Feasibility study of a space-based high pulse energy 2 µm CO2 IPDA lidar.

Sustained high-quality column carbon dioxide (CO2) atmospheric measurements from space are required to improve estimates of regional and continental-scale sources and sinks of CO2. Modeling of a space-based 2 µm, high pulse energy, triple-pulse, direct detection integrated path differential absorption (IPDA) lidar was conducted to demonstrate CO2 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 CO2 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 (H2O) influences on CO2 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 CO2 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.

Double-pulse 2-µm integrated path differential absorption lidar airborne validation for atmospheric carbon dioxide measurement.

Field experiments were conducted to test and evaluate the initial atmospheric carbon dioxide (CO2) measurement capability of airborne, high-energy, double-pulsed, 2-µm integrated path differential absorption (IPDA) lidar. This IPDA was designed, integrated, and operated at the NASA Langley Research Center on-board the NASA B-200 aircraft. The IPDA was tuned to the CO2 strong absorption line at 2050.9670 nm, which is the optimum for lower tropospheric weighted column measurements. Flights were conducted over land and ocean under different conditions. The first validation experiments of the IPDA for atmospheric CO2 remote sensing, focusing on low surface reflectivity oceanic surface returns during full day background conditions, are presented. In these experiments, the IPDA measurements were validated by comparison to airborne flask air-sampling measurements conducted by the NOAA Earth System Research Laboratory. IPDA performance modeling was conducted to evaluate measurement sensitivity and bias errors. The IPDA signals and their variation with altitude compare well with predicted model results. In addition, off-off-line testing was conducted, with fixed instrument settings, to evaluate the IPDA systematic and random errors. Analysis shows an altitude-independent differential optical depth offset of 0.0769. Optical depth measurement uncertainty of 0.0918 compares well with the predicted value of 0.0761. IPDA CO2 column measurement compares well with model-driven, near-simultaneous air-sampling measurements from the NOAA aircraft at different altitudes. With a 10-s shot average, CO2 differential optical depth measurement of 1.0054±0.0103 was retrieved from a 6-km altitude and a 4-GHz on-line operation. As compared to CO2 weighted-average column dry-air volume mixing ratio of 404.08 ppm, derived from air sampling, IPDA measurement resulted in a value of 405.22±4.15 ppm with 1.02% uncertainty and 0.28% additional bias. Sensitivity analysis of environmental systematic errors correlates the additional bias to water vapor. IPDA ranging resulted in a measurement uncertainty of <3 m.

Self-calibration and laser energy monitor validations for a double-pulsed 2-µm CO2 integrated path differential absorption lidar application.

Double-pulsed 2-µm integrated path differential absorption (IPDA) lidar is well suited for atmospheric CO2 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 CO2 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 CO2 measurement uncertainty. IPDA lidar ground validation for CO2 measurement is presented for both calibrated energy monitor and self-calibration options. The calibrated energy monitor resulted in a lower CO2 measurement bias, while self-calibration resulted in a better CO2 temporal profiling when compared to the in situ sensor.

Evaluation of an airborne triple-pulsed 2 µm IPDA lidar for simultaneous and independent atmospheric water vapor and carbon dioxide measurements.

Water vapor and carbon dioxide are the most dominant greenhouse gases directly contributing to the Earth's radiation budget and global warming. A performance evaluation of an airborne triple-pulsed integrated path differential absorption (IPDA) lidar system for simultaneous and independent monitoring of atmospheric water vapor and carbon dioxide column amounts is presented. This system leverages a state-of-the-art Ho:Tm:YLF triple-pulse laser transmitter operating at 2.05 µm wavelength. The transmitter provides wavelength tuning and locking capabilities for each pulse. The IPDA lidar system leverages a low risk and technologically mature receiver system based on InGaAs pin detectors. Measurement methodology and wavelength setting are discussed. The IPDA lidar return signals and error budget are analyzed for airborne operation on-board the NASA B-200. Results indicate that the IPDA lidar system is capable of measuring water vapor and carbon dioxide differential optical depth with 0.5% and 0.2% accuracy, respectively, from an altitude of 8 km to the surface and with 10 s averaging. Provided availability of meteorological data, in terms of temperature, pressure, and relative humidity vertical profiles, the differential optical depth conversion into weighted-average column dry-air volume-mixing ratio is also presented.

Anti-aquaporin-4 immunoglobulin G/anti-myelin oligodendrocyte glycoprotein immunoglobulin G double-positive paraneoplastic neurological syndrome in a patient with triple-negative breast cancer.

We report a rare case of paraneoplastic neurological syndrome with dual seropositivity of anti-aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in a 40 year-old woman with metastatic triple-negative breast cancer. She received multiple lines of anti-neoplastic treatment, including immunotherapy with pembrolizumab, as well as cytotoxic chemotherapy. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis followed by left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid analysis during both episodes showed normal glucose and protein, and elevated white blood cell count. Cytology was negative for malignancy. Cerebrospinal fluid was positive for neuromyelitis optica immunoglobulin G antibody anti-aquaporin-4, and autoimmune myelopathy panel was positive for myelin oligodendrocyte glycoprotein antibody. The patient had significant clinical and radiographic improvement after completion of five cycles of plasmapheresis followed by intravenous immunoglobulin. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every 6 months and daily low-dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case shows that these antibodies can occur concurrently and cause clinical features, such as both neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease, in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or cerebrospinal fluid profile negative for leptomeningeal carcinomatosis.

Performance evaluation of a 1.6-µm methane DIAL system from ground, aircraft and UAV platforms.

Methane is an efficient absorber of infrared radiation and a potent greenhouse gas with a warming potential 72 times greater than carbon dioxide on a per molecule basis. Development of methane active remote sensing capability using the differential absorption lidar (DIAL) technique enables scientific assessments of the gas emission and impacts on the climate. A performance evaluation of a pulsed DIAL system for monitoring atmospheric methane is presented. This system leverages a robust injection-seeded pulsed Nd:YAG pumped Optical Parametric Oscillator (OPO) laser technology operating in the 1.645 µm spectral band. The system also leverages an efficient low noise, commercially available, InGaAs avalanche photo-detector (APD). Lidar signals and error budget are analyzed for system operation on ground in the range-resolved DIAL mode and from airborne platforms in the integrated path DIAL (IPDA) mode. Results indicate system capability of measuring methane concentration profiles with <1.0% total error up to 4.5 km range with 5 minute averaging from ground. For airborne IPDA, the total error in the column dry mixing ratio is less than 0.3% with 0.1 sec average using ground returns. This system has a unique capability of combining signals from the atmospheric scattering from layers above the surface with ground return signals, which provides methane column measurement between the atmospheric scattering layer and the ground directly. In such case 0.5% and 1.2% total errors are achieved with 10 sec average from airborne platforms at 8 km and 15.24 km altitudes, respectively. Due to the pulsed nature of the transmitter, the system is relatively insensitive to aerosol and cloud interferences. Such DIAL system would be ideal for investigating high latitude methane releases over polar ice sheets, permafrost regions, wetlands, and over ocean during day and night. This system would have commercial potential for fossil fuel leaks detection and industrial monitoring applications.

Modeling of intensity-modulated continuous-wave laser absorption spectrometer systems for atmospheric CO(2) column measurements.

The focus of this study is to model and validate the performance of intensity-modulated continuous-wave (IM-CW) CO(2) laser absorption spectrometer (LAS) systems and their CO(2) column measurements from airborne and satellite platforms. The model accounts for all fundamental physics of the instruments and their related CO(2) measurement environments, and the modeling results are presented statistically from simulation ensembles that include noise sources and uncertainties related to the LAS instruments and the measurement environments. The characteristics of simulated LAS systems are based on existing technologies and their implementation in existing systems. The modeled instruments are specifically assumed to be IM-CW LAS systems such as the Exelis' airborne multifunctional fiber laser lidar (MFLL) operating in the 1.57 µm CO(2) absorption band. Atmospheric effects due to variations in CO(2), solar radiation, and thin clouds, are also included in the model. Model results are shown to agree well with LAS atmospheric CO(2) measurement performance. For example, the relative bias errors of both MFLL simulated and measured CO(2) differential optical depths were found to agree to within a few tenths of a percent when compared to the in situ observations from the flight of 3 August 2011 over Railroad Valley (RRV), Nevada, during the summer 2011 flight campaign. In addition, the horizontal variations in the model CO(2) differential optical depths were also found to be consistent with those from MFLL measurements. In general, the modeled and measured signal-to-noise ratios (SNRs) of the CO(2) column differential optical depths (τd) agreed to within about 30%. Model simulations of a spaceborne IM-CW LAS system in a 390 km dawn/dusk orbit for CO(2) column measurements showed that with a total of 42 W of transmitted power for one offline and two different sideline channels (placed at different locations on the side of the CO(2) absorption line), the accuracy of the τd measurements for surfaces similar to the playa of RRV, Nevada, will be better than 0.1% for 10 s averages. For other types of surfaces such as low-reflectivity snow and ice surfaces, the precision and bias errors will be within 0.23% and 0.1%, respectively. Including thin clouds with optical depths up to 1, the SNR of the τd measurements with 0.1 s integration period for surfaces similar to the playa of RRV, Nevada, will be greater than 94 and 65 for sideline positions placed +3 and +10 pm, respectively, from the CO(2) line center at 1571.112 nm. The CO(2) column bias errors introduced by the thin clouds are ≤0.1% for cloud optical depth ≤0.4, but they could reach ∼0.5% for more optically thick clouds with optical depths up to 1. When the cloud and surface altitudes and scattering amplitudes are obtained from matched filter analysis, the cloud bias errors can be further reduced. These results indicate that the IM-CW LAS instrument approach when implemented in a dawn/dusk orbit can make accurate CO(2) column measurements from space with preferential weighting across the mid to lower troposphere in support of a future ASCENDS mission.

Impact of Extended Adjuvant Temozolamide Beyond 6 Months in the Management of Glioblastoma Patients.

OBJECTIVES: Our study aimed to assess the benefit of prolonging adjuvant temozolomide (TMZ) therapy beyond 6 cycles in glioblastoma multiform patients. MATERIALS AND METHODS: The medical records of 329 patients in 2 cancer centers in Egypt were reviewed from January 2008 to December 2018 who were diagnosed with diffuse gliomas. Data were collected on patient demographics, presenting complaints, tumor size, treatment modalities (extent of surgery, radiotherapy dose and technique, concomitant TMZ, and the number of adjuvant TMZ cycles), and reported adverse events. RESULTS: In the studied cohort, 105 patients were treated with adjuvant TMZ, 33 patients received <6 cycles (TMZL), 41 patients received the standard 6 cycles (TMZS), and 31 patients received >6 cycles (TMZE). Our results showed the median overall survival in the TMZL arm was 8.47 months compared with 15.83 months in the TMZS arm and 27.33 months in the TMZE arm ( P < 0.001). Furthermore, a median progression-free survival of 6.35 months was reported in the TMZL group versus, 12.7 and 22.90 months in (TMZS) and (TMZE) groups, respectively( P < 0.001). In the multivariate analysis, the extended adjuvant TMZ with a hazard ratio of 3.106 (95% CI: 2.43-14.46; P < 0.001) was statistically significantly associated with a better outcome. CONCLUSIONS: Extended adjuvant TMZ therapy beyond 6 cycles may significantly improve the progression-free survival and overall survival in patients with glioblastoma multiform.

Analytical dosimetric study of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for prostate cancer.

PURPOSE: The study aimed to compare the dosimetric results and treatment delivery efficiency among four techniques to explore the preferred technique in prostate treatment. MATERIALS AND METHODS: 7 IMRT, 9 IMRT, 1 ARC, and 2 ARC plans were created for 30 prostate cancer patients using the Eclipse™ treatment planning system (Varian Medical Systems). All the plans were designed to deliver 80.0 Gy in 40 fractions to the prostate planning target volume (PTV). Target coverage, organs at risk (OARs), number of monitor units, homogeneity, and conformity were compared across the four techniques to assess the quality of the plans. RESULTS: The study revealed better Planning Target Volume (PTV) dose coverage in the VMAT-2A than in the other plans. At the same time, VMAT-2A plans were found to be significantly lower in terms of Bladder and rectum doses than other techniques. In addition, VMAT has the advantage of considerably reducing the number of monitor units and treatment time. CONCLUSION: For prostate cancer, VMAT may offer a favorable dose gradient profile, conformity, and MU and treatment time compared to IMRT.

MRI-guided Real-time Online Gated Stereotactic Body Radiation Therapy for Liver Tumors.

BACKGROUND: Liver tumors are commonly encountered in oncology. The study aimed to assess the impact of magnetic resonance imaging (MRI)-guided stereotactic body radiation therapy (SBRT) (MRgSBRT) on disease-related outcomes and the toxicity profile. METHODS: Patients who received MRgSBRT from 2019 to 2021 for primary and metastatic liver tumors were included in this analysis. The protocol for treatment simulation included Gadoxetate disodium injection followed by a single-dimensional post-exhale MRI (0.35-T MRI linear accelerator) and computed tomography simulation. The patient demographics and treatment-related outcomes were assessed. The time-to-event curves were analyzed for freedom from local progression (FFLP) and overall survival (OS). RESULTS: A total of 35 patients were eligible for analysis with a median age of 70 years (range 25 to 95). The median follow-up was 19.4 months (range 1 to 37 mo). The one-year OS was 77.7%, with an estimated 3 years of 47.9%. Patients with the locally controlled disease had a better median OS of 27.8 months (95% CI [23.8-31.6]) compared with 13.5 months (95% CI [5.6-21.3], P =0.007) in patients with local disease progression. The 1-year FFLP was 95.6%, and 3-year estimated FFLP was 87.1%. Patients who received a radiation dose of biologically equivalent dose≥100 Gy had FFLP of 30.9 months (95% CI [28.7-33.1]) compared with 13.3 months (95% CI [5.3-21.3], P =0.004) in patients who received <100 Gy biologically equivalent dose. CONCLUSION: MRI-guided SBRT provides optimal local control, associated with improved OS in a heavily morbid, pretreated older cohort of patients with reasonable safety profiles.

Multi-Institutional Patterns of Use of Tumor-Treating Fields for Patients with Malignant Pleural Mesothelioma.

(1) Background: The objective of this analysis was to evaluate the device usage rates and patterns of use regarding Tumor-Treating Fields (TTFields) for patients with malignant pleural mesothelioma (MPM) throughout the US. (2) Methods: We evaluated de-identified data from 33 patients with MPM enrolled in FDA-required HDE protocols at 14 institutions across the US from September 2019 to March 2022. (3) Results: The median number of total TTFields usage days was 72 (range: 6-649 days), and the total treatment duration was 160 months for all patients. A low usage rate (defined as less than 6 h per day, 25%) was observed in 34 (21.2%) months. The median TTFields usage in the first 3 months was 12 h per day (range: 1.9-21.6 h), representing 50% (range: 8-90%) of the potential daily duration. The median TTFields usage after 3 months decreased to 9.1 h per day (range: 3.1-17 h), representing 38% (range: 13-71%) of the daily duration, and was lower than usage in the first 3 months (p = 0.01). (4) Conclusions: This study represents the first multicenter analysis of real-world TTFields usage based on usage patterns for MPM patients in clinical practice. The real-world usage level was lower than the suggested daily usage. Further initiatives and guidelines should be developed to evaluate the impact of this finding on tumor control.

Patterns of utilization and clinical adoption of 0.35 Tesla MR-guided radiation therapy in the United States - Understanding the transition to adaptive, ultra-hypofractionated treatments.

Purpose/Objective: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology. Materials/Methods: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems. Results: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details unavailable for 1223 cobalt courses), of which 21.1% were adapted. Ultra-hypofractionation (UHfx) (1-5 fractions) was used in 70.3% of all courses. At least one adaptive fraction was used for 38.5% of courses (average 1.7 adapted fractions/course), with higher oART use in UHfx dose schedules (47.7% of courses, average 1.9 adapted fractions per course). The most commonly treated organ sites were pancreas (20.7%), liver (16.5%), prostate (12.5%), breast (11.5%), and lung (9.4%). Temporal trends show a compounded annual growth rate (CAGR) of 59.6% in treatment courses delivered, with a dramatic increase in use of UHfx to 84.9% of courses in 2020 and similar increase in use of oART to 51.0% of courses. Conclusions: This is the first comprehensive study reporting patterns of utilization among early adopters of MRIdian in the US. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of adaptive radiation therapy has led to a substantial transition to ultra-hypofractionated regimens. 0.35 T-MRgRT has been predominantly used to treat abdominal and pelvic tumors with increasing use of on-table adaptive replanning, which represents a paradigm shift in radiation therapy.

Looking Back: International Practice Patterns in Breast Radiation Oncology From a Case-Based Survey Across 54 Countries During the First Surge of the COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries. MATERIALS AND METHODS: Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies. Changes in RT decision making during the first surge of the pandemic were evaluated across six hypothetical scenarios, including the management of ductal carcinoma in situ (DCIS), early-stage, locally advanced, and metastatic BC. The significance of changes in responses before and during the pandemic was examined using chi-square and McNemar-Bowker tests. RESULTS: One thousand one hundred three ROs from 54 countries completed the survey. Incomplete responses (254) were excluded from the analysis. Most respondents were from the United States (285), Japan (117), Italy (63), Canada (58), and Brazil (56). Twenty-one percent (230) of respondents reported treating at least one patient with BC who was COVID-19-positive. Approximately 60% of respondents reported no change in treatment recommendation during the pandemic, except for patients with metastatic disease, for which 57.7% (636/1,103; P < .0005) changed their palliative practice. Among respondents who noted a change in their recommendation during the first surge of the pandemic, omitting, delaying, and adopting short-course RT were the most frequent changes, with most transitioning to moderate hypofractionation for DCIS and early-stage BC. CONCLUSION: Early in the COVID-19 pandemic, significant changes in global RT practice patterns for BC were introduced. The impact of published results from the FAST FORWARD trial supporting ultrahypofractionation likely confounded the interpretation of the pandemic's independent influence on RT delivery.

Absolute linearity measurement of photodetectors using sinusoidal modulated radiation.

A method is presented for characterizing the linearity of photodetectors based on time-domain analysis of response to sinusoidal excitation. Nonlinearity is quantified solely from the output distortion. Relative response is converted to absolute response by including two calibration points. For low signal level, one calibration point is required, while using dark current as the second point. The response is mapped over a wider range using a series of overlapping sinusoids for calibration transfer. The method is demonstrated with a relatively linear photodiode and a nonlinear phototransistor. A Michelson interferometer is used to generate sinusoidal modulation of a laser source. Results demonstrate the potential of the proposed technique.

Risk-Stratified Intraoperative Radiation Therapy as a Definitive Adjuvant Radiation Therapy Modality for Women With Early Breast Cancer.

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.

Intraoperative radiation therapy for locally advanced and recurrent head and neck cancer.

The purpose of the present study was to present a single institution experience with intraoperative radiation therapy (IORT) for patients with head and neck cancer (HNC). The present study included all patients with HNC treated consecutively with IORT at Loyola University Medical Center between January 2014 and December 2018. Charts were reviewed for patient and tumor characteristics, IORT technical details, IORT-induced adverse events and treatment outcomes. The study included 23 eligible patients. Median patient age was 66 years (range, 34-91 years). Tumor sites included the parotid gland (43%), lymph nodes (43%), oral tongue (9%) and ear (4%). A total of 48% of patients received IORT upfront with or without postoperative adjuvant external beam radiation therapy (EBRT), whereas 52% received salvage IORT after local tumor recurrence. The median prescribed IORT dose was 7.5 Gy (range, 5-14 Gy) in a single fraction prescribed to 5 mm depth with flat applicators (median diameter, 5 cm). A total of 92% of patients did not experience wound healing complications. One patient (4%) developed postoperative acute thromboembolic stroke and a second patient (4%) experienced protracted wound healing. At a median follow up of 36 months (range, 2-81 months), overall survival was 52%. In addition, 48% of patients were reported to have no evidence of disease, and although two had died of unrelated causes, 13% of patients were alive with disease and 39% died with the disease. The local-regional recurrence rate was 39% (median time to local recurrence, 11 months; range, 1-34 months), the rate of distant metastasis was 35% (median time to distant metastasis, 16 months; range, 4-40 months), and 21% of patients had both local-regional recurrence and distant metastases. The percentages of local-regional recurrence and distant metastases among patients receiving salvage IORT were 58 and 50% respectively, compared with 18 and 18% respectively in those receiving upfront IORT with or without adjuvant EBRT. In the present single institution retrospective study, it was concluded that IORT for patients with locally advanced and recurrent HNC was a safe treatment modality, with tumor control comparable to historical IORT data. Larger prospective studies are needed to further assess the utility of IORT in the management of locally advanced and recurrent HNC.

Impact of Race and Health Insurance Status on Response to Neoadjuvant Chemotherapy for Breast Cancer Patients.

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.

Impact of p53, HIF1a, Ki-67, CA-9, and GLUT1 Expression on Treatment Outcomes in Locally Advanced Cervical Cancer Patients Treated With Definitive Chemoradiation Therapy.

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.

Prognostic Significance of Nuclear Factor Kappa B Expression in Locally Advanced Cervical Cancer Patients Treated Definitively With Concurrent Chemoradiation.

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.

Dose-volume relationship for laryngeal substructures and aspiration in patients with locally advanced head-and-neck cancer.

BACKGROUND: Literature has shown a significant relationship between radiation dose to the larynx and swallowing disorders. We prospectively studied the dose-volume relationship for larynx substructures and aspiration. METHODS: Forty nine patients with stage III/IV head-and-neck (H&N) squamous cell carcinoma were prospectively enrolled in this IRB-approved, federally funded study. All patients received IMRT-based chemoradiation therapy (CRT) and were scheduled for videofluorography (VFG) prior to CRT and at 3, 6, 9, 12, and 24 months post-CRT. Twelve laryngeal substructures were contoured in each patient: thyroid cartilage, cricoid cartilage, total epiglottis, suprahyoid epiglottis, infrahyoid epiglottis, total larynx, supraglottic larynx, subglottic larynx, glottic larynx, arytenoids, aryepiglottic (AE) folds, and glossoepiglottic fold. After exclusions, 29 patients were included in the final analysis. Incidence of aspiration at 1 year following CRT was correlated with dose-volume data to laryngeal substructures using logistic regression. RESULTS: The median age was 54 years with 79% being non-smokers. Tumor sites included oropharynx (22), unknown primary (6), and hypopharynx (1). One year following CRT, 10/29 (34%) showed aspiration on VFG. Dose to the AE folds showed the highest correlation with aspiration at 12 months and was significant on multivariate analysis (p = 0.025). A mean dose cutpoint of 6500 cGy or higher to the AE folds was associated with an increased risk of aspiration at 1 year [positive likelihood ratio (+LR) 2.81, positive predictive value (PPV) 60%, negative predictive value (NPV) 92.9%, relative risk (RR) 8.4]. CONCLUSIONS: In this analysis, mean dose to the AE folds was associated with an increased risk of aspiration at 1 year. However, these are hypothesis-generating data that require further research and validation in a larger patient subset.