Advancing Resident Education: Experiential Success in the Creation of a Comprehensive Clinical Didactic Series in Radiation Oncology.

Purpose: An effective didactic curriculum is a cornerstone for a successful residency program, as it is the basis upon which residents acquire the necessary knowledge and perspective to provide high-quality, evidence-based care. Here we describe our success in creating a standardized curriculum in clinical radiation oncology - one that was well-received and led to significantly improved performance on the national in-service examination. Methods and Materials: One-hundred and fifty topics were outlined in accordance with the American Board of Radiology; to accommodate this breadth of material, didactic frequency was increased from biweekly to daily. As a clinical correlate to these sessions, a teaching library of over 100 real-world cases was compiled for individual learning. Finally, comprehensive dosimetric constraints were compiled to aid residents in radiation therapy plan evaluation. To evaluate these curricular changes, anonymous questionnaires were provided to all residents and faculty, and de-identified resident clinical performance from the annual in-service examination was analyzed. Results: Before the introduction of the standardized curriculum, the mean clinical percentage on the in-service examination was 46%, equivalent to the 17th percentile. Within 2 years of implementation of the new curriculum, both the mean percentage and percentile were significantly improved, with the mean percentage correct at 69.3% and the mean percentile at the 59th percentile (P < .001 and P = .034, respectively). Feedback showed the curriculum to be well-received and used frequently outside of standard didactic hours. Conclusions: This is the first report of the creation of a standardized curriculum and outcomes in radiation oncology. Although there are certainly developmental challenges, addressing these barriers creates an education model that effectively imparts knowledge, fosters multidisciplinary thinking, and prepares residents for the diverse challenges of clinical practice. We present our institutional experience with the intent of publishing this curriculum on a national platform in the coming years.

Screening oral drugs for their interactions with the intestinal transportome via porcine tissue explants and machine learning.

In vitro systems that accurately model in vivo conditions in the gastrointestinal tract may aid the development of oral drugs with greater bioavailability. Here we show that the interaction profiles between drugs and intestinal drug transporters can be obtained by modulating transporter expression in intact porcine tissue explants via the ultrasound-mediated delivery of small interfering RNAs and that the interaction profiles can be classified via a random forest model trained on the drug-transporter relationships. For 24 drugs with well-characterized drug-transporter interactions, the model achieved 100% concordance. For 28 clinical drugs and 22 investigational drugs, the model identified 58 unknown drug-transporter interactions, 7 of which (out of 8 tested) corresponded to drug-pharmacokinetic measurements in mice. We also validated the model's predictions for interactions between doxycycline and four drugs (warfarin, tacrolimus, digoxin and levetiracetam) through an ex vivo perfusion assay and the analysis of pharmacologic data from patients. Screening drugs for their interactions with the intestinal transportome via tissue explants and machine learning may help to expedite drug development and the evaluation of drug safety.

Impact of formulation on solid oxygen-entrapping materials to overcome tumor hypoxia.

Tumor hypoxia, resulting from rapid tumor growth and aberrant vascular proliferation, exacerbates tumor aggressiveness and resistance to treatments like radiation and chemotherapy. To increase tumor oxygenation, we developed solid oxygen gas-entrapping materials (O2-GeMs), which were modeled after clinical brachytherapy implants, for direct tumor implantation. The objective of this study was to investigate the impact different formulations of solid O2-GeMs have on the entrapment and delivery of oxygen. Using a Parr reactor, we fabricated solid O2-GeMs using carbohydrate-based formulations used in the confectionary industry. In evaluating solid O2-GeMs manufactured from different sugars, the sucrose-containing formulation exhibited the highest oxygen concentration at 1 mg/g, as well as the fastest dissolution rate. The addition of a surface coating to the solid O2-GeMs, especially polycaprolactone, effectively prolonged the dissolution of the solid O2-GeMs. In vivo evaluation confirmed robust insertion and positioning of O2-GeMs in a malignant peripheral nerve sheath tumor, highlighting potential clinical applications.

Oral Carbon Monoxide Enhances Autophagy Modulation in Prostate, Pancreatic, and Lung Cancers.

Modulation of autophagy, specifically its inhibition, stands to transform the capacity to effectively treat a broad range of cancers. However, the clinical efficacy of autophagy inhibitors has been inconsistent. To delineate clinical and epidemiological features associated with autophagy inhibition and a positive oncological clinical response, a retrospective analysis of patients is conducted treated with hydroxychloroquine, a known autophagy inhibitor. A direct correlation between smoking status and inhibition of autophagy with hydroxychloroquine is identified. Recognizing that smoking is associated with elevated circulating levels of carbon monoxide (CO), it is hypothesized that supplemental CO can amplify autophagy inhibition. A novel, gas-entrapping material containing CO in a pre-clinical model is applied and demonstrated that CO can dramatically increase the cytotoxicity of autophagy inhibitors and significantly inhibit the growth of tumors when used in combination. These data support the notion that safe, therapeutic levels of CO can markedly enhance the efficacy of autophagy inhibitors, opening a promising new frontier in the quest to improve cancer therapies.

Impacts of embracing 39-week elective induction across an entire labor and delivery unit.

BACKGROUND: Induction of labor among low-risk, 39-week nulliparas increased significantly in the United States following publication of the outcomes of A Randomized Trial of Induction Versus Expectant Management trial. However, the rates of labor induction and outcomes in non-nulliparous patients and the wider impacts on the labor unit have not been reported widely. OBJECTIVE: This study aimed to compare the induction of labor rates and outcomes before and after liberal implementation of 39-week elective induction at a single center. STUDY DESIGN: This was a retrospective cohort study comparing the delivery characteristics of pregnancies 1 year before and 1 year after adoption of a new 39-week elective induction policy at a single, tertiary-care center. Notably, elective induction was not restricted to nulliparas. We examined all live, singleton, in-born deliveries ≥36 weeks gestation, excluding those with fetal anomalies and prolonged antenatal admission. Deliveries at ≥39 weeks gestation were further subcategorized as being high risk (diabetes mellitus, chronic hypertension, intrauterine growth restriction, history of fetal demise or cholestasis) or low risk, nulliparas vs multiparas, and with or without a previous cesarean delivery. Elective deliveries were those without a maternal, fetal, or obstetrical indication. Primary outcomes included gestational age and indications for delivery, rates of labor induction and elective induction, and time from admission to delivery. Secondary outcomes included the rate of cesarean deliveries, indications for cesarean deliveries, and maternal and newborn morbidities. The outcomes were compared using Wilcoxon rank-sum tests or chi-square tests as appropriate. The odds of cesarean delivery were analyzed using multivariate logistic regression and controlling for relevant confounders. RESULTS: A total of 2672 pre-implementation and 2526 post-implementation deliveries were studied. Among patients at ≥39 weeks gestation, elective delivery increased (pre-implementation, 344/1788 [19.2%] vs post-implementation, 684/1710 [40.0%]; P<.01) and admission for labor or ruptured membranes decreased (pre-implementation, 920/1788 [51.5%] vs post-implementation, 579/1710 [33.9%]; P<.01). Labor induction in the 39th week of gestation increased among low-risk and high-risk nulliparas, multiparas, and those with a previous cesarean delivery (P<.05 for each pairwise comparison), and the rate of 39-week elective inductions increased in all low-risk subgroups. Deliveries at 36 to 38 weeks gestation were similar in the proportion, timing, indications for delivery, and rate of labor induction. The odds of cesarean delivery was unchanged overall (adjusted odds ratio, 0.97; 95% confidence interval, 0.83-1.14) and for low-risk, ≥39-week nulliparas (adjusted odds ratio, 0.90; 95% confidence interval, 0.66-1.23) and low-risk, ≥39-week multiparas (adjusted odds ratio, 1.18; 95% confidence interval, 0.71-1.98). Among all deliveries, the median (interquartile range) time from admission to delivery increased significantly (pre-implementation, 12.8 [6.0-21.6] hours vs post-implementation, 15.6 [7.1-25.1] hours; P<.01) and the total cumulative patient care time from admission to delivery increased by 15% (pre-implementation, 41,578 hours vs post-implementation, 47,605 hours) when normalized by delivery volume. Chorioamnionitis incidence increased, whereas other maternal and neonatal morbidities were unchanged. CONCLUSION: Following adoption of a nonrestrictive, 39-week elective induction policy at a single, tertiary-care center, the rates of 39-week induction of labor and elective inductions increased among nulliparas, multiparas, and those with a previous cesarean delivery. The rate of cesarean delivery was unchanged, and the median time from admission to delivery and the cumulative admission to delivery hours increased significantly. Future studies are needed to further explore the full scope of the impacts on labor unit operations, costs, and patient experiences and outcomes.

Low-Cost, High-Pressure-Synthesized Oxygen-Entrapping Materials to Improve Treatment of Solid Tumors.

Tumor hypoxia drives resistance to many cancer therapies, including radiotherapy and chemotherapy. Methods that increase tumor oxygen pressures, such as hyperbaric oxygen therapy and microbubble infusion, are utilized to improve the responses to current standard-of-care therapies. However, key obstacles remain, in particular delivery of oxygen at the appropriate dose and with optimal pharmacokinetics. Toward overcoming these hurdles, gas-entrapping materials (GeMs) that are capable of tunable oxygen release are formulated. It is shown that injection or implantation of these materials into tumors can mitigate tumor hypoxia by delivering oxygen locally and that these GeMs enhance responsiveness to radiation and chemotherapy in multiple tumor types. This paper also demonstrates, by comparing an oxygen (O2 )-GeM to a sham GeM, that the former generates an antitumorigenic and immunogenic tumor microenvironment in malignant peripheral nerve sheath tumors. Collectively the results indicate that the use of O2 -GeMs is promising as an adjunctive strategy for the treatment of solid tumors.

Case report: Robotically visualized and biopsy-confirmed peritoneal carcinomatosis as initial identification of metastatic prostate adenocarcinoma in a patient with a history of prostatic urethral lift.

Background: Peritoneal carcinomatosis is a particularly rare presentation of prostate cancer. Here we report a rare clinical case of surgically identified peritoneal carcinomatosis at the time of a planned robotic prostatectomy in a patient with a history of prostatic urethral lift procedure. Case presentation: A 72-year-old man, with a history of urinary retention managed with tamsulosin, presented to his local urologist. Prostatic urethral lift procedures were performed for symptom management. After a definitive uptrend in his prostate-specific antigen (PSA) values, a biopsy was obtained, which demonstrated prostate adenocarcinoma. On presurgical multidisciplinary review, it was presumed that he had very high-risk localized prostate cancer. However, upon initiation of robotically assisted laparoscopic radical prostatectomy (RALP), he was noted to have numerous punctate white plaques on the peritoneum; biopsy of these lesions confirmed metastatic disease-for which the patient was starting on triple therapy per the PEACE-1 trial. The PSA level responded appropriately, decreasing from 16.8 to 0.08. Genetic testing was performed and returned negative for any clinically significant mutations. Conclusion: Our patient, diagnosed with peritoneal carcinomatosis during a planned RALP, highlights the importance of vigilant laparoscopic exam prior to this prostatectomy. Multidisciplinary discussion is crucial for individualized and optimal treatment planning.

Continuous liquid interface production of 3D printed drug-loaded spacers to improve prostate cancer brachytherapy treatment.

Brachytherapy, which is the placement of radioactive seeds directly into tissue such as the prostate, is an important curative treatment for prostate cancer. By delivering a high dose of radiation from within the prostate gland, brachytherapy is an effective method of killing prostate cancer cells while limiting radiation dose to normal tissue. The main shortcomings of this treatment are: less efficacy against high grade tumor cells, acute urinary retention, and sub-acute urinary frequency and urgency. One strategy to improve brachytherapy is to incorporate therapeutics into brachytherapy. Drugs, such as docetaxel, can improve therapeutic efficacy, and dexamethasone is known to decrease urinary side effects. However, both therapeutics have high systemic side effects. To overcome this challenge, we hypothesized that we can incorporate therapeutics into the inert polymer spacers that are used to correctly space brachytherapy seeds during brachytherapy to enable local drug delivery. To accomplish this, we engineered 3D printed drug-loaded brachytherapy spacers using continuous liquid interface production (CLIP) with different surface patterns to control drug release. These devices have the same physical size as existing spacers, allowing them to easily replace commercial spacers. We examined these drug-loaded spacers using docetaxel and dexamethasone as model drugs in a murine model of prostate cancer. We found that drug-loaded spacers led to higher therapeutic efficacy for brachytherapy, and there was no discernable systemic toxicity from the drug-loaded spacers. STATEMENT OF SIGNIFICANCE: There has been high interest in the application of 3D printing to engineer novel medical devices. However, such efforts have been limited by the lack of technologies that can fabricate devices suitable for real world medical applications. In this study, we demonstrate a unique application for 3D printing to enhance brachytherapy for cancer treatment. We engineered drug-loaded brachytherapy spacers that can be fabricated using Continuous Liquid Interface Production (CLIP) 3D printing, allowing tunable printing of drug-loaded devices, and implanted intraoperatively with brachytherapy seeds. In combined chemotherapy and brachytherapy we are able to achieve greater therapeutic efficacy through local drug delivery and without systemic toxicities. We believe our work will facilitate further investigation in medical applications of 3D printing.

Delivery of therapeutic carbon monoxide by gas-entrapping materials.

Carbon monoxide (CO) has long been considered a toxic gas but is now a recognized bioactive gasotransmitter with potent immunomodulatory effects. Although inhaled CO is currently under investigation for use in patients with lung disease, this mode of administration can present clinical challenges. The capacity to deliver CO directly and safely to the gastrointestinal (GI) tract could transform the management of diseases affecting the GI mucosa such as inflammatory bowel disease or radiation injury. To address this unmet need, inspired by molecular gastronomy techniques, we have developed a family of gas-entrapping materials (GEMs) for delivery of CO to the GI tract. We show highly tunable and potent delivery of CO, achieving clinically relevant CO concentrations in vivo in rodent and swine models. To support the potential range of applications of foam GEMs, we evaluated the system in three distinct disease models. We show that a GEM containing CO dose-dependently reduced acetaminophen-induced hepatocellular injury, dampened colitis-associated inflammation and oxidative tissue injury, and mitigated radiation-induced gut epithelial damage in rodents. Collectively, foam GEMs have potential paradigm-shifting implications for the safe therapeutic use of CO across a range of indications.

Respirators in Healthcare: Material, Design, Regulatory, Environmental, and Economic Considerations for Clinical Efficacy.

Maintaining an ample supply of personal protective equipment continues to be a challenge for the healthcare industry, especially during emergency situations and times of strain on the supply chain. Most critically, healthcare workers exposed to potential airborne hazards require sufficient respiratory protection. Respirators are the only type of personal protective equipment able to provide adequate respiratory protection. However, their ability to shield hazards depends on design, material, proper fit, and environmental conditions. As a result, not all respirators may be adequate for all scenarios. Additionally, factors including user comfort, ease of use, and cost contribute to respirator effectiveness. Therefore, a careful consideration of these parameters is essential for ensuring respiratory protection for those working in the healthcare industry. Here respirator design and material characteristics are reviewed, as well as properties of airborne hazards and potential filtration mechanisms, regulatory standards of governmental agencies, respirator efficacy in the clinical setting, attitude of healthcare personnel toward respiratory protection, and environmental and economic considerations of respirator manufacturing and distribution.

An automated all-in-one system for carbohydrate tracking, glucose monitoring, and insulin delivery.

Glycemic control through titration of insulin dosing remains the mainstay of diabetes mellitus treatment. Insulin therapy is generally divided into dosing with long- and short-acting insulin, where long-acting insulin provides basal coverage and short-acting insulin supports glycemic excursions associated with eating. The dosing of short-acting insulin often involves several steps for the user including blood glucose measurement and integration of potential carbohydrate loads to inform safe and appropriate dosing. The significant burden placed on the user for blood glucose measurement and effective carbohydrate counting can manifest in substantial effects on adherence. Through the application of computer vision, we have developed a smartphone-based system that is able to detect the carbohydrate load of food by simply taking a single image of the food and converting that information into a required insulin dose by incorporating a blood glucose measurement. Moreover, we report the development of comprehensive all-in-one insulin delivery systems that streamline all operations that peripheral devices require for safe insulin administration, which in turn significantly reduces the complexity and time required for titration of insulin. The development of an autonomous system that supports maximum ease and accuracy of insulin dosing will transform our ability to more effectively support patients with diabetes.

Carbon monoxide and a change of heart.

The relationship between carbon monoxide and the heart has been extensively studied in both clinical and preclinical settings. The Food and Drug Administration (FDA) is keenly focused on the ill effects of carbon monoxide on the heart when presented with proposals for clinical trials to evaluate efficacy of this gasotransmitter in a various disease settings. This review provides an overview of the rationale that examines the actions of the FDA when considering clinical testing of CO, and contrast that with the continued accumulation of data that clearly show not only that CO can be used safely, but is potently cardioprotective in clinically relevant small and large animal models. Data emerging from Phase I and Phase II clinical trials argues against CO being dangerous to the heart and thus it needs to be redefined and evaluated as any other substance being proposed for use in humans. More than twenty years ago, the belief that CO could be used as a salutary molecule was ridiculed by experts in physiology and medicine. Like all agents designed for use in humans, careful pharmacology and safety are paramount, but continuing to hinder progress based on long-standing dogma in the absence of data is improper. Now, CO is being tested in multiple clinical trials using innovative delivery methods and has proven to be safe. The hope, based on compelling preclinical data, is that it will continue to be evaluated and ultimately approved as an effective therapeutic.

Patient and Health Care Worker Perceptions of Communication and Ability to Identify Emotion When Wearing Standard and Transparent Masks.

Importance: Adoption of mask wearing in response to the COVID-19 pandemic alters daily communication. Objective: To assess communication barriers associated with mask wearing in patient-clinician interactions and individuals who are deaf and hard of hearing. Design, Setting, and Participants: This pilot cross-sectional survey study included the general population, health care workers, and health care workers who are deaf or hard of hearing in the United States. Volunteers were sampled via an opt-in survey panel and nonrandomized convenience sampling. The general population survey was conducted between January 5 and January 8, 2021. The health care worker surveys were conducted between December 3, 2020, and January 3, 2021. Respondents viewed 2 short videos of a study author wearing both a standard and transparent N95 mask and answered questions regarding mask use, communication, preference, and fit. Surveys took 15 to 20 minutes to complete. Main Outcomes and Measures: Participants' perceptions were assessed surrounding the use of both mask types related to communication and the ability to express emotions. Results: The national survey consisted of 1000 participants (mean [SD] age, 48.7 [18.5] years; 496 [49.6%] women) with a response rate of 92.25%. The survey of general health care workers consisted of 123 participants (mean [SD] age, 49.5 [9.0] years; 84 [68.3%] women), with a response rate of 11.14%. The survey of health care workers who are deaf or hard of hearing consisted of 45 participants (mean [SD] age, 54.5 [9.0] years; 30 [66.7%] women) with a response rate of 23.95%. After viewing a video demonstrating a study author wearing a transparent N95 mask, 781 (78.1%) in the general population, 109 general health care workers (88.6%), and 38 health care workers who are deaf or hard of hearing (84.4%) were able to identify the emotion being expressed, in contrast with 201 (20.1%), 25 (20.5%), and 11 (24.4%) for the standard opaque N95 mask. In the general population, 450 (45.0%) felt positively about interacting with a health care worker wearing a transparent mask; 76 general health care workers (61.8%) and 37 health care workers who are deaf or hard of hearing (82.2%) felt positively about wearing a transparent mask to communicate with patients. Conclusions and Relevance: The findings of this study suggest that transparent masks could help improve communication during the COVID-19 pandemic, particularly for individuals who are deaf and hard of hearing.

Personalized Radiation Attenuating Materials for Gastrointestinal Mucosal Protection.

Cancer patients undergoing therapeutic radiation routinely develop injury of the adjacent gastrointestinal (GI) tract mucosa due to treatment. To reduce radiation dose to critical GI structures including the rectum and oral mucosa, 3D-printed GI radioprotective devices composed of high-Z materials are generated from patient CT scans. In a radiation proctitis rat model, a significant reduction in crypt injury is demonstrated with the device compared to without (p < 0.0087). Optimal device placement for radiation attenuation is further confirmed in a swine model. Dosimetric modeling in oral cavity cancer patients demonstrates a 30% radiation dose reduction to the normal buccal mucosa and a 15.2% dose reduction in the rectum for prostate cancer patients with the radioprotectant material in place compared to without. Finally, it is found that the rectal radioprotectant device is more cost-effective compared to a hydrogel rectal spacer. Taken together, these data suggest that personalized radioprotectant devices may be used to reduce GI tissue injury in cancer patients undergoing therapeutic radiation.

Evolution of the Role of Radiotherapy for Anal Cancer.

Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy prior to abdominoperineal resection. Chemoradiotherapy 5-fluorouracil and mitomycin C afforded patients complete pathologic response and obviated the need for upfront surgery. More recent studies have attempted to alter or exclude chemotherapy used in the Nigro regimen to mitigate toxicity, often with worse outcomes. Reductions in acute adverse effects have been associated with marked advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guidance radiation delivery, resulting in increased tolerance to greater radiation doses. Ongoing trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Studies are also examining the role of newer treatment modalities such as proton therapy in treating anal cancer. Here we review the evolution of radiotherapy for anal cancer and describe recent advances. We also elaborate on radiotherapy's role in locally persistent or recurrent anal cancer.

Prospective Evaluation of the Transparent, Elastomeric, Adaptable, Long-Lasting (TEAL) Respirator.

N95 filtering facepiece respirators (FFR) and surgical masks are essential in reducing airborne disease transmission, particularly during the COVID-19 pandemic. However, currently available FFR's and masks have major limitations, including masking facial features, waste, and integrity after decontamination. In a multi-institutional trial, we evaluated a transparent, elastomeric, adaptable, long-lasting (TEAL) respirator to evaluate success of qualitative fit test with user experience and biometric evaluation of temperature, respiratory rate, and fit of respirator using a novel sensor. There was a 100% successful fit test among participants, with feedback demonstrating excellent or good fit (90% of participants), breathability (77.5%), and filter exchange (95%). Biometric testing demonstrated significant differences between exhalation and inhalation pressures among a poorly fitting respirator, well-fitting respirator, and the occlusion of one filter of the respirator. We have designed and evaluated a transparent elastomeric respirator and a novel biometric feedback system that could be implemented in the hospital setting.

Injection Molded Autoclavable, Scalable, Conformable (iMASC) system for aerosol-based protection: a prospective single-arm feasibility study.

OBJECTIVE: To develop and test a new reusable, sterilisable N95 filtering facepiece respirator (FFR)-comparable face mask, known as the Injection Molded Autoclavable, Scalable, Conformable (iMASC) system, given the dire need for personal protective equipment within healthcare settings during the COVID-19 pandemic. DESIGN: Single-arm feasibility study. SETTING: Emergency department and outpatient oncology clinic. PARTICIPANTS: Healthcare workers who have previously undergone N95 fit testing. INTERVENTIONS: Fit testing of new iMASC system. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome is success of fit testing using an Occupational Safety and Health Administration (OSHA)-approved testing method, and secondary outcomes are user experience with fit, breathability and filter replacement. RESULTS: Twenty-four subjects were recruited to undergo fit testing, and the average age of subjects was 41 years (range of 21-65 years) with an average body mass index of 26.5 kg/m2. The breakdown of participants by profession was 46% nurses (n=11), 21% attending physicians (n=5), 21% resident physicians (n=5) and 12% technicians (n=3). Of these participants, four did not perform the fit testing due to the inability to detect saccharin solution on premask placement sensitivity test, lack of time and inability to place mask over hair. All participants (n=20) who performed the fit test were successfully fitted for the iMASC system using an OSHA-approved testing method. User experience with the iMASC system, as evaluated using a Likert scale with a score of 1 indicating excellent and a score of 5 indicating very poor, demonstrated an average fit score of 1.75, breathability of 1.6, and ease of replacing the filter on the mask was scored on average as 2.05. CONCLUSIONS: The iMASC system was shown to successfully fit multiple different face sizes and shapes using an OSHA-approved testing method. These data support further certification testing needed for use in the healthcare setting.

Parallel evolution of polymer chemistry and immunology: Integrating mechanistic biology with materials design.

To develop new therapeutics involves the interaction of multiple disciplines to yield safe, functional devices and formulations. Regardless of drug function and potency, administration with controlled timing, dosing, and targeting is required to properly treat or regulate health and disease. Delivery approaches can be optimized through advances in materials science, clinical testing, and basic biology and immunology. Presently, laboratories focused on developing these technologies are composed of, or collaborate with, chemists, biologists, materials scientists, engineers, and physicians to understand the way our body interacts with drug delivery devices, and how to synthesize new, rationally designed materials to improve targeted and controlled drug delivery. In this review, we discuss both device-based and micro/nanoparticle-based materials in the clinic, our biologic understanding of how our immune system interacts with these materials, how this diverse set of immune cells has become a target and variable in drug delivery design, and new directions in polymer chemistry to address these interactions and further our advances in medical therapeutics.

Post-operative radiation therapy to the surgical cavity with standard fractionation in patients with brain metastases.

The paradigm for post-operative cavity radiation therapy has shifted to more targeted, less morbid approaches. Single-fraction or hypofractionated radiation therapy is a common approach to treating the postoperative cavity but is associated with a local failure rate 20-40%. We employed an alternative treatment strategy involving fractionated partial brain radiation therapy to the surgical cavity. Patients with brain metastases who underwent radiation treatment 30-42 Gy in 3 Gy/fraction regimens to surgical cavity were retrospectively identified. The 6-month and 12-month freedom from local failure rates were 97.0% and 88.2%. Three patients (7%) experienced local failure at 4, 6, and 22 months. Of these, the histologies were colorectal adenocarcinoma (N = 1) and breast adenocarcinoma (N = 2). The 6-month and 12-month freedom from distant brain metastases rates were 74.1% and 68.8%, respectively, and the 6-month and 12-month overall survival rates were 84.9% and 64.3% respectively. The median overall survival was 39 months, and there were no events of late radionecrosis. Fractionated partial brain irradiation to the surgical cavity of resected brain metastases results in low rates of local failure. This strategy represents an alternative to SRS and WBRT.

Use of iontophoresis for the treatment of cancer.

Despite major advancements in cancer treatments, there are still many limitations to therapy including off-target effects, drug resistance, and control of cancer-related symptoms. There are opportunities for local drug delivery devices to intervene at various stages of cancer to provide curative and palliative benefit. Iontophoretic devices that deliver drugs locally to a region of interest have been adapted for the treatment of cancer. These devices have shown promise in pre-clinical and clinical studies for retinoblastoma, skin, bladder, and pancreatic cancers. Herein, we review iontophoretic devices used in the management of cancer.