The Effect of Body Mass Index and Residence in Food Priority Areas on Patterns-of-Care and Cancer Outcomes in Patients With Stage III Non-Small Cell Lung Cancer.

PURPOSE: Patients living in food priority areas (FPAs), where access to healthy meals is challenging, may be at greater risk of nutritional deficits, leading to poorer cancer outcomes. Currently, there are no published data analyzing how FPAs affect patterns-of-care or outcomes for patients with locally advanced non-small cell lung cancer (NSCLC). We aimed to analyze the effect of residing in an FPA on treatments rendered and cancer outcomes in patients with stage III NSCLC treated at a single institution. METHODS AND MATERIALS: This is a retrospective study of 573 patients with locally advanced NSCLC consecutively treated from January 2000 to January 2020. χ2 and Mann-Whitney U tests were performed to determine differences between select variables. Kaplan-Meier analysis and Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence. Cox regression with forward model selection was used for multivariate analysis. RESULTS: Thirty-two percent of patients resided in an FPA (n = 183) and were more likely to self-identify as Black (P < .0001), single (P < .001), <60 years of age (P = .001), and uninsured (P < .0001), with a lower median income (P < .001). Patients in FPAs also had lower mean pre-chemoradiation (CRT) albumin (P = .002), lower pre-CRT body mass index (BMI) (P = .026), and were less likely to receive trimodality therapy (P ≤ .001) compared with patients not living in FPAs. There was no difference in OS or freedom from recurrence between the 2 cohorts. However, in patients with a normal BMI, either pre-CRT (median OS, 18.4 vs 25.0 months; P = .005) or after CRT (15.1 vs 28.1 months, P = .002), residing in an FPA resulted in an OS detriment. CONCLUSIONS: We demonstrated a clear socioeconomic divide in our patient population with stage III NSCLC, where residing in FPAs was associated with less-aggressive therapy and an OS detriment for patients with a normal-weight BMI. We are currently conducting a prospective study characterizing the nutritional needs of patients, particularly those who live in FPAs.

Robust Institutional Support and Collaboration Between Summer Training Programs in Cancer and Biomedicine Drive the Pivot to a Virtual Format in Response to the COVID Pandemic.

Summer internships serve important roles in training the next generation of biomedical researchers and healthcare providers through laboratory and clinical experiences that excite trainees about these fields and help them make informed decisions about career paths. The SARS-CoV-2 (COVID) pandemic and associated physical distancing restrictions precluded implementation of traditional in-person summer curricula and led to the cancellation of many internships across the USA. COVID-related disruptions also created opportunities for trainees to engage in remote research, become proficient in online learning platforms, and explore multidisciplinary topics. These skills are highly relevant to trainees as virtual interfaces occupy an increasingly mainstream role in their professional paths. The response to the COVID pandemic required real-time adaptations at all levels for major biomedical institutions including the University of Maryland Baltimore (UMB). Pivoting summer programs to a virtual format as part of this response provided a "teachable moment" to expose trainees to the innovation and resilience that are essential components of the biomedical profession. UMB summer programs, which span diverse biomedical disciplines from cancer research to diabetes, consolidated resources and identified mentors with online research projects to develop a robust virtual curriculum. Herein, data from a cancer-focused internship illustrate the collaborative adaptations to established components and creation of new learning modules in the transition to, and implementation of, online training. Outcomes are presented in the context of the COVID pandemic and significant societal issues that arose in the summer of 2020. The utility of virtual components and their impact on future programs is discussed.

Virtual bronchoscopy-guided lung SAbR: dosimetric implications of using AAA versus Acuros XB to calculate dose in airways.

In previous works, we showed that incorporating individual airways as organs-at-risk (OARs) in the treatment of lung stereotactic ablative radiotherapy (SAbR) patients potentially mitigates post-SAbR radiation injury. However, the performance of common clinical dose calculation algorithms in airways has not been thoroughly studied. Airways are of particular concern because their small size and the density differences they create have the potential to hinder dose calculation accuracy. To address this gap in knowledge, here we investigate dosimetric accuracy in airways of two commonly used dose calculation algorithms, the anisotropic analytical algorithm (AAA) and Acuros-XB (AXB), recreating clinical treatment plans on a cohort of four SAbR patients. A virtual bronchoscopy software was used to delineate 856 airways on a high-resolution breath-hold CT (BHCT) image acquired for each patient. The planning target volumes (PTVs) and standard thoracic OARs were contoured on an average CT (AVG) image over the breathing cycle. Conformal and intensity-modulated radiation therapy plans were recreated on the BHCT image and on the AVG image, for a total of four plan types per patient. Dose calculations were performed using AAA and AXB, and the differences in maximum and mean dose in each structure were calculated. The median differences in maximum dose among all airways were ≤0.3Gy in magnitude for all four plan types. With airways grouped by dose-to-structure or diameter, median dose differences were still ≤0.5Gy in magnitude, with no clear dependence on airway size. These results, along with our previous airway radiosensitivity works, suggest that dose differences between AAA and AXB correspond to an airway collapse variation ≤0.7% in magnitude. This variation in airway injury risk can be considered as not clinically relevant, and the use of either AAA or AXB is therefore appropriate when including patient airways as individual OARs so as to reduce risk of radiation-induced lung toxicity.

Validation of a CT-based motion model with in-situ fluoroscopy for lung surface deformation estimation.

Many surrogate-based motion models (SMMs), proposed to guide motion management in radiotherapy, are constructed by correlating motion of an external surrogate and internal anatomy during CT-simulation. Changes in this correlation define model break down. We validate a methodology that incorporates fluoroscopic (FL) images acquired during treatment for SMM construction and update. Under a prospective IRB, 4DCT scans, VisionRT (VRT) surfaces, and orthogonal FLs were collected from five lung cancer patients. VRT surfaces and two FL time-series were acquired pre- and post-treatment. A simulated annealing optimization scheme was used to estimate optimal lung deformations by maximizing the mutual information (MI) between digitally reconstructed radiographs (DRRs) of the SMM-estimated 3D images and FLs. Our SMM used partial-least-regression and was trained using the optimal deformations and VRT surfaces from the first breathing-cycle. SMM performance was evaluated using the MI score between reference FLs and the corresponding SMM or phase-assigned 4DCT DRRs. The Hausdorff distance for contoured landmarks was used to evaluate target position estimation error. For four out of five patients, two principal components approximated lung surface deformations with submillimeter accuracy. Analysis of the MI score between more than 4000 pairs of FL and DRR demonstrated that our model led to more similarity between the FL and DRR images compared to 4DCT and DRR images from a model based on an a priori correlation model. Our SMM consistently displayed lower mean and 95th percentile Hausdorff distances. For one patient, 95th percentile Hausdorff distance was reduced by 11 mm. Patient-averaged reductions in mean and 95th percentile Hausdorff distances were 3.6 mm and 7 mm for right-lung, and 3.1 mm and 4 mm for left-lung targets. FL data were used to evaluate model performance and investigate the feasibility of model update. Despite variability in breathing, use of post-treatment FL preserved model fidelity and consistently outperformed 4DCT for position estimation.

Functionally weighted airway sparing (FWAS): a functional avoidance method for preserving post-treatment ventilation in lung radiotherapy.

Recent changes to the guidelines for screening and early diagnosis of lung cancer have increased the interest in preserving post-radiotherapy lung function. Current investigational approaches are based on spatially mapping functional regions and generating regional avoidance plans that preferentially spare highly ventilated/perfused lung. A potentially critical, yet overlooked, aspect of functional avoidance is radiation injury to peripheral airways, which serve as gas conduits to and from functional lung regions. Dose redistribution based solely on regional function may cause irreparable damage to the 'supply chain'. To address this deficiency, we propose the functionally weighted airway sparing (FWAS) method. FWAS (i) maps the bronchial pathways to each functional sub-lobar lung volume; (ii) assigns a weighting factor to each airway based on the relative contribution of the sub-volume to overall lung function; and (iii) creates a treatment plan that aims to preserve these functional pathways. To evaluate it, we used four cases from a retrospective cohort of SAbR patients treated for lung cancer. Each patient's airways were auto-segmented from a diagnostic-quality breath-hold CT using a research virtual bronchoscopy software. A ventilation map was generated from the planning 4DCT to map regional lung function. For each terminal airway, as resolved by the segmentation software, the total ventilation within the sub-lobar volume supported by that airway was estimated and used as a function-based weighting factor. Upstream airways were weighted based on the cumulative volumetric ventilation supported by corresponding downstream airways. Using a previously developed model for airway radiosensitivity, dose constraints were determined for each airway corresponding to a <5% probability of airway collapse. Airway dose constraints, ventilation scores, and clinical dose constraints were input to a swarm optimization-based inverse planning engine to create a 3D conformal SAbR plan (CRT). The FWAS plans were compared to the patients' prescribed CRT clinical plans and the inverse-optimized clinical plans. Depending on the size and location of the tumour, the FWAS plan showed superior preservation of ventilation due to airflow preservation through open pathways (i.e. cumulative ventilation score from the sub-lobar volumes of open pathways). Improvements ranged between 3% and 23%, when comparing to the prescribed clinical plans, and between 3% and 35%, when comparing to the inverse-optimized clinical plans. The three plans satisfied clinical requirements for PTV coverage and OAR dose constraints. These initial results suggest that by sparing pathways to high-functioning lung subregions it is possible to reduce post-SAbR loss of respiratory function.

Non-cytotoxic radiosensitizers in brain radiotherapy: journey till the first decade of this millennium.

Brain tumors, primary and metastatic, are a cause of significant mortality and morbidity. Radiotherapy (RT) forms an integral part of the treatment of brain tumors. Intrinsic relative tumor radio-resistance, normal tissue tolerance and impact on neurocognitive function, all limit the efficacy of RT. Radiosensitizers can potentially increase efficacy on tumors while maintaining normal tissue toxicity, with or without inherent cytotoxicity. This article reviews the evolution of evidence with use of non-cytotoxic radiosensitizers in brain radiotherapy and their status at the end of the first decade of this millennium. Considering, the era of development and mechanism of action, these agents are classified as first, second and third-generation non-cytotoxic radiosensitizers. The last millennium involved elaboration of first-generation compounds including halogenated pyrimidines, hypoxic cell sensitizers (e.g. imidazoles) and glycolytic inhibitors (e.g. lonidamine). The first decade of this millennium has highlighted redox modulators like motexafin gadolinium and newer hypoxic cell sensitizers like efaproxiral, which have shown promise. However, phase III trials and meta-analyses have not identified a clear winner though the second-generation has shown some rays of hope. Recent research has focused on expanding the horizon by studying modulation of newer molecular pathways like DNA repair, microtubule stabilization, cytokine function and nuclear factor-kappa beta (NF-KB) in order to increase RT efficacy. The review concludes by summarizing the class of evidence and the level of recommendation available for use of non-cytotoxic radiosensitizers in brain RT.

Anesthetic management of the cancer patient undergoing noncardiac thoracic surgery.

The scope of this article is necessarily limited, but we have addressed preoperative assessment, monitoring, and intraoperative support that might be required for surgical patients with lung, mediastinal, and esophageal cancer. The development of the subspecialty of thoracic anesthesia has been responsible for reducing mortality and improving care of all patients undergoing noncardiac thoracic surgery and has been one of the forces behind the surgeon's ability to handle bigger challenges with better results.

A prospective randomized study of cerebrospinal fluid drainage to prevent paraplegia after high-risk surgery on the thoracoabdominal aorta.

This article is concerned with the study of the effect of several variables, principally that of cerebrospinal fluid drainage, on the incidence of neurologic deficit in a prospective randomized series of patients with extensive aneurysms of the descending thoracic and abdominal aorta (thoracoabdominal type I and II). Forty-six patients had cerebrospinal fluid drainage, and 52 were controls, with a total of 98 available for study. Cerebrospinal fluid pressure was continuously monitored in the former group and pressure maintained less than or equal to 10 mm Hg in 20, less than or equal to 15 mm Hg in 20, and greater than 15 mm Hg in 6 patients during period of aortic clamping. The method of treatment including reattachment of intercostal and lumbar arteries (p = 0.2), temporary atriofemoral bypass during aortic occlusion (p = 0.3), and spinal fluid drainage (p = 0.8) were not statistically significant in reducing the incidence of neurologic deficits. Thus cerebrospinal fluid drainage as we used it, was not beneficial in preventing paraplegia. On appropriate statistical analysis we found that the only significant predictor of delayed deficits was postoperative hypotension (p = 0.006).

Heparin monitoring during cardiopulmonary bypass.

Three procedures have been compared for monitoring heparin in patients undergoing cardiopulmonary bypass: (1) activated clotting time (ACT) (2) protamine titration, and (3) fluorometric substrate assay. The ACT monitors the degree of anticoagulation. It is easy to perform and is relatively inexpensive, however, it does not correlate well with heparin levels and may not accurately predict the protamine dose for neutralization of heparin at the completion of bypass. A protamine titration assay or an assay using a thrombin-sensitive fluorometric substrate measures the heparin level and calculates the protamine requirement at the completion of surgery; however, these assays do not indicate the degree of anticoagulation. The fluorometric assay is the less expensive of the two assay measuring heparin, but it requires an experienced technologist to perform the test.