial response (pPR), and any response (pCR or pPR). Sixty-nine patients (23%) identified as African American. One hundred sixty-eight (57%) patients had private insurance, 71 (24%) had Medicare, 40 (14%) had Medicaid, and 17 (6%) had no insurance. Insurance status was a predictor for any clinical response to NAC in both univariable and multivariable analyses ( p <0.01), where odds of pCR or pPR were lower for patients with Medicare compared to private insurance (OR 0.32, 95% CI: 0.15-0.70, p <0.01). Other variables significant for the response to NAC included body mass index, hormone receptor status, clinical group stage, and Ki-67. Race did not influence the response to NAC. Insurance provider, body mass index, hormone receptor status, clinical group stage, and Ki-67 may be useful predictors of treatment outcomes. Future studies that assess the impacts of insurance status and other identified factors on treatment response may help evaluate outcomes in at-risk populations with factors that preclude full benefit from NAC., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2021, Ho et al.)

Purpose/objective: The objective of this study was to assess the association between pretreatment p53, hypoxia inducible factor 1a (HIF1a), Ki-67, carbonic anhydrase-9 (CA-9), and glucose transporter 1 (GLUT1) expression in locally advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), local-regional control (LC), and distant metastases-free survival (DMFS)., Patients and Methods: Twenty-eight patients treated definitively and consecutively for cervical cancer with CRT had p53, HIF1a, Ki-67, CA-9, and GLUT1 protein expression assessed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes. Outcomes were stratified by p53 (H-score: <15 vs. ≥15), HIF1a (H-score: <95 vs. ≥95), Ki-67 (labeling index <41% vs. ≥41%), CA-9 (H-score: <15 vs. ≥15), and GLUT1 (H-score: <175 vs. ≥175) expression. OS, PFS, LC, and DMFS rates were calculated using the Kaplan-Meier method, and differences between groups were evaluated by the log-rank test., Results: Notable clinical characteristics of the cohort included median age of 51 years (range: 32 to 74 y), FIGO stage IIB disease (57.2%), clinical node-negative disease (64.3%), squamous cell carcinoma (89.3%), and adenocarcinoma (10.7%). Treatment outcomes included 5-year OS (57.2%), PFS (48.1%), LC (72.1%), and DMFS (62.9%). For HIF1a H-score <95 and ≥95, the 5-year OS (52.0% and 68.4%, P=0.58), PFS (53.0% and 40.9%, P=0.75), LC (71.6% and 68.2%, P=0.92), and DMFS (59.7% and 52.0%, P=0.91) were not significantly different. For Ki-67 labeling index <41% and ≥41%, the 5-year OS (44.9% and 66.6%, P=0.35), PFS (38.9% and 55.4%, P=0.53), LC (57.7% and 85.7%, P=0.22), and DMFS (67.3% and 61.0%, P=0.94) were not significantly different. For CA-9 H-score <15 and ≥15, the 5-year OS (54.4% and 66.7%, P=0.39), PFS (57.3% and 40.0%, P=0.87), LC (70.0% and 70.0%, P=0.95), and DMFS (70.0% and 46.7%, P=0.94) were not significantly different. For GLUT1 H-score <175 and ≥175, the 5-year OS (43.6% and 43.6%, P=0.32), PFS (55.6% and 49.5%, P=0.72), LC (72.9% and 71.5%, P=0.97), and DMFS (62.5% and 59.6%, P=0.76) were not significantly different. For p53, H-score <15 and ≥15, the 5-year OS (62% and 53%), PFS (63% and 30.3%), LC (87.5% and 52%), and DMFS (79.6% and 41.6%)., Conclusions: In this study population, HIF1a, Ki-67, CA-9, and GLUT1 expression did not predict treatment response or outcomes in locally advanced cervical cancer patients treated definitively with CRT. There was a nonstatistically significant trend towards worse outcomes with p53 expression., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Nuclear factor kappa B (NFkB) is a transcription factor shown to confer treatment resistance in tumors. A previous report suggested an association between pretreatment NFkB and poorer outcomes for cervical cancer patients treated with chemoradiation therapy (CRT). We aimed to validate their findings in a larger patient cohort., Materials and Methods: This Institutional Review Board approved study included patients with locally advanced cervical cancer patients treated with CRT. Evaluation of both nuclear and cytoplasmic immunoreactivity for NFkB was scored semiquantitatively by 3 pathologists. Cytoplasmic positivity incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H-score), whereas nuclear positivity was assessed by percentage of positive cells. Outcomes were stratified by NFkB overexpression and tumor characteristics. Overall survival (OS), progression-free survival (PFS), distant metastases-free survival (DMFS), and local regional control (LC) were obtained using Kaplan-Meier and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained using Cox regression for both univariate and multivariate analyses., Results: The mean age was 51 years old and most (78.57%) had locally advanced disease. Five-year OS, PFS, LC, and DMFS in the entire cohort were 57.18% (confidence interval [CI], 34.06%-74.82%), 48.07% (CI, 25.50%-67.52%), 72.11% (CI, 49.96%-85.73%), and 62.85% (CI, 36.33%-80.82%), respectively. There was no significant association between NFkB expression (H-index ≥180) and 3-year and 5-year OS (P-value=0.34), PFS (P-value=0.21), LC (P-value=0.86), or DMFS (P-value=0.18)., Conclusions: Our study demonstrated that cytoplasmic NFkB-p65 expression (H-index ≥180) was associated with a nonstatistically significant trend toward poor clinical outcomes in locally advanced cervical cancer patients treated definitively with CRT.

The societal benefits of understanding climate change through the identification of global carbon dioxide sources and sinks led to the recommendation for NASA's Active Sensing of Carbon Dioxide Emissions over Nights, Days, and Seasons space-based mission for global carbon dioxide measurements. For more than 15 years, the NASA Langley Research Center has developed several carbon dioxide active remote sensors using the differential absorption lidar technique operating at 2- μ m wavelength. Recently, an airborne double-pulsed integrated path differential absorption lidar was developed, tested, and validated for atmospheric carbon dioxide measurement. Results indicated 1.02% column carbon dioxide measurement uncertainty and 0.28% bias over the ocean. Currently, this technology is progressing toward triple-pulse operation targeting both atmospheric carbon dioxide and water vapor-the dominant interfering molecule on carbon dioxide remote sensing. Measurements from the double-pulse lidar and the advancement of the triple-pulse lidar development are presented. In addition, measurement simulations with a space-based IPDA lidar, incorporating new technologies, are also presented to assess feasibility of carbon dioxide measurements from space.

Purpose: This study aimed to assess the association between pretreatment c-Met overexpression in local-regional advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), distant metastases (DM) control, and local-regional control (LC)., Patients and Methods: This Institutional Review Board-approved study included cervical cancer patients treated definitively and consecutively with CRT. Evaluation of cytoplasmic immunoreactivity for c-Met was performed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes, and incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H score). Treatment outcomes were reviewed and reported. Outcomes were stratified by c-Met overexpression and tumor characteristics. OS, PFS, LC, and DC rates were obtained via the Kaplan-Meier method and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained via Cox regression for both univariate and multivariate analyses., Results: The 5-year OS, PFS, LC, and DC were 57.18%, 48.07%, 72.11%, and 62.85%, respectively. Ten (35.7%) and 18 patients (64.3%) had c-Met H index >30 and<30, respectively. c-Met overexpression was significantly associated with worse 3- and 5-year OS (P=0.003), PFS (P=0.002), LC (P=0.01), and DC (P=0.0003). Patients with c-Met overexpression had a hazard ratio of 6.297, 5.782, 6.28, and 18.173 for the risks of death, disease progression, local recurrence, and DM, respectively., Conclusion: c-Met overexpression could be a potential predictive marker and therapeutic target for local-regional advanced cervical cancer patients treated definitively with CRT.

Sustained high-quality column carbon dioxide (CO 2 ) atmospheric measurements from space are required to improve estimates of regional and continental-scale sources and sinks of CO 2 . Modeling of a space-based 2 μm, high pulse energy, triple-pulse, direct detection integrated path differential absorption (IPDA) lidar was conducted to demonstrate CO 2 measurement capability and to evaluate random and systematic errors. Parameters based on recent technology developments in the 2 μm laser and state-of-the-art HgCdTe (MCT) electron-initiated avalanche photodiode (e-APD) detection system were incorporated in this model. Strong absorption features of CO 2 in the 2 μm region, which allows optimum lower tropospheric and near surface measurements, were used to project simultaneous measurements using two independent altitude-dependent weighting functions with the triple-pulse IPDA. Analysis of measurements over a variety of atmospheric and aerosol models using a variety of Earth's surface target and aerosol loading conditions were conducted. Water vapor (H 2 O) influences on CO 2 measurements were assessed, including molecular interference, dry-air estimate, and line broadening. Projected performance shows a <0.35  ppm precision and a <0.3  ppm bias in low-tropospheric weighted measurements related to column CO 2 optical depth for the space-based IPDA using 10 s signal averaging over the Railroad Valley (RRV) reference surface under clear and thin cloud conditions.

Purpose  This study aims to report long-term clinical outcomes after Gamma Knife radiosurgery (GKRS) for intracranial grade 2 meningiomas. Methods  In this Institutional Review Board approved study, we reviewed records of all patients with grade 2 meningiomas treated with GKRS between 1998 and 2014. Results  A total of 97 postoperative histopathologically confirmed grade 2 meningiomas in 75 patients were treated and are included in this study. After a mean follow-up of 41 months, 28 meningiomas had local recurrence (29.79%). Median time to local recurrence was 89 months (mean: 69, range: 47-168). The 3- and 5-year actuarial local control (LC) rates were 68.9 and 55.7%, respectively. The 3- and 5-year overall survival rates were 88.6 and 81.1%, respectively. There was a trend toward worse LC with tumors treated with radiation doses ≤ 13 versus > 13 Gy. There was no radiation necrosis or second malignant tumors noted in our series. Conclusion  This report, one of the largest GKRS series for grade 2 meningiomas, demonstrates that GKRS is a safe and effective treatment modality for patients with grade 2 meningiomas with durable tumor control and minimal toxicity. Adjuvant GKRS could be considered as a reasonable treatment approach for patients with grade 2 meningiomas.

Objective: The purpose of this study was to report the treatment-induced adverse events and cosmetic and treatment outcomes of accelerated partial breast irradiation (APBI) delivered with the MammoSite radiation therapy system (RTS) in breast cancer patients undergoing breast-conserving therapy (BCT)., Methods: This is a prospective clinical trial that was approved by the institutional review board. The study included female breast cancer patients undergoing breast-conserving therapy in the form of surgery and APBI delivered with the MammoSite RTS. Patients and tumor characteristics, treatment-induced acute adverse events based on the Common Toxicity Criteria for Adverse Events (CTCAE) version 2.0, chronic AEs according to Radiation Therapy Oncology Group (RTOG) scale, treatment outcomes (including local control, disease-free survival, and overall survival), and cosmetic outcomes are reported., Results: The study included 36 eligible patients treated consecutively in our institution between November 2003 and August 2009. The age range was 45-83 years. A total of 29 patients had invasive disease (median size 1.1 cm), while 7 patients had in situ disease only (median size 0.8 cm). The skin distance in most of the patients (91.7 %) was ≥1 cm; only three patients (8.3 %) had skin distance <1 cm. The median balloon diameter was 5 cm (range 4-6 cm). At a median follow-up of 42 months (range 4-65 months), local control, disease-free survival, and overall survival were 100 %. None of the patients experienced any grade 3 or 4 toxicities; 16.7 and 5.6 % of the patients had late grade 2 fibrosis and telangiectasia, respectively. At last follow-up, cosmetic outcome was rated as good or excellent in 94 % of the patients., Conclusion: APBI delivered with the MammoSite RTS is a feasible, tolerable, and effective treatment modality. Multicenter, randomized, controlled clinical trials with a larger number of patients are required for verification.

Double-pulsed 2-μm integrated path differential absorption (IPDA) lidar is well suited for atmospheric CO 2 remote sensing. The IPDA lidar technique relies on wavelength differentiation between strong and weak absorbing features of the gas normalized to the transmitted energy. In the double-pulse case, each shot of the transmitter produces two successive laser pulses separated by a short interval. Calibration of the transmitted pulse energies is required for accurate CO 2 measurement. Design and calibration of a 2-μm double-pulse laser energy monitor is presented. The design is based on an InGaAs pin quantum detector. A high-speed photoelectromagnetic quantum detector was used for laser-pulse profile verification. Both quantum detectors were calibrated using a reference pyroelectric thermal detector. Calibration included comparing the three detection technologies in the single-pulsed mode, then comparing the quantum detectors in the double-pulsed mode. In addition, a self-calibration feature of the 2-μm IPDA lidar is presented. This feature allows one to monitor the transmitted laser energy, through residual scattering, with a single detection channel. This reduces the CO 2 measurement uncertainty. IPDA lidar ground validation for CO 2 measurement is presented for both calibrated energy monitor and self-calibration options. The calibrated energy monitor resulted in a lower CO 2 measurement bias, while self-calibration resulted in a better CO 2 temporal profiling when compared to the in situ sensor.

Introduction: This study aims to report the outcome and toxicity of combined hyperthermia (HT) and radiation therapy (RT) in treatment of locally advanced or loco-regionally recurrent breast cancer., Patients and Methods: Patients treated with HT and RT from January 1991 to December 2007 were reviewed. RT doses for previously irradiated patients were > 40 Gy and for RT naïve patients > 60 Gy, at 1.8-2 Gy/day. HT was planned for 2 sessions/week, immediately after RT, for a minimum of 20 min and for > 4 sessions. Superficial or interstitial applicators were used with temperature measured by superficial or interstitial thermistors based on target thickness. HT treatment was assessed by thermal equivalent dose (TED), > 42.5 °C and > 43 °C. Endpoints included treatment response, lack of local progression (local control), and survival., Results: 127 patients received HT and RT to 167 sites. These included the intact breast (24.4%), chest wall/skin (67.7%), and breast/chest wall and nodes (7.9%). At a median follow-up of 13 months (mean 30 ± 38), improved overall survival was significantly associated with increasing RT dose (p < 0.0001), median TED 42.5 °C ≥ 200 min (p = 0.003), and local control (p = 0.0002). Local control at last follow-up was seen in 55.1% of patients. Complete response was significantly associated with median TED 42.5 °C ≥ 200 min (p = 0.002) and median TED 43 °C ≥ 100 min (p = 0.03)., Conclusion: HT and RT are effective for locally advanced or recurrent breast cancer in patients that have been historically difficult to treat by RT alone. Over 50% of patients achieved control of locoregional disease. Overall survival was improved with local control., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: This study aimed to evaluate the role of pretreatment 18F-Fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET-CT) as a predictor of disease-free survival (DFS), and overall survival (OS) in locally advanced nasopharyngeal carcinoma (LANPC) patients treated definitively with docetaxel-based induction chemotherapy followed by concurrent chemoradiation (CRT)., Materials and Methods: This is a retrospective study approved by the institutional review board and included LANC patients treated definitively and consecutively between January 2008 and December 2012 with induction chemotherapy; docetaxel, cisplatin, and 5-flurouracil (TPF) followed by CRT utilizing weekly cisplatin. All patients had baseline pretreatment 18 F-FDG-PET-CT. We studied the association between the baseline primary tumor maximum standardized uptake value (SUVmax) and the treatment outcomes; OS and DFS., Results: The study included 70 eligible LANPC patients. The 4-year OS and DFS rates were 86.7% and 78.6%, respectively. The median OS and DFS intervals were not reached. On a univariate analysis, the 4-years DFS was significantly higher in patients with pretreatment SUVmax <8 compared versus ≥ 8 (95% vs 57.7%, P=0.002). Furthermore, DFS was significantly correlated with pretreatment T stage (P=0.01), N stage (P=0.02), treatment response (P<0.001) and treatment breaks (P<0.001). On a multivariate analysis, the SUVmax category was the only factor correlated with 4-year DFS (Hazard ratio=10.2, 95% C I 1.3-116.8, P=0.035) but not OS (P=0.085)., Disclosure Statement: There is no actual or potential conflict of interest with the production and publication of this work. No author has a direct or indirect commercial financial incentive associated with the publication of this article., Conclusion: This study shows that the pretreatment primary tumor 18 F-FDG-PET-CT SUVmax is a potential independent prognostic predictor of clinical outcomes in patients with LANC treated definitively with TPF induction chemotherapy followed by CRT. Further controlled clinical trials are worthwhile.